Long-term disease-free survival after MIBG therapy for metastatic pheochromocytoma.

Pheochromocytomas are rare tumours originating in chromaffin cells, representing 0.1%-1% of all secondary hypertension cases. The majority are benign and unilateral, characterised by the production of catecholamines and other neuropeptides. Mainly located in the adrenal gland, they are more frequent between the third and fifth decades of life. Iodine-131 metaiodobenzylguanidine (131I-MIBG), a radiopharmaceutical agent used for scintigraphic localisation of pheochromocytomas, has been employed to treat malignant pheochromocytomas since 1983 in a few specialised centres around the world. We reviewed our clinical experience in one such case of a young lady who presented with history of abdominal pain, headache and lower back pain. On evaluation, ultrasonography revealed a right adrenal mass and elevated urine vanillylmandelic acid levels. Following surgical resection and histopathological confirmation of pheochromocytoma, MIBG scintigraphy revealed osseous metastases and hence, she underwent 131I-MIBG therapy.

Oncocytic adrenal cortical adenoma: a benign lesion mimicking malignancy.

Adrenocortical tumours are rare in children and account for only 0.3%-0.4% of all neoplasms in childhood. They present with variable signs and symptoms, depending on the type of hormonal hypersecretion. The majority of the adrenocortical tumours in children are functional (90%) and malignant (88%). Here, we describe a functional plurihormonal oncocytic adrenal cortical adenoma in a young girl, that mimicked a malignant adrenal lesion, clinically as well as on imaging and biochemical features. This report bears the objective of being aware of the atypical biochemical as well as imaging characteristics of oncocytic adrenal tumours.

Atypical parathyroid adenoma with severe bone manifestations in early adolescence.

This is a case of primary hyperparathyroidism in a female teenager with multiple fractures and severe bone manifestations. The histopathology revealed atypical parathyroid adenoma, an exceedingly rare form of hyperparathyroidism; its main differential diagnosis is parathyroid carcinoma, as it shares both clinical and histological characteristics with it, in addition to its still uncertain malignant potential.

Solitary pleural fibroma causing IGF-2-mediated hypoglycaemia in a non-diabetic patient.

A patient without a diagnosis of diabetes mellitus presented to the hospital due to a fall and hypoglycaemia on admission. The patient was found to have recurrent nocturnal fasting hypoglycaemia. CT revealed a large lung mass consistent with a solitary pleural fibroma, a rare tumour associated with insulin-like growth factor 2 (IGF-2) production. This case is an important reminder that potential causes of hypoglycaemia should be considered in non-diabetic patients.

Rare and aggressive metastatic pheochromocytoma recurrence in a patient with MEN 2A syndrome.

An adult male in his early 30s diagnosed with multiple endocrine neoplasia type 2A syndrome, confirmed through genetic testing, presented as bilateral pheochromocytoma in a metachronous fashion, primary hyperparathyroidism and medullary thyroid carcinoma. Left and right adrenalectomy was done 9 years and 3 years ago, respectively. He was also subjected to total thyroidectomy with neck dissection and left inferior parathyroidectomy. During surveillance monitoring, 24-hour total urine metanephrines were elevated 13.977 mg (Normal value 0-1 mg) 1 year after right adrenalectomy. Adrenal CT scan demonstrated a 2.1 cm ovoid focus in the right suprarenal region, and functional imaging (131I meta-iodobenzylguanidine (MIBG scan) showed an avid uptake on the right frontal bone. Excision of the right adrenal bed and the right frontal bone tumour was performed, and metastatic pheochromocytoma was confirmed histologically. The patient achieved clinical and biochemical remission postoperatively and is currently receiving steroid and thyroxine replacement.

Triad of cluster-like headaches, hypertension and hypercoagulability a pointer to pheochromocytoma.

We report the case of a middle-aged hypertensive woman presenting to the neurology department with short-lasting episodic headaches for 4 years. She was initially diagnosed and treated with cluster headaches for one year. Following this, she presented with right lower limb arterial claudication. Arterial Doppler of lower limbs showed thrombosis of the bilateral common femoral arteries. Further computed tomography (CT) angiogram of the lower limbs confirmed extensive arterial thrombosis in bilateral lower limbs. The CT angiogram incidentally detected a left adrenal lesion. She had elevated urinary vanillylmandelic Acid and 24-hour metanephrines suggesting the presence of a pheochromocytoma. She was initially medically managed and later underwent left open adrenalectomy. Histopathology examination of the sections proved pheochromocytoma. Postsurgery, the patient's symptoms improved remarkably. This case highlights the importance of diagnosing pheochromocytoma when you encounter a patient with refractory short-lasting headaches, hypertension and hypercoagulability.

Immunoassay interferences: laboratory pitfall in the diagnosis of adrenocortical carcinoma.

A woman in her late 50s with recent onset of hypertension, diabetes, lumbar pain and unintentional weight loss was diagnosed with a cortisol and androgen-producing adrenal mass. Despite this, serum adrenocorticotropic hormone (ACTH) concentration was inappropriately elevated, which was investigated thoroughly. Investigations included a brain magnetic resonance imaging to exclude concomitant pituitary adenoma, a corticotropin-releasing hormone stimulation test and a gallium-68 DOTATATE and 18F-FDOPA PET scan, both excluding ectopic ACTH production. Considering the disparity between clinical presentation and biochemical results, the ACTH was reanalysed using the Cobas immunoassay (Roche, Switzerland), ultimately unveiling the cause for ACTH elevation. ACTH levels had previously been measured with ACTH Immulite (Siemens, Germany), a two-site immunoassay which is prone to interferences causing falsely elevated ACTH concentrations. Inaccurate laboratory levels can lead to diagnosis delay and unnecessary diagnostic procedures and a close communication between the physicians and laboratorians is of utmost importance.

Multidisciplinary Endocrine Tumor Board: Assessment of the Patient Experience.

Research surrounding tumor boards has focused on patient outcomes and care coordination. Little is known about the patient experience with tumor boards. This survey examined aspects of the patient experience for patients presented at our multidisciplinary endocrine tumor board (ETB). A 15-item survey was distributed via the online patient portal to patients over the age of 18 whose case had been discussed at our ETB over an 18-month period. Descriptive statistics were reported, and a Fisher's exact test was used to examine relationships between variables. A total of 47 patients completed the survey (46%). A majority (72%) report their provider explained what the ETB is, and 77% report being informed their case would be discussed. Most patients were satisfied their case was being discussed (72%). A number of patients did report moderate or severe anxiety knowing their case was being discussed (15%). Sixty-four percent of patients report the ETB recommendations were clearly explained; however, satisfaction with the recommendations was slightly lower (53%). Despite the somewhat low satisfaction with the recommendations, 75% of patients felt more confident in their treatment plan knowing their case was discussed. Finally, if given the chance, 66% responded that they would have been interested in participating in their own ETB discussion. This study provides some insight into the patient experience surrounding tumor board discussions. Overall, patients are satisfied when their case is discussed at ETB. Patients can also experience anxiety about these discussions, and many patients desire to be present for their own discussions.

Neuroendocrine tumour of the lesser omentum.

A man in his early 20s presented to us in the outpatient department with a history of diarrhoea for 4 months. Investigations revealed elevated serum chromogranin levels and an intensely avid lesion in the gastrohepatic ligament in Gallium DOTATATE positron emission tomography (PET). The tumour was excised laparoscopically, and no other lesions were seen. The patient improved clinically and had a normal serum chromogranin level postoperatively. He is currently much improved at the 1year follow-up. We did an extensive workup to look for a primary tumour. It was concluded that it was a de novo tumour arising from the lesser sac. The recommended investigations in case of neuroendocrine tumour (NET) with unknown primary include blood investigations to look for the functional status of the tumour, histopathological examination, including immunohistochemistry, and radiological imaging, which must include a Gallium DOTATATE PET. An isolated NET of the lesser sac has not been reported in the literature.

Parathyroid carcinoma in a patient with primary hyperparathyroidism mimicking parathyroid adenoma.

Primary hyperparathyroidism caused by parathyroid carcinoma is extremely rare. Clinically, it is very challenging to differentiate between parathyroid carcinoma and adenoma. The correct diagnosis is made based on the histopathology of the resection specimen. This case report presents a woman in her 40s with body aches, knee joint pain, and fatigue, along with chronic kidney disease. Ultrasonography revealed a large hyperechoic lesion in the left parathyroid gland. Serum calcium, parathyroid hormone, urea, and creatinine levels were increased. The inferior parathyroid gland was surgically removed, and histopathological evaluation confirmed a diagnosis of parathyroid carcinoma. Unfortunately, many patients do not undergo complete resection due to a lack of a correct diagnosis during the initial surgery.

Metastatic Follicular Thyroid Carcinoma of the Mandible: A Case Report at Tertiary Care Rural Centre.

The most common endocrine cancer is thyroid carcinoma, however it seldom spreads to the oral cavity. Follicular thyroid carcinoma is the second most common type of thyroid cancer after papillary thyroid carcinoma. Thyroid carcinoma-related mandibular metastases is not very common, and there aren't many cases reported in the literature. We are describing a case in which the underlying cancer was diagnosed before the metastatic mandibular lesion was found. Total thyroidectomy and excision of the affected structures, with or without adjuvant therapy, appear to be the most effective treatments.

Papillary thyroid neoplasm: An incidental malignant nodule.

Papillary thyroid cancer (PTC), a common neoplasm originating from thyroid follicular cells, represents 85% of thyroid malignancy. PTC is known to metastasize to adjacent structures. Studies report that 5-15% of detected thyroid nodules represent malignancy; here, we report a 51-year-old woman with incidental thyroid nodules identified on the cervical spine.

Parathyroid carcinoma presenting as severe hypercalcaemia responding to steroids.

A man in his 50s was referred with profound, symptomatic hypercalcaemia. He was diagnosed with primary hyperparathyroidism, confirmed on 99mTc-sestamibi scan. He was treated for the hypercalcaemia and referred to ear, nose and throat (ENT) surgeons for parathyroidectomy, which was delayed due to the COVID-19 pandemic. In the ensuing 18 months, he had five hospital admissions with severe hypercalcaemia requiring intravenous fluids and bisphosphonate infusions. During the last admission, hypercalcaemia was resistant to maximal medical management. Emergency parathyroidectomy was planned, but delayed due to intervening COVID-19 infection. Due to persistent severe hypercalcaemia (serum calcium: 4.23 mmol/L), he was commenced on intravenous steroids, following which serum calcium normalised. Subsequently, he underwent emergency parathyroidectomy, which normalised his serum parathyroid and calcium levels. On histopathological examination, a diagnosis of parathyroid carcinoma was made. On follow-up, patient remained well and normocalcaemic. In patients with primary hyperparathyroidism unresponsive to standard therapy, but responsive to steroids, underlying parathyroid malignancy should be considered.

Cystic lesions of the adrenal gland.

Cystic lesions of the adrenal glands are relatively uncommon and most of them are clinically silent. Though rarely associated with malignant changes, they may carry clinically detrimental consequences if misdiagnosed. Cystic adrenal lesions exhibit a broad histomorphological spectrum, ranging from pseudocysts, endothelial cysts, epithelial cysts and parasitic cysts. Here we present the case of a young woman with left-sided abdominal pain and contrast-enhanced CT showing a 10.4×7.7×7.8 cm fluid-filled left suprarenal lesion. The patient underwent exploratory laparotomy with cyst excision, and the histopathological examination of the specimen revealed a pseudocyst of the left adrenal gland. Despite being rare, usually benign and asymptomatic, the diagnosis and management of these cystic lesions of the adrenal glands are often unclear. Any functional lesion, potentially malignant lesion or lesion more than 5 cm deserves surgical management, whereas others can be managed conservatively.

Paraganglioma arising from the liver and abutting the heart.

A paraganglioma is a rare extra-adrenal neuroendocrine tumour with a variable clinical presentation. A paraganglioma can arise anywhere along the sympathetic and parasympathetic chains, but it can occasionally emerge from unusual locations such as the liver and the thoracic cavity. We report a rare case of a woman in her 30s who presented to our emergency department with symptoms of chest discomfort, episodic hypertension, tachycardia and diaphoresis. A diagnostic approach including a chest X-ray, an MRI and a positron emission tomography-CT scan showed a large exophytic liver mass protruding into the thoracic cavity. For further characterisation of the mass, a biopsy of the lesion was performed, demonstrating that the tumour is of neuroendocrine origin. This was supported by a urine metanephrine test showing high levels of catecholamine breakdown products. Treatment consisted of a unique multidisciplinary approach involving hepatobiliary and cardiothoracic surgery allowing a safe and complete extermination of the hepatic tumour and its cardiac extension.

FSCN1 as a new druggable target in adrenocortical carcinoma.

Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with a high risk of relapse and metastatic spread. The actin-bundling protein fascin (FSCN1) is overexpressed in aggressive ACC and represents a reliable prognostic indicator. FSCN1 has been shown to synergize with VAV2, a guanine nucleotide exchange factor for the Rho/Rac GTPase family, to enhance the invasion properties of ACC cancer cells. Based on those results, we investigated the effects of FSCN1 inactivation by CRISPR/Cas9 or pharmacological blockade on the invasive properties of ACC cells, both in vitro and in an in vivo metastatic ACC zebrafish model. Here, we showed that FSCN1 is a transcriptional target for ß-catenin in H295R ACC cells and that its inactivation resulted in defects in cell attachment and proliferation. FSCN1 knock-out modulated the expression of genes involved in cytoskeleton dynamics and cell adhesion. When Steroidogenic Factor-1 (SF-1) dosage was upregulated in H295R cells, activating their invasive capacities, FSCN1 knock-out reduced the number of filopodia, lamellipodia/ruffles and focal adhesions, while decreasing cell invasion in Matrigel. Similar effects were produced by the FSCN1 inhibitor G2-044, which also diminished the invasion of other ACC cell lines expressing lower levels of FSCN1 than H295R. In the zebrafish model, metastases formation was significantly reduced in FSCN1 knock-out cells and G2-044 significantly reduced the number of metastases formed by ACC cells. Our results indicate that FSCN1 is a new druggable target for ACC and provide the rationale for future clinical trials with FSCN1 inhibitors in patients with ACC.

The Emerging Role of m6A Modification in Endocrine Cancer.

With the development of RNA modification research, N6-methyladenosine (m6A) is regarded as one of the most important internal epigenetic modifications of eukaryotic mRNA. It is also regulated by methylase, demethylase, and protein preferentially recognizing the m6A modification. This dynamic and reversible post-transcriptional RNA alteration has steadily become the focus of cancer research. It can increase tumor stem cell self-renewal and cell proliferation. The m6A-modified genes may be the primary focus for cancer breakthroughs. Although some endocrine cancers are rare, they may have a high mortality rate. As a result, it is critical to recognize the significance of endocrine cancers and identify new therapeutic targets that will aid in improving disease treatment and prognosis. We summarized the latest experimental progress in the m6A modification in endocrine cancers and proposed the m6A alteration as a potential diagnostic marker for endocrine malignancies.

Primary small cell neuroendocrine cancer of adrenal gland: a rare extrapulmonary small cell cancer.

Small cell cancer is an aggressive neoplasm of neuroendocrine origin that is most commonly found in the lungs. However, up to 5% of cases can be extrapulmonary. These have been reported to be located in the gastrointestinal and genitourinary systems and rarely in other locations. Only five prior cases of small cell cancer have been reported where the primary lesion is at the adrenal gland. Here we present the case of a female patient in her mid-50s who presented with right upper quadrant pain and was diagnosed with metastatic small cell carcinoma of the adrenal gland. The patient received palliative chemotherapy for her metastatic cancer and was ultimately admitted to hospice after progression of her disease. This case and the accompanying literature review highlight a rare manifestation of extrapulmonary small cell cancer.

The role of external beam radiation therapy in the management of thyroid carcinomas: A retrospective study in Iran Cancer Institute.

BACKGROUND: Thyroid cancers are histologically classified into three types; differentiated thyroid carcinoma (DTC), medullary thyroid carcinoma (MTC), and anaplastic thyroid carcinoma (ATC). Among the several therapeutic strategies for treatment and management of thyroid cancer, surgical resection in combination with radioactive iodine therapy (RAI) is indicated for moderate to high-risk differentiated thyroid cancer (DTC) patients- according to current guidelines. However, external radiation therapy (EBRT) can be a viable alternative treatment option for these patients and scarce evidence is available regarding the efficacy and effectiveness of EBRT on thyroid cancer. AIM: This study aims at evaluating the role of EBRT in the management of thyroid carcinomas. METHODS AND RESULTS: In this retrospective cohort study, the records of 59 patients with thyroid cancer were accessed who were treated by EBRT from 2008 to 2016. The indications for EBRT included unresectable primary (definitive) or loco-regional recurrences (salvage) not suitable for RAI, palliation for local disease or metastatic foci (palliative), and the adjuvant treatment for suspected residual disease following resection. Progression-free survival (PFS) and overall survival (OS) were calculated for different types of cancer. PFS was measured from the start of EBRT to the last uneventful follow-up, recurrence, or death. Kaplan-Meier model was used for the survival analysis. Fifty-nine patients were evaluated. The histopathology of the tumors was differentiated and poorly-differentiated, medullary and anaplastic thyroid carcinomas in 22 and 6, 15 and 16 patients, respectively. Twenty-seven patients received external beam radiotherapy (EBRT) as adjuvant therapy and 18 of the cases as palliative therapy while the remaining received salvage or definitive primary EBRT. The stage of patients' cancer was as follows: stage II in 3 and III in 1, IVA in 18 and IVB in 18 and IVC in 19. Stage-based median overall survival was 26 months for IVA, 44 for IVB, and 29 for IVC. The median PFS was 18, 22 and 21 months for stages IVA, IVB and IVC, respectively. CONCLUSION: Based on our findings, EBRT may still play a role in the management of patients with thyroid carcinoma and should be considered in the armamentarium against thyroid cancers.

ACTH-secreting metastatic prostate cancer with neuroendocrine differentiation.

Cushing's syndrome (CS) due to ectopic adrenocorticotropic hormone (ACTH) secretion (EAS) can result from a variety of tumours and rarely from those of prostatic origin. We present a male patient in his early 60s with ACTH-secreting metastatic prostate adenocarcinoma with neuroendocrine differentiation (ICD-O code 8574/3) years after prostatectomy and androgen-deprivation therapy, initially presenting with Cushingoid features. After open radical prostatectomy and bilateral orchiectomy for disease recurrence, the patient was found to have metastatic liver and bone lesions highly suggestive of metastatic prostatic cancer. About 10% of cells on liver biopsy expressed ACTH, a finding consistent with EAS as the cause of CS. His stay was complicated with multiple infections and ultimate death. Hence, we report a case of metastatic prostate adenocarcinoma with neuroendocrine differentiation who presented with CS. We also emphasize the importance of adequate and timely treatment.