Skip to main content
Top
Published in: Familial Cancer 2/2020

01-04-2020 | Hyperparathyroidism | Short Communication

Co-occurrence of multiple endocrine neoplasia type 4 and spinal neurofibromatosis: a case report

Authors: Pamela Brock, Jean Bustamante Alvarez, Amir Mortazavi, Sameek Roychowdhury, John Phay, Raheela A. Khawaja, Manisha H. Shah, Bhavana Konda

Published in: Familial Cancer | Issue 2/2020

Login to get access

Abstract

Multiple Endocrine Neoplasia (MEN) type 4 is a rare genetic condition that results from variants of the CDKN1B gene and predisposes individuals to develop endocrine tumors. Spinal neurofibromatosis (SNF) is an uncommon subtype of neurofibromatosis type 1 (NF1) characterized by bilateral neurofibromas of all spinal roots. Here we report a case of the co-occurrence of these syndromes, which has not yet been described in the literature. A male in his 60s presented with Gleason 5 + 4 localized prostate adenocarcinoma treated with radical prostatectomy. Two years later, he developed liver and bone metastasis consistent with trans-differentiation into small cell carcinoma. He developed hypercalcemia due to primary hyperparathyroidism from a parathyroid adenoma treated surgically. His family history was significant for a first-degree relative with a clinical diagnosis of NF1 and several second-degree relatives with multiple café-au-lait macules. Spine MRI showed multiple bilateral neurofibromas. Germline genetic testing showed a pathogenic variant in the CDKN1B gene, a variant in the NF1 gene, and a normal MEN1 gene. In this rare case of MEN4 and SNF, the patient was asymptomatic for much of his life. In addition to parathyroid adenoma and spinal neurofibromas, he had prostate adenocarcinoma with trans-differentiation into metastatic small cell cancer. Whether this diagnosis was coincidental or related to an emerging phenotype remains to be elucidated.
Literature
1.
go back to reference Alrezk R, Hannah-Shmouni F, Stratakis CA (2017) MEN4 and CDKN1B mutations: the latest of the MEN syndromes. Endocr Relat Cancer 24(10):T195–T208CrossRef Alrezk R, Hannah-Shmouni F, Stratakis CA (2017) MEN4 and CDKN1B mutations: the latest of the MEN syndromes. Endocr Relat Cancer 24(10):T195–T208CrossRef
2.
go back to reference Pellegata N, Quintanilla-Martinez L, Siggelkow H, Samson E, Bink K, Hofler H, Fend F, Graw J, Atkinson M (2006) Germ-line mutations in p27Kip1 cause a multiple endocrine neoplasia syndrome in rats and humans. Proc Natl Acad Sci USA 103(42):15558–15563CrossRef Pellegata N, Quintanilla-Martinez L, Siggelkow H, Samson E, Bink K, Hofler H, Fend F, Graw J, Atkinson M (2006) Germ-line mutations in p27Kip1 cause a multiple endocrine neoplasia syndrome in rats and humans. Proc Natl Acad Sci USA 103(42):15558–15563CrossRef
3.
go back to reference Pulst S, Riccardi V, Fain P, Korenberg J (1991) Familial spinal neurofibromatosis: clinical and DNA linkage analysis. Neurology 41:1923–1927CrossRef Pulst S, Riccardi V, Fain P, Korenberg J (1991) Familial spinal neurofibromatosis: clinical and DNA linkage analysis. Neurology 41:1923–1927CrossRef
4.
go back to reference Corsello G, Antona V, Serra G, Zara F, Giambrone C, Lagalla L, Piccione M, Piro E (2018) Clinical and molecular characterization of 112 single-center patients with Neurofibromatosis type 1. Ital J Pediatr 44(1):45CrossRef Corsello G, Antona V, Serra G, Zara F, Giambrone C, Lagalla L, Piccione M, Piro E (2018) Clinical and molecular characterization of 112 single-center patients with Neurofibromatosis type 1. Ital J Pediatr 44(1):45CrossRef
5.
go back to reference Frederiksen A, Rossing M, Hermann P, Ejersed C, Thakker R, Frost M (2019) Clinical features of multiple endocrine neoplasia type 4: novel pathogenic variant and review of published cases. J Clin Endocrinol Metab 104(9):3637–3646CrossRef Frederiksen A, Rossing M, Hermann P, Ejersed C, Thakker R, Frost M (2019) Clinical features of multiple endocrine neoplasia type 4: novel pathogenic variant and review of published cases. J Clin Endocrinol Metab 104(9):3637–3646CrossRef
6.
go back to reference Agarwal S, Kester M, Debelenko L, Heppner C, Emmert-Buck M, Skarulis M, Doppman J, Kim Y, Lubensky I, Zhuang A et al (1997) Germline mutations of the MEN1 gene in familial multiple endocrine neoplasia type 1 and related states. Hum Mol Genet 6(7):1169–1175CrossRef Agarwal S, Kester M, Debelenko L, Heppner C, Emmert-Buck M, Skarulis M, Doppman J, Kim Y, Lubensky I, Zhuang A et al (1997) Germline mutations of the MEN1 gene in familial multiple endocrine neoplasia type 1 and related states. Hum Mol Genet 6(7):1169–1175CrossRef
7.
go back to reference European Consortium on MEN1 (1997) Identification of the multiple endocrine neoplasia type 1 (MEN1) gene. Hum Mol Genet 6:1177–1183CrossRef European Consortium on MEN1 (1997) Identification of the multiple endocrine neoplasia type 1 (MEN1) gene. Hum Mol Genet 6:1177–1183CrossRef
8.
go back to reference Ellard S, Hattersley AT, Brewer CM, Vaidya B (2005) Detection of an MEN1 gene mutation depends on clinical features and supports current referral criteria for diagnostic molecular genetic testing. Clin Endocrinol 62(2):169–175CrossRef Ellard S, Hattersley AT, Brewer CM, Vaidya B (2005) Detection of an MEN1 gene mutation depends on clinical features and supports current referral criteria for diagnostic molecular genetic testing. Clin Endocrinol 62(2):169–175CrossRef
9.
go back to reference Walther M, Herring J, Enquiest E, Keiser H, Linehand W (1999) Von Recklinghausen’s disease and pheochromocytomas. J Urol 162:1582–1586CrossRef Walther M, Herring J, Enquiest E, Keiser H, Linehand W (1999) Von Recklinghausen’s disease and pheochromocytomas. J Urol 162:1582–1586CrossRef
10.
go back to reference Favere AM, Tsukumo DM, Matos PS, Santos SL, Lalli CA (2015) Association between atypical parathyroid adenoma and neurofibromatosis. Arch Endocrinol Metab 59(5):460–466CrossRef Favere AM, Tsukumo DM, Matos PS, Santos SL, Lalli CA (2015) Association between atypical parathyroid adenoma and neurofibromatosis. Arch Endocrinol Metab 59(5):460–466CrossRef
11.
go back to reference Ruggieri M, Polizzi A, Spalice A, Salpietro V, Caltabiano R, D’Orazi V, Pavone P, Pirrone C, Magro G, Platania N et al (2015) The natural history of spinal neurofibromatosis: a critical review of clinical and genetic features. Clin Genet 87(5):401–410CrossRef Ruggieri M, Polizzi A, Spalice A, Salpietro V, Caltabiano R, D’Orazi V, Pavone P, Pirrone C, Magro G, Platania N et al (2015) The natural history of spinal neurofibromatosis: a critical review of clinical and genetic features. Clin Genet 87(5):401–410CrossRef
Metadata
Title
Co-occurrence of multiple endocrine neoplasia type 4 and spinal neurofibromatosis: a case report
Authors
Pamela Brock
Jean Bustamante Alvarez
Amir Mortazavi
Sameek Roychowdhury
John Phay
Raheela A. Khawaja
Manisha H. Shah
Bhavana Konda
Publication date
01-04-2020
Publisher
Springer Netherlands
Published in
Familial Cancer / Issue 2/2020
Print ISSN: 1389-9600
Electronic ISSN: 1573-7292
DOI
https://doi.org/10.1007/s10689-019-00152-6

Other articles of this Issue 2/2020

Familial Cancer 2/2020 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine