Takahiko Hashimoto

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.

Thymomas associated with pure red cell aplasia. Histologic and follow-up studies

Seventeen cases of pure red cell aplasia (PRCA) with thymoma were studied clinically, histologically, and immunologically. Two cases were associated with myasthenia gravis (MG), and three with hypogammaglobulinemia. Coombs test and antinucleus antibody test were positive in five cases. All thymomas were spindle cell types, and the adjacent thymuses had no germinal center, but showed epithelial clusters frequently. All patients, except one whose tumor was unresectable, had thymo‐thymomectomy. The operation was effective in six cases (37.5%), and the effects were not different between two operative procedures (simple and extended thymectomy). Myasthenic symptoms in two patients remitted after the operation, but effects on hypogammaglobulinemia were conincident with those on PRCA.

Cytokeratins in normal thymus and thymic epithelial tumors

Background. Thymus consists of some distinct epithelial cells that contain different sets of cytokeratins (CK). Epithelium‐derived tumors maintain the expression of some of the CK of the specific nontransformed cells. Therefore, it seems reasonable to hypothesize that thymic epithelial tumors may differentiate toward distinct subsets of intrathymic epithelial cells in terms of CK expression.

Thymic epithelial tumours: evaluation of malignant grade by quantification of proliferating cell nuclear antigen and nucleolar organizer regions.

Cellular proliferation was studied by quantification of proliferating cell nuclear antigen (PCNA) and argyrophilic nucleolar organizer regions (AgNORs) of cells in 29 thymic epithelial tumours: 8 noninvasive (7 cortical and 1 mixed) thymomas, 11 invasive/metastatic (all cortical) thymomas, and 10 thymic carcinomas. Thymic carcinoma showed the highest percentage of cells positive for PCNA (14.73±5.419%) and the largest mean number of AgNORs per nucleus (4.89±0.756). The mean percentage of PCNA-positive cells and number of AgNORs in thymoma groups were as follows: in noninvasive thymoma 2.96±1.256% and 2.73±0.647, respectively, and in invasive/metastatic thymoma 4.41±1.823% and 3.68±1.148, respectively. The differences in PCNA and AgNORs were statistically significant between thymic carcinoma and each of thymoma groups. The overlap of the values between these tumours was minimal in the PCNA stains, although it was considerable in AgNOR counts as previously noted. However, there was no statistically significant difference in these markers between noninvasive and invasive/metastatic thymomas. These results indicate that thymoma in general is a slow-growing tumour compared with thymic carcinoma and that noninvasive thymoma is similar to invasive/metastatic thymoma with regard to proliferative activity; these latter two tumours may represent an essentially identical type in different stages of progression.

The distribution of epithelial membrane antigen in thymic epithelial neoplasms.

Thymic carcinomas arising within a thymoma have been reported, but the relationship between thymoma and thymic carcinoma is poorly understood. Epithelial membrane antigen (EMA) is known to be an effective marker for establishing the epithelial nature of neoplastic cells, and it is reported that staining of tumors is clearly related to the degree of tumor differentiation.

Differential diagnosis of thymic carcinoma and lung carcinoma with the use of antibodies to cytokeratins

There are few specific pathologic findings that can be relied on to distinguish primary thymic carcinomas from lung carcinomas with mediastinal extension or showing metastasis to the anterior mediastinum. The immunohistochemical reactivity on frozen sections of thymic carcinomas and lung carcinomas, which are histologically similar to each other, was examined with the use of monoclonal antibodies to cytokeratins 7 and 13. Among keratinizing squamous cell carcinomas, all thymic carcinomas reacted with antibody specific for cytokeratin 7 (9/9, 0%), whereas no staining reaction was seen in lung carcinomas (0/5, 0%) (p < 0.01). This finding can be used as a diagnostic aid in primary thymic keratinizing squamous cell carcinomas to expedite treatment and prognosis. Cytokeratin 7 and cytokeratin 13 monoclonal antibodies reacted with almost all cases of thymic carcinoma. Applications of monoclonal antibodies specific for certain cytokeratins, especially 7 and 13, may be helpful in the diagnosis of other subtypes of thymic carcinomas.

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.

An immunohistologic study of the epithelial components of 81 cases of thymoma

Eighty‐one cases of thymoma were studied immunohistologically with the use of three mouse monoclonal antibodies: one was specific for subcapsularcortical, one for intra‐cortical, and one for medullary epithelial cells. Twenty‐eight (60.9%) of 46 polygonal cell thymomas were of the cortical type and 1 (2.2%) was of the medullary type. Ten (55.6%) of 18 spindle cell thymomas and 7 (41.2%) of 17 mixed cell thymomas were of the medullary type, and 1 (5.6%) of 18 spindle cell thymomas was of the cortical type. Fourteen (17.3%) of 81 thymomas were composed of epithelial cells that were triple positive immunologically; although these are unusual, they also may be present in the normal thymus, Based on these findings, triple‐positive epithelium in the normal thymus consists of common stem cells that can differentiate into subcapsular‐cortical, intracortical, and medullary epithelium: these cells may be the target cells for tumorigenesis. Epithelium in polygonal cell thymoma tends to differentiate into cortical epithelium, whereas epithelium in spindle and mixed cell thymomas differentiates into medullary epithelium. Cancer 1992; 69:2463‐2468.

Thymic Follicular Hyperplasia Manifested as an Anterior Mediastinal Mass

A rare case of thymic follicular hyperplasia manifested as an asymptomatic anterior mediastinal mass in a 44-year-old man is herein reported. The resected thymus showed prominent medullary lymphoid follicles, an increased number of Hassalls corpuscles, and cysts of varying sizes. This paper discusses the histopathological condition of this lesion.

Distribution of fibronectin and laminin in human thymoma

The distribution of fibronectin and laminin, two extracellular matrix and basement membrane components, was studied in 55 cases of thymoma using immunohistochemistry. The results were compared according to histologic type or clinical stage of the tumor. In addition, electron microscopic observation was done to clarify the extracellular structure of thymoma. Two staining patterns were seen. First, a diffusely or partially intricate network of fibers that contained fibronectin and laminin surrounded tumor cells in 21 out of 55 cases. Most of these cases were spindle cell thymomas and showed low invasive tumors. Second, fibers that contained fibronectin and laminin were restricted only to the septa, blood vessels, and perivascular spaces that did not show a network in the remaining 34 cases. Polygonal cell thymomas showed the latter staining pattern and these were more invasive tumors. We conclude that this network is a characteristic structure of spindle cell thymomas and is related to the invasiveness of the tumor.