Transforming B cell lymphoma: A diagnostic dilemma.

We came across a case where the same patient reported at two different institutes. He underwent biopsies at both institutes and where histopathology and immunohistochemistry profile of the patient showed wide variations reflecting a change in biological and morphological type of the same lesion.

Karadwal et al. in their microscopic examination revealed the presence of parakeratinized stratified squamous epithelium with underlying cellular connective tissue stroma.[1] Connective tissue showed the presence of malignant cells resembling small and large lymphocytes arranged in the form of sheets.[1] The large tumor cells exhibited large, pleomorphic nucleus with hyperchromatic and coarse chromatin.[1] Few cells had prominent, multiple eosinophilic nucleoli.[1] Some large round cells with centrally placed large vesicular nucleus were also seen. These cells were surrounded by a clear halo and exhibited a very lightly stained cytoplasm.[1] Immature large cells with cleaved nucleus were present.[1] Numerous abnormal mitotic figures that were 1–4 per high-power field and, in some areas, large binucleated cells with pale cytoplasm and prominent nucleoli were seen.[1] Numerous smaller cells with dark hyperchromatic nuclei and minimal cytoplasm resembling small lymphocytes were also seen.[1] These cells were at least double the size of small lymphocytes. Numerous endothelial lined blood vessels were seen along with hyalinized collagen fibers.[1]

Histopathology under hematoxylin and eosin staining was consistent with histopathological features of non-Hodgkin's lymphoma, which was further confirmed by the primary immunohistochemical examination.[1] Immunohistochemistry showed that the lymphoid cells were immunopositive for CD20/PAX5 and were immunonegative for CD30/Bcl6.[1] The Ki-67 proliferative index is approximately 30%.[1] The histopathological features together with immunohistochemical profile led to the diagnosis of “diffused B-Cell lymphoma, mixed small and large cell type.”[1]

Mittal et al. in their histopathology reported the lesion to be composed of dysplastic parakeratinized stratified squamous epithelium overlying connective tissue stroma with indistinct basement membrane at few places with infiltrating epithelial cells.[2] The connective tissue stroma was highly cellular in nature.[2] There were diffuse proliferations of large atypical lymphoid cells showing dysplastic features such as nuclear and cellular pleomorphism, nuclear hyperchromatism, increased number of nucleoli and abnormal mitotic figures.[2] Some areas showed invasion of neurovascular bundles. Cells were highly anaplastic.[2] Multinucleated giant cells are also seen.[2] The above-mentioned findings favored the diagnosis of “follicular lymphoma transforming into anaplastic B-cell lymphoma.”[2]

Following this, immunohistochemical analysis was done for the expression of pan B-cell markers CD20, CD3, bcl-2, CD5, CD10 and Ki67.[2] CD20 and bcl-2 were positive in medium and large lymphoid cells in follicle and diffuse patterns.[2] CD3 and CD5 were positive in few scattered lymphocytes.[2] CD10 was positive in few focal areas and Ki67 was positive in 30% area.[2] Based on immunohistochemical report, the lesion was diagnosed as diffuse large b-cell lymphoma (DLBCL) anaplastic variant (70%) and follicular lymphoma, Grade 3A (30%).[2]

In the previous reported cases, the most common histopathology identified in follow-up biopsies of patients with follicular lymphoma (FL) is diffuse large B-cell lymphoma.[3] It has been concluded that FL can transform into DLBCL or less commonly to the intermediate gray-zone category of unclassifiable B cell lymphoma.[4] Increase in the probability of transformation over time and its occurrence in FL patients suggest that the change of FL to a more aggressive histopathology which may be associated with a more aggressive clinical behavior as evident by increase in numbers of mitotic figures in our case.[4]

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