Neoplastic Infiltration Research Articles

1076 AN UNUSUAL PAPILLARY MUSCLE PRESENTATION AT CARDIAC-MRI.

Abstract Background Cardiac-MRI is the gold-standard non-invasive imaging modality to evaluate cardiac masses. Case Summary A 58-year-old man underwent surgical excision of a sacral chordoma. At the time of surgery, there was neoplastic infiltration of bones and soft tissues (immunophenotype: CKMNF116+, EMA+, S100 +/-) and radiotherapy was performed. The patient underwent superior-lobectomy of the left lung six years later because of pulmonary metastasis of the chordoma. Nine years later, the patient was asymptomatic and referred to us for Cardiac-MRI because a suspected cardiac mass at echocardiography. At Cardiac-MRI, we found normal bi-ventricular volumes, wall thickness, wall motion and ejection fraction. Atria, heart valves and pericardium were normal too. In ssFP-cine images, an oval, hypointense mass with sharp margins (26×18 mm) was evident in the context of the posteromedial papillary muscle (Panel, A-B). Compared to the myocardium, the lesion was hyperintense at T2-weighted (Panel, C), native T1-(Panel, D) and T2-mapping sequences (Panel, E). After contrast injection, there was no increased mass signal at first-pass perfusion (Panel, F), whereas the late sequences revealed a soft, heterogeneous enhancement of the central core of the lesion, and a bright peripheral rim (Panel, G-H). These findings were interpreted as a cardiac metastasis of the chordoma and systematic treatment with imatinib was started. Discussion Six cases of cardiac metastasis secondary to chordoma were previously described. The present case is the first to provide advanced, multiparametric Cardiac-MRI assessment and represents the first description of a location within the context of a papillary muscle. Cardiac-MRI was essential to identify cardiac metastasis, leading patient's management and targeting appropriate treatment.

864 ISOLATED CARDIAC METASTASIS FROM CARCINOMA OF THE CERVIX: RARE CASE OF ACS-NSTE. CASE REPORT

Abstract Introduction The heart is a rare site of tumor metastasis. Although rarely, cardiac metastases may be secondary to a primary intra-abdominal tumor. Aim we report the case of a 60-years-old woman, ante-mortem finding of an isolated cardiac metastasis from cervical carcinoma presented as ACS-NSTE, who was evaluated in our Division of Cardiology. Materials and methods electrocardiogram, transthoracic echocardiography, angioTC, cardiac surgery and histopathologic analysis were performed. Results electrocardiogram showed incomplete right branch block with diffuse negative T waves. On the echocardiogram evidence of a voluminous hypo-isoechoic formation almost completely occupying the cavity of the right ventricule (RV) which appeared dilated and dysfunctional; D-shape aspect of the left ventricule as from the overload of the right sections and with moderate pericardial effusion, mildly reduced ejection fraction (EF50%Q). An urgent Angio-CT was performed and revealed a voluminous solid neoformation with inhomogeneous content and progressive contrast enhancement in the right ventricule. Following admission, the patient's haemodynamic status gradually worsened. Therefore, urgent cardiac surgery was performed. After drainage of abundant serum/haematic effusion, probably neoplastic infiltration of RV was seen. Therefore, given the extension it was decided to perform only multiple biopsies. Histopathological examination revealed moderately differentiated squamous cell carcinoma, as from metastasis from K. cervix. Conclusions there is no standardized therapy for the treatment of cardiac metastases, it is necessary to evaluate on a case-by-case basis. The most important prognostic factors are the obstructive effect of the intracardiac mass and the extent of any pericardial effusion. In fact, they can adversely affect hemodynamic stability.

73 WHICH IS THE CULPRIT OF THIS MYOCARDIAL INFILTRATION?

Abstract Introduction Myocardial infiltration by primary cardiac neoplasm is a rare condition and the pathological spectrum includes more widespread benign cell types, providing exceptional diagnostic and therapeutic challenges. Refractory heart failure, pericardial effusion and arrhythmias due to infiltrative mass are the most common clinical manifestations. Multimodality imaging, with echocardiography, computed tomography and magnetic resonance imaging, is essential to determine the characteristics of a cardiac tumor. Clinical case: A 35-year-old man without cardiovascular risk factors presented with two months of shortness of breath and weight loss. A previous history of acute myeloid leukemia undergoing allogenic bone marrow transplant was reported. Transthoracic echocardiography revealed an apical thrombus in left ventricle with inferior and septal hypokinesia conditioning mildly reduced ejection fraction, circumferential pericardial effusion without cardiac tamponade and abnormal right ventricular thickening (Figure 1). The cardiac magnetic resonance imaging confirmed diffuse thickening of the right ventricular free wall (maximum diameter 30 mm), suspected for myocardial infiltration, extending to the right atrium and left ventricle with an ischemic pattern of the inferior wall (Figure 2). No coronary artery disease was found by coronary angiography, but the right coronary artery was incorporated by the pathological tissue in chest computed tomography scan. Cardiac positron emission tomography demonstrated the presence of neoplastic tissue with increased metabolic activity, whose similar characteristics were also evident in the ascending aorta and aortic arch. Being the percutaneous endomyocardial biopsy inconclusive, a pericardiectomy was performed through a median sternotomy incision, showing widespread cardiac neoplastic infiltration. Histopathological analysis, done on samples taken by surgical myocardial biopsy, revealed tissue involvement by a rare and aggressive cardiac anaplastic large T-cell non-Hodgkin lymphoma (ALK -, Ki-67 90%). Few days after surgery, the patient developed a refractory cardiogenic shock and unluckily died before establishing an adequate therapy. Conclusion Primary cardiac lymphoma is very infrequent and the non-specificity of the symptoms makes the diagnosis extremely challenging and often limited to autopsy findings. Our case highlights the importance of an appropriate diagnostic algorithm that can allow an early diagnosis and an adequate therapy of this otherwise fatal pathology. In this condition surgical removal of the tumor in not indicated, being chemotherapy the only effective treatment. However, because of rarity, data are lacking to produce definitive regarding guidelines.

Site-Coded Oral Squamous Cell Carcinoma Evaluation by Optical Coherence Tomography (OCT): A Descriptive Pilot Study

Optical Coherence Tomography (OCT) is an emerging non-invasive method for oral diagnostics, proving to be a practicable device for epithelial and subepithelial evaluation. The potential validity of OCT in oral cancer assessment has been explored but, to date, there are very few investigations conducted with a systematic comparison between clinical/histological and OCT parameters, especially in strict reference to the anatomical site-codification of the oral mucosa. In this regard, our study performed a two-steps evaluation (in vivo OCT and histological investigations) of suspected OSCCs, progressively recruited, using as references the OCT images of the same site-coded healthy mucosa, to provide as much as possible site-specific determinants. Thirty histologically confirmed OSCCs were recruited. Specific OCT mucosal features (SEL-Stratified Epithelial Layer; BM-Basement Membrane; LP-Lamina Propria) were registered and processed using the SRQR (Standards for Reporting Qualitative Research) statement. The systematic dual descriptive OCT analysis revealed that OSCC scans present a complete alteration of epithelial (KL, SEL) and subepithelial (BM, LP) layers with a site-specificity characteristic; moreover, peculiar OCT configurations such as "icicle-like" structures could be strongly suggestive of neoplastic infiltration. This study supports the OCT use for the development of more specific optical structural models applied to oral carcinogenesis.

Summit: A 3-Part, Phase 2 Study of Bezuclastinib (CGT9486), an Oral, Selective, and Potent KIT D816V Inhibitor, in Adult Patients with Nonadvanced Systemic Mastocytosis (NonAdvSM)

Background: Systemic mastocytosis (SM) is characterized by neoplastic mast cell infiltration of extracutaneous tissues and encompasses a spectrum of subtypes that can range from non-advanced to advanced disease. NonAdvSM is characterized by the lack of mast cell-related organ damage (e.g., C-findings) and other features of advanced SM such as associated hematologic neoplasms. NonAdvSM includes two variants of SM: indolent systemic mastocytosis (ISM) and smoldering systemic mastocytosis (SSM). ISM affects nearly 85% of the general SM population and is characterized by symptoms related to mast cell degranulation/mediator release. SSM is characterized by higher mast cell burden in the absence of organ damage or an associated hematologic neoplasm. There are currently no approved therapies for the treatment of the underlying causes of ISM or SSM, and anti-mediator therapies are used for symptom control with variable efficacy and tolerability due to disease heterogeneity. In up to 95% of patients, SM is driven by the somatic KIT D816V gain of function mutation located in exon 17; therefore, agents targeting this mutated kinase have been used to treat advanced SM variants. However, off-target activity of these agents may lead to toxicities that limit dosing and thus efficacy in this population. Therefore, an unmet need remains for safe and effective treatments for patients with NonAdvSM. Bezuclastinib inhibits KIT D816V mutations with high potency and specificity while avoiding other kinases with potential off-target liabilities such as PDGFRα, PDGFRβ, VEGFR2, and CSF1R. Bezuclastinib has demonstrated minimal brain penetration and no central nervous system toxicities were observed in preclinical studies. In an ongoing Phase 2 study (Apex) of patients with AdvSM, early data indicate that bezuclastinib was generally well tolerated and is associated with a meaningful reductions in serum tryptase levels, bone marrow mast cell burden, and KIT D816V variant allele fraction. Additionally, bezuclastinib was safely administered in a completed phase 1/2 clinical study in patients with locally advanced, unresectable or metastatic gastrointestinal stromal tumors (GIST), in which activating KIT mutations are found in a majority of patients. In that study, bezuclastinib led to a reduction in KIT exon 17 mutational burden, which was associated with a reduction in tumor burden. These results support the investigation of bezuclastinib as a potential therapy in GIST as well as AdvSM and NonAdvSM. Study Design and Methods: The Summit study (NCT05186753) is a multi-center, Phase 2, double-blind, placebo-controlled, 3-part clinical trial to evaluate the safety, efficacy, and biomarker correlates (e.g., bone marrow mast cell burden, serum tryptase level, and KIT D816V mutation burden) of bezuclastinib in patients with NonAdvSM. Patients diagnosed with ISM or SSM who have inadequate control of their symptoms despite treatment with at least 2 anti-mediator therapies will be included in this trial. Multiple patient-reported outcome measures (PROMs) will be used to follow symptom scores while on treatment. Part 1 of the study will assess the safety profile of bezuclastinib and will determine the recommended dose for Part 2 through the assessment of changes from baseline of a disease specific PROM. Part 2 will evaluate the efficacy of bezuclastinib at the selected dose as compared with placebo through the evaluation of the PROMs and changes in clinical activity markers such as serum tryptase, bone marrow mast cell burden, and KIT D816V mutation allele burden. All patients will continue to receive their baseline anti-mediator treatments throughout the trial. Serial photographic evaluation will assist in the determination of changes of disease in the skin. Part 3 allows patients who have completed treatment in Part 1 or Part 2 of the study, including those initially randomized to placebo, to participate in a long-term extension study and receive open label bezuclastinib. Conclusions: There are currently no approved therapies for patients with NonAdvSM. Data from the Summit study will support further development of bezuclastinib in SM.

The NPM1-TYK2 Chimeric Fusion Promotes Activation of STAT Family Signaling, Skewing Towards Tfh Functional Subset Differentiation and Mature T-Cell Lymphomagenesis

Introduction Peripheral T cell lymphomas are heterogeneous neoplasms of post thymic T cells with distinct clinical, pathological and genetic characteristics. We previously identified the NPM1-TYK2 fusion in patients with CD30+ lymphoproliferative disorders, including 15% of primary cutaneous ALK− anaplastic large cell lymphoma. The oncogenicity of NPM1-TYK2 and its effect on T cell differentiation, the molecular mechanisms and signaling pathways through which it drives lymphomagenesis invivo remain unknown. Methods To investigate the effect of NPM1-TYK2 on oncogenesis and T cell differentiation, we established a conditional transgenic model (CD4-NPM1-TYK2). To investigate cooperativity with Trp53, CD4-NPM1-TYK2 mice were crossed with Trp53 floxed mice to generate CD4ΔTrp53-NPM1-TYK2 mice with T cell-specific concomitant heterozygous loss of Trp53. Mice (n = 15 per genotype) were monitored over time for tumor development. Hematopoietic organs were harvested and subjected to histolopathological and immunophenotypic analysis. Serum cytokine and immunoglobulin profiles were analyzed by Luminex multiplex immunoassays. The effects of NPM1-TYK2 on the physiological function of T cells were examined by growth curves and cell cycle analysis using anti-CD3/CD28 stimulated CD4+ T cells from CD4-NPM1-TYK2 mice in vitro. To evaluate the signaling sequences of NPM1-TYK2 expression, unbiased mass spectrometry (MS)-driven phosphoproteomics was performed. The pharmacological effect of Deucravacitinib, an allosteric TYK2 inhibitor, on NPM1-TYK2+ murine T cells and human T cell lymphoma-derived cells were examined. ResultsCD4-NPM1-TYK2 mice showed significant splenomegaly (n = 20; 104.8 mg vs 86.5 mg) and developed lymphoma with hepatomegaly due to atypical neoplastic infiltrates. Notably, CD4ΔTrp53-NPM1-TYK2 mice (n = 5; 15.4 months) exhibited an earlier onset of lymphoma compared to CD4-NPM1-TYK2 mice (n = 4; 19.8 months). Immunophenotypic characterization of CD4+ T cells from the spleen of CD4-NPM1-TYK2 mice (n = 7) revealed an increase in effector T cells (CD44+/CD62L−, 51.5% vs 39.4%) and a decrease in naïve T cells (CD44−/CD62L+, 32.9% vs 44.8%), suggesting NPM1-TYK2 promotes effector T cell differentiation in vivo. Among all T helper cell subtypes, increased Tfh cells was observed in CD4-NPM1-TYK2 mice (n = 8; ICOS+/CXCR5+/PD1+/BCL6+, 27.4% vs 15.5%), indicating NPM1-TYK2 mediates the commitment of Tfh cell skewing in vivo. Serum cytokine profile of CD4-NPM1-TYK2 mice also showed elevated Tfh-related cytokines (n = 4; IL-1β, IL-4, IL-6, IL-10, IL-12). Tfh cells are crucial for the formation of germinal center (GC) B cells and their differentiation into plasma cells. Elevated expansion of GC B cells (n = 5; CD95+/PNA+, 4.8% vs 3.8%) was also observed. Increased plasma cells (B220−/CD138+, 9.1% vs 3.8%) and elevated immunoglobulins (n = 6; IgA, IgG2b) in the serum corroborated observed lymphoplasmacytic cells in the histology of CD4-NPM1-TYK2 mice. Among MS-identified phosphoproteins demonstrating the YX(2-5)L motif of JAK family kinase substrates, we observed elevated levels of tyrosine phosphopeptides implicating STAT1/3/5 activation. Western blotting of CD4+ T cells from CD4-NPM1-TYK2 mice revealed hyperphosphorylation of STAT1/3/5. NPM1-TYK2+ T cells (n = 3 per genotype) were hyperreactive to stimulation in vitro, displaying increased activated cells (CD69+/CD25+, 83/80% vs 76/73%). The growth curves of NPM1-TYK2+ T cells showed increased growth (2.6-fold) with more proliferating cells in the S phase of cell cycle (31% vs 25%) whilst control CD4+ T cells stopped proliferating 10 days post-stimulation. Intriguingly, the NPM1-TYK2-mediated growth-promoting effect was attenuated by Deucravacitinib. Conclusion Conditional transgenic expression of NPM1-TYK2 in mature T-cell lineage promotes Tfh cell differentiation accompanied by intense GC B cell and plasma cell expansion, and hepatosplenomegaly with disseminated lymphoma accelerated by concomitant heterozygous ablation of Trp53in vivo. The biologic effects of NPM1-TYK2 expression are propagated through STAT1/3/5 activation. These data provide novel insights on the signaling, cellular immunologic and oncogenic consequences of NPM1-TYK2 expression in CD4+ T cells. Our studies implicate NPM1-TYK2 as a de facto oncogene in vivo and provides a valuable pre-clinical model for precision medicine. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

NIMG-67. MULTI-PARAMETRIC MRI-BASED MACHINE LEARNING ANALYSIS FOR PREDICTION OF NEOPLASTIC INFILTRATION AND RECURRENCE IN PATIENTS WITH GLIOBLASTOMA: UPDATES FROM THE MULTI-INSTITUTIONAL RESPOND CONSORTIUM

Abstract PURPOSE Glioblastoma is extremely infiltrative with malignant cells extending beyond the enhancing rim where recurrence inevitably occurs, despite aggressive multimodal therapy. We hypothesize that important characteristics of peritumoral tissue heterogeneity captured and analyzed by multi-parametric MRI and artificial intelligence (AI) methods are generalizable in the updated multi-institutional ReSPOND (Radiomics Signatures for PrecisiON Diagnostics) consortium and predictive of neoplastic infiltration and future recurrence. METHODS We used the most recent update of the ReSPOND consortium to evaluate and further refine generalizability of our methods with different scanners and acquisition settings. 179 de novo glioblastoma patients with available T1, T1Gd, T2, T2-FLAIR, and ADC sequences at pre-resection baseline and after complete resection with subsequent pathology-confirmed recurrence were included. To establish generalizability of the predictive models, training and testing of the refined AI model was performed through Leave-One-Institution-Out-Cross-Validation schema. The multi-institutional cohort consisted of the Hospital of the University of Pennsylvania (UPenn, 124), Case Western Reserve University/University Hospitals (CWRU/UH, 27), New York University (NYU, 13), Ohio State University (OSU, 13), and University Hospital Río Hortega (RH, 2). Features extracted from pre-resection MRI were used to build the model predicting the spatial pattern of subsequent tumor recurrence. These predictions were evaluated against regions of pathology-confirmed post-resection recurrence. RESULTS Our model predicted the locations that later harbored tumor recurrence with overall odds ratio (99% CI)/AUC (99% CI), 12.0(11.8-12.2)/0.80(0.76-0.85), and per institute, CWRU/UH, 11.0(10.7-11.3)/0.80 (0.64-0.97); NYU, 7.0(6.7-7.3)/0.78(0.56-1.00); OSU, 18.3(17.5-19.1)/0.83(0.54-1.00); RH, 40.0(35.3-45.5)/0.93(0.00-1.00); UPenn, 8.00(7.7-8.3)/0.80(0.75-0.84). CONCLUSION This study provides extensive multi-institutional validated evidence that machine learning tools can identify peritumoral neoplastic infiltration and predict location of future recurrence, by decrypting the MRI signal heterogeneity in peritumoral tissue. Our analyses leveraged the unique dataset of the ReSPOND consortium, which aims to develop and validate AI-based biomarkers for individualized prediction and prognostication and establish generalizability in a multi-institutional setting.

NIMG-23. AI-BASED CONNECTED COMPONENT MARKERS OF BRAIN PERITUMORAL MICROENVIRONMENT USING WATER RESTRICTION INFORMATION

Abstract PURPOSE Glioblastoma is the most aggressive adult brain tumor, with heterogeneous neoplastic cell peritumoral infiltration. Characterization of this infiltrative peritumoral heterogeneity is an unmet clinical need that could contribute to strengthening our understanding of this disease. We propose novel AI-based markers of infiltration using deep-learning (DL) based on water restriction caused by infiltration, identified by diffusion tensor imaging (DTI). These markers could contribute to precision/personalized medicine, towards influencing clinical decision-making, including planning for biopsies, surgery, and radiation. METHOD: We automatically extracted peritumoral patches from free water volume fraction maps (FW-VF) of a retrospective cohort of 44 brain metastases and 66 glioblastomata patients and labelled them as high- and low- free water, respectively. An AI/DL model was then trained on these patches to distinguish differences in water restriction. Our trained AI/DL model was then applied on FW-VF of 264 hold-out glioblastoma patients (survival:0.43-76.9 months, age:21-88, 104 females) to generate a peritumoral microenvironment index (PMI) map quantifying infiltrative heterogeneity. Connected components (CCs) of high PMI values were calculated and their descriptive characteristics of size, number, shape, directionality, and spatial location, were extracted as AI-based markers. Gaussian mixture model clustering was then applied on these markers to determine if their representative infiltrative peritumoral heterogeneity can capture overall survival differences, by partitioning the patients into three clusters: low, moderate, and high risk. RESULTS The log-rank test yielded significant differences (p< 10-5) between low- and high-risk patients, (HR= 0.47, 95% CI:0.34-0.65; P< 0.005). Average PMI values were significantly greater in high-risk patients (P< 0.05). CONCLUSION We introduced novel AI-based markers of infiltration in the peritumoral microenvironment, using information of water restriction extracted from DTI. Our proposed markers can capture overall survival differences, based on the patterns of infiltration using DTI-based characterization of the water restriction, that show promise as clinically relevant prognostic biomarkers.

Efficient adaptive enhanced adaboost based detection of spinal abnormalities by Machine learning approaches

Spinal abnormalities are commonly occurring disorders that are caused by injuries, osteoporosis (benign) and neoplastic infiltration (malignant). Patients with one of the listed malignancies must undergo therapy as soon as possible to prevent the progress of the disease and to avoid further bone damage to preserve a better quality of life. Classification of patients into low or high-risk groups is an important step in diagnosing a disorder, which led biomedical and bioinformatics research teams to investigate the usage of machine learning (ML) technologies. In this paper, ML techniques are adapted to a public lumbar spine dataset to detect vertebral fractures. First, the dataset was preprocessed by using the contour-based hybrid median filter with histogram equalization. Then the Mask LSTM-based R.O.I. segmentation techniques are applied to segment the spinal images. Finally, the suggested stacked Adaptive Enhanced AdaBoost (AE-AdB) gets trained on whole images to enhance the accuracy of the data classification. Results of the experiment show that the attained accuracy (97.86%) of the AE-AdB classifier was significantly higher than that of the other classifiers, namely Convolution Neural Network (CNN) (74%) and Extreme Gradient Boosting Algorithm (XGBoost) (84%).

Disseminated T-cell lymphoma with non-epitheliotropic cutaneous involvement in a cat with erythematous patches and regenerative anemia.

A 14-y-old, castrated male, diabetic, domestic longhaired cat was presented for investigation of anemia. General examination revealed widespread cutaneous erythematous macules and patches. Hematology and bone marrow aspiration revealed severe regenerative anemia and marked erythroid hyperplasia, respectively. Low numbers of intermediate-to-large, atypical lymphocytes were observed in the blood smear and bone marrow aspirates. Various imaging modalities demonstrated a diffuse pulmonary bronchial pattern, multifocal mural thickening of the urinary bladder, splenomegaly, and mild tri-cavitary effusion. Skin biopsies and cytologic examination of the pleural effusion demonstrated round-cell neoplasia consistent with lymphoma. Autopsy confirmed disseminated T-cell lymphoma, mostly affecting the urinary bladder, stomach, lymph nodes, and interscapular subcutis and muscles. Angiocentrism and nerve infiltration were present. The cutaneous erythematous patches, characterized by perivascular neoplastic lymphocytic infiltrates and angiodestruction, were a manifestation of the disseminated lymphoma in this cat, similar to the lesions reported in humans affected by angioimmunoblastic T-cell lymphoma.

Pathogenic and Prognostic Roles of Paraneoplastic Leukocytosis in Cervical Cancer: Can Genomic-Based Targeted Therapies Have a Role? A Literature Review and an Emblematic Case Report.

Tumor-associated leukocytosis has been associated with poor prognosis in cervical cancer. Leukemoid reaction (i.e., white blood cell count > 40,000/μL) is defined paraneoplastic (PLR) when it occurs in the presence of a cytokine-secreting tumor (CST) without neoplastic bone marrow infiltration. Cervical cancers displaying PLR represent a peculiar entity characterized by a rapidly progressive behavior typically associated with chemo-radioresistance. The present paper aims to review the literature about the pathogenetic mechanisms of PLR and its prognostic role in cervical cancer. Moreover, it reports the emblematic case of a patient with an advanced cervical cancer associated with PLR that was chemotherapy resistant. The patient underwent a palliative cytoreductive surgery of high complexity, obtaining a temporary regression of PLR. The tumor sample stained positive for G-CSF and IL-6, thus indicating a CST. Notably, the tumor genomic analysis revealed a PI3CKA mutation. Therefore, at the instrumental evidence of a rapidly progressive disease relapse, which was accompanied by reappearance of PLR, we started a targeted treatment with a selective PIK3 inhibitor alpesilib combined with the JAK1-2 inhibitor ruxolitinib. We achieved a relief of symptoms and leukocytosis; however, severe side effects necessitated the treatment suspension. In conclusion, as therapeutic strategies for cancer with PLR are scarcely reported in literature, our study could contribute to expand our understanding of the topic and provide a basis for further research.

Idiopathic Omental Infarction to Be a Rare Cause of Acute Abdomen: A Case Report

Omental infarction is a rare entity, representing hemorrhagic omental necrosis as a result of impaired omental perfusion. It can occur secondary to omental torsion or to inflammatory and neoplastic infiltration of the omental segment from adjacent organs. If the foregoing reasons can be excluded, omental infarction is called primary or idiopathic omental infarction. Occlusions of small omental arteries are rare and may be found in patients with thromboembolic disease, arteriolosclerosis, arteritis, or amyloidosis. The author presents a case of idiopathic omental infarction in a 66-year-old male presenting with abdominal pain. The patients underwent an emergent operation and recovered without any complication after surgery.

Spontaneous Spleen Rupture Due to Infectious Mononucleosis

Spontaneous spleen rupture (SSR) is a fatal and rare pathology causing acute abdomen. SSR secondary to infectious mononucleosis (IM) is quite rare (0.06-0.5%), and it is the most common cause of IM associated death. A 43 years old male patient, who had no previous severe disease history, chronic drug use, or previous operation applied to our emergency outpatient clinic of general surgery. The patient had complaints of severe abdominal pain, nausea, vomiting, and diarrhea. In abdominal computerized tomography, diffuse free fluid with respectively increased in density (hemorrhage?) was observed. Emergency operation was decided, because patient developed acute peritonitis signs. During exploration in the operation, it was observed that spleen was ruptured at multiple sites, and bleeding was ongoing, and splenectomy was performed. Serology was consistent with the previous EBV infection. It was mentioned in the pathology report that there was no neoplastic infiltration, and infectious causes should be investigated. No problem has been encountered during approximately two years’ follow-up. SSR secondary to EMN is a rare, fatal, and very severe pathology. Diagnosis is delayed, or it is not even diagnosed because there is no trauma. Correct diagnosis on time, and decision of emergency surgical intervention can be life-saving.

P149 AN UNUSUAL CASE OF CARDIAC TAMPONADE AND ST–SEGMENT ELEVATION MYOCARDIAL INFARCTION

Abstract The case of a 70–year–old woman, a heavy smoker with lung cancer diagnosed in November 2020, is described. The patient underwent 4 cycles of chemotherapy and subsequently a maintenance therapy with atezolizumab. In May 2021, a control CT scan was performed, where multiple cerebral and left adrenal metastases were found. In June 2021, she underwent a cycle of panencephalic radiotherapy. On September 9, 2021, she needed to be admitted to the oncology ward of reference for the appearance, for a few days, of dyspnea due to light exertion and asthenia. In the ward, she was dyspnoic at rest with arterial hypotension (BP 90/60 mmHg). The ECG showed sinus rhythm 110 bpm, anterior STEMI in evolution. The cardiologist performed a bedside echocardiogram which showed abundant pericardial effusion and signs of haemodynamic commitment; akinesia of the apex and middle septum of the left ventricle; LVEF 35%. He was conducted in the angiography room and subjected to pericardiocentesis, guided echo, via the subxiphoid route. 650 ml of blood fluid were removed; on echocardiographic control, a clear reduction of the pericardial effusion was noted. The BP after the procedure went back to 140/80 mmHg and the HR was 100 bpm. Coronary angiography was performed which demonstrated critical stenosis of the mid–segment LAD. After a collegial discussion between the cardiologist and the oncologist which took into account: the presence of haematic pericardial effusion, brain metastatic lesions, a life expectancy <6 months and uncertain date of the heart attack, it was decided not to treat the coronary lesion. A total body CT scan, performed on 13 September, demonstrated widespread and irregular pericardial thickening with nodulations and enhancement due to neoplastic infiltration and the appearance of new metastases in the liver and pancreas. On 14 September, the patient died of respiratory failure. In the literature, only 2 cases are reported with some analogy with the one described. Conclusion A rare case of association between haematic pericardial effusion, cardiac tamponade, and myocardial infarction is reported; the priority was to drain the pericardial effusion while the complexity of the case required a collegial assessment between oncologist and cardiologist which led to the decision of not to treat coronary artery lesion on LAD, due to the high risk of bleeding, the short life expectancy and the uncertain date of the heart attack.

NIPA (Nuclear Interaction Partner of ALK) Is Crucial for Effective NPM-ALK Mediated Lymphomagenesis.

The NPM-ALK fusion kinase is expressed in 60% of systemic anaplastic large-cell lymphomas (ALCL). A Nuclear Interaction Partner of ALK (NIPA) was identified as a binding partner of NPM-ALK. To identify the precise role of NIPA for NPM-ALK-driven lymphomagenesis, we investigated various NPM-ALK+ cell lines and mouse models. Nipa deletion in primary mouse embryonic fibroblasts resulted in reduced transformation ability and colony formation upon NPM-ALK expression. Downregulating NIPA in murine NPM-ALK+ Ba/F3 and human ALCL cells decreased their proliferation ability and demonstrated synergistic effects of ALK inhibition and NIPA knockdown. Comprehensive in vivo analyses using short- and long-latency transplantation mouse models with NPM-ALK+ bone marrow (BM) revealed that Nipa deletion inhibited NPM-ALK-induced tumorigenesis with prolonged survival and reduced spleen colonies. To avoid off-target effects, we combined Nipa deletion and NPM-ALK expression exclusively in T cells using a lineage-restricted murine ALCL-like model resembling human disease: control mice died from neoplastic T-cell infiltration, whereas mice transplanted with Lck-CreTG/wtNipaflox/flox NPM-ALK+ BM showed significantly prolonged survival. Immunophenotypic analyses indicated a characteristic ALCL-like phenotype in all recipients but revealed fewer “stem-cell-like” features of Nipa-deficient lymphomas compared to controls. Our results identify NIPA as a crucial player in effective NPM-ALK-driven ALCL-like disease in clinically relevant murine and cell-based models.

Primary nervous system lymphoma in cats.

Here we characterize the neuroanatomic distribution, neuropathology, and immunophenotype of 10 cases of primary nervous system lymphoma in cats. Cases were retrospectively searched from 2 academic institutions. Selected cases were reviewed and subjected to immunohistochemistry (IHC) for CD3, CD20, and Pax5. The mean age of affected cats was 9.1 y, and no sex or breed predilection was observed. The most common clinical sign was ataxia (8 cases). Gross changes reported in 8 cases consisted of white-to-tan masses (7 cases) or swelling (1 case) within the neuroparenchyma (5 cases) or epidural spaces (3 cases). Histologically, intraparenchymal lymphomas occurred in the gray and white matter or perivascular spaces (7 cases); extraparenchymal lymphomas (6 cases) consisted of neoplastic cell infiltration of the perivascular spaces in the leptomeninges, choroid plexus, or epidural spaces. Nerve lymphomas were diffusely infiltrative. Tumors occurred in the brain (4 cases), spinal cord and nerves (3 cases), spinal cord (2 cases), and brain, spinal cord, and nerves (1 case). IHC was consistent with a B-cell lymphoma in 5 cases and with a T-cell lymphoma in 5 cases.

Myeloid sarcoma and extramedullary hematopoiesis expand the spectrum of ERG-positive proliferations: an ancillary tool in the diagnosis

ERG overexpression has been linked to acute myeloid leukemia/myeloid sarcoma (MS). The aim of our study was to identify the frequency of ERG immunohistochemical (IHC) expression in MS (n = 21), blastic plasmacytoid dendritic cell neoplasms (BPDCNs; n = 8), extramedullary hematopoiesis (EMH: n = 9), normal and pathological bone marrow trephine biopsies (BM-TBs, n = 18), and the marrow component of adrenal myelolipomas (n = 15). ERG-positive and ERG-negative immunostains were identified in 68.4% and 31.5% of patients with MS, respectively (2–3+, 20% to >90% of cells), while all BPDCNs were negative. ERG + MS cases were over-represented in those of myeloid differentiation when compared with those of pure monocytic/monoblastic differentiation, which were ERG-negative (P=<0.001). ERG was expressed in immature myeloid cells in 100% of cases of EMH, BM-TBs, and adrenal myelolipomas (n = 42), resulting in a sensitivity of 100% in this setting. Negative ERG immunostaining was also 100% sensitive in discriminating cells of erythroid lineage, mature lymphocytes, and reactive or neoplastic plasma cells. Variable IHC expression occurred in megakaryocytes and neutrophils. In summary, we confirmed a high frequency of ERG expression in MS and identified ubiquitous expression in non-neoplastic immature myeloid lineage cells. We believe that ERG can be of diagnostic utility to identify neoplastic and reactive myeloid infiltrates in peripheral tissues and possibly as an ancillary marker to exclude the diagnosis of BPDCNs when positive. However, ERG must be used in an antibody panel, as expression is not limited to myeloid cells.

Granulomatous Dermatitis Heralding Myelodisplastic/Myeloproliferative Neoplasms. Neoplastic or Reactive Cells? A Study of 2 Cases.

Skin manifestations in the context of underlying hematological malignancies are well known and not an infrequent clinical finding. They can represent specific neoplastic infiltrates or be considered as reactive. In the latter group, where granulomatous dermatitis is included, controversy has emerged recently. According to newly reported data, the histiocytes comprising these granulomata can carry the same molecular alterations found in the primary process. Moreover, the skin manifestations in these patients are sometimes the initial clue for the diagnosis of the underlying malignancy. We present here 2 cases with granulomatous skin infiltrates preceding the diagnosis of myelodysplastic/myeloproliferative neoplasms. In one of them, the same IDH2 mutation was detected in granulomatous lesions on the skin and in the bone marrow. This was performed by pyrosequencing instead of next-generation sequencing, with improved cost-effectiveness.

Primary Kidney Lymphoma in a Dog

Background: Lymphoma is a malignant lymphoid tumor originating in the lymph nodes or other solid organs and comprises 90% of all hematopoietic tumors in dogs. However, primary renal lymphoma is rare and is associated with nonspecific clinical signs. Tumor invasion in both kidneys can cause severe clinical signs due to renal failure, complicating the patient's treatment and prognosis. The aim of this case was to report the case of a dog affected by bilateral primary renal lymphoma. In addition, to characterize the clinical and histopathological presentation due to the intense morphological changes. Case: A 5-year-old male Poodle canine was admitted showing apathy and emesis for 5 days. On physical examination, the dog showed 10% of dehydration, reddish oral mucous membranes, poor body condition (score 1/5), uremic breath, and pain in the kidney area. Complementary tests revealed severe low white blood cells count, high BUN levels, high levels of potassium, calcium, and phosphorus (serum biochemistry). Abdominal ultrasound showed bilateral kidney enlargement. Fine needle aspiration of the mass (guided by ultrasound) revealed round cell tumor. Radiographs showed no alterations. The dog died due to his poor condition and necropsy was performed. On post-mortem examination, the kidneys were both enlarged, pale, and with an irregular subcapsular surface. The histopathological diagnostic was primary renal lymphoma. Immunohistochemical staining revealed that neoplastic cells were strongly positive for anti CD20 and PAX5, while negative for CD3, supporting the diagnosis of B-cell lymphoma. Discussion: The diagnosis was based on clinical, complementary tests, fine needle aspiration, histopathological and immunohistochemical findings. In dogs, primary kidney tumors are uncommon and usually malignant. The presence of vomiting, uremic breath, dehydration, weight loss, and erosive and ulcerative lesions on the tongue (uremic glossitis) are clinical signs of chronic renal failure, and this condition was later confirmed by laboratory tests and histopathological findings. Dogs diagnosed with extra-nodal renal lymphoma, present clinical signs such as polydipsia, polyuria, vomiting, and uremic breath in some cases. These changes are compatible with changes observed in cases of renal failure. In this case, the severe azotemia, hyperphosphatemia, hypocalcemia, and hyperkalemia were due to the neoplastic infiltration in both kidneys. Additionally, the abdominal ultrasound revealed the tumor in both kidneys. Almost 38% of dogs with renal lymphoma presented in urine evaluation normal urine density and a large amount of protein in the urine, similar to those observed in this dog. When the lesions are on both kidneys, kidney failure develops and uremic extra-renal lesions appear, as observed in this case. The prevalence of primary kidney tumors in domestic animals corresponds to less than 1% of the total of the tumors reported, and they are usually in one kidney. In dogs, almost 60 - 70% of lymphomas are B cells, 30 - 40% are T cells, and less than 1% are null cells. B-cell lymphomas usually show less aggressive behavior when compared to T-cell lymphomas. Kidney lymphoma can be included as an important cause of kidney failure, and has slow and progressive development, making early diagnosis and treatment difficult. Keywords: dog disease, lymphoproliferative disorder, renal neoplasm, uremia. Título: Linfoma renal primário em cãoDescritores: doença de cão, distúrbio linfoproliferativo, neoplasma renal, uremia.

Granulocytic sarcoma with unusual localizations (breast and stomach) without bone marrow involvement after the allogeneic transplantation

Granulocytic sarcoma (GS) is a rare extramedullary solid tumor composed of immature myeloid cell that is associated with acute myeloid leukemia or myelodysplastic syndrome. Espe­cially, the involvement of the breast as a pattern of relapse after allogeneic bone marrow transplantation ( allo SCT) is extremely rare. We report the case of a 57-year-old woman who palpated a painless lump in the superior quadrant of her right breast. Her past medical history was a myelodysplastic syndrome ( MDS) treated with bone marrow transplantation. Imaging work-up by mammogram and ultrasonography ( US ) showed solitary mass suspect of malignancy in breast. Tru-cut biopsy was performed from the suspect palpable mass of the right breast. Histologic findings were compatible with a granulocytic sarcoma in breast. While she was also evaluated for mass in the breast, also investigated by endoscopy for the symptoms of gastrointestinal system. The endoscopic biopsy showed diffuse neoplastic infiltration similar the pathology of the breast. GS of the breast is a rare extramedullary involvement of hematologic diseases. There are no the specific radyologic features in the presentation with GS of the breast. Our case also showed that careful histopathological review along with all panel of immunohistochemistry is extremely important for diagnose.