Family History Of Malignancy Research Articles

CDH1 pathogenic variants and cancer risk in an unselected patient population.

CDH1 pathogenic variants confer a markedly elevated lifetime risk of developing diffuse gastric cancer (DGC) and lobular breast cancer (LBC). The aim of this study was to evaluate the prevalence and clinical impact of CDH1 pathogenic variants in the unselected and ancestrally diverse BioMe Biobank. We evaluated exome sequence data from 30,223 adult BioMe participants to identify CDH1 positive individuals, defined as those harboring a variant previously classified as pathogenic or likely pathogenic or a predicted loss-of-function variant in CDH1. We reviewed electronic health records and BioMe enrollment surveys for personal and family history of malignancy and evidence of prior clinical genetic testing. Using a genomics-first approach, we identified 6 CDH1 positive individuals in BioMe (~ 1 in 5000). CDH1 positive individuals had a median age of 42years (range 35-62years), all were non-European by self-report, and one was female. None had evidence of either a personal or family history of DGC or LBC. Our findings suggest a low risk of DGC and LBC in unselected patients harboring a pathogenic variant in CDH1. Knowledge of CDH1-related cancer risk in individuals with no personal or family history may better inform surveillance and prophylactic measures.

The prevalence of secondary neoplasms in acromegalic patients: possible preventive and/or protective role of metformin

BackgroundAcromegaly is a rare disease due to chronic growth hormone (GH) excess and the consequent increase in insulin-like growth factor-1 (IGF-1) levels. Both GH and IGF-1 play a role in intermediate metabolism affecting glucose homeostasis. The association between hyperinsulinemia/impaired glucose tolerance and an increased risk of cancer has been clarified. Insulin has a mitogenic effect through its interaction with the IGF-1 receptor (IGF-1R) that also binds IGF-1. On the other hand, metformin, an anti-hyperglycemic drug that decreases serum levels of insulin and IGF-1, could have a protective role in the treatment of endocrine tumors.MethodsA retrospective, observational, multicenter study in 197 acromegalic patients, receiving/not receiving metformin, was performed to assess whether the prevalence of neoplasms might be correlated with insulin resistance and could eventually be modified by metformin treatment.ResultsIn general, the occurrence of secondary neoplasia among our patients was significantly (pV = 0.035) associated with a positive family history of malignancy and with disease duration; a trend towards significance was observed in patients aged > 50 years. Acromegalic subjects who had undergone surgery showed a lower probability of developing a malignant tumor, whereas a higher prevalence of malignancies was observed in obese patients. No significant statistical difference was found when comparing metformin-treated or -untreated subjects for the presence of a second tumor. More interestingly, a trend towards statistical significance (pV = 0.065) was demonstrated in the metformin-treated group for the onset of a benign neoplasm.ConclusionMetformin could act directly on tumor cell metabolism and may have an adjuvant role in benign lesion progression.

The positive impact of implementing an onsite guideline-based genetic testing procedure for prostate cancer in a multidisciplinary uro-oncology clinic.

234 Background: Prior to the guidelines set forth by the 2017 Philadelphia consensus conference, genetic testing for prostate cancer was conducted based on personal and family history of malignancies pursuant to NCCN recommendations. The 2017 guidelines expanded testing criteria to included age at diagnosis, metastatic disease, and tumor sequencing. In spite of these advancements, limited literature is available regarding successful implementation of a streamlined system for genetic testing in prostate cancer. This paper explores the benefits of implementing an on-site guideline-based genetic testing process for prostate cancer patients treated at a multi-disciplinary uro-oncology practice. Methods: Data was retrospectively reviewed for 561 prostate cancer patients seen in a multi-disciplinary uro-oncology clinic since January 2017. Prior to January, 1, 2019 genetic testing was recommended to patients based on NCCN guidelines, and swabs for testing were procured off-site less than 1 mile from the clinic (n=107). After January, 1, 2019 genetic testing was recommended based on the guidelines set forth by the Philadelphia consensus conference, and swabs for testing were procured at the clinic itself (n=454). Results: A statistically significant increase in compliance with genetic testing was observed after the implementation of an on-site, guideline-based testing process. Patient compliance with genetic testing increased from 33.6% to 96.5%. The time to receive the genetic test results (calculated as the time between referral for genetic testing and obtaining the test results) was also significantly improved from 38 days to 21 days. Conclusions: The implementation of an on-site, guideline-based genetic testing model for prostate cancer patients significantly improved compliance with genetic testing to 96.5% and decreased the time to receive genetic test results by 17 days. Overall, adopting a guide-line based model with on-site genetic testing has the potential to significantly improve the detection rate for pathogenic and actionable mutations, increase the utilization of targeted therapies, and increase cascade testing to include at-risk family members.

Malignant Peritoneal Mesothelioma Associated With Endometriosis: A Clinicopathologic Study of 15 Cases.

Only a few cases of malignant peritoneal mesothelioma (MPeM) associated with endometriosis have been published; with chronic inflammation of the peritoneum associated with the latter being postulated as an inducing factor in the pathogenesis of this tumor. We assessed the clinicopathologic characteristics of MPeM associated with endometriosis to determine if there were other factors besides inflammation that may contribute to the pathogenesis in this patient population. Fifteen MPeM associated with endometriosis were retrieved from our files. Most presented with abdominal/pelvic pain, mass or distention; median age was 45 yr. Only 16% of patients had a history of asbestos exposure. In contrast, a third of the patients had a personal history of other neoplasms, and >80% had a family history of malignancies. Although most tumors had gross and microscopic features typical of MPeM, some had confounding features including "adhesion-like" appearance or gelatinous cysts/nodules, and signet ring cells. Tumors were epithelioid (9) and biphasic (6). MPeM was misdiagnosed as Müllerian carcinoma in 40% of cases. All patients (n=15) had cytoreductive surgery in addition to other therapies. Only 2/12 patients died of disease (17%). The 3- and 5-yr overall survival was 90%. MPeM associated with endometriosis tends to occur in patients with personal/familial history of malignancies, which may be a predisposing factor. In light of this finding, the role of endometriosis in the pathogenesis of MPeM is likely less relevant. The favorable outcome seen in these patients may be related to germline mutations or the hormonal milieu and needs further investigation.

Assessing PD-L1 expression in non-small cell lung cancer and predicting responses to immune checkpoint inhibitors using deep learning on computed tomography images

Rationale: This study aimed to use computed tomography (CT) images to assess PD-L1 expression in non-small cell lung cancer (NSCLC) and predict response to immunotherapy.Methods: We retrospectively analyzed a PD-L1 expression dataset that consisted of 939 consecutive stage IIIB-IV NSCLC patients with pretreatment CT images. A deep convolutional neural network was trained and optimized with CT images from the training cohort (n = 750) and validation cohort (n = 93) to obtain a PD-L1 expression signature (PD-L1ES), which was evaluated using the test cohort (n = 96). Finally, a separate immunotherapy cohort (n = 94) was used to assess the prognostic value of PD-L1ES with respect to clinical outcome.Results: PD-L1ES was able to predict high PD-L1 expression (PD-L1 ≥ 50%) with areas under the receiver operating characteristic curve (AUC) of 0.78 (95% confidence interval (CI): 0.75~0.80), 0.71 (95% CI: 0.59~0.81), and 0.76 (95% CI: 0.66~0.85) in the training, validation, and test cohorts, respectively. In patients treated with anti-PD-1 antibody, low PD-L1ES was associated with improved progression-free survival (PFS) (median PFS 363 days in low score group vs 183 days in high score group; hazard ratio [HR]: 2.57, 95% CI: 1.22~5.44; P = 0.010). Additionally, when PD-L1ES was combined with a clinical model that was trained using age, sex, smoking history and family history of malignancy, the response to immunotherapy could be better predicted compared to either PD-L1ES or the clinical model alone.Conclusions: The deep learning model provides a noninvasive method to predict high PD-L1 expression of NSCLC and to infer clinical outcomes in response to immunotherapy. Additionally, this deep learning model combined with clinical models demonstrated improved stratification capabilities.

Gender-based epidemiological study of lung cancer patients

Background In Egypt, lung cancer represents 5.0–7.0% of all cancers and ranks the fifth in males and both sexes, and ninth among females. The current study aims to characterize a cohort of patients with lung cancer based on their sex regarding risk factors, clinical presentation, and results of investigations. Patients and methods A retrospective comparative cross-sectional study was conducted that included all female lung cancer cases that were referred to the Clinical Oncology and Nuclear Medicine Department from year 2014 to year 2018. An equal number of males were randomly selected within the same year interval (as a comparative group). Data (included epidemiological data, relevant medical history, and the histopathologic type of cancer) were retrieved from the electronic database. Results The family history of malignancy was higher among females (8.8 vs. 0%), but the difference was not significant. There were no significant differences in performance status between male and female group. Apart from chronic obstructive pulmonary disease, the prevalence of most chronic diseases was significantly higher among females than males. Adenocarcinoma is the most common histologic subtype regardless of sex, whereas squamous cell carcinoma represented 18.5% among males and 1.9% among females, with significant difference (P=0.001). Bone was the most common site of metastasis. Overall, 14% of males had suprarenal metastasis, compared with 3.5% of females, with significant difference (P=0.047). Conclusion This 4-year single-center analysis concluded that both male and female present at a late stage of lung cancer. Suprarenal metastasis was more common in males than females. Squamous cell carcinoma was the most common among males. There were no sex differences regarding age of diagnosis, performance status, presenting symptoms, and radiological site of tumor.

Interactions of Consanguinity and Number of Siblings with Childhood Acute Lymphoblastic Leukemia.

Acute lymphoblastic leukemia (ALL) is a common malignancy in children. Consanguinity has a high prevalence in developing countries and increases the probability of homozygosity for many genes which may affect ALL and its prognosis. We conducted a study to explore the impact of consanguinity and number of siblings on ALL as there are currently no studies to describe this effect. Data were collected from patients' records from the Children's University Hospital of Damascus University, which is the major cancer centre for children in Syria. This study included 193 children with ALL over one year. Number of siblings was not with the French–American–British (FAB) classification, gender, ALL subtype, or risk of ALL children. When comparing consanguinity degrees and complete blood counts at diagnosis, significant contradicting data were found in the third-degree and fourth-degree consanguinity when compared to one another and to not having consanguineous parents as third degree consanguinity was associated with normal platelets but lower WBC counts, and fourth-degree consanguinity was associated with normal haemoglobin levels and WBC counts, but lower platelet counts. Having consanguineous parents was also associated with acquiring ALL at an older age, L2 FAB classification, having a positive family history for malignancies, and not having hepatosplenomegaly (P < 0.05). Although L2 is known to be a poor prognosis indicatory, no association was found with consanguinity and risk. Finally, no association was found with ALL subtype or risk (P > 0.05). Although consanguinity and number of siblings have affected some variables and prognostic features of childhood ALL, the aetiology is not clear and we need further studies to clarify such an association as this will help in optimising therapy and accurately determine the risk.

Tumor Genomic Testing: Identifying Characteristics Associated With Germline Risk for Developing Malignancy.

Tumor genomic testing is used primarily to facilitate the selection of the best possible treatment for a malignancy based on the genomic characteristics of the tumor. Germline genomic testing has implications for care and recommendations for cancer prevention and early detection for the patient and their family. Careful review of specific components of tumor genomic testing reports and of the family history of malignancy can help ensure that families with potential germline risk are identified and referred for genetic counseling and genetic testing.

Risk and prognosis factors for systemic sclerosis with lung cancer: A single-centre case-control study in China.

To analyse clinical characteristics, risk and prognosis factors for systemic sclerosis (SSc) patients with lung cancer. SSc patients with lung cancer admitted to Peking Union Medical College Hospital from February 1992 to December 2018 were included. Age and sex-matched controls were selected from a pool of SSc patients without lung cancer during the same period. Conditional logistic regression and Cox proportional-hazard regression were used to identify risk factors and prognosis factors. The Kaplan-Meier method was used to draw the survival curve and calculate median survival. Nineteen SSc patients with lung cancer and 76 controls were included. The mean age at lung cancer diagnosis was 54.4±10.2years. In all 19 cases the lung cancer had been diagnosed after SSc and the median interval between SSc onset and lung cancer onset was 10.5years (range 2.0-36.2years). Among SSc patients with lung cancer, the median follow-up time and median survival were 2.6years and 1.4years, respectively. In the sex and age-matched conditional logistic multivariable regression analysis, family history of malignancy (OR 4.930, 95%CI 1.926-12.619, P = .001), ILD (OR 7.701, 95%CI 1.009-58.767, P = .049) were independent risk factors for lung cancer among SSc patients, and considering sex and age of SSc onset, SSc patients with more advanced staging of lung cancer (HR 3.190, 95%CI 1.127-6.126, P = .06) had poorer prognosis. Lung cancer is not uncommon in SSc patients, especially those with family histories of malignancy or ILD. Early detection of lung cancer is of vital importance for better prognosis.

Metachronous cutaneous squamous cell carcinoma in a young patient as the only presenting symptom to uncover Lynch syndrome with MLH1 Germline mutation

BackgroundCutaneous malignancies are rare complications of Lynch syndrome and can include Muir-Torre and Turcot syndromes that are associated with sebaceous gland tumors and keratoacanthomas. The incidence and clinical course of cutaneous squamous cell carcinoma have not been well documented in Lynch syndrome due to its rarity.Case presentationA 49-year male presented with an enlarging groin skin lesion that was biopsed and demonstrated cutaneous squamous cell carcinoma for which he underwent a surgical resection. The patient experienced later a recurrence of cutaneous squamous cell carcinoma around the resected margins. Next generation sequencing of tumor tissue revealed mutations in MSH6 and MLH1, in addition to high microsatellite instability. The patient underwent pembrolizumab treatment with complete resolution of the cutaneous lesion in the groin, but subsequently developed a new mass in the right antecubital fossa shortly after discontinuation of pembrolizumab. Repeat biopsy of the antecubital fossa lesion revealed a recurrence of cutaneous squamous cell carcinoma. Germline mutation testing revealed MLH1 mutation, compatible with Lynch syndrome, and the patient restarted pembrolizumab which was associated with a complete response. The patient was referred for genetic counseling and cancer screening.ConclusionsCutaneous squamous cell carcinoma, although rare, can be the initial presenting symptom in patients with Lynch syndrome. This association has been described in patients with germline mutations in MLH1. Lynch syndrome should be considered when evaluating young patients presenting with recurrent cutaneous squamous cell carcinoma with positive family history of malignancy and/ or without any identifiable risk factors for skin cancers, including those with a durable and rapid response to immunotherapy.

Oncogenic Genetic Alterations in Non-Small-Cell Lung Cancer (NSCLC) in Southwestern China.

PurposeTo investigate the impact of oncogenic genetic alterations (GAs) on non-small-cell lung cancer (NSCLC) in southwestern China.Patients and MethodsWe first collected 579 pathologically confirmed NSCLC specimens and then used next-generation sequencing (NGS) to evaluate the DNA samples for GAs. Both the tissue and plasma samples were provided by 28 patients. Furthermore, subgroup analyses based on sample type, concordance, and GA type were carried out.ResultsGAs were detected by NGS in 61.8% (358/579) of patients. Two hundred and twenty-nine patients (39.6%) harbored EGFR mutations, 63 (10.9%) harbored KRAS mutations, 13 (2.2%) harbored BRAF mutations, 30 (5.18%) harbored ALK fusions, and 13 (2.2%) had ROS1 fusions. We found that females (p < 0.01), nonsmokers (p < 0.001), adenocarcinoma (p < 0.001), and tissue (p = 0.03) had a relatively high EGFR mutation rate. Notably, NSCLC patients from Xuanwei had a significantly different mutational pattern for EGFR in comparison with that of non-Xuanwei patients (higher G719X + S768I mutations and multiple gene alterations, but fewer exon 19 deletion mutations and single gene alterations). We found that adenocarcinoma (p = 0.02), family history of malignancy (p = 0.03), Xuanwei origin (p < 0.001), and tissue (p = 0.04) were associated with a higher number of KRAS mutations. Subgroup analysis showed that ALK (p < 0.001) and ROS1 (p < 0.05) fusions and rare EGFR mutations (p < 0.001) were associated with non-Han ethnic patients.ConclusionYunnan NSCLC patients from Xuanwei and non-Han ethnic patients had an obviously unique prevalence of GAs.

CARDIAC TAMPONADE AS A PRESENTATION OF AN ASYMPTOMATIC EXTRACARDIAC MALIGNANCY

SESSION TITLE: Medical Student/Resident Lung Cancer Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Pericardial tamponade is a life-threatening event secondary to inhibition of passive diastolic filling by rapid accumulation of fluid leading to right atrioventricular diastolic collapse. Patients with pericardial metastasis showing symptoms of cardiac tamponade as the first presenting sign of extracardiac malignancy is very uncommon. CASE PRESENTATION: A 24-year-old female presented to the hospital with progressive dyspnea and lower extremity swelling that started 3 days ago. She had no significant past medical history and was taking no prescription medications. She denied illicit drug use or smoking. There was no family history of malignancy or autoimmune disorder. Her vital signs were: afebrile, blood pressure 90/60 mmHg, heart rate140bpm, respiratory rate 30/min, oxygen saturation 95% on 10 liters of a nonrebreather mask. On physical examination jugular venous distention was 2 cm.Decreased breath sounds on the right hemithorax. Heart sounds were muffled, tachycardia, with a regular rhythm. The patient had 1+ edema bilaterally in the lower extremities. Other exams were unremarkable. CT angiogram of chest found a large right pleural effusion, 2.6 cm pulmonary nodule at right lower lobe,mediastinal lymphadenopathy, and a large pericardial effusion (Fig.1). An echocardiogram showed signs of pericardial tamponade(Fig.2). Cardiology team was consulted and took the patient for an urgent pericardiocentesis with pericardial chest tube placement which drained 650 mL of hemorrhagic fluid. Pulmonology service was consulted for right-sided chest tube placement which drained 600 mL of straw-colored fluid. The patient was then returned to MICU with significantly improvement in vital signs. Pericardial cytology demonstrated malignant cells positive for BerEP4, CK-7, and TTF-1 indicating pulmonary adenocarcinoma, stage 4 given the pericardial tamponade. DISCUSSION: In a young patient without any recent cardiac procedures, history of heart disease or renal failure, other possibilities for hemorrhagic pericardial effusion should be considered such as metastatic cancers including lymphoma, autoimmune disorders, and infectious causes such as tuberculosis and HIV. The treatment of pericardial tamponade in the setting of non-small cell lung cancer is urgent pericardiocentesis, followed by pericardial window if effusion is recurrent. The overall survival in patients with malignant pericardial effusion is dictated by histological type of the underlying malignant process. CONCLUSIONS: Cardiac metastasis is mostly asymptomatic, and pericardium is most common site of metastasis. Pulmonary adenocarcinoma involves lymphatic drainage of the heart and presents with signs of cardiac tamponade even before signs of pulmonary disease. A careful physical exam, imaging, surgical intervention and critical care management were crucial as demonstrated in our case. Reference #1: Fraser, R.S., Viloria, J.B. and Wang, N.-S. (1980), Cardiac tamponade as a presentation of extracardiac malignancy. Cancer, 45: 1697-1704. doi:10.1002/1097-0142(19800401)45:7<1697::AID-CNCR2820450730>3.0.CO;2-J Reference #2: Muir, Keith & Rodger, J. (1994). Cardiac tamponade as the initial presentation of malignancy: Is it as rare as previously supposed?. Postgraduate medical journal. 70. 703-7. 10.1136/pgmj.70.828.703. Reference #3: Bussani R, De-Giorgio F, Abbate A, Silvestri F. Cardiac metastases. J Clin Pathol. 2007;60(1):27-34. doi:10.1136/jcp.2005.035105 DISCLOSURES: No relevant relationships by Kanak Parmar, source=Web Response No relevant relationships by Wasawat Vutthikraivit, source=Web Response

S2963 Synchronous Adenocarcinoma and Gastrointestinal Stromal Tumor in the Stomach: A Case Report

INTRODUCTION: Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal (GI) tract, however, their association with gastric malignancies is rare and remains poorly understood. Here we present a case of synchronous antral gastric adenocarcinoma and GIST tumor in the fundus. CASE DESCRIPTION/METHODS: A 55-year-old female patient was referred to our Gastroenterology clinic for intermittent abdominal discomfort and watery bowel movements of one-year duration. The patient denied any other significant medical or surgical history. She denied any history of tobacco, alcohol, or recreational drug use. No family history of malignancy was reported. Basic laboratory work up was unremarkable. A computed tomography scan of the abdomen showed a 4 cm gastric mass, and subsequently the patient underwent esophagogastroduodenoscopy (EGD) with endoscopic ultrasound which confirmed the finding of a submucosal mass in the fundus in addition to mild antral H. Pylori gastritis without metaplasia or dysplasia which was treated with confirmed eradication. Biopsy results showed CD117 and CD34 positive spindle cells with low mitotic activity consistent with GIST. Given the size of the mass, the patient underwent partial gastrectomy without complications. The patient’s symptoms persisted and hence underwent repeat EGD three months following her procedure which showed a 3 cm cratered antral ulcer with irregular margins, biopsy results confirmed mixed type HER-2 negative adenocarcinoma subsequently staged as T3N0M0. At the time of writing, the patient is receiving neoadjuvant chemotherapy with docetaxel, oxaliplatin and 5-fluorouracil with good response. DISCUSSION: GIST tumors are rare mesenchymal tumors of the GI tract (1%), most commonly seen in the stomach and synchronous gastrointestinal malignancies, particularly successive gastric adenocarcinoma, are even more scarcely reported. It is unclear whether there is a true association between these two entities or it is merely coincidental, however, careful endoscopic and histopathologic evaluation is recommended to identify those with synchronous malignancies as the treatment options and prognosis may subsequently change.

S2735 Ectopic Hepatic Tissue Causing Mass Effect Presenting as Dysphagia

INTRODUCTION: Ectopic hepatic tissue (EHT) located in the posterior mediastinum is rare. The etiology of EHT is not well understood. We present a case of posterior mediastinal EHT causing mass effect in a middle-aged woman presenting with dysphagia. CASE DESCRIPTION/METHODS: A 50-year-old female presented to the ED with one year of intermittent dysphagia. Described as a “ball-like” sensation in the epigastrium. She denied abdominal pain, nausea, vomiting, hematemesis, early satiety, anorexia or weight loss. Her medical history was significant for peptic ulcer disease. She denied history of abdominal trauma or family history of malignancy. She was hemodynamically stable. Initial labs were nonrevealing. Physical exam was unremarkable. CT chest revealed a well-circumscribed posterior mediastinal mass measuring 3.9 × 3.4 × 3.2 cm. The mass was located to the right of the esophagus, homogeneous and measured 40 Hounsfield units. Her liver was noted to have a similar attenuation coefficient. Endoscopic evaluation revealed an area of mild extrinsic compression at the distal third of the esophagus (35 cm) which was easily traversed by the adult EGD scope. The Z line was seen at 36 cm from the incisors. The posterior mediastinal lesion was noted from 32 to 35 cm. It had an echogenic appearance of hepatic tissue and was noted to be continuous with the left lobe of the liver. This lesion was surrounded by a capsule with well-defined endosonographic borders. The mass was adjacent to the descending aorta and the ventricle. Mediastinal EHT was suspected to be the etiology of her symptoms. Fine needle biopsy was not performed due to proximity to the left ventricle. No other abnormalities were identified. A liver-spleen scan confirmed hepatic tissue in the posterior mediastinum. Outpatient evaluation with cardiothoracic surgery was planned. DISCUSSION: Although typically benign, ectopic hepatic tissue still warrants surgical evaluation and resection. Beyond exerting mass effect on surrounding structures, EHT may also undergo a malignant transformation to hepatocellular carcinoma (HCC). A review of recent medical literature disclosed many cases in which EHT preceded development of HCC, even when the remainder of the liver did not have HCC. Further studies are needed to determine the rate of malignant transformation.We urge consideration of EHT as a differential in the evaluation of posterior mediastinal masses. Given EHT’s propensity for malignant transformation, early recognition and close follow up is of vital importance.Figure 1.: CT Chest demonstrating posterior mediastinal mass continuous with the left lobe of the liver.Figure 2.: Mild extrinsic compression at the distal third of the esophagus approximately 35 cm from the incisors.Figure 3.: Ectopic Hepatic Tissue in the mediastinum.

Personal and Familial Malignancy History in Patients with Malignant Peripheral Nerve Sheath Tumors with a Focus on Sporadic Tumors

Malignant peripheral nerve sheath tumors (MPNSTs) occur sporadically, in patients with neurofibromatosis 1, and in patients with prior radiation therapy. The incidence of unrelated prior malignancies and family history of malignancy in patients with MPNSTs has not been previously described. A retrospective search for cases of MPNSTs at our institution for the years 1994-2019 was performed. The electronic medical record was reviewed for documentation of personal and family history of malignancies. The study included 331 patients. Of patients, 301 had documentation of their personal history of prior unrelated malignancies; 70 (23.3%) of these patients had a personal history of an unrelated previous malignancy. Of patients, 285 had information in the chart regarding family history of cancer; 210 (73.7%) of these patients had a family history of malignancy. Of patients, 145 had sporadic MPNSTs, 118 had neurofibromatosis 1-associated MPNSTs, 31 had radiation-induced MPNSTs, and 37 were missing this information. Among the sporadic cases, 29 had a personal history of an unrelated prior malignancy, and 10 developed an unrelated malignancy following diagnosis of MPNST. A family history of malignancy was present in 109 patients. There was a trend toward longer time to recurrence, time to metastasis, and overall survival in patients with sporadic MPNSTs and negative personal and family histories compared with patients with positive personal or family histories or both. Patients with sporadic MPNSTs had a high incidence of personal and family history of malignancy. The genetics associated with sporadic MPNSTs include RAS and p53 mutations, which are found in multiple oncologic processes and tumor-forming syndromes. This suggests an underlying genetic predisposition to formation of malignancies, including MPNSTs.

MON-244 Adenocarcinoma Pituitary Metastasis with Suprasellar Extension

BackgroundMetastasis to the pituitary gland (MP) is an infrequent clinical problem, however, during the last few decades, MPs is increasing in frequency, due both to the improved cancer survival rates and availability of better imaging techniques. Breast cancer, lung cancer and lymphoma are the most common primary sites. MP mimics pituitary adenoma making the diagnosis difficult, especially when clinical evidence of the primary malignancy is absent. We report a case of histologically confirmed pituitary metastasis (adenocarcinoma) from carcinoma of unknown primary, leading to and presenting as panhypopituitarism.Case details54 year male HBV carrier, asthmatic, non smoker, non alcoholic was seen elsewhere with complaints of increased frequency of micturition associated with nocturia, increased thirst, asthenia and weight loss of 05 kg since 06 months. He also had loss of libido and erectile dysfunction. Patient never experienced headache, vomiting or visual disturbances. There was no personal or family history of malignancy. On physical examination skin was pale, atrophic with fine wrinkles around the eyes. He had BP of 96/60mmHg and PR 100/min but system examination was otherwise unremarkable. Biochemical evaluation confirmed diabetes insipidus, secondary hypothyroidism, adrenal insufficiency and hypogonadism. MRI Brain showed a mass like thickening (11.6 x 11 x 16mm) of the infundibulum and posterior portion of the pituitary gland with upward displacement of optic chiasm. Workup for granulomatous conditions (sarcoidosis/ disseminated Koch’s) was negative. He was initiated on desmopressin, thyroxine, hydrocortisone, testosterone and managed elsewhere as hypophysitis.At presentation to us after 3 months of treatment, visual field examination showed decrease in peripheral vision involving right superior temporal quadrant and an attempt was made to delineate the size and etiology of the lesion. Repeat imaging revealed increase in size of the lesion to 12 x 15 x 18mm. He underwent TSS and the lesion was biopsied. Histopathology showed infiltrative adenocarcinoma with CK20 +, CK7 -, and GATA3 + on IHC. Post procedure WB-PET CT, showed metabolically active residual tumor in suprasellar region and negative for metabolically active disease in other areas. Upper GI Endoscopy, Colonoscopy and Bronchoscopy were also normal. Currently he is on adjuvant radiation therapy for residual suprasellar lesion.ConclusionPituitary metastasis may be difficult to differentiate from other lesions in the sellar/parasellar region, presentation as DI and thickened stalk confounded the diagnosis, given that it is a feature of the commoner lesion- hypophysitis. This case reports the rare occurrence of CK20 positive, CK7 negative adenocarcinoma metastasis to pituitary and no evidence of primary.

Concurrent germline and somatic pathogenic BAP1 variants in a patient with metastatic bladder cancer

Germline pathogenic variants in the BRCA1-associated protein-1 (BAP1) gene cause the BAP1 tumor predisposition syndrome (TPDS). BAP1 TPDS is associated with an increased risk of uveal and cutaneous melanoma, mesothelioma, renal cell carcinoma, and several other cancer subtypes. Here, we report a germline nonsense BAP1 variant (c.850G>T, p.Glu284Ter) in a patient with bladder cancer and a strong family history of malignancy. Concurrently, we identified a somatic frameshift BAP1 variant, and as expected, immunostaining validated the loss of BAP1 protein in patient-derived tumor specimens. Together, these data provide strong evidence of pathogenicity in this case. With the addition of bladder cancer to the tumor types reported with germline BAP1 mutations, our understanding of the BAP1 TPDS continues to evolve, and may affect future screening and surveillance guidelines.

Rare case of bronchoscopic debulking of endobronchial leiomyoma

An endobronchial leiomyoma is a rare benign tumour of lung. It occurs from the smooth muscle of tracheobronchial tree or within lung parenchyma. It presents less than 2% of all benign lung tumours. We present a case report of a 39-year-old male, ex-smoker, with no family history of malignancies, presenting with cough and dyspnoea for 7 months with no symptomatic relief. CAT scan thorax showed well-defined oblong soft tissue mass lesion 24.2 mm × 15.4 mm in right major bronchus compromising central lumen. Flexible bronchoscopy revealed an endobronchial mass at right major bronchus. Patient underwent rigid bronchoscopy with endobronchial mass excision with an electrocautery snare and cryoprobe in the same seating. Complete debulking of tumour was achieved and histopathology report was suggestive of leiomyoma. Prompt investigations and intervention can give favourable outcomes in cases of endobronchial tumours.

SAT-358 THE INCIDENCE OF MALIGNANCY AND ITS RELATED FACTORS IN PATIENTS UNDERGOING KIDNEY TRANSPLANTATION

Renal transplantation is considered as the treatment of choice for patients with ESRD. The underlying causes of death among renal transplant recipients have changed from early immunologic and nonimmunological failure to cardiovascular disease and malignancy. In this study we evaluated the incidence of malignancy and its related factors in renal transplant patients in Razi Hospital of Rasht over a period of 10 years. In this retrospective study, 549 patients who underwent renal transplantation surgery in Razi Hospital between 2008 and 2019 were studied. Demographic and clinical characteristics of patients and other required information were recorded in a checklist. Required patient information was obtained from the case of pre and post-transplant and outpatient follow-up. In this study, it was found that only the patient's age at the time of renal transplantation in recipients of intervention has a confounding and additive role in incidence of malignancy after transplantation (P=0.0001). It was also found that there was no statistically significant relationship between sex of patients, current smoking status, smoking history, family history of malignancy, number of transplants, post-transplant survival, sun exposure, transplant rejection history, patient follow-up, occupational status, the use of daclizumab (Zenapax ATG) induction and incidence of malignancy after kidney transplantation. Estimates of standardized incidence ratio showed that the incidence of malignancy in kidney transplant recipients was 26.9 higher than the incidence rate in Guilan province and 21.7 higher than the incidence of malignancy in the country. The incidence rate of cancer in kidney transplant patients is 26.9 times higher than Guilan province rate (95% CI: 19.7-35.9) and 21.7 times higher than national rate (95% CI: 15.9-28.9). In this study, the incidence rate of cancer is 792 per 100000-person year. In this study, it was found that only the patient's age at the time of kidney transplantation has a confounding and increasing role in the incidence of post-transplant malignancy. It has also been shown that the most common malignancy in these patients is non-melanoma skin malignancy and Kaposi's sarcoma comes in second.

SAT-346 POST-TRANSPLANT MALIGNANCY - OUR CENTRE

Cancer is now increasingly recognized as a major cause of death among patients especially after kidney transplantation. Malignancy represent a major burden in transplantation medicine. The Incidence is about 12 fold higher for PTLD and 3.5 fold higher for non-cutaneous malignancy compare to age-matched population. The increased risk is multifactorial and attributed to oncogenic viruses, immunosuppression and altered T cell immunity. Aim: We attempted to assess the incidence of post-transplant malignancies in patients who underwent renal transplantation at our centre, along with studying the presentation, type and other factors affecting their development. Materials and methods We analysed data retrospectively from 626 patients who underwent renal transplantation at our centre from January 2003 to September 2018. Pre transplant history, post transplant course including duration on hemodialysis, immunosuppression details and duration till diagnosis of malignancies were collected. Details regarding type of malignancy, histopathology, staging and treatment given and outcome were collected. Number of transplant recipient-626. The total number of patients with malignancy is 12. Incidence of malignancy posttransplant is 1.9%. Male-7 and female-6. One patient was detected with 2 malignancies during her post transplant period. The types of malignancies encountered were Type of Malignancy•Squamous cell Ca of tongue – 3•Post transplant lymphoproliferative disease – 6•Squamous cell carcinoma of lung -1•Adenocarcinoma of pancreas – 1•Carcinoma of colon -1•Atypical papillary neoplasm of breast – 1 ( second malignancy)The mean duration of patient on dialysis before transplantation in the study population was 413 days. The mean duration of interval between diagnosis of malignancy and transplantation was 1560 days. None of these patients had any other risk factors for development of malignancies like exposure to radiation, smoking or family history of malignancies. None of the patients had any past history of malignancies. 3 (30%) out of 10 patients had under-gone deceased related donor transplantation, while the rest had live related renal transplant Conclusion The incidence of malignancy – 1.9%. Probable reason for decreased incidence of malignancy is the decreased immunosuppression needed by South Asian people. The most common malignancy was solid organ tumour; tongue being the most common organ. Most common histological variant is squamous cell carcinoma. Non-Hodgkin is more common than Hodgkin. Incidence of malignancy is low. Decision regarding cancer screening should be made on individual basis.