Contents
 

Mesenchymal tumors



6  Skin tumors

6.5  Mesenchymal tumors

6.5.1  Fibroma

Clinical signs:

  • location: friction areas: neck, axillae, internal aspects of thighs
  • soft, small tumors
  • color: pale brown

Histology:

Tumors are formed by connective tissue, fibrocytes are regular, mature, mitoses are not present.

Pictures

Perifollicular fibroma:
Perifollicular fibroma, HE 40x (2431)

6.5.2  Sclerosing fibroma

Clinical signs:

  • solitary lesion
  • multiple in Cowden's disease
  • size: up to 20 mm
  • firm dermal nodule

Histology:

Homogenous, paucicellular, collagenous tumor. Spindle cells are XIIIa positive.

Variant with multinucleated cells is pleomorphic sclerosing fibroma.

6.5.3  Dermatofibroma (histiocytoma of the skin)

Clinical signs:

  • common process, occurs anywhere, often on the extremities
  • usually solitary nodule, firm, roundish, sometimes polypoid
  • color: pink, brown, yellowish

Histology:

Variable appearance with participation of fibroblasts, blood vessels, mature connective tissue. Foamy macrophages (and Touton cells), siderophages and lymphocytes are present as well. The structure is sometimes storiform. Borders are unsharp, usually with typical entrapment of collagen fibres. Mature forms are composed mostly of mature collagen.

Acanthotic proliferation of the overlying epidermis is common, often with increased pigmentation (melanin) and sometimes with follicular induction (which may resemble superficial basalioma).

Less common are cellular histiocytomas, rare are aneurysmatic and epithelioid forms.

Pictures

Dermatofibroma:
Dermatofibroma, HE 40x (2623)

Another case:
Dermatofibroma, HE 40x (2624)

Another case:
Dermatofibroma, HE 40x (4792)
  [zoomify]

Another case:
Dermatofibroma, HE 60x (10568)

Another case:
Dermatofibroma, HE 40x (12664)

Another case:
Dermatofibroma, HE 40x (12665)

Another case:
Dermatofibroma, HE 60x (10660)

Old dermatofibroma:
Dermatofibroma, HE 20x (2208)

Large, cellular histiocytoma:
Cellular histiocytoma, large, HE 10x (2683)

Cellular histiocytoma, large, HE 40x (2684)

Another example of a large histiocytoma:
Dermatofibroma, large, HE 40x (3615)

Dermatofibroma, large, Prussian blue 40x (3614)

Histiocytoma, large, CD68 40x (3628)

Histiocytoma, large, Ki67 40x (3629)

Another case of large histiocytoma:
Dermatofibroma, HE 20x (3659)

Dermatofibroma, HE 40x (3660)

Cellular dermatofibroma:
Cellular dermatofibroma, HE 60x (10567)

Cellular dermatofibroma:
Cellular histiocytoma, HE 60x (10992)

Dermatofibroma with pseudoepithelimatous hyperplasia:
Histiocytoma with pseudoepitheliomatous hyperplasia, HE 60x (12063)

Dermatofibroma with hemosiderin deposits and giant cells:
Histiocytoma with giant cells, HE 40x (12064)

Dermatofibroma with prominent deposits of hemosiderin:
Dermatofibroma with prominent deposits of hemosiderin, HE 40x (3528)

Another case of a large dermatofibroma with prominent deposits of hemosiderin (black histiocytoma):
Black histiocytoma, HE 20x (4842)
  [zoomify]
Black histiocytoma, HE 40x (4764)
  [zoomify]
Black histiocytoma, Prussian blue 40x (4763)

Dermatofibroma of a patient with primary hemochromatosis, heavy hemosiderin pigmentation:
Dermatofibroma, patient with hemochromatosis, HE 20x (3560)

Dermatofibroma, patient with hemochromatosis, Prussian blue 20x (3559)

Dermatofibroma with follicular induction:
Dermatofibroma with follicular induction, HE 20x (3655)

Dermatofibroma with follicular induction, HE 40x (3656)

Keloidal dermatofibroma:
Dermatofibroma, keloidal, HE 40x (4878)

Dermatofibroma, atrophy:
Dermatofibroma, atrophic, HE 20x (5457)

Dermatofibroma with mucin accumulation:
Dermatofibroma, mucinous = vyradit, je to asi nevus, HE 40x (5030)
  [zoomify]
Dermatofibroma, mucinous = vyradit, je to asi nevus, Halle 20x (5029)

Dermatofibroma:
Dermatofibroma, HE 40x (12282)

Cellular histiocytoma with monster cells:
Dermatofibroma with monster cells, HE 40x (5154)

Aneurysmatic histiocytoma:
Aneurysmatic histiocytoma, HE 20x (5444)

Aneurysmatic histiocytoma, HE 40x (5445)

Aneurysmatic histiocytoma, CD34 40x (5442)

Epithelioid histiocytoma:
Epitheloid histiocytoma, HE 60x (6402)

Epitheloid histiocytoma, CD68 60x (6401)

Epithelioid histiocytoma:
Epitheloid histiocytoma, HE 60x (13635)

Scarring histiocytoma:
Scarring dermatofibroma, HE 40x (5446)

Dermatofibroma combined with seborrhoic keratosis (serial sections):
Dermatofibroma and seborrhoic keratosis, HE 20x (13448)

Dermatofibroma and seborrhoic keratosis, HE 20x (13449)

Dermatofibroma, cellular, diff. dg. fibrosarcoma:
Dermatofibroma or fibrosarcoma, HE 20x (13771)

6.5.4  Dermatomyofibroma

Clinical signs:

  • slowly growing, flat, indurated, red-brown lesion
  • size: up to 2 cm
  • localization: shoulder, axilla, other (less common)
  • usually affects young females
  • benign
  • therapy: complete excision

Histology:

Fascicles of spindle-shaped cells with eosinophilic cytoplasm and regular nuclei. Elastic fibres are increased and fragmented. Adnexal structures are preserved.

Imunohistochemistry: half of cases stain for smooth muscle markers.

6.5.5  Atypical fibroxantoma

Clinical signs:

  • tumorous nodule, size up to 2 cm
  • location: head, neck, dorsa of the hands
  • age: elderly people
  • locally aggresive, but capable of metastizing
  • considered to be a superficial malignant fibrous histiocytoma

Histology:

Nodular tumor of spindle-shaped and pleomorphic cells, not encapsulated. Admixture of large, pleomorphic cells. Mitotic activity, ulceration and necroses are present. Variably foam cells are admixtured.

Pictures

Atypical fibroxanthoma:
Atypical fibroxanthoma, AFX, HE 20x (4390)

Another case:
Atypical fibroxanthoma, AFX, HE 20x (4391)
  [zoomify]

Atypical fibroxanthoma, ear:
Atypical fibroxanthoma (ear), HE 2.5x (1166)

Atypical fibroxanthoma, HE 10x (1164)

Atypical fibroxanthoma, HE 20x (1165)

Atypical fibroxanthoma, HE 40x (1167)

Atypical fibroxanthoma, HE 40x (1168)

Another case:
Atypical fibroxanthoma, HE 20x (1169)

Another case, ulcerating AFX (HE, CD10, AE13, MelanA):
Atypical fibroxanthoma, AFX, HE 60x (13943)

Atypical fibroxanthoma, AFX, CD10 20x (13941)

Atypical fibroxanthoma, AFX, AE13 20x (13940)

Atypical fibroxanthoma, AFX, Melan A 20x (13942)

Another case:
Atypical fibroxanthoma, AFX, HE 60x (6447)

Atypical fibroxanthoma, AFX, vimentin 40x (6453)

Atypical fibroxanthoma, AFX, Melan A 40x (6452)

Another case:
Atypical fibroxanthoma, AFX, HE 60x (13630)

Another case:
Atypical fibroxanthoma, AFX, HE 40x (12055)

Another case, MelanA:
Atypical fibroxanthoma, AFX, Melan A 20x (13976)

Atypical fibroxanthoma, spindle cell variant:
Atypical fibroxanthoma, spindle cell variant, HE 60x (10473)

Superficial malignant fibrous histiocytoma:
Malignant fibrous histiocytoma, HE 20x (4819)
  [zoomify]

Atypical fibroxanthoma, malignant fibrous histiocytoma:
Atypical fibroxanthoma or malignant fibrous histiocytoma, HE 40x (12913)

Atypical fibroxanthoma:
Atypical fibroxanthoma, AFX, HE 60x (13764)

Atypical fibroxanthoma, AFX, AE13 20x (13762)

Atypical fibroxanthoma, AFX, Melan A 20x (13763)

Malignant fibrous histiocytoma, radiodermatitis:
Malignant fibrous histiocytoma, HE 20x (4820)
  [zoomify]

6.5.6  Dermatofibrosarcoma protuberans

Clinical signs:

  • malignant tumor, slowly growing lesion
  • metastaes rarely
  • local recurrences often
  • location: trunk, proximal parts of the extremities
  • affects younger persons

Histology:

Spindle, monomorphous cells; often storiform and/or honeycomblike arrangement, infiltration into the subcutis. Sometimes myxomatous areas are present. Polymorphous cells may be present. Mitotic activity is low or moderate. Imuno: CD34 positivity.

6.5.6.1  Bednar tumor, pigmented dermatofibrosarcoma protuberans

Clinical signs:

Clinical features are similar to those of dermatofibrosarcoma protuberans.

Histology:

Histology is similar to those of dermatofibrosarcoma protuberans, some of the tumor cells contain melanin.

6.5.6.2  Malignant fibrous histiocytoma, pleomorphic sarcoma

Clinical signs:

  • malignant tumor, often recurrences and metastases
  • age: midle age or elderly people
  • skin is affected usually as a part of deep involvement of soft tissues

Histology:

Several variants (pleomorphic, inflammatory, myxoid, angiomatoid, giant cell). Sometimes storiform arrangement. May contain foamy cells. Mitotic activity, necroses.

Pictures

Malignant fibrous histiocytoma:
Malignant fibrous histiocytoma, HE 20x (4844)
  [zoomify]

Malignant fibrous histiocytoma:
Malignant fibrous histiocytoma, pleomorfic, HE 20x (4845)
  [zoomify]

Malignant fibrous histiocytoma:
Malignant fibrous histiocytoma, HE 60x (13205)

Malignant fibrous histiocytoma:
Malignant fibrous histiocytoma, HE 40x (12620)

6.5.6.3  Giant cell fibroblastoma

Clinical signs:

  • rare tumor, occuring in children
  • location: chest wall, back, thigh
  • solitary tumorous nodules, poorly circumscribed

Histology:

Variable appearance (myxoid, sclerotic, dermatofibrosarcoma-like areas multinuclear giant cells, sometimes line cleft-like, angiomatoid spaces.

Immuno: CD34+ (regarded as a variant of DFSAP)

Pictures

Giant cell fibroblastoma:
Giant cell fibroblastoma, HE 40x (2393)

6.5.7  Skin tags

6.5.7.1  Fibroepithelial polyp

Clinical signs:

  • polypous tumors, size usually no more than 10 mm
  • covered by the epidermis (sometimes thickened, pigmented, may resemble seborrhoic keratosis
  • location: variable, often neck, axilla, inguinae, eyelids etc.

Histology:

Polyps covered by the epidermis, often with mild hyperkeratosis; usually no parakeratosis; stroma is formed by connective tissue, often with fat tissue and dilated blood vessels; sometimes groups of melanocytes.

Pictures

Skin tag:
Skin tag, HE 20x (5403)

Fibroepithelial polyp, infarsation:
Skin tag, infarsation, HE 20x (6202)

Fibrolipoma:
Fibrolipoma, HE 60x (10668)

Fibroma, skin tag:
Fibroma, HE 60x (10569)

Skin tag, fibroepithelial polyp, fibroma pendulum:
Fibroma pendulum, HE 40x (10167)

Skin tag, fibroepithelial polyp, fibroma pendulum:
Fibroma molle, skin tag, HE 40x (12951)

Mucosal polyp, fibroma:
Mucous fibroma, HE 60x (10587)

Skin tag, fibroepithelial polyp, ligated:
Skin tag, ligation, partial necrosis, HE 20x (13885)

6.5.7.2  Supernumerary digit

Clinical signs:

  • location: hands, feet; usually near the fifth finger
  • inborn

Histology:

Skin colored outgrowth, fibrous stroma, many nerves, sometimes cartilage or bone.

Pacchioni bodies are sometimes present.

Pictures

Supernumerary digit (leg):
Acessory digit, HE 20x (6014)

Supernumerary digit (hands, bilateral), Pacchioni bodies:
Supernumerary digit, HE 60x (13871)

Supernumerary digit, S100 60x (13872)

6.5.7.3  Supranumerary nipple

Clinical signs:

  • location: chest, ventrally
  • verrucous lesion
  • inborn

Histology:

Vertically oriented collagenous fibres, smooth muscle, tubules with two-layered, apocrine lining.

6.5.7.4  Accessory tragus

Clinical signs:

  • age: inborn
  • location: preauricular, neck
  • asymptomatic papule

Pictures

Accessory tragus:
Accessory tragus, CLINIC (2788)

Histology:

Connective tissue, fat, sometimes cartilage. Many hair follicles.

Pictures

Accessory tragus:
Accessory tragus, HE 20x (5120)
  [zoomify]

Accessory tragus:
Accessory tragus, HE 40x (10455)

Accessory tragus:
Accessory tragus, HE 20x (13868)

Accessory tragus or (rare) hair follicle nevus:
Accessory tragus or hair follicle nevus, HE 20x (13559)

6.5.7.5  Fibrous papule of the nose (face)

Clinical signs:

  • papule, usually on the nose
  • size: up to 5 mm
  • common

Histology:

Connective tissue with some larger, stellate, spindle or bizzare cells (fXIII. positive). Often ectatic blood vessels.

Pictures

Fibrous papule of the nose:
Fibrous papule of the nose, HE 60x (10570)

Fibrous papule of the nose:
Fibrous papule of the face, HE 20x (13996)

6.5.7.6  Acral fibrokeratoma

Clinical signs:

  • location: fingers; sometimes palms, soles (but not periungual)
  • solitary lesions, hyperkeratotic

Histology:

Fibrous stroma, prominent hyperkeratosis, often many blood vessels.

6.5.7.7  Acquired periungal fibrokeratoma

Clinical signs:

  • periunguals outgrowths with hyperkeratosis
  • accompanies tuberous sclerosis

Histology:

Fibrous, hyperkeratotic periunguals outgrowths.

Pictures

Acquired periungal fibrokeratoma:
Acquired periungal fibrokeratoma, HE 20x (13629)

6.5.7.8  Vestibular papules of the vulva

Clinical signs:

  • location: vulva
  • papule covered with normal epidermis

Histology:

Papule with fibrous stroma, covered with epidermis.

6.5.7.9  Focal dermal hypoplasia of Golz

Clinical signs:

  • affects only women; inborn
  • location: anywhere
  • papillomatous and polypoid lesion
  • other kind of the lesion are characterized by dermal hypoplasia, where most of the dermis is replaced by the fat, further focal skin atrophy and other anomalied (bone striae, colobomas, hypoplasia of the nails, hair etc.)

Pictures

Skin tag in dermal hypoplasia of Golz:
Skin tag (dermal hypoplasia of Golz), HE 40x (2539)

Focal dermal hypoplasia:
Hypoplasia cutis, HE 40x (6207)

6.5.8  Keloid

Clinical signs:

  • location: scars (esp. after burns), sternal region, earlobes
  • firm, raised, nodular lesions
  • fresh keloid is red, later gets pale

Pictures

Keloid, scar:
Keloid, CLINIC (779)

Keloid, presternal area:
Keloid, CLINIC (1058)

Keloid:
Keloid, CLINIC (1059)

Keloid, earlobe:
Keloid, CLINIC (1060)

Keloid, scar:
Keloid, CLINIC (1061)

Keloid, scar:
Keloid, CLINIC (3046)

Keloid, CLINIC (3047)

Keloid, CLINIC (3048)

Another examples of keloid:

Histology:

Broad strands of hyalinized, eosinophilic collagen within a cellular scar.

6.5.9  Lipoma

Introduction:

Tumor of the fatty tissue, exists in many variants.

6.5.9.1  Common lipoma

Clinical signs:

  • location: arms, shoulders, back, lower extremities
  • solitary or multiple
  • elastic nodules of the subcutis
  • rarely symmetric diffuse hyperplasia of the fat (lipomatosis)
  • sometimes painful

Pictures

Another examples of lipoma:

Histology:

Lipoma is a benign tumor of the mature fat. Its structure corresponds to the fat, but has fine capsule. Its cells are usually slightly larger than normal adipocytes.

6.5.9.1.1  Spindle cell lipoma

Clinical signs:

  • benign tumor
  • location:
    • subcutaneous: posterior neck, upper back or shoulders; well circumscribed
    • dermal: other locations (face, hands, thighs)

Histology:

Fat + spindle cells in variable proportion, no lipoblasts. Nuclear palisading may be sometimes present. CD34 is positive.

6.5.9.1.2  Lipomatosis

Clinical signs:

Multiple subcutaneous lesions (lipomas).

Pictures

Benign symmetric lipomatosis:
Lipoma, CLINIC (797)

Benign symmetric lipomatosis — arm:
Lipoma, CLINIC (798)

Another case of benigh lipomatosis:
Lipomatosis symmetrica, CLINIC (5732)

Lipomatosis symmetrica, CLINIC (5733)

Lipomatosis symmetrica, CLINIC (5734)

Another case of benigh lipomatosis:
Lipomatosis symmetrica, CLINIC (5735)

6.5.9.2  Angiolipoma

Clinical signs:

  • age: usually young adults
  • encapsulated subcutaneous lesions
  • sometimes painful

Histology:

Encapsulated lipomas with focally numerous vascular channels with thrombi.

6.5.9.3  Angiomyolipoma

Clinical signs:

  • location: usually kidney, but rarely affects the skin
  • sometimes associated with tuberous sclerosis

Histology:

Benign tumor consisting of blood vessels, smooth muscle and fat.

6.5.9.4  Liposarcoma

Clinical signs:

  • malignant tumor of soft tissues, rarely found in the subcutis
  • age: over 50 years, children affected rarely

Histology:

4 types:

  • well differentiated (lipoma like, sclerosing, inflammatory)
  • myxoid
  • round cell
  • pleomorphic

Lipoblast is the characteristic cell, containg cytoplasmatic vacuoles with lipid, which cause indentations of the nucleus. The nuclear polymorphism is variable, from low to striking (pleomorphic variant). High grade liposarcomas show unequivocal signs of malignancy (mitotic activity, polymorphism, infiltrative growth). Details are described in specialized literature.

6.5.10  Vascular tumors

6.5.10.1  Benign vascular tumors
6.5.10.1.1  Capillary hemangioma

Clinical signs:

  • some variants present at birth, growth and regression by the age of 8
  • size up to several cm, rarely giant forms
  • lively red color
  • danger of bleeding

Pictures

Capillary hemangioma of the forearm, regression in the center:
Hemangioma, CLINIC (750)

Flat hemangioma, glans penis:
Hemangioma, CLINIC (2967)

Hemangioma, CLINIC (2968)

Hemangioma tuberosum:
Hemangioma tuberosum, CLINIC (2969)

Hemangioma tuberosum, CLINIC (2970)

Hemangioma tuberosum, CLINIC (2971)

Another examples of hemangioma:

Histology:

Tumor of the blood vessels of capillary calibre (no elastic fibres nor smooth muscle within the wall, size is variable) and undifferentiated endothelia. The tumor has no capsule,its borders are unsharp. Superficial form often regress. Larger tumors, which have deep parts, do not regress and grow together with the patient.

6.5.10.1.2  Cavernous hemangioma

Clinical signs:

  • less frequent than capillary hemangioma
  • location: usually upper half of the body
  • larger and deeper than capillary hemangiomas, sometimes very large
  • usually no regression, surgery required
  • bluish color, uneven surface
  • dystrophic calcifications, phleboliths (x-ray), thrombi
  • deep forms affect internal organs
  • Maffucci's syndrome: dyschondroplasia, bone deformities, widespread hemangiomas of various types; blood vessel and bone malignities (spindle cell hemangioendothelioma)

Histology:

Large, cavernous vascular spaces, lined by endothelium; thrombi, calcifications. Sometimes areas corresponding to capillary hemangioma are found as well.

Pictures

Cavernous hemangioma:
Hemangioma, cavernous, HE 20x (1323)

6.5.10.1.2.1  Sinusoidal hemangioma

Clinical signs:

  • variant of cavernous hemangioma
  • solitary lesion
  • age: adults; acquired lesion

Histology:

Ramifying vascular spaces, papillary endothelial infoldings, thrombi.

6.5.10.1.2.2  Venous lake

Clinical signs:

  • small papule of bluish red color
  • location: insolated areas
  • age: usually people over 50

Histology:

Dilatated solitary vascular space with thin wall, sometimes may contain thrombus in variable stage of organisation.

Pictures

Venous lake:
Venous lake, HE 20x (4782)

Venous lake:
Venous lake, HE 20x (5272)

6.5.10.1.2.3  Blue rubber bleb nevus syndrome

Introduction:

Variant of cavernous hemangioma accompanied by similar gastrointestinal lesions. The hemangiomas are compressible, but quickly regain their shape after the pressure ceases. Sometimes accompanied by hyperhidrosis.

6.5.10.1.2.4  Nevus simplex

MUDr. Renata Faberová, PhD.

Clinical signs:

  • location: neck, forehead, glabella, eyelids, nasolabial area
  • dark pink macules, often with teleangiectasia
  • disappears by about 1 year of age (as opposed to nevus flammeus), but in nape location persists in about 50% of children

Pictures

Nevus simplex, child:
Nevus simplex, CLINIC (1925)

Another case, adult:
Nevus flammeus, CLINIC (5774)

Histology:

Dilated dermal capillaries, corresponding to persisting fetal circulation.

6.5.10.1.2.5  Nevus flammeus

MUDr. Renata Faberová, PhD

Introduction:

Inborn vascular tumor, several types

Clinical signs:

  • pink or red wine colored patches
  • age: may be present at birth
  • do not regress, hypertrophy in higher age
  • part of several syndromes: Sturge-Weber (congenital, but nor familial angiomatosis affecting the skin of the face, leptomeninges and brain), Klippel-Trénaunay (nevus flammeus, congenital AV fistula and hypertrophy of the bones and soft tissues in affected area).

Histology:

Flat angiomas consist of variably dilated capillaries. The lesion develops gradually. In early stages of development the histological picture is often inconspicuous: slightly increased number of histologically normal capillaries within the upper dermis is difficult to evaluate. Later variably dilated blood vessels appear. In adults there are usually many cavernous vascular spaces, vascular proliferations and fibrosis.

6.5.10.1.3  Arteriovenous malformation

Introduction:

Arteriovenous malformation (arteriovenous hemangioma) is a vascular lesion, composed of capillaries, veins and arteries.

Clinical signs:

  • location: variable, can occur anywhere
  • size: from small papule to large lesions, often affecting deep soft tissues
  • age: inborn lesion, gradually developing and enlarging
  • can cause blood shutning (and hemodynamic complications)
  • x-ray arteriogram shows filling and draining blood vessels
  • malformation, trophic changes, pain, local venous hypertension, gigantism, destruction of the bone, distal ischemia
  • tinnitus in lesions located on the head
  • heart failure in large lesions
  • pulsating lesions with murmur

Histology:

Mixture of blood vessels separated by connective tissue and fat. The size of blood vessel lumens varies. Some may have thick wall composed of connective tissue and smooth muscle (van Gieson, smooth muscle actin), corresponding to arteries and veins. Staining for elastic tissue will show lamina elastica interna in arteioles; both arteries and veins usually have variable amount of elastic fibres within outer layers of their walls. Capillaries are often crowded and resemble capillary hemangioma closely. These areas may show proliferation with mitotic activity and sometimes resemble Kaposi's sarcoma (pseudo-Kaposi's sarcoma, but this term is used for irregular vascular proliferation caused by stasis in lower extremities as well); hemosiderin deposits may be present as well.

6.5.10.1.4  Venous malformation

Clinical signs:

  • age: inborn, but diagnosed usually in adults
  • location: variable, usually deep soft tissue
  • complex formations, affecting skin, muscle, bone, joints
  • x-ray: venograms required for diagnosis (slow venous flow); sometimes calcifications; often bone abnormalities (thinning, demineralization, hypoplasia, sometimes osteolysis
  • size: usually large; varricosities, venous dilatations and cutaneous spongiform masses
  • worsens during the life
  • dilates during exercise, strain or in vertical position
  • often painful
  • sometimes disorders of hemocoagulation

Pictures

Venous malformation:
Venous malformation, CLINIC (1924)

Histology:

Variable, often large, thick walled venous blood spaces, thrombi, calcifications, variable dilatation of the venous spaces. Connective tissue, fat, muscle usualy separates the blood vessels. Large vascular spaces often dissect the connective tissue and its structures.

6.5.10.1.5  Cutis marmorata teleangiectatica

Clinical signs:

  • inborn condition with tendency to improvement
  • variable areas with prominent superficial blood vessels

Histology:

Inconspicuous areas with increased and dilated thin wall blood vessels. The histology is usually not diagnostic and clinicall correlation is required.

Pictures

Cutis marmorata teleangiectatica, child, buttocks:
Cutis marmorata teleangiectatica, HE 40x (4118)

6.5.10.1.6  Angioma serpiginosum

Clinical signs:

  • starts early in the childhood
  • affects usually girls
  • some cases are familiar
  • location: anywhere (but for palms and soles)
  • linearly, circularly and irregularly arranged dot-like blood vessels (size of about 1 mm)
  • the lesion usualy stops growing after puberty
  • benign, no other clinical complications

Histology:

Dilated superficial capillaries, vascular anomaly.

Pictures

Angioma serpiginosum:
Angioma serpiginosum, HE 20x (4652)
  [zoomify]

6.5.10.1.7  Ectatic superficial capillaries in areas of solar degeneration of elastic fibres

Clinical signs:

  • afects elderly people
  • insolation areas
  • teleangiectatic blood vessels, sometimes with hemorrhage

Histology:

Irregulary dilated capillaries within areas of solar elastosis. Sometimes bleeding is present.

Pictures

Dilated superficial blood vessels and bleeding in areas of solar degeneration of elastic fibres:
Teleangiectatic hemangioma in sun damaged skin, HE 40x (5496)

Another case:
Teleangiectasia in actinic damaged skin, HE 20x (14022)

6.5.10.1.8  Congenital teleangiectatic erythema (Bloom's syndrome)

Clinical signs:

  • autosomal recessive
  • teleangiectases
  • photosensitivity
  • growth retardation, triangular face, increased incidence of malignancies (leukemia, squamous cell carcinoma, lymphomas, adenocarcinomas)
  • hypo- a hyperpigmentations
  • frequent infections

Pictures

Congenital teleangiectatic erythema:
Congenital teleangiectatic erythema Bloom, HE 20x (4429)

6.5.10.1.9  Osler Weber Rendu hereditary haemorrhagic telangiectasia

Pictures

  • rare disease
  • autosomal dominant disorder, starts in childhood
  • mucocutaneous and visceral teleangiectasia
  • bleeding, ulcerations, epistaxis, AV fistulae of internal organs

Histology:

Superficial vascular dilatations, newly formed blood vessels, sometimes with thickened walls.

Pictures

Osler's disease:
M. Osler, HE 20x (5377)

6.5.10.1.10  Spindle cell hemangioma

Clinical signs:

  • age: young adults
  • location: distal extremities (esp. hand)
  • often near a larger veins
  • tumorous vascular spaces contain thrombi, often calcified
  • sometimes associated with Maffucci's and Klippel-Trénaunay syndromes
  • solitary or multiple papule
  • often reccurrs after surgery
  • benign tumor

Histology:

Cavernous vessels with thin walls, containing thrombi. Between these spaces there are areas of spindle cells and fibrocytes (vimentin positive). The spindle cells are positive for ASMA (marker for pericytes) and mostly negative for endothelial markers (CD31, CD34). Spindle cell areas contain polygonal, epithelioid endothelial cells (CD31 and CD34 positive) with vacuolated cytoplasm. The vacuoles are sometimes large, so that these cells may resemble fat.

6.5.10.1.11  Angiokeratoma

Clinical signs:

  • most frequent location: genital, lower extremities, trunk
  • violet papules with hyperkeratosis
  • linear arrangement on lower extremities
  • diffuse angiokeratomas are the sign of Fabry disease (defect of alpha-galactosidase A)
  • Angiokeratoma of Fordyce: multiple small (2 – 4 mm) angiokeratomas on the scrotum
  • Angiokeratoma of Mibelli: verrucous angiokeratomas on the dorsa of the fingers and toes

Pictures

Scrotum and vulva are frequent location of angiokeratomas in elderly people:
Angiokeratoma, CLINIC (658)

Angiokeratoma scroti:
Angiokeratoma scroti, CLINIC (2798)

Angiokeratoma scroti, CLINIC (2800)

Angiokeratoma vulvae:
Angiokeratoma vulvae, CLINIC (2802)

Senile angiokeratoma:
Hemangioma, senile, CLINIC (2803)

Hemangioma, senile, CLINIC (2804)

Histology:

Epidermal hyperplasia with hyperkeratosis in close apposition to capillary spaces (which are dilated, with thin wall).

6.5.10.1.12  Granulation tissue

Clinical signs:

  • occurs in wound healing, chronic ulcerations etc.

Histology:

Loose granulation tissue, many capillaries, mixed inflammatory infiltration with variable number of neutrophils

6.5.10.1.13  Intravascular hemangioma of Masson

Clinical signs:

  • occurs sometimes in organizing of a thrombosed blood vessel or within a vascular tumor or malformation
  • benign

Histology:

Remnants of a thrombosed blood vessel; organizing thrombus, granulation tissue, irregular vascular lumina and multiple papillary endothelial proliferations; endothelial cells are regular.

6.5.10.1.14  Granuloma pyogenicum

Introduction:

Benign vascular tumor (lobular hemangioma) with variable inflammatory infiltrate, which usually does not have granulomatous features. The name refers to granulomatous tissue.

Clinical signs:

  • appear in the sites of small injuries
  • friable, small, easy to bleed tumor, size up to 2 cm
  • color: red or violet
  • sometimes narrowed at the base
  • develops quickly

Histology:

Capillary tumorous proliferation, lobulary arranged. Sometimes with residual inflammatory infiltrate.

6.5.10.1.15  Senile hemangioma

Clinical signs:

  • common finding, more frequent in elderly people
  • tiny macules and tumors, size up to several milimeters
  • lively red color

Pictures

Multiple senile hemangiomas, trunk:
Hemangioma, CLINIC (752)

Histology:

Corresponds to capillary hemangioma.

6.5.10.1.16  Acquired tufted hemangioma

Clinical signs:

  • location: upper part of the body
  • slowly growing macules and plaques
  • small darker nodules within the tumor
  • very rare tumor

Histology:

Roundish nodules of capillaries, partially solid, forming so called cannonballs within the dermis. On the periphery there are slit-like blood vessels and. CD31 and ASMA (marker for pericytes) are positive. No inflammatory infiltrate, no cellular atypia, thromboses nor deposits of hemosiderin. The infiltration is limited to the dermis.

6.5.10.1.17  Microvenular hemangioma

Clinical signs:

  • rare type of hemangioma
  • age: most often young adults
  • location: extremities, axillary region, trunk
  • usually solitary lesion (patch, plaque)
  • size: less than 2 cm

Histology:

Tumor consists of multiple small blood vessels of venular type in hyalinized or sclerotic stroma. The shape of the vessels is irregular, sometimes collapsed, antlers-like. Conspicuous layer of pericytes around these lumens is present (ASMA and smooth muscle actin positive), which is helpful in differential diagnosis against angiosarcoma or Kaposi's sarcoma. No cellular atypias and no inflammatory cells are present.

6.5.10.1.18  Verrucous hemangioma

Clinical signs:

  • location: usually lower extremity, unilateral
  • age: childhood
  • gradually growing verrucous hyperkeratosis and acanthosis
  • no tendency for regression (as opposed to cherry hemangiomas)
  • in not completely removed recurs

Histology:

Histology corresponds to capillary hemangioma (but with hyperkeratosis, acanthosis and papillomatosis), but the tumor has deep part as well (the reason for recurences).

6.5.10.1.19  Targetoid hemosiderotic hemangioma

Clinical signs:

  • location: usually extremities
  • age: usually young adults
  • flat angiomatous patch, often of targetoid appearance (rusty colored papule in the middle, surrounded by paler, erythematous ring, and that is again surrounded by darker area with ecchymoses)

Histology:

Superficially dilated blood vessels with prominent hobnail endothelial cells with intraluminal endothelial tufts (papillary endothelial protrusions). On the deep periphery slitlike vascular lumens. Slight lymphocytic infiltrate, sometimes single thrombi, usually prominent deposits of hemosiderin

6.5.10.1.20  Nevus araneus

Clinical signs:

  • variant of a tiny hemangioma
  • multiple lesions in liver cirrhosis

Pictures

Nevus araneus, cirrhosis:
Hemangioma, CLINIC (1105)

Nevus araneus, spider nevus:
Spider hemagioma, CLINIC (3341)

Spider hemagioma, CLINIC (3342)

Histology:

Tiny hemangioma with central capillary, branching subepidermally.

6.5.10.1.21  Acral arteriovenous hemangioma

Clinical signs:

  • small hemangioma
  • localization: acral areal (nose)

Histology:

Glomeruloid lesion consisting of blood vessels of varying size, thick walled; the lesion is small, roundish, well circumscribed.

6.5.10.1.22  Cherry hemangioma

Clinical signs:

  • red skin papules or macules
  • appear with increasing age, often multiple
  • location: anywhere on the skin
  • common and benign

Histology:

Hemangioma, consisting of dilatated blood vessels with thin, regular endothelium and well defined vascular lumens. Stroma is often fibrotic.

Pictures

Cherry hemangioma:
Cherry hemangioma, HE 40x (4976)
  [zoomify]

Cherry hemangioma:
Cherry hemangioma, HE 60x (10781)

6.5.10.1.23  Epithelioid hemangioma (angiolymphoid hyperplasia)

Clinical signs:

  • nodules and plaques, typically on the head and around the ears

Histology:

Increased number of capillaries with activated endothelium, forming convolutes. Dense lymphocytic infiltrate with (usually many) admixtured eosinophils. Vacuoles within the endothelial cells. The infiltrate often forms reactive centers.

6.5.10.1.24  Kimura disease

Clinical signs:

  • painless skin lesions (and lymphadenitis)
  • location: head, neck (periauricular)
  • age: young adults
  • males prevail 6 : 1

Histology:

Lymphocytic infiltrate with admixtured eosinophils, dilatated blood vessels.

Pictures

Kimura disease:
Kimura's disease, HE 20x (4684)
  [zoomify]

6.5.10.1.25  Bacillary angiomatosis

Etiology:

Clinical signs:

  • tumorous, fast growing, usually multifocal vascular proliferation
  • skin, brain, bones and other organs

Histology:

Vascular proliferation with large, activated epithelioid endothelia, high mitotic activity; inflammation with neutrophils (with leukocytoclasia), accumulations of finely granular material (bacteria) which are visible in HE and can be stained by silver impregnations (Warthin-Starry).

6.5.10.1.26  Acroangiodermatitis

Clinical signs:

  • pseudotumorous proliferation of blood vessels in areas of stasis and bleeding
  • location: lower oxtremities
  • brown macules, plaques

Histology:

Proliferation of capillaries, bleeding, siderophages, chronic inflammation.

6.5.10.1.27  Nevus anemicus

Clinical signs:

Areas with decreased vascular supply forming pale macules (especially when surrounding skis is irritated).

Pictures

Nevus anemicus:
Nevus anemicus, CLINIC (5772)

6.5.10.1.28  Nodi hemorrhoidales

Introduction:

Dilatated veins, sometimes thrombosed.

Pictures

Hemorrhoial nodule with thrombosis:
Haemorrhoidal nodule, HE 40x (10183)

6.5.10.1.29  Vascular dilatation

Introduction:

Vascular dilatation, often thrombozed, without relation to above mentioned units.

6.5.10.2  Vascular tumors of borderline malignancy
6.5.10.2.1  Epithelioid hemangioendothelioma

Clinical signs:

  • age: variable
  • affects superficial and deep soft tissue as well as internal organs
  • low grade malignant tumor, prognosis variable (recurrences, metastases)

Histology:

Tumor with unsharp borders, sometimes of angiocentric growth or association with large blood vessel. Skin infiltration is usually secondary. The cells are epithelioid, with pink, broad cytoplasm, often with vacuoles. High mitotic activity (over 2/10 HPF) and cytologic atypia are signs of more aggressive behaviour. Roundish or (short) spindle cells form nest and short fascicles, with infiltrative growth. Stroma is usually hyalinized or of chondroid appearance. Vascular markers (CD31, CD34, f. VIII.) are positive.

6.5.10.2.2  Retiform hemangioendothelioma

Clinical signs:

  • very rare
  • low grade malignancy
  • unsharp borders
  • recurrences common

Histology:

Vascular tumor with unsharp borders, located within reticular dermis and subcutaneous fat, composed of vertically oriented, braching blood vessels. Deposits of hemosiderin. The tumor usually does not destroy underlying tissue. Cellular atypias are nor prominent. Lymphocytic (B and T lymphocytes) are present within the tumor. Intravascular papillary projections are present. Vascular markers (CD31, CD34, f. VIII.) are positive.

6.5.10.2.3  Kaposiform hemangioendothelioma

Clinical signs:

  • rare, aggressive vascular tumor
  • age: infants and children
  • possible complication: consumption coagulopathy (syndrome Kasabach Merritt)
  • locally aggressive, but no metastatic potential
  • location: trunk, limbs, retroperitoneum
  • skin is affected in about 75% of cases

Histology:

Large tumorous masses, infiltrative, consisting of spindle cells with focal formation of slit-like lumina. Deep extension, infiltration of deep soft tissues and bone. CD31 and CD34 positive, f. VIII. positivity is variable. Areas of fibrosis or vascular differentiation may be present.

Pictures

Kaposiform hemangioendothelioma:
Kaposiform hemangioendothelioma, HE 40x (4977)
  [zoomify]

6.5.10.3  Malignant tumors of blood vessels
6.5.10.3.1  Dabska tumor (papillary hemangioendothelioma)

Clinical signs:

  • low grade angiosarcoma
  • affects children
  • subcutaneous nodules, size several centimeters or more
  • very rare

Histology:

Irregular blood vessels, atypical endothelial cells (reacting rather like lymphatic vessels).

6.5.10.3.2  Kaposi's sarcoma

Etiology:

  • caused by infection by human herpesvirus 8 (HHV 8)
  • immunosupressions is an important co-factor (AIDS, transplantations)

Clinical signs:

  • affects elder men, in younger patients it is the sign of severe immunodeficiency
  • location: often lower extremities, but other locations occur as well (including mucosal surfaces)
  • slightly infiltrated, smooth, circumscribed lesions of variable size
  • color: red, purple
  • small tumors, ulcerating
  • lymphedema may occur on lower extremities

Histology:

3 stages of development:

Macular stage: increased cellularity within the dermis; irregular spaces between colagen fibres lined by endothelium, focally containing erythrocytes. The blood vessels, which were formerly present, remain preserved and bulge into newly formed vascular spaces.

Stage with plaques: irregular vascular dermal spaces are clearly recognisable. Endothelial cells are irregular, with some mitotic activity. Aggregates of fusiform cells with hyaline inclusions and fagocytized erythrocytes are present, as well as coins-like arrangement of erythrocytes. No thromboses can be found. Focally there are deposits of hemosiderin and hemorrhage; plasmocytes are admixtured to the infiltrate.

Tumorous stage: nodules of fusiform cells, mitotic activity, hyalin globules, erythrophagocytosis.

Pictures

Kaposi's sarcoma, macular:
Kaposi's sarcoma, macular, HE 10x (1357)

Kaposi's sarcoma, macular, HE 20x (1358)

Kaposi's sarcoma, macular, HE 40x (1359)

Another case of early Kaposi's sarcoma:
Kaposi sarcoma, macular, early, HE 20x (4741)
  [zoomify]

Kaposi's sarcoma, patch stage:
Kaposi sarcoma, patch stage, HE 60x (10785)

Kaposi sarcoma, patch stage, HE 60x (10786)

Kaposi's sarcoma, patch stage:
Kaposi sarcoma, patch stage, HE 60x (10787)

Kaposi sarcoma, patch stage, HE 60x (10788)

Another case of Kaposi's sarcoma (leg, male, 76 years old, no AIDS):
Kaposi sarcoma, macular, late, HE 40x (4027)

Kaposi's sarcoma, plaque:
Kaposi's sarcoma, plaque, HE 2.5x (1363)

Kaposi's sarcoma, plaque, HE 20x (1362)

Kaposi's sarcoma, plaque, HE 40x (1364)

Kaposi's sarcoma, plaque, HE 40x (1365)

Kaposi's sarcoma, plaque, Prussian blue 10x (1360)

Kaposi's sarcoma, plaque, Prussian blue 20x (1361)

Another case:
Kaposi's sarcoma, plaque stage, HE 40x (2473)

Kaposi's sarcoma, plaque stage, HE 100x (2471)

Kaposi's sarcoma, plaque stage, CD34 40x (2472)

Kaposi's sarcoma:
Kaposi's sarcoma, patch stage, HE 10x (2086)

Kaposi's sarcoma, patch stage, CD34 20x (2088)

Kaposi's sarcoma, patch stage, HE 40x (2087)

Kaposi's sarcoma, plaque stage, HE 40x (2111)

Another case:
Kaposi sarcoma, tumor stage, HE 60x (12072)

Kaposi's sarcoma, plaque stage, HE 20x (4738)
  [zoomify]
Kaposi's sarcoma, plaque stage, HE 20x (4740)
  [zoomify]

Another case with nodules of spindle shaped endothelial cells:
Kaposi sarcoma, tumor stage, HE 40x (12819)

Kaposi's sarcoma, plaque stage, HE 20x (4739)
  [zoomify]

Ulcerated Kaposi's sarcoma:
Kaposi sarcoma, tumor stage, HE 40x (12820)

Kaposi's sarcoma, ulcerated tumor, HE 20x (5341)

Kaposi's sarcoma, AIDS patient:
Kaposi's sarcoma, plaque stage (AIDS), HE 20x (4679)
  [zoomify]
Kaposi's sarcoma, plaque stage, Prussian blue 20x (4678)
  [zoomify]
Kaposi's sarcoma, plaque stage (AIDS), HE 20x (4681)
  [zoomify]
Kaposi's sarcoma, plaque stage (AIDS), Prussian blue 20x (4680)
  [zoomify]

Kaposi's sarcoma:
Kaposi's sarcoma, tumorous stage, HE 20x (4519)
  [zoomify]

Kaposi's sarcoma, patch-plaque:
Kaposi sarcoma, patch-plaque stage, HE 60x (12435)

Kaposiho sarcoma, nodule:
Sarcoma Kaposi, nodule, HE 60x (13932)

Kaposi's sarcoma, tumorous:
Kaposi sarcoma, tumor stage, HE 40x (13028)

Lymphangioma-like Kaposi's sarcoma:
Kaposi sarcoma, macular, early, HE 20x (4533)

6.5.10.3.3  Angiosarcoma

Clinical signs:

  • highly malignant tumor of blood or lymphatic vessels
  • 3 clinical settings:
    • face and scalp of elderly people
    • angiosarcoma secondary to chronic lymphedema (Stewart-Treves, after mastectomy)
    • irradiated skin or after trauma or ulceration
  • Angiosarcoma of the face starts as erythematous patch, which later develops into nodules, plaques and ulcerates. Very poor prognosis.

Pictures

Angiosarcoma of the head (biopsy see bellow):
Angiosarcoma, CLINIC (6151)

Angiosarkom, head, CLINIC (4169)

Histology:

Irregular and slit-like vascular spaces within the dermis; atypical vessels around collagen fibres, dissecting through the dermal collagen; atypical endothelial cells; bleeding.

Case study:

Angiosarcoma
MUDr. Hana Jedličková, PhD.

Introduction:

Angiosarcoma of the skin is the most common type of angiosarcoma. Most commonly it arises in the scalp of elder men, it can occur also in chronic lymphedema, especially as a late complication after mastectomy and radiation therapy (Stewart Treves syndrome). It presents as ill defined violaceous nodules, plaques and ulcers with extensive infiltration of the clinically normal borders. Satellites are common. The prognosis is poor.

Three histopathological patterns have been described:

  • angiomatous
  • spindled
  • undifferentiated

History:

79-year-old man presented with an infiltrated plaque with necrotic areas and purulent secretion in the scalp of 3 month duration. He was treated for seborrhoeic dermatitis of the scalp in the past. The appearance of the lesion was accompanied by severe headaches. He had a history of chronic heart disease, aortal aneurysm, chronic pulmonary disease, chronic renal failure, hypertension, polyneuropathy, transitory ischemic attack and venous insufficiency.

Histopathology showed angiosarcoma, x-ray of the scull was normal, other examinations did not reveal signs of metastatic disease. The patient died in the course of palliative radiotherapy, 3 months after the diagnosis.

Clinical signs:

On the crown of the head there was an alopecic infiltrated plaque 10×10 cm with necrotic areas, draining pus. The lesion was painful, the area of dark red infiltration extended to the forehead.

Histology:

Mixed inflammatory infiltrate with superficial necrosis. In the dermis there are many irregular vessels with atypical endothelial cells dissecting collagen fibers.

Conclusion: angiomatous type of angiosarcoma.

Pictures

Angiosarcoma of the head, excision from the margin of the ulceration (the same patient whose clinical pictures are shown above):
Angiosarcoma, head, HE 40x (4114)

6.5.11  Tumors of lymphatic vessels

6.5.11.1  Lymphangioma

Clinical signs:

  • dilated lymphatic vessels within the corium
  • may resemble vesicles

Histology:

Vascular spaces lined with endothelium, containing eosinophilic fluid (no erythrocytes).

Pictures

Lymfangioma:
Lymphangioma, HE 40x (13194)

Lymphangioma:
Lymphangioma, HE 20x (1971)

Superficial and deep lymphangioma:
Lymphangioma, circumscribed, HE 20x (2414)

Superficial part:
Lymphangioma, circumscribed, superficial part, HE 40x (2412)

Deep part:
Lymphangioma, circumscribed, deep part, HE 40x (2413)

Superficial lymphangioma:
Superficial circumscribed lymphangioma, HE 40x (5179)

Superficial lymphangioma:
Lymphangioma, superficial, HE 100x (5509)

Lymphangioma, superficial, CD31 40x (5510)

Deep lymphangioma:
Deep lymphangioma, HE 40x (5058)
  [zoomify]
Deep lymphangioma, SMA 40x (5059)
  [zoomify]

Biopsy of the 8 years old boy because of lymphedema of the genital region and thighs shows groups of lymphatic vessels within the deep dermis and subcutaneous fat; the finding was signed out as lymphangiomatosis:
Lymfangiomatosis, HE 60x (6397)

6.5.12  Glomus tumor

Clinical signs:

  • benign tumors (malignant forms are very rare)
  • most frequent location: subungual, palms
  • small, bluish dermal nodules (size up to 1 cm)
  • painful (sensitive to changes of temperature and pressure)

Histology:

Perivascularly oriented monomorphic cells with roundish nuclei; smooth muscle actin positive. Mostly solid tumors are glomus tumors, tumors with many blood vessels are glomangiomas; glomangiomyoma contains in addition spindle shaped smooth muscle cells.

6.5.13  Glomangioma

Histology:

Multinodular vascular tumors: vascular spaces are surrounded by a layer of glomus cells, smooth muscle actin positive.

6.5.14  Hemangiopericytoma

Histology:

Branching blood vessels, surrounded by oval or spindle pericytic cells, which are CD34 positive. Epidermis is usually normal.

6.5.15  Tumors of the smooth muscle

6.5.15.1  Pilar leiomyomas

Introduction:

Probably the most common variant of skin leiomyoma.

Clinical signs:

  • location: anywhere (often dorsal aspects of extremities)
  • solitary or multiple nodules
  • firm, sometimes painful
  • color: pink

Pictures

Leiomyomas, forearm:
Leiomyoma, CLINIC (780)

Leiomyomy, neck:
Leiomyoma, CLINIC (781)

Histology:

Fascicles of smooth muscle, unsharp borders. Fusiform cells with longitudinal striation, thin, cigar shaped nuclei with blunt ends.

Malignant variant is larger, with cellular polymorphism, mitotic activity.

Special staining: van Gieson (yellow), trichrome (pink-red), antibodies against smooth muscle actin.

6.5.15.3  Genital leiomyomas

Introduction:

Leiomyomas of dartoic, vulval or mamillary muscles.

6.5.16  Rhabdomyoma, rhabdomyomatous mesenchymal hamartoma

Introduction:

Tumors of skeletal muscle in the skin are rare. The most common is rhabdomyomatous mesenchymal hamartoma, rarely rhabdomyoma.

Histology:

Skeletal muscle within the corium.

Pictures

Rhabdomyoma is characterized by a small focus of skeletal muscle within the dermis.
Skeletal muscle hamartoma, HE 40x (6179)

6.5.17  Adenoma (angiofibroma) sebaceum Pringle

Introduction:

Associated with tuberous sclerosis (familial disease, characterized by multiple small angiofibromas.

Clinical signs:

  • location (skin): face (chin, around the nose), periungual, trunk
  • multiple tiny pink or skin colored papules
  • pink periungual tumors, typically of lower extremities
  • patches of type café au lait a leukodermata
  • other organs involved: CNS, eyes, bones, gums, inner organs (phacomatosis)
  • differential diagnosis: trichoepitheliomas, cylindromas, rosacea
  • transmission is autosomal dominant

Pictures

Multiple angiofibromas, face
Adenoma sebaceum of Pringle, CLINIC (649)

Disorders of the nails
Adenoma sebaceum of Pringle, CLINIC (650)

Adenoma sebaceum of Pringle, face
Adenoma sebaceum of Pringle, CLINIC (651)

Adenoma sebaceum, tuberous sclerosis
Sebaceous adenomas in tuberous sclerosis, CLINIC (1981)

Histology:

Fibrosis, dilated blood vessels and angiofibromas, sometimes with star shaped fibroblasts; sebaceous glands are rather atrophic. No elastic fibres are present.

Pictures

Adenoma sebaceum Pringle:
Adenoma sebaceum of Pringle, HE 20x (4953)
  [zoomify]

6.5.18  Pearly penile papules

Clinical signs:

  • small papules on the corona or in the sulcus of the glans penis
  • no malignant potential, not infectious

Histology:

Angiofibroma, fibroblasts, sometimes with large nuclei. No inflammation.

Pictures

Pearly penile papules:
Pearly penile papules, HE 20x (5229)

6.5.19  Histiocytic tumors and proliferations

6.5.19.1  Xanthoma

Clinical signs:

  • location: eyelids, joints, extensor parts of the extremities, trunk
  • yellowish papules and plaques
  • most xanthomas are signs of hyperlipoproteinaemia

Pictures

Xanthomas, elbow:
Xanthoma, CLINIC (948)

Xanthomas, scrotum:
Xanthoma, CLINIC (949)

Xanthelasma palpebrarum:
Xanthoma, CLINIC (950)

Xanthomatosis:
Xanthomatosis, CLINIC (1148)

Xanthomatosis, palms:
Xanthomatosis, palms, CLINIC (1987)

Xanthoma papulosum:
Xanthoma papulosum, CLINIC (3446)

Xanthoma papulosum, CLINIC (3447)

Xanthelasma, hypercholesterolemia:
Xanthelasma, hypercholesterolemia, CLINIC (3445)

Xanthelasma:
Xanthelasma, HE 20x (4703)
  [zoomify]

Another examples of xanthomas:

Histology:

Many histiocytes with broad, pale, foamy, fat containing cytoplasm and small, roundish, regular nuclei.

6.5.19.2  Juvenile xanthogranuloma

Clinical signs:

  • single or multiple yelowish papules, nodules, rarely plaques
  • age: variable, often children (sometimes inborn); several forms exist
  • size: usually about 5 mm, but large macronodular forms exist

Histology:

Tumors consist of histiocytes, with foamy or eosinophilic or vacuolated cytoplasm. Usually large, multinuclear cells (Touton cells) are present: several, circularly oriented nuclei and foamy cytoplasm. The tumor is usually separated from the epidermis by narow layer of connective tissue (grenz zone).

6.5.19.3  Necrobiotic xanthogranuloma

Clinical signs:

  • large, yelowish plaques
  • atrophy, teleangiectasia, sometimes ulcerations
  • location: periorbital, chest
  • association: paraproteinaemia

Histology:

Large granulomas with prominent necrobiosis or necrosis; cholesterol clefts; foam cells, giant multinuclear cells; admixture of inflammatory cells.

6.5.19.4  Reticulohistiocytoma

Clinical signs:

  • solitary tumor: reticulohistiocytoma
  • multiple tumors: multicentric reticulohistiocytosis

Histology:

Histicytes with eosinophilic cytoplasm, foamy histiocytes, lymphocytes.

6.5.19.5  Benign cephalic histiocytosis

Clinical signs:

  • age: children
  • location: face, sometimes generalization
  • pink or yelowish papules
  • benign course, disappears during several years

Histology:

Infiltrate of histiocytes with eosinophilic cytoplasm and regular nuclei; 3 types: papillary dermal, lichenoid and diffuse. The cells are S100 protein positive and are CD1a negative.

6.5.19.6  Giant cell tumor of the tendon sheath

Clinical signs:

  • benign neoplasm of the synovia; two forms:
    • diffuse form: pigmented villonodular synovitis
    • localized form: giant cell tumor of the tendon sheath
  • localized forms affect especially small joints of the hand
  • pain, effusion, locking of the joint
  • common lesion, affects especially middle aged women

Histology:

Small, regular, mononucleate cells, middle size histiocytoid cells and giant, multinuclear cells in a mixture. Variable amounts of hemosiderin and lymphocytic infiltrate. Localized forms have sharp borders. Stroma may show hyalinization.

6.5.19.7  Giant cell tumor of the skin or soft tissue

Introduction:

Similar to brown (osteoclastic) tumors of the bone.

Histology:

Many multinuclear giant cells, CD68 positive; small, mononuclear cells, lymphocytes, many capillaries.

6.5.19.8  Histiocytic sarcoma

Clinical signs:

  • rare neoplasm
  • widespread macules and papules
  • bad prognosis

Histology:

Dense, superficial and deep infiltrate with destruction of the adnexa. Some histiocytic markers (CD68) are positive, B and T cell markers are negative.

6.5.20  Neurogenic tumors

Introduction:

Tumors of the nerve tissue, benign and malignant. Neuromarkers (eg. S100 protein) are positive. Benign and malignant tumors.

6.5.20.1  Benign neurogenic tumors
6.5.20.1.1  Neurofibroma

Clinical signs:

  • solitary, sporadic forms are soft, often polypoid tumors

Histology:

Fusiform, fine, often wavy cells and fine collagenous fibres; sometimes compact, sometimes loose or even myxoid. S100 protein is positive. Sometimes fine, scattered nerve fibres are present. No capsule is present.

6.5.20.1.2  Recklinghausen's disease

MUDr. Hana Jedličková, PhD.

Introduction:

Segmental neurofibromatosis is a rare variant of neurofibromatosis limited to one or several usually unilateral body areas. It is caused by a postzygotic mutation of the neurofibromatosis I gene, resulting in somatic mosaicism.

Von Recklinghausen neurofibromatosis belongs to the most frequent phakomatoses with estimated incidence 1 : 4000. NF is inherited as an autosomal dominant disorder. New mutation occurs in 30 – 50% of cases.

NF 1 has skin, neurological and orthopedic symptoms. It is caused by point mutation, deletions or mosaicism of NF1 gene on the chromosome 17, coding the protein neurofibromin. Neurofibromin is a tumor suppressor protein.

The risk of systemic disease in the limited form is low, nevertheless can not be excluded. If the mosaicism mutation occurs early, clinically the patient can suffer from generalized NF. In the case of gonadal mosaicism, the disease can be transferred to the offspring.

Classification:

Classification of NF (Viskochil and Carey)

  • Neurofibromatosis 1, NF 1
  • Neurofibromatosis 2, NF 2
  • alternative forms of NF 1 or NF 2 (incomplete or atypical symptoms):
    • mixed type
    • localized NF (segmental, gastrointestinal, spinal, multiple café au lait spots
    • schwannomatosis
  • diseases with other symptoms:
    • Noonan syndrome
    • Watson syndrome

Clinical signs:

Neurofibromatosis 1 diagnostic criteria (2 or more of the following):

  • 6 and more café au lait spots:
    • larger than 0.5 cm in adolescents
    • larger than 1.5 cm in adults
  • 1 – 2 neurofibromas or 1 plexiform neurofibroma
  • axillary or inguinal freckles
  • optic nerve glioma
  • Lisch nodules (iris hamartomas)
  • typical bone deformity: sphenoid bone dysplasia, long bone cortex thinning, pseudoarthrosis
  • a first degree relative fulfilling criteria of NF 1

Clinical features:

  • multiple neurofibromas are characteristic of neurofibromatosis (Recklinghausen's disease), type I.
  • location: mostly trunk
  • roundish, soft, pedunculated and pendulating tumors:
  • color: pink, skin color, light brown
  • some tumors can be pushed into the skin (herniation from the subcutis), slight pain
  • café au lait, nevi, skeletal changes, changes in the nerve system are common
  • typical are plexiform neurofibromas, which are very large (affect large body areas, eg. the whole extremity)

Pictures

Neurofibromas, Recklinghausen's disease:
Neurofibroma, CLINIC (843)

Morbus Recklinghausen, back:
Neurofibroma, CLINIC (844)

Morbus Recklinghausen, patch café au lait:
Neurofibromatosis, cafe au lait spot, CLINIC (845)

Morbus Recklinghausen, neurofibromas (dermatochalasia):
Neurofibroma, CLINIC (846)

Café au lait spot:
Cafe au lait spot, CLINIC (2832)

Neurofibromatosis of Recklinghausen:
Neurofibromatosis of Recklinghausen, CLINIC (3133)

Neurofibromatosis of Recklinghausen, CLINIC (3134)

Neurofibromatosis of Recklinghausen, CLINIC (3135)

Neurofibromatosis of Recklinghausen, CLINIC (3136)

Neurofibromatosis of Recklinghausen, neurofibromas and café au lait spot:
Neurofibromatosis of Recklinghausen, type I., CLINIC (6124)

Neurofibromatosis of Recklinghausen, type I., CLINIC (6125)

Neurofibromatosis of Recklinghausen, type I., CLINIC (6126)

Neurofibromatosis of Recklinghausen, type I., CLINIC (6127)

Another examples of neurofibromatosis:

Another examples of café au lait spots:

Histology:

Histological picture in type I. neurofibromatosis corresponds to multiple neurofibromas. With time malignant transformation is common.

6.5.20.1.3  Schwannoma (neurilemmoma)

Clinical signs:

  • benign tumors arising in any periferal nerve
  • age: usually adults
  • well demarcated, roundish nodules; solitary or multiple
  • the tumors lie adjacent to nerves

Histology:

Well demarcated proliferation of Schwann cells with elongated nuclei with roundish ends; chromatin is fine. The cells form loose fascicles with nuclei aligned in parallel arrays (Verocay bodies): structure Antoni A. Other areas of the tumor are less cellular, myxoid, edematous; aligning of nuclei is usually not conspicuous: Antoni B areas.

S100 protein is positive.

6.5.20.1.4  Traumatic neuroma

Clinical signs:

  • location: sites of trauma, scars
  • papules, nodules

Histology:

Irregular bundles of peripheral nerves, fibrous tissue.

6.5.20.1.5  Neurohamatroma

Introduction:

Rare lesion, characterized by presenece of neural fascicles high within the corium.

6.5.20.1.6  Neurothekeoma

Clinical signs:

  • soft, asyptomatic papules and nodules, 5 – 10 mm
  • age: adults
  • location: usually face or upper extremities

Histology:

Lobules of cells in myxoid matrix; S100 protein, vimentin and collagen IV. positive.

Cellular neurothekeoma is characterized as an dermal neoplasm composed of nests and fascicles of spindle-shaped and epithelioid cells, S100 negative and NKIC3 positive.

6.5.20.1.7  Granular cell tumor, Abrikosoff

Clinical signs:

  • location: subcutaneous tissue, oral mucosa
  • asymptomatic nodules, size up to 2 cm
  • age: usually adults, but inborn forms exist
  • malignant variant is very rare

Histology:

The tumor consists of roundish cells with broad, granular cytoplasm and small, regular, centrally located nuclei. S100 protein, NSE and PGP 9.5 are usually positive.

Pseudoepitheliomatous hyperplasia of overlying skin or mucosa is common.

6.5.20.2  Malignant neurogenic tumors

Metastases of neuroblastoma may be found within the dermis.

6.5.21  Epithelioid sarcoma

Clinical signs:

  • location: extremities
  • age: most often young adults
  • slowly growing malignant tumor with tendency to reccurr locally after incomplete excision
  • metastases: lymph nodes, lungs
  • therapy: wide excision, amputation

Histology:

Nodules of variable size, often with necrotic foci, which may resemble granulomas (e. g. deep granuloma annulare).

The cells are polygonal and spindle, with eosinophilic cytoplasm. The tumor growths in infiltrative fashion along the fascia and tendons and often ulcerates.

Imunoprofile: vimentin +, EMA +, cytokeratins +, CD34 often positive, SMA often positive.

Pictures

Epiteloid sarcoma:
Epitheloid sarcoma, HE 20x (4489)
  [zoomify]

6.5.22  Lymphomas

Werner Kempf, prof. Günter Burg

Introduction:

The following section is based on the lymphoma collection of the Institute of Dermatology, University Hospital, Zurich, Switzerland.

6.5.22.1  WHO classification of skin lymphomas

In addition the classification does not cover some diagnostic units:

Examples of skin lymphomas can be found at:

6.5.22.2  Pseudolymphoma, lymphocytoma

Introduction:

Focal, dense lymphocytic dermal infiltration. Sometimes follows small external injury (insect bite), often idiopathic. Can be difficult to differentiate from lymphoma.

Pictures

Further examples of lymphadenosis cutis benigna:

6.5.22.2.1  B cell pseudolymphoma

Clinical signs:

  • location: usually ear lobes, breasts, face, extremities and other
  • solitary nodules, infiltrated plaques, rarely multiple
  • color dark red or pink

Pictures

Lymphocytoma in borreliosis:
Lymphocytoma, CLINIC (802)

Lymphocytoma, disseminated lesion of the temple:
Lymphocytoma, CLINIC (803)

Lymphocytoma of the nose:
Lymphocytoma, CLINIC (804)

Lymphocytom of the earlobe:
Lymphocytoma, CLINIC (805)

Pseudolymphoma, forhead:
Pseudolymphoma, forehead, CLINIC (4180)

Histology:

Dense, often nodular infiltrate with reaction centers, reaching deep into the dermis or subcutaneous fat. The infiltrate is top heavy. No epidermotropism (grenz zone). Lymphocytes are regular.

Adnexal structures are not destroyed. Admixture of reactive inflammatory cells within the infiltrate (eosinophils, plasma cells). Dendritic cells and tingible body macrophages are present as well.

Immunophenotype and genetic features:

  • T cells (CD3+, CD43+) surround B cells (CD20+).
  • regular network of dendritic cells (CD21+) within the follicular structures.
  • polytypic expression of kappa and lambda Ig light chains

Pictures

Pseudolymphoma B:
Pseudolymphoma, HE 2x (515)

Pseudolymphoma, HE 10x (514)

Pseudolymphoma, HE 20x (516)

Pseudolymphoma, HE 40x (517)

Pseudolymphoma, CD20 20x (518)

Pseudolymphoma, CD45ro 20x (519)

Another case:
Pseudolymphoma B, HE 20x (3272)

Pseudolymphoma B, HE 40x (3273)

Pseudolymphoma B, HE 100x (3270)

Pseudolymphoma B, CD20 20x (3271)

Pseudolymphoma B, CD3 20x (3504)

Pseudolymphoma B, Ki67 20x (3505)

Pseudolymphoma B, child 3 years, FISH 40x (3461)

Pseudolymphoma B, child 3 y, FISH 40x (3465)

Pseudolymphoma B, child 3 y, FISH 40x (3466)

Pseudolymphoma B, child 3 y, FISH 40x (3467)

Another case:
Pseudolymphoma, HE 2.5x (1642)

Pseudolymphoma, HE 10x (1641)

Pseudolymphoma, HE 40x (1644)

Pseudolymphoma, HE 40x (1643)

Another case:
Pseudolymphoma B, HE 40x (2433)

Another case:
Pseudolymphoma B, HE 40x (2256)

Follicular hyperplasia:
Follicular hyperplasia, HE 20x (2390)

Follicular hyperplasia, HE 20x (2392)

Pseudolymphoma B:
Pseudolymphoma B (PSLB), HE 40x (10282)

Pseudolymphoma B (PSLB), CD20 40x (10280)

Pseudolymphoma B (PSLB), CD3 40x (10281)

Pseudolymphoma B:
Pseudolymphoma scroti, HE 40x (12729)

Pseudolymphoma scroti, CD3 40x (12728)

Pseudolymphoma scroti, CD20 40x (12726)

Pseudolymphoma scroti, CD21 40x (12727)

Pseudolymphoma scroti, bcl2 40x (12838)

Pseudolymphoma scroti, bcl6 40x (12631)

Pseudolymphoma B:
Pseudolymphoma B of the skin, follicular, HE 40x (13242)

Pseudolymphoma B of the skin, follicular, HE 40x (13238)

Pseudolymphoma B:
Pseudolymphoma B of the skin, follicular, HE 60x (13240)

Pseudolymphoma B:
Pseudolymphoma, HE 60x (12933)

Pseudolymphoma B:
Pseudolymphoma B of the skin, follicular, HE 60x (13239)

Pseudolymphoma under squamous cell carcinoma:
Pseudolymphoma below squamous cell carcinoma, HE 60x (13243)

Reactive subcutaneous lymphodes:
Reactive lymphnode, subcutaneous, HE 40x (12730)

6.5.22.2.2  T cell pseudolymphoma

Clinical signs:

  • solitary, eczematous patches
  • sometimes realted to phenytoin therapy of parazitic infection
  • excellent prognosis: heal spontaneously or after topic corticosteroid therapy; never disseminate

Histology:

Mimic skin T cell lymphomas; epidermotropism sometimes absent. Differentiation requires combination of clinical and histologic data.

Two types of cutaneous pseudo T cell lymphomas:

  • band like (MF-like) pattern simulating MF
  • nodular pattern mimicking cutaneous T cell lymphomas other than MF

Immunophenotype and genetic features:

  • expression of T markers not distinguishable from MF
  • no clonal rearrangement of T cell receptor genes
6.5.22.3  Cutaneous lymphoproliferative infiltrates other than lymphomas
6.5.22.3.1  Insect bite reaction

Introduction:

Insect bite reaction is described in another chapter.

6.5.22.3.2  Sinus histiocytosis with massive lymphadenopathy Rosai-Dorfman

Clinical signs:

  • usually affects (cervical) lymphnodes, skin is affected in about 10% of cases
  • usually benign course
  • asymptomatic macules, papules, nodules and plaques with tendency to spontaneous involution

Histology:

Dense, polymorphous nodular infiltrate within the dermis. Epidermis is usually uninvolved. The infiltrate is dominated by histiocytes with large, vesicular nuclei with one or several nucleoli and large, sometimes foamy cytoplasm. Phagocytosis of lymphocytes, neutrophils and plasma cells is often present. Scattered are mononuclear cells of middle size, with indented nuclei and eosinophilic cytoplasm. Touton ginat cells are often scattered.

Immunophenotype and genetic features:

  • histiocytes: CD68+, S100+, lysozyme-
  • monocytoid cells: lysozyme+, CD68+, S100-
6.5.22.3.3  Leishmaniasis

Leishmaniasis is discussed in another chapter.

6.5.22.3.4  Angioimmunoblastic lymphadenopathy

Clinical signs:

  • fever, lymphadenopathy, dysproteinemia
  • skin is affected in about 40% of cases: macules, papules

Histology:

Histology is not specific: superficial and deep nodular perivascular lymphohistiocytic infiltrate.

6.5.22.4  Skin lesions in nodal lymphomas

Clinical signs:

  • specific lesions: tumorous infiltration of the skin
  • unspecific lesions: pruritus, prurigo, ichthyosis, bleeding

Pictures

Lymphoblastic lymphoma, skin lesions:
Lymphoma, CLINIC (786)

Facies leonina, leukemia:
Lymphoma, CLINIC (787)

Primary T cell lymphoma of the skin:
Lymphoma, CLINIC (789)

Primary T cell lymphoma of the skin, arm:
Lymphoma, CLINIC (790)

Histology:

Dense, usually prominent infiltration of malignant lymphocytes, corresponding to the malignant lymphoma of the lymphnodes.

6.5.22.5  T cell lymphomas
6.5.22.5.1  Small plaque parapsoriasis

Clinical signs:

  • oval or digitate patches, 2 – 6 cm in diameter
  • surface reddish or yellowish
  • pseudoatrophic wrinkling and slight pityriasiform scaling
  • location: lateral parts of the trunk
  • exceptionally good prognosis
  • variants:
    • small plaque parapsoriasis
    • dermatosis digitata (small, reddish patches on lateral sides of the trunk)
    • xanthoerythroderma perstans (yellowish patches on the distal parts of extremities

Histology:

Epidermis normal or with slight acanthosis, some spongiosis, patchy parakeratosis. No edema, no plasma cells, no eosinophils.

Immunophenotype and genetic features:

  • CD4+ T cells, few CD8+ cells
  • clonality: inconstant finding
6.5.22.5.2  Large plaque parapsoriasis

Clinical signs:

  • a few large (more than 10 cm in diameter), fairly demarcated, iregularly shaped plaques
  • color: reddish
  • pityriasiform scaling
  • location: trunk, extremities
  • poikiloderma atrophicans vasculare: special variant occurs in light protected areas showing reticular network of hyperpigmentation, atrophy and teleangiectasia
  • prognosis: generally good, but later infiltrated plaques may form (mycosis fungoides)

Histology:

Epidermis is normal or slightly acanthotic. In poikilodermatous form is epidermis atrophic. Single cell epidermotropism with arrangement of lymphocytes along the basal layer. Spongiosis is usually low or none. Intraepidermal lymphocytes are often larger than those located intradermally.

In upper dermis there is a band like infiltrate of lymphocytes with focal accumulation around papillary vessels. Dilatation of blood vessels. The perivascular infiltrate is sometimes assymetric, being denser close to the epidermis.

Immunophenotype and genetic features:

  • CD4+, CD8-, CD45RO+, bcl2-
  • clonality in about 50% of cases
6.5.22.5.3  Mycosis fungoides

Introduction:

One of the most common forms of the skin lymphoma.

Clinical signs:

  • location: no predilection, often on the trunk
  • I. premycotic stage: lesions resemble chronic eczema; recurrent pink patches, roundish or digitate
  • II. infiltrative stage: infiltration of the lesions, color gets more prominent, often circular configuration
  • III. tumorous stage: the tumorous lesions sometimes resemble fungi
  • hyperpigmentation, ulceration of the tumors
  • lymphnodes and internal organs are affected in late stages

Pictures

Mycosis fungoides I., eczematous lesions:
Mycosis fungoides - plaque stage, CLINIC (823)

Mycosis fungoides I.:
Mycosis fungoides - plaque stage, CLINIC (824)

Mycosis fungoides I., trunk:
Mycosis fungoides - plaque stage, CLINIC (825)

Mycosis fungoides II., buttocks:
Mycosis fungoides - plaque stage, CLINIC (826)

Mycosis fungoides II.:
Mycosis fungoides - plaque stage, CLINIC (827)

Mycosis fungoides II., breast:
Mycosis fungoides - plaque stage, CLINIC (828)

Mycosis fungoides II., typical configuration:
Mycosis fungoides - plaque stage, CLINIC (829)

Mycosis fungoides II., early infiltration:
Mycosis fungoides - plaque stage, CLINIC (830)

Mycosis fungoides III., chest:
Mycosis fungoides - plaque stage, CLINIC (831)

Mycosis fungoides III., ulcerations:
Mycosis fungoides - plaque stage, CLINIC (832)

Mycosis fungoides III., thigh:
Mycosis fungoides - plaque stage, CLINIC (833)

Mycosis fungoides III., necrotising tumor:
Mycosis fungoides - plaque stage, CLINIC (834)

Mycosis fungoides I., eczematous changes:
Mycosis fungoides - plaque stage, CLINIC (835)

Mycosis fungoides I., neck:
Mycosis fungoides - plaque stage, CLINIC (836)

Mycosis fungoides II., early tumorous stage:
Mycosis fungoides - plaque stage, CLINIC (837)

Mycosis fungoides I., parapsoriasis en plaque:
Mycosis fungoides - plaque stage, CLINIC (838)

Mycosis fungoides I., parapsoriasis digitiformis:
Mycosis fungoides - plaque stage, CLINIC (839)

Histology:

Histology is variable, in early lesions not specific. Differentiation from superficial dermatitis is problematic. Some of more common signs are: infiltration of the papillary dermis, infiltration of the basal layer of the epidermis (especially of the tips of the rete ridges), lymphocytic infiltration of the epidermis (exocytosis), usually without spongiosis (but spongiotic variant of the MF exists). Later epidermal accumulations of lymphocytes (Pautrier's abscesses) appear. At that time the polymorphism of lymphocytes is usually evident. Moreover, intraepidermal lymphocytes are somewhat larger than those located within the dermis. The infiltrate gets denser and scattered eosinophils appear. Papillary dermis gets fibrotic. Perivascular infiltrate in the upper dermis is sometimes asymmetric, denser in upper (epidermal) epidermal part.

Later stages are characterised by dense, polymorphic dermal infiltrate, often with mitotic activity. Tumorous nature of the infiltrate is evident. Atypical lymphocytes enter the follicular epithelium (and may cause secondary follicular mucinosis and/or destruction of the follicles). Blastic transformation is characterized by large lymphoid elements and high mitotic activity.

When initial stages of mycosis fungoides are treated with PUVA, the epidermotropic lymphocytes disappear, but still may be present within the follicular epithelium.

Immunophenotype and genetic features:

  • CD1-, CD2+, CD3+, CD5+, CD 4+, CD45RO+, CD7+ (30%), CD8-, CD30-, TCR-beta+
  • rarely: CD3+, CD4-, CD8+
  • tumor stage: abberant phenotype with loss of T cell antigenes
  • clonality is detectable in most cases

Pictures

Mycosis fungoides:
Mycosis fungoides - plaque stage, HE 40x (2173)

Mycosis fungoides, HE 100x (2516)

Another case:
Mycosis fungoides, HE 40x (2419)

Mycosis fungoides, HE 100x (2418)

Another case:
Mycosis fungoides, HE 40x (2417)

Mycosis fungoides, HE 100x (2416)

Another case:
Mycosis fungoides - tumorous stage, HE 40x (2174)

Mycosis fungoides - tumorous stage, HE 40x (2175)

Mycosis fungoides, HE 100x (2517)

Another case:
Mycosis fungoides, patch, HE 100x (2717)

Mycosis fungoides, patch, HE 40x (2718)

Mycosis fungoides, early:
Mycosis fungoides, patch, HE 100x (2490)

Mycosis fungoides, patch, HE 40x (2176)

Mycosis fungoides, patch:
Mycosis fungoides, MF, patch, HE 100x (4729)
  [zoomify]

Another case, MF patch:
Mycosis fungoides, MF, patch, HE 20x (4689)
  [zoomify]

Mycosis fungoides, epidermotropism:
Mycosis fungoides, pagetoid, epidermotropism, HE 40x (12920)

Mycosis fungoides with strong pagetoid epidermotropism:
Lymphoma, pagetoid, HE 20x (4540)

Mycosis fungoides, Pautrier's microabscesses:
Mycosis fungoides, Pautrier's microabscesses, HE 40x (2096)

Mycosis fungoides - plaque stage, HE 100x (2491)

Mycosis fungoides:
Mycosis fungoides, MF, patch, HE 20x (5367)

Mycosis fungoides, patch:
Mycosis fungoides, patch, HE 40x (2181)

Mycosis fungoides, patch:
Mycosis fungoides, patch stage, HE 40x (12918)

Mycosis fungoides, patch:
Mycosis fungoides, patch stage, HE 40x (12919)

Mycosis fungoides, patch:
Mycosis fungoides, MF - patch, HE 20x (4825)
  [zoomify]
Mycosis fungoides, MF - patch, HE 20x (4823)
  [zoomify]
Mycosis fungoides, MF - patch, HE 20x (4824)
  [zoomify]

Early mycosis fungoides, patch:
Mycosis fungoides, MF, patch, HE 20x (5368)

Mycosis fungoides, patch:
Mycosis fungoides, MF, patch, HE 20x (4846)
  [zoomify]

Mycosis fungoides, early plaque:
Mycosis fungoides, MF - plaque stage, HE 20x (4537)
  [zoomify]

Mycosis fungoides, plaque:
Mycosis fungoides, MF - plaque stage, HE 20x (4544)
  [zoomify]
Mycosis fungoides, MF - plaque stage, CD3 20x (4541)
  [zoomify]
Mycosis fungoides, MF - plaque stage, CD4 20x (4542)
  [zoomify]
Mycosis fungoides, MF - plaque stage, CD8 20x (4543)
  [zoomify]
Mycosis fungoides, MF - plaque stage, Ki67 20x (4545)
  [zoomify]

Mycosis fungoides, plaque:
Mycosis fungoides, MF - plaque stage, HE 20x (5439)

Mycosis fungoides, plaque:
Mycosis fungoides, MF - plaque stage, HE 60x (13208)

Mycosis fungoides, MF - plaque stage, HE 40x (13207)

Mycosis fungoides, plaque stage:
Mycosis fungoides - plaque stage, HE 40x (2178)

Mycosis fungoides - plaque stage, HE 100x (2489)

Mycosis fungoides - plaque stage, HE 100x (2733)

Another case:
Mycosis fungoides, MF - plaque stage, HE 20x (4821)
  [zoomify]

Another case:
Mycosis fungoides, MF - plaque stage, HE 20x (4822)
  [zoomify]

Another case:
Mycosis fungoides, HE 40x (2422)

Another case:
Mycosis fungoides, MF - plaque stage, HE 20x (4687)
  [zoomify]

Another case:
Mycosis fungoides, MF - plaque stage, HE 20x (4688)
  [zoomify]

Another case:
Mycosis fungoides, MF - plaque stage, HE 20x (5369)

Another case:
Mycosis fungoides, MF - plaque stage, HE 20x (4690)
  [zoomify]
Mycosis fungoides, MF, patch, HE 20x (4691)
  [zoomify]

Mycosis fungoides, sole (T clonality verified):
Mycosis fungoides, sole, HE 60x (13956)

Another case, bullous:
Mycosis fungoides, bullous, HE 60x (12707)

Mycosis fungoides, tumorous:
Mycosis fungoides, MF - tumorous stage, HE 60x (12708)

Mycosis fungoides transforming into high grade T lymphoma:
Mycosis fungoides, transformation, HE 40x (2179)

Mycosis fungoides, transformation, HE 40x (2180)

Mycosis fungoides, transformation, HE 100x (2519)

Mycosis fungoides, transformation, HE 40x (2534)

Another case of mycosis fungoides transforming into high grade T lymphoma:
Mycosis fungoides, transformation, HE 20x (4847)
  [zoomify]

Another case of mycosis fungoides with multiform reaction:
Mucosis fungoides, tumor, with multiform reaction, HE 60x (13209)

6.5.22.5.3.1  Folliculotropic mycosis fungoides

Introduction:

Folliculotropic mycosis fungoides is a variant of classic MF, where tumor cells infiltrate especially follicular epithelium. The epidermis is usually spared.

Histology:

In the secondary mucinous alopecia the follicular epithelium contains large amounts of mucin and tumor cells destroy the folllicle. See the corresponding chapter.

Folliculotropic mycosis fungoides without follicular mucinosis is rare. The follicles are infiltrated and destroyed by tumorous cells. This form is rare and differential diagnosis against some other forms of alopecia is difficult.

Pictures

Folliculotrophic mycosis fungoides (without mucinosis):
Mycosis fungoides, MF - follicular, HE 60x (12705)

Folliculotrophic mycosis fungoides with mucinosis:
Follicular mucinosis in mycosis fungoides, HE 60x (12706)

6.5.22.5.3.2  Granulomatous Slack Skin

Clinical signs:

  • very rare disease
  • bulky, hanging folds of lax skin in flexural areas
  • age: 20 – 50 years, very rare in childhood

Histology:

Nodular and diffuse infiltrate in all levels of the dermis. Epidermotropism is usually lacking.

Small, well differentiated T lymphocytes, similar to those in mycosis fungoides. In addition multinucleated giant cells are scattered throughout the infiltrate.

Elastic fibres in papillary and reticular dermis are lost. Fragments of these fibres can be found in the cytoplasm of some giant cells.

Immunophenotype and genetic features:

  • small lymphocytes have T helper phenotype: CD3+, CD4+, CD8-, CD30-
  • giant cells: lysozym+, S100+, CD68+ but vimentin-, MAC387-
  • clonal TCR gene rearrangement can be demonstrated in most cases
6.5.22.5.3.3  Pagetoid reticulosis Worringer Kolopp

Introduction:

Localized superficial low grade skin T cell lymphoma

Clinical signs:

  • solitary, psoriatiform, erythematous plaque
  • scaling, crusts
  • lesions are limited to the skin, no spread to other sites of the body (to lymphnodes, peripheral blood, internal organs or bone marrow
  • lesions are highly resistant against therapy

Histology:

Psoriatiform hyperplasia, hyperkeratosis, parakeratosis. Large, atypical intraepidermal pagetoid lymphoid cells, singly or arranged in clusters or nests.

Pagetoid cells are vacuolized, with no intercellular bridges, pale staining cytoplasm. Nuclei are large, sometimes convoluted and hyperchromatic. Mitotic figures are rare.

Immunophenotype and genetic features:

  • classical pagetoid reticulosis: CD3+, CD4+, CD5+, CD8-
  • epidermotropic cells are activated T cells
  • CD8+ forms were reported
  • clonality: TCR gene rearrangement
6.5.22.5.4  Sézary syndrome

Introduction:

Leukemic, erythrodermic, low grade malignant, peripheral T cell lymphoma involving peripheral lymph nodes in most cases.

Clinical signs:

  • generalised disease
  • multiple infiltrated lesions or pruritic erythroderma
  • peeling, hyperpigmentation
  • facies leonina
  • hyperkeratoses of the palms, soles, alopecia, onychodystrophy
  • pruritus
  • lymphadenopathy, leukocytosis with Sézary cells, infiltration of the bone marrow, hepatosplenomegaly

Pictures

Sézary syndrome: facies leonina
Sézary syndrome, CLINIC (923)

Histology:

Superficial epidermotropic lymphocytic infiltrate with scattered large, atypical lymphocytes with hypercovoluted nuclei; little or no spongiosis, usually some acanthosis. Eosinophils are sometimes present, but their number is usually less than in mycosis fungoides. The infiltrate is usually less pleomorphic than in mycosis fungoides.

Immunophenotype and genetic features:

  • CD2+, CD3+, CD5+,CD45RO+, CD8-, CD30-
  • clonality is present in most cases in skin infiltrates, peripheral blood and involved lymph nodes
6.5.22.5.5  CD 30+ T cell lymphoproliferative disorders of the skin
6.5.22.5.5.1  Lymphomatoid papulosis

Introduction:

Chronic lymphoproliferative disease with benign course over decades, but malignant histologic appearance is based upon cytomorphology of atypical lymphocytes.

Clinical signs:

  • papulo-nodular or patchy, self regressing eruptions (from only a few to hundreds)
  • healing with hyperpigmented scars
  • duration of eruption: several weeks or months
  • duration of the disease: between 3 months up to 40 years, benign
  • location: trunk, proximal parts of the limbs, sometimes on the head
  • preferentially affects females in the third or fourth decades
  • in about 10 – 20% of the cases development of mycosis fungoides, CD30+ CTCL or Hodgkin disease

Histology:

Histology depends on the stage of the disease:

Fully developed lesion (2 – 3 weeks after initial manifestation; type A):
nodular superficial and deep, sometimes wedge shaped dermal infiltrate, which may invade the subcutaneous fat. Variable epidermotrophism. Prominent inflammatory infiltrate with eosinophils. Medium to large, pleomorphic tumor cells. Erythrocyte extravasation.

Resolving lesions (6 – 8 weeks old): necrosis with erosion and neutrophils; scar formation

Medium-sized or large pleomorphic cells. Atypical mitoses (in 70%)

Immunophenotype and genetic features:

  • tumor cells are proliferating activated helper T cells
  • CD30+, CD3+, CD4+, CD5-, CD8-, CD15-, EMA-, PCNA+, Ki67+, MIB-1+.
  • clonal rearrangement of T cell receptor genes in most cases

Pictures

Lymphomatoid papulosis:
Lymphomatoid papulosis, HE 40x (2170)

Lymphomatoid papulosis, HE 100x (2487)

Lymphomatoid papulosis, CD30 40x (2230)

Another case:
Lymphomatoid papulosis, HE 40x (2171)

Lymphomatoid papulosis, HE 100x (2488)

Lymphomatoid papulosis, CD30 40x (2172)

Case of atypical lymphomatoid papulosis, where the infiltrate consists of T cells with scattered atypical cells showing positivity for CD30 and CD56 (NK cells):
Lymphomatoid papulosis, HE 40x (3672)

Lymphomatoid papulosis, CD20 20x (3668)

Lymphomatoid papulosis, CD3 40x (3669)

Lymphomatoid papulosis, CD30 40x (3670)

Lymphomatoid papulosis, CD56 40x (3671)

Lymphomatoid papulosis:
Lymphomatoid papulosis A (LYP), HE 40x (4281)

Lymphomatoid papulosis A (LYP), CD3 40x (4279)

Lymphomatoid papulosis A (LYP), CD30 40x (4280)

Lymphomatoid papulosis A (LYP), Ki67 40x (4282)

Lymphomatoid papulosis A (LYP), CD20 40x (4278)

Lymphomatoid papulosis:
Lymphomatoid papulosis A (LYP), HE 40x (4287)

Lymphomatoid papulosis A (LYP), CD3 40x (4284)

Lymphomatoid papulosis A (LYP), CD30 40x (4285)

Lymphomatoid papulosis A (LYP), Ki67 40x (4288)

Lymphomatoid papulosis A (LYP), Ki67 40x (4289)

Lymphomatoid papulosis A (LYP), CD20 40x (4283)

Lymphomatoid papulosis A (LYP), CD68 40x (4286)

Lymphomatoid papulosis:
Lymphomatoid papulosis A (LYP), HE 20x (4535)
  [zoomify]

Lymphomatoid papulosis:
Lymphomatoid papulosis A (LYP), HE 20x (5358)

Lymphomatoid papulosis:
Lymphomatoid papulosis, LYP, HE 60x (12912)

Lymphomatoid papulosis:
Lymphomatoid papulosis A (LYP), HE 60x (13195)

Lymphomatoid papulosis:
Lymphomatoid papulosis A (LYP), HE 60x (13196)

Lymphomatoid papulosis:
Lymphomatoid papulosis, LYP, HE 60x (12087)

Lymphomatoid papulosis A:
Lymphomatoid papulosis A, HE 40x (4780)

Lymphomatoid papulosis A (LYP), CD30 20x (4803)

Lymphomatoid papulosis A (LYP), CD30 40x (4804)

Lymphomatoid papulosis, type C:
Lymphomatoid papulosis C, HE 20x (4534)
  [zoomify]

6.5.22.5.5.2  Anaplastic large cell lymphoma T

Clinical signs:

  • solitary or multiple nodules confined to one body compartment
  • no preceeding patches or plaques in most of the cases
  • little epidermal involvement or scaling
  • ulceration and transformation in advanced tumor nodules

Histology:

Nodular infiltrate, extending through all levels of the dermis into the subcutis. Epidermotropism is usually present with a few single cells. Tumor cells grow in dense cohesive sheets. Clusters of small reactive lymphocytes are found within and around the tumorous proliferation. Eosinophils, plasma cells and accessory cells are usually lacking.

Large, bizzare cells with large, round, irregularly shaped nuclei, abundant chromatin and one or multiple nucleoli. Cells may be multinucleated. Abundant, clear or eosinophilic cytoplasm.

Immunophenotype and genetic features:

  • CD30+, CD43+, CD45RO+
  • variable loss of pan-T cell antigens (CD2, CD3, CD5), EMA-, CLA+(HECA-452)

Pictures

Anaplastic large cell lymphoma T:
Anaplastic large cell lymphoma T, HE 40x (2194)

Anaplastic large cell lymphoma T, HE 100x (2450)

Anaplastic large cell lymphoma T, HE 100x (2452)

Anaplastic large cell lymphoma T, CD30 40x (2193)

Another case:
Anaplastic large cell lymphoma T, HE 40x (2192)

Anaplastic large cell lymphoma T, HE 100x (2451)

Another case:
Anaplastic large cell lymphoma T, HE 40x (2190)

Anaplastic large cell lymphoma T, HE 40x (2191)

Anaplastic large cell lymphoma T, HE 100x (2449)

Anaplastic large cell lymphoma T, CD30 40x (2189)

Another case, high positivity for proliferation marker Ki67:
Anaplastic large cell lymphoma T, HE 20x (2790)

Anaplastic large cell lymphoma T, HE 40x (2606)

Anaplastic large cell lymphoma T, HE 40x (2607)

Anaplastic large cell lymphoma T, HE 100x (2599)

Anaplastic large cell lymphoma T, HE 100x (2600)

Anaplastic large cell lymphoma T, HE 100x (2601)

Anaplastic large cell lymphoma T, CD20 40x (2602)

Anaplastic large cell lymphoma T, CD3 40x (2603)

Anaplastic large cell lymphoma T, CD45ro 40x (2605)

Anaplastic large cell lymphoma T, CD30 40x (2604)

Anaplastic large cell lymphoma T, HE 20x (2592)

Anaplastic large cell lymphoma T, HE 40x (2597)

Anaplastic large cell lymphoma T, HE 100x (2591)

Anaplastic large cell lymphoma T, CD20 40x (2593)

Anaplastic large cell lymphoma T, CD3 40x (2594)

Anaplastic large cell lymphoma T, CD30 40x (2595)

Anaplastic large cell lymphoma T, CD30 40x (2596)

Anaplastic large cell lymphoma T, Ki67 40x (2598)

Anaplastic large cell T lymphoma, convoluted nuclei:
Anaplastic large cell lymphoma T (ALCL T), HE 60x (12789)

Anaplastic large cell T lymphoma, convoluted nuclei:
Anaplastic large cell lymphoma T (ALCL T), HE 60x (12790)

Anaplastic large cell T lymphoma, convoluted nuclei, CD30+:
Anaplastic large cell T lymphoma, CD30 positive, HE 60x (12959)

Anaplastic large cell T lymphoma, CD30 positive, HE 40x (12958)

Anaplastic large cell T lymphoma, convoluted nuclei, CD30+:
Anaplastic large cell T lymphoma, CD30 positive, HE 60x (12960)

Anaplastic large cell T lymphoma, convoluted nuclei:
Anaplastic large cell lymphoma T (ALCL T), HE 40x (12855)

Anaplastic T cell lymphoma:
Anaplastic T cell lymphoma, HE 60x (12792)

Anaplastic T cell lymphoma:
Anaplastic T cell lymphoma, HE 60x (12793)

Another case:
Anaplastic large T cell lymphoma, CD30+, HE 40x (10907)

Anaplastic large T cell lymphoma, CD30+, CD3 40x (10905)

Anaplastic large T cell lymphoma, CD30+, CD30 40x (10906)

Anaplastic large T cell lymphoma, CD30+, Ki67 40x (10908)

CD30+, large T cell lymphoma:
Anaplastic large cell lymphoma T, HE 40x (3497)

Anaplastic large cell lymphoma T, CD3 40x (3495)

Anaplastic large cell lymphoma T, CD20 20x (3493)

Anaplastic large cell lymphoma T, CD30 40x (3496)

Anaplastic large cell lymphoma T, Ki67 20x (3494)

Another case of CD30 positive large T cell lymphoma:
Anaplastic large cell lymphoma T, HE 20x (4135)

Anaplastic large cell lymphoma T, HE 40x (4138)

Anaplastic large cell lymphoma T, CD3 40x (4136)

Anaplastic large cell lymphoma T, CD30 40x (4137)

Anaplastic large cell lymphoma T, Ki67 40x (4139)

Another case of CD30 positive large T cell lymphoma:
Anaplastic large cell lymphoma T (ALCL T), HE 20x (4202)

Another case of anaplastic large cell T lymphoma (forearm):
Anaplastic large T cell lymphoma, HE 20x (5010)
  [zoomify]

Another case of anaplastic large cell T lymphoma:
Anaplastic large T cell lymphoma, HE 20x (6167)

Anaplastic large cell T lymphoma, CD30+, 9 year old boy:
Anaplastic large cell lymphoma T (ALCL T), HE 60x (6253)

Anaplastic large cell lymphoma T (ALCL T), CD3 40x (6263)

Anaplastic large cell lymphoma T (ALCL T), CD30 40x (6262)

Anaplastic large cell lymphoma T (ALCL T), CD20 40x (6261)

Anaplastic large cell lymphoma T (ALCL T), Ki67 40x (6264)

Anaplastic large cell T lymphoma, CD30+:
Anaplastic large cell T lymphoma, CD30+, HE 60x (6292)

Anaplastic large cell T lymphoma, CD30+, CD30 40x (6289)

Anaplastic large cell T lymphoma, CD30+, granzyme 40x (6290)

Anaplastic large cell T lymphoma, CD30+, perforin 40x (6291)

Anaplastic large cell T lymphoma (TdT positive?, unusual):
ALL T, HE 40x (10124)

ALL T, CD3 40x (10122)

ALL T, TdT 40x (10126)

ALL T, CD20 40x (10121)

ALL T, CD79a 40x (10123)

ALL T, Ki67 40x (10125)

6.5.22.5.6  Subcutaneous panniculitis-like alpha/beta T cell lymphoma

Clinical signs:

  • lesions resemble erythema nodosum type of panniculitis
  • the course of the disease is usually non-aggressive

Histology:

Nodular subcutaneous nonepidermotropic infiltrate simulating panniculitis. The tumor cells are small (as in MF) or large pleomorphic or anaplastic. Tumorous cells form rimms around adipocytes. In addition foamy and vacuolated macrophages are present; in some cases erythrophagocytosis was detected.

Immunophenotype and genetic features: CD2+, CD3+, CD5+, CD4-, CD8+, TIA-1, granzyme B and perforin.

Clonal rearangement of the genes for alpha/beta chains of the T cells receptor is found in contrast to CD56+ NK lymphomas showing germline configuration.

6.5.22.5.7  Primary cutaneous peripheral T cell lymphoma, unspecified

Introduction:

All T-cell neoplasms that do not fit into any of the better defined subtypes of T-cell lymphoma/leukemia. As such it constitutes a heterogeneous group of diseases, representing less than 10% of all CTCL, usually CD30 negative and showing variable clinical course.

6.5.22.5.7.1  CD8 positive T cell lymphoma (cytotoxic)

Clinical signs:

  • aggressive course in most cases (as opposed to the MF variant with CD8+ cells)
  • erosive plaques
  • bad prognosis with rapid progress

Histology:

Resembles mycosis fungides; strong, pagetoid epidermotropism. Acanthosis, necrosis, erosions, sometimes angiocentric growth.

Immunophenotype and genetic features:

  • CD8+, CD3, CD45RO, CD7, CD45RA, betaF1, TIA-1
6.5.22.5.7.2  T cell receptor gamma/delta chain positive cutaneous lymphoma

Introduction:

Most peripheral T cell lymphomas express the clone specific alpha/beta heterodimer. T lymphocytes bearing the gamma/delta heterodimer usually consist of less than 5% of the peripheral blood lymphocytes and show an increase in distinct infectious conditions like leprosy. About 3% of CDTL arise form the gamma/delta positive clone of lymphocytes, showing primary or preferential homing into the skin.

Clinical signs:

  • simulate MF or pagetoid reticulosis (cases of so called generalized pagetoid reticulosis of Ketron Goodman belong to this category)
  • clinical course is highly progressive in most cases, but may also be slowly progressive over many years
  • subcutaneous, pagetoid, erythrodermic and tumorous forms exist
  • subcutaneuous form resembles panniculitis, but the clinical course is more aggresive than that of subcutaneous panniculitis-like lymphoma of alpha/beta cell type

Histology:

The infiltrate is localized within the upper dermis or epidermis (sometimes epidermotropic: pagetoid type) or in the subcutaneous tissue (panniculitic type); consists of the medium-sized to large pleomorphic cells with abundant cytoplasm. Tissue necroses and vascular invasion are common.

Immunophenotype and genetic features:

  • CD3+, CD43+, CD45RO+, CD4+/-, CD8+/-, CD56+/-, CD5-, CD30-, CD15-
  • TIA-1, granzyme B, granzyme M and perforin are usually positive
  • hallmark: positivity for the gamma/delta TCR (and lack betaF1 epitope of the alpha/beta receptor)
6.5.22.5.7.3  Pleomorphic small to medium-sized T cell lymphoma

Clinical signs:

  • solitary or multiple nodular lesions

Histology:

Diffuse or nodular infiltrate, perivascular and periadnexal, extending to the subcutaneous tissue. Small to medium lymphocytes with irregular hyperchromatic nuclei and scanty cytoplasm with mitotic activity. Admixture of large pleomorphic cells may be present. Eosinophils, plasma cells and macrophages may be present as well. No epidermotropism.

Immunophenotype and genetic features: CD3+, CD4+, CD8-, CD30-; cytotoxic proteins are not present.

6.5.22.5.8  NK cell lymphoma (CD56+)

Introduction:

Uncommon lymphoma consisting of cells positive natural killer cell marker.

Clinical signs:

  • aggressive course, most patients die despite therapy
  • to the nasal type of NK lymphoma belong cases with destruction of soft tissues of the face (lethal midline granuloma of Krause Woods)

Histology:

Features resemble angiocentric T cell lymphoma. Epidermotropism in 50% of cases.

Cytology: small round lymphocytes, small cells with cleaved nuclei or medium sized to large cells. In many cases the azophilic granules typical for LGL are seen.

Immunophenotype and genetic features:

  • CD2+, CD3-, CD4-, CD8+/-, CD16+, CD56+, CD57+/-
  • T cell markers are negative in medium to large lymphoid tumor cells
6.5.22.5.9  Adult T cell lymphoma

Etiology:

Associated with human T cell leukemia virus I. (HTLV-1)

Clinical signs:

  • acute and smoldering are recognized
  • skin involved in 50% of cases: papules, plaques, nodules, erythrodermia
  • leukemic blood picture, hypercalcemia, bone lesions, lymphadenopathy

Histology:

Dense diffuse infiltrate of medium to large pleomorphic cells with or without epidermotropism.

Immunophenotype and genetic features:

  • pronounced heretogenity of the phenotype of neoplastic cells. Usually helper/inducer T cell phenotype (CD4+, CD8-); however, other phenotypic profiles may be seen in some of the cases (CD4-, CD8+ or CD4-, CD8-)
  • in endemic variants retroviral DNA is integrated into the host cell genome
6.5.22.5.10  Syringolymphoid hyperplasia with alopecia

Clinical signs:

  • numular eczematous and psoriatiform lesions
  • circumscribed alopecia caused by destruction of hair follicles
  • good prognosis

Histology:

Exclusive involvement of the sweat glands and ductal structures with small cerebriform lymphocytes around and between epithelial cells. Involvement of hair follicules may lead to circumscribed alopecia without follicular mucinosis.

6.5.22.5.11  Pleomorphic medium-sized and large T cell lymphoma (HTLV-1 +/-)

Clinical signs:

  • solitary or multiple nodular lesions

Histology:

Medium sized or large pleomorphic cells with multishaped nuclei. Small reactive lymphocytes, eosinophils and plasma cells. Significant epidermotropism with formation of intraepidermal microabscesses in the HTLV-1 positive leukemic form (adult T-cell lymphoma/leukemia).

Immunophenotype and genetic features:

  • CD30- variants
  • CD2+, CD3+, CD5+, CD7-, CD4+, CD8+ (rare cases)
  • clonal rearrangement of TCR genes

Pictures

Pleomorphic medium sized and large T cell lymphoma:
Pleiomorphic T cell lymphoma, medium to large cells, HE 40x (2245)

Another case:
Pleiomorphic T cell lymphoma, medium to large cells, HE 40x (2247)

Pleomorphic medium to large T cell lymphoma, HE 100x (2500)

Pleiomorphic T cell lymphoma, medium to large cells, CD30 40x (2246)

Another case:
Pleiomorphic T cell lymphoma, medium to large cells, HE 40x (2250)

Pleiomorphic T cell lymphoma, medium to large cells, HE 40x (2251)

Pleomorphic medium to large T cell lymphoma, HE 100x (2501)

Pleiomorphic T cell lymphoma, medium to large cells, CD30 40x (2248)

Pleiomorphic T cell lymphoma, medium to large cells, CD30 40x (2249)

Another case:
Pleomorphic medium to large T cell lymphoma, HE 20x (2503)

Pleiomorphic T cell lymphoma, medium to large cells, HE 40x (2252)

Pleomorphic medium to large T cell lymphoma, HE 100x (2502)

Pleomorphic medium to large T cell lymphoma, CD30 40x (2432)

Another case:
Pleiomorphic T cell lymphoma, medium to large cells (PTCL), HE 20x (4583)
  [zoomify]
Pleiomorphic T cell lymphoma, medium to large cells (PTCL), CD3 20x (4579)

Pleiomorphic T cell lymphoma, medium to large cells (PTCL), CD30 20x (4580)
  [zoomify]
Pleiomorphic T cell lymphoma, medium to large cells (PTCL), CD4 20x (4581)

Pleiomorphic T cell lymphoma, medium to large cells (PTCL), CD8 20x (4582)

Pleiomorphic T cell lymphoma, medium to large cells (PTCL), Ki67 20x (4584)
  [zoomify]

Another case:
Pleiomorphic T cell lymphoma, medium to large cells (PTCL), HE 20x (4653)
  [zoomify]

Another case:
Pleiomorphic T cell lymphoma, medium to large cells (PTCL), HE 20x (4654)
  [zoomify]

6.5.22.5.12  Juvenile granulomatous cutaneous T cell lymphoma

Introduction:

Provisional group of low grade, slowly progressive cutaneous T cell lymphoma with distinct clinical features and associated with high risk of development of systemic lymphoma.

Clinical signs:

  • patchy or nodular, localized or disseminated skin lesions
  • age: childhood or young adults (4 – 23 years, median 13)
  • slow progression
  • after 20 years nodal Hodgkin's disease (nodular sclerosis) or extracutaneous large cell anaplastic Ki-1+ lymphoma in 50% of cases

Histology:

Patchy or nodular infiltrate consisting of histiocytes, epithelioid cells and a few multinucleated giant cells with a variable admixture of small well differentiated lymphocytes.

Immunophenotype and genetic features:

  • clonal rearrangement for TCR genes
6.5.22.5.13  B cell rich T cell lymphoma

Clinical signs:

  • patches, plaques or tumors (as in mycosis fungoides)

Histology:

Non-epidermotropic nodular infiltrate extending into the deep dermis. Medium size to large pleomorphic mononuclear cells with islands of small, chromatin rich B lymphocytes.

Immunophenotype and genetic features:

  • T cell markers: CD3+, CD43+, CD45RO+
  • reactive cells express B cell phenotype CD20+ and may be positive for bcl2 protein (indicating lack of apoptosis in these areas)
  • clonal rearrangement of TCR beta chain gene but not of the Ig heavy chain gene locus
6.5.22.5.14  Angiocentric and angiodestructive lymphoma

Clinical signs:

  • erythroderma
  • infiltrating plaques or flat ulcerations
  • sometimes pulmonary involvement

Histology:

Angiocentric and angioinvasive infiltrate composed of a mixture of well differentiated or cerebriform small lymphocytes and variable numbers of atypical lymphoid cells as well as immunoblasts, along with plasma cells, eosinophils and histiocytes.

Infiltration of blood vessels walls causes vascular occlusion and is associated with ischemic necrosis and superficial ulceration.

Immunophenotype and genetic features:

  • T cell markers positive: CD2+, CD5+, CD4+ or CD8+, often CD56+
  • TCR and Ig genes are usually in germline.
6.5.22.5.15  T zone lymphoma, Lennert and Mohri

Introduction:

Lymphoproliferative disorder, considered to be the T-cell lymphoma equivalent of follicular B cell lymphoma.

Clinical signs:

  • lymphadenopathy, later hepatomegaly and/or splenomegaly and in 40% of cases lung involvement
  • unspecific skin reactions (rash, pruritus) in 30%
  • erythematous plaques or deep nodular livid lesions on the face or trunk
  • prognosis is bad (extracutaneous spread)

Histology:

Diffuse, non epidermotropic infiltration of atypical small to medium-sized pleomorphic T lymphocytes in the expanded interfollicular areas (T-zones), affecting the entire dermis and subcutis.

Hallmark: remnants of follicular structures.

Small foci of chromatin-dense well differentiated small B lymphocytes, some immunoblasts and histiocytes and proliferation of postcapillary venules with high endothelial cells.

Immunophenotype and genetic features:

  • CD3+, CD4+, CD43+, CD45RO
  • CD8-, CD45RA-, CD20-, CD30-
  • S100 protein shows a dense network of interdigitating reticulum cells typical for the T-zone of the lymphnode
  • clonal rearangement of TCR beta genes in a majority of cases while the immunoglobulin genes remain in germinal configuration
6.5.22.5.16  Intravascular T lymphoma

Introduction:

T counterpart of intravascular B lymphoma.

6.5.22.6  B cell lymphomas
6.5.22.6.1  Follicular lymphoma

Clinical signs:

  • most common cutaneous B cell lymphoma
  • reddish papules and nodules, solitary or grouped
  • location: head, neck (and dorsum)
  • excellent prognosis

Histology:

Follicular, follicular + diffuse and diffuse categories are distinguished.

Dense infiltrate involving all dermal layers and often extending into the subcutis, diffuse or nodular, bottom heavy. No epidermotropism (grenz zone is present), periadnexal and perivascular arrangement.

Follicular and pseudofollicular structures are often present, consisting of centroblasts (at least 20%) and centrocytes (centrocytes dominate). Centroblasts are medium to large cells with a vesicular roudish nucleus containing few distinct nucleoli attached ot the nuclear membrane and basophilic (Giemsa) cytoplasm.

Centrocytes are small or medium sized cells with irregular nuclei showing nuclear clefts.

In addition some immunoblasts and only a few histiocytes are present. About 10 – 40% of the infiltrate are reactive T lymphocytes.

Immunophenotype and genetic features:

  • B cell markers: CD20+, CD79a+
  • CD5-, CD43-
  • expression of surface Ig with monotypic pattern (either lambda or kappa light chains)
  • CD21+ dendritic cells within the follicular infiltrates, forming irregular network
  • clonal rearrangement of Ig heavy or light chain genes (PCR or Southern blot); negative results does not exclude the diagnosis of the follicular lymphoma.
  • bcl2 is usually negative
6.5.22.6.1.1  Secondary skin infiltration in nodal follicular lymphoma

Introduction:

Generalized nodal follicular lymphoma infiltrating the skin.

Histology:

Similar to primary cutaneous follicular lymphoma.

6.5.22.6.2  Marginal zone lymphoma

Introduction:

Monocytoid B cell lymphoma. Reffered by some authors as mucosa associated lymphoid tissue lymphoma (MALT) or skin associated lymphoid tissue lymphoma (SALT). Association with Borrelia burgdorferi has been suggested.

Clinical signs:

  • red-brown papules, plaques or nodules
  • tendency to recurrences, but excellent long term prognosis

Histology:

Nodular or diffuse infiltrates in the dermis and subcutis without involvement of the epidermis. Sometimes reactive follicles are present within the infiltrate.

Cytology: small to medium sized cells with convoluted monocytoid nuclei and a pale cytoplasm resembling centrocytes. Additional cell types such as plasma cells, histiocytes and eosinophils are present.

Immunophenotype and genetic features:

  • Tumor cells: CD20+, CD79a+, but CD5- a CD10-
  • Typical feature: granular cytoplasmic staining pattern using the Ki-M1p antibody reacting with monocytoid B cells
  • expression of Ig light chains only in 50% of cases
  • Genotype: clonal rearrangement of Ig heavy chain gene in some cases

Pictures

Marginal zone lymphoma:
Marginal zone lymphoma, HE 40x (2231)

Marginal zone lymphoma, HE 100x (2498)

Marginal zone lymphoma, HE 100x (2548)

Another case:
Marginal zone lymphoma, HE 40x (2562)

Marginal zone lymphoma, HE 100x (2499)

Another case:
Marginal zone lymphoma, HE 20x (2425)

Marginal zone lymphoma, HE 40x (2426)

Marginal zone lymphoma, HE 100x (2512)

Another case:
Marginal zone lymphoma (MZL), HE 20x (4556)
  [zoomify]
Marginal zone lymphoma (MZL), bcl2 20x (4551)
  [zoomify]
Marginal zone lymphoma (MZL), bcl2 20x (4552)
  [zoomify]
Marginal zone lymphoma (MZL), bcl6 20x (4553)
  [zoomify]
Marginal zone lymphoma (MZL), bcl6 20x (4554)
  [zoomify]
Marginal zone lymphoma (MZL), CD21 20x (4555)
  [zoomify]

Another case:
Marginal zone lymphoma (MZL), HE 20x (4564)
  [zoomify]
Marginal zone lymphoma (MZL), bcl2 20x (4558)
  [zoomify]
Marginal zone lymphoma (MZL), bcl6 20x (4559)
  [zoomify]
Marginal zone lymphoma (MZL), CD79a 20x (4562)
  [zoomify]
Marginal zone lymphoma (MZL), CD21 20x (4560)
  [zoomify]

Another case:
Marginal zone lymphoma (MZL), HE 20x (4864)

Another case:
Marginal zone lymphoma (MZL), HE 20x (4865)
  [zoomify]

Another case:
Marginal zone lymphoma (MZL), HE 20x (4866)
  [zoomify]

Another case:
Marginal zone lymphoma (MZL), HE 20x (4867)
  [zoomify]

Another case:
Marginal zone lymphoma (MZL), HE 20x (5316)

Another case:
MALT lymphoma, skin, HE 60x (74588)

MALT lymphoma, skin, CD20 60x (10047)

MALT lymphoma, skin, bcl2 40x (10042)

MALT lymphoma, skin, bcl6 40x (10043)

MALT lymphoma, skin, CD10 40x (10044)

MALT lymphoma, skin, CD5 40x (10045)

MALT lymphoma, skin, CD3 60x (10048)

MALT lymphoma, skin, Ki67 40x (10046)

Marginal zone lymphoma destroying hair follicles:
Marginal zone lymphoma (MZL), HE 40x (6046)

Marginal zone lymphoma (MZL), HE 40x (6047)

Marginal zone lymphoma (MZL), CD20 40x (6048)

Marginal zone lymphoma, CD3 40x (6050)

Marginal zone lymphoma (MZL), bcl2 40x (6044)

Marginal zone lymphoma (MZL), bcl6 40x (6045)

Marginal zone lymphoma:
Marginal zone lymphoma (MZL), HE 60x (12983)

6.5.22.6.2.1  Marginal zone lymphoma, immunocytoma variant

Introduction:

Variant of marginal zone lymphoma, where neoplastic cells show tendency to differentiate into plasma cells.

Histology:

Dense, nodular infiltrate reaching into the deep dermis. Epidermis is uninvolved (grenz zone). The cell population consists of small B lymphocytes, lymphoplasmocytoid cells and mature plasma cells arranged in clusters. Histiocytes and eosinophils can be observed.

Intranuclear Dutcher bodies and intracytoplasmatic Russel bodies (PAS+ Ig deposits) within plasmocytoid tumorous cells.

Immunophenotype and genetic features:

  • small lymphocytes: CD20+, CD79a+; but CD5 or CD10 are negative
  • lymphoplasmocytoid cells and plasma cells: no expression of B markers
  • proliferating cells are monotypic and usually express IgM kappa
  • Genotype: clonal rearrangement of Ig heavy and light chain genes
6.5.22.6.2.2  Marginal zone lymphoma, plasmocytoma variant

Clinical signs:

  • most cases of skin infiltration are caused by multiple myeloma of bone marrow
  • primary plasmocytoma of the skin is very rare
  • solitary violaceous nodule
  • elderly patients
  • location: face, trunk
  • slow progression, benign course

Histology:

Dense monomorphous infiltrate of plasmocytes in the deep dermis, sometimes extending into subcutaneous fat.

Variably mature plasma cells with Russel bodies. Mitotic activity. Amyloid and needle-like crystalloid intracytoplasmatic inclusions within macrophages.

Immunophenotype and genetic features:

  • lack of reactivity for some B cell markers (CD20) or variable expression (CD79a)
  • neoplastic cells express only one type of Ig light chain (kappa or lambda) or show intracytoplasmic Ig deposits, usually IgA

Pictures

Marginal zone lymphoma with plasma cells:
Marginal zone lymphoma (MZL) with plasmocytes, HE 20x (4550)
  [zoomify]

6.5.22.6.3  Large cell diffuse B cutaneous lymphoma
6.5.22.6.3.1  Large B cell diffuse lymphoma, leg type

Introduction:

Large B cell lymphomas comprise about 1 – 3% of all cutaneous lymphomas and about 5 – 10% of cutaneous B cell lymphomas. The most common large cell B lymphoma of the skin.

Clinical signs:

  • elderly female patients
  • solitary or multiple red to violaceous dense nodules, predominantly on the legs
  • bad prognosis (5 year survival rate is about 50%)
  • recurrences after therapy are common

Pictures

Large B cells lymphoma of the lower legs (65 years old woman):
Large cell B cell lymphoma, CLINIC (2611)

Large cell B cell lymphoma, CLINIC (2612)

Histology:

Diffuse growth pattern with infiltrate involving the whole dermis and extending into subcutaneous fat. Remnants of large follicle-like structures.

Neoplastic cells resemble either centroblasts with large non-cleaved nuclei and nucleoli attached to the nuclear membrane, or immunoblasts with large vesicular nucleus and centrally placed prominent nucleolus. In addition multilobated, anaplastic or large cleaved cells may be present. Centrocytes are not present.

Mitotic activity is usually high.

In some cases epidermotropism of the infiltrate may lead to confusion with T cell lymphoma.

Immunophenotype and genetic features:

  • tumor cells: CD20 and CD79a are positive (but loss of B markers may occur)
  • CD10, CD5, CD138 and cyclin D1 are negative
  • Ig light chains expressed on the cell surface or intracytoplasmatically
  • bcl-2 and MUM 1 are positive (important for differentiation from diffuse FCL)
  • bcl-6 is usually positive
  • chromosomal translocation (t8;14) occurs in secondary skin infiltrations in nodal lymphoma cases, but is not present in primary LBCL of the skin
6.5.22.6.3.2  Large cell diffuse B lymphoma, other than leg type

To this category belong lymphomas with diffuse growth pattern, composed of large trans- formed B-cells that lack the typical features of DLBCL, leg type and do not belong to the diffuse FCL category. Bcl-2 protein may be negative, whereas bcl-6 is usually positive.

6.5.22.6.3.2.1  T cell rich B cell lymphoma

Clinical signs:

  • most cases are nodal lymphomas
  • T cell rich B cell lymphoma limited to the skin is extremely rare
  • classified as member of diffuse large B cell lymphoma, non leg
  • plaques and nodular lesions
  • location: face, trunk (and erythema nodosum-like lesions)

Histology:

Small, well differentiated T lymphocytes (more than 75% of the infiltrating cells) and medium-sized to large cells are disseminated as single units or small clusters (representing the malignant clone).

Immunophenotype and genetic features:

  • reactive, small cells: CD3, CD43, CD45RO positive
  • tumor cells: CD20 and CD79a positive
  • genotype: clonal rearangement of Ig heavy chain disease
6.5.22.6.3.2.2  Intravascular B lymphoma

Clinical signs:

  • very rare disease
  • erythematous and violaceous plaques or nodules
  • location: face, trunk, extremities (and other organs)
  • neurological defects are common
  • bad prognosis

Histology:

Dense proliferation of atypical, usually large lymphoid cells with round or oval nuclei within the lumina of blood vessels. Blood vessels may get occluded or thrombosed. Mitoses are frequent. Spread into surrounding tissue occurs.

Immunophenotype and genetic features:

  • B markers, sometimes CD5, CD10, CD11a, and CD49d
  • bcl-2 overexpression was found in most cases
  • Cases of identical appearance but with T phenotype were described.
6.5.22.6.3.2.3  Lymphoblastic lymphoma B

Clinical signs:

  • usually secondary skin involvement in patients suffering from acute lymphoblastic leukemia; primary cases belong to the LBCL, non leg type category
  • rare disease
  • age: adolescents, young adults
  • solitary or multiple livid nodules

Histology:

Diffuse dense infiltrate consisting of medium-sized to large cells in dermis and subcutis. Lymphoblasts with round or convoluted nuclei and thin inconspicuous cytoplasm. Mitotic activity. Presence of macrophages can result in starry sky picture.

Immunophenotype and genetic features:

  • B cell markers (CD19, CD79a, cytoplasmic IgM heavy chain are positive
  • CD10 (CALLA antigen), TdT and CD34 are positive
6.5.22.6.4  Lymphomatoid granulomatosis (Liebow)

Clinical signs:

  • rare multisystemic disease affecting lungs, skin and nervous system
  • exact nature is unclear
  • skin is involved in more than 50% of the patients
  • scattered nodules, eroded and crusted lesions, recurrent skin ulcerations, facial edema, papules and folliculitis like eruptions
  • bad prognosis

Etiology:

Caused by EBV infection.

Histology:

Polymorphous nodular skin lesions with dense angiocentric and angiodestructive infiltrate in the dermis and subcutaneous tissue. No epidermal involvement. Almost exclusive vasocentricity of the lesions.

Immunophenotype and genetic features:

  • T helper (memory) cells (CD2+, CD3+, CD4+, CD5+, CD7+, CD45RO+)
  • variable expression of activation antigenes (CD25-, CD38+, CD71+, HLA-DR+)
  • Ki67 positive in 20% of nuclei
  • virus Epstein-Barr is positive in some cells of the infiltrate
6.5.22.6.5  Lymphatic leukemia B

Introduction:

Secondary infiltrates in chronic lymphatic leukemia.

Histology:

Mature, small, almost normal lymphocytes (B), in dense superficial and deep infiltrates. Low or none mitotic activity.

Immunologic profile: simultaneously CD5, CD20, CD23.

6.5.22.6.6  Mantle cell lymphoma

Clinical signs:

  • disease is rarely limited to the skin; dissemination from the lymphodes is much more common

Histology:

Nodular growth, no follicular structures with CD21+ dendritic cells and admixture of eosinophils and plasmocytes.

Cells are of medium size with irregular, cleaved nuclei.

Immunophenotype and genetic features:

  • neoplastic cells: CD20+, CD79a+, CD5+
  • genotype: rearangement of bcl-1 gene in nodal MCL
6.5.22.6.7  Burkitt lymphoma

Clinical signs:

  • affects children in equatorial Africa and sporadically children and young adults in other countries
  • affects immunodeficient patients as well
  • extranodal forms (bones of the face, abdomen), leukemisation
  • secondary infiltration of the skin occurrs rarely
  • aggressive, responsive to therapy

Histology:

Diffuse homogenous proliferation of middle size lymphoid cells, with large nuclei and narrow cytoplasm, forming dense infiltrates. Among these dark background are pale macrophages scattered, giving the picture of starry sky. No epidermotropism. High mitotic activity.

Immunohistochemistry: CD20+, CD10+, CD5-, bcl-.

Genotype: various generic anomalies (immunoglobulin genes, c-myc and other).

Pictures

Burkitt lymphoma, secondary infiltration of the skin:
Burkitt lymphoma, HE 20x (4435)
  [zoomify]

6.5.22.7  Acute hematopoietic malignancies
6.5.22.7.1  Blastic NK cell lymphoma CD4+/CD56+ hematodermic neoplasm

Clinical signs:

  • massive skin infiltrates or bruise-like circumscribed swelling in majority of patients
  • oral mucosa is commonly infiltrated
  • aggressive course, most patients die within weeks despite therapy

Histology:

Mononomorphous, dense and diffuse infiltrate of medium or large cells within the dermis. No epidermotropism (grenz zone). Erythrocytic extravasations.

Immunophenotype and genetic features:

  • CD4, CD56, CD123 and TCL-1 positive.
  • negative for other T, B, NK cell or myeloid markers
  • some cells may express CD68 or TdT
  • no clonal arrangement of TCR genes

Pictures

Blastic NK lymphoma CD4+/CD56+:
CD4 CD56 positive blastic lymphoma, HE 20x (4892)
  [zoomify]

6.5.22.7.2  Precursor lymphoblastic leukemia/lymphoma
6.5.22.7.2.1  Precursor lymphoblastic leukemia/lymphoma B

Clinical signs:

  • affects usually children
  • massive bone marrow infiltration, often leukemic
  • pancytopenia, fatigue, fever, bleeding
  • infiltration of the spleen, lymphodes, liver, skin, CNS
  • aggresive, but responds well to chemotherapy

Histology:

Diffuse, dense infiltrate of cells with moderate amount of cytoplasm, condensed chromatin.

Immunophenotype and genetic features:

  • TdT+, CD19+, CD10+
  • chromosomal anomalies are present in 90% of cases; variable (Philadelphia chromosome and other)
  • some chomosome abnormalities are associated with worse prognosis: t(9,12)
6.5.22.7.2.2  Precursor lymphoblastic leukemia/lymphoma T

Clinical signs:

  • affects usually adolescents
  • massive bone marrow infiltration, often leukemic
  • pancytopenia, fatigue, fever, bleeding
  • infiltration of the thymus, spleen, lymphodes, liver, skin, CNS
  • aggresive, but responds well to chemotherapy

Histology:

Diffuse, dense infiltrate of cells with moderate amount of cytoplasm, condensed chromatin.

Immunophenotype and genetic features:

  • TdT+, CD1+, CD2+, CD5+, CD7+; more mature cases are positive for CD3, CD4 and CD8
  • chromosomal anomalies are present in 90% of cases; variable (Philadelphia chromosome and other)
  • some chomosome abnormalities are associated with worse prognosis: t(9,12)
6.5.22.8  Hodgkin's disease of the skin

Introduction:

Primary Hodgkin's lymphoma is very rare in the skin, its existence is doubted. It is necessary to rule out secondary infiltration of nodal lymphoma.

Histology:

Dense dermal infiltrates with histological signs of Hodgkin's disease (admixtured granulocytes, Hodgkin's cells, diagnostic cells of Reed-Sternberg).

6.5.23  Skin infiltrates in granulocytic malignancies

6.5.23.1  Acute myeloic leukemia

Pictures

Acute myeloic leukemia, thorax:
Acute myeloic leukemia, CLINIC (6160)

Histology:

Diffuse, superficial and deep infiltrate consisting of myeloblastic cells.

6.5.23.1.2  Chloroma

Histology:

Tumoriform lesion consisting of dense granulocytic infiltrate similar to that in chronic myeloic leukemia.



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