Toshikazu Yusa

Diagnostic Usefulness of p16/CDKN2A FISH in Distinguishing Between Sarcomatoid Mesothelioma and Fibrous Pleuritis

The distinction between sarcomatoid mesothelioma and fibrous pleuritis is difficult based on histology, especially when the amount of tumor tissue examined via biopsy is small and immunohistochemical examination is inconclusive. We studied the usefulness of deletion of p16 with fluorescence in situ hybridization (FISH) and p16 hypermethylation with polymerase chain reaction for the diagnosis and prognosis of malignant pleural mesothelioma (MPM). We analyzed 50 MPMs, including 22 sarcomatoid mesothelioma cases and 10 fibrous pleuritis cases. We set the cutoff value of homozygous deletion pattern as 14.4% based on FISH signaling patterns using samples of fibrous pleuritis. The percentage of homozygous deletion pattern was higher than 14.4% in 55.6% of the epithelioid mesotheliomas (10/18) and in all of the sarcomatoid mesotheliomas (22/22). Methylation of p16 was observed in 7 (20.6%) of 34 informative cases. p16 FISH analysis can be a reliable test for distinguishing between sarcomatoid mesothelioma and fibrous pleuritis and a prognostic factor for MPM.

Castleman’s disease in the posterior mediastinum: Report of a case

We report a case of Castleman’s disease which developed in the posterior mediastinum, with a review of the Japanese literature. A 19-year-old female patient with asthma was pointed out to have an abnormal shadow in the right posterior mediastinum on chest X-ray. We had tried to perform thoracoscopic surgery for this tumor, but we had to convert the surgical approach from thoracoscopy to a thoracotomy because of both tight adhesion of the tumor and muscle and profuse bleeding from the tumor. The tumor was diagnosed to be the hyaline vascular type of Castleman’s disease histopathologically. In the Japanese literature, Castleman’s disease, which develops in the posterior mediastinum, has been reported to often accompany tight adhesion between the tumor and surrounding tissue, and profuse bleeding thus cannot be avoided at surgery. The large amount of bleeding observed during the surgery of a patient with Castleman’s disease in the posterior mediastinum may be due to tight adhesion and hypervascularity of the tumor. Therefore, care should be exercised in choosing the surgical approach if Castleman’s disease is suspected in cases of posterior mediastinal tumor.

Expression of vascular endothelial growth factor in thoracic sarcomas.

BACKGROUND A body of data indicates that vascular endothelial growth factor (VEGF) expression by carcinomas is closely related to the prognosis of carcinomas. However, the relationship between VEGF expression and the prognosis of sarcomas is contradictory. METHODS Tissue from 27 cases of thoracic sarcoma was analyzed immunohistochemically for VEGF expression while tumor vascularity was quantified using an antibody directed against endothelial CD34. The relationship between VEGF expression and the prognosis of patients with sarcomas was then evaluated semiquantitatively. RESULTS The microvessel count in sarcomas with strong VEGF expression was significantly higher than that in sarcomas with absent or faint VEGF expression. The disease-free survival rates of sarcomas with strong VEGF expression were significantly lower than those of sarcomas with absent or faint VEGF expression. We found that strong VEGF expression impacted on the disease-free survival in multivariate analyses. CONCLUSIONS VEGF expression of thoracic sarcomas is directly related to angiogenesis and tumor vascularity, and our findings suggest that strong VEGF expression is an independent prognostic factor in patients with thoracic sarcomas.

Descending Necrotizing Mediastinitis : Report of a Case

A 47-year-old man was admitted to our hospital for treatment of an odontogenic infection. He presented with a fever, signs of sepsis, and neck swelling, and was initially diagnosed as having a neck abscess. After cervical drainage, he showed no improvement, and mediastinitis was detected by chest X-ray and computed tomography. A thoracotomy and mediastinal drainage was subsequently performed for descending necrotizing mediastinitis, which resulted in marked improvement. To data, only 83 cases of descending necrotizing mediastinitis have been reported in Japan. We present herein an additional case, followed by a review of the Japanese literature.

Mucoepidermoid carcinoma of the thymus

Mucoepidermoid carcinoma of the thymus is a rare carcinoma and there is little agreement about the treatment of this tumor. According to the analysis of previously reported tumors, biologic behavior of the tumor correlated with the spread of the lesion and degree of differentiation. We report a case of this tumor in a 31-year-old man. Resection of the tumor included the left upper lobe of the lung, the phrenic nerve, pericardium and disseminations in the pleura. The clinicopathological feature of this case was high-stage disease and low-grade histology. Postoperative chemotherapy and radiotherapy were performed, and the patient is alive without recurrence 14 months after surgery.

Cytologic Differential Diagnosis of Malignant Mesothelioma and Reactive Mesothelial Cells With FISH Analysis of p16

Mesothelioma patients often present with serosal effusions, which are ideal for cytopathological diagnoses. However, the morphological overlap between malignant and benign mesothelial proliferation can make a conclusive cytological diagnosis of mesothelioma elusive because immunohistochemical staining does not discriminate definitively between the two in this setting. p16 is deleted in up to 80% of pleural mesotheliomas. The aim of this study was to establish the correlation between the p16 deletion status of the cell block with that of its corresponding tumor using fluorescence in situ hybridization (FISH) analysis for individual patient tumors.

CD90 Is a Diagnostic Marker to Differentiate Between Malignant Pleural Mesothelioma and Lung Carcinoma With Immunohistochemistry

OBJECTIVES To pathologically distinguish mesothelioma from lung carcinoma, particularly adenocarcinoma. METHODS We conducted immunohistochemical analyses on clinical specimens, including 26 cases of mesothelioma, 28 cases of lung adenocarcinoma, and 33 cases of lung squamous cell carcinoma. RESULTS We found that CD90 expression was useful in making a differential diagnosis between epithelioid mesothelioma and lung adenocarcinoma, whereas sarcomatoid mesothelioma and lung carcinoma specimens, irrespective of the histologic types, were negative in general. The sensitivity and specificity of CD90 expression in epithelioid mesothelioma and lung adenocarcinoma were comparable to those of well-established markers used for the differential diagnosis. CONCLUSIONS These data collectively indicate that CD90 is a novel diagnostic marker that contributes to a diagnosis of epithelioid mesothelioma.

Diffuse malignant pleural mesothelioma: A multi-institutional clinicopathological study

PurposeThe relative rarity of malignant pleural mesothelioma (MPM) in Japan makes it difficult to perform a large-scale clinicopathological study of this tumor at a single institute. Thus, we performed a multiinstitutional study to evaluate the current status of diagnosis and treatment in Japan.MethodsWe analyzed the records of 65 patients with MPM, obtained from the 13 institutions comprising the Japanese Chiba Multicenter Study Group.ResultsIn 56 patients, the tumor was detected after a visit to a medical facility for subjective symptoms such as chest pain, shortness of breath, and cough. It took a median period of 2 months from the initial visit to establish the diagnosis. The overall survival rates of 33 patients with unresectable MPM 1, 2, and 3 years after the diagnosis were 40.5%, 10.8%, and 0%, respectively, whereas those of 32 patients who underwent surgery were 67.9%, 35.0% and 10.9%, respectively (P = 0.0035). According to multivariate analysis, histological type, International Mesothelioma Interest Group clinical stage, sex, and the presenting symptom of shortness of breath were significant prognostic factors.ConclusionsThe definitive diagnosis of early MPM is difficult, but establishing the best diagnostic modality would improve survival rates, since radical surgery is likely to be effective for resectable disease.

HEG1 is a novel mucin-like membrane protein that serves as a diagnostic and therapeutic target for malignant mesothelioma

The absence of highly specific markers for malignant mesothelioma (MM) has served an obstacle for its diagnosis and development of molecular-targeting therapy against MM. Here, we show that a novel mucin-like membrane protein, sialylated protein HEG homolog 1 (HEG1), is a highly specific marker for MM. A monoclonal antibody against sialylated HEG1, SKM9-2, can detect even sarcomatoid and desmoplastic MM. The specificity and sensitivity of SKM9-2 to MM reached 99% and 92%, respectively; this antibody did not react with normal tissues. This accurate discrimination by SKM9-2 was due to the recognition of a sialylated O-linked glycan with HEG1 peptide. We also found that gene silencing of HEG1 significantly suppressed the survival and proliferation of mesothelioma cells; this result suggests that HEG1 may be a worthwhile target for function-inhibition drugs. Taken together, our results indicate that sialylated HEG1 may be useful as a diagnostic and therapeutic target for MM.

Usefulness of p16/CDKN2A fluorescence in situ hybridization and BAP1 immunohistochemistry for the diagnosis of biphasic mesothelioma ☆

Malignant mesothelioma is a highly aggressive neoplasm, and the histologic subtype is one of the most reliable prognostic factors. Some biphasic mesotheliomas are difficult to distinguish from epithelioid mesotheliomas with atypical fibrous stroma. The aim of this study was to analyze p16/CDKN2A deletions in mesotheliomas by fluorescence in situ hybridization (FISH) and BAP1 immunohistochemistry to evaluate their potential role in the diagnosis of biphasic mesothelioma. We collected 38 cases of pleural mesotheliomas. The results of this study clearly distinguished 29 cases of biphasic mesothelioma from 9 cases of epithelioid mesothelioma. The proportion of biphasic mesotheliomas with homozygous deletions of p16/CDKN2A in total was 96.6% (28/29). Homozygous deletion of p16/CDKN2A was observed in 18 (94.7%) of 19 biphasic mesotheliomas with 100% concordance of the p16/CDKN2A deletion status between the epithelioid and sarcomatoid components in each case. Homozygous deletion of the p16/CDKN2A was observed in 7 (77.8%) of 9 epithelioid mesotheliomas but not in fibrous stroma. BAP1 loss was observed in 5 (38.5%) of 13 biphasic mesotheliomas and in both epithelioid and sarcomatoid components. BAP1 loss was observed in 5 (62.5%) of 8 epithelioid mesotheliomas but not in fibrous stroma. Homozygous deletion of p16/CDKN2A is common in biphasic mesotheliomas, and the analysis of only one component of mesothelioma is sufficient to show that the tumor is malignant. However, compared with histology alone, FISH analysis of the p16/CDKN2A status and BAP1 immunohistochemistry in the spindled mesothelium provide a more objective means to differentiate between biphasic mesothelioma and epithelioid mesothelioma with atypical stromal cells.