Are You Confident of the Diagnosis?
Characteristic findings on physical examination
Trichilemmal carcinoma usually presents as a solitary exophytic or polypoid nodule (0.3 to 6cm) on the sun-exposed hair-bearing skin of older individuals. It may be keratotic or ulcerated, but is otherwise asymptomatic. The lesion is usually present for less than 1 year, with an accelerated growth phase. Rarely, multiple lesions may be present.
Expected results of diagnostic studies
A skin biopsy is usually needed for a definitive diagnosis of trichilemmal carcinoma, as clinically, the lesion is most often confused with basal cell carcinoma.
Histopathology shows the pilosebaceous unit with trichilemmal keratinization, defined as compact nonlamellar keratin with hypogranulosis. Biopsy also reveals prominent lobular proliferation of the follicular epithelium and epidermis (Figure 1). The invasive lobules exhibit peripheral palisading and contain clear, glycogen-rich keratinocytes that are periodic acid-Schiff-positive, diastase sensitive, and cytokeratin 17-positive due to their outer root sheath origin. Unlike trichilemmoma, there is cytologic atypia and high mitotic activity.
Trichilemmal carcinoma must be differentiated from other cutaneous carcinomas such as basal cell carcinoma (histopathology with proliferation of basaloid rather than epidermal clear cells), clear cell squamous cell carcinoma (epidermal, rather than trichilemmal, keratinization on biopsy), invasive Bowen’s (quite a difficult distinction on biopsy, as invasive Bowen’s often shows adnexal differentiation, but epidermal, rather than trichilemmal, keratinization is present), and sebaceous carcinoma (histopathology with cells containing foamy cytoplasm and central nuclei).
It is also important to distinguish trichilemmal carcinoma from melanocytic nevi and malignant melanoma (which may have balloon cells on biopsy, but stain positive for S-100 and negative for cytokeratin).
Finally, one must rule out other adnexal tumors such as trichilemmoma and desmoplastic trichilemmoma (both with histopathology similar to trichilemmal carcinoma but without cytologic atypia and high mitotic activity), proliferating trichilemmal tumor (histopathology with intradermal mass of squamous epithelium), trichoepithelioma (keratin-containing horn cysts on biopsy), and trichofolliculoma (keratin-containing cystic cavity on biopsy).
Who is at Risk for Developing this Disease?
Trichilemmal carcinoma appears on sun-exposed sites, in patients who are usually older than age 50. Men and women appear to be equally affected. The exact incidence is unknown, but chronic actinic damage appears to be the biggest risk factor. There is one report of a trichilemmal carcinoma on the face of a 9-year-old girl, but she had xeroderma pigmentosum supporting actinic damage as a risk factor for trichilemmal carcinoma, since patients with xeroderma pigmentosum cannot repair UV-damaged DNA.
What is the Cause of the Disease?
Trichilemmal carcinoma is a carcinoma of the outer root sheath. The exact etiology is unknown, but it appears to be related to actinic damage.
Immunosuppression may also be a contributing factor, as there is a case report of a lesion in a transplant patient on the mid-chest, a traditionally less sun-exposed site. X-irradiation may also be a risk factor, as there is a case report of three trichilemmal carcinomas occurring on the chest of a 67-year-old male who had a distant history of treated tuberculosis and had received several chest X-rays during his life.
It is unknown whether trichilemmal carcinoma develops from an existing benign lesion or de novo. Few trichilemmal carcinomas show evidence of a coexisting trichilemmoma.
Patients with Cowden syndrome, a rare autosomal dominant disorder in which multiple facial trichilemmomas appear, do not seem to be at increased risk of trichilemmal carcinoma, as there is only one case report of such a circumstance; however, there is a case report of trichilemmal carcinoma arising in the wall of a proliferating trichilemmal cyst on the scalp of a 77-year-old Japanese woman.
Polymerase chain reaction (PCR) analysis of DNA from both lesions investigating the wild-type p53 gene allele, a tumor suppressor gene, revealed loss of heterozygosity in the proliferating trichilemmal cyst and complete loss of the wild-type allele in the trichlemmal carcinoma. Such evidence suggests that total loss of the tumor suppressor gene p53 may contribute to the development of trichilemmal carcinoma.
Systemic Implications and Complications
Trichilemmal carcinoma is generally cured with surgical excision. Recurrence, perineural invasion, and metastasis are extremely rare, but reported.
Treatment options are summarized in Table I.
|Medical Treatment||Surgical Procedures|
|Topical imiquimod 5% cream||Wide excision (1cm) with clear margins|
|Systemic chemotherapy, e.g. cisplatin and cyclophosphamide||Mohs surgery|
Optimal Therapeutic Approach for this Disease
After a diagnosis of trichilemmal carcinoma is made on biopsy, surgical excision is the first choice for curative treatment. The decision between a wide excision (1cm) with clear margins versus Mohs micrographic surgery is based on anatomical site and aesthetic result optimization.
There is a case report of trichilemmal carcinoma successfully treated with imiquimod 5% cream (used three times a week for 8 weeks), but this option should only be used if patients refuse surgery. The authors warn that imiquimod may mask tumor recurrence or create disconnected foci of tumor, so long-term surveillance is important.
While recurrence, perineural invasion, and metastasis are extremely rare, patients should be evaluated for these sequelae with periodic monitoring. If symptoms occur, imaging studies such as computed tomography (CT) scans are helpful for evaluating disease extent. There is no established chemotherapy regimen for metastatic trichilemmal carcinoma, but regimens used for highly advanced cases of squamous cell carcinoma, such as cisplatin and cyclophosphamide, have been used.
Once biopsy results are obtained, explain to patients that trichilemmal carcinoma is a rare type of skin cancer that is usually cured with surgical excision with clear margins. Recurrence, perineural invasion, and metastasis are extremely rare, but reported. Patients should be monitored with periodic surveillance, and any symptoms can be further evaluated with imaging studies such as CT scans.
Unusual Clinical Scenarios to Consider in Patient Management
Although it is not known whether trichilemmal carcinoma develops from an existing benign lesion or de novo, multiple trichilemmomas are not thought to be a risk factor for trichilemmal carcinoma. Multiple facial trichilemmomas occur in patients with Cowden syndrome, a rare autosomal-dominant disorder affecting the skin, breast, thyroid, gastrointestinal tract, endometrium, and brain. There is only one report of trichilemmal carcinoma occurring in a patient with Cowden syndrome. The recommendation is to biopsy any changing lesions in these patients.
What is the Evidence?
Wong, TY, Suster, S. “Tricholemmal carcinoma. A clinicopathologic study of 13 cases”. Am J Dermatopathol. vol. 16. 1994. pp. 463-73. (A study of 13 cases of trichilemmal carcinoma, all occurring on sun-exposed, hair-bearing skin. All tumors were treated with surgical excision with clear margins, without recurrence nor metastasis reported after 2-8 years of clinical follow-up.)
Reis, JP, Tellechea, O, Cunha, MF, Baptista, AP. “Trichilemmal carcinoma: review of 8 cases”. J Cutan Pathol. vol. 20. 1993. pp. 44-9. (A study of of trichilemmal carcinoma in seven elderly individuals with sun-exposed skin and a 9-year-old girl with xeroderma pigmentosum. No recurrences or metastases were observed.)
Garrett, AB, Azmi, FH, Ogburia, KS. “Trichilemmal carcinoma: a rare cutaneous malignancy: a report of two cases”. Dermatol Surg. vol. 30. 2004. pp. 113-5. (A report of two cases of trichilemmal carcinoma, one of which was a kidney transplant patient. Both patients were treated with Mohs surgery without recurrence after 4-5 years of clinical follow-up.)
Chan, KO, Lim, IJ, Baladas, HG, Tan, WTL. “Multiple tumor presentation of trichilemmal carcinoma”. Br J Plast Surg. vol. 52. 1999. pp. 665-7. (This is the first case report of multiple trichilemmal carcinomas occurring in the same patient. The patient was a 67-year-old Chinese male with a distant history of treated tuberculosis who presented with three trichilemmal carcinomas on his upper chest, one of which was recurrent. The authors hypothesize that the lesions may be due to multiple exposures to x-irradiation. Surgical excision with a 1cm margin was performed on all lesions. There was no recurrence after 18 months of clinical follow-up.)
O’Hare, Am, Cooper, PH, Parlette, HL. “Trichilemmomal carcinoma in a patient with Cowden’s disease (multiple hamartoma syndrome)”. J Am Acad Dermatol. vol. 36. 1997. pp. 1021-3. (A case report of a 56-year-old man with Cowden’s disease who presented with trichilemmal carcinoma on his face, and was treated with Mohs surgery.)
Allee, JE, Cotsarelis, G, Solky, B, Cook, JL. “Multiply recurrent trichilemmal carcinoma with perineural invasion and cytokeratin 17 positivity”. Dermatol Surg. vol. 29. 2003. pp. 886-9. (A case report of multiply recurrent trichilemmal carcinoma with perineural invasion occurring on the cheek of a 65-year-old Caucasian male. The patient was treated with Mohs surgery with a split-thickness skin graft, but 1 year later the lesion returned. The lesion was again treated with Mohs surgery and it did not return after 2 years.)
Jo, JH, Ko, HC, Jang, HS, Kim, MB, Oh, CK, Kwon, KS. “Infiltrative trichilemmal carcinoma treated with 5% imiquimod cream”. Dermatol Surg. vol. 31. 2005. pp. 973-6. (A case report of trichilemmal carcinoma occurring on the cheek of a 90-year-old woman. Since the patient refused surgical removal, she was treated with imiquimod 5% cream used 3 times a week for 8 weeks, without recurrence after 16 months.)
Yi, HS, Sym, SJ, Park, J, Cho, EK, Ha, SY, Shin, DB. “Recurrent and metastatic trichilemmal carcinoma of the skin over the thigh: a case report”. Cancer Res Treat. vol. 42. 2010. pp. 176-9. (A case report of metastatic trichilemmal carcinoma occurring on the thigh of a 63-year-old woman. The initial lesion was excised with clear margins, but 2 years later metastasized to regional lymph nodes. The patient was then treated with cisplatin and cyclophosphamide combination chemotherapy, which was discontinued after four cycles at the patient’s request. Six months later, lung and bone involvement occurred and the patient died.)
Takata, M, Rehman, I, Rees, JL. “A trichilemmal carcinoma arising from a proliferating trichilemmal cyst: the loss of wild-type p53 is a critical event in malignant transformation”. Hum Pathol. vol. 29. 1998. pp. 193-5. (A case report of trichilemmal carcinoma arising in the wall of a proliferating trichilemmal cyst on the scalp of a 77-year-old Japanese woman. PCR analysis of the DNA from both lesions revealed loss of heterozygosity in the proliferating trichilemmal cyst, and complete loss of the wild-type p53 gene allele in the trichilemmal carcinoma. Such findings suggest that total loss of the tumor suppressor gene may contribute to the development of trichilemmal carcinoma.)
Dalton, SR, LeBoit, PE. “Squamous cell carcinoma with clear cells: how often is there evidence of tricholemmal differentiation?”. Am J Dermatopathol. vol. 30. 2008. pp. 333-9. (An excellent study investigating the histopathological differentiation of squamous cell carcinoma with clear cells (SCC-C) from trichilemmal carcinoma by studying 40 cases of SCC-C. It was found that none of the SCC-C exhibited all the features expected in a trichilemmal carcinoma, and 85% were negative for antigens found in the outer root sheath epithelium.)
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