Pathological Findings Associated With SARS-CoV-2 on Postmortem Core Biopsies: Correlation With Clinical Presentation and Disease Course.

Background: Autopsies can shed light on the pathogenesis of new and emerging diseases. Aim: To describe needle core necropsy findings of the lung, heart, and liver in decedents with COVID-19. Material: Cross-sectional study of needle core necropsies in patients who died with virologically confirmed COVID-19. Histopathological analyses were performed, and clinical data and patient course evaluated. Results: Chest core necropsies were performed in 71 decedents with a median age of 81 years (range 52-97); 47 (65.3%) were men. The median interval from symptoms onset to death was 17.5 days (range 1-84). Samples of lung (n = 62, 87.3%), heart (n = 48, 67.6%) and liver (n = 39, 54.9%) were obtained. Fifty-one lung samples (82.3%) were abnormal: 19 (30.6%) showed proliferative diffuse alveolar damage (DAD), 12 (19.4%) presented exudative DAD, and 10 (16.1%) exhibited proliferative plus exudative DAD. Of the 46 lung samples tested for SARS-CoV-19 by RT-PCR, 39 (84.8%) were positive. DAD was associated with premortem values of lactate dehydrogenase of 400 U/L or higher [adjusted odds ratio (AOR) 21.73; 95% confidence interval (CI) 3.22-146] and treatment with tocilizumab (AOR 6.91; 95% CI 1.14-41.7). Proliferative DAD was associated with an onset-to-death interval of over 15 days (AOR 7.85, 95% CI 1.29-47.80). Twenty-three of the 48 (47.9%) heart samples were abnormal: all showed fiber hypertrophy, while 9 (18.8%) presented fibrosis. Of the liver samples, 29/39 (74.4%) were abnormal, due to steatosis (n = 12, 30.8%), cholestasis (n = 6, 15.4%) and lobular central necrosis (n = 5, 12.8%). Conclusion: Proliferative DAD was the main finding on lung core needle necropsy in people who died from COVID-19; this finding was related to a longer disease course. Changes in the liver and heart were common.

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.

Atypical pediatric presentation of lymphocytic thrombophilic arteritis: Diagnostic difficulties and recent nosological clarification.

A 4-year-old girl presented with a 2-month history of round, hypopigmented, slightly scaly patches measuring 1-6 cm and encircled by an erythematous halo, first appearing on the lower limbs then spreading to the whole body. Three biopsies were taken as the condition progressed, each showing a lymphocytic infiltrate affecting a medium-sized artery at the dermal-subcutaneous junction, with a concentric fibrin ring. These findings are characteristic of lymphocytic thrombophilic arteritis (LTA). The young age of our patient and the type of skin lesions she developed make this an atypical presentation of LTA, which usually manifests as hyperpigmented macules on the lower extremities, predominantly in dark-skinned women.

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.

Increased E2F1 mRNA and miR-17-5p Expression Is Correlated to Invasiveness and Proliferation of Pituitary Neuroendocrine Tumours.

miR-17-5p and E2F1 have been described as deregulated in cancer, but they have scarcely been studied in pituitary neuroendocrine tumours (PitNETs). This study evaluates the relationship of E2F1 and miR-17-5p with the invasiveness and proliferation of PitNETs. In this cross-sectional descriptive study, we evaluated the expression of E2F1, MYC, and miR-17-5p by quantitative real time PCR analysis in 60 PitNETs: 29 gonadotroph (GT), 15 functioning somatotroph (ST), and 16 corticotroph (CT) tumours, of which 8 were silent (sCT). The clinical data were collected from the Spanish Molecular Register of Pituitary Adenomas (REMAH) database. We defined invasiveness according to the Knosp classification and proliferation according to a molecular expression of Ki-67 ≥ 2.59. E2F1 was more expressed in invasive than in non-invasive tumours in the whole series (p = 0.004) and in STs (p = 0.01). In addition, it was overexpressed in the silent subtypes (GTs and sCTs; all macroadenomas) and normoexpressed in the functioning ones (fCTs and STs; some microadenomas). miR-17-5p was more expressed in proliferative than in non-proliferative tumours (p = 0.041) in the whole series but not by subtypes. Conclusions: Our study suggests that in PitNETs, E2F1 could be a good biomarker of invasiveness, and miR-17-5p of proliferation, helping the clinical management of these tumours.

Primary peritoneal clear cell carcinoma. A case report and literature review.

Primary peritoneal malignant tumors are exceptional. Among them, clear cell carcinoma is extremely rare, being only thirteen cases previously reported in the literature since 1990. We report a case of a 48-year-old Caucasian woman who was treated at the University General Hospital of Alicante. She consulted because of progressive abdominal pain over the last seven months, with the initial diagnosis of renal-ureteral colic. Ultrasound and computed tomography of the abdomen and pelvis revealed a 25 × 15 cm, well-defined cystic lesion with papillary projections, centrally located in the abdomen. The radiology report suggested a primary ovarian tumor versus peritoneal implant as the first option. The patient underwent an exploratory laparotomy showing a large cystic mass located in the urinary bladder peritoneum, firmly attached to the mesentery. The entire abdominal tumor was completely excised, and total hysterectomy with bilateral salpingo-oophorectomy and infra-colical omentectomy were performed. The final histological study revealed a new case of primary peritoneal clear cell carcinoma located in the urinary bladder peritoneum, firmly attached to the mesentery. Grossly, it was well-circumscribed and multicystic with papillary growth involving part of the inner wall. Microscopically, it showed tubulocystic and papillary patterns with highly atypical tumor cells. After an extensive immunohistochemical analysis, the most relevant finding was an ARID1A loss that was corroborated by molecular analysis showing an ARID1A deletion. The patient received systemic chemotherapy with carboplatin and paclitaxel protocol (Å ~ 4 cycles). Patient follow-up after the eighth month showed peritoneal implants predominantly in the right diaphragmatic cupule that were histologically confirmed as recurrence. She has just received another six cycles of chemotherapy with carboplatin and paclitaxel. Recognition of primary peritoneal clear cell carcinoma in this uncommon location, and exclude metastasis from the ovary, represents a diagnostic challenge.

How Valuable Is the RT-qPCR of Pituitary-Specific Transcription Factors for Identifying Pituitary Neuroendocrine Tumor Subtypes According to the New WHO 2017 Criteria?

The classification of pituitary neuroendocrine tumors (PitNETs) subtypes continues generating interest. In 2017, the World Health Organization (WHO) proposed considering the immunohistochemical (IHC) analysis of pituitary-specific transcription factors (TF) for their typification. The present study targeted the quantification of pituitary-specific TF (TPIT, PIT-1, SF-1, GATA2, ESR1) gene expression by RT-qPCR to overcome the shortcomings of IHC and to complement it. We analyzed 251 tumors from our collection of PitNETs and performed additional IHC studies in a subset of 56 samples to analyze the concordance between gene and protein expression of the TF. The molecular and IHC studies allowed us to significantly reduce the percentage of null cell tumors in our series, most of which were reclassified as gonadotroph tumors. The concordance between the molecular and the immunohistochemical studies was good for tumors coming from the corticotroph and Pit-1 lineages but worsened for the rest of the tumors. Indeed, the RT-qPCR helped to improve the typification of plurihormonal Pit-1 and unusual tumors. Overall, our results suggest that the RT-qPCR of pituitary-specific TF and hormone genes could help pathologists, endocrinologists, and neurosurgeons to improve the management of patients with pituitary tumors.