Strong SOX10 expression in human papillomavirus-related multiphenotypic sinonasal carcinoma: report of 6 new cases validated by high-risk human papillomavirus mRNA in situ hybridization test.

Human papillomavirus (HPV)-related multiphenotypic sinonasal carcinoma (HMSC) is associated with high-risk HPV (HR-HPV) infection. Using HR-HPV messenger RNA (mRNA) in situ hybridization (ISH), we reported 6 new HMSC cases and compared their histopathology with that of sinonasal adenoid cystic carcinoma. Using p16 immunohistochemistry (IHC) and HR-HPV ISH, we retrospectively identified 6 HMSC cases. All HMSC cases were positive for HR-HPV mRNA ISH and p16 IHC. Two HMSC cases had overlying atypical squamous epithelium, and 1 had invasive squamous cell carcinoma (SCC). All HMSC cases were SOX10 positive, whereas the overlying atypical squamous epithelium and the SCC were SOX10 negative. One atypical HMSC-like case was also identified, which was positive for HR-HPV mRNA ISH, HR-HPV DNA ISH, and SOX10 IHC, but negative for p16 IHC. This study showed that HR-HPV mRNA ISH was a useful tool to diagnose HMSC and had stronger signals compared with HR-HPV DNA ISH. HR-HPV E6/E7 mRNA could be identified in the overlying atypical squamous epithelium and the invasive SCC. A combination of p16 and SOX10 IHC will be a useful screening panel for HMSC followed by confirmatory HR-HPV mRNA ISH test.

Hsieh MS ，Lee YH ，Jin YT ，Huang WC ... -  《-》

HPV-related Multiphenotypic Sinonasal Carcinoma: An Expanded Series of 49 Cases of the Tumor Formerly Known as HPV-related Carcinoma With Adenoid Cystic Carcinoma-like Features.

Bishop JA ，Andreasen S ，Hang JF ，Bullock MJ ，Chen TY ，Franchi A ，Garcia JJ ，Gnepp DR ，Gomez-Fernandez CR ，Ihrler S ，Kuo YJ ，Lewis JS Jr ，Magliocca KR ，Pambuccian S ，Sandison A ，Uro-Coste E ，Stelow E ，Kiss K ，Westra WH ... -  《-》

p16 Immunoexpression in sinonasal and nasopharyngeal adenoid cystic carcinomas: a potential pitfall in ruling out HPV-related multiphenotypic sinonasal carcinoma.

Adenoid cystic carcinoma (AdCC) is frequent in the sinonasal region. The recently described human papilloma virus (HPV)-related multiphenotypic sinonasal carcinoma (HMSC) histopathologically resembles solid AdCC, but has a better outcome. Thus, clinical and pathogenetic differences between HMSC and sinonasal AdCC necessitate their distinction. We conducted this study to assess p16 immunoexpression in previously diagnosed AdCC cases, and to identify HMSC cases in p16 immunopositive cases. Cases diagnosed as sinonasal and nasopharyngeal AdCC were retrieved. Histomorphological features were reviewed. Immunohistochemistry (IHC) for p16 was performed. HPV testing was performed in p16-positive cases by mRNA in-situ hybridisation (mRNA ISH) and polymerase chain reaction (PCR) assay. MYB rearrangement was assessed by fluorescence in-situ hybridisation. One hundred and two AdCC cases were retrieved. Six cases (5.9%) showed diffuse p16 positivity. HPV mRNA ISH and PCR were negative in p16-positive cases. Two cases showed MYB rearrangement. p16-positive cases were composed of basaloid cells demonstrating a cribriform pattern, at least focally. The predominant pattern was cribriform in three and solid in three cases. One case showed two distinct components: keratinising squamous cell carcinoma and cribriform AdCC. Other morphological patterns seen were tubular, reticular, epithelial-myoepithelial carcinoma-like, and glomeruloid, forming a minor component of the tumour area. p16 staining alone, even when diffuse and strong, cannot be used as a surrogate for HPV testing to distinguish sinonasal AdCC from HMSC. p16 IHC should be accompanied by more specific methods, such as mRNA ISH, so as not to erroneously diagnose HMSC over sinonasal AdCC, bearing in mind the highly aggressive nature of the latter.

Antony VM ，Kakkar A ，Sikka K ，Thakar A ，Deo SVS ，Bishop JA ，Jain D ... -  《-》

The utility of high-risk human papillomavirus E6/E7 mRNA in situ hybridization in assessing HPV status on cell block.

Assessment of human papillomavirus (HPV) status is critical to the treatment and prognosis of patients with oropharyngeal squamous cell carcinoma. Patients often present with enlarged cervical lymph nodes which are amenable to fine needle aspiration (FNA) and cell block creation. The most widely used method for assessing HPV status is the surrogate marker p16. Other HPV specific methods such as high-risk HPV E6/E7 mRNA in situ hybridization (ISH) have been shown to perform as well as p16 and are easier to interpret. Our study evaluates the utility of high-risk HPV mRNA ISH in cell block specimens. Thirty-six cases of metastatic squamous cell carcinoma in cervical neck lymph node FNAs were identified over a 3-year period. All cases had p16 immunohistochemistry (IHC) performed on cell block. HR HPV mRNA ISH was performed on the cell block and compared to the p16 results. Additionally, p16 and HR HPV mRNA ISH status was assessed in those cases with corresponding surgical resections. HR HPV mRNA ISH confirmed the p16 IHC (either positive or negative) in 24 of the 36 cases (66.7%). Six false negative cases were p16 negative/HR HPV mRNA ISH positive. HR HPV mRNA ISH was positive in 75% of the four p16 equivocal cases. Two cases were p16 positive/HR HPV mRNA ISH negative. HR HPV mRNA ISH is no more difficult to perform in the IHC lab and is easier to interpret than p16 IHC. HR HPV mRNA ISH is a useful alternative to p16 in cell block specimens.

Wilson BL ，Israel AK ，Lott Limbach AA 《-》

High-Risk Human Papillomavirus E6/E7 mRNA Is Rarely Detected in Nonanogenital Cutaneous Squamous Cell Carcinoma: An RNA In Situ Hybridization-Based Tissue Microarray Study.

Fujimoto M ，Matsuzaki I ，Takahashi Y ，Iwahashi Y ，Warigaya K ，Kojima F ，Jinnin M ，Murata SI ... -  《-》