Cases
50-year-old man with painful solitary nodule   

Discussion

Spiradenoma

Pathophysiology

Even though spiradenomas have been classically categorized as eccrine sweat gland tumors, recent evidence based on an immunohistochemical study of stem cell markers and OX2 membrane glycoprotein (CD200) has demonstrated that they arise from the hair follicle bulge rather than the eccrine sweat gland. This makes them the least differentiated follicular tumors, and they seem to be caused by a defective tumor suppressor gene, leading to increased activity of the nuclear factor kappa B (NF-κB) pathway. In Brooke-Spiegler syndrome, a defect exists in the CYLD gene. However, not all spiradenomas have this mutation and many show ALPK1 gene alterations, which has also been related to high-grade spiradenocarcinomas.

Epidemiology

Spiradenomas are rare and most of them are sporadic. They arise in persons between the ages of 15 and 35, but can occur at any age, with equal predominance in men and women.

Malignant spiradenomas tend to develop after age 50.

No sexual predilection exists for spiradenomas or malignant spiradenomas.

Clinical presentation

Spiradenomas typically appear as solitary painful, slow-growing, blue, gray, or pink nodules on the head, neck, or trunk, and less commonly the extremities or genitalia. Other patterns such as multiple lesions, zosteriform, blaschkoid/linear, nevoid, familial, congenital, or giant spiradenomas have also been described.

Malignant spiradenoma can develop in long-standing lesions, although malignant transformation overall is rare. A history of rapid growth, often associated with an ulceration and a change in color, is suggestive of malignant transformation.

Microscopic features

Hematoxylin and eosin show one or more large, sharply contrasted, and basophilic nodules in the dermis, unattached to the epidermis and sometimes extending into the subcutis (vertical growth). The nodules consist of groups of cells in cords, islands, and/or sheets (sometimes with trabecular arrangement) around tubular structures comprised of periodic acid-Schiff (PAS)-positive hyaline basal membrane material as well as focal ductal differentiation and homogeneous pink material.

Prognostic and molecular features

Spiradenomas are usually benign. They can be painful, and they may continue to grow. Even though the rate of malignant transformation is low (5-10%), lifetime clinical monitoring and genetic counseling are therefore recommended.

In cases of malignant spiradenoma, the rate of metastasis is about 20% and results in death in about 10% of patients.

References

  1. Bowen S, Gill M, Lee DA, Fisher G, Geronemus RG, Vazquez ME, Celebi JT. Mutations in the CYLD gene in Brooke-Spiegler syndrome, familial cylindromatosis, and multiple familial trichoepithelioma: lack of genotype-phenotype correlation. J Invest Dermatol. 2005 May;124(5):919-20. doi: 10.1111/j.0022-202X.2005.23688.x.
  2. Grossmann P, Vanecek T, Steiner P, Kacerovska D, Spagnolo DV, Cribier B, Rose C, Vazmitel M, Carlson JA, Emberger M, Martinek P, Pearce RL, Pearn J, Michal M, Kazakov DV. 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 Feb;35(1):34-44. doi: 10.1097/DAD.0b013e31824e7658.
  3. Kazakov DV, Schaller J, Vanecek T, Kacerovska D, Michal M. Brooke-Spiegler syndrome: report of a case with a novel mutation in the CYLD gene and different types of somatic mutations in benign and malignant tumors. J Cutan Pathol. 2010 Aug;37(8):886-90. doi: 10.1111/j.1600-0560.2010.01511.x.
  4. Rashid M, van der Horst M, Mentzel T, Butera F, Ferreira I, Pance A, Rütten A, Luzar B, Marusic Z, de Saint Aubain N, Ko JS, Billings SD, Chen S, Abi Daoud M, Hewinson J, Louzada S, Harms PW, Cerretelli G, Robles-Espinoza CD, Patel RM, van der Weyden L, Bakal C, Hornick JL, Arends MJ, Brenn T, Adams DJ. ALPK1 hotspot mutation as a driver of human spiradenoma and spiradenocarcinoma. Nat Commun. 2019 May 17;10(1):2213. doi: 10.1038/s41467-019-09979-0.
  5. Sellheyer K. Spiradenoma and cylindroma originate from the hair follicle bulge and not from the eccrine sweat gland: an immunohistochemical study with CD200 and other stem cell markers. J Cutan Pathol. 2015 Feb;42(2):90-101. doi: 10.1111/cup.12406.
  6. Staiger RD, Helmchen B, Papet C, Mattiello D, Zingg U. Spiradenocarcinoma: A Comprehensive Data Review. Am J Dermatopathol. 2017 Oct;39(10):715-725. doi: 10.1097/DAD.0000000000000910.