A Case of Untreated Myeloid Sarcoma of the Pancreas Head Region: Diagnostic Process of AML Subtyping in an Autoptic Case

This study describes an autopsy case of pancreatic/peripancreatic myeloid sarcoma in a 70-year-old man, initially presenting with obstructive jaundice. Pathologically, diffuse infiltration of round cells containing atypical nuclei with marked cleavage was observed mainly in the pancreas head, peripancreatic lymph nodes, spleen, bilateral lung, and bone marrow. Immunohistochemically, the tumor cells were negative for CD20, CD79a, CD3, CD5, c-kit, CD34, and TdT and positive for myeloperoxidase, CD33, CD68, and CD163. Flow cytometry of the peripheral blood showed underexpression of CD11c and aberrant expression of CD56 in the monocyte subset. The peripheral blood smear showed an increase in monocytes and atypia in neutrophils and monocytes, as well as enlarged platelets and polychromatic erythroblasts. Hence, it was suggested that the myeloid sarcoma was derived from the acute transformation of chronic myelomonocytic leukemia. Myeloid sarcoma is an extramedullary-mass-forming hematologic malignancy that is difficult to diagnose, especially when the initial presentation is a pancreatic mass. However, early diagnosis is important for appropriate therapy. Although bone marrow examination could not be performed because of the patients’ severe condition, the pathological specimen obtained with autopsy helped subtype the patient’s leukemia. The immunohistochemical features of this case merit attention.

PATHOHISTOLOGICAL CHANGES IN PIGS WITH MYCOPLASMOSIS

A pathological autopsy was performed on 6 corpses of piglets in the first week of life who died from mycoplasmosis. Examination of the visible mucous membranes revealed hyperemia of the mucous membrane of the nasal cavity and thymus. Simultaneous lesions of the pharyngeal, parotid, cervical, mandibular lymph nodes were noted. They were slightly enlarged, from dark pink to dark red. The heart is irregularly shaped due to the expansion of the right ventricle or the diffuse expansion of all departments. Lungs have doughy consistency, uneven color. In some cases, there are diffuse red areas covering the entire lobe of the lungs, in other cases, there is a defeat of small areas. The liver has a smooth surface, soft or pasty consistency, the parenchyma pattern is slightly smoothed in section. The color of the liver is different: dark red areas, without clear boundaries turn into creamy-clay. Flatulence was a characteristic feature of the stomach and intestines. Catarrhal enteritis was registered in animals, which manifested itself in the form of moderate hyperemia of the intestinal mucosa and serous membranes. Microscopically, there is a significant blood supply to the vessels in the lungs. Alveoli are half fall down, in the form of slit-like lumens. In areas of tissue infiltration by inflammatory infiltrate, the alveolar wall is thickened, alveocytes are in a state of turbid swelling and vacuolar dystrophy, they are impregnated with erythrocytes. Peribronchial pneumonia of lymphocytic character is observed. The liver is in a state of acute venous hyperemia. The central and intraparticle capillaries are sharply dilated and filled with blood in some lobes, and the hepatic beams are compressed accordingly. In the center of other lobes, diffuse infiltration of liver tissue by erythrocytes as a consequence of diapedesis is noted. Hepatocytes are in a state of granular dystrophy. Destructive changes are strongly expressed in the mucous membrane of the small intestine: desquamation of the epithelium, necrosis of epitheliocytes and villi, destruction of crypts. In the brain tissue, there is dilation of the lumens of large and small blood vessels, extracellular and perivascular edema, areas of reactive necrosis.

57 Undifferentiated heart sarcoma in young adult: from differential diagnosis to management

A 34-year-old patient arrived in Emergency Department (ED) with a history of haemoptysis, fever, and night sweats. Echocardiographic examination revealed a large isoechoic thickening that totally encompassed posterior mitral leaflet and which extended contiguously, both inferiorly with subvalvular apparatus with chordal fusion, and superiorly up to left atrial wall. This alteration caused a moderate mitral stenosis with an estimated average gradient of 10–15 mmHg (with possible overestimation due to temporary state of hyperdynamic circulation secondary to anaemization). There also was an anteriorly directed, eccentric jet of mitral regurgitation (2 +/4 + grade).Differential diagnosis of the aforementioned mitral formation included infectious etiology (endocarditic vegetation), pure phlogistic (inflammatory/rheumatic valvulitis), aseptic vegetation, and thrombosis. Transesophageal echocardiographic evaluation showed the extension of the mass into posterior leaflet, the latter completely englobed from commissure to commissure, and cranially adhered to posterior wall of left atrium with estimated dimensions of 1.9 × 12 mm; inferiorly, contiguity with diffusely thickened subvalvular apparatus and chordal fusion, was appreciated. Resulting stenosis was about 13–14 mmHg. Planimetric mitral valve area was estimated to be about 1 cm with associated mild-moderate regurgitation. Global systolic function was preserved with normal segmental kinesis and without significant anomalies affecting other valves. On cardiac magnetic resonance (CMR) with contrast medium, known sleeve thickening of left atrium (maximum thickness 12 mm in lateral area and 7.5 mm at the level of atrial septum) was extended caudocranially for 2.5 cm in lateral area and for 3.2 cm in the side of the atrial septum and with subocclusion of left inferior pulmonary vein. An esophagogastroduodenoscopy (EGDS) was performed with biopsy examination and subsequent histological typing. It concluded for ‘undifferentiated pleomorphic sarcoma’ according to the WHO classification of thoracic tumours. In the stomach there was a diffuse infiltration of lamina propria by atypical, pleomorphic, and large cellular elements. Following cancer evaluation, first-line chemotherapy with ifosfamide and doxorubicin was undertaken. Two days later, due to finding of hyperpyrexia, with a feverish peak of up to 39°, infusion of chemotherapy was interrupted and empiric antibiotic therapy (piperacillin tazobactam) was started. Blood and urine cultures were carried out with search for antigens of legionella and pneumococcus, (MRSA), fungi, and respiratory viruses but all of them were negative for active infection. The following day, an episode of acute respiratory failure occurred, so we performed an urgent chest CT with finding of pneumonia with bilateral pleural effusion and linezolid was started. Because of sudden worsening of clinical conditions, patient was transferred to ICCU (Intensive Cardiac Care Unit) with gradual resolution of desaturation. Cardiac ultrasound imaging, from the very first performed in ED, has been fundamental in documenting the presence of a mass in mitral valve. The timeliness in identifying first and then characterizing it certainly had a positive impact on cancer management, especially in such an aggressive neoplasm in a young patient. Furthermore diagnostic process, corroborated by instrumental data provided by ecocardiography, CT, MRI, PET, and scintigraphy, allowed a better staging of the disease and highlighted other organ involvement in order to manage optimal therapeutic approach.

COT-12 Clinical feature of end-stage glioblastomas

Glioblastoma is the most common and most aggressive primary brain tumor. Even with optimal treatment, tumors repeatedly recur and grow, eventually invading the entire brain. Few studies have evaluated the pathogenesis and pathophysiology of terminal glioblastoma. In this study, we describe the pathological characteristics of 26 glioblastoma cases (including 18 autopsy cases) that were analyzed from initial treatment to confirmation of death at our hospital. The mean age of the 26 patients was 60.7 years, and mean overall survival was 16.7 months. The interval of clinical symptoms from coma to death was 36.2 days, and the interval from onset of respiratory depression to death was 12 days. Steroids and antiepileptic drugs were often continued after completion of active treatment. Psychiatric symptoms and central fever were observed in patients with intrathecal dissemination, and disease progression was rapid in these patients. These patients presented with a variety of symptoms, including psychiatric symptoms, headache, neck pain, and central fever. In addition, a case of diffuse infiltration from the brain parenchyma to the periventricular area in a patient treated with bevacizumab suggested a possible change in the form of recurrence. In the terminal stage of glioblastoma, hypoxemia due to disturbance of the respiratory center results in progression from impaired consciousness to death. Because convulsive seizures are rare when patients are close to death, continuation of antiepileptic drugs may not be necessary. Although many patients develop local recurrences, new treatments may change the mode of recurrence or alter tumor cell characteristics. The number of patients receiving home care and end-of-life care has recently been increasing because of medical improvements, such as home care. Further study of the pathophysiology of glioblastoma may yield better end-of-life care.

553 Myocarditis after COVID-19 vaccination—a case series

Myocarditis has been recognized as a rare complication of SARS-CoV-2 infection even in the absence of lung involvement and recent histological findings suggest that COVID-19-related myocardial damage may differ from other typical lymphocytic myocarditis associated with other viruses and could be possibly linked to diffuse infiltration of monocytes and macrophage leading to microvascular dysfunction and cell necrosis. SARS-CoV-2 vaccines have been well tolerated and associated with decreasing burden of disease in areas with high vaccination rates. Minor side-effects have been frequently described, mainly after second dose. Here, we report our findings in four male patients consistent with acute myocarditis at our Institutional Hospital; all four had recently received a second-dose mRNA vaccine. All presented with acute chest pain associated with biomarker evidence of myocardial injury and were hospitalized. None of them had a previous history of SARS-CoV2 infection. All of them showed markedly abnormal EKG findings with diffuse ST segment elevation and laboratory tests revealed elevated high-sensitivity (hs) troponin T levels and C-reactive protein with no peripheral eosinophilia. All patients underwent nasopharyngeal swabbing and the specimens were tested for common respiratory viruses by RT-PCR and resulted all negative. All patients underwent CMR scan during hospitalization. The hospital course was benign for all patients without evidence of arrhythmias or heart failure, in all cases we performed a conservative treatment with nonsteroidal anti-inflammatory drugs and colchicine with progressive normalization of troponin levels before discharge. Our cases presented features of acute myocarditis with a temporal association with the mRNA Covid-19 vaccination, in absence of other apparent causes (in fact none had viral prodromes) nor COVID-19 infection in the prior year. Several reports in the past months had suggested a possible association between the mRNA Covid-19 and myocarditis, most of the cases presenting in young males, after the second dose and with a favourable course. Thus, given the potential risk of cardiac involvement after SARS-CoV-2 infection even in younger adults, the risk-benefit decisions favours vaccination for population immunity. Despite this, the potential mechanisms of SARS-CoV-2 vaccine-related myocarditis seem different from the previously described eosinophilic myocarditis after smallpox vaccination remain unclear and vaccine adverse event reporting remains of high importance. Figure 1 shows one acute MRI scan with STIR, T2-map and LGE in short-axis and apical four-chamber view.

EXTH-49. FOCUSED ULTRASOUND AND 5-ALA MEDIATED ELIMINATION OF DIFFUSE MIDLINE GLIOMA

Diffuse midline glioma (DMG) is a devastating and incurable childhood brain cancer. With a median survival of only 9 to 11 months, over 90% of children affected by DMG die within two years of diagnosis. Despite decades of research and a growing understanding of the biology of these tumors, there have been no advancements in therapies for DMGs. Tumor heterogeneity and diffuse infiltration in inoperable brain regions make these tumors uniquely difficult to manage both surgically and pharmacologically. Therefore, there is an urgent need for the exploration of novel treatment regimens. Focused Ultrasound (FUS) is an emerging technology with significant clinical potentials. Sonodynamic therapy (SDT) is an up-and-coming treatment strategy aiming to non-invasively eliminate tumor cells by acting through compounds known as sonosensitizers, which render tumor cells sensitive to ultrasound energy. Recently, 5-Aminolevulinic acid (5-ALA), an FDA-approved molecule, has been proposed as a sono-sensitizing agent. 5-ALA mediated SDT prolonged survival in C6 rat glioma models by selective elimination of tumor cells upon sonication. Mechanistically, it is thought that 5-ALA uptake and metabolic conversion into Protoporphyrin IX (PpIX) occurs preferentially in tumor cells due to differential activity of enzymes involved in heme metabolism. Here, we investigated SDT in DMG cells treated with 5-ALA. PpIX fluorescence increased linearly up to 24 h upon 5-ALA treatment and accumulated significantly more (1.6-fold, p < 0.01) when compared to C6 cells. Consequently, FUS sonication of 5-ALA treated DMG cells at 250 kHz significantly (p < 0.05) decreased DMG cell viability compared to treatment with 5-ALA or FUS alone. Here, we show the first 5-ALA mediated sonodynamic effect in DMG cells, leading to enhanced cell death. Our findings provide a rationale for considering clinical investigation of 5-ALA mediated sonodynamic therapy in DMG.

Hodgkin Variant of Richter’s Transformation in Chronic Lymphocytic leukemia (CLL): An Illustrative Case Report and Literature Review

Hodgkin lymphoma variant of Richter’s transformation (HL-RT) is a rare event, occurring in < 1% chronic lymphocytic leukemia (CLL) cases, of which, in < 10% cases, HL is the first finding leading to a diagnosis of CLL that co-exists simultaneously. Here we report a 60 years old male patient who presented with an outside diagnosis of lymphocyte-rich classical HL. On evaluation, he had only B-symptoms in the form of low-grade fever and weight loss. Peripheral smear revealed mild leukocytosis with an absolute lymphocytosis and a few smudge cells. Bone marrow (BM) aspirate and biopsy exhibited diffuse infiltration by a small cell, low grade, Non-Hodgkin’s lymphoma with no immunohistochemical evidence of HL. Flow cytometry performed on BM was consistent with classical immunoprofile of CLL. Meanwhile the lymph node received for review revealed diffuse effacement of nodal architecture by small mature lymphocytes with immunoprofile of CLL expressing CD20, CD5, and CD23. Interspersed between these cells, were a few eosinophils along with classical Reed Sternberg cells, expressing CD30, MUM-1, CD15, and dim PAX-5, with a surrounding rosette of T-Cells highlighted by CD3 and PD-1 and negative for CD45, CD20, and EBV immunohistochemistry. Fluorodeoxyglucose positron emission tomography (FDG-PET) scan revealed hepatosplenomegaly with multiple supra/infra diaphragmatic lymph nodes. So, a final diagnosis of HL-RT in CLL was considered. The patient is currently doing well after the first cycle of ABVD chemotherapy. HL-RT occurring in CLL is a rare event with heterogeneous clinical presentation, morphology, clonal origin, disease course, prognostic features, and survival.

Breast myeloid sarcoma presenting as a palpable breast lump after allogeneic stem cell transplantation for acute myelomonocytic leukemia: a rare case report

Background Myeloid sarcoma (MS) is a tumor secondary to myeloid leukemia that consists of immature granulocytes with or without mature granulocytes and is a rare extramedullary manifestation of acute myeloid leukemia (AML). Case presentation We report a case of a 34-year-old woman diagnosed with AML-M4 who achieved remission after chemotherapy and received allogeneic stem cell transplantation (allo-SCT) for consolidation. Her past medical history showed that she received bilateral breast implants 7 years ago. This patient underwent ultrasound examination of the breast and multiple bilateral breast nodules were revealed that were not considered by clinicians to be concerning. Several months later, the patient’s bilateral nodules rapidly progressed to large palpable masses. Ultrasound-guided biopsy revealed diffuse infiltration of undifferentiated tumor cells and immunohistochemistry (IHC) indicated that the tumor was positive for myeloperoxidase (MPO), cluster of differentiation (CD) 34, CD43, CD68, CD117, and Ki67. The pathological diagnosis was extramedullary recurrence of AML as MS of breast. After the diagnosis, the patient received systemic chemotherapy and drugs containing cytarabine, azacitidine, and methotrexate. However, 1 year after achieving partial remission, the patient died from intracranial invasion of leukemia, brain herniation, and respiratory failure. Conclusion It is necessary for the specialist to have a high suspicion index by careful inquiry of the patient’s medical history if a patient presents at the breast clinic with a breast tumor as the chief complaint. Combining information from the patient’s medical history with a tumor biopsy is critical for obtaining the correct diagnosis of the disease.

The Presence and Potential Role of ALDH1A2 in the Glioblastoma Microenvironment

Glioblastoma (GBM) is the most aggressive malignant glioma. Therapeutic targeting of GBM is made more difficult due to its heterogeneity, resistance to treatment, and diffuse infiltration into the brain parenchyma. Better understanding of the tumor microenvironment should aid in finding more effective management of GBM. GBM-associated macrophages (GAM) comprise up to 30% of the GBM microenvironment. Therefore, exploration of GAM activity/function and their specific markers are important for developing new therapeutic agents. In this study, we identified and evaluated the expression of ALDH1A2 in the GBM microenvironment, and especially in M2 GAM, though it is also expressed in reactive astrocytes and multinucleated tumor cells. We demonstrated that M2 GAM highly express ALDH1A2 when compared to other ALDH1 family proteins. Additionally, GBM samples showed higher expression of ALDH1A2 when compared to low-grade gliomas (LGG), and this expression was increased upon tumor recurrence both at the gene and protein levels. We demonstrated that the enzymatic product of ALDH1A2, retinoic acid (RA), modulated the expression and activity of MMP-2 and MMP-9 in macrophages, but not in GBM tumor cells. Thus, the expression of ALDH1A2 may promote the progressive phenotype of GBM.