AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Multimedia
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Multimedia
• References

Background

Trichoepithelioma (TE) is a benign adnexal neoplasm. According to some authors, TE may be a superficial form of trichoblastoma. The gene involved in the familial form of TE is located on band 9p21.¹ Other cases are associated with Brooke-Spiegler syndrome (BSS) caused by mutations of the cylindromatosis oncogene (CYLD), which maps to 16q12-q13.² A 2006 study has suggested that abnormalities in this gene may result in either of three syndromes: BSS, familial cylindromatosis, and multiple familial TE.³

Pathophysiology

The gene associated with the familial type of TE links to the short arm of chromosome 9. Because several tumor suppressor genes (ie, p16, p15, and the gene for the basal cell nevus syndrome) are in this region, the gene for the development of familial TE also encodes for a tumor suppressor. If altered, cellular proliferation may be up-regulated because of a poorly functioning or absent tumor suppressor. Due to the presence of significant numbers of Merkel cells within the tumor nest and the detection of a sheath of CD34-positive dendrocytes around the tumor nests, it appears that TE differentiates toward or derives from hair structures, particularly the hair bulge. Rare instances of tumors resembling TE have been reported in animals.⁴

Frequency

United States

One dermatopathology laboratory reported 2.14 and 2.75 cases per year (9000 specimens).

Mortality/Morbidity

Most lesions show slow growth. In cases of multiple lesions, it may be disfiguring because of the involvement of the face. The rare cases described as having aggressive behavior (ie, ulceration, recurrence) are probably follicular tumors within the basal cell nevus syndrome and not TE.

Sex

Since TE is inherited in an autosomal dominant fashion, males and females receive the gene equally, but because of lessened expressivity and penetrance in men, most patients are women.

Age

TE typically occurs in young to aging adults; however, the hereditary form may be seen in younger individuals. A single case study has reported a congenital lesion of desmoplastic TE.⁵

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Multimedia
• References

History

• Slow-growing, single or multiple papules or nodules are typically observed on the face (see Media File 1).
• The occurrence of multiple TEs is transmitted as an autosomal dominant trait. Lesions first appear in childhood and gradually increase in number.
• In patients with multiple lesions, interview the patient's family for a familial history of TE.

Physical

The primary lesions of TE are characterized by the following:

• The lesions are rounded, skin-colored, firm papules or nodules that are 2-8 mm in diameter.
• The lesions are located mainly on the nasolabial folds, the nose, the forehead, the upper lip, and the scalp; 50% of lesions occur on the face and the scalp. Occasionally, lesions also occur on the neck and the upper part of the trunk.
• Ulceration is rare.
• In the autosomal dominant form, multiple TEs may be present, usually on the nasolabial folds.
• In some cases, the distribution is dermatomal. An association may exist with other cutaneous tumors (eg, cylindroma or BSS, spiradenoma, basal cell carcinoma, ungual fibromas) or dystrophia unguis congenita.
• TE may be part of the Rombo syndrome (ie, vermiculate atrophoderma, milia, hypertrichosis, TE, basal cell carcinoma, peripheral vasodilatation).
• Solitary giant TE presents as a large, polypoid lesion, usually in the lower part of the trunk or in the gluteal area.

Causes

• Familial cases appear to be related to a mutation in a gene encoding a tumor suppressor located on band 9q21. Also, the gene involved in basal cell carcinoma (PTCH, human patched gene located on band 9q22.3) appears to participate in the pathogenesis of TE.
• BSS patients have a high incidence of multiple skin appendage tumors such as cylindroma, TE, and spiradenoma. These patients may show mutations of the CYLD gene (cylindromatosis gene) that maps to 16q12-q13.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Multimedia
• References

Other Problems to be Considered

Histologic differential diagnoses (see Histologic Findings)
Basal cell carcinoma
Microcystic adnexal carcinoma
Trichoadenoma
Tumor of follicular infundibulum
Basaloid follicular hamartoma

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Multimedia
• References

Other Tests

• If necessary, genetic studies may be used to detect the abnormalities in band 9p21.

Procedures

• Perform a shave or small punch biopsy to allow a histologic diagnosis.

Histologic Findings

As many as 30% of TEs connect with the overlying epidermis. In the upper dermis, multiple nodules are composed of uniform, basaloid cells, frequently with central, keratin-filled cysts (Media Files 2-3). Peripheral palisading is present, but artifactual clefting is uncommon. Apoptotic and mitotic figures are rarely present; central necrosis or atypical mitotic figures are not a feature. The stroma is generally fibrous, with little myxoid component. Calcification is common, typically associated with the rupture of the keratinous cysts. A distinctive feature is the papillary-mesenchymal body (fibroblastic aggregate resembling abortive follicular papillae) (see Media File 4).⁶

Immunohistochemical studies reveal expression of the cytokeratins associated with the outer root sheath (ie, cytokeratins 5, 6, 8, and 17) and expression of bcl-2, predominantly in the peripheral cell layer of the nests. The intervening stromal cells express CD34 (see Media File 5). Transforming growth factor beta is expressed in most TEs. Merkel cells can be detected in all TE variants. Some studies have shown that TEs frequently have Merkel cells (detectable with chromogranin or cytokeratin 20). TEs apparently lack expression of androgen receptors, while many basal cell carcinomas are positive. CD10, a marker commonly studied in hematopathology, is consistently expressed by the stromal cells in TE, but it is only rarely present in those cells of basal cell carcinoma.⁷

Although extremely rare, some TEs may develop high-grade carcinomas and biphasic tumors (epithelial and sarcomatous) with aggressive behavior (including metastasis).

TE variants

The desmoplastic variant, as its name indicates, is characterized by a prominent, sclerotic stroma (see Media File 6).⁸ It occurs in the same population as the classic type and presents as a plaque located in the same anatomical areas as the classic form. Histologically, it shows narrow strands of tumor cells, a desmoplastic stroma, and keratinous cysts (see Media File 7). Pleomorphism, palisading, or peripheral clefting are not seen. Features favoring desmoplastic TE include a rim of compact collagen around groups of epithelial cells, granulomas, calcification of cornified cells within cysts, absence of necrotic neoplastic cells, and only rare mitotic figures. In contrast to basal cell carcinoma, fibroblasts surrounding TE nests do not express the matrix metalloproteinase stromelysin-3 (ST-3).^{9, 10}

The solitary giant variant is characterized by deep involvement of the reticular dermis and subcutaneous tissue.

Differential diagnoses based on histologic study

Features of basal cell carcinoma include a combination of basaloid cells, necrotic keratinocytes, mitotic figures, palisading and peripheral clefting, and myxoid stroma. The main differential features are stroma, clefting, and absence of papillary mesenchymal bodies.

In microcystic adnexal carcinoma, small keratinous cysts are present in the upper portion; syringomalike small ducts in an infiltrative fashion are present in the deep dermis.

In trichoadenoma, similarly sized clusters of basaloid cells contain numerous keratin cysts.

In tumor of follicular infundibulum (infundibuloma), platelike growth of basaloid cells having several points of attachment to the epidermis and the follicles is observed.

In basaloid follicular hamartoma, solitary, localized, linear/nevoid, or generalized papules or plaques are observed. Thin, anastomosing cords of basaloid cells, sometimes with peripheral palisading, may be seen. Occasionally, keratin cyst formation is present.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Multimedia
• References

Medical Care

The treatment of this lesion is primarily surgical.

Surgical Care

Solitary lesions can be excised. In the case of multiple tumors, this surgical approach may not be feasible.

• Split-thickness skin grafting, dermabrasion, and laser surgery have been proposed, but the results of these procedures vary.^{11, 12}
• Management of either form (ie, solitary, multiple/hereditary) by superficial biopsy is usually adequate.
• Recurrence of solitary TE is uncommon. When the multiple facial lesions are surgically flattened by dermabrasion or laser therapy, they tend to regrow into elevated papules or nodules. This regrowth may occur rapidly within months, or it may take several years. Some patients find a prolonged cosmetic improvement to be worthwhile even if repeated procedures are necessary.

FOLLOW-UP

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Multimedia
• References

Deterrence/Prevention

No preventive measures for TE are known.

Complications

The persistence or recurrence of tumors is a complication, and scarring may occur after treatment.

Prognosis

Slow growth is characteristic of TE. Partial removal may result in persistence or recurrence. Although rare, tumors can develop high-grade carcinomas and mixed (epithelial/sarcomatous) tumors. Familial TE has shown an aggressive, recurrent behavior in rare cases.

Patient Education

Inform the patient that some degree of scarring will be present after treatment.

MISCELLANEOUS

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Multimedia
• References

Medical/Legal Pitfalls

• Failure to inform the patient of the possibility of scarring is a pitfall. As with many benign skin neoplasms, the patient is mainly concerned about the aesthetic appearance of the lesion. Scarring may result from all available methods for tumor removal. In patients with multiple lesions, treating 1 or 2 of the lesions and showing the patient the final result may be helpful before embarking on extensive aggressive therapy.
• Failure to order histologic analysis to distinguish among cutaneous neoplasms presenting as small facial papules is a pitfall. The most important diagnosis would be basal cell nevus syndrome because of the much higher rate of aggressive behavior of the tumor.
• Failure to histologically distinguish a TE from a basal cell carcinoma is a pitfall. Because the latter has a much higher risk of recurrence, most authors would recommend complete removal of such lesions.
• Failure to obtain a sufficiently deep biopsy sample to allow the dermatopathologist to study most of the lesion in cases of a solitary TE is a pitfall. In particular, a shave biopsy of a plaquelike lesion on the lip may result in identifying the superficial portion of a microcystic adnexal carcinoma (an aggressive adnexal neoplasm) as a TE. Some adnexal carcinomas may show a very limited degree of cytologic atypia. In such cases, only by examining the periphery of the lesion with the characteristic infiltrative pattern allows correct diagnosis.

MULTIMEDIA

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Multimedia
• References

Media file 1:  Characteristic clinical morphologic features. Notice the numerous, small papules, predominantly close to the midline.
	View Full Size Image
Media type:  Photo

Media file 2:  Well-circumscribed, superficial lesion composed of clusters of basaloid cells within a fibrous stroma. This arrangement of epithelial cells and stroma is described as organoid.
	View Full Size Image
Media type:  Micrograph

Media file 3:  The cystic spaces contain keratin. Notice the lack of mitotic figures or apoptotic bodies.
	View Full Size Image
Media type:  Micrograph

Media file 4:  Papillary-mesenchymal bodies are structures associated with hair follicle differentiation. They are characterized by an aggregate of spindle, stromal cells, closely apposed to a hair bulb (darkly staining, basaloid epithelial cells).
	View Full Size Image
Media type:  Micrograph

Media file 5:  Immunohistochemical studies detect expression of CD34 by many of the dendritic cells that surround the tumor aggregates (anti-CD34, diaminobenzidine, and hematoxylin).
	View Full Size Image
Media type:  Micrograph

Media file 6:  Desmoplastic variant. Notice that many of the aggregates of basaloid cells are small, resembling a syringoma; however, they contain keratin instead of eccrine secretion. Also notice the characteristic markedly fibrous stroma.
	View Full Size Image
Media type:  Micrograph

Media file 7:  High-powered view of desmoplastic trichoepithelioma. Notice the cluster of squamous cells surrounding a small cystic area containing keratin. Intervening stroma is markedly fibrous.
	View Full Size Image
Media type:  Micrograph

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Multimedia
• References

1. Harada H, Hashimoto K, Ko MS. The gene for multiple familial trichoepithelioma maps to chromosome 9p21. J Invest Dermatol. Jul 1996;107(1):41-3. [Medline].
2. Bowen S, Gill M, Lee DA, Fisher G, Geronemus RG, Vazquez ME, et al. Mutations in the CYLD gene in Brooke-Spiegler syndrome, familial cylindromatosis, and multiple familial trichoepithelioma: lack of genotype-phenotype correlation. J Invest Dermatol. May 2005;124(5):919-20. [Medline].
3. Young AL, Kellermayer R, Szigeti R, Tészás A, Azmi S, Celebi JT. CYLD mutations underlie Brooke-Spiegler, familial cylindromatosis, and multiple familial trichoepithelioma syndromes. Clin Genet. Sep 2006;70(3):246-9. [Medline].
4. Martín de Las Mulas J, Molina AM, Millán Y, Carrasco L, Moyano R, Mozos E. Spontaneous trichoepithelioma in a laboratory mouse: gross, microscopic and immunohistochemical findings. Lab Anim. Jan 2007;41(1):136-40. [Medline].
5. Carter JJ, Kaur MR, Hargitai B, Brown R, Slator R, Abdullah A. Congenital desmoplastic trichoepithelioma. Clin Exp Dermatol. Sep 2007;32(5):522-4. [Medline].
6. Brooke JD, Fitzpatrick JE, Golitz LE. Papillary mesenchymal bodies: a histologic finding useful in differentiating trichoepitheliomas from basal cell carcinomas. J Am Acad Dermatol. Sep 1989;21(3 Pt 1):523-8. [Medline].
7. Pham TT, Selim MA, Burchette JL Jr, Madden J, Turner J, Herman C. CD10 expression in trichoepithelioma and basal cell carcinoma. J Cutan Pathol. Feb 2006;33(2):123-8. [Medline].
8. Brownstein MH, Shapiro L. Desmoplastic trichoepithelioma. Cancer. Dec 1977;40(6):2979-86. [Medline].
9. Takei Y, Fukushiro S, Ackerman AB. Criteria for histologic differentiation of desmoplastic trichoepithelioma (sclerosing epithelial hamartoma) from morphea-like basal-cell carcinoma. Am J Dermatopathol. Jun 1985;7(3):207-21. [Medline].
10. Thewes M, Worret WI, Engst R, Ring J. Stromelysin-3: a potent marker for histopathologic differentiation between desmoplastic trichoepithelioma and morphealike basal cell carcinoma. Am J Dermatopathol. Apr 1998;20(2):140-2. [Medline].
11. Sajben FP, Ross EV. The use of the 1.0 mm handpiece in high energy, pulsed CO2 laser destruction of facial adnexal tumors. Dermatol Surg. Jan 1999;25(1):41-4. [Medline].
12. Shaffelburg M, Miller R. Treatment of multiple trichoepithelioma with electrosurgery. Dermatol Surg. Oct 1998;24(10):1154-6. [Medline].
13. Bettencourt MS, Prieto VG, Shea CR. Trichoepithelioma: a 19-year clinicopathologic re-evaluation. J Cutan Pathol. Sep 1999;26(8):398-404. [Medline].
14. España A, García-Amigot F, Aguado L, García-Foncillas J. A novel missense mutation in the CYLD gene in a Spanish family with multiple familial trichoepithelioma. Arch Dermatol. Sep 2007;143(9):1209-10. [Medline].
15. Hartschuh W, Schulz T. Merkel cells are integral constituents of desmoplastic trichoepithelioma: an immunohistochemical and electron microscopic study. J Cutan Pathol. Oct 1995;22(5):413-21. [Medline].
16. Hunt SJ, Abell E. Malignant hair matrix tumor ("malignant trichoepithelioma") arising in the setting of multiple hereditary trichoepithelioma. Am J Dermatopathol. Jun 1991;13(3):275-81. [Medline].
17. Izikson L, Bhan A, Zembowicz A. Androgen receptor expression helps to differentiate basal cell carcinoma from benign trichoblastic tumors. Am J Dermatopathol. Apr 2005;27(2):91-5. [Medline].
18. Johnson SC, Bennett RG. Occurrence of basal cell carcinoma among multiple trichoepitheliomas. J Am Acad Dermatol. Feb 1993;28(2 Pt 2):322-6. [Medline].
19. Kechijian P, Connors RC, Ackerman AB. Trichoepithelioma vs. basal-cell carcinoma: criteria for histologic differentiation. J Dermatol Surg. Dec 1975;1(4):22-3. [Medline].
20. Kirchmann TT, Prieto VG, Smoller BR. CD34 staining pattern distinguishes basal cell carcinoma from trichoepithelioma. Arch Dermatol. May 1994;130(5):589-92. [Medline].
21. Lee YS, Fong PH. Secondary localized amyloidosis in trichoepithelioma. A light microscopic and ultrastructural study. Am J Dermatopathol. Oct 1990;12(5):469-78. [Medline].
22. Matt D, Xin H, Vortmeyer AO, Zhuang Z, Burg G, Böni R. Sporadic trichoepithelioma demonstrates deletions at 9q22.3. Arch Dermatol. May 2000;136(5):657-60. [Medline].
23. Pariser RJ. Multiple hereditary trichoepitheliomas and basal cell carcinomas. J Cutan Pathol. Apr 1986;13(2):111-7. [Medline].
24. Rosso R, Lucioni M, Savio T, Borroni G. Trichoblastic sarcoma: a high-grade stromal tumor arising in trichoblastoma. Am J Dermatopathol. Feb 2007;29(1):79-83. [Medline].
25. Schulz T, Proske S, Hartschuh W, Kurzen H, Paul E, Wünsch PH. High-grade trichoblastic carcinoma arising in trichoblastoma: a rare adnexal neoplasm often showing metastatic spread. Am J Dermatopathol. Feb 2005;27(1):9-16. [Medline].
26. Swanson PE, Fitzpatrick MM, Ritter JH, Glusac EJ, Wick MR. Immunohistologic differential diagnosis of basal cell carcinoma, squamous cell carcinoma, and trichoepithelioma in small cutaneous biopsy specimens. J Cutan Pathol. Mar 1998;25(3):153-9. [Medline].

Article Last Updated: Jan 9, 2008