Merkel cell carcinoma is a rare and aggressive cutaneous tumor, and the use of checkpoint inhibitors immunotherapy is a recent indication in its metastatic setting, both first and second line. However, the widespread use of immunotherapy is associated with an increase of acute and late immune-mediated adverse events. We present a case of an elderly fit patient with metastatic Merkel cell carcinoma treated with pembrolizumab who developed diabetic ketoacidosis, a severe immune-mediated adverse event. A multidisciplinary approach was crucial to overcome the life-threatening event. Even with early treatment stop, the patient had a significant and durable response to the treatment for 15 months. Meanwhile, a progressive pancerebellar syndrome emerged, possible due to a paraneoplastic syndrome with a negative onco-neuronal antibody panel, although an autoimmune etiology associated with immunotherapy could not be excluded. Unfortunately, the situation was irreversible and refractory to immunomodulatory treatment. Despite the unpredictable toxicity, it is important to note the efficacy profile, with a progression-free survival of 15 months, which is higher than the one reported in reference clinical trials in this setting.

The first thousand days of life from conception have a significant impact on the health status with short, and long-term effects. Among several anthropometric and maternal lifestyle parameters birth weight plays a crucial role on the growth and neurological development of infants. Recent genome wide association studies (GWAS) have demonstrated a robust foetal and maternal genetic background of birth weight, however only a small proportion of the genetic hereditability has been already identified. Considering the extensive number of phenotypes on which they are involved, we focused on identifying the possible effect of genetic variants belonging to taste receptor genes and birthweight. In the human genome there are two taste receptors family the bitter receptors (TAS2Rs) and the sweet and umami receptors (TAS1Rs). In particular sweet perception is due to a heterodimeric receptor encoded by the TAS1R2 and the TAS1R3 gene, while the umami taste receptor is encoded by the TAS1R1 and the TAS1R3 genes. We observed that carriers of the T allele of the TAS1R1-rs4908932 SNPs showed an increase in birthweight compared to GG homozygotes Coeff: 87.40 (35.13–139.68) p-value = 0.001. The association remained significant after correction for multiple testing. TAS1R1-rs4908932 is a potentially functional SNP and is in linkage disequilibrium with another polymorphism that has been associated with BMI in adults showing the importance of this variant from the early stages of conception through all the adult life.

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Introduction Cancer survivors are at an increased risk of adverse outcomes, including thyroid neoplasms, given the high radiosensitivity of this gland. The aim of this study is to assess the incidence and timeframe of thyroid complications in cancer patients, followed systematically since their radiation therapy, and to identify risk factors for the development of hypothyroidism and thyroid cancer. Methods We performed a retrospective study, including 282 subjects, who received neck, craniospinal, or total body irradiation (TBI). Patients were grouped into four primary diagnostic clusters: leukaemia, Hodgkin's disease, central nervous system, and head and neck tumours. Results Hypothyroidism was observed in 56.7% of patients, on average 6.8 ± 5.9 years after the treatment. Neck and craniospinal irradiation presented a 3.5‐fold increased risk for the development of hypothyroidism compared to TBI. Papillary thyroid cancer was diagnosed in 8.5% of the patients, on average, 18.5 ± 4.9 years after radiotherapy (RT). Female gender, younger age, and lower irradiation doses were independently associated with thyroid cancer development. Conclusion Our study provides useful information about the risk of hypothyroidism and thyroid cancer after RT, as it was performed in a cohort of patients closely followed since the oncological therapies, and, thus, may give new insights into the follow‐up management of these patients.

Objective Parathyroid Carcinoma is a rare malignant neoplasm, accounting for less than 1% of primary hyperparathyroidism cases. Parathyroid carcinomas are characterized by markedly elevated levels of PTH, severe hypercalcemia and established target organ damage. The authors report the experience of a single centre regarding the management and outcome of patients with parathyroid carcinomas and revise relevant literature. Design Retrospective review of all patients with parathyroid carcinoma evaluated at a tertiary oncologic centre from 1991 until 2021. Results Seventeen patients were identified (10 males), with a mean age at diagnosis of 53 ± 16 years and a median follow‐up of 16.5 years. Most patients presented with hypercalcemia (n = 15), with a mean serum calcium concentration of 13.5 mg/dl (9.6–16.5) and mean PTH of 1173 pg/ml (276–2500). Hyperparathyroidism‐mediated organ damage was observed in most patients (n = 16), with predominant renal (n = 12) and skeletal (n = 9) complications. En bloc surgical resection was performed in nine patients. Three patients underwent adjuvant radiotherapy. Recurrence was observed in 8 cases (47.1%) after a median of 24 months following surgery and no independent predictors of recurrence were identified. The overall survival and disease specific survival at 5‐year was 88% and 94%, respectively. CDC73 mutations were present in 38.5% of analysed patients and one patient was diagnosed with MEN1. Conclusion Parathyroid carcinoma is associated with a significant rate of recurrence and limited effective treatment beyond initial complete surgical resection. Therefore, preoperatively high index of suspicion is paramount to optimize patient care. This is, to our knowledge, the largest Portuguese cohort published so far.

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