Faculty Bibliography

Angiomyolipoma with epithelial cysts (AMLEC) is a rare variant of angiomyolipoma with minimal fat that contains epithelial-lined cysts and may mimic a cystic renal cell carcinoma. While 17 cases have been described in the pathology literature since this entity was first described in 2006, the radiologic appearance was not demonstrated in any of these cases. We report the CT and MRI appearance of AMLEC found incidentally in a patient with lupus nephritis

Cytologically atypical stromal cells were found in the perinephric adipose tissue, mimicking well-differentiated liposarcoma in 12 of 59 (20%) consecutive nephrectomy specimens that were resected for renal cell carcinoma. Morphologically, the atypical cells included enlarged, hyperchromatic spindle cells and floret-type multinucleate cells. Of 59, 10 (17%) renal cell carcinomas invaded through the renal capsule into the perinephric adipose tissue. Of these cases, three (30%) contained the aforementioned atypical cells. In contrast, 9 of 49 cases without extrarenal invasion (18%) contained the atypical stromal cells. Of the 12 cases with atypical stromal cells, 3 (25%) were associated with extrarenal involvement. The atypical spindle cells exhibited focal to variable positivity for smooth muscle actin and desmin in 3 of the 14 cases (including two cases from our consultation files) each. Cytokeratin AE1/AE3, cytokeratin Cam 5.2, cytokeratin 7, epithelial membrane antigen, and S-100 were negative in all cases. Amplification of MDM2 gene region, which is commonly observed in well-differentiated liposarcoma, was absent by fluorescence in situ hybridization (FISH) in the atypical stromal cells. Immunohistochemistry and FISH suggest that the atypical cells are most consistent with reactive fibroblasts/myofibroblasts. Recognition of these atypical fibroblasts/myofibroblasts may help in avoiding the potential pitfall of misdiagnosing them as well-differentiated liposarcoma.Modern Pathology advance online publication, 12 June 2009; doi:10.1038/modpathol.2009.84

Invasive micropapillary carcinoma (IMC) is generally an aggressive morphologic variant that has been described in the bladder, lung, breast, salivary gland, gastrointestinal tract, and ovary. Given the morphologic similarities between IMCs arising from different organ systems and the high propensity of this histologic subtype for lymphatic metastasis, it may be necessary to use immunohistochemical (IHC) markers to determine the primary site of an IMC. Few studies have compared the IHC profiles of IMCs originating from different sites. We tested a panel of 11 IHC markers for their ability to distinguish urothelial, lung, breast, and ovarian IMC using a tissue microarray constructed with primary tumor tissue from 47 patients with IMC (13 bladder, 6 lung, 16 breast, and 12 ovarian). For each tumor, correct classification as IMC was verified by reverse polarity MUC1 expression. We found that immunostaining for uroplakin, CK20, TTF-1, estrogen receptor (ER), WT-1 and/or PAX8, and mammaglobin was the best panel for determining the most likely primary site of IMC. The best markers to identify urothelial IMC were uroplakin and CK20, whereas p63, high molecular weight cytokeratin, and thrombomodulin were less sensitive and specific. Lung IMC was uniformly TTF-1 positive. Breast IMC was ER positive, mammaglobin positive, and PAX8/WT-1 negative, while ovarian IMC was ER positive, mammaglobin negative, and PAX8/WT-1 positive. In the metastatic setting, or when IMC occurs without an associated in situ or conventional carcinoma component, staining for uroplakin, CK20, TTF-1, ER and WT-1, and/or PAX8, and mammaglobin is the best panel for accurately classifying the likely primary site of IMC

Preneoplastic lesions for renal oncocytosis have not been well defined. We have attempted to identify the putative in-situ or dysplastic change in nephrectomy specimens with oncocytosis. Cases of multiple oncocytoma previously identified in radical nephrectomy specimens (n = 5) were reviewed for early lesions of renal oncocytosis by light microscopic analysis and by immunohistochemical studies for p53, bcl2 and MIB-1. Microscopic analysis showed that the renal cortical regions in all cases contain isolated groups of tubules partially or completely replaced by oncocytic cells with morphologic features resembling tumor cells in oncocytosis. The oncocytic cells within these tubules are increased in number and are arranged either as solid groups or as single layers in cystically dilated tubules, and may assume a hobnail appearance. They can be distinguished from small foci of oncocytosis as they do not form a coalescent group but are separated in part by intervening normal-appearing tubules. Cytologically, the cells have abundant eosinophilic, granular cytoplasm with a low nuclear/cytoplasmic ratio and demonstrate distinct cell borders. A very characteristic feature of these cells is the retraction space ('windows') between the oncocytic cells. Nuclear features of these cells are not distinctive from normal tubules. Immunostaining with Bcl-2, p53 and MIB-1 antibodies also does not differentiate the putative preneoplastic lesions from normal tubules. Thus, recognition of a putative dysplastic lesion for oncocytosis is possible by routine microscopic analysis. Identification of this lesion in a biopsy or partial nephrectomy specimen should raise the possibility of the existence of renal oncocytosis (multifocality), leading to adequate clinical management