Primary Cutaneous Squamous Cell Carcinoma Research Articles

Predicting adjuvant radiation therapy benefit in cutaneous squamous cell carcinoma with the 40-gene expression profile.

Aim: To independently confirm that the 40-gene expression profile (40-GEP) test can identify patients with high-risk cutaneous squamous cell carcinoma who are more or less likely to benefit from adjuvant radiation therapy (ART).Materials & methods: Primary cutaneous squamous cell carcinoma tumors from two academic centers received retrospective 40-GEP testing and were analyzed for 5-year metastasis-free survival and projected time to event.Results: Random sampling of matched patient pairs (n=52 ART-treated; 371no ART) showed a median 50% decrease in 5-year progression rate for ART-treated patients (vs no ART) with 40-GEP Class 2B. Class 2A was associated with a modest ART benefit, but not Class 1.Conclusion: The 40-GEP identified patients most likely to benefit from ART (Class 2B) and those that can consider deferring treatment (Class 1).

A Case Series of Primary Cutaneous Sarcomatoid Carcinoma With Aberrant Smooth Muscle Actin Expression: A Clinicopathologic and Immunophenotypic Study.

Primary cutaneous sarcomatoid squamous cell carcinoma can show significant histologic overlap with other malignant spindle cell tumors, posing a diagnostic challenge. Even with a wide array of immunohistochemical markers, the exact line of differentiation can be a challenge to identify in some cases. The picture is further complicated by the aberrant expression of myofibroblastic markers [such as smooth muscle actin (SMA)] by these neoplasms, along with a concomitant loss of conventional epithelial markers. The histologic differential diagnoses of primary cutaneous sarcomatoid squamous cell carcinoma include desmoplastic melanoma, leiomyosarcoma, and spindle cell atypical fibroxanthoma/pleomorphic dermal sarcoma (AFX/PDS). A retrospective analysis of 16 cases of PCSSCCs with SMA expression, obtained from large academic institutions, was performed and is summarized below. The tumors were in the scalp (6 cases), arm (4 cases), leg (2 cases), face (2 cases), hand (1 case), and neck (1 case). Immunohistochemical studies were performed in all cases with the following antibodies: AE1/AE3, CAM 5.2, MNF-116, p63, p40, CK5/6, S-100, SOX10, SMA, desmin, calponin, H-caldesmon, CD10, CD68, CD163, and CD34. Histopathologically, all cases were classified as high-grade malignant poorly differentiated neoplasms. Tumors were characterized by an infiltrative neoplasm that involved the entire reticular dermis and, in 7 cases, the subcutaneous fat. Three cases were associated with a well-differentiated squamous cell component. The neoplasms were composed of atypical spindle and epithelioid cells arranged in long and intersecting fascicles. All neoplasms were positive for epithelial markers (at least 1 marker), and all cases were strongly positive for SMA. Our data emphasize the diagnostic utility of multiple epithelial markers as a first screening tool in the detection and workup of malignant cutaneous sarcomatoid neoplasms. Awareness of SMA expression in these tumors can complicate its diagnosis, and it is important to recognize this aberrant immunophenotype to facilitate definitive diagnosis and avoid misdiagnosis.

CD73 Is an Immunometabolic Biomarker of Poor Prognosis in Patients With Primary Cutaneous Squamous Cell Carcinoma and Hematologic Malignancy.

Impaired immunity may drive the increased incidence and aggression of cutaneous squamous cell carcinoma (cSCC) in patients with hematologic malignancy; however, precise mechanisms and prognostic biomarkers remain undefined. CD73 maintains elevated immunosuppressive adenosine levels and is associated with poor prognosis in several tumor microenvironments. Identify poor outcome biomarkers in patients with cSCC and hematologic malignancy. Differentially expressed genes in tumors from patients with hematologic malignancy experiencing good (n = 8) versus poor (n = 7) outcomes were identified by NanoString analysis. Results were validated at the protein level using CD73 immunohistochemistry in cSCC patients with (n = 38) and without (n = 29) hematologic malignancy. Forty-eight genes were differentially expressed in tumors from patients with hematologic malignancy experiencing good versus poor outcomes. CD73 gene expression was >2-fold higher in patients with poor versus good outcomes or normal skin. Significantly increased CD73 protein levels were observed in cSCC tumors with poor versus good outcomes from patients with hematologic malignancies (p < .01), whereas no differences were noted in tumors with poor versus good outcomes from patients without hematologic malignancies (p = .49). CD73 is highly expressed in poor prognosis cSCC from patients with hematologic malignancy and may represent a useful biomarker and potential therapeutic target.

Differential Immunoexpression of Inhibitory Immune Checkpoint Molecules and Clinicopathological Correlates in Keratoacanthoma, Primary Cutaneous Squamous Cell Carcinoma and Metastases.

Beyond established anti-programmed cell death protein 1/programmed cell death ligand 1 immunotherapy, T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domain (TIGIT) and its ligand CD155 are promising novel inhibitory immune checkpoint targets in human malignancies. Yet, in cutaneous squamous cell carcinoma, evidence on the collective expression patterns of these inhibitory immune checkpoints is scarce. Complete tumour sections of 36 cutaneous squamous cell carcinoma, 5 cutaneous metastases and 9 keratoacanthomas, a highly-differentiated, squamoproliferative tumour, with disparately benign biologic behaviour, were evaluated by immunohistochemistry for expression of programmed cell death ligand 1 (Tumor Proportion Score, Immune Cell Score), TIGIT, CD155 and CD8+ immune infiltrates. Unlike keratoacanthomas, cutaneous squamous cell carcinoma displayed a strong positive correlation of programmed cell death ligand 1 Tumor Proportion Score and CD115 expression (p < 0.001) with significantly higher programmed cell death ligand 1 Tumor Proportion Score (p < 0.001) and CD155 expression (p < 0.01) in poorly differentiated G3-cutaneous squamous cell carcinoma compared with keratoacanthomas. TIGIT+ infiltrates were significantly increased in programmed cell death ligand 1 Immune Cell Score positive primary tumours (p = 0.05). Yet, a strong positive correlation of TIGIT expression with CD8+ infiltrates was only detected in cutaneous squamous cell carcinoma (p < 0.01), but not keratoacanthomas. Providing a comprehensive overview on the collective landscape of inhibitory immune checkpoint expression, this study reveals associations of novel inhibitory immune checkpoint with CD8+ immune infiltrates and tumour differentiation and highlights the TIGIT/CD155 axis as a potential new target for cutaneous squamous cell carcinoma immunotherapy.

Comprehensive profiling identifies tumour and immune-microenvironmental differences in clinical subsets of cutaneous squamous cell carcinoma.

Cutaneous squamous cell carcinomas (CSCC) are the second most diagnosed skin cancer worldwide, however, little is known about the pathobiological factors contributing to the diverse clinical outcomes observed. To comprehensively profile CSCC and identify pathological processes contributing to the disparities in clinical behaviour observed. We characterised the genomic, transcriptomic and immunohistochemical profiles of 206 CSCC tumours, including 37 CSCC from immunocompromised patients. CSCC from immunocompromised patients are characterised by the lack of B cells in the peri-tumoural stromal compared to immunocompetent patients. Further, the abundance of a memory B cell-like population in the peritumoural stroma is associated with better prognosis in all patients (immunocompetent and immunocompromised) as well as only immunocompetent patients. No differences in genetic variants, tumour mutational burden or mutational signatures were observed between CSCC from immunocompetent and immunocompromised patients. Thus, differences in survival between CSCC from immunocompromised patients and immunocompetent patients are not likely to be driven by tumour genomic factors, but rather associated with differential host immune response. Non-head and neck primary site CSCC have lower tumour mutational burden and exhibit upregulation of the epithelial-mesenchymal transition programme compared to head and neck CSCC. Both factors are implicated with poorer responses to immune checkpoint inhibition, and the latter with poorer survival. In summary, we identify tumour and host immune factors that contribute to the disparate clinical behaviour of CSCC with broad translational application including prognostication, treatment prediction to current therapies and identifying novel anti-cancer therapy approaches in CSCC.

Patterns of Tumor-Infiltrating Lymphocytes Used to Distinguish Primary Cutaneous Squamous Cell Carcinomas That Metastasize

This case-control study examines the type, location, and density of tumor-infiltrating lymphocytes in adult patients with vs without metastatic cutaneous squamous cell carcinoma.

Pilonidal sinus disease carcinoma: Survival and recurrence analysis.

The study aims to determine the survival and recurrence rates of pilonidal sinus disease (PSD) carcinoma. The data were collected retrospectively by searching the worldwide literature for all reports of carcinoma developing on the background of PSD. The results were presented using Kaplan-Meier curves. Between 1900 and 2022, 140 cases of PSD carcinoma were published in 103 papers, with follow-up data available in 111 cases. Squamous cell carcinoma constituted 94.6% of the cases (n = 105). The disease-specific survival rate was 61.7% for 3 years, 59.8% for 5 years, and 53.2% for 10 years. There was a significant survival difference between stages: 80.0% in stages I and II, 70.8% in stage III, and 47.8% in stage IV (p = 0.01). The 5-year survival in G1-tumors was better than G2 and G3-tumors at 70.5% and 32.0%, respectively (p = 0.002). Recurrence occurred in 46.6% of the patients. The time-to-recurrence in patients treated with curative intention averaged 15.1 months (1-132 months). Local, regional, and distant recurrence was observed in 75.6%, 33.3%, and 28.9% of the recurrent tumors, respectively. Pilonidal sinus carcinoma has a worse prognosis than primary cutaneous squamous cell carcinoma. Poor prognostic factors include advanced-stage disease and poor differentiation.

Like Versus Unlike: Closure of a Moderate-sized Circular Tissue Defect Following Wide Local Excision of Primary Cutaneous Squamous Cell Carcinoma of Face by Rhombic Transposition Flap with Modification.

Closure of a circular tissue defect in the head-neck-face region is challenging because most transposition flaps are rhombic or triangular. For a tension-less closure, both rhombic transposition flap and the circular tissue defect need to be engineered maintaining strict geometric calculations. The present illustration demonstrates a modified rhombic transposition flap with greater freedom in rotation and mobility for closing a moderate-sized circular defect resulting from wide local excision of cutaneous squamous cell carcinoma in the mid-face. The circular shape of the primary tissue defect did not need to be altered. The authors revisited an earlier published technique in the process, adding their own modification to the rhombic transposition flap.

272 Tertiary lymphoid structures in primary cutaneous squamous cell carcinomas are associated with subsequent metastasis

272 Tertiary lymphoid structures in primary cutaneous squamous cell carcinomas are associated with subsequent metastasis

The Cutaneous Squamous Cell Carcinoma - An Update

The cutaneous squamous cell carcinoma (CSCC) is the second most common nonmelanoma skin cancer with an increasing incidence rate. Patients presenting with high-risk lesions associated with locally advanced or metastatic CSCC face high rates of recurrence and mortality. Selective literature review based on PubMed and consideration of current guidelines "Aktinische Keratosen und Plattenepithelkarzinom der Haut" and "Prävention von Hautkrebs". Complete surgical excision with histopathological control of excision margins is the gold standard in the treatment of primary CSCC. Radiotherapy can be used as an alternative treatment of inoperable CSCCs. In 2019, the PD1-antibody cemiplimab, has been approved for the treatment of locally advanced and metastatic CSCC by the European Medicines Agency. After 3 years of follow up, Cemiplimab shows overall response rates of 46 %, the median overall survival and median response rate had not been reached yet. Additional immunotherapeutics, combinations with other agents and oncolytic viruses are all potentially worth study to try, so clinical trial data will be forthcoming over the next few years to guide optimal use of these agents. Multidisciplinary board decisions are mandatory for all patients with advanced disease who require more than surgery. Further development of existing therapeutic concepts, identification of new combination therapies and the development of new immunotherapeutics will be the key challenge over the next few years.

Host and primary tumor factors for the development of multiple cutaneous squamous cell carcinomas among a retrospective cohort in Rhode Island

Risk factors for a primary cutaneous squamous cell carcinoma (CSCC) are well-established; however, the host and primary tumor risk factors for subsequent CSCC have not been fully explored. We performed a retrospective chart review of patients diagnosed with CSCC in an academic dermatology clinic in Rhode Island from 2016-2019. Logistic regression was used to evaluate the associations between host factors and multiple CSCC and between primary tumor characteristics and the risk of subsequent CSCC. Adjusted odds ratios (aORs) and 95% CIs were calculated. A total of 1312 patients with CSCC diagnoses were included. Host risk factors significantly associated with multiple CSCCs included: aged >80years (aOR, 2.18; 95% CI, 1.46-3.31); history of: solid organ transplant (aOR, 2.41; 95% CI, 1.20-4.80); skin cancer (aOR, 1.96; 95% CI, 1.52-2.54); other cancer (aOR, 1.49; 95% CI, 1.11-2.00); family history of skin cancer (aOR, 1.36; 95% CI, 1.03-1.78); and actinic keratosis (aOR, 1.52; 95% CI, 1.18-1.95). Tumor location, diameter, histologic differentiation, and treatment were not significant predictors of subsequent CSCCs. Study patients were predominantly White and from a single institution, limiting the generalizability of results. Certain host characteristics were associated with the development of subsequent CSCC, which may inform clinical guidelines for follow-up.

Understanding the squamous cell carcinoma immune microenvironment.

Primary cutaneous squamous cell carcinoma (cSCC) is the second most common human cancer with a rising incidence of about 1.8 million in the United States annually. Primary cSCC is usually curable by surgery; however, in some cases, cSCC eventuates in nodal metastasis and death from disease specific death. cSCC results in up to 15,000 deaths each year in the United States. Until recently, non-surgical options for treatment of locally advanced or metastatic cSCC were largely ineffective. With the advent of checkpoint inhibitor immunotherapy, including cemiplimab and pembrolizumab, response rates climbed to 50%, representing a vast improvement over chemotherapeutic agents used previously. Herein, we discuss the phenotype and function of SCC associated Langerhans cells, dendritic cells, macrophages, myeloid derived suppressor cells and T cells as well as SCC-associated lymphatics and blood vessels. Possible role(s) of SCC-associated cytokines in progression and invasion are reviewed. We also discuss the SCC immune microenvironment in the context of currently available and pipeline therapeutics.

Association of Patient Risk Factors, Tumor Characteristics, and Treatment Modality With Poor Outcomes in Primary Cutaneous Squamous Cell Carcinoma

Primary cutaneous squamous cell carcinoma is usually curable; however, a subset of patients develops poor outcomes, including local recurrence, nodal metastasis, distant metastasis, and disease-specific death. To evaluate all evidence-based reports of patient risk factors and tumor characteristics associated with poor outcomes in primary cutaneous squamous cell carcinoma and to identify treatment modalities that minimize poor outcomes. PubMed, Embase, and SCOPUS databases were searched for studies of the topic in humans, published in the English language, from database inception through February 8, 2022. Two authors independently screened the identified articles and included those that were original research with a sample size of 10 patients or more and that assessed risk factors and/or treatment modalities associated with poor outcomes among patients with primary cutaneous squamous cell carcinoma. Data extraction was performed by a single author, per international guidelines. The search terms, study objectives, and protocol methods were defined before study initiation. A total of 310 studies were included for full-text assessment. Owing to heterogeneity of the included studies, a random-effects model was used. Data analyses were performed from May 25 to September 15, 2022. For studies of risk factors, risk ratios and incidence proportions; and for treatment studies, incidence proportions. In all, 129 studies and a total of 137 449 patients with primary cutaneous squamous cell carcinoma and 126 553 tumors were included in the meta-analysis. Several patient risk factors and tumor characteristics were associated with local recurrence, nodal metastasis, distant metastasis, disease-specific death, and all-cause death were identified. Among all factors reported by more than 1 study, the highest risks for local recurrence and disease-specific death were associated with tumor invasion beyond subcutaneous fat (risk ratio, 9.1 [95% CI, 2.8-29.2] and 10.4 [95% CI, 3.0- 36.3], respectively), and the highest risk of any metastasis was associated with perineural invasion (risk ratio, 5.0; 95% CI, 2.3-11.1). Patients who received Mohs micrographic surgery had the lowest incidence of nearly all poor outcomes; however, in some results, the 95% CIs overlapped with those of other treatment modalities. This meta-analysis identified the prognostic value of several risk factors and the effectiveness of the available treatment modalities. These findings carry important implications for the prognostication, workup, treatment, and follow-up of patients with primary cutaneous squamous cell carcinoma. PROSPERO Identifier: CRD42022311250.

In transit metastases of cutaneous squamous cell carcinoma: A single institution case series

To the Editor: In transit metastasis of cutaneous squamous cell carcinoma (cSCC), defined as foci of cSCC originating within dermal or subcutaneous tissue, clinically distinct from the primary tumor, and occurring before the first echelon of regional lymph nodes, is a rare entity and manifestation of end-stage disease. Immunosuppressed patients, specifically solid organ transplant recipients, are at an increased risk of invasive and metastatic cSCC. Since 2004, there have been 3 published case series describing in transit metastasis of cSCC including a total of 124 patients. 1 Carucci J.A. Martinez J.C. Zeitouni N.C. et al. In-transit metastasis from primary cutaneous squamous cell carcinoma in organ transplant recipients and nonimmunosuppressed patients: clinical characteristics, management, and outcome in a series of 21 patients. Dermatol Surg. 2004; 30: 651-655 Crossref PubMed Google Scholar , 2 Ma J.H.Y. Wu A. Veness M. et al. In-transit metastasis from squamous cell carcinoma. Dermatol Surg. 2016; 42: 1285-1292 Crossref PubMed Scopus (14) Google Scholar , 3 Smile T.D. Ruiz E.S. Kus K.J.B. et al. Implications of satellitosis or in-transit metastasis in cutaneous squamous cell carcinoma: a prognostic omission in cancer staging systems. JAMA Dermatol. 2022; 158: 390-394 Crossref Scopus (0) Google Scholar Since the first 2 case series, therapy has shifted to multimodal treatment. 1 Carucci J.A. Martinez J.C. Zeitouni N.C. et al. In-transit metastasis from primary cutaneous squamous cell carcinoma in organ transplant recipients and nonimmunosuppressed patients: clinical characteristics, management, and outcome in a series of 21 patients. Dermatol Surg. 2004; 30: 651-655 Crossref PubMed Google Scholar ,2 Ma J.H.Y. Wu A. Veness M. et al. In-transit metastasis from squamous cell carcinoma. Dermatol Surg. 2016; 42: 1285-1292 Crossref PubMed Scopus (14) Google Scholar We performed a retrospective review of cSCC patients with in transit metastasis from 2015 to 2021 at a single academic institution.

449 Identification of tertiary lymphoid structures in primary cutaneous squamous cell carcinoma

Cutaneous squamous cell carcinoma (cSCC) is one of the most common types of human cancer which can metastasise. Dysfunctional immunity promotes cSCC development and anti-PD-1 immunotherapy can provide effective anti-tumour activity in advanced/metastatic cSCC. Tertiary lymphoid structures (TLSs) containing B-cells, T-cells and dendritic cells have been described in melanoma and other cancer types, and associate with improved clinical outcome and responses to anti-PD-1. However, the presence and role of TLSs in cSCC has yet to be determined.

Pristimerin mediated anticancer effects and sensitization of human skin cancer cells through modulation of MAPK signaling pathways

Squamous cell carcinoma is a frequent skin cancer still demanding to understand the underlying mechanisms for better clinical outcomes. Pristimerin, a natural quinonemethide triterpenoid, has shown promising therapeutic outcome due to its anti-cancer activity and multi-targeting potential. We explored the underlying mechanisms of pristimerin-induced programmed cell death of primary (A431) and metastatic (A388) cutaneous squamous cell carcinoma (cSCC) cells. Our results show that pristimerin inhibits growth and proliferation of cSCC through JNK activation. Moreover, pristimerin causes cell cycle arrest and induces cell death via apoptosis and autophagy. Interestingly, use of apoptosis (z-VAD-FMK) and autophagy (3-methyladenine) inhibitors confirmed vital role of programmed cell death in pristimerin-mediated anti-cancer actions. JNK inhibitor, SP600125, also mitigated pristimerin-induced apoptotic and autophagic actions. Moreover, pristimerin-mediated anti-cancer activity acts by generating reactive oxygen species (ROS) thereby inducing JNK signaling. Use of N-acetyl cystine (NAC), a universal ROS scavenger, significantly reversed pristimerin-induced programmed cell death through downregulation of JNK. Pristimerin sensitized skin cancer cells to conventional anticancer drugs cisplatin, azacytidine and doxorubicin through JNK activation, as confirmed by SP600125. Our results indicate that pristimerin mediates programmed cell death and sensitized skin cancer cells to conventional anti-cancer drugs via ROS-mediated JNK activation.

Dermatologic Disease-Directed Targeted Therapy (D3T2): The Application of Biomarker-Based Precision Medicine for the Personalized Treatment of Skin Conditions-Precision Dermatology.

Precision dermatology uses individualized dermatologic disease-directed targeted therapy (D3T2) for the management of dermatoses and for the evaluation and therapy of cutaneous malignancies. Personalized/precision strategies are based on biomarkers that are most frequently derived from tissue transcriptomic expression or genomic sequencing or from circulating cytokines. For instance, the pathologic diagnosis of a pigmented lesion and determining the prognosis of a malignant melanocytic neoplasm can be enhanced by genomic/transcriptomic analysis. In addition to biopsy, innovative techniques have been developed for obtaining transcriptomes in skin conditions; as an example, patches can be applied to a psoriasis plaque for a few minutes to capture the epidermis/upper dermis transcriptome. Atopic dermatitis and prurigo nodularis may also be candidate conditions for precision dermatology. Precision dermatology has a role in managing melanoma and nonmelanoma skin cancers and rare cutaneous tumors—such as perivascular epithelioid cell tumor (PEComa)—that can originate in or metastasize to the skin. For instance, advanced/metastatic basal cell carcinomas can be treated with Hedgehog inhibitors (vismodegib and sonidegib) targeting the smoothened (SMO) or patched 1 (PTCH1) gene alterations that are a hallmark of these cancers and activate the Hedgehog pathway. Advanced/metastatic basal and cutaneous squamous cell cancers often have a high tumor mutational burden (which predicts immunotherapy response); immune checkpoint blockade with cemiplimab, a programmed cell death protein 1 (PD1) inhibitor, is now approved for these malignancies. Gene expression profiling of primary cutaneous squamous cell carcinoma can identify those individuals at high risk for subsequent metastases. In the realm of rare neoplasms, PEComas—which can originate in the skin, albeit uncommonly—have tuberous sclerosis complex 1 (TSC1)/tuberous sclerosis complex 2 (TSC2) gene alterations, which activate mammalian target of rapamycin (mTOR) signaling, and can be suppressed by nab-sirolimus, now approved for this condition. In summary, precision dermatologic techniques/strategies are an important emerging approach for evaluation and management of skin disorders and cutaneous neoplasms, and may serve as a paradigm for the application of precision medicine beyond dermatology.

34405 Host and primary tumor factors for the development of multiple cutaneous squamous cell carcinomas

Introduction: Risk factors for the development of a primary cutaneous squamous cell carcinoma (CSCC) are well-established, but risk factors for subsequent CSCCs are not. While history of prior CSCC is considered the single strongest predictor for development of subsequent CSCCs, the host and primary tumor risk factors at play have not been fully explored.

Risk Factors and Clinicopathological Features for Developing a Subsequent Primary Cutaneous Squamous and Basal Cell Carcinomas.

Simple SummaryPatients with basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (SCC) often develop new keratinocyte carcinoma (KC), but information is limited on the frequency and timing of these subsequent tumors. This information is crucial to guide follow-up care. Given the significant clinical differences of the characteristic feature of individual skin cancer, estimation of the risk of a subsequent tumor should be estimating separately. The aim of our retrospective study was to assess risk factors for a subsequent skin cancer development. We demonstrated that patients with multiple tumors must be followed up carefully and for a long time. Moreover, we indicated the connection between the BCC subtype and increased risk for further KC development. BCC subtypes with an aggressive growth pattern predispose not only to increased risk for the recurrence but also are expected to be at an increased risk for a subsequent tumor. The non-invasive diagnosis, monitoring and follow up should be more comprehensive for those patients compared to low-risk BCC.Background: Patients with diagnosed keratinocyte carcinomas (KCs) have an increased risk of subsequent skin cancers development. Current studies indicate that patients with subsequent tumors should be followed up regularly. However, none of the studies indicate the connection between the specific subtypes and an increased risk for further KCs development. The study assesses the differences in the risk of developing a subsequent skin cancer after a previous diagnosis of KC, especially considering individual types of skin malignances, and identifies potential factors associated with an increased risk of new cutaneous tumor describing non-invasive diagnosis and monitoring. Methods: Pathology and medical records were examined to identify the characteristics of patients with multiple KCs diagnosed between 1999 and 2019. Results: The study group comprised 13,913 KCs occurring in 10,083 patients. Multiple KCs were observed in 2300 patients (22.8%). The analysis showed aggressive subtypes, multiple tumors, and male sex as significant prognostic factors. Conclusions: The most crucial risk factors for developing subsequent KC are being of a male gender, an aggressive tumor subtype, and previous history of multiple skin cancers. Basal cell carcinoma subtypes, such as infiltrative basosquamous, with aggressive growth patterns predispose not only to increased risk for the recurrence but are also expected to be at higher risk of subsequent KCs.

Identification of metastatic primary cutaneous squamous cell carcinoma utilizing artificial intelligence analysis of whole slide images

Cutaneous squamous cell carcinoma (cSCC) harbors metastatic potential and causes mortality. However, clinical assessment of metastasis risk is challenging. We approached this challenge by harnessing artificial intelligence (AI) algorithm to identify metastatic primary cSCCs. Residual neural network-architectures were trained with cross-validation to identify metastatic tumors on clinician annotated, hematoxylin and eosin-stained whole slide images representing primary non-metastatic and metastatic cSCCs (n = 104). Metastatic primary tumors were divided into two subgroups, which metastasize rapidly (≤ 180 days) (n = 22) or slowly (> 180 days) (n = 23) after primary tumor detection. Final model was able to predict whether primary tumor was non-metastatic or rapidly metastatic with slide-level area under the receiver operating characteristic curve (AUROC) of 0.747. Furthermore, risk factor (RF) model including prediction by AI, Clark’s level and tumor diameter provided higher AUROC (0.917) than other RF models and predicted high 5-year disease specific survival (DSS) for patients with cSCC with 0 or 1 RFs (100% and 95.7%) and poor DSS for patients with cSCCs with 2 or 3 RFs (41.7% and 40.0%). These results indicate, that AI recognizes unknown morphological features associated with metastasis and may provide added value to clinical assessment of metastasis risk and prognosis of primary cSCC.