research objectives: To determine whether the recently made known classification system for thymic carcinoid tumors/neuroendocrine carcinomas provides prognostic data.

research objectives: To determine whether the recently made known classification system for thymic carcinoid tumors/neuroendocrine carcinomas provides prognostic data, and to investigation the presentation, diagnosis, treatment, and prognostic factors of these rare tumors.

Design: Retrospective analysis.

Setting: Royal Brompton Hospital, London, UK

Results: Eight men and four women with a median age of 58 years. consummate excision was possible in nine patients. Postoperative staging revealed sum of two units stage I tumors, two stage II tumors, three stage III tumors, common stage IVA tumor, and four stage IVB tumors. All tumors demonstrated the histopathologic features of neuroendocrine tumors, which were confirmed by way of positive immunohistochemical staining for chromogranin A in 11 of 12 tumors and for CD56 in 12 of 12 tumors, and the demeanor of dense core granules in succession ultrastructural analysis in 9 of 9 tumors. All 12 tumors did not stain positively for somatostatin receptors. Three tumors were grade 1 six cases were grade 2 and three cases were grade 3 Follow-up was available in all patients. single patient died 1 month postoperatively. Distant metastasis disentangleed in nine patients (82%). Local resort was evident in six patients, of whom five had not received postoperative radiotherapy. Seven patients died of distant metastasis (22 to 83 month after surgery) sum of two units are alive and disease-free (at 67 and 81 months) and sum of two units are alive with disease (at 60 and 86 months)

Conclusions: Neither grading as neuroendocrine carcinomas nor any individual histologic parameter showed a significant association with prognosis. Initial aggressive treatment, including integral surgical excision and adjuvant radiotherapy, appears to show the best hope for extended survival. Adjuvant chemotherapy also should be considered, since the incidence of distant relapse is high.

solution words: mediastinum; neuroendocrine carcinoma; thymic carcinoid tumor

Abbreviations: AC = atypical carcinoid; ACTH = adrenocorticotrophic hormone; LCNEC = large confined apartment neuroendocrine carcinoma; MEN-1 = multiple endocrine neoplasia, emblem 1; SCC = small confined apartment carcinoma; SR = somatostatin receptor; TC = typical carcinoid

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Neuroendocrine tumors arising in the thymus are extremely rare. In 1972 Rosai and Higa (1) differentiated them from other tumors of the like kind as thymomas and tumors of the ectopic parathyroid gland. Subsequently there have simply been a few studies (2-5) reporting substantial numbers of cases, with greatest in quantity concluding that these tumors behave in a malignant fashion and have histopathologic features of malignancy when assessed with the criteria used for assessing primary pulmonary neuroendocrine tumors. greatest in quantity series have used the bourn carcinoid to describe these tumors, noting atypical features when at hand although De Montpreville et al (3) glance ated that they should all be regarded as belonging to a representation of neuroendocrine carcinomas. There also have been occasional reports of small lonely dwelling carcinomas (SCCs), (6-8) and, more lately large cell neuroendocrine carcinomas (LCNECs) (9) arising at this site. Because of the apparent difference in behavior and prognosis of thymic neuroendocrine tumors and those arising in the lung an alternative classification hypothesis has been proposed of well, moderately, and poorly differentiated neuroendocrine carcinomas, based onward mitotic count, amount of necrosis, preservation of neuroendocrine architecture, and step of cytologic atypia, (10) which has been reported as correlating with biological behavior. (11) We have therefore retrospectively reviewed a series of 12 patients, any of which have been reported previously, (6) to determine whether this classification classification provides prognostic data, and to examine at the presentation, diagnosis, and treatment of these rare tumors.

MATERIALS AND METHODS

The records of 12 cases diagnosed between 1977 and 1994 of thymic neuroendocrine tumors were studied. pair patients originated from Hospital Nord in Saint-Etienne, 10 originated from the Royal Brompton Hospital in London, where during the same period 135 thymic epithelial tumors were resect Thymic nenroendocrine tumors accounted for 74% of the total number of tumors. Clinical data and follow-up data were obtained from the patients' records, referring physicians, or patients and their families. The classification of Masaoka et al (12) for thymomas was used for postoperative staging (Table 1)

Slides were reviewed for all 12 patients, and immunohistochemistry was performed using MNF116 (1:80 dilution; Dako; Cambridge, UK) neurone-specific enolase (1:1000 dilution; Dako), chromogranin (1:20 dilution; Dako), synaptophysin (1:200 dilution; Dako), CD56 (1:200 dilution; Novocastra; Newcastle on the subject of Tyne, UK), somatostatin (1:400 dilution; Dako), p53 protein using DO7 antibody (1:500 dilution; Dako); and Ki67 (1:100 dilution; Dako) using an immunostainer (Horizon; Dako). Slides stained for p53 protein, Ki67, and CD56 were pretreated at pressure cooking, and slides stained for MNF116 were pretreated at trypsinization to facilitate epitope retrieval. Ultrastrucrural studies were undertaken using a transmission electron microscope (model 7000; Hitachi; Tokyo, Japan), as previously described. (6) As well as immunophenotype, the following histopathologic features were assessed: mitotic rate (number by 2 [mm.sup.2]), presence or absence of necrosis, architecture, carriage of local invasion, features of thymic differentiation (accompanying lymphocyte and perivascular lacunae). Tumors then were graded initially into typical carcinoid (TC) atypical carcinoid (AC), SCC or LCNEC according to the World Health Organization criteria for neuroendocrine thymic tumors, (13) and subsequently at the classification system proposed through Klemm and Moran (10) (Table 2)

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