Laboratory Studies
If clinical evidence of Cowden syndrome is present, the following tests may be considered in establishing the diagnosis and in searching for potential malignancies:
- Triiodothyronine and thyroxine serum levels
- CBC count with differential
- Electrocardiogram
Imaging Studies
No imaging studies are needed for the evaluation of a trichilemmoma. However, the following imaging studies may be of use when completing a workup for Cowden syndrome:
- Mammography
- Thyroid scan
- Upper and lower GI imaging series
- Chest radiography
- Radiographs of the long bones, the pelvis, and the skull
Procedures
A skin biopsy is used to establish the diagnosis of a trichilemmoma. A shave biopsy is most commonly performed (see Histologic Findings below).
Histologic Findings
The following are histologic features found in a trichilemmoma (see the images below); these features assist in establishing the diagnosis:
- The epidermis usually reveals hyperkeratosis, mild acanthosis, and, occasionally, a cutaneous horn.
- A lobular or platelike epidermal growth projecting downward into the dermis
- Cells high in the epidermis may be vacuolated and contain coarse keratohyaline granules.
- Cells located toward the center of the lobular growth are often pale staining or have clear cytoplasm. These cells contain glycogen and are periodic acid-Schiff (PAS) positive but diastase labile.
- Cells at the periphery of the tumor are more basophilic and exhibit palisading.
- An eosinophilic hyaline basement membrane zone surrounds the tumor. This eosinophilic rim is PAS positive and diastase resistant.
- Foci of epidermal keratinization with formation of squamous eddies may be present.
The histologic differential diagnosis includes a hidroacanthoma simplex, which usually demonstrates ductal differentiation. A clear basal cell carcinoma should also be considered but can be excluded based on the presence of mucinous stroma, mitoses, and peripheral palisading with an absence of an eosinophilic hyaline cuticle. In tumor tissue in mice, nestin immunoreactivity was observed in immunoreactivity but not in basal cell carcinoma.[20]
Other epithelial neoplasms, such as the tumor of the follicular infundibulum (see the image below), may be considered in the differential diagnosis. Trichilemmal carcinoma may be considered, but excluded, based on its invasive growth pattern and many mitoses. An immunohistochemical study of cytokeratins suggests that an absence of cytokeratins 15 and 16 in trichilemmal carcinoma may be related to transformation from trichilemmoma to its trichilemmal carcinoma.[21]
Tumor of the follicular infundibulum. Several reports have stated that the use of CD34 immunostaining in tumors completely or partially differentiated toward the external root sheath of the hair follicle, such as trichilemmoma.[22]
Desmoplastic trichilemmoma demonstrates a biphasic growth pattern, having features of a lobulated tumor and cells that form narrow, irregular cords, which penetrate into the dermis. The stroma surrounding the tumor cords appears sclerotic. An inflammatory cell infiltrate is often seen surrounding the epithelial strands of the tumor. Because of these features, differentiating this tumor from an invasive squamous cell carcinoma or a sclerosing basal cell carcinoma is important.[23] CD34 expression has been particularly useful in the differentiation of desmoplastic trichilemmoma from other cutaneous tumors with dense collagenous stroma.[24]
Low-power histologic view of a desmoplastic trichilemmoma.
High-power histologic view of a desmoplastic trichilemmoma. Headington JT, French AJ. Primary neoplasms of the hair follicle. Histogenesis and classification. Arch Dermatol. Oct 1962;86:430-41. [Medline].
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