Basal cell carcinoma with perineural invasion: reexcision perineural invasion?

BACKGROUND: Perineural invasion (PI) in basal cell and squamous cell carcinomas, especially of the head and neck, has been reported to indicate an increased morbidity. Reexcision perineural invasion (RPI), a benign mimic of tumoral perineural invasion, may present a difficult histologic differential diagnosis. METHODS: We surveyed the medical literature for PI occurring in basal cell carcinomas to investigate the degree to which the reported cases occurred in reexcision specimens vs. primary biopsy specimens. RESULTS: We found large retrospective studies of 14,120 basal cell carcinomas evaluated for PI in which 310 cases of PI were identified (2.2%), and 20 sporadic case reports of basal cell carcinomas with PI. Of 310 cases of basal cell carcinoma with PI, 196 (63%) were in reexcision specimens. Of 20 sporadic reports, 17 (85%) were in reexcision specimens. CONCLUSION: The high percentage of PI occurring in reexcision specimens vs. primary excisions may indicate that many of the reported cases of basal cell carcinomas with PI are actually examples of RPI.

Cutaneous pigmentation after photosensitivity induced by vandetanib therapy.

BACKGROUND: Photosensitivity has been reported in patients who were treated with vandetanib (ZD6474), an inhibitor of epidermal growth factor receptor, vascular endothelial growth factor receptor, and the RET (rearranged during transfection) kinases. OBSERVATIONS: We describe the occurrence of cutaneous hyperpigmentation after photosensitivity in 2 patients who were treated with vandetanib. The pigmentation patterns were variable within and between patients. Biopsy specimens from different sites revealed variability in Perls and Fontana staining patterns. CONCLUSIONS: These 2 cases highlight the unusual occurrence of cutaneous hyperpigmentation after vandetanib-associated photosensitivity, a reaction that demonstrates that medications are important causes of acquired photosensitivity and hyperpigmentation. Aggressive photoprotection may facilitate the resolution of diffuse hyperpigmentation. Dermatologists should endeavor to identify and report novel cutaneous adverse effects as new targeted therapies are developed.

Evidence of ultraviolet type mutations in xeroderma pigmentosum melanomas.

To look for a direct role of ultraviolet radiation (UV) exposure in cutaneous melanoma induction, we studied xeroderma pigmentosum (XP) patients who have defective DNA repair resulting in a 1000-fold increase in melanoma risk. These XP melanomas have the same anatomic distribution as melanomas in the general population. We analyzed laser capture microdissection samples of skin melanomas from XP patients studied at the National Institutes of Health. The tumor suppressor gene PTEN was sequenced and analyzed for UV-induced mutations. Samples from 59 melanomas (47 melanomas in situ and 12 invasive melanomas) from 8 XP patients showed mutations in the PTEN tumor suppressor gene in 56% of the melanomas. Further, 91% of the melanomas with mutations had 1 to 4 UV type base substitution mutations (occurring at adjacent pyrimidines) (P < 0.0001 compared to random mutations). We found a high frequency of amino-acid-altering mutations in the melanomas and demonstrated that these mutations impaired PTEN function; UV damage plays a direct role in induction of mutations and in inactivation of the PTEN gene in XP melanomas including in situ, the earliest stage of melanoma. This gene is known to be a key regulator of carcinogenesis and therefore these data provide solid mechanistic support for UV protection for prevention of melanoma.

p16 expression in keratoacanthomas and squamous cell carcinomas of the skin: an immunohistochemical study.

CONTEXT: Distinguishing between keratoacanthoma (KA) and squamous cell carcinoma (SCC) is not an uncommon histologic diagnostic dilemma. OBJECTIVE: To determine if p16 expression is useful in the differential diagnosis of SCC and KA. DESIGN: We studied the expression of p16 by immunohistochemistry in 24 KAs, 24 infiltrating SCCs of the skin, 4 histologically indeterminate lesions, and 8 nonmalignant keratoses. RESULTS: A range of immunohistochemical p16 expression was seen in KAs and SCCs in terms of the thickness of lesional staining and the percentage of cells staining. No significant difference in measures of p16 expression was identified among the KAs, the SCCs, the indeterminate lesions, or the benign keratoses. CONCLUSIONS: These findings suggest that p16 is not a useful marker to distinguish between KA and SCC, supporting the similarity between the 2 lesions; p16 alterations appear to play a role in the pathogenesis of both KA and SCC.

Subepidermal calcified nodules.

Subepidermal calcified nodules (SCNs) are uncommon, benign lesions usually presenting in childhood which occasionally involve the eyelids. Only a handful of cases have been reported in the ophthalmologic literature. We present 2 cases, one in a 7-year-old Hispanic boy, the other in a 13-year-old African American boy, with eyelid lesions which were clinically thought to be possible juvenile xanthogranuloma, but which on histopathologic examination showed the characteristic features of SCNs.

Tyrosinase expression in malignant melanoma, desmoplastic melanoma, and peripheral nerve tumors.

CONTEXT: Pathologists may encounter problems in the differential diagnosis of malignant melanoma, spindle and epithelioid neoplasms of peripheral nerves, and fibrohistiocytic tumors. Tyrosinase has been demonstrated to be a sensitive marker for melanoma. OBJECTIVE: To determine the specificity of tyrosinase expression in the differential diagnosis of melanoma, desmoplastic melanoma, and peripheral nerve sheath tumors. DESIGN: Immunoreactivity for tyrosinase, HMB-45 (anti-gp100 protein), S100 protein, CD34, and vimentin was studied in 70 tumors, including 15 melanomas (5 desmoplastic, 4 amelanotic, 6 melanotic), 13 malignant peripheral nerve sheath tumors; 10 schwannomas (1 pigmented), 12 neurofibromas (4 pigmented), and 20 fibrohistiocytic tumors (10 dermatofibrosarcoma protuberans and 10 dermatofibromas). Microwave-based antigen retrieval was performed in 10mM citrate buffer, pH 6.0, for 20 minutes at 121 degrees C. RESULTS: All melanomas demonstrated positive immunostaining for tyrosinase, HMB-45, and S100 protein. Immunoreactivity for HMB-45 was generally stronger than that for tyrosinase in amelanotic lesions and significantly stronger in 1 of the desmoplastic lesions. The 4 pigmented neurofibromas were focally positive for tyrosinase, but did not stain for HMB-45. The pigmented schwannoma was focally positive for both tyrosinase and HMB-45. The malignant peripheral nerve sheath tumors, dermatofibrosarcoma protuberans, and dermatofibromas were nonreactive for tyrosinase and HMB-45. CONCLUSIONS: Our results support the sensitivity of tyrosinase expression and demonstrate the relative specificity of tyrosinase as a marker for melanocytic lesions, including desmoplastic melanoma, although pigmented peripheral nerve tumors may demonstrate focal positive staining. Immunoreactivity for tyrosinase and HMB-45 may have been enhanced by the microwave-based antigen-retrieval technique used in this study.