Cylindroma (Benign neoplasm of skin)
Are You Confident of the Diagnosis?
Characteristic findings on physical examination
Cylindromas are skin adnexal tumors that typically present as a skin colored, reddish or bluish nodule(s) that may range in size from a few millimeters to several centimeters (Figure 1). Lesions are typically located on the scalp, head or neck. They occur sporadically, are solitary and occasionally painful. The lesions are benign but incomplete biopsy/removal may result in local recurrence. Multiple tumors may be seen in familial cylindromatosis/ Brooke-Spiegler syndrome, multiple familial trichoepitheliomas syndrome and have been associated with other adnexal neoplasms. When nodular lesions coalesce on the scalp they have been called “turban” tumors.
Expected results of diagnostic studies
Biopsy is required to confirm the diagnosis and to histologically characterize the neoplasm. Histologically, angular and ovoid dermal islands composed of an inner larger basaloid polygonal cell population and outer small round cell population are delineated from the stroma by a basement membrane (Figure 2) and are arranged in a mosaic or jigsaw pattern (Figure 3). Lobules may contain hyaline deposits and small tubular lumina.
Cylindromas are distinguished microscopically from basal cell carcinomas, which contain irregular basaloid lobules with peripheral palisading of nuclei, often with a connection to the epidermis, that have artifactual retractions from a mucinous stroma on sun-damaged skin. Cylindromas may have similar cytologic features similar to those of spiradenomas; however, the rounded tumor lobules in spiradenomas often contain a vascular stroma containing lymphocytes and lack the mosaic pattern.
Who is at Risk for Developing this Disease?
Lesions may occur at any age but solitary lesions most often occur between the ages of 20 and 40 with a female predilection. Lesions in familial autosomal dominant cylidromatosis/Brooke-Spiegler syndrome (cylindromas, trichoepitheliomas, and spiradenomas) typically appear after puberty with slowly growing and often numerous lesions.
What is the Cause of the Disease?
Sporadic, nonhereditary cylindromas are skin adnexal tumors with immunohistochemical and cytologic features of apocrine differentiation. Brooke-Spiegler syndrome/familial cylindromatosis is characterized by a heterozygous germ-line mutation in the carboxyl-terminal end of the CYLDgene (16q12-q13).
The CYLD gene appears to function in tumor-suppressor gene regulation, since tumorigenic epidermal cells have been shown to diminish the deubiquitinating activity of the endogenous CYLD, resulting in increased expression of several angiogenic factors leading to accelerated proliferation and migration of tumoral cells.
Systemic Implications and Complications
Malignant transformation is rare. Multiple lesions are disfiguring and require extensive surgical management to restore anatomic appearance. An association with familial autosomal dominant cylindromatosis and basal cell carcinoma has been reported. Brooke-Speigler syndrome has been associated with other cutaneous findings, unilateral hearing loss, and manifesting with pegged teeth.
Electrodesiccation and curettage
Rajan N, et al report the following settings for laser ablation:
-CO2: 1mm spot, 400-mm focal length lens, continuous mode 8W, 1020 W/cm2, extrusion after deroofing
-Nd:YAG: 1,064 nm wavelength, continuous cutting mode, 40W
-Er:YAG: 2,940 nm wavelength, 2mm diameter, 0.4 J/cm2 at 4 pulses for tissue ablation, CO2 laser for hemostasis (2mm, 5W)
Optimal Therapeutic Approach for this Disease
Biopsy is needed to confirm diagnosis. Palpation of the head, parotid gland, neck, and lymph nodes should be performed. Complete removal should be considered for incomplete biopsies to prevent recurrence and to avoid sampling error of an unexamined focus of residual tumor. Multiple lesions need multidisciplinary management to monitor tumor development or progression. Intervention is based on clinical and patient presentation.
Solitary lesions are removed surgically. Follow-up is individual for recurrence or development of new lesions. Patients with syndromic and multiple lesions can be seen at regular intervals to evaluate for change in clinical appearance or the development of an associated cutaneous or salivary tumor (basal cell adenoma of the parotid).
Unusual Clinical Scenarios to Consider in Patient Management
Malignant cylindromas are rare. They may occur in the syndromic types when multiple lesions are present. Histologically, malignant cylindromas contain anaplastic cells, lack organoid characteristics, and show loss of the hyaline sheath. Infiltration into the stroma of tumor cells are associated with scattered, numerous mitotic figures, some atypical. Exceptional cases describe underlying bone destruction and calvarian defects.
What is the Evidence?
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. vol. 124. 2005. pp. 919-20. (Three families with Brooke-Spiegler syndrome, one with familial cylindromatosis, and two with multiple familial trichoepithelioma phenotypes associated with novel and recurrent mutations in CYLD. Description of the cutaneous tumors in these syndromes.)
Clarke, J, Ioffreda, M, Helm, KF. “Multiple familial trichoepitheliomas: a folliculosebaceous-apocrine genodermatosis”. Am J Dermatopathol. vol. 24. 2002. pp. 402-5. (A family with multiple hereditary trichoepitheliomas is described. The authors conclude that tumors develop from undifferentiated germinative cells of the folliculosebaceous-apocrine unit.)
Bignell, GR, Warren, W, Seal, S, Takahashi, M, Rapley, E, Barfoot, R. “Identification of the familial cylindromatosis tumour-suppressor gene”. Nat Genet. vol. 25. 2000. pp. 160-5. (The CYLD gene is detected in germline mutations in 21 cylindromatosis families and somatic mutations in one sporadic and five familial cylindromas. All mutations predict truncation or absence of the encoded protein, which encodes three cytoskeletal-associated-protein-glycine-conserved (CAP-GLY) domains that are found in proteins that coordinate the attachment of organelles to microtubules.)
Alameda, JP, Moreno-Maldonado, R, Navarro, M, Bravo, A, Ramírez, A, Page, A, Jorcano, JL, Fernández-Aceñero, MJ, Casanova, ML. “An inactivating CYLD mutation promotes skin tumor progression by conferring enhanced proliferative, survival and angiogenic properties to epidermal cancer cells”. Oncogene. vol. 29. 2010 Dec 16. pp. 6522-32. (In contrast with previous studies showing the development of benign tumors by mutations in the CYLD gene, the authors provide evidence that the occurrence of mutations in the CYLD gene in tumorigenic epidermal cells (carrying previous mutations) increases the aggressiveness of carcinomas, mainly through enhancement of the expression of angiogenic factors.)
Scott, AR, Faquin, WC, Deschler, DG. “Parotid mass in a woman with multiple cutaneous cylindromas”. Head Neck. vol. 32. 2010. pp. 684-7. (The authors review 18 cases in which cylindromatosis with coexistent salivary gland membranous basal cell adenoma was reported. Seventeen cases involved the parotid gland with two reports of malignant transformation.)
Biernat, W, Biernat, S. “Cutaneous adnexal carcinoma arising within a solitary cylindroma-spiradenoma”. Am J Dermatopathol. vol. 18. 1996. pp. 77-82. (Malignant transformation within an adnexal neoplasm with features of spiradenoma and cylindroma is reported in a 60-year-old woman.)
Parren, LJ, Bauer, B, Hamm, H, Frank, J. “Brooke-Spiegler syndrome complicated by unilateral hearing loss”. Int J Dermatol. vol. 47. 2008. pp. 56-9. (Report on a man with multiple cylindroma with neoplasms in the meatus externus of the right ear leading to unilateral hearing loss, a complication that has been documented only on a few occasions in this disease.)
Carlson, RM, Haddad, L, Pui, JC. “Brooke-Spiegler syndrome with associated pegged teeth”. Cutis. vol. 82. 2008. pp. 345-9. (The occurrence of pegged teeth in association with BSS is reported.)
Rajan, N, Trainer, AH, Burn, J, Langtry, JA. “Familial cylindromatosis and brooke-spiegler syndrome: a review of current therapeutic approaches and the surgical challenges posed by two affected families”. Dermatol Surg. vol. 35. 2009. pp. 845-52. (Review of treatment options for cylindromas.)
Kuklani, RM, Glavin, FL, Bhattacharyya, I. “Malignant cylindroma of the scalp arising in a setting of multiple cylindromatosis: a case report”. Head Neck Pathol. vol. 3. 2009. pp. 315-9. (Report of a case of malignant cylindroma of the scalp in a patient with multiple cylindromatosis.)
Friedrich, RE. “Dermal cylindroma of the scalp (turban tumour) and subjacent calvarian defects”. Anticancer Res. vol. 30. 2010 May. pp. 1793-7. (A case report of a cylindroma with bone destruction but without evidence of malignant transformation in a patient with Brooke-Spiegler syndrome.)
Corda, G, Sala, A. “Cutaneous cylindroma: it’s all about MYB”. J Pathol. vol. 239. 2016 Aug. pp. 391-3. (Only the wild-type MYB oncoprotein is activated in the majority of these tumours. RNA interference studies in cells derived from BSS patients indicate that ablating MYB expression results in a striking reduction of cylindroma cell proliferation, suggesting that MYB plays a pivotal role in the biology of this cancer.)
Farkas, K, Deák, BK, Sánchez, LC, Martínez, AM, Corell, JJ, Botella, AM, Benito, GM, López, RR, Vanecek, T, Kazakov, DV, Kromosoeto, JN, van den Ouweland, AM, Varga, J, Széll, M, Nagy, N. “The CYLD p.R758X worldwide recurrent nonsense mutation detected in patients with multiple familial trichoepithelioma type 1, Brooke-Spiegler syndrome and familial cylindromatosis represents a mutational hotspot in the gene”. BMC Genet. vol. 17. 2016 Feb 9. pp. 36(p.R758X is a mutational hotspot on the gene and patients carrying the mutation exhibit high phenotypic diversity.)
Tantcheva-Poór, I, Vanecek, T, Lurati, MC, Rychly, B, Kempf, W, Michal, M, Kazakov, DV. “Report of Three Novel Germline CYLD Mutations in Unrelated Patients with Brooke-Spiegler Syndrome, Including Classic Phenotype, Multiple Familial Trichoepitheliomas and Malignant Transformation”. Dermatology. vol. 232. 2016. pp. 30-7. (3 novel CYLD mutations in 3 unrelated BSS patients, including the classic phenotype, multiple familial trichoepitheliomas phenotype and malignant transformation are reported.)
Malzone, MG, Campanile, AC, Losito, NS, Longo, F, Perri, F, Caponigro, F, Schiavone, C, Ionna, F, Maiello, F, Martinuzzi, C, Nasti, S, Botti, G, Fulciniti, F. “Brooke-Spiegler syndrome presenting multiple concurrent cutaneous and parotid gland neoplasms: cytologic findings on fine-needle sample and description of a novel mutation of the CYLD gene”. Diagn Cytopathol. vol. 43. 2015 Aug. pp. 654-8. (Multiple dermal cylindromas and membranous basal cell adenoma of parotid gland in a 67-year-old woman with Brooke-Spiegler syndrome (BSS) were examined by fine-needle cytology.)
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