Thymic carcinoid associated with multiple endocrine neoplasia type 1

We report a case of a thymic carcinoid associated with multiple endocrine neoplasia type 1( MEN-1). A 37-year-old man was referred to our hospital for further examination of an abnormal chest shadow. A chest computed tomography (CT) showed an anterior mediastinal mass measuring 6.5 cm in diameter. A pathological diagnosis of thymic carcinoid was made from a CT-guided needle biopsy specimen. Preoperative workup including endocrinological examination revealed a pituitary adenoma and hyperparathyroidism, and MEN-1 was clinically diagnosed. We performed total parathyroidectomy with autotransplantation and thymectomy with lymph node dissection through cervical collar incision and median sternotomy. The diagnosis of MEN-1 was confirmed by the genomic analysis postoperatively. Since 25% of thymic carcinoids are MEN-1 related and 95% of MEN-1 patients develop hyperparathyroidism, it should be kept in mind that this condition can be treated by thymectomy and concurrent parathyroidectomy.     

Simultaneous double thymic carcinoids: a rare initial manifestation of multiple endocrine neoplasia type 1

A 53-year-old man was referred to our hospital for treatment of two anterior mediastinal tumors. The anterior mediastinal tumors were resected by thymectomy under the probable diagnosis of double thymomas. The final pathological diagnosis was multiple thymic carcinoids. Although 20%–25% of patients with thymic carcinoid have a family history of multiple endocrine neoplasia type 1 (MEN-1), radiographic screening just after the operation did not detect any endocrine tumors. However, the patient had a urinary calculus 4 months 7 months after the operation. Endocrinological examination then revealed mild hypercalcemia, hypophosphatemia, hyperinsulinemia, and hyperprolactinemia. Radiologically, a parathyroid tumor and a pancreatic tumor were found. The patient was referred to a university hospital and a mutation of MEN-1 gene was detected. The diagnosis of MEN-1 was confirmed about 1 year after the operation.     

Gastric carcinoid tumors in multiple endocrine neoplasia-1 patients with Zollinger-Ellison syndrome can be symptomatic, demonstrate aggressive growth, and require surgical treatment

BACKGROUND: Gastric carcinoid tumors occur in 15% to 50% of patients with multiple endocrine neoplasia-1/Zollinger-Ellison syndrome (MEN-1/ZES) but are thought to be benign. We report 5 patients with MEN-1/ZES with symptomatic, aggressive gastric carcinoid tumors that required surgical procedures. METHODS: This was a retrospective chart review. RESULTS: Each patient had MEN-1/ZES. Each patient had innumerable gastric carcinoid tumors with symptoms. The fasting gastrin level was 47,000 pg/mL (normal, <200 pg/mL); the basal acid output was 79 mEq/hr (n = 3), and the age at surgical exploration was 47 +/- 6 years, with a duration of MEN-1 of 21 +/- 3 years and of ZES of 15 +/- 2 years. All patients had elevated 5-HIAA or serotonin levels. Somatostatin receptor scintigraphy showed increased stomach uptake in 4 patients (80%). Four patients had a total gastrectomy; 4 patients had lymph node metastases removed, and 3 patients had liver metastases resected. One patient who did not have a total gastrectomy had liver carcinoid metastases. CONCLUSIONS: These results demonstrate that gastric carcinoid tumors in patients with longstanding MEN-1/ZES may be symptomatic, aggressive, and metastasize to the liver. With increased long-term medical treatment and life expectancy, these tumors will become an important determinant of survival.     

Thymic carcinoids in multiple endocrine neoplasia type 1.

OBJECTIVE: To study the clinical, pathologic, and genetic features of thymic carcinoids in the setting of multiple endocrine neoplasia type 1 (MEN1) and to study means for detection and prevention of this tumor in patients with MEN1. SUMMARY BACKGROUND DATA: Thymic carcinoid is a rare malignancy, with approximately 150 cases reported to date. It may be associated with MEN1 and carries a poor prognosis, with no effective treatment. Its underlying etiology is unknown. METHODS: Ten patients with MEN1 from eight families with anterior mediastinal tumors were included in a case series study at tertiary referring hospitals. Clinicopathologic studies were done on these patients, with a review of the literature. Mutation analysis was performed on the MEN1 gene in families with clusterings of the tumor to look for genotype-phenotype correlation. Loss of heterozygosity was studied in seven cases to look for genetic abnormalities. RESULTS: Histologic studies of all tumors were consistent with the diagnosis of thymic carcinoid. Clustering of this tumor was found in some of the families-three pairs of brothers and three families with first- or second-degree relatives who had thymic carcinoid. All patients described here were men, with a mean age at detection of 44 years (range 31 to 66). Most of the patients had chest pain or were asymptomatic; none had Cushing's or carcinoid syndrome. All tumors were detected by computed tomography (CT) or magnetic resonance imaging (MRI) of the chest. The results of octreoscans performed in three patients were all positive. Histopathologic studies were consistent with the diagnosis of thymic carcinoid and did not stain for ACTH. Mutation analysis of the families with clustering revealed mutations in different exons/introns of the MEN1 gene. Loss of heterozygosity (LOH) studies of seven tumors did not show LOH in the MEN1 region, but two tumors showed LOH in the 1p region. CONCLUSIONS: MEN1-related thymic carcinoids constitute approximately 25% of all cases of thymic carcinoids. In patients with MEN1, this is an insidious tumor not associated with Cushing's or carcinoid syndrome. Local invasion, recurrence, and distant metastasis are common, with no known effective treatment. We propose that CT or MRI of the chest, as well as octreoscanning, should be considered as part of clinical screening in patients with MEN1. We also propose performing prophylactic thymectomy during subtotal or total parathyroidectomy on patients with MEN1 to reduce the risks of thymic carcinoid and recurrence of hyperparathyroidism. Its male predominance, the absence of LOH in the MEN1 region, clustering in close relatives, and the presence of different MEN1 mutations in these families suggest the involvement of modifying genes in addition to the MEN1 gene. A putative tumor suppressor gene in 1p may be involved.     

Prevalence of the neuroendocrine phenotype in thymus neoplasms

To determine the prevalence of neuroendocrine differentiation in human thymic neoplasms, which are unusual tumours that may range from well-differentiated to overtly malignant, poorly differentiated lesions, an immunohistochemical study was conducted in 23 thymic neoplasms re-classified on the basis of the new 1999 WHO classification. Immunohistochemical evidence of neuroendocrine differentiation in the form of reactivity to the markers synaptophysin, neuron-specific enolase and chromogranin A was found in 6 of 23 tissues (26%). Two of 3 patients with thymic carcinoids (or well-differentiated thymic neuroendocrine carcinoma) were affected by multiple endocrine neoplasia type 1 (MEN-1). Myasthenia gravis was present in 2/6 patients with neuroendocrine differentiation. This study demonstrates the high prevalence of neuroendocrine markers in human thymic neoplasms. Whether and in what percentage of cases immunohistochemical reactivity may be correlated with clinical behaviour and outcome remains a controversial issue. Finally, the association between thymic carcinoids and MEN-1 is a strong indication for clinical and possibly genetic screening of all patients presenting this feature, just as all MEN-1 patients have to undergo thoracic imaging and prophylactic thymectomy in selected cases.     

Thymic carcinoid tumor--report of 3 operative cases]

Three cases of thymic carcinoid were surgically treated in our hospital. All 3 cases belonged to stage IVb (Masaoka's classification) because of anterior lymph nodes metastasis. A 44-year-old male patient died of multiple metastasis of bone and liver in 94 months after the operation. A 45-year-old female patient who had undergone operation 4 years ago, was re-operated on for recurrent carcinoid tumor but complete resection of the tumor could not be performed because of the tumorous invasion to superior vena cava, pericardium and costal bone. After the operation she has been treated by radiotherapy and any re-growth of the tumor has never been detected for 1 year. Another 50-year-old male patient who had been operated and treated by chemo-radiotherapy for thymic carcinoid before 50 months was diagnosed as recurrent tumor at left interpectoral lymph node. Radiotherapy is now preparing for this patient. 160 cases of thymic carcinoid reports in Japan were reviewed. 37 cases were stage IVb and 36 cases had supraclavicular or mediastinal lymph nodes metastasis. Those cases which had been underwent complete resection followed by radiotherapy seemed to have better prognosis. We conclude that patients of thymic carcinoid should be treated with complete resection including supraclavicular and mediastinal lymph nodes dissection, followed by radiotherapy.     

Multiple thymic carcinoids

We present a very rare case of simultaneous thymic carcinoids with similar size, one of which showed spontaneous regression. A 68-year-old man was admitted to the hospital because of two similar abnormal masses at his anterior mediastinum on chest computed tomography, one of which had decreased from 25 to 16 mm in diameter. A total thymectomy was performed and the pathologic examinations revealed that both tumors were atypical carcinoids. There have been seldom reports of multiple thymic carcinoids, and this case might suggest that total thymectomy is the best way to treat thymic carcinoid because of the possibility of multicentric origins.     

Coexistence of sarcoidosis and thymic carcinoid

We report a case of coexistence of sarcoidosis and thymic carcinoid. A 57-year-old man was pointed out the anterior mediastinal tumor when his generator of pacemaker was exchanged. The tumor was diagnosed as atypical carcinoid by percutaneous needle biopsy. Chest computed tomography (CT) revealed the mediastinal and right hilar lymphadenopathy. Preoperative transbronchial aspiration cytology revealed no malignancy and extirpation of the anterior mediastinal tumor was carried out together with left diagraphmatic nerve and pericardium. The histopathological examination of the pretracheal lymph node was sarcoidosis. Postoperative radiation was performed because the thymic carcinoid invaded the pericardium. The right hilar lymph node was enlarged after the radiation. Five months later, follow-up chest CT showed reduction of the right lymph node. He has been alive without recurrence of the thymic carcinoid for 3 years. Simultaneous occurrence of sarcoidosis and thymic carcinoid is extremely rare. Assessment of mediastinal lymph node is difficult either preoperatively and postoperatively. Histological confirmation of the lymph node and careful follow-up are necessary.     

Thymic carcinoid in association with MEN syndromes.

Although carcinoid tumors in association with multiple endocrine neoplasia syndrome (MEN) has been well described, thymic carcinoid in association with MEN is extremely rare (only 23 cases in the world literature). A patient with thymic carcinoid and MEN-I was treated with surgical resection and postoperative radiation therapy, which was later followed by subtotal parathyroidectomy for hyperparathyroidism. Four years later, a symptomatic recurrence of his thymic carcinoid was resected from below his right clavicle. Six years after his original operation, the patient came to the hospital with pancreatitis, and a 5 cm, distal, pancreatic metastasis was resected. He now has symptomatic paraspinal and pleural metastases and is receiving somatostatin. Review of the world's literature shows that the majority of patients with thymic carcinoid and MEN-I are men with an average age of 37 years. Their clinical course is indolent, and surgery represents the only means of cure. Adjuvant chemotherapy and radiation therapy confer no survival advantage. The surgical decision making involved in treating a patient with thymic carcinoid and hyperparathyroidism associated with MEN is also discussed.     

Lymphogenous and hematogenous metastasis of thymic epithelial tumors

BACKGROUND: A TNM classification has been established for various tumors. However, the TNM classification of thymic epithelial tumor has not been established yet. METHODS: We received replies to a questionnaire on thymic epithelial tumors from 115 institutes. We compiled a database of 1,320 patients with thymic epithelial tumor (1,093 thymomas, 186 thymic carcinomas, and 41 thymic carcinoids) who were treated between 1990 and 1994. We used a tentative TNM classification of thymoma presented by Yamakawa and associates in 1991. The regional lymph nodes of the thymus were classified into three groups: anterior mediastinal lymph nodes (N1), intrathoracic lymph nodes (N2), and extrathoracic lymph nodes (N3). RESULTS: The rate of lymphogenous metastasis in thymoma, thymic carcinoma, and thymic carcinoid was 1.8%, 27%, and 28%, respectively. Most tumors with lymph node metastasis metastasized to N1 (thymoma, 90%; thymic carcinoma, 69%; thymic carcinoid, 91%). The 5-year survival rates of N0, N1, and N2 thymoma were 96%, 62%, and 20%, respectively. The 5-year survival rates of N0, N1(,) N2, and N3 thymic carcinoma were 56%, 42%, 29%, and 19%, respectively. The 5-year survival rates of M0 and M1 thymoma were 95% and 57%. The 5-year survival rates of M0 and M1 thymic carcinoma were 51% and 35%. Multivariate analysis demonstrated that survival of patients with thymoma was dependent on the clinical stage of Masaoka and complete resection. In thymic carcinoma, survival was dependent on lymph node metastasis and complete resection. CONCLUSIONS: The N factor was one of the predictors of survival in thymoma and thymic carcinoma. However, M factor showed less influence on survival than T or N factors.     

胸腺类癌外科治疗的长期结果

目的探讨胸腺类癌的临床表现,分类与预后的关系,以及手术方式及术后辅助治疗特点,以提高对该病的认识。方法回顾性分析北京协和医院1980年1月至2006年1月18例胸腺类癌的外科治疗和随诊结果。开胸探查活检2例,姑息性切除2例,完整切除14例,包括2例上腔静脉系统切除移植人工血管。采用寿命表法计算生存率,用Cox单因素回归模型分析胸腺类癌预后的影响因素。结果2例行开胸探查患者分别于术后1年和2年死亡;2例姑息性切除术后患者症状暂时缓解;完整切除患者除1例合并柯兴综合征术后2周死于败血症,其余13例术后完全恢复,随诊5个月至15年良好。全组3年、5年、10年生存率分别为72.6%、60.5%和40.3%。经Cox单因素分析结果:纵隔淋巴结转移(P=0.047)、病理类型(P=0.000)、手术方式(P=0.000)和术后综合治疗(P=0.018)是影响预后的因素。结论胸腺类癌不同于胸腺瘤、胸腺癌,临床诊断困难;病理学分典型和不典型胸腺类癌,两者临床表现和预后明显不同。不典型类癌恶性程度高,切除后容易复发和转移,预后较差。彻底切除肿瘤以及受侵的组织和器官,可以明显提高长期生存率。术后放疗、化疗有一定辅助作用。     

Thymic Carcinoid Associated With Multiple Endocrine Neoplasia Syndrome Type I

Thymic carcinoids are a rare entity that may be associated with endocrine diseases like Cushing's syndrome or multiple endocrine neoplasia syndrome type I (MEN1). These tumors represent 4% of anterior mediastinal tumors and are characterized by their very aggressive behavior.We present the case of a patient with a previous MEN 1 diagnosis in whom, during the follow up of his disease, a thoracic image compatible with thymic carcinoid was detected. After an extended thymectomy that included peri-thymic fat resection, the clinical diagnosis was confirmed. A follow-up examination 14 months later revealed a suspicious lesion that suggested local recurrence, therefore the patient was reoperated on. The pathology report of this surgery indicated post-radiation fibrosis.Likewise, we present a review of the current diagnostic and therapeutic management of patients with MEN1 syndrome who are diagnosed with thymic carcinoid.     

Resected invasive thymoma with multiple endocrine neoplasia type 1

We report a rare case of multiple endocrine neoplasia (MEN) type 1 with thymoma. A 57-year-old woman with a chronic duodenal ulcer and hypoglycemia had been seen at a nearby clinic. Abdominal echogram revealed two nodules in the pancreas and she was referred to our hospital for evaluation. Her diagnosis was MEN type 1, gastrinoma and hyperparathyroidism with anterior mediastinal tumor. There were high calcium levels in the blood and urine. Gastrin was quite high. A chest X-ray revealed a retrosternal tumor. Computed tomography revealed an anterior mediastinal tumor without sign of invasion to the surrounding organs, and two small masses in the pancreas. Cervical echogram revealed a few masses in both sides behind the thyroid. From these findings, her preoperative diagnosis was MEN type 1 with thymic carcinoid or thymoma. We performed thymectomy and parathyroidectomy concomitantly. The mediastinal tumor was diagnosed as invasive thymoma. (Jpn J Thorac Cardiovasc Surg 2006; 54:171-173)     

Thymic carcinoid tumor with Cushing syndrome

A case of a 71-year-old male with ectopic adrenocorticotropic polypeptide (ACTH)-producing thymic carcinoid tumor presenting Cushing's syndrome was reported. This patient had symptoms of fatigue and a polyposia for 2 years before a mediastinal tumor was detected. Chest computed tomography (CT) scan demonstrated an anterior mediastinal mass, and serum ACTH and cortisol level revealed very high. Secretion of cortisol was not inhibited in an 8-mg dexamethazone suppression test. We diagnosed ectopic ACTH-producing tumor, and performed complete excision of the thymus including thymic tumor. Histologically, the tumor demonstrated typical carcinoid with the positivity of ACTH immunostaining. After the operation, ACTH and cortisol levels were reduced and the clinical symptoms were improved rapidly. We have concluded that it is important to control serum perioperative cortisol level for the prevension of morbidity.     

Adrenal involvement in multiple endocrine neoplasia type 1: results of 7 years prospective screening

Background Adrenal tumors are a common manifestation of the multiple endocrine neoplasia type 1 (MEN-1) syndrome. Prevalence in recent studies varies between 9 and 45%. A genotype–phenotype correlation has been described as well as the development of adrenocortical carcinomas. Long-term prospective data are still lacking. Materials and methods Thirty-eight MEN-1 patients with proven germline mutations have been prospectively observed in a regular screening program in our hospital. Adrenal glands have been screened by biochemical analysis and either by endoscopic ultrasound (EUS) or computed tomography (CT) or both. Median follow-up was 48 months (12–108 months). Age at diagnosis of MEN-1, type of adrenal tumor, genotype, therapy, and clinical characteristics have been analyzed. Results In 21 (55%) patients, adrenal involvement of the disease was detected. Adrenal lesions were detected in average 6.9 years after the initial diagnosis of MEN-1. Median tumor size was 12 mm (5–40 mm). Tumor size smaller than 10 mm was observed in 11 patients. Twelve patients had unilateral while nine had bilateral adrenal lesions. EUS detected all adrenal tumors, whereas CT failed in seven cases. In three patients, functioning tumors (one pheochromocytoma, one bilateral Cushing adenoma, and one adrenocortical carcinoma) and one nonfunctioning adenoma were diagnosed by histology and biochemical assessment. Two laparoscopic adrenalectomies and one laparoscopic subtotal resection were performed. Nonfunctioning adrenal lesions, not characterized by histology yet, were found in 18 patients. There was no statistical difference with regard to adrenal involvement between patients with germline mutations in exons 2 and 10 (12/21) and those with mutations in exons 3–9 (6/11). Conclusion MEN-1-associated adrenal tumors are mostly small, benign, and nonfunctioning and much more common than previously reported. EUS was the most sensitive imaging procedure. The genotype–pheotype correlation previously suggested by our group could not be confirmed. This work was presented at the 2nd Biennial Congress of the ESES, May 2006, in Krakow, Poland.     

Thymic carcinoid with lymph node metastases; report of a case

A 71-year-old man was admitted to our hospital because of the detection of an anterior mediastinal tumor. Fluorodeoxyglucose-positron emission tomography (FDG-PET) showed abnormal accumulations in the tumor and the hilar and the supra-clavicular lymph nodes. Preoperatively, percutaneous needle biopsy of the tumor revealed thymic carcinoid. Tumor resection and thymectomy with mediastinal and supra-clavicular lymph nodes dissection were performed because of suspecting metastasis to the lymph nodes from FDG-PET. Postoperative pathological diagnosis revealed atypical carcinoid and metastases to the mediastinal and supra-clavicular lymph nodes. In our case, FDG-PET was useful in detecting the thymic carcinoid and lymph node metastasis. It is desirable to perform clinical research by many facilities for the assessment of FDG-PET as a diagnostic tool and postoperative chemo-radiation therapy for thymic carcinoid.     

Thymic Carcinoid in a Patient with Multiple Endocrine Neoplasia Type 1: Report of a Case

We report herein the rare case of a 33-year-old man found to have a multiple endocrine neoplasia type 1 (MEN1)-associated carcinoid tumor in the thymus. A chest roentgenogram demonstrated an asymptomatic anterior mediastinal mass, 7 cm in diameter, and ultrasound-guided percutaneous Tru-Cut biopsy revealed a carcinoid tumor of the thymus. An extended thymectomy was performed through a median sternotomy and pathological examination confirmed the diagnosis of a thymic carcinoid tumor, which was mainly encapsulated with locally invasive growth into the pleura. Despite the absence of a family history of MEN1, he was treated for two pancreatic islet cell tumors, hyperparathyroidism, an adrenal tumor, and a retroperitoneal lipoma. MEN1 mutations were detected both in blood samples and pancreatic tumor tissues. He is now well without any evidence of tumor recurrence 27 months after the operation for the thymic carcinoid. MEN1 mutations were screened by direct nucleotide sequencing of all protein-coding regions of exons 2–10 of the MEN1 gene. Heterozygous germline mutation was detected in the blood sample analyses. Moreover, fresh-frozen pancreatic tumor tissues showed a loss of heterozygosity in the MEN1 region. Received: January 25, 2000 / Accepted: November 20, 2000     

Prospective Evaluation of Imaging Procedures for the Detection of Pancreaticoduodenal Endocrine Tumors in Patients with Multiple Endocrine Neoplasia Type 1

Early identification of pancreaticoduodenal endocrine tumors (PETs) in multiple endocrine neoplasia type 1 (MEN-1) is mandatory, because these tumors represent the most common cause of death within the syndrome. The diagnostic value of imaging procedures has therefore been evaluated in a prospective observational study. Between December 1997 and June 2003 twenty-two MEN-1 patients with genetically confirmed disease were followed for PETs using a standardized screening program with serum hormone measurements, endoscopic ultrasonography (EUS), computed tomography (CT), and somatostatin-receptor scintigraphy (SRS). Results could be validated by surgery and histopathology in 13 patients during 18 operations. In 12 asymptomatic patients with tumors measuring 10 mm or less, who have not yet undergone operation, PETs were detected by EUS in 12/12, by CT in 1/12, and by SRS in 2/11 cases. In 13 patients who have undergone surgical exploration EUS, CT, and SRS were true positive in 12 of 16, 7 of 13, and 12 of 17 cases, respectively, although the number of tumors detected by each imaging procedure alone was lower than the number detected intraoperatively and histopathologically in almost every case. A solitary liver metastasis in one patient and a nonfunctioning PET recurrence in another were identified only by SRS. Endoscopic untrasonography is the most sensitive imaging procedure for the detection of small ( 10 mm) PETs in MEN-1, whereas SRS is the procedure of choice for the identification of metastases of MEN-1 PETs—i.e., for staging. Detection of PETs at an early stage by an aggressive screening program using EUS may lead to prompt surgical intervention and improved prognosis of MEN-1 PETs.This article was presented at the International Association of Endocrine Surgeons meeting, Uppsala, Sweden, June 14–17, 2004.     

Complete resection of recurrent thymic carcinoid using cardiopulmonary bypass.

We report a case of recurrent thymic carcinoid (multiple episodes of recurrence over a 14-year period) invading the right atrium and superior vena cava, which was resected using cardiopulmonary bypass. In our case with dense adhesion between the great vessels and the sternum as a result of repeated operations and therapeutic irradiation, the innominate artery was injured while re-sternotomy, which was successfully repaired under deep hypothermic circulatory arrest. Repeated aggressive surgical resection might improve prognosis of the recurrent thymic carcinoid even in patients with extended lesions, which could be completely resected only on cardiopulmonary bypass.     

Thymic carcinoid tumor

In this report on 3 cases of thymic carcinoid, tumors recurred in 2 patients not undergoing lymph node dissection. We review 47 cases of this disease taken from the Japanese literature, and discuss surgical procedures for reducing recurrence. In 9 of 20 cases of recurrence in encapsulated thymic carcinoid, lymph nodes were not dissected in eight. Differential diagnosis of an anterior mediastinal tumor should include thymic carcinoid, for which lymph nodes should be routinely dissected, even when the tumor is encapsulated.