Cutaneous immune-related adverse events: incidence rates, risk factors and association with extracutaneous toxicity - a prospective study of 189 patients treated with checkpoint inhibitors at a Spanish tertiary care hospital.

BACKGROUND: Clinicians are increasingly prescribing immune checkpoint inhibitors (ICIs) to treat cancer, but the real-world incidence, characteristics and risk factors of cutaneous immune-related adverse events (cirAEs) are unclear. OBJECTIVES: To determine the incidence, features and risk factors of cirAEs and to measure their possible association with extracutaneous toxicity. METHODS: We conducted a prospective observational study in a Spanish tertiary care hospital, including people who started an ICI between March 2020 and May 2022. We used a survival analysis and a log-rank test to obtain and compare incidence rates, and a multivariate Cox model to detect risk factors for cirAEs. RESULTS: We included 189 patients, 82 (43.4%) of whom presented cutaneous toxicity. The incidence of cirAEs was 75.0 per 100 person-years, with a 50.0% probability of the appearance of a cirAE at 10 months of follow-up. The most frequent cirAE category was inflammatory dermatoses, and the most frequent types were pruritus, eczema and maculopapular eruptions. ICI combination therapy, a family history of psoriasis and rheumatological and pulmonary immune-related adverse events increased the risk of cirAEs. CONCLUSIONS: We found a high incidence of cirAEs, and they occurred early in the follow-up period. Dermatologists should be involved in the management of cirAEs, especially in people with risk factors.

A Case Series of 18 Congenital Haemangiomas: Clinical, Histological and Ultrasound Features, and their Relationship with Complications and Atypical Behaviour.

Recent studies have advanced our understanding of the clinical, histological and imaging characteristics of congenital haemangiomas (CHs), and have reported possible complications and atypical behaviour. The aim of this study is to describe the clinical, histological and ultrasound features of a series of CHs and to analyse their association with complications and atypical behaviour, with a view to providing diagnostic and management recommendations. The medical records, histology results and ultrasound images of all patients with CH diagnosed in the Dermatology Department of Alicante University General Hospital between 2006 and 2021 were retrospectively reviewed. A total of 18 patients were included, of whom 4 (22.2%) had complications. The most severe was 1 case with heart failure. There was a significant association between large CH size (> 5 cm) and the occurrence of complications (p = 0.019). The study identified 3 different lobule patterns, but found no relationship with CH subtype or other findings. The associations of venous ectasia, venous lakes and arteriovenous microshunts with occurrence of complications was borderline significant (p = 0.055). Study limitations were the small sample and the retrospective analysis. To conclude, haematological and cardiological assessment is indicated in large CHs and should be considered in CHs with ultrasound findings of venous ectasia, venous lakes or arteriovenous microshunts, as these cases present a greater risk of complications.

Plexiform Xanthomatous Tumor, Variety of Xanthoma or Subtype of Fibrohistiocytic Tumors?

Plexiform xanthomatous tumor was proposed as an independent neoplasm within fibrohistiocytic tumor group a few years ago. The arguments were based on their different clinical features as well as their own morphological and immunohistochemical findings. Nevertheless, it has not been widely studied yet, and there are few reports about this entity. Regarding a case, we reviewed the diagnostic characteristics of this underdiagnosed tumor.

Proposal of a clinically relevant working classification of pituitary neuroendocrine tumors based on pituitary transcription factors.

The immunohistochemistry (IHC) characterization of pituitary transcription factors (PTFs) PIT1, TPIT, and SF1, which enable the identification of three different adenohypophyseal cell lines, has been incorporated into the latest classification system of the World Health Organization (WHO) for pituitary adenomas. This change overturns the concept of the adenoma as solely a hormone producer and classifies these tumors based on their cell lineage. The aim of the study was to provide a diagnostic algorithm, based on IHC expression of hypophyseal hormones with potential use in diagnostic practice, contributing to an improved classification of pituitary adenomas. Our sample included 146 pituitary adenomas previously classified based on hormonal subtypes by IHC (former 2004 WHO criteria) and re-evaluated after the IHC quantification of PIT1, TPIT, and SF1 expression, under WHO 2017 recommendations. We assessed the correlation between expression of PTFs and the classification as per hormonal IHC and correlated clinicopathological profiles based on PTFs. The IHC study of PTFs allowed reclassification of 82% of tumors that were negative for all pituitary hormones, with 21 positive cases for SF1 (reclassified as gonadotroph tumors), 1 positive case for TPIT (reclassified as a corticotroph tumor), and 4 positive cases for PIT1. Using SF1 enabled detection of a substantial portion of gonadotroph tumors, reducing the estimated prevalence of null cell tumors to less than 5%, and identification of plurihormonal pituitary neuroendocrine tumors with PIT1-SF1 coexpression and hormone-negative PIT1s, a group in which we did not observe differences in the clinical behavior compared with the rest of the tumors of the same cell lineage.Our results suggest that applying a diagnostic algorithm based on the study of PTFs could contribute to improving the classification of pituitary adenomas. By adding TPIT assessment, we propose a two-step algorithm, with hypophyseal hormones being used in a selective modality, depending on initial results.

[Microglandular adenosis of the breast in a patient with a history of mediastinal radiotherapy]. / Adenosis microglandular mamaria en paciente con antecedente de radioterapia mediastínica.

The risk of secondary tumors in patients who have received mediastinal radiation therapy is well-known. Microglandular adenosis of the breast is a rare lesion that is considered benign, although its possible role as a precursor of invasive breast carcinoma has been considered. We present a case of microglandular adenosis in a patient who received mediastinal radiation therapy in childhood for Hodgkin's lymphoma. To our knowledge, this is the first reported case of microglandular adenosis in a patient with mediastinal radiotherapy which may shed light on its pathogenesis.

Cardiac Tamponade Associated with the Presentation of Anaplastic Large Cell Lymphoma in a 2-Year-Old Child.

The anaplastic large cell lymphoma is a rare entity in pediatric patients. We present an unusual case of pericardial involvement, quite uncommon as extranodal presentation of this type of disorder, that provoked a life-risk situation requiring an urgent pericardiocentesis. To our knowledge, this is the first report on a child with pericardial involvement without an associated cardiac mass secondary to anaplastic large cell lymphoma in pediatric age. We report the case of a 21-month-old Caucasian male infant with cardiac tamponade associated with the presentation of anaplastic large cell lymphoma. Initially, the child presented with 24-day prolonged fever syndrome, cutaneous lesions associated with hepatomegaly, inguinal adenopathies, and pneumonia. After a 21-day asymptomatic period, polypnea and tachycardia were detected in a clinical check-up. Chest X-ray revealed a remarkable increase of the cardiothoracic index. The anaplastic large cell lymphoma has a high incidence of extranodal involvement but myocardial or pericardial involvements are rare. For this reason, we recommend a close monitoring of patients with a differential diagnosis of anaplastic large cell lymphoma.