Utility of p63 in the differential diagnosis of atypical fibroxanthoma and spindle cell squamous cell carcinoma

Abstract

Atypical fibroxanthoma (AFX), spindle cell squamous cell carcinoma (SCSCC) and spindle cell melanoma are the primary entities in the differential diagnosis of a cytologically atypical spindle cell tumor arising on sun-damaged skin. AFX is generally regarded as a diagnosis of exclusion in this context: in the absence of S100 or keratin reactivity, a diagnosis of AFX is favored. However, keratin reactivity may be focal or even absent in SCSCC, and although numerous positive markers of AFX have been proposed, none has shown sufficient sensitivity and specificity for routine diagnostic use. We evaluated 20 AFX and 10 SCSCC with a panel of cytokeratins and p63 to assess the utility of the latter antibody in this differential diagnosis. All 10 SCSCC showed strong expression of p63, whereas all 20 AFX were p63 negative. Two additional cases (excluded from the study) were negative for keratins and S100 on initial shave biopsies, resulting in a favored diagnosis of AFX, but p63 stains performed retrospectively were positive. However, review of the excision specimens in both cases revealed deep subcutaneous extension, excluding AFX. p63 reactivity argues against the diagnosis of AFX and is therefore a useful addition to the standard immunohistochemical panel for cutaneous spindle cell neoplasms.

Desmoplastic spindle cell squamous cell carcinoma of skin

“…The present tumor is carcinoma. Atypical fibroxanthoma and desmoplastic melanoma was excluded because the present tumor expressed various CKs and did not express HMB45, Melan-A, SOX10, MITF; [3][4][5][6][7][8][9][10] the specificity of S100 protein is low, [3][4][5][6][7][8][9][10] the possibility of desmoplastic melanoma is quite unlikely. Because the present tumor expressed CKs, it is carcinoma.…”

“…[4][5][6][7][8][9][10] These two variants of skin SCC lack keratinization and intercellular bridge, thus causing diagnostic problems. [1][2][3][4][5][6][7][8][9][10] The author herein reports a case of desmoplastic SCC composed predominantly of spindle cells.…”

Atypical fibroxanthoma: differential diagnosis from other sarcomatoid skin lesions

“…In view of the documentation of metastasizing AFX in which the primary tumour showed prominent subcutaneous involvement, some authors have proposed a more restrictive definition of AFX to those tumours confined to the dermis (without subcutaneous extension) and absence of lymphovascular invasion, perineural infiltration, and tumour necrosis. 33 The advantage of adopting such a restrictive definition of AFX is that the predicted incidence of metastasis would be extremely low. Thus, we endorse this construct.…”

“…Recently, it has been reported that nuclear p63 labelling is common in sarcomatoid SCCs; thus, positive staining for that marker militates against the diagnosis of AFX. 33 Spindle-cell melanoma Melanoma is typified histologically by pleomorphic epithelioid cells in the epidermis and dermis. Those elements have characteristic cytologic features such as the presence of large nucleoli, intranuclear pseudoinclusions, and intracytoplasmic melanin pigmentation.…”

Immunohistochemistry in Dermatopathology

“…It is normally expressed in keratinocytes of the basal and lower spinous layers. Many authors 66 have reported nuclear p63 expression in spindle cell SCC. However, p63 is not entirely specific and shows focal labeling in rare cases of AFX and leiomyosarcoma.…”