Intravascular Invasion Research Articles

Analysis of risk factors for lymph node metastasis in 1096 patients with early gastric cancer and establishment of a predictive nomogram

Objective: To investigate the risk factors for lymph node metastasis in patients with early gastric cancer and establish a model for prediction of risk. Methods: The cohort of this retrospective observational study comprised 1096 patients who had undergone radical gastric cancer surgery combined with standard D1 lymphadenectomy and been diagnosed with early gastric cancer by postoperative pathology in Zhongshan Hospital affiliated with Fudan University from January 2016 to July 2022. The patients were allocated to groups with and without lymph node metastases. Clinicopathological characteristics were compared between the two groups and multi-factor logistic regression analysis used to identify independent risk factors for lymph node metastasis in patients with early gastric cancer. Indications for endoscopic resection in the Japanese Gastric Cancer Association (JGCA) guideline were also incorporated into construction of the model. The patient cohort was divided into training and validation sets in a 6:4 ratio. The identified independent risk factors were used to construct a predictive nomogram. Receiver operating characteristic curves were plotted separately and the difference between them in predictive efficacy was compared using the area under the curve (AUC). Results: A total of 1,096 patients with early gastric cancer were included, with 750 males and 346 females. Their average age was (61.4±10.9) years old, and the mean tumor diameter was (23.8±11.4) mm. Among them, 188 patients (17.2%) had positive lymph node metastasis, with 109 cases in N1 stage, 42 cases in N2 stage, and 37 cases in N3 stage. Additionally, 462 patients were in T1a stage, while 634 patients were in T1b stage. Univariate analysis showed that tumor diameter, location, Lauren classification, gross morphology, histological type, intravascular invasion, ulceration, differentiation type and tumor T stage were associated with lymph node metastasis after radical gastrectomy for early gastric cancer (all P<0.05). Multifactorial analysis showed that the presence of intravascular invasion (OR=14.822, 95%CI: 9.323-23.572, P<0.001), undifferentiated type (OR=3.095, 95%CI: 1.649-5.811, P<0.001), tumor T1b (OR=1.798, 95%CI: 1.053-3.079, P=0.032), and tumor diameter ≥2 cm (OR=1.229, 95%CI: 1.031-1.469, P=0.022) were independent risk factors for lymph node metastasis. The baseline data of the training set and validation set were consistent in terms of balance (all P>0.05). We used the above variables to establish a predictive nomogram for lymph node metastasis in patients with early gastric cancer. The AUC values obtained from the validation of the model in the training and validation sets were 0.880 (95%CI: 0.849-0.911) and 0.881 (95%CI: 0.841-0.921), respectively, and were significantly better than the predictive efficacy based on the JGCA guideline (AUC=0.777, 95%CI: 0.746-0.809, P<0.001). Conclusions: Patients with early gastric cancer and intravascular invasion, undifferentiated tumors, tumor T1b, and diameter ≥2 cm are at higher risk of postoperative lymph node metastasis than other patients. The predictive model developed in this study more accurately predicts lymph node metastasis in patients with early gastric cancer than previously proposed methods.

Cutaneous Squamous Cell Carcinoma of the Head and Neck: A Retrospective Analysis of Loco-Regional Recurrences and Survival Rates Over a Consecutive 10-Year Period.

Cutaneous squamous cell carcinoma (cSCC) is one of the most common skin cancers worldwide. Due to the ever-increasing sun exposure and life expectancy, cSCCs are increasing worldwide. The aim of our study was to identify specific risk factors leading to local and regional recurrences, determine patients' survival rates, and identify best practices for the management of cSCC. This study retrospectively analyzed 1197 head and neck cSCCs in 945 patients who consecutively presented to the clinics from January 2007 to December 2016. Patients were followed up for a minimum of 18 months. A total of 29 patients (3%) developed loco-regional recurrences (26 local, one regional, and two both local and regional) with a median time to recurrence of 25 (range, 1-81) months. The mean follow-up was 32 (range, 5-90) months. Treatment modality (p=0.027), depth of invasion (p<0.001), diameter > 20 mm (p<0.001), gender (p=0.022), histological differentiation (p<0.001), site of the lesion (p<0.001), perineural and intravascular invasion (p<0.001), positive lymphadenopathy (p=0.021), immunosuppression (p<0.001), and history of treatment (p=0.008) proved to be strong predictors for loco-regional recurrences. At one and five years after diagnosis, 95.6% and 59.9% of all patients were recurrence-free, respectively. The median survival time from recurrence was 2.6 years. Our study identifies prognostic indicators for reoccurrence by analyzing data from a large continuous cohort in the management of cSCCs.

Significance of Basal Cell Carcinomas Exhibiting Intravascular Invasion.

Intravascular invasion of tumor cells can be associated with metastasis in many cancers. Basal cell carcinomas (BCCs), however, rarely metastasize; therefore, the clinical impact of intravascularly invasive BCC (IVBCC) is currently unclear. Because of these facts and the rarity of IVBCC, questions have arisen on whether IVBCC truly exists. We present 4 cases of IVBCC: one case with obvious tumor islands within immunolabeled blood vessels in the context of advanced disease and 3 cases found incidentally during Mohs micrographic surgery. We discuss the difficulty in studying IVBCC, the idea that it could be due to artifact, and the lack of direct clinical-pathological correlation. Given these challenges, we propose diagnostic criteria for IVBCC to decrease ambiguity for pathological diagnosis. Such criteria may facilitate further studies on the clinical significance of IVBCC.

Percutaneous thrombectomy of upper extremity and thoracic central veins using Inari ClotTriever System: Experience in 14 patients.

In the present report, we have described the technical and clinical outcomes of percutaneous thrombectomy in the deep veins of the upper extremity and thorax using the ClotTriever system (Inari Medical, Irvine, CA). Fourteen patients with symptomatic deep venous occlusive disease in the upper extremity deep veins and thoracic central veins who had undergone thrombectomy using the ClotTriever system between October 2020 and January 2022 were reviewed. The technical results, adverse events, imaging follow-up data, and clinical outcomes were recorded. Fourteen patients (seven men and seven women; mean age, 53.6± 13.3years) constituted the study cohort. Of the 14 patients, 9 (64.3%) had had DVT due to intravascular invasion or external compression from known malignancy, 2 (14.3%) had had infected thrombi and/or vegetation due to Staphylococcus aureus refractory to intravenous antibiotic therapy, and 3 (21.4%) had had a benign etiology for thrombus formation. The presenting symptoms included upper extremity and/or facial swelling (n= 14), upper extremity pain (n= 6), fever (n= 2), and dyspnea (n= 1). Thrombectomy with the ClotTriever system was successfully completed in all 14 patients. Seven patients (50.0%) had required additional venous stent reconstruction after thrombectomy to address the underlying stenosis. No major adverse events were noted. All the patients had experienced resolution of the presenting symptoms. For the management of symptomatic deep venous occlusive disease of the upper extremity deep veins and thoracic central veins, thrombectomy using the ClotTriever system was feasible with excellent technical and clinical success.

Гангрена Фурнье: эволюция представлений о патогенезе, современное состояние диагностики и лечения

The article is devoted to one of the rare forms of necrotizing fasciitis - Fourniers gangrene (FG). In chronological order, key aspects related to epidemiology, etiology, pathogenesis, classification, clinic, diagnosis and treatment are highlighted, according to extensive literature. It is postulated that according to modern scientific provisions, Fournier gangrene is a private clinical model of critical conditions in surgery, which is characterized by progressive purulent-necrotic lesion and putrefactive decay of soft tissue and fascial structures and is accompanied by phenomena of systemic endotoxicosis (sepsis) and high mortality, varying from 35 to 76-86%. It is declared that the trigger pathogenetic mechanism of the development of FG is disseminated thrombosis of the microcirculatory bed of the superficial fascia of the scrotum due to intravascular invasion of various strains of causative microbes. The methods of clinical, laboratory and instrumental diagnostics and methods of treatment are described, taking into account modern achievements of evidence-based medicine. Based on a multifactorial analysis of literature data and their own experience, the authors stated that the cornerstone that completely affects the outcome of treatment and prognosis of the disease is a multidisciplinary approach to solving diagnostic and therapeutic and tactical tasks with the participation of doctors of related specialties (surgeon, resuscitator, radiologist, cardiologist, coloproctologist, urologist, microbiologist). It is shown that the unshakable priority of treating patients with FG is still urgent surgical intervention in the format of "aggressive surgery", which provides for extremely wide excision of necrotic and non-viable tissues, followed by programmed (stage-by-stage) rehabilitation necrectomy. The issues of laser irradiation and hydropressive wound treatment with ozonated saline solution are touched upon. Adjuvant wound treatment using vacuum therapy and hyperbaric oxygenation are given.

SUPERIOR VENA CAVA SYNDROME DUE TO A MEDIASTINAL MASS WITH RIGHT ATRIAL INVOLVEMENT

SUPERIOR VENA CAVA SYNDROME DUE TO A MEDIASTINAL MASS WITH RIGHT ATRIAL INVOLVEMENT

Transforming growth factor-β-induced secretion of extracellular vesicles from oral cancer cells evokes endothelial barrier instability via endothelial-mesenchymal transition

BackgroundDuring metastasis, cancer cells undergo epithelial-mesenchymal transition (EMT) in response to transforming growth factor-β (TGF-β), which is abundant in the tumor microenvironment, and acquire invasive and metastatic potentials. Metastasis to distant organs requires intravascular invasion and extravasation of cancer cells, which is accompanied by the disruption of the adhesion between vascular endothelial cells. Cancer cell-derived extracellular vesicles (EVs) have been suggested to induce the destabilization of normal blood vessels at the metastatic sites. However, the roles of EVs secreted from cancer cells that have undergone EMT in the destabilization of blood vessels remain to be elucidated. In the present study, we characterized EVs secreted by oral cancer cells undergoing TGF-β-induced EMT and elucidated their effects on the characteristics of vascular endothelial cells.MethodsInduction of EMT by TGF-β in human oral cancer cells was assessed using quantitative RT-PCR (qRT-PCR) and immunocytochemistry. Oral cancer cell-derived EVs were isolated from the conditioned media of oral cancer cells that were treated with or without TGF-β using ultracentrifugation, and characterized using nanoparticle tracking analysis and immunoblotting. The effects of EVs on human umbilical artery endothelial cells were examined by qRT-PCR, cellular staining, and permeability assay. The significant differences between means were determined using a t-test or one-way analysis of variance with Tukey’s multiple comparisons test.ResultsOral cancer cells underwent EMT in response to TGF-β as revealed by changes in the expression of epithelial and mesenchymal cell markers at both the RNA and protein levels. Oral cancer cells treated with TGF-β showed increased EV production and altered EV composition when compared with untreated cells. The EVs that originated from cells that underwent EMT by TGF-β induced endothelial-mesenchymal transition, which was characterized by the decreased and increased expression of endothelial and mesenchymal cell markers, respectively. EVs derived from oral cancer cells also induced intercellular gap formation which led to the loss of endothelial cell barrier stability.ConclusionsEVs released from oral cancer cells that underwent TGF-β-induced EMT target endothelial cells to induce vascular destabilization. Detailed characterization of oral cancer-derived EVs and factors responsible for EV-mediated vascular instability will lead to the development of agents targeting metastasis.

Clear cell squamous cell carcinoma of the tongue exhibits characteristics as an undifferentiated squamous cell carcinoma

Clear cell squamous cell carcinoma (CCSCC), where cells show abundant clear cytoplasm, –is a variant of squamous cell carcinoma (SCC) and a rare entity in the oral cavity. The characteristics of CCSCC, especially in immunohistochemical features, remain unclear. We characterized a case of CCSCC arising from the oral mucosal epithelium of tongue, where the clear cell lesion accounted for a predominant portion of the tumor. This CCSCC, which was partially surrounded by conventional SCC, exhibited cellular atypia immunohistopathologically and histopathologically with a high Ki-67 index, increased number of mitotic figures and enlarged nuclei. Intravascular invasion of the carcinoma cells was also observed. Furthermore, the CCSCC recurred and metastasized to the cervical lymph nodes and both lungs three months after resection. Immunohistochemical analyses demonstrated decreased expression of p40 (an isoform of SCC marker p63), ADP-ribosylation factor (ARF)-like 4c (ARL4C), yes-associated protein (YAP) and 5-methylcytosine (5mC) in the CCSCC lesion compared with the surrounding SCC lesion, where the expression of ARL4C was upregulated compared with non-tumor region and YAP showed nuclear translocation. In addition, siRNA loss-of-function experiments revealed that p63 expression was required for ARL4C expression and DNA methylation was induced by p63 and YAP/transcriptional co-activator with PDZ-binding motif (TAZ) signaling in oral SCC cell lines. These results suggest that CCSCC, in which several markers of SCC-associated intracellular signaling pathways are downregulated, together with evidence of altered epigenetic regulation, is characterized as an undifferentiated SCC variant.

Attempting to Solve the Pigmented Epithelioid Melanocytoma (PEM) Conundrum: PRKAR1A Inactivation Can Occur in Different Genetic Backgrounds (Common, Blue, and Spitz Subgroups) With Variation in Their Clinicopathologic Characteristics.

Pigmented epithelioid melanocytoma is a rare cutaneous melanocytic proliferation considered high-grade melanocytoma in the 2018 WHO Classification of Skin Tumors. Little has been reported about the associated genetic drivers in addition to BRAF and MAP2K1 mutations or PRKCA gene fusions. Here, we present a series of 21 cases of PRKAR1A -inactivated melanocytic tumors in which we could assess the associated genetic background. We identified 9 different driver genes related to the common, Spitz, blue nevi, and PRKC -fused groups. Nine cases were associated with a canonical BRAF p.V600E mutation, a hallmark of the common nevus group. They occurred mainly in young adults. All were combined (biphenotypic) cases with a variable proportion of compound nevus. The pigmented epithelioid melanocytoma component was made of thin fascicules or isolated epithelioid cells covered by a dense hyperpigmented melanophage background and was predominantly located in the upper dermis. One such case was malignant. Six cases were associated with Spitz-related genetic anomalies ranging from HRAS or MAP2K1 mutations to gene fusions involving MAP3K8 , MAP3K3 , and RET . They occurred mainly in children and young adults. Morphologically, they showed large confluent junctional nests in a hyperplastic epidermis and a fascicular dermal component of spindled and epithelioid melanocytes with a frequent wedged silhouette. Intravascular invasion was observed in 4/6 cases. Five cases were associated with canonical mutations of the blue nevus group with 4 CYSLTR2 p.L129Q and 1 GNAQ p.Q209L mutations. They were removed mainly in adults and showed a frequent junctional component with epidermal hyperplasia. The dermal component showed dense fascicules of spindled and epithelioid melanocytes predominating over melanophages. One case occurred in a PRKCA -fused tumor in an adolescent with classic morphologic features. These results could potentially shift the concept of PRKAR1A -inactivated melanocytoma, changing from a rather unified model to a more complex one, including genetic subgroup variations with clinical and morphologic specificities. The genetic background of PRKAR1A -inactivated melanocytic tumors should be systematically explored to better understand the extent and clinical behavior of these complex lesions.

Clinical Significance of ADAMTS19, BMP7, SIM1, and SFRP1 Promoter Methylation in Renal Clear Cell Carcinoma.

BackgroundClear cell renal cell carcinoma (ccRCC) is the most common subtype of kidney tumors, accounting for the majority of deaths from genitourinary cancers. The currently used nomograms for predicting patient outcomes are based on clinical-pathological characteristics only; however, a significant number of ccRCC survivors with similar radiological and histological features still demonstrate a different clinical course of the disease. This study aimed at the identification of novel DNA methylation biomarkers for the monitoring of patients with ccRCC.MethodsGene expression profiling by SurePrint G3 Human GE 8×60K Microarrays was performed in 4 ccRCC tissues and adjacent non-cancerous renal tissue (NRT) samples. Four down-regulated genes were selected for further DNA methylation status analysis in 123 ccRCC and 45 NRT samples using methylation-specific PCR (MSP).ResultsDNA methylation changes of ADAMTS19, BMP7, SIM1, and SFRP1 were cancer-specific with significantly (P<0.050) higher methylation frequency (37%, 20%, 18%, and 42%, respectively) in tumor tissues. The methylated status of at least one gene was significantly related to various clinical-pathological parameters, including tumor size, Fuhrman and WHO/ISUP grades, intravascular invasion, and necrosis. Moreover, the methylated status of multimarker panel ADAMTS19, BMP7 & SFRP1 was predictive for poorer overall survival (HR, 4.11; 95% CI, 1.22–13.86).ConclusionIn conclusion, DNA methylation of the three-gene panel consisting of ADAMTS19, BMP7 & SFRP1 supposedly predicts the outcome of patients diagnosed with ccRCC and possibly might be used to enrich the current prognostic tools.

SYNCHRONOUS OCCURRENCE OF ACINIC CELL CARCINOMA OF SOFT PALATE AND SQUAMOUS CELL CARCINOMA OF LUNG: A CASE REPORT

Acinic cell carcinoma (AcCC) is a low-grade malignant salivary neoplasm and constitutes approximately 6% to 8% of all salivary gland neoplasms. Although it has low-grade histology, AcCC has a significant tendency to metastasize. We report the first case of AcCC in our facility of a 74-year-old man who presented with a slow-growing mass on the left soft palate. A diagnosis of AcCC was made based on the characteristic histologic features of an infiltrative tumor of large polygonal cells with dark, round, eccentric nuclei and having PAS-D-positive basophilic granules along with immunohistochemical findings positive for CK7. The presence of intravascular invasion was evident. Concurrently, contrast-enhanced computed tomography of the thorax showed a suspicious nodule at the right upper lobe of the lung. Initially we suspected lung metastatic tumor based on the fact that AcCC has a significant tendency to metastasize to the lung and cervical lymph nodes. A wedge biopsy from the lung was done and revealed squamous cell carcinoma. Immunohistochemical studies on this tumor also showed different findings with immunopositivity with P63 and negativity for CK7. A probability of tumor metastasis to the lung was ruled out with the finding of a new primary tumor of the lung. AcCC can be misinterpreted due to its benign appearance, absence of malignant features, and histologic similarity to normal acinar cells. Pathologists should be aware and vigilant when reporting this entity. AcCC of the soft palate in this case is relatively rare and synchronous occurrence of other primary tumors makes it extremely unusual.

Efficacy of epirubicin plus cyclophosphamide followed by taxanes versus carboplatin plus taxanes as adjuvant chemotherapy in triple-negative breast cancer: 8.1 years median follow-up on a randomized clinical trial.

529 Background: Four cycles of adjuvant taxanes (paclitaxel or docetaxel) after four cycles of adjuvant doxorubicin plus cyclophosphamide (ECT) are considered a standard adjuvant treatment and improves survival outcomes of triple negative breast cancer (TNBC). The purpose of this analysis was to further assess whether adjuvant carboplatin plus taxanes (TP) was non-inferior to or superior to standard ECT chemotherapy in prolonging the survival time. Methods: This randomized, open-label, multicenter clinical trial conducted at three hospital in China from June, 2009 and October, 2015. Eligible early triple-negative breast cancer (TNBC) patients were randomized (1:1) to receive ECT (four cycles of epirubicin 90 mg/m2 + cyclophosphamide 600 mg/m2 followed by four cycles of docetaxel 75 mg/m2 or paclitaxel 175 mg/m2 every 3 weeks, ECT arm, n = 154) or receive TP (six cycles of docetaxel 75 mg/m2 or paclitaxel 175 mg/m2 + carboplatin AUC 5 every 3 weeks; TP arm, n = 154), which was then followed by surgery. Results: Three hundred and eight patients were recruited in this trial and final date of follow-up was January 20, 2021. Baseline characteristics were balanced between ECT arm and TP arm. Median follow-up was 97.6 months. Median disease free survival (DFS) was not reached; 8-year DFS rate was 78.35% with ECT arm and 81.73% with TP arm (hazard ratio [HR] = 0.84; 95% confidence interval [CI] = 0.50 - 1.40; P = 0.496). Median overall survival (OS) was also not reached; 8-year OS rate was 87.15% with ECT arm and 89.14% with TP arm (HR = 0.87; 95% CI = 0.44 - 1.70; P = 0.676). For TNBC patients with DFS &gt; 4 year, TP arm had a longer DFS than ECT ( P = 0.01), and had a tendency with better OS ( P = 0.4). In this subgroup analysis of SPARC &gt; 50%, TP arm had a longer DFS than ECT ( P &lt; 0.05), and also had a tendency with better OS ( P = 0.06). In subgroup analysis of PD-1 (-) and intravascular invasion (+), TP arm had a better DFS ( P = 0.02) and OS ( P = 0.03) than ECT arm. DFS or OS had no significant differences in ECT and TP arm with BRCA mutation or BRCA wild ( all P values &gt; 0.05). Conclusions: TP chemotherapy showed significant non-inferiority for PFS and OS versus ECT in the first-line adjuvant treatment of early TNBC. For some particular subgroup of TNBC, TP may be a more effective chemotherapy than ECT. TP may be considered an effective alternative to early TNBC. Clinical trial information: NCT01150513.

“The Way to a Man’s Heart” - Adrenocortical Carcinoma With Vascular Invasion Into the Right Atrium and Ventricle

Abstract Background: Adrenocortical carcinoma (ACC) is a rare aggressive malignant neoplasm which may present with intravascular extension into the inferior vena cava (IVC) and rarely into the right atrium (RA). Clinical Case: 62-year-old male with no prior known significant medical history presented to ED with 2-day history of mild hematuria with 3-week history of headache. Vital signs were normal other than blood pressure of 198/88 while physical exam was unremarkable. Headache subsided and blood pressure improved to 130/60 range after IV labetalol administration. CT abdomen and pelvis with contrast revealed a large right suprarenal mass extending into the right hepatic vein, IVC, and RA. The right adrenal gland was not visualized while the left adrenal gland and bilateral kidneys were normal. MRI chest, heart and abdomen with contrast showed heterogeneously enhancing lobulated right adrenal mass measuring 11.4 x 11 x 14 cm (AP, transverse, CC, respectively) with extensive tumor thrombus invading the right hepatic vein, IVC, RA and notably protruding into the right ventricle (RV) through the tricuspid valve during diastole. Technitium-99m MDP whole body scan did not show any uptake suspicious for metastases. Pre-op lab assessment showed mildly abnormal 1 mg dexamethasone suppression test but no evidence of ACTH suppression, elevated catecholamines or excess adrenal steroidogenesis. He underwent combined cardiothoracic and abdominal surgery on cardiopulmonary bypass with resection of adrenal mass, removal of thrombus from IVC, RA, RV and patch angioplasty of IVC with bovine pericardium. Pathology report was consistent with ACC (AJCC stage III). On 1 month postoperative follow-up, patient is clinically doing well with plans to start mitotane with addition of etoposide/doxorubicin/cisplatin (EDP) chemotherapy. Conclusion: ACC is a rare, highly aggressive malignancy which may produce extensive intravascular invasion. It may rarely extend to the RA and even rarer into the RV; with 42 and 1 reported cases, respectively. No study has conclusively found that vascular extension of ACC is a poor prognostic factor, hence surgical management is the primary strategy including cases with RA/RV involvement. There is lack of data and consensus regarding adjuvant or palliative medical therapy. However, in phase II trials combination of EDP chemotherapy and mitotane have shown response rates ranging from 11% to 54%. Reference: Alghulayqah, Abdulaziz, et al. “Long-term recurrence-free survival of adrenocortical cancer extending into the inferior vena cava and right atrium: Case report and literature review.” Medicine 96.18 (2017).

Prognostic value of SH3PXD2B (Tks4) in human hepatocellular carcinoma: a combined multi-omics and experimental study

BackgroundHepatocellular carcinoma (HCC) is one of the most common and fatal cancers worldwide. HCC invasion and metastasis are crucial for its poor prognosis. SH3PXD2B is a scaffold protein and critical for intravascular and extravascular invasion and metastasis of various types of tumors. However, the role of SH3PXD2B in HCC progression remains unclear.MethodsThe levels of SH3PXD2B mRNA transcripts in the TCGA database and SH3PXD2B protein expression in the Human Protein Atlas were analyzed. Furthermore, the levels of SH3PXD2B expression in clinical samples were analyzed by quantitative RT-PCR and immunohistochemistry. The potential association of the levels of SH3PXD2B expression with clinicopathological characteristics, overall survival (OS), and recurrence-free survival (RFS) of HCC patients was analyzed. The impact of SH3PXD2B silencing by shRNA-based lentivirus transduction on the proliferation and invasion of human HCC Hep3B and Huh7 cells was determined.ResultsSH3PXD2B expression was up-regulated in HCC tissues in the TCGA and Human Protein Atlas as well as clinical samples, relative to that of non-tumor liver samples. The levels of SH3PXD2B expression in HCC tissues were significantly associated with higher HBV infection rate, higher HCC grades and TNM stages, higher Ki-67 expression, higher serum α-fetoprotein (AFP), a shorter OS and RFS of HCC patients. Functionally, SH3PXD2B silencing significantly inhibited the formation and function of invadopodia and the invasion of Hep3B and Huh7 cells, but did not affect their proliferation in vitro.ConclusionsOur data suggest that SH3PXD2B may promote the invasion and metastasis of HCC and be a valuable therapeutic target and biomarker for treatment and prognosis of HCC.

Endoscopic eyebrow-eyelid sparing orbital exentration in mucormycosis

&lt;p class="abstract"&gt;The intra-vascular invasion progressively halts the blood flow in the arterial distributaries and the venous tributaries and finally a “blue black”, wet gangrenous region is noted. Later the underlying bone too becomes fragile and crumbles off. Removal of necrotic debris remains the main stay of management. Removal of foci of infection, the orbital soft tissues utilizing high resolution endoscopic modality is elaborated upon.&lt;/p&gt;

Diffuse large B-cell lymphoma (DLBCL) with significant intravascular invasion. Close resemblance of its clinicopathological features to intravascular large B-cell lymphoma, but not to DLBCL-not otherwise specified.

Intravascular large B-cell lymphoma (IVLBCL) is defined by the World Health Organization (WHO) Classification as one type of extranodal large B-cell lymphoma and it is characterized by the selective growth of lymphoma cells within blood vessels with minimal extravascular invasion. According to the criteria, however, several reported cases of IVLBCL with significant extravascular invasion cannot be classified as IVLBCL. The purpose of the present study was to assess the clinicopathological significance of the WHO criteria for IVLBCL. We characterized clinical, histopathological, and immunohistochemical features of 11 patients with extranodal diffuse large B-cell lymphoma (DLBCL) with significant intravascular invasion (DLBCL-IV), and statistically compared their features with those of 11 patients with IVLBCL and 15 patients with extranodal DLBCL with virtually no intravascular invasion (DLBCL-noIV). When compared with the DLBCL-noIV group, the DLBCL-IV group was characterized by significantly higher rates of splenomegaly, hemophagocytosis, advanced stage disease, and CD5 expression; higher average platelet count, serum lactate dehydrogenase level, and serum ferritin level. Progression-free survival was significantly shorter in the DLBCL-IV group than the DLBCL-noIV group. In contrast, there were no significant differences in clinicopathological features between the DLBCL-IV and the IVLBCL groups. Our study suggests that DLBCL-IV should be regarded as IVLBCL-related.

Surgical treatment of an abnormally positioned right adrenal tumor on segmental caudal vena cava aplasia in two dogs.

Segmental caudal vena cava (CVC) aplasia is a rare congenital vascular anomaly in dogs. Two dogs were diagnosed by CT imaging to have right adrenal tumors with concomitant segmental CVC aplasia. During surgery, a firm connection between the right adrenal gland and CVC was observed in both cases. The adrenal glands were found ventral to the CVC and the adrenal tumor was resected including the vascular wall. CVC venectomy for tumor removal will be required if the right adrenal gland is displaced in dogs with segmental CVC aplasia, even if there is no intravascular invasion.

LUNG AS THE PRIMARY SOURCE OF INTRAVASCULAR LARGE B CELL LYMPHOMA: A DIAGNOSTIC CHALLENGE

SESSION TITLE: Medical Student/Resident Pulmonary Manifestations of Systemic Disease Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Intravascular large B cell lymphoma (IVLBCL) is a rare form of Non-Hodgkin’s Lymphoma (NHL) that, in most cases, is disseminated at time of diagnosis with majority of manifestations in the central nervous system, cutaneous lesions, or hematologic syndromes. Lung involvement, though not uncommon, is most likely found during autopsy as early diagnosis of IVLBCL has proven to be difficult. CASE PRESENTATION: A 67 year-old male with no known medical history presented with progressive, subacute dyspnea and fatigue. On exam he was hypoxic with fine rales to auscultation and decreased air entry bibasally. Labs revealed moderate anemia, lactic acidosis, acute renal impairment, and transaminitis. CT chest non-contrast showed diffuse ground glass appearance with no acute consolidations or effusions. Peripheral blood smear showed no schistocytes; serum protein electrophoresis and erythrocyte sedimentation rate were unremarkable; ANCA and HIV were negative. Bone marrow biopsy was performed revealing hypercellularity with no evidence of malignancy; bronchoscopy was non-diagnostic. PET scan revealed areas of tracer uptake in the lungs and subsequent VATS with lung biopsy showed nonspecific pneumonitis: hilar membranes, reactive pneumocytes and collapsed vessels, making visualization of intravascular cell invasion difficult. Findings seemed consistent with interstitial lung disease, however, due to unknown origin of lung disease and acute onset of symptoms, the sample was sent for further pathologic review. Subsequent staining of cells revealed positive MUM-1, BCL-6 & BCL-2, CD45, CD20, PAX5, c-myc (20%) and Ki67. CD34 was negative. The final diagnosis was IVLBCL. DISCUSSION: IVLBCL is rare and characterized by the presence of tumor cells within blood vessels. The disease is highly malignant and carries a poor prognosis, as the majority of patients present late in disease course. The lung as a primary source of IVLBCL is a very rare occurrence with only a few cases reported. Although in this case diffuse ground glass appearance was present on chest CT, there was no explanation for pathology findings of interstitial lung disease, which necessitated further testing ultimately revealing a diagnosis. It is apparent that a confirmatory diagnosis of IVLBCL is quite difficult and involves intensive pathologic review. CONCLUSIONS: It is important for physicians to consider a diagnosis of IVLBCL, albeit rare, in patients who present with respiratory symptoms and no apparent cause. Ruling out other possible causes of clinical presentation, as well as adequate pathology samples, are paramount. Reference #1: 1.Yamashita, Hiroyuki, et al. “Intravascular Large B-Cell Lymphoma with Diffuse FDG Uptake in the Lung by 18FDG-PET/CT without Chest CT Findings.” Annals of Nuclear Medicine, vol 26, 27 Apr. 2012, pp. 515-521 Reference #2: 2.M. Fiegl, R. Greil, C. Pechlaner, J. Krugmann, S. Dirnhofer, Intravascular large B-cell lymphoma with a fulminant clinical course: a case report with definite diagnosis post mortem, Annals of Oncology, Volume 13, Issue 9, 2002 September, pp.1503–1506 Reference #3: 3.Ponzoni, Maurilio, et al. “Definition, Diagnosis, and Management of Intravascular Large B-Cell Lymphoma: Proposals and Perspectives From an International Consensus Meeting.” Journal of Clinical Oncology, vol 25, no. 21, 20 July 2007, pp. 3168-3173 DISCLOSURES: No relevant relationships by Lewis Attas, source=Admin input No relevant relationships by Alyssa Foster, source=Web Response No relevant relationships by Manuel Katz, source=Web Response No relevant relationships by Dan Ran-Castillo, source=Web Response No relevant relationships by Jonathan Shammash, source=Web Response No relevant relationships by Matthew Tavares, source=Web Response

TUMORAL PULMONARY HYPERTENSION: A RARE BUT DEADLY COMPLICATION OF METASTATIC CANCER

SESSION TITLE: Medical Student/Resident Pulmonary Vascular Disease Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Pulmonary tumor microembolism (PTE) and pulmonary tumor thrombotic microangiopathy (PTTM) are rare complications of metastatic cancer that can mimic acute pulmonary embolism (PE). They can present as fulminant right heart failure and are invariably fatal. They are usually associated with gastric and bronchogenic carcinomas. We report a patient with metastatic breast cancer who rapidly developed severe right ventricular failure with no evidence of PE on imaging, thought to be due to tumoral pulmonary hypertension (PH). CASE PRESENTATION: A 33-year-old female with recently diagnosed invasive ductal breast cancer with liver metastases presented with dyspnea for a few days. She had tachycardia, tachypnea and tender hepatomegaly, along with elevated D-dimer and liver enzymes. CT angiogram (CTA) of the lung was negative for PE. Echocardiogram (ECHO) showed severe PH and mildly dilated right ventricle (RV). She received one dose of paclitaxel. On day 3, the patient was intubated for worsening respiratory distress. Repeat CTA of the lung was negative for PE. ECHO now showed a severely dilated RV with decreased systolic function highly suggestive of thromboembolism for which alteplase was administered empirically. Despite thrombolysis and vasopressor support, she continued to deteriorate and developed multiorgan failure leading to death within 24 hours of intubation. DISCUSSION: Tumoral PH includes microvascular conditions (PTE and PTTM), tumor macroembolism, and intravascular invasion of tumors. PTE is the occlusion of small pulmonary arteries by tumor cells. PTE along with activation of coagulation and growth factors causing intimal proliferation becomes PTTM. PTTM is commonly seen in adenocarcinoma with only 3% cases occurring with breast cancer. Patients present with dyspnea, hypoxemia, and PH of unknown origin invariably progressing to right heart failure and death. Routine imaging such as CTA of the lung is usually normal. Cytology of the aspirate from a wedged pulmonary artery catheter has a reported sensitivity of 80–88% and a specificity of 82– 94%. However, there is rapid clinical deterioration and associated high mortality. High index of suspicion is required for diagnosis which is rarely made antemortem. Decreasing tumor burden with chemotherapy in combination with dexamethasone, warfarin and aspirin, also immunotherapy with PDGF inhibitor (imatinib) and VEGF inhibitor (bevacizumab) can be beneficial. CONCLUSIONS: Unexplained acute PH in patients with metastatic cancer should prompt concern for tumoral PH. Some advances in antemortem diagnosis have given hope for the treatment of this once thought to be an exclusively postmortem diagnosis. Treatment targeting growth factors looks promising and needs further investigation. Reference #1: Price LC, Seckl MJ, Dorfmüller P, Wort SJ. Tumoral pulmonary hypertension. Eur Respir Rev. 2019;28(151):180065. Published 2019 Feb 6. doi:10.1183/16000617.0065-2018 Reference #2: Mury, C., Schneider, A. G., Nobile, A., Rotman, S., & Liaudet, L. (2015). Acute Pulmonary Hypertension Caused by Tumor Embolism: A Report of Two Cases. Pulmonary Circulation, 5(3), 577-579. doi:10.1086/682225 Reference #3: Mury, C., Schneider, A. G., Nobile, A., Rotman, S., & Liaudet, L. (2015). Acute Pulmonary Hypertension Caused by Tumor Embolism: A Report of Two Cases. Pulmonary Circulation, 5(3), 577-579. doi:10.1086/682225 Ho, A. L., Szulakowsi, P., & Mohamid, W. H. (2015). The diagnostic challenge of pulmonary tumour thrombotic microangiopathy as a presentation for metastatic gastric cancer: A case report and review of the literature. BMC Cancer, 15(1). doi:10.1186/s12885-015-1467-7 DISCLOSURES: No relevant relationships by Kristin Fless, source=Web Response No relevant relationships by Delyse Garg, source=Web Response No relevant relationships by Davita Mabourakh, source=Web Response No relevant relationships by Nirav Mistry, source=Web Response No relevant relationships by Aditi Saha, source=Web Response No relevant relationships by Sohaib Tariq, source=Web Response No relevant relationships by Lalithaa Thirunavukarasu Murugan, source=Web Response

Use of Contrast-Enhanced Ultrasonography for the Characterization of Tumor Thrombi in Seven Dogs.

Simple SummarySome neoplasia—such as adrenal and thyroid glands tumors—have been associated with “tumor thrombi” both in humans and dogs. The detection and characterization of these venous tumor thrombi is important for both surgical planning and prognosis. In human medicine, contrast-enhanced ultrasonography (CEUS) is considered an accurate diagnostic technique for differentiating malignant from benign portal vein thrombosis in hepatocellular carcinomas. Data regarding the characteristics of tumor thrombi in dogs are currently lacking. Therefore, the aim of this study was to assess the feasibility of CEUS for the characterization of malignant venous thrombosis in dogs. On the basis of our results, CEUS appeared to be useful in the detection of malignant intravascular invasion; contrast uptake of the thrombus was present in all cases. In addition, CEUS may clearly detect newly formed vessels within the thrombus, and arterial-phase enhancement and washout in the venous phase were the main features in malignant thrombosis in our dogs. As CEUS is an easy to perform, noninvasive technique, its application in the detection of malignant thrombosis in dogs may be used to improve the diagnosis in oncological canine patients.Tumors of adrenal and thyroid glands have been associated with vascular invasions—so-called tumor thrombi, both in humans and dogs. The detection and characterization of venous thrombi is an important diagnostic step in patients with primary tumors for both surgical planning and prognosis. The aim of this study was to describe the use of contrast-enhanced ultrasonography (CEUS) for the characterization of tumor thrombi. Dogs with tumor thrombus who underwent bi-dimensional ultrasound (B-mode US) and CEUS were included. Seven dogs were enrolled in this retrospective case series. On B-mode US, all thrombi were visualized, and vascular distension and thrombus-tumor continuity were seen in three and two cases, respectively. On color Doppler examination, all thrombi were identified, seemed non-occlusive and only two presented vascularity. On CEUS, arterial-phase enhancement and washout in the venous phase were observed in all cases. Non-enhancing areas were identified in the tumor thrombi most likely representing non-vascularized tissue that could potentially be embolized in the lungs after fragmentation of the tumor thrombi. On the basis of these preliminary study, CEUS appeared to be useful for the characterization of malignant intravascular invasion.