Keratoacanthoma and Infundibulocystic Squamous Cell Carcinoma

Kossard, Steven; Tan, Kong-Bing; Choy, Carolyn

doi:10.1097/dad.0b013e318161310c

Cited by 76 publications

(71 citation statements)

References 29 publications

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“…Follicular dystrophic lesions and perforating folliculitis are obviously follicular lesions and relics of hair follicles were indeed observed in every biopsy sample. Follicular ontogeny for KA is also well documented (20). The microscopically lamellar structure as well as the type of cytokeratins found in KA suggest that they are hair follicle-derived tumors (21).…”

Section: A B C D E F G H Discussionmentioning

confidence: 88%

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Skin Tumors Induced by Sorafenib; Paradoxic RAS–RAF Pathway Activation and Oncogenic Mutations of HRAS, TP53, and TGFBR1

Arnault

Mateus

Escudier

et al. 2012

Clinical Cancer Research

114

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Purpose: The emergence of skin tumors in patients treated with sorafenib or with more recent BRAF inhibitors is an intriguing and potentially serious event. We carried out a clinical, pathologic, and molecular study of skin lesions occurring in patients receiving sorafenib.Experimental Design: Thirty-one skin lesions from patients receiving sorafenib were characterized clinically and pathologically. DNA extracted from the lesions was screened for mutation hot spots of HRAS, NRAS, KiRAS, TP53, EGFR, BRAF, AKT1, PI3KCA, TGFBR1, and PTEN. Biological effect of sorafenib was studied in vivo in normal skin specimen and in vitro on cultured keratinocytes.Results: We observed a continuous spectrum of lesions: from benign to more inflammatory and proliferative lesions, all seemingly initiated in the hair follicles. Eight oncogenic HRAS, TGFBR1, and TP53 mutations were found in 2 benign lesions, 3 keratoacanthomas (KA) and 3 KA-like squamous cell carcinoma (SCC). Six of them correspond to the typical UV signature. Treatment with sorafenib led to an increased keratinocyte proliferation and a tendency toward increased mitogen-activated protein kinase (MAPK) pathway activation in normal skin.Sorafenib induced BRAF-CRAF dimerization in cultured keratinocytes and activated CRAF with a dosedependent effect on MAP-kinase pathway activation and on keratinocyte proliferation.Conclusion: Sorafenib induces keratinocyte proliferation in vivo and a time-and dose-dependent activation of the MAP kinase pathway in vitro. It is associated with a spectrum of lesions ranging from benign follicular cystic lesions to KA-like SCC. Additional and potentially preexisting somatic genetic events, like UV-induced mutations, might influence the evolution of benign lesions to more proliferative and malignant tumors.

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Section: A B C D E F G H Discussionmentioning

confidence: 88%

“…KA is a rapidly growing keratotic and crateriform tumor, very similar clinically and pathologically to well-differentiated SCC (16). It is characterized by frequent spontaneous resolution and originates from hair follicles (17). For some authors, it is considered to be low-grade SCC (18).…”

Section: A B C D E F G H Discussionmentioning

confidence: 99%

Skin Tumors Induced by Sorafenib; Paradoxic RAS–RAF Pathway Activation and Oncogenic Mutations of HRAS, TP53, and TGFBR1

Arnault

Mateus

Escudier

et al. 2012

Clinical Cancer Research

114

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“…Surgical or destructive treatment is usually indicated; however, they can regress spontaneously. TheyareconsideredatypeofSCCbysomepathologists,although others consider them to be distinct tumors [17]. Diagnosis requires complete or near-complete sampling, and routine or partial histologic sections may make a diagnosis inaccurate [16,18].…”

Section: Discussionmentioning

confidence: 99%

Analysis of Dermatologic Events in Vemurafenib-Treated Patients With Melanoma

et al. 2013

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Background. Vemurafenib has been approved for the treatment of patients with advanced BRAF V600E -mutant melanoma. This report by the Vemurafenib Dermatology Working Group presents the characteristics of dermatologic adverse events (AEs) that occur in vemurafenib-treated patients, including cutaneous squamous cell carcinoma (cuSCC). Methods. Dermatologic AEs were assessed from three ongoing trials of BRAF V600E mutation-positive advanced melanoma. Histologic central review and genetic characterization were completed for a subset of cuSCC lesions. Results. A total of 520 patients received vemurafenib. The most commonly reported AEs were dermatologic AEs, occurring in 92%-95% of patients. Rash was the most common AE (64%-75% of patients), and the most common types were rash not otherwise specified, erythema, maculopapular rash, and folliculitis. Rash development did not appear to correlate with tumor response. Photosensitivity occurred in 35%-63% of patients, and palmar-plantar erythrodysesthesia (PPE) occurred in 8%-10% of patients. The severity of rash, photosensitivity, and PPE were mainly grade 1 or 2. In all, 19%-26% of patients developed cuSCC, mostly keratoacanthomas (KAs). The majority of patients with cuSCC continued therapy without dose reduction after resection. Genetic analysis of 29 cuSCC/KA samples demonstrated HRAS mutations in 41%. Conclusions. Dermatologic AEs associated with vemurafenib treatment in patients with melanoma were generally manageable with supportive care measures. Dose interruptions and/or reductions were required in Ͻ10% of patients. The Oncologist 2013;18:314 -322 Implications for Practice: Vemurafenib has been approved for the treatment of patients with advanced BRAF-mutant melanoma. Skin toxicity is common with vemurafenib therapy, and the majority of patients are able to tolerate and continue therapy following symptomatic and/or local management (e.g., surgical resection). Clinicians should be aware of these toxicities to better educate and manage their patients.

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“…Another rare subset of SCC has been described as follicular, infundibular, or infundibulocystic SCC. [32][33][34][35] Some of the histologic features overlap with the cases in our series, such as the absence of associated AK or the welldifferentiated morphology with a somewhat glassy cytoplasm. However, we did not identify a clear infundibular or otherwise follicular origin of the tumors in any of our cases.…”

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confidence: 72%

Cutaneous Squamous Cell Carcinomas of the Lower Extremities Show Distinct Clinical and Pathologic Features

2015

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Cutaneous squamous cell carcinomas mainly affect older, predominantly male patients. Most are due to chronic ultraviolet exposure, and associated with actinic keratoses. On the lower extremities, they occur more commonly in women. However, data on these tumors as a distinct group are scarce. We evaluated 61 squamous cell carcinomas of the lower extremities. Overall, 69% of patients were female. Mean age was 75 years. More than 90% of tumors were well differentiated, 3% showed perineural invasion, and none lymphovascular invasion. In all, 63.9% showed evidence of severe chronic sun damage. Associated actinic keratoses were identified in only 13% of cases. By contrast, 80% were associated with distinctive basal epidermal proliferations with a retiform growth pattern. These proliferations were evaluated immunohistochemically for keratinocyte stem cell markers, p53 and Notch1 in 15 cases. All cases were positive for cytokeratin 14, p53, and Notch1 (with variable intensity in the latter 2), and predominantly negative for cytokeratin 19. Interestingly, basal retiform proliferations were positive for cytokeratin 15 in 66% of cases. Fifteen head and neck squamous cell carcinomas were evaluated in comparison. Those lacked associated basal retiform proliferations except in 1 case. In contrast, 87% were associated with actinic keratoses and 100% with severe chronic sun damage. Actinic keratoses associated with head and neck tumors showed cytokeratin 15 staining only in 7% of cases (P = .003 compared with cytokeratin 15 in basal retiform proliferations associated with leg carcinomas). These findings support the hypothesis that lower extremity squamous cell carcinomas are distinct and may exhibit a pathogenesis less reliant on actinic damage.

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Keratoacanthoma and Infundibulocystic Squamous Cell Carcinoma

Cited by 76 publications

References 29 publications

Skin Tumors Induced by Sorafenib; Paradoxic RAS–RAF Pathway Activation and Oncogenic Mutations of HRAS, TP53, and TGFBR1

Skin Tumors Induced by Sorafenib; Paradoxic RAS–RAF Pathway Activation and Oncogenic Mutations of HRAS, TP53, and TGFBR1

Analysis of Dermatologic Events in Vemurafenib-Treated Patients With Melanoma

Cutaneous Squamous Cell Carcinomas of the Lower Extremities Show Distinct Clinical and Pathologic Features

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