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Summary: We report the case of an 88-year-old man hospitalized for COVID-19 with persistently very high procalcitonin (proCt) levels despite infection resolution. Since proCt is an adjunct tumor marker in the diagnosis of medullary thyroid carcinoma (MTC), serum calcitonin (Ct) was also measured showing very high levels. Computed tomography (CT) scan showed the presence of a thyroid mass and neck ultrasound revealed a solid isoechoic, inhomogeneous, 50 mm nodule in the right thyroid lobe, extended into the mediastinum. Fine needle aspiration (FNA) of the thyroid nodule confirmed the diagnosis of MTC. An 18F-fluorodopa positron emission tomography/computed tomography (PET/CT) scan revealed the presence of distant metastases in ribs, vertebrae, in the right iliac wing and the liver. Since surgery was not feasible, the patient was started on cabozantinib 40 mg/dL. After 16 months the patient is still on cabozantinib at the same dose, he reports complete autonomy in daily life activities, and serum Ct is still elevated; however, the imaging evaluation does not show signs of disease progression. Learning points: High procalcitonin serum values despite the absence of infection are suggestive of MTC. Advanced MTC with multiple metastases can have an indolent course and can go unrecognized for years. Cabozantinib is a valuable option for the treatment of advanced MTC.
RESUMEN
BACKGROUND & AIMS: Germline variations in allele-specific expression (ASE) are associated with highly penetrant familial cancers, but their role in common sporadic cancers is unclear. ASE of adenomatous polyposis coli (APC) is associated with pathogenesis of familial adenomatous polyposis. We investigated whether moderate variations in ASE of APC contribute to common forms of colorectal cancer (CRC). METHODS: Denaturing high-performance liquid chromatography was used to analyze germline ASE of APC in blood samples from patients with CRC (cases, n = 53) and controls (n = 68). Means, medians, and variances of ASE were compared. Variants in the APC gene region also were analyzed. RESULTS: The distribution of ASE differed significantly between groups; cases had significantly larger amounts of variance than controls (P = .0004). Risk for CRC increased proportionally with the degree of deviation from the mean. The odds ratio for individuals with levels of ASE that deviated more than 1 standard deviation from the mean was 3.97 (95% confidence interval, 1.71-9.24; P = .001); for those with levels greater than 1.645 standard deviations, the odds ratio was 13.46 (95% confidence interval, 1.76-609.40; P = .005). Sequence analysis revealed that a patient with a high level of ASE who did not have a family history of CRC carried a nonsense mutation in APC (p.Arg216X). Genotype analysis of APC associated multiple single-nucleotide polymorphisms with ASE values and/or variance among cases, but not controls. Cis variants, therefore, might account for some of the variance in ASE of APC. CONCLUSIONS: Patients with CRC have a larger variance in germline levels of ASE in APC than controls; large distances from the mean ASE were associated with risk for common forms of CRC.