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Spiradenoma


Spiradenoma

Article Author:
Alyssa Miceli
Article Editor:
Sarah Ferrer-Bruker
Updated:
8/14/2020 11:25:58 PM
For CME on this topic:
Spiradenoma CME
PubMed Link:
Spiradenoma

Introduction

Spiradenomas are well-differentiated, benign, dermal neoplasms originating from the sweat glands. Most spiradenomas occur between the ages of 15 to 35 years. Typically, they present as small solitary nodules that can grow to several centimeters, often with a blue, gray, or purple hue.[1]They are strikingly painful. Spiradenomas usually arise on the head, neck, and trunk; however, cases in other areas such as the breast have occurred. Spiradenomas with varying morphology like multiple linear, zosteriform, blaschkoid, and nevoid spiradenomas have also been reported. Spiradenomas can occur concomitantly with cylindromas, trichoepitheliomas, and/or trichoblastomas. In patients with Brooke-Spiegler, multiple spiradenomas, cylindromas, and trichoepitheliomas can be seen.[2]

Etiology

Spiradenomas appear to be caused by a defective tumor suppressor gene. A mutation in the CYLD gene on chromosome 9 is found in Brooke-Spiegler syndrome, which features multiple spiradenomas. [3]The specific cause of solitary spiradenomas is not clear. Originally thought to be of eccrine differentiation, recent studies have suggested that spiradenomas may be derived from apocrine glands or the folliculosebaceous unit.

The cause of malignant spiradenomas is also unknown. Increased expression of p53 is seen, though the significance of this finding in the malignant transformation of spiradenomas has not been determined.[4]

Epidemiology

Spiradenomas are usually benign and most often occur in patients between the ages of 15 and 35, though cases have been reported in infants. There is no racial or sexual predilection for spiradenomas. To date, approximately 15 cases of either linear, zosteriform, nevoid, blaschkoid, or multiple spiradenomas have been reported in the literature.[5][6][7] Although benign spiradenomas are quite rare, malignant spiradenomas are even rarer and occur in patients older than the age of 50 years, with an average age of 59 years.[8]

Pathophysiology

The pathogenesis of the formation of spiradenomas is not completely understood. A defect in the tumor suppressor gene, CYLDis thought to contribute to their development in Brooke-Spiegler syndrome, which also features multiple cylindromas.[3] A transition between cylindromas and spiradenomas has been shown to occur in patients with CYLD gene mutations. Derangements in intercellular bridge proteins that maintain epithelial organization, including claudin-4, cadherin, and beta-catenin, have also been suggested as contributing to neoplasm formation. [9]Two studies found intense nuclear immunoreactivity for beta-catenin in spiradenomas, supporting a role of alterations in the beta-catenin pathway in their development. Professionals postulate that an abnormal clone arising during embryogenesis produces multiple abnormal cells that result in presentations involving multiple nevoid, blaschkoid, or linear spiradenomas.

Historically, spiradenomas were thought to be of eccrine lineage, though many lesions have been shown to demonstrate apocrine differentiation. Alternatively, one study using immunohistochemical markers for stem cells and CD200 suggests that both spiradenomas and cylindromas are follicular-based tumors as opposed to being derived from eccrine or apocrine glands. Other studies have shown spiradenomas to have either apocrine or folliculosebaceous differentiation.[10]

Increased expression of p53 has been observed in malignant spiradenomas.[11]

Histopathology

On histopathology, spiradenomas show one or more large, sharply demarcated basophilic nodules of the dermis. Two types of cells are seen in the nodules. These cells are either small, dark, basaloid cells with hyperchromatic nuclei, or larger, pale, and with ovoid nuclei. These lighter cells tend to be toward the center of the lesion. Duct-like structures of uninterpretable differentiation and cystic cavities filled with finely granular eosinophilic material may be seen. [12][13]The material within the cystic cavities is diastase resistant and periodic acid-Schiff positive. A lymphangiectatic variant has rarely been described. Immunohistochemical staining shows increased expression of S-100 in the large, pale-staining cells, and human milk fat globulin (HMFG) and lysozyme in the tubular cells.[10] Spiradenomas will also stain positive for epithelial membrane antigen, carcinoembryonic antigen and the myoepithelial stains p63 and SMA. The cytokeratin patterns include expression of keratins 7, 8, 14, and 18.[14][15]

Malignant spiradenomas demonstrate increased mitotic rates, necrosis, nuclear atypia, pleomorphism, hyperchromasia, loss of nested growth patterns, and loss of the dual cell population. In histologic studies, two patterns of malignant spiradenomas were observed. One was an abrupt transition between a benign spiradenoma and high-grade carcinoma, while the second showed contiguity between the benign and malignant areas.

History and Physical

Spiradenomas typically present as dermal or subcutaneous nodules on any area, though more commonly are seen on the head, neck, and trunk, and less commonly on the arms and legs. Several spiradenomas have been reported on the ears and eyelids, as well as papular lesions of the proximal nail fold. On physical examination, lesions are typically small, though they can grow to several centimeters in diameter, and have a blue, gray, or purple hue. Spiradenomas can be strikingly painful, though most are asymptomatic. Although the typical presentation is a solitary lesion, there can be linear, blaschkoid or grouped spiradenomas. Multiple spiradenomas can be seen and, if present with cylindromas and trichoblastomas, Brooke-Spiegler syndrome must be considered. [16]Based on the physical exam, the differential diagnosis of spiradenomas typically includes cylindromas, epidermal inclusion cysts, dermatofibromas, leiomyomas, poromas, and basal cell carcinomas.

Though rare, spiradenomas have occurred in infancy, representing less than 1% of all reported cases of spiradenoma. These typically present as more superficial dermal nodules than seen in adults.

Rapid growth in a long-standing lesion may be an indication of malignant transformation. Malignant spiradenomas also tend to ulcerate and have a predilection for the trunk and extremities. A change in color of the lesion can be a sign of malignant transformation. Metastases from malignant spiradenomas can occur in lymph nodes, lung, brain, or liver.

Evaluation

Lesions should be excised for histopathologic examination. On histopathology, spiradenomas show one or more large, sharply demarcated basophilic nodules of the dermis. Two types of cells are seen in the nodules. These cells are either small, dark, basaloid cells with hyperchromatic nuclei, or larger, pale, and with ovoid nuclei. Malignant spiradenomas demonstrate increased mitotic rates, necrosis, nuclear atypia, pleomorphism, hyperchromasia, loss of nested growth patterns, and loss of the dual cell population.[4]

Imaging studies, including MRI, CT, or ultrasound can help to determine if metastatic foci are present in the case of malignant spiradenoma.

Treatment / Management

Although spiradenoma is considered a benign adnexal neoplasm with low recurrence rate, malignant transformation can occur in long-standing lesions, particularly in patients older than the age of 50. The rate of metastasis for malignant spiradenocarcinoma is about 50%. Conservative surgical excision of spiradenomas is therefore recommended. In cases of multiple spiradenomas, adjunctive treatment with carbon dioxide laser may be employed after surgical debulking.

Malignant spiradenomas tend to be aggressive tumors with high rates of metastasis and mortality. Radiation and chemotherapy may be used after tumor resection for malignant spiradenomas.

Differential Diagnosis

  • Angiolipoma
  • Dermatofibroma
  • Epidermal Inclusion Cyst
  • Leiomyoma
  • Poroma
  • Schwannoma

Enhancing Healthcare Team Outcomes

Dermatologists often coordinate care with other specialists as well as primary care physicians.   Dermatologists are trained in both clinical dermatology and dermatopathology, making clinicopathologic correlation a crucial part of the management of cutaneous conditions by dermatologists.  Given this unique training, it is important for dermatologists to effectively communicate with primary care and other specialty physicians about the proper management of both benign and malignant cutaneous neoplasms.  It is this collaborative decision making that provides the best care and outcomes for patients.  In the case of spiradenomas, though a benign neoplasm, complete surgical excision is recommended given the potential for malignant transformation.  With proper evidence-based management, the risk for this malignant transformation diminishes, improving the long-term prognosis for the patient.


References

[1] Kaleeswaran AV,Janaki VR,Sentamilselvi G,Kiruba MC, Eccrine spiradenoma. Indian journal of dermatology, venereology and leprology. 2002 Jul-Aug;     [PubMed PMID: 17656951]
[2] Bumgardner AC,Hsu S,Nunez-Gussman JK,Schwartz MR, Trichoepitheliomas and eccrine spiradenomas with spiradenoma/cylindroma overlap. International journal of dermatology. 2005 May;     [PubMed PMID: 15869542]
[3] Mohiuddin W,Laun J,Cruse W, Brooke-Spiegler Syndrome. Eplasty. 2018;     [PubMed PMID: 30093932]
[4] Huang A,Vyas NS,Mercer SE,Phelps RG, Histological Findings and Pathologic Diagnosis of Spiradenocarcinoma: A Case Series and Review of the Literature. Journal of cutaneous pathology. 2018 Dec 27;     [PubMed PMID: 30588645]
[5] Salim S,Bounniyt H,El Amraoui M,Benzekri A,Senouci K,Hassam B, Malignant transformation of a spiradenoma with blaschkoïd pattern. Clinical case reports. 2018 Nov;     [PubMed PMID: 30455896]
[6] Rosales Santillan M,ATajnert K,Swaby MG,Migden MR,Silapunt S, Multiple eccrine spiradenomas in a zosteriform pattern. Dermatology online journal. 2017 Aug 15;     [PubMed PMID: 29469747]
[7] Ψ Multiple eccrine spiradenomas with a zosteriform pattern-Report of a rare case diagnosed on fine needle aspiration cytology., Agnihotri M,Kothari K,Naik L,, Diagnostic cytopathology, 2017 May 28     [PubMed PMID: 28556514]
[8] Tripathi R,Ezaldein HH,Scott JF,Bordeaux JS, Trends in the Incidence and Survival of Eccrine Malignancies in the United States: A SEER Population-Based Study. Journal of the American Academy of Dermatology. 2018 Oct 1;     [PubMed PMID: 30287321]
[9] Alteration of the β-catenin pathway in spiradenoma., Im M,Kim DH,Park JS,Chung H,Lee Y,Kim CD,Seo YJ,Lee JH,, Journal of cutaneous pathology, 2011 Aug     [PubMed PMID: 21518380]
[10] Meybehm M,Fischer HP, Spiradenoma and dermal cylindroma: comparative immunohistochemical analysis and histogenetic considerations. The American Journal of dermatopathology. 1997 Apr;     [PubMed PMID: 9129700]
[11] Granter SR,Seeger K,Calonje E,Busam K,McKee PH, Malignant eccrine spiradenoma (spiradenocarcinoma): a clinicopathologic study of 12 cases. The American Journal of dermatopathology. 2000 Apr;     [PubMed PMID: 10770427]
[12] Tran K,DeFelice T,Robinson M,Patel R,Sanchez M, Spiradenomas. Dermatology online journal. 2012 Dec 15;     [PubMed PMID: 23286805]
[13] Kanwaljeet S,Chatterjee T, Eccrine spiradenoma: A rare adnexal tumor. Indian journal of cancer. 2017 Oct-Dec;     [PubMed PMID: 30082561]
[14] Missall TA,Burkemper NM,Jensen SL,Hurley MY, Immunohistochemical differentiation of four benign eccrine tumors. Journal of cutaneous pathology. 2009 Feb;     [PubMed PMID: 18564284]
[15] Kurokawa I,Nishimura K,Tarumi C,Hakamada A,Isoda K,Mizutani H,Tsubura A, Eccrine spiradenoma: co-expression of cytokeratin and smooth muscle actin suggesting differentiation toward myoepithelial cells. Journal of the European Academy of Dermatology and Venereology : JEADV. 2007 Jan;     [PubMed PMID: 17207189]
[16] Brooke-Spiegler syndrome associated with cylindroma, trichoepithelioma and eccrine spiradenoma., Chen M,Liu H,Fu X,Yu Y,Yu G,Tian H,Zhou G,Lu X,Chen S,, International journal of dermatology, 2013 Dec     [PubMed PMID: 24261740]