Abstract
We hereby present a rare variant of multiple endocrine neoplasia type 2A (MEN2A) associated with a rare skin disease primary cutaneous lichen amyloidosis and discrete malignant pheochromocytoma in both adrenal glands and pancreatic tail, and interestingly accompanied ganglioneuroma located in retroperitoneum in a 34-yr-old female. The presence of composite tumor of pheochromocytoma and ganglioneuroma arising in the adrenal glands has been described previously in MEN2A and in sporadic cases. The patient displayed classical signs and symptoms of catecholamine excess. Biochemical screening proved pheochromocytoma. Computed tomography revealed multiple mass lesions in both adrenal glands. It also showed a large heterogeneous mass that clearly discriminated from right adrenal gland in retroperitoneal location. After surgical exploration, both adrenal glands and the suspicious mass in pancreatic tail were removed successfully together with subtotal resection of the retroperitoneal tumor. Histopathologic examinations confirmed the presence of pheochromocytoma in both adrenal glands as well as pancreatic lesion. A retroperitoneal ganglioneuroma was also present. Symptomatic and biochemical evidence of pheochromocytoma subsided after the operation. Further evaluation for medullary thyroid carcinoma and primary hyperparathy-roidism confirmed MEN2A. Mutation analysis of the ret proto-oncogene revealed a missense point mutation at position 634 in exon 11, which gives rise to the substitution of a cysteine codon with a tyrosine residue.
Similar content being viewed by others
References
Padberg BC, Holl K, Schroder S. Pathology of multiple endocrine neoplasia 2A and 2B. Horm Res 1992, 38(Suppl 2): 24–30.
Raue F, Frank-Raue K, Grauer A. Multiple endocrine neoplasia type 2, clinical features and screening. Endocrinol Metab Clin North Am 1994, 23: 137–56.
Chabre O, Labat F, Pinel N, Berthod F, Tarel V, Bachelot I. Cutaneous lesion associated with multiple endocrine neoplasia type 2A: Lichen amyloidosis or notalgia paresthetica? Henry Ford Hosp Med J 1992, 40: 245–8.
Ceccherini I, Romei C, Barone V, et al. Identification of the Cys634->Tyr mutation of the RET proto-oncogene in a pedigree with multiple endocrine neoplasia type 2A and localized cutaneous lichen amyloidosis. J Endocrinol Invest 1994,17: 201–4.
Gagel RF, Levy ML, Donovan DT, Alford BR, Wheeler T, Tschen JA. Multiple endocrine neoplasia type 2a associated with cutaneous lichen amyloidosis. Ann Intern Med 1989, 111: 802–6.
Nunziata V, Giannattasio R, Di Giovanni G, D’Armiento MR, Mancini M. Hereditary localized pruritus in affected members of a kindred with multiple endocrine neoplasia type 2A (Sipple syndrome). Clin Endocrinol (Oxf) 1989, 30: 57–63.
Ferrer JP, Halperin I, Conget I, et al. Primary localized cutaneous amyloidosis and familial thyroid carcinoma. Clin Endocrinol (Oxf) 1991, 34: 435–9.
Bugalho MJGM, Limbert E, Sobrinho LG, et al. A kindred with multiple endocrine neoplasia type 2A associated with pruritic skin lesions. Cancer 1992, 70: 2664–7.
Robinson MF, Furst E, Nunziata V, et al. Characterization of the clinical features of five families with hereditary primary cutaneous lichen amyloidosis and multiple endocrine neoplasia type 2. Henry Ford Hosp Med J 1992, 40: 249–55.
Pacini F, Fugazzola L, Bevilacqua G, et al. Multiple endocrine neoplasia type 2Aand cutaneous lichen amyloidosis: Description of a new family. J Endocrinol Invest 1993, 16: 295–6.
Seri M, Celli I, Betsos N, Claudiani F, Camera G, Romeo G. A Cys634Gly substitution of the RET proto-oncogene in a family with recurrence of multiple endocrine neoplasia type 2A and cutaneous lichen amyloidosis. Clin Genet 1997, 51: 86–90.
Kousseff B, Espinoza C, Zamore GA. Sipple syndrome with lichen amyloidosis as a paracrinopathy: pleiotropy, heterogeneity, or a contigous gene? J Am Acad Dermatol 1991, 25: 651–7.
Lemos MC, Carrilho F, Rodrigues FJ, et al. Early onset of medullary thyroid carcinoma in a kindred with multiple endocrine neoplasia type IIA associated with cutaneous lichen amyloidosis. Endocr Pract 2002, 8: 19–21.
Vasily DB, Bhatia SG, Uhlin SR. Familial primary cutaneous amyloidosis. Clinical, genetic, and immunofluorescentstudies. Arch Dermatol 1978, 114: 1173–6.
Mulligan LM, Kwok JB, Healey CS, et al. Germ-line mutations of the RET protooncogene in multiple endocrine neoplasia type 2A. Nature 1993, 363: 458–60.
Donis-Keller H, Dou S, Chi D, et al. Mutations in RET protooncogene are associated with MEN 2A and FMTC. Hum Mol Genet 1993, 2: 851–6.
Romeo G, McKusick VA. Phenotypic diversity, allelic series and modifier genes. Nature Genet 1994, 7: 451–3.
Hofstra RM, Sijmons RH, Stelwagen T, et al. RET mutation screening in familial cutaneous lichen amyloidosis and in skin amyloidosis associated with multiple endocrine neoplasia. J Invest Dermatol 1996, 107: 215–8.
Dietrich WF, Lander ES, Smith JS, et al. Genetic identification of Mom-1, a major modifier locus affecting Min-induced intestinal neoplasia in the mouse. Cell 1993, 75: 631–9.
Howe JR, Norton JA, Wells SA Jr. Prevalence of pheochro-mocytoma and hyperparathyroidism in multiple endocrine neoplasia type 2A: results of long-term followup. Surgery 1993, 4: 1070–7.
Neumann HP, Berger DP, Sigmund G, et al. Pheochromocytomas, multiple endocrine neoplasia type 2, and von Hip-pel-Lindau disease. N Engl J Med 1993, 329: 1531–8.
Umemoto Y, Ito T, Tsugaya M, et al. Composite pheochro-mocytoma with ganglioneuroma in the adrenal gland: a case report. Hinyokika Kiyo 1998, 44: 575–7.
Brady S, Lechan RM, Schwaitzberg SD, Dayal Y, Ziar J, Tischler AS. Composite pheochromocytoma/ganglioneuroma of the adrenal gland associated with multiple endocrine neoplasia 2A: case report with immunohistochemical analysis. Am J Surg Pathol 1997, 21: 102–8.
Califano D, D’Alessio A, Colucci-D’Amato GL, et al. A potential pathogenetic mechanism for multiple endocrine neoplasia type 2 syndromes involves ret-induced impairment of terminal differentiation of neuroepithelial cells. Proc Natl Acad Sci USA 1996, 93: 7933–7.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Gullu, S., Gursoy, A., Erdogan, M.F. et al. Multiple endocrine neoplasia type 2A/localized cutaneous lichen amyloidosis associated with malignant pheochromocytoma and ganglioneuroma. J Endocrinol Invest 28, 734–737 (2005). https://doi.org/10.1007/BF03347557
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/BF03347557