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Anatomic Pathology Selected Abstracts, 12/13

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Anatomic pathology abstracts editors: Michael Cibull, MD, professor and vice chair, Department of Pathology and Laboratory Medicine, University of Kentucky College of Medicine, Lexington; Rouzan Karabakhtsian, MD, attending pathologist, Department of Pathology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY; and Thomas Cibull, MD, dermatopathologist, Evanston Hospital, NorthShore University HealthSystem, Evanston, Ill.

Human papillomavirus-related carcinomas of the sinonasal tract

High-risk human papillomavirus is an established cause of head and neck carcinomas arising in the oropharynx. Human papillomavirus (HPV) has also been reported in some carcinomas arising in the sinonasal tract, but little is known about the overall incidence or clinicopathologic profile of these carcinomas. The surgical pathology archives of The Johns Hopkins Hospital were searched for all carcinomas arising in the sinonasal tract from 1995 to 2011, and tissue microarrays were constructed. P16 immunohistochemical analysis and DNA in situ hybridization for high-risk types of HPV were performed. Demographic and clinical outcome data were extracted from patient medical records. Of 161 sinonasal carcinomas, 34 (21 percent) were positive for high-risk HPV DNA, including type 16 (82 percent), type 31/33 (12 percent), and type 18 (six percent). HPV-positive carcinomas consisted of 28 squamous cell carcinomas and variants (15 nonkeratinizing or partially keratinizing, four papillary, five adenosquamous, and four basaloid), one small cell carcinoma, one sinonasal undifferentiated carcinoma, and four carcinomas that were difficult to classify but exhibited adenoid cystic carcinoma-like features. Immunohistochemistry for p16 was positive in 59 of 161 (37 percent) cases, and p16 expression strongly correlated with presence of HPV DNA; 33 of 34 (97 percent) HPV-positive tumors exhibited high p16 expression, whereas only 26 of 127 (20 percent) HPV-negative tumors were p16 positive (P<.0001). The HPV-related carcinomas occurred in 19 men and 15 women who ranged in age from 33 to 87 years (mean, 54 years). A trend toward improved survival was observed in the HPV-positive group (hazard ratio, 0.58; 95 percent confidence interval, 0.26, 1.28). The presence of high-risk HPV in 21 percent of sinonasal carcinomas confirms HPV as an important oncologic agent of carcinomas arising in the sinonasal tract. Although nonkeratinizing squamous cell carcinoma is the most common histologic type, there is a wide morphologic spectrum of HPV-related disease that includes a variant that resembles adenoid cystic carcinoma. The distinctiveness of these HPV-related carcinomas of the sinonasal tract with respect to risk factors, clinical behavior, and response to therapy remains to be clarified.

Bishop JA, Guo TW, Smith DF, et al. Human papillomavirus-related carcinomas of the sinonasal tract. Am J Surg Pathol. 2013;37(2):185–192.

Correspondence: J. A. Bishop at jbishop@jhmi.edu

Localized and metastatic myxoid/round cell liposarcoma

Myxoid liposarcoma, a disease especially of young adults that has potential for local recurrence and metastasis, lacks solid prognostic factors and therapeutic targets. The authors evaluated the natural history of the disease and outcome of patients with myxoid liposarcoma (MLPS) and commonly deregulated protein biomarkers. They retrospectively reviewed the medical records for patients who presented to their institution with localized (n=207) or metastatic (n=61) MLPS from 1990 to 2010. A tissue microarray of MLPS patient specimens (n=169) was constructed for immunohistochemical analysis of molecular markers. The five- and 10-year disease-specific survival rates among patients with localized disease were 93 percent and 87 percent, respectively. Male gender, age greater than 45 years, and recurrent tumor predicted poor outcome. The local recurrence rate was 7.4 percent, and the risk of local recurrence was associated with recurrent tumors and nonextremity disease location. Male gender was the main risk factor for metastatic disease, which occurred in 13 percent of patients. Forty percent of patients who had localized disease received chemotherapy, primarily in the neoadjuvant setting. Immunohistochemical analysis revealed significantly higher expression of C-X-C chemokine receptor type 4 (CXCR4) and platelet-derived growth factor receptor beta (PDGFR-β) in metastatic lesions versus localized lesions. Tumors with a round cell phenotype expressed increased levels of CXCR4, p53, adipophilin, PDGFR-α, PDGFR-β, and vascular endothelial growth factor relative to myxoid phenotype. Only the receptor tyrosine kinase encoded by the AXL gene was identified as a prognosticator of disease-specific survival in univariate analysis.

Hoffman A, Ghadimi MP, Demicco EG, et al. Localized and metastatic myxoid/round cell liposarcoma: clinical and molecular observations. Cancer. 2013;119(10):1868–1877.

Correspondence e-mail not available.

Urothelial carcinoma with prominent squamous differentiation in neurogenic bladder: role of HPV infection

Squamous cell carcinomas of the urinary bladder are rare in the Western world; the majority of cases are reported in countries where Schistosoma parasitic infections are prevalent. Unlike with squamous tumors of the uterine cervix or oropharynx, human papillomavirus (HPV) is not commonly associated with bladder squamous cell carcinomas. However, the authors reported on two cases of HPV-positive urothelial carcinomas of the urinary bladder with extensive squamous differentiation showing the typical basaloid, poorly differentiated morphology of HPV-associated tumors. These occurred in patients with neurogenic bladders who had long-standing histories of self-catheterization and tumors that tested positive for HPV by in situ hybridization. A retrospective review of the authors’ institutional database revealed four additional patients with bladder tumors showing squamous differentiation arising in the neurogenic bladder. Assessment of these cases showed the more common well-differentiated keratinizing appearance of squamous cell carcinomas of the bladder. These tumors showed only patchy positivity for p16 immunohistochemical stain (not the diffuse strong staining seen in HPV-positive tumors), and the one tested case was negative for HPV by in situ hybridization. HPV infection and neurogenic bladder have been independently associated with increased risk of developing carcinoma in the urinary bladder. However, this is the first report of squamous tumors arising in the concurrent neurogenic bladder and HPV infection. The morphology of these tumors is similar to that of other high-risk HPV-associated squamous carcinomas, with a basaloid, poorly differentiated appearance and little to no keratin formation.

Blochin EB, Park KJ, Tickoo SK, et al. Urothelial carcinoma with prominent squamous differentiation in the setting of neurogenic bladder: role of human papillomavirus infection. Mod Pathol. 2012;25:1534–1542.

Correspondence: Dr. K. J. Park at gynbreast@mskcc.org

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