Adrenal Involvement Research Articles

Association of BRAF V600E with Hypothalamic-Pituitary-Adrenal Axis Involvement in Erdheim-Chester Disease

• Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis characterized by uncontrolled inflammation resulting in fibro-inflammatory damage of multiple organs, including the hypothalamic-pituitary-adrenal (HPA) axis. • Glucocorticoid insufficiency may occur and is associated with an increased burden of disease and an increased risk of adrenal crisis. • HPA axis in ECD tends to involve the adrenal glands in BRAF V600E-positive individuals, without influencing the rates of low cortisol levels, although there is a poor biochemical-radiological concordance in ECD. • In this cohort, most subjects with HPA axis involvement did not require glucocorticoid or mineralocorticoid therapy. • This study systematically demonstrates an association between the somatic activating BRAF V600E variant and the presence of radiographic and biochemical HPA axis involvement in ECD subjects. Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis characterized by uncontrolled inflammation resulting in fibro-inflammatory damage of multiple organs, including the hypothalamic-pituitary-adrenal (HPA) axis. Glucocorticoid insufficiency may occur and is associated with an increased burden of disease and an increased risk of adrenal crisis. Sixty-one ECD subjects (46 males, age 54.3 ± 10.8 years) were evaluated; 56.1% (32/57) harbored a somatic activating BRAF V600E variant. Adrenal gland and sellar or suprasellar involvement was present in 18/57 (31.6%) and 9/57 (15.8%) subjects on computed tomography or magnetic resonance imaging, respectively. The BRAF -positive group was more likely to have adrenal gland involvement (56.2% vs. 20.0%; odds ratio (OR) 5.8, 95% confidence interval (CI) 1.5-17.1, P=0.008), with comparable rates for sellar or suprasellar involvement (28.1% vs. 20.0%; OR 1.6, 95% CI 0.5-5.4, P=0.5) and low random morning cortisol values (37.5% vs. 32.0%; OR 1.3, 95% CI 0.4-3.8, P=0.7). High-sensitivity C-reactive protein was significantly higher in the BRAF V600E-positive group with adrenal involvement when compared to the BRAF V600E-negative group without adrenal involvement (mean concentration: 40 mg/dL vs. 5 mg/dL, P=0.046). HPA axis in ECD tends to involve the adrenal glands in BRAF V600E-positive individuals, without influencing the rates of low cortisol levels, although there is a poor biochemical-radiological concordance in ECD. In this cohort, most subjects with HPA axis involvement did not require glucocorticoid or mineralocorticoid therapy. This study systematically demonstrates an association between the somatic activating BRAF V600E variant and the presence of radiographic and biochemical HPA axis involvement in ECD subjects. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01417520

Short treatment with antalarmin alters adrenal gland receptors in the rat model of endometriosis.

Endometriosis is a chronic inflammatory disorder in which endometrial tissue is found outside the uterine cavity. Previous reports suggest that there is a dysregulation of the hypothalamic pituitary adrenal axis during the progression of endometriosis. Our previous report showed that a short-term treatment with antalarmin, a corticotrophin releasing hormone receptor type 1 (CRHR1) antagonist decreases the number and size of endometriotic vesicles in the auto-transplantation rat model of endometriosis. Our current goal was to examine the mRNA expression of intra-adrenal receptors to better understand the mechanisms of the hypothalamic pituitary adrenal (HPA) axis involvement in endometriosis. We used two groups of female rats. The first received sham surgery or endometriosis surgery before collecting the adrenals after 7 days of the disease progression. The second group of animals received endometriosis surgery and a treatment of either vehicle or antalarmin (20 mg/kg, i.p.) during the first 7 days after endometriosis induction and then the disease was allowed to progress until day 60. Rats with sham surgery served as controls. Results showed that the mRNA expression of the mineralocorticoid (MRC2) receptor was lower in the rats after 7 days of endometriosis surgery and in rats with endometriosis that received antalarmin. In addition, the CRHR1 was significantly elevated in animals that received antalarmin and this was counteracted by a non-significant elevation in CRHR2 mRNA. The glucocorticoid receptor mRNA within the adrenals was not affected by endometriosis or antalarmin treatment. This report is one of the first to explore intra-adrenal mRNA for receptors involved in the HPA axis signaling as well as in the sympatho-adrenal signaling, calling for additional research towards understanding the role of the adrenal glands in chronic inflammatory diseases such as endometriosis.

THE ROLE OF TUMOR-SEEKING RADIOPHARMACEUTICALS IN THE DIAGNOSIS AND MANAGEMENT OF ADRENAL TUMORS.

The variety of tumor-seeking radiopharmaceuticals, which are currently in clinical use, may have a potential role as imaging agents for adrenal gland tumors, due to physiological characteristics of this organ. The purpose of this study was to evaluate the diagnostic potential of 99mTc-HYNIC-TOC, 99mTc(V)-DMSA, and 99mTc-MIBI in the assessment of adrenal tumors, by correlating with imaging findings and histopathologic results. The research is designed as a cross-sectional prospective study. The study included 50 patients with adrenal tumors (19 hormone-secreting and 31 nonfunctioning) and 23 controls without adrenal involvement. In all patients, single-photon emission computed tomography (SPECT) was performed, using qualitative and semiquantitative analysis. The tumor to non-tumor tracer uptake was conducted by using a region-of-interest technique. Adrenal to background (A/B) ratio was calculated in all cases. 99mTc-HYNIC-TOC scintigraphy showed a high statistical significance between A/B ratios, while other two tracers resulted in a lower sensitivity, specificity and accuracy. Futhermore, 99mTc-HYNIC-TOC could have a high diagnostic yield to detect adrenal tumors (the receiver-operating-characteristic curve analysis, A/B ratio cut-off value of 8.40). A semiquantitative SPECT analysis showed that 99mTc-HYNIC-TOC is a highly sensitive tumor-seeking agent for the accurate localization of adrenal tumors.

Neoplastic metastases to the endocrine glands.

Endocrine organs are metastatic targets for several primary cancers, either through direct extension from nearby tumour cells or dissemination via the venous, arterial and lymphatic routes. Although any endocrine tissue can be affected, most clinically relevant metastases involve the pituitary and adrenal glands with the commonest manifestations being diabetes insipidus and adrenal insufficiency respectively. The most common primary tumours metastasing to the adrenals include melanomas, breast and lung carcinomas, which may lead to adrenal insufficiency in the presence of bilateral adrenal involvement. Breast and lung cancers are the most common primaries metastasing to the pituitary, leading to pituitary dysfunction in approximately 30% of cases. The thyroid gland can be affected by renal, colorectal, lung and breast carcinomas, and melanomas, but has rarely been associated with thyroid dysfunction. Pancreatic metastasis can lead to exo-/endocrine insufficiency with renal carcinoma being the most common primary. Most parathyroid metastases originate from breast and lung carcinomas and melanoma. Breast and colorectal cancers are the most frequent ovarian metastases; prostate cancer commonly affects the testes. In the presence of endocrine deficiencies, glucocorticoid replacement for adrenal and pituitary involvement can be life saving. As most metastases to endocrine organs develop in the context of disseminated disease, surgical resection or other local therapies should only be considered to ameliorate symptoms and reduce tumour volume. Although few consensus statements can be made regarding the management of metastases to endocrine tissues because of the heterogeneity of the variable therapies, it is important that clinicians are aware of their presence in diagnosis.

Isolated left adrenal gland involvement in testicular tuberculosis

Testicular tuberculosis (TB) is commonly associated with genitourinary TB or as a part of miliary TB. In miliary type of testicular TB, there is often bilateral involvement of the adrenal gland. Our case presented with enlargement of the left adrenal gland only. This may be due to anomalous communication between the left gonadal vein and the left adrenal vein. He was started with antituberculous treatment with rifampicin, isoniazid, pyrazinamide, and ethambutol. The patient failed to respond to anti-TB treatment; therefore, he underwent left low inguinal orchidectomy, and the histopathology confirmed the diagnosis. The adrenal lesion started disappearing following orchidectomy and antituberculous treatment.

CNS Prophylaxis in Diffuse Large B-Cell Lymphoma & Its Outcomes- an Institutional Review

Background: Diffuse large B-cell lymphoma (DLBCL) has an approximately 5% risk of recurrence in the central nervous system, and carries a very poor prognosis. Prophylactic intrathecal chemotherapy (ITC) with agents such as Methotrexate (MTX) can mitigate the risk of recurrence and improve survival. We report a single-institution, retrospective analysis of the effect of ITC administration on outcomes in patients with DLBCL, based on CNS-IPI risk stratification. Methods: We screened 325 DLBCL patients from our tumor registry- of these only 292 had clinical information to risk-stratify per IPI scoring- low-risk, n = 54, intermediate-risk, n = 198, and high-risk n = 40. These patients then further categorized based on the NCCN prognostic model to assess the risk of CNS disease (CNS-IPI) which includes age >60, LDH >normal, ECOG >1, Stage III or IV, Extranodal involvement >1 site, kidney or adrenal gland involvement with scores 0-1 low-risk, 2-3 intermediate-risk, and 4-6 or kidney or adrenal involvement as high-risk. The effect of ITC administration on outcomes such as overall survival (OS) at 1-year (yr) and 5-yr were calculated using univariate two-group comparisons. Results: Demographic and clinical variables include- Age >60- 61% (n=201); mostly Caucasians- 71%(n=199); Germinal Center(GC) 25%(n=73), non-GC 74%(n=212); mean IPI score-2.8(n=196), R-CHOP-87%(n=233); and, ITC in 15%(n=45). Seven patients in low-risk patients received ITC for unclear reasons. Intermediate risk patients treated with ITC showed a trend towards 90% (n=26) 1yr OS, and 67%(n=8) 5-yr survival compared to who did not receive ITC (non-ITC) who had 84%(n=127) 1-yr, and 55%(n=52) 5-yr OS (p-value 0.57 and 0.43 respectively). High-risk patients treated with ITC showed a trend towards 100%(n=3) 1-yr, and 0% 5-yr OS compared to non-ITC who had 85%(n=23) 1-yr , and 29%(n=5) 5-yr OS (p-value 1.0 and 1.0 respectively). Conclusions: Our results suggest that in DLBCL patients with the intermediate-risk group may benefit from intrathecal chemotherapy. Our study is limited owing to small sample size in each subset of CNS risk stratification- this limits the interpretation of the results, and should be interpreted cautiously given nonsignificant P-values. However, we believe these results can encourage further research to evaluate the effect of CNS prophylaxis in the intermediate-risk group of DLBCL patients. Disclosures Kuriakose: Alexion: Consultancy, Honoraria, Speakers Bureau; Bayer: Consultancy.

The Magnitude of Lactate Dehydrogenase Elevation As a Predictive Factor for Central Nervous System Relapse in Diffuse Large B-Cell Lymphoma

Introduction: The incidence of central nervous system (CNS) relapse in diffuse large B-cell lymphoma (DLBCL) is approximately 5%. Although the introduction of rituximab for the treatment of DLBCL has reduced the risk of CNS relapse, the median overall survival of these patients remains only few months, emphasizing the need to accurately identify at-risk patients, screen for CNS disease, and develop effective therapeutic/prophylactic strategies. Aim: To identify risk factors for CNS relapse in patients with DLBCL. Methods: Retrospective analysis of patients with DLBCL diagnosed from January 2012 to December 2017 at a Cancer Institute. Patients with exclusive extranodal (EN) disease were excluded. Factors associated with CNS relapse were evaluated using Chi-square, Fisher's Exact Test, Mann-Withney U or T-Test, according to variable types and distributions. Survival was evaluated by Kaplan-Meier method and groups were compared by Log-rank test. Independent predictive factors were identified using Logistic Regression. A p value < 0.05 was considered statistically significant. Results: Four hundred and seventy-nine patients were identified, 122 were excluded due to exclusive EN disease, and 357 patients were included in the study. With a median follow-up of 33 months, there were 10 (3%) CNS relapses. According to International Prognostic Index (IPI) factors in addition to involvement of kidneys and/or adrenal glands (CNS-IPI), 5 (50%) of these patients were classified as high risk, 4 (40%) intermediate risk and 1 (10%) low risk. Patients who development CNS involvement were significantly younger (57 vs. 65 years, p=0.036), presented higher levels of lactate dehydrogenase (LDH) (median 738 vs. 282 U/L, p<0.001) and lower levels of hemoglobin (median 10,3 vs. 12,1 g/dL, p=0.010) at diagnosis. No differences were found regarding to performance status, stage or number of EN areas. Two patients (18%) in the CNS relapse group had done CNS prophylaxis versus twenty two (6,3%) patients in the group without CNS relapse. In multivariate analysis, LDH >600 was the only independent predictive factor (HR 15.3, CI 95% 3.5 - 65.8, p<0.001). Overall survival in CNS relapse group was 22 months, versus not reached (p<0.001). Conclusion: Although CNS-IPI is a robust model to estimate the risk of CNS relapse, it does not capture the full spectrum of those at high risk. Other clinical risk factors and biomarkers beyond this model might play an important role in this setting, such as the magnitude of LDH elevation Disclosures No relevant conflicts of interest to declare.

1644 Isolated Metastatic Colorectal Cancer Involving the Kidney and Adrenal Gland: A Rare Occurrence

INTRODUCTION: Distant metastases in colorectal cancer (CRC) commonly involve liver, lung, brain and bone. Adrenal gland involvement is not uncommon on autopsy in the setting of diffuse metastatic disease. In most reported cases, it is seen as metachronous disease and is diagnosed during extensive work up or on follow up. Isolated synchronous disease involving the kidney and adrenal gland is extremely rare. We present a case where the diagnosis was established intraoperatively during a laparotomy performed for suspected primary adrenocortical malignancy. CASE DESCRIPTION/METHODS: A 66-year-old man presented with sudden worsening lower abdominal pain for 6 hours. The pain had started 4 weeks ago and was persistent, non-radiating. He reported a 50 pounds weight loss over the last 3 months. Physical exam was significant for tenderness over the right lower quadrant. Laboratory data showed anemia with hemoglobin of 8.3 g/dl. CT of abdomen and pelvis revealed a mass that was possibly originating from the right adrenal gland. MRI revealed a large heterogeneous, multilobulated, adrenal mass measuring 10 × 7.4 × 13.2 cm. A primary adrenocortical malignancy was suspected. Endocrine and metastatic work up was negative and a laparotomy was planned for adrenalectomy and possible nephrectomy. Intraoperatively, he was found to have an ulcerative tumor involving the terminal ileum and appendix penetrating through the serosa. Right hemicolectomy and nephrectomy with adrenalectomy were performed. Histopathology was consistent with poorly differentiated adenocarcinoma of colon with metastasis to right adrenal gland and kidney. DISCUSSION: Common primary tumors that metastasize to the adrenal gland include breast, lung and kidney. In most cases of CRC, adrenal or kidney metastases usually indicate distant hematogenous spread and are associated with poor prognosis. The mean survival is 7 to 8 months. However, CRC with isolated metastasis to adrenal gland and kidney is extremely rare. Retrospectively, an interesting feature in this case was the presumption of the metastatic lesion as the primary tumor as there was no radiologic abnormality involving the gastrointestinal tract. Surgical resection followed by chemotherapy has been shown to promote long term survival in several studies, but there is no prospective data due to the rarity of this condition. In patients with incidental finding of an isolated adrenal/renal mass, an evaluation for occult GI malignancy should be considered.

ADRENAL TB AS A CAUSE OF PRIMARY ADRENAL INSUFFICIENCY

SESSION TITLE: Monday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/21/2019 02:30 PM - 03:15 PM INTRODUCTION: Addison’s disease refer to a chronic endocrine disorder characterized by primary adrenal insufficiency. Adrenal involvement in tuberculosis is most often the result of hematogenous spread of Pulmonary tuberculosis. Isolated Adrenal Tuberculosis was noted in only 1- 2% of Addison’s Disease and one such rare case is presented here CASE PRESENTATION: A 36 yr old male, admitted with complaints of weight loss, generalised fatigue and discoloration of the body for past 6months. On admission, his BP 80/60mmHg, HR 64/min, temperature 101F & RR 22/min. His skin over the face, arms, palms and soles were darkly pigmented. Clinical examination of respiratory, cardiac, abdominal and nervous system were normal. Blood results revealed RBS 76mg/dl, urea 37, creatinine 2.2, serum Na 126mEq/L, serum K 6.5 and other parameters were normal. Serum Cortisol is 2.57 μg/dl [ 6.2 to 19.4] and ACTH is >1250 pg/ml [7.2to 63.3]. A chest radiograph and chest CT revearled no abnormalities. Bronchial wash CBNAAT MTB not detected. Mantoux 11mm. CECT of abdomen showed bilateral diffuse thickening of adrenal glands without calcifications. CT guided biopsy of Adrenals showed granulamatous adrenalitis thus confirming the diagnosis of primary adrenal tuberculosis DISCUSSION: PAI is caused by destruction of Adrenocortical tissue due to Autoimmume ds.,TB, Cryptococcosis, Fungal infections, Primary or Metastatic tumours,etc. The symptoms of PAI manifests when >90% of the Adrenals have been destroyed. Primary Tubercular Adrenalitis is a rare clinical entity & based on the clinical, serological, radiological & biopsy findings diagnosis was made. A prompt clinical & radiological response was seen in our patient. CONCLUSIONS: Isolated adrenal tuberculosis is a rare cause of Addison’s disease especially with enlargement of adrenal glands causing diagnostic problems and require differentiation from primary or secondary neoplastic disease. It is a rare but important disease entity that must be identified early and treated promptly and aggressively Reference #1: Textbook of Tuberculosis by Surendra K Sharma, 2nd Edition Reference #2: Textbook of Tuberculosis & Non Tuberculous Mycobacterial Infections by David Schlossberg, 5th Edition Reference #3: Nakaoka K, Branch J, Ozeki T, et al (2012) Acase of Primary Adrenal TB – Endocrinal Metabolic Syndrome DISCLOSURES: No relevant relationships by ALLWYN VIJAY GOWRI SHANKAR, source=Web Response No relevant relationships by Sathya Natarajan, source=Web Response

SYSTEMIC AIR EMBOLISM AFTER PERCUTANEOUS CT-GUIDED LUNG BIOPSY

SESSION TITLE: Global Case Report Posters SESSION TYPE: Global Case Reports PRESENTED ON: 10/23/2019 09:45 AM - 10:45 AM INTRODUCTION: Computed-tomography (CT) guided transthoracic needle biopsy (TTNB) is widely performed to establish a histological diagnosis of peripheral lung tumors. Systemic air embolism is described as a rare complication. CASE PRESENTATION: In a 70-year-old man with systemic arterial hypertension and benign prostatic hypertrophy a peripheral pulmonary consolidation in the left upper lobe and multiple brain nodules were detected after an acute episode of epilepsy. As a primary lung tumor was suspected, he underwent a total body positron emission tomography-CT scan, showing pathological glucose uptake in the left lung lesion (Figure 1) and metastatic involvement of mediastinal lymph nodes, adrenal glands and vertebral bodies. His coagulation profile, hemoglobin and platelets levels were normal, so a bronchoscopy with transbronchial lung biopsy under fluoroscopy was set. The histological analysis showed bronchial inflammatory cells, so the patient underwent a CT-guided TTNB. Under local anesthesia, two bioptic samples were collected using the 18-gauge outer coaxial needle by an expert interventional radiologist (Figure 2A). During the procedure the onset of air embolism in both heart ventricles, main pulmonary artery and ascending aorta was immediately detected on CT scans (Figure 2B). A layer of ipsilateral pneumothorax (maximum thickness 12 mm) together with chest wall subcutaneous emphysema were present. The patient complained about general malaise with signs of hypotension and desaturation. No electrocardiographic alterations were recorded. After he was administered 100% oxygen through a mask and hydrated, his clinical conditions rapidly improved. Two hours later a chest and brain CT scans were repeated. While cardiac, aortic and pulmonary artery air embolisms were solved, the pneumothorax layer increased (20 mm) (Figure 3). No ischemic lesions were detected in brain CT scans. The patient was maintained on close monitoring and after four days the pneumothorax was no longer radiologically detectable. An invasive lung adenocarcinoma was diagnosed and the patient was referred to the Oncology Department. DISCUSSION: Systemic air embolism is described in 0.02-0.07% of TTNB (1). Direct exposure of pulmonary vein to air through the needle, bronchovenus fistula formation and air penetration from the pulmonary arterial circulation to the pulmonary vein are all possible pathogenic mechanisms (2). Possible prevention strategies include avoiding coughing and straining during the procedure and ventilation with positive pressure (3). No specific treatment has established yet other than supplying 100% oxygen and hyperbaric chamber. The patient has to be strictly monitored because potential life-threatening complications may rise and the repetition of a chest-brain CT scan may be urgently needed (3). CONCLUSIONS: Even if uncommon, systemic air embolism after TTBN must be always considered and rapidly handled. Reference #1: Sinner WN. Complications of percutaneous transthoracic needle aspiration biopsy. Acta Radiol. 1976;17:813-28 Reference #2: Mokhlesi B, Ansaarie I et al. Coronary artery air embolism complicating CT.guided transthoracic needle biopsy of the lung. Chest. 2002;121:993-996 Reference #3: Hare SS, Gupta ATC et al. Systemic arterial air embolism after percutaneous lung biopsy. Clin Radiol. 2011;66:589-596. DISCLOSURES: No relevant relationships by Paolo Ceruti, source=Web Response No relevant relationships by SARA ALESSANDRA LONNI, source=Web Response

An Unusual Presentation of CNS Histoplasmosis Mimicking Metastatic Cancer

Histoplasma Capsulatum is a thermally dimorphic fungus that is known to cause histoplasmosis. Inhalation of Histoplasma microconidia into alveolar spaces transforms them into yeasts. Most histoplasma infections are mild or asymptomatic in immunocompetent individuals. However, affected individuals often present with manifestations of an inflammatory response to this infection. Patients often present with bone marrow suppression (pancytopenia) and elevated liver enzymes [1]. Clinical evaluation reveals a flu-like illness with findings of fever, headache, myalgia, dyspnea, chest pain and infection localized to the lungs [2]. Additional manifestations can include involvement of adrenal glands, central nervous system, and skin [3]. Herein, we present a case of disseminated histoplasmosis complicated by CNS and adrenal gland involvement.

Outcome and long-term follow-up of adrenal lesions in multiple endocrine neoplasia type 1.

To describe the prevalence, clinical characteristics and outcome of adrenal lesions in long-term follow-up of Multiple endocrine neoplasia type 1 (MEN1) patients. We retrospectively studied sixteen patients from six families of individuals with MEN1. Adrenal involvement was evaluated using clinical, biochemical and imaging data. Adrenal lesions were identified in nine of sixteen (56.3%) patients: seven women and two men (mean age: 52.2 years). Adrenal involvement was detected at MEN1 diagnosis in more than half of the patients. Eighteen adrenal nodules were founded (median of two nodules per patient) with mean adrenal lesion diameter of 17.4 mm. Three patients had unilateral adrenal involvement. Hormonal hypersecretion (autonomous cortisol secretion) was found in two patients. None of the patients was submitted to adrenalectomy, presented an aldosterone-secreting lesion, a pheochromocytoma, an adrenal carcinoma or metastatic disease during the follow-up. A predominance of stable adrenal disease, in terms of size and hormonal secretion, was observed. Adrenal lesions were evenly distributed between the germline mutations. Adrenal tumours are a common feature of MEN1 that can affect more than half of the patients. Most of the tumours are bilateral non-functional lesions, but hormonal secretion may occur and should be promptly identified to reduce the morbidity/mortality of the syndrome. Periodic surveillance of these patients should be performed.

Combined Endosonographic Mediastinal Lymph Node Staging in Positron Emission Tomography and Computed Tomography Node-Negative Non–Small-Cell Lung Cancer in High-Risk Patients

Positron emission tomography (PET) with computed tomography (CT) is routinely utilized to investigate lymph node (LN) metastases in non-small-cell lung cancer. However, it is less sensitive in normal-sized LNs. This study was performed in order to define the prevalence of mediastinal LN metastases discovered on combined endosonography by endobronchial ultrasound (EBUS) and endoscopic ultrasound (EUS) fine needle aspiration in patients with a radiologically normal mediastinum. This study consists of a retrospective, single-institution, tertiary care referral center review of a prospectively maintained database. Patients were identified from a cohort between January 2009 and December 2014. One hundred and sixty-one patients with biopsy-proven, non-small-cell lung cancer were identified in whom both the preendosonography CT and PET-CT were negative for mediastinal LN metastases. Combined endosonography (EBUS + EUS-FNA) was performed in all patients. Z test was used for statistical analysis. A P value of <0.05 was considered statistically significant. A total of 161 consecutive patients were included. Patients were staged if they had central tumor, tumor size >3 cm, N1 lymph node involvement on PET-CT/CT, or if there was low SUV (<2.5) in the primary tumor. A total of 416 lymph nodes were biopsied in the 161 patients using combined endosonography; 147 with EBUS and 269 with EUS. Mean and median number of lymph nodes biopsied per patient using combined EBUS/EUS was 2.5 and 3, respectively (mean and median EBUS: 0.91 and 2.5; mean and median EUS 1.6 and 3). Endosonographic staging upstaged 13% of patients with radiologically normal lymph nodes in the mediastinum, hilum, lobar, and sublobar regions (confidence interval 8.22-19.20). Twenty-one out of 161 patients (13%) with radiologically normal mediastinum were positive on combined EBUS/EUS staging. Out of 21 patients upstaged on endosonography, 15 (71%) had tumor size >3 cm. Six (28%) had occult N1 disease. Thirteen (61%) had occult N2 disease and 2 (9%) had adrenal involvement. None of the upstaged patients had N1 LN involvement on PET-CT or CT scan. Combined endosonographic lymph node staging should be considered in the pretreatment staging of high-risk patients with non-small-cell lung cancer in the presence of radiologically normal mediastinal lymph nodes due to the significant rate of radiologically occult lymph node metastases.

Diagnosis of intravascular large B cell lymphoma: novel insights into clinicopathological features from 42 patients at a single institution over 20 years

SummaryThis study aimed to clarify the comprehensive clinical, laboratory, pathological and imaging features of intravascular large B‐cell lymphoma (IVLBCL) using data on 42 IVLBCL patients diagnosed at our hospital over the past 20 years. The majority of patients were diagnosed via random skin biopsy (29/42, 69·0%) followed by bone marrow biopsy alone (8/42, 19·0%). Characteristic features included persistent fever (41/42, 97·6%), decreased performance status (≥2) (100%), hypoxaemia (32/40, 80·0%), impaired consciousness (19/42, 45·2%), hypoalbuminemia (42/42, 100%) and extreme elevation of lactate dehydrogenase and soluble interleukin 2 receptor levels. Brain magnetic resonance imaging showed abnormal findings in 32/37 patients (86·4%). Hyperintense lesion in the pons was a peculiar finding that was unrelated to the neurological deficits. Positron emission tomography‐computed tomography revealed a high incidence of bone marrow (26/34, 76·5%), spleen (19/34, 55·9%) and adrenal gland (9/34, 26·5%) involvement. Neurolymphomatosis was noted in 6 patients during the course of the disease. About 60% of IVLBCL patients in whom in vivo diagnosis was possible survived more than 5 years with combination chemotherapy. Our observations provide additional insight into the diagnosis of IVLBCL and indicate that early disease recognition via random skin biopsy combined with imaging, enables in vivo diagnosis of the disease and improved survival for many patients.

Stand-alone intrathecal central nervous system (CNS) prophylaxis provide unclear benefit in reducing CNS relapse risk in elderly DLBCL patients treated with R-CHOP and is associated increased infection-related toxicity.

Central nervous system (CNS) relapse following R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) occurs in 2-5% of patents with diffuse large B-cell lymphoma (DLBCL). Many patients aged ≥70years are unsuitable for high-dose methotrexate (HDMTX) prophylaxis and therefore often receive stand-alone intrathecal prophylaxis. The CNS international prognostic index (CNS-IPI) is a clinical CNS relapse risk score that has not specifically been validated in elderly patients. The value of CNS prophylaxis in patients aged ≥70years remains uncertain. Data on 690 consecutively R-CHOP-treated DLBCL patients aged ≥70years were collected across 8 UK centres (2009-2018). CNS prophylaxis was administered per physician preference. Median age was 77·2years and median follow-up was 2·8years. CNS-IPI was 1-3 in 60·1%, 4 in 23·8%, 5 in 13·0% and 6 in 3·3%. Renal and/or adrenal (R/A) involvement occurred in 8·8%. Two-year overall CNS relapse incidence was 2·6% and according to CNS-IPI, 1-3:0·8%, 4:3·6%, 5:3·8% and 6:21·8%. Two-year CNS relapse incidence for R/A was 10·0%. When excluding HDMTX (n=31) patients, there remained no change in unadjusted/adjusted CNS relapse for intrathecal prophylaxis effect according to CNS-IPI. CNS-IPI is valid in elderly R-CHOP-treated DLBCL patients, with the highest risk in those with CNS-IPI 6 and R/A involvement. We observed no clear benefit for stand-alone intrathecal prophylaxis but observed an independent increased risk of infection-related admission during R-CHOP when intrathecal prophylaxis was administered.

PF311 ISOLATED PRIMARY ADRENAL LYMPHOMA (IPAL) ‐ AN EMERGING LYMPHOMA ENTITY? RESULTS OF A RETROSPECTIVE MULTICENTER STUDY

Background:Primary adrenal lymphoma (PAL) is a rare lymphoid malignancy that primarily involves the adrenal gland(s) in patients without a previous history of lymphoma.Aims:To refine the clinical picture of primary adrenal lymphomaMethods:We retrospectively analyzed clinical and pathological features of 97 patients from 14 centers in Europe, Canada and the United States. PAL was defined as histologically proven extra‐nodal lymphoma that primarily affects the adrenal gland(s). If there was involvement of other organs and/or lymph nodes, the diagnosis of PAL was accepted only in case of unequivocal dominant involvement of the adrenal gland(s). We divided the disease into two subtypes: cases with synchronous extra‐adrenal involvement at diagnosis (PAL+), and cases with isolated involvement of the adrenal(s) (iPAL). Statistical analyses were carried out using the Fisher exact test, Kaplan‐Meier method, log‐rank test, and Cox proportional hazard models.Results:Median age at diagnosis was 66 (25–89) years, and the male/female ratio was 2.3. 19/81 (23%) patients with available imaging data had isolated adrenal involvement (iPAL), while the other 62 (77%) had additional extra‐adrenal involvement (PAL+). The most common manifestations of PAL were B symptoms (55%), fatigue (45%), and abdominal pain (35%). With a median follow‐up of 41.6 months, the 3‐year progression‐free survival (PFS) and overall survival (OS) were 35.5% and 39.4%, respectively. Immunochemotherapy according to the R‐CHOP protocol showed no significant difference in outcome compared to other treatment regimens. On multivariate analysis of variables including age, tumor size, uni‐ vs. bilateral involvement, histopathology of B cell lymphoma, elevated LDH, adrenal insufficiency, and iPAL versus PAL+, iPAL was the only factor with independent, statistically significant impact on PFS. The hazard ratios of iPAL for PFS and OS were 40.1 (95% CI: 2.63–613.7, p = 0.008) and 2.69 (95% CI: 0.61–11.89, p = 0.191), respectively. PFS was much shorter in iPAL versus PAL+ (median 4 months vs. not reached, p = 0.006), and there was a trend for shorter OS (median 16 vs. not reached, p = 0.16). Isolated PAL was more frequent in females (OR = 3.81; P = 0.01) and less frequently associated with B symptoms at diagnosis (OR = 0.159; p = 0.004).Summary/Conclusion:Comprehensive characterization of rare diseases is facilitated by multi‐institutional collaboration. Our retrospective analysis of 97 patients from fourteen centers is the largest analysis of PAL so far. We showed for the first time that PAL is a heterogeneous disease, which comprises cases with isolated involvement of adrenal tissue (iPAL) and cases with additional extra‐adrenal organ manifestations (PAL+). Unexpectedly, patients with iPAL showed an unusual male/female ratio, less B symptoms and significantly worse clinical outcome than those with involvement of additional, extra‐adrenal sites. This finding should stimulate further investigation to see whether the clinical distinction between iPAL and PAL+ is corroborated by differences in molecular biology.image

Systemic and prophylactic intrathecal chemotherapy for primary adrenal lymphoma: A retrospective study of 20 case reports.

Primary adrenal lymphoma (PAL) is a rare entity of lymphoma with dismal prognosis using systemic chemotherapy. More clinical reports are needed to guide the treatment for PAL.We performed a retrospective analysis of 20 patients diagnosed with PAL who presented to our center between January 2005 and January 2014.Median age at presentation was 48 years (range: 27–73) with a male-to-female ratio of 7:3. Bilateral and right-sided adrenal involvement were seen in 11 of 20 and 7 of 20 patients, respectively. Adrenal insufficiency (AI) was seen in 6 of 10 evaluated patients. Diffuse large B cell lymphoma (DLBCL) was the most common immunophenotype (85.0%). Two patients died due to rapid disease progression before treatment. Two patients received autologous stem cell transplantation as consolidation therapy. All patients received prophylactic intrathecal chemotherapy. The estimated 5-year overall survival (OS) and progression-free survival (PFS) were 52.5% [95% confidence interval (95% CI: 28.2–72.0)] and 53.2% (95% CI: 29.0–72.5), respectively.These findings suggest that PAL should always be considered in differential diagnosis of adrenal mass with AI. Despite the contrasting previous reports, long-term prognosis of PAL is not necessarily inferior to that of non-Hodgkin lymphoma in general.

MON-350 Disseminated Histoplasmosis Manifesting as Adrenal Insufficiency: A Rare Presentation of a Common Infection

Background: Histoplasmosis is a common fungal infection in endemic areas, however it can rarely cause symptomatic disease requiring medical care in some patients. 1 We describe the case of a patient with untreated human immunodeficiency viral (HIV) infection who developed adrenal insufficiency (AI) from disseminated histoplasmosis (DH). Clinical Case: A 56-year-old male with untreated HIV infection and hypertension was evaluated for left upper jaw swelling and pain of 3 months duration. Exam was remarkable for palpable cervical lymph nodes, oral thrush, mass in the posterior maxillary region near the left molars and generalized rash on the upper chest and back. CT chest showed bilateral adrenal gland enlargement measuring 4.1 x 3.6 cm on the left and 2.7 x 2.3 cm on the right with ground glass opacity on the right lower lobe of the lung and hilar lymphadenopathy. MRI brain showed a 3.9 x 5.8 x 4.3 cm soft tissue mass in the posterior aspect of the left maxilla with erosion into maxillary sinus. Biopsy from maxillary mass was positive for histoplasmosis. Laboratory testing showed significant hyponatremia and hyperkalemia. A 250 mcg cosyntropin test was obtained and was consistent with primary AI with an elevated ACTH level of 86 pg/ml (7-69 pg/ml). He was treated with amphotericin for histoplasmosis with good clinical response. He was also started on mineralocorticoid and glucocorticoid replacement for adrenal insufficiency and eventually weaned off mineralocorticoids. Repeat adrenal CT scan 3 years after treatment showed reduction in the size of the adrenal gland however patient continues to be on glucocorticoid replacement for AI. Conclusion: Adrenal involvement is not commonly seen in DH. Even in patients with adrenal involvement, development of adrenal insufficiency in DH is rare.2 Addison’s disease was reported in 14.3% of patients with adrenal histoplasmosis in one case series 3. Kauffman et al reported only 12 out of 58 elderly patients with histoplasmosis had adrenal involvement and none of them had adrenal insufficiency. Adrenal histoplasmosis though rare, should be considered as a differential in patients presenting with unilateral or bilateral adrenal masses and adrenal insufficiency, especially in endemic areas. Our case demonstrates the importance of being vigilant about this association, since delay in treatment could result in life threatening consequences.

MON-343 Nocardia Farcinia Adrenal Abscess Mimicking Adrenal Adenoma

Background: Infection by Nocardia in immunocompetent individuals is uncommon. Isolated adrenal involvement by Nocardia is rare. We report a case of unilateral Nocardia adrenal abscess that presented as lesion mimicking adrenal adenoma which resulted in dissemination in an immunocompetent host. Case Presentation: A 67 years old male with past medical history of coronary artery disease presented to his physician’s office with 5/10 pain in the left flank area for two weeks that radiated into the left upper quadrant. He had weight loss more than 10 pounds in one month, anorexia and night sweats. On examination, he was hemodynamically stable and there was no abdominal tenderness. Routine blood work and a computed tomography [CT] scan of abdomen was obtained that showed a heterogeneously enhancing 8.1 cm x 4 cm x 5 cm partially necrotic left adrenal mass [Figure 1]. Lab work revealed that serum aldosterone, serum renin, plasma metanephrine and urine free cortisol were in normal range. In a few days, patient presented with acute episode of hypotension to the Emergency department. A CT scan of abdomen was that revealed he had large retroperitoneal fluid collection. He received intravenous fluid resuscitation and was started on empiric treatment with Vancomycin and Piperacillin-tazobactam for concern of sepsis. He underwent surgical exploration, incision and drainage of left retroperitoneal abscess collection with removal of two liters of purulent fluid [Figure 2]. Initial gram stain had shown filamentous, acid fast bacteria. He was started on treatment empirically with Amikacin, Trimethoprim–sulfamethoxazole [TMP–SMX] and Imipenem- Cilastatin. The patient was found to have disseminated nocardiosis with positive blood cultures and abdominal abscess growing Nocardia farcinica. Antibiotics were tapered to Imipenem- Cilastatin, Amikacin and Moxifloxacin to complete six weeks of antibiotic therapy. CT scans of chest and head were obtained which did not reveal any signs of abscess. Patient recovered well with repeat imaging studies showing resolution of the abscess. Conclusion: Nocardia involvement of adrenal gland is a rare phenomenon, it can present as solitary adrenal lesion or with dissemination. This can mimic adrenal adenoma on CT scan. On review of existing medical research, less than ten cases of isolated Nocardia adrenal abscess leading to dissemination has been described so far. Isolated involvement of the adrenal gland poses diagnostic challenge because of non-localizing symptoms and late presentation with dissemination. Figure 1 Partially necrotic left adrenal massFigure 2 Retroperitoneal abscess

MON-356 Disseminated Histoplasmosis Mimicking Metastatic Rectal Cancer

Background: Various etiologies account for bilateral adrenal masses including infections, malignancies and adrenal hemorrhage. Accurate diagnosis is needed to provide the best care for the patient. Clinical case: A 63-year-old Thai male patient with locally advanced rectal cancer was treated with concurrent chemoradiotherapy in 2013. He had been followed up at the oncology clinic regularly after his cancer treatment and there was no evidence of cancer recurrence. In early 2018, he presented with anorexia, weight loss and non-productive cough. His chest X-ray showed the presence of patchy opacity of the left lung. The CT of the chest and whole abdomen revealed multiple bilateral pulmonary nodules, bilateral adrenal masses (sized 3.4x5.4 and 4.3x5.5 cm) and an enlarged spleen without definite space-taking lesion. At that time, he was diagnosed with recurrent rectal cancer and presented at the emergency department due to acute diarrhea and hypotension. Multiple discrete umbilicated papules at face, tongue and hands were noted on the physical examination. Hypotension persisted after volume resuscitation. Random cortisol level was 11 µg/dL before hydrocortisone was initiated. Wright stain of the skin lesion showed intracellular yeast-like organism and culture of the skin biopsy showed Histoplasma capsulatum. Bone marrow involvement from the same organism was also documented. After reviewing his clinical course, the diagnosis was compatible with disseminated histoplasmosis (skin, pulmonary, adrenal, spleen and bone marrow involvement). He was treated with amphotericin B for 3 weeks before switching to itraconazole. Two months after antifungal treatment, CT showed increased in size and number of multiple hypodensity lesions at spleen. Therefore, bilateral adrenalectomy with splenectomy was performed without complication. Pathological findings showed diffuse necrotizing areas with surrounded histiocytes, foamy macrophages and multinucleated giant cells in both adrenal glands and spleen. GMS showed presence of numerous small ovoid yeasts, compatible with histoplasmosis. This patient had been doing well with his long-term treatment with itraconazole and glucocorticoid replacement. Conclusion: This was the case of disseminated histoplasmosis whose presentation mimicked metastatic rectal cancer. Misdiagnosis caused delay in the diagnosis and treatment of adrenal insufficiency.