Cylindroma Workup

Updated: Nov 08, 2019
  • Author: Angela (Angel) M Crotty, MD; Chief Editor: Dirk M Elston, MD  more...
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Workup

Laboratory Studies

A breast cylindroma that displays MYB expression is a benign tumor, with CYLD gene mutations differing from an adenoid cystic carcinoma. In the breast, the diagnosis of a benign cylindroma was made using reverse-transcription polymerase chain reaction, fluorescence in situ hybridization, whole-exome sequencing, immunohistochemistry, and revealing a MYB-NFIB fusion gene absence and decreased levels of expression of MYB protein with a clonal somatic CYLD splice site mutation accompanying a wild-type allele linked with an absence of heterozygosity showing a benign cylindroma. [46] Additionally, the expression of both MYB and GATA3 may prove to be useful in differentiating cutaneous adnexal carcinomas and cylindroma (where it is common) from breast and salivary gland metastases (who tend to favor one over the other). [47, 48]

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Imaging Studies

Dermatoscopic examination of cylindromas demonstrates arborizing telangiectasia and scattered white globules on a background of white to salmon-pink. The vascular branches appear more pronounced when examined at the periphery. The vascular branches extend from the periphery into the center of the cylindroma. [49]

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Procedures

A skin biopsy may be performed. Light microscopy with ordinary hematoxylin and eosin (H&E) staining is sufficient for diagnosis of cylindroma.

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Histologic Findings

Cylindroma is a dermal tumor without attachment to the epidermis. The lesion is composed of numerous oval and polygonal nests molded into a jigsawlike pattern. Masses of epithelial cells are surrounded and penetrated by a hyaline sheath closely resembling a basement membrane, giving it a cylindrical appearance on histologic cross-section, hence the name cylindroma. This sheath separates the tumor from the dermal mesenchyme, yet it does not interfere with tumor growth and proliferation.

Malignant cylindromas demonstrate islands of cells displaying marked anaplasia and pleomorphism of nuclei. Mitoses are increased and are abnormal. Besides invasion into surrounding tissue, loss of the delicate hyaline sheath occurs.

Tumor islands are composed of two cell types. Peripheral cells are small and highly basophilic; palisading is suggested. Larger, more pale-staining cells are seen centrally. Small tubal lumina are sometimes found with careful observation.

A lack of lymphoid tissue is a histological feature that differentiates cylindromas from spiradenomas. Spiradenomas show a unique prominent presence of lymphocytes. Cylindromas, on the other hand, demonstrate a large number of prominent dendritic cells that most likely represent Langerhans cells that permeate the tumor. S-100 protein–, HLA-DR–, and CD1a-positive cells can be seen in cylindromas and represent the existence of Langerhans cells.

Hyaline bands, which surround tumor islands, are mostly composed of type IV collagen. This is equivalent to the subepidermal lamina densa. Fragments of anchoring fibrils, identical to type VII collagen, are also seen. These anchoring fibrils can also be seen embedded in basement membrane on electron microscopy (EM).

The hyaline membrane is highly enlarged compared with the dermoepidermal junction, as observed by EM. EM demonstrates a basement membrane of 2.7-4.3 µm, compared with the dermoepidermal junction average basement membrane thickness of 60-90 nm. EM also demonstrates that cylindromas lack clear distinction of lamina densa. Numerous abnormal inclusions of fibrillar material are noted and appear similar to lamina lucida.

Although hemidesmosomes (HDs) are seen with EM, they are irregularly spaced and can only be seen in high power, compared with normal basal keratinocytes, in which HDs are seen at low power. HDs noted in the cylindroma cells have greater size variation and half the normal number of basal keratinocytes.

Immunohistochemical studies on cylindromas demonstrate a variation in cell matrix proteins compared with normal epidermal basal keratinocytes. Alpha-6-beta-4 integrin expression in tumor cells is weaker. In normal basal keratinocytes, laminin-5 is understood as necessary for HD and basement membrane formation. Further studies have shown an improper processing of laminin-5 in cylindromas. This may explain the lower percentage of HDs in cylindromas. Cylindromas also demonstrate low expression of alpha-6-beta-4 integrins. These changes may be the cause the structural abnormalities seen in the basement membranes of cylindromas.

Immunohistochemical analysis has demonstrated myoepithelial, apocrine, eccrine, ductal, and secretory features in both cylindromas and spiradenomas. Alpha-SMA, indicating myoepithelial differentiation, has been shown to be expressed in the basaloid cells of both tumors. Both tumors also demonstrate S-100 protein expression, a marker designating eccrine differentiation and apocrine markers, human milk fat globulin, and lysozyme. In addition, expression of keratin polypeptides 10 and 14, specific for ductal epithelium, and keratins 7, 8, and 18, specific for secretory cells, have been observed in both cylindromas and spiradenomas.

Nerve growth factor, S-100 protein, CD44, and CD34 are other markers that have been found to be expressed in or surrounding eccrine coils and are not expressed in the eccrine duct or apocrine gland. These markers have all been found to varying degrees in cylindromas. Other immunohistochemical studies linking cylindromas to eccrine differentiation include positive expression of cytokeratins 19 and 1/10/11. IKH-4 is a monoclonal antibody specific for the eccrine gland and will not stain apocrine glands. This marker can also be used to differentiate eccrine from apocrine tumors and is positive in eccrine cylindromas and spiradenomas. [50]

Immunohistochemical studies linking cylindromas to apocrine differentiation include the expression of alpha-1-antichymotrypsin, alpha smooth muscle actin (1A4), and cytokeratins 8 and 18.

Staining for cytokeratin 15, a marker specific for hair follicle stem cells, has also been shown in some cylindromas and spiradenomas. The expression of follicular, apocrine, and eccrine features in cylindromas suggests that the tumor may be derived from epithelial stem cells of immature differentiation.

Markers expressed in cylindromas and both eccrine and apocrine glands include epithelial membrane antigen, carcinoembryonic antigen, mucinlike carcinoma-associated antigen (B12), laminin, collagen IV, fibronectin, and CD34(QBEND/10).

See the image below.

Dermal cylindroma. Hematoxylin and eosin stain. Hi Dermal cylindroma. Hematoxylin and eosin stain. High magnification. Courtesy of Nephron (own work), via Wikimedia Commons.
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Other Tests

A genetic test can be done for CYLD mutations in both sporadic singular or multiple cylindromas. This test uses a tissue sample (preferably blood in EDTA [ethylenediaminetetraacetic acid]) and polymerase chain reaction amplification of exons 4-20, followed by Sanger sequencing. [29]

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