Case 3 Ann T. Moriarty,MD
Case 3 59 year old male with asymptomatic cervical lymphadenopathy. These images are from a fine needle biopsy of a left cervical lymph node. Image 1 Papanicolaou Stained smear,100x.
Case 3 Image 2: Wright-Giemsa stained smear, 100x.
Case 3 What is your morphologic differential diagnosis?
Compare the lymphocytes to the histiocyte nucleus (Arrow). Most of the lymphocytes are small, with coarse chromatin, without prominent nucleoli. Image 3
The lymphocytes look larger in air-dried preparations than in ethanol fixed preparations. They also appear more monotonous and have slightly more cytoplasm than normal appearing small lymphocytes (arrow). Image 4
Morphologic Differential The morphologic diagnosis should include the lymphomas with small nuclear size. Small lymphocytic lymphoma Follicular lymphoma, Grade I Mantle cell lymphoma Lymphoplasmacytic lymphoma Nodal marginal zone lymphoma
Case 3 What additional information do you need?
Flow Cytometry Histograms of Case 3 A B C D Image 5: The cells are small in forward scatter versus side scatter display(a), brightly positive for CD45 in the CD45 versus side scatter display(b). There is coexpression of CD19 (B cell lineage) and CD5 (T cell marker) in C at arrow. No CD23 expression is seen in D.
Flow Cytometry Histograms of Case 3 A B C Image 6: No CD10 was identified (A). CD20 is brightly fluorescent as shown by increasing log intensity in B (arrow). There was strong kappa light chain expression (bright fluorescent intensity) in C.
Immunologic Differential The immunologic differential diagnosis for CD5 and CD19 coexpression includes: Small lymphocytic lymphoma Mantle cell lymphoma
Case 3 What is your Diagnosis?
Differential diagnosis Small lymphocytic lymphoma Compare the cells of small lymphocytic lymphoma seen in the next image with our unknown case. The cells are small as compared to the nucleus of a histiocyte. The chromatin of chronic lymphocytic leukemia is coarse and regularly dispersed in a soccer ball pattern. Early descriptions of these cells by French investigators referred to this pattern as grumlé or clotted chromatin.
Small lymphocytic lymphoma Image 7: Papanicolaou stained smear, 100x. Compare these cells to the histiocyte nucleus (arrow). They are small with coarse chromatin which has been called clotted chromatin.
Differential diagnosis Small lymphocytic lymphoma The immunophenotyping of chronic lymphocytic leukemia or small lymphocytic B cell lymphoma is seen in this image. CD19 and CD5 are both expressed on the cell surface (arrow in A). CD23 is expressed dimly in B. A B Image 8
Differential diagnosis Small lymphocytic lymphoma There is weak fluorescent intensity of CD20 characterized as a shift of fluorescence that overlaps the baseline in A (arrow). Lambda chain expression is also of weak or low fluorescent intensity at arrow in B. A B Image 9
Differential diagnosis Follicular lymphoma, Grade I Follicular lymphoma, grade I, has been variably called small cleaved cell lymphoma and poorly differentiated lymphocytic lymphoma in older classification schemes. Follicular lymphomas arise from cells that are similar to those found within follicles or germinal centers. Cytologic grade I refers to the small cell size and coarse chromatin found in the majority of the cells of the follicle. Grade II follicular lymphoma (WHO) or Grade II or III follicular lymphoma (REAL) refers to those follicular lymphomas with greater numbers of centroblastic cells. The cells of Grade I follicular lymphoma are smaller than histiocyte nuclei, appear more variable than chronic lymphocytic leukemia and have coarse chromatin. Nuclear irregularities are seen in histologic sections, but may not be as obvious cytologically.
Follicular lymphoma, Grade I Follicular lymphoma, Grade I Image 10: Papanicolaou Stained smear, 100x. These cells are slightly more variable. There is coarse chromatin and nuclear irregularity. The cells are still smaller than histiocyte nuclei (arrow).
Differential diagnosis Follicular lymphoma, Grade I Follicular lymphoma expresses bright CD20(A), CD10(B), and intense light chain fluorescence (C). It does not express CD5 as does small lymphocytic lymphoma or mantle cell lymphoma. A B C Image 11
Differential diagnosis Lymphoplasmacytic lymphoma Lymphoplasmacytic lymphoma is also a small lymphoma. It is the lymphoma most often associated with the clinical syndrome of Waldenström s Macroglobulinemia. The cells are small with eccentric cytoplasm and nuclear features which may closely resemble plasma cells. Image 12: Wright stained smear, 100x.
Differential diagnosis Lymphoplasmacytic lymphoma The flow cytometric findings are variable. However, while lymphoplasmacytoid lymphomas express CD19 and CD20. They do not coexpress CD5 and lack CD10. They often contain cytoplasmic immunoglobulins which can be seen with immunocytochemical stains. Image 13
Image 14: Marginal zone lymphoma is composed of small cells with a variable appearance. Cells range from small cleaved type cells to cells with more abundant cytoplasm Papanicolaou stain, 100x Differential diagnosis Marginal Zone lymphoma Image 15: Marginal zone lymphoma. Some cells have a monocytoid appearance with more abundant cytoplasm (arrow).
Differential diagnosis Marginal Zone lymphoma Marginal zone lymphoma will express CD19. It does not express CD5 and CD10. It is usually negative for CD23. Light chain expression is usually strongly positive. Image 16
Case 3 Diagnosis Mantle Cell Lymphoma CD19+/CD20+/CD5+/CD23-/kappa+
Discussion Mantle cell lymphoma is a mature B cell neoplasm which arises from the normal counterpart of B cells that rim the germinal centers. When originally described, mantle cell lymphomas were called intermediate lymphocytic lymphoma and lymphocytic lymphoma of intermediate differentiation describing their morphologic features as intermediate between small lymphocytic lymphoma and small cleaved lymphocytic lymphoma. Mantle cell lymphoma is rare and accounts for about 6% of all lymphomas, although with increasing recognition, the incidence is expected to rise. Mantle cell lymphoma occurs in older patients, males, and present with widespread lymphadenopathy, splenomegaly, bone marrow involvement, and occasionally leukemic involvement.
Mantle cell lymphoma Image 17: The classic variant of mantle cell lymphoma is composed of small, slightly larger than normal lymphocytes, with scant cytoplasm, chromatin that is more dispersed than normal lymphocytes, and inconspicuous nucleoli. The small cells are rounder than follicular cells, with more cytoplasm. Small nucleoli are sometimes visible. Papanicolaou stain, left, Wright s stain, right x 100.
Discussion A second variety has been characterized as blastic mantle cell due to its morphologic similarity to lymphoblasts. The blastic variant has larger cells with more dispersed chromatin. Mantle cell lymphoma is not a low grade lymphoma and has a more aggressive course than either small lymphocytic lymphoma or follicular lymphoma. Median survival is 3-5 years and is treated with more aggressive therapy than the low grade lymphomas in the differential diagnosis. The characteristic immunophenotype of mantle cell lymphoma has lent consistency to the diagnosis and allows accurate classification of the lymphoma in fine needle biopsies. The malignant cells express both CD19 and CD5 without CD23 expression. They demonstrate bright light chain fluorescent intensity as well as bright CD20 positivity. Mantle cell lymphoma also has a characteristic chromosomal translocation t(11;14) which results in the expression of cyclin D1. Cyclin D1 can also be detected by immunostains and used as a diagnostic aid.
Discussion This case is a classic example of mantle cell lymphoma with the characteristic monotonous small cell population, characteristic clinical features, and classic immunophenotype. Mantle cell lymphoma is one of the lymphomas which can be accurately classified by cytologic evaluation and immunophenotyping.
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