Detection of Residual Tumor Cells in Bladder Biopsy Specimens: Pitfalls in the Interpretation of Cytokeratin Stains
Johns Hopkins University, Baltimore, Maryland, United StatesAmerican Journal of Surgical Pathology (Impact Factor: 5.15). 04/2007; 31(3):390-7. DOI: 10.1097/01.pas.0000213367.41251.5d
Some patients who have had prior bladder biopsies or transurethral resections undergo a repeat resection within several months for various reasons. The detection of a few residual tumor cells in bladder specimens with prior biopsy site changes can be challenging based on histology alone. Immunohistochemistry for cytokeratins may be used as an adjunct in this situation. We have noted several cases in which keratin stains were performed and positive cells were noted, raising the issue as to whether the cytokeratin positive cells were residual tumor cells or stromal cells. Immunohistochemistry for a panel of antibodies [AE1/AE3, CAM 5.2, high molecular weight cytokeratin, smooth muscle actin (SMA), desmin, and anaplastic lymphoma kinase (ALK)] was performed on 29 cases of bladder biopsies with prior biopsy site changes. Of 29 patients, 25 had a prior history of bladder tumor: 17 had invasive high-grade urothelial carcinoma (T1, 5 cases; T2, 11 cases; T3,1 case); 7 had noninvasive high-grade papillary urothelial carcinoma; 1 had noninvasive low-grade papillary urothelial carcinoma). One of the patients with noninvasive high-grade papillary urothelial carcinoma and one of the patents with invasive high-grade urothelial carcinoma had associated carcinoma in-situ. Four patients had prior benign bladder diagnoses: cystitis cystica et glandularis; polypoid cystitis; follicular cystitis; and neurogenic bladder with benign prostate hyperplasia. Of the 29 cases, 6 (21%) had cells with staining for at least 2 of the cytokeratin markers. Cytokeratin (CK) AE1/ AE3 was positive for cells in 8/29 cases (28%). In 6 of these cases, cells displayed a spindle cell and 2 cases a more epithelioid morphology. CAM 5.2 was positive in cells in 5/29 cases (17%); 3 of the cases had spindle cell and 2 cases epithelioid morphology. High molecular weight cytokeratin was expressed in cells in 2/29 cases (7%) with 1 case having spindle cell and 1 epithelioid morphology. SMA was positive in cells with a spindle cell morphology and negative in the more epitheloid cytokeratin positive cells. Desmin was positive in 3/6 keratin positive spindle cells and negative in keratin positive epithelioid cells. ALK was negative in all the cases. Three cases with spindle cell morphology and positivity for at least 1 of the keratins and SMA stains were interpreted as aberrant keratin expression in myofibroblastic cells based on the staining and the morphology of the spindle cells. Another 3 cases with concurrent staining for at least 1 of the keratins, SMA and desmin were consistent with smooth muscle cells on the basis of their cellular morphology. Another 2 cases had cells, which expressed at least 2 CK markers but did not express SMA, desmin, or ALK and a more epithelioid morphology. These cells were interpreted as residual tumors cells. When interpreting CK stains for the detection of residual tumor cells, one should pay attention to the nature of the cells and not assume all CK staining cells are residual tumor cells.
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ABSTRACT: Cystitis cystica et glandularis (CCEG) and intestinal metaplasia (IM) have been suggested to represent precursors of bladder adenocarcinoma. The relationship between these entities and the subsequent development of bladder carcinoma remains unclear. We retrospectively evaluated the association among florid CCEG, IM, and bladder carcinoma. The records and imaging findings of patients with a pathologic diagnosis of florid CCEG and/or IM were reviewed for a concurrent or future diagnosis of bladder carcinoma or pelvic lipomatosis. We identified 136 patients from 1982 to 2006 with florid CCEG (n = 117) or IM (n = 19). Of the 117 patients with CCEG, a subset was identified with concurrent mucinous adenocarcinoma (n = 1; <1%), squamous cell carcinoma (n = 4; 3%), or urothelial carcinoma (n = 34; 29%) at diagnosis. Pure IM was identified concurrently with adenocarcinoma in 2 (10%), urothelial carcinoma in 4 (21%), and urothelial carcinoma with glandular differentiation in 1 (5%) of 19 patients. Follow-up for 103 patients (75%) ranged from 7 days to 23.7 years (median 2.6 years, mean 4.4). Only 1 new case of urothelial carcinoma was identified after 3 months in 1 patient with CCEG. None of the patients in our series had associated pelvic lipomatosis. Both florid CCEG and IM can be identified in benign bladder specimens or in conjunction with bladder carcinoma. Although IM can be associated with a concurrent diagnosis of carcinoma, we found no evidence that it increases the future risk of malignancy and our findings do not support a recommendation for surveillance cystoscopy in such patients. No association was identified between either CCEG or IM and pelvic lipomatosis.
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ABSTRACT: Inflammatory pseudotumour is a generic term applied to a variety of neoplastic and non-neoplastic entities that share a common histological appearance, namely a cytologically bland spindle cell proliferation with a prominent, usually chronic inflammatory infiltrate. Over the last two decades, inflammatory myofibroblastic tumour (IMT) has emerged from within the broad category of inflammatory pseudotumour, with distinctive clinical, pathological and molecular features. IMT shows a predilection for the visceral soft tissues of children and adolescents and has a tendency for local recurrence, but only a small risk of distant metastasis. Characteristic histological patterns include the fasciitis-like, compact spindle cell and hypocellular fibrous patterns, which are often seen in combination within the same tumour. Chromosomal translocations leading to activation of the ALK tyrosine kinase can be detected in approximately 50% of IMTs, particularly those arising in young patients. This review will examine the clinical, pathological, and molecular genetic features of IMT and discuss an approach to diagnosis and differential diagnosis.
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ABSTRACT: Over-expression of ki 67 and vascular endothelial growth factor (VEGF) is a frequent finding in squamous cell carcinoma (SCC) of the oral mucosa. The expression of VEGF and ki 67 proteins was studied in a cohort of 87 patients with primary, previously untreated SCC of the tongue, using computerized image analysis (CIA) in order to determine the potential prognostic significance of these factors. Immunohistochemical analysis was performed with monoclonal anti-ki 67 (MIB 1) and anti-VEGF antibodies. A digital image analysis assay was applied for the evaluation of the results. Using CIA, VEGF over-expression was observed in 24/87 (27.5%) of the examined cases and this finding correlated to the stage of the disease (p=0.05). ki 67 was over-expressed in 49/87 (56.3%) of the cases and correlated to the size of the tumors (p=0.05). Cox regression analysis showed that there was no prognostic significance associating VEGF protein expression to survival status of the examined patients (p=0.77), whereas ki 67 over-expression was strongly correlated to poor prognosis (p=0.017). The size of the primary tumors was also strongly correlated to survival status of the patients (p=0.024), whereas stage of disease showed a borderline statistical significance (p=0.091).
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