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

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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.

About the authors

Tatiana A. Gaydina

The Russian National Research Medical University named after N.I. Pirogov; Federal Center of Brain Research and Neurotechnologies

Author for correspondence.
Email: doc429@yandex.ru
ORCID iD: 0000-0001-8485-3294
SPIN-code: 5216-2059

MD, Cand. Sci. (Med.), Associate Professor

Russian Federation, Moscow; Moscow

Anton S. Dvornikov

The Russian National Research Medical University named after N.I. Pirogov

Email: dvornikov_as@rsmu.ru
ORCID iD: 0000-0002-0429-3117
SPIN-code: 2023-5783

MD, Dr. Sci. (Med.), Professor

Russian Federation, Moscow

Polina A. Skripkina

The Russian National Research Medical University named after N.I. Pirogov

Email: polina.skripkina@mail.ru
ORCID iD: 0000-0001-9953-1095
SPIN-code: 3706-1349

MD, Cand. Sci. (Med.), Associate Professor

Russian Federation, Moscow

Olga I. Patsap

Federal Center of Brain Research and Neurotechnologies

Email: cleosnake@yandex.ru
ORCID iD: 0000-0003-4620-3922
SPIN-code: 6460-1758

MD, Cand. Sci. (Med.)

Russian Federation, Moscow

Anastasiia A. Buianova

The Russian National Research Medical University named after N.I. Pirogov

Email: anastasiiabuianova97@gmail.com
ORCID iD: 0000-0001-7894-9222
SPIN-code: 5725-7792
Russian Federation, Moscow

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. 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
  3. 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).
  4. Kazakov D, Michal M, Kacerovska D, McKee PH. Cutaneous adnexal tumors. Lippincott Wialliams & Wilkins, Philadelphia, PA; 2012. 814 p.
  5. 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
  6. 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
  7. 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
  8. Kubanov AA, Sysoeva TA, Gallyamova YuA, et al. Algorithm for examining patients with skin neoplasms. Lechaschi Vrach. 2018;(3):83–88. (In Russ).
  9. 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
  10. 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
  11. 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
  12. Paller AS, Mancini AJ. Hurwitz clinical pediatric dermatology: A textbook of skin disorders of childhood and adolescence. 5th ed. Elsevier Health Sciences; 2016.
  13. 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
  14. Lopes S, Vide J, Moreira E, Azevedo F. Cowden syndrome: clinical case and a brief review. Dermatol Online J. 2017;23(8):13030/qt0023k3x0.
  15. 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
  16. 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
  17. 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.
  18. 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
  19. 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
  20. 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
  21. Ahmed C, Trope BM, Amorim G, et al. Clouston syndrome. Skinmed. 2021;19(1):54.
  22. 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
  23. 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
  24. 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
  25. 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
  26. 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
  27. 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
  28. 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
  29. 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
  30. 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
  31. 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
  32. 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
  33. 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
  34. 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
  35. 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
  36. 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
  37. 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
  38. 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.
  39. 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

Supplementary files

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1. JATS XML
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2. Fig. 1. Patient N. born in 2001: the pathological skin process of the face is widespread, the rashes are relatively symmetrical.

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3. Fig. 2. The same patient: the maximum number of elements is grouped in the area of the nasolabial triangle.

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4. Fig. 3. The same patient: а ― photo of the patient’s face, in a red circle, a large skin neoplasm on the back of the nose, taken later for histological examination (biopsy 1); b ― dermatoscopy of skin neoplasms on the back of the nose: lobular structure with grayish rounded inclusions, thin convoluted vessels.

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5. Fig. 4. The same patient: а ― photo of the patient’s face with a large neoplasm on the left wing of the nose, taken later for histological examination (biopsy 2); b ― dermatoscopy of neoplasms on the wing of the nose: thin convoluted vessels, milium-like cysts.

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6. Fig. 5. The same patient: a fragment of the skin of the nasal dorsum with subepithelial growth of a formation constructed from monomorphic basaloid cells forming isolated epithelial complexes in a dense fibrous stroma (red circle), with the presence of microcysts containing keratin masses (black circle), with focal lining of epithelial cells with infundibular differentiation (green circle). Staining with hematoxylin and eosin, ×100.

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7. Fig. 6. The same patient: a fragment of the skin of the nasal wing with a subepithelial growth of the formation, constructed from monomorphic basaloid cells forming isolated complexes in a dense fibrous stroma (red circle). Staining with hematoxylin and eosin, ×400.

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8. Fig. 7. The same patient face 6 months after the third stage of neoplasm removal.

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Copyright (c) 2022 Gaydina T.A., Dvornikov A.S., Skripkina P.A., Patsap O.I., Buianova A.A.

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This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
 


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