Slide Box - Lymphoma 1
Cases
Review of the H&E sections reveal completely effaced lymph node architecture by a diffuse polymorphous lymphoid infiltrate consisting of small-to large lymphocytes, numerous plasma cells, and abundant epithelioid histiocytes, some of which form small epithelioid granulomas. Occasional reactive germinal centers are noted in the peripheral cortical tissue. There is some degree of increased vascularity noted as well. Per immunohistochemistry, CD20 highlights large clusters of B-cells as well as immunoblasts. Most of the lymphoid infiltrate consists of CD3+ T-cells with cytologic atypia. The atypical T-cell infiltrate is positive for CD4, and demonstrates only partial expression of CD5 and CD7, but is negative for CD8 or CD10. CD21 highlights focal perivascular follicular dendritic networks. CD138 and immunoglobulin surface light chains highlight numerous polyclonal plasma cells in the background. EBER shows rare EBV positive cells. All other immunostains are non-contributory to the final diagnosis.
Peripheral t-cell lymphoma with features of angioimmunoblastic t-cell lymphoma (AILT)
IHC CD4/CD8 ratio is 4:1
PCR reactions designed to detect TCR beta gene rearrangement showed one band consistent with the expansion of a single T cell clone.
Peripheral T-cell lymphoma, unspecified (2009 diagnosis ? new terminology WHO classification)
Castleman’s disease, hyaline vascular variant (angiofollicular lymphoid hyperplasia)
H&E sections of the lymph node demonstrate lymphoid follicles with small hyalinized germinal centers and broad mantle zones. Some follicles contain more than one germinal center (“twinning”), and an increased proportion of follicular dendritic cells and endothelial cells. Mantle zone lymphocytes are arranged in concentric rings (“onion skin” pattern) around the germinal centers. The interfollicular region, as well as large subcapsular regions, shows increased number of high endothelial venules and some hyalinized vascular walls. Fibrotic bands are seen focally running through the lymph node extending out from peripheral areas. Occasional follicles are radially penetrated by a hyalinized blood vessel. There are focal areas of subcapsular angiomatous hyperplasia with associated hemorrhage. In summary, the morphologic features are characteristic for Castleman’s disease, hyaline-vascular type.
Castleman disease, hyaline-vascular type with focal angiomatous hyperplasia
Metastatic carcinoma, morphologically and immunophenotypically consistent with the patient’s known lung primary
Squamous epithelial inclusion cyst (lymphoepithelial cyst), focally ruptured
Histologic sections of the lymph node demonstrate nearly effaced normal nodal architecture by prominent nonnecrotizing granulomatous inflammation. Scattered large multinucleated cells with abundant eosinophilic cytoplasm, irregular nuclei, and inclusion-type nucleoli are seen through the lymph node. Numerous mummified cells are also noted. Occasional residual lymphoid follicles are seen. Interspersed eosinophils, plasma cells, and small-medium lymphocytes are present in the background.
Special stains: Cytochemical stains for fungal organisms (GMS) and mycobacteria (AFB) are negative.
Immunohistochemistry: The lesional Hodgkin-type cells are positive for CD20 (subset), CD30, Pax-5, and EBV (minor subset).
Pertinent negative markers include CD3, CD4, CD8, and CD43 (T-cell markers), ALK-1, CD45, and CD15.
Recurrent Classical Hodgkin Lymphoma, in a background of prominent non-necrotizing
granulomatous inflammation
Tumor consisting predominantly of large lymphoid cells with abundant eosinophilic cytoplasm and highly irregular and pleomorphic nuclei. The immunophenotype (CD45 positive, CD20 positive, CD30 positive and ALK-1 negative).
PCR reactions designed to detect IgH gene rearrangement showed one band consistent with the expansion of a single lymphoid clone.
Diffuse large B-cell Lymphoma
Sections of the lymph node biopsy demonstrate nearly effaced lymph node architecture by a neoplastic proliferation of intermediate-sized lymphocytes with scant cytoplasm, round-oval nuclei with clumped chromatin pattern, and 2-3 nucleoli. The background also shows many tingle-body macrophages imparting a “starry sky” pattern on low-power view. Numerous apoptotic cells are also present in the background. One area of the lymph node appears to show somewhat preserved architecture with rare lymphoid follicles and paracortical hyperplasia. By immunohistochemistry, the neoplastic cells are positive for B-cell markers (CD20, CD79a), Bcl-6, and CD10(small subset). The neoplastic cells are negative for CD3, CD5, Bcl-2, CD23, EBV, and TdT. The Ki-67 immunostains reveals a proliferative index of 100%. By molecular studies, the neoplastic infiltrate overexpresses EBV and is positive for clonal immunoglobulin heavy chain (IgH) rearrangement. FISH studies for the MYC/IgH fusion t(8;14) are POSITIVE. Flow cytometry studies were not contributory.
Burkitt Lymphoma
Histologic sections contain lymph node tissue with preserved architecture with marked pale expansion of the paracortex by
histiocytes, Langerhans’ cells and dendritic cells. Many of the histiocytes contain phagocytosed melanin pigment. Molecular studies
show that there is no clonal rearrangement of T-cell receptor beta or gamma.
Lymph node with dermatopathic lymphadenopathy
Sections of the lymph node demonstrate complete effacement of normal lymphoid architecture. The node is replaced by a neoplastic proliferation of mostly medium-sized lymphocytes with irregular nuclei, coarse chromatin pattern and inconspicuous nucleoli. Intermixed larger neoplastic lymphocytes are also noted. Numerous mitoses are identified averaging 12 mitoses per 10 high-power fields. Per flow cytometry, the neoplastic lymphocytes coexpress CD5 and CD19, and are also positive for FMC7, partial CD21, CD38, CD52, CD24, and kappa light chain restricted. Additional immunohistochemistry demonstrates that the infiltrate is positive for cyclin D1. Ki-67 immunostain demonstrates an increased proliferative index of approximately 45-50%.
Mantle cell lymphoma
Sections of the lymph node demonstrate complete effacement of normal lymphoid architecture by a relatively polymorphous infiltrate of numerous eosinophils, plasma cells, and small to medium sized lymphocytes. Intermixed are large cells with moderate to abundant eosinophilic cytoplasm, with mononucleated forms and polylobated nuclei with open chromatin pattern and prominent inclusion-like cherry-red nucleoli. Occasional binucleated classic Reed-Sternberg cells are noted. The infiltrate is transected by variably broad fibrous bands imparting a nodular pattern. Certain areas of the infiltrate demonstrate an increased number of large cells occurring in large nodular clusters, but with a polymorphous background infiltrate. By immunohistochemistry, the large neoplastic cells are positive for CD20, CD30, CD15, and focally positive for CD79a and CD45. The cells are negative for CD10 and CD3 (highlights scattered T. Previous biopsy of 4R mediastinal node is reviewed and morphologically similar to present material.
B-cell lymphoma, unclassifiable with features intermediate between diffuse large b-lymphoma and classical Hodgkin lymphoma
Although focal positivity for CD79a (mature B-cell marker) and CD45 (pan-leukocyte marker) is unusual in Hodgkin lymphomas, aberrant expression of these antigens has been reported in the literature status-post chemotherapy. In addition, although approximately 20-25% of Hodgkin lymphomas express CD20 (pan B-cell marker), the intensity of CD20 expression in the previous and current biopsies is also somewhat unusual. In addition, there certainly is a degree of aberrant immunophenotypic expression, suggesting the possibility of a so-called gray zone lymphoma (morphologic and immunophenotypic features of both traditional Hodgkin lymphoma and diffuse large B-cell lymphoma). Molecular studies for immunoglobulin heavy chain rearrangement (IgH), EBV, and T-cell receptor rearrangements (beta and gamma) are NEGATIVE. The lack of IgH chain rearrangement does not exclude diffuse large B-cell lymphoma component but does support lack of a second malignant clone by molecular studies. The transitional features between classical Hodgkin lymphoma and diffuse large B-cell lymphoma, both in terms of morphology and immunophenotype, are consistent with the WHO 2008 category “B-cell lymphoma, unclassifiable, with feature intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma”.
Cases provided by Dariusz Stachurski, MD, digitized by Arlen Brickman, MD, and organized, and uploaded by Fazilet Yilmaz, MD.