Non-melanocytic Skin Tumors
Moderator: Dr. Philip E. LeBoit
Case 3-3 -
Desmoplastic Squamous Cell Carcinoma
Philip E. LeBoit, M.D.
Depts. of Pathology and Dermatology
University of California, San Francisco
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
Diagnosis: Desmoplastic squamous cell carcinoma
Features in these sections include:
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.
- 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
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 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 melanoma
- Desmoplastic leimomyosarcoma
- Adenosquamous carcinoma
- Desmoplastic trichilemmoma
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.
- 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
- Diaz-Cascajo C, Borghi S, Weyers W. Desmoplastic leiomyosarcoma of the skin. Am J Dermatopathol. 2000 Jun;22(3):251-5.