CASE REPORT: FETAL DEATH in UTERO COMPLICATED by DISSEMINATED INTRAVASCULAR COAGULATION in MATERNAL COVID-19 INFECTION

Background: COVID-19 infection during pregnancy is associated with an increased risk of stillbirth, likely due to placental insufficiency through the associated inflammatory response and hypoperfusion. A spectrum of associated placental changes has been reported. Whilst pregnancy alone is a hypercoagulable state, concurrent COVID-19 further increases the risk of coagulopathy. Disseminated intravascular coagulation (DIC) is uncommon in pregnancy but is increased in both COVID-19 infection and fetal death in utero (FDIU). Method(s): Case report. Informed written consent was obtained from the patient. Result(s): A 31-year-old G5P2 presented with a FDIU at 23 + 3 weeks gestation, in the setting of maternal COVID-19 infection without respiratory symptoms or oxygen requirements. The pregnancy had been uncomplicated, and her presenting issue was two days of reduced fetal movements, when FDIU was confirmed on ultrasound. On admission, the case was further complicated by disseminated intravascular coagulopathy (DIC). This DIC could have resulted from COVID-19 infection, FDIU or a combination of both. Placental histopathology showed evidence of inflammation, with chronic histiocytic intervillositis (CHI) and massive perivillous fibrin deposition (MPFD). The inflammatory response, evidenced by histopathological findings of CHI and MPFD, likely contributed to placental insufficiency and FDIU. Conclusion(s): COVID-19 infection is associated with increased risk of hematological abnormalities, placental inflammation and pregnancy loss. This case is the first to report both DIC and CHI in the context of FDIU in COVID-19 infection. We present this case to highlight the impact of COVID-19 infection on placental function, coagulation disturbances and subsequently adverse pregnancy outcomes.

Unusual Myositis of the Temporalis Muscle Occurring with Acute Covid-19

Background. SARS-CoV-2 infection can be accompanied by neuromuscular disorders. Rhabdomyolysis and Guillain-Barre syndrome have been described repeatedly. There are case reports of inflammatory myopathies manifesting during COVID-19, presenting as dermatomyositis, polymyositis or immune-mediated necrotizing myopathy, with dermatomyositis-like presentations most commonly reported. Larger cases series are from postmortem examinations of COVID-19 patients, where variable inflammatory pathology of the skeletal muscle has been found frequently but without local detection of the actual virus. Thus, autoimmune mechanisms or the systemic interferon response are discussed as causes. We report a case of focal inflammatory myopathy with perimysial pathology of the temporalis muscle occurring with acute, but mild COVID-19. Methods. Case report of clinical observations, cranial MRI, histopathological, and laboratory findings. 3T cranial MRI was performed with gadolinium contrast. Open temporalis muscle biopsy was performed. The sample underwent standard cryohistological studies as well as immunohistochemistry with antibodies against MHC-I and II, CD3, CD4, CD19, CD68, anti-MAC, p62 and MxA. Testing for auto-antibodies was based on immunoblots or ELISA. RT-PCR for SARS-CoV-2 was run with RNA extracted from cryopreserved muscle. Results. A Caucasian woman in her 60s with no history of autoimmune or muscle complaints developed swelling and pain of the right jaw musculature five days after testing positive for SARS-CoV-2 due to respiratory tract symptoms. In addition, she experienced trismus, but no further neuromuscular complaints. The course of respiratory tract symptoms stayed mild. She had been vaccinated previously with single shot SARS-CoV-2 vector vaccine. Due to persistent swelling and complaints, giant cells arteritis was excluded by unresponsiveness to five days oral steroids and sonography of the temporal artery. Cranial MRI was performed nearly four weeks after the SARS-CoV-2 infection and showed marked swelling and oedema of the temporalis muscle. Its biopsy showed numerous CD68 and acid phosphatase positive cells infiltrating from perimysial perivascular foci towards the endomysium with perimysial damage but little damage of adjacent, perifascicular muscle fibres. Muscle fibres did not react with anti-MHC-II, anti-MAC or -MxA. Capillaries did not react with anti-MAC or -MxA. SARS-CoV-2 RNA was not detected in muscle tissue. Serum creatine kinase was not elevated in the subacute phase. Slightly elevated ANA titre led to detection of autoantibodies against proliferating cell nuclear antigen (PCNA). No pathological results for other autoantibodies, including myositis-specific antibodies and anti-ds-DNA, were found in blood. Neither were antibodies against hepatitis C and B viruses. Retesting 15 weeks after infection, anti-PCNA immunoblot was still positive, but ELISA did not indicate a pathologic titre. The swelling, myalgia and trismus regressed spontaneously a month after onset, yet the latter still persists at the time of reporting. Conclusion. Our case diverges from the majority of COVID-19 associated my-ositis reports in the unusual location of the focal myositis and the histopathological pattern of predominantly perimysial damage and histiocytic infiltration. It concurs with the literature as no SARS-CoV2 RNA could be detected in the muscle. Anti-PCNA is associated very rarely with myositis. Other associated disorder (systemic lupus erythematosus, chronic viral hepatitis B or C) were not found. Increased levels of autoantibodies are reported in COVID-19 and mostly attributed to loss of self-tolerance during the acute disease phase. Interestingly, the structural protein M of SARS-CoV-2 appears to interact notably with PCNA in infected cells. Still, the causal connection between the myositis and COVID-19 in this case is based on the close temporal association in the absence of alternative, competing explanations from the medical history and findings.

Placenta histological features in three cases of supposed SARS-CoV-2 vertical transmissions in second and third trimester of pregnancy

Objective. We described three cases of SARS-CoV-2 positive new-borns with both symptomatic and asymptomatic mothers. Materials and Methods. Placentas were analyzed in the pathology department and showed chronic histiocytic intervillositis with presence of CD68+ macrophages, syncytiotrophoblast necrosis and positivity of the syncytiotrophoblast for SARS-CoV-2 antigen or RNA. Results. The first case dates back to March 2020, when a symptomatic COVID-19 positive patient gave birth to a healthy neonate at 37.6 weeks of gestation. Skin to skin contact was not permitted but breastfeeding with a face mask was allowed. The newborn, that remained asymptomatic throughout the entire hospital stay, resulted positive to SARS-CoV-2 immediately after birth, at 24 hours of life and after 7 days. The second was delivered at 35.1 weeks of gestation by caesarean section for non-reassuring fetal status. The mother presented with fever, cough and a positive COVID-19 swab test. The newborn resulted positive on day 7, despite not having contact with the mother. No neonatal complications were observed. The third positive mother was admitted asymptomatic to the obstetric department in September 2021 due to preterm premature rupture of membranes at 20 weeks of gestation in a high-risk twin pregnancy. At 21.4 weeks of gestation her clinical conditions deteriorated, and she delivered two stillborn fetuses: SARSCoV- 2 was detected in all tissues samples. The lung of the first fetus only showed interstitial pneumonia features. Conclusions. We detected SARS-CoV-2 in placentas of both the second and third trimester, implying the passage of the virus through the placenta to the fetuses as the presence of SARSCoV- 2 RNA was demonstrated in swabs and foetal tissues.

PATHOMORPHOLOGICAL FEATURES OF ACUTE RESPIRATORY DISTRESS SYNDROME IN COMPETING LUNG DISEASES: COVID-19 AND SARCOIDOSIS

The COVID-19 pandemic is a worldwide problem. The clinical spectrum of SARS-CoV-2 infection varies from asymptomatic or paucity-symptomatic forms to conditions such as pneumonia, acute respiratory distress syndrome and multiple organ failure. Objective was to describe a clinical case of SARS-CoV-2 infection in the patient with sarcoidosis and cardiovascular pathology developing acute respiratory syndrome and lung edema. Material and methods. There were analyzed accompanying medical documentation (outpatient chart, medical history), clinical and morphological histology data (description of macro- and micro-preparations) using hematoxylin and eosin staining. Results. Lung histological examination revealed signs of diffuse alveolar damage such as hyaline membranes lining and following the contours of the alveolar walls. Areas of necrosis and desquamation of the alveolar epithelium in the form of scattered cells or layers, areas of hemorrhages and hemosiderophages are detected in the alveolar walls. In the lumen of the alveoli, a sloughed epithelium with a hemorrhagic component, few multinucleated cells, macrophages, protein masses, and accumulated edematous fluid were determined. Pulmonary vessels are moderately full-blooded, surrounded by perivascular infiltrates. Signs of lung sarcoidosis were revealed. Histological examination found epithelioid cell granulomas consisting of mononuclear phagocytes and lymphocytes, without signs of necrosis. Granulomas with a proliferative component and hemorrhage sites were determined. Giant cells with cytoplasmic inclusions were detected — asteroid corpuscles and Schauman corpuscles. Non-caseous granulomas consisting of clusters of epithelioid histiocytes and giant Langhans cells surrounded by lymphocytes were detected in the lymph nodes of the lung roots. Hamazaki–Wesenberg corpuscles inside giant cells were found in the zones of peripheral sinuses of lymph nodes. In the lumen of the bronchi, there was found fully exfoliated epithelium, mucus. Granulomas are mainly observed subendothelially on the mucous membrane, without caseous necrosis. Histological examination of the cardiovascular system revealed fragmentation of some cardiomyocytes, cardiomyocyte focal hypertrophy along with moderate interstitial edema, erythrocyte sludge. Zones of small focal sclerosis were determined. The vessels of the microcirculatory bed are anemic, with hypertrophy of the walls in small arteries and arterioles. Virological examination of the sectional material in the lungs revealed SARS-CoV-2 RNA. Conclusion. Based on the data of medical documentation and the results of a post-mortem examination, it follows that the cause of death of the patient R.A., 50 years old, was a new coronavirus infection COVID-19 that resulted in bilateral total viral pneumonia. Сo-morbidity with competing diseases such as lung sarcoidosis and cardiovascular diseases aggravated the disease course, led to the development of early ARDS and affected the lethal outcome. © 2022 Saint Petersburg Pasteur Institute. All rights reserved.

Hemophagocytic Lymphohistiocytosis syndrome (HLH) associated with acute pancreatitis: A case report.

Hemophagocytic Lymphohistiocytosis syndrome is fatal hyper-inflammatory condition due to over-activation of the immune system, being of primary and secondary types. This case report emphasizes the difficulty and challenge in and of the HLH diagnosis, and therapy should be employed promptly given the high mortality associated with HLH.

PATHOMORPHOLOGICAL FEATURES OF ACUTE RESPIRATORY DISTRESS SYNDROME IN COMPETING LUNG DISEASES: COVID-19 AND SARCOIDOSIS

The COVID-19 pandemic is a worldwide problem. The clinical spectrum of SARS-CoV-2 infection varies from asymptomatic or paucity-symptomatic forms to conditions such as pneumonia, acute respiratory distress syndrome and multiple organ failure. Objective was to describe a clinical case of SARS-CoV-2 infection in the patient with sarcoidosis and cardiovascular pathology developing acute respiratory syndrome and lung edema. Material and methods. There were analyzed accompanying medical documentation (outpatient chart, medical history), clinical and morphological histology data (description of macro- and micro-preparations) using hematoxylin and eosin staining. Results. Lung histological examination revealed signs of diffuse alveolar damage such as hyaline membranes lining and following the contours of the alveolar walls. Areas of necrosis and desquamation of the alveolar epithelium in the form of scattered cells or layers, areas of hemorrhages and hemosiderophages are detected in the alveolar walls. In the lumen of the alveoli, a sloughed epithelium with a hemorrhagic component, few multinucleated cells, macrophages, protein masses, and accumulated edematous fluid were determined. Pulmonary vessels are moderately full-blooded, surrounded by perivascular infiltrates. Signs of lung sarcoidosis were revealed. Histological examination found epithelioid cell granulomas consisting of mononuclear phagocytes and lymphocytes, without signs of necrosis. Granulomas with a proliferative component and hemorrhage sites were determined. Giant cells with cytoplasmic inclusions were detected — asteroid corpuscles and Schauman corpuscles. Non-caseous granulomas consisting of clusters of epithelioid histiocytes and giant Langhans cells surrounded by lymphocytes were detected in the lymph nodes of the lung roots. Hamazaki–Wesenberg corpuscles inside giant cells were found in the zones of peripheral sinuses of lymph nodes. In the lumen of the bronchi, there was found fully exfoliated epithelium, mucus. Granulomas are mainly observed subendothelially on the mucous membrane, without caseous necrosis. Histological examination of the cardiovascular system revealed fragmentation of some cardiomyocytes, cardiomyocyte focal hypertrophy along with moderate interstitial edema, erythrocyte sludge. Zones of small focal sclerosis were determined. The vessels of the microcirculatory bed are anemic, with hypertrophy of the walls in small arteries and arterioles. Virological examination of the sectional material in the lungs revealed SARS-CoV-2 RNA. Conclusion. Based on the data of medical documentation and the results of a post-mortem examination, it follows that the cause of death of the patient R.A., 50 years old, was a new coronavirus infection COVID-19 that resulted in bilateral total viral pneumonia. Сo-morbidity with competing diseases such as lung sarcoidosis and cardiovascular diseases aggravated the disease course, led to the development of early ARDS and affected the lethal outcome.

Multidisciplinary management of a quickly growing pediatric atypical Spitz nevus, mimicking melanoma, during the COVID-19 pandemic

Spitzoid melanoma is very rare tumour in the pediatric population, with clinical and non-uniform behaviour, different from adult melanoma [1]. It can be difficult to differentiate an atypical Spitz nevus from a Spitzoid melanoma, resulting in diagnostic problems. In addition, in our clinical case, the COVID-19pandemiccaused significant delays both in the diagnosis and in the surgical treatment of our patient. We present the clinical case of a 4-year-old child suffering from a localized polypoid cutaneous neoformation on the dorsum of the left hand, which started immediately before the lockdown and steadily increased during the COVID-19 pandemic. After a general clinical framing, the child underwent an excisional biopsy at our Department of Plastic and Reconstructive Surgery, at the Policlinico of Foggia. Subsequently, two independent anatomic pathology groups examined the specimen. Definitive diagnosis was made only after careful genetic analysis in combination with supporting histological and immunohistochemical examinations. This clinical case shows how during the pandemic we have been facing advanced forms of tumours, compared to the previous period and highlight show an interdisciplinary and multicenter collaboration allowed a quick diagnosis of certainty, demonstrating the utility of molecular pathology as a fundamental aid in clinical/surgical practice. © 2022 The Authors

PATHOMORPHOLOGICAL FEATURES OF ACUTE RESPIRATORY DISTRESS SYNDROME IN COMPETING LUNG DISEASES: COVID-19 AND SARCOIDOSIS.

The COVID-19 pandemic is a worldwide problem. The clinical spectrum of SARS-CoV-2 infection varies from asymptomatic or paucity-symptomatic forms to conditions such as pneumonia, acute respiratory distress syndrome and multiple organ failure. Objective was to describe a clinical case of SARS-CoV-2 infection in the patient with sarcoidosis and cardiovascular pathology developing acute respiratory syndrome and lung edema. Material and methods. There were analyzed accompanying medical documentation (outpatient chart, medical history), clinical and morphological histology data (description of macro- and micro-preparations) using hematoxylin and eosin staining. Results. Lung histological examination revealed signs of diffuse alveolar damage such as hyaline membranes lining and following the contours of the alveolar walls. Areas of necrosis and desquamation of the alveolar epithelium in the form of scattered cells or layers, areas of hemorrhages and hemosiderophages are detected in the alveolar walls. In the lumen of the alveoli, a sloughed epithelium with a hemorrhagic component, few multinucleated cells, macrophages, protein masses, and accumulated edematous fluid were determined. Pulmonary vessels are moderately full-blooded, surrounded by perivascular infiltrates. Signs of lung sarcoidosis were revealed. Histological examination found epithelioid cell granulomas consisting of mononuclear phagocytes and lymphocytes, without signs of necrosis. Granulomas with a proliferative component and hemorrhage sites were determined. Giant cells with cytoplasmic inclusions were detected - asteroid corpuscles and Schauman corpuscles. Non-caseous granulomas consisting of clusters of epithelioid histiocytes and giant Langhans cells surrounded by lymphocytes were detected in the lymph nodes of the lung roots. Hamazaki-Wesenberg corpuscles inside giant cells were found in the zones of peripheral sinuses of lymph nodes. In the lumen of the bronchi, there was found fully exfoliated epithelium, mucus. Granulomas are mainly observed subendothelially on the mucous membrane, without caseous necrosis. Histological examination of the cardiovascular system revealed fragmentation of some cardiomyocytes, cardiomyocyte focal hypertrophy along with moderate interstitial edema, erythrocyte sludge. Zones of small focal sclerosis were determined. The vessels of the microcirculatory bed are anemic, with hypertrophy of the walls in small arteries and arterioles. Virological examination of the sectional material in the lungs revealed SARS-CoV-2 RNA. Conclusion. Based on the data of medical documentation and the results of a post-mortem examination, it follows that the cause of death of the patient R.A., 50 years old, was a new coronavirus infection COVID-19 that resulted in bilateral total viral pneumonia. So-morbidity with competing diseases such as lung sarcoidosis and cardiovascular diseases aggravated the disease course, led to the development of early ARDS and affected the lethal outcome. Copyright © 2022 Saint Petersburg Pasteur Institute. All rights reserved.

Kikuchi-Fujimoto disease following COVID-19 infection in a 13-year- old girl

Background/Purpose: Kikuchi-Fujimoto disease (KFD) is a rare, self-limited histiocytic necrotizing lymphadenitis. Although it is of uncertain aetiology, it is associated with viral infections and autoimmune diseases. Hence, it is crucial to identify KFD from other conditions with lymphadenopathy. Here we present a case of KFD after COVID-19 infection. Method(s): Medical records were traced and reviewed Results: A previously healthy 13-year- old girl was admitted in April 2022 with four weeks of fever, dry cough, loss of weight, followed by 1 week history of painful cervical lymphadenopathy and nonspecific maculopapular rash. She received her second dose of Covid 19 vaccine in January 2022. Unfortunately, she was diagnosed with CAT II, COVID 19 infection in March 2022. There was no history of allergy, recent traveling and cat scratch injury. Clinically there was no strawberry tongue, erythema of the lips, conjunctivitis or distal extremities changes to suggest Kawasaki disease. She was initially diagnosed with infection related lymphadenitis, treated with oral azithromycin for three days and intravenous ceftriazone for one week with no improvement. Her laboratory results showed hypochromic microcystic anaemia with leucopenia, raised inflammatory markers and lactate-dehydrogenese levels. Extensive workup for infection was unremarkable. Immunology test showed ANA, ANCA, ENA were negative with normal complements. Ultrasound abdomen was normal. Excisional lymph node biopsy revealed confluent areas of necrosis surrounded by histiocytes (CD68+) with absent of neutrophils. No granuloma or atypical lymphoid cells seen. Based on histopathology report, diagnosis of KFD was established. As she was not able tolerate orally, IV hydrocortisone was started and subsequently switched to oral prednisolone. She responded well to corticosteroids with fever subsided within a day and cervical lymphadenopathy reducing in size and resolved in one month. Prednisolone was able to taper off by two months. She showed complete recovery with no recurrence during follow-up. Conclusion(s): In persistent febrile painful lymphadenopathy, excision lymph node biopsy is essential to establish definite diagnosis. This case highlights the possible association between COVID-19 and KFD.

Immunohistochemical Interferon Gamma Expression in Chronic Intervillositis of Unknown Etiology

Background. Chronic intervillositis of unknown etiology (CIUE) is a rare cause of recurrent early pregnancy loss. Upregulated interferon gamma (IFNg) expression in syncytiotrophoblast has been shown in a small cohort of high grade CIUE cases suggesting this may play a role in pathogenesis;however, the extent of IFNg expression in this disease remains unclear. This study compares IFNg expression in CIUE to placenta from non-CIUE spontaneous early pregnancy losses and normal early gestations by immunohistochemistry. Method(s): Ethics approval is obtained for a tissue-based study comparing late first to mid second trimester archival placental tissue from high grade CIUE (CHG;18 cases), low grade CIUE (CLG, 12 cases), elective termination (NP, 13 cases), euploid spontaneous pregnancy losses (ESPL, 18 cases), and aneuploid spontaneous pregnancy losses (ASPL, 17 cases). 2 cases of third trimester pregnancy loss associated with placental COVID19 infection are included as examples of chronic histiocytic intervillositis of a known etiology. Atypical mycobacterial granuloma is employed as a positive control. IFNg expression is assessed on whole tissue sections by automated immunostaining and graded semiquantitatively by multiplying staining intensity (3+ same as control staining;2+ between 3+ and 1+;1+ just visible at 200x;0+ no staining visible at 200x) by distribution (1 <5%;2 5-50%;3 >50%) for a score from 0-9. Data are compared by 2-tailed independent t-test. Result(s): Focal positive syncytiotrophoblast IFNg staining is seen in 35% of CHG, 42% of LGH, and 4% of non-CIUE cases (0% NP, 0% ESPL, 12% ASPL). IFNg expression in CIUE placenta is characterized by luminal orientation in syncytiotrophoblast while the ASPL cases show non-luminally oriented cytoplasmic staining. IFNg is not expressed in other placental cell types. The average IFNg grade is 1.3 (range 1-9) for CHG, 0.7 (range 1-2) for CLG, 0 for NP and ESPL, and 12% (range 1-2) for ASPL. There is a statistically significant difference between CIUE and non-CIUE placenta (p = .0015) but not between CHG and CLG (overall p = .42;positive cases only p = .17). Occasional lymphocytes in the maternal intervillus space strongly express IFNg and these appear more abundant in areas with more prominent histiocytic inflammation. COVID19 placental tissue does not express IFNg but IFNgpositive lymphocytes are present in the intervillus space. Conclusion(s): A subset of high grade and low grade CIUE express IFNg suggesting this represents a distinct subgroup of CIUE. IFNg expression appears to correlate with grade implying IFNg expression is related to inflammation intensity although the difference is not statistically significant. Future studies of CIUE, particularly those assessing therapies, may benefit from separate assessment of IFNg positive cases.

Maternal thrombocytopenia due to inflammatory changes in the placenta precedes fetal death associated with COVID-19

Introduction: Acute coagulopathy, specific placental change, and fetal death are reported in pregnant women with COVID-19;however, the pathogenesis of them remains unknown. We report two cases of stillbirth in pregnant women with COVID-19 who showed acute coagulopathy and their placentas showed characteristic pathological findings due to COVID-19. Case: Case 1: A 28-year-old pregnant woman (gravida 3, para 2) who had undergone two cesarean sections had a fever of 39 degree and was positive for SARS-CoV-2 at 26 weeks of gestation. She showed thrombocytopenia and subsequent coagulopathy on day 7, and her fetus was dead on day 9. She underwent a cesarean section after blood transfusion and her coagulability thereafter improved. Case 2: A 35-year-old pregnant woman (gravida 3, para 2) who had no symptoms was positive for SARS-CoV-2 at 20 weeks of gestation. She also presented with thrombocytopenia on day 5. Her fetus was dead, and she went into labor spontaneously and virginally delivered a stillborn baby on day 9. Her coagulability thereafter returned to normal. Placental histology of both cases showed intervillous infiltration of histiocytes, necrosis of trophoblast, and fibrin deposition, and the expression of SARS-CoV-2 spike protein was observed in the syncytiotrophoblasts of the villi. Discussion(s): Specific placental changes related to COVID-19 are thought to be the result of an immune response rather than direct infection with SARS-CoV-2. The placental changes induced by COVID-19 might have caused fetal death. When managing pregnant women with COVID-19, thrombopenia may be a predictive marker of fetal death following placental inflammatory changes. Copyright © 2022

SMARCA4-DEFICIENT UNDIFFERENTIATED TUMOR: A RARE THORACIC MALIGNANCY

SESSION TITLE: Rare Malignancies SESSION TYPE: Case Reports PRESENTED ON: 10/17/2022 03:15 pm - 04:15 pm INTRODUCTION: SMARCA4 deficient undifferentiated tumors (SMARCA4-DUT) are rare and aggressive neoplasms that are most commonly encountered in young male smokers and portend a poor prognosis (1,2). They are characterized by loss of SMARCA4, a subunit of chromatin remodeling complexes, and loss of the tumor suppressor brahma-related gene 1 (BRG1). We present a case of an elderly female with an extensive smoking history who was diagnosed with SMARCA4-DUT. CASE PRESENTATION: An 84 year old female with approximately 70 pack year smoking history, emphysema, ischemic cardiomyopathy, and coronary artery disease, presented to the emergency room with upper abdominal pain which started one day prior to admission. She endorsed an unintentional 10 pound weight loss in the past two months. The patient was admitted for an incarcerated ventral hernia for which she underwent repair. Of note, one and a half years ago, she was found to have a right lower lobe 7mm nodule but was unable to follow up due to the COVID pandemic. On this admission, a CT chest revealed a 4.2 x 3.8 x 3.7cm mediastinal mass and subcarincal lymphadenopathy. She underwent an EBUS with biopsy of the mediastinal mass and subcarinal lymph node. Cytology showed highly atypical epitheloid cells, concerning for a neoplasm with neuroendocrine differentiation and granulomas. Given the high suspicion for malignancy, she had a PET CT (figure 1) which showed FDG activity (SUV 11) in the mass with areas of necrosis and was referred to thoracic surgery. She underwent thoracoscopy with mediastinal mass resection and lymph node dissection and pathology showed diffuse sheets of epithelioid cells with large foci of necrosis. Neoplastic cells showed preserved INI (SMARCB1) expression, non-reactivity for NUT, and complete loss of BRG1 (SMARCA4) expression, consistent with a SMARCA4-DUT with positive margins (figure 2). She was referred to Radiation Oncology with plans to pursue further therapy thereafter. DISCUSSION: SMARCA4-DUT is a new and distinctive clinicopathological entity of aggressive thoracic tumors (1). The novelty of this class of tumors poses challenges in terms of treatment. Immune checkpoint inhibitors have shown compelling outcomes in case reports (3), however larger studies are needed to delineate optimal treatment regimens. CONCLUSIONS: SMARCA4-DUT are are rare but highly aggressive thoracic neoplasms. They present as large tumors and are smoking related. Prompt recognition may aid in early diagnosis. No definitive therapy exists but immunotherapy has shown promising results. Reference #1: Chatzopoulos, K., Boland, J.M. Update on genetically defined lung neoplasms: NUT carcinoma and thoracic SMARCA4-deficient undifferentiated tumors. Virchows Arch 478, 21–30 (2021). Reference #2: Roden AC. Thoracic SMARCA4-deficient undifferentiated tumor-a case of an aggressive neoplasm-case report. Mediastinum. 2021;5:39. Published 2021 Dec 25. Reference #3: Henon C, Blay JY, Massard C, Mir O, Bahleda R, Dumont S, Postel-Vinay S, Adam J, Soria JC, Le Cesne A. Long lasting major response to pembrolizumab in a thoracic malignant rhabdoid-like SMARCA4-deficient tumor. Ann Oncol. 2019 Aug 1;30(8):1401-1403. DISCLOSURES: No relevant relationships by Sathya Alekhya Bukkuri No relevant relationships by Erin Meier No relevant relationships by Mangalore Amith Shenoy No relevant relationships by Alexandra Zavin

COVID-19: A CONFOUNDING MIMICKER OF HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS

SESSION TITLE: Challenging Cases of Hemophagocytic Lymphohistiocytosis SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/19/2022 12:45 pm - 1:45 pm INTRODUCTION: Hemophagocytic lymphohistiocytosis (HLH) is a rare syndrome involving pathologic immune activation that is often fatal. The link between the cytokine storm related to COVID-19 and development of HLH has been reported since the onset of the pandemic, but little is known about clinical manifestations of HLH, thereby delaying treatment. CASE PRESENTATION: A 50 year-old male presented with a several day history of progressive weakness in the setting of missed dialysis session. Medical history was significant for ESRD on dialysis and diastolic heart failure (EF 35%). Initial vitals were unremarkable. Physical exam was notable for peripheral edema bilaterally. Laboratory studies were consistent with hyperkalemia, elevated ferritin (28,383) and elevated liver function tests. COVID-19 PCR was positive upon admission. Chest x-ray, CTA chest and a right upper quadrant ultrasound were unremarkable. He was admitted to the medical ICU for emergent dialysis. Soon after arrival to the ICU, he became lethargic and confused with increasing oxygen requirements and a subsequent a code blue was called. Cardiopulmonary resuscitation was immediately initiated, with a first rhythm consistent with ventricular fibrillation. He was shocked and placed on an amiodarone infusion with return of spontaneous circulation. TTE revealed a severely reduced EF <10%. Despite initiation of advanced COVID-19 therapies with Solu-Medrol and tocilizumab he remained ventilator dependent. Due to hemodynamic instability and persistent metabolic acidosis, he was transitioned to continuous renal replacement. Further blood work showed worsening inflammatory markers (ferritin 33,500, LDH 6981). Because of the significantly elevated ferritin, there were concerns for possible HLH. Triglycerides and IL-2 receptor were 395 mg/dL and 9300 pg/mL respectively. Total NK cells were decreased to 1.2%. He remained persistently unstable despite aggressive measures. He suffered a second cardiopulmonary arrest, which was unable to achieve return of spontaneous circulation and he ultimately passed away. DISCUSSION: HLH is characterized by uncontrolled activation and proliferation of benign macrophages in reticuloendothelial organs. This results in histiocytic hemophagocytosis, worsening peripheral blood cytopenia(s), cytokine storm, and cytokine mediated biochemical alteration ultimately culminating in multiorgan dysfunction and disseminated intravascular coagulation. Although a distinctive constellation of features has been described for HLH, diagnosis remains challenging as patients have diverse presentations associated with a variety of triggers. CONCLUSIONS: As HLH is a medical emergency with poor prognosis, prompt recognition and early treatment is crucial for improving clinical outcomes. We hope this case will create increased awareness and timely diagnosis of cytokine storm syndromes in patients with severe COVID-19 infection. Reference #1: Meazza Prina M, Martini F, Bracchi F, Di Mauro D, Fargnoli A, Motta M, Giussani C, Gobbin G, Taverna M, D'Alessio A. Hemophagocytic syndrome secondary to SARS-Cov-2 infection: a case report. BMC Infect Dis. 2021 Aug 13;21(1):811. doi: 10.1186/s12879-021-06532-7. PMID: 34388982;PMCID: PMC8361241. Reference #2: Schnaubelt, Sebastian MDa,*;Tihanyi, Daniel MDb;Strassl, Robert MDc;Schmidt, Ralf MDc;Anders, Sonja MDb;Laggner, Anton N. MDa;Agis, Hermine MDd;Domanovits, Hans MDa Hemophagocytic lymphohistiocytosis in COVID-19, Medicine: March 26, 2021 - Volume 100 - Issue 12 - p e25170 doi: 10.1097/MD.0000000000025170 DISCLOSURES: No relevant relationships by Garrett Fiscus No relevant relationships by Niala Moallem No relevant relationships by Resham Pawar

SEVERE COVID-19 COMPLICATED WITH HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS: A CASE REPORT

SESSION TITLE: Challenging Cases of Hemophagocytic Lymphohistiocytosis SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/19/2022 12:45 pm - 1:45 pm INTRODUCTION: Worsening respiratory disease is the most common complication of severe COVID-19. However, when patients develop multi-organ dysfunction, clinicians must have a high index of suspicion for rare syndromes such as hemophagocytic lymphohistiocytosis (HLH). CASE PRESENTATION: A 39-year-old male smoker presented with 1 week of shortness of breath and malaise. Initial physical examination revealed T 37.3 C, pulse 85 min-1, respiratory rate 18 breaths min-1, SPO2 96% and clear breath sounds without labored respirations. Chest X-ray showed bilateral patchy airspace opacities in the mid and lower lung fields. A SARS-COV2 PCR test was positive. The patient was prescribed antibiotics and discharged home. Subsequently, the patient's symptoms worsened and he presented 1 week later with SPO2 90% (O2 10 L/min via nasal cannula). He was admitted to the hospital with COVID-19 pneumonia and began remdesivir, barcitinib, systemic steroids, albuterol and IV antibiotics. On admission his complete blood count and complete metabolic panel were unremarkable. After 3 weeks of hospitalization, he developed multi-organ failure with acute liver injury, acute kidney injury, shock, pancytopenia and worsening hypoxemia leading to endotracheal intubation and mechanical ventilation. CT chest imaging showed bilateral ground glass opacities in the lungs with superimposed consolidation (figure 1). Blood cultures remained sterile, HIV, hepatitis B and C viral serologies were negative. Serum viral polymerase chain reaction detected Herpes Simplex Virus-1 (HSV-1) and Epstein Barr Virus (EBV) infections. Trans-jugular liver biopsy confirmed HSV-1 hepatitis and showed sub-massive hemorrhagic necrosis of the liver (figure 2). Bone marrow biopsy demonstrated phagocytic histiocytes engulfing red blood cells and platelets consistent with HLH (figure 3). The patient began HLH targeted therapy with anakinra and high dose steroids. Despite this, the patient continued to deteriorate, developed refractory shock and subsequently expired. DISCUSSION: HLH is a rare disease of the immune system in which a genetic or infectious trigger causes uncontrolled T cell activation. T cell activation triggers macrophage activation, cytokine storm and macrophage phagocytosis of erythrocytes, leukocytes, platelets and precursors in the bone marrow and other tissues. If the syndrome is unrecognized, it can quickly lead to multi-organ failure and death. EBV is the most common infectious trigger of HLH;however, infection with HSV-1 and SARS-COV-2 viruses have been identified as rare and independent causes. CONCLUSIONS: This case illustrates the high index of suspicion providers should have for HLH in patients with severe COVID-19 who develop multi-organ injuries. Once HLH is suspected, prompt initiation of HLH-94 protocol with etoposide and dexamethasone may be lifesaving. For those patients with liver failure, other agents (e.g. anakinra) may be provided. Reference #1: Ramos-Casals M, Brito-Zerón P, López-Guillermo A, et al.: Adult haemophagocytic syndrome. Lancet 2014;383:1503–1516 Reference #2: Risma K, Jordan MB: Hemophagocytic lymphohistiocytosis: updates and evolving concepts. Curr Opin Pediatr 2012;24:9–15 Reference #3: Trottestam H, Horne A, Aricò M, et al.: Chemoimmunotherapy for hemophagocytic lymphohistiocytosis: long-term results of the HLH-94 treatment protocol. Blood 2011;118:4577–4584 DISCLOSURES: No relevant relationships by Erin Biringen No relevant relationships by Christine Brennan No relevant relationships by Joann Hutto No relevant relationships by Daniel Puebla Neira

A CASE OF PNEUMOCYSTIS JIROVECI PNEUMONIA MIMICKING METHOTREXATE-INDUCED PNEUMONITIS

SESSION TITLE: Procedures in Chest Infections Case Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Pneumocystis jirovecii pneumonia (PJP) is known to cause potentially life-threatening pneumonia in patients on immunosuppressive therapy. Here we describe a case of an elderly man on low dose methotrexate with PJP pneumonia initially mistaken for drug induced pneumonitis. CASE PRESENTATION: A 79 year old man with T-cell large granular lymphocytic leukemia on methotrexate, indeterminate colitis on azathioprine and sulfasalazine and interstitial lung disease was admitted for 3 week history of worsening dyspnea, lethargy and cough. On arrival his oxygen saturation was 87% on room air, requiring 5 liters oxygen via nasal canula. Lung examination was notable for bilateral crackles. Laboratory studies showed white blood cell count 12.4k/μL, lactate 2.7mmol/L, procalcitonin 0.137ng/mL, lactate dehydrogenase(LDH) 925 IU/L, 1,3 β-D glucan elevated at 154pg/mL. Infectious work up including COVID-19 testing was unremarkable. Chest radiograph showed bilateral diffuse interstitial infiltrates (figure 1) and computed tomography (CT) scan showed peripheral reticular changes and patchy ground glass opacities bilaterally (figures 2;3). He was initially treated for possible bacterial pneumonia;then with 125mg of methylprednisolone for presumed methotrexate induced pneumonitis without improvement. He underwent bronchoscopy with bronchoalveolar lavage(BAL) gram stain showing numerous histiocytes and scattered lymphocytes;no infectious organisms were isolated. PJP PCR from BAL came back positive and trimethoprim-sulfamethoxazole (TMP-SMX) was started. Despite maximum therapy he deteriorated clinically, transitioned to comfort care and expired. DISCUSSION: Diagnosis of PJP is made by visualization of cystic or trophic forms in respiratory tissue obtained via biopsy, BAL or sputum. Fungal burden is typically lower in non-HIV patients with PJP, and may result in negative BAL or sputum stain. Thus PCR testing is a useful diagnostic tool. Positive PCR alone cannot distinguish between colonization and active disease, and should be performed when clinical suspicion is high. 1,3 β-D glucan and LDH are nonspecific markers that help in presumptive diagnosis. First line therapy for PJP is TMP-SMX, with atovaquone, dapsone and pentamidine available as alternative therapies. Duration of therapy should be at least 21 days. Adjunctive corticosteroids show survival benefit in HIV-infected individuals. In severely hypoxic patients, corticosteroids are beneficial if started within 72 hours of antibiotic initiation. Their use in non-HIV PJP cases remains controversial. CONCLUSIONS: This case highlights the risk of PJP with long term methotrexate therapy. Cough, hypoxemia and bilateral interstitial infiltrates should prompt work-up for PJP. Timely recognition and early treatment are crucial to prevent mortality. Further studies are needed to assess the efficacy and provide guidelines for primary prophylaxis in this population. Reference #1: Wilson JW, Limper AH, Grys TE, Karre T, Wengenack NL, Binnicker MJ. Pneumocystis jirovecii testing by real-time polymerase chain reaction and direct examination among immunocompetent and immunosuppressed patient groups and correlation to disease specificity. Diagn Microbiol Infect Dis. 2011 Feb;69(2):145-52. doi: 10.1016/j.diagmicrobio.2010.10.021. PMID: 21251557;PMCID: PMC6855182. Reference #2: Salzer HJF, Schäfer G, Hoenigl M, Günther G, Hoffmann C, Kalsdorf B, Alanio A, Lange C. Clinical, Diagnostic, and Treatment Disparities between HIV-Infected and Non-HIV-Infected Immunocompromised Patients with Pneumocystis jirovecii Pneumonia. Respiration. 2018;96(1):52-65. doi: 10.1159/000487713. Epub 2018 Apr 10. PMID: 29635251 DISCLOSURES: No relevant relationships by Rutendo Jokomo-Nyakabau No relevant relationships by Richard Swaney No relevant relationships by Manasa Velagapudi

EVALUATION OF BONE MARROW & PERIPHERAL BLOOD SMEAR FINDINGS IN SARS-COV-2 PATIENTS, CENTRAL INDIA

This study was done to assess the morphological changes in peripheral blood smears during COVID-19 infection .We aimed to examine the characteristics of the cells detected in the peripheral blood smear and bone marrow at the time of diagnosis in COVID-19 patients. Clinical features, laboratory data, peripheral blood smear of 35patients diagnosed with COVID-19 by PCR was evaluated at diagnosis. Peripheral smear samples of the patients were compared with the age and sex-matched 35 healthy controls. The relationship between the laboratory values of all patients and the duration of hospitalization was analyzed. Peripheral smear shows neutrophilic leucocytosis, lymphopenia and thrombocytopenia while Bone marrows were normocellular to hypercellular, most showing maturing trilineage hematopoiesis with myeloid left shift. In 09 out of 35 evaluable bone marrows, hemophagocytic histiocytes were identified.

A Case of Pulmonary Cryptococcosis After Severe COVID-19 Pneumonia T. Roesch

Introduction / Case Presentation:46yo female with a history of CKD, atrial flutter, bioprosthetic valve with mitral ring, and recent COVID-19 pneumonia who presented to the emergency department (ED) with shortness of breath, fevers, and fatigue. Three months prior, she had been diagnosed with severe COVID-19 pneumonia, for which she received dexamethasone, remdesivir, tocilizumab, anakinra, and IVIG. She was discharged to a nursing facility with a prolonged steroid taper, ending 1 month prior to admission.In the ED, the patient had a chest x-ray that demonstrated bibasilar atelectasis and opacification, and a CT chest revealed right lower lobe consolidation and surrounding ground glass opacities. A respiratory pathogen PCR swab was negative. Sputum culture was negative for bacterial and fungal growth. Blood cultures did not grow any organisms. Given recent immunosuppression and imaging findings, a serum Cryptococcal antigen was drawn, which was positive with a titer of 1:128. A transthoracic needle biopsy of the patient's right lower lung was then performed. The specimen did not grow any bacteria or fungi and AFB stain on the tissue was negative. Pathology demonstrated a collection of histiocytes, neutrophils, and necrotic debris. PAS, GMS, and mucicarmine stains were positive for fungal organisms consistent with Cryptococcus species. Discussion: Cryptococcosis is a fungal infection due predominately to one of two encapsulated yeasts, Cryptococcus neoformans or Cryptococcus gattii. C. neoformans is found in soil worldwide, and infection typically begins with spore inhalation. Clinically significant disease is seen mostly in immunocompromised patients.Corticosteroids and interleukin inhibitors, such as anakinra (IL-1) and tocilizumab (IL-6), are used in the treatment of COVID-19. These medications have been associated with increased risk for opportunistic infections, including invasive fungal infections. The diagnosis of pulmonary cryptococcosis may be challenging, as symptoms are often nonspecific and may radiographically resemble bacterial pneumonia, malignancy, or other infections. Serum cryptococcal antigen detection tests may be helpful in establishing the diagnosis, as well as histopathology showing narrow-based budding yeast. Conclusion: Patients with prior COVID-19 infection commonly return to healthcare settings with sequelae of their previous coronavirus infection. In our case, it was the prior treatment of COVID-19, which included immunomodulating therapy, that lead to a secondary pulmonary cryptococcal infection. When evaluating pulmonary processes that evolve after an acute infection with COVID-19, it is important to keep a broad differential, including uncommon and/or opportunistic infectious etiologies, particularly when a patient has received prolonged courses of steroids and tocilizumab.

Placental pathologies and fetal outcome in pregnant women with COVID-19: A retrospective study

Objective: To describe histopathologic findings in the placentas in women with coronavirus disease 2019 (COVID-19) during pregnancy. Methods: In a cross-sectional study, 38 pregnant women with COVID-19 and undergoing delivery between March 2020 and January 2022, were included. The patients had positive polymerase chain reaction (PCR) test for SARS-CoV-2 infection and the placentas after delivery were sent for histopathologic evaluation based on the Amsterdam Placental Workshop Group Consensus Statement and assessed by two pathologists. Results: Our results showed that maternal vascular malperfusion was the most common and was present in 17 cases (44.7%). These features included accelerated villous maturation (36.8%) distal villous hypoplasia (5.3%), placental infarction (5.3%) and intervillous fibrin deposition (10.5%). Other pathologic findings included focal calcification (10.5%), intravillous congestion and hemorrhage (10.5%), sub-chorionic hemorrhage (5.3%), acute villitis, chronic histiocytic intervillositis and delayed villous maturation each in one case (2.6%). Twelve out of 38 cases showed no significant pathologic changes. Fetal outcomes included neonatal intensive care unit admission rate of 13.2%, dyspnea 31.6%, newborn's anosmia 7.9%, intrauterine fetal demise 2.6%, asphyxia 2.6% and neonate COVID infection 5.3%. Conclusions: Microvasculopathy, as a sign of maternal vascular malperfusion, is a common finding in placentas from SARS-CoV-2 positive pregnant women in the present study. Further studies with larger sample sizes and comparative studies between COVID-19 positive and negative, as well as information from patient follow-up are suggested.

MISDIAGNOSIS OF KIKUCHI-FUJIMOTO DISEASE: THE IMPORTANCE OF TIMELY HISTOPATHOLOGY IN LYMPHADENITIS

Background: Febrile lymphadenopathy not responding to first line antibiotics in a patient hailing from or with a history of travel to tuberculosis endemic countries is often primarily diagnosed as extra-pulmonary tuberculosis. However, histiocytic necrotizing lymphadenitis or Kikuchi-Fujimoto Disease(KFD) presents with similar clinical features. Etiological theories of KFD include viral agents, autoimmunity, and physicochemical factors such as leaking implants. Although KFD has classically been described in young Asian females, recent studies show men and women can be equally affected, with cases increasingly being reported from the USA and Europe as well. Availability bias amongst physicians can lead to misdiagnoses, especially in patients from tuberculosis endemic countries. Objectives: To describe a case of misdiagnosis of KFD in an adolescent. Design/Method: Case report. Results: A 16-year-old male from a tuberculosis endemic country, with a history of asthma, eczema and excision of omental infarct, presented with sub-occipital lymphadenopathy which resolved with antibiotics. Six months later, he complained of tender left cervical lymphadenopathy, associated with fever and fatigue, which lasted for a month. Two courses of antibiotics failed to decrease symptoms. Based on his clinical history, he was started on empirical anti-tubercular medications despite negative tests for tuberculosis. However, his symptoms began to worsen after three weeks of this treatment, and he developed high evening rise of temperature associated with chills, night sweats, frontal headache, pedal edema and generalized pruritic maculopapular rash. Laboratory workups revealed leukopenia (WBC:3830/μL);elevated Erythrocyte sedimentation rate (29 mm/h), C-reactive protein (68.6 mg/dL), Aspartate Aminotransferase(95 U/L) and Alanine Aminotransferase(61 U/L). Rapid antigen test for SARS-CoV2 was negative, and no appreciable levels of SARS-CoV-2 IgG antibodies were detected. Investigations for Tuberculosis, EBV, CMV, Dengue, Malaria, Typhoid, Leptospirosis and Scrub typhus were all negative. Chest X-ray and abdomen ultrasound scan were normal. Histopathological analysis of the excised cervical lymph nodes demonstrated crescentic histiocytes and karyorrhexis in a background of coagulative necrosis. Neutrophils, granulomas and acid-fast bacilli were absent. Immunohistochemistry was positive for CD3, CD20, CD68;and negative for CD15, CD30 and PAX-5. A diagnosis of KFD was made, and patient was given supportive treatment only. His symptoms rapidly resolved within 48 hours, with complete resolution by three months. Conclusion: It is important to raise awareness of KFD, a benign and self-limiting condition with good prognosis, which has many clinical symptoms mimicking grave conditions like extra-pulmonary tuberculosis, SLE and lymphomas. Timely histopathological analysis can help avoid anxiety surrounding a misdiagnosis and adverse reactions due to unnecessary toxic treatments.