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Genotype–Phenotype Correlation in Indian Patients with MEN2-Associated Pheochromocytoma and Comparison of Clinico-Pathological Attributes with Apparently Sporadic Adrenal Pheochromocytoma

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Abstract

Introduction

Pheochromocytoma (PCC) manifests in up to 50 % of MEN2 patients. We correlated the clinico-pathological features of MEN2-associated PCC (MEN-PCC) with RET mutations and compared them with non-MEN adrenal-PCCs.

Methods

In this retrospective single institution study on a large PCC database (n = 208, 1997–2014) 24 MEN-PCC patients with known RET mutations were reviewed. Excluding 7 with incomplete data, the study cohort of 17 MEN-PCC patients from 11 kindreds (M:F::7:10) was identified. Clinical, biochemical, pathological attributes, and outcomes in the MEN-PCC group were correlated with the genotype, and further compared with non-MEN, apparently sporadic adrenal-PCCs (n = 132, excluding 37 extra-adrenal and 15 VHL/NF1/SDH-associated PCC).

Results

Components of MEN2 encountered included MTC in 13(76.5 %), Marfanoid habitus in 2, and PHPT, cutaneous lichen amyloidosis and mucosal neuromas in 1 patient each. In 11(64.7 %), PCC was the first detected MEN2 component (Symptomatic:8, Incidentaloma:3). Four (23.5 %) were normotensive; 8(47.1 %) had bilateral PCC (7 synchronous, 1 metachronous). Surgery for PCC included laparoscopic adrenalectomy in 12; and cortical-sparing adrenalectomy in 2 of 8 bilateral PCC patients. Mean MEN-PCC tumor size was 6.9 ± 3.9 cm, and 6(35 %) had additional adrenal medullary hyperplasia. Four different genotypes were encountered, commonest involving codon 634, others being 804 and 918. Mean age in MEN-PCC (27.7 ± 12.2 years) was lower than non-MEN PCC (39.4 ± 15.7, p = 0.018). Proportion of pediatric patients (35.3 % in MEN-PCC vs. 12.9 % in non-MEN-PCC, p = 0.007), bilateral tumors (47.1 % in MEN-PCC, 4.5 % in non-MEN-PCC, p < 0.001), and adrenal medullary hyperplasia (35.2 % in MEN-PCC, 0.7 % in non-MEN-PCC, p < 0.001) were different. Median 24-hour urinary metanephrines was significantly higher in index MEN-PCC patients, than non-MEN-PCC (634 vs. 214 mcg/24 h, p value = 0.006), but was non-significantly higher in non-index MEN-PCC patients. Mean tumor sizes were comparable in the two groups. None of MEN-PCC patients had malignant PCC, compared to 7(5.3 %) in non-MEN-PCC.

Conclusions

In this cohort of MEN-PCC from India, the commonest causative RET mutations for MEN-PCC involved codon 634. MEN-PCC patients were younger, and more frequently had bilateral PCC than non-MEN disease. MEN-PCC patients in India are diagnosed with large tumors and extremely high catecholamine/metanephrine levels.

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    Authors and Affiliations

    1. Department of Endocrine & Breast Surgery, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Rae Bareilly Road, Lucknow, 226014, Uttar Pradesh, India

      Sendhil Rajan, Gaurav Agarwal, Anjali Mishra, Amit Agarwal & Saroj Kanta Mishra

    2. Department of Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Lucknow, Uttar Pradesh, India

      Ghazala Zaidi & Eesh Bhatia

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    1. Sendhil Rajan
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    2. Ghazala Zaidi
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    Correspondence to Gaurav Agarwal.

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    Drs. Sendhil Rajan and Ghazala Zaidi have contributed equally to this work, and should be considered joint first authors.

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    Rajan, S., Zaidi, G., Agarwal, G. et al. Genotype–Phenotype Correlation in Indian Patients with MEN2-Associated Pheochromocytoma and Comparison of Clinico-Pathological Attributes with Apparently Sporadic Adrenal Pheochromocytoma. World J Surg 40, 690–696 (2016). https://doi.org/10.1007/s00268-015-3255-6

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