Thymic Carcinoid Tumor Research Articles

Thymic Neuroendocrine Tumour Results Cushing’s Syndrome

Background: Thymic Neuroendocrine Tumor (TNET) is a rare clinical condition with approximate incidence rate of 2–5%. Carcinoid tumor of thymus with Cushing’s syndrome (CS) is also a rare co-morbid condition. Case information: Here we report a case of a 22-year-old gentleman presented with uncommon features suggestive of CS. He was evaluated and diagnosed with ectopic Adrenocorticotropic hormone (ACTH)–dependent CS due to a TNET. Results: Extensive thymectomy was performed and histopathology confirmed the diagnosis of thymic carcinoma with neuroendocrine differentiation and local and pericardial invasion. Conclusion: Thymic carcinomas may present with symptoms due to mass effect but Cushing syndrome is the most common endocrine manifestation of these tumors. Surgery is the most effective treatment of thymic carcinoma, although chemotherapy and radiotherapy also have been reported to be effective in some cases.

Cushing\u2019s syndrome caused by ACTH-producing thymic typical carcinoid with local invasion and regional lymph node metastasis: a case report

BackgroundEctopic ACTH-producing thymic carcinoid tumors are rare, but often behave aggressively with local invasion and distant metastasis. We herein report a case of ACTH-producing thymic typical carcinoid tumor with lymph node metastasis treated by surgery and postoperative radiation therapy.Case presentationA 61-year-old woman was admitted to be evaluated for hypoglycemia and hypokalemia. Laboratory data revealed elevation of serum cortisol and ACTH levels. Overnight administration of 8 mg dexamethasone did not suppress plasma ACTH. Chest CT demonstrated a tumor of 30 mm in diameter and enlargement of the lymph node at the anterior mediastinum. Ectopic ACTH syndrome was suspected and total thymectomy and lymph node dissection were performed. The histopathological examination indicated typical carcinoid tumor and mediastinal lymph node metastasis, and immunohistochemical staining was positive for ACTH. The plasma ACTH level decreased immediately after surgery. She received postoperative radiation therapy of 60 Gy.ConclusionEctopic ACTH-producing thymic typical carcinoid tumors are rare, and it is important to consider this disease and perform appropriate treatment.

Use of DOTATATE PET/CT Scan in the Diagnosis and Staging of Thymic Atypical Carcinoid Tumor in a Patient with Secondary ACTH-dependent Cushing Syndrome: Look Twice and Cut Once

Use of DOTATATE PET/CT Scan in the Diagnosis and Staging of Thymic Atypical Carcinoid Tumor in a Patient with Secondary ACTH-dependent Cushing Syndrome: Look Twice and Cut Once

Investigation on Computed Tomography Features of Primary Thymic Atypical Carcinoid Tumors.

The thymic atypical carcinoid tumors (aTCs) are rare. The computed tomography (CT) features of aTC were poorly studied, and researches under this topic with large samples are in a small quantity in the literature. Our aim was to investigate the CT features of aTC. Eleven cases of aTC (7 men and 4 women; mean age, 56 ± 16 years) proved by pathology were retrospectively analyzed. All the patients underwent contrast-enhanced CT scans with dual phase (25-30 and 60-70 seconds) after contrast agent injection. Two experienced radiologists analyzed the imaging findings. The observing indexes of CT features were based on standard CT reporting terms of mediastinal masses suspicious for thymic malignancy, particularly on the findings of marginal cystic/necrotic component (MCC) sign and hypervascular sign in tumors. All the tumors were located in the anterior and/or middle mediastinum and heterogeneous parenchyma, with moderate to marked enhancement, and had multiple cystic/necrotic components. The maximum diameter of lesions ranged from 5 to 24 cm. Among the 11 patients involved in this study, 6 patients had distant metastases, all of which were identified as skeletal metastases; 9 cases showed MCC sign only at the margin (3 cases) or at both marginal and central margins (6 cases), and 5 cases showed hypervascular sign. Our results suggested that the MCC and hypervascular signs should be included as characterization in addition to the standard features for the diagnosis of aTC.

AB040. PS02.04: DOTATATE PET/CT in thymic atypical carcinoid tumor with secondary ACTH-dependent Cushing’s syndrome

: Neuroendocrine thymic tumors represent the least common type of primary thymic tumor with a prevalence of 2–5%. We present a case of locally advanced thymic atypical carcinoid tumor diagnosed incidentally while investigating progressive Cushing’s syndrome. CT scan demonstrated a large 2.9 cm exophytic thyroid nodule and a 2.0 cm anterior mediastinal mass. Biopsy of the thyroid nodule demonstrated benign thyroid tissue, and Octreotide scan revealed avid uptake in the right thyroid lobe with minimal uptake in the thymic tumor. 68-Gallium DOTATATE PET-CT scan showed intense uptake in the thyroid gland followed by a moderate amount of activity in the anterior mediastinal mass. The patient underwent a median sternotomy and radical thymectomy with en bloc resection of the left innominate vein and primary repair of the superior vena cava. On further evaluation, the presumed thyroid nodule appeared contiguous with the thymic lesion and separate from the thyroid. Final pathology demonstrated a poorly differentiated 4.4 cm atypical carcinoid tumor with nine positive lymph nodes. On the third postoperative day, the serum cortisol level precipitously decreased to a level of 6.8 µg/dL. This case highlights the challenges surrounding the diagnosis of hormonally active thymic carcinoids, and demonstrates the utility of 68-Gallium DOTATATE PET scan in localizing somatostatin-positive neuroendocrine tumors, and surgical planning.

Ectopic Cushing Syndrome Due to ACTH Secreting Atypic Thymic Carcinoid Tumor

Ectopic Cushing Syndrome Due to ACTH Secreting Atypic Thymic Carcinoid Tumor

A thymic carcinoid tumor causing Cushing syndrome in the setting of a multiple endocrine neoplasia syndrome type 1

A thymic carcinoid tumor causing Cushing syndrome in the setting of a multiple endocrine neoplasia syndrome type 1

When and how should patients with multiple endocrine neoplasia type 1 be screened for thymic and bronchial carcinoid tumours?

Patients with multiple endocrine neoplasia type 1 (MEN1) are commonly evaluated for clinical manifestations of this syndrome with the rationale that early diagnosis and adequate treatment will result in improved survival and quality of life. Thymic and bronchial carcinoid tumours are uncommon but important manifestations of MEN1. Current practice guidelines recommend evaluation with computed tomography or magnetic resonance imaging scan of the chest every 1-2 years to detect these neoplasms. However, the certainty that patients will be better off (increased survival or quality of life) as a result of this case detection strategy is based on evidence at moderate-high risk of bias that yields only imprecise results of indirect relevance to these patients. In order to improve the care that patients with MEN1 receive, co-ordinated efforts from different stakeholders are required so that large, prospective, multicentre studies evaluating patient important outcomes are carried out.

Thymus cancers: A clinical observation

Thymic tumors including thymomas, thymic carcinomas, and thymic carcinoid tumors are rare tumors with an incidence of 0.13/100,000. A literature search was performed to identify recent findings on epidemiology, classification, and various therapeutic approaches. These tumors with a wide spectrum of histologic and biologic features may be clinically unapparent for a long time or show a very aggressive behavior with local invasion and distant metastases. Surgical resection is the mainstay in stageI and II thymomas, whereas in stageIII thymomas and in thymomas with pleural dissemination surgery in context of a multimodal treatment should be discussed. Thymic tumors are chemoreactive. Targeted therapies show poor results and should only be considered in the palliative situation after failure of chemotherapy. The new TNM (T: tumor, N: node, M: metastasis) classification of thymic tumors will help to identify the best treatment options.

Thymic and Bronchial Carcinoid Tumors in Multiple Endocrine Neoplasia Type 1: The Mayo Clinic Experience from 1977 to 2013.

The clinical features of thymic carcinoid (TC) and bronchial carcinoid (BC) tumors as part of multiple endocrine neoplasia type 1 (MEN1) have been rarely described and their importance in clinical practice is debated. The objective of this study was to describe the clinical presentation and outcome of this uncommon manifestation of MEN1 in a tertiary care center setting. We present the clinical features of patients with MEN1 and either TC or BC evaluated at the Mayo Clinic from 1977 to 2013. A total of 348 patients with MEN1 were evaluated and the prevalence of TC was 2.0% (n = 7) and of BC 4.9% (n = 17). The majority of the patients with BC were men (61%) diagnosed on routine screening (77%) and BC was not the confirmed cause of death in any patient. In contrast, TC patients were all men and during follow-up 43% died due to TC complications. We conclude that TC and BC tumors are uncommon, but important components of MEN1. BC were most commonly diagnosed during routine screening and associated with an indolent course. TC were predominantly seen in men and associated with a more aggressive behavior.

Spontaneous Rupture of Thymic Neuroendocrine Carcinoma: A Case Report

Thymic neuroendocrine carcinoma (NEC), also known as thymic carcinoid tumors, are uncommon thymic neoplasms with neuroendocrine differentiation. Among primary thymic malignancies, NEC is the least common, accounting for less than 5% of thymic tumors (1). Thymic NEC tends to be locally invasive towards adjacent structures, such as mediastinal fat, lung, pericardium, and great vessels (2). Metastatic spread can occur by either hematogenous or lymphatic routes, and mediastinal lymph node metastasis is found in about 30 percent of patients at presentation (3). Although thymic NEC is typically identified as a large, usually invasive, anterior mediastinal mass with hemorrhage and necrosis (4, 5), it is extremely rare for it to present rupture. Herein, we report a case of the thymic NEC that was initially presented as a potentially fatal hemorrhage by capsular rupture. CASE REPORT

Multiple endocrine neoplasia type 1 associated with breast cancer: A case report and review of the literature.

Multiple endocrine neoplasia type 1 (MEN1) is a cancer predisposition syndrome that includes a combination of endocrine and non-endocrine tumors. The present study reports a rare case of MEN1 associated with breast cancer with the MEN1 gene mutation. A 45-year-old female was diagnosed with breast cancer subsequent to presenting with a right breast mass. Pre-operative radiological studies indicated right breast cancer with a suspicious metastatic nodule of the lung. Further studies demonstrated bilateral thyroid nodules, a neuroendocrine tumor of the pancreas, paraganglioma, a left adrenal adenoma, gallstones, uterine subserosal myoma and pituitary macroadenoma. Laboratory examinations revealed hypercalcemia, hypophosphatemia and an increased intact parathyroid hormone level. The workup for the suspected MEN syndrome revealed an increased basal plasma level of insulin-like growth factor-1, prolactin and calcitonin, and an increased 24-h urinary free cortisol level. The patient underwent surgical removal of the breast cancer and the tumors of the pancreas, adrenal gland, thyroid and parathyroid glands, uterus, anterior mediastinum and lung. The pathological diagnosis of the resected breast was of invasive ductal carcinoma. Otherwise the pathological diagnosis was of calcitonin-producing pancreatic endocrine carcinoma, adrenal cortical adenoma, bilateral papillary thyroid carcinomas, parathyroid adenomas, uterine leiomyoma with adenomyosis, a thymic carcinoid tumor and lung hamatoma. Gene analysis was performed to determine the association between gene mutations and the development of tumors in this patient, and a germ-line MEN1 gene mutation was consequently detected. It could be assumed that MEN1 syndrome may have possibly predisposed the present patient to breast cancer. However, additional observations and further studies are required to demonstrate this association.

Simultaneous video-assisted thoracoscopic surgery sleeve lobectomy and thymectomy

Thymic carcinoid tumour associated with pulmonary squamous cell carcinoma is very rare. We present a case of synchronous lung cancer and mediastinal tumour treated with simultaneous video-assisted thoracoscopic surgery (VATS) sleeve lobectomy and thymectomy. A 67-year old man presented with cough and bloody sputum. Chest computed tomography showed an anterior mediastinal mass with a right hilar nodule. A right upper sleeve lobectomy and a thymectomy were performed via a VATS approach. Thymic carcinoid tumour associated with pulmonary squamous cell carcinoma was diagnosed, and the patient received adjuvant radiochemotherapy.

Thymic Atypical Carcinoid with Cyclical Cushing?s Syndrome in A 7-Year-Old Boy: a Case Report and Review of the Literature

Thymic carcinoid tumors very rarely occur during childhood and are often associated with the production of adrenocorticotropic hormone (ACTH), which leads to Cushing’s syndrome. We describe a 7-year-old male patient with a thymic atypical carcinoid tumor who presented with cyclical Cushing’s syndrome. His tumor was initially overlooked on computed tomography scanning in the anterior mediastinum, and was later identified by magnetic resonance imaging scanning. There was an interval of 154 days observed between periods of cyclic hormone production. In addition, we discuss the findings of our literature search of the PubMed database. This report emphasizes the importance of considering thymic carcinoid in the differential diagnosis of ectopic ACTH production in children.

Recurrent thymic carcinoid tumor in familial isolated primary hyperparathyroidism

Familial isolated primary hyperparathyroidism(FIPH) is associated with multiple endocrine neoplasia type 1(MEN1) syn-drome, primary hyperparathyroidism accompanied by jaw-tumor syndrome, and familial hypocalciuric hypercalcemia. FIPH may be an early stage of MEN1 or an allelic variant of MEN1. Thymic carcinoid tumor is a rare tumor in MEN1 syndrome. Here, the authors report the case of a 40-year-old man diagnosed with recurrent thymic carcinoid tumor and FIPH. Both the patient and his elder sister had been previously diagnosed to have FIPH with a novel frameshift mutation in the MEN1 gene. Initially, the patient underwent thymectomy because of an incidental finding of a mediastinal mass in his chest X-ray, and had remained asymptomatic over the following 4 years. Pancreas computed tomography conducted to evaluate MEN1 syndrome revealed anterior and middle mediastinal masses, and resultantly, massive mass excision was performed. Histological findings disclosed atypical carcinoids with infiltrative margins. In view of the thymic carcinoid tumor relapse that occurred in this patient, the authors recommend that regular pancreas and pituitary imaging studies be conducted for FIPH associated with a MEN1 gene mutation.

Ectopic Cushing syndrome associated with thymic carcinoid tumor as the first presentation of MEN1 syndrome-report of a family with MEN1 gene mutation

Multiple endocrine neoplasia type 1(MEN1) is an autosomal dominant syndrome. Although thymic carcinoid tumor is recognized as a part of MEN1 syndrome but functioning thymic carcinoid tumor as the first presentation of the MEN1 seems to be very rare. In this report, we present a 29-year-old male who developed ectopic Cushing syndrome secondary to thymic carcinoid tumor and was diagnosed as MEN1 syndrome 2years later. Further evaluation revealed the presence of carcinoid tumor and other MEN 1 manifestations in several other member of family. Genetic evaluation showed presence of a previously reported mutation in exon 10(R527X) of MEN1 gene in these patients. This presentation showed that thymic neuroendocrine tumor could be the first manifestation of the MEN1 syndrome and it might be diagnosed as a dominant manifestation of this syndrome in a family. We suggest biochemical or genetic screening for MEN-1 syndrome for patients with thymic carcinoid.

Causes of Death and Prognostic Factors in Multiple Endocrine Neoplasia Type 1

Multiple endocrine neoplasia type 1 (MEN1) is classically characterized by the development of functional or nonfunctional hyperplasia or tumors in endocrine tissues (parathyroid, pancreas, pituitary, adrenal). Because effective treatments have been developed for the hormone excess state, which was a major cause of death in these patients in the past, coupled with the recognition that nonendocrine tumors increasingly develop late in the disease course, the natural history of the disease has changed. An understanding of the current causes of death is important to tailor treatment for these patients and to help identify prognostic factors; however, it is generally lacking.To add to our understanding, we conducted a detailed analysis of the causes of death and prognostic factors from a prospective long-term National Institutes of Health (NIH) study of 106 MEN1 patients with pancreatic endocrine tumors with Zollinger-Ellison syndrome (MEN1/ZES patients) and compared our results to those from the pooled literature data of 227 patients with MEN1 with pancreatic endocrine tumors (MEN1/PET patients) reported in case reports or small series, and to 1386 patients reported in large MEN1 literature series. In the NIH series over a mean follow-up of 24.5 years, 24 (23%) patients died (14 MEN1-related and 10 non-MEN1-related deaths). Comparing the causes of death with the results from the 227 patients in the pooled literature series, we found that no patients died of acute complications due to acid hypersecretion, and 8%–14% died of other hormone excess causes, which is similar to the results in 10 large MEN1 literature series published since 1995. In the 2 series (the NIH and pooled literature series), two-thirds of patients died from an MEN1-related cause and one-third from a non-MEN1-related cause, which agrees with the mean values reported in 10 large MEN1 series in the literature, although in the literature the causes of death varied widely. In the NIH and pooled literature series, the main causes of MEN1-related deaths were due to the malignant nature of the PETs, followed by the malignant nature of thymic carcinoid tumors. These results differ from the results of a number of the literature series, especially those reported before the 1990s. The causes of non-MEN1-related death for the 2 series, in decreasing frequency, were cardiovascular disease, other nonendocrine tumors > lung diseases, cerebrovascular diseases. The most frequent non-MEN1-related tumor deaths were colorectal, renal > lung > breast, oropharyngeal. Although both overall and disease-related survival are better than in the past (30-yr survival of NIH series: 82% overall, 88% disease-related), the mean age at death was 55 years, which is younger than expected for the general population.Detailed analysis of causes of death correlated with clinical, laboratory, and tumor characteristics of patients in the 2 series allowed identification of a number of prognostic factors. Poor prognostic factors included higher fasting gastrin levels, presence of other functional hormonal syndromes, need for >3 parathyroidectomies, presence of liver metastases or distant metastases, aggressive PET growth, large PETs, or the development of new lesions.The results of this study have helped define the causes of death of MEN1 patients at present, and have enabled us to identify a number of prognostic factors that should be helpful in tailoring treatment for these patients for both short- and long-term management, as well as in directing research efforts to better define the natural history of the disease and the most important factors determining long-term survival at present.

A thymic carcinoid tumour causing Zollinger-Ellison and Cushing’s syndromes due to ectopic ACTH and gastrin secretion

Cushings’s syndrome due to ectopic adrenocorticotrophin (ACTH) secretion was first described nearly a century ago by Hurst Brown. Bronchial carcinomas, usually bronchial carcinoids, were the first to be described and continue to be the leading cause of the ectopic ACTH syndrome; however, thymic carcinoids account for approximately 10% of cases. The Zollinger Ellison syndrome, excessive gastrin secretion from a neuroendcorine tumour, has been described as exclusively due to neuroendocrine tumours of entero-pancreatic origin, while secretion of gastrin from a thymic carcinoid tumour has not been reported to our knowledge. We report a unique case of a 34-year-old woman with ACTH-dependent Cushing’s syndrome and Zollinger-Ellison syndrome due to a thymic carcinoid tumour. caSe report

Cushing's Syndrome Secondary to a Thymic Carcinoid Tumor Due to Multiple Endocrine Neoplasia Type 1

Objective To present an Iranian patient with a nonclassic form of multiple endocrine neoplasia type 1 (MEN 1) who presented with ectopic Cushing syndrome (CS) secondary to a corticotropin (ACTH)-producing thymic neuroendocrine tumor (NET), recurrent renal stones, and a giant cell granuloma of the jaw due to primary hyperparathyroidism (PHPT) without involvement of the pituitary or pancreas. Methods Relevant imaging and hormonal evaluations were performed. The patient was operated on 2 occasions for a thymic NET and on 3 occasions for PHPT. DNA from a peripheral blood sample was extracted for sequencing of the MEN1 gene. Result Histopathologic evaluation of the thymic tumor removed during the first surgery showed an atypical carcinoid tumor with a Ki-67 labeling index of 5%. Evaluation after the second surgery revealed an invasive carcinoid tumor with a Ki-67 labeling index of 30%. Parathyroid pathology was suggestive of glandular hyperplasia. Menin gene sequencing revealed a novel frameshift mutation c.1642_1648dup in exon 10. Conclusion This case of MEN 1 is unusual because most thymic NETs in MEN 1 are nonfunctional, and secretion of ACTH or other ectopic hormones rarely occurs. In patients presenting with thymic NETs, the possibility of MEN 1 should be considered, especially in the presence of hyperparathyroidism. This case also demonstrates that the behavior of thymic NETs can change over time from slow-growing tumors to highly invasive neoplasia, and that ectopic ACTH can be produced by these tumors in the context of MEN 1. (Endocr Pract. 2011;17:e92-e96)

Thymic neuroendocrine tumour (carcinoid): clinicopathological features of four patients with different presentation

Thymic carcinoids are aggressive and present at an advanced stage. This article describes the utility of (68)Gallium-1,4,7,10-traazacyclododecane-NI, NII, NIII, NIIII-tetra acetic acid-(D)-Phel1-Tyr3-octreotide positron emission tomography ((68)Ga DOTATOC PET-CT-scan) and clinicopathological features of four thymic carcinoid tumours. Two typical, one atypical, and one large cell neuroendocrine carcinoma (LCNEC) were analysed. There were three males and one female with a mean age of 33 years. Three patients had a stage III and one had a stage II tumour. Preoperative (68)Ga DOTATOC PET-CT-scan of three patients did not show uptake of radiotracer in the tumour. Three patients were disease free at 19-27 months follow-up. The patient with LCNEC developed recurrence in the lumbar vertebrae. There is no locoregional recurrence of tumour in any of our patients. Complete surgical resection of the tumour with invaded adjacent structures, postoperative radiotherapy to the tumour bed helps in obtaining disease free survival.