Primary thymic carcinomas

Within a 75-year period, 20 patients with primary nonteratomatous carcinomas of the thymus were seen at the Mayo Clinic. Fourteen were males and six were females, with a mean age of 48 years. Thirteen of the lesions were classified as poorly differentiated or spindling squamous cell carcinomas. One neoplasm was a sarcomatoid carcinoma, and two showed both squamous cell and neuroendocrine ultrastructural features. The remaining four tumors had both light- and electron-microscopic features of neuroendocrine carcinomas. In all 20 patients, careful clinical and pathologic examinations, including autopsy in fatal cases, excluded malignant lymphomas and metastasis to the thymus from epithelial tumors in other anatomic sites. Thirteen patients underwent surgery, with or without postoperative radiotherapy; of these, one was alive and apparently disease-free 43 months after diagnosis. There were two operative deaths. The remaining patients received primary radiotherapy or chemotherapy, or both. The mean survival of the 16 patients who died (excluding operative deaths) was 18.7 months for the 14 patients with tumors of squamous cell differentiation and 36.0 months for the two patients with pure neuroendocrine carcinomas. Among patients with squamous cell carcinoma, 11 developed metastases to lungs, liver, bones, adrenal glands, or extrathoracic lymph nodes; nine of these died of massive local growth within the mediastinum. Among patients with neuroendocrine carcinomas, two of four patients died of local growth within the mediastinum; one of these also had metastases to the liver and adrenal glands. One patient with oat cell carcinoma was alive with residual thoracic tumor and cervical lymph node metastasis 18 months after diagnosis.     

Thymoma and thymic carcinoma

Thymic tumors comprise a heterogeneous group of neoplasms with a wide spectrum of clinical presentations. The evolution of the disease is often unpredictable, ranging from an indolent attitude to the possibility of intra- and extrathoracic spread. From the histological point of view, thymoma and thymic carcinoma are the most frequent subtypes and arise only from thymic epithelial cells. Other histological types are even more rare and are usually considered separately. A number of prognostic factors have been validated as predictors of outcome: staging, World Health Organization histological classification, diameter of the tumor, associated paraneoplastic syndromes, completeness of resection, and early onset of recurrence. Complete surgical resection is the key factor for cure and should be considered the gold standard at any stage. Especially for more aggressive lesions, surgery should be considered with a multimodality approach, involving induction and adjuvant therapy according to the stage. Multimodality therapy protocols have been designed based on the integration of clinical staging and histology. Neoadjuvant therapy is now administered before surgical resection in patients with tumors considered inoperable as it improves resectability and survival and reduces the risk of recurrence. Adjuvant treatment has been extensively reported after both complete or partial resection. New targeted therapies are in the developmental stage, and in the future they will be part of the standard protocols. Integrated treatment modalities require strict cooperation between medical and radiation oncologists, thoracic surgeons, and pathologists.     

Primary thymic epithelial neoplasms in children

Primary epithelial neoplasms of the anterior mediastinum in children are very rare. We have studied 10 cases of thymic epithelial neoplasms in children aged 16 years or less and correlated their histologic features with the clinical outcome. The patients' ages ranged from one to 16 years (mean: 10.2); with a male:female ratio of 1.5:1. Nine patients had symptoms attributable to their tumors; one was asymptomatic. Four patients presented in clinical stage I, one in stage IIb, and five in stage IVb. Histologically, the tumors comprised a heterogenous group displaying a range of morphologic appearances: one tumor had the classic features of lymphocyte-rich thymoma of the adult; four were of the lymphocyte-rich type with associated unusual stromal features; two were spindle cell thymomas with cytologic and architectural atypia; and three displayed obvious cytologic features of malignancy (i.e., thymic carcinoma); two in the last group showed features of small cell carcinoma, and the other was an undifferentiated/anaplastic carcinoma. The epithelial nature of the tumors was supported in six cases by positive staining of the tumor cells with keratin antibodies and in two cases by electron microscopic demonstration of desmosomes and intracytoplasmic bundles of tonofilaments within the tumor cells. The prognosis for these patients correlated well with the degree of atypicality exhibited by the epithelial components; it was very poor in patients with small cell and undifferentiated/anaplastic carcinoma (8 months average survival), better for those with atypical spindle cell thymomas (multiple recurrences and metastases but no fatalities over a 15- to 72-month period), and best in those with lymphocyte-rich thymomas without cytologic atypia (no recurrences or metastases over an 8-month to 3-year follow-up).     

A case of thymic carcinoma

A 41-year-old male visited with chief complaints of chest pain and cough. The patient was operated on under a diagnosis of invasive thymoma. The tumor was located in the left lobe of the thymus and measured 6 X 9 cm. Since the tumor invaded the left innominate vein, pericardium, and the upper lobe of the left lung, we resected it with adjacent structures. Postoperative pathological examination indicated squamous cell carcinoma of the thymus. Because the tumor metastasized also to the mediastinal lymph nodes, the patient was treated postoperatively by radiation therapy and adjuvant chemotherapy mainly with CDDP. The patient is well presently 2 years after operation without signs of recurrence.     

Tiny thymic carcinoma completely surrounded by thymic tissue. The possibility of de novo carcinoma.

We report a case of a 61-year-old man with a tiny thymic carcinoma completely surrounded by thymic tissue. First, a thoracoscopic resection of about two-thirds of the right inferior part of the thymus containing the tumor was performed to obtain the histological diagnosis. Frozen-section diagnosis at operation revealed a thymic carcinoma. Therefore we performed a median sternotomy and resected the remnant of the thymus. A tiny thymic carcinoma completely surrounded by thymic tissue is extremely rare. In this case, as the tumor was tiny and there was a homogeneous mass without a thymoma-like component, we concluded that this tumor was de novo.     

CD70 expression in thymic carcinoma

CD70, a type II transmembrane glycoprotein, is a member of the tumor necrosis factor (TNF) family that mediates the interaction between B- and T-lymphocytes. CD70 has been shown to be expressed by malignant lymphoma, especially Hodgkin's disease, and by nasopharyngeal carcinoma, both of which are frequently associated with Epstein-Barr virus (EBV). In this study, we investigated the expression of CD70 in epithelial cells of various types of thymic epithelial tumors and its association with EBV. Immunohistochemical expression of CD70 was studied on frozen tissue. In a series of 27 thymic epithelial tumors, including thymic carcinomas (n = 8), atypical thymomas (n = 5), thymomas (n = 13), and thymic carcinoid (n = 1), 7 (88%) thymic carcinomas and 1 (20%) atypical thymoma showed positive immunoreactivity for CD70, whereas CD70 was not detected in other tumors. Twenty-four intrathoracic malignant epithelial tumors of nonthymic origin, including lung (n = 17), esophagus (n = 5), and mesothelium (n = 2), showed no immunoreactivity for CD70. Northern blot analysis also revealed that CD70 messenger RNA was expressed in 2 of 2 thymic carcinomas, 0 of 2 atypical thymomas. and 0 of 2 thymomas. All of the 27 thymic epithelial tumors were EBV-negative as assessed by EBV-encoded small RNA in situ hybridization. The expression of CD70 is closely related to the pathogenesis of thymic carcinoma but unrelated to EBV infection in the thymus.     

Paraneoplastic dermatomyositis as presentation of thymic carcinoma

Thymic carcinomas are very rare and heterogeneous groups of anterior mediastinum neoformations with an extremely aggressive behavior. Often, the diagnosis is made in the advanced stages. Paraneoplastic syndromes associated with thymic carcinoma are extremely rare. We report a case of a 64-year-old man presenting with early stage thymic carcinoma which was discovered because of associated paraneoplastic dermatomyositis. The dermatomyositis disappeared completely after radical resection of the tumor. After 20-month follow-up, the patient is in good clinical condition without recidivism of disease.     

Combined partial sternectomy for thymic carcinoma.

For thymic carcinoma, a 67-year-old Japanese female underwent combined chemotherapy, to which a partial response was registered. Afterwards, total thymectomy with combined en bloc resection of the biopsy site, the partial sternum and the partial mediastinal components were completed with a clear margin. Skeletal reconstruction was performed using polypropylene mesh. Paradoxical movement of the chest wall was tolerable. Functional and cosmetic appearance of the chest wall following the reconstruction was satisfactory. Thirty-nine months had passed since the onset of the chemotherapy, when local recurrence was detected in the approximated major pectoral muscle. The patient underwent salvage radiation therapy that resulted in a complete response, and is currently alive and disease free at 46 months after the onset of the combined chemotherapy.     

The multimodality treatment of thymic carcinoma.

OBJECTIVES: Thymic carcinoma is a rare neoplasm more invasive and with a poorer prognosis than ordinary thymoma. Complete curative resection is sometimes not possible, but good response rates to chemotherapy are reported in literature. We report our experience with seven cases of thymic carcinoma, who took part to a multimodality treatment including neoadjuvant chemotherapy, surgery and post-operative radiotherapy in our center. METHODS: Since June 1989, seven previously untreated patients were enrolled. The primary chemotherapy consisted of three courses of cisplatin (P; 75 mg/m(2) i.v., day 1), epidoxorubicin (E; 100 mg/m(2) i.v., day 1) and etoposide (VP16; 120 mg/m(2) i.v., days 1, 3 and 5), every 3 weeks. Surgery was performed following complete hematological recovery. After surgery, all patients underwent radiation therapy to the tumor areas, operatively marked with clips, at doses of 45 (complete resection) or 60 Gy (incomplete resection). RESULTS: The pre-operative diagnosis of thymic carcinoma was performed in four cases by a mediastinotomy, and in the remaining cases, by an ultrasound-guided (n=2) or a computed tompography-guided (n=1) fine needle aspiration. All patients responded (one completely) to the chemotherapy regimen. Surgical resection was complete in four cases (histological examination negative in one case). Three patients are still alive and well (62-136 months from the diagnosis), two are alive with relapse at 16 and 85 months, one patient died at 86 months from another cause, and one patient died at 18 months from local relapse and lung metastases. CONCLUSIONS: A pre-operative shrinkage of the thymic carcinoma by means of neoadjuvant multi-drug chemotherapy may improve the resectability, and therefore, the survival rate. Our experience, although preliminary, is encouraging and merits additional study in a multicenter trial with a sufficient number of patients to draw definitive conclusions.     

Concurrent metastatic thymic carcinoma and postirradiation sarcoma

We present a case of concurrent metastatic thymic carcinoma and postirradiation sarcoma in the same lobe of the lung in a woman who had received partial resection of thymic carcinoma with chemoradiotherapy 11 years ago. One tumor showed similar histology to the previous carcinoma. The other tumor was a pleomorphic sarcoma, suggestive of a postirradiation sarcoma. Irradiation-induced sarcomas are rare and have not been reported in patients with thymic carcinoma. This case may serve as a model in considering the possibility of postirradiation sarcoma for patients encountering recurrent masses with the history of radiotherapy for thymic carcinoma several years ago.     

Hepatoid thymic carcinoma: report of a case

We describe the clinicopathologic findings in a so far unrecognized thymic tumor. The tumor occurred in a 70-year-old woman with respiratory distress but neither myasthenia gravis nor other symptoms. Metastases or another primary tumor were absent. The well-circumscribed neoplasm was located in the thymic region, measured 18 x 12 x 8 cm, and showed a homogeneous, tan-colored, soft cut surface. By histology, the tumor lacked a true capsule and a lobular growth pattern, was almost devoid of stroma, and infiltrated among remnant thymus lobules. The polygonal tumor cells formed solid sheets, trabeculae, or occurred as single cells that resembled hepatocytes. Proliferative activity was low. Portal structures, sinuses, and bile were absent as were areas of conventional thymoma, adenocarcinoma, or germ cell tumor. The tumor expressed cytokeratins 7 and 19, alpha1-antitrypsin, alpha1-antichymotrypsin, and hep-Par-1. Alpha-fetoprotein (AFP), human beta-chorionic gonadotropin (beta-HCG), placental alkaline phosphatase, CD5, CD30, CD31, CD34, CD45, CD68, CD99, S-100, HMB45, desmin, actin, or neuroendocrine markers were not expressed, and intratumorous CD1a+ or TdT+ immature T cells were absent. AFP was repeatedly undetectable in the blood. Mediastinal tumor recurrence was detected 6 months after surgery. Following radiochemotherapy, the patient has remained free of disease for 26 months. We conclude that this tumor is a thymic carcinoma (WHO type C thymoma). A diagnosis of hepatoid yolk sack tumor appears unlikely considering absence of a bona fide germ cell component, lack of AFP expression, and the patient's female gender. Because of its morphologic and immunohistochemical features, we propose the term "hepatoid thymic carcinoma" for this new type of thymic carcinoma.     

Effect of preoperative concurrent chemo-radiotherapy for thymic carcinoma

Ten cases of thymic carcinoma were operated in our hospital from 1975 to 2000. Preoperative concurrent chemo-radiotherapy was performed in 3 cases among them according to same protocol. The 3 patients had same poorly differentiated carcinomas. They underwent 2 courses of systemic chemotherapy [cisplatin (CDDP) + etoposide (VP-16)] with concurrent radiotherapy (40 Gy). We had one complete-response, one partial-response and one no-response by the induction therapy. Only the no-responder underwent one more course of chemotherapy [CDDP + gemcitabine (GEM)]. Operations were performed four weeks after the end of the induction therapy. All patients underwent complete resections, but the no-responder needed cardiopulmonary bypass for combined resection of right atrium. Two cases are living without recurrence more than 2 years and half, but the no-responder died from infection (empyema) at 34th postoperative day. Therefore, it was revealed that the induction concurrent chemo-radiotherapy for thymic carcinomas is extremely effective for some patients but invalid for other cases.     

Primary ureteral carcinoma

A report of 22 cases of true primary transitional carcinoma of the ureter is presented. Evaluation of these cases shows that grades III and IV lesions have a poorer prognosis than grades I and II and that staging in ureteral tumors is a difficult task and unreliable for predicting survival. A conservative approach at management of low-grade lesions is suggested.     

原发性胆囊癌

目的探讨胆囊癌的早期诊断及各种手术对其预后的影响。方法对５６例胆囊癌患者的致病因素进行分析。结果按照Ｎｅｖｉｎ分期Ⅰ期５例,Ⅱ期７例,Ⅲ期１０例,Ⅳ期１３例,Ⅴ期１０例。行各类切除性手术３２例（５７１％）,剖腹探查取活检１３例（２３２％）,非手术行放疗或化疗１１例（１９７％）。各类切除性手术的１,３,５年生存率分别为５６３％（１８／３２）,２８１％（９／３２）,１２５％（４／３２）,探查活检的１３例及非手术治疗的１１例均在明确诊断后５个月内死亡。结论早期诊断和及时行根治性手术是改善胆囊癌预后的关键     

Primary branchiogenic carcinoma

An extensive historical review of branchial cleft cyst carcinoma is undertaken and a critical analysis of all 67 cases reported in the English literature since Martin's landmark report is carried out and tabulated. Forty-one of the 67 cases were definitely ruled out as carcinomas of branchial cysts. Though only eight of the remaining 26 cases satisfied Martin's criterion of 5-year follow-up without evidence of primary carcinoma elsewhere, 14 patients had incontrovertible evidence of branchiogenic carcinoma, evidenced by a branchial cyst with histologic evidence of epithelial dysplasia progressing to squamous cell carcinoma within the cyst wall. Two previously unreported cases are presented. A therapeutic approach including wide local excision, radical neck dissection, and radiotherapy is recommended. A more thorough search for an occult head and neck primary, and a clearer understanding of the histopathology of branchiogenic carcinoma, are suggested as alternate requirements for this diagnosis.     

A case of thymic carcinoma, sarcomatoid type]

A 53-year-old man was found to have a mediastinal mass. Chest X-ray, CT scan, bronchofiber and superior vena vasography showed a left upper giant mediastinal tumor with invasion to left upper lobe and pericardium. And it was performed a surgical treatment and diagnosed a thymic carcinoma (sarcomatoid type) by histological examination. We reported a rare type of thymic carcinoma and added discussion.