bromochloroacetic-acid and Mediastinal-Neoplasms

Primary mediastinal endodermal sinus tumor is rare, and to date only 49 cases have been described in the English-language literature. Seven new cases are reported. Light microscopic examination showed characteristic features including papillary, reticular, tubular and solid growth patterns, complete or incomplete Schiller-Duval bodies and intracellular or extracellular periodic acid-Schiff-positive material. Immunohistochemical studies showed alpha-1-antitrypsin in seven, alpha-fetoprotein in seven, keratin in six, and carcinoembryonic antigen in four cases. The beta subunit of human chorionic gonadotropin, albumin, fibronectin, and transferrin were not found in any case. Electron microscopic studies performed in four cases showed intracellular and extracellular basement membrane-like material, multiple large multivesicular bodies, desmosomes and microvilli. Mediastinal endodermal sinus tumor can and must be differentiated from poorly differentiated adenocarcinoma metastatic or extending to the mediastinum because of the distinctly different prognoses and therapies. In spite of modern chemotherapy, the prognosis of mediastinal endodermal sinus tumor remains poor. The single most important prognostic indicator is whether the tumor mass can be completely excised before or after chemotherapy.

Topics: Adolescent; Adult; alpha 1-Antitrypsin; alpha-Fetoproteins; Carcinoembryonic Antigen; Child; Child, Preschool; Female; Follow-Up Studies; Histocytochemistry; Humans; Keratins; Male; Mediastinal Neoplasms; Mediastinum; Mesonephroma; Microscopy, Electron

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

Primary mediastinal germ cell tumors are uncommon tumors that can pose diagnostic difficulties due to their morphologic spectrum and unusual site. Immunohistochemistry plays an increasing role in the diagnosis of these tumors. Whereas the immunophenotype of testicular yolk sac tumors (YST) is rather well known, the opposite is true for primary mediastinal YST leading us to investigate the immunohistochemical features of 14 such neoplasms. Fourteen cases of primary mediastinal YST were reviewed and representative whole tissue sections were selected for immunohistochemical analysis using antibodies directed against CAM5.2, SALL4, OCT3/4, glypican-3, CD30, α-fetoprotein (AFP), CD117, placental alkaline phosphatase (PLAP), GATA-3, and CDX2. The percentage of positive tumor cells and the intensity of staining were evaluated and scored. All cases (100%) showed strong and diffuse expression of CAM5.2 and SALL4, 10 cases (71%) reacted with glypican-3 and AFP in a patchy manner, 5 cases (36%) showed focal positivity with PLAP and GATA-3, 4 cases (29%) showed staining for CDX2, 3 (21%) showed expression of CD117, and a single case was positive for CD30 (7%). None of the cases showed any staining for OCT3/4. Primary mediastinal YST appear to have a similar immunohistochemical phenotype as their testicular counterparts. Coexpression of CAM5.2, SALL4, glypican-3, and AFP provides the best support for YST differentiation; however, it has to be noted that none of these markers is specific for these tumors and immunohistochemical results will always have to be interpreted in the context of morphologic, clinical, and radiologic information.

Topics: Adolescent; Adult; Biomarkers; Cell Differentiation; Child; Diagnosis, Differential; Endodermal Sinus Tumor; Humans; Immunohistochemistry; Immunophenotyping; Keratins; Male; Mediastinal Neoplasms; Middle Aged; Octamer Transcription Factor-3; Testicular Neoplasms; Transcription Factors; Young Adult

The cytologic diagnosis of synovial sarcoma (SS) can be difficult when it occurs in unusual locations, atypical age groups, and/or have unusual morphology. We report a case of primary mediastinal SS in a 65-year-old male with a long smoking history who presented with increasing shortness of breath and was found to have a 14.2 cm mediastinal mass. Smears from the endobronchial ultrasound guided fine needle aspiration of the mass were moderately cellular consisting of loosely cohesive clusters, some of which demonstrated nuclear molding, and dispersed single cells. The relatively uniform tumor cells had a high nuclear-to-cytoplasmic ratio, finely granular chromatin, and inconspicuous nucleoli. Some of the single cells had spindled morphology with unipolar wispy tails and naked nuclei. Based on the clinical presentation and the cytomorphologic features, our initial differential diagnoses included atypical carcinoid, small cell carcinoma, basaloid squamous cell carcinoma, sarcoma, and lymphoma. Immunohistochemical studies on the cell block sections revealed that the tumor cells were focally positive for cytokeratin and diffusely positive for CD56, while negative for CD45, synaptophysin and chromogranin. Ultimately, an immunohistochemical stain for TLE-1 demonstrated diffusely strong nuclear positivity and molecular studies showed the presence of the t(X; 18) SYT/SSX1 translocation confirming the diagnosis of SS. In this report, we describe the cytomorphologic features of SS, its diagnostic pitfalls, and potential mimics in the mediastinum.

Topics: Aged; Biomarkers, Tumor; Biopsy, Fine-Needle; CD56 Antigen; Co-Repressor Proteins; Humans; Keratins; Ki-67 Antigen; Male; Mediastinal Neoplasms; Neoplasm Proteins; Pulmonary Disease, Chronic Obstructive; Repressor Proteins; Sarcoma, Synovial; Smoking; Translocation, Genetic

Topics: Adenofibroma; Adult; DNA-Binding Proteins; Humans; Immunohistochemistry; Keratins; Male; Mediastinal Neoplasms; Transcription Factors

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

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

Primary pulmonary and mediastinal synovial sarcoma is rare and poses a diagnostic challenge particularly when unusual histological features are present. We present 60 cases of primary pulmonary and mediastinal synovial sarcoma (29 male and 27 female subjects; mean age, 42 years) and compare our results with five prior series to better define unusual histological features. Clinically, patients with mediastinal synovial sarcoma were younger with a male gender bias. Radiologically, tumors were well delineated with distinctive magnetic resonance imaging features and little vascular enhancement. In all, 21/46 patients died of disease within 5 years. Histologically, all tumors had dense cellularity, interlacing fascicles, hyalinized stroma, and mast cell influx. Hemangiopericytoma-like vasculature (48/60), focal myxoid change (30/60), and entrapped pneumocytes (23/60) were seen. Calcification was not prevalent (10/60). Unusual histological features included Verocay body-like formations (7/60), vague rosettes (6/60), well-formed papillary structures (3/60), adenomatoid change (3/60), and rhabdoid morphology (2/60). Immunohistochemistry demonstrated expression of pancytokeratin (39/58), epithelial membrane antigen (29/53), cytokeratin 7 (26/40), cytokeratin 5/6 (5/7), calretinin (15/23), CD99 (19/23), bcl-2 (24/24), CD56 (11/11), S-100 (9/51), and smooth muscle actin (8/32). In total, 92% (36/39) of primary pulmonary and mediastinal synovial sarcomas studied were positive for t(x;18). In conclusion, our study confirms the clinical, histological, immunohistochemical, and molecular data from previous large series of primary pulmonary and mediastinal synovial sarcoma. Compared with soft tissue synovial sarcoma, primary pulmonary and mediastinal synovial sarcoma has less calcification, less obvious mast cell influx, and less radiologic vascularity, but similar magnetic resonance imaging features, percentage of poorly differentiated tumors, and number of t(x;18)-positive tumors. Awareness of focal unusual histology can prevent misdiagnosis particularly in t(x;18)-negative tumors.

Topics: 12E7 Antigen; Adult; Antigens, CD; Calbindin 2; CD56 Antigen; Cell Adhesion Molecules; Chromosomes, Human, Pair 18; Chromosomes, Human, X; Female; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Male; Mediastinal Neoplasms; Oncogene Proteins, Fusion; Proto-Oncogene Proteins c-bcl-2; S100 Calcium Binding Protein G; S100 Proteins; Sarcoma, Synovial; Survival Rate; Translocation, Genetic

This study was designed to screen occult cancer cells by CK19 mRNA detection using reverse transcriptase-polymerase chain reaction (RT-PCR) in mediastinal lymph nodes stations (MLNS) in non-small cell lung carcinoma (NSCLC). In 49 NSCLC patients free of mediastinal adenopathy on computed tomograph, 254 MLNS were evaluated by histopathology, immunohistochemistry (IHC) and RT-PCR. Of 225 non-tumoral MLNS on histopathology, 32 (14.2%) were positive by RT-PCR. IHC did not provide significant additional results. Seventeen patients were without mediastinal tumoral extension on histopathology and RT-PCR (Group 1), 16 were upgraded by RT-PCR (Group 2) and 16 pN2 on histopathology (Group 3). The two-year cancer-related death survival in Groups 1 (100%) and 2 (64.5%) was significantly different (P=0.04). The relative risk of recurrence in Group 2 compared with Group 1, evaluated by the Cox model multivariate analysis, was 5.61 (P=0.02). In conclusion, CK19 mRNA detected by RT-PCR in MLNS was significantly associated with an increased risk of rapid recurrence.

Topics: Adult; Aged; Carcinoma, Non-Small-Cell Lung; Female; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Lymph Node Excision; Lymphatic Metastasis; Male; Mediastinal Neoplasms; Middle Aged; Multivariate Analysis; Neoplasm Recurrence, Local; Reverse Transcriptase Polymerase Chain Reaction; Risk Factors; RNA, Messenger; RNA, Neoplasm; Survival Analysis

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

Three cases of serous borderline tumors of the ovary with areas of serous low-grade carcinoma metastatic to the anterior mediastinum simulating multilocular thymic cysts are presented. The patients are women between the ages of 33 and 50 years. The 3 women had a prior history of primary ovarian neoplasms diagnosed over a period ranging from 3 to 20 years; the 3 patients were in stages IIIA, IIIB, and III. Follow-up radiologic examination revealed the presence of an anterior mediastinal tumor. The 3 patients underwent surgical resection of the mediastinal tumor. Grossly, the mediastinal tumors measured from 7 to 9 cm in greatest diameter and were described as cystic with solid areas. Focal areas of hemorrhage were present, but frank necrosis was not identified. Histologically, all the tumors basically showed similar histopathologic features, namely, those described in multilocular thymic cysts, ie, cystic structures lined by either squamous or low cuboidal epithelium, lymphoid hyperplasia, cholesterol cleft granulomas, and remnants of thymic tissue. In addition, within the cystic structures, there was a neoplastic cellular proliferation with papillary architecture, nuclear atypia, and scattered mitotic figures. Immunohistochemical studies for keratin, MOC31, and CA-125 showed positive staining in tumor cells while placental-like alkaline phosphatase was negative. Two patients remain alive and well after follow-up ranging from 6 to 18 months and 1 patient died of tumor 18 years after initial diagnosis.

Topics: Adult; Biomarkers, Tumor; Cystadenocarcinoma, Serous; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Mediastinal Cyst; Mediastinal Neoplasms; Mediastinum; Middle Aged; Ovarian Neoplasms

A series of 15 cases of primary mediastinal neoplasms displaying histopathologic, immunohistochemical, and ultrastructural features of synovial sarcoma is presented. The patients' ages ranged from 3 to 83 years, with a male-to-female ratio of 2:1. Nine cases presented as anterior mediastinal masses with chest pain, shortness of breath, and pleural effusion, and 6 cases were in paravertebral location in the posterior mediastinum and presented with neck or back pain and pleural effusion. The tumors measured from 5 to 20 cm in greatest diameter and showed a tan white, soft to rubbery cut surface with areas of hemorrhage and necrosis and foci of gelatinous material. Four cases showed areas of cystic degeneration. In 7 cases, the tumors were well circumscribed; in 6 cases, the tumors grossly invaded the pleura, pericardium, heart, great vessels, chest wall, rib, and vertebra. Histologically, 5 cases displayed a biphasic growth pattern, with well-formed glandular elements admixed with a monotonous spindle cell population. Ten cases were exclusively composed of a monotonous atypical spindle cell proliferation. Immunohistochemical studies showed focal positivity of the tumor cells for cytokeratin and/or epithelial membrane antigen, and strong positivity for vimentin and bcl-2 in the spindle cells in all cases studied (10 of 10). Eight cases also showed focal positivity for CD99. Electron microscopic examination in 5 cases showed oval to spindle tumor cells with closely apposed cell membranes, abundant cytoplasmic intermediate filaments and rough endoplasmic reticulum, and immature desmosome-type cell junctions. Ten patients were treated by complete surgical excision and two by partial excision followed by radiation therapy. In 4 patients, the tumors were inoperable and treated with radiation therapy only. Clinical follow-up was available in 5 patients and showed local recurrence with metastases to lung, lymph nodes, and epidural space from 1 to 3 years in 4 cases and liver metastases and death due to tumor after 6 month in 1 case. Synovial sarcoma should be considered in the differential diagnosis of biphasic and monophasic spindle cell neoplasms of the mediastinum.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Cell Nucleus; Child, Preschool; Combined Modality Therapy; Desmosomes; Female; Humans; Keratins; Male; Mediastinal Neoplasms; Microscopy, Electron, Transmission; Middle Aged; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Radiography, Thoracic; Sarcoma, Synovial; Tomography, X-Ray Computed

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

Neuroendocrine carcinoma of the posterior mediastinum is extremely rare. Described here is a patient with neuroendocrine carcinoma of the posterior mediastinum arising from a foregut cyst. A paravertebral mass detected in the posterior mediastinum of a 64-year-old man was spherical, solid and yellowish white. Some cystic or cleft-like spaces were present. Microscopically, the lesion was composed of proliferating round or polygonal tumor cells in a diffuse, solid or trabecular fashion with extensive necrosis and high mitotic activity. Components of glandular epithelia and smooth muscle layers were evident in the cystic wall. Immunohistochemically, the tumor cells were positive for both epithelial and neuroendocrine markers, including pan-cytokeratin, chromogranin A and synaptophysin. Neuroendocrine marker-positive cells were also present in the glandular epithelium of the cystic walls. It was considered that posterior mediastinal neuroendocrine carcinoma arose from a foregut cyst. Malignant change within a foregut cyst is very uncommon. This is the first report of a neuroendocrine carcinoma of the posterior mediastinum arising from a foregut cyst.

Topics: Carcinoma, Neuroendocrine; Chromogranin A; Chromogranins; Cysts; Fatal Outcome; Gastrointestinal Tract; Humans; Immunohistochemistry; Keratins; Male; Mediastinal Neoplasms; Middle Aged; Synaptophysin

Cytokeratin-positive interstitial reticulum cells (CIRCs) have been described as a subset of fibroblastic reticulum cells (FBRCs) normally found in lymph nodes, the spleen, and tonsils. Although tumors derived form other reticulum (dendritic) cells, specifically follicular dendritic cells, interdigitating dendritic cells, and cytokeratin-negative FBRCs, have been well documented and are now accepted, this is not the case for tumors of CIRCs. A possible reason for this failure is the difficulty in distinguishing them from other tumors, particularly carcinoma. We report three cases of cytokeratin-positive malignant tumors with a reticulum cell morphology: two located in the mediastinum and one in the soft tissue in the proximal forearm. All cases coexpressed vimentin, and one case coexpressed smooth muscle actin and desmin, resulting in a phenotype similar to that of some normal CIRCs. Although metastatic carcinoma from an occult or regressed primary tumor cannot be excluded completely, we raise the possibility of a CIRC origin for these cases.

Topics: Actins; Adult; Aged; Biopsy; Cytoplasm; Dendritic Cells; Desmosomes; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Lymph Nodes; Lymphatic Metastasis; Male; Mediastinal Neoplasms; Mediastinum; Middle Aged; Phenotype; Soft Tissue Neoplasms; Vimentin

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Choriocarcinoma; Chorionic Gonadotropin, beta Subunit, Human; Endodermal Sinus Tumor; Fatal Outcome; Humans; Keratins; Lung Neoplasms; Male; Mediastinal Neoplasms; Radiography, Thoracic; Tomography, X-Ray Computed

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

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

Primary choriocarcinoma of the anterior mediastinum is by far the rarest and most controversial form of extragonadal germ cell tumor. A clinicopathologic study of eight primary mediastinal neoplasms bearing the histopathologic and immunohistochemical features of choriocarcinoma is presented. The patients were all men between the ages of 21 and 63 years (mean, 42 years). Clinical symptoms included shortness of breath, chest pain, cough, and superior vena cava syndrome; one patient also had gynecomastia. All patients presented with large anterior mediastinal masses on chest radiographs that measured an average of 10 cm in greatest diameter. Grossly, the tumors were described as large, soft, extensively hemorrhagic, and with foci of necrosis. Histologically, they were characterized by a dual cell population composed of cytotrophoblastic cells with uniform, round nuclei, clear cytoplasm, and prominent nucleoli admixed with large, multinucleated syncytiotrophoblastic cells with bizarre nuclei, prominent nucleoli, and abundant eosinophilic cytoplasm. Immunohistochemically, the tumors were notable for strong keratin and beta-human chorionic gonadotropin (HCG) positivity. Seven patients presented at the time of diagnosis with thoracic and extrathoracic (liver, adrenal, kidney, and spleen) metastases. In one case, the tumor was entirely confined to the mediastinum. All patients died over a period of 1 to 2 months. Complete autopsies were performed in all cases; none of the patients showed evidence of a testicular tumor or scar after thorough examination of the testes on serial sectioning. The present cases demonstrate the widespread distribution of germ cells in the human body and lend further support to the existence of primary extragonadal choriocarcinoma arising in the thymic region.

Topics: Adrenal Gland Neoplasms; Adult; Alkaline Phosphatase; alpha-Fetoproteins; Biomarkers, Tumor; Carcinoembryonic Antigen; Choriocarcinoma; Chorionic Gonadotropin; Diagnosis, Differential; Humans; Immunohistochemistry; Isoenzymes; Keratins; Kidney Neoplasms; Liver Neoplasms; Male; Mediastinal Neoplasms; Middle Aged; Placental Lactogen; Splenic Neoplasms; Testicular Neoplasms

Three cases of primary mediastinal yolk sac tumors with prominent spindle cell features are presented. The patients were three men 24-34 years of age (mean 29). Clinically, two patients presented with symptoms of chest pain and cough; no clinical information was provided for the third patient. Grossly, the tumors were described as large mediastinal masses, with a hemorrhagic and necrotic cut surface. Histologically, the tumors were characterized by a predominantly atypical spindle cell proliferation admixed with areas that showed focally the characteristic reticular growth pattern of yolk sac tumors, with the presence of Schiller-Duval bodies and intra- and extracellular hyaline globules. Immunohistochemical studies performed in one case showed positive staining for keratin and alpha-fetoprotein in both the spindle cell and reticular components of the tumor. Follow-up information was obtained in two patients; they both died of tumor with metastases to the lungs 1 year after initial diagnosis. The present cases expand the spectrum of histopathologic growth patterns that may be observed in yolk sac tumors of the mediastinum and stress the issue of careful sampling and evaluation of mediastinal neoplasms for arriving at the correct diagnosis.

Topics: Adult; alpha-Fetoproteins; Biomarkers; Endodermal Sinus Tumor; Fatal Outcome; Humans; Immunohistochemistry; Keratins; Male; Mediastinal Neoplasms

Four cases of primary hepatoid yolk sac tumors of the anterior mediastinum are described. The patients were all men between the ages of 26 and 40 years (median 33). Clinically, they all presented with a history of shortness of breath and chest pain of several weeks' duration. None of the patients had a history of germ cell tumor elsewhere or evidence of any hepatic abnormality. Grossly, all the tumors were described as large mediastinal masses that impinged on adjacent structures. Histologically, they were characterized by sheets of medium-sized, round to polygonal neoplastic cells with moderate amounts of eosinophilic cytoplasm and round to oval nuclei with prominent nucleoli. The cellular proliferation was homogeneous and displayed moderate cellular atypia and scattered mitotic activity. All the tumors showed focally the presence of more conventional areas of yolk sac tumor, with islands of tumor cells showing a reticular pattern of growth admixed with scattered intra- and extracellular hyaline globules and occasional Schiller-Duval bodies. Immunohistochemical studies showed strong positivity of the tumor cells for alpha-fetoprotein in both components of the lesions. Follow-up information was available in three patients, all of whom developed lung metastases within a year after initial diagnosis. Two of these patients died of tumor within the same period, whereas a third patient has been lost to follow-up. The present cases illustrate an unusual histologic pattern of yolk sac tumor in the mediastinum and highlight the importance of considering this tumor in the differential diagnosis of lesions showing a hepatoid pattern of growth in the mediastinal area.

Topics: Adult; alpha-Fetoproteins; Biomarkers, Tumor; Diagnosis, Differential; Endodermal Sinus Tumor; Fatal Outcome; Humans; Immunohistochemistry; Keratins; Liver Neoplasms; Male; Mediastinal Neoplasms

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

Even when clinical data strongly suggest the presence of a metastatic neoplasm in the breast, this occurrence almost invariably raises great problems in diagnostic pathology. Both cases presented here had a well-recognized primitive neoplasm located elsewhere. Nonetheless, great importance was given to the application of ancillary techniques; the immunostains for "breast discriminants"--GCDFP15, HMFG1, and HMFG2--on tissue sections helped the recognition of a metastatic renal cell carcinoma; and the stains for S100 protein, smooth muscle actin, cytokeratins, and neurofilaments on cytologic material allowed the identification of a metastatic mediastinal leiomyosarcoma.

Topics: Actins; Adult; Biopsy, Needle; Breast Neoplasms; Carcinoma, Renal Cell; Fatal Outcome; Female; Humans; Keratins; Kidney Neoplasms; Leiomyosarcoma; Mediastinal Neoplasms; Middle Aged; S100 Proteins; Vimentin

The distribution of thymic tissue in the anterior mediastinal, retrocarinal, and preaortic fat was examined histologically in 27 autopsy subjects. Thymic tissue was found in the anterior mediastinal fat in 12 subjects (44.4%), in the retrocarinal fat in two (7.4%), and in the preaortic fat in none. The finding of ectopic thymic tissue in these areas has not been reported previously, would appear to be surgically inaccessible via a median sternotomy, and may be responsible in part for some of the failures of thymectomy in the treatment of myasthenia gravis.

Topics: Adipose Tissue; Adolescent; Adult; Aged; Aged, 80 and over; Child; Child, Preschool; Choristoma; Female; Humans; Immunohistochemistry; Infant; Infant, Newborn; Keratins; Male; Mediastinal Neoplasms; Middle Aged; Thymus Gland

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

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

Germ cell neoplasms were reviewed for the investigation of a mesenchyme-like component of yolk sac tumor (YST) characterized by spindle cells with few mitoses in a myxoid, vascular background. Nineteen YSTs with this pattern were identified. The mesenchyme-like component of these YSTs appeared to derive from the epithelial elements of YST, since cytokeratin as well as vimentin positivity occurred in the spindle cells of the mesenchyme-like areas and foci of epithelial-spindle cell transition were present. In some cases the mesenchyme-like component showed differentiated mesenchymal elements (usually skeletal muscle). Similar features were identified in 13 chemotherapy-treated cases of YST that consisted only of this mesenchyme-like component. The mesenchyme-like component of YST appears to represent a chemoresistant, pluripotential cell population arising from metaplasia of YST epithelium; it may give rise to sarcomas occurring in some patients with treated germ cell tumors.

Topics: alpha-Fetoproteins; Female; Humans; Immunohistochemistry; Keratins; Male; Mediastinal Neoplasms; Mesonephroma; Ovarian Neoplasms; Testicular Neoplasms; Vimentin

Fifteen cases of non-Hodgkin's lymphoma of the anterior mediastinum are reported. In the first group of four, fresh tissue was available and immunohistochemical studies demonstrated their B-cell origin, with monotypic immunoglobulin production in two. Only fixed tissue was available in the second group of 11 patients. All stained with antibody to leucocyte common antigen (PD7/26) and three showed monotypic immunoglobulin production. If the two groups are combined seven of the 15 tumours were clearly of B-cell origin. Classification on morphological grounds was difficult, with most tumours showing mixtures of centroblasts and large centrocytes, and the original diagnoses had included Hodgkin's disease (three), thymoma (one) and undifferentiated carcinoma (two). None of the patients had evidence of extra-thoracic disease at presentation and when this developed the organs involved were liver (one), kidney (two) and thyroid (one). Direct extension within the chest led to infiltration of chest wall, sternum, lung, superior vena cava and other structures. The site of origin, lack of nodal involvement and, in one case, presence of residual thymus around the tumour indicate an origin in thymic B-cells.

Topics: Adolescent; Adult; Antibodies, Monoclonal; Antigens, Surface; B-Lymphocytes; Female; Histocompatibility Antigens; Humans; Immunoenzyme Techniques; Immunoglobulin D; Immunoglobulin G; Immunoglobulin M; Keratins; Leukocyte Common Antigens; Lymphoma; Male; Mediastinal Neoplasms; Middle Aged; Thymus Gland

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

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