27. Acute lymphoblastic leukemia/lymphoma

B cursor ALL WBC 92.4 x 109/L (RI 6-17.5) - Abnormal cells – 86% PLT 18 x 109/L (RI 150-440)

Cytochemical stains on bone marrow smears in a patient with ALL Cytochemical stains on bone marrow smears in a patient with ALL. A, PAS stain demonstrates PAS+ cytoplasmic granules in blast cells (dark purple black dots). B, Oil red O stain is positive in cytoplasmic vacuoles of Burkitt type ALL. B-ALL immunohistochemical demonstration of nuclear TdT in a bone marrow biopsy

FAB Classification L1 (A), L2 (B), and L3 (C) immunoblasts

B-ALL FIGURE 1 A, Acute lymphoblastic leukemia/lymphoma. Lymphoblasts with condensed nuclear chromatin, small nucleoli, and scant agranular cytoplasm. B and C represent the phenotype of the ALL shown in A, analyzed by flow cytometry. B, Note that the lymphoblasts represented by the red dots express terminal deoxynucleotidyl-transferase (TdT) and the B-cell marker CD22. C, The same cells are positive for two other markers, CD10 and CD19, commonly expressed on pre-B lymphoblasts. Thus, this is a B-ALL

Burkitt Lymphoma FIGURE 2  Burkitt lymphoma. A, At low power, numerous pale tingible body macrophages are evident, producing a “starry sky” appearance. B, At high power, tumor cells have multiple small nucleoli and high mitotic index. The lack of significant variation in nuclear shape and size lends a monotonous appearance

28. Chronic lymphocytic leukemia and small lymphocytic lymphoma

B-cell CLL/SLL RBC 4.02 x 1012/L WBC 51.3 x 109/L (RI 4.5-11) Neutrophils 10 % (RI 40-70) Lymphocytes 89 % (RI 22-44) Monocytes 1 % (RI 4-11) Most of the lymphocytes are small and mature appearing with clumped chromatin and a high nuclear to cytoplasmic ratio

Small lymphocytic lymphoma/chronic lymphocytic leukemia (lymph node) Small lymphocytic lymphoma/chronic lymphocytic leukemia (lymph node). A, Low-power view shows diffuse effacement of nodal architecture and vague pseudofollicles. B, At high power the majority of the tumor cells are small round lymphocytes. A “prolymphocyte,” a larger cell with a centrally placed nucleolus, is also present in this field (arrow)

Small lymphocytic lymphoma/chronic lymphocytic leukemia involving the liver. Low-power view of a typical periportal lymphocytic infiltrate. Chronic lymphocytic leukemia: This peripheral blood smear is flooded with small lymphocytes with condensed chromatin and scant cytoplasm. A characteristic finding is the presence of disrupted tumor cells (smudge cells). A coexistent autoimmune hemolytic anemia explains the presence of spherocytes (hyperchromatic, round erythrocytes). A nucleated erythroid cell is present in the lower left-hand corner of the field. In this setting, circulating nucleated red cells could stem from premature release of progenitors in the face of severe anemia, marrow infiltration by tumor (leukoerythroblastosis), or both. Lymph node from a patient with chronic lymphocytic leukemia (B-cell CLL) undergoing Richter transformation. The monotonous infiltrate of small lymphocytes on the left side, representing the pre-existing B-cell CLL, contrasts with the large B-cells on the right, representing transformation to a diffuse large B-cell lymphoma.

29. Acute myelogenous leukemia

AML, FAB M1 Bone Marrow Biopsy: - Aspirate – 93.6% blasts - Sections – hypercellular The abnormal cells are medium-sized blasts. The nuclei are often irregular in shape, and some have invaginations or deep clefts. Most have a fine chromatin pattern and one or more prominent nucleoli. The cytoplasm is basophilic, and thin Auer rods are seen

Immunophenotypic studies The cytochemical staines used routinely for diagnosis and classification of AMLs are myeloperoxidase (MPO, A) and Sudan black B (SBB, B) in granulocytic precursors; alpha naphthyl or butyrate esterase (nonspecific esterase, NSE, C) in monocytic precursors; and chloroacetate esterase (CAE, D) in a segmented and band granulocytes:

AML vs ALL

AML Subtypes Acute myeloid leukemia subtypes. A, Acute promyelocytic leukemia with the t(15;17) (FAB M3 subtype). Bone marrow aspirate shows neoplastic promyelocytes with abnormally coarse and numerous azurophilic granules. Other characteristic findings include the presence of several cells with bilobed nuclei and a cell in the center of the field that contains multiple needle-like Auer rods. B, Acute myeloid leukemia with monocytic differentiation (FAB M5b subtype). Peripheral smear shows one monoblast and five promonocytes with folded nuclear membranes.

Auer rods in myeloblasts The arrows on row C

AML-M0 AML-M0: Minimally differentiated AML. Bone marrow smear shows sheets of blasts with scanty, nongranular cytoplasm. The blast cells were myeloperoxidase negative, but expressed CD13 and 33 by flow cytometry.

AML-M1 AML-M1: AML without maturation. Bone marrow biopsy section (left) shows increased blasts and scattered plasma cells. Bone marrow smear (middle) shows myeloblasts and a few promyelocytes. Myeloperoxidase stain (right) shows scattered positive immature cells (arrow).

AML-M2 AML-M2: AML with maturation. Bone marrow smear (left) shows myeloid preponderance with left shift and increased blasts. Some have convoluted nuclei and appear monocytoid, however they were positive for sudan black B (right) and myeloperoxidase, and expressed CD 13 and 33 while negative for monocytic markers.

AML-M3 AML-M3: Acute promyelocytic leukemia. Bone marrow biopsy section (images on the left) show hypercellular marrow and sheets of immature cells with abundant granular cytoplasm and prominent nucleoli. Bone marrow smear (right) shows promyelocytes with bundles of Auer rods (faggot cells).

AML-M4 AML-M4: Acute myelomonocytic leukemia. Bone marrow smear (top) shows increased blasts, some with convoluted nuclei and occasional promonocytes. Cytochemical stains (bottom) show a mixture of myeloperoxidase positive (left image) and nonspecific esterase positive (middle image) immature cells. Flow cytometry results of bone marrow aspirate (bottom right two histograms) showed leukemia cells expressed CD14, 33, and 64.

AML-M5 AML-M5b: Acute monoblastic leukemia with monocytic differentiation. Bone marrow biopsy section (left) shows increased blasts and immature monocytic cells, many with nuclear folding and convolutions, and an immunohistochemical stain (middle) shows sheets of CD68 positive cells. Blood smear (right) shows several promonocytes and one blast cell. In AML-M4 and –M5 the monocytic component of the peripheral blood often appears more mature than the bone marrow. AML-M5a: Acute monoblastic leukemia with minimal monocytic differentiation. Bone marrow smear (left) shows sheets of blast cells with abundant cytoplasm, round nuclei and prominent nucleoli with minimal differentiation. Nonspecific esterase stain (right) of the bone marrow smear shows numerous positive cells.

AML-M6 AML-M6: Erythroid leukemia. Bone marrow biopsy section (left) shows increased cellularity and blasts. Bone marrow smear (middle and right) show a mixture of myeloblasts and early erythroid precursors with a reversed M:E ratio (normally 2-3:1).

AML-M7 AML-M7: Megakaryoblastic leukemia. Bone marrow biopsy section (left) shows aggregates of blast cells. Blood smear (middle) shows several blasts with cytoplasmic budding. Flow cytometric analysis (right) shows leukemia cells that express CD33, 34, 61(tope left image shows two populations, one CD61+ and one CD61-), and HLA-DR.

30. Chronic myelogenous leukemia

CML Two left images: Marked hypercellularity with an elevated M:E ratio and progressive myeloid maturation. Peripheral blood smear on the right shows granulocytosis with a shift to the left. Hypercellularity with numerous megakaryocytes and marked myeloid preponderance. Granulocytosis with a shift to the left, and mature stages and precursors all within normal morphologic limits

31. Plasma cell neoplasms

Multiple Myeloma Bone Marrow biopsy: The plasma cells show variable morphology. Many have a normal appearance, but immature forms with prominent nucleoli are also present. Multinucleated plasma cells and occasional very large forms are noted. Peripheral Blood Smear – normal

Multiple Myeloma Multiple myeloma of the skull (radiograph, lateral view). The sharply punched-out bone lesions are most obvious in the calvarium. A bone marrow biopsy of a patient with multiple myeloma shows clusters of plasma cell (A, H&E stain), that are positive for CDE138 by immunohistochemistry (B) and shows light chain restriction (C and D) with demonstration of kappa chains without detectable lambda chains.

Bone marrow biopsy of a patient with multiple myeloma (left, Giemsa stain) shows an interstitial infiltrate of immature plasma cells with eccentrically placed nuclei, vesicular nuclei, prominent central nucleoli with sparse other normal hematopoietic elements. Bone marrow aspirate of the patient (right, Wright-Giemsa stain) shows increased immature plasma cells with occasional abnormally large plasma cells. Multiple myeloma (bone marrow aspirate): Normal marrow cells are largely replaced by plasma cells, including forms with multiple nuclei, prominent nucleoli, and cytoplasmic droplets containing Ig (Mott cells).

The globular inclusions are referred to as Dutcher bodies (if nuclear) or Russell bodies (if cytoplasmic). A Russell body refers to a large spherical inclusion displacing the nucleus. Mott cells are plasma cells characterized by an accumulation of multiple Russell bodies. Rouleaux formation of RBC in a peripheral blood smear (arrow)

32. Hodgkin Lymphoma

Hodgkins Reed-Sternberg cells and variants. A, Diagnostic Reed-Sternberg cell, with two nuclear lobes, large inclusion-like nucleoli, and abundant cytoplasm, surrounded by lymphocytes, macrophages, and an eosinophil. B, Reed-Sternberg cell, mononuclear variant. C, Reed-Sternberg cell, lacunar variant. This variant has a folded or multilobated nucleus and lies within an open space, which is an artifact created by disruption of the cytoplasm during tissue sectioning. D, Reed-Sternberg cell, lymphohistiocytic variant. Several such variants with multiply infolded nuclear membranes, small nucleoli, fine chromatin, and abundant pale cytoplasm are present. Chest X-ray in a patient with Hodgkin’s disease - showing enlarged mediastinal lymph nodes

Nodular Sclerosis Hodgkin’s Nodular sclerosis Hodgkin’s disease:  On gross examination, white fibrous bands divide the lymph node into tan-yellow nodules. A low-power view of an H&E stained section shows well-defined bands of pink, acellular collagen that subdivide the tumor into nodules.

Mixed Cellularity Hodgkins

Lymphocyte predominance Hodgkin Hodgkin lymphoma, lymphocyte predominance type. Numerous mature-looking lymphocytes surround scattered, large, pale-staining lymphohistiocytic variants (“popcorn” cells).

33. Follicular lymphoma and Burkitt lymphoma

Follicular lymphoma Bone marrow involvement occurs in 85% of cases and characteristically takes the form of paratrabecular lymphoid aggregates:

Follicular lymphoma (spleen gross image): Prominent nodules represent white pulp follicles expanded by follicular lymphoma cells. Other indolent B-cell lymphomas (small lymphocytic lymphoma, mantle cell lymphoma, marginal zone lymphoma) can produce an identical pattern of involvement. BCL2 expression in reactive and neoplastic follicles: BCL2 protein was detected by using an immunohistochemical technique that produces a brown stain. In reactive follicles (A), BCL2 is present in mantle zone cells but not follicular-center B cells, whereas follicular lymphoma cells (B) show strong BCL2 staining.

Burkitt lymphoma Burkitt lymphoma. A, At low power, numerous pale tingible body macrophages are evident, producing a “starry sky” appearance. B, At high power, tumor cells have multiple small nucleoli and high mitotic index. The lack of significant variation in nuclear shape and size lends a monotonous appearance. The abnormal cells are medium sized with rounded to slightly irregular nuclei, condensed chromatin, and one or two distinct nucleoli. There is a moderate amount of deeply basophilic cytoplasm. Some cells contain prominent vacuoles, which at times overlay the nucleus.