Human papillomavirus‐associated small cell carcinoma with synchronous squamous cell carcinoma in the nasopharynx: Report of a rare case

Cytopathology ◽  
2020 ◽  
Author(s):  
Weihong Ma ◽  
Guy Betts ◽  
Michael Dykes ◽  
Dominic St Leger ◽  
Alexandra Sargent ◽  
...  
2021 ◽  
pp. mcs.a006102
Author(s):  
Kuniaki Sato ◽  
Kazuo Nishiyama ◽  
Kenichi Taguchi ◽  
Rina Jiromaru ◽  
Hidetaka Yamamoto ◽  
...  

Human papillomavirus (HPV)-related oropharyngeal small cell carcinoma (OPSmCC) is a rare malignancy with aggressive behavior, whereas HPV-related oropharyngeal squamous cell carcinoma (OPSqCC) displays a favorable prognosis. Notably, these two malignancies occasionally arise in an identical tumor. In this case study, we explored the molecular characteristics that distinguishes these two carcinomas employing a rare case of HPV-related oropharyngeal carcinoma (OPC) with the combined histology of SmCC and SqCC. Immunohistochemical analysis and HPV-RNA in situ hybridization (ISH) suggested that both SmCC and SqCC were HPV-related malignancies. Targeted exome sequencing revealed that SmCC and SqCC had no significant difference in mutations of known driver genes. In contrast, RNA sequencing followed by bioinformatic analyses suggested that aberrant transcriptional programs may be responsible for the neuroendocrine differentiation of HPV-related OPC. Compared to SqCC, genes upregulated in SmCC were functionally enriched in inflammatory and immune responses (e.g., arachidonic acid metabolism). We then developed a SmCC-like gene module (top 10 upregulated genes) and found that OPC patients with high module activity showed poor prognosis in The Cancer Genome Atlas (TCGA) and GSE65858 cohort. Gene set enrichment analysis of the SmCC-like gene module suggested its link to MYC proto-oncogene in the TCGA dataset. Taken together, these findings suggest that the SmCC-like gene module may contribute to acquisition of aggressive phenotypes and tumor heterogeneity of HPV-related OPC. The present case study is the first report of genetic and transcriptomic aberrations in HPV-related OPSmCC combined with SqCC.


2012 ◽  
Vol 2 (1) ◽  
Author(s):  
Aymen Lagha ◽  
Nadia Bouzid ◽  
Samia Kanoun Belajouza ◽  
Soumaya Labidi ◽  
Asma Saiidi ◽  
...  

2004 ◽  
Vol 18 (1) ◽  
pp. 111-118 ◽  
Author(s):  
Hong Zhang ◽  
Jing Liu ◽  
Philip T Cagle ◽  
Timothy C Allen ◽  
Alvaro C Laga ◽  
...  

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 391-391
Author(s):  
Samuel L Washington ◽  
Thomas Sanford ◽  
Michael S. Leapman ◽  
Maxwell V. Meng ◽  
Sima P. Porten

391 Background: Variant histology is increasingly recognized but its impact on outcomes is less well known compared to urothelial carcinoma (UC). We aim to evaluate the impact of variant histology on bladder cancer outcomes using the National Cancer Database (NCDB), a U.S. population-based cohort capturing approximately 70% of newly diagnosed cancer cases. Methods: We identified patients with bladder cancer from 2004 to 2013 treated with radical cystectomy. We compared clinical and pathologic characteristics between those with UC and those with variant histology. Chi-square test was utilized for categorical variables and Independent Samples t-test for continuous variables. Multivariable Cox regression was used with hazard ratios (HR) and 95% confidence intervals (CI) to identify independent predictors of overall survival. Results: A total of 40,918 patients were identified with mean age 67 years, with male (75%) and Caucasian (90.9%) predominance. Median follow-up was 36.9 months (IQR 16.1-67.5). Squamous cell carcinoma (4.4%), small cell carcinoma (1.6%) and micropapillary (0.9%) were the most common variant histologies. Variant histology was found more commonly in women (35.6% vs 23.4%, p < 0.05), black (8.8% vs 5.6%, p < 0.05), stage pT3 or T4 (67% vs 50.2%, p < 0.05) and node positive (30.8% vs 26.9%, p < 0.05). In adjusted models squamous cell carcinoma (HR 1.3, 95% CI 1.2-1.4), small cell carcinoma (HR 1.6, 95% CI 1.5-1.8) and black ethnicity (HR 1.2, 95% CI 1.1-1.2) were independent predictors of increased mortality risk while micropapillary was associated with decreased risk (HR 0.8, 95% CI 0.7-1.0) after controlling for age, gender, surgical margin status, pathologic T stage, pathologic N stage and history of chemotherapy. All associations remained statistically significant (p < 0.05). Conclusions: Non-urothelial histology was associated with worse overall survival in patients with bladder cancer treated with radical cystectomy; however, contrary to some previous reports, micropapillary variant was associated with lower risk of death. In addition, black ethnicity was associated with worse survival. Further investigation is needed to explore the impact of variant histology as well as other socioeconomic factors on survival after cystectomy.


2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 380-380
Author(s):  
Samuel L Washington ◽  
Maxwell V. Meng ◽  
Sima P. Porten

380 Background: Bladder cancer (BC) affecting young patients is not well characterized but seems to be increasingly diagnosed. We aim to describe pathologic findings and BC outcomes in patients less than 40 years old using the National Cancer Database (NCDB), a US population based cohort capturing approximately 70% of newly diagnosed cancer cases. Methods: We identified 362,091 patients diagnosed with BC from 2004 to 2013. We compared demographic, clinical and pathologic information between those younger and older than 40 years. Univariate analysis was performed using Chi-square test for categorical variables and Independent Samples t-test for continuous variables. Multivariable Cox regression was used for survival analysis with hazard ratios (HR) and 95% confidence intervals (CI). Multivariable model was used to identify independent predictors of mortality (overall survival, OS). Results: 3,799 patients (1.1%) were 40 or younger with mean age of 34.5 years. Fewer young patients were women (25.2% vs 30.3%, p<0.001). More identified as nonwhite (11.6% vs 7.3%, p<0.001), had lower clinical T stage (cTa 51.4% vs 38.3%, cT1 13.3% vs 19.6; p<0.001), and longer median follow-up (46.4 months IQR 23.3-73.9 vs 35.3 months IQR 16.7-61.6). Age less than 40 (HR 0.3, 95% CI 0.2-0.3), chemotherapy (HR 0.9, 95% CI 0.9-0.9) and cystectomy (HR 0.8, 95% CI 0.8-0.9) were associated with decreased mortality when controlling for clinical characteristics (p<0.001). In sub-analysis of young patients with cystectomy, more had pT0 disease (20.3% vs 18.2%, p=0.005) with squamous cell carcinoma (13.6% vs 4%) and small cell (3.2% vs 1.6%) more prevalent (p<0.001). In adjusted models, squamous cell carcinoma (HR 1.1, 95% 1.1-1.2), small cell carcinoma (HR 1.5, 95% CI 1.4-1.7), RT (HR 1.2, 95% CI 1.!-1.3) and black ethnicity (HR 1.1, 95% CI 1.1-1.2) were independent predictors of worse OS. Conclusions: Younger patients with BC were more commonly non-white, men, and had low stage disease. In young patients undergoing cystectomy, squamous cell carcinoma, small cell carcinoma and black ethnicity were associated with worse OS. Further exploration in this younger patient cohort is needed to better characterize the optimal oncologic management for these patients.


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