Sézary’s syndrome, buffy coat preparation. The nuclear pleomorphism and convolutions are prominent with many cells showing the frank cerebriform appearance of Sézary cells.


Marginal zone lymphoma (?), peripheral blood. This 75-year-old man had slight splenomegaly, no lymphadenopathy, and a history of increasing lymphocytosis over the prior 4 years. The Hb was 8.0 g/dL, WBC 45 ´ 109/L, and platelets 183 ´ 199/L. The lymphocytes were C19+, CD20+, CD22+, CD5-, CD11c weakly positive, CD25-, and light chain restricted.


CLL with Richter’s transformation, peripheral blood. This 47-year-old male presented with an abdominal mass and hepatosplenomegaly. There are a mixture of small cells with clumped nuclear chromatin and scanty cytoplasm, and large cells with fine nuclear chromatin and more abundant basophilic cytoplasm. Immunophenotype showed a marker profile typical of CLL: dim surface immunoglobulin, positive for CD5 and CD23, negative for FMC7 and CD22. Cytogenetic analysis revealed a complex karyotype.


Circulating follicular NHL lymphoma cells. This is a peripheral blood smear from a patient with follicular lymphoma showing three lymphoma cells and a normal large granular lymphocyte. The last, in the center of the field, has abundant clear cytoplasm and fine granules. The three follicular lymphoma cells have deep clefts, small size (slightly larger than erythrocytes), and a homogeneously stained nuclear chromatin without nucleoli. This appearance differs from that of a CLL cell. These cells also have a lack of visible cytoplasm.


Mantle cell lymphoma, peripheral blood. The picture is pleomorphic with a predominant medium sized lymphoid population having nuclei with dense but not clumped chromatin, occasional nuclear clefts, and a single small nucleoli. Immunophenotype showed a clonal B-cell population with strong expression of surface immunoglobulins and membrane CD22. The cells were positive for FMC7 and CD5, and negative for CD23. This profile differs from B-cell chronic lymphocytic leukemia, which typically shows dim surface immunoglobulin and CD23 positivity. Cytogenetic analysis revealed a t(11:14)(q13;q32), and spleen histology showed diffuse involvement by medium size lymphocytes with a cleaved nucleus, confirming the diagnosis of mantle-cell lymphoma in this 66-yearold man.


Waldenström’s macroglobulinemia, peripheral blood. There are abundant plasmacytoid lymphocytes and a suggestion of rouleaux formation.


Post-transplant B cell lymphoma, peripheral blood. This 38-year-old man was 156 days post unrelated donor bone marrow transplant for chronic myeloid leukemia and was being treated with cyclosporin A. Immunophenotyping of the plasmacytic-lymphocytic cells in the blood showed an IgG kappa light chain restricted population. Molecular studies revealed immunoglobulin heavy chain gene rearrangement. The patient expired two days later.


Anaplastic large cell non-Hodgkin’s lymphoma. Peripheral blood film from a 52-year-old man with large-cell lymphoma evolving into leukemia. The cells are large (>3 times the size of a red blood cell) and have reticular chromatin, deeply basophilic cytoplasm, and one to three nucleoli. The mature B lymphoid nature of the cells was confirmed by immunological analysis that showed a clonal B cell population positive for kappa, CD19, and FMC7 and negative for lambda, CD5, CD23, and CD2.


Splenic lymphoma with circulating villous lymphocytes (SLVL). There are four lymphoid cells of medium to small size, with condensed nuclear chromatin, nucleolus, basophilic cytoplasm, and irregular projections at the end of the cell. The differential diagnosis includes HCL and HCL variant. The SLVL cells have a higher nuclear to cytoplasmic ratio and are smaller in size. In contrast to CLL, SLVL cells have irregular and slightly more abundant cytoplasm. Compared to B-PLL, SLVL cells have more condensed chromatin and prominent villi. (Mulligan and Catovsky, Leukemia and Lymphoma 6:97, 1992)


This composite view shows B chronic lymphocytic leukemia on the left and T chronic lymphocytic leukemia on the right, peripheral blood. In this instance one cannot discern a great deal of difference between the lymphocytes. However, two destroyed cells, characteristic of B cell CLL, are seen on the left.


Hairy cell leukemia. The cytoplasmic strands and the very reticular appearance of the nuclear chromatin are characteristic.


Hairy cell leukemia, variant (HCL-V), peripheral blood. Cells are medium to large in size and have an abundant villous cytoplasm and a prominent single nucleolus. Thus, the nuclear features are similar to those of prolymphocytes while the cytoplasm resembles that of hairy cells. (Sainati et al. Blood 76:157, 1990). The patient presented with splenomegaly and a high white cell count, and was not monocytopenic. Immunological markers demonstrated the B-cell nature of the cells with light chain restriction (lambda+, kappa-), CD19+, FMC7+ with strong expression of CD11c and CD103 (two markers positive in typical HCL). However, the cells did not express two other typical hairy cell antigens, CD25 and HC2. The differential diagnosis includes typical HCL, prolymphocytic leukemia and splenic lymphoma with villous lymphocytes. Cell morphology and immunological markers are useful to distinguish between typical HCL and its variant form while morphology and histology helps to distinguish HCL variant from the splenic lymphoma with villous lymphocytes and prolymphocytic leukemia.

B cell chronic lymphocytic leukemia with more than 10% prolymphocytes, CLL/PL. (See Noell et al. Br J Haematol 63:377, 1986.) Typically, this abnormality shows two cell populations. There is one large population of small CLL lymphocytes. The second, smaller population is of large, nucleolated prolymphocytes. In this case, the latter are represented by a large cell with two nucleoli, which almost resembles a blast. Also, note some smudges in the photograph and the typical nuclear chromatin pattern of the CLL lymphocytes.


Burkitt’s lymphoma. Composite: bone marrow biopsy (L) and bone marrow aspirate (R). This 19- year-old male presented with a submandibular tumor in 1997. A biopsy revealed non-Hodgkin’s lymphoma, Burkitt’s type, according to the REAL classification. Staging revealed stage I disease. He was treated with aggressive polychemotherapy for Burkitt’s lymphoma and an allogeneic bone marrow transplant was planned for March 1998. Two weeks before BMT, the patient complained of back pain, and there was a sharp rise of LDH. A bone marrow smear and biopsy revealed massive infiltration by Burkitt lymphoma blasts. Few tumor cells were seen in the blood smear. The slide (R) shows typical Burkitt’s lymphoma with vacuolated cytoplasm (ALL-L3 blasts according to the FAB classification). The bone marrow biopsy (L) also shows the typical, leukemia type, interstitial infiltration, leaving the fat cells intact.


Chronic lymphocytic and acute myeloblastic leukemia, simultaneously at presentation, bone marrow aspirate. This 75-year-old man, presenting with enlarged lymph nodes and hepatosplenomegaly, had been desperately ill for several days with severe anemia, thrombocytopenia and spontaneous tumor lysis. Bone marrow smears show a mixture of small cells with clumped nuclear chromatin and scanty cytoplasm, and larger cells with finely dispersed nuclear chromatin and basophilic cytoplasm with vacuolization. A presumed diagnosis of CLL with Richter’s transformation was made. Immunophenotype of the small cells confirmed the CLL population (dim surface immunoglobulin, positive for CD5, CD 19 and CD23 and negative for FMC7 and CD22). However, immunophenotype of the larger blast cells could not confirm a lymphoid origin. The large cells were negative for lymphoid markers and, surprisingly, were positive for HLA-DR, CD33, CD15 and cytoplasmic myeloperoxidase (cyMPO), compatible with blast cells of myeloid origin.



T cell large granular lymphocyte leukemia (T-LGL). Peripheral blood smear shows typical LGLs with intracytoplasmic granules. Photo courtesy of Bruce Cheson, MD.


Plasma cell leukemia, peripheral blood. Five neoplastic plasma cells are seen, one of which is binucleate. Slight rouleaux formation of some red blood cells are seen.


Multiple myeloma, bone marrow aspirate. Virtually every cell in the field is a neoplastic plasma cell. They show nuclear eccentricity, pleomorphism, and a tendency to stick together in clumps.


Multiple myeloma, bone marrow aspirate. The marrow has been completely replaced by abnormal plasma cells. A binucleate plasma cell is seen in the center of the field.


Multiple myeloma, bone marrow aspirate. The cytoplasmic periphery of these cells has a much more intense pink stain, therefore the names flaming myeloma cells or flaming plasma cells.


Multiple myeloma, bone marrow aspirate. There are binucleate myeloma cells with granules. This patient had a chronic reactive plasmacytosis and adult Fanconi syndrome for many years prior to having dissemination of the myeloma. The needle-like cytoplasmic inclusions in the plasma cells were also found in the renal tubular cells.


Multiple myeloma, bone marrow biopsy, Giemsa stain. There is complete replacement of the normal marrow by neoplastic plasma cells. These again are recognized primarily by their nuclear eccentricity.