Utility of a Comprehensive Immunohistochemical Panel in the Differential Diagnosis of Spindle Cell Lesions of the Urinary Bladder

Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
The American journal of surgical pathology (Impact Factor: 5.15). 11/2008; 33(1):99-105. DOI: 10.1097/PAS.0b013e318180c899
Source: PubMed


Spindle cell lesions of the urinary bladder are uncommon, but when encountered in clinical practice, pose a difficult diagnostic challenge as the differential diagnostic considerations are vast. Pseudosarcomatous processes significantly overlap with malignant tumors (sarcomatoid urothelial carcinoma and leiomyosarcoma) in their morphology and published immunohistochemical profile [pancytokeratin pan (CK), smooth muscle actin (SMA), and desmin]. p63 has been studied rarely and CK 5/6 and CK 34betaE12 have not been analyzed in the bladder in this diagnostic context. In the current study, 45 typical examples of spindle cell lesions [10 pseudosarcomatous myofibroblastic proliferations (PMP), 22 sarcomatoid urothelial carcinomas, and 13 smooth muscle tumors] of the urinary bladder were immunostained with a panel containing broad spectrum anticytokeratin antibodies (OSCAR or AE1/AE3), as well as antibodies to CK 34betaE12, CK 5/6, p63, SMA, and anaplastic lymphoma kinase (ALK). The immunoreactivity was as follows: PMP-CK (OSCAR) 7/10 (70%), CK (AE1/AE3) 7/9 (78%), CK 34betaE12 0/10 (0%), CK 5/6 0/9 (0%), p63 0/9 (0%), SMA 10/10 (100%), ALK 2/10 (20%); sarcomatoid urothelial carcinoma-CK (OSCAR) 15/22 (68%), CK (AE1/AE3) 14/20 (70%), CK 34betaE12 5/20 (25%), CK5/6 6/22 (27%), p63 11/22 (50%), SMA 16/22 (73%), ALK 0/22 (0%); and smooth muscle tumors-CK (OSCAR) 7/13 (54%), CK (AE1/AE3) 7/12 (58%), CK 34betaE12 0/12 (0%), CK 5/6 0/12 (0%), p63 3/13 (23%), SMA 11/13 (85%), ALK 0/13 (0%). Positivity for keratin was typically focal to moderate in smooth muscle tumors and more commonly moderate to diffuse in sarcomatoid carcinomas and PMP. Our data indicate that there is significant immunohistochemical overlap between the different spindle cell lesions, each of which has unique clinicopathologic, prognostic, and therapeutic ramifications. Within the context of morphology, an immunohistochemical panel composed of broad-spectrum antibodies to cytokeratin as well as antibodies to SMA, ALK, p63, and CK 5/6 will be a useful diagnostic adjunct: a combination of pankeratin, SMA, and ALK positivity favors PMP; expression of several cytokeratin and especially CK 34betaE12 and CK 5/6 with p63 favors sarcomatoid carcinoma and SMA positivity with overall absence of other markers favors leiomyosarcoma.

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    • "Some authors [24, 25] stated that the differential diagnosis of sarcomatoid variant of urothelial carcinoma includes benign or locally aggressive conditions and some of these conditions include: pseudosarcomatous myofibroblastic proliferations (post-operative spindle cell nodules) and pseudo-tumours (inflammatory myofibroblastic tumours) of the urinary bladder, urothelial carcinoma with chondroid or osseous metaplasia (e.g., the absence of atypical cartilage or osteoid, resp.), primary sarcomas, mainly leiomyosarcomas. "
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    ABSTRACT: Background. Sarcomatoid variant of urothelial carcinoma (SVUC) was added to the WHO classification in 2004. Aims. To review the literature. Materials and Method. Various internet databases were used. Result. SVUCs are rare biphasic malignant neoplasms exhibiting morphologic/immunohistochemical evidence of epithelial and mesenchymal differentiation with the presence or absence of heterologous elements. Some cases of SVUC have been associated with radiation therapy and cyclophosphamide treatment. Patients' ages range from 50 to 77 years (mean age 66). Patients tend to be younger and they more commonly presented with high-grade histology and advanced stage disease, in comparison with patients who had conventional urothelial carcinoma (CUC). Results of molecular/genetic studies strongly argue for a common monoclonal cell origin of both the epithelial and mesenchymal components in SUVC. The cancer specific survival of SVUC is poor in comparison with CUC. Radical surgical excision and chemoradiation may be associated with improved prognosis; chemoradiation as an organ preserving alternative to radical excision may be associated with improved outcome. There is no consensus opinion on the best treatment modalities for SUVC. Conclusions. SVUC is rare and is associated with inferior outcome compared with CUC. A multicentre trial of various treatment options is required. Cases of SVUC should be reported.
    Full-text · Article · Jan 2014
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    • "Another immunohistochemical finding was the nuclear expression in epithelial and mesenchymal component for p63. In spindle cell lesions of the urinary bladder, expression of several cytokeratins with p63 could help to the diagnostic of sarcomatoid carcinoma [14]. In our case, the expression of cytokeratin and p63, coupled within the context of morphology, help to reach final diagnostic. "
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    ABSTRACT: Sarcomatoid carcinoma (SC) of prostate gland is a rare biphasic tumour. In about half of cases, initial diagnosis is acinar adenocarcinoma, followed by nonsurgical therapy, with a subsequent diagnosis of SC. The survival rate is lower. We report a case of an 59-years-old man with unusual histopathologic finding of prostate sarcomatoid carcinoma, showing characteristics of ductal prostatic adenocarcinoma and prostatic stromal sarcoma-like appearance. Ductal adenocarcinoma was characterized by tall columnar cells with abundant amphophilic to eosinophil cytoplasm. Pleomorphic sarcoma was characterized to have overall glandular growth pattern, simulating a malignant phyllodes tumour. Estrogen and progesterone receptors showed nuclear immunostaining in mesenchymal multinucleated giant cells. In conclusion, SC of the prostate is an exceedingly rare tumour. Retrospective analyses render prostate SC as one of the most aggressive prostate malignancies. The prognosis is dismal regardless of other histologic or clinical findings.
    Full-text · Article · Jul 2011
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    ABSTRACT: Urothelial carcinoma is morphologically heterogeneous and many variant forms have been described. We have encountered several invasive urothelial carcinomas with a unique chordoid morphology characterized by prominent cellular cording and associated myxoid stromal matrix, a pattern closely resembling extraskeletal myxoid chondrosarcoma. This morphologic appearance, to our knowledge, has not been formally described in urothelial carcinoma. A series of 166 consecutive invasive urothelial carcinomas were reviewed to identify cases with cellular cording and myxoid stroma. The patient age, sex, tumor stage, morphologic features, association with typical urothelial carcinoma, and clinical outcome were recorded. Immunostains for p63, cytokeratin (CK) 34BE12, CK20, calponin, glial fibrillary acidic protein, S-100 protein, oncofetal protein glypican-3, and brachyury were performed on 7 cases. Mucin histochemistry was performed on 8 cases to evaluate the extracellular myxoid material. Eleven of the 166 (7%) consecutive invasive urothelial carcinomas had areas with a chordoid appearance. A total of 12 cases were analyzed including the addition of a consult case. The patients' ages ranged from 50 to 85 years (mean: 68 y); there were 8 males and 4 females. The specimens consisted of 5 cystectomies, 6 transurethral resections, and 1 anterior exenteration with right nephroureterectomy. Morphologically, each case had at least focal areas in which acellular myxoid stroma was associated with the carcinoma cells. When well developed, the neoplastic cells had scant eosinophilic cytoplasm and were arranged into cords closely mimicking extraskeletal myxoid chondrosarcoma, chordoma, mixed tumor/myoepithelioma of soft tissue, and yolk sac tumor. The percentage of tumor with a chordoid appearance ranged from 5% to 95% (mean: 39%; median: 25%). No conventional sarcomatous differentiation, no intracytoplasmic mucin, and no glandular formation were present in any case. All 12 cases had foci of typical urothelial carcinoma present at least focally and a gradual transition to the chordoid pattern was commonly seen. Immunophenotypically, all 7 cases evaluated showed strong immunoreactivity for p63 (nuclear) and CK34BE12 (cytoplasmic). Immunostains for CK20, calponin, glial fibrillary acidic protein, oncofetal protein glypican-3, and brachyury and were negative in the 7 cases studied (0 out of 7), whereas S-100 protein had focal staining (<5%) in 1 case. The myxoid stromal component was diffusely colloidal iron and Alcian blue positive in all 8 cases examined; periodic acid Schiff was negative in all 8 cases, whereas mucicarmine was only focally positive in 2 of 8 cases. Most cases were high stage (pT4: 5, pT3: 4, pT2: 2, and pT1: 1), and 6 of 8 cases (75%) with nodal sampling had metastatic disease. In 1 case, the lymph node metastasis had areas with chordoid morphology. Nine of 12 patients had available follow-up: 2 were dead of disease (1 and 10 mo), 4 were alive with disease (5 to 8 mo) with distant metastasis in 3, and 3 had no evidence of disease at last follow-up (2 to 120 mo). In summary, we describe a morphologic pattern of urothelial carcinoma with a distinct chordoid appearance that may potentially mimic a spectrum of primary vesical and nonvesical neoplasms with myxoid or mucinous components. These carcinomas maintain an immunophenotype characteristic of urothelial carcinoma and usually present with high stage disease.
    No preview · Article · Jun 2009 · The American journal of surgical pathology
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