Thymic Carcinoid Research Articles

A tentative tumor–node–metastasis classification of thymoma

To establish a tumor-node-metastasis (TNM) classification of thymoma, 207 thymoma patients seen at the First Department of Surgery, Osaka University, and the Second Department of Surgery, Nagoya City University, were evaluated. Lymphogenous and hematogenous metastases of thymoma were infrequent, but their frequency increased with the duration of the course. Lymphogenous metastasis was observed in few cases, but it was considered to progress from anterior mediastinal lymph nodes to intrathoracic and then to extrathoracic lymph nodes. No particular characteristics were observed in hematogenous metastasis. On the basis of these observations, a TNM classification of thymoma was established and applied it to 207 thymoma cases, but it had little advantage over conventional clinical staging. High percentages of thymic carcinomas and thymic carcinoids were in Stage IVB, and the TNM classification of these tumors was considered to be more useful.

Giant thymic carcinoid

Thymic carcinoid is a rare tumour. It may present with ectopic endocrine secretion or with symptoms of compression as a result of its size. A case is reported which presented with symptoms of compression where the size of the tumour was uniquely large such as to warrant the term giant thymic carcinoid. The typical histological features are described, together with its possible origin and its likely prognosis.

Clinicopathological study of malignant tumor of the thymus (invasive thymoma, thymic carcinoma and thymic carcinoid)

Clinicopathological study of malignant tumor of the thymus (invasive thymoma, thymic carcinoma and thymic carcinoid)

Coexisting thymic carcinoid tumor and thymoma

Thymic carcinoid tumors are unusual neoplasms that are different from thymomas. We report a case of coexisting thymic carcinoid tumor and thymoma associated with myasthenia gravis. The clinicopathological findings are discussed with a review of the literature.

Thymic carcinoid—A case report and review of the literature

We report herein a case of a patient with thymic carcinoid who was operated on twice and has been followed for 9 years. In 1979, the original tumor was removed through an emergency left thoracotomy incision done for a hemothorax caused by an anterior mediastinal biopsy. Tumor recurrence was found 6 years later and removal carried out through a median sternotomy. The patient has been working and enjoying life following radiation and chemotherapy for a total of 9 years after his first operation. Recurrent thymic carcinoid has been thought to carry a poor prognosis, but this successfully treated case has been followed up for a long time after the removal of his recurrent tumor. We present this case and discuss other such cases reported in the Japanese literature.

Carcinoid tumors of the thymus

Carcinoid tumors arising in the thymus are rare. Since Rosai and Higa in 1972 distinguished these neoplasms from thymomas, fewer than 100 cases have been reported in the world literature. In a 38-year review (1950 to 1938) of surgically treated thymic tumors at Henry Ford Hospital, only 7 cases of thymic carcinoids were identified. These 6 men and 1 woman ranged in age from 27 to 70 years (mean, 48 years) at diagnosis. Follow-up was available in all patients with the longest survival being 12 years in 2 patients, and the shortest, 1 year, in 1. Recurrences and/or metastases developed in 4 of 7 patients between 1 and 9 years after initial resection. Recurrences were treated by reexcision in addition to radiation treatment and chemotherapy in 3 patients and reexcision with radiation treatment alone in 1 patient. A review of the literature along with our experience suggests that thymic carcinoids have a biological behavior distinct from thymoma in terms of cell origin, associated syndromes, neoplastic behavior, and prognosis. An aggressive surgical approach with complete initial excision of the tumor and of subsequent recurrences, along with radiation and probably chemotherapy, is the best available treatment today.

Management of the ectopic ACTH syndrome due to thoracic carcinoids

The association of a bronchial or thymic carcinoid as a source for the ectopic production of adrenocorticotropic hormone (ACTH) has been reported since 1957, with approximately 72 cases in the literature. These patients are characterized by young age, long duration of Cushing's syndrome because of the inability to find the ectopic source, and a high incidence of hypophysectomy or adrenalectomy without curing the disease. A substantial number of patients, upon discovery of the thoracic ectopic source, are also found to have malignant carcinoid tumors with lymph node metastases. Fifteen patients have been explored for a presumed intrathoracic source of ACTH at our institution since 1983 and 14 carcinoids (13 bronchial, one thymic) have been resected. Seventy-one percent (10/14) of the patients appear cured with normal plasma ACTH levels 5 to 57 months after resection, despite a 50% incidence of positive lymph node disease. Management of these patients demands an aggressive evaluation to prevent unnecessary adrenalectomy or hypophysectomy and to allow earlier resections before these potentially curable malignancies metastasize. When the tumor is discovered, thorough exploration and complete lymph node mapping with resection must be performed.

Monoclonal antibodies raised against mid‐gut carcinoid tumor cells

Three monoclonal IgG 2a antibodies were produced after immunization of mice with dispersed cells from a human mid-gut carcinoid tumor. Acetone-fixed cryosections of 57 primary and metastatic mid-gut carcinoid tumors as well as 2 hind-gut (rectal) carcinoids showed a conspicuous immunoreaction while a thymic carcinoid was essentially unstained with the antibodies. The 3 antibodies yielded a similar pattern of immunostaining. The immunoreaction comprised more than 95% of the carcinoid tumor cells, and it was more uniform and intense in primary tumors than in mesenteric, hepatic, and ovarian metastases of the mid-gut carcinoid tumors. Immunofluorescence studies on suspended carcinoid tumor cells showed that the antibodies bound to the surface membrane of the cells. The antibodies immunostained enterocytes of the small and large bowel, intestinal metaplasia of the stomach mucosa as well as colorectal adenocarcinomas. Endocrine pancreatic tumors producing vasoactive intestinal polypeptide, gastrin, somatostatin, and/or pancreatic polypeptide as well as the epithelium of pancreatic ducts were also stained with the antibodies, whereas a large number of other normal and abnormal human tissues, including benign and malignant insulinomas, were unreactive. The findings indicate that the antibodies recognize differentiation antigens on the carcinoid tumor cell surface preserved also on endocrine and nonendocrine cells of the normal bowel mucosa. The restricted tissue reactivity of the antibodies suggests that they may constitute useful tools in the histological characterization of carcinoid tumors. Further studies may reveal if they are applicable for immunolocalization and perhaps even immunotherapy of these neoplasms.

Thymic carcinoid: a case report

Thymic carcinoid: a case report

Ectopic adrenocorticotropic hormone syndrome: localization studies in 28 patients.

A variety of imaging procedures were performed in 28 patients with ectopic adrenocorticotropic hormone (ACTH) syndrome in an attempt to localize the ACTH-producing tumor. Diagnosis was made on the basis of removal of an ACTH-producing tumor or biopsy of metastases in the 19 patients with a proved source and the absence of ACTH gradients in bilateral samples of the inferior petrosal sinuses in the nine patients in whom an ACTH-secreting tumor had not been localized. Eleven bronchial carcinoids, two thymic carcinoids, three pheochromocytomas, and three islet-cell tumors constituted the proved sources. The condition has been cured in eight patients, six are alive with residual tumor, and five have died. Of the nine patients with undetected sites of ACTH production, one has died of pneumocystis pneumonia and eight are being treated medically or with bilateral adrenalectomy. Computed tomography (CT) of the chest and abdomen was the most helpful study in the detection of these tumors. Selective arteriography (bronchial and visceral), systemic and portal venous sampling, and iodine-131 meta-iodobenzylguanidine scintigraphy failed to demonstrate tumors when findings at CT were negative. Bronchial carcinoids constituted most of the ACTH-secreting tumors in this study (58%) and in a review of four large series (47%). To assure early detection of these potentially malignant tumors, pulmonary CT should be performed every 6 months, even after hypercortisolism has been medically or surgically controlled.

Expression of the Alpha Subunit of Human Chorionic Gonadotropin in Normal and Neoplastic Neuroendocrine Cells

The alpha subunit of human chorionic gonadotropin (HCG) was localized Immunohistochemically in paraffin sections of normal human tissues and neuroendocrine tumors. A small subset of dispersed neuroendocrine cells was positive in normal adult tissues, including gastric antrum, urachal remnant, anal glands and prostate. Positive cells were consistently present in perinatal lung but rare in adult lung. In contrast, the beta subunit was absent from these cells. Seventy-two of 151 extrapituitary neuroendocrine tumors (48%) were alpha subunit-positive. Thirty-three of 37 bronchial carcinoids (92%) were immunoreactive, with a high percentage of the tumors (54%) containing moderate to large numbers of positive cells. The alpha subunit was further demonstrated in 9 of 45 small cell lung carcinomas (20%), 19 of 35 extrapulmonary carcinoids (54%), 3 of 11 islet cell tumors (27%) and 8 of 13 medullary thyroid carcinomas (62%). Two of three malignant islet cell tumors were positive. Positive cells were usually few in number, except for two small cell lung carcinomas, two rectal carcinoids, one thymic carcinoid and one malignant islet cell tumor. Pheochromocytomas (n = 10) were negative. Eleven of 19 pulmonary tumorlets (58%) were alpha subunit-immunoreactive. A few beta subunit-positive cells were detected in only 6 lung lesions. The physiological significance of the imbalance of expression of HCG subunits by certain neuroendocrine cells and their tumors remains unknown.

Expression of Adrenocorticotropin-Releasing Hormone Precursor Gene in Placenta and Other Nonhypothalamic Tissues in Man

Adrenocorticotropin-releasing hormone (CRH) is a peptide originally isolated from the hypothalamus. Immunocytochemical and RIA studies have revealed that CRH-like peptide is also localized in human nonhypothalamic tissues and some tumors. To see if CRH is synthesized in these nonhypothalamic tissues and tumors, we examined preproCRH mRNA in these tissues by Northern blot analysis using a cloned human preproCRH gene as a probe. PreproCRH mRNA was detected in human hypothalamus, cerebral cortex, adrenal gland, placenta, pheochromocytoma, and thymic carcinoid. The content of preproCRH mRNA in placenta was apparently greater than that in the whole hypothalamus.

Neuroendocrine Neoplasms of the Thymus

Neuroendocrine tumors of the thymus bear many similarities to "carcinoids" and "oat-cell carcinomas" in other organs, and are clinicopathologically distinct from thymomas, thymic seminomas, and other primary tumors of this gland. They are associated with Cushing's syndrome or multiple endocrine neoplasia in 35% of cases, and are often locally aggressive. Approximately 30-40% of patients have distant metastases of their tumors that ultimately result in fatality, since the response of thymic neuroendocrine neoplasms to irradiation and chemotherapy is poor. Ultrastructural studies and immunohistochemical stains for chromogranin, protein gene product 9.5, and synaptophysin are effective tools for the diagnosis of thymic carcinoid and oat-cell carcinoma.

Carcinoid Tumors in the Chest

Bronchial carcinoids were found in eight of 620 patients with primary lung tumors (1.3%), and thymic carcinoids in three of 75 patients with tumors of the thymus (4%). Five of the bronchial carcinoids were in central sites and three were in peripheral sites.Seven of the bronchial carcinoids were removed by lobectomy and one by partial resection. There were no recurrences or metastases, but it was sometimes very difficult to distinguish between carcinoid and small cell lung cancer. The diagnosis was made by immunohistochemical staining using monoclonal antibodies derived from non-small cell lung cancer.It was difficult to differentiate between thymic carcinoid and invasive thymoma by chest X-ray or other imaging methods. Two thymic carcinoids could be resected only partially and one completely, but all three patients had recurrences or metastases.

胸腺カルチノイドの３例

胸腺カルチノイドの3症例を経験したので報告した.1例は術前に穿刺吸引細胞診にて診断し得た. 3例とも腫瘍による圧迫症状または上大静脈症候群により発症し, 胸部X-Pにて異常陰影を指摘された.得られた細胞はいずれも大小不同の軽度な円～類円形の核, 細類粒状のクロマチン, ライトグリーンに淡染する細胞質を有し, ときにロゼット形成を示す定型的なカルチノイドの所見であった. 電顕的にはいずれも神経内分泌穎粒が認められた.組織学的には, 髄様増殖巣の中央が壊死に陥る“Ba11”構造を特徴とする異型カルチノイドで, 2例で転移を認め, 1例は上大静脈症候群発症の9年後に転移により死亡した

Carcinoids associated with multiple endocrine neoplasia syndromes

Carcinoids occur in association with MEN types 1 and 2. To determine the relationship between carcinoids and MEN, we reviewed nine patients with carcinoids and other endocrine tumors. Analyzing these 9 patients and 56 other patients previously described in the literature, we found several clinically important relationships. In contrast to the usual midgut and hindgut origin, most carcinoids associated with MEN (69 percent) are of foregut origin (thymus 24 percent, bronchus 27 percent, stomach 3 percent, and duodenum 14 percent). Carcinoids are more commonly associated with MEN type 1 than MEN type 2 (59 patients and 6 patients, respectively). Thymic carcinoids associated with MEN are more common in men (15 versus 2), and most (82 percent) are malignant. Bronchial carcinoids associated with MEN are more common in women (15 versus 4), and most (74 percent) are benign. There is a strong association between thymic carcinoids and parathyroid tumors and between bronchial carcinoids and pituitary tumors. Most patients with carcinoids and hyperparathyroidism (82 percent) have had parathyroid hyperplasia or multiple parathyroid adenomas. Thus, carcinoids may occur in association with both MEN type I and MEN type II. MEN should be suspected in patients with foregut carcinoids. Patients with MEN and ectopic ACTH production should be considered to have bronchial carcinoids if they are female and thymic carcinoid if they are male. The thymus should be routinely removed in patients with MEN type I because of the possible presence of an ectopic parathyroid gland in this tissue and to prevent subsequent development of a carcinoid tumor.

Thymic lesions. Experience with computed tomography in 24 patients.

The value of computed tomography in the treatment of 24 patients with thymic lesions was analyzed. These included 21 patients with thymomas, and one each with thymic carcinoid, thymic lymphoma, and thymic cyst. Twelve patients were seen before therapy and 12 after treatment elsewhere. Computed tomography gave additional information in 14 of 24 cases and management was altered in two. The presence or absence of invasion of adjacent structures was predicted in 16 of 17 patients in whom computed tomographic-surgical correlation was available.

Problems of treatment of malignant thymic tumors

In a series of 52 malignant thymic tumors at our institution between 19751986, there were 34 thymomas, 4 thymic carcinomas, 5 germ cell tumors, 1 thymic carcinoid, 1 thymic malignant fibrous histiocytoma, and 7 malignant lymphomas.Aggressive surgical resection of tumors combined with chemotherapy and/or irradiation were tried to perform for these tumors. Thymomas, thymic carcinomas, and a thymic carcinoid seem to be good after the treatment.On the other hand, germ cell tumors and malignant lymphomas seem to be not good. Treatment effects for complications of thymomas were not satisfactory except for myasthenia gravis. Localized recurrences could be managed by surgical resection and/or irradiation, and W-CT is a useful examination to detect recurrences of tumors at early stage.

A Case Report of Thymic Carcinoid

A Case Report of Thymic Carcinoid

Thymic epithelial neoplasms.

We studied 57 tumors of the thymus seen at Vanderbilt University Medical Center between 1957 and 1982. By applying current diagnostic criteria, the classification of 13 tumors was changed. There were 45 epithelial tumors of thymus, including 32 thymomas, two thymic carcinomas, eight carcinoids, and three germinomas. The gross and microscopic features of these neoplasms overlap each other and several other tumors, but with knowledge of the variations it was usually possible to establish a diagnosis with light microscopy. In more difficult cases, electron microscopy was the most useful diagnostic method. New developments in immunologic staining were also of value. The diagnosis of thymoma was used for circumscribed and invasive neoplasms of thymic epithelium without anaplasia. Cytologically malignant thymic epithelial tumors were classified as thymic carcinoma. Thymic carcinomas were more aggressive than thymomas and were not associated with syndromes such as myasthenia gravis or anemia. Thymic carcinoids were frequently aggressive, and several of them produced corticotrophin or calcitonin. Thymic germinomas were histologically identical to testicular seminoma, but may be confused with thymoma because of their lymphocytic infiltrate. Invasive germinomas were radiosensitive.