A woman undergoing BRAF inhibitor targeted therapy for advanced melanoma has presented with invasive spindle cell squamous carcinoma masquerading as a secondary cutaneous squamous cell carcinoma, highlighting the importance of histologic evaluation of these lesions.
"Secondary cutaneous squamous cell carcinomas (cSCCs) are adverse effects of BRAF inhibitor targeted therapy for advanced melanoma," wrote Dr. Daniel N. Cohen and his associates online Feb. 26 in JAMA Dermatology.
The most commonly seen histologic type of secondary cutaneous squamous cell carcinomas is keratoacanthoma-like cSCC (cSCC-KA), which is thought to have a low risk of metastasis or recurrence, said lead author Dr. Cohen of the Vanderbilt University Medical Center, Nashville, Tenn.
In this case report, however, a woman in her 50s with BRAF-mutant metastatic melanoma developed more than 100 new cutaneous squamous proliferations across her face, trunk, and extremities within 4 weeks of starting treatment with the BRAF inhibitor dabrafenib as part of a clinical trial, with some lesions appearing to be a more aggressive type upon analysis.
The lesions began as acrochordons on her face and extremities, as well as new nevi on her torso and axilla. She also developed fever, chills, and fatigue and had enlarging, tender, and bleeding lesions on her trunk and extremities.
Seven large, tender, and indurated lesions were removed using a deep scoop shave biopsy, revealing a biphasic malignant growth pattern (JAMA Dermatology 2014 Feb 26 [doi:10.1001/jamadermatol.2013.7784]).
"The superficial portion demonstrated conventional cSCC-KA features of hyperkeratosis, epidermal acanthosis, and central core of glassy eosinophilic keratin with pseudopapillomatosis and a base with focal invasive lobules of cytologically atypical keratinocytes, consistent with previously reported cSCC-KA" the study authors reported.
However, they added, "in stark contrast to prior reports, the deep aspects of 6 of 7 lesions showed invasive spindled and epithelioid cells with monomorphic elongated nuclei with condensed chromatin and mitoses consistent with spindle cell squamous carcinoma, an aggressive subtype of squamous cell carcinoma."
The cells were strongly immunoreactive for cytokeratin CK5/6 and CK903, and both the squamous and spindle components were vimentin reactive and showed increased proliferation index. In contrast to the usual pattern of a spindle cell melanoma, the spindle tumor cells were also MART-1 and S100 negative.
The authors said this was the first known report of invasive spindle cell squamous carcinoma that mimicked keratoacanthoma-like secondary SCC appearing during BRAF inhibitor therapy and suggested that the discovery has implications for management of secondary squamous cell carcinoma.
"Because the clinical appearance of cSCC-KA and the spindle cell squamous carcinomas in our patient are indistinguishable, histologic evaluation of the entire lesion (via saucerization biopsy or incisional biopsy) is vital to prevent inadequate treatment of a deeply invasive process with a probable higher malignant potential," Dr. Cohen and his associates wrote.
The patient stopped BRAF inhibitor therapy and had no recurrence or new development of cutaneous secondary SCCs. A single later recurrence of melanoma was resected but she remains disease free.
One author declared a consultancy with Bristol-Myers Squibb and Genentech, as well as grant support from Genentech. There were no other financial disclosures reported.