Cutaneous immune-related adverse events: incidence rates, risk factors and association with extracutaneous toxicity. A prospective study of 189 patients treated with checkpoint inhibitors in 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. OBJECTIVE: To determine the incidence, features and risk factors of cirAEs and 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 of cirAEs. RESULTS: We included 189 patients, of whom 82 (43.4%) presented cutaneous toxicity. The incidence of cirAEs was 75.0 per 100 person-years, with a 50% probability of cirAE appearance 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, family history of psoriasis and rheumatologic and pulmonary irAEs increased the risk of cirAEs. Limitations: Single-center design. CONCLUSION: We found a high incidence of cirAEs, and they occurred early in follow-up. 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.

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.

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

El riesgo de tumores secundarios en los pacientes que han recibido radioterapia mediastínica es ampliamente conocido. La adenosis microglandular de la mama es una lesión poco frecuente considerada como benigna, aunque se plantea su papel precursor del carcinoma infiltrante de mama. Presentamos un caso de adenosis microglandular en una paciente que recibió radioterapia mediastínica en la infancia por linfoma de Hodgkin. Hasta la fecha este es el primer caso informado en la literatura de adenosis microglandular en paciente con radioterapia mediastínica, planteando un interrogante en la contribución en la patogénesis

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

[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.

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.

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.

Ependimoma de células gigantes de la cauda equina. A propósito de un caso / Giant cell ependymoma of the cauda equina. A case report

Los ependimomas constituyen la neoplasia más frecuente de la médula espinal. Se desarrollan a partir de células que revisten el canal ependimario. Un subtipo infrecuente es el ependimoma de células gigantes, del que se han descrito solo 8 casos en dicha localización. Describimos el caso de un varón de 42 años con lumbalgia de varios meses de evolución. La RMN mostró un tumor bien circunscrito intradural en L1, que se resecó en su totalidad. El estudio histológico demostró proliferación fusocelular de distribución perivascular con formación de pseudorrosetas y moderada atipia citológica con células gigantes multinucleadas. El estudio inmunohistoquímico confirmó el diagnóstico de ependimoma de células gigantes(AU)

Ependymomas are the most frequent neoplasms of the spinal cord, arising from the cells lining the spinal canal. Among them, giant cell ependymoma is a rare subtype with only 8 cases previously reported to date. We present a further case in a 42-year-old man who presented with a history of lower back pain for several months. The MRI revealed a well-circumscribed interdural mass at L1. The tumour was totally resected and histologically it was seen to be comprised of a proliferation of fusiform cells arranged in a perivascular pattern with pseudorosettes and cytologic atypia with multinucleated giant cells. Immunohistochemistry confirmed the diagnosis of giant cell ependymoma(AU)

Adenoma hipofisario: estudio de la actividad proliferativa con Ki-67 / Pituitary adenoma: study of proliferative activity with Ki-67

Antecedentes: Los adenomas hipofisarios son neoplasiasbenignas que pueden tener un comportamiento localmenteagresivo. Métodos: En el presente trabajo se analiza el significadode la actividad proliferativa mediante inmunotincióncon Ki-67 en una serie de 107 adenomas hipofisarios. Resultados:La actividad proliferativa media fue de 1,99% (rango0%-18%) y la mayoría (81%) presentaron Ki-67 <3%. Seobservó una tendencia a la asociación entre mayor nivel deKi-67 y extensión extraselar, tipo inmunohistoquímico hormonal(prolactinomas y adenomas gonadotropos), sexo masculinoy menor edad. Sin embargo, no se demostró asociaciónsignificativa con la densidad mitocondrial y la densidadmicrovascular (DMV), la actividad funcional o la apariciónde recidiva. Conclusiones: El estudio de la actividad proliferativacon Ki-67 puede definir un subgrupo de adenomashipofisarios con comportamiento localmente más agresivo

Introduction: Pituitary adenomas are benign neoplasias,but they may behave locally more aggressive.Methods: The present study analyzes the significance ofproliferative activity by Ki-67 staining in a series of 107pituitary adenomas. Results: The mean proliferative activityrate was 1.99% (range 0%-18%) and the majority(81%) showed Ki-67 <3%. We showed a trend towards ahigher Ki-67 in adenomas with extrasellar extension, hormonalsubtype (prolactinomas and gonadotroph cell adenomas),male gender and younger age. However, no significantdifferences were found between Ki-67 and mitochondrialor microvascular densities, functional activity orrecurrence. Conclusions:We conclude that the proliferativeactivity evaluated by Ki-67 can define a subset of pituitaryadenomas with a more aggressive behavior

Patología de los adenomas hipofisarios / Pathology of pituitary adenomas

Los adenomas hipofisarios son neoplasias benignas originadas en células de la adenohipófisis. Representan el tumor más habitual en la silla turca y constituyen un 10-15 por ciento de las neoplasias intracraneales. Inicialmente fueron clasificados, según sus características tintoriales, en adenomas acidófilos, basófilos y cromófobos. La aplicación de técnicas morfológicas como la microscopía electrónica y la inmunohistoquímica, y la integración de los hallazgos morfológicos con los datos clínicos, de laboratorio y de las técnicas de imagen han permitido el desarrollo de la nueva clasificación de los adenomas hipofisarios. Las técnicas genéticas y moleculares están proporcionando información que ayuda a entender la patogénesis de algunas variedades de adenoma hipofisario. Por otra parte, la aplicación de determinados marcadores puede aportar información pronóstica y ayudar a predecir la respuesta a modalidades terapéuticas específicas (AU)