Differential diagnosis of Brooke–Spiegler syndrome in a young woman with multiple trichoepitheliomas

Abstract

Brooke–Spiegler syndrome (Brooke-Spiegler syndrome; OMIM #605041) is a rare, autosomal dominant inherited monogenic disease caused by mutations in gene CYLD with its different penetrance.

It is clinically manifested by the development of multiple neoplasms of skin appendages such as spiradenoma, cylindroma, spiradenocylindroma and trichoepithelioma. Several phenotypic variants with mutations in gene CYLD have been described in the scientific literature. They are classic Brooke–Spiegler syndrome; multiple familial trichoepithelioma syndrome (multiple trichoepitheliomas without cylindromas, spiradenomas, etc.); familial cylindromatosis (multiple cylindromas on the scalp i.e., "turban tumor"); syndrome of multiple spiradenomas or spiradenocylindromas without other neoplasms of the skin appendages. For four diseases associated with CYLD mutations, the prevalence is <1/1 000 000.

The scientific literature describes more than 200 cases of Brooke–Spiegler syndrome, which is more common in women. Phenotypic manifestations of the CYLD mutation are variable, so there is no reliable statistics on the frequency of occurrence of clinical variants of Brooke–Spiegler syndrome. The variety of neoplasms of the skin appendages, the commonality of their histogenesis, the similarity of clinical and histological patterns significantly complicate the diagnosis. Verification of the diagnosis of Brooke–Spiegler syndrome is based on histological examination and sequencing of the CYLD gene.

Keywords

Brooke–Spiegler syndrome / multiple family trichoepitheliomas / c.2501dupC / CYLD gene sequencing / CO2-laser / treatment

References

[1] Blake PW, Toro JR. Update of cylindromatosis gene (CYLD) mutations in Brooke-Spiegler syndrome: Novel insights into the role of deubiquitination in cell signaling. Hum Mutat. 2009;30(7):1025–1036. doi: 10.1002/humu.21022

[2] Blake P.W., Toro J.R. Update of cylindromatosis gene (CYLD) mutations in Brooke-Spiegler syndrome: novel insights into the role of deubiquitination in cell signaling // Hum Mutat. 2009. Vol. 30, N 7. Р. 1025–1036. doi: 10.1002/humu.21022

[3] Kazakov DV. Brooke-spiegler syndrome and phenotypic variants: an update. Head Neck Pathol. 2016;10(2):125–130. doi: 10.1007/s12105-016-0705-x

[4] Kazakov D.V. Brooke-Spiegler syndrome and phenotypic variants: An update // Head Neck Pathol. 2016. Vol. 10, N 2. Р. 125–130. doi: 10.1007/s12105-016-0705-x

[5] Kubanov AA, Sysoeva TA, Kovaleva YP, et al. Сutaneous adnexal tumors. Brook-Spiegler syndrome. Russ Med J Medical Review. 2019;(12):42–45. (In Russ).

[6] Кубанов А.А., Сысоева Т.А., Ковалева Ю.П., и др. Опухоли придатков кожи. Синдром Брука-Шпиглера // Русский медицинский журнал. Медицинское обозрение. 2019. Т. 3, № 12. С. 42–45.

[7] Kazakov D, Michal M, Kacerovska D, McKee PH. Cutaneous adnexal tumors. Lippincott Wialliams & Wilkins, Philadelphia, PA; 2012. 814 p.

[8] Kazakov D., Michal M., Kacerovska D., McKee P.H. Cutaneous adnexal tumors. Lippincott Wialliams & Wilkins, Philadelphia, PA, 2012. 814 p.

[9] Nagy N, Dubois A, Szell M, Rajan N. Genetic testing in CYLD cutaneous syndrome: An update. Appl Clin Genet. 2021;(14):427–444. doi: 10.2147/TACG.S288274

[10] Nagy N., Dubois A., Szell M., Rajan N. Genetic testing in CYLD cutaneous syndrome: An update // Appl Clin Genet. 2021. N 14. Р. 427–444. doi: 10.2147/TACG.S288274

[11] Berghe VT, Linkermann A, Jouan-Lanhouet S, et al. Regulated necrosis: The expanding network of non-apoptotic cell death pathways. Nat Rev Mol Cell Biol. 2014;15(2):135–147. doi: 10.1038/nrm3737

[12] Berghe V.T., Linkermann A., Jouan-Lanhouet S., et al. Regulated necrosis: The expanding network of non-apoptotic cell death pathways // Nat Rev Mol Cell Biol. 2014. Vol. 15, N 2. Р. 135–147. doi: 10.1038/nrm3737

[13] Ryzhkova OP, Kardymon OL, Prohorchuk EB, et al. Guidelines for the interpretation of human DNA sequence data obtained by mass parallel sequencing methods (edition 2018, version 2). Medical genetics. 2019;18(2):3–23. (In Russ). doi: 10.25557/2073-7998.2019.02.3-23

[14] Рыжкова О.П., Кардымон О.Л., Прохорчук Е.Б., и др. Руководство по интерпретации данных, полученных методом массового параллельного секвенирования (MPS) (редакция 2018, версия 2) // Медицинская генетика. 2019. Т. 18, № 2. С. 4–17. doi: 10.25557/2073-7998.2019.02.3-24

[15] Kubanov AA, Sysoeva TA, Gallyamova YuA, et al. Algorithm for examining patients with skin neoplasms. Lechaschi Vrach. 2018;(3):83–88. (In Russ).

[16] Кубанов А.А., Сысоева Т.А., Галлямова Ю.А., и др. Алгоритм обследования пациентов с новообразованиями кожи // Лечащий врач. 2018. № 3. С. 83–88.

[17] Patel P, Nawrocki S, Hinther K, Khachemoune A. Trichoblastomas mimicking basal cell carcinoma: The importance of identification and differentiation. Cureus. 2020;12(5):e8272. doi: 10.7759/cureus.8272

[18] Patel P., Nawrocki S., Hinther K., Khachemoune A. Trichoblastomas mimicking basal cell carcinoma: The importance of identification and differentiation // Cureus. 2020. Vol. 12, N 5. Р. e8272. doi: 10.7759/cureus.8272

[19] Schierbeck J, Vestergaard T, Bygum A. Skin cancer associated genodermatoses: A literature review. Acta Derm Venereol. 2019;99(4):360–369. doi: 10.2340/00015555-3123

[20] Schierbeck J., Vestergaard T., Bygum A. Skin cancer associated genodermatoses: A literature review // Acta Derm Venereol. 2019. Vol. 99, N 4. Р. 360–369. doi: 10.2340/00015555-3123

[21] Brown S, Brennan P, Rajan N. Inherited skin tumour syndromes. Clin Med (Lond). 2017;17(6):562–567. doi: 10.7861/clinmedicine.17-6-562

[22] Brown S., Brennan P., Rajan N. Inherited skin tumour syndromes // Clin Med (Lond). 2017. Vol. 17, N 6. Р. 562–567. doi: 10.7861/clinmedicine.17-6-562

[23] Paller AS, Mancini AJ. Hurwitz clinical pediatric dermatology: A textbook of skin disorders of childhood and adolescence. 5th ed. Elsevier Health Sciences; 2016.

[24] Paller A.S., Mancini A.J. Hurwitz clinical pediatric dermatology: A textbook of skin disorders of childhood and adolescence. 5th ed. Elsevier Health Sciences, 2016.

[25] Schmidt LS, Linehan WM. FLCN: The causative gene for Birt-Hogg-Dubé syndrome. Gene. 2018;(640):28–42. doi: 10.1016/j.gene.2017.09.044

[26] Schmidt L.S., Linehan W.M. FLCN: The causative gene for Birt-Hogg-Dubé syndrome // Gene. 2018. N 640. P. 28–42. doi: 10.1016/j.gene.2017.09.044

[27] Lopes S, Vide J, Moreira E, Azevedo F. Cowden syndrome: clinical case and a brief review. Dermatol Online J. 2017;23(8):13030/qt0023k3x0.

[28] Lopes S., Vide J., Moreira E., Azevedo F. Cowden syndrome: Clinical case and a brief review // Dermatol Online J. 2017. Vol. 23, N 8. Р. 13030/qt0023k3x0.

[29] Gosein MA, Narinesingh D, Nixon CA, et al. Multi-organ benign and malignant tumors: recognizing Cowden syndrome: A case report and review of the literature. BMC Res Notes. 2016;(9):388. doi: 10.1186/s13104-016-2195-z

[30] Gosein M.A., Narinesingh D., Nixon C.A., et al. Multi-organ benign and malignant tumors-recognizing Cowden syndrome: A case report and review of the literature // BMC Res Notes. 2016. N 9. Р. 388. doi: 10.1186/s13104-016-2195-z

[31] Tayeb C, Parc Y, Andre T, Lopez-Trabada Ataz D. Polypose adénomateuse familiale, tumeurs desmoïdes et syndrome de Gardner [Familial adenomatous polyposis, desmoid tumors and Gardner syndrome]. (French). Bull Cancer. 2020;107(3):352–358. doi: 10.1016/j.bulcan.2019.10.011

[32] Tayeb C., Parc Y., Andre T., Lopez-Trabada Ataz D. Polypose adénomateuse familiale, tumeurs desmoïdes et syndrome de Gardner [Familial adenomatous polyposis, desmoid tumors and Gardner syndrome]. (French) // Bull Cancer. 2020. Vol. 107, N 3. Р. 352–358. doi: 10.1016/j.bulcan.2019.10.011

[33] Gay JT, Troxell T, Gross GP. Muir-Torre syndrome. StatPearls [cites: 2022 July 4]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK513271/. Accessed: 25.10.2022.

[34] Gay J.T., Troxell T., Gross G.P. Muir-Torre Syndrome. StatPearls [cites: 2022 July 4]. Режим доступа: https://www.ncbi.nlm.nih.gov/books/NBK513271/. Дата обращения: 25.10.2022.

[35] John AM, Schwartz RA. Muir-Torre syndrome (MTS): An update and approach to diagnosis and management. J Am Acad Dermatol. 2016;74(3):558–566. doi: 10.1016/j.jaad.2015.09.074

[36] John A.M., Schwartz R.A. Muir-Torre syndrome (MTS): An update and approach to diagnosis and management // J Am Acad Dermatol. 2016. Vol. 74, N 3. Р. 558–566. doi: 10.1016/j.jaad.2015.09.074

[37] Al Sabbagh MM, Baqi MA. Bazex-Dupré-Christol syndrome: Review of clinical and molecular aspects. Int J Dermatol. 2018;57(9):1102–1106. doi: 10.1111/ijd.14065

[38] AlSabbagh M.M., Baqi M.A. Bazex-Dupré-Christol syndrome: Review of clinical and molecular aspects // Int J Dermatol. 2018. Vol. 57, N 9. Р. 1102–1106. doi: 10.1111/ijd.14065

[39] Kamilaris CD, Faucz FR, Voutetakis A, Stratakis CA. Carney complex. Exp Clin Endocrinol Diabetes. 2019;127(2-3):156–164. doi: 10.1055/a-0753-4943

[40] Kamilaris C.D., Faucz F.R., Voutetakis A., Stratakis C.A. Carney complex // Exp Clin Endocrinol Diabetes. 2019. Vol. 127, N 2-3. Р. 156–164. doi: 10.1055/a-0753-4943

[41] Ahmed C, Trope BM, Amorim G, et al. Clouston syndrome. Skinmed. 2021;19(1):54.

[42] Ahmed C., Trope B.M., Amorim G., et al. Clouston syndrome // Skinmed. 2021. Vol. 19, N 1. Р. 54.

[43] Cammarata-Scalisi F, Rinelli M, Pisaneschi E, et al. Novel clinical features associated with Clouston syndrome. Int J Dermatol. 2019;58(8):e143–e146. doi: 10.1111/ijd.14507

[44] Cammarata-Scalisi F., Rinelli M., Pisaneschi E., et al. Novel clinical features associated with Clouston syndrome // Int J Dermatol. 2019. Vol. 58, N 8. Р. e143–e146. doi: 10.1111/ijd.14507

[45] Bartoš V, Kullovа M, Adamicovа K, Paučinovа I. Gorlin-Goltz syndrome. Gorlinov-Goltzov syndrоm. Klin Onkol. 2019;32(2):124–128. doi: 10.14735/amko2019124

[46] Bartoš V., Kullová M., Adamicová K., Paučinová I. Gorlin-Goltz syndrome. Gorlinov-Goltzov syndróm // Klin Onkol. 2019. Vol. 32, N 2. Р. 124–128. doi: 10.14735/amko2019124

[47] Vetrо Е, Olаh J, Nagy D, et al. A Gorlin-Goltz-szindróma genetikai aspektusai [Genetic aspects of Gorlin-Goltz syndrome]. (Hungarian). Orv Hetil. 2020;161(49):2072–2077. doi: 10.1556/650.2020.31933

[48] Vetró É., Oláh J., Nagy D., et al. A Gorlin-Goltz-szindróma genetikai aspektusai [Genetic aspects of Gorlin-Goltz syndrome]. (Hungarian) // Orv Hetil. 2020. Vol. 161, N 49. Р. 2072–2077. doi: 10.1556/650.2020.31933

[49] Trocoli Drakensjö I, Björck E, Bradley M, Hedblad MA. Schöpf-Schulz-Passarge syndrome with multiple angiomas on the tongue: a new feature? Int J Dermatol. 2021;60(5):641–642. doi: 10.1111/ijd.15363

[50] Trocoli Drakensjö I., Björck E., Bradley M., Hedblad M.A. Schöpf-Schulz-Passarge syndrome with multiple angiomas on the tongue: A new feature? // Int J Dermatol. 2021. Vol. 60, N 5. Р. 641–642. doi: 10.1111/ijd.15363

[51] Ismail FF, McGrath J, Sinclair R. Schopf-Schulz-Passarge syndrome: A rare ectodermal dysplasia with a delayed diagnosis. Int J Dermatol. 2020;59(2):257–258. doi: 10.1111/ijd.14616

[52] Ismail F.F., McGrath J., Sinclair R. Schopf-Schulz-Passarge syndrome: A rare ectodermal dysplasia with a delayed diagnosis // Int J Dermatol. 2020. Vol. 59, N 2. Р. 257–258. doi: 10.1111/ijd.14616

[53] Castori M, Ruggieri S, Giannetti L, et al. Schöpf-Schulz-Passarge syndrome: Further delineation of the phenotype and genetic considerations. Acta Derm Venereol. 2008;88(6):607–612. doi: 10.2340/00015555-0547

[54] Castori M., Ruggieri S., Giannetti L., et al. Schöpf-Schulz-Passarge syndrome: Further delineation of the phenotype and genetic considerations // Acta Derm Venereol. 2008. Vol. 88, N 6. Р. 607–612. doi: 10.2340/00015555-0547

[55] Northrup H, Aronow ME, Bebin EM, et al. Updated international tuberous sclerosis complex diagnostic criteria and surveillance and management recommendations. Pediatr Neurol. 2021;(123):50–66. doi: 10.1016/j.pediatrneurol.2021.07.011

[56] Northrup H., Aronow M.E., Bebin E.M., et al. Updated international tuberous sclerosis complex diagnostic criteria and surveillance and management recommendations // Pediatr Neurol. 2021. N 123. Р. 50–66. doi: 10.1016/j.pediatrneurol.2021.07.011

[57] Brook-Carter PT, Peral B, Ward CJ, et al. Deletion of the TSC2 and PKD1 genes associated with severe infantile polycystic kidney disease-a contiguous gene syndrome. Nat Genet. 1994;8(4):328–332. doi: 10.1038/ng1294-328

[58] Brook-Carter P.T., Peral B., Ward C.J., et al. Deletion of the TSC2 and PKD1 genes associated with severe infantile polycystic kidney disease--a contiguous gene syndrome // Nat Genet. 1994. Vol. 8, N 4. Р. 328–332. doi: 10.1038/ng1294-328

[59] Grossmann P, Vanecek T, Steiner P, et al. Novel and recurrent germline and somatic mutations in a cohort of 67 patients from 48 families with Brooke-Spiegler syndrome including the phenotypic variant of multiple familial trichoepitheliomas and correlation with the histopathologic findings in 379 biopsy specimens. Am J Dermatopathol. 2013;35(1):34–44. doi: 10.1097/DAD.0b013e31824e7658

[60] Grossmann P., Vanecek T., Steiner P., et al. Novel and recurrent germline and somatic mutations in a cohort of 67 patients from 48 families with Brooke-Spiegler syndrome including the phenotypic variant of multiple familial trichoepitheliomas and correlation with the histopathologic findings in 379 biopsy specimens // Am J Dermatopathol. 2013. Vol. 35, N 1. Р. 34–44. doi: 10.1097/DAD.0b013e31824e7658

[61] Lobo Y, Blake T, Wheller L. Management of multiple trichoepithelioma: A review of pharmacological therapies. Australas J Dermatol. 2021;62(2):e192–e200. doi: 10.1111/ajd.13537

[62] Lobo Y., Blake T., Wheller L. Management of multiple trichoepithelioma: A review of pharmacological therapies // Australas J Dermatol. 2021. Vol. 62, N 2. Р. e192–e200. doi: 10.1111/ajd.13537

[63] Baur V, Papadopoulos T, Kazakov DV, et al. A case of multiple familial trichoepitheliomas responding to treatment with the Hedgehog signaling pathway inhibitor vismodegib. Virchows Arch. 2018;473(2):241–246. doi: 10.1007/s00428-018-2397-y

[64] Baur V., Papadopoulos T., Kazakov D.V., et al. A case of multiple familial trichoepitheliomas responding to treatment with the Hedgehog signaling pathway inhibitor vismodegib // Virchows Arch. 2018. Vol. 473, N 2. Р. 241–246. doi: 10.1007/s00428-018-2397-y

[65] Engels PE, Fritsche E, Pabst G, Hug U. Surgical treatment of Brooke-Spiegler Syndrome. J Craniofac Surg. 2021;32(4):e356–e358. doi: 10.1097/SCS.0000000000007144

[66] Engels P.E., Fritsche E., Pabst G., Hug U. Surgical treatment of Brooke-Spiegler Syndrome // J Craniofac Surg. 2021. Vol. 32, N 4. Р. e356–e358. doi: 10.1097/SCS.0000000000007144

[67] Portincasa A, Cecchino L, Trecca EM, et al. A rare case of Brooke-Spiegler syndrome: Integrated surgical treatment of multiple giant eccrine spiradenomas of the head and neck in a young girl. Int J Surg Case Rep. 2018;(51):277–281. doi: 10.1016/j.ijscr.2018.08.021

[68] Portincasa A., Cecchino L., Trecca E.M., et al. A rare case of Brooke-Spiegler syndrome: Integrated surgical treatment of multiple giant eccrine spiradenomas of the head and neck in a young girl // Int J Surg Case Rep. 2018. N 51. Р. 277–281. doi: 10.1016/j.ijscr.2018.08.021

[69] Gaydina TA, Dvornikov AS, Skripkina PA. Case report: Removal of a proliferating pilomatricoma with a CO2 laser. Bulletin of Russian State Medical University. 2019;(6):110–113. (In Russ). doi: 10.24075/vrgmu.2019.077

[70] Гайдина Т.А., Дворников А.С., Скрипкина П.А. Клинический случай: удаление пролиферирующей пиломатриксомы СО2-лазером // Вестник Российского государственного медицинского университета. 2019. № 6. С. 110–113. doi: 10.24075/vrgmu.2019.077

[71] Gaydina TA, Dvornikov AS, Skripkina PA, Arutyunyan GB. Rationale for removing nevus sebaceus of jadassohn in young patients. Bulletin of Russian State Medical University. 2018;(3):80–83. (In Russ). doi: 10.24075/vrgmu.2018.033

[72] Гайдина Т.А., Дворников А.С., Скрипкина П.А., Арутюнян Г.Б. Актуальность удаления невуса Ядассона у лиц молодого возраста // Вестник Российского государственного медицинского университета. 2018. № 3. С. 80–83. doi: 10.24075/vrgmu.2018

[73] Liu D, Zhou EY, Chen D, et al. Epidermoid cyst removal with CO2 laser fenestration: A retrospective cohort study. J Cosmet Dermatol. 2021;20(6):1709–1713. doi: 10.1111/jocd.13766

[74] Liu D., Zhou E.Y., Chen D., et al. Epidermoid cyst removal with CO2 laser fenestration: A retrospective cohort study // J Cosmet Dermatol. 2021. Vol. 20, N 6. Р. 1709–1713. doi: 10.1111/jocd.13766

[75] Thomas LW, Pham CT, Coakley B, Lee P. Treatment of Brooke-Spiegler syndrome trichoepitheliomas with erbium-yttrium-aluminum-garnet laser: A case report and review of the literature. J Clin Aesthet Dermatol. 2020;13(7):41–44.

[76] Thomas L.W., Pham C.T., Coakley B., Lee P. Treatment of Brooke-Spiegler syndrome trichoepitheliomas with erbium: yttrium-aluminum-garnet laser: A case report and review of the literature // J Clin Aesthet Dermatol. 2020. Vol. 13, N 7. Р. 41–44.

[77] Rentka A, Grygar J, Nemes Z, Kemeny-Beke A. Evaluation of carbon dioxide laser therapy for benign tumors of the eyelid margin. Lasers Med Sci. 2017;32(8):1901–1907. doi: 10.1007/s10103-017-2309-4

[78] Rentka A., Grygar J., Nemes Z., Kemeny-Beke A. Evaluation of carbon dioxide laser therapy for benign tumors of the eyelid margin // Lasers Med Sci. 2017. Vol. 32, N 8. Р. 1901–1907. doi: 10.1007/s10103-017-2309-4

RIGHTS & PERMISSIONS

Gaydina T.A., Dvornikov A.S., Skripkina P.A., Patsap O.I., Buianova A.A.