Jay H. Beckstead

Use of antibodies to RCC and CD10 in the differential diagnosis of renal neoplasms

The majority of renal neoplasms can be distinguished on the basis of histologic examination alone; however, there are morphologic similarities between clear cell renal carcinoma and chromophobe cell carcinoma, as well as between the granular/eosinophilic variants of these tumors and renal oncocytoma. Only a limited number of histochemical markers are available to aid in the differential diagnosis of these neoplasms. Hales colloidal iron usually yields strong, diffuse cytoplasmic staining of chromophobe cell carcinomas whereas clear cell carcinomas are generally negative; however, interpretation of this stain is not always straightforward. By immunohistochemistry, vimentin is detectable in most clear cell carcinomas and is absent from most chromophobe cell tumors and oncocytomas, but reliance on a single antibody can be misleading. In this report we examine the use of commercially available monoclonal antibodies to RCC and CD10 in the differential diagnosis of common renal tumors. Eighty-five percent of clear cell carcinomas (53 of 62) had detectable surface membrane staining for RCC, and 94% (58 of 62) were positive for CD10. Papillary carcinomas were likewise strongly positive for RCC and CD10 in nearly all cases (13 of 14 each). In contrast, all 19 chromophobe cell carcinomas examined were completely negative for surface membrane staining with both of these markers. Oncocytomas were also negative for RCC (0 of 9), but CD10 was detectable in some cases (3 of 9). These results suggest that the presence of surface membrane staining for RCC and CD10 may be used to confirm a diagnosis of suspected clear cell or papillary renal carcinoma. Chromophobe cell carcinomas should be negative for both markers. The absence of RCC staining may also be helpful in the diagnosis of renal oncocytoma.

Juvenile xanthogranuloma: A clinical, histopathologic and immunohistochemical study

Juvenile xanthogranuloma (JXC) is a benign histiocylic proliferation of uncertain histogenesis which usually resolves spontaneously. Histopathologically, classic lesions are characterized by diffuse proliferations of foamy histiocytes, many of which may be multinucleated (Toulon cells), admixed with lymphocytes and eosinophils. Histologic variants of JXG, perhaps representing evolving lesions, may lack these typical histopathological features, showing diffuse infiltrates of non‐foamy mononuclear histiocytes without Toulon cells, posing problems in differentiation from other histiocylic or melanocylic proliferations. Immunohistochemically, JXG is characterized by variable expressions of several histiocytic markers as well as the absence of staining for SI00 protein. To assess better the spectrum of histopathological and immunohistochemical features of JXG, we studied nine cases of classic or histologic variant of JXG. The cases were evaluated by light microscopy and with an extensive battery of antibodies. All 9 cases, regardless of their light microscopic appearance, showed markedly positive staining with histiocytic markers including CD68, HAM56, cathepsin B and vimentin, but did not stain for S100 protein. Antibodies to factor XIIIa stained positively in 8 cases while staining for other markers was variable. Our results suggest that the histiocytes in JXG lesions have macrophagic differentiation, probably representing a reactive process to an unknown stimulus.

Angiomatoid melanoma: A case of metastatic melanoma mimicking a vascular malignancy

We present a case of melanoma metastatic to forehead skin and sacral vertebra, without known primary, which, in the cutaneous metastasis, displayed striking histologic features suggesting vascular differentiation. Histopathologic examination of the lesion revealed a large, deeply extending spindle cell malignancy with numerous, cavernous, erythrocyte-filled spaces throughout and only scant melanin pigmentation, making initial diagnosis challenging. The neoplastic cells demonstrated positive staining with antibodies to S-100 protein, HMB 45, and vimentin. We suggest the term angiomatoid melanoma for this histopathologic variant.

Nodular sclerosing Hodgkin disease with primary manifestation in the orbit

Summary: Hodgkin disease with primary manifestation in the orbit is extremely rare, and even when suspected can be very difficult to diagnose. Its clinical and histological presentation can be nearly impossible to differentiate from that of a benign inflammatory process, and it is necessary to utilize immunohistochemical techniques to confirm the diagnosis. This article focuses on a case of nodular sclerosing Hodgkin disease with initial manifestation in the orbit. A comparison of the clinical, histological, and immunohistochemical presentations associated with both Hodgkin disease and benign inflammation is discussed. A brief review of the immunohistochemistry specific for Hodgkin disease is also provided.

Wistar Furth Rat Megakaryocytes Lack Dense Compartments and Intercellular Plaques, Membranous Structures Rich in Cytoskeletal Proteins

Wistar Furth (WF) rats have an abnormal thrombopoietic phenotype with morphologically aberrant megakaryocytes, larger than normal mean platelet volume, and platelet alpha-granule protein deficiency. Here, ultrastructural comparisons of WF rat megakaryocytes to those of rats (Wistar) with normal platelet formation during stimulated megakaryocytopoiesis following 5-fluorouracil administration, have revealed a previously unrecognized membrane structure in normal rat megakaryocytes, and two additional abnormalities in WF megakaryocytes. The novel structures were zones of electron density on the cytoplasmic face of apposed plasma membranes of adjoining normal megakaryocytes. These modified focal adhesion-type contacts were distributed at intervals between adjacent megakaryocytes, and were spaced by deposits of extracellular material. These structures also were present between apposed plasma membranes of Wistar rat megakaryocytes in unperturbed marrows, but were absent between megakaryocytes of WF rats. The second WF rat megakaryocyte abnormality is the absence of cytoplasmic dense compartments, another specialized membranous structure that is continuous with the megakaryocyte demarcation membrane system. Both the intercellular plaques and dense compartments of Wistar rat megakaryocytes were found to be rich in cytoskeletal proteins including actin, alpha-actinin, talin, and vinculin as indicated by ultrastructural immunogold labeling. We hypothesize that an abnormality in cytoskeletal protein function may be responsible for the lack of these structures in the WF rat.