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Presented by Fred Askin, M.D. and prepared by Greg Seidel, M.D.
Case 1: The patient is a middle-aged woman with an enlarged spleen
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1. Question
Week 132: Case 1
The patient is a middle-aged woman with an enlarged spleen/images/0419031a.jpg
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/images/0419031d.jpgCorrect
Answer: Metastatic malignant melanoma
Histology: The lesion is composed of nests of large, pleomorphic cells with pink cytoplasm and large nucleoli. In some foci, pink internuclear “pseudo-inclusions” are present. In this particular case there were multiple nodules in the spleen. In some of the nodules, intracytoplasmic melanin pigment was obvious, but in others, as shown in the illustrations here, no pigment was present. The tumor cells in this lesion were immunoreactive for a variety of melanoma markers including S-100 protein, Melan-A, HMB-45 and MITF. They were negative for cytokeratins.
Discussion: Splenic metastases are quite rare and are usually indicative of diffuse dissemination of tumor. The origin of splenic metastases appears to be different with respect to multiple and solitary metastases. Multiple metastasis are more common in melanoma, a tumor characterized by unusual behavior, and carcinomas of the breast, lung and ovary. Solitary splenic metastases, in the absence of diffuse disseminated disease is rare, and approximately 60% of reported cases appear to be associated with gynecologic tumors. Ovarian and endometrial tumors represented the highest association, followed by colorectal tumors, in a report and review by Agha-Mohammadi, et al (American Journal of Clinical Oncology 24:306-10, 2001.) Clinically, a solitary splenic mass is most suggestive of a primary splenic lesion such as lymphoma or hemangioma, hematoma, abcess or infart. Melanoma should always be in the differential diagnosis of pleomorphic neoplasms or metastases to unusual sites. In this particular case, the histologic features were fairly characteristic involving the diagnosis of “pink cell tumor”. The large, atypical cells with huge nucleoli and nuclear pseudo inclusions (cytoplasmic invaginations into the ncleus) should raise the suspicion of melanoma. In the absence of cytoplasmic melanin pigment, the diagnosis can be confirmed with a variety of antibodies as noted above. Other “pink cell” tumors would include hepatocellular carcinoma and adrenal carcinoma. The nested pattern of the cells militates against a diagnosis of lymphoma. Large cell lymphoma would be more likely to involve the spleen as a solitary nodule than would more common small B-cell lymphomas, which usually present as multiple splenic nodules. Splenic angiosarcoma can present as a diffuse disease or as a solitary nodule. It may present clinically as a splenic rupture. Microscopically, the lesion is represented by proliferation of atypical endothelial cells of varying degrees of differentiation. Immunostains for CD-31 and Factor-VIII related protein would be helpful in the differential diagnosis.
Incorrect
Answer: Metastatic malignant melanoma
Histology: The lesion is composed of nests of large, pleomorphic cells with pink cytoplasm and large nucleoli. In some foci, pink internuclear “pseudo-inclusions” are present. In this particular case there were multiple nodules in the spleen. In some of the nodules, intracytoplasmic melanin pigment was obvious, but in others, as shown in the illustrations here, no pigment was present. The tumor cells in this lesion were immunoreactive for a variety of melanoma markers including S-100 protein, Melan-A, HMB-45 and MITF. They were negative for cytokeratins.
Discussion: Splenic metastases are quite rare and are usually indicative of diffuse dissemination of tumor. The origin of splenic metastases appears to be different with respect to multiple and solitary metastases. Multiple metastasis are more common in melanoma, a tumor characterized by unusual behavior, and carcinomas of the breast, lung and ovary. Solitary splenic metastases, in the absence of diffuse disseminated disease is rare, and approximately 60% of reported cases appear to be associated with gynecologic tumors. Ovarian and endometrial tumors represented the highest association, followed by colorectal tumors, in a report and review by Agha-Mohammadi, et al (American Journal of Clinical Oncology 24:306-10, 2001.) Clinically, a solitary splenic mass is most suggestive of a primary splenic lesion such as lymphoma or hemangioma, hematoma, abcess or infart. Melanoma should always be in the differential diagnosis of pleomorphic neoplasms or metastases to unusual sites. In this particular case, the histologic features were fairly characteristic involving the diagnosis of “pink cell tumor”. The large, atypical cells with huge nucleoli and nuclear pseudo inclusions (cytoplasmic invaginations into the ncleus) should raise the suspicion of melanoma. In the absence of cytoplasmic melanin pigment, the diagnosis can be confirmed with a variety of antibodies as noted above. Other “pink cell” tumors would include hepatocellular carcinoma and adrenal carcinoma. The nested pattern of the cells militates against a diagnosis of lymphoma. Large cell lymphoma would be more likely to involve the spleen as a solitary nodule than would more common small B-cell lymphomas, which usually present as multiple splenic nodules. Splenic angiosarcoma can present as a diffuse disease or as a solitary nodule. It may present clinically as a splenic rupture. Microscopically, the lesion is represented by proliferation of atypical endothelial cells of varying degrees of differentiation. Immunostains for CD-31 and Factor-VIII related protein would be helpful in the differential diagnosis.