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AbstractEngineered nanomaterials (ENMs) are used in diverse consumer products including, but not limited to antibacterial agents, paints, food additives, cosmetics, rubber-curing agents, textile UV-absorbers, contrast elements for magnetic resonance imaging, heating agents for cancer thermotherapy, and carriers for drug and gene delivery. Nanomaterials possess a greater surface area to volume ratio yielding a greater reactive surface area and unique physiochemical properties, but potentially possessing greater biological activity and possible toxicity than their bulky counterparts. With more than 1800 ENM-based consumer products on the market, greater demands for nanomaterials may pose increased risk for consumer and occupational exposure, in particular for workers who manufacture, handle, and package ENMs and ENM-based products. Hence, there is a need to better understand and test the hazards of these nanomaterials and their effects on human health and the environment.The aim of this study was to assess the potential implications of silver silicate (Ag-SiO2), zinc oxide (ZnO) and reduced graphene oxide (rGO) to the respiratory tract, especially when inhaled. The focus of this study was on the upper respiratory tract composed of the nasal cavity and possible transport to the brain (via the olfactory bulb) and the lower respiratory tract formed by the bronchial tree and lung parenchyma. These two regions of the respiratory system were selected for study, based on unique patterns of particle deposition for each region and the potential implications for nanoparticles being retained in each of these regions following deposition. To address the aim of our study, an acute, single day nose-only inhalation exposure regimen to aerosols of each nanomaterial was conducted in Sprague Dawley rats. Aerosols were well-characterized before and during the study. Animals were necropsied immediately (day 0) and on days 1, 7, 21 or day 56 post-exposure to ENMs. Bronchoalveolar lavage fluid, lung tissues and the nasal cavity with the contiguous olfactory bulbs were collected for assessment. Experiments were conducted to evaluate the pulmonary toxicity via BALF analysis, histological examination, gene expresssion and immunohistochemical staining. For the nasal cavity and olfactory bulb, histological examination and studies of microglial activation were conducted.

Elastin and collagen are the main components of the lung connective tissue network, and together provide the lung with elasticity and tensile strength. In pulmonary pathology, elastin staining is used to variable extents in different countries. These uses include evaluation of the pleura in staging, and the distinction of invasion from collapse of alveoli after surgery (iatrogenic collapse). In the latter, elastin staining is used to highlight distorted but pre-existing alveolar architecture from true invasion. In addition to variable levels of use and experience, the interpretation of elastin staining in some adenocarcinomas leads to interpretative differences between collapsed lepidic patterns and true papillary patterns. This review aims to summarise the existing data on the use of elastin staining in pulmonary pathology, on the basis of literature data and morphological characteristics. The effect of iatrogenic collapse and the interpretation of elastin staining in pulmonary adenocarcinomas is discussed in detail, especially for the distinction between lepidic patterns and papillary carcinoma.

Abstract: Exposure to environmental toxicants such as Arsenic (As) can result in As-induced alterations in immune regulators. Consequently, people who are more prone to viral infections like influenza A or B, H1N1, SARS CoV (Severe Acute Respiratory Syndrome Coronavirus), and SARS CoV2 may devel-op a susceptibility to immune responses in their lungs. Our previous reports delineated the ability of QIAPI 1®, a melanin precursor, to dissociate water molecules with simultaneous therapeutic efficacy against central nervous system (CNS) diseases, retinopathy, and As-induced renal toxicity. Considering the commonalities of lung pathology of SARS CoV and As-induced toxicity, the aim of this study is to decipher the efficacy of QIAPI 1® against pentavalent As-induced lung toxicity by examining the pul-monary pathology. Hematoxylin & Eosin (H&E) staining was used for ascertaining the lung pathology in Wistar rat models. Animals were divided into 3 groups: control group, group treated with pentavalent As, and a group treated with pentavalent As and QIAPI 1®. There were no significant changes in lung histopathology in the control group as indicated by intact morphology. The As-treated group revealed damage to the histoarchitecture with pulmonary edema, interstitial fibrosis, diffuse alveolar damage, Bronchiolitis obliterans organizing pneumonia (BOOP)-lesions, formation of hyaline membrane, multi-nucleated giant pneumocytes, atypical pneumocytes, inflammatory cell infiltration, and interstitial ede-ma. The group treated with As and QIAPI 1® significantly associated with mitigated histological signs of lung inflammation induced by Arsenic. Therefore, QIAPI 1® can be recommended as antagonistic to As-induced lung toxicity. In conclusion, this model could be preferred as a hypothetical model to examine the efficacy of QIAPI 1® in SARS CoV2-induced pulmonary damage. Future studies are warranted to delineate the efficacy of QIAPI 1® against SARS CoV and SARS CoV2 lung pathology.

Background Infection by SARS‐CoV‐2 produces significant pulmonary pathology including endothelial damage with resultant thrombotic events. While pathologic features were described, there are limited data on the relationship of these changes to the inflammatory response and the production of thromboses. Objective To investigate pathology of COVID‐19‐related immunothrombosis. Patients/Methods Tissue samples from lung, kidney, brain and heart that were collected from 45 patients who died of COVID‐19. Histopathological examination was performed after H&E and Picro‐Mallory staining in combination with (immuno)fluorescence to visualize neutrophil extracellular traps. Ultrastructural alterations in lungs were studied with scanning and transmission electron microscopy. Results Inflammatory changes and thrombosis were substantially more pronounced in the lung than in the kidney, heart, and brain. The most common pathologic finding was diffuse alveolar damage. In addition, most lung samples showed thrombi in vessels. The cause of death in single cases was massive pulmonary embolism. Ultrastructural examination revealed neutrophils attached to endothelium, perhaps as a step towards transendothelial migration. In addition, platelets were identified in the midst of fibrin as individual procoagulant balloon‐like cells. Ultrastructural examination demonstrated numerous virion‐like particles. Conclusions Studying (ultra)structural features of the autopsy lung samples from patients with COVID‐19 has provided evidence for a pathogenic link between inflammation and thrombosis. The major features in the lungs of COVID‐19 patients comprised primary inflammatory thrombosis associated with diffuse alveolar damage. The lungs had pronounced circulatory changes with inflammation‐dependent intravascular blood clotting, whereas heart, brain, and kidneys had predominantly degenerative changes that were distinct from the lung pathology.

Nannizziopsis guarroi is a highly pathogenic fungal organism affecting various lizard species which often manifests as cutaneous disease. Pulmonary involvement with Nannizziopsis infections has rarely been reported in reptiles. An 8-year-old, female green iguana was presented for clinical evaluation following a chronic history of upper and lower respiratory tract signs and fistula formation in the right maxilla communicating with the oral cavity. Pulmonary infiltrates were noted on serial computed tomography scans and repeated baseline bloodwork was unremarkable. Based on a poor response to chronic antibiotic therapy, rigid pulmonoscopy was elected. The lung parenchyma contained multifocal clusters of yellow-brown ovoid masses. Biopsy of the lesions revealed granulomas with intralesional fungal hyphae. Fungal culture had no growth but panfungal PCR identified the organism Nannizziopsis guarroi. The iguana failed to completely recover postprocedure and died despite further supportive care. Computed tomography helped determine the extent of pulmonary pathology but pulmonoscopy, lung biopsy and molecular diagnostic methods were ultimately required to obtain a definitive diagnosis. Nannizziopsis fungal pneumonia should be considered a differential diagnosis in squamates with respiratory clinical signs.

This study aimed to assess the suitability of hyperpolarized 129Xe (HPXe) MRI for noninvasive longitudinal evaluation of pulmonary function in preclinical lung cancer models. A mouse model of lung cancer (LC) was induced in 5 mice by intraperitoneal injection of urethane, while a negative-control (NC) mice (N = 5) was prepared by injection of saline solution. Longitudinal HPXe MRI was performed over a 5-month period to monitor lung ventilation and gas exchange. The treatment efficacy of ethyl pyruvate (EP), an anti-inflammatory drug, to the mouse LC model was monitored using HPXe MRI by commencing administration of EP pre (early-phase) and 1-month post (late-phase) injection of urethane (N = 5 mice for each group). Gas-exchange function in LC mice was significantly reduced at 1-month after urethane injection compared with NC mice administered with saline ( P < 0.01 ). Thereafter, it remained consistently lower than that of the NC group for the full 5-month measurement period. In contrast, the ventilation function of the LC model mice was not significantly different to that of the NC mice. Histological analysis revealed alveolar epithelial hyperplasia in LC mice alveoli at 1 month after urethane injection, and adenoma was confirmed 3 months after the injection. The early- and late-phase EP interventions were found to improve HPXe MRI metrics (reduced at 1 month postinjection of urethane) and significantly inhibit tumor growth. These results suggest that HPXe MRI gas-exchange metrics can be used to quantitatively assess changes in the precancerous lesion microenvironment and to evaluate therapeutic efficacy in cancer. Thus, HPXe MRI can be utilized to noninvasively monitor pulmonary pathology during LC progression and can visualize functional changes during therapy.

The lung is the main affected organ in severe coronavirus disease 2019 (COVID-19) caused by the novel coronavirus SARS-CoV-2, and lung damage is the leading cause of death in the vast majority of patients. Mainly based on results obtained by autopsies, the seminal features of fatal COVID-19 have been described by many groups worldwide. Early changes encompass edema, epithelial damage, and capillaritis/endothelialitis, frequently combined with microthrombosis. Subsequently, patients with manifest respiratory insufficiency exhibit exudative diffuse alveolar damage (DAD) with hyaline membrane formation and pneumocyte type 2 hyperplasia, variably complicated by superinfection, which may progress to organizing/fibrotic stage DAD. These features, however, are not specific for COVID-19 and can be found in other disorders including viral infections. Clinically, the early disease stage of severe COVID-19 is characterized by high viral load, lymphopenia, massive secretion of pro-inflammatory cytokines and hypercoagulability, documented by elevated D-dimers and an increased frequency of thrombotic and thromboembolic events, whereas virus loads and cytokine levels tend to decrease in late disease stages, when tissue repair including angiogenesis prevails. The present review describes the spectrum of lung pathology based on the current literature and the authors’ personal experience derived from clinical autopsies, and tries to summarize our current understanding and open questions of the pathophysiology of severe pulmonary COVID-19.

Background: Pathological anatomy, patogenesis and the morphogenesis of manifestations and complications of COVID-19 remain insufficiently studied. The fullest information on structural bases of organs and tissues alterations by new coronavirus disease can be obtained as a result of autopsies. Aims: The aim of the study was to study the morphological changes of lungs and other organs of the autopsies of COVID-19 deceased persons. Results of 2000 autopsies of people who died of a severe form of COVID-19 in Moscow, consisting of 1212 men and 788 women, from March 20 to May 22, 2020 (a ratio 1.54:1) aged from 20 to 99 years (on average 68.515.63 years) were presented. This experience was previously generalized in the Atlas COVID-19 pathology. Autopsies were made in the converted interstationary pathoanatomical offices at strict observance of rules of biosafety according to standard and legal documents of WHO, Russian Ministry of Health and Rospotrebnadzor. Results: Morphological changes of lungs with varying severity and extent were detected in all examined cases; however, damage to other organs was also common, which in some cases prevailed over pulmonary changes and was the cause of death. The main morphological changes in lungs were diffuse alveolar damage and microangiopathy, alveolar hemorrhage syndrome, thrombosis, and thromboembolism. Conclusion: The involvement of the lungs, other organs, and vascular system in the pathological process is a result of multiple factors. It is advisable to implement clinical and morphological masks of COVID-19.

Cytauxzoon felis is a tick-borne haemoprotozoan parasite that often causes fatal disease in domestic cats. Histological studies have described substantial pulmonary pathology due to cytauxzoonosis. Published reports were not found describing the thoracic radiographic signs associated with acute cytauxzoonosis in cats. The purpose of this retrospective descriptive study was to describe thoracic radiographic findings in a group of felines with confirmed acute cytauxzoonosis. A total of 37 cats with confirmed cytauxzoonosis and with available thoracic radiographs were included. A subset of 7 cats in this sample also had histopathologic evaluation of their lung parenchyma. Thoracic radiographs were retrieved and reviewed. A bronchial pulmonary pattern was identified as the most common finding (n = 27/37; 73%). Other radiographic findings included cardiomegaly (n = 19/37; 51%), interstitial pattern (n = 17/37; 46%), pleural effusion (n = 12/37; 32%), arterial vascular distension (n = 10/37; 27%), arterial and venous distension (n = 10/37; 27%), and venous distension (n = 1/37; 3%). The primary histological features present in 7 cats with additional histopathologic evaluation, similar to previously published studies, were vascular occlusion. Our study suggests that, despite severe histologic evidence of disease, there are no pathognomonic thoracic radiographic findings in cats with acute cytauxzoonosis.

SARS-CoV-2, the etiologic agent of COVID-19, is a global pandemic with substantial mortality dominated by acute respiratory distress syndrome. We systematically evaluated lungs of 68 autopsies from 3 institutions in heavily hit areas (2 USA, 1 Italy). Detailed evaluation of several compartments (airways, alveolar walls, airspaces, and vasculature) was performed to determine the range of histologic features. The cohort consisted of 47 males and 21 females with a median age of 73 years (range 30-96). Co-morbidities were present in most patients with 60% reporting at least three conditions. Tracheobronchitis was frequently present, independent from intubation or superimposed pneumonia. Diffuse alveolar damage (DAD) was seen in 87% of cases. Later phases of DAD were less frequent and correlated with longer duration of disease. Large vessel thrombi were seen in 42% of cases but platelet (CD61 positive) and/or fibrin microthrombi were present at least focally in 84%. Ultrastructurally, small vessels showed basal membrane reduplication and significant endothelial swelling with cytoplasmic vacuolization. In a subset of cases, virus was detected using different tools (immunohistochemistry for SARS-CoV-2 viral spike protein, RNA in situ hybridization, lung viral culture, and electron microscopy). Virus was seen in airway epithelium and type 2 pneumocytes. IHC or in situ detection, as well as viable form (lung culture positive) was associated with the presence of hyaline membranes, usually within 2 weeks but up to 4 weeks after initial diagnosis. COVID-19 pneumonia is a heterogeneous disease (tracheobronchitis, DAD, and vascular injury), but with consistent features in three centers. The pulmonary vasculature, with capillary microthrombi and inflammation, as well as macrothrombi, is commonly involved. Viral infection in areas of ongoing active injury contributes to persistent and temporally heterogeneous lung damage.

An ongoing pandemic of coronavirus disease (COVID-19) is caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Characterization of the histopathology and cellular localization of SARS-CoV-2 in the tissues of patients with fatal COVID-19 is critical to further understand its pathogenesis and transmission and for public health prevention measures. We report clinicopathologic, immunohistochemical, and electron microscopic findings in tissues from 8 fatal laboratory-confirmed cases of SARS-CoV-2 infection in the United States. All cases except 1 were in residents of long-term care facilities. In these patients, SARS-CoV-2 infected epithelium of the upper and lower airways with diffuse alveolar damage as the predominant pulmonary pathology. SARS-CoV-2 was detectable by immunohistochemistry and electron microscopy in conducting airways, pneumocytes, alveolar macrophages, and a hilar lymph node but was not identified in other extrapulmonary tissues. Respiratory viral co-infections were identified in 3 cases; 3 cases had evidence of bacterial co-infection.

Intravenous injection of medications intended for oral use can lead to pulmonary hypertension and death. Pathologic findings in the lung include embolization of foreign material, with the specific identification of excipients accomplished through special stains. Risk factors for this type of drug abuse include indwelling venous access and chronic medical problems. These risk factors, especially in adolescent and young adult patients, should prompt intravenous drug use as a possibility of lung disease/lesions. We describe 2 patients from a pediatric hospital with pulmonary pathology indicative of intravenous drug use, identified in autopsy and surgical pathology cases. Drug abuse was not clinically suspected in either patient until the time of pathologic exam, emphasizing a need for the pathologist to be able to recognize the associated histologic changes.

The pandemia of coronavirus disease 2019 (COVID-19) has caused more than 355,000 confirmed deaths worldwide. However, publications on postmortem findings are scarce. We present the pulmonary findings in four cases of fatal COVID-19 with a spectrum of lung pathology reflecting disease course and duration, invasive therapies, and laboratory features. Early disease is characterized by neutrophilic, exudative capillaritis with microthrombosis and high levels of IL-1beta and IL-6. Later stages are associated with diffuse alveolar damage and ongoing intravascular thrombosis in small to medium-sized pulmonary vessels, occasionally with areas of infarction equivalents, accompanied by laboratory features of disseminated intravascular coagulation. In late stages, organizing pneumonia with extensive intra-alveolar proliferation of fibroblasts and marked metaplasia of alveolar epithelium can be observed. Viral RNA is encountered in the lung, with virus particles in endothelial cells and pneumocytes. In many patients, multi-organ failure with severe liver damage sets in finally, possibly as consequence of an early-onset pro-inflammatory cytokine storm and/or thrombotic microangiopathy. Electronic supplementary material The online version of this article (10.1007/s00428-020-02881-x) contains supplementary material, which is available to authorized users.

Relevance. Ozone increases the oxygen transport function of the blood. The use of ozone therapy for pulmonary pathology is promising. The effect of ozone therapy is associated with the ability of ozone to eliminate hypoxemia and tissue hypoxia, which is always present in patients with pathology of the bronchopulmonary apparatus. Objective: to study morphofunctional changes in liver tissue, in the dynamics of the use of ozonized water in rats in an experimental model of chronic purulent pneumonia.Materials and methods. Three groups were formed from 30 male white rats (180-200 g). In group 1 (n = 10) healthy rats were injected intraperitoneally with 5 ml of ozonated (0.02 mg / L) 0.9% NaCl once a day for 10 minutes. Course 10 days. Animals of the 2 (n = 10) and 3 (n = 10) groups were first modeled for chronic pneumonia. For this, under local novocaine anesthesia, a 1.5-2.0 cm long incision was made on the animal's neck. A nylon thread with a diameter of 0.4 mm and a length of 10-12 cm was inserted into the lumen of the trachea, between its rings, on a thin piercing needle. The distal end of the thread was located in the lumen of the trachea, and its proximal end was fixed on the skin. The wound was sutured tightly in layers. After 45 days, the thread was removed without opening the trachea. Subsequently, animals of group 2 did not receive treatment. And rats of group 3 were injected once a day with 5 ml of ozonized (0.02 mg / l) 0.9% NaCl for 10 minutes. Course 10 days. The animals were removed from the experiment by instant decapitation. The taken pieces of the liver were fixed in formalin. Histological sections were stained with hematoxylin and eosin. Microscopy was performed using an XS-213 light microscope and a Leica microscope. Results. With prolonged irritation of the respiratory tract, structural changes in the liver, characteristic of toxic hepatitis, were revealed. After treatment with ozonated saline, the morphological picture of the liver improved. In healthy rats, ozone therapy did not have a negative effect on the general condition and behavior of the animals. Conclusions. Treatment with ozonated saline improves the morphological picture of the liver of rats with chronic pneumonia.

Sclerosing pneumocytoma (SP) is a rare benign low-grade tumour of the lung, and typically presents as single discrete coin lesions on imaging. Multiple SP is an exceedingly rare entity and thus reported sparingly. We review the literature on multiple SP, their clinical presentations, histopathology, relevant differential diagnoses and molecular histogenesis of this entity. SP has a predilection for East Asian origin females who have never smoked. Patients are either asymptomatic or have symptoms such as cough, haemoptysis that may be persistent, chest pain if involving the pleura and presents as discrete coin lesion on chest X-ray. Histologically, they are papillary, solid, angiomatoid or sclerotic, or combinations of these four basic patterns. Multiple lesions have the same or slightly different histological patterns. They can be distributed in either lung, in any lobe and can even be bilateral.AKT-1molecular pathways are pivotal in their molecular pathogenesis. In this review, we further propose a classification based on five types of distribution of multiple SP.

Common variable immunodeficiency (CVID) and selective immunoglobulin A deficiency (IgAD) often cause chronic lung disease, but the pulmonary pathologic features of these systemic diseases are poorly recognized by pathologists. It has been claimed that CVID cases show a characteristic combination of noncaseating granulomas-lymphoid proliferations termed granulomatous-lymphocytic interstitial lung disease (GLILD). We present 34 surgical lung biopsy cases of CVID and 4 of IgAD. Noncaseating granulomas were seen in 23/34 (68%) CVID and 2/4 (50%) IgAD cases. A statistically identical pattern of benign lymphoid proliferation was found in CVID and IgAD whether or not granulomas were present. Organizing pneumonia, sometimes considered a part of GLILD, was seen in 25/34 (74%) CVID and 2/4 (50%) IgAD cases and did not correlate with the presence of granulomas. On follow-up, 3 CVID patients died (only 1 of pulmonary disease), while 21 others are alive at 1 to 300 months with no difference by presence or absence of granulomas. Three IgAD patients with follow-up are alive. We conclude that CVID and IgAD are indistinguishable in surgical lung biopsies and a subset of both show patterns that would qualify as GLILD, while other cases lack granulomas but have identical patterns of lymphoid infiltration and organizing pneumonia. We suggest that GLILD is neither a specific nor a useful entity, and biopsies from CVID and IgAD patients should be diagnosed simply by microscopic pattern(s) observed. The prognosis of CVID with lymphoid infiltrates with or without granulomas in this series was good, contrary to claims in the literature about GLILD.

BackgroundRecently in Japan, six workers at a chemical plant that manufactures resins developed interstitial lung diseases after being involved in loading and packing cross-linked water-soluble acrylic acid polymers (CWAAPs). Since CWAAPs are not on the list of occupational diseases, the present study examined the lung damage potential of two CWAAPs (CWAAP-A and CWAAP-B) in rats, investigated pathological mechanisms, and established a method to rapidly evaluate the harmfulness of CWAAPs.MethodsUsing a whole-body inhalation exposure system, male F344 rats were exposed once to 40 or 100 mg/m3 of CWAAP-A for 4 hours or to 15 or 40 mg/m3 of CWAAP-A for 4 hours per day once per week for 2 months (a total of 9 exposures). In a separate set of experiments, male F344 rats were administered 1 mg/kg CWAAP-A or CWAAP-B by intratracheal instillation once every two weeks for 2 months (a total of five doses). Lung tissues, mediastinal lymph nodes, and bronchoalveolar lavage fluid were collected and subjected to biological and histopathological analyses.ResultsA single 4-hour exposure to CWAAP caused alveolar injury, and repeated exposures resulted in regenerative changes in the alveolar epithelium with activation of TGFβ signaling. During the recovery period after the last exposure, some alveolar lesions were partially healed, but other lesions developed into alveolitis with fibrous thickening of the alveolar septum. Rats administered CWAAP-A by intratracheal instillation developed qualitatively similar pulmonary pathology as rats exposed to CWAAP-A by inhalation. At 2 weeks after intratracheal instillation, rats administered CWAAP-B appeared to have a slightly higher degree of lung lesions compared to rats administered CWAAP-A, however, there was no difference in these lesions of CWAAP-A and CWAAP-B in rats examined 18 weeks after administration of these materials.ConclusionsThe present study provides evidence of rat lung pathogenesis after inhalation exposure to CWAAP-A. This study also demonstrates that the lung pathology of rats exposed to CWAAP-A by systemic inhalation was qualitatively similar to that of rats administered CWAAP-A by intratracheal instillation. The use of intratracheal instillation as an adjunct to systemic inhalation is expected to significantly accelerate the risk assessment for a variety of CWAAPs.

Proteus syndrome is characterized by a progressive segmental or patchy growth of bone, skin, adipose tissue, and central nervous system, associated with a wide range of neoplasms, pulmonary pathology, and thrombotic risk. The main histological findings are diffuse patchy overgrowth of skin and subcutaneous tissue, plantar cerebriform connective tissue nevus, and ossification defects. Case report: We present a patient that met the clinical and histological criteria necessary for the diagnosis of the disease. He required multiple surgical interventions, including amputation of the right foot. Genetic evaluation confirmed an AKT1 mutation. Discussion: CLOVES syndrome, neurofibromatosis 1 or PTEN hamartoma tumor syndrome are partially superimposable entities to Proteus syndrome and may generate diagnostic doubt. Although the clinical criteria and histologic findings are indicative, the diagnostic confirmation of this entity is genetic.

Tuberculosis (TB) treatment regimens are lengthy, causing non-adherence to treatment. Inadequate treatment can lead to relapse and the development of drug resistance TB. Furthermore, patients often exhibit residual lung damage even after cure, increasing the risk for relapse and development of other chronic respiratory illnesses. Host-directed therapeutics are emerging as an attractive means to augment the success of TB treatment. In this study, we used C3HeB/FeJ mice as an experimental model to investigate the potential role of rapamycin, a mammalian target of rapamycin inhibitor, as an adjunctive therapy candidate during the treatment of Mycobacterium tuberculosis infection with moxifloxacin. We report that administration of rapamycin with or without moxifloxacin reduced infection-induced lung inflammation, and the number and size of caseating necrotic granulomas. Results from this study strengthen the potential use of rapamycin and its analogs as adjunct TB therapy, and importantly underscore the utility of the C3HeB/FeJ mouse model as a preclinical tool for evaluating host-directed therapy candidates for the treatment of TB., Summary: Rapamycin, an mTOR inhibitor, with or without moxifloxacin, reduces lung inflammation and the number and size of caseating necrotic granulomas in Mycobacterium tuberculosis-infected C3HeB/FeJ mice.

Context Invasive micropapillary adenocarcinoma (MPC) is an aggressive variant of lung adenocarcinoma, frequently manifesting with advanced stage lymph node metastasis and decreased survival. Objective Identification of this morphology is important, as it is strongly correlated with poor prognosis regardless of the amount of MPC component. To date, no study has investigated the morphological criteria used to objectively diagnose it. Design Herein, we selected 30 cases of potential MPC of lung, and distributed 2 digital images per case among 15 pulmonary pathology experts. Reviewers were requested to diagnostically interpret, assign the percentage of MPC component, and record the morphological features they identified. The noted features included: columnar cells, elongated slender cell nests, extensive stromal retraction, lumen formation with internal epithelial tufting, epithelial signet ring-like forms, intracytoplasmic vacuolization, multiple nests in the same alveolar space, back-to-back lacunar spaces, epithelial nest anastomosis, marked pleomorphism, peripherally oriented nuclei, randomly distributed nuclei, small/medium/large tumor nest size, fibrovascular cores, and spread through air-spaces (STAS). Results Cluster analysis revealed three subgroups with the following diagnoses: “MPC”, “combined papillary and MPC”, and “others”. The subgroups correlated with the reported median percentage of MPC. Intracytoplasmic vacuolization, epithelial nest anastomosis/confluence, multiple nests in the same alveolar space, and small/medium tumor nest size were the most common criteria identified in the cases diagnosed as MPC. Peripherally oriented nuclei and epithelial signet ring-like forms were frequently identified in both the “MPC” and “combined papillary and MPC” groups. Conclusions Our study provides objective diagnostic criteria to diagnose MPC of lung.

Following respiratory viral infections or local immunizations, lung resident-memory T cells (TRM) of the CD8 lineage provide protection against the same pathogen or related pathogens with cross-reactive T cell epitopes. Yet, it is now clear that, if homeostatic controls are lost following viral pneumonia, CD8 TRM cells can mediate pulmonary pathology. We recently showed that the aging process can result in loss of homeostatic controls on CD8 TRM cells in the respiratory tract. This may be germane to treatment modalities in both influenza and coronavirus disease 2019 (COVID-19) patients, particularly, the portion that present with symptoms linked to long-lasting lung dysfunction. Here, we review the developmental cues and functionalities of CD8 TRM cells in viral pneumonia models with a particular focus on their capacity to mediate heterogeneous responses of immunity and pathology depending on immune status.

Purpose of review COVID-19 lung injury is a common manifestation of severe illness. Lung tissue examination has been largely derived from autopsy - a combination of case reports, small and moderately sized series with international scope. Common and uncommon histopathology provides insight into the progression of severe, fatal disease. Recent findings COVID-19 lung histology is most commonly diffuse alveolar damage as part of acute respiratory distress syndrome. Lung injury can be temporally heterogeneous, with patterns of healing alongside new injury. Viral studies, including immunohistochemistry, RNA in-situ hybridization, and tissue-based Polymerase chain reaction (PCR) assist in discerning complications of therapy (e.g. ventilator-associated pneumonia) from primary viral-induced injury. Response to viral infection produces systemic effects, and one major manifestation is thrombosis of micro-circulation and larger vessels. Less common patterns include neutrophil-rich inflammation, raising speculation that neutrophil extra-cellular traps may play a role in both viral control and exaggerated immune response. Summary The heterogeneity of fatal cases- persistence of viral infection in lung, clearance of virus but severe lung injury, thrombosis, and exaggerated immune response - suggest that antiviral, antithrombotic, anti-inflammatory, and supportive therapy play a role in treatment, but that the patient-specific cause and timing of the lung injury is important in choosing intervention.

Pediatric pulmonary pathology is a challenging topic within pathology. There are several reasons, such as diseases of the lung are rare. Most pulmonary diseases within childhood are infections, which do not need a tissue analysis. Lung diseases in childhood do occur in two peaks: the first during the first 2 years of life, the second usually at the “Kindergarden” age. The first group comprises many developmental lung diseases, whereas the second group includes diseases based on gene mutations, immune system dysfunction, and infections. For the analysis of pediatric pulmonary diseases, the knowledge of lung development is essential, and the analysis of genetic abnormalities is becoming important.

The use of immunohistochemistry for the determination of pulmonary carcinoma biomarkers is a well-established and powerful technique. Immunohistochemisty is readily available in pathology laboratories, is relatively easy to perform and assess, can provide clinically meaningful results very quickly, and is relatively inexpensive. Pulmonary predictive biomarkers provide results essential for timely and accurate therapeutic decision making; for patients with metastatic non–small cell lung cancer, predictive immunohistochemistry includes ALK and programmed death ligand-1 (PD-L1) (ROS1, EGFR in Europe) testing. Handling along proper methodologic lines is needed to ensure patients receive the most accurate and representative test outcomes.

Objectives Current knowledge of the pulmonary pathology of coronavirus disease 2019 (COVID-19) is based largely on postmortem studies. In most, the interval between disease onset and death is relatively short ( Methods We conducted a retrospective case series. Results The first patient developed acute respiratory failure and was started on extracorporeal membrane oxygenation (ECMO) on day 21, with subsequent hemothorax. Debridement (day 38) showed extensive lung infarction with diffuse alveolar damage and Candida overgrowth. The second patient developed acute respiratory failure requiring mechanical ventilation that did not improve despite ECMO. Surgical lung biopsy on day 74 showed diffuse interstitial fibrosis with focal microscopic honeycomb change. The third patient also required ECMO and underwent bilateral lung transplantation on day 126. The explanted lungs showed diffuse interstitial fibrosis with focal microscopic honeycomb change. Conclusions This series provides histologic confirmation that complications of COVID-19 after 8 weeks to 4 months of severe disease include lung infarction and diffuse interstitial fibrosis.

Thymoma is the commonest epithelial neoplasm arising from thymus gland. Tumour is slow growing and in the absence of metastasis, surgery is the treatment of choice. Complete resection and bland morphology are important prognostic features. However, a significant proportion of these tumours tend to recur. These recurrent tumours, advanced thymomas and thymic carcinomas require platinum-based combination chemotherapy and radiotherapy. Efforts are being made to explore additional treatment modalities to control disease with the aim of improving survival. Number of thymoma cases worldwide is small in comparison to lung cancers. As a result, fewer studies have been carried out to enhance our understanding of molecular events responsible for the initiation, maintenance, and progression of thymomas. Inspite of this there are advances in understanding the pathology of thymic epithelial neoplasms including genetics, PD-L1 and molecular testing which has bearing on the prognosis, post-surgical management, and testing algorithm. Similar to pulmonary pathology, thymic epithelial tumours will require adequate tumour sampling to carry out ancillary testing. Mutational analytical tests include EGFR, RAS, BRAF, RET, AKT1, PIK3CA and T53 genes. If adequate sample is available (upto100 cells), PD-L1 testing should be considered for immunotherapy in recurrent/ advanced thymomas and thymic carcinomas. This list is likely to expand in future with increasing emphasis on molecular testing to support treatment with newer therapies.

A growing number of international postmortem studies identify acute and organizing diffuse alveolar damage (DAD) as the main pathologic feature of lung injury in patients with COVID-19. Other forms of acute lung injury, including organizing pneumonia, and acute fibrinous and organizing pneumonia are seen. Acute neutrophilic infiltrates have been observed, most frequently as the manifestation of a superimposed bacterial pneumonia. SARS-CoV-2 has been detected in type I and type II pneumocytes and bronchial epithelial cells using electron microscopy, immunohistochemistry, and in situ hybridization, and likewise, viral transcripts were localized with RNA probes in pneumocytes. However, the presence of true viral cytopathic effect seen with light microscopy remains to be defined. Interestingly, vascular changes are frequently observed in association with DAD, which include severe endothelial injury/endothelialitis, hemorrhage, and thrombotic and microangiopathic vasculopathy. Since similar vascular changes also occur in cases of DAD independent of the etiology, whether the vascular pathology in COVID lungs has unique features and represents a separate pathologic process is under investigation.

We aimed to investigate the relationship of radiological features and the corresponding pulmonary pathology of patients with Coronavirus Disease (COVID-19) pneumonia.In this multicenter study, serial chest CT and radiographic images from 9 patients (51-85 years old, 56% male) were reviewed and analyzed. Postmortem lungs were sampled and studied from these autopsies, with a special focus on several corresponding sites based on imaging features.The predominant pattern of pulmonary injury in these 9 cases was diffuse alveolar damage (DAD) and interstitial inflammation. Moreover, acute fibrinous exudates, organization, inflammatory cell infiltration, hyaline membranes, pulmonary edema, pneumocyte hyperplasia, and fibrosis were all observed. The histopathology features varied according to the site and severity of each lesion. In most of the 9 cases, opacities started from a subpleural area and peripheral structures were more severely damaged based on gross views and pathological examinations. Fibrosis could occur in early stages of infection and this was supported by radiological and pathological findings. The radiological features of COVID-19 pneumonia, at the critically ill stage, were diffuse ground-glass opacities with consolidation, interstitial thickening, and fibrous stripes, which was based in the fibrous tissue proliferation in the alveolar and interlobular septa, and filled alveoli with organizing exudation. Fungal and bacterial co-infections were also observed in 6 cases.Typical imaging features can be correlated with underlying pathological findings. Combining assessments of imaging features with pathological findings therefore can enhance our understanding of the histopathological mechanism of COVID-19 pneumonia, and facilitate early radiological diagnosis and prognosis estimation of COVID-19 pneumonia, which has important implications for the development of clinical targeted treatments and research related to COVID-19 pneumonia.

Background Coronavirus disease 2019 (COVID-19), which started in Wuhan, China, in late December 2019, was declared a pandemic, infecting more than twelve million people worldwide. Few studies have reported the findings of lung biopsies in COVID-19. Here, granulomatous inflammation was reported for the first time in COVID-19 lung biopsy. Case presentation A 54-year-old woman presented to a primary care facility with fever, dry cough, and fatigue. Antibiotherapy was administered for 10 days with the diagnosis of upper respiratory tract infection. However, her condition did not improve and she was admitted to the hospital. In physical examination, crepitant rales were heard in both lungs. Anemia and thrombocytopenia were detected in laboratory tests and she was referred to the hematology clinic. Bone marrow aspiration and flow cytometry showed she had acute myeloid leukemia. Computed tomography-integrated positron emission tomography with a history of previous breast cancer revealed a heterogeneous mass-like lesion in the left lung. The primary malignancy could not be ruled out and tru-cut biopsy was performed. Tests for tuberculosis were negative. Throat swab sample was taken and a real-time polymerase chain reaction confirmed that she had COVID-19. Radiological findings were evaluated as the progression of COVID-19 pneumonia on computed tomography 6 days after biopsy. Alveolar damage, edema, vascular congestion, mild inflammatory infiltration, type-2 pneumocyte hyperplasia, interstitial fibrosis, early fibrotic changes, fibrinous, organized pneumonia pattern, noncaseating granulomatous inflammation, and desquamation in alveolar epithelial cells were noted in lung biopsy. Conclusions There were only a few case reports that described lung biopsy findings in COVID-19 at the time of manuscript preparation. This was the first case of noncaseating granulomatous inflammation described in a COVID-19 case.

Objective — to determine the diagnostic indicators of various histochemical and immunohistochemical methods for the detection of M. tuberculosis and their antigens in lung tissue in HIV-infected patients.Materials and methods. The morphological study included 37 cases of biopsy, surgical and autopsy material of fragments of the lungs, lymph nodes and parietal pleura in HIV-infected patients. Serial sections were stained with hematoxylin and eosin, method of Ziehl—Neelsen (ZN), the traditional fluorescence method (FM), and immunohistochemical studies, without (IHC) and with a fluorescent label (FITC). The sensitivity, specificity and effectiveness of each method were calculated taking into account the final clinical diagnosis and the results of the microbiological detection of M. tuberculosis.Results and discussion. At the time of hospitalization of HIV-infected patients in 56.8 % of cases the results of clinical, laboratory and radiological data did not allow to determine the nature of the pathological process. According to the results of our study, the highest sensitivity was established for IHC and FM methods — 100.0 and 88.5 % respectively. The ZN method showed the highest specificity index (100.0 %), while the specificity of the FITC and FM method was 75.0 and 60.0 % respectively. The highest diagnostic efficacy indicators were established for IHC and FM methods — 83.8 and 72.2 %. The overall effectiveness of all 4 special histological examination methods was 72.1 %. As a result of an extended histological examination, the main diagnosis of mycobacterial infection was confirmed in 64.8 % cases, including an association with fungal infection in 29.7 % cases. In 10.8 % cases, the diagnosis of mycobacterial infection was withdrawn, and in these cases a fungal infection was diagnosed as the main pulmonary pathology. In 10.8 % cases the presence of mycobacterial infection as a background pathology with other diseases of the chest cavity was proved. The result of a comprehensive histological examination allowed to establish a final clinical diagnosis in 94.6 % cases, and to confirm the presence of mycobacterial infection in 81.1 % cases. In 13.5 % cases there was discrepancy in the histological picture at traditional staining and the results of additional histological methods of staining the preparations.Conclusions. Taking into account the variety of respiratory pathology in HIV-infected patients, including infectious ones, in order to establish a final clinical diagnosis during the diagnostic process, if there is a suspicion of mycobacterial infection, it is advisable to conduct a comprehensive morphological study using various histological methods for diagnosing infections., Цель работы — определить диагностические показатели различных гистохимических и иммуногис­тохимических методов выявления M. tuberculosis и их антигенов в легочной ткани ВИЧ-инфицирован­ных пациентов.Материалы и методы. Морфологическое исследование включало 37 случаев биопсийного, опера­цион­ного и аутопсийного материала фрагментов легких, лимфатических узлов и париетальной плевры ВИЧ-инфицированных пациентов. Серийные срезы окрашивали гематоксилином и эозином, по Цилю—Нильсену (ЦН), традиционным флуоресцентным методом (ФМ) и с применением иммуногис­тохимического (ИГХ) исследования, без и с флуоресцентной меткой (FITC). Рассчитывали чувствительность, специфичность и эффективность каждого из методов с учетом заключительного клинического диагноза и результатов микробиологического выявления M. tuberculosis.Результаты и обсуждение. На момент госпитализации ВИЧ-инфицированных пациентов в 56,8 % случаев результаты клинико-лабораторных и рентгенологических данных не позволили определить характер патологического процесса. По результатам нашего исследования наибольшая чувствительность установлена для ИГХ и ФМ-методов — 100,0 и 88,5 % соответственно. Метод ЦН продемонстрировал самый высокий показатель специфичности (100,0 %), тогда как специфичность FITC и ФМ-ме­­тода составила 75,0 и 60,0 % соответственно. Самые высокие показатели диагностической эффективнос­ти установлены для ИГХ и ФМ-методов — 83,8 и 72,2 %. Общая эффективность всех 4 специальных методов гистологического исследования составила 72,1 %. В результате расширенного гистологического исследования в 64,8 % случаев подтвержден основной диагноз микобактериальной инфекции, в том числе в 29,7 % случаев установлена ассоциация с грибковой инфекцией. В 10,8 % случаев диагноз микобактериальной инфекции был снят, и в этих случаях диагностировали грибковую инфекцию как основную легочную патологию. В 10,8 % случаев доказано наличие микобактериальной инфекции как фоновой патологии при других заболеваниях органов грудной полости. Результат комплексного гистологического исследования дал возможность установить окончательный клинический диагноз в 94,6 % случаев и подтвердить наличие микобактериальной инфекции в 81,1 % случаев. В 13,5 % случаев имело место расхождение гистологической картины при традиционном окрашивании и результатов дополнительных гистологических методов окраски препаратов.Выводы. Учитывая разнообразие патологии органов дыхания у ВИЧ-инфицированных пациентов, в том числе инфекционной, для установления окончательного клинического диагноза в ходе диагностического процесса, при наличии подозрения микобактериальной инфекции, целесообразно проводить комплексное морфологическое исследование с использованием различных гистологических методов диагностики инфекций., Мета роботи — визначити діагностичні показники різних гістохімічних та імуногістохімічних методів виявлення M. tuberculosis та їхніх антигенів у легеневій тканині ВІЛ-інфікованих пацієнтів.Матеріали та методи. Морфологічне дослідження включало 37 випадків біопсії, операційного та автопсійного матеріалу фрагментів легень, лімфатичних вузлів та парієтальної плеври ВІЛ-інфікованих пацієнтів. Серійні зрізи фарбували гематоксиліном та еозином, за Цілем—Нільсеном (ЦН), традиційним флуоресцентним методом (ФМ), із застосуванням імуногістохімічного дослід­ження, без ІГХ та з флуоресцентною міткою (FITC). Розраховували чутливість, специфічність та ефективність кожного з методів з урахуванням остаточного клінічного діагнозу та результатів мікробіологічного виявлення M. tuberculosis.Результати та обговорення. На момент госпіталізації ВІЛ-інфікованих пацієнтів у 56,8 % випадків результати клініко-лабораторних та рентгенологічних даних не дали змоги визначити характер патологічного процесу. За результатами нашого дослідження найбільшу чутливість встановлено для ІГХ та ФМ-методів — 100,0 та 88,5 % відповідно. Метод ЦН продемонстрував найвищий показник специфічності (100,0 %), тоді як специфічність FITC та ФМ-методу склала 75,0 і 60,0 % відповідно. Найвищі показники ефективності встановлено для ІГХ та ФМ-методів — 83,8 та 72,2 %. Загальна ефективність усіх 4 спеціальних методів гістологічного дослідження склала 72,1 %. У результаті розширеного гістологічного дослідження у 64,8 % випадків підтверджено основний діагноз мікобактеріальної інфекції, у тому числі у 29,7 % випадків встановлено асоціацію з грибковою інфекцією. У 10,8 % випадків діагноз мікобактеріальної інфекції було знято, та у цих випадках діагностували грибкову інфекцію як основну легеневу патологію. У 10,8 % випадків доведено наявність мікобактеріальної інфекції як фонової патології при інших захворюваннях органів грудної порожнини. Результат комплексного гістологічного дослідження дав можливість встановити остаточний клінічний діагноз у 94,6 % випадків та підтвердити наявність мікобактеріальної інфекції у 81,1 % випадків. У 13,5 % випадків мала місце розбіжність гістологічної картини при традиційному фарбуванні та результатів додаткових гістологічних методів фарбування препаратів.Висновки. З огляду на різноманітність патології органів дихання у ВІЛ-інфікованих пацієнтів, зокрема й інфекційної, для встановлення остаточного клінічного діагнозу в ході діагностичного процесу, за наявності підозри на мікобактеріальну інфекцію, доцільно проводити комплексне морфологічне дослідження з використанням різних гістологічних методів діагностики.

ObjectivesAlthough diffuse alveolar damage, a subtype of acute lung injury (ALI), is the most common microscopic pattern in coronavirus disease 2019 (COVID-19), other pathologic patterns have been described. The aim of the study was to review autopsies from COVID-19 decedents to evaluate the spectrum of pathology and correlate the results with clinical, laboratory, and radiologic findings.MethodsA comprehensive and quantitative review from 40 postmortem examinations was performed. The microscopic patterns were categorized as follows: “major” when present in more than 50% of cases and “novel” if rarely or not previously described and unexpected clinically.ResultsThree major pulmonary patterns were identified: ALI in 29 (73%) of 40, intravascular fibrin or platelet-rich aggregates (IFPAs) in 36 (90%) of 40, and vascular congestion and hemangiomatosis-like change (VCHL) in 20 (50%) of 40. The absence of ALI (non-ALI) was novel and seen in 11 (27%) of 40. Compared with ALI decedents, those with non-ALI had a shorter hospitalization course (P = .02), chest radiographs with no or minimal consolidation (P = .01), and no pathologically confirmed cause of death (9/11). All non-ALI had VCHL and IFPAs, and clinically most had cardiac arrest.ConclusionsTwo distinct pulmonary phenotypic patterns—ALI and non-ALI—were noted. Non-ALI represents a rarely described phenotype. The cause of death in non-ALI is most likely COVID-19 related but requires additional corroboration.

This paper collates the pathological findings from initial published autopsy reports on 23 patients with coronavirus disease 2019 (COVID-19) from 5 centers in the United States of America, including 3 cases from Houston, Texas. Findings confirm that COVID-19 is a systemic disease with major involvement of the lungs and heart. Acute COVID-19 pneumonia has features of a distinctive acute interstitial pneumonia with a diffuse alveolar damage component, coupled with microvascular involvement with intra- and extravascular fibrin deposition and intravascular trapping of neutrophils, and, frequently, with formation of microthombi in arterioles. Major pulmonary thromboemboli with pulmonary infarcts and/or hemorrhage occurred in 5 of the 23 patients. Two of the Houston cases had interstitial pneumonia with diffuse alveolar damage pattern. One of the Houston cases had multiple bilateral segmental pulmonary thromboemboli with infarcts and hemorrhages coupled with, in nonhemorrhagic areas, a distinctive interstitial lymphocytic pneumonitis with intra-alveolar fibrin deposits and no hyaline membranes, possibly representing a transition form to acute fibrinous and organizing pneumonia. Multifocal acute injury of cardiac myocytes was frequently observed. Lymphocytic myocarditis was reported in 1 case. In addition to major pulmonary pathology, the 3 Houston cases had evidence of lymphocytic pericarditis, multifocal acute injury of cardiomyocytes without inflammatory cellular infiltrates, depletion of splenic white pulp, focal hepatocellular degeneration and rare glomerular capillary thrombosis. Each had evidence of chronic cardiac disease: hypertensive left ventricular hypertrophy (420 g heart), dilated cardiomyopathy (1070 g heart), and hypertrophic cardiomyopathy (670 g heart). All 3 subjects were obese (BMIs of 33.8, 51.65, and 35.2 Kg/m2). Overall, the autopsy findings support the concept that the pathogenesis of severe COVID-19 disease involves direct viral-induced injury of multiple organs, including heart and lungs, coupled with the consequences of a procoagulant state with coagulopathy.

Background. Currently, the patho- and morphogenesis of the new coronavirus infection (COVID-19) is being studied in depth. A comparative analysis of the morphological changes in the lungs of deceased patients is of importance, for various time periods after the onset of the first clinical symptoms. The clinical and morphological comparison should help to increase the qualified medical care for patients in the resuscitation profile and reduce the hospital mortality. The aim of the study was to formulate a working hypothesis for a conceptual scheme of clinical and morphological phases of development of the new coronavirus infection (COVID-19). Methods. An analysis of 80 fatal cases was carried out in the COVID-center of the Federal Research Clinical Center of FMBA of Russia. Along with the assessment of macro- and microscopic changes in the respiratory tract, additional histochemical van Gieson staining was applied and immunohistochemical studies were performed to assess the condition of the COVID-19-affected lungs. Results. The revealed features of diffuse alveolar damage in the case of the new coronavirus infection (COVID-19) made it possible to present a working hypothesis of the pathomorphogenesis of COVID-19 interstitial pneumonia. It proceeds through 3 phases: fulminant, persistent and fibrotic. Each phase is conditionally limited by certain time parameters and is characterized by certain morphological signs Dysregulatory activation of monocytic phagocytes, development of generalized microthrombosis, persistent signs of the exudative phase, pathological repair, progressive intraalveolar and interstitial fibrosis are the main links in the pathomorphogenesis of COVID-19 interstitial pneumonia. In response to the penetration of SARS-CoV-2, the T-cell immunity reactions prevail at the exudative and proliferative stages. At the fibrotic stage, the overall number of T-lymphocytes is drastically decreased, the cells of humoral immunity are not revealed. The CD8+ T-lymphocytes prevailing over CD4+ T-lymphocyte helpers is probably related to the autoimmune damage mechanisms. Conclusions. Damage to the lungs with the development of COVID-19 interstitial pneumonia is the main cause of the severe course of the disease and deaths. The revealed features of the pathomorphogenesis of the clinical and morphological phases of COVID-19 interstitial pneumonia will improve the quality of diagnosis and treatment of a new coronavirus infection (COVID-19).

We detail a novel presentation of tuberculosis associated with intestinal perforation in an endangered Australian sea lion (Neophoca cinerea) from South Australian waters and confirm the presence of this disease in the region of highest pup production. In February 2017, a 3-yr-old juvenile male died shortly after hauling out at the Kingscote beach on Kangaroo Island. On postmortem examination, we found a mid-jejunal intestinal perforation and partial obstruction (from a strangulating fibrous and granulomatous mesenteric mass), a marked multicentric abdominal fibrosing granulomatous lymphadenitis, and a large volume serosanguinous peritoneal effusion. Acid-fast bacteria were detected postmortem in cytologic preparations of the mesenteric lymph node and in histologic sections of jejunum and the encircling mass. Mycobacterial infection was confirmed by positive culture after 3 wk. Molecular typing using mycobacterial interspersed repetitive-unit-variable-number tandem-repeat typing with 12-locus analysis identified Mycobacterium pinnipedii. This case highlights the need for vigilance of zoonotic disease risk when handling pinnipeds, including in the absence of specific respiratory signs or grossly apparent pulmonary pathology. Increased serologic population surveillance is recommended to assess the species' risk from this and other endemic diseases, especially given its endangered status.

There is currently a lack of pathologic data on the novel coronavirus (severe acute respiratory syndrome coronavirus 2) pneumonia, or coronavirus disease 2019 (COVID-19), from autopsy or biopsy. Two patients who recently underwent lung lobectomies for adenocarcinoma were retrospectively found to have had COVID-19 at the time of the operation. These two cases thus provide important first opportunities to study the pathology of COVID-19. Pathologic examinations revealed that apart from the tumors, the lungs of both patients exhibited edema, proteinaceous exudate, focal reactive hyperplasia of pneumocytes with patchy inflammatory cellular infiltration, and multinucleated giant cells. Hyaline membranes were not prominent. Because both patients did not exhibit symptoms of pneumonia at the time of operation, these changes likely represent an early phase of the lung pathology of COVID-19 pneumonia.

Objectives To report the methods and findings of two complete autopsies of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive individuals who died in Oklahoma (United States) in March 2020. Methods Complete postmortem examinations were performed according to standard procedures in a negative-pressure autopsy suite/isolation room using personal protective equipment, including N95 masks, eye protection, and gowns. The diagnosis of coronavirus disease 2019 (COVID-19) was confirmed by real-time reverse transcriptase polymerase chain reaction testing on postmortem swabs. Results A 77-year-old obese man with a history of hypertension, splenectomy, and 6 days of fever and chills died while being transported for medical care. He tested positive for SARS-CoV-2 on postmortem nasopharyngeal and lung parenchymal swabs. Autopsy revealed diffuse alveolar damage and chronic inflammation and edema in the bronchial mucosa. A 42-year-old obese man with a history of myotonic dystrophy developed abdominal pain followed by fever, shortness of breath, and cough. Postmortem nasopharyngeal swab was positive for SARS-CoV-2; lung parenchymal swabs were negative. Autopsy showed acute bronchopneumonia with evidence of aspiration. Neither autopsy revealed viral inclusions, mucus plugging in airways, eosinophils, or myocarditis. Conclusions SARS-CoV-2 testing can be performed at autopsy. Autopsy findings such as diffuse alveolar damage and airway inflammation reflect true virus-related pathology; other findings represent superimposed or unrelated processes.

There is currently a lack of pathologic data on the novel coronavirus (severe acute respiratory syndrome coronavirus 2) pneumonia, or coronavirus disease 2019 (COVID-19), from autopsy or biopsy. Two patients who recently underwent lung lobectomies for adenocarcinoma were retrospectively found to have had COVID-19 at the time of the operation. These two cases thus provide important first opportunities to study the pathology of COVID-19. Pathologic examinations revealed that apart from the tumors, the lungs of both patients exhibited edema, proteinaceous exudate, focal reactive hyperplasia of pneumocytes with patchy inflammatory cellular infiltration, and multinucleated giant cells. Hyaline membranes were not prominent. Because both patients did not exhibit symptoms of pneumonia at the time of operation, these changes likely represent an early phase of the lung pathology of COVID-19 pneumonia.

Since its initial recognition in December 2019, Coronavirus disease 19 (COVID-19) has quickly spread to a pandemic infectious disease. The causative agent has been recognized as a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), primarily affecting the respiratory tract. To date, no vaccines are available nor any specific treatment. To limit the number of infections, strict directives have been issued by governments that have been translated into equally rigorous guidelines notably for post-mortem examinations by international and national scientific societies. The recommendations for biosafety control required during specimen collection and handling have strongly limited the practice of autopsies of the COVID-19 patients to a few adequate laboratories. A full pathological examination has always been considered an important tool to better understand the pathophysiology of diseases, especially when the knowledge of an emerging disorder is limited and the impact on the healthcare system is significant. The first evidence of diffuse alveolar damage in the context of an acute respiratory distress syndrome has now been joined by the latest findings that report a more complex scenario in COVID-19, including a vascular involvement and a wide spectrum of associated pathologies. Ancillary tools such as electron microscopy and molecular biology used on autoptic tissue samples from autopsy are also significantly contributing to confirm and/or identify new aspects useful for a deeper knowledge of the pathogenetic mechanisms. This article will review and summarize the pathological findings described in COVID-19 until now, chiefly focusing on the respiratory tract, highlighting the importance of autopsy towards a better knowledge of this disease.

Pulmonary immunity requires tight regulation, as interstitial inflammation can compromise gas exchange and lead to respiratory failure. Here we found a greater number of aged CD11bhiL-selectinloCXCR4+ polymorphonuclear leukocytes (PMNs) in lung vasculature than in the peripheral circulation. Using pulmonary intravital microscopy, we observed lung PMNs physically interacting with B cells via β2 integrins; this initiated neutrophil apoptosis, which led to macrophage-mediated clearance. Genetic deletion of B cells led to the accumulation of aged PMNs in the lungs without systemic inflammation, which caused pathological fibrotic interstitial lung disease that was attenuated by the adoptive transfer of B cells or depletion of PMNs. Thus, the lungs are an intermediary niche in the PMN lifecycle wherein aged PMNs are regulated by B cells, which restrains their potential to cause pulmonary pathology.

OBJECTIVES: Assess the pathologic changes in the lungs of COVID-19 decedents and correlate these changes with demographic data, clinical course, therapies, and duration of illness. METHODS: Lungs of 12 consecutive COVID-19 decedents consented for autopsy were evaluated for gross and histopathologic abnormalities. A complete Ghon "en block" dissection was performed on all cases; lung weights and gross characteristics recorded. Immunohistochemical studies were performed to characterize lymphocytic infiltrates and to assess SARS-CoV-2 capsid protein. RESULTS: Two distinct patterns of pulmonary involvement were identified. Three of 12 cases demonstrated a predominance of acute alveolar damage (DAD) while 9 of 12 cases demonstrated a marked increase in intra-alveolar macrophages in a fashion resembling desquamative interstitial pneumonia or macrophage activation syndrome (DIP/MAS). Two patterns were correlated solely with a statistically significant difference in the duration of illness. The group exhibiting DAD had duration of illness of 5.7 days while the group with DIP/MAS had duration of illness of 21.5 days (t-test p = 0.014). CONCLUSIONS: The pulmonary pathology of COVID-19 patients demonstrates a biphasic pattern, an acute phase demonstrating DAD changes while the patients with a more prolonged course exhibit a different pattern that resembles DIP/MAS-like pattern. The potential mechanisms and clinical significance are discussed.

This case series analyzes brains from autopsies of patients who died of coronavirus disease 2019 as confirmed by nucleic acid test and with severe pulmonary pathology.