Chromophobe thyroid carcinoma (CTC) is a rare thyroid carcinoma with distinct morphology, often occurring in patients with tuberous sclerosis complex (TSC). The molecular drivers remain poorly understood. We report two additional CTC cases and review the literature including genetic query. Patient 1, an 11-year-old boy, had a 10.3-cm bilateral thyroid mass with tumoral capsular and vascular invasion. Microscopically, the tumor showed trabecular and nested growth, prominent cell membranes, raisinoid nuclei, eosinophilic granular cytoplasm, and perinuclear halos resembling chromophobe renal cell carcinoma. The tumor expressed thyroid markers (TTF-1, PAX-8, thyroglobulin) and renal cell markers (colloidal iron, parvalbumin, CD117) with peripheral mitochondrial accentuation by anti-mitochondrial staining. A somatic TSC2 p.Y1650Cfs*4 frameshift mutation was identified. Patient 2, a 24-year-old woman, had a 3.8-cm infiltrative, angioinvasive right lobe tumor with similar morphology and marker expression and positive lymph nodes. Molecular analysis showed somatic TSC2 c.2071dupC p.R691Pfs*12 and TSC2 c.2353C > T p.Q785* mutations. A cBioPortal query (2285 cases) found TSC1 alterations in 2% and TSC2 in 1%, mostly deletions, enriched in poorly differentiated and anaplastic thyroid carcinomas. Literature review identified seven CTC cases; 42.8% had TSC association and 42.8% showed locoregional recurrence. Median follow-up of 36 months showed all patients alive. Common morphologic and immunophenotypic features were consistent; 85.7% exhibited vascular invasion. None harbored common mutations like BRAF p.V600E and RAS. CTC is a distinct, rare thyroid carcinoma often linked to TSC or TSC mutations, characterized by unique morphology and immunophenotype.

Intrathyroidal thymic carcinoma is a rare thyroid carcinoma characterized by thymic epithelial differentiation. Given its relatively favorable prognosis, it is essential to differentiate it preoperatively from other more aggressive tumors. Fine-needle aspiration is widely used for the preoperative diagnosis of thyroid nodules. However, there is limited information on the cytological diagnosis, and its cytomorphological features remain poorly characterized. We perform a literature review of intrathyroidal thymic carcinoma and briefly describe two cases to further characterize its cytological features.

Medullary thyroid cancer (MTC) is a rare thyroid carcinoma that often presents at an advanced stage. The efficacy of adjuvant postoperative radiotherapy (PORT) in treating MTC remains a topic of debate. We aimed to assess whether PORT enhances survival outcomes in patients with MTC. We conducted a systematic review of databases, including EMBASE, PubMed, Cochrane Library, and CINAHL to identify relevant studies. Hazard ratios (HRs) and 95% confidence intervals (CIs) for overall survival (OS) and local recurrence-free survival (LRFS) were extracted, and pooled analyses were performed using random-effects models. Ten studies were finally included. Two separate pooled analyses of OS revealed no statistically significant differences between the PORT and observation groups (HR 1.59, 95% CI 0.87-2.92 and HR 1.67, 95% CI 0.92-3.02, including two different National Cancer Database studies with overlapping periods, respectively). Similarly, no significant differences were noted for LRFS (HR 0.90, 95% CI 0.44-1.82; I2 = 0%, p = 0.442). Although PORT did not demonstrate significant differences in survival outcomes compared to observation, personalized treatment considerations are essential due to heterogeneity among high-risk patients. Further prospective studies are required to define optimal adjuvant treatment strategies for MTC.

Spindle epithelial tumor with thymus-like element should be included in the differential diagnosis of thyroid gland cancers, particularly in medullary carcinoma, younger patients and indolent clinical presentation, because it may influence treatment and prognosis.

Cribriform-morular thyroid carcinoma is a rare type of thyroid cancer. It has a strong association with familial adenomatous polyposis (FAP), a hereditary genetic disorder that predisposes individuals to the development of numerous polyps in the colon and rectum. We describe the case of a young female patient who presented with an enlarging goiter, notably without detectable thyroid nodules or masses on ultrasound, who after total thyroidectomy was found to have cribriform-morular thyroid carcinoma. This diagnosis led to genetic testing and diagnosis of FAP syndrome. We demonstrate that this rare thyroid carcinoma may present with nonsuspicious findings on sonographic evaluation while being a valuable harbinger in the diagnosis of FAP syndrome.