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 1988) 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.     

Neuroendocrine tumors of the thymus

Neuroendocrine tumors of the thymus (NETTs) are unusual thymic neoplasms that were misdiagnosed as thymomas until the 1970s, when they eventually acquired a distinct identity. No collective large series have been published so far, and information about clinical presentation, diagnosis, histology, and treatment is derived from analysis of the case series and case reports published over a long period. NETTs are more aggressive than their pulmonary and abdominal counterparts, presenting at a more advanced stage, often with distant metastases, and are associated with poor long-term survival. Most patients are symptomatic at presentation as a result of the local invasion. Twenty percent to 30% of the cases are associated with endocrine disorders, mostly Cushing syndrome and multiple endocrine neoplasia syndrome. There is no official staging system for these tumors and investigators rely on the Masaoka staging system used for thymomas. Histologically, 2 classification are used: the World Health Organization and the Armed Forces Institute of Pathology classifications. Histologically, most tumors show moderately to poorly differentiated histologic features, reflecting their aggressive clinical behavior. Surgery is the most effective treatment option, although the aggressiveness of the tumor often requires extensive resection. Chemotherapy and radiotherapy may be used either preoperatively or postoperatively, although the small number of patients does not allow the design of standard guidelines about optimal schedules and doses. Survival depends on stage at presentation, histologic degree of differentiation, associated endocrine syndromes, and resectability rate. Recurrences are frequent after surgery and may be locoregional or distant. Surgery is recommended when feasible in the treatment of locoregional recurrences.     

Primary neuroendocrine tumors of the thymus

Primary neuroendocrine tumors of the thymus are highly aggressive tumors that rarely occur. A little more than 200 cases have been reported, many of which were single case reports. Only a few articles contained modest series from single centers for analysis. A review of 157 cases collected from the major series reported to-date show a clinical pattern with male preponderance (male:female ratio, 3:1) and a mean age of 54 years. Most patients presented with symptoms and signs of local compression. Almost 50% of these tumors were functionally active and were associated with endocrinopathies. Several histologic variants have been described, all with similar ultrastructural features. The biologic behavior of these tumors shows a direct relation to the degree of differentiation. Whenever possible, surgical resection is the treatment of choice as adjuvant therapy is controversial and has been used with variable success. Potential therapies exploit the presence of somatostatin receptors on a variety of these tumors. Use of radiolabeled Octreotide for radionuclide therapy has yielded tumor inhibition in animal models and may have clinical application. Fifty-one percent of the patients survived 3 years, 27% survived 5 years, and less than 10% survived beyond 10 years. Histologic grade, tumor extension, and early detection are the most important factors affecting survival. Other prognostic factors that impact outcome include presence of endocrinopathy, incomplete resectability, nodal status, and presence of distant metastasis.     

Clinical and pathological aspects of thymic epithelial tumors

A histological classification of thymic epithelial tumors was presented by the World Health Organization (WHO) in 1999 and again in 2004 following slight modifications, in which thymic epithelial tumors were categorized as thymomas and thymic carcinomas. Whereas thymoma is defined as an organotypic (thymuslike) tumor, thymic carcinoma is a malignant epithelial neoplasm with a morphology similar to that of malignant neoplasms arising from other organs. Herein, the recent progress in research of thymic epithelial tumors is reviewed with reference to the WHO histological classification system, with the focus on thymomas. Thymomas are classified into five types—A, AB, B1, B2, B3—according to the shape and atypia of their epithelial cells as well as the abundance of lymphocytes. The invasiveness, prognosis, and genetic imbalance of thymomas have been shown to be related to this classification system. Myasthenia gravis is frequently associated with types B1 and B2. The WHO histological classification of thymomas is not only useful for treatment but reflects their biological characteristics, including genetic alterations. Advances are expected in future studies of thymomas from the standpoint of their clinical, pathological, and biological aspects. This review was submitted at the invitation of the editorial committee.     

Management of malignant tumors of the thymus

Twenty-eight patients with malignant tumors of the thymus were surgically treated during the 15-year period from 1969 to 1984. Twenty-six patients had far advanced disease when treatment was began. Of fifteen patients with malignant thymoma, the tumors were successfully removed in five patients by using the technique of combined resection of SVC. Of two patients with carcinoid, one is alive and another died two years after extended operation. Of two patients with malignant lymphoma, one with non Hodgkin's disease died three years after operation, and the other with Hodgkin's disease is alive with tumor bearing. It is important to distinguish malignant lymphoma from other types of thymic tumors, because chemo-radiotherapy is superior to surgical therapy. Of nine patients with germ cell tumor, two patients with seminoma have been well for 11 and 5 years. CDDP and radiotherapy were effective on their long survival. Three patients with embryonal carcinoma responded well to combined surgical and chemo-radiotherapy. But only one of them is alive with tumor free one year after operation. Prosthetic grafts were employed in 7 cases for replacement of the innominate and superior caval vein. Angiogram taken one month after operation disclosed the overall patency rate with 92% and the longest patent period confirmed was 4 years. Extended operation by using the prosthetic graft should be performed in the advanced cases to achieve a complete removal and to aim better prognosis for this kind of disease. In conclusion, aggressive surgical removal followed by radio-chemotherapy offers best cure of the malignant thymic tumor.     

Diagnosis and therapy of thymus tumors

In this paper we report about the treatment process of thymic tumours. Dominating among our patients are thymomas with lymphocyte predominance (n = 16) followed by epithelioid (n = 8) and spindle cell (n = 2) thymomas. For classification and for estimation of prognosis all thymomas were divided into macroscopical and histological stadiums I-IV. In the long-term process a better survival rate for patients with thymomas with lymphocyte predominance and histological stadium of invasion I was 93% over seven years. The worst results were reached by patients of the infiltration groups III and IV-the survival rate was 50%. By 17 of 26 patients suffering from a thymoma the tumours were associated with myasthenia gravis. Especially frequently we found class IIB and III according to Osserman. The survival rate in this patients was 76.5% (13 patients) in the treatment process. An improvement and stabilization of myasthenia gravis was possible for 13 patients. If the complete removal is limited by the growth of the tumor and by the infiltration rate, the further additional therapy--radiation therapy and polychemotherapy--will help to improve the prognosis.     

Surgical therapy for neuroendocrine tumors of the thymus

Summary. Neuroendocrine tumors of the thymus, also known as thymic carcinoids, are rare tumors of the anterior mediastinum. They occur sporadically or in association with the MEN I syndrome. We present five patients (four male, one female; age of first manifestation 19–53 years) who were operated on at our hospital between 1984 and 1995 for neuroendocrine thymic tumors. A hormone-producing tumor presented with Cushing's syndrome in two patients. Two patients had MEN I syndrome. Only in the female patient the primary tumor was confined to the thymus. We found lymph node metastases in three patients and a distant metastasis in one. The neuroendocrine tumors have a high rate of local recurrences and thus we performed 11 operations using a transthoracic or transsternal approach. Since there was no operative mortality and adjuvant therapies are of limited value, we recommend surgery even in case of recurrence.      

Clinical and functional aspects of the World Health Organization histologic classification of thymic epithelial tumors

The World Health Organization (WHO) histologic classification was presented by the international committee to provide a universal system for clinicians and researchers in 1999 and was further modified in 2004. This classification is mainly based on Müller-Hermelink et al.'s system and six distinct types were defined. Thymomas were classified into type A, AB, B1, B2, and B3 tumors, according to the shape and atypia of epithelial cells and also the abundance of lymphocytes. Another type of tumor is thymic carcinomas, which have apparent atypia of neoplastic cells. Neuroendocrine tumor (carcinoid) of the thymus was categorized as thymic carcinoma because of the resemblance of genetic aberrations. Several studies have shown that the WHO histologic type is correlated with the proportion of invasive tumors and is an independent prognostic factor along with Masaoka stage. Furthermore, association with myasthenia gravis, ability to induce CD4+CD8+T cells and express HLA-DR molecules, and chromosomal imbalances such as loss of heterogeneity were found to be correlated with the WHO histologic type. Thus, the WHO histologic classification system reflects the oncologic, immunologic, and genetic characteristics of thymic epithelial tumors. The clinical application of this classification system is expected.     

Synchronous primary epithelial tumors of the pancreas

INTRODUCTIONPancreatic incidentalomas are diagnosed at increased rates due to advanced pancreatic imaging. Coexistence of such lesions with another pancreatic pathology, however, is uncommon and their management might be perplexed by the anatomical location and the histological features of the lesion.PRESENTATION OF CASEA patient with obstructive jaundice was diagnosed with adenocarcinoma of the pancreatic head and underwent routine pancreatic imaging (CT) which revealed the coexistence of a small cystic lesion at the pancreatic body. Further investigation with MRCP and ERCP was unable to confirm a benign lesion and total pancreatoduodenectomy was performed. Histological examination showed a rare type of mixed serous–mucinous cystadenoma of borderline malignancy at the pancreatic body coexistent with an adenocarcinoma of the pancreatic head.DISCUSSIONCoexistence of a peripheral pancreatic cystic tumor with a ductal adenocarcinoma of the pancreatic head is a very rare incidence in medical literature. The management of the peripheral lesion is not straightforward and there can be uncertainty as to the extent of the pancreatic resection that may be required.CONCLUSIONAppropriate preoperative imaging has a significant impact on the definitive management of synchronous pancreatic tumors. Implications of a common pathogenetic pathway are also raised for this rare occurrence of two primary epithelial pancreatic tumors.     

Neuroendocrine tumors of the thymus: a clinicopathological and prognostic study

BACKGROUND: Neuroendocrine tumors of the thymus are rare, histologically diverse neoplasms with an unpredictable clinical behavior. This study provides a useful clinicopathological classification and determines the relevance of specific prognostic factors. METHODS: Ten neuroendocrine tumors of the thymus were analyzed for specific clinical and pathological features. Prognostic factors of these cases and 71 previously published cases were evaluated by Kaplan-Meier survival curves and Cox multivariate hazard model. RESULTS: There were 7 males and 3 females, with ages ranging from 26 to 77 years. Cases were classified as carcinoid tumor (2), atypical carcinoid tumor (6), and small cell carcinoma (2). An advanced clinical stage was evident in all instances with frequent recurrence (4) and metastases (8), and a short disease-free survival. Overall mortality was 60%. Statistical analysis of current and previously published cases (n = 81 total) revealed that unresectability (p = 0.0001), extent of surgical resection (p = 0.0002), and advanced clinical stage at presentation (p = 0.03) were associated with higher mortality. By multivariate Cox regression analysis, unresectability (p = 0.02) and advanced clinical stage (p = 0.03) were associated with decreased survival. CONCLUSIONS: Neuroendocrine tumors of the thymus can be classified into distinct clinicopathological entities, and specific factors have prognostic relevance.