bromochloroacetic-acid and Thymoma

Topics: Antigens, CD; Biomarkers, Tumor; Carcinoma; Chromogranins; Humans; Keratins; Neoplasm Proteins; Neoplasm Staging; Thymoma; Thymus Neoplasms

To report the pathologic features of intrapericardial thymoma and discuss their possible clinical relevance.. Retrospective evaluation of autopsy cases and the available clinical records.. A large autopsy population (>31,000 postmortem examinations between 1980 and 1995) in an Italian general hospital.. Two cases of thymoma showing an exclusive intrapericardial growth were retrieved from autopsy files. The patients were 61 and 82 years of age, both were women, and both were referred to the hospital with terminal conditions due to either neoplastic or chronic diseases. Myasthenia gravis and/or immunologic dysfunctions were not noted, although one of the patients had serum hypogammaglobulinemia. Roentgenography showed enlargement of mediastinal profiles and suggested cardiomegaly. At autopsy, tumors were bulky, noninvasive, and from 6 to 10 cm in largest dimension. Histologically, they were spindle cell "medullary" thymomas, frequently showing cell arrangement around microcystic spaces. They were strongly immunoreactive for epithelial markers.. This study confirms that thymomas may occur in the pericardium. Tumor-related symptoms may be overlooked owing to concomitant heart disease or equivocal instrumental features, especially in the absence of immune system disturbances. Based on these premises, they may deserve a specific distinction in the expanding chapter of ectopic thymomas.

Topics: Aged; Aged, 80 and over; Antibodies; Female; Humans; Keratins; Middle Aged; Pericardium; Retrospective Studies; Thymoma; Thymus Neoplasms

Thymomas are cytologically benign epithelial neoplasms of the thymus gland. They compose 10% of mediastinal tumors, and are most common in the anterosuperior compartment. Seven to 36% of thymomas are malignant, as determined by tissue invasion, yet they metastasize in less than 3% of cases. Distinguishing lymphoma from lymphocyte-predominant thymoma is imprecise due to their histologic similarities. We present a 45-year-old man with intracranial metastatic thymoma. The lesion was interpreted radiographically as meningioma, and as possible lymphoma by frozen section. Flow cytometry proved this neoplasma to be a metastatic thymoma. Sixteen monoclonal antibodies were used to immunophenotype the CD45+ component of this tumor. Coexpression of CD4 and CD8 along with CD1 demonstrated lymphocytes of late cortical thymocyte origin; a second component was cytokeratin positive. This is the first reported case of extrathoracic metastases of thymoma diagnosed using flow cytometry. We propose this method as an invaluable technique to diagnose these histologically difficult neoplasms.

Topics: Aneuploidy; Antibodies, Monoclonal; Antigens, CD; Antigens, Neoplasm; Biomarkers, Tumor; Brain Neoplasms; Combined Modality Therapy; Diagnosis, Differential; DNA, Neoplasm; Flow Cytometry; Frozen Sections; Humans; Immunophenotyping; Keratins; Lymphoma, Non-Hodgkin; Magnetic Resonance Imaging; Male; Meningioma; Middle Aged; Neoplasm Proteins; Neoplastic Stem Cells; Parietal Lobe; T-Lymphocyte Subsets; Thymectomy; Thymoma; Thymus Neoplasms

Five cases of a heretofore unreported rare variant of thymic carcinoma characterized by a striking resemblance to adamantinoma of the mandible are described. The tumors occurred in 4 women and 1 man aged 58 to 76 years (mean: 67.8 y); they arose in the anterior mediastinum and measured from 5.3 to 12.0 cm in greatest diameter (mean: 8.9 cm). Presenting symptoms included chest pain, shortness of breath, and in 2 patients, pleural effusion. One tumor was asymptomatic and discovered incidentally. Histologically, the tumors were extensively desmoplastic, and the cellular proliferation was characterized by multiple islands of squamous epithelium with striking peripheral palisading of nuclei and central areas containing clear cells resembling a stellate reticulum. Areas of preexisting spindle cell thymoma were identified in 2 cases; these areas gradually merged with the higher-grade component of the lesion. Cystic changes were noted in 3 cases. Immunohistochemical studies in 3 cases showed the tumor cells were positive for cytokeratins, p40 and p63, and all showed a high proliferation rate (>50% nuclear positivity) with Ki-67. Next-generation sequencing was performed in 2 cases that showed amplification of the AKT1 gene (copy numbers 6 and 13). Clinical follow-up in 3 patients showed recurrence and metastasis after 1 and 2 years; 1 patient passed away 2 years after diagnosis due to the tumor. Desmoplastic adamantinoma-like thymic carcinoma represents an unusual histologic variant of thymic carcinoma that needs to be distinguished from metastases from similar tumors to the mediastinum.

Topics: Adamantinoma; Aged; Ameloblastoma; Biomarkers, Tumor; Epithelium; Female; Humans; Hyperplasia; Keratins; Male; Middle Aged; Thymoma; Thymus Neoplasms

Twelve cases of thymomas with prominent alveolar-like growth pattern are presented.. The 12 cases were identified during a review of more than 350 cases of thymomas.. The patients were five women and seven men between the ages of 48 and 69 years (mean, 58.5 years). Clinically, all patients presented with nonspecific symptoms. Grossly the tumors varied in size from 3.5 to 5 cm in greatest diameter. Histologically, all tumors showed a predominant alveolar-like growth pattern without a significant lymphocytic component. Immunohistochemistry showed positive staining for pan-keratin, keratin 5/6, and p63. Clinical follow-up showed that nine patients have remained alive and well with no recurrence, while no follow-up was obtained in three patients.. The cases herein described highlight the spectrum of growth patterns that thymomas may show and also highlight the importance to keep thymomas in the differential diagnosis of tumor with prominent alveolar-like growth pattern.

Topics: Aged; Biomarkers, Tumor; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Thymoma; Thymus Neoplasms

Eight cases of primary thymic epithelial neoplasms corresponding to 7 thymomas and 1 thymic carcinoma with sebaceous differentiation are presented. The patients are 5 men and 3 women between the ages of 45 and 63 years (average, 54 years) who presented with nonspecific symptoms related to their mediastinal mass. All patients underwent complete surgical resection of the mediastinal mass. Grossly, all the tumors were described as round to oval measuring from 3.5 to 6.0 cm in greatest diameter. In 4 cases, the tumors were described as with infiltrative borders. Histologically, 1 tumor corresponded to thymic carcinoma characterized by irregular islands of tumors cells showing cellular atypia and mitotic activity. Six of the 7 thymomas showed mixed histologies corresponding to spindle cell, lymphocyte predominant, and mixed lymphocyte/epithelial types (World Health Organization types A, B1, and B2). One thymoma was mixed lymphocyte/epithelial (World Health Organization type B2). The areas of sebaceous differentiation characterized by clusters or strands of epithelial cells with ample clear cytoplasm were present within the lymphocytic component, whereas in the thymic carcinoma, the areas of sebaceous differentiation were identified within the epithelial component of the tumor. Follow-up information was obtained in 5 patients, showing that the patient with thymic carcinoma died 20 months after initial diagnosis, whereas the patients with thymoma whether encapsulated or minimally invasive remained alive without recurrence 12 to 24 months after initial diagnosis. The current cases represent an unusual feature that occasionally may be seen in thymomas and thymic carcinomas.

Topics: Biomarkers, Tumor; Carcinoma; Cell Differentiation; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Perilipin-2; Thymoma; Thymus Neoplasms

A 76-year-old man was referred to our division because of an abnormal shadow on chest computed tomography (CT). CT revealed a 20 mm nodule in the anterior mediastinum. Non-ivasive thymoma was suspected and thymomectomy and resection of right thymus was performed. The resected tumor was 25×25×13 mm in size. Pathologically the tumor was composed with polygonal cell components and spindle cell components, partially invading surrounding tissue. Cytokeratin AE1/3 and epithelial membrane antigen (EMA) were strongly positive, and the pathological diagnosis was biphasic, metaplastic thymoma.

Topics: Aged; Humans; Keratins; Male; Mediastinum; Mucin-1; Thymoma; Thymus Neoplasms; Tomography, X-Ray Computed

Due to its profound therapeutic consequences, the distinction between thymoma and T-lymphoblastic lymphoma in needle biopsies is one of the most challenging in mediastinal pathology. One essential diagnostic criterion favouring thymoma is the demonstration of increased numbers of keratin-positive epithelial cells by immunohistochemistry. Loss of keratin expression in neoplastic epithelial cells could lead to detrimental misdiagnoses. We here describe a series of 14 thymic epithelial tumours (11 type B2 and B3 thymomas, 3 thymic carcinomas) with loss of expression of one or more keratins. Cases were analysed for expression of various keratins and desmosomal proteins by immunohistochemistry and immunofluorescence and compared with 45 unselected type B thymomas and 24 thymic carcinomas arranged in a multitissue histological array. All 14 cases showed highly reduced expression of at least one keratin, three cases were completely negative for all keratins studied. Of the 14 cases, 13 showed strong nuclear expression of p63. Expression of desmosomal proteins was preserved, suggesting intact cell contact structures. Loss of expression of broad-spectrum-keratins and K19 was observed in 3 and 5 % of unselected thymomas and in 30 and 60 % of thymic carcinomas. A proportion of keratin-depleted thymomas contained giant cells, reminiscent of thymic nurse cells. Loss of keratin expression in type B2 and B3 thymomas is an important diagnostic pitfall in the differential diagnosis with T-lymphoblastic lymphoma and can be expected in 5 % of cases. A panel of epithelial markers including p63 is warranted to ensure correct diagnosis of keratin-negative mediastinal tumours.

Topics: Adult; Aged; Aged, 80 and over; beta Catenin; Cadherins; Female; Giant Cells; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Thymoma; Thymus Neoplasms

Fourteen cases of spindle cell thymoma with prominent desmoplastic changes are presented. The patients are 9 women and 5 men between the ages of 46 and 79 years. Clinically, the patients presented with symptoms of chest pain, shortness of breath, and dyspnea. Radiographic imaging showed the presence of an anterior mediastinal mass, and surgical resection of the tumor mass was accomplished in all of the cases. Grossly, all the tumors were described as ovoid tumor masses measuring between 4 and 9 cm in greatest dimension. At cut surface, the tumors were described as solid and light tan-brown in color. Necrosis and hemorrhage were not recorded in any of the cases. Histologically, 8 cases were invasive, and 6 were encapsulated tumors. Extensive areas of young fibrocollagen and a prominent fibroblastic proliferation characterized the tumors. Scattered areas of more conventional spindle cell thymoma were present in all cases but mitotic activity, necrosis, and/or hemorrhage were not identified. Immunohistochemical stains were performed in 9 cases, showing tumor cells positive for pancytokeratin, cytokeratin 5/6, Bcl-2, Pax8, and vimentin. Clinical follow-up in 8 patients showed that all are alive and well 1 to 8 years after diagnosis. The current growth pattern of spindle cell thymomas is unusual and should be kept in mind when evaluating mediastinoscopic biopsies.

Topics: Aged; Biomarkers, Tumor; Cell Proliferation; Female; Fibroblasts; Humans; Immunohistochemistry; Keratins; Male; Mediastinal Neoplasms; Middle Aged; Neoplasm Invasiveness; Paired Box Transcription Factors; PAX8 Transcription Factor; Proto-Oncogene Proteins c-bcl-2; Thymoma; Thymus Neoplasms; Treatment Outcome; Vimentin

Topics: Adult; Antigens, CD20; Carcinoma; Diagnosis, Differential; DNA Nucleotidylexotransferase; Female; Follow-Up Studies; Humans; Keratins; Lymphoma; Male; Middle Aged; Necrosis; Seminoma; Thymoma; Thymus Neoplasms; Tuberculosis

Topics: Adult; Antibodies, Monoclonal; DNA Nucleotidylexotransferase; Female; Follow-Up Studies; Humans; Keratins; Male; Middle Aged; Prognosis; Thymoma; Thymus Neoplasms

To study the clinicopathologic characteristics of thymic epithelial tumors and to evaluate the diagnostic reproducibility and clinical relevance of the 2004 WHO histologic classification system.. The morphology and immunophenotype of 52 cases of thymic epithelial tumor were reviewed. The tumors were classified according to the new WHO classification system and the clinical data were analyzed.. Of the 52 cases studied, 45 were thymomas and 7 were thymic carcinomas. Amongst the 45 cases of thymoma, 6 (13.4%) were type A, 15 (33.3%) were type AB, 4 (8.9%) were type B1, 9 (20.0%) were type B2, 9 (20.0%) were type B3 and 2 (4.4%) were metaplastic thymoma. Amongst the 7 cases of thymic carcinoma, 6 were squamous cell carcinomas and 1 was neuroendocrine carcinoma. The commonest presentations were cough and chest pain. Some cases were incidentally discovered by routine physical examination. Thirteen cases (25.0%) of thymoma were associated with myasthenia gravis. CT scan showed that 49 cases (94.2%) were located in the anterior mediastinum. All cases of type A, AB and B1 thymoma and most cases of B2 thymoma appeared as well-defined homogeneous mass, whereas a few cases of type B2 thymoma and most cases of type B3 thymoma and thymic carcinoma were poorly demarcated and heterogeneous. According to Masaoka staging system, 20 cases (41.7%) belonged to stage I, 15 cases (31.3%) stage II, 11 cases (22.9%) stage III and 2 cases (4.1%) stage IV. The histologic subtypes of thymic epithelial tumors significantly correlated with the clinical stages (chi(2) = 32.5, P < 0.01).. The 2004 revision of WHO histologic classification system for thymic epithelial tumors shows a high degree of reproducibility. Correlation with the radiologic, clinical and prognostic parameters is helpful in determining the management strategy for individual patients.

Topics: Adult; Aged; Antibodies, Monoclonal; Antigens, CD20; Carcinoma, Neuroendocrine; Carcinoma, Squamous Cell; CD5 Antigens; Female; Follow-Up Studies; Humans; Keratins; Male; Middle Aged; Myasthenia Gravis; Neoplasm Recurrence, Local; Neoplasm Staging; Prognosis; Radiotherapy, Adjuvant; Retrospective Studies; Thymoma; Thymus Neoplasms; Tomography, X-Ray Computed

To investigate the correlation of cytokeratin pan (CKP), vascular endothelial growth factor (VEGF) expression and microvessel density (MVD) to spiral CT manifestations of thymoma.. Eighty-four thymoma patients were underwent spiral CT examination, and 40 of the patients also had enhanced CT examination. All the CT findings were carefully reviewed to analyze their correlation to the expressions of CKP, VEGF and MVD.. The enhancement on spiral CT images increased with the levels of VEGF expression and MVD counting (P<0.01). Significant correlations were observed between VEGF expression, MVD counting and such spiral CT findings as lobular contours, cusp-like or sawtooth-like margins and tumor invasions of the pleural membrane, pericardium and great vessels (P<0.05). CKP expression showed no obvious correlation to these findings by spiral CT.. Spiral CT can reflect the pathological characteristics of thymoma, and may serve as a noninvasive modality for preoperative evaluation of thymoma.

Topics: Adolescent; Adult; Aged; Female; Humans; Keratins; Male; Microvessels; Middle Aged; Thymoma; Thymus Neoplasms; Tomography, Spiral Computed; Vascular Endothelial Growth Factor A; Young Adult

Twenty cases of adenomatoid spindle cell thymomas are presented. The patients are 13 males and 7 females between 7 and 82 years of age (mean: 55 y). Clinically, all patients presented with symptoms of chest pain and shortness of breath. Radiologically, an anterior mediastinal mass was discovered, and complete surgical resection was performed in all of the patients. Grossly, the tumors were described as well-defined solid tumor masses surrounded by membranous tissue, which at cut surface show a light tan homogenous surface. Areas of necrosis, hemorrhage, and/or cystic degeneration were not observed in any of the cases. Histologically, all tumors showed similar histological features and were characterized by the presence of a spindle cellular proliferation with an "adenomatoid-like" appearance, which at higher magnification showed the presence of cells with a signet-ring cell-like appearance. Rare mitotic figures were seen in some cases. Seven tumors showed transcapsular invasion, whereas 13 cases were encapsulate. Immunohistochemical studies showed positive staining for broad-spectrum keratin and keratin 7 with only scattered cells positive for calretinin and epithelial membrane antigen. Other markers including S-100 protein, desmin, smooth muscle actin, and α-feto protein were negative. Follow-up information ranging from 4 to 96 months (average: 32.3 mo) was obtained in 17 patients showing that all patients were alive. The cases herein described highlight the importance of recognizing this unusual pattern of spindle cell thymomas to avoid misdiagnosis with other tumors, namely, when dealing with small mediastinoscopic biopsies.

Topics: Adenoma; Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Child; Female; Humans; Keratins; Male; Middle Aged; Thymoma; Thymus Neoplasms; Young Adult

Topics: Diagnosis, Differential; Fibroadenoma; Humans; Keratins; Lipoma; Male; Middle Aged; Mucin-1; Neoplasms, Multiple Primary; Thymoma; Thymus Neoplasms; Vimentin

A 57-year-old woman was admitted to our hospital with complaints of recent onset of dyspnea on exertion. A chest computed tomography revealed a large mediastinal mass which extrinsically compressed the heart and mediastinal structures, occupying one half of the hemithorax. A needle biopsy was performed to find a thymoma with type AB according to the WHO classification. Based on the radiological and histological finding a surgery for the tumor was achieved by exploratory VATS thoracotomy followed by thymectomy through a median sternotomy with tumor extirpation of 910 g in weight. A definite diagnosis of thymoma (Masaoka I) without capsular invasion was obtained from the pathologic findings, including positive immunohistochemical staining for CD1a and cytokeratin.

Topics: Antigens, CD1; Biopsy, Needle; Female; Humans; Immunohistochemistry; Keratins; Middle Aged; Practice Guidelines as Topic; Respiratory Distress Syndrome; Sternum; Terminology as Topic; Thoracic Surgery, Video-Assisted; Thoracotomy; Thymectomy; Thymoma; Thymus Neoplasms; Tomography, X-Ray Computed; Treatment Outcome; World Health Organization

A mediastinal tumor in a 49-year-old woman with myasthenia gravis is reported. The tumor was well-demarcated and located in the supero-anterior mediastinum. Microscopically, the tumor consisted of thymic and neuroblastic tumor components, the latter of which consisted of immature and maturing neuronal cells, abundant neuropils, and Schwannian stroma. The two components intermingled with each other inside the tumor capsule. The tumor was diagnosed as thymoma with a ganglioneuroblastomatous component. The coexistence of epithelial and neuronal tissues in the thymic neoplasm is extremely rare.

Topics: 12E7 Antigen; Antigens, CD; CD3 Complex; CD5 Antigens; Cell Adhesion Molecules; Female; Ganglioneuroblastoma; Humans; Immunohistochemistry; Keratins; Mediastinal Neoplasms; Middle Aged; Myasthenia Gravis; Thymectomy; Thymoma; Thymus Neoplasms

The present study sought to determine the effects of long-term kindled seizures of the basal amygdala upon immune function in rat, utilizing the thymus, as a principal target for study. Histopathology from kindled Sprague-Dawley rats revealed the presence of epithelial cell thymoma in 70% of these rats. The results revealed an increased rate of apoptosis and proliferation in thymic epithelial cells. Analysis of thymocytes indicated a decrease in the ratio of CD4 to CD8 positive T cells and reduced proliferative response to T-cell mitogens. To determine whether these effects were mediated through the sympathetic nervous system, animals were treated with guanethidine, which blocked the development of epithelial cell thymomas, while mifepristone treatment, employed to determine the possible role of the hypothalamic-pituitary axis, was ineffective in attenuating thymoma development. Thus, the present study demonstrated that functional and pathological changes in the thymus during kindled seizures are mediated through the sympathetic nervous system.

Topics: Amygdala; Animals; Antibodies; Apoptosis; Cell Division; Epilepsy; Epithelial Cells; Female; Guanethidine; Hormone Antagonists; In Situ Nick-End Labeling; Keratins; Kindling, Neurologic; Mifepristone; Rats; Rats, Sprague-Dawley; Receptors, Adrenergic; Sympathetic Nervous System; Sympatholytics; T-Lymphocytes; Thymoma; Thymus Gland; Thymus Neoplasms

Topics: Aged; Carcinoma; Carcinoma, Medullary; CD5 Antigens; Cell Differentiation; Choristoma; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Thymoma; Thymus Gland; Thyroid Gland; Thyroid Neoplasms

Topics: Actins; Adult; Biomarkers, Tumor; Diagnosis, Differential; Female; Humans; Keratins; Neoplasms, Glandular and Epithelial; Sarcoma, Synovial; Thymoma; Thymus Gland; Thyroid Neoplasms; Vimentin

Ectopic hamartomatous thymoma (EHT) is a rare benign tumor. We present a case of EHT, which was seen as subcutaneous mass on the left supraclavicular area in a 19-year-old man. The tumor consisted of spindle cells, epithelial cells, adipose cells, and a small amount of lymphocytes, as described previously. Immunohistochemically, spindle cells were positive for keratin, a-smooth muscle actin, CD34 and vimentin, but negative for desmin and S-100 protein. Lymphocytes were positive for CD45RO but negative for CD20, CD1a, and CD99. Approximately, 5% of cells were positive for MIB-1 and no cells stained for p53 and bcl-2. Recognition of EHT is important and needs to be differentiated from high-grade sarcomas such as synovial sarcoma or glandular malignant peripheral nerve sheath tumor.

Topics: 12E7 Antigen; Adult; Antigens, CD; Antigens, CD1; Antigens, CD20; Antigens, CD34; Cell Adhesion Molecules; Choristoma; Diagnosis, Differential; Hamartoma; Humans; Keratins; Leukocyte Common Antigens; Male; Nerve Sheath Neoplasms; Sarcoma, Synovial; Soft Tissue Neoplasms; Thymoma; Thymus Neoplasms; Vimentin

To study the clinicopathologic characteristics of metaplastic thymoma.. Resection specimens of 3 cases of metaplastic thymoma were studied by light microscopy, immunohistochemistry and electron microscopy.. All the 3 patients were females and aged 33, 58 and 45 years respectively. Histologically, a biphasic growth pattern, consisting of intimate admixture of epithelial cells and spindle cells, was noted. The epithelial cells showed mild cytologic atypia, sometimes nuclear grooves and pseudonuclear cytoplasmic inclusions. These cells were arranged in nests and anastomosing cords. Mitotic figures were rarely seen. On the other hand, the spindle cells were bland-looking, mitotically inactive and arranged in fascicles. Immunohistochemical study showed that the epithelial cells strongly expressed cytokeratin (AE1/AE3) but not vimentin or CD5. The proliferation index, as demonstrated by Ki-67 immunostaining, was about 3% to 5%. In contrast, the spindle cells were diffusely positive for vimentin and epithelial membrane antigen. Staining for CD5 and CD20 was negative. The background lymphocytes were positive for CD3, but not for TdT and CD99. Ultrastructurally, well-formed desmosomes or hemidesmosomes were identified in the epithelial element. They were not detected within the spindle cells.. Metaplastic thymoma is a rarely encountered indolent or low-grade thymic tumor and may represent a distinct clinicopathologic entity.

Topics: Adult; CD5 Antigens; Diagnosis, Differential; Female; Follow-Up Studies; Humans; Immunohistochemistry; Keratins; Mediastinum; Microscopy, Electron; Middle Aged; Thymoma; Thymus Neoplasms; Vimentin

Thymic carcinoma is a rare mediastinal neoplasm with a poor prognosis due to delayed diagnosis and highly malignant behavior. To evaluate 7 serum tumor markers and the outcome of treatment, 11 stage III-IVb thymic carcinomas undergoing multimodality treatment were reviewed. High levels of serum CYFRA21-1 were detected in 5 patients (45%) and correlated with the progression of disease. Of the patients, 6 underwent surgery. The median survival time was 38.4 months, and the 5-year survival rate was 15.6%. The metastatic stage (IVb) and treatment without resection were significantly associated with poorer overall survival (p=0.0034 and p=0.0041, respectively). Our data demonstrated that serum CYFRA21-1 may represent a potential new biomarker in thymic carcinoma. Stage may provide a basis for prognosis in stage III-IVb thymic carcinoma, and resection is one of the most important parts of multimodality treatment for advanced thymic carcinoma. Effective neoadjuvant treatment is therefore essential.

Topics: Aged; Antigens, Neoplasm; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Combined Modality Therapy; Disease Progression; Female; Humans; Keratin-19; Keratins; Male; Mediastinal Neoplasms; Middle Aged; Neoplasm Staging; Prognosis; Radiotherapy Dosage; Survival Rate; Thymoma; Thymus Neoplasms; Treatment Outcome

This study documents the characteristics of a large series of spontaneously occurring thymomas in a laboratory colony of European hamsters (Cricetus cricetus). Thymomas are rare organotypic neoplasms originating from the thymic epithelial compartment. Because the hamster thymomas largely resembled their human counterparts, the recent World Health Organization (WHO) classification of human thymic epithelial tumors was used. Forty hamsters of both sexes aged 3-29 months were examined macroscopically and histologically. In 22 (55%) of the 40 animals, necropsy revealed enormous whitish masses in the anterior mediastinum, with a diameter ranging from 0.5 to 4.5 cm and a lobulated structure. The anatomy of the thymus region was normal in the remaining 18 hamsters. Histologically, the tumors presented as thymuslike organoid structures with areas of medullary and cortical differentiation and a predominance of lymphoid cells. A network of epithelial cells in the cortical areas, demonstrated immunohistochemically with a cross-reactive antibody against pancytokeratin, supported the diagnosis of thymoma. Cortical lymphocytes showed positive staining with cross-reacting antibodies against CD3 and terminal deoxynucleotidyl transferase, characteristic of immature T cells. On the basis of these findings, the tumors were classified as B1 thymomas, in some cases with AB or B2 components, according to the new WHO classification for human thymic epithelial tumors.

Topics: Animals; CD3 Complex; Cricetinae; DNA Nucleotidylexotransferase; Female; Immunohistochemistry; Immunophenotyping; Keratins; Lymphoid Tissue; Male; Mediastinum; Polymerase Chain Reaction; Thymoma; Thymus Neoplasms

Ectopic hamartomatous thymoma is a rare benign tumor that consists of spindle, epithelial, and adipose cell elements. We present a case of this lesion arising in the supraclavicular region of a 59-year-old man, including the characteristic immunohistochemical and ultrastructural findings. DNA flow cytometry revealed diploidy with a low proliferation index (6.73%). The tumor contained CD99+ lymphocytes; CD99 (MIC2) can serve as a useful marker of immature T cells. These findings suggest that ectopic hamartomatous thymoma may develop from the third branchial pouch or thymic anlage.

Topics: 12E7 Antigen; Antigens, CD; Antigens, CD34; CD3 Complex; Cell Adhesion Molecules; Cell Division; Choristoma; Hamartoma; Humans; Immunohistochemistry; Keratins; Leukocyte Common Antigens; Lymphocytes; Male; Microscopy, Electron; Middle Aged; Mitotic Index; Mucin-1; Thymoma; Thymus Neoplasms

We have studied responses in thymoma patients to interferon-alpha and to the acetylcholine receptor (AChR) in early-onset myasthenia gravis (EOMG), seeking clues to autoimmunizing mechanisms. Our new evidence implicates a two-step process: (step 1) professional antigen-presenting cells and thymic epithelial cells prime AChR-specific T cells; then (step 2) thymic myoid cells subsequently provoke germinal center formation in EOMG. Our unifying hypothesis proposes that AChR epitopes expressed by neoplastic or hyperplastic thymic epithelial cells aberrantly prime helper T cells, whether generated locally or infiltrating from the circulation. These helper T cells then induce antibody responses against linear epitopes that cross-react with whole AChR and attack myoid cells in the EOMG thymus. The resulting antigen-antibody complexes and the recruitment of professional antigen-presenting cells increase the exposure of thymic cells to the infiltrates and provoke local germinal center formation and determinant spreading. Both these and the consequently enhanced heterogeneity and pathogenicity of the autoantibodies should be minimized by early thymectomy.

Topics: Age of Onset; Animals; Autoantibodies; Autoimmunity; B-Lymphocytes; Bungarotoxins; Enzyme-Linked Immunosorbent Assay; Epithelial Cells; Epitopes; Fluorescent Antibody Technique; Germinal Center; Histocompatibility Antigens Class II; Humans; Insulin; Interferon-alpha; Interleukin-2; Keratins; Models, Immunological; Mutation; Myasthenia Gravis; Receptors, Cholinergic; Stromal Cells; T-Lymphocytes; Thymoma; Thymus Gland; Thymus Neoplasms; Troponin I

Topics: Antigens, CD; Antigens, Differentiation, B-Lymphocyte; Cell Adhesion Molecules; Child; DNA-Binding Proteins; Humans; Hyperplasia; Immunohistochemistry; Keratins; Lectins; Myasthenia Gravis; Nerve Tissue Proteins; Nuclear Proteins; Receptors, Steroid; Receptors, Thyroid Hormone; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Sialic Acid Binding Ig-like Lectin 2; Thymoma; Thymus Gland; Transforming Growth Factor beta; Transforming Growth Factor beta1

A case of ectopic hamartomatous thymoma (EHT) arising in the supraclavicular region of a 52-year-old male is presented. The well-defined tumor measuring 1.7x1.5x0.7 cm consisted of three components: spindle cell (70%), epithelial (25%), and adipose (5%). The spindle cell component was characterized by sheet-like, haphazard and short fascicular arrangements of bland spindle cells. Neither mitotic figures nor cellular pleomorphism were found. Admixed with, and adjacent to, the spindle cell areas was an obviously epithelial component of variable appearance, ranging from glandular spaces lined by mainly cuboidal clear cells, irregularly anastomosing cords, and strands of epithelial cells to irregular solid nests of squamous epithelium with dark and clear cytoplasm. Myoepithelial cells were also observed. Immunohistochemically, the spindle cells were strongly and diffusely positive for cytokeratins and some of them were positive for BRST2, alpha-smooth muscle actin, and CD10. The tumor was negative for S-100 protein, glial fibrillary acidic protein, and CD34. Ultrastructurally, tonofilaments and desmosomes were observed in the spindle cells. The findings indicate an epithelial origin. The patient was well without recurrence or metastasis 8 months after excision. Pathologists and clinicians should be aware of the existence of ectopic hamartomatous thymoma in the supraclavicular or suprasternal region and should differentiate it from a high-grade sarcoma, such as biphasic synovial sarcoma or glandular malignant peripheral nerve sheath tumor.

Topics: Actins; Apolipoproteins; Apolipoproteins D; Carrier Proteins; Glycoproteins; Hamartoma; Head and Neck Neoplasms; Humans; Immunohistochemistry; Keratins; Male; Membrane Transport Proteins; Microscopy, Electron; Middle Aged; Neprilysin; Thymoma

Topics: Humans; Immunohistochemistry; Infarction; Keratins; Stromal Cells; Thymoma; Thymus Neoplasms

Topics: Actins; Choristoma; Cysts; Desmin; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Mucus; Myoglobin; Pericardium; Rhabdomyoma; Thymoma; Thymus Gland

Twenty-five cases of thymoma with prominent cystic and hemorrhagic changes and areas of necrosis and infarction are presented. The patients were 11 women and 14 men between the ages of 18 and 73 years (median 45.5 years). Clinically, nine patients were asymptomatic and their mediastinal tumor was discovered on routine chest radiograph. Sixteen patients presented with symptoms of chest pain and cough. All patients underwent surgical resection of their tumor. Grossly, the tumors were described as well circumscribed and encapsulated, with the exception of two that showed infiltration of pleura and pericardium. The tumors measured from 4 to 13 cm in greatest dimension. On cut surface they showed prominent cystic areas and foci of hemorrhage and necrosis. Histologically, the tumors contained solid areas showing an admixture of round to oval epithelial cells devoid of atypia admixed with small lymphocytes in varying proportions. Cystic changes with areas of necrosis, infarction, and hemorrhage were present in all cases and comprised extensive areas of the tumors. The areas of infarction showed features of ischemic necrosis and were always intimately associated with vaso-occlusive and thrombotic phenomena and with cystic and hyperplastic changes of adjacent thymic epithelium. Clinical follow-up in 14 patients showed that 11 were alive and well from 1 to 18 years after surgery (median follow-up 9 years). Three patients died: one of complications during the immediate postoperative period, one because of colonic adenocarcinoma 9 years after diagnosis of the mediastinal tumor, and one because of pneumonia 6 years later. The two patients with invasive tumors were lost to follow-up. The present study appears to indicate that areas of hemorrhage and necrosis in well encapsulated, noninvasive thymomas do not portend an adverse prognosis.

Topics: Adolescent; Adult; Aged; Cysts; Female; Follow-Up Studies; Hemorrhage; Humans; Immunoenzyme Techniques; Infarction; Keratins; Male; Middle Aged; Necrosis; Retrospective Studies; Thymoma; Thymus Neoplasms

Since cytokeratins (CKs) are useful as differentiation markers for histogenetic and classification studies, we investigated the CK profiles of the thymus and thymomas in an attempt to understand the histogenetic correlation and to propose a histological classification.. Nine thymuses and 34 thymomas were immunostained for various CKs of different molecular weights and involucrin. Based on cytomorphology and histoarchitecture, thymomas were classified into spindle cell (SC), small polygonal cell (SPC), mixed, organoid, large polygonal cell (LPC) and squamoid (SQ) thymomas for compiling CK profiles. The thymus was shown to comprise four epithelial compartments, each expressing a different CK profile. Different histological types of thymoma expressed different CK profiles. By correlating the CK profiles of the thymus and thymoma, SPC, SC and LPC thymomas appeared to be related to subcapsular, medullary and cortical cells, respectively. Organoid thymoma recapitulated the structure and CK profile of the normal thymus, while SQ thymoma acquired additional squamous type CK. The applicability and usefulness of the proposed histological classification were evaluated on 147 thymomas by correlating the results with their invasive behaviour. One hundred and thirty-nine cases (95%) could be classified and different histological types correlated strongly with their invasive behaviour.. The thymus is a complex epithelial organ composed of heterogeneous cell types giving rise to various related histological types of thymoma. The results of the CK profile study supports the proposed histological classification, which is pathologically applicable and clinically useful in correlating with invasiveness. This cytomorphological classification, supported by the CK expression patterns, is comparable to Müller-Hermelink classification and the new WHO histological classification except that a separate group of SPC thymoma expressing only CK14 and CK19 was identified and separated from mixed thymoma.

Topics: Biomarkers, Tumor; Humans; Keratins; Thymoma; Thymus Gland; Thymus Neoplasms

There have been several cell kinetic studies of thymoma, but the effectiveness of using Ki67 antibody as a tool to measure proliferative activity in this tumour was rarely evaluated. We carried out an immuno-histochemical study using this antibody to assess the clinicopathological correlation and the prognostic significance of this technique.. Ninety-one cases of thymoma were collected. Double immunostaining with Ki67 and cytokeratin KL-1 antibodies was performed on paraffin sections. Ki67 labelling index (LI) was expressed as a percentage of Ki67 immunopositive nuclei by counting at least 1000 epithelial cells. The LIs were correlated with stages, histological subtypes based on both Lattes-Bernatz and Müller-Hermelink-Kirchner classifications, and length of survival. There were statistically significant differences of LIs between stage I and stage III and between stage I and stage IV tumours. Histologically, statistically significant differences were identified between predominantly epithelial thymoma and every other subtype of the Lattes-Bernatz classification and between well-differentiated thymic carcinoma and medullary or mixed thymomas of the Müller-Hermelink-Kirchner classification. Regarding the prognostic implication of Ki67 LI, although there appeared a trend that patients with tumours of higher LIs had slightly worse survival, the difference was not statistically significant in both univariate and multivariate survival analyses.. We have demonstrated the proliferative potential in thymoma is associated with stage and histology. However, its clinical usefulness is limited on account of the overlap of LIs and lack of prognostic significance.

Topics: Adult; Aged; Female; Follow-Up Studies; Humans; Immunohistochemistry; Keratins; Ki-67 Antigen; Male; Middle Aged; Prognosis; Survival Rate; Thymoma

Thymic carcinoma is an uncommon tumor. Most cases appear to arise de novo, but in rare instances they can arise in thymomas. We report the clinicopathologic features and immunohistochemical profile of five cases of thymic carcinoma accompanied by a component of thymoma. Immunohistochemical studies were performed with the avidin-biotin-peroxidase complex method using monoclonal antibodies to p53(DO7), CD99(O13), epithelial membrane antigen, CD5(NCL-CD5-4C7), vimentin (V9), and cytokeratins 7, 8, 18, and 19. The patients consisted of three men and two women with a median age of 57 years. One patient had myasthenia gravis, and the other four presented with chest symptoms. One patient had concurrent adenocarcinoma of the lung with metastasis. Four of the patients died within 15 months. The thymomas consisted of two large polygonal cell thymomas, two squamoid thymomas, and one spindle cell thymoma. The malignant components included two undifferentiated carcinomas, one spindle cell carcinoma, one squamous cell carcinoma, and one clear cell carcinoma with squamous differentiation. There was no correlation between the histologic types of the thymoma and the thymic carcinoma. In three cases, excluding the two squamoid thymomas, the thymic carcinomas occurred in the necrotic areas of the thymoma. They showed upregulated expression of epithelial membrane antigen and cytokeratins 7, 8, 18, and 19, similar to the so-called "interface phenomenon" described in the invasion front of other types of carcinoma. Increased p53 protein expression was observed in all five carcinomas, and there was loss of CD99+ immature T lymphocytes. Among the thymic carcinomas, only the squamous component of the clear-cell carcinoma stained for CD5, a marker commonly expressed in thymic carcinomas. Paradoxically, a squamoid thymoma, but not its associated spindle cell carcinoma, expressed CD5, suggesting the acquisition of an "aggressive" phenotype by the squamoid thymoma, but with loss of the marker on malignant transformation. One undifferentiated carcinoma acquired vimentin immunoreactivity, whereas four other carcinomas and all five thymomas were negative. In conclusion, thymic carcinoma can arise in any histologic type of thymoma, including spindle cell thymoma, which is generally regarded as a benign neoplasm. The prognosis appears to be poor. Tumor necrosis in a thymoma should alert the pathologist to search for malignant change. The malignant change is commonly associated with increas

Topics: Adult; Aged; Biomarkers, Tumor; Carcinoma; CD5 Antigens; Female; Humans; Immunoenzyme Techniques; Keratins; Male; Middle Aged; Mucin-1; Neoplasms, Second Primary; Thymoma; Thymus Neoplasms; Tumor Suppressor Protein p53

A 33-yr-old African-American male with known human immunodeficiency virus (HIV) positivity underwent CT guided fine-needle aspiration biopsy of an anterior mediastinal mass. The aspirate was composed of a dimorphic population of cells that included small mature lymphoid cells and scattered cohesive groups of large epithelial cells in equal numbers. The neoplasm stained strongly for low weight molecular cytokeratin, epithelial membrane antigen (EMA), leukocyte common antigen (LCA), and Leu-7 which was consistent with a diagnosis of thymoma. Subsequent biopsies determined the neoplasm to be a malignant (invasive) thymoma. This case emphasizes the efficacy of FNA biopsy for the evaluation of anterior mediastinal masses in HIV infected individuals. Additionally, the differential cytologic diagnoses for HIV infected individuals for this anatomic site are discussed.

Topics: Adult; CD57 Antigens; Diagnosis, Differential; HIV Seropositivity; Humans; Immunoenzyme Techniques; Keratins; Leukocyte Common Antigens; Lung Neoplasms; Male; Radiography, Thoracic; Thymoma

The cytologic diagnosis of primary mediastinal lesions is challenging due to the large number of lesions which may arise (i.e., lymphoma, thymoma, germ cell tumor), often with overlapping cytomorphologic features. We present an instructive case of primary mediastinal non-Hodgkin's large-cell lymphoma with sclerosis, entrapping thymic epithelium. Preoperative fine-needle aspiration yielded predominantly epithelial fragments and few lymphoid cells leading to the cytologic misdiagnosis of thymoma. The entity of primary mediastinal large-cell lymphoma (LCL) is discussed and correlated with the cytologic features seen. In addition, histologic sections from 15 additional cases of primary mediastinal LCL were evaluated to determine the frequency with which significant numbers of epithelial fragments may be observed.

Topics: B-Lymphocytes; Biopsy, Needle; Cytodiagnosis; Diagnosis, Differential; Epithelium; Humans; Immunohistochemistry; Keratins; Lymphoma; Male; Mediastinal Neoplasms; Middle Aged; Thymoma; Thymus Gland

Thymic ID cells are involved in the differentiation of mature T cells which are resistant against apoptosis. TRX/ADF is a potent thiol-related reducing agent, acts as a redox regulator, and it can attenuate the induction of apoptosis of T lineage lymphocytes. In the present study, 42 thymoma-free thymus and 40 thymoma samples were examined to identify the expression of TRX/ADF in human thymic tissue. TRX/ADF high-producer (TRXh) cells with cytoplasmic protrusions were found distributed in the thymic medulla. These TRXh cells were negative for CD3, a lymphocyte marker, keratin, an epithelial cell marker, and CD68 or lysozyme, macrophage/monocyte markers, but were positive for S100 protein and HLA-DR complex. Our results revealed that the TRXh cells in the thymic medulla were ID cells. As TRX/ADF has an important and fundamental role in cellular responses acting against oxidative stress, TRX/ADF may provide an explanation of cellular interaction between the medullary ID cells and the mature T cells.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antigens, CD; Antigens, Differentiation, Myelomonocytic; CD3 Complex; Cell Differentiation; Child; Cytokines; HLA-DR Antigens; Humans; Immunohistochemistry; Keratins; Middle Aged; Muramidase; Neoplasm Proteins; Oxidative Stress; S100 Proteins; Thioredoxins; Thymoma; Thymus Gland; Thymus Neoplasms

Six cases are described of an unusual type of primary thymic epithelial neoplasm characterized by a biphasic epithelial/spindle cell morphology that closely resembled a carcinosarcoma. The patients were two women and four men 28-70 years of age. The tumors presented clinically as asymptomatic anterior mediastinal masses found incidentally on routine chest radiographs. All patients were treated by complete surgical excision. Grossly, the tumors consisted of well-circumscribed, encapsulated masses that measured 6-14 cm in greatest diameter and showed a gray-white, homogeneous, rubbery cut surface. Histologically, the lesions were composed of anastomosing islands and cords of oval to polygonal epithelial cells displaying large nuclei with occasional prominent nucleoli and rare mitotic figures, separated by areas containing a highly cellular spindle cell proliferation without nuclear atypia. Thymic remnants could be identified in the periphery of the lesions in four cases. Immunohistochemical stains showed diffuse strong positivity for keratin and focally for epithelial membrane antigen (EMA) in the epithelial cell component, and strong positivity for vimentin and focally for actin in the spindle cell stromal component. Stains for keratin, EMA, desmin, S-100 protein, and CD34 were negative in the spindle stromal cells in all cases except one, in which EMA positivity was present; CD5 stains were negative in the epithelial cells in all cases examined. Electron microscopic examination in one case showed well-formed desmosomes and tonofilaments in the epithelial elements, as well as features indicative of fibroblastic differentiation in the spindle stromal cells. Because of the unusually florid spindle cell stromal component and the focally atypical features of the epithelial cells, some of these tumors initially were misinterpreted as examples of carcinosarcoma. Clinical follow-up in five cases showed that the patients were alive and without evidence of disease over a period of 5-20 years (mean follow-up 10 years), suggesting a benign or very low grade malignant biologic behavior. The present cases appear to represent an unusual, previously undescribed morphologic variant of thymoma characterized by a prominent pseudosarcomatous stromal component. Because of the distinctive histologic appearance and indolent clinical behavior, these lesions should be distinguished from other more aggressive anterior mediastinal neoplasms displaying a biphasic morphology.

Topics: Adult; Aged; Biomarkers, Tumor; Carcinosarcoma; Diagnosis, Differential; Epithelium; Female; Humans; Immunohistochemistry; Keratins; Male; Microscopy, Electron; Middle Aged; Thymoma; Thymus Neoplasms; Vimentin

The association of multilocular thymic cysts (MTC) with thymoma is exceedingly rare, and the pathogenesis of this combination is controversial. We describe the case of a 42-year-old man with an anterior mediastinal mass found to contain MTC and thymoma. A multilocular cystic mass, measuring 13 x 6.5 x 2 cm, was found in the right lobe of the thymus, and contained a 4.7 x 2 cm thymoma in its center. Microscopic thymomas, lipomatously involuted remaining thymic tissue, and lymphoid follicles with germinal centers were found in the walls of MTC as well as in the left thymic lobe. Non-specific chronic inflammation was also present in the walls. In addition, microcysts, which were only found at the periphery of the thymoma and covered with epithelium, might have been formed secondarily by dilatation of the perivascular spaces and of Hassall's corpuscles. These findings suggest that a chronic inflammatory process was responsible for the early formation and enlargement of this patient's MTC, and that while the cavities of the MTC expanded to various degrees, the thymoma, which originated from one of the microscopic thymomas in the walls of MTC, increased in size, and grew to involve the remaining thymic tissue.

Topics: Adult; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Epitopes, B-Lymphocyte; HLA Antigens; Humans; Keratins; Male; Mediastinal Cyst; S100 Proteins; Thymoma

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.

Topics: Antibodies, Monoclonal; Carcinoma, Squamous Cell; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Lung; Lung Neoplasms; Thymoma; Thymus Gland; Thymus Neoplasms

During the treatment of five cases of thymic carcinoma, we conducted a clinicopathological and immunohistochemical study. The patients included four males and one female, whose ages ranged from 50 to 69 years. The histologic breakdown was squamous cell carcinoma in four and small cell carcinoma in one. Immunohistochemically, the squamous cell carcinomas were positive for cytokeratin (intermediate molecular weight) and keratin. However, staining was negative for Leu-7 and chromogranin. A complete resection was achieved in only one case. In all four of the remaining cases, the resection was incomplete due to invasion into adjacent organs and disseminated lesions. Thymic carcinoma is a tumor for which a higher response rate can be expected from multidisciplinary therapy than that for lung cancer. Therefore, it is desirable, from the clinical view, to determine clinical staging and to establish standard operative procedures comprising mediastinal lymph node dissection as well as effective chemotherapy. With respect to pathology, it is hoped that an improved histologic classification will be developed.

Topics: Carcinoma, Small Cell; Carcinoma, Squamous Cell; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Phosphopyruvate Hydratase; Thymoma; Thymus Gland; Thymus Neoplasms

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.. Eighty-one thymomas and 14 thymic carcinomas were studied immunohistologically using monoclonal antibodies specific for a single CK or a CK pair.. 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.. 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.

Topics: Adenocarcinoma; Carcinoma; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Child; Child, Preschool; Humans; Infant; Keratins; Thymoma; Thymus Gland; Thymus Neoplasms

A cystic mass in the anterior mediastinum of a 9-year-old female European Shorthair cat was classified as a lymphocytic thymoma based on its histopathological features which were in accordance with those reported in the literature concerning feline thymomas. The application of a polyclonal keratin antiserum and monoclonal keratin antisera RCK 102, RKSE 60 and RGE 53 resulted in staining of foetal feline thymic cells, oesophageal epithelial cells as well as numerous stellate tumour cells and Hassall's corpuscles. As a result, the epithelial origin of the neoplastic cells could be established and the classification of thymoma confirmed. The results indicate the value of keratin antisera in the differentiation of thymoma and non-epithelial tumours in the anterior mediastinum.

Topics: Animals; Cat Diseases; Cats; Female; Immune Sera; Keratins; Staining and Labeling; Thymoma; Thymus Neoplasms

Forty-seven thymomas were histologically classified to 28 cases of cortical type, 13 cases of medullary type, and 6 cases of mixed type. They were analyzed morphometrically and immuno-histochemically, and the results were examined with their invasiveness and association with myasthenia gravis (MG). Thirty-seven resected thymic tissues were used as controls. Cortical thymomas were more often invasive ones and associated with MG than the medullary type, with significant difference. Epithelial cell nuclei of the cortical thymomas were significantly larger than those of the medullary ones. Epithelial cell nuclei of cortical and medullary thymomas were significantly larger than those of thymic cortex and medulla, respectively. Morphometrical results showed that the cortical thymomas were more malignant than the medullary ones. Immunohistochemically, all cases of thymomas were positive for Leu7 and keratin, but stainability of them were variable among each subtype. In thymic tissues epithelial cells in outer cortex were positive for Leu7 and keratin, whereas those in inner cortex and medulla were negative for Leu7 and positive for keratin.

Topics: Adult; Aged; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Myasthenia Gravis; Neoplasm Invasiveness; Thymoma; Thymus Neoplasms

Four new cases of ectopic hamartomatous thymoma are presented. The tumor occurred either superficially or deep in the area of the sternoclavicular joint and consisted of solid islands of squamous epithelium which blended with spindled cells. Cysts lined by squamous epithelium, small glands, and fat also occurred in variable amounts. Both the spindled and epithelial regions of the tumor expressed keratin and muscle actin, but neither desmin nor S100 protein. The tumor probably originates from thymic anlage associated with the third pharyngeal pouch (thymus III), although origin from other structures such as thymus IV and the cervical sinus of His are discussed. Our experience indicates that the large size and extreme cellularity of the spindled portion of some tumors may result in the mistaken diagnosis of sarcoma.

Topics: Actins; Adult; Aged; Carcinoma; Desmin; Diagnosis, Differential; Hamartoma; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; S100 Proteins; Sarcoma, Synovial; Thymoma; Thymus Neoplasms

The cytokeratin pattern of medullary, mixed and cortical thymomas and thymic carcinomas were analyzed by two-dimensional equilibrium electrophoresis. Extracts from a medullary thymoma and normal, total thymi showed a similar pattern. On the other hand in cortical thymomas and very similar in thymic carcinomas there were marked changes in the cytokeratin pattern. These findings support the classification of thymomas as described by MULLER-HERMELINK.

Topics: Electrophoresis, Gel, Two-Dimensional; Humans; Intermediate Filaments; Keratins; Reference Values; Thymoma; Thymus Gland; Thymus Neoplasms

Primary cultures are introduced as a method for an immunocytochemical and functional characterization of epithelial cells (ECs) from human thymic epithelial tumors. Neoplastic ECs were obtained after enzymatic digestion of the tumor tissue with dispase. The ECs were kept in culture for up to 1.5 months. Over this period a progressive decline in their proliferation rate was observed. In all five cases studied, ECs showed a co-expression of keratin and vimentin intermediate filaments in vitro as well as strong expression of major histocompatibility complex (MHC)-class I antigens and a progressive loss of MHC-class II antigens. Acetylcholine receptor (AchR)-epitopes were detected immunohistochemically by using monoclonal antibodies (mAbs) to the cytoplasmic site of the alpha-chain if the AchR. Epitopes were found in three of five thymomas in vivo and to a varying degree in all five cases in vitro.

Topics: Antibodies, Monoclonal; Carcinoma; Cell Adhesion; Humans; Immunoenzyme Techniques; Immunohistochemistry; Keratins; Phenotype; Thymoma; Thymus Neoplasms; Tumor Cells, Cultured

Four cases of a biphasic mediastinal tumor histologically identical to synovial sarcoma of soft tissue were observed. The tumors presented as solitary mediastinal masses. Although the tumors were frequently adherent to adjacent pleura or pericardium, none appeared to be arising from a mesothelial surface. All cases were composed of an intimate admixture of keratin-positive epithelial cells and vimentin-positive spindle cells with areas of transition, hyalinization, and calcification. Follow-up was available on three patients, who died of their disease 10 months, 14 months, and 4 years after diagnosis, respectively. Although synovial sarcoma usually occurs in deep soft tissues near joints in the extremities, it has been reported in locations removed from synovial, tendon sheath, and bursal structures. This report adds a previously unrecognized location for synovial sarcoma, the mediastinum. Occurrence in this location further supports an origin from pluripotential mesenchyme as opposed to synovium. The differential diagnosis includes mesothelioma, thymoma, germ cell tumors, malignant peripheral nerve sheath tumor with glandular differentiation, and metastatic carcinoma.

Topics: Adult; Aged; Diagnosis, Differential; Humans; Keratins; Male; Mediastinal Neoplasms; Mesothelioma; Middle Aged; Sarcoma, Synovial; Thymoma; Vimentin

Topics: Humans; Immunohistochemistry; Keratins; Neoplasm Invasiveness; Thymoma; Thymus Neoplasms

Fifteen human thymomas were analyzed by immunoperoxidase studies on frozen and paraffin-embedded tissue sections in an attempt to identify the existence of immunologically defined microenvironments. All nine lymphocyte predominant thymomas contained a predominance of lymphocytes bearing the phenotype of cortical thymocytes and dendritic Class II major histocompatibility complex antigen-positive epithelial cells, thus defining cortical-like microenvironments. Medullary-like foci were also seen in all of these cases. Minor phenotypic abnormalities in Leu-2 and -3 antigen expression were seen in three cases. In contrast, the two epithelial predominant thymomas and four mixed thymomas all exhibited features of aberrant microenvironmental differentiation, with only two cases showing demarcation into cortical and medullary foci. A lack of Class II major histocompatibility complex antigens was associated with a decrease in the lymphoid populations and an increase in Leu-1 antigen expression by T cells of otherwise normal cortical phenotype when lymphocytes were present. In contrast, lack of Class I antigen on epithelial cells was not associated with any abnormality in lymphocyte phenotype or microenvironmental organization. We document for the first time abnormal microenvironments in thymomas that may offer insights into understanding normal thymic differentiation.

Topics: Antibodies, Monoclonal; Antigens, Differentiation, T-Lymphocyte; Cell Differentiation; Epithelium; HLA Antigens; HLA-DR Antigens; Humans; Keratins; S100 Proteins; T-Lymphocytes; Thymoma; Thymus Neoplasms

Eleven cases of epithelial tumours of the thymus or thymoma and two thymuses without tumour were studied, using immunohistochemistry with anti-keratin antibodies (KL-1) which recognise cyto-keratin with a high molecular weight. In the normal thymus, KL-1 positivity seems to be limited to medullary epithelial elements and in particular Hassal's corpuscles. All the epithelial thymic tumours studied showed a net positivity for KL-1 overall in the tumour cells. This result and the demonstration of more or less well differentiated Hassal's corpuscles in these tumours make one think that these epithelial thymic tumours express some characters in relation with a differentiation of medullary type.

Topics: Antibodies, Monoclonal; Humans; Keratins; Thymoma; Thymus Gland; Thymus Hyperplasia; Thymus Neoplasms

200 cases of thymoma operated on at the surgical centre of Marie-Lannelongue between 1955 and 1982 were reviewed and analysed statistically; their histology was compared and their evolutionary potential. Based on their degree of differentiation of the epithelial tumour component and on the proportion of non tumour associated lymphocytes, 4 histological types were defined: 1) Spindle-or-oval-cell thymomas where tumour cells reminiscent of normal involutive thymic cells were of small size with a tendency to form clusters, whorls or a glandular appearance; 2) Lymphocyte-rich thymomas where normal epithelial cells, few in number, reproduce the appearance of normal thymic cells; 3) Differentiated epithelial thymomas, comprised of large epithelial cells with abundant cytoplasm and clearly demarcated and often less numerous lymphocytes; 4) Undifferentiated epithelial thymomas, characterised by a poverty of lymphocytes and anaplastic epithelial cells with a raised nuclear cytoplasmic ratio, nuclear irregularity and mitosis. Statistically, there was a significant correlation between the degree of differentiation of the tumor and prognosis. Spindle-or-oval cell thymomas (type 1) and lymphocyte-rich thymomas (type 2) have an 80% survival at 5 years and a 75% survival at 10 years. Well differentiated epithelial thymomas of type 3 have a 75% survival at 5 years and a 50% survival at 10 years, finally undifferentiated epithelial thymomas (type 4); the survival rate was nil at 5 years.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Anaplasia; Epithelium; Humans; Keratins; Lymphocytes; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Prognosis; Thymoma; Thymus Neoplasms

Two monoclonal antibodies respectively recognizing cytokeratins (CK) 18 and 19 were applied to the human thymic epithelium (in vivo and in vitro) in normal and pathological conditions, including 12 thymomas. We observed that in both normal and hyperplastic thymuses (from patients with myasthenia gravis) virtually the entire epithelial network was CK19-positive as were the majority of cells growing in culture. In four thymomas, however, the expression of cytokeratin 19 was not detected by immunofluorescence. On the other hand, CK18 was expressed by a discrete subset of medullary thymic epithelial cells in normal and in hyperplastic thymuses. Among the thymomas a large majority was either negative or contained few isolated CK18-positive cells scattered within the tumour. Conversely, in the two undifferentiated epithelial thymomas, virtually all the tumoral network was strongly labeled with the anti-CK18 monoclonal antibody. The present investigation thus not only defines the human thymic epithelial cell subset on the basis of differential cytokeratin expression but also indicates that anti-CK antibodies with single cytokeratin specificities can be regarded as useful tools to study the heterogeneity of thymomas.

Topics: Antibodies, Monoclonal; Child, Preschool; Epithelial Cells; Epithelium; Fetus; Humans; Hyperplasia; Immunoblotting; Immunohistochemistry; Infant; Keratins; Thymoma; Thymus Gland; Thymus Neoplasms

The histological and clinical features of 22 thymomas were reviewed. Immunohistochemical studies were performed using antibodies to cytokeratins (CAM 5.2 and S29) and to desmosomal protein. The heterogeneity of staining patterns seen in the epithelial cells supported the concept of separating thymomas into cortical, medullary, or mixed groups. Interdigitating cells were identified by antibody to S100 protein, and these varied in number between different tumours. Clustering of interdigitating reticulum cells occurred in association with foci of mature lymphocytes which were shown by staining of the leucocyte common antigen (CD45). The extent to which this occurred was used to assess the degree of medullary differentiation within the thymomas and this was correlated with the histological and clinical features. The lymphocyte population of six of the thymomas was studied using a range of antibodies to T and B cells; this showed the presence of B lymphocytes in thymomas.

Topics: Adult; Aged; Aged, 80 and over; Antigens, Differentiation; B-Lymphocytes; Desmosomes; Female; Histocompatibility Antigens; Humans; Keratins; Leukocyte Common Antigens; Male; Middle Aged; S100 Proteins; T-Lymphocytes; Thymoma; Thymus Neoplasms

Four monoclonal antibodies (BH11, T2/30, AG3, and BC3) were produced against different epithelial components of the normal thymus. An immunohistologic study was performed on 13 thymomas by the use of these and other stromal and lymphocyte-specific reagents. The aim of this study was to find possible relationships between the proliferating thymoma epithelial cell type and the T cell composition of thymomas. Our results indicate that cortical T cell differentiation is present in thymomas, and that this differentiation is induced in the absence of detectable levels of MHC class II antigens on the epithelial component in most cases. The role of the MHC class II antigens cannot be excluded, however, because these antigens were always present on macrophages. Analysis of the selected group of thymomas, each of which contained epithelial cells homogeneously stained by at least one of the described monoclonal antibodies, showed that the cortical type T cell inducer capacity of thymomas is independent of the epithelial type predominant in the tumor.

Topics: Antibodies, Monoclonal; Antigens, Surface; Cell Differentiation; Child; Child, Preschool; Epithelium; HLA-D Antigens; Humans; Infant; Infant, Newborn; Keratins; Macrophages; T-Lymphocytes; Thymoma; Thymus Gland; Thymus Neoplasms

The authors report an immunohistologic study of primary thymomas from 23 cases with myasthenia gravis (MG) and 7 without. Typical T6+ cortical thymocytes were usually abundant. Most epithelial cells initially appeared to be of cortical type, too, though many bore subcapsular markers in most samples. However, two-color immunofluorescence revealed unexpected heterogeneity, numerous epithelial cells simultaneously expressing some or all of the markers of both these subsets (even in two pleural metastases). It is inferred that there is a common tumor stem cell whose normal counterpart may be related to the rare patches of similar phenotype in the cortex in control samples. The authors could detect no major differences in 5 of 7 samples from nonmyasthenics; thus, most thymoma cases may risk the development of MG. Finally, thymomas from 6 of 7 further MG cases pretreated with corticosteroids showed very few cortical thymocytes, and the (phenotypically similar) epithelium was more obvious.

Topics: Adult; Aged; Antibodies, Monoclonal; Antigens, Surface; Epithelium; Fluorescent Antibody Technique; Humans; Immunosuppression Therapy; Keratins; Middle Aged; Myasthenia Gravis; Neoplasm Metastasis; T-Lymphocytes; Thymoma; Thymus Neoplasms

Eight cases of human thymoma have been analyzed on cryostat sections with the monoclonal antibody Ki67, which reacts with cells in the proliferative phases of the cell cycle. The aim was to assess the proportion of proliferating thymocytes among lymphoid cells in the thymoma samples. In all cases a large number of cells (mean, 58.75%; range, 35-80%), recognized as thymocytes by morphology and lack of cytokeratin expression in a combined immunohistochemical assay, exhibited nuclear Ki67 staining. These findings differ from the reactivity pattern observed in age-matched nonneoplastic thymuses where lower growth activity of cortical thymocytes was observed (15-20% Ki67+ cells). Intensive thymocyte proliferation in thymomas may represent one of the factors which lead to autoimmunity in myasthenia gravis and thymomas.

Topics: Adult; Aged; Antibodies, Monoclonal; Antigens; Cell Division; Cell Nucleus; Epithelium; Female; Histocytochemistry; Humans; Immunoenzyme Techniques; Keratins; Male; Middle Aged; T-Lymphocytes; Thymoma; Thymus Gland; Thymus Neoplasms

Twenty-four cases of thymic epithelial tumors, including 18 cases of thymoma, five cases of squamous cell carcinoma, and one case of undifferentiated carcinoma, were studied immunohistochemically using monoclonal antibody Leu-7 (HNK-1) and antikeratin antibody. Seven cases of non-neoplastic thymic tissues were also studied. Leu-7 antibody stained epithelial cells in the outer cortex of the normal thymus, and antikeratin antibody stained thymic epithelial cells in both cortex and medulla of the normal thymus. Seventeen thymomas and one undifferentiated carcinoma were focally or diffusely stained with Leu-7, some showing cortical and medullary differentiation as seen in the normal thymus. On the other hand, none of the five squamous cell carcinomas were stained with Leu-7. All thymomas stained for keratin in varying degrees, and all squamous cell carcinomas were diffusely and strongly stained with antikeratin antibody. It is concluded that normal thymic epithelial cells showed zonal differentiation, and neoplastic cells were considered to retain these characteristics to some extent; i.e., thymomas had the same phenotype of epithelial cells of the cortex, especially the outer cortex of the thymus in some instances (Leu-7-positive, keratin-positive) and of both cortex and medulla (mixture of Leu-7-positive and -negative cells) with organoid arrangement in other instances, and thymic squamous cell carcinoma had the same phenotype as epithelial cells in the thymic medulla (Leu-7-negative, keratin-positive).

Topics: Antigens, Surface; Carcinoma; Carcinoma, Squamous Cell; Epithelium; Humans; Immunoenzyme Techniques; Keratins; Thymoma; Thymus Neoplasms

A case of thymic carcinoma arising within a lymphocyte rich thymoma is reported. The undifferentiated carcinoma contained cellular elements resembling choriocarcinoma but could be differentiated therefrom by positive staining for prekeratin antigen and an absence of staining for B-HCG antigen utilizing immunohistochemical techniques.

Topics: Adult; Female; Histocytochemistry; Humans; Immunoenzyme Techniques; Keratins; Microscopy, Electron; Protein Precursors; Thymoma; Thymus Neoplasms

The clinicopathological features of 32 thymomas were reviewed and tumours were staged according to their degree of invasion. Their antigenic profiles were studied using monoclonal antibodies to cytokeratins (CAM 5.2 and DAKO-CK1), HNK-1 (Leu 7), and HLA-DR (TAL-IB5). Stage I (non-invasive) tumours were mainly of the spindle cell (SC) or predominantly lymphocytic (PL) types, whilst all the predominantly epithelial (PE) tumours were either locally invasive (stage II) or showed more extensive spread (stage III). Neoplastic epithelial cells all expressed cytokeratin, but varied in their degree of positivity. CAM 5.2 was more uniformly positive with cells at the periphery of tumour nodules and lining tubulo-cystic areas staining most strongly. DAKO-CK1 gave less uniform positivity but highlighted areas of medullary differentiation. HNK-1 was variably expressed in all tumour groups but was found more often in the invasive tumours (73 per cent stage III, 62 per cent stage II, 50 per cent stage I), particularly those of PE or mixed (M) type. In general, TAL-IB5 expression was lost in the more invasive thymomas. Focal medullary differentiation in tumours suggests a common origin for cortical and medullary epithelium, indicating that sub-division of tumours into cortical or medullary types is not valid. Immunohistochemistry may usefully complement clinical and macroscopic findings in the assessment of malignancy in thymoma.

Topics: Adolescent; Adult; Aged; Antibodies, Monoclonal; Antigens, Neoplasm; Cell Transformation, Neoplastic; Child; Child, Preschool; Female; Humans; Immunoenzyme Techniques; Infant; Keratins; Male; Middle Aged; Neoplasm Staging; Thymoma; Thymus Gland; Thymus Neoplasms

Topics: Antibodies, Monoclonal; Humans; Immunoenzyme Techniques; Intercellular Junctions; Keratins; Microscopy, Electron; Rosette Formation; Thymoma; Thymus Neoplasms

Six thymomas were classified histologically and studied immunohistochemically with a panel of mouse and rat monoclonal antibodies directed against thymic epithelial and lymphoid components. The antibodies included monoclonal antibodies directed against cytokeratin, medullary epithelial cells (ER-TR5), and HLA-DR and HLA-ABC antigens, as well as antibodies with specificity for thymocytes. Histologically, one thymoma was characterized by epithelial predominance (EP type), two showed lymphoid predominance (LP type), and two showed mixed lymphoid/epithelial composition (MLE type); one thymoma was a malignant pure epithelial thymoma (PE type). In the thymomas of the MLE and EP types the major populations of cells consisted of HLA-DR-negative, cytokeratin-positive epithelial cells with large ER-TR5-positive subpopulations (i.e., the phenotype of medullary epithelium). In the thymomas of the LP type, the neoplastic population was composed of cytokeratin-positive, ER-TR5-negative cells that expressed the HLA-DR antigen (i.e., the phenotype of cortical epithelium). The thymoma of the PE type consisted of cytokeratin-positive cells, some of which were ER-TR5- and HLA-DR-positive. Double immunofluorescence studies revealed the presence of varying numbers of additional nonepithelial (nonlymphoid) HLA-DR-positive cells in thymomas of the LP, MLE, and EP types. The intervening lymphoid population in the thymomas of the LP, MLE, and EP types consisted largely of cortical thymocytes, as defined by immunologic characterization. These results suggest that thymomas can be classified as medullary or cortical epithelial neoplasms on the basis of their immunologic phenotypes.

Topics: Adult; Aged; Anemia, Aplastic; Antibodies, Monoclonal; Antigens, Differentiation, T-Lymphocyte; Antigens, Surface; Child, Preschool; DNA Nucleotidylexotransferase; Epithelium; Female; Histocompatibility Antigens Class II; HLA Antigens; HLA-DR Antigens; Humans; Infant; Keratins; Male; Middle Aged; Myasthenia Gravis; Thymoma; Thymus Neoplasms

17 thymomas were studied by indirect immunofluorescence for the presence of thymic hormones and antigens of the major histocompatibility complex (MHC). The thymoma epithelial cells (specifically identified by their keratin content) contained thymic hormones (thymulin and thymosin alpha 1), a finding corroborated by the observation of elevated thymulin serum levels. In contrast with normal or hyperplastic thymuses, thymoma epithelial cells did not express HLA-DR and HLA-DC antigens as assessed by immunofluorescence as well as immunoblot analyses. Conversely, MHC class I antigens (HLA-ABC) were normally expressed. Thus, we conclude that thymoma epithelial cells are endocrinologically active but are defective for the expression of some MHC products (class II molecules) known to play an essential role in intrathymic T cell differentiation.

Topics: Adult; Aged; Epithelium; Histocompatibility Antigens Class II; HLA Antigens; HLA-A Antigens; HLA-B Antigens; HLA-C Antigens; HLA-DQ Antigens; HLA-DR Antigens; Humans; Keratins; Middle Aged; Myasthenia Gravis; Thymoma; Thymus Hormones; Thymus Neoplasms

We analyzed lymphocyte surface markers in seven thymomas. In six mixed thymomas, the staining patterns were similar for T11, OKT8, OKT6, OKT4, Coulter clone T4, and Leu 3a/3b. Staining patterns for Ia and keratin showed a dendritic pattern. Occasional S 100-positive interdigitating dendritic cells were identified. In three patients with associated myasthenia gravis, no significant differences in staining patterns were identified. A different pattern was seen in a patient with hypogammaglobulinemia, red blood cell aplasia, and a spindle cell thymoma: T11-, T8-, and T6-positive cells each comprised 70% to 80% of the tumor; but, cells of the helper/inducer phenotype differed when measured with OKT4 antibody (0%) vs Coulter clone T4 antibody (60%) and Leu 3a/3b (60%). This unusual phenotype, which was present on both tumor cells and peripheral T cells, appears related to the antigenic polymorphism of the T4 antigen and is believed to have no functional significance. Importantly, this discrepancy among commercial antibodies has significant implications in the general use of these reagents in clinical evaluations.

Topics: Adult; Aged; Antibodies, Monoclonal; Antigens, Surface; Female; Histocompatibility Antigens Class II; Humans; Keratins; Lymphocytes; Male; Middle Aged; Myasthenia Gravis; Thymoma; Thymus Neoplasms

Epithelial cells (ECs) from spontaneously developed thymomas in BUF/Mna rats were cultured, characterized and compared with ECs from normal thymuses. The ECs from thymomas had many more keratin filaments and PAS-positive vesicles in the cytoplasm than ECs from normal thymuses. The size and shape of ECs and their nuclei were heterogeneous and about 20% of ECs from thymomas had more than one nucleus. However, the growth rates and saturation densities of ECs from thymomas in monolayer culture were not markedly different from those of normal thymuses. The ECs from thymomas cultured in soft agar did not form any colonies. The distribution of the numbers of chromosomes found in ECs from thymomas was slightly broader than that in normal ECs, but no specific abnormalities nor marker chromosomes were noted. These findings indicate that ECs from thymomas are abnormal, but suggest that they are not malignant in nature.

Topics: Animals; Cell Cycle; Cell Nucleus; Cells, Cultured; Clone Cells; Cytoskeleton; Epithelium; Keratins; Periodic Acid-Schiff Reaction; Rats; Rats, Inbred ACI; Rats, Inbred BUF; Thymoma; Thymus Gland

The presence of intracellular keratin was examined in 230 human neoplasms using indirect immunofluorescence on fresh frozen, acetone-fixed sections. The use of antikeratin antibodies raised in rabbits against human callus and purified by affinity chromatography proved to be a rapid, sensitive, and reliable method of demonstrating keratin. Epithelial tissues and epithelial-derived neoplasms were found to contain keratin, whereas tissues and neoplasms of mesenchymal, lymphoreticular, or neural crest origin did not contain intracellular keratin. This technic is a useful adjunct for the surgical pathologist in the diagnosis of poorly differentiated neoplasms. Its application either confirmed, modified, or in several instances, changed the original light microscopic impression. The modified or changed diagnoses were confirmed by transmission electron microscopy.

Topics: Adult; Aged; Antibodies; Breast Neoplasms; Carcinoma, Basal Cell; Female; Fluorescent Antibody Technique; Humans; Keratins; Lymphoma, Large B-Cell, Diffuse; Male; Mediastinal Neoplasms; Middle Aged; Neoplasms; Skin Neoplasms; Thymoma

This paper reports three cases of lupus erythematosus (LE) associated with thymomas, all of which were discovered after the onset of LE. The diagnosis of LE was established by clinical and laboratory data. Histologically, the thymomas were of the three main types: epithelial, lympho-epithelial, and predominantly fusiform. In two cases, thymectomy did not modify the course of LE; in one vase, the absence of cytoplasmic secretory vesicles in the epithelial cells and the non-labelling of these cells by an antiserum thymic factor monoclonal antibody represented direct evidence of a functional thymus deficiency. Antikeratin antibodies were used to distinguish thymomas from lymphomas; epithelial thymomas exhibited the same keratin specificities as normal thymus, although the labelling pattern (net-like) was different. Labelling of epidermis with the same antiserum confirmed the theory of an epidermis-thymus relationship.

Topics: Aged; Animals; Antibodies, Monoclonal; Diagnosis, Differential; Epithelium; Female; Fluorescent Antibody Technique; Humans; Immune Sera; Keratins; Lupus Erythematosus, Systemic; Lymphoma; Male; Mice; Middle Aged; Rabbits; T-Lymphocytes; Thymoma; Thyroid Neoplasms

Autopsy specimens of normal human thymus, from cases of accidental involution, follicular hyperplasia, thymomas and a teratoma were investigated by immunocytochemistry using specific immune sera to small and large keratins. Keratin antisera represent a "marker" of both Hassall's corpuscles (HC) and so-called epithelial reticular cells. There were no apparent differences in keratin polypeptides distribution between cortical and medullary thymic epithelial cells. In accidental involution, the epithelial framework became prominent: epithelial cortical borders and epithelial perivascular sheaths appeared often to be discontinuous structure. The central and occasionally cystic spaces of HC did not react with keratin antisera. In follicular hyperplasia, almost solid epithelial aggregates were seen which were located around germinal centers. In thymic tumours, neoplastic epithelial cells displayed a marked immunoreactivity with keratin antisera. Immune sera against keratin filaments represent an interesting tool in thymus research and in the diagnostic pathology of thymic tumours.

Topics: Aged; Autopsy; Child; Child, Preschool; Epithelium; Female; Histocytochemistry; Humans; Hyperplasia; Immunoenzyme Techniques; Infant; Infant, Newborn; Keratins; Male; Middle Aged; Teratoma; Thymoma; Thymus Gland; Thymus Neoplasms

Indirect immunofluorescence staining in two thymomas, one case of thymic hyperplasia, 10 malignant lymphomas and three seminomas was done with an antibody prepared against keratins from human epidermis. Staining was observed only in the epithelial cells of the thymomas and thymic hyperplasia and correlated well with electron microscopic studies. Immunofluorescence staining of thymic tumors with antikeratin antibody provides a simple, specific, and sensitive method for distinguishing thymoma from lymphoma and seminoma. The method may also prove to be useful in other instances in the distinction between epithelial and nonepithelial tumors.

Topics: Adult; Aged; Diagnosis, Differential; Female; Fluorescent Antibody Technique; Humans; Immune Sera; Keratins; Lymphoma; Middle Aged; Thymoma; Thymus Neoplasms