Systemic Immunotherapy for Advanced Cutaneous Squamous Cell Carcinoma.

OPINION STATEMENT: Advanced (i.e., unresectable) cutaneous squamous cell carcinoma (cSCC) is a rare condition with a dismal prognosis. Although less than 5% of cSCC patients develop metastases or local recurrence after complete excision, advanced cSCC is difficult to treat. These conditions tend to develop in elderly patients, although, at times, metastases are noted in middle-aged patients. Once metastasis occurs in cSCC, the 10-year survival rates fall to less than 20% for patients with regional lymph node involvement and less than 10% for patients with distant metastases, indicating that cSCC can be difficult to treat effectively when it is advanced. Traditionally, platinum-based therapy has been considered as a conventional option for advanced cSCC. It is efficacious to some degree, but the toxic effects of the combination treatments often prohibit their use in elderly patients. It has been a decade since the development of epidermal growth factor receptor (EGFR) inhibitors as agents that are less toxic. However, evidence regarding systemic therapy for advanced cSCC is limited because of a lack of high-quality prospective studies. Remarkably, the US Food and Drug Administration (FDA) approved an anti-PD-1 antibody treatment (cemiplimab) for the treatment of patients who are not candidates for curative surgery or curative radiation. It will be a promising treatment option for these types of rare conditions.

[Beyond actinic keratoses: Field cancerization of the skin]. / Au-delà des kératoses actiniques, le champ de cancérisation cutané.

Lesions occurring in actinic keratoses (AK) form erythematous, squamous, crusty and keratotic papules that appear on skin chronically exposed to the sun due to ultraviolet radiation. They are formed by the proliferation of atypical keratinocytes limited to the epidermis and may progress to squamous cell carcinoma in situ and to cutaneous squamous cell carcinoma (CEC). Although low, the metastatic risk associated with the CEC is not negligible. The concept of field cancerization was introduced in 1953 following studies of neoplastic lesions of the oral mucosa. A cancer field is a normal-looking pre-tumoral zone with subclinical, multifocal anomalies, which may constitute a base for new neoplastic lesions. Such fields are frequently seen in areas of photo-exposed skin and around the edges of AK and CEC. In this event, treatment should not be limited to visible or palpable AK lesions, and if a cancer field is suspected, treatment involving the physical destruction or elimination of atypical keratinocytes from the entire area should be considered. Such an approach may improve the long-term prognosis, reduce treatment costs and ensure optimal cosmetic outcome.

The incidence and body site of skin cancers in the population groups of South Africa.

BACKGROUND/PURPOSE: Data regarding basal cell carcinoma (BCC), squamous cell carcinoma of the skin (SSCC) and cutaneous melanoma (CM) in multiracial populations are sparse. Here the incidence and body site of these tumours in the South African population in 2000-2004 were analysed. METHODS: Annual age-standardized incidences and body sites of BCC, SSCC and CM in black, coloured, Asian and white groups were obtained from histological confirmed cases, reported to the National Cancer Registry. RESULTS: Highest annual incidences of BCC, SSCC and CM occurred in the white group, followed by coloured, then Asian and then black. BCCs and SSCCs were about twice as common in males than females. CM was the least frequent skin tumour, and BCC the most frequent, except in black people. The head was the commonest body site for SSCC and BCC in all groups and both sexes, whereas the lower limb was the predominant site for CM in black people. Mean age at diagnosis was generally mid-50s for CM, and mid-60s for BCC and SSCC. CONCLUSIONS: In South Africa, differences in reported incidence rates and body sites of skin tumours by population group and sex occur. Host characteristics, particularly skin phototype, and personal behaviour are likely to affect the risk of these cancers.

Visor flap: A solution for the reconstruction of large skin defects on the frontal and parietal parts of the skull.

BACKGROUND: Reconstruction of skin defects after oncological surgery for a cutaneous squamous cell carcinoma is often mandatory to facilitate adjuvant treatment and/or to prevent chronic wound problems. Some of the most challenging regions to reconstruct after resection of a skin tumor are the frontal and parietal parts of the skull. METHODS: This article describes three patients with large skin defects after oncological surgery that were reconstructed with the use of a (hemi) visor flap. RESULTS: The (hemi) visor flap is easy to harvest, resulting in a concise procedure and short hospitalization with maximum wound control. CONCLUSION: The (hemi) visor flap is a safe and reliable option for the closure of large skin defects on the skull. Especially in the older and frail patient group.

Rapidly Growing and Aggressive Squamous Cell Carcinoma of the Forearm: A Report of Successful Treatment With Mohs Surgery and Complex Reconstruction With Rhombic Triple Z-Plasty.

Reconstruction of complex post-surgical wounds requires functional and aesthetic considerations. We present a case of a complex radial-dorsal forearm defect in a patient who underwent Mohs surgery for an aggressive and rapidly growing squamous cell carcinoma. Following complete tumor excision, we utilized a modified rhombic flap for complete wound coverage with long-term conservation of extensor function. The rhombic flap modification included three Z-plasties at the flap base to add rotational components to the flap transposition. Long-term follow-up showed acceptable cosmesis, preserved extensor tendon function, and no evidence of tumor recurrence.

Excision of Invasive Squamous Cell Carcinoma Complicated by Osteomyelitis and Tobacco Use: A Case Report.

Squamous cell carcinoma (SCC) is a common type of skin cancer that can be treated through surgical excision using Mohs micrographic surgery (MMS) which results in minimal scarring and low complications. Soft tissue defects as a result of MMS that are too large to be primarily closed can be repaired with secondary intention healing through the use of biologic prosthetics that promote dermal regeneration and tissue remodeling with high success rates. Other non-surgical treatment options include chemotherapy (topical or systemic), radiation, or immunotherapy for advanced skin cancers. In this case, our patient is a 76-year-old male with a history of tobacco use who presented with ulcerative SCC and developed a necrotic soft-tissue infection of Pseudomonas aeruginosa complicated by calvarial osteomyelitis six weeks following wide excision of scalp SCC and wound defect repair with application of Integra® Bilayer Wound Matrix (Integra LifeSciences, Princeton, New Jersey, United States) to promote re-vascularization and tissue regrowth. The patient is currently recovering well after the excision of the necrotic scalp lesion and second-stage reconstruction with right scalp fasciocutaneous flap and full-thickness skin graft with proper antibiotic administration. Complications were likely due to delayed wound healing from post-operative cigar use increasing his risk for infection and application of biologic prosthetics that potentially served as a nidus for bacterial adherence and biofilm production of P. aeruginosa, which led to osteomyelitis, an exceedingly rare complication for patients that undergo MMS.

Eight Patients With Pilonidal Carcinoma in One Decade-Is the Incidence Rising?

INTRODUCTION: Carcinoma secondary to pilonidal disease is very rare with fewer than 130 reported cases so far. It is presumed that underreporting and underpublishing contribute to the low reported incidence. METHODS: A post was published on a closed Facebook group with about 30,000 Syrian doctors asking if anyone had ever seen a patient with pilonidal carcinoma before. The patients' data were collected retrospectively from the treating physicians. RESULTS: Between 2010 and 2019, we identified eight patients with pilonidal carcinoma. All patients were males with a mean age of 55.5 years. The mean interval between diagnosis of pilonidal disease and diagnosis of carcinoma was 6.9 years. A growing ulcer on the background of a pilonidal sinus disease was the presenting complaint in 50% of cases. Three patients were lost from follow-up after the diagnosis due to referral. All other five patients underwent surgical resection and three of them received postoperative chemoradiation. Four patients were followed for six months or longer: two died of metastases, one survived after recurrence and re-excision, and one survived with no recurrence. CONCLUSION: This paper presents the largest cohort of pilonidal carcinoma so far and the first that describes the disease in the Syrian population. Due to underreporting, the real incidence of pilonidal carcinoma exceeds what is reported so far in the literature.

Fluorouracil sensitivity in a head and neck squamous cell carcinoma with a somatic DPYD structural variant.

Head and neck squamous cell carcinoma (HNSCC) is one of the most common cancers worldwide and represents a heterogeneous group of tumors, the majority of which are treated with a combination of surgery, radiation, and chemotherapy. Fluoropyrimidine (5-FU) and its oral prodrug, capecitabine, are commonly prescribed treatments for several solid tumor types including HNSCC. 5-FU-associated toxicity is observed in ∼30% of treated patients and is largely caused by germline polymorphisms in DPYD, which encodes dihydropyrimidine dehydrogenase, a key enzyme of 5-FU catabolism and deactivation. Although the association of germline DPYD alterations with toxicity is well-described, the potential contribution of somatic DPYD alterations to 5-FU sensitivity has not been explored. In a patient with metastatic HNSCC, in-depth genomic and transcriptomic integrative analysis on a biopsy from a metastatic neck lesion revealed alterations in genes that are associated with 5-FU uptake and metabolism. These included a novel somatic structural variant resulting in a partial deletion affecting DPYD, a variant of unknown significance affecting SLC29A1, and homozygous deletion of MTAP There was no evidence of deleterious germline polymorphisms that have been associated with 5-FU toxicity, indicating a potential vulnerability of the tumor to 5-FU therapy. The discovery of the novel DPYD variant led to the initiation of 5-FU treatment that resulted in a rapid response lasting 17 wk, with subsequent relapse due to unknown resistance mechanisms. This suggests that somatic alterations present in this tumor may serve as markers for tumor sensitivity to 5-FU, aiding in the selection of personalized treatment strategies.

Functional genomic analysis identifies drug targetable pathways in invasive and metastatic cutaneous squamous cell carcinoma.

Although cutaneous squamous cell carcinoma (cSCC) is treatable in the majority of cases, deadly invasive and metastatic cases do occur. To date there are neither reliable predictive biomarkers of disease progression nor FDA-approved targeted therapies as standard of care. To address these issues, we screened patient-derived primary cultured cells from invasive/metastatic cSCC with 107 small-molecule inhibitors. In-house bioinformatics tools were used to cross-analyze drug responses and DNA mutations in tumors detected by whole-exome sequencing (WES). Aberrations in molecular pathways with evidence of potential drug targets were identified, including the Eph-ephrin and neutrophil degranulation signaling pathways. Using a screening panel of siRNAs, we identified EPHA6 and EPHA7 as targets within the Eph-ephrin pathway responsible for mitigating decreased cell viability. These studies form a plausible foundation for detecting biomarkers of high-risk progressive disease applicable in dermatopathology and for patient-specific therapeutic options for invasive/metastatic cSCC.

A novel missense variant and multiexon deletion causing a delayed presentation of xeroderma pigmentosum, group C.

Pathogenic variants in the XPC complex subunit, DNA damage recognition, and repair factor (XPC) are the cause of xeroderma pigmentosum, group C (MIM: 278720). Xeroderma pigmentosum is an inherited condition characterized by hypersensitivity to ultraviolet (UV) irradiation and increased risk of skin cancer due to a defect in nucleotide excision repair (NER). Here we describe an individual with a novel missense variant and deletion of exons 14-15 in XPC presenting with a history of recurrent melanomas. The proband is a 39-yr-old female evaluated through the Mayo Clinic Department of Clinical Genomics. Prior to age 36, she had more than 60 skin biopsies that showed dysplastic nevi, many of which had atypia. At age 36 she presented with her first melanoma in situ, and since then has had more than 10 melanomas. The proband underwent research whole-exome sequencing (WES) through the Mayo Clinic's Center for Individualized Medicine and a novel heterozygous variant of uncertain significance (VUS) in XPC (c.1709T > G, p.Val570Gly) was identified. Clinical confirmation pursued via XPC gene sequencing and deletion/duplication analysis of XPC revealed a pathogenic heterozygous deletion of ∼1 kb within XPC, including exons 14 and 15. Research studies determined the alterations to be in trans Although variants in XPC generally result in early-onset skin cancer in childhood, the proband is atypical in that she did not present with her first melanoma until age 36. Review of the patient's clinical, pathological, and genetic findings points to a diagnosis of delayed presentation of xeroderma pigmentosum.

The incidence and body site of skin cancers in the population groups of Astana, Kazakhstan.

BACKGROUND AND AIMS: Data on cutaneous malignant melanoma (CMM), squamous cell carcinoma of the skin (SCC), and basal cell carcinoma (BCC) in populations consisting of multi-racial groups in the Commonwealth of Independent States are limited. Here, the main aim was to analyse the incidence and body site of these cancers in the population groups of Astana, Kazakhstan (2007-2016). METHODS: Annual age standardised incidences and body sites of BCC, SCC, and CMM in Astana's population, divided into "Kazakhs and other Turkic/Asian" and "Russian and other European/Caucasian" groups, were calculated from histologically confirmed cases reported to Astana Oncology Centre. RESULTS: During the period January 2007 to October 2016, 647 skin cancers were diagnosed. The age and sex standardised incidence of BCC, SCC, and CMM increased significantly between 2007 to 2011 and 2012 to 2016. Higher incidences occurred in the Russian and other European/Caucasian group compared with the Kazakh and other Turkic/Asian group for the 3 skin cancers. BCC was the most common type of skin tumour, followed by SCC, and then CMM, in both population groups and sexes. The head/neck was the commonest site for BCC and SCC in all groups. For CMM, the most frequent site was the trunk in the Russian group and the head/neck in the Kazakh group. CONCLUSION: The incidence of skin tumours in Astana rose over the past 10 years. Differences in skin phototypes and sun exposure/ protection behaviours may account for the more frequent occurrence of skin tumours in the Russian population group compared with the Kazakh population group.

Recurrent squamous cell carcinoma of the skin treated successfully with single agent cetuximab therapy.

Recurrent squamous cell carcinoma of the skin is a rare but difficult to treat condition. Frequently, the disease presents itself in elderly patients with poor performance status and bearing many comorbidities, thus the decision to administer systemic chemotherapy becomes difficult to make. In addition, current chemotherapeutic protocols response rates are far from satisfactory. Recently cetuximab, a chimeric antibody against epidermal growth factor receptor, is increasingly being reported as an alternative treatment. We therefore report this case of a recurrent squamous cell carcinoma of the skin in an elderly woman with poor performance status and who had an excellent clinical response to single agent cetuximab therapy with complete resolution of the disease and minimal toxicity during the course of the treatment to provide evidence for future prospective clinical trials.

Treatment of unresectable squamous cell carcinoma of the skin with epidermal growth factor receptor antibodies--a case series.

BACKGROUND: Non-melanoma skin cancer (NMSC), including squamous cell carcinoma (SCC) and basal cell carcinoma (BCC), is the most common malignancy. Unresectable or metatstatic SCC is rare and therapy can be difficult because of advanced age and comorbidities. Targeted therapy with monoclonal antibodies (mAbs) against EGFR is an option in these patients. OBJECTIVE: The aim of this presentation is to provide additional evidence on the safety of anti-EGFR mAbs in long-term palliation and adjuvant treatment of advanced SCC. MATERIALS AND METHODS: This is a retrospective analysis of 4 patients with locally advanced or metastatic SCC who received cetuximab and/or panitumumab. RESULTS: 3 patients (2 females, 1 male, ages 86 to 93) received cetuximab for the treatment of unresectable SCC. In 2 patients partial remissions were achieved and maintained with continuous treatment for 17 and 18 months. Another patient achieved complete remission after 16 cetuximab treatments and is still free of disease with ongoing therapy after an overall observation period of 16 months. In a fourth patient, with recurrent loco-regional metastatic disease of the scalp and neck, adjuvant cetuximab followed by panitumumab was introduced after extensive surgery. 2 patients had a grade II-III skin rash successfully treated with topical erythromycin, systemic doxycyclin and dose modification. CONCLUSION: Cetuximab is suitable for palliation in elderly patients, able to maintain remissions and prevent disease progression over extended periods of continuing treatment without significant toxicity. Furthermore, adjuvant anti-EGFR therapy may be a promising treatment strategy in patients with a high risk of recurrence.