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Thymoma is one of the most common solid tumors in the mediastinum. As there is no typical cell line for human thymoma, the development and use of molecular-based therapy for thymoma will require detailed molecular genetic analysis of patients' tissues. The recent reports showed that the gain of chromosome 1q regions was frequent in thymoma. We investigated the use of oligonucleotide arrays to monitor in vivo gene expression levels at chromosome 1q regions in the early- (stage I or II) and late-stage (stage IVa) thymoma tissues from patients. These in vivo gene expression profiles were verified by real-time quantitative reverse transcription polymerase chain reaction (RT-PCR) using LightCycler for 36 thymoma patients. Using both the methods, candidate genes were come up. These are Arg tyrosine kinase and death-associated protein 3 (DAP3), which are known as ionizing radiation resistance conferring proteins. The Arg/GAPDH mRNA level in stage IV thymoma (90.716 +/- 177.851) was significantly higher than in stage I thymoma (10.335 +/- 25.744, P = 0.0465). The DAP3/GAPDH mRNA level in stage IV thymoma (17.424 +/- 20.649) was significantly higher than in stage I thymoma (5.184 +/- 3.878, P = 0.0305). DAP3 expression was also correlated with the WHO classification. The combined use of oligonucleotide microarray and real-time RT-PCR analyses provided a candidate molecular marker surrounding the development and progression of thymoma correlated with chromosome 1q.

Objectives: We used palindromic polymerase chain reaction-driven complementary deoxyribonucleic acid differential display to identify and isolate a gene, the human homolog of the Schizosaccharomyces pombe checkpoint gene rad17 (Hrad17), from colon cancer tissue. The loss of checkpoint control in mammalian cells results in genomic instability, leading to the amplification, rearrangement, or loss of chromosomes--events associated with tumor progression. We hypothesized that the Hrad17 may be expressed in thymoma, especially in invasive thymoma. We attempted to determine the influence of Hrad17 expression on clinicopathological features for patients with thymoma who had undergone surgery., Methods: Expression of Hrad17 messenger ribonucleic acid (RNA) was evaluated by reverse transcription-polymerase chain reaction using a LightCycler in 38 thymomas and 10 adjacent histologically normal thymus samples from patients for whom follow-up data was available., Results: Hrad17 transcripts were detected in all 38 tumor samples (8.789 +/- 7.337) at levels significantly higher than those in normal thymus samples (1.908 +/- 2.267, p < 0.0001). No relationship was seen between Hrad17 gene expression and age, gender, or pathological thymoma subtypes. Hrad17 mRNA expression in invasive thymomas (stage II-IV, 10.067 +/- 5.293) was significantly higher than that in stage I thymomas (5.193 +/- 4.485, p = 0.0168). Immunohistochemistry showed that Hrad17 protein was highly expressed in invasive thymoma tumor tissue but not within the normal thymus tissue., Conclusions: Hrad17 was highly expressed in invasive thymoma.

Background: Matrix metalloproteinases (MMPs) are proteolytic enzymes which degrade extracellular matrix and basement membrane. There is much evidence that their increased expression is correlated with tumor aggressiveness in various carcinomas. Tissue inhibitor of metalloproteinases (TIMPs) are the specific inhibitors of MMPs. MMPs and TIMPs are considered to play an important role in carcinoma invasion and metastasis. We hypothesized that MMPs and TIMPs also play an important role in thymoma., Materials and Methods: This study included 34 thymoma cases. The mRNA levels of MMP-1, -7, and -9, TIMP-1 and -2, and GAPDH were quantified by real-time polymerase chain reaction using LightCycler. We also performed immunohistochemistry for TIMP-1., Results: The TIMP-1/GAPDH mRNA expression level was significantly higher in invasive (stage II-IV) thymomas (means +/- SE, 81.4 +/- 28.1) than in noninvasive (stage I) thymomas (30.9 +/- 8.3, P = 0.026). The MMP-1/GAPDH mRNA expression level was also higher in invasive thymomas (19.7 +/- 7.5) than in non invasive thymomas (2.26 +/- 1.72, P = 0.020). Immunopositivity of TIMP-1 was localized in stromal cells adjacent to the advancing margin of the tumor., Conclusions: These findings suggest that TIMPs and MMPs play an important role in the invasion of thymoma.

Purpose: Thymoma is one of the most common solid tumors in the mediastinum. However, there is no definitive consensus regarding the optimal adjuvant chemotherapy for advanced thymoma., Methods: To predict tumor sensitivity to 5-fluorouracil (5-FU) in thymoma, we investigated the mRNA levels of thymidylate synthase (TS), the key enzyme that catalyzes the methylation of deoxyuridine monophosphate, and correlates with the resistance of 5-FU and dihydropyrimidine dehydrogenase (DPD), which degrades 5-FU in thymoma. We used real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) using the LightCycler to monitor the TS and DPD gene expression levels in thymoma tissue specimens from patients, coamplified with glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as an internal standard., Results: In the resected tumor specimens, TS and DPD mRNA levels were 3.876 and 14.651, respectively. Both the TS and DPD mRNA levels were significantly higher in the tumor tissue specimens than in the normal adjacent thymus tissue specimens. No significant correlations were observed between the TS or DPD levels and other clinicopathological factors., Conclusions: The combined use of measurements of TS and DPD mRNA levels using real-time RT-PCR analyses may provide an indication of the selective cytoxicity of 5-FU on thymoma. In general, 5-FU itself is not considered to be a useful treatment for thymoma. The usufulness of DPD-inhibiting fluoropyrimidine (DIF) drugs for thymoma should therefore be further considered.

Introduction: Thymoma is a neoplasm of thymic epithelial cells which is characteristically associated with a large number of non-neoplastic T lymphocytes. These T cells are induced by epithelial cells and show a unique phenotype of CD4(+)8(+) double positive (DP), when studied by flow cytometry. This DP phenotype can be used as one of the diagnostic criteria to indicate a thymoma. The preoperative diagnosis of thymoma and other thymic tumors is an important problem because the treatment differs according to the diagnosis., Methods: A flow-cytometric analysis of needle biopsy specimens was performed on ten thymic tumors. The results were then compared with the findings of a histological diagnosis using conventional hematoxylin-eosin (H&E) staining., Results: Six cases with high frequencies of DP cells were diagnosed as thymoma by a flow-cytometric analysis, and were confirmed by a histological analysis of the resected specimen. Flow cytometry did not suggest a thymoma in the other four cases with few DP cells. The final diagnoses of the resected specimen of these four cases were: one thymic carcinoma, one malignant lymphoma, and two germ-cell tumors. The accuracy and specificity of diagnosis of thymoma using a fluorescence-activated cell sorting analysis from needle biopsy specimens were 6/6 (100%). On the other hand, the specificity of H&E staining from needle biopsy specimens for the diagnosis of thymoma was 6/6 (100%), but the accuracy was only 6/9 (66.7%)., Discussion: Flow cytometry can be applied to needle biopsy specimens and thus is considered to offer useful information for the preoperative diagnosis of thymic tumors.

Objectives: The Ets-1 protooncogene transcription factor is involved in several cellular functions, including the activation of several proteases, and reportedly plays an important role in carcinoma invasion and metastasis. We hypothesize that Ets-1 mRNA expression could be a predictor of thymoma development and invasion., Methods: Subjects were 37 patients with thymoma whose mRNA expression was quantified by real-time reverse-transcription polymerase chain reaction (RT-PCR) using LightCycler, a microvolume multisample fluorimeter., Results: No significant difference was found in Ets-1 mRNA expression for gender, age, or pathological subtype. Ets-1 mRNA expression in tumor tissues from stage II-IV thymoma (25.311 +/- 42.336) was more elevated than in that from stage I thymoma (2.097 +/- 4.492) (p = 0.0374). Ets-1 mRNA expression may thus serve as a marker of higher thymoma stages., Conclusions: With use of the Light Cycler RT-PCR assay, Ets-1 expression may play an important role in the extension and progression of thymoma as in other cancers. Further study and longer follow-up are, however, needed to confirm the Ets-1 impact on biological tumor behavior.

This study reports clinicopathologic features, treatment, and outcome of 107 thymomas, especially focusing on a combined modality program using hemithorax irradiation (HI) and restaging surgery using corticosteroid for advanced thymoma showing disseminative lesions. The use of HI after presumably total resection of the dissemination under posterolateral thoracotomy had no effect on reducing the incidence of relapsing. On the other hand, our own experience revealed that corticosteroid caused degenerative changes in the epithelial cells and lymphocytes of thymomas. The fact led us administer corticosteroid not only in preoperative setting but during postoperative HI. A better prognosis may be anticipated, although the follow up period is short and the number of patients involved is small.

Thymoma is one of the most common solid tumors in the mediastinum. The recent development of high-density oligonucleotide arrays provides a unique opportunity to generate gene expression profiles of cells from various stages of tumor progression as it occurs in actual neoplastic tissues. We used oligonucleotide arrays to monitor in vivo gene expression levels in early- (stage I or II) and late- (stage IVa) stage thymoma tissues in 36 patients. These in vivo gene expression profiles were verified by real-time quantitative RT-PCR using LightCycler. Using both methods, 2 candidate genes were identified that were more highly expressed in advanced-stage thymomas. One was a well-known gene, c-JUN, and another was an unknown gene, AL050002. AL050002 expression, but not c-JUN expression, was also correlated with the WHO classification (type B3 vs. type B1, B2 or AB). The combined use of oligonucleotide microarray and real-time RT-PCR analyses provides a powerful new approach to elucidate the in vivo molecular events correlated with tumor stage of thymoma., (Copyright 2002 Wiley-Liss, Inc.)

Purpose: There is increasing evidence that matrix metalloproteinases (MMPs) play important roles in tumor invasion and metastasis. Using a one-step sandwich enzyme immunoassay, we investigated whether serum pro-MMP2 levels could be predictors of the development and extension of thymoma., Methods: The subjects of this study were 33 patients with thymoma and 26 patients with nonmalignant thoracic disease., Results: Serum pro-MMP2 levels were elevated in patients with stage IV thymoma (938.6+/-80.2ng/ml) compared with those in the controls (P = 0.03). Patients with stage IVb thymoma had significantly higher serum pro-MMP2 levels than patients with other stages, being 1088.7+/-440ng/ml in stage IVb, 686.0+/-74.0ng/ml in stage I (P = 0.01), 685.8+/-48.6ng/ml in stage II (P = 0.01), and 691.7+/-74.0 ng/ml in stage III (P = 0.02). Serum pro-MMP2 levels were elevated in patients with polygonal cell type thymoma compared with those with mixed cell type thymoma, being 823.1+/-55.5ng/ml vs 613.6+/-59.9ng/ml, respectively (P = 0.04). Using the reference limit of 850ng/ml (mean +/- 2SD) set from analyses in the control group, all patients who had pro-MMP2 levels below the cutoff level survived. On the other hand, four of nine patients who had an elevated pro-MMP2 level died from recurrence., Conclusion: Serum pro-MMP2 levels may serve as a marker that could be used as an indicator of distant metastases in thymoma. Elevated pro-MMP2 levels may be correlated with poor survival.

The MTA1 gene is a recently identified metastasis-associated gene which has been implicated in the signal transduction or regulation of gene expression. We examined the mRNA expression levels of the MTA1, the human homologue of the rat mta1 gene in thymoma. Expression of MTA1 mRNA was evaluated by reverse transcription polymerase chain reaction (RT-PCR) in 30 thymoma samples using LightCycler. The data was analyzed in reference to clinicopathological data. There was no relationship between MTA1 gene expression and age and gender. MTA1/GAPDH mRNA level in stage IV thymoma (6.431+/-3.404) was significantly higher than the level in stage I thymoma (2.592+/-1.902, P=0.0081). There was a tendency towards higher MTA1/GAPDH mRNA level in stage IV thymoma when compared to stage II thymoma (3.746+/-3.292, P=0.072). Thus our results show that the expression of the MTA1 gene is closely related to invasiveness in thymoma. The gene MTA1 could potentially provide information on the mechanism of tumor invasion and metastasis.

Periostin protein shares structural and sequence homology with fasciclin I, which is an insect adhesion molecule. Periostin has a typical signal peptide at the N-terminal end suggesting it is a secreted protein. Recently, we developed a novel sandwich chemiluminescence assay to determine serum concentrations of periostin. We investigated the serum periostin level in thymoma patients, and attempted to determine the correlation between serum periostin level and clinicopathological factors of thymoma patients who had undergone surgery between January 1994 and July 1996. Serum periostin levels were not significantly different between the thymoma patients (1264.4+/-122.9 ng/ml) and the normal control (962.0+/-118.6 ng/ml) (P=0.0877). There was no relationship between serum periostin level and age, gender or pathological subtype. However the serum periostin level of stage IV patients (1497.0+/-285.8 ng/ml) was significantly higher than normal control (P=0.0460). These data suggest that serum periostin level may indicate tumor invasion and progression of thymoma.

Neovascularization, an essential event for the growth of solid tumors, is regulated by a number of angiogenic factors, among which vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), are considered to exert potent angiogenic activity. In this study, we investigated whether serum VEGF and bFGF levels could be predictors of the development and extension of thymic epithelial neoplasms. The subjects of this study were 37 patients with thymoma, 6 with thymic carcinoma, and 23 healthy volunteers. Serum samples were collected before clinical treatment. Serum VEGF levels were significantly (P < 0.05) elevated in the patients with thymic carcinoma (1,080 +/- 1,185pg/ml) compared with those in the healthy volunteers (407 +/- 589 microg/ml). Serum bFGF levels were also significantly (P < 0.05) elevated in the patients with thymic carcinoma (2740 +/- 631 pg/ml) compared with those in the healthy volunteers (1728 +/- 1,192 pg/ml). However, the serum VEGF and bFGF levels did not significantly differ between the patients with thymoma and the healthy volunteers. Serum VEGF and bFGF levels did not significantly differ according to the stage and pathological subtype of thymoma. Moreover, there was no correlation between the serum levels of VEGF and those of bFGF. Thus, while serum VEGF and bFGF levels may serve as markers for thymic epithelial tumors, it is unlikely that circulating VEGF and bFGF could be used as markers for assessing the progression of thymoma tumors.

We report a rare case of anterior mediastinal thymic cyst together with a thymoma and its intracystic dissemination. More attention should be given to intramural nodules, especially in patients with an anterior mediastinal thin wall cystic lesion.

PE-35 monoclonal antibody, detecting a cell-surface antigen of various types of carcinoma and normal epithelium, reacts exclusively with the medullary epithelium in the thymus; therefore, the antigen has been considered as a marker of medullary differentiation in thymomas. Using the catalyzed signal amplification method, which made it possible to apply PE-35 to routinely processed, archival tissues, we examined expression of this antigen, together with CD1a reactivity of lymphocytes, in 40 thymic epithelial tumors subclassified using the Mü1ler-Hermelink system. Medullary thymomas infiltrated with a small number of CD1a-negative lymphocytes were PE-35 positive, although many of the long spindle tumor cells were PE-35 negative. Mixed thymomas and predominantly cortical thymomas, both with prominent CD1a-positive lymphocytes, were also PE-35 positive, although some areas of the latter type were PE-35 negative. Cortical thymomas with decreased numbers of CD1a-positive lymphocytes were largely PE-35 negative. In well-differentiated thymic carcinomas with a few CD1a-positive lymphocytes, two cases were negative, but four cases were at least focally positive with PE-35. All high-grade thymic carcinomas infiltrated with some CD1a-negative lymphocytes were PE-35 positive. These results suggested that medullary thymoma generally possesses the medullary nature, although the latter tends to be lost in the long spindle tumor cells. Mixed and predominantly cortical thymomas may have mixed medullary phenotype and cortical function. Cortical thymoma and many well-differentiated thymic carcinomas may possess the cortical nature, while the large polygonal tumor cells tend to lose immature T-lymphocyte-retaining function.

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.

Three hundred ninety patients who underwent thymectomy for myasthenia gravis (MG) were followed up to investigate the development of associated malignancies. There were 102 patients with thymoma and 288 without thymoma. Malignant neoplasms were detected in ten patients, four of whom already had the tumor at the time MG was diagnosed. Thus, malignancy developed after thymectomy in six patients. Malignant fibrous histiocytoma (MFH) developed in three patients, as well as gastric cancer, gastric leiomyosarcoma, rectal cancer, liver cancer, lung cancer, breast cancer, and thymic carcinoid in one patient each. Nine of the ten malignancies developed in the thymoma group, and only one in the non-thymoma group. The predicted number of patients with malignancy was 2.63 in the thymoma group and 2.65 in the non-thymoma group. Our findings suggest that the presence of thymoma facilitates the occurrence of extrathymic malignancy, and that thymectomy never enhances the occurrence of malignancy but possibly inhibits it.

Thymosin alpha 1-like immunoreactivity was assessed in human thymus and thymoma tissue extracts by means of a new radioimmunoassay that included an anti-thymosin alpha 1 mouse monoclonal antibody. Thymosin alpha 1-like immunoreactivity levels decreased with age in normal thymuses but not in thymomas. The average thymosin alpha 1-like immunoreactivity level was 45.0 +/- 52.1 ng/mg protein in normal thymuses and 273.9 +/- 205.0 ng/mg protein in thymomas. The average thymosin alpha 1-immunoreactivity level in thymomas was higher than that in normal thymuses. Thymosin alpha 1-like immunoreactivity levels in thymomas appeared to have no relationship to the clinical stage of the thymoma or associated diseases. When viewed according to histologic characteristics, the average thymosin alpha 1-like immunoreactivity level in polygonal cell thymomas (382.5 +/- 192.6 ng/mg protein) was significantly higher than that in the spindle cell thymoma (101.8 +/- 81.2 ng/mg protein). When viewed according to the degree of lymphocyte infiltration, thymomas could be classified according to four grades: absent, scant, moderate, and predominant. In predominant or moderate thymomas, the average thymosin alpha 1-like immunoreactivity level was higher than that in scant or absent thymomas. Also, thymosin alpha 1-like immunoreactivity levels in thymuses of patients with myasthenia gravis were relatively higher than those in patients with normal thymuses.

We applied the tentative TNM classification of thymoma to 24 cases of IV b thymoma, 59 cases of thymic carcinoma, and 26 cases of thymic carcinoma (109 cases in total). This classification was useful in these cases because cases could be divided into different grades (e.g. N 0, N 1, N 2, N 3) of the factor N (lymph node metastasis) without any shift to particular grades. Based on this finding, we hereby propose a TNM classification of thymic epitherial tumors which was prepared by slightly modifying the tentative TNM classification of thymoma.

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., Methods: Eighty-one thymomas and 14 thymic carcinomas were studied immunohistologically using monoclonal antibodies specific for a single CK or a CK pair., Results: Thymic epithelial neoplasms could not be distinguished from each other on the basis of the profile of CK expression because the degree of overlap was extensive. However, polygonal cell thymomas differentiate toward a CK13-positive cortical subset that is rare in normal thymus. Spindle cell thymomas differentiate toward a CK13-positive medullary subset. Mixed cell thymomas are comprised of a CK13-positive medullary subset and a CK13-negative medullary subset, both of which are typical in normal thymus. CK18 was expressed to a greater extent on the epithelium of thymic carcinomas than on that of thymomas. Polygonal cell thymomas more frequently were invasive than spindle and mixed cell thymomas., Conclusions: There is a possibility that the epithelium of polygonal cell thymomas is immature because it is a phenotypically unusual subset in normal thymus. A thymic carcinoma arising in a thymoma has been reported, although the relationship between the thymoma and the thymic carcinoma was not clear. Nevertheless, given the similar cellular differentiation of thymoma and thymic carcinoma, CK18-positive epithelium in thymomas may be transformed into thymic carcinoma cells in certain conditions.

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. Eighty-one thymomas (59 noninvasive, 22 invasive) and 14 thymic carcinomas were studied immunohistologically using antiepithelial membrane antigen (anti-EMA) monoclonal antibody. Thymic carcinomas tended to express much larger quantities of EMA than thymomas, and instances of EMA-positive thymoma were seen significantly more often in invasive thymomas than in noninvasive ones (P < 0.05). However, EMA positivity was also associated with gland-like structures, which were not necessarily associated with malignant disease. Nevertheless, in view of the concept that thymoma and thymic carcinoma show a similar cellular differentiation, EMA-positive epithelial cells in thymoma with no relation to gland-like configurations might represent a pool of cells having a latent potential for malignant disease and might be transformed into thymic carcinoma cells under certain conditions. Immunolabeling for EMA appears to be a useful tool for determining the degree of malignant disease among thymic epithelial neoplasms.

The case in this study was a 34-year-old male with a small thymoma associated with myasthenia gravis. The patient had been treated with corticosteroids for 10 months against myasthenia gravis. During the course of the treatment a chest CT revealed that the tumor had reduced. Thereafter the extended thymectomy was performed. A close examination of the excised thymus revealed the presence of a flat cystic tumor measuring 1.5 x 0.8 x 0.5 cm at the site corresponding to the CT image. This tumor was histologically ascertained to be a thymoma. The thymoma is sensitive to corticosteroids, which can effectively reduce it. As conclusion, it is necessary to check thoroughly on the presence of thymoma prior to the initiation of corticosteroid therapy to treat myasthenia gravis.

Eighty-one cases of thymoma were studied immunohistologically with the use of three mouse monoclonal antibodies: one was specific for subcapsular-cortical, 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, intra-cortical, 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.

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.

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.

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.

PE-35 monoclonal antibody, detecting a cell-surface antigen of various types of carcinoma and normal epithelium, reacts exclusively with the medullary epithelium in the thymus; therefore, the antigen has been considered as a marker of medullary differentiation in thymomas. Using the catalyzed signal amplification method, which made it possible to apply PE-35 to routinely processed, archival tissues, we examined expression of this antigen, together with CD1a reactivity of lymphocytes, in 40 thymic epithelial tumors subclassified using the Mü1ler-Hermelink system. Medullary thymomas infiltrated with a small number of CD1a-negative lymphocytes were PE-35 positive, although many of the long spindle tumor cells were PE-35 negative. Mixed thymomas and predominantly cortical thymomas, both with prominent CD1a-positive lymphocytes, were also PE-35 positive, although some areas of the latter type were PE-35 negative. Cortical thymomas with decreased numbers of CD1a-positive lymphocytes were largely PE-35 negative. In well-differentiated thymic carcinomas with a few CD1a-positive lymphocytes, two cases were negative, but four cases were at least focally positive with PE-35. All high-grade thymic carcinomas infiltrated with some CD1a-negative lymphocytes were PE-35 positive. These results suggested that medullary thymoma generally possesses the medullary nature, although the latter tends to be lost in the long spindle tumor cells. Mixed and predominantly cortical thymomas may have mixed medullary phenotype and cortical function. Cortical thymoma and many well-differentiated thymic carcinomas may possess the cortical nature, while the large polygonal tumor cells tend to lose immature T-lymphocyte-retaining function. [ABSTRACT FROM AUTHOR]