Case 3-3 -

Desmoplastic Squamous Cell Carcinoma Philip E. LeBoit, M.D. Depts. of Pathology and Dermatology University of California, San Francisco

Clinical history: A 69 year old woman had a 1 cm. dome shaped plaque on the forearm, thought clinically to be a scar or dermatofibroma. Case 3-3 - Slide 1 Click to view with ImageScope Click to view with a Web-Based Viewer Diagnosis: Desmoplastic squamous cell carcinoma Features in these sections include: Large intradermal fibrous proliferation Increased spindled cells Some spindled cells with large, hyperchromatic nuclei Some spindled cells have eosinophilic cytoplasm Fibrous and mucinous stroma Lymphocytes near nerve fascicles Absence of solar keratosis or Bowen's disease The subject of cutaneous squamous cell carcinoma (SCC) has not been one of the most attractive in dermatopathology, as SCCs are so common, and metastasis is rare. Yet, because they are in fact so common, uncommon variants are important and have not been adequately studied. The first formal study of desmoplastic squamous cell carcinoma per se was in 1997 by Breuninger et al. Desmoplastic squamous cell carcinoma is unusual but not exotically rare. In Breuninger's series, it comprised almost 8% of cutaneous squamous cell carcinomas, but this figure may be too high. They included cases in which there were areas of solid growth, with a desmoplastic pattern only at the edges of aggregates, sometimes only seen well with anti-keratin staining. They found recurrence rates of about 27%, with a high rate of metastasis- 22%, exceptional for cutaneous squamous cell carcinoma. Increased metastatic rates are evident in desmoplastic squamous cell carcinomas of the lip, but the extraordinarily high rate of metastasis that Breuninger et al. report remains to be confirmed. Confirmation by immunohistochemical studies is important. Keratin cocktails (AE1/AE3/Cam5.2) as well as HMWK903 are reliable. The p53-like protein, p63 is over-expressed by the nuclei in desmoplastic squamous cell carcinoma. The differential diagnosis includes: Desmoplastic melanoma Desmoplastic leimomyosarcoma Adenosquamous carcinoma Desmoplastic trichilemmoma Desmoplastic melanoma does not feature aggregates of squamous keratinocytes or single cell keratinization, as many cases of desmoplastic squamous cell carcinoma may have. Only about a half have melanoma in situ, so this cannot be relied on. Immunoperoxidase stains are key, as almost all desmoplastic melanomas are S100+ and keratin-. While melanomas can be S100-, this is rare. Unfortunately, HMB45, Melan-A/MART-1, tyrosinase and MiTF have limited sensitivity in melanomas in which spindled cells predominate. Desmoplastic leimomyosarcoma can be difficult to recognize. Its cells have vacuolated eosinophilic cytoplasm, and like melanoma will not be found alongside aggregations of keratinocytes or have keratinized cytoplasm. Key reactivities include alpha smooth muscle actin, desmin and caldesmon. In the absence of desmin or caldesmon staining, only strong actin positivity for nearly all cells is diagnostic, as many spindle cell neoplasms are actin+. Adenosquamous carcinoma of the skin is also an aggressive neoplasm, in which small jagged aggregates of cells with large, hyperchromatic nuclei infiltrate the dermis. Lumens containing mucicarmine positive mucin and sometimes calcification are present. As is the case with desmoplastic squamous cell carcinoma, perineural invasion can be frequent. Desmoplastic trichilemmoma may not be a true variant of trichilemmoma so much as an appearance- the result of trauma to a conventional trichilemmoma. The center of the lesion is altered by strands of keratinocytes with pale cytoplasm seen in between thickened collagen bundles. Small, partial biopsies can be deceiving. A large enough specimen will show the typical lobules of pale staining cells with monomorphous nuclei that enable the diagnosis. References: Breuninger H, Schaumburg-Lever G, Holzschuh J, Horny HP. Desmoplastic squamous cell carcinoma of skin and vermilion surface: a highly malignant subtype of skin cancer. Cancer. 1997 Mar 1;79(5):915-9. Frierson HF Jr, Cooper PH. Prognostic factors in squamous cell carcinoma of the lower lip. Hum Pathol. 1986 Apr;17(4):346-54. Cassarino DS, Derienzo DP, Barr RJ. Cutaneous squamous cell carcinoma: a comprehensive clinicopathologic classification. Part one. J Cutan Pathol. 2006 Mar;33(3):191-206. Cassarino DS, Derienzo DP, Barr RJ. Cutaneous squamous cell carcinoma: a comprehensive clinicopathologic classification--part two. J Cutan Pathol. 2006 Apr;33(4):261-79. Breuninger H, Holzschuh J, Schaumburg Lever G, Schippert W, Horny HP. In German, abstract in English- Desmoplastic squamous epithelial carcinoma of the skin and lower lip. A morphologic entity with great risk of metastasis and recurrence. Hautarzt. 1998 Feb;49(2):104-8. Dotto JE, Glusac EJ. p63 is a useful marker for cutaneous spindle cell squamous cell carcinoma. J Cutan Pathol. 2006 Jun;33(6):413-7. Diaz-Cascajo C, Borghi S, Weyers W. Desmoplastic leiomyosarcoma of the skin. Am J Dermatopathol. 2000 Jun;22(3):251-5.