BackgroundCutaneous squamous cell carcinoma (CSCC) is the second most common skin cancer whose incidence is growing parallel to the lengthening of the average lifespan. Cemiplimab, an antiPD-1 monoclonal antibody, is the first approved immunotherapy for patients with locally advanced CSCC (laCSCC) or metastatic CSCC (mCSCC) thanks to phase I and II studies showing high antitumor activity and good tolerability. Nevertheless, at present, very few data are available regarding cemiplimab in real-life experience and in frail, elderly, and immunosuppressed patients as well as regarding biomarkers able to predict response so as to guide therapeutic choices.Patients and MethodsWe built a retroprospective cohort study including 30 non-selected patients with laCSCC (25) and mCSCC (five) treated with cemiplimab from August 2019 to November 2020. Clinical outcomes, toxicity profile, and correlations with disease, patients, and peripheral blood parameters are explored.ResultsThe median age was 81 years (range, 36–95), with 24 males and five patients having an immunosuppressive condition, while the frailty prevalence was 83% based on index derived from age, Eastern Cooperative Oncology Group performance status, and Charlson Comorbidity Index. We reported 23 responses (76.7%) with nine complete responses (30%). A statistically significant higher response rate was observed in head and neck primary tumors and in patients with hemoglobin level >12 g/dl. No difference was observed with respect to frailty, median age, sex, and body mass index. The baseline low neuthophil/lymphocyte ratio and low platelet/lymphocyte ratio resulted to be also correlated with a better response. Moreover, lymphocyte, neutrophil, and monocyte behaviors had an opposite trend in responders and non-responders. An overall response was reported in four of five immunosuppressed patients. Seventeen patients (57.6%) have an ongoing response and are still alive. Six responders had interrupted treatment (two for toxicity and four for personal choice) but maintained their response. The treatment was well tolerated by the majority of patients. The most common adverse events were fatigue in seven patients (23.3%) and skin toxicity in 10 patients (33.3%), including pruritus in six patients, rash in three patients, and bullous erythema in one patient.ConclusionsIn our real-life experience, cemiplimab showed a high antitumor activity with acceptable safety profile similar to those in trials with selected patients. Moreover, its antitumor activity resulted to be not impaired in very elderly patients and in those with immunocompromised status.

A case of multiple gastric carcinoids and nonantral atrophic gastritis in which the larger tumor was a composite carcinoid-adenocarcinoma is presented. The two components of the composite tumor immunohistochemically showed clear-cut diverging functional differentiations although the available evidence supported a common histogenesis from the metaplastic intestinal epithelium of the gastric mucosa. The carcinoid tissue of the composite tumor, which showed "atypical" features, also differed from the other, pure carcinoids, in which the histologic appearance was "typical." Total gastrectomy performed 1 month after the original gastric resection with antrectomy disclosed regressive changes in the endocrine cell proliferations of the gastric stump consistent with the withdrawal of a stimulating effect of the antral gastrin.Cancer 64: 1534-1539. 1989.HE SYNDROME of multiple carcinoid tumors and T chronic atrophic gastritis of the nonantral mucosa of tlie stomach is a well recognized entity.'-3 In this syndrome an interesting although not universally accepted stimulating role of the consistently occurring hypergastrinemia in the growth of the endocrine neoplasms has been ~uggested.~ In accordance with such a hypothesis is the recent observation that regression of the carcinoid tumors may be induced by antrectomy alone, a procedure which removes the source of the sustained gastrin secretion of these patients and normalizes serum gastrin This study illustrates a case of the syndrome in which the multiple carcinoids were associated with a composite carcinoid-adenocarcinoma tumor of the stomach. This is the first report of such an association although in a previous case' carcinoids and adenocarcinoma were described as concomitant but separate neoplasms. Although both components of the composite tumor of our patient likely had the same histogenetic origin, immunohistochemically they revealed clear-cut divergences in their functional differentiation.Owing to the unexpected finding of adenocarcinomatous tissue, the gastric resection originally performed in the patient was followed by total gastrectomy. This condition allowed us to document regressive cell changes consistent with the withdrawal of gastrin trophic activity in the endocrine proliferations of the remaining gastric mucosa as early as one month after antrectomy. Case ReportIn October 1987, a 53-year-old woman was admitted to the hospital (Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Castellana Grotte, Italy) for evaluation of two pol ypoid lesions located in the anterior wall of the gastric body and measuring l .5 and l cm in diameter, respectively. The smaller polyp was excised endoscopically and found to correspond to a carcinoid tumor penetrating beyond the muscularis mucosae on histologic examination. Therefore, a gastric resection was performed. Owing to the histologic diagnosis of composite carcinoidadenocarcinoma in the larger polyp (described below) the patient underwent total gastrectomy 1 month later. Intraoperative examination did not rev...

Frizzled (FZD) proteins, a family of Wnt receptors, are involved in carcinogenesis in different organs. One interesting FZD protein is FZD-10 highly expressed in embryogenesis but completely absent in the membrane or cytosol of healthy proliferated cells. We studied in detail the expression level and the location of Frizzled-10 protein in different cancerous tissues, such as colon, melanoma and gastric cancer and in function of different staging of the tumor and in metastases. We observed a correlation between cancer evolution and FZD-10 expression, and localization of protein during carcinogenesis. In colon, we have an increase of cytoplasmic FZD-10 expression from hyperplastic mucosa to metastatic tissues, while the amount in the nucleus decreases significantly in T3 and T4 staging tumors as well as in metastases. In melanoma and gastric cancer, we observed the opposite trend of FZD-10 protein in the cytosol but both show a decrease in the T3 and T4 stage of the tumor and in metastases. However, the decrease is less prominent in gastric cancer.Our findings indicate an important role of FZD-10 in tumor progression especially in the later stages of tumor. The nuclear expression of FZD-10 or its absence can give a new tool for tumor staging to pathologists. For target therapy, at least for colon cancer, the high presence of FZD-10 in the later stages of tumor progression and the absence in healthy tissue present a promising new approach.