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Trichoepithelioma Workup

  • Author: Victor G Prieto, MD, PhD; Chief Editor: William D James, MD  more...
 
Updated: May 19, 2016
 

Approach Considerations

In vivo studies such as high-definition optical coherence tomography have been applied to distinguish trichoepithelioma from other cutaneous tumors.[17] If necessary, genetic studies may be used to detect the abnormalities in band 9p21 in trichoepithelioma patients.

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Procedures

Perform a shave or small punch biopsy to allow a histologic diagnosis of trichoepithelioma. Ensure that the biopsy sample is sufficiently deep to allow the dermatopathologist to study most of the lesion in cases of a solitary trichoepithelioma. 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 trichoepithelioma. 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.

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Histologic Findings

As many as 30% of trichoepitheliomas connect with the overlying epidermis, but in general they are circumscribed, dermal nodules.

In the upper dermis, multiple nodules are composed of uniform, basaloid cells, frequently with central, keratin-filled cysts, as in the images below.

Well-circumscribed, superficial lesion composed of 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.
The cystic spaces contain keratin. Notice the lack The cystic spaces contain keratin. Notice the lack of mitotic figures or apoptotic bodies.

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), as shown in the image below.[18]

Papillary-mesenchymal bodies are structures associ 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 (arrow; darkly staining, basaloid epithelial cells).

Because trichoepitheliomas recapitulate hair differentiation, they may contain scattered melanocytes, as shown in the image below.

Because trichoepitheliomas recapitulate follicular Because trichoepitheliomas recapitulate follicular differentiation, they may contain cells commonly seen in hair follicles such as melanocytes. This image illustrates both melanocytes (black arrow) and dermal melanophages (white arrow).

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, as shown in the image below.

Immunohistochemical studies detect expression of C Immunohistochemical studies detect expression of CD34 by many of the dendritic cells that surround the tumor aggregates (anti-CD34, diaminobenzidine, and hematoxylin).

Transforming growth factor-beta is expressed in most trichoepitheliomas. Merkel cells can be detected in all trichoepithelioma variants. Some studies have shown that trichoepitheliomas frequently have Merkel cells (detectable with chromogranin or cytokeratin 20).[19] CK19 is reportedly more frequently detected in basal cell carcinoma than in trichoepithelioma.[20] Trichoepitheliomas apparently lack expression of androgen receptors,[21] while many basal cell carcinomas are positive. CD10, a marker commonly studied in hematopathology, is consistently expressed by the stromal cells in trichoepithelioma, but it is only rarely present in those cells of basal cell carcinoma.[22, 23]

Although extremely rare, some trichoepitheliomas may develop high-grade carcinomas and biphasic tumors (epithelial and sarcomatous) with aggressive behavior (including metastasis).[12, 13]

Trichoepithelioma variants

The desmoplastic variant, as its name indicates, is characterized by a prominent, sclerotic stroma, as shown in the image below.[24]

Desmoplastic variant. Notice that many of the aggr 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.

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, as shown in the image below.

High-powered view of desmoplastic trichoepitheliom High-powered view of desmoplastic trichoepithelioma. Notice the cluster of squamous cells surrounding a small cystic area containing keratin. Intervening stroma is markedly fibrous.

Pleomorphism, palisading, or peripheral clefting are not seen. Features favoring desmoplastic trichoepithelioma 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 trichoepithelioma nests do not express the matrix metalloproteinase stromelysin-3 (ST-3).[25, 26]

A possible pitfall is the observation of perineural involvement in some cases of desmoplastic trichoepithelioma, a feature more frequently associated with malignancy.[27] Also interesting is the observation of pseudoepitheliomatous hyperplasia above desmoplastic trichoepitheliomas that may result in a misdiagnosis of squamous cell carcinoma.[28]

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.[29, 30, 31] A study with a tissue microarray indicated that the best markers to differentiate between trichoepithelioma and basal cell carcinoma include a combination of CD10, cytokeratin 15, cytokeratin 20, and D2-40. CK15 and D2-40 commonly are expressed in the peripheral layer of trichoepithelioma nests. CK20 Merkel cells are more common in trichoepitheliomas. CD10 is more commonly expressed in the stroma of trichoepithelioma and in the tumor cells in basal cell carcinoma.[32]

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. A review indicated that invasion of skeletal muscle and subcutaneous tissue, perineural invasion, ductal differentiation, and expression of CK19 are much more common in microcystic adnexal carcinoma.[33]

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.

The malignant counterpart is distinctly uncommon. Such lesions are characterized by a poorly circumscribed, infiltrative pattern of growth with areas of necrosis, as shown in the image below.

The malignant counterpart, trichilemmal carcinoma, The malignant counterpart, trichilemmal carcinoma, typically shows areas with infiltrative growth and necrosis.

Tumor cells in these cases show pleomorphic nuclei and large, pale staining cytoplasm. Some cells may contain characteristic red cytoplasmic trichohyalin granules, as shown in the image below.

Trichilemmal carcinoma cells have large, lightly s Trichilemmal carcinoma cells have large, lightly stained cytoplasm with large, pleomorphic nuclei. As a sign of follicular differentiation, some cells may display the characteristic cytoplasmic, red, trichohyalin granules (arrows).
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Contributor Information and Disclosures
Author

Victor G Prieto, MD, PhD Director of Dermatopathology, Professor, Departments of Pathology and Dermatology, University of Texas MD Anderson Cancer Center

Victor G Prieto, MD, PhD is a member of the following medical societies: American Society of Dermatopathology, College of American Pathologists, American Association for the Advancement of Science, International Society of Dermatopathology, European Society of Pathology, American Medical Association, American Society for Clinical Pathology, Society for Investigative Dermatology, United States and Canadian Academy of Pathology

Disclosure: Nothing to disclose.

Coauthor(s)

Christopher R Shea, MD Professor and Chief, Section of Dermatology, Department of Medicine, University of Chicago, The Pritzker School of Medicine

Christopher R Shea, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Society of Dermatopathology, Society for Investigative Dermatology, Association of Professors of Dermatology, International Society of Dermatopathology, Arthur Purdy Stout Society, Chicago Dermatological Society, Dermatology Foundation, Illinois Dermatological Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Richard P Vinson, MD Assistant Clinical Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine; Consulting Staff, Mountain View Dermatology, PA

Richard P Vinson, MD is a member of the following medical societies: American Academy of Dermatology, Texas Medical Association, Association of Military Dermatologists, Texas Dermatological Society

Disclosure: Nothing to disclose.

Warren R Heymann, MD Head, Division of Dermatology, Professor, Department of Internal Medicine, Rutgers New Jersey Medical School

Warren R Heymann, MD is a member of the following medical societies: American Academy of Dermatology, American Society of Dermatopathology, Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Chief Editor

William D James, MD Paul R Gross Professor of Dermatology, Vice-Chairman, Residency Program Director, Department of Dermatology, University of Pennsylvania School of Medicine

William D James, MD is a member of the following medical societies: American Academy of Dermatology, Society for Investigative Dermatology

Disclosure: Nothing to disclose.

References
  1. Harada H, Hashimoto K, Ko MS. The gene for multiple familial trichoepithelioma maps to chromosome 9p21. J Invest Dermatol. 1996 Jul. 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. 2005 May. 124(5):919-20. [Medline].

  3. Vanecek T, Halbhuber Z, Kacerovska D, Martinek P, Sedivcova M, Carr RA, et al. Large Germline Deletions of the CYLD Gene in Patients With Brooke-Spiegler Syndrome and Multiple Familial Trichoepithelioma. Am J Dermatopathol. 2014 Nov. 36(11):868-74. [Medline].

  4. Guardoli D, Argenziano G, Ponti G, Nasti S, Zalaudek I, Moscarella E, et al. A novel CYLD germline mutation in Brooke-Spiegler syndrome. J Eur Acad Dermatol Venereol. 2014 Jul 30. [Medline].

  5. Young AL, Kellermayer R, Szigeti R, Teszas A, Azmi S, Celebi JT. CYLD mutations underlie Brooke-Spiegler, familial cylindromatosis, and multiple familial trichoepithelioma syndromes. Clin Genet. 2006 Sep. 70(3):246-9. [Medline].

  6. Sehrawat M, Jairath V, Jain VK. Nonfamilial Multiple Trichoepithelioma: Few and Far Between. Indian J Dermatol. 2016 Jan-Feb. 61 (1):78-80. [Medline].

  7. Wang FX, Yang LJ, Li M, Zhang SL, Zhu XH. A novel missense mutation of CYLD gene in a Chinese family with multiple familial trichoepithelioma. Arch Dermatol Res. 2010 Jan. 302(1):67-70. [Medline].

  8. Huang TM, Chao SC, Lee JY. A novel splicing mutation of the CYLD gene in a Taiwanese family with multiple familial trichoepithelioma. Clin Exp Dermatol. 2009 Jan. 34(1):77-80. [Medline].

  9. Blake PW, Toro JR. Update of cylindromatosis gene (CYLD) mutations in Brooke-Spiegler syndrome: novel insights into the role of deubiquitination in cell signaling. Hum Mutat. 2009 Jul. 30(7):1025-36. [Medline].

  10. Martín de Las Mulas J, Molina AM, Millan Y, Carrasco L, Moyano R, Mozos E. Spontaneous trichoepithelioma in a laboratory mouse: gross, microscopic and immunohistochemical findings. Lab Anim. 2007 Jan. 41(1):136-40. [Medline].

  11. Carter JJ, Kaur MR, Hargitai B, Brown R, Slator R, Abdullah A. Congenital desmoplastic trichoepithelioma. Clin Exp Dermatol. 2007 Sep. 32(5):522-4. [Medline].

  12. Rosso R, Lucioni M, Savio T, Borroni G. Trichoblastic sarcoma: a high-grade stromal tumor arising in trichoblastoma. Am J Dermatopathol. 2007 Feb. 29(1):79-83. [Medline].

  13. 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. 2005 Feb. 27(1):9-16. [Medline].

  14. Heller J, Roche N, Hameed M. Trichoepithelioma of the vulva: report of a case and review of the literature. J Low Genit Tract Dis. 2009 Jul. 13(3):186-7. [Medline].

  15. Matt D, Xin H, Vortmeyer AO, Zhuang Z, Burg G, Boni R. Sporadic trichoepithelioma demonstrates deletions at 9q22.3. Arch Dermatol. 2000 May. 136(5):657-60. [Medline].

  16. Espana A, Garcia-Amigot F, Aguado L, Garcia-Foncillas J. A novel missense mutation in the CYLD gene in a Spanish family with multiple familial trichoepithelioma. Arch Dermatol. 2007 Sep. 143(9):1209-10. [Medline].

  17. Oliveira A, Arzberger E, Zalaudek I, Hofmann-Wellenhof R. Imaging of desmoplastic trichoepithelioma by high-definition optical coherence tomography. Dermatol Surg. 2015 Apr. 41 (4):522-5. [Medline].

  18. Brooke JD, Fitzpatrick JE, Golitz LE. Papillary mesenchymal bodies: a histologic finding useful in differentiating trichoepitheliomas from basal cell carcinomas. J Am Acad Dermatol. 1989 Sep. 21(3 Pt 1):523-8. [Medline].

  19. Hartschuh W, Schulz T. Merkel cells are integral constituents of desmoplastic trichoepithelioma: an immunohistochemical and electron microscopic study. J Cutan Pathol. 1995 Oct. 22(5):413-21. [Medline].

  20. Bedir R, Sehitoglu I, Yurdakul C, Saygin I, Üstüner P, Dilek N. The importance of cytokeratin 19 expression in the differentiation of Basal cell carcinoma and trichoepithelioma. J Clin Diagn Res. 2015 Jan. 9 (1):EC01-4. [Medline].

  21. Izikson L, Bhan A, Zembowicz A. Androgen receptor expression helps to differentiate basal cell carcinoma from benign trichoblastic tumors. Am J Dermatopathol. 2005 Apr. 27(2):91-5. [Medline].

  22. Pham TT, Selim MA, Burchette JL Jr, Madden J, Turner J, Herman C. CD10 expression in trichoepithelioma and basal cell carcinoma. J Cutan Pathol. 2006 Feb. 33(2):123-8. [Medline].

  23. Ramos-Ceballos FI, Pashaei S, Kincannon JM, Morgan MB, Smoller BR. Bcl-2, CD34 and CD10 expression in basaloid follicular hamartoma, vellus hair hamartoma and neurofollicular hamartoma demonstrate full follicular differentiation. J Cutan Pathol. 2008 May. 35(5):477-83. [Medline].

  24. Brownstein MH, Shapiro L. Desmoplastic trichoepithelioma. Cancer. 1977 Dec. 40(6):2979-86. [Medline].

  25. 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. 1985 Jun. 7(3):207-21. [Medline].

  26. 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. 1998 Apr. 20(2):140-2. [Medline].

  27. Jedrych J, Leffell D, McNiff JM. Desmoplastic trichoepithelioma with perineural involvement: a series of seven cases. J Cutan Pathol. 2012 Mar. 39(3):317-23. [Medline].

  28. McFaddin C, Sirohi D, Castro-Echeverry E, Fernandez MP. Desmoplastic trichoepithelioma with pseudocarcinomatous hyperplasia: a report of three cases. J Cutan Pathol. 2015 Feb. 42 (2):102-7. [Medline].

  29. Kechijian P, Connors RC, Ackerman AB. Trichoepithelioma vs. basal-cell carcinoma: criteria for histologic differentiation. J Dermatol Surg. 1975 Dec. 1(4):22-3. [Medline].

  30. Kirchmann TT, Prieto VG, Smoller BR. CD34 staining pattern distinguishes basal cell carcinoma from trichoepithelioma. Arch Dermatol. 1994 May. 130(5):589-92. [Medline].

  31. 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. 1998 Mar. 25(3):153-9. [Medline].

  32. Tebcherani AJ, de Andrade HF Jr, Sotto MN. Diagnostic utility of immunohistochemistry in distinguishing trichoepithelioma and basal cell carcinoma: evaluation using tissue microarray samples. Mod Pathol. 2012 Jun 8. [Medline].

  33. Tse JY, Nguyen AT, Le LP, Hoang MP. Microcystic Adnexal Carcinoma Versus Desmoplastic Trichoepithelioma: A Comparative Study. Am J Dermatopathol. 2012 Jun 20. [Medline].

  34. Alessi SS, Sanches JA, de Oliveira WR, Messina MC, Pimentel ER, Festa Neto C. Treatment of cutaneous tumors with topical 5% imiquimod cream. Clinics (Sao Paulo). 2009. 64(10):961-6. [Medline]. [Full Text].

  35. Fisher GH, Geronemus RG. Treatment of multiple familial trichoepitheliomas with a combination of aspirin and a neutralizing antibody to tumor necrosis factor alpha: A case report and hypothesis of mechanism. Arch Dermatol. 2006 Jun. 142 (6):782-3. [Medline].

  36. Brinkhuizen T, Weijzen CA, Eben J, Thissen MR, van Marion AM, Lohman BG, et al. Immunohistochemical analysis of the mechanistic target of rapamycin and hypoxia signalling pathways in basal cell carcinoma and trichoepithelioma. PLoS One. 2014. 9 (9):e106427. [Medline].

  37. 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. 1999 Jan. 25(1):41-4. [Medline].

  38. Shaffelburg M, Miller R. Treatment of multiple trichoepithelioma with electrosurgery. Dermatol Surg. 1998 Oct. 24(10):1154-6. [Medline].

  39. Richard A, Chevalier JM, Verneuil L, Sergent B, Tesnière A, Dolfus C, et al. [CO2 laser treatment of skin cylindromas in Brooke-Spiegler syndrome]. Ann Dermatol Venereol. 2014 May. 141(5):346-53. [Medline].

 
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Characteristic clinical morphologic features. Notice the numerous, small papules, predominantly close to the midline.
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.
The cystic spaces contain keratin. Notice the lack of mitotic figures or apoptotic bodies.
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 (arrow; darkly staining, basaloid epithelial cells).
Because trichoepitheliomas recapitulate follicular differentiation, they may contain cells commonly seen in hair follicles such as melanocytes. This image illustrates both melanocytes (black arrow) and dermal melanophages (white arrow).
Immunohistochemical studies detect expression of CD34 by many of the dendritic cells that surround the tumor aggregates (anti-CD34, diaminobenzidine, and hematoxylin).
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.
High-powered view of desmoplastic trichoepithelioma. Notice the cluster of squamous cells surrounding a small cystic area containing keratin. Intervening stroma is markedly fibrous.
The malignant counterpart, trichilemmal carcinoma, typically shows areas with infiltrative growth and necrosis.
Trichilemmal carcinoma cells have large, lightly stained cytoplasm with large, pleomorphic nuclei. As a sign of follicular differentiation, some cells may display the characteristic cytoplasmic, red, trichohyalin granules (arrows).
 
 
 
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