Spiradenoma

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Spiradenoma

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The histogenesis of spiradenomas remains in question, but many lesions demonstrate apocrine differentiation. The term eccrine spiradenoma may join the list of other misnomers in dermatology, including mycosis fungoides and granuloma faciale. Lesions usually manifest as solitary, 1-cm-diameter, gray, pink, purple, red, or blue nodules on the upper half of the ventral side of the body. Spiradenomas can be painful, often in paroxysms. Multiple spiradenomas have been reported. Their initial elaboration is attributed to Kersting and Helwig. [1]

Spiradenomas are usually benign. It can occur in infancy but most commonly arises in persons aged 15-35 years. About 15 cases of linear/zosteriform/nevoid/blaschkoid multiple spiradenomas exist in the literature. [2, 3] About 50 case reports of malignant spiradenoma exist in the literature. Dabska [4] first described malignant spiradenoma in 1972.

Spiradenomas can occur in Brooke-Spiegler syndrome, which manifests with cylindromas, spiradenomas, and trichoepitheliomas. In this syndrome, lesions can have combined features of both cylindromas and spiradenomas. [5, 6]

Spiradenoma and cylindroma have their basis in the hair follicle bulge rather than the eccrine sweat gland, based on immunohistochemical study stem cell markers and with CD200 according to Sellheyer. [7] Cytokeratin 15 allowed cylindroma and spiradenoma to be distinguished. Cytokeratin 19 and pleckstrin homology–like domain, family A, member 1 (PHLDA1), did not distinguish or define cylindromas and spiradenomas. Sellheyer concluded that both cylindroma and spiradenoma are not eccrine tumors, rather they are follicular tumors, asserting that both adnexal neoplasms derive from the hair follicle bulge and represent the least differentiated follicular tumors.

A defective tumor suppressor gene is believed to result in the development of spiradenomas. In Brooke-Spiegler syndrome, of which spiradenomas are a manifestation, the defective gene is the CYLD gene on chromosome 9. Work remains to be performed on the genetic defect causing isolated and sporadic spiradenomas. The CYLD seems to be a hot spot of mutations as novel mutations continue to be reported. [8]

The expression of p53 in malignant spiradenomas seems to be increased.

The cells of origin of spiradenomas appear to have apocrine and trichoepitheliomatous differentiation, ie, they have complex hair follicle (folliculosebaceous apocrine) differentiation rather than eccrine differentiation.

In cases of linear/zosteriform/nevoid/blaschkoid multiple spiradenomas, an abnormal clone arising during embryogenesis is postulated to produce the multiple abnormal cells that result in such spiradenomas.

In a cytogenetic study, Dijkhuizen et al [9] found a spiradenoma and 2 lymph node metastases, with a growth pattern and microscopic appearance typical for benign spiradenoma, a 46,XY-5,del(16)(q22),+mar(t(?;5)(?::5q13—-5qter)) karyotype.

These similar genetic defects seem to support a relationship between the chromosomal abnormalities and the clinical malignant action of this benign-appearing neoplasm.

In a study of 379 specimens of Brooke-Spiegler syndrome, of the 76 tumors from 32 Brooke-Spiegler syndrome patients with a germline CYLD mutation, 12 tumors were spiradenomas, and 15 were spiradenocylindromas. The authors concluded that there is an absence of firm genotype-phenotype correlation in Brooke-Spiegler syndrome. The presence of a subset of patients with Brooke-Spiegler syndrome/multiple familial trichoepithelioma who do not have a demonstrable germline CYLD mutation is notable. [10]

In one study, expression of erythroid differentiation regulator 1 was weak in eccrine spiradenoma, sebaceous hyperplasias, and seborrheic keratosis. [11] The significance of this has yet to be further defined.

Spiradenomas are rare worldwide. Malignant spiradenomas are very rare worldwide.

No racial link exists for spiradenomas.

No sexual predilection exists for spiradenomas or malignant spiradenomas.

Spiradenomas have been reported to arise in infancy, but this is rare. A case of a neonatal spiradenoma in a 4-week-old infant has been reported. [12] However, most spiradenomas arise in persons aged 15-35 years. Malignant spiradenomas tend to develop after age 50 years. Malignant spiradenomas present at an average age of 59 years (range, 21-92 y).

Spiradenomas can be painful. The rate of malignant transformation is very low, [13] and, sometimes, malignant transformation has been reported to develop spontaneously. The rate of metastasis is about 50% and can result in death. Malignant eccrine spiradenomas of the scalp have been noted and result in increased morbidity and mortality. [14] This remains a rare event.

Patients must understand that the lesions can be painful and that only surgery is curative.

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Park HR, Im SB, Kim HK, Shin DS, Park YL. Painful eccrine spiradenoma containing nerve fibers: a case report. Dermatology. 2012. 224(4):301-6. [Medline].

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Jamshidi M, Nowak MA, Chiu YT, Perry EA, Fatteh SM. Giant malignant eccrine spiradenoma of the scalp. Dermatol Surg. 1999 Jan. 25(1):45-8. [Medline].

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Jariwala A, Evans A, McLeod G. Not all stubbed toes are innocuous–A case report of rare malignant eccrine spiradenoma (spiradenocarcinoma) of the toe. Foot Ankle Surg. 2010 Jun. 16(2):e32-3. [Medline].

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Rodriguez-Martin M, Sanchez Gonzalez R, Saez-Rodríguez M, Garcia-Bustínduy M, Martín-Herrera A, Noda-Cabrera A. An unusual case of congenital linear eccrine spiradenoma. Pediatr Dermatol. 2009 Mar-Apr. 26(2):180-3. [Medline].

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Bosch MM, Boon ME. Fine-needle cytology of an eccrine spiradenoma of the breast: diagnosis made by a holistic approach. Diagn Cytopathol. 1992. 8(4):366-8. [Medline].

Yiğit N, Çelik E, Yavan İ, Günal A, Kurt B, Karslıoğlu Y, et al. Distinctive immunostaining of claudin-4 in spiradenomas. Ann Diagn Pathol. 2016 Feb. 20:44-7. [Medline].

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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. 1998 Feb. 25(2):100-5. [Medline].

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Saboorian MH, Kenny M, Ashfaq R, Albores-Saavedra J. Carcinosarcoma arising in eccrine spiradenoma of the breast. Report of a case and review of the literature. Arch Pathol Lab Med. 1996 May. 120(5):501-4. [Medline].

Kurokawa I, Nishimura K, Tarumi C, et al. Eccrine spiradenoma: co-expression of cytokeratin and smooth muscle actin suggesting differentiation toward myoepithelial cells. J Eur Acad Dermatol Venereol. 2007 Jan. 21(1):121-3. [Medline].

Ko JY, Lee CW, Moon SH, Song KW, Park CK. Giant vascular eccrine spiradenoma: report of a case with immunohistochemical study. J Korean Med Sci. 2006 Feb. 21(1):172-6. [Medline]. [Full Text].

Ohtsuki Y, Ohtsuka H, Kurabayashi A, et al. Immunohistochemical and electron microscopic studies of Langerhans cells in a case of multiple eccrine spiradenomas. Med Mol Morphol. 2007 Dec. 40(4):221-5. [Medline].

Sridhar KS, Benedetto P, Otrakji CL, Charyulu KK. Response of eccrine adenocarcinoma to tamoxifen. Cancer. 1989 Jul 15. 64(2):366-70. [Medline].

Mirza I, Kloss R, Sieber SC. Malignant eccrine spiradenoma. Arch Pathol Lab Med. 2002 May. 126(5):591-4. [Medline].

Martins C, Bartolo E. Brooke-Spiegler syndrome: treatment of cylindromas with CO2 laser. Dermatol Surg. 2000 Sep. 26(9):877-80; discussion 881. [Medline].

Richard A, Chevalier JM, Verneuil L, Sergent B, Tesnière A, Dolfus C, et al. CO2 laser treatment of skin cylindromas in Brooke-Spiegler syndrome. Ann Dermatol Venereol. 2014 May. 141(5):346-53. [Medline].

Rahim RR, Rajan N, Langtry JA. Infiltrative Recurrent Eccrine Spiradenoma of the Anterior Neck Treated Using Mohs Micrographic Surgery. Dermatol Surg. 2013 Oct 1. [Medline].

Noah S Scheinfeld, JD, MD, FAAD Assistant Clinical Professor, Department of Dermatology, Weil Cornell Medical College; Consulting Staff, Department of Dermatology, St Luke’s Roosevelt Hospital Center, Beth Israel Medical Center, New York Eye and Ear Infirmary; Assistant Attending Dermatologist, New York Presbyterian Hospital; Assistant Attending Dermatologist, Lenox Hill Hospital, North Shore-LIJ Health System; Private Practice

Noah S Scheinfeld, JD, MD, FAAD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

David F Butler, MD Former Section Chief of Dermatology, Central Texas Veterans Healthcare System; Professor of Dermatology, Texas A&M University College of Medicine; Founding Chair, Department of Dermatology, Scott and White Clinic

David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Society for MOHS Surgery, Association of Military Dermatologists, Phi Beta Kappa

Disclosure: Nothing to disclose.

Jeffrey P Callen, MD Professor of Medicine (Dermatology), Chief, Division of Dermatology, University of Louisville School of Medicine

Jeffrey P Callen, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, American College of Rheumatology

Disclosure: Received income in an amount equal to or greater than $250 from: Lilly; Amgen <br/>Received honoraria from UpToDate for author/editor; Received honoraria from JAMA Dermatology for associate editor; Received royalty from Elsevier for book author/editor; Received dividends from trust accounts, but I do not control these accounts, and have directed our managers to divest pharmaceutical stocks as is fiscally prudent from Stock holdings in various trust accounts include some pharmaceutical companies and device makers for i inherited these trust accounts; for: Allergen; Celgene; Pfizer; 3M; Johnson and Johnson; Merck; Abbott Laboratories; AbbVie; Procter and Gamble; Amgen.

Dirk M Elston, MD Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Spiradenoma

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