bromochloroacetic-acid and Thymus-Neoplasms

Solitary fibrous tumor is a rare mesenchymal neoplasm, characterized by peculiar histological features composed by the proliferation of spindle cells in "patternless pattern". Although it has been known to sometimes be accompanied by epithelioid cells, the presence of a well-formed epithelial structure is far more rare. We describe herein the case of a 60-year-old female with the radiological finding of a single nodular lesion in the anterior mediastinum. Histopathological examination of the surgically resected specimen led to the diagnosis of solitary fibrous tumor of the thymus with a spectrum of well-formed epithelial components: i) glandular structure, reminiscent of breast or eccrine gland, ii) neural tube-like structure, and iii) clusters of endocrine-like cells. Immunohistochemical analysis revealed that the spindle cells expressed CD34, vimentin, bcl-2 and Stat-6, but not keratin (cytokeratin-AE1/AE3) or epithelial membrane antigen. In contrast, the epithelial components lost expression of most of these marker proteins, including Stat-6, but continued to express vimentin and strongly expressed keratin. Since no relevant past literature was found, the current case could be interpreted as a unique and previously undescribed variant of solitary fibrous tumor comprising conventional spindle cells with a spectrum of well-formed epithelial components. Pathogenesis that may have given rise to these variegated mixtures of spindle cells and epithelial components in a single tumor is also discussed.

Topics: Antigens, CD34; Biomarkers, Tumor; Epithelial Cells; Female; Humans; Immunohistochemistry; Keratins; Middle Aged; Proto-Oncogene Proteins c-bcl-2; Solitary Fibrous Tumors; Spindle Apparatus; STAT6 Transcription Factor; Thymus Neoplasms; Vimentin

Neuroendocrine tumors of the thymus (NETTs) are unusual thymic neoplasms that were misdiagnosed as thymomas until the 1970s, when they eventually acquired a distinct identity. No collective large series have been published so far, and information about clinical presentation, diagnosis, histology, and treatment is derived from analysis of the case series and case reports published over a long period. NETTs are more aggressive than their pulmonary and abdominal counterparts, presenting at a more advanced stage, often with distant metastases, and are associated with poor long-term survival. Most patients are symptomatic at presentation as a result of the local invasion. Twenty percent to 30% of the cases are associated with endocrine disorders, mostly Cushing syndrome and multiple endocrine neoplasia syndrome. There is no official staging system for these tumors and investigators rely on the Masaoka staging system used for thymomas. Histologically, 2 classification are used: the World Health Organization and the Armed Forces Institute of Pathology classifications. Histologically, most tumors show moderately to poorly differentiated histologic features, reflecting their aggressive clinical behavior. Surgery is the most effective treatment option, although the aggressiveness of the tumor often requires extensive resection. Chemotherapy and radiotherapy may be used either preoperatively or postoperatively, although the small number of patients does not allow the design of standard guidelines about optimal schedules and doses. Survival depends on stage at presentation, histologic degree of differentiation, associated endocrine syndromes, and resectability rate. Recurrences are frequent after surgery and may be locoregional or distant. Surgery is recommended when feasible in the treatment of locoregional recurrences.

Topics: Combined Modality Therapy; Diagnosis, Differential; Humans; Keratins; Magnetic Resonance Imaging; Neoplasm Recurrence, Local; Neoplasm Staging; Neuroendocrine Tumors; Prognosis; Radiography; Thymus Neoplasms

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

A 57-year-old woman presented with a 10 x 10 cm anterior mediastinal mass. The tumor had invaded the pericardium, both lungs and the left brachiocephalic vein, and was treated by partial resection and postoperative radiation therapy. Pathological examination of the tumor revealed squamous cell carcinoma with a spindle cell sarcomatous component. Immunohistochemically, keratin and epithelial membrane antigen were positive in both the spindle cell sarcomatous areas and the squamous cell carcinomatous area and thus, a diagnosis of thymic carcinoma of sarcomatoid type was made. The patient died of recurrent disease 1 year after surgery. This case is the seventh reported in the English literature. Because of the poor outcome, adjuvant therapy is recommended.

Topics: Carcinoma, Squamous Cell; Female; Humans; Immunohistochemistry; Keratins; Middle Aged; Mucin-1; Neoplasm Invasiveness; Sarcoma; 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

In a 52-year-old Caucasian man osteopoikilosis had been misdiagnosed roentgenologically 2 years before his death. Gradually he developed Cushing's syndrome and ultimately superior vena caval obstruction. At autopsy a primary thymic carcinoid with extensive osteoblastic bone metastasis was found. Immunohistochemically the tumor was shown to be positive for adrenocorticotropic hormone (ACTH), cytokeratin (KL1), neuron-specific enolase, synaptophysin, chromogranin and glucagon. Remarkably the tumour was negative for serotonin despite high urinary hydroxyindolacetic acid levels. Bilateral hyperplasia of the adrenal cortex was found. The adenohypophysis showed a considerable reduction of ACTH-producing cells and numerous Crooke's cells with a characteristic immunohistochemical pattern.

Topics: Adrenal Cortex; Adrenocorticotropic Hormone; Bone Neoplasms; Carcinoid Tumor; Cushing Syndrome; Diagnostic Errors; Humans; Keratins; Male; Middle Aged; Osteopoikilosis; Phosphopyruvate Hydratase; Radiography; Thymus Neoplasms; Vena Cava, Superior

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

A 67-year-old woman was referred to our hospital for cough and fever. Chest computed tomography (CT) showed some masses showing slightly enhanced effect in the pericardium. FDG-PET showed the accumulation of FDG in the masses. Thoracoscopic surgical biopsy was performed to establish the diagnosis. The histological study showed proliferation of short spindle-shaped cells surrounded by lymphocyte, and the spindle cells were immunohistochemically positive for cytokeratin AE1/AE3, WT-1, D2-40, CAM5.2, intelectin-1 and negative for CEA, TTF-1, napsin A, claudin-4, calretinin, MUC4, PAX8, CD30. These findings were compatible with epithelial pericardial malignant mesothelioma.

Topics: Aged; Calbindin 2; Claudin-4; Female; Fluorodeoxyglucose F18; Heart Neoplasms; Humans; Keratins; Lung Neoplasms; Mediastinal Neoplasms; Mesothelioma; Mesothelioma, Malignant; 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

Primary thymic adenocarcinoma is an extremely rare tumor, and thymic enteric type adenocarcinoma has recently been proposed as a distinct pathological entity. Herein, we report the first cytological description of thymic enteric type adenocarcinoma. A 29-year-old Japanese female without a significant past medical history was found to have an abnormal chest shadow. Chest computed tomography demonstrated a well-circumscribed tumor in the anterior mediastinum, and thymectomy was performed. The Papanicolaou staining of the touch smear of the resected tumor demonstrated tightly cohesive epithelial cell clusters in a necrotic background. These cells were cuboidal to columnar in shape and had large round to oval nuclei with conspicuous nucleoli. Some of these neoplastic cells had intracytoplasmic mucin. Immunocytochemically, the neoplastic cells were positive for cytokeratin 20 and CDX-2. Histopathological study revealed tubular and papillotubular neoplastic growth composed of cuboidal to columnar neoplastic cells that contained large round to oval nuclei. Some of the neoplastic cells had intracytoplasmic mucin. Immunohistochemical study confirmed the expression of cytokeratin 20 and CDX-2. The final diagnosis of thymic enteric type adenocarcinoma was made. The cytological and immunocytochemical features of this case led to a diagnosis of enteric type adenocarcinoma. However, these features alone cannot be differentiated from a metastatic adenocarcinoma arising from the gastrointestinal tract. Cytological examination of a fine-needle aspiration of the mediastinal tumor has been reported to be useful in making a diagnosis. Therefore, an awareness of this new pathological entity is important for differentiating a thymic tumor from a metastatic carcinoma in the thymus.

Topics: Adenocarcinoma; Adult; CDX2 Transcription Factor; Diagnosis, Differential; Female; Gastrointestinal Neoplasms; Humans; Keratins; Papanicolaou Test; 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

Primary thymic adenocarcinoma is an extraordinarily rare malignancy; only 49 cases have been reported in the medical literature to date. Because of its rarity, clinical and pathologic characteristics of thymic adenocarcinoma are unclear. We present nine cases of primary thymic adenocarcinoma and discuss clinicopathologic findings in the context of the existing literature. Two-hundred twenty-six thymic carcinoma cases were diagnosed at Samsung Medical Center in Korea, from January, 2001 to July, 2016. Nine of these 226 cases were primary thymic adenocarcinomas. The mean age of primary thymic adenocarcinoma patients was 53.6 years, slightly younger than the mean age of patients with thymic squamous cell carcinomas. The male to female ratio was 2:1. Symptoms, if present, were usually due to compression by the tumor. Tumors showed an extra- or intra-cellular mucin and tubular growth pattern, with CK20- and CDX2-immunoreactivity, similar to adenocarcinomas of the lower intestinal tract. Twenty-five previously reported cases, classified as mucinous adenocarcinoma and adenocarcinoma, not otherwise specified, also had similar characteristics to enteric-type adenocarcinoma and generally expressed CK20, CDX2, CEA, and/or MUC2. Some of these cases had a thymic cyst. These characteristics are different from those of papillary thymic carcinomas, which are morphologically similar to papillary thyroid carcinomas, express CK7 but not CK20, and are often associated with thymoma. The prognosis of thymic adenocarcinoma, enteric type appeared to be worse than the prognosis of papillary thymic carcinoma or carcinoma with adenoid cystic carcinoma-like features. In summary, we demonstrated that common primary thymic adenocarcinomas show enteric-type differentiation with mucin. This tumor type has distinct clinical, pathological, immunohistochemical and prognostic characteristics and is different from other subtypes of thymic adenocarcinoma, papillary thymic carcinoma, and carcinoma with adenoid cystic carcinoma-like features.

Topics: Adenocarcinoma; Adult; Aged; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Squamous Cell; Female; Humans; Keratins; Male; Middle Aged; Mucins; Thymus Neoplasms

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

The observation of cytokeratins (CK's) in mass spectrometry based studies raises the question of whether the identified CK is a true endogenous protein from the sample or simply represents a contaminant. This issue is especially important in proteomic studies of the corneal epithelium where several CK's have previously been reported to mark the stages of differentiation from corneal epithelial stem cell to the differentiated cell.. Here we describe a method to distinguish very likely endogenous from uncertain endogenous CK's in a mass spectrometry based proteomic study. In this study the CK identifications from 102 human corneal samples were compared with the number of human CK identifications found in 102 murine thymic lymphoma samples.. It was anticipated that the CK's that were identified with a frequency of <5%, i.e. in less than one spot for every 20 spots analysed, are very likely to be endogenous and thereby represent a 'biologically significant' identification. CK's observed with a frequency >5% are uncertain endogenous since they may represent true endogenous CK's but the probability of contamination is high and therefore needs careful consideration. This was confirmed by comparison with a study of mouse samples where all identified human CK's are contaminants.. CK's 3, 4, 7, 8, 11, 12, 13, 15, 17, 18, 19, 20 and 23 are very likely to be endogenous proteins if identified in a corneal study, whilst CK's 1, 2e, 5, 6A, 9, 10, 14 and 16 may be endogenous although some are likely to be contaminants in a proteomic study. Further immunohistochemical analysis and a search of the current literature largely supported the distinction.

Topics: Animals; Cornea; Electrophoresis, Gel, Two-Dimensional; Humans; Immunohistochemistry; Keratins; Lymphoma; Mass Spectrometry; Mice; Mice, Inbred C57BL; Proteomics; Sequence Analysis, Protein; Thymus Neoplasms

Spindle cell thymomas are an uncommon subset of thymomas that have been regarded as benign by some. There are no comprehensive immunohistochemical studies focusing on this histological variant of thymoma. Therefore, our knowledge on the variability of its immunohistochemical profile is limited. Thirty cases of spindle cell thymomas were reviewed and immunohistochemical studies performed using antibodies against pancytokeratin, cytokeratin 5/6 (CK5/6), CK7, CK20, thyroid transcription factor-1 (TTF-1), S-100, CD34, chromogranin, synaptophysin, epithelial membrane antigen (EMA), calretinin, desmin, smooth muscle actin (SMA), and Bcl-2. The percentage and intensity of staining were evaluated and scored. The neoplastic thymic epithelial cells were diffusely positive for CK and CK5/6 and negative for CK20, S-100, chromogranin, and desmin in all 30 cases. Eighty three percent of cases showed variable reactivity for CK7 and Bcl-2. Although 97% of cases showed focal staining for calretinin, 23% for synaptophysin, and 13% for SMA, only a single case was TTF-1 positive. An interesting staining pattern was observed for CD34 and EMA, which stained the fibrous bands in some of the cases. EMA only reacted with the epithelial cells of 1 case. Spindle cell thymomas display a strong epithelial immunohistochemical phenotype as demonstrated by their reactivity for CK and CK5/6. However, tumor cells may also show positive staining for calretinin, Bcl-2, and synaptophysin and rarely for SMA and TTF-1, which can pose a problem in the evaluation of small mediastinoscopic biopsies in separating these tumors from other more aggressive neoplasms of either epithelial or mesenchymal origin.

Topics: Adult; Aged; Biomarkers, Tumor; Calbindin 2; Carcinoma; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Neoplasm Staging; Predictive Value of Tests; Proto-Oncogene Proteins c-bcl-2; S100 Calcium Binding Protein G; Sensitivity and Specificity; Thymus Neoplasms

To study the clinicopathologic features, immunophenotypes and differential diagnosis of thyroid carcinoma showing thymus-like differentiation (CASTLE).. The clinical and pathologic features of 8 cases of CASTLE were reviewed. Immunohistochemical study was performed using a panel of antibodies. In-situ hybridization for Epstein-Barr virus-encoded RNA (EBER) was also carried out.. There were altogether 4 males and 4 females. The age of the patients ranged from 25 to 57 years (mean = 48.8 years). All of them presented with painless mass at the anterior neck. Two patients also complained of hoarseness of voice. On CT scan, the tumor had a low density with contrast enhancement. Seven cases were located in the mid to lower pole and the remaining one in the upper pole of thyroid gland. Four cases were relatively circumscribed. The other 4 cases showed evidence of extrathyroidal invasion. Grossly, the tumor had a nodular or lobulated appearance and was gray-white in color, with a mean diameter of 4.3 cm. Microscopically, the tumor was infiltrative and consisted of islands, nests or lobules of epithelial cells separated by thick fibrous septa. The fibrous stroma showed various degree of lymphoplasmacytic infiltration, resulting in a prominent lymphoepithelioma-like pattern in 3 cases. Two cases showed squamoid differentiation, mimicking thymic Hassall corpuscles. Immunohistochemically, the tumor was consistently positive for cytokeratins, CD5, bcl-2, p63 and CD117. CEA was variably expressed. The staining for thyroglobin and TTF1 was negative. There was no labeling for EBER in all the cases. Two patients experienced local recurrence at 22 months and 12 years after surgery, respectively. They were treated with re-resection. All patients remained well on follow up. The duration of follow up ranged from 4 to 55 months.. CASTLE is a low-grade thyroid carcinoma with the morphologic features and immunophenotypes overlapping with those of thymic carcinoma. Awareness of this rare entity is important to both the pathologists and clinicians.

Topics: Adenoma; Adult; Carcinoma; CD5 Antigens; Cell Differentiation; Disease-Free Survival; Female; Follow-Up Studies; Humans; Keratins; Male; Middle Aged; Neoplasm Recurrence, Local; Proto-Oncogene Proteins c-bcl-2; Reoperation; Thymus Gland; Thymus Neoplasms; Thyroid Neoplasms; Tomography, X-Ray Computed

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

There were investigated 22 cases from which the thymic tissue was removed either during surgery for cardiovascular malformations (n = 14), or for myasthenia gravis (n = 8). Histological sections were stained with routine morphologic methods, and immunohistochemistry was performed for cytokeratin, CD20, CD3, and S100 protein. Aspects characteristic for thymus involution were found in 11 cases without myasthenia gravis and in all cases with myasthenia gravis. Morphological changes of the thymus of involution are age-dependent. There were characterized stages of involution, with special reference to cortical - medulla inversion, lymphocyte depletion and sequestration. In advanced-stage of involution, epithelial cells are arranged in cords or compact islands, and could mimic a thymoma or a metastatic carcinoma. The immunohistochemical profile is similar but not identical to the active thymus. We noticed a decreased expression of cytokeratin, and a reduced number of CD3, CD20, and S100 positive cells. Morphologic and immunohistochemical peculiarities of the thymus of involution are discussed in relation with the specific pathology of the organ.

Topics: Adolescent; Adult; Antigens, CD20; Atrophy; Carcinoma; Cardiovascular Abnormalities; CD3 Complex; Child; Child, Preschool; Diagnosis, Differential; Humans; Infant; Infant, Newborn; Keratins; Lymphatic Diseases; Middle Aged; Myasthenia Gravis; Thymus Gland; 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

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

Primary thymic adenocarcinoma, mucinous subtype, is extremely rare with only one case reported to date. We describe herein a case of thymic mucinous adenocarcinoma. A 59-year-old man was identified to have an anterior mediastinal tumor and was diagnosed as mucinous adenocarcinoma. Clinical and radiographic examinations disclosed no evidence of tumor elsewhere. The patient received radiotherapy, but the general condition deteriorated and died 11 months after tumor detection. Thoracic autopsy revealed an anterior mediastinal tumor measuring greater than 10 cm, uncapsulated, and white. The tumor had clear margins and was clearly isolated from the lung. Histologically, the tumor demonstrated papillary, acinar, and cribriform structure and produced abundant extracellular mucin. Immunohistochemically, most tumor cells were positive for cytokeratin 7, were partially positive for CD5, and were negative for TTF-1, Sp-A, CDX-2, MUC2, napsin A, and cytokeratin 20. Collectively, the diagnosis of the tumor was primary mucinous adenocarcinoma of the thymus. We propose that the mucinous subtype should be recognized as one of the histopathological entities of thymic adenocarcinoma.

Topics: Adenocarcinoma, Mucinous; Biomarkers, Tumor; Fatal Outcome; Humans; Immunohistochemistry; Keratin-7; Keratins; Male; Mediastinal Neoplasms; Middle Aged; Thymus Neoplasms

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

To assess the diagnostic accuracy and to study the histologic typing of mediastinal lesions using core needle biopsies.. The histopathology and immunophenotype of 65 mediastinal core needle biopsy specimens were studied retrospectively by light microscopy and immunohistochemical staining (ABC method). Gene rearrangement studies were performed in some of the non-Hodgkin's lymphomas cases using PCR. Follow-up records were also analyzed.. Morphologically, all specimens showed a combination of epithelioid cells, lymphoid cells and fibrous tissue in different proportions. The pathologic diagnoses included lymphoma (21 cases), pulmonary carcinoma (20 cases), thymoma (14 cases), thymic carcinoma (4 cases), seminoma (3 cases) and chronic inflammation (1 case). Definitive diagnosis was not possible in 2 cases due to insufficient material. The tumor cells in lymphoma (21 cases) expressed CD20, CD3, TDT, CD30, CD15 or EMA, depending on their histologic subtypes. Tumor cells in the 17 pulmonary carcinoma cases expressed cytokeratin (CK), except 3 cases of small cell carcinoma of lung. Synaptophysin, chromogranin A and neuron-specific enolase were all positive in the 10 cases of small cell carcinoma of lung and 1 case of thymic small cell carcinoma (which was also CD5 negative). The 3 cases of adenocarcinoma of lung showed positivity for thyroid transcription factor-1 (TTF-1) and they were negative for CD5. The 14 thymoma cases expressed CK, CD3 or CD20. The 3 thymic carcinoma cases expressed CK and CD5. Placental-like alkaline phosphatase (PLAP) was positive in 3 seminoma cases which were CK-negative. Immunoglobulin heavy chain gene was rearranged in the 3 cases of diffuse large B-cell lymphoma and 1 B-cell anaplastic large cell lymphoma case. T-cell receptor beta gene was rearranged in 5 T-cell lymphoblastic lymphoma cases.. Microscopic assessment of tissue samples from mediastinal core needle biopsies should be made in combination with clinical and radiologic information. Ancillary investigations, including immunohistochemical staining and/or gene rearrangement studie, are needed in both non-lymphoma and lymphoma cases of mediastinum.

Topics: Adolescent; Adult; Aged; Biopsy, Needle; CD5 Antigens; Child; Child, Preschool; Diagnosis, Differential; Female; Follow-Up Studies; Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; Humans; Keratins; Lung Neoplasms; Lymphoma; Male; Mediastinal Diseases; Mediastinum; Middle Aged; Retrospective Studies; Thymus Neoplasms

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

A 54-year-old man was admitted to our hospital because of dyspnea. Radiographic examination showed an anterior mediastinal mass and pericardial effusion. Serum calcium and parathyroid hormone-related protein (PTHrP) levels were elevated, and serum CYFRA 21-1 level was extremely high. Results of percutaneous needle biopsy under computed tomography guidance led to a diagnosis of moderately differentiated squamous cell carcinoma. Immunohistological staining showed the tumor cells to be positive for PTHrP and cytokeratin monoclonal antibodies. Postmortem findings were considered to indicate thymic carcinoma. Thymic carcinoma is rare, but our case indicates that thymic squamous cell carcinoma can be identified in terms of paraneoplastic hypercalcemia.

Topics: Antigens, Neoplasm; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Biopsy; Carcinoma, Squamous Cell; Cisplatin; Cyclophosphamide; Diphosphonates; Doxorubicin; Fatal Outcome; Humans; Keratin-19; Keratins; Male; Mediastinum; Middle Aged; Pamidronate; Parathyroid Hormone-Related Protein; Thymus Neoplasms; Vincristine

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

To illustrate the macroscopic, light microscopic and immunophenotypic similarities that exist between primary pleural thymic epithelial tumours and diffuse malignant mesothelioma. To investigate the expression of the mesothelial markers, cytokeratin (CK) 5/6, calretinin and thrombomodulin in a series of mediastinal thymic epithelial tumours.. Over a 10-year period, 64 diffuse pleural tumours of non-mesothelial histogenesis were identified in the files of referrals to the South Wales regional thoracic centre (Llandough Hospital, Cardiff). Of these, five pleural tumours were diagnosed as primary pleural thymic epithelial neoplasms. From the files of the Mesopath group, Caen, three additional cases of thymic epithelial tumours with pleural involvement were identified. The study group comprised eight cases (four males, four females) with median age at presentation of 56 years (range 19-75 years). In one case there was a history of asbestos exposure. Macroscopically, seven tumours formed diffuse pleural masses. No mediastinal abnormality or intraparenchymal lesions were seen in five cases. By light microscopy, seven thymic epithelial neoplasms showed a lobulated architecture, one appeared extensively cystic. The tumours were of varied morphological subtypes: one medullary (WHO Type A), two mixed (WHO Type AB), three predominantly cortical (WHO Type B1) and two cortical (WHO Type B1). The subtypes morphologically mimicked sarcomatoid, biphasic, lymphohistiocytoid variant and epithelioid mesothelioma. The pleural thymic epithelial tumours showed immunoreactivity with broad spectrum cytokeratin AE1/AE3 (8/8; 100%), CK5/6 (8/8; 100%), and 1/8 (13%) expressed thrombomodulin. Calretinin showed variable nuclear and cytoplasmic expression in all cases, but equivocally in the thymic epithelial cell component. In 7/8 (88%) the thymic epithelial cells exhibited focal aberrant expression of CD20. Epithelial membrane antigen (EMA) showed focal expression in the perivascular and organoid areas in 6/8 (75%) cases. Carcinoembryonic antigen (CEA) and CD34 were uniformly negative. In 4/8 (50%) cases the lymphoid cell component was of immature phenotype expressing CD99, terminal deoxynucleotidyl transferase (TdT) and lymphoid precursors had a high proliferation fraction with Ki67. In the series of 20 primary mediastinal thymic epithelial tumours tested, mesothelial marker expression revealed CK5/6 (20/20), thrombomodulin (3/20; 15%) and calretinin (0/20; 0%). Varying amounts of calretinin-positive stromal cells were present.. Primary pleural thymic epithelial tumours are rare but may mimic malignant mesothelioma by forming diffuse serosal-based masses. In addition, both tumours may show morphological diversity (with epithelial, spindled and mixed components present). An awareness that thymic epithelial tumours may variably express the mesothelial markers CK5/6, calretinin and thrombomodulin prevents misdiagnosis. In the distinction from malignant mesothelioma a lobulated architecture and organoid features favour a thymic epithelial neoplasm. The presence of aberrant CD20 expression in a cytokeratin-positive epithelial neoplasm and/or the presence of an immature lymphoid population (by demonstration of CD1a, CD2, CD99 and TdT) indicates a thymic epithelial neoplasm. In contrast, nuclear calretinin expression favours malignant mesothelioma.

Topics: Adult; Aged; Biomarkers, Tumor; Calbindin 2; Diagnosis, Differential; Female; Humans; Keratins; Male; Mediastinum; Mesothelioma; Middle Aged; Neoplasms, Glandular and Epithelial; Neoplasms, Mesothelial; Pleural Neoplasms; S100 Calcium Binding Protein G; Thrombomodulin; Thymus Neoplasms

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

A 58-year-old woman with a history of Cushing's syndrome for three years presented with a mediastinal mass and received the diagnosis of small cell neuroendocrine carcinoma of the thymus invading the pericardium. On immunohistochemical study, the neoplastic cells reacted with antibodies against cytokeratin, epithelial membrane antigen, neuron-specific enolase, chromogranin, synaptophysin, and ACTH. Clinicopathologic findings of this rare case of ectopic adrenocorticotropic hormone (ACTH) syndrome are discussed with a literature review.

Topics: Adrenocorticotropic Hormone; Carcinoma, Neuroendocrine; Carcinoma, Small Cell; Chromogranins; Cushing Syndrome; Dexamethasone; Female; Humans; Immunoenzyme Techniques; Keratins; Middle Aged; Mucin-1; Phosphopyruvate Hydratase; Radiography, Thoracic; Synaptophysin; Thymus Neoplasms

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

Twelve cases of carcinoid tumors of the thymus were reviewed in terms of clinicopathologic, histochemical, and immunohistochemical features and DNA ploidy patterns. The collective consisted of nine male and three female patients, aged 34 to 74 years, of whom five (42%) had symptoms. Eleven patients underwent surgical resection, and one with systemic metastases was autopsied. In the 11 resected patients, tumors had invaded surrounding structures in four cases, and mediastinal lymph node metastases were detected in six. Recurrence occurred in two of the resected patients (18%), and the 5-year survival rate was 82%. Histologically, all tumors showed an organoid growth pattern with delicate fibrovascular stroma. In addition, three tumors had unusual morphologic features such as combined features of carcinoid tumor and thymoma and solid growth pattern with occasional large tumor cells. Mitotic counts ranged from 1 to 14 per 10 high-power fields with a mean count of 4.9. Central necrosis within solid nests was observed in nine tumors. Classification of this series using the WHO histologic classification system resulted in categorization of all 12 tumors as atypical carcinoids. All tumors were positive for Grimelius staining and for cytokeratin. Immunohistochemical staining documented the presence of moderately to strongly positive neuroendocrine markers such as neuron-specific enolase, chromogranin A, synaptophysin, and neural cell adhesion molecule. No correlation between proliferative activity based on the Ki67 labeling index and prognosis or lymph node metastasis was found. Concerning DNA ploidy patterns, only one tumor with multiple lymph node metastases was considered to be aneuploid. In conclusion, although all of our cases were histologically classified as atypical carcinoid tumors of the thymus, most were diploid, and the patients enjoyed a relatively good prognosis.

Topics: Adrenocorticotropic Hormone; Adult; Aged; Carcinoid Tumor; Cholecystokinin; Chromogranin A; Chromogranins; DNA, Neoplasm; Female; Flow Cytometry; Humans; Immunohistochemistry; Keratins; Ki-67 Antigen; Male; Middle Aged; Neural Cell Adhesion Molecules; Phosphopyruvate Hydratase; Ploidies; S100 Proteins; Silver Staining; Somatostatin; Survival Analysis; Synaptophysin; 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

Twenty-two cases of oncocytic thymic neuroendocrine carcinomas (carcinoid tumors) are presented. The patients were 17 men and 5 women between the ages of 26 and 84 years (median, 55 years). Nine were asymptomatic, and the tumor was found on routine examination; four patients presented with chest pain, two with weight loss, two with multiple endocrine neoplasia I syndrome, and one with Cushing's syndrome. Surgical resection of the mediastinal tumor was performed in all cases. The lesions were described as soft, light tan to brown, measuring from 3 to 20 cm in greatest diameter. On cut section, the tumors showed a homogeneous surface, soft consistency, and focal areas of hemorrhage. Microscopically, the lesions were characterized by nests or trabeculae of tumor cells that contained abundant granular to densely eosinophilic cytoplasm, with round to oval nuclei and in some areas prominent nucleoli. Mitotic figures ranged from 2 to 10 per 10 high-power fields; foci of comedonecrosis were seen in all cases. Immunohistochemical studies including broad spectrum keratin, CAM 5.2, chromogranin, synaptophysin, Leu-7, and p53 were performed in 12 cases. All of the tumors were strongly positive for CAM 5.2 low-molecular-weight cytokeratin, 11 showed strong positive reaction for Leu-7, 10 for broad-spectrum keratin, 8 for chromogranin, 7 for synaptophysin, and only 1 case showed focal positive staining of the tumor cells for p53. Clinical follow-up of 14 patients showed that 10 were alive between 2 and 11 years, and 4 patients had died of tumor from 4 to 11 years after diagnosis. Patients with good clinical outcome were those whose tumors showed low mitotic activity and minimal nuclear pleomorphism, whereas those who had died of their tumors were those whose tumors were characterized by marked nuclear atypia and higher mitotic rates. Oncocytic thymic carcinoids should be added to the differential diagnosis of anterior mediastinal neoplasms characterized by a monotonous population of tumor cells with prominent oncocytic features.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Carcinoma, Neuroendocrine; CD57 Antigens; Chromogranins; Female; Follow-Up Studies; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Synaptophysin; Thymus Neoplasms

A neuroendocrine carcinoma originating in the thymus was found in a 7-month-old, castrated male, Japanese Black calf. The neoplasm consisted largely of very primitive cells, characterized by the paucity of cytoplasmic organelles, but a few cells were immunoreactive for somatostatin or neurofilaments. The expression of both cytokeratin and neurofilament protein was a feature of neuroendocrine differentiation. This neoplasm considered to be a tumor of a thymic stem cell, with little but indubitable evidence of differentiation into somatostatin-producing cells.

Topics: Animals; Carcinoma, Neuroendocrine; Cattle; Cattle Diseases; Keratins; Male; Microvilli; Orchiectomy; Thymus Neoplasms

Two cases of pigmented thymic carcinoids are presented. The patients were two men, 32 and 47 years of age. The two patients were asymptomatic and the tumor was discovered on routine chest radiographic evaluation. The tumors were treated by surgical excision in both patients. Grossly, they presented as tan-white tumors without evidence of necrosis or hemorrhage or any visible pigmentation. Histologically, the tumors were characterized by a monotonous proliferation of tumor cells arranged in a trabecular or nesting pattern. The tumor cells showed moderate amounts of pale eosinophilic cytoplasm, round to oval nuclei, and inconspicuous nucleoli. Mitotic activity varied from three to eight per 10 high-power fields. In addition, both tumors showed prominent areas of intra- and extracellular dark pigment deposition. The pigment reacted positively with the Fontana-Masson stain and was negative for iron stain. Immunohistochemical studies performed in one case showed immunoreactivity of the tumor cells for chromogranin, Leu 7, and keratin. Synaptophysin and P53 immunostains were negative. Clinical follow-up was obtained in one patient who was alive and well 10 years after surgical resection. The presence of abundant melanin pigment in thymic carcinoids highlights an important pitfall for diagnosis in these tumors that should be taken into consideration in the evaluation of anterior mediastinal lesions.

Topics: Adult; Carcinoid Tumor; CD57 Antigens; Chromogranins; Humans; Immunohistochemistry; Keratins; Male; Melanins; Middle Aged; Thymus Neoplasms

The majority of thymic lymphomas are either lymphoblastic lymphoma, large B cell lymphoma or Hodgkin's disease, and other types of non-Hodgkin lymphoma are rare. A case of low-grade B cell lymphoma of mucosa-associated lymphoid tissue (MALT) in the thymus is reported. A 55-year-old Japanese female with a history of rheumatoid arthritis (RA) complained of back pain. A mediastinal tumor was identified by computerized tomography and magnetic resonance imaging, and the thymus was resected through median sternotomy. The solid and nodular tumor had several small satellite extensions and was completely confined to within the thymus. Histologically, monotonous medium-sized centrocyte-like cells occupied the medulla of the thymus and infiltrated Hassall's corpuscles (lymphoepithelial lesions). Immunohistochemically, tumor cells were positive for CD20 and CD79a. IgA and kappa light chain restriction were also found in plasmacytoid cells in the tumor. Clonal rearrangement of the immunoglobulin heavy chain gene was demonstrated by polymerase chain reaction. This case was diagnosed as MALT-type low-grade B cell lymphoma in the thymus. This is the first report of low-grade B cell lymphoma in the thymus associated with RA. As autoimmune diseases are known to be associated with lymphoid neoplasms, it is suggested that the RA played an important role in the development of malignant lymphoma in this case.

Topics: Antigens, CD20; Arthritis, Rheumatoid; Biomarkers, Tumor; Blotting, Southern; Clone Cells; Female; Humans; Immunoglobulin Heavy Chains; Immunoglobulin kappa-Chains; Immunohistochemistry; Keratins; Lymphoma, B-Cell, Marginal Zone; Middle Aged; Proto-Oncogene Proteins c-bcl-2; Thymus Neoplasms

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

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

We report three cases of neuroblastoma arising within the thymus of elderly patients. All tumors consisted of primitive neuroblasts showing focal gangliocytic differentiation within nests of neuropil. All stained for neuroendocrine markers but were negative for cytokeratins and for the MIC2 gene product. One tumor was associated with the syndrome of inappropriate secretion of antidiuretic hormone, an endocrinopathy we found in three of five case reports of thymic neuroblastoma in adults. Immunohistochemical stains confirmed production of antidiuretic hormone by this tumor. One patient died of progressive disease, one patient is disease free at 18 months, and the other patient died of unrelated causes, a spectrum that reflects the variable clinical behavior others have reported. The possible histogenesis of these purely neural tumors includes malignant transformation of a mediastinal teratoma, aberrantly located sympathetic ganglia, neuroectodermal cells native to the normal thymus, and precursors of thymic epithelial cells that have differentiated along neural lines.

Topics: Aged; Aged, 80 and over; Carcinoid Tumor; Chromogranins; Female; Humans; Immunohistochemistry; Inappropriate ADH Syndrome; Keratins; Male; Mediastinal Neoplasms; Microscopy, Electron; Neuroblastoma; Phosphopyruvate Hydratase; Synaptophysin; Thymus Gland; Thymus Neoplasms

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

Topics: Adult; Apudoma; Carcinoid Tumor; Follow-Up Studies; Humans; Keratins; Male; Phosphopyruvate Hydratase; Thymus Neoplasms

FF-6 is a transplantable squamous cell carcinoma which originally arose in the facial skin of a DA rat. It was established after maintaining the tumor in the subcutaneous tissue or peritoneal cavity of DA rats conventionally for over 30 generations. When the soybean-sized original FF-6 tumor was transplanted subcutaneously, it became an oval, hard, whitish, solitary and thumb-head-sized nodule within one month. After intraperitoneal transplantation of FF-6, it formed many nodules ranging from miliary to thumb-head size, which adhered and/or metastasized to many abdominal organs. When FF-6, cut into small pieces, was injected into the lower lip, the tumor grew bigger in situ, and metastasized to regional lymph nodes. Histologically, FF-6 was characterized as a well-differentiated squamous cell carcinoma, showing positive staining with anti-keratin, anti-laminin, anti-collagen type IV, anti-fibronectin and UB-14 antibodies. This transplantable tumor may be useful for analyzing the mechanisms of proliferation and metastasis of squamous cell carcinoma in vivo, and the host defence mechanism in rats, as well as being a suitable model of human squamous cell carcinoma.

Topics: Animals; Carcinoma, Squamous Cell; Cell Division; Cell Line; Collagen; Fibronectins; Humans; Immunohistochemistry; Keratins; Laminin; Lymphatic Metastasis; Neoplasm Metastasis; Neoplasm Transplantation; Rats; Rats, Inbred Strains; Skin Neoplasms; 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

Ten infant thymuses and 13 primary thymic tumors obtained from archived paraffin-embedded tissue were examined for the presence of tissue blood group O antigen (H), peanut agglutinin receptor antigen (PNA-r), Saphora japonica agglutinin receptor antigen (SJA-r), carcinoembryonic antigen (CEA), cytokeratin (CK), and epithelial membrane antigen (EMA). In the thymuses studied, Hassall's corpuscles contained abundant immunoreactive CK, PNA-r, and H antigens, whereas CEA, SJA-r, and EMA were present focally in Hassall's corpuscles. Immunoreactive CK, PNA-r, and CEA were demonstrated focally in the subcapsular region, cortical nurse cells, and subcapsular-perivascular monocytic cells, respectively. PNA-r was present in all 12 epithelial type tumors, including all eight thymomas. CEA was present in nine tumors, including six thymomas. Six thymomas contained H antigen and SJA-r; five continued CK and EMA. SJA-r and EMA were also present in one carcinoid tumor of thymic origin. In epithelial thymomas, the antigens stained nests of epithelial cells resembling the pattern of staining in Hassall's corpuscles. Membrane staining of spindle cells of both spindle cell and epithelial thymomas was less intense than staining of epithelial type cells.

Topics: ABO Blood-Group System; Antigens, Neoplasm; Carcinoembryonic Antigen; Cell Membrane; Cytoplasm; Epithelium; Histocytochemistry; Humans; Immunoenzyme Techniques; Infant; Keratins; Membrane Glycoproteins; Mucin-1; Receptors, Mitogen; Thymus Gland; Thymus Neoplasms

Thymic carcinoma (TCA) is a thymic epithelial neoplasm with obvious cytologic atypia. We studied 13 cases of TCA by light microscopy, immunohistochemistry, and electron microscopy and correlated the findings with clinical features. The patients' mean age was 54.2 years (range 30-74); the male/female ratio was 7/6. Twelve of the 13 patients presented with signs and symptoms caused by compression of mediastinal organs; the other patient was asymptomatic. Paraneoplastic syndromes were never seen. At thoracotomy, 11 tumors invaded or adhered to surrounding structures; the other two were encapsulated. The histologic types include squamous carcinoma including the lymphoepithelioma-like subtype (seven cases), small cell carcinoma (four cases), clear cell carcinoma (one case), and adenosquamous carcinoma (one case). Positive immunoperoxidase studies were as follows: keratin (13 cases), epithelial membrane antigen (EMA) (13 cases), leukocyte common antigen (none), carcinoembryonic antigen (CEA) (five cases), B72.3 (seven cases), Leu 7 (two cases), human placental alkaline phosphatase (none), vimentin (none), and chromogranin (one case). This profile is similar to those of normal thymus and thymoma except for the absence of CEA, B72.3, EMA in normal thymus, and the absence of CEA and B72.3 in thymoma. Electron-microscopic studies performed on eight cases showed glandular and squamous differentiation in one adenosquamous carcinoma, squamous differentiation in five squamous carcinomas, and neuroendocrine differentiation in one small-cell carcinoma. Nine patients died (three due to postoperative complications and six due to recurrences or metastasis at 3-36 months). Four patients (all with squamous carcinoma) were alive without disease at 2-60 months. The clinical and pathologic features were comparable with those of approximately 62 other cases of TCA previously reported. There are a number of well-defined histologic types of TCA that allow the pathologist to make a differential diagnosis of TCA from tumors extending or metastatic to thymus or other primary mediastinal tumors. Although neither asymptomatic presentation nor encapsulation improves the poor prognosis of TCA, the squamous carcinoma subtype is associated with a better outcome than the other subtypes. Based on the electronmicroscopic and immunohistochemical findings, the presence of normal thymic tissue at the periphery of several tumors, and the observation that several TCA arose from preexisting thymomas

Topics: Adenocarcinoma; Adult; Aged; Alkaline Phosphatase; Carcinoembryonic Antigen; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Female; Humans; Immunohistochemistry; Isoenzymes; Keratins; Male; Membrane Glycoproteins; Middle Aged; Mucin-1; 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

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

Eighteen cases of primary thymic carcinoma were reviewed from the viewpoint of glandular differentiation. Squamous differentiation was evident in 14 cases (83%). Immunohistochemical study revealed secretory component (SC)-positive carcinoma cells in 12 cases (67%), most of which were also associated with squamous differentiation. Three of these 12 cases contained areas with a definite glandular or microcystic structure with occasional epithelial mucin, and were diagnosed as adenosquamous carcinoma. Review of patients' medical records revealed that thymic carcinomas with a glandular element were more often resectable at surgery, and had a much better prognosis than those without a glandular element. However, further study on larger number of cases is necessary to confirm this relationship. Because SC-positive epithelial cells do exist in the non-neoplastic thymus, the presence of a glandular component suggests another direction of morphological and/or functional differentiation of thymic carcinoma cells in addition to the well-known squamous differentiation.

Topics: Biomarkers, Tumor; Carcinoma; Carcinoma, Squamous Cell; Cell Differentiation; Cell Transformation, Neoplastic; Humans; Immunohistochemistry; Keratins; Prognosis; Thymus Gland; 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: Humans; Keratins; Neoplasms; 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

Antibodies against different fractions of keratins can be helpful in various fields of special pathology. Antibodies against "small" and "large" keratins permit to evaluate epithelial maturation in skin and oral mucosa. In addition, disturbances of keratinization during inflammatory processes and malignant transformation can be analyzed. The main application of antibodies against the entire fractions of keratins is the detection of the epithelial nature of a neoplasm. By this tool, particular problems in surgical pathology concerning differential diagnosis can be handled in an easier way. Among the different tissues and their neoplasms, examples of the analysis of thymus tumours and salivary gland tumours are presented. Immunoreactivity with keratin antibodies depends crucially on tissue processing. In the normal diagnostic procedure, good results are regularly obtained if cryostat or Bouin-fixed paraffin-embedded sections are used.

Topics: Adenoma; Carcinoma in Situ; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Cytoskeleton; Humans; Keratins; Mouth Mucosa; Mouth Neoplasms; Parakeratosis; Salivary Gland Neoplasms; Salivary Glands; Skin; Skin Neoplasms; Thymus Gland; Thymus 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