Can thyroid histomorphology identify patients with PTEN hamartoma tumour syndrome?

AIMS: The phosphatase and tensin homologue (PTEN) hamartoma tumour syndrome (PHTS) is a genetic disorder with variable clinical presentation and increased lifetime risk of multiorgan malignancies. The thyroid gland is commonly affected with follicular nodular disease (FND) and follicular cell-derived carcinomas. Histopathological and immunohistochemical assessment of thyroid disease in PHTS is essential to identify patients at-risk. METHODS AND RESULTS: In all, 30 PHTS patients with available thyroidectomy specimen material (2000-2023) and 31 control patients with FND and "adenomatous nodules" were retrieved. Histologic criteria, including the frequency of adenomatous-type nodules versus hyperplastic-type nodules, background and nodular lipomatous metaplasia, chronic lymphocytic thyroiditis, cytoplasmic clearing of follicular cells in nodules, nodule-in-nodule appearance, and spectrum of nuclear atypia between nodules were evaluated in both cohorts and a Thyroid Histomorphologic PHTS Score (THiPS) system was established with a cutoff of 4 points or higher being considered concerning for PHTS. In all, 27 PHTS (90%) and five control (16.1%) cases had THiPS ≥4. A PTEN immunohistochemical stain was evaluated in 25 cases of each cohort and showed nuclear and cytoplasmic loss of expression in all or most of the nodules of 24/25 PHTS cases. In 3/25 control cases, two with THiPS ≥4, had loss of expression in one to multiple nodules. Conventional papillary thyroid carcinomas in PHTS patients retained PTEN cytoplasmic expression. CONCLUSIONS: Our study supports that, although not specific, the finding of multiple histologic features is found more frequently in patients with PHTS compared to the non-PHTS control group. The THiPS system has high sensitivity for thyroid specimens from patients with PHTS.

Salivary duct carcinoma with squamous differentiation: histomorphological and immunophenotypical analysis of six cases.

BACKGROUND AND AIMS: Salivary duct carcinoma (SDC) is an aggressive salivary malignancy with multiple morphological subtypes. Primary salivary squamous cell carcinoma (SCC) requires exclusion of high-grade salivary malignancies and metastatic disease and is considered exceptionally rare. We report six cases of SDC with resemblance to SCC on account of variable, but often extensive, squamous differentiation. METHODS AND RESULTS: A retrospective review (2009-2023) at two institutions of SDC with histological and immunophenotypical evidence of squamous differentiation identified six cases. Medical charts and available glass slides were reviewed. There were five males and one female with a median age of 63 years, with tumours involving the parotid (five of six) and submandibular (one of six) glands. All six tumours showed a conventional SDC component comprising < 5-90% of viable tumour. Squamous differentiation comprised 10-95%+ (> 75% in three of six cases) of total viable tumour, and demonstrated CK5/6, p63 and/or p40 immunoexpression in all cases. A sarcomatoid component, comprising 10-60% of viable tumour, was present in three of six (50%) cases. All tumours were androgen receptor (AR)-positive, but only two of six (33.3%) retained AR immunoreactivity in the squamous component. Metastatic SDC to regional lymph nodes exhibited exclusive squamous differentiation in two of six (33.3%) cases. CONCLUSION: Squamous differentiation, histologically and immunophenotypically, can be extensive in SDC. AR expression may be lost in the squamous component and metastases may demonstrate only squamous differentiation. These findings cast further doubt on the existence of primary salivary SCC. SDC should be considered whenever encountering a carcinoma with squamous differentiation in major salivary glands or within cervical lymph nodes in the setting of a salivary mass.

Extramammary Paget Disease of Oral Mucosa: Case Report with Literature Review.

Extramammary Paget disease (EPMD) of the oral mucosa is an unusual and extremely rare condition, with fewer than ten cases documented. Here, we report a case of EMPD extensively involving oral mucosa and underlying salivary ducts in a 72-year-old male and review published clinical, histologic, immunophenotypic, and prognostic features of this rare entity.

Human papillomavirus 16/18/45 are not the most frequent genotypes in African American women: analysis in cervical Papanicolaou smears of women in an inner-city hospital.

INTRODUCTION: Cervical cancer is considered the most common human papillomavirus (HPV)-associated disease in women. Primary and secondary prevention methods have been established through Pap tests, HPV molecular testing, and vaccines. Although the most common high-risk HPV (HR-HPV) genotypes in the United States are 16, 18, and 45, there is reported ethnic disparity in the distribution of these genotypes. MATERIALS AND METHODS: Data analysis of HPV genotype results on cervical pap tests in our institution between late 2018 and early 2020 was performed. The distribution of HPV genotypes in each Bethesda category was evaluated. RESULTS: A total of 13,160 smears were evaluated; 75.5% were from African American women. Of those tested for HR-HPV (10,060), 1412 (14%) were HR-HPV positive. In all diagnostic categories of the Bethesda classification system, non-16/18/45 HR-HPV genotypes were more prevalent, ranging from 60.8% even in high-grade squamous intraepithelial lesion to 90.4% in negative for intraepithelial lesion or malignancy. CONCLUSIONS: In this study with a predominantly African American population, non-16/18/45 HR-HPV genotypes were prevalent in the majority (60.8%) of high-grade squamous intraepithelial lesion cases. Ethnic variability should be considered when deciding which HPV genotypes to integrate into the HPV vaccine.

Sebaceous Lymphadenoma: Radiology-Pathology Correlation.

Sebaceous lymphadenoma is a rare salivary gland neoplasm most commonly occurring in the sixth to eighth decades of life. Cross sectional imaging typically demonstrates a multicystic expansile mass, most commonly occurring in the parotid gland, where the radiographic differential diagnosis would include Warthin tumor in this location and age group. Ultimately, the diagnosis is confirmed with the histopathologic findings of tubuloglandular epithelial profiles with sebaceous differentiation and cystic change set within a dense, benign lymphocytic infiltrate. These features are exemplified in this sine qua non radiology-pathology correlation article.