Thyroid Gland Medullary Carcinoma

Dynamic changes in ProGRP were more strongly associated with adverse outcomes than traditional markers in advanced medullary thyroid carcinoma and may reflect aggressive tumor behavior not captured by CT. Due to the limited number of disease-related deaths, hazard ratio estimates for overall survival were imprecise and prospective validation in larger cohorts is warranted.

P1, N=16, Not yet recruiting, University of Pennsylvania

This article reviews genotype-phenotype correlations, clinical manifestations, and current therapeutic strategies, including the use of selective tyrosine kinase inhibitors. In addition, we propose an algorithm for the treatment of advanced medullary thyroid carcinoma and metastatic pheochromocytoma.

Upon evaluation of the cervical lymph nodes, metastatic medullary carcinoma was noted. Confirmation of the presence of calcitonin in the MTC component and thyroglobulin expression in the PTC component through immunohistochemistry illustrated the importance of using meticulous histopathological and immunohistochemical analysis in making accurate diagnoses and providing individualized treatment options.

Systematic genetic screening and counselling are essential for the early diagnosis and appropriate management of MEN2A, particularly in sporadic cases. Broader implementation of molecular testing and genetic counselling in Algeria is recommended to improve patient outcomes and prevent transmission to future generations.

Compared with the detection of either marker alone, the combined detection of Ctn and CEA improved the diagnostic accuracy for MTC but did not enhance the PPV. The combined detection also improved the predictive accuracy for cervical and lateral lymph node metastases and disease recurrence.

Resistance to RET inhibitors can be acquired through RET copy-number gain and secondary mutations as well as NF1 loss-mediated MAPK pathway activation. This mechanism of resistance can be overcome with dual inhibition of RET and downstream RAS/MAPK signaling, demonstrating clinical potential in RET-mutant MTC.

Among cases with follow-up data (n=35), all 17 tumors with disease progression were DLL3 positive (13 RET-mutated tumors, 1 RAS-mutated tumor, and 3 RET/RAS wild-type tumors), including 5 with moderate expression and 12 with high expression. Most MTCs express DLL3; moreover, DLL3 expression is associated with lymph node metastases at diagnosis and disease progression, indicating that DLL3 may be an effective therapeutic target in MTC.

The present investigation suggests that tumor progression in MTC before clinical detection is a function of the time passed since tumor onset, whereas tumor onset is defined by the transformatory strength of the RET mutation. This notion, debunking the myth of immanent tumor 'aggressiveness' or "risk" imparted by RET mutations in favor of the concept of genetically encoded tumor onset, emphasizes the need for early diagnosis and intervention, ideally while tumors are still confined to the thyroid.

This study proposes an evidence-based imaging algorithm for radiologists according to serum markers, tracer advantages and theranostic needs. Further prospective trials, standardized SSTR thresholds and investigations of novel tracers are still required to fill existing research gaps.

P=N/A, N=51, Not yet recruiting, British Columbia Cancer Agency

B7-H3 was identified as the only consistently and strongly expressed surface antigen in a clinically heterogeneous MTC cohort. These findings identify B7-H3 as a potential therapeutic opportunity for advanced MTC and underscore the limited number of targetable surface antigens in this disease.