Expanding the spectrum of thyroid carcinoma with somatic DICER1 mutation: a survey of 829 thyroid carcinomas using MSK-IMPACT next-generation sequencing platform.

DICER1 gene encodes an RNaseIII endoribonuclease essential for the cleavage of pre-microRNA to mature microRNA. Germline DICER1 mutation results in DICER syndrome, a cancer predisposition syndrome which manifests in the thyroid gland as early-onset multinodular goiter and increased risk for differentiated thyroid carcinoma. Recently, somatic DICER1 mutations were described in various thyroid neoplasms, including follicular adenoma, papillary thyroid carcinoma, follicular carcinoma, and poorly differentiated thyroid carcinoma. In this study, we identified and described 14 cases (1.7%) with somatic DICER1 mutations from a cohort of 829 patients with thyroid follicular cell-derived thyroid carcinomas which were sequenced using MSK-IMPACT targeted next-generation sequencing platform. We expanded the histologic spectrum of thyroid carcinomas with somatic DICER1 mutations to include Hurthle cell carcinoma, high-grade differentiated thyroid carcinoma, and anaplastic thyroid carcinoma. All patients were adults with a median age of diagnosis of 59 years (range: 22-82). Although rare, a subset of thyroid cancers, including the aggressive subtypes, display somatic DICER1 mutations, some of which have oncogenic potential.

Clinicopathologic Characteristics of Young Patients with Oral Squamous Cell Carcinoma.

Oral squamous cell carcinoma (OSCC) occasionally occurs in young patients and is likely to be distinct from OSCC in older patients. In this retrospective study, we described the clinicopathologic features and outcome of 150 OSCCs that were diagnosed in patients 40-year-old or younger. Most patients (63%) were non-smokers. The most common site of the primary tumor was oral tongue (n = 131, 87%), followed by gingiva (n = 9), buccal mucosa (n = 8) and lip (n = 2). The median patients' age at presentation was 34 (range: 16-40). Seven patients (5%) had Fanconi anemia with the gingiva being the most common location (4/7, 57%). All OSCCs were of keratinizing type. All cases tested for high-risk HPV (n = 34) were negative. On univariate analysis, high tumor budding was associated with decreased overall survival (OS) and distant metastasis free survival (DMFS), pattern of invasion correlated with OS and tumors with high stromal tumor infiltrating lymphocytes (sTIL) were associated with improved locoregional recurrence free survival (LRFS). Compared with patients 31 to 40-year-old, OSCC in the younger group was associated with significant less alcohol consumption (p = 0.011) and decreased DSS (p = 0.003) and DMFS (p = 0.023). On multivariate analysis, younger age (30 years or younger) was an independent prognostic factor for worse OS and DSS, whereas histologic grade was an independent prognostic factor for DSS. In summary, most OSCC in young patients occurred in non-smokers and did not occur in association with Fanconi anemia. Independent prognostic factors included age at presentation (30 years or younger) for OS and DSS, and histologic grade for DSS.

Metastasis to the thyroid gland: a single-institution 16-year experience.

AIMS: Metastasis to the thyroid gland is a rare occurrence that may pose a diagnostic challenge. In this study, we aimed to report the clinicopathological features, immunoprofile, molecular alterations and outcome of 30 patients treated at our centre from 2003 to 2019. METHODS AND RESULTS: The most common site of the primary tumour was the kidney, followed by the lung, lower gastrointestinal tract and breast. In seven (23%) patients, the thyroid metastases were resected prior to the diagnosis of the primary tumours. Six patients (20%) had thyroid as the sole metastatic site. Three (10%) patients harboured tumour-to-tumour metastasis; 71% had a unilateral unifocal thyroid mass, which might be mistaken for a primary thyroid tumour. Among the 13 cases that were initially diagnosed at an outside hospital, four (31%) were misinterpreted as a thyroid primary. An immunohistochemical panel of thyroid follicular cell markers was most useful to differentiate primary thyroid tumours from metastasis. Molecularly, the metastasis showed alterations characteristic of the primary tumour, which may be helpful in establishing the diagnosis and primary site. Although the prognosis was poor, with a 5-year disease specific survival of 58%, a long-term cure was possible in cases with oligometastasis successfully treated with surgery. CONCLUSIONS: Metastasis to the thyroid gland is an uncommon phenomenon, with an incidence of 0.36% in all thyroid malignancies. It may present as a solitary thyroid mass before the discovery of the primary tumour, posing a diagnostic challenge. Although the overall prognosis is poor, a subset of patients with oligometastasis can be managed surgically.