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Presented by Risa Mann, M.D. and prepared by Angelique W. Levi, M.D.
Case 1: 40-year-old woman with lymph node enlargement
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1. Question
Week 11: Case 1
40-year-old woman with lymph node enlargement
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Correct
Answer: Ki-1 positive large cell lymphoma
Histology: The specimen is a lymph node that shows reactive hyperplasia. However, within the sinuses there is a proliferation of large atypical cells. The cells have abundant cytoplasm and large nuclei often with prominent nucleoli. Some of the cells have multiple nuclei and others show a horseshoe ring-like appearance. There does not appear to be a proliferation of other inflammatory cells such as eosinophils or plasma cells associated with the proliferation. Also, there is no pigment present within the cells. Scattered mitotic figures are observed. The tumor cells appear to primarily involve the sinuses.
Discussion: In metastatic carcinoma to lymph nodes, the tumor would involve and fill the sinuses, as in this case. However, in metastatic carcinoma, the cells are more cohesive and often show evidence of epithelial differentiation such as gland formation or squamous differentiation. In this tumor, the cells are non-cohesive. This tumor can be easily confused with metastatic malignant melanoma because the cells are large and often have a prominent nuclei and maybe binucleated. However, the tumor cells in ki-1 lymphoma lack pigment on H&E stain and do not show evidence of melanin production using special staining techniques. Hodgkin’s Disease can involve the sinuses, but is not usually primarily localized to the sinuses. In addition, Hodgkin’s Disease usually has other inflammatory cells associated with it, such as plasma cells and eosinophils. Immunohistochemical staining can be particularly helpful in establishing the diagnosis of ki-1 lymphoma. The neoplastic cells stain with CD30 (ki-1). They are +/- with epithelial membrane antigen. This fact is important since the differential diagnosis does include metastatic carcinomas which can be positive for EMA, but in general, most epithelial tumors are ki-1 negative. The tumor cells in a ki-1 positive lymphoma also show evidence of T-cell differentiation and are CD3 positive, and lack keratin expression. Additionally, the cells in some cases of ki-1 lymphoma stain for alk protein, the product of the t(2:5) translocation that has been associated with ki-1+ large cell lymphoma. The tumor can be distinguished from Hodgkin’s Disease because classic Reed-Sternberg cells are not usually very prominent. In addition, the cells of Hodgkin’s Disease are usually negative for CLA and stain positively for CD15 as well as CD30. Reed-Sternberg cells may on occasion be positive for CD20. Of course the cells in carcinoma would stain for various keratins and the cells of malignant melanoma would stain positive for S100, melan A and HMB45.
Incorrect
Answer: Ki-1 positive large cell lymphoma
Histology: The specimen is a lymph node that shows reactive hyperplasia. However, within the sinuses there is a proliferation of large atypical cells. The cells have abundant cytoplasm and large nuclei often with prominent nucleoli. Some of the cells have multiple nuclei and others show a horseshoe ring-like appearance. There does not appear to be a proliferation of other inflammatory cells such as eosinophils or plasma cells associated with the proliferation. Also, there is no pigment present within the cells. Scattered mitotic figures are observed. The tumor cells appear to primarily involve the sinuses.
Discussion: In metastatic carcinoma to lymph nodes, the tumor would involve and fill the sinuses, as in this case. However, in metastatic carcinoma, the cells are more cohesive and often show evidence of epithelial differentiation such as gland formation or squamous differentiation. In this tumor, the cells are non-cohesive. This tumor can be easily confused with metastatic malignant melanoma because the cells are large and often have a prominent nuclei and maybe binucleated. However, the tumor cells in ki-1 lymphoma lack pigment on H&E stain and do not show evidence of melanin production using special staining techniques. Hodgkin’s Disease can involve the sinuses, but is not usually primarily localized to the sinuses. In addition, Hodgkin’s Disease usually has other inflammatory cells associated with it, such as plasma cells and eosinophils. Immunohistochemical staining can be particularly helpful in establishing the diagnosis of ki-1 lymphoma. The neoplastic cells stain with CD30 (ki-1). They are +/- with epithelial membrane antigen. This fact is important since the differential diagnosis does include metastatic carcinomas which can be positive for EMA, but in general, most epithelial tumors are ki-1 negative. The tumor cells in a ki-1 positive lymphoma also show evidence of T-cell differentiation and are CD3 positive, and lack keratin expression. Additionally, the cells in some cases of ki-1 lymphoma stain for alk protein, the product of the t(2:5) translocation that has been associated with ki-1+ large cell lymphoma. The tumor can be distinguished from Hodgkin’s Disease because classic Reed-Sternberg cells are not usually very prominent. In addition, the cells of Hodgkin’s Disease are usually negative for CLA and stain positively for CD15 as well as CD30. Reed-Sternberg cells may on occasion be positive for CD20. Of course the cells in carcinoma would stain for various keratins and the cells of malignant melanoma would stain positive for S100, melan A and HMB45.