Faculty Bibliography

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

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

Signal transducer and activator of transcription 3 (Stat3) plays a vital role in signal transduction pathways that mediate transformation and inhibit apoptosis. Oncogenic Stat3 is persistently activated in several human cancers and transformed cell lines. Previous studies indicate activation of Stat3 in renal cell carcinoma (RCC). However, the detailed characterization of the Stat3 expression pattern in different histologic types of RCC is lacking. We have analyzed the immunoprofile of activated or phosphorylated Stat3 (pStat3) in a tissue microarray of renal tumors of different histologic types, including 42 cases of conventional clear cell type, 24 chromophobe, and 7 papillary, 15 oncocytoma, 7 urothelial carcinoma and 21 normal kidney tissues using an anti-pStat3 antibody (recognizes only activated STAT3). pStat3 nuclear staining was observed in 25 of 42 conventional clear cell RCC (59.5 %), 8 of 24 chromophobe RCC (33.3%), 4 of 7 papillary RCC (57.1%). In the other tumor groups, 4 of 15 oncocytomas (26.7%) and 6 of 7 urothelial carcinomas (85.7%) showed positive nuclear staining. Weak nuclear immunoreactivity for pStat3 was seen in 4 of 21 cases of non-neoplastic kidney tissue (19.0%). The extent of Stat3 activation as determined by nuclear expression of its phosphorylated form is increased in histologic types of renal tumors with greater malignant potential, specifically conventional clear cell RCC, papillary RCC and urothelial carcinoma, only slightly increased in chromophobe RCC, and not increased in oncocytoma. These results suggest a role of Stat3 activation in different types of renal neoplasia, possibly serving as a prognostic marker or therapeutic target

Chronic monomyelocytic leukemia (CMML) is a relatively rare clonal hematologic disorder with features of myelodysplastic syndrome and myeloproliferative disease. Renal impairment from CMML is infrequent and can result from both direct (ie, infiltrative) and indirect (eg, vasculitis, infarction) mechanisms. This case report describes a patient with refractory gross hematuria requiring nephroureterectomy with diffuse involvement of the upper tract by CMML and accompanying extramedullary hematopoiesis. Underscored are the need to maintain a broad differential diagnosis for upper tract lesions in the setting of gross hematuria, and the potential need for drastic measures to control upper tract bleeding if conservative measures fail

Colorectal cancer (CRC), is the second-leading cause of cancer-related deaths in the USA, affecting both men and women. Current projections show little or no change since the publication of a morbidity and mortality study in 2005. The projected number of new cases for 2008 is 154,000, and the projected number of CRC cancer deaths for 2008 is 53,000. The standard diagnostic paradigm is based on histopathology of either biopsy or surgical specimens. This article suggests a new paradigm for colon cancer diagnosis and staging using matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS or IMS). IMS may identify potential tumors in normal tissue of cancer patients and predict those cancer patients who are at risk for recurrent cancer

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