Synovial sarcoma of the viscera (lung and jejunum): a case report.

We report the case of a woman nearing 70 years old who was admitted to the hospital with a complaint of "epigastric distension for 1 month". Her main signs and symptoms were progressive abdominal distension and occasional abdominal pain. Computed tomography suggested an abdominal mass. She had a surgical history of synovial sarcoma (SS) of the lungs. After admission, she was diagnosed with jejunal SS following a puncture biopsy and laparoscopic surgery. This disease usually occurs in the soft tissues of the limbs, and it is extremely rare for SS to originate in the jejunum. The morphologic heterogeneity of SS overlaps with other tumors and makes the diagnosis particularly difficult. Imaging studies usually lack specificity; however, measuring multiple immunohistochemical markers can greatly assist in the diagnosis and differential diagnosis of SS. This case not only enriches our understanding of SS and describes a rare site of origin, but also emphasizes the importance and challenges of achieving an accurate diagnosis. Immunohistochemical and molecular biological testing have important roles in the definitive diagnosis, highlighting the need for precise and innovative diagnostic and therapeutic approaches in SS.

Time since death: The histological chronotanatognostic.

The time since death is an important aspect of forensic medicine; however, there is not an accurate single method to determine this data. Therefore, this research aimed to evaluate parameters and procedures based on the morphological analysis of cells and tissues to determine the time since death, using animal models. Pigs were chosen in this research because of their similarities with human anatomy, physiology, and pathophysiology. We identified the cells and tissue alterations in the viscera of pig cadavers according to the time since death, also describing the changes in the temperature of the organs and the bodies. The environmental temperature during the sample collection was also registered. The viscera analysis was performed for 24 h, with a 2-h variation period. After the sample collection, microscope slides were prepared for optical microscopy analysis. Through this 24-h analysis, we observed that the pancreas, small intestine, and large intestine presented more cellular alterations than the other organs. The alterations observed in the other viscera have significance when analyzed in combination. The meninges presented higher stability and few changes in 24 h, which could be relevant in an investigation of the time since death in a period greater than 24 h. Our results showed that histological evaluation is an excellent method to determine the time since death.

Recurrent RET fusions in fibrosarcoma-like neoplasms in adult viscera: expanding the clinicopathological and genetic spectrum.

AIMS: RET-fused mesenchymal neoplasms mostly affect the soft tissue of paediatric patients. Given their responsiveness to selective RET inhibitors, it remains critical to identify those extraordinary cases occurring in the visceral organs of adults. In this study, we report three RET-rearranged spindle-cell tumours occurring in the visceral organs of adults. METHODS AND RESULTS: Clinicopathological features were assessed and partner agnostic targeted next-generation sequencing on clinically validated platforms were performed. The patients were 18, 53, and 55 years old and included one male and two females. The tumours were located in the kidney (case 1), small intestine (case 2), and ureter (case 3), with maximum diameters of 14, 5, and 1 cm, respectively. Histologically, all tumours displayed a morphological spectrum typical of fibrosarcoma, including moderately to highly cellular, nonpleomorphic, ovoid to spindle-shaped cells arranged in long fascicles or haphazardly within collagenised to myxohyaline stroma. Foci of irregular alveolar oedema-like structures and areas with microcystic and reticular arrangements were identified in the renal tumour. Staghorn-type vessels and foci of band-like stromal hyalinisation were observed in the small intestine tumour. Cases 1 and 2 were high-grade and pursed a highly aggressive clinical course, while case 3 was of intermediate grade with no tumour recurrence or metastasis 14 years after surgery. All three tumours expressed CD34, which was coexpressed with S100 protein in cases 2 and 3. Molecular genetic testing revealed PRKAR1A::RET, KIF5B::RET, and SPECC1L::RET in-frame gene fusions. CONCLUSION: Our study expands the clinicopathological and genetic spectrum of mesenchymal neoplasms associated with RET fusions.

Adult NTRK-rearranged spindle cell neoplasms of the viscera: with an emphasis on rare locations and heterologous elements.

NTRK-rearranged mesenchymal neoplasms mostly affect the soft tissues of pediatric patients. Given the responsiveness to selective NTRK inhibitors, it remains critical to identify those ultra-rare cases occurring in the viscera of adults. In five females and two males aged 18-53 years, we characterized visceral mesenchymal tumors harboring TPM3-NTRK1 [uterine cervix (N = 2), pleura, prostate], LMNA-NTRK1 (lung), SQSTM1-NTRK3 (heart), and NTRK3 rearrangement with unknown fusion partner (colon/mesocolon) with RNA sequencing, FISH, RT-PCR, and immunohistochemistry. The tumors exhibited spindled to ovoid/epithelioid or pleomorphic cells, often arranged in fascicles, and were low-to-intermediate-grade and high-grade in three and four cases, respectively. Keloid-like stromal collagen and perivascular hyalinization was noted in five. Adenosarcoma-like appearances were observed in two, manifesting frond-like protrusions in one cervical tumor and phyllodes-like architecture in the prostatic tumor. Abrupt high-grade transformation into pleomorphic liposarcoma was found in another cervical tumor, while the pleural tumor contained intermixed rhabdomyoblasts. Pan-TRK immunostaining was positive in all cases. All cases expressed CD34, while five were S100-positive. CDKN2A homozygous deletion with concomitant p16 loss occurred in 4/7. Whole-exome sequencing identified TP53 mutation (c.672+2T>C, involving a splice site, with concomitant protein loss) in a cervical sarcoma, limited to its heterologous liposarcomatous component. At least moderate pan-TRK immunoreactivity was present in varying proportions of potential pathologic mimics, with BCOR-positive sarcoma (56%, 5/9), undifferentiated uterine sarcoma (50%, 3/6), and spindle cell/sclerosing rhabdomyosarcoma (33%, 2/6) being among the most frequent. This underscored the unsatisfactory specificity of pan-TRK immunohistochemistry and warranted molecular confirmation in the diagnosis of adult NTRK-rearranged visceral mesenchymal neoplasms. The current report highlights the ever-expanding clinicopathologic and genetic spectrum of this entity by describing the unprecedented cardiac and pleural locations and heterologous differentiation, as well as the second NTRK-rearranged "prostatic stromal sarcoma," while substantiating CDKN2A deletion as a frequent occurrence.

Examination of the Novel Sigma-1 Receptor Antagonist, SI 1/28, for Antinociceptive and Anti-allodynic Efficacy against Multiple Types of Nociception with Fewer Liabilities of Use.

Neuropathic pain is a significant problem with few effective treatments lacking adverse effects. The sigma-1 receptor (S1R) is a potential therapeutic target for neuropathic pain, as antagonists for this receptor effectively ameliorate pain in both preclinical and clinical studies. The current research examines the antinociceptive and anti-allodynic efficacy of SI 1/28, a recently reported benzylpiperazine derivative and analog of the S1R antagonist SI 1/13, that was 423-fold more selective for S1R over the sigma-2 receptor (S2R). In addition, possible liabilities of respiration, sedation, and drug reinforcement caused by SI 1/28 have been evaluated. Inflammatory and chemical nociception, chronic nerve constriction injury (CCI) induced mechanical allodynia, and adverse effects of sedation in a rotarod assay, conditioned place preference (CPP), and changes in breath rate and locomotor activity were assessed after i.p. administration of SI 1/28. Pretreatment with SI 1/28 produced dose-dependent antinociception in the formalin test, with an ED50 (and 95% C.I.) value of 13.2 (7.42-28.3) mg/kg, i.p. Likewise, SI 1/28 produced dose-dependent antinociception against visceral nociception and anti-allodynia against CCI-induced neuropathic pain. SI 1/28 demonstrated no impairment of locomotor activity, conditioned place preference, or respiratory depression. In summary, SI 1/28 proved efficacious in the treatment of acute inflammatory pain and chronic neuropathy without liabilities at therapeutic doses, supporting the development of S1R antagonists as therapeutics for chronic pain.

Aerobic exercise improves LPS-induced sepsis via regulating the Warburg effect in mice.

We investigated the impact of aerobic exercise (AE) on multiple organ dysfunction syndrome (MODS), aortic injury, pathoglycemia, and death during sepsis. ICR mice were randomized into four groups: Control (Con), Lipopolysaccharide (LPS), Exercise (Ex), and Exercise + LPS (Ex + LPS) groups. Mice were trained with low-intensity for 4 weeks. LPS and Ex + LPS mice received 5 mg/kg LPS intraperitoneally for induction of sepsis. Histopathological micrographs showed the organ morphology and damage. This study examined the effects of AE on LPS-induced changes in systemic inflammation, pulmonary inflammation, lung permeability, and bronchoalveolar lavage fluid (BALF) cell count, oxidative stress-related indicators in the lung, blood glucose levels, plasma lactate levels, serum insulin levels, plasma high-mobility group box 1 (HMGB1) levels, glucose transporter 1 (Glut1) and HMGB1, silent information regulator 1 (Sirt-1), and nuclear factor erythroid 2-related factor 2 (Nrf-2) mRNA expression levels in lung tissue. AE improved sepsis-associated multiple organ dysfunction syndrome (MODS), aortic injury, hypoglycemia, and death. AE prominently decreased pulmonary inflammation, pulmonary edema, and modulated redox balance during sepsis. AE prominently decreased neutrophil content in organ. AE prominently downregulated CXCL-1, CXCL-8, IL-6, TNF-α, Glu1, and HMGB1 mRNA expression but activated IL-1RN, IL-10, Sirt-1, and Nrf-2 mRNA expression in the lung during sepsis. AE decreased the serum levels of lactate and HMGB1 but increased blood glucose levels and serum insulin levels during sepsis. A 4-week AE improves sepsis-associated MODS, aortic injury, pathoglycemia, and death. AE impairs LPS-induced lactate and HMGB1 release partly because AE increases serum insulin levels and decreases the levels of Glut1. AE is a novel therapeutic strategy for sepsis targeting aerobic glycolysis.

Nonskeletal injuries related to cardiopulmonary resuscitation: An autopsy study.

The current standard technique for cardiopulmonary resuscitation (CPR), initially described in the early 1960s, has quickly become the expected response for all persons found without a pulse or respiration. Despite the potentially lifesaving properties of external cardiac massage, the mainstay of resuscitation, it consists of repeated blunt force trauma to the chest, which can lead to extensive traumatic skeletal and nonskeletal injuries. Numerous autopsy-based studies have documented the incidence and patterns of rib and sternal fractures associated with attempted CPR, but there is relatively little data on the incidence and severity of nonskeletal CPR-related injuries. We reviewed reports from 1878 autopsies performed between September 2017 and December 2019 (inclusive), for documentation of CPR-related injuries. Among these cases, there were 93 cases with resuscitation-related nonskeletal injuries. The most common type of injury identified were visceral contusions, documented in 57.0% of cases. These contusions predominantly involved the heart, lungs, neck soft tissue, and surrounding structures. Resuscitation-related lacerations were seen in 17.2% of the cases, most predominantly involving the pericardium, heart, and liver. Statistical analysis of the data demonstrated that lacerations were more likely to be seen in females and with associated sternal fractures. Additionally, hemothoraces were present in 34.4% of cases and hemopericardium was seen in 8.6% of cases. This study provides additional documentation of the range, severity, and incidence of various types of resuscitation-related visceral injuries to better assist autopsy pathologists in distinguishing these injuries from other antecedent traumatic injuries.

Management of visceral vascular anomalies.

Visceral vascular anomalies are common in patients with vascular malformations in other parts of the body and can include lymphatic, venous, and arteriovenous malformations. Depending on the organ or organs involved they may present differently and pose different treatment challenges. Defining the malformation and understanding its extent is paramount in devising management regimens. Medical, interventional, and surgical therapies are often required in combination to treat these complex lesions. There are new and promising advances in the development of therapeutic agents targeting the PI3K/AKT/mTOR pathway. Due to the complex nature of these lesions a coordinated, multi-disciplinary approach is necessary to manage and mitigate symptoms and complications of this diverse group of vascular malformations.

Visceral Metastases as Predictors of Response and Survival Outcomes in Patients of Castration-Resistant Prostate Cancer Treated With 177Lu-Labeled Prostate-Specific Membrane Antigen Radioligand Therapy: A Systematic Review and Meta-analysis.

BACKGROUND: The presence of visceral metastases is associated with poor prognosis in patients of metastatic castration-resistant prostate cancer (mCRPC) treated with hormonal therapy and chemotherapy. However, studies evaluating its impact on treatment outcomes with Lu-labeled prostate-specific membrane antigen (PSMA) radioligand therapy (RLT) are currently limited and show inconsistent results. This systematic review was conducted to precisely evaluate the impact of visceral metastases on biochemical response and survival outcomes in patients of mCRPC treated with Lu-PSMA RLT. METHODS: This systematic review followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines. Searches in PubMed, Scopus, and EMBASE were made using relevant keywords, and articles up to May 2020 were included. Univariate and multivariate odds ratios and hazard ratios (HRs) were extracted from the individual articles, and pooled estimates were generated using meta-analysis. RESULTS: Twelve articles comprising 1504 patients were included in this review. Presence of visceral metastases not only predicted low biochemical response rate (pooled univariate odds ratio: 0.38, 95% confidence interval [CI], 0.22-0.66) but was also a significant prognosticator of worse progression-free survival (pooled univariate HR, 1.85; 95% CI, 1.39-2.46; and pooled multivariate HR, 1.48; 95% CI, 1.15-1.92) and overall survival (pooled univariate HR, 1.77; 95% CI, 1.29-2.44; and pooled multivariate HR, 2.22; 95% CI, 1.82-2.70). There was no evidence of publication bias. CONCLUSIONS: Presence of visceral metastases was associated with poor response and survival outcomes in patients of mCRPC treated with Lu-PSMA RLT. The results are clinically significant for pretreatment risk stratification of such patients and to guide optimal treatment strategies.

Multivisceral resection of locally advanced colorectal cancer in an African referral centre.

BACKGROUND: Colorectal cancer (CRC) is common and often presents with advanced disease in Africa. Multivisceral resection (MVR) improves survival in locally advanced (T4b) CRC. The aim was to describe the management and outcomes of patients with clinical T4b CRC without metastatic disease who underwent MVR. METHODS: A retrospective review of patients with T4 CRC who underwent MVR between January 2008 and December 2013. RESULTS: Four hundred and ninety-four patients were included. Of the 158 with suspected T4 cancer, 44 had MVR, of which one was excluded due to metastases. The mean age was 64 years. The male to female ratio was 1:1. The most commonly resected extra-colorectal structure was the abdominal wall (21%). The median survival was 68 months (SD 13.9). The 5-year disease free (DFS) and overall survival (OS) were 46% and 55%, respectively. Survival of patients with colon and rectum cancer was similar. Intraoperative tumour spillage, vascular/perineural invasion, and anastomotic leakage were independent predictors of survival. CONCLUSION: Multivisceral resection of locally advanced (T4b) CRC is feasible in the African context. Complete resection improves survival and should be the goal.

Enfermedad de Paget perianal: un trastorno raro que enmascara un carcinoma anorrectal subyacente / Perianal Paget's disease: A rare disorder masking an underlying anorectal carcinoma

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Abdominal Visceral Infarction in 3 Patients with COVID-19.

A high incidence of thrombotic events has been reported in patients with coronavirus disease (COVID-19), which is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. We report 3 clinical cases of patients in Italy with COVID-19 who developed abdominal viscera infarction, demonstrated by computed tomography.

Daratumumab plus CyBorD for patients with newly diagnosed AL amyloidosis: safety run-in results of ANDROMEDA.

Although no therapies are approved for light chain (AL) amyloidosis, cyclophosphamide, bortezomib, and dexamethasone (CyBorD) is considered standard of care. Based on outcomes of daratumumab in multiple myeloma (MM), the phase 3 ANDROMEDA study (NCT03201965) is evaluating daratumumab-CyBorD vs CyBorD in newly diagnosed AL amyloidosis. We report results of the 28-patient safety run-in. Patients received subcutaneous daratumumab (DARA SC) weekly in cycles 1 to 2, every 2 weeks in cycles 3 to 6, and every 4 weeks thereafter for up to 2 years. CyBorD was given weekly for 6 cycles. Patients had a median of 2 involved organs (kidney, 68%; cardiac, 61%). Patients received a median of 16 (range, 1-23) treatment cycles. Treatment-emergent adverse events were consistent with DARA SC in MM and CyBorD. Infusion-related reactions occurred in 1 patient (grade 1). No grade 5 treatment-emergent adverse events occurred; 5 patients died, including 3 after transplant. Overall hematologic response rate was 96%, with a complete hematologic response in 15 (54%) patients; at least partial response occurred in 20, 22, and 17 patients at 1, 3, and 6 months, respectively. Renal response occurred in 6 of 16, 7 of 15, and 10 of 15 patients, and cardiac response occurred in 6 of 16, 6 of 13, and 8 of 13 patients at 3, 6, and 12 months, respectively. Hepatic response occurred in 2 of 3 patients at 12 months. Daratumumab-CyBorD was well tolerated, with no new safety concerns versus the intravenous formulation, and demonstrated robust hematologic and organ responses. This trial was registered at www.clinicaltrials.gov as #NCT03201965.

Visceral Metastasis: A Prognostic Factor of Survival in Patients with Spinal Metastases.

OBJECTIVE: To characterize the visceral metastasis as a predictive tool for the survival of patients with spinal metastases through an exploratory meta-analysis. METHODS: Two investigators independently searched PubMed and Embase databases for eligible studies from 2000-2016. The effect estimates for the hazard ratio (HR) or risk ratio (RR) and 95% confidence interval (CI) were collected and pooled with a random- or fixed-effect model. RESULTS: In total, 18 eligible studies were retrieved with 5468 participants from nine countries. The overall pooled effect size for HR and RR was 1.50 and 3.79, respectively, which was proved to be statistically significant. In the subgroup of prostate cancer (PCa) and non-small cell lung cancer (NSCLC), statistical significance and marginal statistical significance was presented for the pooled HR (HR = 1.76, 95% CI 1.35-2.29) and (RR = 1.56, 95% CI 0.99-2.48), respectively. However, in the subgroup of thyroid cancer, breast cancer, and renal cancer, statistical significance was not achieved (HR = 1.17, 95% CI 0.75-1.83, Z = 0.70, P = 0.486). The results did not show any evidence of publication bias. CONCLUSIONS: This study demonstrated that visceral metastasis was a significant prognostic factor in patients with spinal metastases as a whole. Interestingly, the onset of visceral metastases differentially impacted the survival in different primary tumors. Therefore, the prognostic value of visceral metastasis might be related to the type of primary tumor.

Cyclin-dependent kinase inhibitors plus aromatase inhibitor in first-line treatment hormone-receptor-positive/HER2-negative advanced breast cancer women with or without visceral disease: time to turn page?

Breast cancer is the most common female tumour type and accounts for the leading cancer mortality in women worldwide. Up to 75% of breast cancers express the oestrogen receptor or progesterone receptor (hormone-receptor-positive). Aromatase inhibitors were the preferred first-line treatment option. New and acquired resistance to hormonal blockade has led to the development of targeted treatments. Cyclin-dependent kinases (CDKs) are a large family of serine-threonine kinases that play an important role in regulating cell cycle progression: palbociclib, ribociclib, and abemaciclib. We conducted a study to evaluate the efficacy of CDK inhibitors (CDKi) plus aromatase inhibitor in hormone-receptor-positive/HER2-negative ABC patients with visceral disease, postponing the use of chemotherapeutic agents and strengthening the power of endocrine agents. We enrolled 22 patients treated with CDKi (palbocilib) plus aromatase inhibitor (group A) and 38 patients treated with chemotherapy (group B). Our small study confirms the effectiveness of treatment with CDKi plus aromatase inhibitor, even in patients with visceral metastases, when compared with chemotherapy.

A morphologic and molecular reappraisal of myoepithelial tumors of soft tissue, bone, and viscera with EWSR1 and FUS gene rearrangements.

Myoepithelial tumors (MET) represent a clinicopathologically heterogeneous group of tumors, ranging from benign to highly aggressive lesions. Although MET arising in soft tissue, bone, or viscera share morphologic and immunophenotypic overlap with their salivary gland and cutaneous counterparts, there is still controversy regarding their genetic relationship. Half of MET of soft tissue and bone harbor EWSR1 or FUS related fusions, while MET arising in the salivary gland and skin often show PLAG1 and HMGA2 gene rearrangements. Regardless of the site of origin, the gold standard in diagnosing a MET relies on demonstrating its "myoepithelial immunophenotype" of positivity for EMA/CK and S100 protein or GFAP. However, the morphologic spectrum of MET in soft tissue and bone is quite broad and the above immunoprofile is nonspecific, being shared by other pathogenetically unrelated neoplasms. Moreover, rare MET lack a diagnostic immunoprofile but shows instead the characteristic gene fusions. In this study, we analyzed a large cohort of 66 MET with EWSR1 and FUS gene rearrangements spanning various clinical presentations, to better define their morphologic spectrum and establish relevant pathologic-molecular correlations. Genetic analysis was carried out by FISH for EWSR1/FUS rearrangements and potential partners, and/or by targeted RNA sequencing. Then, 82% showed EWSR1 rearrangement, while 18% had FUS abnormalities. EWSR1-POU5F1 occurred with predilection in malignant MET in children and young adults and these tumors had nested epithelioid morphology and clear cytoplasm. In contrast, EWSR1/FUS-PBX1/3 fusions were associated with benign and sclerotic spindle cell morphology. Tumors with EWSR1-KLF17 showed chordoma-like morphology. Our results demonstrate striking morphologic-molecular correlations in MET of bone, soft tissue and viscera, which might have implications in their clinical behavior.

Genetic background modifies phenotypic severity and longevity in a mouse model of Niemann-Pick disease type C1.

Niemann-Pick disease type C1 (NPC1) is a rare, fatal neurodegenerative disorder characterized by lysosomal accumulation of unesterified cholesterol and glycosphingolipids. These subcellular pathologies lead to phenotypes of hepatosplenomegaly, neurological degeneration and premature death. NPC1 is extremely heterogeneous in the timing of clinical presentation and is associated with a wide spectrum of causative NPC1 mutations. To study the genetic architecture of NPC1, we have generated a new NPC1 mouse model, Npc1em1PavNpc1em1Pav/em1Pav mutants showed notably reduced NPC1 protein compared to controls and displayed the pathological and biochemical hallmarks of NPC1. Interestingly, Npc1em1Pav/em1Pav mutants on a C57BL/6J genetic background showed more severe visceral pathology and a significantly shorter lifespan compared to Npc1em1Pav/em1Pav mutants on a BALB/cJ background, suggesting that strain-specific modifiers contribute to disease severity and survival. QTL analysis for lifespan of 202 backcross N2 mutants on a mixed C57BL/6J and BALB/cJ background detected significant linkage to markers on chromosomes 1 and 7. The discovery of these modifier regions demonstrates that mouse models are powerful tools for analyzing the genetics underlying rare human diseases, which can be used to improve understanding of the variability in NPC1 phenotypes and advance options for patient diagnosis and therapy.This article has an associated First Person interview with the first author of the paper.

Acute Toxic Injuries of Rat's Visceral Tissues Induced by Different Oximes.

Certain AChE reactivators, asoxime, obidoxime, K027, K048, and K075, when taken in overdoses and sometimes even when introduced within therapeutic ranges, may injure the different organs. As a continuation of previously published data, in this study, Wistar rats have sacrificed 24 hrs and 7 days after single im application of 0.1LD50, 0.5LD50 and 1.0LD50 of each reactivator, and examinated tissue samples were obtained for pathohistological and semiquantitative analysis. A severity of tissue alteration, expressed as different tissue damage scores were evaluated. Morphological structure of examinated tissues treated with of 0.1LD50 of all reactivators was comparable with the control group of rats. Moderate injuries were seen in visceral tissues treated with 0.5LD50 of asoxime, obidoxime and K027. Acute damages were enlarged after treatment with 0.5LD50 and 1.0LD50 of all reactivators during the next 7 days. The most prominent changes were seen in rats treated with 1.0LD50 of K048 and K075 (P < 0.001 vs. control and asoxime-treated group). All reactivators given by a single, high, unitary dose regimen, have an adverse effect not only on the main visceral tissue, but on the whole rat as well, but the exact mechanism of cellular injury remains to be confirmed in further investigation.

Comparative Genomics Reveals Shared Mutational Landscape in Canine Hemangiosarcoma and Human Angiosarcoma.

Angiosarcoma is a highly aggressive cancer of blood vessel-forming cells with few effective treatment options and high patient mortality. It is both rare and heterogenous, making large, well-powered genomic studies nearly impossible. Dogs commonly suffer from a similar cancer, called hemangiosarcoma, with breeds like the golden retriever carrying heritable genetic factors that put them at high risk. If the clinical similarity of canine hemangiosarcoma and human angiosarcoma reflects shared genomic etiology, dogs could be a critically needed model for advancing angiosarcoma research. We assessed the genomic landscape of canine hemangiosarcoma via whole-exome sequencing (47 golden retriever hemangiosarcomas) and RNA sequencing (74 hemangiosarcomas from multiple breeds). Somatic coding mutations occurred most frequently in the tumor suppressor TP53 (59.6% of cases) as well as two genes in the PI3K pathway: the oncogene PIK3CA (29.8%) and its regulatory subunit PIK3R1 (8.5%). The predominant mutational signature was the age-associated deamination of cytosine to thymine. As reported in human angiosarcoma, CDKN2A/B was recurrently deleted and VEGFA, KDR, and KIT recurrently gained. We compared the canine data to human data recently released by The Angiosarcoma Project, and found many of the same genes and pathways significantly enriched for somatic mutations, particularly in breast and visceral angiosarcomas. Canine hemangiosarcoma closely models the genomic landscape of human angiosarcoma of the breast and viscera, and is a powerful tool for investigating the pathogenesis of this devastating disease. IMPLICATIONS: We characterize the genomic landscape of canine hemangiosarcoma and demonstrate its similarity to human angiosarcoma.

An unusual presentation of ACE inhibitor-induced visceral angioedema.

ACE inhibitors (ACEi) are common anti-hypertensive drugs that can cause angioedema. Though classic, or facial angioedema is rare, visceral angioedema is even less common. When angioedema occurs, it typically presents early, within 30 days of initiating therapy. Visceral angioedema most commonly presents with nausea, emesis, abdominal pain and diarrhoea, and thus is often mistaken for an episode of gastroenteritis. When a CT scan is obtained, it typically shows characteristic findings, including ascetic fluid, mild mesenteric oedema and thickening of the small bowel. In this case report, we present a patient who did not experience her first episode of visceral angioedema until after she had been on ACEi therapy for 5-7 years. In addition, she experienced recurrent episodes of visceral angioedema that were separated by approximately 4 years at a time. Both of these features make for a particularly unique presentation.