The PRKD1 E710D hotspot mutation is highly specific in separating polymorphous adenocarcinoma of the palate from adenoid cystic carcinoma and pleomorphic adenoma on FNA.

BACKGROUND: Polymorphous adenocarcinoma (PAC) of the palatal minor salivary glands, previously known as polymorphous low-grade adenocarcinoma, is the second most common intraoral malignant salivary gland carcinoma after adenoid cystic carcinoma (ACC) and carries an excellent prognosis. Unfortunately, PAC demonstrates cytological overlap with 2 other salivary gland tumors frequently encountered in the same location, namely ACC and pleomorphic adenoma (PA). Recently, the protein kinase D1 (PRKD1) hotspot mutation E710D was demonstrated to be specific for PAC and to be present in the majority of cases. The objective of the current study was to investigate the value of PRKD1 hotspot sequencing in identifying PAC in paired fine-needle aspiration (FNA) and surgical specimens from cases of PAC, ACC, and PA. METHODS: Paired May-Grunwald-Giemsa-stained FNA and corresponding surgical specimens were collected from 18 PAC cases, 25 ACC cases, and 21 PA cases. Both sets of specimens were subjected to dideoxynucleotide sequencing of PRKD1 exon 15, including the PRKD1 E710D hotspot. RESULTS: Of the PAC cases, approximately 50% demonstrated identical PRKD1 E710D hotspot mutations on the FNA specimen and corresponding surgical specimen. Two ACC specimens had point mutations within the sequenced region in the FNA specimen as well as the surgical specimen, but none were located in the hotspot region. None of the PA cases demonstrated PRKD1 mutations. The specificity of the PRKD1 hotspot mutation for identifying PAC among ACC and PA cases was 100% whereas the sensitivity was 50%. CONCLUSIONS: The PRKD1 E710D hotspot mutation is highly specific for identifying PAC on FNA among cases of ACC and PA, whereas the sensitivity is only modest. Alternative PRKD1 mutations exclude PAC, and are more suggestive of ACC. Cancer Cytopathol 2018;126:275-81. © 2017 American Cancer Society.

Risk Factors for Dysplasia in Recurrent Respiratory Papillomatosis in an Adult and Pediatric Population.

AIM: Recurrent respiratory papillomatosis (RRP) is classically described as a benign neoplasm of the larynx caused by the low-risk human papillomavirus (HPV) viral subtypes. Nevertheless, transformation to dysplasia and invasive carcinoma can occur. We aimed to assess the prevalence of dysplasia and carcinoma-ex-papilloma in both adult-onset and juvenile-onset RRP and identify patient risk factors for this dysplastic transformation. MATERIAL AND METHODS: Ten-year retrospective chart review of a tertiary otolaryngology referral center. Patients with papilloma were identified from a review of a pathology database and clinical records. Patient demographics, pathologic data, and treatment history, including use of cidofovir as an adjunctive therapy for papilloma, were extracted from electronic medical records. RESULTS: One hundred fifty-nine RRP patients were identified, 96 adult-onset (AORRP) and 63 juvenile-onset (JORRP) cases. Of this cohort, 139 (87%) had only benign papilloma as a pathologic diagnosis. In the AORRP cohort, 10 patients (10%) were diagnosed with dysplasia or carcinoma in situ in addition to papilloma, and 5 patients (5%) had malignant transformation to invasive carcinoma-ex-papilloma. There was a significantly higher age of disease onset for those with dysplasia or carcinoma versus those without dysplasia or carcinoma (56 vs 45 years old; P = .0005). Of the 63 JORRP patients, there were no cases of dysplasia but 3 (5%) cases of invasive carcinoma-ex-papilloma, all involving pulmonary disease. The JORRP patients with carcinoma-ex-papilloma had a younger average disease onset (2 vs 6 years old; P = .009) and a higher rate of tracheal involvement than those without carcinoma. Gender, smoking history, number of operations, or use of cidofovir showed no association with the development of dysplasia or carcinoma-ex-papillomatosis in either the AORRP or JORRP population. CONCLUSION: In a large series of RRP, age of disease onset is the strongest predictor of dysplastic transformation in the adult and pediatric population. Carcinoma-ex-papillomatosis was uniformly associated with pulmonary disease in the JORRP population in this series. No other demographic or behavioral factors, including adjunctive therapy with cidofovir, were statistically associated with dysplasia or carcinoma-ex-papilloma.