eMedicine Specialties > Dermatology > Benign Neoplasms

Cylindroma

Author: Noah S Scheinfeld, MD, JD, FAAD, Assistant Clinical Professor, Department of Dermatology, Columbia University; Consulting Staff, Department of Dermatology, St Luke's Roosevelt Hospital Center, Beth Israel Medical Center, New York Eye and Ear Infirmary; Private Practice
Coauthor(s): Anusuya Mokashi, MS, MD, Radiology Resident, Staten Island University Hospital; Julide Tok Celebi, MD, Assistant Professor of Dermatology, Columbia University, College of Physicians and Surgeons; Consulting Staff, Department of Dermatology, New York Presbyterian Medical Center; Arnold R Oppenheim, MD, Assistant Professor, Department of Internal Medicine, Division of Dermatology, Eastern Virginia School of Medicine
Contributor Information and Disclosures

Updated: Jan 7, 2010

Introduction

Background

Cylindromas are benign skin appendage tumors. They can be seen in conjunction with spiradenomas and trichoepitheliomas. Cases of spiradenocylindromas, demonstrating characteristics of both spiradenoma and cylindroma in the same tumor mass, have also been observed, suggesting similar derivation of both tumors.

They most commonly occur on the head and neck as solitary or multiple tumors. Solitary cylindromas occur sporadically and typically are not inherited. Multiple tumors are observed in an autosomal dominantly inherited manner. When nodules enlarge and coalesce on the scalp, they form the distinctive turban tumor feature.

Malignant cylindromas are very rare. Malignant transformation may develop within solitary cylindromas, or they may complicate the multiple variant (more common).

Pathophysiology

Cylindromas are appendage tumors previously thought to be of apocrine differentiation. While phenotypic features differ between cylindromas and spiradenomas, recent studies have shown immunohistological and cytomorphological overlap, with both tumors exhibiting apocrine, eccrine, secretory, and ductal features. Therefore, the cellular origin of cylindromas remains unknown. Cylindromas are most likely a very primitive sweat gland tumor differentiating toward either the eccrine or apocrine line.

Brooke-Spiegler syndrome (BSS) has been described as an autosomal dominant disease characterized by the development of multiple skin appendage tumors such as cylindromas, trichoepitheliomas, and spiradenomas, with a variable preponderance of any of the aforementioned subsets. Other lesions reported with BSS include parotid basal cell adenomas, organoid nevi, syringomas, and basal cell carcinomas. Despite variable phenotypic expressions of a predominant tumor in BSS, the gene responsible for multiple cylindromas, CYLD, is localized to band 16q12-q13. The mechanism of genotypic similarity and phenotypic variance is not yet understood.1,2

In 2006, Zhang et al3  reported a large consanguineous Chinese family with BSS demonstrating intrafamily phenotypic variability. Upon examination, some persons only manifested discrete, small, skin-coloured growths, while the proband manifested an expansion of multiple large growths on the nose and numerous dome-shaped papules on the scalp. Biopsy showed both trichoepitheliomas and cylindromas in the affected persons. By sequence analysis, Zhang et al identified a recurrent mutation 2272C→T (R758X) of the CYLD gene in the affected familial persons that had been previously identified in other ethnic kindreds with familial cylindromatosis.

In 2007, Stegmeier et al4 noted that the CYLD gene encodes a deubiquitinating enzyme. The enzyme removes Lys-63–linked ubiquitin chains from I-kappaB kinase signaling components. By this mechanism, the enzyme inhibits NF-kappaB pathway activation. They demonstrated that CYLD is also required for the cell's timely entry into mitosis. Consistent with a cell-cycle regulatory function, CYLD localizes to microtubules in interphase and the midbody during telophase. CYLD 's protein levels decrease as cells exit from mitosis. Stegmeier et al identified the protein kinase Plk1 as a potential target of CYLD as a regulator of mitotic entry, and they suggested this because of the physical interaction and similar loss-of-function and over-expression phenotypes.
 
These findings raise the possibility that, as with other genes that regulate tumorigenesis, CYLD has both tumor-suppressing (apoptosis regulation) and tumor-promoting activities (enhancer of mitotic entry). They suggested that this additional function of CYLD could provide an explanation for the benign nature of most cylindroma lesions.

Massoumi and Paus5 and explained the manner in which CYLD interferes with tumor necrosis factor-alpha or Toll-like receptor – mediated signaling and with JNK or NF-kappaB-dependent p65/50 signaling to limit inflammation. Additionally, the manner by which CYLD interferes with activation of the proto-oncogene BCL3 and with cyclin D1 expression to limit tumorigenesis was also explained. Finally, the researchers discussed  how tumor growth-promoting agents or UV light and inflammatory mediators may activate CYLD.

Frequency

United States

Cylindromas are uncommon. The exact incidence is not known.

International

The exact international incidence of cylindromas is not known.

Mortality/Morbidity

Most cylindromas remain benign; however, at least 14 reports have described malignant transformation. Multiple cylindromas can cover the entire scalp and cause the disfiguring turban tumor appearance, which necessitates extensive reconstructive surgery.

Race

No racial disparity is reported for cylindromas.

Sex

The incidence of cylindroma is more common in females than in males. Female-to-male ratios of 6:1 and 9:1 have been reported.

Age

Solitary cylindromas are lesions that affect middle-aged and elderly persons. Multiple, inherited cylindromas usually begin in early adulthood and increase in size and number throughout life.

Clinical

History

  • The solitary form usually begins in middle age or later as a slow-growing, rubbery nodule exhibiting no symptoms.
  • The dominantly inherited, multiple variety appears shortly after puberty as numerous, rounded nodules of various sizes ranging from several millimeters to larger than 6 cm. Lesions grow slowly, and additional lesions develop over time.
  • Loss of CYLD can be linked with development of salivary gland cancers.6
  • Brooke-Spiegler syndrome associated with unilateral hearing loss has been reported.7
  • Brooke-Spiegler syndrome manifesting with pegged teeth has been reported.8

Physical

Except for BSS, pertinent findings are largely limited to the skin. Histologically similar tumors have been found in the breast, parotid glands, salivary glands, lacrimal gland of the eye, Bartholin glands, the brain, lungs, and kidneys.

  • Skin lesions associated with cylindromas 
    • Solitary lesions are firm, rubbery nodules with pink, red, or sometimes blue coloring that range in size from a few millimeters to several centimeters.
    • The multiple form has numerous masses of pink, red, or blue nodules, sometimes resembling bunches of grapes or small tomatoes (sometimes called a tomato tumor).
  • Skin distribution of cylindromas 
    • The solitary form is typically found on the head and neck.
    • The multiple form most commonly occurs on the head and neck but can also be seen on the trunk and the extremities.

Causes

  • The cause of sporadic, solitary cylindromas is largely unknown; however, genetic studies of sporadic cylindromas show loss of heterozygosity at and around the CYLD locus in a substantial number of cases, suggesting that this gene also plays a role in the development of sporadic tumors.
  • Familial cylindromatosis is inherited in an autosomal dominant fashion, and the responsible gene, CYLD, is located on band 16q12-13. Tumors exhibit loss of heterozygosity, implicating the gene as a tumor suppressor gene.
    • The precise biological function of the CYLD gene is yet to be elucidated. It has 4 functional motifs: CAP-GLY domains, proline-rich domains, metal-binding fingerlike domains, and regions with homology to UCH-catalytic domains.
    • The CYLD gene consists of 20 exons; the first 3 are untranslated and the latter 17 are coding exons. Various mutations have been observed, such as frameshift, nonsense, or splice site mutations. Most mutations occur in 3'2/3rds of the C-terminal coding portion of the gene, in exons 9-20.

More on Cylindroma

Overview: Cylindroma
Differential Diagnoses & Workup: Cylindroma
Treatment & Medication: Cylindroma
Follow-up: Cylindroma
References
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References

  1. Bignell GR, Warren W, Seal S, et al. Identification of the familial cylindromatosis tumour-suppressor gene. Nat Genet. Jun 2000;25(2):160-5. [Medline].

  2. Bowen S, Gill M, Lee DA, et al. Mutations in the CYLD gene in Brooke-Spiegler syndrome, familial cylindromatosis, and multiple familial trichoepithelioma: lack of genotype-phenotype correlation. J Invest Dermatol. May 2005;124(5):919-20. [Medline].

  3. Zhang G, Huang Y, Yan K, et al. Diverse phenotype of Brooke-Spiegler syndrome associated with a nonsense mutation in the CYLD tumor suppressor gene. Exp Dermatol. Dec 2006;15(12):966-70. [Medline].

  4. Stegmeier F, Sowa ME, Nalepa G, Gygi SP, Harper JW, Elledge SJ. The tumor suppressor CYLD regulates entry into mitosis. Proc Natl Acad Sci U S A. May 22 2007;104(21):8869-74. [Medline].

  5. Massoumi R, Paus R. Cylindromatosis and the CYLD gene: new lessons on the molecular principles of epithelial growth control. Bioessays. Dec 2007;29(12):1203-14. [Medline].

  6. Fukuda M, Hiroi M, Suzuki S, Ohmori Y, Sakashita H. Loss of CYLD might be associated with development of salivary gland tumors. Oncol Rep. Jun 2008;19(6):1421-7. [Medline].

  7. Parren LJ, Bauer B, Hamm H, Frank J. Brooke-Spiegler syndrome complicated by unilateral hearing loss. Int J Dermatol. Nov 2008;47 Suppl 1:56-9. [Medline].

  8. Carlson RM, Haddad L, Pui JC. Brooke-Spiegler syndrome with associated pegged teeth. Cutis. Nov 2008;82(5):345-9. [Medline].

  9. Ishihara M, Mehregan DR, Hashimoto K, et al. Staining of eccrine and apocrine neoplasms and metastatic adenocarcinoma with IKH-4, a monoclonal antibody specific for the eccrine gland. J Cutan Pathol. Feb 1998;25(2):100-5. [Medline].

  10. Rallan D, Harland CC. Brooke-Spiegler syndrome: treatment with laser ablation. Clin Exp Dermatol. Jul 2005;30(4):355-7. [Medline].

  11. Retamar RA, Stengel F, Saadi ME, et al. Brooke-Spiegler syndrome - report of four families: treatment with CO2 laser. Int J Dermatol. Jun 2007;46(6):583-6. [Medline].

  12. Kacerovska D, Szepe P, Vanecek T, et al. Spiradenocylindroma-like basaloid carcinoma of the anus and rectum: case report, including HPV studies and analysis of the CYLD gene mutations. Am J Dermatopathol. Oct 2008;30(5):472-6. [Medline].

  13. Albores-Saavedra J, Heard SC, McLaren B, Kamino H, Witkiewicz AK. Cylindroma (dermal analog tumor) of the breast: a comparison with cylindroma of the skin and adenoid cystic carcinoma of the breast. Am J Clin Pathol. Jun 2005;123(6):866-73. [Medline].

  14. Berberian BJ, Sulica VI, Kao GF. Familial multiple eccrine spiradenomas with cylindromatous features associated with epithelioma adenoides cysticum of Brooke. Cutis. Jul 1990;46(1):46-50. [Medline].

  15. Biernat W, Biernat S. Cutaneous adnexal carcinoma arising within a solitary cylindroma-spiradenoma. Am J Dermatopathol. Feb 1996;18(1):77-82. [Medline].

  16. Biggs PJ, Chapman P, Lakhani SR, Burn J, Stratton MR. The cylindromatosis gene (cyld1) on chromosome 16q may be the only tumour suppressor gene involved in the development of cylindromas. Oncogene. Mar 21 1996;12(6):1375-7. [Medline].

  17. Cardenas AA, Norton SA, Fitzpatrick JE. Solitary violaceous nodule on the face. Dermal cylindroma (also known as cylindroma, dermal eccrine cylindroma, Spiegler's tumor, turban tumor, and tomato tumor). Arch Dermatol. Apr 1993;129(4):498-9, 501. [Medline].

  18. Choi HR, Batsakis JG, Callender DL, Prieto VG, Luna MA, El-Naggar AK. Molecular analysis of chromosome 16q regions in dermal analogue tumors of salivary glands: a genetic link to dermal cylindroma?. Am J Surg Pathol. Jun 2002;26(6):778-83. [Medline].

  19. Chu L, Gu J, He Z, Xiao T, Liu X. Adenoviral vector expressing CYLD augments antitumor activity of TRAIL by suppression of NF-kappaB survival signaling in hepatocellular carcinoma. Cancer Biol Ther. Jun 2006;5(6):615-22. [Medline].

  20. De Francesco V, Frattasio A, Pillon B, et al. Carcinosarcoma arising in a patient with multiple cylindromas. Am J Dermatopathol. Feb 2005;27(1):21-6. [Medline].

  21. Ferrándiz C, Campo E, Baumann E. Dermal cylindromas (turban tumour) and eccrine spiradenomas in a patient with membranous basal cell adenoma of the parotid gland. J Cutan Pathol. Feb 1985;12(1):72-9. [Medline].

  22. Fukuda M, Fukuda F, Horiuchi Y, et al. Expression of CYLD, NF-kappaB and NF-kappaB-related factors in salivary gland tumors. In Vivo. Jul-Aug 2006;20(4):467-72. [Medline].

  23. Galadari E, Mehregan AH, Lee KC. Malignant transformation of eccrine tumors. J Cutan Pathol. Feb 1987;14(1):15-22. [Medline].

  24. Gerber JE, Descalzi ME. Eccrine spiradenoma and dermal cylindroma. J Cutan Pathol. Feb 1983;10(1):73-8. [Medline].

  25. Gerretsen AL, Beemer FA, Deenstra W, Hennekam FA, van Vloten WA. Familial cutaneous cylindromas: investigations in five generations of a family. J Am Acad Dermatol. Aug 1995;33(2 Pt 1):199-206. [Medline].

  26. Gerretsen AL, van der Putte SC, Deenstra W, van Vloten WA. Cutaneous cylindroma with malignant transformation. Cancer. Sep 1 1993;72(5):1618-23. [Medline].

  27. Goette DK, McConnell MA, Fowler VR. Cylindroma and eccrine spiradenoma coexistent in the same lesion. Arch Dermatol. Apr 1982;118(4):274-4. [Medline].

  28. Gokaslan ST, Carlile B, Dudak M, Albores-Saavedra J. Solitary cylindroma (dermal analog tumor) of the breast: a previously undescribed neoplasm at this site. Am J Surg Pathol. Jun 2001;25(6):823-6. [Medline].

  29. Headington JT, Batsakis JG, Beals TF, Campbell TE, Simmons JL, Stone WD. Membranous basal cell adenoma of parotid gland, dermal cylindromas, and trichoepitheliomas. Comparative histochemistry and ultrastructure. Cancer. Jun 1977;39(6):2460-9. [Medline].

  30. Heinritz W, Grunewald S, Strenge S, et al. A case of Brooke-Spiegler syndrome with a new mutation in the CYLD gene. Br J Dermatol. May 2006;154(5):992-4. [Medline].

  31. Kazakov DV, Soukup R, Mukensnabl P, Boudova L, Michal M. Brooke-Spiegler syndrome: report of a case with combined lesions containing cylindromatous, spiradenomatous, trichoblastomatous, and sebaceous differentiation. Am J Dermatopathol. Feb 2005;27(1):27-33. [Medline].

  32. Kim C, Kovich OI, Dosik J. Brooke-Spiegler syndrome. Dermatol Online J. Jan 27 2007;13(1):10. [Medline].

  33. Lin PY, Fatteh SM, Lloyd KM. Malignant transformation in a solitary dermal cylindroma. Arch Pathol Lab Med. Aug 1987;111(8):765-7. [Medline].

  34. Lotem M, Trattner A, Kahanovich S, Rotem A, Sandbank M. Multiple dermal cylindroma undergoing a malignant transformation. Int J Dermatol. Sep 1992;31(9):642-4. [Medline].

  35. Martinez W, Yebra MT, Arnal F, Casado M, Borbujo J. Multiple linear cylindromas. J Am Acad Dermatol. May 1992;26(5 Pt 2):821-4. [Medline].

  36. Massoumi R, Podda M, Fassler R, Paus R. Cylindroma as tumor of hair follicle origin. J Invest Dermatol. May 2006;126(5):1182-4. [Medline].

  37. Meybehm M, Fischer HP. Spiradenoma and dermal cylindroma: comparative immunohistochemical analysis and histogenetic considerations. Am J Dermatopathol. Apr 1997;19(2):154-61. [Medline].

  38. Michal M, Lamovec J, Mukensnabl P, Pizinger K. Spiradenocylindromas of the skin: tumors with morphological features of spiradenoma and cylindroma in the same lesion: report of 12 cases. Pathol Int. May 1999;49(5):419-25. [Medline].

  39. Misago N, Inoue T, Narisawa Y. Subcutaneous epithelioid angiomatous nodule: a variant of epithelioid hemangioma. J Dermatol. Jan 2006;33(1):73-4. [Medline].

  40. Munger BL, Graham JH, Helwig EB. Ultrastructure and histochemical characteristics of dermal eccrine cylindroma (turban tumor). J Invest Dermatol. Dec 1962;39:577-95. [Medline].

  41. Nonaka D, Rosai J, Spagnolo D, Fiaccavento S, Bisceglia M. Cylindroma of the breast of skin adnexal type: a study of 4 cases. Am J Surg Pathol. Aug 2004;28(8):1070-5. [Medline].

  42. Novo-Torres A, Laredo-Ortiz C, Castellar-Najera E, Lorda-Barraguer E, Alenda-Gonzalez C. [Familial presentation of multiple scalp tumors]. Actas Dermosifiliogr. Mar 2007;98(2):109-11. [Medline].

  43. Oiso N, Mizuno N, Fukai K, Nakagawa K, Ishii M. Mild phenotype of familial cylindromatosis associated with an R758X nonsense mutation in the CYLD tumour suppressor gene. Br J Dermatol. Nov 2004;151(5):1084-6. [Medline].

  44. Penneys NS, Kaiser M. Cylindroma expresses immunohistochemical markers linking it to eccrine coil. J Cutan Pathol. Feb 1993;20(1):40-3. [Medline].

  45. Pfaltz M, Bruckner-Tuderman L, Schnyder UW. Type VII collagen is a component of cylindroma basement membrane zone. J Cutan Pathol. Dec 1989;16(6):388-95. [Medline].

  46. Scheinfeld N, Hu G, Gill M, Austin C, Celebi JT. Identification of a recurrent mutation in the CYLD gene in Brooke-Spiegler syndrome. Clin Exp Dermatol. Sep 2003;28(5):539-41. [Medline].

  47. Tellechea O, Reis JP, Ilheu O, Baptista AP. Dermal cylindroma. An immunohistochemical study of thirteen cases. Am J Dermatopathol. Jun 1995;17(3):260-5. [Medline].

  48. Tunggal L, Ravaux J, Pesch M, et al. Defective laminin 5 processing in cylindroma cells. Am J Pathol. Feb 2002;160(2):459-68. [Medline].

  49. Urbanski SJ, From L, Abramowicz A, Joaquin A, Luk SC. Metamorphosis of dermal cylindroma: possible relation to malignant transformation. Case report of cutaneous cylindroma with direct intracranial invasion. J Am Acad Dermatol. Jan 1985;12(1 Pt 2):188-95. [Medline].

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Further Reading

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Keywords

cylindroma, turban tumor, tomato tumor, Brooke-Spiegler syndrome, BSS, benign adnexal tumor, dermal eccrine cylindroma, Spiegler's tumor, epithelioma adenoides cysticum of Brooke, Ancell-Spiegler cylindroma, adenoid cystic carcinoma, ACC, cribriform carcinoma

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Contributor Information and Disclosures

Author

Noah S Scheinfeld, MD, JD, FAAD, Assistant Clinical Professor, Department of Dermatology, Columbia University; Consulting Staff, Department of Dermatology, St Luke's Roosevelt Hospital Center, Beth Israel Medical Center, New York Eye and Ear Infirmary; Private Practice
Noah S Scheinfeld, MD, JD, FAAD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Optigenex Consulting fee Independent contractor

Coauthor(s)

Anusuya Mokashi, MS, MD, Radiology Resident, Staten Island University Hospital
Disclosure: Nothing to disclose.

Julide Tok Celebi, MD, Assistant Professor of Dermatology, Columbia University, College of Physicians and Surgeons; Consulting Staff, Department of Dermatology, New York Presbyterian Medical Center
Julide Tok Celebi, MD is a member of the following medical societies: American Academy of Dermatology, American Association for Cancer Research, Society for Investigative Dermatology, and Society for Melanoma Research
Disclosure: Nothing to disclose.

Arnold R Oppenheim, MD, Assistant Professor, Department of Internal Medicine, Division of Dermatology, Eastern Virginia School of Medicine
Arnold R Oppenheim, MD is a member of the following medical societies: American Academy of Dermatology and American Society for Clinical Pathology
Disclosure: Nothing to disclose.

Medical Editor

Abby S Van Voorhees, MD, Assistant Professor, Director of Psoriasis Services and Phototherapy Units, Department of Dermatology, University of Pennsylvania School of Medicine, Hospital of the University of Pennsylvania
Abby S Van Voorhees, MD is a member of the following medical societies: American Academy of Dermatology, American Medical Association, National Psoriasis Foundation, Phi Beta Kappa, Sigma Xi, and Women's Dermatologic Society
Disclosure: Amgen Honoraria Consulting; Abbott Honoraria Consulting; Genentech Honoraria Consulting; Incyte Grant/research funds Other; Warner Chilcott Honoraria Consulting; Merck Salary Management position; Abbott  Speaking and teaching

Pharmacy Editor

Richard P Vinson, MD, Assistant Clinical Professor, Department of Dermatology, Texas Tech University School of Medicine; Consulting Staff, Mountain View Dermatology, PA
Richard P Vinson, MD is a member of the following medical societies: American Academy of Dermatology, Association of Military Dermatologists, Texas Dermatological Society, and Texas Medical Association
Disclosure: Nothing to disclose.

Managing Editor

Christen M Mowad, MD, Associate Professor, Department of Dermatology, Geisinger Medical Center
Christen M Mowad, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, and Phi Beta Kappa
Disclosure: Nothing to disclose.

CME Editor

Joel M Gelfand, MD, MSCE, Medical Director, Clinical Studies Unit, Assistant Professor, Department of Dermatology, Associate Scholar, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania
Joel M Gelfand, MD, MSCE is a member of the following medical societies: Society for Investigative Dermatology
Disclosure: AMGEN Consulting fee Consulting; AMGEN Grant/research funds Investigator; Genentech Grant/research funds investigator; Centocor Consulting fee Consulting; Abbott Grant/research funds investigator; Abbott Consulting fee Consulting; Novartis  investigator; Pfizer Grant/research funds investigator; Celgene Consulting fee DMC Chair; NIAMS and NHLBI Grant/research funds investigator

Chief Editor

Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center
Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

 
 
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