Metastatic pheochromocytoma in multiple endocrine neoplasia type 2A
D. V. Rebrova,
V. F. Rusakov,
L. M. Krasnov,
E. A. Fedorov,
I. K. Chinchuk,
N. V. Vorokhobina,
S. S. Shikhmagomedov,
A. A. Semenov,
R. A. Chernikov,
I. V. Sleptsov,
G. I. Gavton,
E. N. Imyanitov https://doi.org/10.14341/probl13332
Abstract
Pheochromocytoma (PHEO) currently is considered to be malignant due to metastatic potential. One of the most common familial forms of PHEO is multiple endocrine neoplasia syndrome (MEN) type 2. The penetrance of PHEO in MEN2 syndrome is up to 50% of cases. It may be one- or two-sided, but metastases occur extremely rare. The fact that in majority of cases of MEN2 syndrome the source of distant metastases is medullary thyroid carcinoma (MTC) complicates differential diagnosis in case of PHEO metastasis.
Isolated cases of PHEO with metastases to the lymph nodes, lungs, liver, bones, brain in MEN2 patients were described. In the available literature, we have found a description of 31 cases of metastatic PHEO in MEN2 syndrome. The available data of those cases is presented as a table in the article.
We present a description of a 40-year-old woman with MEN2A syndrome (mutation of the RET proto-oncogene p.Cys634Tyr), with a history of twice-performed surgical treatment of MTC, with daily crises of arterial hypertension accompanied by vegetative symptoms, with a giant bilateral PHEO (up to 200 m on the right and up to 150 mm on the left) with synchronous large metastasis (up to 50 mm) into the pubic bone with the destruction. The patient underwent several surgeries: bilateral adrenalectomy, then a bilateral revision of the neck, removal of the right upper and right lower parathyroid glands, residual thyroid tissue, then resection of the right pubic bone with a tumor.
About the Authors
D. V. Rebrova
Saint Petersburg State University, Saint Petersburg State University Hospital
Russian Federation
Russian Federation
Dina V. Rebrova, MD, PhD
154 Fontanka river embankment, 190103, Saint Petersburg
V. F. Rusakov
Saint Petersburg State University, Saint Petersburg State University Hospital
Russian Federation
Russian Federation
Vladimir F. Rusakov, MD, PhD
St. Petersburg
L. M. Krasnov
Saint Petersburg State University, Saint Petersburg State University Hospital
Russian Federation
Russian Federation
Leonid M. Krasnov, MD, PhD
St. Petersburg
E. A. Fedorov
Saint Petersburg State University, Saint Petersburg State University Hospital
Russian Federation
Russian Federation
Elisey A.Fedorov, MD, PhD
St. Petersburg
I. K. Chinchuk
Saint Petersburg State University, Saint Petersburg State University Hospital
Russian Federation
Russian Federation
Igor K. Chinchuk, MD, PhD
St. Petersburg
N. V. Vorokhobina
North-Western State Medical University n.a. I.I. Mechnikov
Russian Federation
Russian Federation
Natalya V. Vorokhobina, MD, PhD, Prof.
St. Petersburg
S. S. Shikhmagomedov
Saint Petersburg State University, Saint Petersburg State University Hospital
Russian Federation
Russian Federation
Shamil S. Shikhmagomedov, MD
St. Petersburg
A. A. Semenov
Saint Petersburg State University, Saint Petersburg State University Hospital
Russian Federation
Russian Federation
Arseny A. Semenov, MD, PhD
St. Petersburg
R. A. Chernikov
Saint Petersburg State University, Saint Petersburg State University Hospital
Russian Federation
Russian Federation
Roman A. Chernikov, MD, PhD
St. Petersburg
I. V. Sleptsov
Saint Petersburg State University, Saint Petersburg State University Hospital
Ilya V. Sleptsov, MD, PhD
St. Petersburg
G. I. Gavton
National Medical Research Center of Oncology n.a. N.N. Petrov
Russian Federation
Russian Federation
Georgy I. Gavton, MD, DSc, Prof.
St. Petersburg
E. N. Imyanitov
National Medical Research Center of Oncology n.a. N.N. Petrov
Russian Federation
Russian Federation
Evgeny N. Imyanitov, MD, PhD, Prof., Corresponding Member of RAS
St. Petersburg
References
1. Lloyd RV, Osamura RY, Kloppel G, Rosai J, editors (2017). WHO Classification of Tumours of Endocrine Organs (4th edition). IARC: Lyon, 2017
2. Lam AK. Update on Adrenal Tumours in 2017 World Health Organization (WHO) of Endocrine Tumours. Endocr Pathol. 2017;28:213–227. doi: https://doi.org/10.1007/s12022-017-9484-5
3. Ayala-Ramirez M, Feng L, Johnson MM, et al. Clinical risk factors fro malignancy and overall survival in patients with pheochromocytomas and sympathethic paragangliomas: primary tumor size and primary tumor location as prognostic indicators. J Clin Endocrinol Metab. 2011;96(3):717-725. doi: https://doi.org/10.1210/jc.2010-1946
4. Fishbein L. Pheochromocytoma/Paraganglioma: Is This a Genetic Disorder? Curr Cardiol Rep. 2019;21(9):104. doi: https://doi.org/10.1007/s11886-019-1184-y
5. Реброва Д.В., Ворохобина Н.В., Имянитов Е.Н. и др. Клиническолабораторные особенности наследственных феохромоцитом и параганглиом. Проблемы эндокринологии. 2022;68(1):8-17. doi: https://doi.org/10.14341/probl12834
6. Hamidi O, Young WF, Inguez-Ariza NM, et al. Malignant pheochromocytoma and paraganglioma: 272 patients over 55 years. J Clin Endocrinol Metab. 2017;102(9):3296-3305. doi: https://doi.org/10.1210/jc.2017-00992
7. Thosani S, Ayala-Ramirez M, Palmer L, et al. The characterization of pheochromocytoma and its impact on overall survival in multiple endocrine neoplasia type 2. J Clin Endocrinol Metab. 2013;98(11):E1813-1819. doi: https://doi.org/10.1210/jc.2013-1653
8. Oishi S, Sasaki M, Yamauchi J, et al. Analysis of eight Sipple’s syndrome patients and review of eighty-two cases from the Japanese literature. Jpn J Clin Oncol. 1990;20(4):392-406
9. Kotecka-Blicharz A, Hasse-Lazar K, Jurecka-Lubieniecka B, et al. Occurrence of phaeochromocytoma tumours in RET mutation carriers - a single-centre study. Endokrynol Pol. 2016;67(1):54-8. doi: https://doi.org/10.5603/EP.2016.0008
10. Kumar , Lila AR, Memon SS, et al. Metastatic cluster 2-related pheochromocytoma/paraganglioma: a single-center experience and systematic review. Endocr Connect. 2021;10(11):1463-1476. doi: https://doi.org/10.1530/EC-21-0455
11. 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. 2016;40(3):690-6. doi: https://doi.org/10.1007/s00268-015-3255-6
12. Carney JA, Sizemore GW, Sheps SG. Adrenal medullary disease in multiple endocrine neoplasia, type 2: pheochromocytoma and its precursors. Am J Clin Pathol. 1976;66(2):279-90. doi: https://doi.org/10.1093/ajcp/66.2.279
13. Wilson RA, Ibanez ML. A comparative study of 14 cases of familial and nonfamilial pheochromocytomas. Hum Pathol. 1978;9(2):181-8. doi: https://doi.org/10.1016/s0046-8177(78)80109-9
14. Westfried M, Mandel D, Alderete MN, et al. Sipple’s syndrome with a malignant pheochromocytoma presenting as a pericardial effusion. Cardiology. 1978;63(5):305-11. doi: https://doi.org/10.1159/000169909
15. Sissin JC, Shapiro B, Beierwaltes WH. Scintigraphy with I-131 MIBG as an aid to the treatment of pheochromocytomas in patients with the multiple endocrine neoplasia type 2 syndromes. Henry Ford Hosp Med J. 1984;32(4):254-61
16. Spapen H, Gerlo E, Achten E, et al. Pre- and perioperative diagnosis of metastatic pheochromocytoma in multiple endocrine neoplasia type 2a. J Endocrinol Invest. 1989 Nov;12(10):729-31. doi: https://doi.org/10.1007/BF03350044
17. Namba H, Kondo H, Yamashita S, et al. Multiple endocrine neoplasia type 2 with malignant pheochromocytoma--long term follow-up of a case by 131I-meta-iodobenzylguanidine scintigraphy. Ann Nucl Med. 1992;6(2):111-5. doi: https://doi.org/10.1007/BF03164652
18. Bonnin F, Schlumberger M, Gardet P, et al. Screening for adrenal medullary disease in patients with medullary thyroid carcinoma. J Endocrinol Invest. 1994;17(4):253-7. doi: https://doi.org/10.1007/BF03348970
19. Sasaki M, Iwaoka T, Yamauchi J, et al. A case of Sipple’s syndrome with malignant pheochromocytoma treated with 131I-metaiodobenzyl guanidine and a combined chemotherapy with cyclophosphamide, vincristine and dacarbazine. Endocr J. 1994;41(2):155-60. doi: https://doi.org/10.1507/endocrj.41.155
20. Scopsi L, Castellani MR, Gullo F, et al. Malignant pheochromocytoma in multiple endocrine neoplasia type 2B syndrome. Case report and review of the literature. Tumori. 1996;82(5):480-4. doi: https://doi.org/10.1177/030089169608200514
21. Hinze R, Machens A, Schneider U, et al. Simultaneously occurring liver metastases of pheochromocytoma and medullary thyroid carcinoma--a diagnostic pitfall with clinical implications for patients with multiple endocrine neoplasia type 2a. Pathol Res Pract. 2000;196(7):477-81. doi: https://doi.org/10.1016/S0344-0338(00)80049-7
22. Gentle S, Rainero I, Savi L, et al. Brain metastasis from pheochromocytoma in a patient with multiple endocrine neoplasia type 2A. Panminerva Med. 2001;43(4):305-6
23. Hamdan A, Hirsch D, Green P, et al. Pheochromocytoma: unusual presentation of a rare disease. Isr Med Assoc J. 2002 Oct;4(10):827-8
24. Ishida E, Nakamura M, Shimada K, et al. Autopsy case prostate cancer with multiple endocrine neoplasia 2A. Pathol Int. 2004;54(12):918-23. doi: https://doi.org/10.1111/j.1440-1827.2004.01773.x
25. Gullu S, Gursoy A, Erdogan MF, et al. Multiple endocrine neoplasia type 2A/localized cutaneous lichen amyloidosis associated with malignant pheochromocytoma and ganglioneuroma. J Endocrinol Invest. 2005;28(8):734-7. doi: https://doi.org/10.1007/BF03347557
26. Duquia RP, Almeida HL, Traesel M, Jannke HA. Cutaneous metastasis of pheochromocytoma in multiple endocrine neoplasia IIB. J Am Acad Dermatol. 2006;55(2):341-4. doi: https://doi.org/10.1016/j.jaad.2005.11.1080
27. Szalat A, Fraenkel M, Doviner V, et al. Malignant pheochromocytoma: predictive factors of malignancy and clinical course in 16 patients at a single tertiary medical center. Endocr. 2011;39:160-166. doi: https://doi.org/10.1007/s12020-010-9422-5
28. Crona J, Nordling M, Maharjan R, et al. Integrative genetic characterization and phenotype correlations in pheochromocytoma and paraganglioma tumours. PLoS One. 2014;9(1):e86756. doi: https://doi.org/10.1371/journal.pone.0086756
29. Lang BHH, Yu HW, Lo CY, et al. Bilateral pheochromocytomas in MEN2A syndrome: a two-institution experience. World J Surg. 2015;39(10):2484-91. doi: https://doi.org/10.1007/s00268-015-3117-2
30. Martins AF, Martins JM, Vale S, et al. A rare missense variant in RET exon 8 in Portuguese family with atypical multiple endocrine neoplasia type 2A. Hormones. 2016;15(3):435-440. doi: https://doi.org/10.14310/horm.2002.1691
31. Pal R, Rastorgi A, Kumar S, Bhansali A. Metastatic pheochromocytoma in MEN 2A: a rare association. BMJ Case Rep. 2018;2018:bcr2017222758. doi: https://doi.org/10.1136/bcr-2017-222758
32. Ma X, Li M, Tong A, et al. Genetic and clinical profiles of pheochromocytoma and paraganglioma: a single center study. Front Endocrinol (Lausanne). 2020;11:574662. doi: https://doi.org/10.3389/fendo.2020.574662
33. Jester G, Hassanein H, El-Far A. Late Diagnosis of metastatic pheochromocytoma in multiple endocrine neoplasia 2B with rapid clinical decline. BMJ Case Rep. 2021;14(2):e240488. doi: https://doi.org/10.1136/bcr-2020-24048
34. Ku CF, Lo CY, Chan WF, et al. Resection of phaechromocytoma extending into the right atrium in a patient with multiple endocrine neoplasia type 2A. Hong Kong Med J. 2005;11:59-62
Supplementary files
|
|
1. Figure 1. Computed tomography of the abdominal organs with contrast: a — arterial phase, coronary plane; b — venous phase, axial plane; c — arterial phase, sagittal plane. Giant multiple pheochromocytomas of both adrenal glands are marked with arrows. | |
| Subject | ||
| Type | Исследовательские инструменты | |
View
(1MB)
|
Indexing metadata ▾ | |
|
|
2. Figure 2. Computed tomography of the pelvic organs with contrast: a — arterial phase, bone window, axial plane; b — delayed phase, soft tissue window, axial plane. Arrows indicate pheochromocytoma metastasis to the pubic bone. | |
| Subject | ||
| Type | Исследовательские инструменты | |
View
(742KB)
|
Indexing metadata ▾ | |
Review
For citations:
Rebrova D.V., Rusakov V.F., Krasnov L.M., Fedorov E.A., Chinchuk I.K., Vorokhobina N.V., Shikhmagomedov S.S., Semenov A.A., Chernikov R.A., Sleptsov I.V., Gavton G.I., Imyanitov E.N. Metastatic pheochromocytoma in multiple endocrine neoplasia type 2A. Problems of Endocrinology. 2024;70(6):35-44. (In Russ.) https://doi.org/10.14341/probl13332
Views:
685
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND 4.0).
Email this article 
.jpg){kind=logo}
