304 First Reported Case of Metachronous Tumours With Delayed Recurrence from The Neuroendocrine Tumour Arising in A Tailgut Cyst

Background Malignant transformation of tailgut cysts (benign retrorectal cysts) into Neurodendocrine tumours (NETS) is extremely rare with less than 30 reported cases in the literature. A tiny proportion of these cases report early recurrence (within 2 years) and to our knowledge none have reported delayed recurrence 6 years after primary resection. Case history We report a 55-year-old male who underwent laparoscopic excision of a 5 cm presacral tumour found incidentally and confirmed histologically to be a G1 NET (WHO Classification) arising from a pre-existing tail gut cyst, with no evidence of metastasis.16 months later the patient presented with bowel obstruction secondary to adenocarcinoma of the colon at the splenic flexure. The patient underwent laparoscopic left hemicolectomy; histology confirming a moderately differentiated adenocarcinoma (TNM stage pT3pN0). The patient underwent adjuvant chemotherapy post-operatively based upon immunohistochemistry. The patient was followed up for both tumours with CEA, serum chromogranin A, colonoscopies, and CT scans. At 5th year post hemicolectomy, CT scan revealed a new asymptomatic 18 mm left internal iliac lymph node which was avid on octreotide scan consistent with metastasis secondary to NET resected previously. He, therefore, underwent 30Gy sabre radiotherapy. Conclusions There is no consensus regarding follow up duration post early NET resection. The recurrent NET was picked up incidentally as part of the 5-year colorectal adenocarcinoma follow up at our unit. The recurrent NET would not have been identified had this not been a metachronous case. Thus, consideration must be given to both radiological and biochemical follow up post NET resections.

Oncogenic osteomalacia secondary to glomus tumor

Summary Oncogenic osteomalacia secondary to glomus tumor is extremely rare. Localization of causative tumors is critical as surgical resection can lead to a complete biochemical and clinical cure. We present a case of oncogenic osteomalacia treated with resection of glomus tumor. A 39-year-old woman with a history of chronic sinusitis presented with chronic body ache and muscle weakness. Biochemical evaluation revealed elevated alkaline phosphatase hypophosphatemia, increased urinary phosphate excretion, low calcitriol, and FGF23 was unsuppressed suggestive of oncogenic osteomalacia. Diagnostic studies showed increase uptake in multiple bones. Localization with MRI of paranasal sinuses revealed a sinonasal mass with concurrent uptake in the same area on the octreotide scan. Surgical resection of the sinonasal mass was consistent with the glomus tumor. The patient improved both clinically and biochemically postoperatively. Along with the case of oncogenic osteomalacia secondary to a glomus tumor, we have also discussed in detail the recent development in the diagnosis and management of oncogenic osteomalacia. Learning points Tumor-induced osteomalacia is a rare cause of osteomalacia caused by the secretion of FGF23 from mesenchymal tumors. Mesenchymal tumors causing TIO are often difficult to localize and treat. Resection of the tumor can result in complete resolution of biochemical and clinical manifestations in a very short span of time. Glomus tumor can lead to tumor induced osteomalacia and should be surgically treated.

Late Onset of Abiraterone Severe Hypokalemia Due to Unsuspected ACTH-Secreting NEC

Clinical Case: 68-year-old male, Active smoker (30-40 packs/year), and moderate alcohol drinker. An increase in urinary frequency, nocturia, and a PSA of 116 µg/L led to the diagnosis of disseminated castration-sensitive prostate cancer (CSPC), advanced Gleason score (3 + 4 pT2), with bone and retroperitoneal metastases (CT). By 02/2018, he started androgen deprivation therapy (ADT) with Abiraterone (AB) 1000 mg, prednisone, and LHRH agonist. 15 months later, PSA levels decreased to 0.75 ng/ml without side effects and normal K+(3.7 mEq/L), when a CT scan revealed both liver and bone metastasis. During the progression study, two months later, the patient was admitted to the hospital for severe hypoK+ (1.7 mEq / L), normal renal function and metabolic alkalosis. Although abiraterone was discontinued, up to 460 mEq iv per day of K+ and spironolactone were required to maintain serum K+ above 2.5. 3 days later, the hormonal study revealed TSH 1.13 mU /L, ACTH 162 pmol/L, cortisol 258 nmol/L, aldosterone 105 pmol/L, renin (protein) 0.7 µU/mL and deoxycorticosterone 507 pmol/L. 11 days later, plasma cortisol was 967 nmol/L, ACTH 132pmol/L, and cortisoluria 1456 nmol/d. The suppression test with 1 mg of DXM for cortisol was 1162,5 nmol/L. DHEAS was < 407 nmol/L. Liver biopsy showed a small cell neuroendocrine carcinoma (NEC), chromogranin (+), synaptophysin (+), CD56 (+), TTF-1 (+), PSA (-), Ki-67 90% and the granular cytoplasmic ACTH (+). The octreotide scan (+) revealed pathological uptake in L4, multiple uptakes in the liver, and in the axial skeleton. Treatment with Carboplatin plus Paclitaxel for NEC was started, completing 3 weekly doses with good tolerance and clinical benefit, but with the persistence of severe hypoK+ (2.5 mEq/L). Treatment with lanreotide 120 mg every 4 weeks was added, following a feeling of clinical improvement, the disappearance of edema, asthenia, and normalization of plasma K+ (3,4mEq/L). The patient died two months later from respiratory sepsis. Discussion: Several clinical trials have demonstrated that the combination of AB plus ADT prolongs overall survival in DCSPC. The CYP17 inhibition by AB increases ACTH leading to early secondary mineralocorticoid excess with hypokalemia and hypertension while the cortisol levels remain normal or low. Cortisol serum levels increased after AB was discontinued, whereas aldosterone serum levels remained low due to K+ regulatory feedback. The hormonal profile and the pathological and radiological studies revealed an ACTH-producing small cell NEC. In this patient, the previous treatment with BA has masked the clinical and hormonal profile of an ectopic Cushing syndrome. Therefore, Cyp17 inhibitors can mask adrenal or extra-adrenal processes characterized by alterations in steroid metabolism. This case has suggested a more thorough assessment of the adrenal hormonal profile including ACTH during BA treatment.

Olfactory Neuroblastoma: The Adjunctive Role of Somatostatin Agonists After Surgery

Clinical Case: A 54 years old woman who had a right-sided nasal obstruction, rhinorrhea, and sometimes purulent discharge in 2016. In 2002 she had hyperthyroidism by Graves disease and treated for two years with remission after that. The examination of the nose revealed a dark red bleeding mass filling the area from the right nasal cavity to the nasopharynx. The biochemical and serum hormonal values were in a normal range. Urine 5 -HIIAA was 2,5 mg/24h. MRI T1 and T2-weighted images revealed a mass of 4,1 x 4,2 cm, slightly higher signal in T2 and isointense in T1, that extended into the right nasal cavity and ethmoidal sinus. A biopsy was performed, which revealed neuroendocrine characteristics. Octreotide scan with SPECT showed an intense nasal uptake. Right internal maxillary artery embolization was performed. In the next two days, the tumor was resected through a right lateral rhinotomy. Histopathological examination revealed olfactory neuroblastoma, score low grade, ki67<2%. Positive immunohistochemical staining to CD56, synaptophysin, NSE, GFAP, calretinin, S-100 and chromogranin A, and negative staining to cytokeratins (CKs) (CKAPM, CKBPM, CK8/18), CD99 and Bcl-2. The resection was almost total, with no octreotide scan uptake. The post-MRI revealed a minimal residual lesion. Lanreotide treatment was introduced after surgery; the dose was 120 mg every four weeks the first year and every 8 weeks after that. No secondary effects or biochemical alterations were observed. In 2020 the octreotide scan again revealed nasal uptake showing local recurrence. This local recurrence was treated with surgery, followed by lanreotide 120 mg every 4 weeks. No residual disease has been found afterward. Discussion: A limited number of cases have been reported, but none of them were treated with somatostatin agonists. As in our case, the majority of the ON is slow-progressive and non-secreting. The patients mainly complain of local symptoms such as nasal congestion. Surgery is considered to be the first-line treatment for localized disease. In the case of a close margin of the lesion or a residual tumor, the recommendation was radiotherapy or chemotherapy for more advanced disease. We confirmed that the tumor expressed somatostatin receptors. The octreotide scan has been found helpful in the diagnosis and follow-up. We treated the patient with lanreotide with no progression of the disease for three years. Local recurrence could be treated with surgery, following by lanreotide treatment, no residual disease has been found to date. The somatostatin analogs may be a useful adjuvant therapy for stable disease without evident residual disease after surgery.

A rare case of ectopic ACTH syndrome caused by primary renal neuroendocrine tumor

Summary Ectopic adrenocorticotropic hormone (ACTH) secretion is responsible for 5–15% of Cushing’s syndrome (CS). Neuroendocrine tumor (NET) is a common cause of ectopic ACTH syndrome (EAS). However, primary renal NET is exceedingly rare. Fewer than 100 cases have been reported and only a few cases presented with CS. Because of its rarity and lack of long-term follow-up data, clinical manifestations, biological behavior and prognosis are not well understood. Here, we report the case of a 51-year-old man who presented with clinical and laboratory findings compatible with EAS. CT scan revealed a lesion of uncertain nature at the lower pole of the left kidney. Octreotide scan found a filling defect at the lower pole of left kidney. It was difficult to determine if this finding was the true etiology or an incidental finding. Unfortunately, the patient’s clinical status rapidly deteriorated with limited medical treatment. The patient underwent left nephrectomy and left adrenalectomy. Histopathological examination confirmed NET with oncocytic features. Immunohistochemistry staining was positive for ACTH. The patient’s condition gradually improved. Additionally, glucocorticoid replacement was required only 6 months during a gradual recovery of hypothalamic pituitary adrenal axis achieved approximately three years after tumor removal. Although extremely rare, primary renal NET should be considered as a cause of EAS particularly in a patient with rapid clinical deterioration. Thorough investigation, early diagnosis and careful management are crucial to reduce morbidity and mortality. Learning points Primary renal NET is an extremely rare cause of ectopic ACTH syndrome. Ectopic ACTH syndrome has a rapid onset with severe clinical manifestations. In this case, the patient’s condition deteriorated rapidly, resulting from severe hypercortisolism. Resection of the tumor is the most effective treatment. Localization of ectopic ACTH-secreting tumors is very challenging. Multimodality imaging including CT, MRI, octreotide scan, and positron emission tomography plays a crucial role in identifying the tumors. However, each imaging modality has limitations.

ECTOPIC THYROID TISSUE MASQUERADING AS A FUNCTIONAL CAROTID BODY PARAGANGLIOMA

Objective: Ectopic thyroid tissue (ETT) is a rare entity resulting from thyroid gland dysembryogenesis. We present a case of ETT confirmed by histopathology that was misdiagnosed clinically as a carotid body tumor. Methods: A 34-year-old female with a history of thyroidectomy for a goiter presented with 1 year of worsening tachycardia (heart rate ranging from 82 to 111 beats per minute), anxiety, hot flashes, and intolerance to heat. For further evaluation, we obtained imaging of her neck, including a thyroid ultrasound, a computed tomography (CT) scan, and an octreotide scan. We also performed laboratory studies including fractionated 24-hour urine meta-nephrines and thyroid function tests. Results: Her thyroid ultrasound showed a mass at the right carotid bifurcation, which was confirmed on CT as well as on an octreotide scan. Her free thyroxine was 0.6 ng/dL (normal, 0.7 to 1.5 ng/dL) and her thyroid-stimulating hormone was 4.51 mIU/L (normal, 0.45 to 4.5 mIU/L). Her fractionated 24-hour total urine metanephrines were 1,502 mcg/24-hour (normal, 149 to 535 mcg/24-hour). She underwent resection of a vascular mass from the carotid bifurcation. Histologic examination revealed ETT with dilated follicles filled with colloid with no evidence of paraganglioma/carotid body tumor. Conclusion: The somatostatin receptor is typically present in paragangliomas; however, there are reports of octreotide uptake within thyroid goiters. It has been demonstrated that psychoactive medications can increase urine metanephrines. Given the patient's psychiatric history and that no other tumors were identified on imaging, it was felt that the elevated urine normetanephrine in this case was most likely due to psychoactive medication use. This case demonstrates the preoperative imaging findings and postoperative pathologic confirmation of an unusual presentation of ETT.

A rare case of pancreatic adenocarcinoma and subsequent metastatic insulinoma causing severe hypoglycemia

Objective: To report an unusual case of concurrent pancreatic adenocarcinoma and metastatic insulinoma causing severehypoglycemia in a patient with diabetes.Methods: The clinical presentation, biochemical studies, and relevant imaging of this patient are presented and the pertinentliterature is reviewed.Results: A 59-year-old man with a history of unresectable pancreatic adenocarcinoma and diabetes was admitted for persistenthypoglycemia, meeting all criteria for Whipple’s triad and requiring high-dose dextrose infusion. Prior outpatient abdominalimaging had revealed hepatic lesions that were biopsied and found to be a high-grade neuroendocrine carcinoma. On admission, laboratory evaluation revealed inappropriately suppressed beta-hydroxybutyrate levels, and inappropriately elevated insulin, C-peptide, and proinsulin levels. An octreotide scan revealed uptake in the hepatic lesions but not in the pancreatic head mass. Immunohistochemistry staining of prior liver biopsy samples was negative for insulin. Diazoxide therapy was initiated, butdiscontinued after the onset of hypotension. The hypoglycemia resolved only after trans-arterial chemoembolization of lesionsboth in the left and the right liver lobes, in combination with continued octreotide. Unfortunately, he subsequently developedrecurrent hypoglycemia three weeks later and ultimately passed away after transitioning to hospice care.Conclusions: Insulinomas are rare neoplasms of the pancreas that are characterized by insulin hypersecretion, which can bedebilitating and potentially life-threatening. The diagnosis of metastatic insulinoma is difficult to make in the setting of multiplecomorbidities and requires precise biochemical studies. Multiple medical treatments are available but the overall prognosis ispoor.