Metastatic cluster 2-related pheochromocytoma/paraganglioma: a single-center experience and systematic review

Objective: Risk of metastatic disease in the cluster 2-related pheochromocytoma/paraganglioma (PPGL) is low. In MEN2 patients, identification of origin of metastases from pheochromocytoma (PCC) or medullary thyroid carcinoma (MTC) is challenging as both are of neuroendocrine origin. We aim to describe our experience and perform a systematic review to assess prevalence, demographics, biochemistry, diagnostic evaluation, management and predictors of cluster 2-related metastatic PPGL. Design: Retrospective study with systematic review of literature. Methods: Data of 3 cases from our cohort and 43 cases from world literature were analyzed. For calculation of prevalence, all reported patients (n=3063) of cluster 2 were included. Results: The risk of metastasis in cluster 2-related PPGL was 2.6% (2% in RET, 5% in NF1, 4.8% in TMEM127 and 16.7% in MAX variation). In metastatic PCC in MEN2, median age was 39 years, bilateral tumors were present in 71% and median tumor size was 9.7 cm (range 4-19) with 43.5% mortality. All patients had primary tumor size ≥4cm. Origin of primary was diagnosed by histopathology of metastatic lesion in 11(57.9%), 131I-MIBG scan in 6(31.6%), and selective venous sampling and computed tomography in one (5.3%) each. In subgroup of NF1, median age was 46 years (range 14-59) with median tumor size 6cm and 57% mortality. Conclusion: The risk of metastatic disease in cluster 2-related PPGL is 2.6%, being especially high in tumors with size ≥4cm and is associated with high mortality. One-third patients of NF1 with metastatic PPGL had presented in 2nd decade of life. Long-term studies are needed to formulate management recommendations.

PRIMARY HYPOTHYROIDISM IN A HIGH-RISK NEUROBLASTOMA PATIENT AFTER 131I-MIBG THERAPY: A CLINICAL CASE REPORT AND LITERATURE REVIEW

In recent decades, there has been marked progress in understanding the biology of the most common extracranial solid tumor of childhood – neuroblastoma (NB), which led to a significant improvement in treatment outcomes due to stratification of patients into risk groups, intensification of treatment of patients with metastatic disease and the presence of unfavorable molecular genetic markers. Survivors who have received multimodal therapies, including chemotherapy, high-dose therapy and autologous peripheral stem-cell transplantation, 131I-metaiodobenzylguanidine (131I-MIBG) therapy, radiation therapy, and immunotherapy have a high risk of developing long-term side effects of treatment (LT SE). The study of the nature and frequency of LT SE after completion of therapy in patients with NB is important to ensure the quality of life and minimize severe health disorders. This article presents a literature review and description of a clinical case report of primary hypothyroidism in a high-risk patient with NB who received multicomponent treatment, including 131I-metaiodobenzylguanidine therapy due to the persistence of MIBG-positive foci after the induction chemotherapy.