Pancreatic Neuroendocrine Tumor Presenting Research Articles

8282 A Diagnostically Challenging Case of Ectopic ACTH Secreting Pancreatic Neuroendocrine Tumor Presenting with Cushing’s Syndrome

Abstract Disclosure: O.A. Aluko: None. S. Patel: None. S.V. Silparshetty: None. T. Gallagher: None. Introduction: Ectopic ACTH mediated Cushing’s syndrome is an uncommon but treatable condition that poses time constrained diagnostic and therapeutic challenge due to severe morbidity as illustrated by our case below. Clinical case:A 65-year-old male was admitted with profound generalized weakness. He became restricted to wheelchair from being able to hike a trail at Yosemite national park 8 weeks prior. Recent history included hospitalization with uncontrolled diabetes and hypertension, new vertebral compression fractures, AKI, hypokalemia, proximal myopathy, anasarca, upper GI bleed and acute upper extremity DVT. Initial testing there revealed hypercortisolemia, elevated ACTH and a normal pituitary MRI. Further workup at our center revealed elevated 24hr urinary cortisol 2598 (n = 5 - 64 μg/24hr), random cortisol 55 (n= 4.2 -22.4 μg/dL) with elevated ACTH 194 (n= 7.2 - 63.3 pg/mL) consistent with ACTH dependent hypercortisolism. IPSS deferred due to AKI, underlying comorbidities and severe cervical stenosis with myelopathy. ACTH and cortisol remained elevated with an 8mg dexamethasone suppression test suggesting ectopic source ACTH. CT with contrast of chest, abdomen and pelvis showed 5mm right lower lobe lung nodule and bilateral adrenal nodularity. Bronchoscopic FNAC was negative for NET.Ketoconazole 400 mg twice daily was started pending localization of culprit lesion with improvement in 24 hr urinary cortisol to 554μg/24 hr however this was stopped within 4 weeks due to acute transaminasemia. Repeat imaging with Gallium-68 dotatate PET CT showed a 1.8 X 2.4 X 1.7 cm pancreatic mass. He underwent distal pancreatectomy with splenectomy. Pathology confirmed a 2.2cm well differentiated neuroendocrine tumor limited to the pancreas with immunohistochemistry strongly for ACTH and weakly for Gastrin. Postoperatively, patient was given hydrocortisone replacement. ACTH was 14.3 pg/mL and cortisol 6.2μg/dL a few weeks later. His diabetes, hypertension, hypokalemia, transaminasemia and proximal myopathy improved. Discussion:Ectopic ACTH mediated Cushing’s syndrome is responsible for about 5 - 20% of all Cushing’s syndrome cases. Pancreatic neuroendocrine tumor secreting Ectopic ACTH is rarer but can be aggressive. Clinical presentation can be confounding due to secretion of >1 neurohormone i.e ACTH and Gastrin in our patient. Gallium-DOTATATE PET/CT tracer has a very high sensitivity and specificity. Early use of this imaging may prevent comorbidity and mortality as surgical resection of ectopic ACTH secreting neuroendocrine tumor is first line therapy. Other diagnostic principles to consider are that severely elevated ACTH levels correlate only with a pituitary macroadenoma, IPSS is invasive and has relative contraindication in sick patients and Desmopressin stimulation test is not widely available. Presentation: 6/1/2024

8257 Pancreatic Neuroendocrine Tumor Presenting as Carcinoid Syndrome

Abstract Disclosure: D. Phung: None. Introduction Pancreatic neuroendocrine tumors (NETs) are rare tumors that arise in neuroendocrine cells of the pancreas. These tumors secrete a wide array of hormones. Carcinoid syndrome is a result of well-differentiated neuroendocrine tumors that secrete biologically active amines and peptides that cause the clinical manifestation of flushing, diarrhea, cardiac involvement, and wheezing. Case Presentation A 57-year-old male presented to the clinic for symptoms of tachycardia, shortness of breath, dizziness, and sweating for the past year. He had past medical history of chronic kidney disease, history of previous cardiac arrest, history of previous myocardial infarction, congestive heart failure, hypertension and gastric reflux disease. No history of tobacco, alcohol, or drug consumption. No previous surgeries. Family history with heart disease and prostate cancer in his father. His symptoms began over the course of the past year. Initially began with shortness of breath, chest pain, weight gain which then developed into dizziness with standing, episodes of night time sweating. He had associated headaches that were occurring daily. Vomiting would occur intermittently three to four times weekly. He noted episodes of flushing with rash occurring in the upper chest and bilateral arms. Diarrhea and loose bowel movements would occur occasionally. On examination he had tachycardia with heart rate at 103 BPM. Lung fields clear throughout. Abdomen was soft, nontender, without masses palpated. On biochemical testing chromogranin A was highly elevated and remained elevated upon repeat testing. Initial imaging with CT abdomen and pelvis with contrast was negative. PET scanning confirmed and localized his NET, revealing increased tracer uptake and hypervascularity in the neck of pancreas as well as two regions in the right lower lobe of the liver. Following confirmation and localization of his tumor he was then referred for surgical evaluation and treatment. Discussion In our presented case, the patient presented with symptoms suggestive of carcinoid syndrome which was confirmed biochemically with elevated chromogranin A. Clinical suspicion remains critical in diagnosis of NETs. The patient presented with clinically suspicious carcinoid syndrome, but initial testing with CT scan was negative and required further PET-based tracing to uncover tumors. Our case highlights the importance of clinical examination and acumen in diagnosing neuroendocrine tumors. Presentation: 6/2/2024

Pancreatic neuroendocrine tumor presenting with recurrent confusion and recent posterior circulation stroke

Pancreatic neuroendocrine tumor presenting with recurrent confusion and recent posterior circulation stroke

A rare case of malignant pancreatic non-functional neuroendocrine tumor presenting as huge abdominal lump

We present a case of an exceptionally large size non-functioning pancreatic neuroendocrine tumor (PNET) in a young female. The tumor occupied the whole abdomen and pelvis and was clinically masqueraded as an ovarian tumor. Imaging with contrast enhanced CT scan and magnetic resonance imaging of the abdomen aided in preoperative diagnosis of origin of the tumor from the pancreas. Distal pancreatectomy with splenectomy and left hemicolectomy was done. Primary colocolic anastomosis was done for reconstruction. Postop course was uneventful, and patient was discharged with advice to undergo adjuvant chemotherapy. Surgical excision of large size locally advanced non-functional PNET should be done with curative intention/ to treat symptoms and improve patient survival

Pancreatic Neuroendocrine Tumor Presenting with Chylous Ascites: Multidisciplinary Workup to Differentiate from Malignant Ascites.

Pancreatic Neuroendocrine Tumor Presenting with Chylous Ascites: Multidisciplinary Workup to Differentiate from Malignant Ascites.

Necrolytic migratory erythema (glucagonoma syndrome) associated with pancreatic neuroendocrine tumor presenting with superimposed cellulitis

Necrolytic migratory erythema (glucagonoma syndrome) associated with pancreatic neuroendocrine tumor presenting with superimposed cellulitis

Abstract #846 ACTH Secreting Malignant Pancreatic Neuroendocrine Tumor Presenting as Rapid Onset Severe Cushings Syndrome in a 53 Years Old Woman

Abstract #846 ACTH Secreting Malignant Pancreatic Neuroendocrine Tumor Presenting as Rapid Onset Severe Cushings Syndrome in a 53 Years Old Woman

A Case of Pancreatic Neuroendocrine Tumor presenting Iron Deficiency Anemia in a Patient with Neurofibromatosis Type 1

A Case of Pancreatic Neuroendocrine Tumor presenting Iron Deficiency Anemia in a Patient with Neurofibromatosis Type 1

Anti-Hu paraneoplastic brainstem encephalitis caused by a pancreatic neuroendocrine tumor presenting with central hypoventilation

Paraneoplastic neurological syndromes are rare autoimmune manifestations of malignancies associated with specific antibodies. Anti-Hu associated brainstem encephalitis, a well-described syndrome, usually presents subacutely with preferential involvement of the medulla. Anti-Hu antibodies target intraneuronal antigens and are therefore highly correlated with neurological syndromes when present concomitantly with a neoplasm. Reported is a case of anti-Hu brainstem encephalitis associated with a pancreatic neuroendocrine tumor (PNET) presenting with central hypoventilation. This is the first described case of brainstem encephalitis associated with a well-differentiated PNET as well as the first case of Anti-Hu antibodies associated with a PNET. There are no standardized protocols for the treatment of paraneoplastic brainstem encephalitis however, as in the present case, surgical resection and oncological treatment of the tumor is the first line treatment.

Pancreatic Neuroendocrine Tumor Presenting with Arthritis and Panniculitis

Pancreatic Neuroendocrine Tumor Presenting with Arthritis and Panniculitis

Endoscopic ultrasound-guided needle-based confocal laser endomicroscopy for diagnosis of solid pancreatic lesions (ENES): a pilot study.

Background and study aims: Endoscopic ultrasound-guided needle-based confocal laser endomicroscopy (EUS-nCLE) has been shown to aid in the diagnosis of cystic pancreatic lesions. This is a pilot project to study its findings in patients with solid pancreatic lesions (SPLs) with a prospective single-blinded study design. Methods: Patients with SPLs undergoing trans-gastric EUS fine needle aspiration (EUS-FNA) from July 2013 to March 2014 were prospectively enrolled. The nCLE diagnoses were compared with the final diagnoses. Researchers learned about the EUS-nCLE findings from previously published studies and applied it to diagnose SPLs. In the meantime, the findings were recorded. Results: In total, 22 patients were recruited (mean age 62.7 years, SD 13.8 years; 14 men and eight women). The mean maximal tumor diameter was 36.0 mm (SD 10.9 mm). EUS-nCLE yielded satisfactory images in all patients during the first EUS procedure and diagnosed benign and malignant SPLs in 3 and 19 patients, respectively. Final diagnoses of malignant SPLs were made in 19 patients. Benign SPLs were eventually diagnosed in three patients, with confirmed the cytology and disease stability during the 12-month follow-up period. At the end of the project, based on the results of this current study, EUS-nCLE findings for malignant SPLs were dark clumping with or without dilated vessels (> 40 μm). There were two criteria for diagnosing benign lesions which were white fibrous bands and normal acini cells. The accuracy rate of EUS-nCLE was 90.9 % (20/22). One falsely diagnosed malignant SPL was an inflammatory mass from a recent acute pancreatitis. Another one with a pancreatic neuroendocrine tumor presenting with a symptomatic pseudocyst was incorrectly diagnosed as an inflammatory mass. This was likely from sampling error of the EUS-nCLE probe in an inflammatory area. Only one patient had post EUS-FNA bleeding but did not require a blood transfusion. The inter-observer agreement among three blinded endoscopists was almost perfect (Kappa 0.82). Conclusion: EUS-nCLE is a promising technique for the diagnosis of SPLs with good inter-observer agreement.Study registration‎: TCTR20140402001

GLP1 and glucagon co-secreting pancreatic neuroendocrine tumor presenting as hypoglycemia after gastric bypass.

SummaryPost-prandial hypoglycemia is frequently found after bariatric surgery. Although rare, pancreatic neuroendocrine tumors (pNET), which occasionally are mixed hormone secreting, can lead to atypical clinical manifestations, including reactive hypoglycemia. Two years after gastric bypass surgery for the treatment of severe obesity, a 54-year-old female with previous type 2 diabetes, developed post-prandial sweating, fainting and hypoglycemic episodes, which eventually led to the finding by ultrasound of a 1.8-cm solid mass in the pancreatic head. The 72-h fast test and the plasma chromogranin A levels were normal but octreotide scintigraphy showed a single focus of abnormal radiotracer uptake at the site of the nodule. There were no other clinical signs of hormone secreting pNET and gastrointestinal hormone measurements were not performed. The patient underwent surgical enucleation with complete remission of the hypoglycemic episodes. Histopathology revealed a well-differentiated neuroendocrine carcinoma with low-grade malignancy with positive chromogranin A and glucagon immunostaining. An extract of the resected tumor contained a high concentration of glucagon (26.707 pmol/g tissue), in addition to traces of GLP1 (471 pmol/g), insulin (139 pmol/g) and somatostatin (23 pmol/g). This is the first report of a GLP1 and glucagon co-secreting pNET presenting as hypoglycemia after gastric bypass surgery. Although pNET are rare, they should be considered in the differential diagnosis of the clinical approach to the post-bariatric surgery hypoglycemia patient.Learning points pNETs can be multihormonal-secreting, leading to atypical clinical manifestations.Reactive hypoglycemic episodes are frequent after gastric bypass.pNETs should be considered in the differential diagnosis of hypoglycemia after bariatric surgery.

A successful case of pancreaticoduodenectomy with resection of the hepatic arteries preserving a single aberrant hepatic artery for a pancreatic neuroendocrine tumor: report of a case

A 65-year-old male with a pancreatic neuroendocrine tumor presenting with a duodenal ulcer was referred to our department. The tumor involved the common hepatic artery, gastroduodenal artery, left hepatic artery and the right posterior hepatic artery, but not the right anterior hepatic artery originating from the superior mesenteric artery. The hepatic arteries, except the aberrant right anterior hepatic artery, were embolized using coils 18 days before the surgery. The patient underwent pancreaticoduodenectomy with resection of the tumor-encased hepatic arteries, while preserving the aberrant artery. The patient was discharged uneventfully on postoperative day 13 with no ischemic complications. A histopathological examination revealed a grade 2 pancreatic neuroendocrine tumor according to the classification of the World Health Organization, and the surgical margin was negative. The patient developed hepatic metastases 16 months after surgery; hence, hepatic resection was performed. The present surgical strategy is applicable in patients with relatively low-grade pancreatic malignancies involving major hepatic arteries.

Pancreatic Neuroendocrine Tumor Presenting as a Cushing’s Syndrome Associated with Hypertension

A young female was evaluated in the emergency department (ED) for persistent headache and fatigue one week after being started on antihypertensive therapy with poor response. Her medications were Amlodipine 10 mg daily, Hydrochlorothiazide 25 mg daily, Atenolol 100 mg daily and Hydralazine 50 mg three times daily. Further evaluation revealed cushingoid appearance, her blood pressure was 171/100 mmHg despite compliance with multiple antihypertensive therapy. Her clinical manisfestation prompted the evaluation for secondary causes of hypertension with laboratory evidence of hypokalemia, hyperglycemia, hypercortisolism with high ACTH that did not respond to low and high dose dexamethasone suppression. A splice mutation in MEN 1gene was found with the eventual diagnosis of metastatic pancreatic neuroendocrine tumor. Her turbulent course unravels how complex medical problems continue to masquerade as general medical ailments.

A Case of ACTH-producing Pancreatic Neuroendocrine Tumor Presenting with Cushing Syndrome

Pancreatic neuroendocrine tumors are rare neoplasm arising from pancreatic islet cells. Occasionally they are functioning tumors secreting a variety of hormones such as insulin, gastrin, glucagon, and vasoactive intestinal peptides. Adrenocorticotropic hormone (ACTH) secreting pancreatic neuroendocrine tumors (ACTHomas) are very rare and there have been about 110 case reports worldwide. Due to excessive ectopic ACTH production and resulting hypercortisolemia, patients with ACTHoma usually present with Cushing syndrome. ACTHomas have a poor prognosis with severe and rapidly progressive clinical courses. They often present with unresectable liver metastases and there remains little consensus on its standard treatment. We report a 55-year-old female with ACTH-producing pancreatic neuroendocrine tumor, who was treated with surgical resection of pancreatic tail, spleen, and a portion of stomach. Sixteen months later, abdomen computed tomography scan showed multiple liver metastases, which were treated with transarterial chemoembolization.

Unusual Complication of a Pancreatic Neuroendocrine Tumor Presenting with Malignant Hypercalcemia

Hypersecretion of PTHrP is a relatively common cause of malignancy-related hypercalcemia but has only been described in a few cases of neuroendocrine tumors (NET). The aim of this case report is to describe the clinical syndrome, complex therapeutic interventions, and unusual complications caused by persistent PTHrP hypersecretion in a patient with a pancreatic NET. A 58-yr-old male patient presented with nonspecific abdominal pain and was found to have severe hypercalcemia secondary to a well-differentiated NET of the pancreas associated with extensive liver metastases. Elevated ionized calcium levels accompanied by low serum PTH and remarkably elevated PTHrP concentrations were consistent with PTHrP-related hypercalcemia that proved to be resistant to various chemotherapeutic regimens and supportive therapy. Partial control of the humoral syndrome was obtained only after the application of cytoreductive interventions and the introduction of various molecular targeted therapies. Due to persistent PTHrP action, bone disease emerged in the form of brown tumors. The manifestation of paraneoplastic syndrome due to PTHrP hypersecretion, despite its rareness in NET, should be considered in the differential diagnosis of hypercalcemia in such tumors. Moreover, the appearance of bone lesions in this setting may be in the context of metabolic bone disease and could be misdiagnosed as bone metastases.

Rare Presentation of Cystic Nonfunctioning Pancreatic Neuroendocrine Tumor: A Case-Series

Purpose: Pancreatic cysts are often identified incidentally on body imaging. Cysts >3 cm are often evaluated by endoscopic ultrasound (EUS), and those <1 cm followed by serial imaging. We present two cases in which EUS of pancreatic cysts <1.5 cm in size revealed nonfunctioning pancreatic neuroendocrine tumors (PNET). A 36-year-old man presented with an exacerbation of chronic epigastric pain. He also reported subjective fevers, skin flushing and pruritus. Computed tomography (CT) of the abdomen and pelvis showed a subcentimeter hypodensity in the body of pancreas. EUS showed a thick walled, anechoic, single compartment cyst in the pancreatic body measuring 10 x 7 mm. Fine needle aspiration (FNA) was consistent with a well-differentiated neuroendocrine tumor. Nuclear octreotide scan and hormonal studies were normal and the tumor was determined to be localized and nonfunctioning. A 59-year-old man presented with two weeks of right flank pain. CT scan revealed a 1.5 cm exophytic cystic area in the tail of the pancreas contiguous with the posterior wall of the stomach. EUS showed a 15 x 15 mm anechoic, multicystic, distally enhancing lesion with peripheral mural nodularity in the pancreatic tail. FNA revealed neoplasm and the patient underwent distal pancreatectomy and splenectomy. Surgical resection specimen pathology showed a low-grade PNET with negative margins. Lymph nodes sampled were negative for malignancy and this was determined to be a nonfunctioning neuroendocrine tumor. Pancreatic cysts are increasingly discovered as abdominal imaging studies have improved in sensitivity and are more frequently performed. EUS with FNA has emerged as the modality of choice for obtaining tissue and fluid from these lesions. The majority are pseudocysts while a growing minority represent pancreatic cystic neoplasms. PNETs are rare and comprise less than 5% of pancreatic malignancies. They are commonly divided into functioning (hormone-producing) and nonfunctioning tumors. In 2006, a pancreatic neuroendocrine tumor presenting with vision changes due to demyelinization of the optic nerve was reported. In 1998, Koutalas et al. reported an 18 cm nonfunctioning PNET. In 1994, Schwartz et al. reported 3 cases of large nonfunctioning PNET presenting with symptoms due to mass effect. There are no previously reported cases of a small cystic nonfunctioning PNET. Although diagnosis of cystic pancreatic neuroendocrine tumors is rare, our experience shows that endosonographic evaluation of incidentally found small (<3 cm) pancreatic cysts should be considered. Once diagnosed, an assessment for hormone production should be conducted as well as referral for consideration of surgical resection.

Metastatic pancreatic neuroendocrine tumor presenting as a pituitary space occupying lesion: a case report

Neuroendocrine tumor metastases to the pituitary gland are very rare. There are few case reports of carcinoid tumor metastases to the pituitary, but no cases of pancreatic neuroendocrine pituitary metastases have been reported. In this report we present a 55-year-old female with a sellar mass, ophthalmoplegia and headaches initially thought to represent an invasive null cell pituitary adenoma. However a histological (trans-sphenoidal and liver biopsies) and systemic investigation proved it to be a metastasis of an undiagnosed pancreatic neuroendocrine tumor. Our patient was unique in respect to the location of the metastasis and the uncharacteristically high proliferative index of her tumor. She received conventional therapy consisting of Sandostatin, chemotherapy and radiotherapy as well as labeled somatostatin following an avid uptake on octreotide scanning. Despite a radiological improvement the patient suffered progressive clinical deterioration and died.

ACTH-Secreting Islet Cell Tumor of the Pancreas Presenting as Bilateral Ovarian Tumors and Cushing's Syndrome

A 41-year-old woman presented with hirsutism, a pelvic mass, and Cushing's syndrome. Imaging studies revealed bilateral ovarian masses and a solid and cystic mass within the pancreas. Partial pancreatectomy, bilateral oophorectomy, and excision of several peritoneal tumor nodules were performed. Pathological examination revealed a neuroendocrine islet cell tumor of the pancreas with bilateral ovarian metastases. The tumor was immunoreactive for ACTH, chromogranin, neuron-specific enolase, and keratin. The patient received postoperative chemotherapy and has been disease-free for 6 years. To our knowledge, this is the first reported case of an ACTH-secreting pancreatic neuroendocrine tumor presenting as bilateral ovarian metastases.