Ectopic Cushing’s Syndrome secondary to Recurrent Thymic Neuroendocrine Carcinoma with Bilateral Ovarian Metastases: A case report / Journal of the ASEAN Federation of Endocrine Societies

@#Cushing’s syndrome due to ectopic adrenocorticotrophic hormone (ACTH) secretion is uncommon, accounting for 9 to 18% of cases; approximately 10% of ACTH producing tumours are caused by thymic carcinomas.1 We describe a young lady who presented with Cushing’s syndrome secondary to a primary neuroendocrine tumour (NET) arising from the thymus. She had surgical resection of her primary tumour with remission of her Cushing’s syndrome however subsequently went on to have locoregional recurrence followed by distant metastases to her bilateral ovaries. She underwent 6 surgeries including bilateral adrenalectomy and had 3 cycles of chemotherapy over the course of the 8 years since her diagnosis. Due to the rarity and highly aggressive nature of this disease, we highlight the need for a multidisciplinary team approach and use of multiple modalities in the management of our patient. Timely use of bilateral adrenalectomy particularly in young patients is important to prevent further complications and facilitate other treatment modalities.

Merkel cell carcinoma: Preparing to go the distance

@#Merkel cell carcinoma (MCC) is a rare and aggressive malignancy of the skin, with poor clinical outcomes. Typical conditions include a rapidly growing, solitary dome-shaped, violaceous nodule. Several root causes have been identified - sun exposure, age, lighter skin, immunocompromised state, and polyomavirus infection. Wide local excision is the best treatment. The tumour is radiotherapy-responsive. However, the success rate of the treatment with chemotherapy is rather limited. Immunotherapy has shown promising results. Early detection is important to prevent morbidity and mortality. Case Report: In this literature work, we reported on a particular case of MCC, as exhibited by an 84-year-old Chinese woman, and discussed the clinical features and management of MCC. Discussion: We highlighted that MCC cases have a link to the polyomavirus 5. Patients who were identified with the Polyomavirus 5, and underwent immunotherapy, were seen to depict much better prognosis.

Elastography of the Pancreas, Current View

Ultrasound elastography (USE) of the pancreas allows pancreatic tissue stiffness assessment by virtual palpation. Two main types of USE are used. For the pancreas strain elastography applying by endoscopic ultrasound has been established for the characterisation of small solid pancreatic lesions (SPL). In larger SPL >30 mm the results are less convincing mainly due to the heterogenicity of the lesions but also by concomitant changes of the surrounding pancreatic parenchyma. The current role of shear wave elastography has to be determined. This article reviews the current use of elastography of the pancreas.

Impact of ⁶⁸Ga-DOTA-Peptide PET/CT on the Management of Gastrointestinal Neuroendocrine Tumour (GI-NET): Malaysian National Referral Centre Experience / 대한핵의학회잡지

PURPOSE: The National Cancer Institute is the only referral centre in Malaysia that provides ⁶⁸Ga-DOTA-peptide imaging. The purpose of this study is to determine the impact of ⁶⁸Ga-DOTA-peptide PET/CT on the management of gastrointestinal neuroendocrine tumours (GI-NET).MATERIALS AND METHODS: A cross-sectional study was performed to review the impact of ⁶⁸Ga-DOTA-peptide (⁶⁸Ga-DOTATATE or ⁶⁸Ga-DOTATOC) PET/CT on patients with biopsy-proven GI-NET between January 2011 and December 2015. Suspected NET was excluded. Demographic data, tumoral characteristics, change of disease stage, pre-PET intended management and post-PET management were evaluated.RESULTS: Over a 5-year period, 82 studies of ⁶⁸Ga-DOTA-peptide PET/CT were performed on 44 GI-NET patients. The most common primary site was the rectum (50.0%) followed by the small bowel, stomach and colon. Using WHO 2010 grading, 40.9%of patients had low-grade (G1) tumour, 22.7% intermediate (G2) and 4.5% high (G3). Of ten patients scheduled for pre-operative staging, ⁶⁸Ga-DOTA-peptide PET/CT only led to therapeutic change in three patients. Furthermore, false-negative results of ⁶⁸Ga-DOTA-peptide PET/CT were reported in one patient after surgical confirmation. However, therapeutic changes were seen in 20/36 patients (55.6%) scheduled for post-surgical restaging or assessment of somatostatin analogue (SSA) eligibility. When ⁶⁸Ga-DOTApeptide PET/CT was used for monitoring disease progress during systemic treatment (sandostatin, chemotherapy, everolimus and PRRT) in metastatic disease, impact on management modification was seen in 19/36 patients (52.8%), of which 84.2% had inter-modality change (switch to everolimus, chemotherapy or PRRT) and 15.8% had intra-modality change (increased SSA dosage).CONCLUSIONS: ⁶⁸Ga-DOTA-peptide PET/CT has a significant impact on management decisions in GI-NET patients as it can provide additional information on occult metastasis/equivocal lesions and supply the clinician an opportunity to select patients for targeted therapy.

A retrospective analysis of neuroendocrine tumour of pancreas: a single institute study.

Background: The aim of the work was the clinical characteristics and analysis of preliminary results for surgical treatment of pancreatic neuroendocrine tumors (PNETs). This article deals with the classification of the Pancreatic Neuroendocrine Tumors (PNETs) and discusses their presentation, behaviour, treatment and prognosis. Methods: This was a retrospective study of 70 patients of PNET done over a period of 3 years in The Gujarat Cancer and Research Institute, Ahmedabad. 24 patients who underwent surgical treatment for PNET were further evaluated for surgical outcome, 5yr disease free survival and overall survival. Results: In this study of 70 patients, 61(87.14%) were non-functional. Approximately 77% of PNETs were advanced on presentation (57% metastatic and 20% locally advanced). 20 patients had disease resectable on presentation (11 NF + 9 F). These 20 patients belong to stage I and II of TNM staging system. Only 4 out of 40 metastatic diseases had locally resectable tumor. Of 24 patients who underwent surgery, 12 underwent pancreatico-duodenectomy, 6 underwent enucleation and 6 underwent distal pancreatectomy. Conclusions: PNETs are uncommon tumor of pancreatic origin with presentation more commonly in males than females, usually in the 5th decade. Approximately 77% of patients are advanced or metastatic at presentation. Among those resectable, the Overall Survival for FPNETs and NFPNETs was 90% and 94% respectively and 5yr Disease Free Survival for the same was 100% and 84% respectively.

Cushing’s Disease and High Dose Cabergoline Monotherapy: Rapid and Sustained Clinical and Biochemical Improvement, with Reversal of Diabetes, Hypertension and Infertility.

Aims: To assess the effects of high dose long term cabergoline monotherapy in a patient with Cushing's disease refusing any form of surgical intervention. Presentation of the Case: A 32-year-old Omani female with hypertension, diabetes mellitus and secondary infertility of 10 years and amenorrhoea of 2 years duration, was referred with recurrent thigh abscesses. She was on 100 units of mixed insulin in two divided doses, metformin 1 gm bd, lisinopril 20 mg od, amlodipine 10 mg od and indapamide 1.5 mg od ."She had all the features of Cushing’s syndrome, with a blood pressure (BP) of 180/110 mmHg, plethoric facies, central obesity and striae". Investigations revealed diabetes, HBA1c 10.7% and ACTH-dependant Cushing’s syndrome, "cortisol 720 nmol/L (normal <624) and ACTH 14.9 pmol/L. (normal 1.6-13.8)". The pituitary MRI and computerised tomographic ( CT) scans from neck to pelvis “ were normal” A neuroendocrine tumour (NET) was deemed unlikely as serum cortisol levels did not “suppress during by a 72 hours trial” of octreotide 100 mcg 8 hourly and her serum chromogranin- A level (CgA) was normal. A diagnosis of Cushing’s disease was made. She refused inferior petrosal sinus sampling (IPSS) and any form of surgery. A trial of cabergoline was agreed upon. Her response was dramatic: On 1 mg daily initially, the serum cortisol was normal after one week, and by 4 months her blood sugar and blood pressure were normal off all other medications. The HBA1c had fallen from 10.7% to 5.4%. Shortly afterwards she became pregnant and on a reduced dose of cabergoline (1.5 mg/week), she delivered a healthy full term baby, echocardiography was normal in both mother and baby. She has now been in complete remission for more than 4 years on cabergoline 0.5 mg 3 times a week without any side effects. Conclusion: This case provides an example of successful acute and sustained primary “monotherpy” with initially high dose cabergoline in Cushing’s disease. The additional positive metabolic effects and the lack of significant side effects makes high dose cabergoline monotherapy an attractive first or second line treatment for patients with Cushing's disease.

A rare variant of carcinoma of the cervix: neuroendocrine tumour.

Neuroendocrine neoplasm that occurs in the uterine cervix is rare. It accounts for 0.5-1% of all malignant tumours of the uterine cervix. A 55 years old female patient complained of postmenopausal bleeding and history of foul smelling discharge per vagina since 1 month. On examination cervix appeared bulky, both lips indurated, bleeds on touch, both parametrium involved but not up to pelvic wall with bulky uterus. Vagina and per rectal mucosa was free. Clinical diagnosis of carcinoma cervix, stage 2B was made. Cervix biopsy with HPE revealed squamous epithelium of cervix showing neoplastic cells arranged in nests and prominent perivascular pattern, small round cells with minimal cytoplasm and hyperchromatic nucleus, abundant mitosis, cells showed rosette pattern and isolated foci of cell debris and necrosis. Diagnosis of neuroendocrine tumour of cervix was considered. Immunohistochemistry for cytokeratin, neuron specific enolase, chromogranin and synaptophysin was positive, confirming the final diagnosis of neuroendocrine carcinoma cervix (High grade of small cell type). Recognition of Neuroendocrine carcinoma cervix is important for appropriate therapy & management since these patients have worse clinical outcomes when compared with conventional squamous /adeno carcinoma of cervix. Immunohistochemistry should be supplemented with ultrastructural studies for confirmation and correct categorisation of carcinoma cervix for appropriate management.