آزمايشگاه رز - Ackerman Atlas(chaptr39)

Bone Marrow

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Figure 39.1 Marrow biopsy obtained at site of a biopsy performed 14 days previously. The marrow space is replaced by granulation tissue

Figure 39.2 Marrow biopsy from patient with multiple myeloma reacted with polyclonal antibody to lambda light chain; the blastic appearing plasma cells show intense cytoplasmic reaction. (Immunoperoxidase.)

Figure 39.3 Marrow from patient with pure erythroleukemia reacted with antibody to hemoglobin A; many of the erythroblasts show a positive cytoplasmic reaction. Intensity of reaction varies from very slight to marked. (Immunoperoxidase.)

Figure 39.4 Marrow biopsy from a 2-year-old child with congenital neutropenia reacted with antibody to glycophorin A. There are numerous positive erythroid precursors at all stages of maturation. (Immunoperoxidase.)

Figure 39.5 Bone marrow biopsy from a patient with hypocellular acute myeloid leukemia reacted with polyclonal antibody to myeloperoxidase. The predominant myeloblasts and promyelocytes show intense cytoplasmic reactivity. (Immunoperoxidase.)

Figure 39.6 Bone marrow biopsy from a patient with chronic myeloid leukemia in accelerated phase reacted with polyclonal antibody to factor VIII-related antigen (von Willebrand factor). There are numerous dysplastic megakaryocytes with hypolobulated nuclei which show intense cytoplasmic reactivity. (Immunoperoxidase.)

Figure 39.7 Bone marrow biopsy from an adult man with therapy-related myelodysplastic syndrome and hypocellular marrow reacted with antibody to CD34. The number of positive cells approximates the 18.5% blasts in the marrow smear. (Immunoperoxidase.)

Figure 39.8 Marrow biopsy from a child with precursor B acute lym- phoblastic leukemia reacted with polyclonal antibody to TdT; the lym- phoblasts show intense nuclear reactivity. (Immunoperoxidase.)

Figure 39.9 Marrow biopsy from an adult man with recurrent follicular lymphoma positive for CD20. Numerous positive lymphocytes are present in a paratrabecular location. (Immunoperoxidase.)

Figure 39.10 Marrow biopsy from a child with neuroblastoma with ganglion differentiation reacted with antibody to neuron-specific enolase. The tumor cells are intensely reactive. (Immunoperoxidase.)

Figure 39.11 Normocellular bone marrow from 42-year-old man obtained as part of evaluation as potential donor for bone marrow transplantation. Hematopoietic cells and adipose tissue are present in approximately equal quantities

Figure 39.12 Marrow biopsy from a 70-year-old man being evaluated for metastatic tumor. The marrow is approximately 30%-35% cellular, normal for age. There was no evidence of tumor

Figure 39.13 Bone Marrow Section From a 7-Year-Old Girl With Idiopathic Acquired Aplastic Anemia. Hematopoietic cells are almost totally absent. Sinuses and capillaries are prominent. Iron-laden macro- phages reflecting increased iron stores from repeated red blood cell transfusions are present

Figure 39.14 A, Marrow biopsy from a 75-year-old man with invasive thymoma and nonclonal T-cell CD3+, CD4+, CD5+, CD8+ lymphocytosis. The markedly hypocellular marrow contains several large aggregates of small lymphocytes as illustrated; the predominant lymphocytes in the marrow specimen had the same phenotype as the blood and were nonclonal by molecular studies. The repeat marrow biopsy following thymectomy showed regression of the lymphocytic aggregates but persistence of hypoplasia. B, High magnification of specimen in A

Figure 39.15 Osteitis Fibrosa Cystica. Marrow biopsy from posterior iliac spine from a patient with chronic renal disease and secondary hyperparathyroidism. A portion of normal-appearing marrow is at the top. The remainder of this area shows new bone formation, loose marrow fibrosis, and increased osteoblasts and osteoclasts

Figure 39.16 Bone marrow section from a 19-year-old man with anorexia nervosa and severe weight loss showing marked serous degeneration (gelatinous transformation). There is marked reduction in hematopoietic and fat cells with accumulation of an amorphous, eosinophilic substance

Figure 39.17 Decalcified Posterior Iliac Spine Bone Marrow Trephine Biopsy From an 8-Month-Old Girl With Osteopetrosis. Marrow space is markedly reduced as consequence of widely expanded bone structure. Lighter areas in bone structure represent cartilaginous plates. Numerous osteoclasts are present in some areas along the endosteal surface

Figure 39.18 Marrow Biopsy From a Patient With Marrow Involvement by Burkitt Lymphoma. Most of the lymphoma cells show evidence of karyolysis; a few scattered pyknotic cells are present

Figure 39.19 Multiple noncaseating granulomas in marrow biopsy of a 33-year-old man admitted with marked hypercalcemia. A clinical diagnosis of sarcoidosis was established

Figure 39.20 Marrow biopsy with scattered granuloma-like lesions; many of the lesions had a central lumen and were interpreted as "doughnut" granulomas. No etiologic basis was identified

Figure 39.21 Marrow Biopsy From a Patient With Treated Hodgkin Disease. Numerous granulomas contain macrophages with numerous organisms (A) which were intensely PAS positive (B). Culture studies were positive for histoplasmosis

Figure 39.22 A, Pre-transplant marrow biopsy from a 4-year-old child with Hunter syndrome (acid mucopolysaccharides, type II) and erythroid aplasia. Several cells that reacted with antihemoglobin A contained intranuclear inclusions. Giant erythroblasts were present in the marrow smear and biopsy as illustrated and the findings were interpreted as consistent with infection with parvovirus B19. B, Marrow biopsy from a 17-year-old being treated for metastatic medulloblastoma; occasional, very large erythroblasts with abundant cytoplasm and very prominent nucleoli were present. These cells and the overall marked erythroid hypoplasia are characteristic findings in parvovirus B19 infection. (Wright-Giemsa) C, Marrow biopsy from an adult male with AIDS and concurrent parvovirus B19 infection. There are numerous erythroid precur- sors at all stages of maturation. Many of the more immature erythroblasts contain prominent intranuclear inclusions. (C, Contributed by Dr. Robert W. McKenna, Dallas, USA.)

Figure 39.23 Post-Chemotherapy Marrow Biopsy From Patient With Marrow Involvement by Mantle Cell Lymphoma. Several granulomas containing microorganisms interpreted as cryptococcus are shown. The organisms were positive with Gomori methenamine silver; culture studies were confirmatory of cryptococcus

Figure 39.24 Marrow from a patient with AIDS with scattered Pneumo- cystis jiroveci microorganisms occurring both singly and in small clusters. Microorganisms are not associated with any recognizable tissue response. (Periodic acid-Schiff.)

Figure 39.25 Marrow Biopsy From an AIDS Patient. No granulomas were identified but numerous macrophages containing acid-fast bacilli were scattered throughout the marrow interstitium, some in perivascular locations as illustrated

Figure 39.26 A, Section of bone marrow trephine biopsy from a child with primary oxaluria. Calcium oxalate crystals in giant cells form a radial pattern. B, Calcium oxalate crystals are doubly refractile in polarized light

Figure 39.27 A, Marrow biopsy from a patient with AIDS showing granuloma without evident necrosis. B, One of the granulomas in A showing numerous intracellular acid-fast bacilli. (B Fite.)

Figure 39.28 A, One of several lymphocytic-histiocytic aggregates in marrow biopsy from a patient with advanced AIDS. Acid-fast bacilli were also identified in this specimen. B, High magnification of specimen in A illustrating polycellular characteristics of the lesion

Figure 39.29 Marrow From a Patient With Acute Megakaryoblastic Leukemia. The predominant cell population consists of blasts and numerous megakaryocytes at varying stages of maturation. Mature megakaryocytes have abundant cytoplasm that is uniformly eosinophilic

Figure 39.30 A, Marrow biopsy from a 14-month-old child with acute megakaryoblastic leukemia with an associated t(1;22)(p13.3;q13.1) cytogenetic abnormality. The blasts frequently have a spindle shape and sometimes form intertwining bundles resembling metastatic tumor. B, High magnification of the specimen in A showing undifferentiated blasts

Figure 39.31 Bone marrow biopsy from an adult woman with a mediastinal mass and partial marrow involvement by precursor T-lymphoblastic lymphoma. In this area the lymphoblasts are the predominant cells; some of the lymphoblasts have convoluted nuclei. Scattered erythroid precursors are present

Figure 39.32 A, Marrow section from a 67-year-old man with acute myeloid leukemia with markedly hypocellular marrow. B, Higher magnifica- tion of the same specimen showing numerous blast cells in the interstitium

Figure 39.33 Marrow biopsy 14 days after institution of therapy with daunorubicin and cytosine arabinoside for acute myeloid leukemia. Marrow is markedly hypocellular with dilated sinuses. Interstitial areas contain lightly eosinophilic, proteinaceous debris that represents residue of leukemic cell necrosis

Figure 39.34 Marrow biopsy from an adult woman with acute promy- elocytic leukemia following two courses of chemotherapy which did not include all-trans-retinoic acid. Large areas of marrow are replaced by leukemic promyelocytes

Figure 39.35 A, Biopsy of orbital myeloid sarcoma from a 6-year-old child who presented with bilateral proptosis. Numerous blasts are present. Cytogenetic studies of this lesion showed t(8;21)(q22;q22.1) chromo- some abnormality. Blood and marrow smears showed acute myeloid leukemia with maturation. B, The same specimen reacted with antibody to myeloperoxidase. Virtually all blasts are positive. (B, Immunoperoxidase.)

Figure 39.36 Biopsy of a Myeloid Sarcoma From Subcutaneous Tissue of the Chest Wall of a 49-Year-Old Man. The tumor is composed of poorly differentiated blast cells interpreted as myeloid sarcoma. There is essentially no evidence of differentiation. Blood and marrow showed no evidence of leukemia

Figure 39.37 Marrow biopsy from a 2-year-old child with myelodysplastic syndrome associated with isolated monosomy 7 cytogenetic abnormality. Marrow is moderately to markedly hypocellular for age with increased fat and prominent interstitial cell depletion. Small megakaryocytes with hypolobulated nuclei are present

Figure 39.38 Bone marrow biopsy from an adult man with MDS with excess blasts-2 based on presence of 18% marrow blasts and myeloblasts with Auer rods. There is marked fibrosis with numerous megakaryocytes

Figure 39.39 Marrow Biopsy From an Adult With MDS With Excess Blasts-2. Marrow is hypercellular. There are occasional foci of immature myeloid cells in the central marrow in nonparatrabecular and nonperi- vascular locations (ALIP)

Figure 39.40 Marrow from a patient with MDS with single lineage dysplasia (refractory anemia) with marked erythroid hyperplasia and dyserythropoiesis. Several erythroid precursors with apoptotic nuclei are present

Figure 39.41 Marrow biopsy from an adult woman with de novo myelodysplastic syndrome associated with an isolated del(5q) (q21;q32) cytogenetic abnormality. There is an increase in megakaryocytes, many of which have hypolobulated nuclei. The majority of megakaryocytes are normal in size; small megakaryocytes are present

Figure 39.42 Portion of a myeloid sarcoma presenting as a subcutaneous chest wall mass in an elderly woman with a 1-year history of chronic myelomonocytic leukemia with less than 5% blasts in marrow and blood. The mass consists of a relatively uniform population of blasts; scattered mitotic figures are present. Numerous tingible body macrophages impart a "starry sky" appearance to the lesion. Many of the blasts reacted with antibody to myeloperoxidase and CD68 (KP1). Blood and marrow examination at the time of appearance of the chest wall mass was essentially unchanged from the previous year, with less than 5% blasts

Figure 39.43 Bone Marrow Biopsy From a Patient With Therapy- Related Myelodysplasia With Myelofibrosis. There is predominance of neutrophils and megakaryocytes. Megakaryocytes show marked dysplasia

Figure 39.44 Marrow Biopsy From a Patient in Accelerated Phase of Chronic Myeloid Leukemia. There is marked reticulin fibrosis and small clusters of blasts

Figure 39.45 Erythroblastic Crisis of Chronic Myeloid Leukemia. The marrow to the left of the bone trabecula shows the findings of treated chronic phase. The proliferation of primitive erythroblasts to the right of the bone represents a focus of blast transformation

Figure 39.46 High magnification of marrow biopsy from a patient with erythroblastic transformation of chronic myeloid leukemia. Cells are large with prominent nucleoli and basophilic cytoplasm

Figure 39.47 Hyperplastic Bone Marrow From a Patient With Polycythemia Vera. All cellular elements are increased. Megakaryocytes are prominent and show considerable variation in size; many are unusually large with hyperlobulated nuclei

Figure 39.48 Marrow Biopsy From a Patient in Spent Phase of Polycythemia Vera. Marrow is markedly hypercellular as a result of granulocytic and megakaryocytic hyperplasia. Megakaryocytes show dysplastic features

Figure 39.49 A, Marrow biopsy from a patient with essential thrombo- cythemia. Marrow is normocellular with numerous scattered large megakaryocytes. B, High magnification of specimen in A showing the very large megakaryocytes, some with hyperlobulated nuclei

Figure 39.50 A, Marrow biopsy from the prefibrotic stage of primary myelofibrosis. There is a cluster of megakaryocytes which vary in size. Several are large with marked variation in nucleocytoplasmic ratio. B, Bone marrow section from prefibrotic stage of primary myelofibrosis stained with antibody to CD61. This highlights the megakaryocytes, which vary in size from small to large. The nuclei show markedly abnormal chromatin clumping. (B, Contributed by Dr. J. Thiele, Cologne, Germany, and reproduced from Jaffe ES, Harris NL, Stein H, Vardiman JW, eds. World Health Organization Classification of Tumours: Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues. Lyon: IARC Press; 2001.)

Figure 39.51 Bone marrow biopsy from a patient with primary myelo- fibrosis showing prominent intrasinusoidal hematopoiesis. Predominant cells in the sinusoid are erythroid precursors and megakaryocytes

Figure 39.52 Trephine biopsy from an adult with a 7-year history of primary myelofibrosis (agnogenic myeloid metaplasia). There is extensive marrow fibrosis with marked reduction in hematopoietic tissue

Figure 39.53 Marrow biopsy from a patient with primary myelofibrosis shows extensive osteosclerosis and a cellular area composed predomi- nantly of blasts

Figure 39.54 A, Bone marrow biopsy from an adult man with a WBC count of 18.6 x 109/L with 86% eosinophils. The marrow is markedly hypercellular with a marked increase in mature eosinophils. B, Another area of the same biopsy showing an aggregate of intertwining mast cells, most of which are fusiform in shape. The mast cell infiltrate is partly juxtaposed to a bone trabecula. C, Mast cell tryptase of the lesion in B highlighting the mast cells. Genetic studies showed a deletion of CHIC2, a surrogate marker for PDGFRA/FIP1L1 fusion gene. The patient is in remission 3 years following initiation of therapy with imatinib. (Contributed by Dr. Curt Hanson, Rochester, MD.)

Figure 39.55 Radiograph of pelvis and upper femurs from a patient with systemic mastocytosis; both osteosclerotic and osteolytic changes are prominent

Figure 39.56 Lesion in Bone Marrow From a Patient With Systemic Mastocytosis and No Evidence of Urticaria Pigmentosa. A central focus of well-differentiated lymphocytes is surrounded by lighter-staining mast cells

Figure 39.57 High Magnification of a Marrow Lesion in Systemic Mastocytosis. The mast cells have a spindle appearance. There are numerous interspersed eosinophils

Figure 39.58 A, Marrow biopsy from an adult man with systemic mastocytosis associated with a myeloproliferative disorder and no evidence of urticaria pigmentosa. There is extensive paratrabecular fibrosis and widening of bone trabeculae. The intervening marrow is markedly hypercel- lular, principally due to myeloid hyperplasia. Radiographic studies showed diffuse osteoblastic changes. B, Mast cell tryptase stain of the lesion in A showing numerous reactive cells

Figure 39.59 A, Bone marrow biopsy from a patient with concurrent acute myeloid leukemia and systemic mastocytosis. Mast cell infiltration in this area of biopsy was associated with new bone formation. No other areas in bilateral biopsies show this finding. This was the patient's first marrow biopsy. B, Specimen in A reacted with antibody to mast cell tryptase. (B, Immunoperoxidase.)

Figure 39.60 A, Marrow biopsy from a patient with chronic lymphocytic leukemia (CLL) showing diffuse pattern of involvement. The small lym- phocytes completely replace normal marrow cells. B, Marrow biopsy from a patient with CLL with focal involvement. Leukemic cells occur in relatively well-demarcated foci, which are randomly distributed and surrounded by normal-appearing marrow. C, Marrow section from a patient with CLL illustrating an interstitial pattern of involvement; overall marrow architecture is preserved

Figure 39.61 A, Marrow biopsy from an adult woman with a 4-year history of untreated B-cell chronic lymphocytic leukemia. There are two morphologic populations of lymphocytes; the lower portion of the figure is predominantly small lymphocytes; the upper portion is predominantly prolymphocytoid lymphocytes and paraimmunoblasts. B, High magnifica- tion of the upper area of the specimen illustrating the prominent prolym- phocytoid lymphocytes and paraimmunoblasts with very prominent, usually single, nucleoli

Figure 39.62 A, Marrow biopsy illustrating a proliferation center in a patient with B-CLL. B, High magnification of the central portion of the proliferation center with prominent prolymphocytoid lymphocytes and paraimmunoblasts

Figure 39.63 Bone marrow trephine biopsy from a patient with a history of chronic lymphocytic leukemia who developed a pleomorphic lymphoma (B-immunoblastic lymphoma) and a clinical picture typical of Richter syndrome. Biopsy contains two distinct cell populations, small lymphocytes, and large pleomorphic cells, some of which are multinucleated

Figure 39.64 Marrow Biopsy From an Adult Man With a 9-Year History of B-CLL. The patient had recent onset of fever, night sweats, myalgia, and axillary, cervical, and inguinal adenopathy prior to this biopsy. A population of small lymphocytes is at lower left. Burkitt lymphoma cells predominate at upper right. Blood and marrow smears contained two lymphocyte populations: small well-differentiated lymphocytes and Burkitt lymphoma cells. Cytogenetic studies of the marrow specimen showed t(8;22)(q24;q11) cytogenetic abnormality

Figure 39.65 A, Bone marrow section from a patient with extensive replacement by hairy cell leukemia; scattered foci of normal hematopoiesis are present. B, High magnification of specimen in A. Hairy cells are loosely spaced, in contrast to aggregates of lymphocytes in chronic lymphocytic leukemia and small lymphocyte lymphoma. Hairy cells have a relatively abundant, lightly eosinophilic cytoplasm. Many of their nuclei are folded or irregular in outline. Nucleoli are inconspicuous and mitotic figures rare. The halo effect around nuclei, characteristic of formalin-fixed tissue, is not prominent in this specimen fixed with Zenker acetic acid

Figure 39.66 A, Marrow biopsy from a patient with the stromal variant of hairy cell leukemia. B, High magnification of the biopsy in A. Many leukemia cells are elongated or spindle shaped

Figure 39.67 Bone Marrow Biopsy From a Patient With Hairy Cell Leukemia Reacted With Antibody to CD20. Reactivity accentuates the leukemic infiltrate. Scattered normal myeloid cells, principally erythroid precursors, are present. (Immunoperoxidase.)

Figure 39.68 Hairy Cell Leukemia Variant. Several lymphoid cells in the blood smear of an adult man with markedly elevated leukocyte count. The hairy cell variant lymphocytes are large with a moderate amount of basophilic cytoplasm with stellate projections. The nuclei of several cells contain variably prominent nucleoli. (Wright-Giemsa.)

Figure 39.69 A, Lymphocytes in blood smear from an adult male with splenic marginal zone lymphoma (SMZL) with villous lymphocytes. The cytoplasm of two of the lymphocytes has small villous projections. Nuclear chromatin is coarse. There are distinct but not prominent nucleoli. B, Bone marrow biopsy from a patient with SMZL showing a paratrabecular, poorly demarcated aggregate of lymphocytes. C, High magnification of a lesion from a patient with SMZL showing a predominant population of small lymphocytes with scattered large cells with abundant cytoplasm and prominent nucleoli. (A, Wright-Giemsa.)

Figure 39.70 Bone Marrow Biopsy From a Patient With Splenic Marginal Zone Lymphoma Illustrating Two Well-Circumscribed Foci of Lymphocytes. The lesion on the left contains a central area suggesting remnants of a germinal center with several centroblast-like cells

Figure 39.71 Several Focal Aggregates of Lymphocytes in Marrow in a Patient With Small Lymphocytic Lymphoma. Foci of lymphocytes vary in size and have irregular, poorly circumscribed outlines

Figure 39.72 Bone marrow section from a patient with follicular lymphoma illustrating the prominent paratrabecular distribution of the infiltrate

Figure 39.73 Marrow from a patient with marrow involvement by follicular lymphoma with prominent paratrabecular involvement reacted with antibody to CD20. The infiltrate is accentuated by CD20 antibody. (Immunoperoxidase.)

Figure 39.74 Marrow Biopsy From a Patient With Follicular Lymphoma With Focal Paratrabecular and Nonparatrabecular Involvement. A few of the nonparatrabecular foci, as illustrated, recapitulate neoplastic follicles. Amorphous eosinophilic proteinaceous debris is deposited in the central portion of the lesion

Figure 39.75 Neoplastic Follicle in Marrow Reacted With Antibod- ies to CD21 and BCL2. The dendritic cells express CD21 and the lymphocytes express CD20. (Immunoperoxidase.) (Reproduced from Am J Clin Pathol. 2002 American Society for Clinical Pathology. Reprinted with permission.)

Figure 39.76 A, Bone marrow biopsy from an adult man with extensive blood and marrow involvement by mantle cell lymphoma. Lymphoma cells expressed pan-B-cell markers, CD5, and intense surface immuno- globulin. In some areas, lymphoma marginates along the bone trabecula. B, Focus of marrow involvement from the same biopsy showing structure with remnants of germinal center including dendritic histiocytes

Figure 39.77 High Magnification of a Marrow Biopsy From a Patient Being Treated for Follicular Lymphoma. There is an infiltration of the interstitium by a population of small lymphocytes, several of which have irregular and cleaved nuclei

Figure 39.78 A, Bone marrow biopsy from a patient with splenic marginal zone B-cell lymphoma showing a preferential intrasinusoidal localization of the lymphoma cells. B, The same specimen as A reacted with antibody to CD20 illustrating the preferential intrasinusoidal location of lymphoma cells. (B, Immunoperoxidase.)

Figure 39.79 Bone Marrow Section From a Patient With a 6-Year History of Follicular Lymphoma. Cells resembling Reed-Sternberg cells and mononuclear variants are present

Figure 39.80 A, Marrow from a patient with T-cell/histiocyte-rich B-cell lymphoma. Histiocytes predominate in this area. B, The specimen in A reacted with antibody to CD20. The numerous lymphocytes are reactive, contrasting with the negative histiocytes. C, The marrow biopsy in A reacted with antibody to CD68 (KP1). The numerous positively reacting histiocytes in this area contrast with the negatively reacting lymphoma cells. (B and C, Immunoperoxidase.)

Figure 39.81 Post-transplant B-Cell Lymphoma. A, The lymphoma cells extensively infiltrate the marrow interstitium in this area; some residual myelopoiesis is present. B, The same specimen as A reacted with antibody to CD20; large lymphoma cells are positive. C, Numerous lymphoma cells are positive for EBV. (B, Immunoperoxidase; C, EBER.)

Figure 39.82 Blood Smear From an Adult Man With Leukemic Mantle Cell Lymphoma. The lymphoma cells vary considerably in size, nuclear lobulation, and degree of chromatin clumping. The large cell with a prominent nucleolus resembles a prolymphocyte. The smear is from the same patient as the specimen illustrated in Fig. 39.76

Figure 39.83 A, Marrow section from a patient with partial involvement by peripheral T-cell lymphoma. The lymphoma population is poorly demarcated and infiltrates the interstitium with some preservation of normal architecture. B, Margin of the lesion in A reacted with antibody to CD3. Numerous large lymphocytes, some with prominent nucleoli, are positive. (B, Immunoperoxidase.)

Figure 39.84 Marrow biopsy from a patient with peripheral T-cell lym- phoma, showing extensive diffuse marrow involvement. The predominant cell population consists of small lymphocytes with a focus of large lymphocytes that have prominent nucleoli

Figure 39.85 Marrow Biopsy From a Patient With Adult T-Cell Leukemia and Hypercalcemia. Marked osteoclastic activity with bone resorption is present

Figure 39.86 A, Three Sézary cells in blood smear. The nucleus in the larger cell in the upper field has delicate folds imparting a "cerebriform" appearance. The two smaller cells in the lower field have a more condensed chromatin and markedly lobulated nuclei. B, Ultrastructure of a Sézary cell; extreme convolution of the nucleus is a characteristic feature. (B, Uranyl acetate-lead citrate; x22000.)

Figure 39.87 A, Bone marrow biopsy from an adult woman with large granulated T-cell lymphocytic leukemia. The leukemic lymphocytes are interspersed in the interstitium. B, Specimen in A reacted with antibody to CD8. There are numerous CD8-positive cells in the interstitium. (B, Immunoperoxidase.)

Figure 39.88 Bone marrow biopsy from a patient with lymph node diagnosis of angioimmunoblastic T-cell lymphoma. Marrow is diffusely involved by the process with a heterogeneous cell population

Figure 39.89 A, Area of marrow biopsy from a patient with anaplastic large cell lymphoma. The lymphoma cells are intermixed with normal marrow cells. B, Specimen in A reacted with antibody to CD30. The lymphoma cells are positive. (B, Immunoperoxidase.)

Figure 39.90 A, Lymphoma cell in blood smear from a 17-year-old male with small cell variant of anaplastic large cell lymphoma with associated t(2;5)(p23;p35). The cell has a convoluted nucleus. B, Bone marrow section from the same patient. The few lymphoma cells are scattered in the interstitium and difficult to recognize in this H&E stain. C, The same specimen as B reacted with antibody to CD30, which highlights the small and large lymphoma cells. (C, Immunoperoxidase.)

Figure 39.91 A, Bone marrow smear from a 17-year-old male with hepatosplenic gamma/delta T-cell lymphoma. The lymphoma cells vary in appearance and some have blast-like features. B, The marrow biopsy is markedly hypercellular, with extensive involvement and both an interstitial and intrasinusoidal pattern. C, Specimen in B reacted with anti-CD3 which highlights the intrasinusoidal pattern. (C, Immunoperoxidase.)

Figure 39.92 Post-Transplant T-Cell Lymphoma. A, Bone marrow smear from a 40-year-old woman, 28 and 8 years following renal transplantation. The lymphoma cells, which expressed CD2 and CD3, are large with abundant cytoplasm and very prominent nucleoli. B, High magnification of marrow section showing extensive interstitial involvement by noncohesive lymphoma cells. There is substantial depletion of normal hematopoiesis with cellular debris

Figure 39.93 Aggressive NK-Cell Leukemia. A, Bone marrow smear from a patient with aggressive NK-cell leukemia. The lymphoma cells have relatively abundant cytoplasm containing numerous coarse azurophilic granules; the lymphoma cells are distinguished from neutrophil myelocytes by the lack of specific granules. B, Marrow biopsy from the patient in A showing extensive replacement. The lymphoma cells are relatively uniform in appearance with round nuclei and abundant cytoplasm. (Slides contributed by Dr. John K.C. Chan, Hong Kong.)

Figure 39.94 Paratrabecular germinal center formation in marrow of a patient receiving interleukin-2 therapy for metastatic melanoma. Several vacuolated macrophages are present at the margin of the lesion

Figure 39.95 Post Rituximab Therapy. A, One of several paratrabecular and nonparatrabecular lymphocytic aggregates in bone marrow biopsy following rituximab therapy. B, Same specimen as A evaluated with antibody to CD20; the lymphocytes are nonreactive. Similar results were found with antibody to CD79a. C, Same specimen as A and B reacted with antibody to CD3. Most of the lymphocytes are intensely reactive. Similar results were found in other lymphocytic aggregates. (B and C, Immunoperoxidase.)

Figure 39.96 Bone marrow biopsy from a patient with mixed cellularity Hodgkin lymphoma. There is extensive involvement in this area of the biopsy

Figure 39.97 Marrow With Several Scattered Foci of Hodgkin Lymphoma. The lesions, which contain several Reed-Sternberg cells, are indistinctly demarcated from normal marrow

Figure 39.98 Two foci of Hodgkin lymphoma in a large area of necrotic debris in a post-treatment marrow specimen

Figure 39.99 A, Marrow biopsy from a patient with Hodgkin lymphoma. The marrow space is completely replaced by dense fibrous connective tissue. Numerous vascular structures and small foci of distorted cells resembling Reed-Sternberg cells and mononuclear variants are present. B, Same specimen as A showing several focal collections of cells that resemble distorted Reed-Sternberg cells and mononuclear variants

Figure 39.100 A, Marrow biopsy from an adult woman with marrow involvement by a histiocytic proliferation with an associated clonal t(9;11) (p21.3;q23.3) cytogenetic abnormality. The histiocytes have a somewhat bland appearance with abundant cytoplasm. B, The biopsy in A reacted with antibody to CD68 (KP1). C, Smear from the specimen in A and B showing several histiocytes, most of which have lobulated nuclei and abundant cytoplasm. (B, Immunoperoxidase.)

Figure 39.101 Marrow biopsy from an adult man who developed hemophagocytic syndrome associated with bacterial infection. Numerous histiocytes, some showing hemophagocytosis, are present in sinusoids and interstitium

Figure 39.102 Bone marrow smear from a lupus erythematosus patient with virus-associated hemophagocytic syndrome. Numerous macrophages with ingested red blood cells and erythroblasts are present. (Wright-Giemsa.)

Figure 39.103 A, Marrow biopsy from a child with Langerhans cell histiocytosis showing extensive replacement. B, High magnification of the lesion in A showing giant cells and several histiocytes. Some residual myeloid cells are present. C, Bone marrow smear from the case illustrated in A and B. The Langerhans cells are very large with abundant cytoplasm; several histiocytes contain nonspecific debris and occasionally red blood cells

Figure 39.104 A, Marrow biopsy from a patient with plasma cell myeloma with extensive diffuse replacement by myeloma cells. B, Marrow biopsy with a large focus of myeloma cells. C, Marrow biopsy showing essentially normal marrow architecture and interstitial infiltration by myeloma cells

Figure 39.105 A, Marrow from a patient with anaplastic myeloma; many of the plasma cells are large with lobulated nuclei. B, Specimen in A reacted with antibody to lambda light chains. The plasma cells show intense cytoplasmic reactivity. Numerous nonreactive residual myeloid cells are present. (B, Immunoperoxidase.)

Figure 39.106 Marrow biopsy from a 63-year-old patient with plasma cell myeloma with hypogammaglobulinemia and kappa light chain Bence Jones proteinuria. The cytoplasm of myeloma cells is distended by numerous, frequently confluent eosinophilic inclusions

Figure 39.107 Marrow biopsy from a patient with plasma cell myeloma and marked reticulin fibrosis

Figure 39.108 Blood smear from a 47-year-old woman with leukocytosis of 24.0 x 109/L and 90% plasma cells. Many of the plasma cells have "lymphoid" features. There was a serum IgG kappa monoclonal protein. (Wright-Giemsa.) (Reproduced from Brunning RD, McKenna RW. Tumors of the Hematopoietic System. Atlas of Tumor Pathology, series 3, fascicle 9. Washington, DC: Armed Forces Institute of Pathology; 1994.)

Figure 39.109 A, An osteosclerotic bone lesion from a patient with osteosclerotic myeloma. B, High magnification of the marrow in the specimen in A. This area shows a large number of plasma cells that were lambda light chain restricted on immunohistochemical study. C, Marrow biopsy from a nonsclerotic area from a patient with osteo- sclerotic myeloma with POEMS syndrome. There was a thrombocytosis. The marrow in this area shows an infiltration by immature plasma cells. There was also an increase in large megakaryocytes, two of which are at right

Figure 39.110 A, Extramedullary plasmacytoma from the region of the nasopharynx. B, Plasmacytoma reacted with antibody to kappa light chains. The plasma cells show intense cytoplasmic reactivity. (B, Immunoperoxidase.)

Figure 39.111 Marrow From a Patient With Lymphoplasmacytic Lymphoma and Associated IgM Gammopathy. The predominant lymphocytes have nuclei with very clumped chromatin and a slight to moderate amount of cytoplasm. Some lymphocytes contain small cytoplasmic and intranuclear inclusions. There is an increase of tissue mast cells

Figure 39.112 A, Marrow section from a patient with lymphoplasmacytic lymphoma associated with serum IgM monoclonal gammopathy. Marrow is replaced by an infiltrate of lymphocytes and plasma cells; many of the plasma cells contain numerous cytoplasmic inclusions. Some lymphocytes contain prominent intranuclear inclusions (Dutcher bodies). B, Specimen illustrated in A reacted with PAS stain. Inclusions in plasma cells are strongly positive

Figure 39.113 Marrow with amyloid accumulation from a 50-year-old woman with primary amyloidosis

Figure 39.114 Proteinaceous Myelopathy. A, Marrow biopsy from a 25-year-old woman with a 10-year history of lupus erythematosus. There is extensive intercellular accumulation of an amorphous eosinophilic substance resembling amyloid but lacking the histochemical and ultra- structural findings of amyloid. There is an associated proliferation of plasma cells and small lymphocytes. The plasma cells consisted of both kappa and lambda light chain positive populations. B, High magnification of the specimen in A. C, Ultrastructure of the intracellular and extracellular material. There was complete regression of the finding following high dose steroid and vinblastine therapy

Figure 39.115 A, Marrow biopsy from a 28-year-old woman with an autoimmune disorder characterized by extensive infiltration of marrow by plasma cells, lymphocytes, and immunoblasts. B and C, Specimen in A demonstrated balanced reactivity for kappa (B)- and lambda (C)- reacting cells. (B and C Immunoperoxidase.)

Figure 39.116 Marrow biopsy from a child with metastatic neuroblastoma. Several foci of tumor are present

Figure 39.117 A, Low (left) and high (right) magnification of a marrow biopsy from a child with metastatic neuroblastoma with small focal lesions. B, Specimen reacted with antibody to neuron-specific enolase. Small clusters of reactive cells are present. This was the only involved area in the biopsy. (B, Immunoperoxidase.)

Figure 39.118 Marrow from a patient with metastatic carcinoma of breast with osteosclerotic reaction and foci of tumor cells

Figure 39.119 Marrow biopsy from a patient with metastatic carcinoma of prostate with a marked osteoblastic lesion

Figure 39.120 A, Bone marrow biopsy from a 17-year-old male with partial replacement of marrow by a pleomorphic population of cells, some of which are large with very abundant cytoplasm. Larger cells have one or two nuclei with distinct and frequently prominent nucleoli. The majority of the cells reacted with antibodies to actin (B) and desmin; chromosome studies of the cells showed a t(2;13)(q35;q14) abnormality, a characteristic cytogenetic finding in alveolar rhabdomyosarcoma

Figure 39.121 A, Marrow biopsy from a child with metastatic neuro- blastoma with ganglion differentiation. B, High magnification of the specimen in A showing marked variability in size of the tumor cells. In contrast to megakaryocytes, some tumor cells contain single, very prominent, nuclei. (See Fig. 39.10, which is the same specimen reacted with antibody to neuron-specific enolase.)

Figure 39.122 Bone marrow section from an adult with type I chronic non-neuronopathic Gaucher disease. The cytoplasm of many Gaucher cells has a fibrillary or granular appearance. Nuclei are small and usually eccentric in location

Figure 39.123 Biopsy From a 14-Month-Old Child With Niemann-Pick Disease. Focal accumulations of foam cells are present. The cytoplasm of the foam cells is clear, with the suggestion of numerous confluent vacuoles

Figure 39.124 A, Marrow biopsy 4 days post allogeneic marrow transplantation for blast crisis of chronic myeloid leukemia. The marrow is markedly hypocellular with scattered cells and abundant interstitial proteinaceous debris. B, Marrow biopsy from the patient illustrated in A 28 days post transplant. Evidence of engraftment is characterized principally by erythroid precursors at a late stage of maturation and foci of more immature forms. There was no evidence of a t(9;22) cytogenetic abnormality in either biopsy

Figure 39.125 Marrow biopsy from a 7-year-old child 14 days post allogeneic bone marrow transplantation for aplastic anemia. The marrow is moderately to markedly hypocellular. Subsequent biopsies showed failure of engraftment

Figure 39.126 Marrow from an adult man 18 days post unrelated marrow transplantation for acute myeloid leukemia. The marrow is markedly hypocellular with scattered clusters of normal-appearing megakaryocytes; there is no evidence of leukemia

Figure 39.127 Marrow from an adult woman 21 days post autologous marrow transplantation for chronic myeloid leukemia illustrating a focus of erythroid precursors at an early stage of maturation in an overall hypocellular marrow. Erythroid precursors at a late stage of maturation are located in the surrounding interstitium; there are several normal- appearing megakaryocytes

Figure 39.128 Marrow biopsy 20 days post allogeneic sibling transplanta- tion for chronic myeloid leukemia; 3 days prior to the biopsy the patient received granulocyte colony-stimulating factor for marked neutropenia. The cells in the interstitium are neutrophil precursors at the promyelo- cyte-myelocyte stage of maturation, a characteristic early effect of growth factor stimulation

Figure 39.129 Marrow biopsy from an 11-year-old child 100 days following unrelated donor marrow transplantation for chronic myeloid leukemia. The marrow is moderately to markedly hypocellular with erythroid and granulocyte precursors and only rare megakaryocytes

Figure 39.130 Marrow biopsy from an adult 8 months following autologous marrow transplantation for chronic myeloid leukemia. The marrow is markedly hypocellular with markedly decreased granulocytes and megakaryocytes. The interstitium is markedly depleted with principally late-stage erythroid precursors

Figure 39.131 A, Marrow biopsy with marked osteosclerosis from a 32-year-old patient with Philadelphia chromosome-positive chronic myeloid leukemia immediately prior to marrow transplantation. B, Marrow biopsy from the patient illustrated in A 5 months post allogeneic marrow transplantation. There is complete resolution of the osteosclerosis. The cytogenetics from this specimen were normal