Approach Considerations
In vivo studies such as high-definition optical coherence tomography have been applied to distinguish trichoepithelioma from other cutaneous tumors. [18] If necessary, genetic studies may be used to detect the abnormalities in band 9p21 in trichoepithelioma patients.
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.
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 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.
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. [19]
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 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 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). [20] CK19 is reportedly more frequently detected in basal cell carcinoma than in trichoepithelioma. [21] Trichoepitheliomas apparently lack expression of androgen receptors, [22] 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. [23, 24]
Although extremely rare, some trichoepitheliomas may develop high-grade carcinomas and biphasic tumors (epithelial and sarcomatous) with aggressive behavior (including metastasis). [13, 14]
Trichoepithelioma variants
The desmoplastic variant, as its name indicates, is characterized by a prominent, sclerotic stroma, as shown in the image below. [25]
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 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). [26, 27]
A possible pitfall is the observation of perineural involvement in some cases of desmoplastic trichoepithelioma, a feature more frequently associated with malignancy. [28] Also interesting is the observation of pseudoepitheliomatous hyperplasia above desmoplastic trichoepitheliomas that may result in a misdiagnosis of squamous cell carcinoma. [29]
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. [30, 31, 32] 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. [33]
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. [34]
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, 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 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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Characteristic clinical morphologic features. Notice the numerous, small papules, predominantly close to the midline.
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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).
