SFTS has been endemic to Japan, and SFTSV has been circulating naturally within the country.

To provide practical guidelines for the cytopathologic diagnosis of malignant mesothelioma (MM). Cytopathologists involved in the International Mesothelioma Interest Group (IMIG) and the International Academy of Cytology (IAC), who have an interest in the field contributed to this update. Reference material includes peer-reviewed publications and textbooks. This article is the result of discussions during and after the IMIG 2012 conference in Boston, followed by thorough discussions during the 2013 IAC meeting in Paris. Additional contributions have been obtained from cytopathologists and scientists, who could not attend these meetings, with final discussions and input during the IMIG 2014 conference in cape town. During the previous IMIG biennial meetings, thorough discussions have resulted in published guidelines for the pathologic diagnosis of MM. However, previous recommendations have stated that the diagnosis of MM should be based on histological material only.[12] Accumulating evidence now indicates that the cytological diagnosis of MM supported by ancillary techniques is as reliable as that based on histopathology, although the sensitivity with cytology may be somewhat lower.[345] Recognizing that noninvasive diagnostic modalities benefit both the patient and the health system, future recommendations should include cytology as an accepted method for the diagnosis of this malignancy.[67] The article describes the consensus of opinions of the authors on how cytology together with ancillary testing can be used to establish a reliable diagnosis of MM.

BACKGROUND:In malignant pleural mesothelioma (MPM), most patients first present with pleural effusion; thus, cytologic analysis is the primary diagnostic approach. However, the cytologic distinction between MPM and reactive mesothelial cells (RMCs) in effusions can be extremely difficult due to the lack of both well-established immunocytochemical markers and definite cytological criteria for MPM. Moreover, the existence of both MPM cells and RMCs in effusions from the same patient makes the differentiation even more challenging. Homozygous deletion of the 9p21 locus, the site of the cyclin-dependent kinase inhibitor 2A/p16 (CDKN2A/p16) gene, frequently occurs in MPM but has never been reported in RMCs. The aim of this study was to define the cytomorphological characteristics of MPM cells, identified by the presence of 9p21 homozygous deletion by fluorescence in situ hybridization (FISH). METHODS: For this purpose, cells on smear preparations were recorded using a virtual microscope system and were subjected to FISH analysis. Thereafter, 9p21 homozygous deletion-positive cells were identified in the recorded virtual slides, followed by analysis of their morphological characteristics. RESULTS: Mesothelioma cells positive for the 9p21 homozygous deletion exhibited significantly more frequent cellin-cell engulfment, multinucleation (more than 2 nuclei), and larger multicellular clusters composed of more than 10 cells than did 9p21 deletion-negative RMCs. Possible cutoff values are also proposed for these morphological markers to differentiate MPM cells from RMCs. CONCLUSIONS: These morphological differences and cutoff values are useful for cytological differentiation of mesothelioma cells from RMCs. In addition, the novel technique of a combination of virtual microscopy and FISH is introduced for tumor morphological analysis. Cancer (Cancer Cytopathol) 2013;121:415-22. V C 2013 American Cancer Society.KEY WORDS: pleural mesothelioma; cytology; fluorescence in situ hybridization; 9p21 homozygous deletion; p16.

Malignant pleural mesothelioma is a refractory tumor with poor prognosis associated with asbestos exposure. Pleural effusion is frequently observed in patients with malignant pleural mesothelioma, and cytological analysis is effective to detect malignant pleural mesothelioma. However, cytological discrimination between malignant pleural mesothelioma and reactive mesothelium is often difficult. Increased expression of CD146, a cell adhesion molecule, has been reported to be closely associated with an advanced stage of malignant melanoma, prostate cancer, and ovarian cancer. In this study, to evaluate the diagnostic utility of CD146 for discrimination between malignant pleural mesothelioma and reactive mesothelium, we examined immunocytochemical expression of CD146 in malignant pleural mesothelioma and reactive mesothelium using two clones of CD146 antibody, OJ79 and EPR3208, on smear specimens of effusion fluids. Immunocytochemical stains were semiquantitatively scored on the basis of immunostaining intensity (0, negative; 1, weak positive; 2, moderate positive; and 3, strong positive). CD146 expression was detected in 15 of 16 malignant pleural mesothelioma with median immunostaining score of 3 by OJ79, and in 19 of 21 malignant pleural mesothelioma with median immunostaining score of 2 by EPR3208. Strong immunoreactivity of CD146 was observed at the apposing surfaces of cell-cell interactions on the plasma membrane of mesothelioma cells. In addition, one OJ79-negative case of malignant pleural mesothelioma was positive for CD146 by EPR3208 and two EPR3208-negative cases of malignant pleural mesothelioma were CD146 positive by OJ79, showing that all 23 malignant pleural mesothelioma cases were positive for CD146 by either OJ79 or EPR3208. On the other hand, CD146 expression was undetectable in all reactive mesothelium cases by OJ79 and EPR3208. The sensitivity of OJ79 and EPR3208 was 94 and 90%, respectively, and the specificity was 100% for both clones. We propose that CD146 is a sensitive and specific immunocytochemical marker enabling differential diagnosis of malignant pleural mesothelioma from reactive mesothelium.

Background. The breast is rarely primary site for extranodal malignant lymphoma. Most reported primary non‐Hodgkin malignant lymphomas of the breast (PBL) are of B‐cell phenotype. Methods. Histologic and immunohistochemical analyses of seven patients with PBL and statistical analysis of 152 patients with PBL reported in the Japanese literature were performed. Results. Malignant lymphoma could not be predicted preoperatively with clinical and radiologic findings; breast carcinoma, fibroadenoma, and phyllodes tumor were the preoperative diagnoses. All patients were women; they ranged in age from 31 to 80 years (mean, 57.6 years). The right breast was involved initially in five patients. In four, only the breast was involved (Stage I), whereas in three, the ipsilateral axillary lymph nodes (Stage II) were involved at diagnosis. According to the Working Formulation, all patients belonged to the intermediate grade and were classified as having diffuse large cell (five patients) or mixed (two patients) lymphoma. Immunophenotypic analysis revealed that all patients had B‐cell lymphoma. No patients had lymphoepithelial lesions, which is the characteristic feature in categorizing lymphoma as mucosa‐associated lymphoid tissue (MALT) lymphoma. A statistical analysis of the patient reported in the Japanese literature has divided PBL into two types: bilateral type that affects younger women and unilateral type that has broad age distribution, but preponderantly occurs in older women. The age and stage at diagnosis were significant prognostic factors in predicting the survival time, but the location and size of the tumor at initial presentation, histopathologic type, terminal leukemic manifestation, and treatment modality were not. Conclusions. This study indicates that most PBL are diffuse large cell lymphoma of B‐cell phenotype and that the age and stage at diagnosis are significant prognostic factors.