Lung Aspergillus niger infection after SARS-CoV2

A 64-year-old never-smoker man, with professional exposure, presented to Marius Nasta Pneumophtisiology Institute for fatigability to effort, in the context of severe SARS-COV2 infection one month previously. His medical history includes pulmonary tuberculosis (55 years ago) and newly diagnosed type II diabetes (261 mg/dL glycemia). The thoracic tomography computer in the immediate post-COVID period (Fig. 1A) revealed the presence of glass ground lesions and a 3 cm nodule with cystic degeneration in the upper left lobe. A gross examination of the specimen identified a condensation area of 2.5 cm diameter, brown-grey colored, with necrosis and central ulceration. Microscopic examination showed the presence of bronchiectasis with squamous metaplasia of the epithelium, which appears ulcerated;numerous calcium oxalate crystals with adjacent foreign body granulomatous reaction;endobronchial are present fibrinous and inflammatory debris, brown-black pigment, and septate, dichotomous branching hyphae, suggestive of Aspergillus spp. A periodic acid-Schiff stain was performed, identifying the fungal hyphae. The histopathological diagnosis was bronchiectasis supra-infected and colonized with fungal filaments (Aspergillus niger).

Esophageal Mucosal Calcinosis: A Rare Site of Calcium Deposition in End-Stage Renal Disease

Introduction: Calciphylaxis, otherwise known as calcium uremic arteriolopathy, is defined as calcium deposition around blood vessels in skin and fat tissue which occurs in 1-4% of patients with end-stage renal disease (ESRD). Calcium deposition in the esophagus is extremely rare;to date, there have been only 4 cases reported worldwide. We report the fifth case of esophageal mucosal calcinosis occurring in a young male with ESRD. Case Description/Methods: A 37-year-old Thai man with ESRD on peritoneal dialysis since 2005 presented with generalized weakness and odynophagia due to oral ulcers, resulting in poor PO intake. He denied drinking alcohol, illicit drug use, or smoking. On exam his abdomen was soft, non-distended, non-tender, without any guarding. Past medical history included hypertension and COVID-19 in January 2022. Laboratory tests revealed neutropenia and pancytopenia, hyperphosphatemia, and hypocalcemia. EGD revealed distal esophageal esophagitis and hemorrhagic erosive gastropathy. Biopsy showed ulcerative esophagitis with dystrophic calcification, consistent with esophageal mucosal calcinosis .No intestinal metaplasia was noted. Immunohistochemistry was negative for CMV, HSV1, and HSV2. The patient was treated with pantoprazole 40mg IV every 12 hours, Magic Mouthwash 5ml qid, and Carafate 10mg qid. He was transferred to a cancer center where he had a bone marrow biopsy formed which was negative. His symptoms resolved and the patient was discharged to home (Figure). Discussion(s): Esophageal mucosal calcinosis is extremely rare. It is due to a combination of factors involving acidosis and the phenotypic differentiation (and apoptosis) of vascular smooth muscle cells (VSMC) into chondrocytes or osteoblast-like cells. These changes, along with the passive accumulation of calcium and phosphate, induce calcification. Acidosis is well-known to promote inflammation of the arterial walls, releasing cytokines that induce vascular calcification. The benefits of treatment with sodium thiosulfate remain unclear. An ample collection of cases should help devise standardized treatment options and establish management guidelines for this condition.

A case of type 2 autoimmune pancreatitis with spontaneous remission.

A 70-year-old man with epigastric pain was referred to our hospital. Computed tomography and magnetic resonance imaging showed the diffusely enlarged pancreas compared to his normal pancreas 6 months prior to presentation. Serum levels of IgG4 and amylase were normal, while C-reactive protein was slightly elevated. Endoscopic ultrasound-guided fine-needle biopsy of the pancreas revealed acinar-ductal metaplasia with neutrophil infiltration and without infiltration of IgG4-positive plasma cells. After the clinical diagnosis of type 2 autoimmune pancreatitis (AIP), his symptoms spontaneously improved without steroid therapy. Three months later, radiological findings showed improved pancreas size and serological findings. The pathological diagnosis of type 2 AIP using endoscopic ultrasound-guided fine-needle biopsy is challenging, particularly for proving granulocyte epithelial lesions. This was a valuable type 2 AIP case in which the images before, at the time of onset, and at the time of spontaneous remission were evaluated.

COVID-Associated Mucormycosis in Case of Fibrous Dysplasia of Maxilla: Freeing 2 Birds With 1 Key

Introduction: India is one of the countries most affected by COVID-19. COVID-19-associated mucormycosis (CAM) has added to the woes of the already devastating effects of the virus. About 97.6% of cases in India presented with rhino-orbito-cerebral disease. Fibrous dysplasia (FD) is characterized by abnormal mixtures of fibrous and osseous elements leading to bony deformities and pathological fractures. Monostotic and polyostotic varieties have been described, with the latter being more common in children. The monostotic type of FD accounts for about 70% to 80% of FD, affecting the second and third decade. Method(s): We present a case of 44-year-old man with fibrous dysplasia of left maxilla with CAM, an angioinvasive fungal disease associated with high morbidity and mortality. As India and the entire world is struck by the COVID-19 pandemic, the use of corticosteroids has proven somewhat helpful in managing severe COVID infection. Evidence shows it has also led to CAM. Our patient was treated with radical surgical treatment of lesion with gross removal of all necrotic tissues from the sinuses along with antifungal treatment with amphotericin B. FD is a benign disorder characterized by replacement of normal bone with cellular fibrous connective tissue. Result(s): Our case presented with CAM of maxilla with palatal involvement requiring urgent surgical intervention and antifungal therapy. It incidentally happened to be a case of FD. Maxillectomy took care of the patient's FD as well. Conclusion(s): FD is a disorder characterized by dystrophy and bony metaplasia, and treatment depends on the zone of involvement. Early diagnosis and surgical intervention, with good antifungal therapy with strict glycemic control, are critical features to prevent its onslaught. Sometimes treatment of one condition can cure the others as well.

ROLE OF DEBULKING FOR BENIGN ENDOBRONCHIAL LESIONS: A CASE OF CHRONICALLY ASPIRATED FOREIGN BODY PRESENTING AS NECROTIZING PNEUMONIA

SESSION TITLE: Case Reports of Procedure Treatments Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Foreign body aspiration can affect ventilation-oxygenation dynamics causing significant morbidity and mortality in children and adults. Patient presentation can range from asymptomatic to life-threatening hypoxia. A thorough history and physical examination helps in narrowing differential diagnosis and provision of timely management. A myriad of complications can occur from aspirated Foreign body including recurrent pneumonia, lung abscess, obstructive emphysema, and death. Here we present a case of a patient with recurrent pneumonia from a chronically aspirated foreign body. CASE PRESENTATION: 37-year-old male with past medical history of a recent COVID-19 infection and bronchus intermedius endobronchial mass (squamous metaplasia on biopsy 2009) who presented with fever, chest pain, worsening dyspnea. Initial workup was consistent with severe sepsis. A CT chest showed complete collapse, cavitation in right lower lobe and presence of right bronchus stent. Patient was treated with IV fluids and antibiotics during the hospitalization. He underwent bronchoscopy for airway examination and bronchoalveolar lavage. Airway exam showed a large endobronchial mass in the bronchus intermedius. Endobronchial biopsies were taken, followed by tissue debulking using flexible forceps and cryoprobe. A yellow plastic foreign object was then visualized dislodged in the right lower lobe. This was successfully removed with grasping forceps. Patient had to be extubated and be reintubated to remove foreign object in one piece as it did not fit the endotracheal tube. Post debulking, bronchus intermedius and right lower lobe were patent and procedure was completed. Our patient responded well to treatment he was ultimately transitioned to oral antibiotics and discharged home with outpatient follow up. Repeat bronchoscopy 6 weeks later showed normal airways. DISCUSSION: Our case illustrated the importance of thorough investigation while treating patients with recurrent pneumonia, and this sometimes should include bronchoscopy with airway exam. In our case a bronchoscopy was done several years ago, however the foreign body was not identified as the cause of the endobronchial lesion. A lingering foreign body in the long run has significant morbidity as seen in our case despite appropriate treatment with antibiotics patient continued to have recurrent post obstructive pneumonias. Bronchoscopy remains the gold standard in definitive diagnosis and management of foreign body. Since the refinement of bronchoscopy and debulking, the rate of mortality from foreign body aspiration has been remarkably reduced. CONCLUSIONS: In summary patients with history suggestive of potential foreign body aspiration presenting with recurrent pneumonias at a particular anatomical location should prompt physicians to perform diagnostic bronchoscopy, which remains the gold standard for diagnosing of foreign body aspiration Reference #1: Foreign Body Aspiration Natan Cramer;Noel Jabbour;Melissa M. Tavarez;Roger S. Taylor. DISCLOSURES: No relevant relationships by Maria Abril No relevant relationships by Bilal Bangash No relevant relationships by Imran Tarrar

EXTREMELY RARE CASE OF CARTILAGINOUS TUMOR IN THE POSTERIOR WALL OF THE TRACHEA

SESSION TITLE: Lung Cancer Case Report Posters 3 SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: Tracheal tumor accounts for 0.4% of all tumors and only 10% of them are benign (1). We present, to our knowledge, the first case of a primary benign tracheal tumor with features of chondroid metaplasia arising from the posterior wall of the trachea. CASE PRESENTATION: 58-year-old male non—smoker with non-significant past medical history, presented to the Emergency department for COVID-19 pneumonia. CTA chest was done showing bilateral pulmonary embolism and a 12 mm polypoid tracheal mass arising from the posterior wall of the trachea extending into the lumen (Figure#1). The patient was asymptomatic prior to his COVID 19 infection;he denied any chest pain, hemoptysis, trauma, or prior intubation. After recovering from COVID-19, the patient was scheduled for an outpatient rigid bronchoscopy which revealed a tracheal polyp arising from the mid-distal posterior membranous trachea. (Figure#2). An electrocautery snare was used to simultaneously cut and cauterize the stalk using a lasso technique. The polyp was removed in its entirety without complication. Histopathology examination demonstrated a respiratory epithelium lined cyst with cartilaginous tissue, favoring chondroid metaplasia. DISCUSSION: Primary benign tracheal tumors with cartilaginous features are uncommon, especially in the posterior membrane of the trachea, which lacks cartilaginous support. Diagnosis of any benign tracheal tumor is usually delayed since most patients are asymptomatic. The majority of such tumors are found incidentally, as in this case. One of the most common benign tracheal tumors is hamartoma, which can have respiratory epithelium and cartilaginous tissue, however they do not have features of chondroid metaplasia, and are generally found in the lateral or anterior wall of the trachea. Furthermore, endobronchial lesions only account for 3% of all pulmonary hamartomas. (2) Reports of airway chondroid metaplasia are usually described in the larynx and are commonly associated with prior trauma or inflammation in the area which is not known to have occurred in this case (3). The histopathologic findings and unusual location of this tumor makes this case unique. CONCLUSIONS: The tracheal origin of this benign tumor, arising from the posterior membrane with cartilaginous features is extremely rare, and has not previously been described in the literature. Reference #1: Park CM, Goo JM, Lee HJ, Kim MA, Lee CH, Kang MJ. Tumors in the tracheobronchial tree: CT and FDG PET features. Radiographics. 2009 Jan-Feb;29(1):55-71. doi: 10.1148/rg.291085126. PMID: 19168836. Reference #2: Hurst IJ Jr, Nelson KG. Tracheal hamartoma. Chest. 1977 Nov;72(5):661-2. doi: 10.1378/chest.72.5.661. PMID: 913152. Reference #3: Orlandi A, Fratoni S, Hermann I, Spagnoli LG. Symptomatic laryngeal nodular chondrometaplasia: a clinicopathological study. J Clin Pathol. 2003 Dec;56(12):976-7. doi: 10.1136/jcp.56.12.976. PMID: 14645364;PMCID: PMC1770148. DISCLOSURES: No relevant relationships by Jorge Cedano Consultant relationship with Olympus America Please note: 8/1/21-present Added 04/18/2022 by Lucas Pitts, value=Consulting fee

THE INTRODUCTION OF CYTOSPONGE TO NHS SCOTLAND: INITIAL REPORTS

Introduction In recent years, endoscopy services throughout NHS Scotland were under substantial strain due to supply/ demand mismatch: these pressures were significantly exacerbated by the COVID-19 pandemic, which saw cessation of all routine and surveillance endoscopies. Cytosponge is a nonendoscopic diagnostic tool demonstrating good specificity and sensitivity for detection of Barrett's oesophagus and dysplasia in the trial setting. Cytosponge was introduced as a triage tool in a real world pilot across NHS Scotland in 2020 under closely audited conditions in response to the COVID-19 pandemic. This presents the initial results of this audit. Methods A national Cytosponge group was formed with representatives from all Scottish health boards and the Scottish government. The two indications for Cytosponge were: Barrett's oesophagus surveillance patients;and new referrals with reflux-predominant symptoms. Cytosponge was introduced in the secondary care setting following appropriate nurse training, with data collected from September 2020 to January 2022. Indications and cytology codes were obtained from Cyted Labs. Results During the study period, Cyted Labs received 3180 specimens from NHS Scotland;3020 of these were formally reported. Indication for Cytosponge was Barrett's surveillance in 2271 samples (75.2%) and reflux symptoms in 749 samples (24.8%). Within the Barrett's oesophagus cohort, 143 samples (6.3%) did not provide adequate cells for analysis. of the remaining 2128 patients, 246 samples (11.6%) demonstrated cellular atypia or aberrant p53 expression and 1425 samples (67.0%) showed simple Barrett's oesophagus. of interest, 457 samples (21.5%) in the Barrett's surveillance group did not demonstrate intestinal metaplasia. Full results for patients with reflux-predominant symptoms were available in 679 samples;70 samples (9.3%) did not yield adequate cells for cytology. Intestinal metaplasia was identified in 83 samples (12.2%), with an additional 23 specimens (3.4%) demonstrating atypia or aberrant p53 expression. Conclusions Cytosponge is a useful diagnostic tool to demonstrate pathology in cohorts of patients unable to access endoscopy during the COVID-19 pandemic due to service pressures. Our initial results give an indication of endoscopy resources required to support Cytosponge;with only 11.6% of Barrett's oesophagus surveillance patients and 15.6% of reflux patients requiring endoscopy to exclude adenocarcinoma or precursor lesions. This significantly reduces the burden on endoscopy services. The study does not describe patients undergoing endoscopy for reflux with other pathologies. However, early results suggest that Cytosponge, combined with nurse-led clinical assessment, is beneficial in these patient pathways.

CYTOSPONGE IN THE REAL-WORLD: TRIAGE OF BARRETT'S SURVEILLANCE AND REFLUX IN A SINGLE NON-SPECIALIST HOSPITAL

Introduction During the COVID-19 pandemic gastroscopy was halted with large burden on recovery and risk of late diagnosis. We established an early diagnosis service using Cytosponge to triage patients to timely gastroscopy and management Methods 2 patient cohorts were used: 1. Barrett's oesophagus (BO) on endoscopic surveillance 2. Patients with symptoms of gastro-oesophageal reflux referred for routine gastroscopy. Exclusions were patients with dysplasia on last gastroscopy, fundoplication, pregnancy and patient preference. Triage of patients on the waiting list was from endoscopy referrals, Barrett's surveillance database and telephone triage. 2 research nurses and 2 clinical nurse specialists were trained in delivering Cytosponge. A patient satisfaction survey was completed. All cytology specimens were analysed by Cyted. Results were relayed to patients within 4 weeks by consultant led nurse-run teleclinic and letter. Clinical triage was according to the table below. TFF3+ was used as a marker for intestinal metaplasia (IM), P53+ve and atypia for potential dysplastic change. Results 470 patients agreed to Cytosponge over 14 months November 2020-January 2022. 22 cancelled-mostly COVID related. 34 failed to swallow (5.5% of Barrett's, 8.9% reflux). of those successfully swallowing the sponge 6% were inadequate samples in Barrett's and 9% reflux. No major adverse events occurred. Conclusion We report on the largest single site series of Cytosponge in non-specialist clinical practice in England and its pragmatic use in patients management and pandemic recovery. Significant benefits in the Barrett's cohort were timely identification of dysplasia and those longer requiring surveillance. Benefits in the reflux group include identification of new BO, avoiding unnecessary gastroscopy and early discharge. Overall reduced endoscopy resulted in reduced cost, lower carbon footprint and improved patient experience. Careful follow up and longer-term outcomes will provide confidence to continue this new technique in routine clinical practice.

CLINICAL USE OF CYTOSPONGER TO TRIAGE PATIENTS FOR GASTROSCOPY OVER A 1-YEAR PERIOD DURING THE COVID-19 PANDEMIC -A LARGE SINGLE CENTRE UK STUDY

Background-During the COVID-19 pandemic all routine and surveillance gastroscopy was halted or delayed in the UK with considerable burden on recovery and risk of late diagnosis of significant pathology. We established an early diagnosis service using CytospongeR minimally invasive cell sampling device to help triage patients to timely gastroscopy and identify patients who could be managed without endoscopy. Methods-2 patient cohorts were identified: 1. Known Barrett's oesophagus on endoscopic surveillance 2. Patients with symptoms of gastrooesophageal reflux referred for routine gastroscopy. Exclusions were previous dysplasia of any grade on last gastroscopy, previous fundoplication, pregnancy and patient preference. Triage of patients on the waiting list was done initially from referrals to endoscopy and those on the Barrett's surveillance database, and then telephone clinic. 2 research nurses and 2 clinical nurse specialists were fully trained in delivering CytospongeR . All patients provided informed consent. All Cytology specimens were analysed by Cyted. Results were relayed to patients within 4 weeks of the procedure by consultant led nurse-run teleclinic or by letter for the Barrett's surveillance cohort. Clinical triage was according to the table below. TFF3+ was used as a marker for intestinal metaplasia, P53+ve and atypia for potential dysplastic change. Results-408 patients agreed to CytospongeR over 12 months November 2020-2021. 157 for Barrett's surveillance. 251 for Investigation of reflux. 28 failed to swallow (5% of Barrett's, 7.5% reflux). In the Barrett's Cohort 148 patients successfully swallowed, 139 for analysis 8 inadequate (5.4%) first samples. In the reflux cohort 232 successfully swallowed, 200 for analysis 32 inadequate first samples (13.8%) Discussion-Overall 205 (60.5%) of patients had low risk CytospongeR findings (no Barretts/short segment not requiring surveillance under BSG guidance) were managed symptomatically without initial gastroscopy, 114 (33.6%) had evidence of non dysplastic Barrett's and could be managed on a routine pathway. 20 (5.9%) had high risk findings suggesting dysplasia and had urgent gastroscopy. Conclusion-We report the largest single site series of CytospongeR in clinical practice in England and its pragmatic use in patients management and service recovery during the Pandemic. Notable benefits in the Barrett's cohort were timely identification of high numbers of potential dysplasia and also of those no longer requiring surveillance. Identification of new potential Barrett's for surveillance and the avoidance of unnecessary gastroscopy and early discharge were notable benefits in the Reflux cohort. Careful follow up and long-term outcomes of these patients will provide more data and safety netting for adoption of this new technique into routine clinical practice and help avoid unnecessary gastroscopy. (Table Presented)Table 1. CytospongeR findings and triage pathways in Barrett's oesophagus and gastrooesophageal reflux

UTILISATION OF THE CYTOSPONGE DEVICE AS A TOOL FOR RISK STRATIFICATION IN PATIENTS WITH BARRETT'S OESOPHAGUS WHO ARE OVERDUE ENDOSCOPIC SURVEILLANCE DUE TO THE COVID-19 PANDEMIC

Introduction: At the onset of the COVID-19 pandemic, all patients undergoing endoscopic surveillance for Barrett's Oesophagus (BE) in the UK were indefinitely postponed. As well as the potential for missed progression to dysplasia, the negative impact on patients' quality of life is immeasurable. The Cytosponge® is a minimally invasive cell sampling device which has been researched in screening for BE. We describe the first worldwide use of the Cytosponge® outside of a clinical trial to support the triage of BE patients unable to undergo endoscopic surveillance due to COVID-19. Aims and Methods: Consecutive patients with non-dysplastic BE (NDBE) or those deemed to be low risk after previous treatment for BErelated dysplasia, DBE (more than 18 months after completion of therapy with no visible BE and no intestinal metaplasia/dysplasia at last endoscopy) with no prior history of stenosis who were overdue endoscopy (OGD) were invited to have the Cytosponge®. The sample was analysed for TFF3 (a marker of intestinal metaplasia), cellular atypia and p53. Fisher's test was used to examine the association between the overall cytosponge result and its individual components with follow-up OGD outcomes. Results: To date, 153 patients (mean age 66 years, 126 male) have undergone the Cytosponge® procedure. The median maximal length of BE was 3cm (1-15cm). Three patients were unable to swallow the device and 19 (12%) needed a repeat procedure as no columnar cells were present suggesting that the sponge had not entered the stomach. 87 patients (80%) with NDBE had a either a low-risk result (TFF3 positive only – 62) or required a repeat Cytosponge® routinely (TFF3/atypia/ p53 negative – 25). The remaining 21 patients (20%) needed an OGD within 3 months, 17 of which have since had an OGD. Of these 17 patients, 4 had a new diagnosis of dysplasia (indefinite - 2, low grade dysplasia – 1, intramucosal cancer - 1) and 2 a new diagnosis of cancer. 18/87 patients in the low-risk NDBE cohort have undergone follow-up OGD (NDBE 17/18, high grade dysplasia 1/18). Of the 23 patients in the post-treatment BE cohort, 1 patient had a high-risk result and subsequent OGD confirmed HGD (Table 1). A high-risk cytosponge result and the presence of both p53 and typia were all associated with a positive OGD result. Over-expression of p53 appeared to be the most sensitive marker (Table 2). In treatment naive patients, a low-risk cytosponge result was closely associated with no dysplasia detected at follow-up OGD with a negative predictive value of 94%. Conclusions: Cytosponge® has proved to be a useful non-endoscopic tool for patients with BE under surveillance where OGD is not possible. Preliminary data are promising to help triage patients and may in turn offer a less invasive approach to monitoring patients compared to endoscopy, particuarly for low risk patients. (Table Presented) (Table Presented)

REAL-WORLD IMPLEMENTATION OF THE CYTOSPONGE TEST IN SECONDARY CARE FOR PATIENTS AT RISK OF EARLY OESOPHAGEAL CANCER

Introduction The CytospongeTM test is a non-endoscopic method to collect cells from the oesophagus and test for biomarkers of early oesophageal cancer and its precancerous form, Barrett's oesophagus. The real-world implementation pilots of the Cytosponge has been accelerated in response to the COVID-19 pandemic. At the onset of the pandemic, when endoscopy services were paused, guidelines from the British Society of Gastroenterology were updated to recommend the use of alternatives including the Cytosponge. In December 2020, NICE published a Medtech Innovation Briefing for use of the Cytosponge test as a triage tool for endoscopy to identify people at risk of oesophageal cancer. Aims & methods Implementation pilots were launched within the NHS in England and Scotland, as well as the Innovate UK-funded research project, Project DELTA. The Cytosponge test was offered to two patient cohorts as an alternative to endoscopy: (1) patients already diagnosed with Barrett's Oesophagus, and so in need of routine surveillance;and (2) patients referred from primary care with reflux symptoms. Samples were received, processed and analysed at the ISO 15189:2012 accredited laboratory at Cyted. Pathology reports were issued with TFF3, p53 and atypia biomarker results and clinical recommendations. Any reports positive for p53/atypia biomarkers were double reported. Here, we evaluate the real-world laboratory metrics for the Cytosponge test in secondary care. Results Between August 2020 and November 2021, Cytosponge tests were delivered to 5373 patients at 48 hospitals across England and Scotland. For 4842 diagnostic reports issued by mid-November, 2807 patients had Barrett's Oesophagus and 2034 reflux symptoms. For Barrett's surveillance, 2629 (93.7%) of patient samples had sufficient cellular material for analysis, including sampling the gastric cardia. Of these 324 (12.3%) exhibited cellular atypia (including uncertain significance), dysplasia, or aberrant p53 expression. These patients were recommended to have an endoscopy. Patients without evidence of atypia/dysplasia/p53 were recommended surveillance by Cytosponge or endoscopy after the recommended interval by clinical guidelines. In the symptomatic reflux cohort, 1854 (91.2%) patient samples had sufficient cellular material for analysis, including sampling the gastric cardia. Of these 185 (10.0%) exhibited intestinal metaplasia corroborated by TFF3 expression and a further 44 (2.4%) exhibited atypia/ dysplasia/p53. These patients were recommended to have an endoscopy. Otherwise, patients were recommended management according to symptoms. Discussion A high-quality centralised laboratory service has enabled accelerated real-world implementation of the Cytosponge in the secondary care setting. This has enabled triage and care of patients who have not been able to access endoscopy during the COVID-19 pandemic.

Pathology of Double Lung Transplantation of 12 Cases Following COVID-19

Background: Pulmonary failure is one of the major causes of death in COVID-19 (SARS-CoV-2) patients. Lung transplantation has been evolving to rescue those patients' lives with promising success. Explanted native lungs post COVID-19 are valuable to understand the long-term pulmonary pathology of this deadly disease, as currently available data is very limited. Design: Lung transplantation cases post COVID-19 were collected through the pathology database in our institution from January 2020 through September 2021. Patient clinical courses, CT imaging data prior to transplantation and pathological findings are evaluated. Results: The cohort consisted of 12 male patients with a median age of 46.5 years (range 24 - 67). Co-morbidities were present in 6 patients including obesity, diabetes mellitus and hypertension. No prior known pulmonary specific disease was present in any of the patients. Extracorporeal membrane oxygenation (ECMO) was used in 10 of 12 patients for 54 - 130 days. CT imaging pretransplantation showed extensive bilateral consolidation (5 cases), extensive bilateral ground-glass (3 cases) or extensive infiltration/air space disease (4 cases). All patients survived post double lung transplantation (including one patient with concurrent heart transplantation) and no significant pathologic alteration was identified on most recent surveillance biopsies (26 - 183 days post transplantation). The most prominent pathological finding in the explanted lungs is nonspecific interstitial pneumonia (NSIP)- like interstitial fibrosis (100%, 12 cases). Other findings include collections of numerous hemosiderin-laden macrophages (8 cases), patchy diffuse alveolar damage (DAD) (hyaline membrane formation and/or organizing DAD) (5 cases), intrapulmonary small vessel thrombosis (5 cases), organizing pneumonia (5 cases), necrosis (2 cases), calcifications (5 cases), acute pneumonia (3 cases), peribronchiolar metaplasia (8 cases), and microscopic honeycombing (8 cases). No viral cytopathic changes were seen. The pathologic findings of the two patients who did not receive ECMO are similar to those in patients with variable length of ECMO treatment. Conclusions: Lung transplantation is a successful treatment option for eligible candidates with pulmonary fibrosis and failure post COVID-19. NSIP-like interstitial fibrosis is a universal finding, consistent with a sequala of DAD. A spectrum of acute, subacute, vascular and airway-related changes are also prominent findings in respiratory failure post COVID-19.

Pulmonary Pathology in Post-Acute COVID-19 Syndrome Treated with Bilateral Orthotopic Lung Transplantation

Background: Lung transplantation has been performed as a life-saving treatment in a small number of post-acute COVID- 19 patients who develop severe pulmonary insufficiency. We report a detailed clinicopathologic analysis of 7 such patients that underwent bilateral orthotopic lung transplantation at our institution. Design: The time interval between initial diagnosis of Covid-19 infection and lung transplantation, other clinical findings, and imaging features of the 7 patients were reviewed. The pathologic findings in the 14 explants were assessed and histologic abnormalities were classified into parenchymal, airway and vascular changes. The extent (1+-to 4+ based on # of slides with the abnormality) and severity (mild, moderate, marked) of histologic abnormalities were recorded. Results: Patients ranged in age from 34 to 55 years old and were transplanted at 10.4 to 24 weeks after initial diagnosis of Covid- 19 (median 16 weeks). Six of these patients had been previously treated with ECMO for 82-145 days. Other clinical and imaging features are summarized in Table 1. All 14 explants showed diffuse marked interstitial fibrosis with a nonspecific interstitial pneumonia (NSIP) pattern. Other pathologic changes included extensive alveolar hemosiderosis (n=7 patients);prominent peribronchial metaplasia (n=7);focal multinucleated giant cells in either the parenchyma, vascular wall or peribronchiolar location (n=6);focal thrombosis involving medium to large vessels (n=4) and lung cysts associated with delicate calcifications and multinucleated giant cells (n=1). No diffuse alveolar damage changes (DAD) or vasculitis were identified. Conclusions: Lung explants from patients with post-acute COVID-19 syndrome show severe NSIP pattern of fibrosis and other pathologic changes that do not resemble the extensive fibrotic changes resulting from organizing phase of DAD or the extensive vascular changes seen in patients dying during the acute or subacute phases of COVID-19 infection. Further studies with lung biopsies are needed to understand the mechanism of fibrosis in post-acute COVID-19 syndrome and identify individuals who are likely to develop severe pulmonary fibrosis requiring lung transplantation.

First rigid bronchoscopy in COVID-19 pneumonia to treat a rare endobronchial tumor during extracorporeal membrane oxygenation

During the COVID-19 pandemic in Northern Italy, a young man with fever and dyspnea was admitted to the Emergency Department. The sudden development of severe hypoxemia and respiratory acidosis forced the emergency medical team to intubate the patient. Fiberoptic bronchoscopy and chest CTscan showed the presence of a bleeding neoformation, occluding the majority of tracheal lumen requiring the connection to a veno-venous extracorporeal respiratory support. Arigid bronchoscopy was performed to clear the tracheal lumen, obtaining a diagnosis of "composite hemangioendothelioma."All personnel involved was equipped with personal protective equipment (PPE) and power air-purifying respirators (PAPR). ECMOand mechanical ventilation were soon weaned, lung CTshowed an almost complete patency of tracheo-bronchial tree. To the best of our knowledge, this is the first rigid bronchoscopic procedure reported in a SARS-CoV-2 virus pneumonia respiratory failure requiring ECMO, allowing to diagnose an extremely rare endobronchial tumor.

Cerebral venous thrombosis and myeloproliferative neoplasms: A three-center study of 74 consecutive cases

Background The recent association of cerebral venous thrombosis (CVT) with COVID-19 vaccinations (JAMA;2021;325, N Engl J Med 2021;384) motivated the current review of CVT and MPN. Our objectives were, i) provide an estimation of the incidence of CVT in the context of MPN, followed by a description of clinical phenotype and therapeutic strategies, ii) determine long term outlook in terms of recurrent thromboses, hemorrhage, and survival, iii) identify salient features which distinguish MPN associated from COVID vaccine- related CVT. Methods 74 consecutive MPN patients with CVT that underwent evaluation at the Mayo Clinic, Rochester MN, USA (n=36), Catholic University, Rome, Italy, (n=23), and University of Florence, Italy (n=15) between 1991 and 2021 were included. The cohort from a previously published multi-center study that included 42 MPN cases with CVT, which were not included in the current study, was used for comparison of observations. Diagnosis of CVT was established with computed tomography or magnetic resonance imaging with venography. Results Patient characteristics at time of CVT Among 74 patients with CVT and MPN (median age 44 years, range 15-85;61% females);disease-specific frequencies were 1.3% (39/2,893), 1.2% (21/1,811) and 0.2% (3/1,888) for essential thrombocythemia (ET), polycythemia vera (PV) and primary myelofibrosis (PMF), respectively. CVT occurred prior to (n=20, 27%, median time to MPN diagnosis 16.5 months), at (n=32, 44%) or after (n=21, 29%, median time to CVT 26 months) MPN diagnosis. 72% of patients presented with headaches, 22% visual changes, 12% nausea/vomiting, 8% neurological deficits, and 6% seizures. Transverse (51%), sagittal (43%) and sigmoid (35%) sinuses were involved with central nervous system hemorrhage in 10 (14%) patients. MPN phenotype included ET (n=39, 53%), PV (n=21, 28%), pre-fibrotic MF (n=6, 8%), MPN-unclassified (n=4, 5%), PMF (n=3, 4%) and post-PV MF (n=1, 1%). Driver mutation testing was performed in 65 patients: 91% harbored JAK2V617F, 3% CALR type 1, 2% MPL, 5% triple negative;moreover, JAK2V617F was mutated in 27/33 (82%) ET patients. An underlying thrombophilia was identified in 19 (31%) cases. No patient had thrombocytopenia. (Table 1). Notably, one patient received the Ad26.COV2.S vaccine, five days prior to presenting with CVT, not associated with thrombosis in other sites, thrombocytopenia or platelet factor 4 antibodies. A history of thrombosis was documented in 10 (14%) patients with three splanchnic venous events. These observations were similar to those noted in our comparative group from a previously published report that included 42 cases;(ET (n=25, 60%), PV (n=11, 26%), PMF (n=5, 12%);median age 51 years, range 16-84;55% females;81% JAK2V617F mutated). Prior thrombosis occurred in 8(19%) patients with four splanchnic venous events. Treatment for CVT included systemic anticoagulation alone in 27 (36%) patients or in conjunction with aspirin (n=24, 32%), cytoreductive therapy (n=14, 19%), or both aspirin and cytoreduction (n=9, 12%). 5/21 (24%) patients with CVT post MPN diagnosis, were on anticoagulation at the time of CVT. 1. Outcome following CVT At a median follow-up of 5.1 years (range;0.1-28.6), recurrent CVT was documented in 3 (4%) patients;incidence rates for other arterial and venous thromboses and hemorrhage were 11% (2 per 100 patient-years), 9% (1.9 per 100 patient-years) and 14% (3 per 100 patient-years), respectively. 3 of 7 (43%) venous thromboses were splanchnic events. Antithrombotic therapy was ongoing in 53% and 80% of patients with thrombotic recurrences and hemorrhage, respectively. A higher incidence of venous thrombosis was noted in the aforementioned previously published cohort (12 (29%) vs 7 (9%), p=0.01);with 5/12 (42%) splanchnic events. Incidence rates for arterial thrombosis and major hemorrhage were similar. Fibrotic and leukemic transformation occurred in 5 (8%) and 1(1%) patient, respectively, with five (7%) deaths unrelated to CVT. Conclusions The current study highlights close association of CVT w th JAK2V617F, younger age, and female gender. Clinical features distinguishing COVID vaccine-related from MPN-associated CVT include lower likelihood of concomitant non-CVT venous thromboses with the latter;moreover, the absence of thrombocytopenia resulted in a lower rate of intracerebral hemorrhage in MPN cases;as a result, MPN-CVT was not fatal. (Figure Presented).

Pathological Features of Lung in COVID-19 Disease Subjects: A Postmortem Study

Introduction: The current Coronavirus Disease-19 (COVID-19) pandemic is considered as one of the most serious public health crises which caused more than 1.62 million deaths from October 2020 to November 2020. Acute respiratory failure is leading cause of death followed by sepsis, cardiac failure and hemorrhage. Since the pathological findings are diverse in COVID-19 and majority of studies in literature were by open autopsy;the present study was done using percutaneous core needle biopsy. Postmortem lung biopsies are rather easy and quick to perform and decrease the infective risk caused by full autopsies. This could be an essential tool for diagnosis, surveillance and research. Aim: To study the pathological features of lung in COVID-19 deceased patients by postmortem. Materials and Methods: This cross-sectional study was conducted in the Department of Pulmonary Medicine, Dr. Pinnamaneni Siddhartha Institute of Medical Sciences and Research Foundation, Vijayawada, Andhra Pradesh, India from October 2020 to November 2020. In present study, postmortem percutaneous core needle biopsies from lung were performed within two hours of death from eight deceased patients who died of COVID-19. Clinical history, inflammatory markers and treatment details were collected from case sheets, biopsy was done, specimen was collected and sent for pathological examination. Data was presented in the descriptive form for each variable. Results: Out of eight cases, five were men and three were women with a mean age of 54.12 years. Majority of patients presented with complaints of shortness of breath and fever. Hypertension, type 2 diabetes mellitus, obesity, hypothyroidism, history of pulmonary tuberculosis were the co-morbidities noticed. Four biopsies presented acute lung injury with hyaline membrane changes, Diffuse Alveolar Damage (DAD) with hyaline membrane was seen in two cases, squamous metaplasia was seen in two cases and acute lung injury with organising pneumonia was seen in two cases. Conclusion: Postmortem lung biopsies are safe, easy to perform and provide insights of possible undergoing pathology of the disease with regard to clinical presentation.

A Rare Case of Extramedullary Blastic Transformation(Myeloid Sarcoma-Megakaryoblastic) in a Patient with Primary Myelofibrosis

Introduction: Myeloid sarcoma is a tumour composed of myeloidblasts, with or without maturation ocurring at extramedullary sites.Myeloid sarcoma with megakaryoblastic transformation in chronicmyelofibrosis is very rare. Only a few cases have been reported tilldate.Aims &Objectives: A 54 year old male, known case of primarymyelofibrosis since 5 years, diagnosed and treated in a tertiary hospital was referred to our hospital. He was on Hydroxurea andsymptomatic treatment. However due to absence of follow up andfurther treatment as a result of Covid 19 pandemic, he presented witha flare up of the disease, in the form of generalised significant lymphadenopathy (cervical, mediastinal, abdominopelvic) along withhepatosplenomegaly.Materials &Methods: Peripheral smear and bone marrow weresuggestive of a myeloproliferative neoplasm. Bone marrow showedMF grade 2 fibrosis with atypical megakaryocytes/blasts. Biospy fromcervical and abdominal lymph nodes were done.Result: Histology and IHC studies revealed myeloid sarcoma (AMLM7 type).Conclusions: Myeloid sarcomas are an infrequent neoplasms withonly around 2000 case reports in Pubmed. Myeloid sarcoma withmegakaryoblastic transformation in chronic myelofibrosis is veryrare, with extremely poor prognosis. The incidence of myeloid sarcoma occurring at multiple anatomical sites is less than 10%. Sinceonly a few comprehensive studies have been published, treatment alsoposes many difficulties. Hence reporting of cases of myeloid sarcomais significant.

TROPISM OF SARS-COV-2 FOR BARRETT'S ESOPHAGUS MAY INCREASE SUSCEPTIBILITY TO DEVELOPING COVID-19

Background and Aims: In addition to pulmonary and thrombotic sequalae, gastrointestinal (GI) manifestations of COVID-19 are common. Although enterocytes express ACE2 and TMPRSS2, the proteins that determine SARS-CoV-2 tropism, prior studies have suggested that the virus is inactivated by gastric acid and other luminal fluids as it transits the gastrointestinal tract. However, we reason here that individuals with intestinal metaplasia of the esophagus and stomach might have ectopic, proximal SARS-CoV-2 receptor expression that would predispose them to infection from ingested oral secretions or respiratory sputum. Methods: Histology, immunohistochemistry, and immunofluorescence were performed on human tissue and organoid cultures derived from biopsied human Barrett’s esophagus. Organoid cultures were infected with a chimeric virus expressing the SARS-CoV-2 spike protein (rVSV-eGFP-SARS-CoV-2). Both fixed and live cells were imaged by light, epifluorescence, and live confocal microscopy. Results: Unlike normal esophagus and stomach, Barrett’s esophagus and gastric intestinal metaplasia both strongly express apical ACE2 and TMPRSS2 at the protein level. Organoids derived from Barrett’s esophagus are readily infected by the chimeric rVSV-eGFP-SARSCoV- 2 virus as demonstrated by the GFP fluorescence observed in both epifluorescence as well as three-dimensional, time-lapse confocal imaging of live infected organoids. We observed that fluorescence persisted for greater than 2 weeks in culture suggesting ongoing viral infection and intestinal identity correlated with increased viral entry. Conclusions: SARS-CoV-2 has a previously undescribed tropism for Barrett’s esophagus and gastric intestinal metaplasia, placing these individuals at higher risk of infection via the orogastric route.

Temporal Patterns of COVID-19-Associated Pulmonary Pathology: An Autopsy Study.

Introduction The novel coronavirus variant - severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2) and the disease it causes clinically (novel coronavirus disease 2019 or COVID-19) have placed medical science into a frenzy due to the significant morbidity and mortality, as well as the myriad of clinical complications developing as a direct result of infection. The most notable and one of the most severe changes in COVID-19 develops in the lungs. Materials and methods All cases of real-time polymerase chain reaction (rtPCR)-proved COVID-19 subjected to autopsy were withdrawn from the central histopathology archive of a single tertiary medical institution - St. Marina University Hospital - Varna, Varna, Bulgaria. Pulmonary gross and histopathology changes observed on light microscopy with hematoxylin and eosin as well with other histochemical and immunohistochemical stains were compared with the time from patient-reported symptom onset to expiration, to compare the extent and type of changes based on disease duration. Results A total of 27 autopsy cases fit the established criteria. All cases clinically manifested with severe COVID-19. From the selected 27 cases, n=14 were male and n=13 were female. The mean age in the cohort was 67.44 years (range 18-91 years), with the mean age for males being 68.29 (range 38-80 years) and the mean age for females being 66.54 (range 18-91 years). Gross changes in patients who expired in the first 10 days after disease onset showed a significantly increased mean weight - 1050g, compared to a relatively lower weight in patients expiring more than 10 days after symptom onset - 940g. Histopathology changes were identified as intermittent (developing independent from symptom onset and persisting) - diffuse alveolar damage with hyaline membranes - acute respiratory distress syndrome, endothelitis with vascular degeneration and fibrin thrombi; early (developing within the first week, but persisting) - type II pneumocyte hyperplasia, alveolar cell multinucleation and scant interstitial mononuclear inflammation; intermediate (developing within the late first and second weeks) - Clara cell hyperplasia and late (developing after the second week of symptom onset) - respiratory tract and alveolar squamous cell metaplasia and fibrosis. Conclusion COVID-19-associated pulmonary pathology, both gross and histopathology, show a time-related dynamic with persistent early and a myriad of later developing dynamic changes in patients with severe disease. These changes underline both the severity of the condition, as well as the mechanisms and the probability of long-lasting severe complications in patients with post-COVID syndrome.