Final Diagnosis -- Pilomatrix carcinoma of the skin and soft tissue

FINAL DIAGNOSIS

Pilomatrix carcinoma of the skin and soft tissue arising on the right thigh with metastases to three right groin lymph nodes.

DISCUSSION

Pilomatrix carcinoma is a rare malignant neoplasm composed of cells that resemble the matrix of hair follicles. While its benign counterpart is much more common, previous molecular and immunohistochemical studies have revealed activating mutations in the gene encoding for β-catenin present in both entities.[1, 2] It generally arises in adult males as a solitary tumor without history of a precursor lesion; although rarely pilomatrixomas can undergo malignant transformation.[3] They occur most frequently in the head and neck area, and they can also arise in the trunk and extremities.[4] Pilomatrix carcinomas are generally poorly circumscribed grossly and composed of nests, cords, and sheets of basaloid cells. There are generally two morphologically distinct cell populations: basaloid cells and eosinophilic keratinized "ghosts" cells with only a large pale nuclear outline. Diagnosis is based on presence of mitotic activity, atypical mitotic figures and infiltrative pattern of growth microscopically.[4, 5] Although they have been reported to recur in up to 83% of the cases treated with simple excision, prognosis is significantly better for localized disease treated with wide excision. Local recurrence occurs in approximately 23% of the cases. Metastases to regional lymph nodes, lungs, bones, and other organs are reported in 13% of the cases.[6]

The demographics of our patient fit the most frequently seen in cases of pilomatrix carcinoma: male above the sixth decade of age.[4] However, the location and size of the lesion put a potential sarcoma at the top of the clinical differential diagnosis. Most pilomatrix carcinomas reported in the literature thus far ranged between 0.5 and 7 cm in size,[6] making a large -10 cm- mass unusually big for this diagnosis and more suggestive of a tumor of mesenchymal origin, especially considering the involved site. Furthermore, the overall incidence of sarcomas is much higher than that of rare pilomatrix carcinomas. Based on clinical features, other differential diagnoses cited in the literature include basal cell carcinomas especially in cases that present ulceration of the overlying skin; pilar or epidermal cysts, considerations probably related to the degree of necrosis of the tumor and subsequent softer consistency; and melanoma particularly in cases of pigmented pilomatrix carcinomas.[4, 6-8] The spectrum of tumors with matrical differentiation comprises benign pilomatrixoma, proliferating pilomatrixoma and pilomatrix carcinoma. A combination of clinical and histological features is taken into consideration when assessing tumor malignant potential. Lesions that show good circumscription grossly, and microscopically pushing advancing borders are associated with benign behavior.[4] Our case is unusual in that in spite of showing tumor-stroma interface features suggestive of low malignant potential it also showed features concerning for malignancy such as high proportion of basaloid cells, nuclear pleomorphism, desmoplastic stroma, necrosis, and numerous mitotic figures.[6, 9] Taken together, the findings were deemed sufficient to diagnose this challenging case as a pilomatrix carcinoma, although there were no perineural or lymphovascular invasion and no evidence of metastatic disease at the time of the initial tumor resection.

In the literature, metastases have been observed in approximately 13% of the reported cases of pilomatrix carcinoma, with local tumor recurrence as the only significant risk factor for the development of metastases.[6] Although our patient did not present local recurrent disease, the malignant nature of the lesion was confirmed when six months after the excision of the primary tumor the patient presented with nodules in the right groin that on fine needle aspiration showed clusters of basaloid and keratinizing squamous cells in a background of blood and necrotic debris.

REFERENCES

1. Lazar, A.J., et al., Pilomatrix carcinomas contain mutations in CTNNB1, the gene encoding beta-catenin. J Cutan Pathol, 2005. 32(2): p. 148-57.
2. Hassanein, A.M. and S.M. Glanz, Beta-catenin expression in benign and malignant pilomatrix neoplasms. Br J Dermatol, 2004. 150(3): p. 511-6.
3. Nishioka, M., et al., Pilomatrix carcinoma arising from pilomatricoma after 10-year senescent period: Immunohistochemical analysis. J Dermatol, 2010. 37(8): p. 735-9.
4. Hardisson, D., et al., Pilomatrix carcinoma: a clinicopathologic study of six cases and review of the literature. Am J Dermatopathol, 2001. 23(5): p. 394-401.
5. Lopansri, S. and M.C. Mihm, Jr., Pilomatrix carcinoma or calcifying epitheliocarcinoma of Malherbe: a case report and review of literature. Cancer, 1980. 45(9): p. 2368-73.
6. Herrmann, J.L., et al., Pilomatrix carcinoma: 13 new cases and review of the literature with emphasis on predictors of metastasis. J Am Acad Dermatol, 2014. 71(1): p. 38-43 e2.
7. Monteagudo, C., et al., Matrical carcinoma with prominent melanocytic hyperplasia (malignant melanocytic matricoma?) A report of two cases. Am J Dermatopathol, 2003. 25(6): p. 485-9.
8. Jani, P., R. Chetty, and D.M. Ghazarian, An unusual composite pilomatrix carcinoma with intralesional melanocytes: differential diagnosis, immunohistochemical evaluation, and review of the literature. Am J Dermatopathol, 2008. 30(2): p. 174-7.
9. Cornejo, K.M. and A. Deng, Pilomatrix carcinoma: a case report and review of the literature. Am J Dermatopathol, 2013. 35(3): p. 389-94.

Contributed by Cecilia Lezcano, MD and Uma N Rao, MD