Synchronous Thymoma and Thymic Carcinoid in A Woman With Multiple Endocrine Neoplasia Type 1: Case Report and Review

ObjectiveTo report a rare case of multiple endocrine neoplasia type 1 (MEN 1) in conjunction with concomitant thymoma and thymic carcinoid.MethodsWe describe a never before reported case involving a 63-year-old female patient with MEN 1 who had synchronous thymoma and thymic carcinoid tumors. A review of the pertinent literature is also undertaken.ResultsAlthough prognosis is stage dependent for patients with thymoma, patients with thymic carcinoids and MEN 1 have been reported to have an extremely poor prognosis, with many patients dying of complications from thymic carcinoid rather than dying of other manifestations of MEN 1. Our patient underwent successful surgical treatment and remains under surveillance for all aspects of the MEN 1 syndrome.ConclusionThymic tumors are rare, and thymic carcinoids, while very rare in occurrence overall, have a definite association with MEN 1. Thus, it is important for practitioners to screen for thymic tumors routinely in patients with MEN 1 and to treat such tumors aggressively when found because they can be a major cause of mortality. Many thymic carcinoids are far advanced before diagnosis, and optimal screening for and treatment of thymic carcinoid are still being developed. (Endocr Pract. 2008;14:713-716)     

Cytopathology of thymoma

From 1967 to 1981, 37 cases were diagnosed as thymoma by transthoracic fine needle aspiration biopsy. All were verified histologically, with no false-positive results. The various cytomorphologic patterns of thymoma are presented. All aspirates from the thymomas were reviewed and found to be composed of epithelial elements, with an admixture of lymphocytes in various proportions. There were 13 cases of lymphocytic predominance, 11 of epithelial-cell predominance, 4 of spindle-cell predominance, and 9 of mixed cell types. In the cytologic preparations the epithelial elements from different tumors exhibited different cytologic appearances and were tentatively subclassified into five types: small, intermediate, large, large pleomorphic and spindle shaped. The cytologic features of thymoma observed in aspiration biopsies are sufficiently distinctive from those of other anterior mediastinal tumors to be diagnostic. It appears feasible to investigate an anterior mediastinal mass with percutaneous fine needle aspiration for the purpose of establishing the diagnosis of thymoma prior to median sternotomy or thoracotomy.     

The Role of Radiation Therapy in Myasthenia Gravis

Myasthenia gravis is a serious and debilitating disease associated with conduction defects occurring at the myoneural junction. About 15 per cent of the patients have associated tumors of the thymus and 80 per cent of the remaining patients show abnormalities of the thymus. Although a definite relationship between cause and effect has not been proved, thymectomy or radiotherapy of the thymus does seem to influence the disease.Seven cases of myasthenia gravis in which radiation therapy was used at the University of California Medical Center are reported and compared with those described in the literature. It is concluded that patients whose disease is progressing and not well managed medically, and who have no evidence of thymoma, should be treated by irradiation—whether pre-operatively or as definitive treatment, depending on the result of irradiation. Those patients with evidence of thymoma should be irradiated before surgical procedure. Small tumors, or patients in whom surgical risk is increased, may be managed by radiation therapy alone.     

Epithelial cytologic atypia in a fine needle aspirate of an invasive thymoma. A case report.

Fine needle aspiration of a superior-anterior mediastinal mass in a 35-year-old man revealed sheets and clusters of epithelial cells intermingled with a few lymphocytes, characteristic of a thymoma. The presence of atypical cytologic features, such as nuclear pleomorphism, large and vesicular nuclei, prominent nucleoli and frequent mitotic figures, in the epithelial cells caused diagnostic confusion with a thymic carcinoma. However, the subsequent clinical and histologic findings were consistent with an invasive epithelial thymoma. The cytologic features in the present case showed that thymoma with intermediate cytology between that of an ordinary thymoma and thymic carcinoma may be encountered in fine needle aspirates of mediastinal tumors. The cytologic differentiation from a carcinoma may be difficult when the degree of epithelial atypia is high. Histologic confirmation is necessary for a definitive diagnosis.     

Octreotide in the treatment of malignant thymoma – Case report

Thymomas are the most common mediastinal tumors. Systemic therapy for patients with unresectable or recurrent thymomas is a challenging field in the current oncology research. There is some evidence that somatostatin analogs combined with corticosteroids may have a role in the treatment of advanced malignant thymoma; however, the role of these agents have not been fully evaluated.Case reportA 39-year-old man with metastatic thymoma was administered long-acting depot injection form of octreotide. Octreotide scan before the treatment initiation revealed low uptake. CT control after three months of the treatment revealed marked regression of pleural metastases, while the primary tumor mass remained stable. The treatment response was lasting for 9 months.ConclusionWe describe an interesting case of marked clinical and radiological response of advanced malignant thymoma to the treatment with octreotide in a heavily pre-treated patient, even though octreotide scan revealed low uptake.     

Combination percutaneous cryotherapy and iodine-125 seed implantation for unresectable malignant thymoma: Experience in 19 patients

Thymomas are the most common tumors of the mediastinum. These tumors often compress vital mediastinal organs and severely impact the quality of life of thymoma patients. To avoid the side effects of chemoradiotherapy, some patients with unresectable malignant thymomas have opted to undergo cryotherapy in our hospital. We reviewed the cryosurgery, nursing and follow-up records of our hospital for the past 8 years, and evaluated the safety and efficiency of cryotherapy in 19 patients with unresectable malignant thymomas. No severe complications involving the vital organs surrounding the tumor occurred during or after cryosurgery. The most common side effect was pleural effusion, which occurred in 11 patients and healed after drainage within 1 week. Cough, mediastinal and pericardial effusions, pneumothorax, mild fever and chest tightness also occurred and resolved 1 week after symptomatic treatment. Since our patients had high KPS scores and mild myasthenia gravis symptoms before the treatment, myasthenia gravis did not occur after the treatment. The progression-free survival of the patients was 14–29 months (median, 18 months), and did not differ between patients with large tumors and those with small tumors (P = 0.6753). In conclusion, cryotherapy is a safe and efficient method for the treatment of unresectable malignant thymoma.     

直径大于3厘米的周围型肺癌血流动力学的多排螺旋CT动态增强扫描研究

目的:研究直径3厘米以上周围型肺癌血流动力学的螺旋CT(电子计算机断层扫描,Computed Tomography)动态增强扫描的特点。方法:选取我院收治的肿瘤直径3 cm的周围型肺癌患者55例,肺部腺瘤(良性)患者10例,肺部炎性结节患者26例。分别进行螺旋CT动态增强扫描,记录其CT值、强化峰值(Peak enhancement,PH),绘制动态增强时间-密度曲线,计算并比较曲线最大增强线性斜率(steepes slope,SS)以及血流灌注量(blood perfusion,BP)。结果:肺部炎性结节患者的密度曲线在120 s达到最大值;肺癌患者的密度曲线至65 s达到高峰;胸腺瘤患者的密度曲线变化不明显。肺癌组PH平均值大于胸腺瘤组,差异有统计学意义(P0.05);胸腺瘤组PH平均值小于肺部炎性结节组,差异有统计学意义(P0.05);肺癌组SS和BP大于胸腺瘤组,差异有统计学意义(P0.05);胸腺瘤组SS和BP小于肺部炎性结节组,差异有统计学意义(P0.05)。结论:螺旋CT动态增强扫描能够反映直径3厘米以上周围型肺癌的血流动力学特点从而有助于在肺癌的诊断和鉴别诊断。     

Diagnosis of cervical thymoma by fine needle aspiration biopsy with flow cytometry. A case report

BACKGROUND: Cervical thymoma is a rare entity. To our knowledge, this is the 20th reported case of cervical thymoma and the fourth case of fine needle aspiration biopsy (FNAB) of this entity. To our knowledge, this is the only case in which cervical thymoma was a diagnostic consideration at the time of the FNAB diagnosis. The diagnosis was rendered because, unlike in previous cases, flow cytometric immunophenotyping was performed. CASE: A 46-year-old, white female presented with what was clinically thought to be a left thyroid nodule. The patient underwent FNAB at an outside institution, and the diagnosis of "possible mixed lymphoma" was made by morphology alone. The patient was referred to our institution for repeat FNAB. Based upon the cytologic findings (cells with lymphoid morphology), flow cytometry was performed, and a diagnosis of cervical thymoma (versus ectopic thymic tissue) was based upon flow cytometry findings combined with morphology. CONCLUSION: When FNAB of a cervical mass, particularly one clinically thought to be a thyroid nodule, shows lymphoid cells without thyroid follicular cells, immunophenotyping may be extremely helpful in arriving at the correct diagnosis.     

Evaluation of SHOX copy number variations in patients with Müllerian aplasia

Background

Thymic epithelial tumours (thymoma and carcinoma) are exceptionally rare in children. We describe a national multicentre series with a view to illustrating their clinical behaviour and the results of treatment.

Methods

From January 2000 all patients under 18 years of age diagnosed with "rare paediatric tumours" were centrally registered by the Italian centres participating in the TREP project (Tumori Rari in Età Pediatrica [Rare Tumours in Paediatric Age]). The clinical data of children with a thymic epithelial tumour registered as at December 2009 were analyzed for the purposes of the present study.

Results

Our series comprised 4 patients with thymoma and 5 with carcinoma (4 males, 5 females; median age 12.4 years). The tumour masses were mainly large, exceeding 5 cm in largest diameter. Based on the Masaoka staging system, 3 patients were stage I, 1 was stage III, 1 was stage IVa and 4 were stage IVb. All 3 patients with stage I thymoma underwent complete tumour resection at diagnosis and were alive 22, 35 and 93 months after surgery. One patient with a thymoma metastasizing to the kidneys died rapidly due to respiratory failure. Thymic carcinomas were much more aggressive, infiltrating nearby organs (in 4 cases) and regional nodes (in 5), and spreading to the bone (in 3) and liver (in 1). All patients received multidrug chemotherapy (platinum derivatives + etoposide or other drugs) with evidence of tumour reduction in 3 cases. Two patients underwent partial tumour resection (after chemo-radiotherapy in one case) and 4 patients were given radiotherapy (45-54 Gy). All patients died of their disease.

Conclusions

Children with thymomas completely resected at diagnosis have an excellent prognosis while thymic carcinomas behave aggressively and carry a poor prognosis despite multimodal treatment.     

Absence of the Epstein-Barr virus genome in the normal thymus, thymic epithelial tumors, thymic lymphoid hyperplasia in a European population

It has previously been shown that the Epstein-Barr virus (EBV) genome may be detected in some thymic tumors. We have investigated specimens of normal thymus, thymitis with lymphoid hyperplasia and a large spectrum of thymic epithelial tumors obtained from european patients for the presence of EBV genome by in situ hybridization and DNA-blotting methods. Cell lines established from seven of the thymic tumors were also tested for EBV. No EBV genome was demonstrated in any of the tumors examined, which included various types of thymoma and thymic carcinomas, nor in the non-neoplastic thymic specimens. However, unlike previous reports, no examples of lymphoepithelial-like thymic carcinoma, nor specimen from Asian patients were included in this study. We suggest that EBV is linked to a specific epithelial tumor type, namely the lymphoepithelial-like carcinoma, regardless of its site, and not to thymic tumors in general.     

Contribution of flow cytometric immunophenotyping to the evaluation of tissues with suspected lymphoma?

BACKGROUND: A critical analysis of the contribution of flow cytometric immunophenotyping (FCI) to the evaluation of lymph nodes and extranodal tissues with suspected lymphoma by a large, retrospective approach has not been reported previously and represents the purpose of this study. METHODS: A total of 278 lymph nodes and 95 extranodal tissue specimens submitted over a 2-year period with complete histologic, FCI, and immunohistochemical (IH) data formed the basis of the study. RESULTS: The FCI data contributed significantly to or was consistent with the final tissue diagnosis in the majority (94%) of the tissue samples. There is no well-described utility of flow cytometry markers for Hodgkin's lymphoma (HL) due to the usual scarcity of tumor cells in the final cell suspensions obtained from these tumors. However, the FCI data excluded non-Hodgkin's lymphoma (NHL) and suggested the possible usefulness of CD15 and CD30 by FCI in HL. In addition, immunophenotypic data by FCI in combination with touch imprint cytomorphology was useful in excluding a diagnosis of NHL in cases of nonhematopoietic malignancies and was particularly useful in defining the following hematopoietic tumors and malignancies: thymoma, T-cell lymphoblastic lymphoma, leukemia cutis, and plasma cell dyscrasia. Thus, IH was not essential for the diagnosis in these latter cases and was performed in only two cases (one thymoma and one plasma cell dyscrasia). Of interest, FCI supported the diagnosis in 3 cases of Ewing's sarcoma/primitive neuroectodermal tumor by detection of CD56 on the surface of the malignant cell. Only 11% of NHL were "negative" by FCI (i.e., an aberrant T-cell or monoclonal B-cell population was not identified). Reasons for these discrepancies included partial tissue involvement by the NHL with sampling differences, T-cell rich or lymphohistiocytic-rich variants with a small population of monoclonal B cells, marked tumoral sclerosis, poor tumor preservation, and T-cell NHL without an aberrant immunophenotype. Only 60% of CD30+ anaplastic large cell lymphomas (ALCL) were CD30+ by FCI. CONCLUSIONS: FCI data should always be correlated with light microscopy if no FCI abnormalities are detected; IH may need to be performed in selected cases. It is less necessary to perform microscopic examination of tissues when the FCI data are positive and indisputable. However, in selected cases in which FCI data is diagnostic, microscopic observations may provide additional information due to sampling.     

Malignant melanoma of mediastinum misdiagnosed as a spindle cell thymoma in a fine needle aspirate: a case report

BACKGROUND: Malignant melanomas in the medastinum are extremely rare. Both primary melanomas and metastatic lesions from a primary elsewhere can occur in the mediastinum. Aspiration biopsy of a melanoma at this unusual site may pose problems in diagnosis. CASE: A 35-year-old woman presented with an anterior mediastinal mass. Cytologic smears were hemorrhaghic and revealed a loosely dispersed population of spindle cells with prominent nucleoli. In view of the location, the possibility of spindle cell thymoma was suggested on cytology. Subsequent histology revealed a malignant melanoma. CONCLUSION: This case stresses that the cytopathologist should keep in mind the remote differential diagnosis of a malignant melanoma while evaluating spindle cell neoplasms of the mediastinum, especially in tumors with prominent cell dispersal and with cells that have prominent nucleoli even without melanin pigment. Accurate diagnosis helps in evaluating patients and avoids unnecessary surgery when the lesion represents a metastasis to the mediastinum from a primary elsewhere.     

Absence of the Epstein-Barr virus genome in the normal thymus,thymic epithelial tumors,thymic lymphoid hyperplasia in a European population

It has previously been shown that the EpsteinBarr virus (EBV) genome may be detected in some thymic tumors. We have investigated specimens of normal thymus, thymitis with lymphoid hyperplasia and a large spectrum of thymic epithelial tumors obtained from european patients for the presence of EBV genome by in situ hybridization and DNA-blotting methods. Cell lines established from seven of the thymic tumors were also tested for EBV. No EBV genome was demonstrated in any of the tumors examined, which included various types of thymoma and thymic carcinomas, nor in the non-neoplastic thymic specimens. However, unlike previous reports, no examples of lymphoepithelial-like thymic carcinoma, nor specimen from Asian patients were included in this study. We suggest that EBV is linked to a specific epithelial tumor type, namely the lymphoepithelial-like carcinoma, regardless of its site, and not to thymic tumors in general. Supported by the SFB 172, C8, grant to BB and by the Deutsche Forschungsgemeinschaft, grant Ki 370/1-1     

Entire hemithorax irradiation for Masaoka stage IVa thymomas

Thymomas are rare neoplasms that have an indolent growth with a preferentially intra-thoracic dissemination pattern. Surgery is currently the standard treatment of thymomas; however radiotherapy is often used in an adjuvant setting due to a high sensitivity of these tumors to such treatment. Postoperative entire hemithoracic irradiation has been used in selected Masaoka stage IVa cases after complete surgical excision of metastatic lesions.In the present article, the authors report three cases of Masaoka stage IVa thymoma that underwent entire hemithorax irradiation after surgical excision of metastatic lesions. The first two patients presented as stage IVa thymomas. The third case consisted of a pleural recurrence of a thymoma.Hemithoracic irradiation with low doses has been used by different authors; the available data shows that it is a well-tolerated treatment that could potentially lead to better loco-regional control and increased overall survival.     

Cardiac tamponade as a presentation of malignant thymoma

Morphologic, cytochemical and immunocytochemical studies of pericardial fluid from a 30-year-old man presenting with cardiac tamponade are described. Based on the results of the immunocytochemical studies and the histologic examination of excised pericardium, a diagnosis of malignant thymoma was made. This is the first documented case in which malignant cells were found in the pericardial effusion in a patient with invasive thymoma. The significance of using a multidisciplinary approach to the study of body fluids is discussed.     

Carcinoembryonic antigen content in fine needle aspirates of the lung. A diagnostic adjunct to cytology.

Carcinoembryonic Antigen (CEA) was measured in 59 consecutive fine needle aspirates (FNAs) of the lung from 58 patients to determine if the CEA content would enhance the sensitivity of the cytologic diagnosis. Twenty-eight males and 30 females with tumors 1-40 cm in diameter were studied. Final diagnoses were correlated with the clinical history, radiologic studies, tissue (when available) and follow-up. Image-guided FNAs were performed by radiologists using a 22-gauge Chiba needle and 20-mL syringe with one to four passes per specimen. Cytologic examination included rapid assessment in the radiology suite and a final diagnosis in 24 hours. CEA was measured by enzyme immunoassay using monoclonal antibody. Nine benign aspirates and 50 malignant aspirates were diagnosed. The sensitivity of cytology was 86% and specificity, 100%. Using 5 ng/mL as the cutoff, the sensitivity of CEA for malignant aspirates was 50% and specificity, 90%. The combined sensitivity of CEA and cytology was 95%. The mean CEA in malignant aspirates was 131 ng/mL and in benign aspirates, 2.41. The highest mean CEA was seen in adenocarcinoma, 402.6 ng/mL. Lower CEA content was seen in epidermoid carcinoma (58.6 ng/mL), large cell carcinoma (8.09), oat cell carcinoma, metastatic carcinoma of the kidney and breast, thymoma and lymphoma (each less than 1 ng/mL). Elevated CEA alone was diagnostic in two aspirates of bronchioloalveolar carcinoma; carcinoma with an unknown primary source, three; and large cell carcinoma, one. The adjunctive use of CEA in FNAs of the lung enhances the sensitivity of the cytologic diagnosis.     

Onconeural antibodies in sera from patients with various types of tumours

Purpose  We assessed the frequency and levels of onconeural antibodies in 974 patients with various types of tumours, but without apparent paraneoplastic neurological syndromes (PNS). Patients and methods  We included patients with the following tumours: 200 small-cell lung cancer (SCLC) patients, 253 breast cancer patients, 182 ovarian cancer patients, 266 uterine cancer patients and 73 thymoma patients, as well as 52 patients with PNS and cancer and 300 healthy blood donors. Sera were screened for amphiphysin, CRMP5, Hu, Ma2, Ri and Yo antibodies using a multi-well immunoprecipitation technique. Results  The most frequently detected antibodies were Hu followed by CRMP5. Ma2, Yo, amphiphysin and Ri antibodies were less common, but each was found at similar frequencies. Onconeural antibodies were present at similar levels in sera from the PNS control group and from cancer patients. Hu antibodies were rare in cancers other than SCLC. CRMP5 was the only antibody found in patients with thymoma and this antibody was more common among patients with thymoma than in other tumour patients. With one exception, coexisting antibodies were only found in patients with SCLC. The presence of onconeural antibodies in SCLC patients was not associated with prolonged survival. Conclusion  Onconeural antibodies are associated with various types of tumours suggesting that all antibodies should be included in the serological screening for possible PNS. The levels of onconeural antibody are not sufficiently sensitive to discriminate between cancer patients with PNS and those without.     

Diagnosis of intra- and pericardial tumor with transthoracic and transesophageal 2D echocardiography

To examine the value of the combined approach of transthoracic and transesophageal 2D-echocardiography in diagnosis of heart tumors this study was performed on 30 patients (11 males, 19 females, age 15 to 82 years) with atrial (n = 17) and pericardial (n = 13) tumors. Echocardiography was performed using an electronic sector scanner (Varian 3400 R) and a 2.25 MHz transducer for the transthoracic approach and a 3.5 MHz transducer at the tip of a 9 mm gastroscope for examination from the esophagus. In 9 of 11 patients with atrial myxoma diagnosis was established by transthoracic echocardiography, whereas in 2 cases with reduced image quality at the conventional approach the tumor was identified by the transesophageal technique. In one of 5 patients with atrial thrombi acoustic properties and mobility could be better judged by transesophageal echocardiography. In 7 of 13 cases with pericardial tumors diagnosis was established by transthoracic echocardiography, whereas in 6 cases diagnosis was achieved by the transesophageal approach only. Thus, transesophageal echocardiography is suggested a decisive additional tool in diagnosis of heart tumors.