PMC6180998_01
Case 1: lymph node biopsy showing relapsed splenic marginal zone lymphoma with prolymphocytic transformation and acquired CD5 (dim) and cyclin D1 (diffuse, strong) expression. Lymphoma cells consist of both small lymphoid cells with condensed nuclear chromatin, nuclear membrane irregularities, and monocytoid features and transformed cells with prolymphocytic features including intermediate to large size, more abundant cytoplasm, and prominent nucleoli (a, b). Lymphoma cells expressed CD20 (c), were negative for CD3 (d), a subset expressed dim CD5 (e), and cyclin D1 expression was diffuse and strong (f). (a and b) Hematoxylin and eosin staining, (a) 100 times magnification, (b) 500 times magnification, (c, d, and f) 200 times magnification, (e) 400 times magnification, and inset in (f) 1000 times magnification.
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Excisional biopsy of the axillary lymph node showed extensive involvement by lymphoma composed of both small, cytologically atypical lymphoid cells with abundant cytoplasm admixed with more predominant intermediate to large-sized lymphoma cells with variably abundant cytoplasm, large nuclei, and prominent, centrally located nucleoli, consistent with prolymphocytes (Figures 1 and 1). By immunohistochemistry, lymphoma cells were positive for CD20, CD5 (dim, subset), BCL2, and cyclin D1 (diffuse, positive in small lymphoma cells and those with prolymphocytic features), and negative for CD3, CD10, LEF1, and SOX11 (Figures 1-1).
Case 1: splenic marginal zone lymphoma and staging bone marrow biopsy. Lymphoma cells are seen in a micronodular distribution expanding splenic white pulp and infiltrating adjacent red pulp (a) and are small with monocytoid morphologic features and minimal cytologic atypia (b). Tumor cells expressed CD20 (not shown) and were negative for CD5 and cyclin D1 (c and d). Bone marrow staging biopsy showed extensive involvement by lymphoma present predominantly in an interstitial nodular distribution with a focal sinusoidal pattern of involvement (inset in (e) showing focal sinusoidal distribution). Lymphoma cells were small in size and prolymphocytic or large cell transformation was not seen (f). (a, b, e, and f) Hematoxylin and eosin stain, (a and e) 100 times magnification, (b and f) 500 times magnification; CD5 (c) and cyclin D1 (d) immunohistochemistry stains shown at 400 and 200 times magnification, respectively.
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fig2
In the splenic resection, the lymphoma cells were present in a micronodular pattern within white pulp, invaded red pulp, and were composed of small-sized lymphoma cells with monocytoid morphologic features, negative for CD5 and cyclin D1 (Figure 2). Staging bone marrow biopsy performed at the time of initial splenectomy showed extensive involvement by low-grade lymphoma with an interstitial nodular and focally intrasinuoidal pattern (Figure 2).
Case 1: FISH studies for IgH-CCND1 fusion were negative (a). This assay was repeated in a reference lab and was again negative. PCR analysis was performed in the original splenic marginal zone lymphoma (b), and in the relapsed lymphoma (lymph node, and clonal PCR amplification products (c) were compared. Amplification products of the same size in base pairs in the initial and relapsed lymphomas were present, supporting that the tumors were clonally related.
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Given the confirmation of the initially diagnosed SMZL, we performed FISH for t(11; 14)(CCND1-IgH) using IgH and CCND1 dual-labeled probes in the lymph node sample both at our institution as well as at an external reference lab, and both were negative for CCND1-IgH rearrangement (Figure 3). The same monoclonal IgH peaks (framework region (FR) 1: splenectomy: 342.24, lymph node: 342.38; FR2: splenectomy: 277.71, 285.58; lymph node: 277.69 and 285.36; FR3: splenectomy: 146.14, lymph node: 146.3, Figures 3 and 3) were identified in the original and current samples, supporting that the two lymphomas were clonally related.
PMC6180998_02
Case 2: PET imaging study confirmed massive splenomegaly, spleen measuring 31 cm in craniocaudal dimension, and with diffusely hypermetabolic activity, SUV 5.6, considered to be in keeping with lymphomatous involvement. There were also numerous subcapsular wedge-shaped areas of photopenia and hypodensities measuring up to 3.5 cm, which were suspected to be splenic infarcts.
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fig4
There were also numerous subcapsular wedge-shaped areas of photopenia and hypodensities measuring up to 3.5 cm, which were suspected to be splenic infarcts (Figure 4).
Case 2: peripheral blood and bone marrow biopsy. Wright Giemsa-stained peripheral blood smear shows lymphocytosis with many of the circulating lymphoma cells being small in size with round nuclear contours and minimal cytoplasm (a) 500x magnification. Approximately 50% of circulating lymphoma cells had more abundant cytoplasm and prominent nucleoli, consistent with prolymphocytic morphologic features (b) 1000x magnification. Bone marrow aspirate smear shows extensive involvement by lymphoma with a predominance of cells having prolymphocytic features (c 1000x magnification). Hematoxylin and eosin-stained slides of bone marrow core biopsy show extensive marrow involvement by lymphoma ((d) 200x and (e) 500x magnification) with lymphoma cells being diffusely positive for cyclin D1 protein (f) 500x magnification.
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fig5
Peripheral blood smear confirmed lymphocytosis with many circulating lymphoma cells being small to intermediate in size with mature nuclear chromatin (Figure 5). Approximately 50% of circulating lymphoma cells were large with abundant cytoplasm, more open and vesicular nuclear chromatin and prominent nucleoli, consistent with prolymphocytes (Figure 5). Bone marrow core biopsy showed diffuse infiltration by intermediate-sized cytologically atypical lymphoma cells, and aspirate smear showed that most lymphoma cells had prolymphocytic morphologic features in the bone marrow (Figures 5-5).