Malignant Infiltration Research Articles

Complete Resolution of Lymphoid Interstitial Pneumonia in a Patient With Juvenile Myelomonocytic Leukemia Treated With Allogeneic Bone Marrow Transplant: Killing 2 Birds With 1 Stone.

Lymphoid interstitial pneumonia (LIP) is a rare disease characterized by benign reactive polyclonal proliferation of bronchus-associated lymphoid tissue after exposure to inhaled or circulating antigen(s), leading to a disease symptomatology similar to idiopathic interstitial pneumonia. Its association with diseases that are caused due to immune dysregulation (autoimmune diseases, congenital/acquired immunodeficiency, and allogeneic bone marrow transplant) and response to immunomodulatory/suppressive medications suggests an immunologic pathophysiology. Although LIP has been reported in association with lymphoproliferative diseases like Castleman disease, it has never been described in patients with leukemia. We report the first case of LIP in a patient with juvenile myelomonocytic leukemia (JMML) who was found to have a novel germline mutation of unknown significance in additional sex combs-like-1 (ASXL1) gene and a pathogenic somatic mutation of protein tyrosine phosphatase, nonreceptor type 11 (PTPN11) gene at diagnosis. The patient underwent a matched unrelated bone marrow transplant for JMML with complete resolution of JMML and LIP with no recurrence to date. We also emphasize the importance of considering LIP in differential diagnosis of pulmonary lesions seen in conjunction with hematologic malignancies and distinguishing it from malignant infiltration of the lung.

Abstract 1873: Preclinical activity of tipifarnib in cutaneous T-cell lymphoma

Abstract Cutaneous T-cell lymphoma (CTCL) is a rare form of non-Hodgkin lymphoma characterized by malignant infiltration of skin-homing CD4+ T-cells, manifesting clinically as patches and plaques on the skin (Wong HK, et al. Br J Haematol 2011). The disease will often progress from an indolent skin-limited form, Mycosis Fungoides (MF), to an aggressive leukemic variant, Sezary Syndrome (SS) (Kohnken R, et al. Curr Hematol Malig Rep 2016). As there are few effective therapies available for advanced-stage CTCL, we sought to explore potential novel therapeutic modalities. Farnesyl transferase inhibitors (FTIs) are a relatively new class of anticancer drugs, the exact mechanism of which is unknown. Tipifarnib is one such FTI, which has demonstrated clinical activity as a single agent in patients with relapsed and refractory lymphomas (Witzig, TE, et al. Blood 2011). We utilized CTCL patient-derived cell lines to evaluate the potential efficacy of tipifarnib in vitro. EC50 doses ranged from 7.5nM for HuT78 to 50nM for SeAx. Importantly, there was no cytotoxic effect on normal donor CD4+ T-cells in vitro. Based on these promising findings, we evaluated tipifarnib in vivo using a recently described interleukin-15 (IL-15) transgenic mouse model of CTCL (Mishra A, et al. Can Discov 2016). Following two weeks of dosing in 5-week old mice, we found a significant decrease in gross lesion severity in tipifarnib-treated mice (0.5±1.22 out of a possible score of 5) compared to vehicle-treated mice (3.33±0.57, p=0.0076). Histologically, IL-15 transgenic mice develop characteristic malignant CD4+ T-cell infiltrates in the dermis and epidermis. Tipifarnib-treated mice, however, have minimal lesions in the skin. These dramatic changes are reflected in a significantly decreased histologic severity score in tipifarnib-treated mice (3.8±0.75 out of a possible score of 7 compared to vehicle-treated mice (7±0, p=0.0002). These findings demonstrate that tipifarnib is active in patient-derived cell lines and the mouse model of cutaneous T-cell lymphoma. Further studies to elucidate the mechanism of antitumor activity of farnesyl transferase inhibition in this cell type are in progress. Citation Format: Rebecca Kohnken, Betina McNeil, Jing Wen, Kathleen McConnell, Francis Burrows, Pierluigi Porcu, Anjali Mishra. Preclinical activity of tipifarnib in cutaneous T-cell lymphoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1873.

Invasive Ductal Mammary Carcinoma in a Cow

Background: Mammary gland carcinoma is a malignant epithelial neoplasm that can be classified as solid, papillary, ductal, invasive micropapillary, or invasive ductal. They are rarely diagnosed in livestock animals. Reports describing the breast as primary site of tumor in cows are scarce. In this case report, pathological and clinical findings of primary carcinoma ofthe mammary gland in a cow are reported.Case: A 7-year-old crossbred pregnant cow exhibited an increase in volume in the posterior region of the udder. Palpation raised suspicion of mastitis. The prefemoral lymph nodes (LNs) were enlarged. After calving, the clinical condition worsened, and edema was observed in the ventral region, from the udder to the neck. Poisoning by Amaranthus sp. was suspected. The cow died fifteen days after calving. Necropsy was performed. The affected mammary gland and its LNs, fragments of abdominal organs, brain, pelvic limbs, and udder skin were routinely prepared and stained with hematoxylin and eosin. Gross examination revealed significant alterations in the mammary gland, and in the mammary and prefemoral LNs. The mammary gland was firm and swollen; with loss of normal architecture, and released purulent, pinkish, fetid contents. The mammary LNs were enlarged, with diffuse coalescentmultifocal lesions, loss of corticomedullary delimitation, and the content was similar to that observed in the udder. The internal prefemoral LNs were also enlarged and contained the same fetid contents. Histopathology revealed proliferation of neoplastic ducts coated by numerous neoplastic cells; some areas were solid. There was moderate to severe pleomorphism, with moderate anisocytosis and anisokariosis. Most of the cells had vesicular nuclei, with up to two evident nucleoli. Other cells had dense chromatin, and moderately eosinophilic cytoplasm. There was marked cell dissociation, and cell detachment. The central portionsof the ducts were necrotic, with a predominantly neutrophilic inflammation. The mitotic index was low, but some areas had up to four mitotic figures per high power field. Numerous areas exhibited multiple foci of deposition of organized granular basophilic material, interpreted as mineralized areas, and stained positively for Von Kossa stain. Some areas of the mammary gland exhibited proliferative acini and ducts, composed of a single layer of cuboidal or columnar cells with moderately eosinophilic, vacuolated cytoplasm, and a basal rounded nucleus of generally aggregated chromatin (mammary hyperplasia). Many acini were dilated, and some contained circumscribed basophilic material (corpora amylacea). The structural architecture of the LNs was altered by malignant neoplastic infiltration, similar to that found in the mammary gland. No metastatic lesions were detected in the other organs. Immunohistochemistry (IHC) was performed using the streptavidin-biotin-peroxidase technique. Anti-pan-cytokeratin and antivimentin antibodies were used. Neoplastic cells exhibited strong and uniform cytoplasmic immunoreactivity for pan-cytokeratin. Expression of vimentin was absent in the neoplastic cells, but was present in the connective tissue associated with the neoplasm.Discussion: Invasive ductal mammary carcinoma was confirmed by histopathological and IHC analyses. Edema can be explained by the neoplasm in the mammary gland and in the mammary LNs, with accumulation of fluid in the interstitium, caused by growth of the tumor and compression of large blood and lymphatic vessels. IHC confirmed the epithelial origin of the tumor and demonstrated the presence of epithelial tumor cells in the LNs, proving to be metastatic. Similar findingswere reported in a cow with a highly aggressive secretory mammary carcinoma, in which neoplastic cells exhibited immunoreactivity to cytokeratin, indicative of their epithelial origin.Keywords: histology, immunohistochemistry, neoplasms, ruminant.

The painless combination of anatomically contoured titanium plates and porcine dermal collagen patch for chest wall reconstruction.

A plethora of new biomaterials and dedicated rib fixator implant systems have been introduced into the field of chest wall reconstruction. The aim of our study is to evaluate the surgical outcomes of a novel combination of the anatomically contoured titanium rib implant and porcine dermal collagen patch for chest wall reconstruction. We performed a retrospective review of eight consecutive patients who underwent chest wall resection and reconstruction between January 2014 to August 2015 in a single institution. MatrixRib Fixation System and Permacol Surgical Implant were utilized to achieve chest wall reconstruction. The indication for reconstruction was malignant infiltration in 50% of patients. Three other subjects (37.5%) had chest wall resections to achieve adequate and safe surgical exposure. One patient had a right lung apical mycetoma with chest wall invasion. All patients underwent lung resections with the removal of 2 to 6 (median 3) ribs. Reconstruction was performed using the MatrixRib system, with a median of 2.5 (range, 2-4) ribs fixed in each patient. There was no post-operative mortality. One patient had a superficial wound infection which resolved with one week of oral antibiotics. Upon discharge, the pain scores were near zero with minimal analgesic requirements. None of the patients required repeat surgery or removal of their implants. Our early experience indicates that the combination of the MatrixRib system and Permacol patch for chest wall reconstruction is safe and feasible with promising results in terms of anatomical restoration of the chest wall mechanics, infection and pain.

Risk factors for and characteristics of pneumonitis in patients treated with anti-programmed death-1 therapy.

128 Background: Pneumonitis is an uncommon but potentially fatal toxicity of anti–programmed death-1 (PD-1) monoclonal antibodies (mAbs), but its prevalence, risk factors and clinical features are poorly described. Methods: The medical records of 234 patients with advanced cancer who underwent anti–PD-1mAbs therapies between September 2015 and September 2017 at the Cancer Center of the Chinese PLA (People’s Liberation Army) General Hospital were analyzed with regard to patient background and clinical features. Pneumonitis was diagnosed by the treating investigator; cases with confirmed malignant lung infiltration or infection were excluded. Univariate and multivariate analyses were performed to identify independent predictive factors for pneumonitis. Clinical features, management and prognosis of pneumonitis were also collected. Results: A total of 55 patients (23.5%) developed pneumonitis. Anti–PD-1mAbs induced pneumonitis was significantly associated with male sex, a history of prior thoracic radiotherapy, combination therapy and underlying lung condition (odds ratios 3.380, 3.081, 2.538 and 2.559, respectively). Time to onset of pneumonitis ranged from 2 days to 277days (median time was 85days). 85.4% (47 of 55) of cases were grade 1 to 2, 25.5% (14 of 55) were treated with steroid therapy, of which 85.7% (12 of 14) resolved/ improved. Nine (16.4%) patients worsened clinically and one died during the course of pneumonitis treatment. Conclusions: Pneumonitis associated with anti–PD-1 mAbs is a serious adverse effect in the clinical setting that cannot be ignored. However, patient selection based on sex, history of prior thoracic radiotherapy, combination therapy and underlying lung condition can minimize pneumonitis risk. Most events are low grade and resolved/ improved with steroid therapy. Rarely, pneumonitis worsens despite steroid therapy, and may result in death.

Local Glioma Cells Are Associated with Vascular Dysregulation.

Malignant glioma is a highly infiltrative malignancy that causes variable disruptions to the structure and function of the cerebrovasculature. While many of these structural disruptions have known correlative histopathologic alterations, the mechanisms underlying vascular dysfunction identified by resting-state blood oxygen level-dependent imaging are not yet known. The purpose of this study was to characterize the alterations that correlate with a blood oxygen level-dependent biomarker of vascular dysregulation. Thirty-two stereotactically localized biopsies were obtained from contrast-enhancing (n = 16) and nonenhancing (n = 16) regions during open surgical resection of malignant glioma in 17 patients. Preoperative resting-state blood oxygen level-dependent fMRI was used to evaluate the relationships between radiographic and histopathologic characteristics. Signal intensity for a blood oxygen level-dependent biomarker was compared with scores of tumor infiltration and microvascular proliferation as well as total cell and neuronal density. Biopsies corresponded to a range of blood oxygen level-dependent signals, ranging from relatively normal (z = -4.79) to markedly abnormal (z = 8.84). Total cell density was directly related to blood oxygen level-dependent signal abnormality (P = .013, R2 = 0.19), while the neuronal labeling index was inversely related to blood oxygen level-dependent signal abnormality (P = .016, R2 = 0.21). The blood oxygen level-dependent signal abnormality was also related to tumor infiltration (P = .014) and microvascular proliferation (P = .045). The relationship between local, neoplastic characteristics and a blood oxygen level-dependent biomarker of vascular function suggests that local effects of glioma cell infiltration contribute to vascular dysregulation.

Multivisceral resections for locally advanced colorectal cancer after preoperative treatment.

Multivisceral resection for colorectal cancer invading into the adjacent organs may often be difficult and may involve serious complications. Preoperative therapy may facilitate resection with safe margins. Between August 2007 and July 2016, 23 patients with colorectal cancer invading into the adjacent organs treated with preoperative treatment (chemoradiotherpay, chemotherapy, radiotherapy) were retrospectively investigated. All 23 patients received surgery with curative intent. Four patients had distant metastases at the time of diagnosis. Two patients had distant metastasis after preoperative treatment. The mean operative time was 535.3±185.5 min and the median amount of blood loss was 1,050 ml. Histopathological examination revealed malignant infiltration of the adjacent organs in 14 patients (60.9%). R0 resection rate was 73.9%. Postoperative complications were identified in nine patients (39.1%) and a high incidence of infectious complications was observed. Patients with curative resection showed a significantly better survival than patients with R1 or R2 resection (P<0.01). Multivisceral resection for locally advanced colorectal cancer invading into the adjacent organ after preoperative treatment may be performed with acceptable morbidity and minimal mortality. R0 resection improves the prognosis of patients with locally advanced colorectal cancer invading into the adjacent organ after preoperative treatment.

A predicting model of bone marrow malignant infiltration in 18F-FDG PET/CT images with increased diffuse bone marrow FDG uptake.

Purpose: To demonstrate the relationship between the etiologies of increased diffuse bone marrow (BM) 18F-FDG uptake and PET/CT imaging/clinical features, as well as to explore a predicting model of BM malignant infiltration (MI) based on decision tree.Methods: 84 patients with increased diffuse BM uptake were retrospectively enrolled. Their complete case record and PET/CT images were reviewed, with the maximal standardized uptake values of bone marrow (SUVmaxBM) and other imaging/clinical features were noted. At the same time, the differences in imaging/clinical features between bone marrow MI and non-MI groups were compared. The decision tree for predicting MI was established by C5.0 component of SPSS Clementine.Results: In patients with homogenously increased BM uptake, 21 patients had MI resulted from leukemia, lymphoma and small cell lung cancer (SCLC). MI group had higher SUVmaxBM than non-MI group (6.7±3.1 vs 4.2±0.9, p=0.001). However, a considerable proportion of MI patients had similar SUVmaxBM to non-MI patients, which were mainly seen in lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (LPL/WM), chronic myeloid leukemia (CML) and multiple myeloma (MM). There were significant differences in other factors between the two groups. MI patients were highly associated with SUVmaxAP/AX≥1 (the ratio of SUVmaxBM of appendicular skeleton to that of axial skeleton), hepatosplenomegaly, older age and lower rate of fever. The decision tree combining SUVmaxBM, SUVmaxAP/AX, fever and hepatosplenomegaly achieved a sensitivity of 81.0%, a specificity of 98.4% and an accuracy of 94.0% for predicting MI.Conclusion: Increased diffuse BM 18F-FDG uptake can be attributed to both bone marrow MI and benign etiologies. A decision tree based on C5.0 algorithm, combining PET/CT imaging and clinical features, is of potential use in discriminating BM malignant infiltration from patients with increased diffuse BM uptake.

Dermoscopy of inflammatory breast cancer

Inflammatory breast cancer is an aggressive and infiltrative malignancy that is often misdiagnosed as an infection because of its symptoms and signs of inflammation, delaying proper diagnosis and treatment. We report a case of inflammatory breast cancer showing correlation between dermoscopic and histopathological diagnoses. We highlight the utility of dermoscopy for skin biopsy site selection.

Role of Immunostaining in Detecting Extra-Pattern and Subtle Lymphomatous Infiltration in Bone Marrow Biopsies of NHL Patients

Introduction: Immunohistochemistry (IHC) enables the examination of a greater number of trephine biopsy levels and is helpful in determining additional scattered malignant cells. The aim of this study is to detect extra-pattern and subtle lymphomatous infiltration in bone marrow biopsies using CD20 and CD3 immunostaining. Patients and Methods: This study was conducted on 100 newly diagnosed Non Hodgkin Lymphoma (NHL) patients. Their bone marrow trephine biopsies were assessed on routine histology [Hematoxylin and Eosin (H & E)], and were further subjected to IHC using CD20 and CD3. Results: Pattern of involvement by H & E was highlighted by IHC. It showed additional interstitial pattern in 9 cases, parasinusoidal streaks in one case and highlighted a patchy pattern in another case with interstitial involvement on H & E. IHC also detected subtle infiltrations on additional 5.5% cases compared with histology alone. It helped in differentiating reactive (12 cases) and malignant lymphoid infiltration (33 cases). Conclusion: CD20 and CD3 immunostaining performed routinely on bone marrow trephine biopsies has the ability to reveal extra-pattern of infiltration and improve detection of subtle lymphoid involvement. A combined procedure identifying several distinctive features, in particular histotopography and IHC, provides a promising way of discriminating reactive from neoplastic lymphoid infiltrates in bone marrow trephine biopsies.

Correlation Between Contrast-enhanced Ultrasound Characteristics (Qualitative and Quantitative) and Pathological Prognostic Factors in Breast Cancer.

Little is known about the correlation between contrast-enhanced ultrasound (CEUS) characteristics and pathological prognostic factors in breast cancer. The aim of this study was to explore the correlation between CEUS characteristics and pathological prognostic factors. A retrospective study with 34 malignant breast lesions was conducted. CEUS characteristics included qualitative characteristics (e.g. lesion's enhancement degree and order, internal lesion homogeneity etc.) and quantitative characteristics (e.g. peak intensity, time to peak etc.). Also, pathological prognostic factors were included (e.g. tumor grade, estrogen receptor status etc.). Blurred lesion margins were observed more often in tumors of high histological grade (p=0.01) and in estrogen receptor-negative tumors (p=0.049). Furthermore, perilesional enhancement was associated with positive Ki-67 expression (p=0.049), while heterogeneous internal sentinel lymph node enhancement was associated with malignant infiltration of the node (p=0.002). CEUS has the potential to provide a prevision of pathological prognostic factors in malignant breast lesions, helping in the better early patient management.

Fat fraction mapping using magnetic resonance imaging: insight into pathophysiology.

Adipose cells have traditionally been viewed as a simple, passive energy storage depot for triglycerides. However, in recent years it has become clear that adipose cells are highly physiologically active and have a multitude of endocrine, metabolic, haematological and immune functions. Changes in the number or size of adipose cells may be directly implicated in disease (e.g. in the metabolic syndrome), but may also be linked to other pathological processes such as inflammation, malignant infiltration or infarction. MRI is ideally suited to the quantification of fat, since most of the acquired signal comes from water and fat protons. Fat fraction (FF, the proportion of the acquired signal derived from fat protons) has, therefore, emerged as an objective, image-based biomarker of disease. Methods for FF quantification are becoming increasingly available in both research and clinical settings, but these methods vary depending on the scanner, manufacturer, imaging sequence and reconstruction software being used. Careful selection of the imaging method-and correct interpretation-can improve the accuracy of FF measurements, minimize potential confounding factors and maximize clinical utility. Here, we review methods for fat quantification and their strengths and weaknesses, before considering how they can be tailored to specific applications, particularly in the gastrointestinal and musculoskeletal systems. FF quantification is becoming established as a clinical and research tool, and understanding the underlying principles will be helpful to both imaging scientists and clinicians.

Relationship between the Type of Non-Small Cell Lung Cancer and Infiltration of Lymphatic Drainage

Introduction: Malignant cells invasion of lymphatic drainage represents the basic precondition of metastasis and the disease progress. The invasion of tumor depends on its pathomorphologic characteristics, out of which one of the most significant role is the type. Aim of the Study: Descriptive analysis of operated patients, estimation of frequency and representativeness of the stated types of NSCLC in the monitored group, analysis of malignant cells of lung cancer in lymphatic drainage on the basis of the type of primary tumor. Patients and Methods: The study included 331 patients, who underwent the surgery during which the malignant infiltration was removed, in addition to the dissection of lymph nodes drainage. Results: Out of the total number of operated patients, 257 of them were male gender, while 74 were female gender, with the average age of 63.52 years (21-80). The relation of gender structure of the patients in relation to gender was statistically significant (p=0.00). The ratio between squamous cell carcinoma to adenocarcinoma was 182:140, while the other types of tumor were insignificant. Statistically, there was no significant difference in the frequency of two most common types of lung cancer (χ2test= 3.02; p=0.09). There was no statistically significant connection between the type of tumor and N1 metastasis (χ2=1.55; p=0.46), as well as in the ratio between the type of tumor and malignant infiltration of lymph nodes, level N2 (χ2=2.33; p=0.32). Conclusion: There is no connection between the type of lung cancer and invasion of levels N1 and N2 of lymph nodes.

Acute Liver Failure From Small Cell Carcinoma of the Lung

Acute liver failure (ALF) is characterized by liver damage along with encephalopathy and encephalopathy in patients without any prior history of liver disease. It is most commonly associated with acetaminophen hepatotoxicity, viral hepatitis or ischemic injury. Malignant infiltration has also been described as a cause of ALF, but small cell carcinoma (SCC) of the lung is an uncommon etiology. Here, we describe a patient who was admitted with ALF and was revealed to have SCC of the lung. A 75-year-old woman who had undergone elective laparoscopic cholecystectomy three weeks prior for symptomatic cholelithiasis presented with encephalopathy, abdominal pain and abnormal liver enzymes including AST 118, ALT 79, alkaline phosphatase 260, total bilirubin 3.8, direct bilirubin 2.8 and INR 1.7. Serologic evaluation of liver dysfunction was unremarkable including hepatitis testing, drug levels, infectious work-up, and chronic liver disease testing. Abdominal doppler was normal. CT scan of the abdomen showed hepatomegaly with a large area of decreased attenuation in the left lobe of the liver. Hepatomegaly with a mottled appearing liver and infiltrative signal abnormality in the lateral segment of the left lobe of the liver was observed on MRCP. Hepatic mass biopsy revealed small cell carcinoma, favoring lung primary. Given her poor performance status and liver failure, she was deemed not a candidate for chemotherapy and hospice care was pursued; she ultimately died 10 days after admission. Malignant infiltration of the liver from SCC of the lung has been described due to its aggressive nature to metastasize to other organs, but it is unusual for SCC to manifest as ALF. Prompt liver biopsy with a rapid immunostaining is essential to establish a diagnosis so that chemotherapy may be started. In our patient, evaluation for common causes of ALF was negative making malignant infiltration from SCC the likely etiology. Our case is unique from prior reports of ALF due to SCC of the lung in that it did not reveal significantly elevated aminotransferase levels but had other hallmark features of ALF including elevated bilirubin, INR and encephalopathy. Additionally, the temporal relation to the recent cholecystectomy prompted testing for surgical complications and questioning whether the initial presentation was indeed secondary to symptomatic cholelithiasis. This case demonstrates that malignancy, particularly SCC of the lung, should be considered in patients with ALF.Figure: Large vague area of decreased attenuation in the lateral segment of the left lobe of the liver on CT.Figure: Signal abnormality in the lateral segment of the left lobe of the liver on MRCP.

Bleeding Varices as the First Presenting Sign of a Neuroendocrine Tumor

Introduction: Noncirrhotic portal hypertension NCPH is defined as a syndrome with portal-caval pressure gradient exceeding 5mm Hg in the absence of cirrhosis. A wide spectrum of systemic diseases can result in NCPH, including infiltrative diseases and malignancy. To our knowledge, we report the first case of neuroendocrine tumors (NET) resulting in NCPH. Case: A 60 year old female presented with one day of melena, worsening fatigue, and dyspnea. Per patient report, she was admitted 2-3 months prior at an outside hospital with melena. She underwent upper and lower endoscopy at that time, reportedly requiring the removal of several tumors and polyps. She reported multiple bowel movement with black streaks that later developed into large volume black, tarry stools. She was hemodynamically stable and physical exam was unremarkable. Bloodwork was remarkable for microcytic anemia. She subsequently underwent upper endoscopy that revealed a 2cm submucosal lesion at the gastroesophageal junction (GEJ) and bleeding gastric varix. Hemostasis was achieved during the procedure. CT liver showed several hepatic hypodensities, some ill-defined. IR guided liver biopsy revealed well-differentiated intermediate grade NET, most likely gastrointestinal in origin due to the positive CDX2 stain. The surrounding liver parenchyma was normal without evidence of fibrosis. MRI liver showed innumerable hepatic metastasis and portal hypertensive changes. Liver metastasis was confirmed on octreoscan obtained prior to discharge - no extrahepatic sites of metastasis were found. Patient's hemoglobin stabilized, and he was discharged with close follow up.Figure: MRI of Liver.Discussion: NETs arise throughout the body. However, NETs of the digestive tract are an uncommon finding, with an annual incidence of 3.65 per 100,000. These tumors are typically indolent in their course, but up to 40% have already metastasized at diagnosis. NET is not usually directly associated with portal hypertension. The liver is the most common site of metastasis, but have never been reported in the literature to result in NCPH. Other infiltrative diseases such as sarcoidosis, mastocytosis, and lymphoma are more commonly associated with NCPH. Here we illustrate an unusual presenting sign for NET, variceal bleeding resulting from noncirrhotic portal hypertension.Figure: Endoscopy showing bleeding gastric varies.Figure: Octreotide scan.

Pseudocirrhosis: A Cause of Acute Liver Failure (ALF)

Introduction: Drug toxicity and viral hepatitis are the most common causes of ALF. A rarely reported cause of ALF is malignant infiltration of the liver due to either a solid organ tumor or hematological malignancy. Here we present a case of an ALF in a breast cancer patient. Case: 80 year old woman diagnosed with invasive ductal carcinoma of the breast, estrogen receptor positive, progesterone receptor negative & HER2 negative and was started on anastrozole in view of her advanced age and comorbidities. She was then admitted to the hospital for altered mental status, fatigue, and abdominal pain. Initial laboratory assessment showed derangement of liver test showing alkaline phosphatase (ALP): 517, aspartate aminotransferase (AST): 687, alanine transaminase (ALT):171, total bilirubin 5.2, INR 1.9. Hepatitis panel and autoimmune panel were unremarkable. Abdominal ultrasound revealed heterogeneous nodular liver without biliary ductal dilatation and mild ascites. No focal hepatic lesion was noted. Patient's liver function continued to deteriorate despite avoidance of hepatotoxic medications including anastrozole. Laboratory findings on hospital day 10 showed ALP: 406, AST: 1099, ALT: 247, INR 4.4. Provisional diagnosis of pseudocirrhosis was made in the setting of breast cancer without history of chronic liver disease. Liver biopsy was not pursued for the lack of definite therapeutic benefit. Patient was discharged to hospice in view of poor prognosis. Patient died of multiorgan failure due to fulminant hepatic failure.Table: Table. Laboratory valuesDiscussion: Clinically severe hepatic dysfunction with coagulopathy and encephalopathy because of metastatic tumor involvement is rare. Liver metastases usually present as radiographically detectable lesions that do not significantly compromise liver function. Rarely, metastatic carcinoma can diffusely infiltrate hepatic sinusoids, a pattern of metastasis that may be missed on imaging studies, and can result in liver failure. ‘Pseudocirrhosis' refers to morphological changes of the liver that mimic cirrhosis without histological changes caused by hepatic metastasis in setting of chemotherapy. The common malignancies are breast cancer, lymphoma or leukemia, colon cancer and others are rare. Prognosis is poor with after hospitalization mortality rate reported between 90-100%. The diagnosis of ALF secondary to malignancy can be challenging and may elude clinicians initially, particularly in patients with no previous cancer history.

P343 The electrophysiologic features of neurolymphomatosis

Background Neurolymphomatosis is defined as a malignant lymphoid infiltration of the peripheral nervous system. However, few studies revealed the clinical and electrophysiological features of neurolymphomatosis. The objective of this study is to investigate the clinical and electrophysiological features of neurolymphomatosis. Method We found eleven patients (six male and five female) with following two conditions from medical records at Severance hospital from January 2004 to February 2016: (i) patients with pathologically confirmed lymphoma or leukemia, and (ii) patient with the evidence of malignant cell infiltration of peripheral nervous system in imaging studies. We retrospectively analyzed eleven patients with neurolymphomatosis. Results The median age of neurologic symptom onset was 53 years (range, 36–70 years). Among eleven patients with neurolymphomatosis, ten had non-Hodgkin’s lymphoma and the most common subtype was diffuse large B-cell lymphoma and the other patient had acute lymphoblastic leukemia. Eight patients were expired and their mean survival time is eight months (range, 1–23 months) after the diagnosis of neurolymphomatosis. Neurologic deficits were presented as first clinical presentation of lymphoma in five (46%) patients and as relapse or progression of a previous hematologic malignancy in six (54%) patients. Patients frequently demonstrated cranial nerve involvement (six patients; 55%) and severe pain (ten patients; 91%). 18FDG-PET/CT scan excellently revealed abnormality in ten (91%) of eleven patients and malignant lymphoid cells usually infiltrated from root and/or plexus to distal peripheral nerve. Nerve conduction study (NCS) revealed partial conduction block in ten nerves and simple axonal degeneration in 26 nerves. The mean interval from neurologic symptom onset to test was significantly longer in nerves with simple axonal degeneration than that in the nerves with partial conduction block. All nerves demonstrated simple axonal degeneration in the test more than 25 days after symptom onset. Conclusions Partial conduction block on NCS may lead to misdiagnosis of neurolymphomatosis. However, if patients have progressive painful multiple mononeuropathies with cranial neuropathy, the possibility of neurolymphomatosis should be considered.

Angiomyofibroblastoma of the vulva diagnosed preoperatively: A case report.

A 50-year-old woman (gravida 2, para 2) first noticed a small nodule in the right labium majus 2 years prior to the initial visit to the Hachinohe Red Cross Hospital (Hachinohe, Japan), which had gradually increased in size. On physical examination, a well-circumscribed, elastic, firm, goose egg-sized, subcutaneous mass protruding from the right labium majus was identified. On magnetic resonance imaging (MRI), the lesion was hypointense on T1-weighted images and was well-circumscribed, strongly enhanced and homogeneous on gadolinium-enhanced images, measuring 7.5×4 cm. The same tumor had measured 2.6 cm on an MRI performed 6 years earlier. Based on the clinical course and imaging findings, angiomyofibroblastoma was diagnosed and surgical resection of the tumor was performed. The tumor was well-circumscribed and highly vascular. The intraoperative blood loss was 70 ml. Histopathologically, the tumor cells were concentrated around blood vessels, were spindle-shaped to oval with mild atypia, and were positive for vimentin, desmin, neural cell adhesion molecule (N-CAM), CD-34, estrogen receptor and progesterone receptor, and negative for S-100. Based on these findings, the diagnosis of angiomyofibroblastoma was confirmed. Angiomyofibroblastoma is a benign mesenchymal tumor that occurs in the female external genitalia. Differentiation of this tumor from aggressive angiomyxoma, a fast-growing infiltrative malignancy that occurs in the same region, may be challenging. The diagnosis of angiomyofibroblastoma is usually based on the histopathological findings of the resected specimen. The present case is of value, as the angiomyofibroblastoma was successfully diagnosed preoperatively based on the clinical course and imaging findings.

Two microRNA signatures for malignancy and immune infiltration predict overall survival in advanced epithelial ovarian cancer

MicroRNAs have been established as key regulators of tumor gene expression and as prime biomarker candidates for clinical phenotypes in epithelial ovarian cancer (EOC). We analyzed the coexpression and regulatory...

Metastatic Renal Cell Carcinoma With Hepatic Dysfibrinogenemia—A Case Report

Background and Aim: Anaemia and edema have been shown to be poor prognostic factors in advanced malignancy. Thrombocytopenia, functional factor deficiency and accelerated fibrinolysis are possible hepatic causes of abnormal bleeding. Secondary dysfibrinogenemia due to increased fibrinogen sialylation which impairs the ability to form fibrin polymers is seen in advanced liver disease and renal cell carcinoma. Intravenous albumin infusion has been used to prevent paracentesis induced circulatory dysfunction (post LVP) and provide nephroprotection by improving microcirculation. Intravenous albumin and terlipressin have been used in hepatorenal syndrome due to malignant infiltration, which is often considered the functional equivalent of cirrhosis. Case Summary: 27-year-old male, a known case of metastatic renal cell carcinoma with distant spread to the liver and spleen with history of malignant ascites (post therapeutic paracentesis) presented with complaints of haematuria (multiple episodes). Examination findings revealed anasarca, hepatosplenomegaly and inferior vena caval obstruction. Coagulation profile was suggestive of an elevated PT and INR. Component transfusion with fresh frozen plasma (FFP) or cryoprecipitate and intravenous albumin infusion was considered. He showed clinical improvement after receiving tranexamic acid and three units of FFP. Conclusion: Management of bleeding and preservation of hepatic function form an important component of supportive management. Presence of active bleeding and need for interventional procedures are indications for component transfusion. Eight to ten units of cryoprecipitate may be required in severe liver disease. Intravesical installation of tranexamic acid, endoscopic ligation of the bleeding vessel, application of local haemostyptic agents and application of adrenaline soaked gauze have been to control bleeding. Role of intravenous albumin infusion in advanced cancer need to be evaluated further. Management of hepatic encephalopathy (in the absence of well defined cirrhosis) also needs to be discussed. The author has none to declare.