Cutaneous Carcinoma Research Articles

Viral Status Predicts the Patterns of Genome Methylation and Decitabine Response in Merkel Cell Carcinoma

Merkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine carcinoma that is classified as Merkel cell polyomavirus-positive (virus positive [VP]) or Merkel cell polyomavirus-negative (virus negative [VN]). Epigenetic changes, such as DNA methylation, can alter gene expression and influence cancer progression. However, patterns of DNA methylation and the therapeutic efficacy of hypomethylating agents have not been fully explored in MCC. We characterized genome-wide DNA methylation in 16 MCC cell lines from both molecular subclasses in comparison with other cancer types and found that the overall profile of MCC is similar to that of small-cell lung carcinoma. Comparison of VP MCC with VN MCC revealed 2,260 differentially methylated positions. The hypomethylating agent decitabine upregulated the expression of antigen-presenting machinery in MCC cell lines and stimulated membrane expression of HLA-A in VP and VN MCC xenograft tumors. Decitabine also induced prominent caspase- and large T antigen‒independent cell death in VP MCC, whereas VN MCC cell lines displayed decreased proliferation without increased cell death. In mouse xenografts, decitabine significantly decreased the size of VP tumors but not that of VN tumors. Our findings indicate that viral status predicts genomic methylation patterns in MCC and that decitabine may be therapeutically effective against MCC through antiproliferative effects, cell death, and increased immune recognition.

English

Primary cutaneous mucinous carcinoma (PCMC) also known as primary mucinous carcinoma of the skin (PMCS) or primary mucinous eccrine carcinoma (PMEC) is a rare malignant adnexal tumour of eccrine origin. Many visceral mucinous carcinomas especially of the breast and gastrointestinal tract can metastasize to the skin mimicking PCMC. Hence it is very important to rule out metastatic mucinous carcinomas before making a diagnosis of PCMC. Usually, PCMC presents as a slowgrowing tumour of considerably smaller size compared to our case. The large size and shorter duration are the key features of this case report. Here we report an unusually large-sized rare malignant tumour of skin appendage. Our patient was a 54-year-old lady who presented with progressive swelling of one year duration in the right frontoparietal area. Ultrasonography showed an ill-defined lesion in the subcutaneous plane with multiple cystic spaces within it. No bone involvement was noted. The excised lesion measured 13 x 7 x 2 cms and was diagnosed as primary cutaneous mucinous carcinoma on histopathological examination. The possibility of cutaneous secondaries from elsewhere was ruled out by detailed clinical and radiological investigations. The case is reported considering the unusually bigger size and shorter duration of this rare entity.

LB748 An epidemiological study on Cutaneous Melanoma, Basal Cell and Epidermoid Carcinomas diagnosed in a sunny city in southeast Brazil in a five-year period

Skin cancer is increasing worldwide; in tropical places the population is exposed to high levels of solar radiation, raising the risk for developing cutaneous carcinoma. Aimed at encouraging prevention measures and the early diagnosis of these tumors, this study analyzed data on cutaneous melanomas, basal cell and epidermoid carcinomas, using as source the medical records of all patients diagnosed with skin cancer in a pathology service in a Brazilian city from 2015 to 2019. The incidence of skin cancer cases was correlated with the histological type, sex, age, and location. Significant association was observed between age and type of cancer (p=0.0085); age and sex (p=0.0298); and type of cancer and body region affected (p<0.01). Those 161 cases analyzed comprised 93 basal cell, 66 epidermoid carcinomas, and only 2 melanomas. In the group aged 19 to 30 years, the epidermoid form was most prevalent; from 31 to 59 years, the basal cell prevailed; in 60-year-olds or over, both types had higher frequencies. Associating age and sex, in groups aged 19 to 30 women were most affected. There was a gender balance in the age group 60-year-olds or over. As for topography, there was a high prevalence in the head and neck, followed by upper limbs. Relating histological type and topography, there was a prevalence of basal cell carcinomas in head/neck and chest. In upper limbs, the epidermoid form prevailed. About 82% of patients 60-year-olds or over had head and neck skin carcinoma. In conclusion, young people were more affected by the epidermoid form, which manifested itself significantly in the upper limbs, presenting a behavior of this histological type. Patients aged 60 years or older were the most affected; in gender balance, they present intense head and neck involvement, while areas such as chest and lower limbs are little affected, revealing that body areas continuously exposed to solar radiation are more predisposed to the development of skin cancer.

Traitement par chimiothérapie orale (sonidegib) de carcinomes basocellulaires étendus, à propos de 4 cas

Basal cell carcinoma (BCC) is the most frequent cutaneous carcinoma. Its incidence is constantly increasing, primarily due to sun exposure during the two first decades of life. The lower lid and medial canthus are the most common locations. In the majority of cases, surgery with sufficient margins is the first-line treatment. In the case of inoperable tumors (extensive lesions, poor general health, high surgical morbidity, unacceptable cosmetic sequelae), oral chemotherapy can be suggested. We report the follow-up of 4 patients with advanced non-metastatic basal cell carcinoma (BCC) treated with oral chemotherapy (sonigegib). All patients were female with a mean age of 80years. The first patient had an infiltrative BCC of the right lower lid with orbital invasion, the second a nodular BCC of the right inferior lid with massive cutaneous and orbital invasion extending to the controlateral medial canthal angle, the third an advanced infiltrative BCC invading both orbits and nasal cavities, and the fourth, an infiltrative BCC with extension to the ipsilateral skin of the face. The diagnosis of BCC was confirmed by multiple biopsies in our four patients prior to starting chemotherapy. Because of the locally advanced lesions, surgery was contraindicated in all cases, chemotherapy was undertaken (sonidegib 200mg daily), and ophthalmological and dermatological examinations were performed every 3months. In all 4 patients, the outcome was very favorable, with one clear regression in tumor size and infiltration and 3 partial regressions. Many side effects were noted, including nausea, muscle cramping, dysgeusia resulting in significant weight loss, and malnutrition in the elderly patients. The treatment had to be discontinued after 11months in the patient with total macroscopic regression because of major side effects. The treatment is still underway for the other patients and will be continued as long as a clinical benefit is observed. The treatment will be discontinued if intolerable side effects develop. Oral chemotherapy (sonidegib) is an effective alternative treatment when surgery cannot be realized, especially in the case of extensive infiltrative non-metastatic BCC.

Place de la radiothérapie dans le traitement des carcinomes cutanés

Basal cell carcinomas and cutaneous squamous cell carcinomas are among the most common cancerous tumors in the world. Their treatment is most often based on surgery. Adjuvant radiotherapy may be indicated in case of risk factors for recurrence or as an alternative to surgery if surgery is not feasible due to the patient's advanced age and/or co-morbidities or as an alternative to potentially mutilating surgery. Radiotherapy is also part of the therapeutic arsenal for rarer skin tumors such as Merkel cell carcinoma, cutaneous lymphomas, Kaposi's disease and cutaneous adnexal carcinomas.

Relationship between p63 and p53 expression in Merkel cell carcinoma and corresponding abnormalities in TP63 and TP53: a study and a proposal

Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous neuroendocrine carcinoma. Oncogenesis occurs via Merkel cell polyomavirus-mediated (MCPyV+) and/or ultraviolet radiation-associated (MCPyV-) pathways. Advanced clinical stage and an MCPyV- status are important adverse prognostic indicators. There is mounting evidence that p63 expression is a negative prognostic indicator in MCC and that it correlates with MCPyV- status. p63 is a member of the p53 family of proteins amongwhich complex interactions occur. It has two main isoforms (proapoptotic TAp63 and oncogenic ΔNp63). Paradoxically, TAp63 predominates in MCC. To explore this quandary, we examined relationships between p63 and p53 expression and corresponding abnormalities in the TP63 and TP53 genes in MCC. A cohort of 26MCCs (12 MCPyV+ and 14 MCPyV-) was studied. Comparative immunohistochemical expression of p63 and p53 was evaluated semiquantitatively (H scores) and qualitatively (aberrant patterns). The results were compared with genetic abnormalities in TP63 and TP53 via next-generation sequencing. p63 was positive in 73% of cases. p53 showed "wild-type" expression in 69%, with "aberrant" staining in 31%. TP63 mutations (predominantly low-level copy gains; 23% of cases) and mainly pathogenic mutations in TP53 (50% of cases) featured in the MCPyV- subset of cases. p63 expression correlated quantitatively with p53 expression and qualitatively with aberrant patterns of the latter. Increased expression of p63 and p53 and aberrant p53 staining correlated best with TP53 mutation. We propose that p63 expression (ie, proapoptotic TAp63) in MCC is most likely functionally driven as a compensatory response to defective p53 tumor suppressor activity.

Basal cell carcinoma-not always the 'good guy': Case report of a life-threatening basosquamous carcinoma and review of the literature.

Cutaneous basosquamous carcinoma is a variant of basal cell carcinoma that is characterized by histopathological features of both basal and squamous cell carcinoma. Due to its local invasiveness, high frequency of recurrence, and its metastatic potential, it is considered to be one of the most aggressive subtypes of basal cell carcinoma. We present the case of an 81-year-old male who was admitted to the hospital with incessant hemorrhage arising from a cutaneous tumor that later proved to be a basosquamous carcinoma. Due to the COVID-19 pandemic at the time, the patient did not seek medical attention as soon as the bleeding was observed, although he did present when the symptom increased in intensity and became incessant. To our knowledge, this is the first case report of a cutaneous basosquamous carcinoma that presents with a massive life-threatening hemorrhage tumor, thus endangering the patient's life. The clinical and histopathological features, the behavior and the treatment of cutaneous basosquamous carcinoma are further reviewed in this article.

Pembrolizumab for patients with leptomeningeal metastasis from solid tumors: efficacy, safety, and cerebrospinal fluid biomarkers

BackgroundThe benefit of immune checkpoint inhibitors (ICIs) in patients with leptomeningeal metastases (LMM) is unknown.MethodsWe undertook a phase II trial of pembrolizumab in patients with LMM from solid tumors. Eligible...

Lifetime Ambient UV Radiation Exposure and Risk of Basal Cell Carcinoma by Anatomic Site in a Nationwide U.S. Cohort, 1983–2005

Cutaneous basal cell carcinoma (BCC) has long been associated with UV radiation (UVR) exposure, but data are limited on risks by anatomic site. We followed 63,912 cancer-free White U.S. radiologic technologists from cohort entry (1983-1989/1994-1998) to exit (date first BCC via 2003-2005 questionnaire). We estimated associations between cumulative ambient UVR and relative/absolute risks of self-reported BCC by anatomic location via Poisson models. For incident first primary BCC in 2,124 subjects (mean follow-up, 16.9 years) log[excess relative risks] (ERR) of BCC per unit cumulative ambient UVR = 1.27/MJ cm-2 [95% confidence interval (CI): 0.86-1.68; P trend < 0.001] did not vary by anatomic site (P = 0.153). However, excess absolute risks of BCC per unit cumulative ambient UVR were large for the head/neck = 5.46/MJ cm-2/104 person-year (95% CI: 2.92-7.36; P trend < 0.001), smaller for the trunk (2.56; 95% CI: 1.26-3.33; P trend = 0.003), with lesser increases elsewhere. There were lower relative risks, but higher absolute risks, for those with Gaelic ancestry (P < 0.001), also higher absolute risks among those with fair complexion, but relative and absolute risks were not generally modified by other constitutional, lifestyle or medical factors for any anatomic sites. Excess absolute and relative risk was concentrated 5-15 years before time of follow-up. BCC relative and absolute risk rose with increasing cumulative ambient UVR exposure, with absolute risk highest for the head/neck, to a lesser extent in the trunk. These associations should be evaluated in other White and other racial/ethnic populations along with assessment of possible modification by time outdoors, protective, and behavioral factors.

Updates on the diagnosis, current and future therapeutic options in Merkel-cell carcinoma.

Merkel-cell carcinoma (MCC) is a rare and extremely aggressive nonmelanocytic cutaneous neuroendocrine carcinoma. Historically, it has been associated with limited therapy options and poor prognosis. While its incidence has been rising over the last two decades, recent discoveries and a better understanding of its pathogenesis, viral association and immunologic features have allowed for the emergence of new therapies. Surgical excision with or without radiotherapy remains the first-line therapy for primary lesions without evidence of metastatic disease. The majority of MCC cases are regrettably diagnosed at advanced stages and oftentimes require systemic therapy. There have been several significant advances in the treatment of MCC in the last decade. Among these have been the development of immune checkpoint inhibitors targeting the programmed death protein-1 (PD-1)/programmed death ligand-1 (PDL-1). Despite recent success of immunotherapy, nearly 50% of patients diagnosed with MCC still succumb to the disease. Fortunately, there has been a number of new targeted therapies that hold great promise. Among them are phosphatidylinositide-3kinase (Pl3K) inhibitors, adoptive T-cell immunotherapy, activated NK-92 cells infusions and therapeutic vaccines. Additional emerging therapeutic targets include cellular ubiquitin-specific processing protease 7 (Usp7) that restricts viral replication and IFN genes (STING), activation of which promotes an antitumor inflammatory response.

Cemiplimab for Locally Advanced and Metastatic Cutaneous Squamous-Cell Carcinomas: Real-Life Experience from the French CAREPI Study Group.

Simple SummaryPrognosis of advanced cutaneous squamous-cell carcinoma (CSCC) is poor. Recent clinical trials have shown that immunotherapy achieves significantly improved survival of patients with advanced CSCCs. However, few real-world data are available on treatment patterns and clinical outcomes of patients with advanced CSCCs receiving anti-programmed cell-death protein-1 (PD-1). To approach this issue, we conducted a retrospective study on 245 patients with advanced CSCCs from 58 centers who had been enrolled in an early-access program; 240 received cemiplimab. Our objectives were to evaluate, in the real-life setting, best overall response rate, progression-free survival, overall survival and safety. Results demonstrated cemiplimab efficacy in patients with advanced CSCCs, regardless of immune status. Patients with good Eastern Cooperative Oncology Group performance status benefited more from cemiplimab. The safety profile was acceptable.Although cemiplimab has been approved for locally advanced (la) and metastatic (m) cutaneous squamous-cell carcinomas (CSCCs), its real-life value has not yet been demonstrated. An early-access program enrolled patients with la/mCSCCs to receive cemiplimab. Endpoints were best overall response rate (BOR), progression-free survival (PFS), overall survival (OS), duration of response (DOR) and safety. The 245 patients (mean age 77 years, 73% male, 49% prior systemic treatment, 24% immunocompromised, 27% Eastern Cooperative Oncology Group performance status (PS) ≥ 2) had laCSCCs (35%) or mCSCCs (65%). For the 240 recipients of ≥1 infusion(s), the BOR was 50.4% (complete, 21%; partial, 29%). With median follow-up at 12.6 months, median PFS was 7.9 months, and median OS and DOR were not reached. One-year OS was 73% versus 36%, respectively, for patients with PS < 2 versus ≥ 2. Multivariate analysis retained PS ≥ 2 as being associated during the first 6 months with PFS and OS. Head-and-neck location was associated with longer PFS. Immune status had no impact. Severe treatment-related adverse events occurred in 9% of the patients, including one death from toxic epidermal necrolysis. Cemiplimab real-life safety and efficacy support its use for la/mCSCCs. Patients with PS ≥ 2 benefited less from cemiplimab, but it might represent an option for immunocompromised patients.

Whole‑genome identification and systematic analysis of lncRNA‑mRNA co‑expression profiles in patients with cutaneous basal cell carcinoma.

Cutaneous basal cell carcinoma (BCC) is a common subtype of malignant skin tumor with low invasiveness. Early diagnosis and treatment of BCC and the identification of specific biomarkers are particularly urgent. Long non-coding RNAs (lncRNAs) have been shown to be associated with the development of various tumors, including BCC. The present study conducted a comparative analysis of the differential expression of lncRNAs and mRNAs through whole-genome technology. Microarray analyses were used to identify differentially expressed (DE) lncRNAs and DE mRNAs. Reverse transcription-quantitative (RT-q) PCR confirmed the differential expression of 10 lncRNAs in BCC. Subsequently, a lncRNA-mRNA co-expression network was constructed using the top 10 DE lncRNAs. Finally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to investigate the possible biological effects of the identified mRNAs and to speculate on the possible biological effects of the lncRNAs. A total of 1,838 DE lncRNAs and 2,010 DE mRNAs were identified and 10 of the DE lncRNAs were confirmed by RT-qPCR. A lncRNA-mRNA co-expression network comprising 166 specific co-expressed lncRNAs and mRNAs was constructed using the top 10 DE lncRNAs. According to the results of the GO and KEGG analyses, lncRNA XR_428612.1 may serve an important role in mitochondrial dysfunction and the progression of BCC by modulating TICAM1, USMG5, COX7A2, FBXO10, ATP5E and TIMM8B. The present study provided whole-genome identification and a systematic analysis of lncRNA-mRNA co-expression profiles in BCC.

Trends of cutaneous basal cell carcinoma, squamous cell carcinoma, and melanoma among the Chinese, Malays, and Indians in Singapore from 1968-2016

BackgroundPrevious analysis showed that the incidence rates of skin cancer in Singapore increased from 1968 to 2006, especially among older Chinese, and particularly for basal cell carcinoma (BCC).ObjectiveWe updated the skin cancer incidence rates and time trends among the Chinese, Malays, and Indians in Singapore.MethodsWe analyzed the skin cancer incidence from the nationwide Singapore Cancer Registry from 1968 to 2016.ResultsAmong 12,692 cases diagnosed from 1968 to 2016, there were 8367 (65.9%) cases of BCC, 3598 (28.3%) of squamous cell carcinoma (SCC), and 727 (5.8%) of melanoma. The mean ages at skin cancer diagnosis were 72.7 years for SCC, 66.9 years for BCC, and 59.8 years for melanoma. Sun-exposed areas accounted for 81.3% of BCCs, 61.6% of SCCs, and 26.7% of melanomas. The age-standardized incidence rate of cutaneous BCC was highest in the Chinese and increased by 2.5 fold over the study period, followed by a lower rate and slower increase in the Malays, and the lowest rate among the Indians. The SCC and melanoma incidences remained low in all 3 ethnicities during this study period. The Chinese had the highest relative risk for developing any skin cancer (P < .0001) compared with those of the Malays and Indians. Most cases of skin cancer were diagnosed at age ≥60, with men showing a higher incidence of SCC compared with that of women.ConclusionIncidence rates of BCC have increased in Singapore, especially among the Chinese, in the past 5 decades. The SCC and melanoma incidence rates remained low and stable.

P-204 Case report of cutaneous papillary thyroid carcinoma 16 years post total thyroidectomy for benign goiter

P-204 Case report of cutaneous papillary thyroid carcinoma 16 years post total thyroidectomy for benign goiter

Constitutive Hedgehog/GLI2 signaling drives extracutaneous basaloid squamous cell carcinoma development and bone remodeling.

Uncontrolled activation of the Hedgehog (Hh) signaling pathway, operating through GLI transcription factors, plays a central role in the pathogenesis of cutaneous basal cell carcinoma and contributes to the development of several malignancies arising in extracutaneous sites. We now report that K5-tTA;tetO-Gli2 bitransgenic mice develop distinctive epithelial tumors within their jaws. These tumors consist of large masses of highly proliferative, monomorphous, basaloid cells with scattered foci of keratinization and central necrosis, mimicking human basaloid squamous cell carcinoma (BSCC), an aggressive upper aerodigestive tract tumor. Like human BSCC, these tumors express epidermal basal keratins and differentiation-specific keratins within squamous foci. Mouse BSCCs express high levels of Gli2 and Hh target genes, including Gli1 and Ptch1, which we show are also upregulated in a subset of human BSCCs. Mouse BSCCs appear to arise from distinct epithelial sites, including the gingival junctional epithelium and epithelial rests of Malassez, a proposed stem cell compartment. Although Gli2 transgene expression is restricted to epithelial cells, we also detect striking alterations in bone adjacent to BSCCs, with activated osteoblasts, osteoclasts and osteal macrophages, indicative of active bone remodeling. Gli2 transgene inactivation resulted in rapid BSCC regression and reversal of the bone remodeling phenotype. This first-reported mouse model of BSCC supports the concept that uncontrolled Hh signaling plays a central role in the pathogenesis of a subset of human BSCCs, points to Hh/GLI2 signaling as a potential therapeutic target and provides a powerful new tool for probing the mechanistic underpinnings of tumor-associated bone remodeling.

Auricular reconstruction after Mohs micrographic surgery: analysis of 101 cases

BackgroundThe ear is a region that has a high prevalence of cutaneous carcinomas and several guidelines indicate Mohs micrographic surgery as the first-choice treatment in such cases. Although the technique allows maximum preservation of healthy tissue, many auricular surgical wounds constitute a challenge due to the peculiar local anatomy, with evident curves and reliefs. Auricular reconstruction should prioritize function before aesthetics, but without leaving the latter aside, since postoperative distortions can have a significant psychological impact. ObjectiveTo describe the authors’ experience in auricular reconstruction after Mohs surgery and to evaluate the most frequently used repair methods. MethodsRetrospective study of consecutive cases submitted to Mohs surgery and auricular reconstruction, over a period of 3 years. ResultsOne hundred and one cases were included and the most common repair method was primary closure (n = 35), followed by full-thickness skin graft (n = 30) and flaps (n = 24). In thirty cases, reconstruction methods were associated. Seven patients had complications (partial graft necrosis, postoperative bleeding or infection). Study limitationsRetrospective design and the absence of long-term follow-up of some cases. ConclusionsThe dermatologic surgeon should be familiarized with different options for auricular reconstruction. Primary closure and skin grafts were the most frequently used repair methods.

Transcriptomic analysis of mechanism of melanoma cell death induced by photothermal therapy.

Melanoma is a malignancy with poor prognosis. Its incidence rate has been on the rise and it poses high health and economic challenges to different populations. Photothermal therapy (PTT) served as an effective local therapy in treating various tumors, particularly cutaneous carcinoma like melanoma. To fully understand the mechanisms of tumor cell death induced by PTT, we investigated gene expression and immune cells compositions of B16-F10 tumors after PTT treatment. A total of 256 differentially expressed genes (DEGs) were identified, with 215 being downregulated and 41 upregulated by PTT. Functional annotation showed that most DEGs involved in immune response and inflammatory response. Immune cells compositions inference revealed changes in many immune cells including regulatory T cells, M2 macrophage and B cells after PTT treatment. Our results help delineate the mechanism of cell death at the transcriptional level triggered by non-invasive PTT treatment of melanoma without exogenous light absorbing agents.

Ex vivo analysis of DNA repair targeting in extreme rare cutaneous apocrine sweat gland carcinoma.

Cutaneous apocrine carcinoma is an extreme rare malignancy derived from a sweat gland. Histologically sweat gland cancers resemble metastatic mammary apocrine carcinomas, but the genetic landscape remains poorly understood. Here, we report a rare metastatic case with a PALB2 aberration identified previously as a familial susceptibility gene for breast cancer in the Finnish population. As PALB2 exhibits functions in the BRCA1/2-RAD51-dependent homologous DNA recombination repair pathway, we sought to use ex vivo functional screening to explore sensitivity of the tumor cells to therapeutic targeting of DNA repair. Drug screening suggested sensitivity of the PALB2 deficient cells to BET-bromodomain inhibition, and modest sensitivity to DNA-PKi, ATRi, WEE1i and PARPi. A phenotypic RNAi screen of 300 DNA repair genes was undertaken to assess DNA repair targeting in more detail. Core members of the HR and MMEJ pathways were identified to be essential for viability of the cells. RNAi inhibition of RAD52-dependent HR on the other hand potentiated the efficacy of a novel BETi ODM-207. Together these results describe the first ever CAC case with a BRCAness genetic background, evaluate combinatorial DNA repair targeting, and provide a data resource for further analyses of DNA repair targeting in PALB2 deficient cancers.

Prognostic Role of Tumoral PD-L1 and IDO1 Expression, and Intratumoral CD8+ and FoxP3+ Lymphocyte Infiltrates in 132 Primary Cutaneous Merkel Cell Carcinomas.

The association of immune markers and clinicopathologic features and patient outcome has not been extensively studied in Merkel cell carcinoma (MCC). We correlated tumoral PD-L1 and IDO1 expression, and intratumoral CD8+ and FoxP3+ lymphocytes count with clinicopathologic variables, Merkel cell polyomavirus (MCPyV) status, and patient outcomes in a series of 132 MCC. By univariate analyses, tumoral PD-L1 expression >1% and combined tumoral PD-L1 >1% and high intratumoral FoxP3+ lymphocyte count correlated with improved overall survival (OS) (p = 0.016, 0.0072), MCC-specific survival (MSS) (p = 0.019, 0.017), and progression-free survival (PFS) (p = 0.043, 0.004, respectively). High intratumoral CD8+ and FoxP3+ lymphocyte count correlated with longer MSS (p = 0.036) and improved PFS (p = 0.047), respectively. Ulceration correlated with worse OS and worse MSS. Age, male gender, and higher stage (3 and 4) significantly correlated with worse survival. MCPyV positivity correlated with immune response. By multivariate analyses, only ulceration and age remained as independent predictors of worse OS; gender and stage remained for shorter PFS. Tumoral PD-L1 expression and increased density of intratumoral CD8+ lymphocytes and FoxP+ lymphocytes may represent favorable prognosticators in a subset of MCCs. Tumoral PD-L1 expression correlated with intratumoral CD8+ and FoxP3+ lymphocytes, which is supportive of an adaptive immune response.

Clinical and Histopathologic Characteristics of Metastatic and Locally Advanced Cutaneous Basal Cell Carcinomas.

Locally advanced or metastatic basal cell carcinomas (laBCCs or mBCCs) are rare, with few case series providing information on their epidemiology. We aimed to describe the clinical and histologic features of locally advanced and metastatic basal cell carcinomas. Forty cases of laBCC or mBCC were identified by searching Vanderbilt's database from 1984 to January 2019. A retrospective chart review was performed. Pathology slides were available for 23 cases (13 mBCCs and 10 laBCCs). Twenty-one of 23 cases were Clark level IV or V, with a mean depth of invasion of >7 mm for both types. The mean mitotic rate was 4.4 mitoses/mm2 for laBCCs and 3.3 mitoses/mm2 for mBCCs. Ulceration was identified in 7 laBCC and 8 mBCC cases. Perineural invasion was present in 2 laBCC and 6 mBCC cases, with 3 mBCCs invading nerves >0.1 mm. Of 13 mBCC cases, histologic subtypes included infiltrative (n = 9), nodular (n = 7), morpheaform (n = 4), and superficial (n = 2), with multiple patterns present in some specimens. 10 of 13 patients with mBCC had local recurrence before metastasis. In summary, we identified several potential markers of high-risk BCC, including perineural invasion, deep invasion, elevated mitotic rate, and local recurrence of the primary tumor.