Introduction:
A collection of clonal disorders affecting hematopoietic stem cells. It is characterised by dysplastic changes in one or more lineages and ineffective hematopoiesis.
Etiology:
Clinical signs:
Classification:
WHO 2008:
Histology:
Clinical signs:
Histology:
The number of myeloblasts in bone marrow is less than 5%.
Clinical signs:
Histology:
Pictures
Refractory anemia with ringed sideroblasts, iron stain:
Refractory anemia with ring sideroblasts, Prussian blue 100x (72496)
Clinical signs:
Clinical signs:
Histology:
Clinical signs:
Histology:
Dysplastic changes and increased numbers of small megakaryocytes with dysplastic hypolobated nuclei.
Pictures
MDS with isolated 5q deletion:
5q-syndrome, HE 100x (72892)
Introduction:
A group of clonal disorders of the hematopoietic stem cells, which are characterised by proliferation of one or more hematopoietic lineages. Maturation is relatively normal — effective hematopoiesis.
Etiology:
Most often unclear.
Clinical signs:
Classification:
WHO classifies MPNs into tho categories according to the presence of the BCR/ABL1 fusion gene:
Grades of bone marrow fibrosis in myeloproliferative neoplasms:
Introduction:
Etiology:
More than 95% of patients carry the somatic JAK2 V617F mutation.
Clinical signs:
Histology:
Pictures
Bone marrow, polycythemia vera:
Polycytemia vera, bone marrow, HE 100x (73031)
Polycytemia vera, bone marrow, PAS 100x (73032)
Polycytemia vera, bone marrow, Gömöry 100x (73030)
Clinical signs:
Etiology:
Approx. 40 – 50% of patients carry the somatic JAK2 V617F mutation, qpprox. 1% carry the MPL W515K/L mutation.
Histology:
Normocellular bone marrow, increased numbers of clusters formed by huge megakaryocytes,
which have hyperlobated
Pictures
Essential thrombocythemia, bone marrow:
Essential thrombocytopenia, bone marrow, HE 100x (72624)
Clinical signs:
Histology:
Pictures
Chronic idiopathic myelofibrosis:
Chronic idiopathic myelofibrosis, HE 100x (72423)
Chronic idiopathic myelofibrosis, HE 100x (72424)
Chronic idiopathic myelofibrosis, van Gieson 100x (72425)
Chronic idiopathic myelofibrosis, Gömöry 100x (72427)
Another case:
Chronic idiopathic myelofibrosis (CIMF), PAS 100x (72887)
Introduction:
Clinical signs:
Etiology:
Caused by the BCR-ABL1 fusion gene, which in approximately 90 – 95% of all cases comes from reciprocal translocation t(9,22)(q34,q11.2) — Ph chromosome.
Histology:
Introduction:
A rare disorder characterised by neutrophilia in peripheral blood and expansion of neutrophilic granulopoiesis. The BCR-ABL1 fusion gene is absent as well as other reactive causes and MPNs.
Etiology:
90% of all cases show a normal genetic prophile, BCR-ABL1 is absent, however JAK 2 mutation may occasionally occure.
Clinical signs:
Histology:
Hypercellular bone marrow with predominant neutrophilic granulopoiesis (M:E is 20:1 or more), the number of myeloblasts and promyelocytes is not increased, myelocytes and mature neutrophils predominate. Erythroid and megakaryocytic preliferation may occur. Significant dysplastic changes are absent.
Clinical signs:
Etiology:
The BCR-ABL1 gene or the PDGFRA, PDGFRB rebuild is absent. JAK2 mutation is occasionally present.
Histology:
Hypercellular bone marrow with predominatnt eosinophilic proliferation, the number of myeloblasts may be increased between 5 – 19%, Charcot-Leyden crystals are often present. Erythropoiesis and megakaryocytes are usually normal. Fibrosis may sometimes be found.
Introduction:
Clonal neoplastic mast cell proliferation. Mast cells accummulate in one or more organs. Mastocytosis is characterized by multifocal cohesive aggregates or infiltrates formed by abnormal mast cells.
Classification:
Introduction:
Clonal hematopoietic disorders, which show both myeolodysplastic and myeloprliferative features.
Clinical signs:
Classification:
WHO 2008:
Introduction:
Clonal disease of the hematopoietic stem cell, defined by persistent monocytosis (at least 3 months).
Clinical signs:
Approximately 40% of cases show a RAS gene mutation, are BRC-ABL1 negative, and the PDGFRA and PDGFRB transformations are absent.
Clinical signs:
Pictures
Chronic myelomonocytic leukemia:
Chronic myelomonocytic leukemia, bone marrow, HE 100x (72740)
Chronic myelomonocytic leukemia, bone marrow, PAS 100x (72737)
Introduction:
Leukemia with both myelodysplastic and myeloproliferative features with predominant affection of the granulocytic lineage, BCR-ABL1 negative.
Clinical signs:
BCR-ABL1 gene and PDGFRA and PDGFRB transformation are absent, mutation JAK2 V617F is sometimes present, 30% of cases show NRAS or KRAS mutation.
Clinical signs:
Introduction:
Clonal hematopoietic disorder which affects children. It is characterised by granulocytic and monocytic proliferation.
Etiology:
25% monosomy 7, 35% mutation of PTPN11, 20% mutation of NRAS, KRAS2 and NF1, BCR-ABL1 is absent.
Clinical signs:
Introduction:
Clonal expansion of myeloid blasts in bone marrow, peripheral blood or other organs.
Etiology:
Clinical signs:
Classification:
FAB classification:
WHO classification:
Histology:
Bone marrow is markedly hypercellular, sometimes hypocellular (especially therapy-related AML), myelopoiesis is usually markedly increased with a differentiation arrest and increased myeloblast (monoblast) levels above 20%. Megakaryocytes and erythropiesis are residual (except M6 and M7), M7 leukemia causes significant fibrosis.
Most common sites of infiltration are the spleen, liver, lymph nodes and other, however significant organomegaly is uncommon. Sometimes tumoriform lesions (myelosarcoma) may be found.
Secondary symptoms: bleeding, infections, anemia.
Pictures
Acute myeloid leukemia, hypoplastic, bone marrow:
Hypoplastic acute myeloic leukemia, HE 100x (73112)
Hypoplastic acute myeloic leukemia, PAS 100x (73113)
Acute meyloid leukemia, kidney, infiltration into the glomerulus:
Kidney in acute myeloic leukemia, HE 100x (72796)
Introduction:
There are two basic categories of lymphoproliferative disorders:
Lymphomas and leukemias often overlap, because lymphomas may undergo leukemisation and vice versa. For example small lymphocytic lymphoma/chronic lymphocytic leukemia or precursor lymphoblastic lymphoma/acute lymphoblastic leukemia: they are the same disorders with different manifestation.
Lymphomas are detailed in the chapter
Histology:
Types of tumorous bone marrow infiltration:
Types of malignant bone marrow infiltration:
Pathogenesis:
Caused by lymphoid precursors — lymphoblasts.
Clinical signs:
Histology:
Same as precursor lymphoblastic lymphoma — small to middle-sized cells with round nuclei and finely dispersed chromatin, without prominent nucleoli, with a narrow rim of basophilic cytoplasm.
Imunophenotype:
T lineage (CD3+) or B lineage (CD20+ a CD79a+),
Pathogenesis:
The offending cells are mature
Clinical signs:
Histology:
Same as small lymphocytic lymphoma — small cells with the appearance of mature lymphocytes, with round nuclei, dense chromatin, and inconspicuous nucleoli, a narrow rim of basophilic cytoplasm. Proliferation centres also contain prolymphocytes and paraimunoblasts.
Imunophenotype: B lineage (CD20+ a CD79a+), CD5+, CD23+.
Pictures
Chronic lymphocytic leukemia, bone marrow:
Chronic lymphatic leukemia, bone marrow, HE 100x (73238)
Chronic lymphatic leukemia, bone marrow, PAS 100x (73239)
A different case:
Chronic lymphatic leukemia B, HE 100x (73355)
Chronic lymphatic leukemia B, PAS 100x (73356)
Chronic lymphatic leukemia B, CD20 100x (73352)
Chronic lymphatic leukemia B, CD5 100x (73354)
Chronic lymphatic leukemia B, CD23 100x (73353)
Pathogenesis:
The offending cell line is either the peripheral B (postgerminal) or T (post-thymic) cell (?).
Clinical signs:
Histology:
Prolymphocytes — middle-sized cells with round nuclei, dispersed chromatin, prominent nucleoli and a narrow rim of slightly basophilic cytoplasm.
Imunophenotype: B lineage (CD20 a CD79a+) nebo T lineage (CD3+), CD23-
Pathogenesis:
Arises from postgerminal cells (?).
Clinical signs:
Histology:
Intersticial infitration of the bone marrow, middle-sized cells
with round or kidney-shaped nuclei with diffuse chromatin without nucleoli,
abundant pale cytoplams with thin
Imunophenotype: B lineage (CD20 a CD79a+), DBA44+, CD103+, TRAP+
Introduction:
Immunosecretive tumorous disorders caused by expansion of a particular clone of differentiated B cells, which produce a single type of immunoglobulin. Previously called plasma cell dyscrasias.
Classification:
Introduction:
Systemic bone marrow disease, with an occasional formation of osteolytic lesions.
Clinical signs:
Complex diagnostic criteria — Durie-Salmon staging system.
Histology:
The marrow is infiltrated with monoclonal plasma cells at various stages of differentiation (mature plasma cells, immature plasma cells, plasmablasts), with an occassional formation of osteolytic lesions.
Imunophenotype: CD138+, monoclonality according to the light chains of imunoglobulins kappa and lambda.
Pictures
Myeloma, bone marrow infiltration:
Multiple myeloma, bone marrow, HE 100x (73120)
Myeloma, bone marrow infiltration:
Myeloma, trephine biopsy, CD138 60x (74200)
Myeloma, trephine biopsy, HE 60x (74201)
Myeloma, trephine biopsy, HE 60x (74202)
Myeloma, trephine biopsy, kappa 60x (74203)
Myeloma, trephine biopsy, lambda 60x (74204)
Introduction:
Localized tumours which arise in bones or soft tissues. They contain cells morphologically identical to the cells of plasma cell myeloma. This myeloma develops in about 55% of cases.
Monoclonal gammopathies which do not meet the criteria of plasma cell myeloma, plasmocytoma or B-Cell lymphoma with plasmacytic differentiation. Monoclonal immunoglobulin serum levels are lower than 30 g/l, the marrow contains less than 10% of monocloal plasma cells with no signs of organ affection (no hypercalcemia, renal insufficiency, anemia or osteolytic lesions).
Bone marrow may be affected by all types of lymphomas. A bone marrow sample is always obtained in order to establish the stage of the disease and decide on adequate therapy.
Reasons for performing a trephine biopsy: quantification of the infiltrate, post-treatment moitoring, restaging (in case of a relapse).
Pictures
Hodgkin's disease, bone marrow:
Hodgkin disease, PAS 100x (72679)
Hodgkin disease, CD15 100x (72678)
Folicular lymphoma, bone marrow:
Follicular lymphoma, bone marrow, HE 100x (72692)
Follicular lymphoma, bone marrow, CD20 100x (72738)
Lymphoplasmocytoid lymphoma, bone marrow:
Lymphoplasmocytoid lymphoma, bone marrow, HE 100x (72903)
Lymphoplasmocytoid lymphoma, bone marrow, PAS 100x (72904)
Diffuse large B cell lymphoma, bone marrow:
Diffuse large cell B lymphoma, bone marrow, PAS 100x (73109)
Introduction:
Histiocytoses are a heterogenous group of disorders characterised by excessive proliferation of the histiocyte lineage. Some are reactive processes (for example cutaneous histiocytoma), some are malignant and others are very rare and therefore difficult to classify. This group of disorders also contains dendritic cell proliferations, while a relatively common malignant fibrous histiocytoma is classified among soft tissue tumors (because its histiocytic origin is not unequivocal).
Introduction:
Histiocytosis X is a clonal proliferation of cutaneous dendritic (Langerhans) cells, with their characteristic CD1a antigen expression and typical Birbeck granules, which may be observed ultramicroscopically. Tumorous forms of Langerhans cells can be found at various locations (bones, parenchymal organs), which is probably caused by presence of abnormal chemokine receptors that attract the cells into these organs. chemokinových receptorů, které je atrahují do příslušných orgánů.
Normally, dendritic cells are distributed in the epidermis. After antigen stimulation they change and lose the CD1 antigen as well as the Birbeck granules. Then they migrate into the lymph nodes, where they present the antigen to the T4 lymphocytes.
Classification:
Histiocytosis X is divided into:
Apart from histiocytosis X, there are other (usually cutaneous) disorders, which originate in temporary forms of dendritic cells (which for example express the CD1a antigen, but do not contain Birbeck granules). Prognosis is usually good (self limiting histiocytosis of the head in children, undetermined cell histiocytosis and others).
Pictures
Histiocytosis X, infiltration of the lymphnode:
Histiocytosis X, HE 60x (74191)
Histiocytosis X, CD1a 40x (74189)
Histiocytosis X, S100 40x (74190)
Clinical signs:
Clinical signs:
Clinical signs:
Histology:
The accumulation of Langerhans´s cells, eosinophils and additional plasma cells and neutrofils.
Immunophenotype: S100 protein, specifically CD1a; Birbeck´s granules may be observed using electron microscopy.
Clinical signs:
Histology:
Polymorphous infiltration by histiocytes with wide cytoplasm and kidney-shaped nuclei.
Immunophenotype: in pure form only histiocytic markers are positive (CD68, MAC).
Introduction:
Metastatic infiltration of the bone marrow with solid tumours is relatively frequent (28 – 85%). Sarcomas most often infiltrate the marrow of children and adolescents (Ewing´s sarcoma, rhabdomyosarcoma, osteosarcoma) and neuroblastoma, while adult bone marrow is most often infiltrated with carcinomas (breast, prostate, lung, etc.).
Trephine biopsy indications in oncology: suspected metastatic cancer, staging, post-treatment monitoring.
Histology:
Histological image matches the primary tumour but metastasis may me less differentiated. It is possible (with certain probability) to determine the primary tumour by the appearance and immunohistological characteristics of the metastases.
The determination of the primary tumour may not be reliable and is nearly always expensive. Therefore it is usually better to determine tumour origin using different methods (clinical examination, screening methods).
Pictures
Diffuse gastric carcinoma, bone marrow infiltration:
Dissociated carcinoma of the stomach, infiltration of the bone marrow, HE 100x (72552)
Diffuse adenocarcinoma of the stomach, bone marrow infiltration, PAS 100x (72607)
Carcinoma of the breast, bone marrow infiltration:
Carcinoma of the breast, bone marrow infiltration, HE 100x (72554)
Paroxysmal night hemoglobinuria:
Paroxysmal night hemoglobinuria, PAS 100x (72784)