Thyroid Gland Medullary Carcinoma

P=N/A, N=40, Recruiting, M.D. Anderson Cancer Center | Suspended --> Recruiting

Herein, we present a rare case of MTC that caused hypercalcemia via PTHrP production. Although HHM is uncommon in thyroid cancer, the condition can cause severe hypercalcemia requiring prompt diagnosis and treatment. HHM should be considered in patients with thyroid cancer with hypercalcemia, and PTHrP measurement may aid in the diagnosis.

Upon re-evaluation one year later, imaging revealed recurrent paratracheal, pulmonary, hepatic, and possible adrenal metastases, prompting re-initiation of selpercatinib at a reduced dose, which she tolerated and continues to this day with surveillance of symptoms, serial electrocardiograms, laboratory work, and imaging. This case illustrates the aggressive course of RET M918T-mutated MEN2B and underscores the importance of early genetic diagnosis, vigilant surveillance, and continuity of selective RET inhibitor therapy to optimize disease control.

HRas proto-oncogene (HRAS) and STAG2 cohesin complex component (STAG2) were synchronously identified as the driver genes, while the OTUB2 deletion mutation may contribute to tumor proliferation and disease progression in TCTs.

P2, N=137, Active, not recruiting, Canadian Cancer Trials Group | Trial completion date: Dec 2025 --> Jun 2026

However, QTc prolongation occurred in both of our patients, suggesting that it may represent a clinically relevant concern in selected individuals. Appropriate dose adjustment and careful monitoring may facilitate continued treatment in selected patients.

P=N/A, N=40, Suspended, M.D. Anderson Cancer Center | Initiation date: Dec 2025 --> Aug 2025 | Not yet recruiting --> Suspended

P3, N=291, Active, not recruiting, Loxo Oncology, Inc. | Trial completion date: Feb 2026 --> Nov 2027

These proteins showed increased stability and their expression in an MTC cell line increased cell proliferation and clonogenic capacity, supporting an oncogenic role. These findings expand the genetic background of fMTC beyond RET mutations and implicate translation reinitiation in the etiology of cancer susceptibility syndromes secondary to structural genomic variants.

We propose a clinician-facing three-panel workflow: Panel A standardizes initial evaluation and mandates germline RET testing for all patients; Panel B outlines genotype- and staging-informed surgery and surveillance for hereditary disease, including pediatric carriers; and Panel C provides a staged approach for sporadic MTC in which imaging directs compartment selection and early postoperative DSR and biochemical response tailor surveillance intensity and thresholds for re-staging and re-intervention. By aligning decision nodes with real-world scenarios and using consistent surgical terminology, this framework offers a testable blueprint for precision surgery, surveillance stratification, and genotype-directed systemic therapy.

P=N/A, N=0, Active, not recruiting, Eli Lilly and Company | Recruiting --> Active, not recruiting

CD15 demonstrates high specificity for PTC. However, its limited sensitivity and variable expression in follicular-patterned lesions make its prognostic value unclear. CD15 should not be used as a standalone marker; instead, it may improve diagnostic accuracy when combined with other markers in multiparametric immunohistochemical panels.