UNASSIGNED: Gastroenteropancreatic neuroendocrine tumours (GEP-NETs) are a relatively rare, heterogenous group of malignancies originating from secretory cells of the neuroendocrine system. Carcinoid syndrome is a complication of neuroendocrine tumours, characterized by a triad of flushing, bronchospasm, and diarrhoea. This is due to the release of serotonin and other vasoactive substances by the tumour. Elevated levels of serotonin can also cause fibrotic changes in the structures of the heart, which can lead to cardiac complications termed carcinoid heart disease. We report the case of a 64-year-old man diagnosed with carcinoid heart disease 19 years after his initial diagnosis of grade 2 GEP-NET with liver metastases.
UNASSIGNED: The patient presented with symptoms of shortness of breath, lower limb swelling, abdominal swelling, and chest pain. He was on treatment with subcutaneous lanreotide 120 mg twice weekly prior to admission. An echocardiogram showed moderate tricuspid regurgitation and mitral regurgitation but preserved left ventricular systolic function, consistent with right heart failure. A CT pulmonary angiogram showed a small volume left lingula pulmonary embolism with bilateral pleural effusions and stable pericardial effusion with evidence of right ventricular strain. The patient was started on IV furosemide 40 mg twice daily, SC octreotide 100 μg three times daily, and therapeutic tinzaparin. The patient was discharged following successful diuresis.
UNASSIGNED: This case report highlights the importance of regular echocardiogram and cardiovascular checkups in patients with carcinoid tumours and liver metastases. A multidisciplinary approach involving medical oncologists, cardiothoracic surgeons, and cardiologists is vital in ensuring early treatment and preventing late-stage complications of carcinoid heart disease.

Neuroendocrine tumours can originate from any part of the body. The most common site in the head and neck is the larynx, accounts for less than 0.6%. The neuroendocrine carcinomas (NECs) of the larynx are rare tumours with high incidence of widespread metastases and poor prognosis. Here we report a 50-year-old male with localised primary moderately differentiated NEC of the larynx. He was treated with surgery followed by adjuvant chemotherapy and concurrent chemoradiation. He is free of his disease and is doing well.

An insulinoma is a rare functional pancreatic neuroendocrine tumour that is usually sporadic and solitary. The hallmark is hypersecretion of insulin, which leads to neuroglycopenia symptoms and uncontrolled sympathoadrenal activity. Neuroendocrine tumours can have a varied presentation, with symptoms often ascribed to a different diagnosis, thus delaying correct diagnosis and treatment. We present the case of a 26-year-old female who had a 3-year delay before diagnosing insulinoma after being initially assessed with epilepsy and schizophrenia. The case report below provides a detailed review of the diagnosis, tumour localization, and surgical interventions implemented for the patient during the COVID-19 pandemic.

OBJECTIVE: Pituitary metastases (PM) are uncommon findings and are mainly derived from breast and lung cancers. No extensive review of PM from neuroendocrine neoplasms (NENs) is on record. Here we describe a clinical case of PM from pancreatic NEN and review the clinical features of PM from NENs reported in the literature.
METHODS: A case of PM from a pancreatic NEN followed at our institution is described. We also reviewed the 43 cases of PM from NENs reported in the literature.
RESULTS: A 59-year old female patient, previously submitted to duodeno-cephalo-pancreasectomy for a well-differentiated pancreatic NEN, with known hepatic metastases, underwent a 68 Ga-DOTATOC PET/CT that revealed an uptake in the pituitary gland. A subsequent MRI displayed a pituitary lesion, with suprasellar extension. After a hormonal and genetic diagnostic workup that excluded the diagnosis of MEN 1, the worsening of headache and visual impairment and the growth of the lesion lead to its surgical removal. A pituitary localization of the pancreatic NEN was identified. Regarding the published cases of PM from NENs, the most common tumour type was small cell lung cancer (SCLC), accounting for nearly half of the cases, followed by bronchial and pancreatic well differentiated NENs. The most frequent symptom was a variable degree of visual impairment, while headache was reported in half of the cases. Partial or total anterior hypopituitarism was present in approximately three quarters of the cases, while diabetes insipidus was less common. The most frequent treatment for PM was surgical resection, followed by radiotherapy and chemotherapy. The clinical outcome was in line with previous reports of PM from solid tumours, with a median survival of 14 months. Surgery of PM was associated with prolonged survival.
CONCLUSIONS: PM from NENs have clinical features similar to metastases derived from other solid tumours, albeit the involvement of the anterior pituitary seems more frequent; a thorough pituitary hormonal evaluation is mandatory, after focused radiological studies, particularly if a surgical approach is considered. The optimal management of PM remains disputed and seems mainly driven by the aggressiveness of the primary tumour and the presence of symptoms. In well-differentiated NENs, particularly in the case of symptomatic PM, surgical removal may be a reasonable approach.

Paragangliomas represent a group of neuroendocrine tumours which occur in various localizations. Most of them produce catecholamines, and in advanced cases present with typical symptoms and signs such as palpitations, headache and hypertension. The only curative treatment is radical resection. About one-quarter of paragangliomas are malignant, defined by the presence of distant metastases. There are multiple treatment options for unresectable metastatic tumours. They include radionuclid therapy, chemotherapy, and radiotherapy, although none of them are curative. Cytoreductive surgery can also be considered, especially when the goal is to decrease symptoms related to advanced disease. We present a rare case of a large paraganglioma of the left retroperitoneum. Despite radical surgery, early recurrence of the disease was observed.

UNASSIGNED: Metastatic neuroendocrine tumours (NETs) to the breast are very rare entities.
UNASSIGNED: A 26-year-old lady presented with anterior neck swelling with symptoms of superior vena cava syndrome for 6 months. Imaging study revealed a mediastinal mass which was preceded with core biopsy which was consistent with high-grade small cell NETs. Despite second-line adjuvant chemotherapy and radiotherapy, her disease became advanced which was confirmed via restaging scan. There were bilateral breast lesions discovered during the scan which was deemed to be metastatic NETs histologically. Despite prompt initiation of treatment, she succumbed 1 year after the radiotherapy due to disease progression.
UNASSIGNED: High suspicion of an index is needed for diagnosis when patients with known primary NETs present with suspicious breast lesions. Triple assessment is mandatory, however histopathology assessment and immunohistochemistry staining are the mainstay of diagnosis.

UNASSIGNED: Primary neuroendocrine neoplasms (NENs) in the breast are very rare. Until 2011, the prevalence was 0.1% of all breast lesions and 1% of all NENs, whereas metastatic breast NENs represent 1%-2% of all breast tumours. However, it seems that over the last 5 years the diagnostic frequency of breast NENs has increased, probably for more alert specialists and advanced diagnostic tools, leading to a prevalence of 2%-5% of diagnosed breast cancers, mostly in the elderly population. Breast metastases from extramammary malignancies are uncommon and bilateral ones are even more uncommon, with few reported in the literature. We describe four clinical settings of breast metastases from different NENs and the multidisciplinary approach for diagnosis and treatment.
UNASSIGNED: Four patients were found to have NEN primaries metastasised to the breast. A literature review was conducted to identify similar cases and characterise breast metastases from neuroendocrinal tumors (NETs).
UNASSIGNED: Two patients presented with bilateral breast metastases (one with well-differentiated panNET and another with atypical lung carcinoid) and two had unilateral (one with moderately differentiated lung NET and one with atypical lung carcinoid). There are about 13 cases of NEN breast metastases reported in the English literature. The ileum is the most common primary site, followed by the appendix, duodenum, pancreas and lung.
UNASSIGNED: Breast lesions from extramammary primary often pose a diagnostic challenge, since a breast nodule can be the first and often the only presentation of the disease. However, differentiating between primary and secondary NEN breast lesions is essential, owing to different clinical management and prognosis.

Appendiceal neuroendocrine neoplasms (ANEN) are uncommon entities, which run mostly an indolent course. Appendicectomy alone is usually curative, except for in a selected group of patients that are deemed to be at risk of loco-regional metastases, in whom a completion right hemicolectomy (RHC) is recommended. The current \"Guidelines\" criteria for the latter have been controversial, and may result in overtreatment, which is concerning for a young patient population.
The aim of this study is to evaluate the prognostic value of the current criteria in identifying more accurately those at-risk patients.
This was a retrospective study of the 263 cases of ANEN referred for advice or management to a tertiary referral unit over a 10-year period. Seventy-two patients underwent RHC, based on criteria, suggested by International Guidelines. Each one of those was assessed to identify whether it correlated with lymph node invasion (LNI) at the RHC surgical specimen.
Tumour grade (p < 0.001), vascular (p = 0.044) and lymph vessel invasion (p < 0.001) were all found to be statistically significant independent risk factors for LNI identified following RHC, whilst tumour size (p = 0.375) and mesoappendiceal invasion (MAI) (p = 0.317) were not statistically significant. However, deep MAI and tumour size >2 cm showed a correlation with each other on LNI positive subgroup analysis. Location in appendiceal base made LNI more likely but again was not significant (p = 0.133).
Higher tumour grade and lymphovascular invasion should be considered as the most important risk prognosticators. Surprisingly, tumour size was not found to be significant in our cohort. Further international multicentre studies with large numbers of patients are needed to fully validate those data.

BACKGROUND: Primary hepatic neuroendocrine tumours (PHNET) were first described by Edmondson et al. in 1958 and are rare, accounting for only 0.3% of all neuroendocrine tumours. Only several hundred cases have been reported.
METHODS: We present two cases. The first is a 65-year-old asymptomatic male referred with a liver lesion on ultrasound performed to investigate a mildly elevated Alanine Aminotransferase (ALT). Hepatitis serology and tumour markers were normal. He had an unremarkable colonoscopy and gastroscopy. CT and MRI revealed a single liver lesion adjacent to the gallbladder suspicious for malignancy. He underwent a segment IVb/V liver resection. Histology was consistent with a 65 mm grade 2 PHNET. Subsequent Dotatate PET/CT scans have been normal at 5 years. The second is an asymptomatic 73-year-old male referred with fluctuating hepatic enzymes and a history of alcohol overuse. Imaging revealed a suspicious lesion in segment III of the liver. He underwent a left lateral liver resection. Histology revealed an 18 mm grade 1 PHNET. A subsequent Dotatate PET/CT was normal with no new disease at six months.
CONCLUSIONS: PHNET, albeit rare are in the differential diagnosis for primary hepatic malignancies. Tumour markers are usually normal and radiological imaging can mimic other hypervascular hepatic tumours. Surgery is the only curative treatment for localised disease to date.
CONCLUSIONS: PHNET needs to be considered in asymptomatic patients with hypervascular hepatic lesions. More research is required before other adjunct treatment options can be suggested.

Somastostatin receptors are frequently expressed in phaeochromocytoma but data on somatostatin receptor subtyping are scanty and the functional response to the somatostatin analogue octretide is still debated.We report an unusual case of pheochromocytoma, causing ectopic Cushing\'s syndrome due to CRH production by the tumour cells, in a 50-yr-old woman. Abdominal computed tomography revealed an inhomogeneous, 9-cm mass in the right adrenal gland, and [111In-DTPA0] octreotide scintigraphy showed an abnormal uptake of the radiotracer in the right perirenal region, corresponding to the adrenal mass. The patient underwent laparoscopic surgery and formalin-fixed and paraffin-embedded samples were studied. The tumour was extensively characterized by immunohistochemistry and somatostatin receptor (SSTRs) subtypes expression was analyzed. Histological and immunohistochemical examination of the surgical specimens displayed a typical pheochromocytoma, which was found to be immunoreative to S-100, chromogranin A and neurofilaments. Immunostaining for SSTR subtypes showed a positive reaction for SSTR1, SSTR2A, SSTR2B, antisera on tumour cells. The intense and diffuse immunostaining for corticotropin releasing hormone (CRH) antiserum indicated that Cushing\'s disease was dependent on CRH overproduction by the pheochromocytoma, in which no immunostaining for adrenocorticotropic hormone was found. Our report confirms the heterogeneity of the pattern of SSTR expression in pheochromocytomas, and provide further evidence for functional SSTR subtype SSTR2a in a subgroup of pheochromocytomas, suggesting that these tumours may represent potential target for octreotide treatment.