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.     

ACTH-secreting thymic carcinoid associated with multiple endocrine neoplasia type 1

Thymic carcinoids are classified into three categories: (1) nonsecretory tumors, (2) hormonal secretory tumors, and (3) tumors associated with multiple endocrine neoplasia type 1. We report a rare case with adrenocorticotropic hormone secreting thymic carcinoid with multiple endocrine neoplasia type 1. Radiologic examination showed an anterior mediastinal mass and a parathyroid tumor. Blood analysis revealed high levels of parathyroid hormone and adrenocorticotropic hormone. Urine cortisol and 17-hydroxycorticoids levels were also elevated. Extended thymectomy was performed. Subsequently adjuvant radiation therapy and parathyroid tumor resection were performed. A germline mutation of exon 7 in the multiple endocrine neoplasia type 1 gene was detected and a somatic mutation of exon 9 was demonstrated in the thymic tumor.     

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.     

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.     

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.     

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.     

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 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.     

Atypical carcinoid of thymus associated with multiple endocrine neoplasia syndrome type 1

Thymic carcinoid associated with multiple endocrine neoplasia syndrome type 1 (MEN-1) is a rare tumor. We report a case of MEN-1-related thymic carcinoid. The patient reported herein had already been diagnosed with MEN-1 and was found to have a mediastinal mass. She underwent thymectomy with partial resection of the left innominate vein and lung. Histological examination revealed atypical carcinoid with infiltration. MEN-1 gene mutation was detected by employing the direct nucleotide sequencing method. Postoperative 2-fluoro-2-deoxyglucose positron emission tomography showed probable multiple metastases in the vertebrae and myocardium. However, she has been alive and asymptomatic for 2 years postoperatively. MEN-1-related thymic carcinoid is often insidious with a poor prognosis. We suggest chest computed tomography scan or magnetic resonance imaging for MEN-1 patients and serological or genetic screening for patients with thymic carcinoid to screen for MEN-1.     

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.     

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.     

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)     

Prevention of syngeneic graft-versus-host disease by recovery of thymic microenvironment after cyclosporine

Following a course of cyclosporine, syngeneic rat radiation chimeras consistently develop a GVHD-like syndrome. Correlation of the thymic immunopathology with conditions leading to syngeneic graft-versus-host disease (sGVHD) suggested the hypothesis that reconstitution of the normal thymic microenvironment after CsA is necessary for self-tolerance. When thymic regeneration is impaired, as in rats receiving previous mediastinal irradiation, then self-reactive effector cells are not regulated and proceed to damage the target tissues. Alternately, it could be argued that the observed thymic abnormalities are irrelevant to sGVHD. To test the primary hypothesis, post-CsA thymic reconstitution was prevented by total thymectomy in unirradiated rats. These rats consistently developed acute type sGVHD seen at 7 and 21 days post-CsA while rats from the CsA-treated sham thymectomy control group failed to develop sGVHD. Because thymectomy prior to CsA blocks sGVHD, most likely the peripheral effector cells in the post-CsA thymectomy group were derived from the CsA-altered thymus. The absence of sGVHD in the sham group indicates that the thymus led to active regulation of these cells after stopping CsA. If regeneration of the thymus restored only negative selection, then the sham thymectomy group should have also developed sGVHD. Flow cytometry and morphology of the spleen and lymph nodes demonstrated that the thymectomized rats, like CsA-treated radiation chimeras, experienced a significant delay in maturation of T cells following CsA. In contrast to the usual model in radiation chimeras, however, the post-CsA thymectomized rats did not convert to chronic type sGVHD. The importance of an abnormal thymus for this transition was confirmed in syngeneic radiation chimeras. Thymectomy after CsA in these rats also blocked the rapid transition to chronic sGVHD.     

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.     

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.     

Evaluation of 342 cases of mediastinal/thymic carcinoids collected from literature: a comparative study between typical carcinoids and atypical varieties.

This study is aimed to provide extensive and useful information based on an analysis of a large and reliable series of cases regarding mediastinal/thymic carcinoids, both typical and atypical. It also serves to assist investigators to improve their research activities in this particular field. In the present study, 342 patients (3.8%) with mediastinal/thymic carcinoids from amongst a total series of 8,970 patients with carcinoids, registered in the Niigata Registry for gut-pancreatic endocrinomas, were analyzed to clarify their detailed clinicopathological characteristics. Added to an analysis of mediastinal/thymic series including a comparison between typical and atypical carcinoid varieties, another comparative study was performed between the present series and a bronchopulmonary series. Mediastinal/thymic carcinoids may be briefly characterized by 1) no significant difference in major factors statistically demonstrable between typical carcinoids and atypical varieties, 2) a male preponderance, 3) difficult (delayed) preoperative diagnosis, 4) a high rate of metastasis, 5) a large tumor size on average (delayed detection), 6) a low rate of the carcinoid syndrome, 7) a high rate of association of the Cushing syndrome, and 8) low postoperative survival rates.     

Thymic mucosa-associated lymphoid tissue lymphoma involving lymph nodes

INTRODUCTIONThymic mucosa-associated lymphoid tissue (MALT) lymphoma involving lymph nodes is quite rare with only 13 previous cases reported in the literature.PRESENTATION OF CASEThe 33-years-old female was referred to our department for the investigation of abnormalities on computed tomographic (CT) scans. CT scans showed a 9-cm × 3-cm mass composed of a mixture of soft tissue and fat at the anterior mediastinum with lymphadenopathy in the neck, axillary and mediastinal regions. She was underwent complete surgical resection of the mass with regional lymph node dissection through a median sternotomy. Histological examination of the surgical specimens confirmed the diagnosis of MALT lymphoma arising in the thymus with nodal metastasis. She achieved complete remission after postoperative rituximab combined chemotherapy.DISCUSSIONThymic MALT lymphoma occurs most frequently in Asian female aged 40–60 years and commonly appears anterior mediastinal masses on CT scans. The excised tissue is necessary to confirm the accurate histological diagnosis. The disease usually remains localized for a long time, making local surgical resection highly effective. However, when the lymph nodes are involved, effective treatment approaches of the disease is still undefined.CONCLUSIONWe report a case of thymic MALT lymphoma involving lymph nodes, in which the patient was successfully treated with primary site resection with regional lymph node dissection followed by rituximab combined chemotherapy. Surgery provided not only a useful approach for collecting tissue for an accurate histological diagnosis, but also an effective local treatment, even in the case of advanced-stage thymic MALT lymphoma.     

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     

Multilocular thymic cyst associated with Sjögren's syndrome

A 61-year-old woman, who had been diagnosed as having Sj?gren's syndrome, developed an anterior mediastinal mass. She was diagnosed with Sj?gren's syndrome with thymoma, preoperatively. Extended thymectomy was performed. Macroscopically, the mediastinal mass showed thick-walled multiloculated cavities filled with turbid yellow fluid. Microscopically, the cyst lining was continuous with thymic lobules in the wall with inflammatory process, cholesterol granuloma formation, and prominent lymph follicular hyperplasia. She was diagnosed with multilocular thymic cysts associated with Sj?gren's syndrome.     

Microthymoma and microscopic thymomas associated with a thymic cyst without solid component

A 75-year-old asymptomatic man presented with an anterior mediastinal cyst without a solid component on computed tomography. Pathologic examination of the specimens obtained by thoracoscopic resection showed a thymic cyst with a 1.6-mm type A microthymoma in the surrounding thymic tissue. In addition, there were multiple hyperplastic nodules smaller than 1 mm histologically corresponded to microscopic thymomas. The patient underwent completion thymectomy through median sternotomy; thereafter, there was no residual thymic neoplasm detected. This was the first case report of a type A microthymoma. Microthymoma or microscopic thymoma could be present concomitantly with a thymic cyst without a solid component.