Hirokuni Kakinuma

Diagnostic findings of bronchial brush cytology for pulmonary large cell neuroendocrine carcinomas: comparison with poorly differentiated adenocarcinomas, squamous cell carcinomas, and small cell carcinomas.

Large cell neuroendocrine carcinoma (LCNEC) of the lung has been proposed as a new disease entity. To establish diagnostic features, bronchial brush cytologic findings were evaluated.

Cell cannibalism and nucleus-fragmented cells in voided urine : Useful parameters for cytologic diagnosis of low-grade urothelial carcinoma

OBJECTIVE To clarify whether the 3 parameters of cell clusters, cell cannibalism and nucleus-fragmented cells could improve diagnostic accuracy for grade 1 urothelial carcinoma (G1UC). STUDY DESIGN A total of 52 voided urine samples from 31 patients histologically diagnosed as having G1UC were reviewed. In addition, 10 voided urine samples from cases with grade 3 demonstration urothelial carcinoma (G3UC) and 30 voided urine samples from 25 patients with a histologic diagnosis of chronic inflammation of the bladder were evaluated for comparison. Areas of tumor cells with cannibalism were measured. RESULTS Cell cannibalism was evident in 12 of 31 G1UC cases (38.7%), significantly less often than with G3UC, but never identified in the control group. Mean areas of tumor cells featuring cannibalism were significantly smaller in G1 UC than in G3UC cases. Nucleus-fragmented cells were also less frequent in G1UC than in G3UC, but more common than in the control group. CONCLUSION Cell cannibalism and nucleus-fragmented cells in voided urine with special attention to areas of tumor cell with cannibalism could be applied as a parameter to improve diagnostic accuracy for G1UC.

Differential diagnosis of reactive mesothelial cells and malignant mesothelioma cells using the cell proliferation markers minichromosome maintenance protein 7, geminin, topoisomerase II alpha and Ki-67.

Objective: The aim of this study was to evaluate whether the immunocytochemical expression of cell proliferation markers, such as minichromosome maintenance protein 7 (MCM 7), geminin, topoisomerase II alpha (topo IIα) and Ki-67, which are different types of cell proliferation markers, could be useful for their differential diagnosis in reactive mesothelial cells and malignant mesothelioma cells obtained from body cavity fluids. Study Design: Samples diagnosed and later histologically confirmed as reactive mesothelial cells (39 cases) or malignant mesothelioma (32 cases) in body cavity fluids were examined. Immunocytochemical staining of MCM 7, geminin, topo IIα and Ki-67 was performed with the immunoperoxidase polymer method. Results: Labeling indices (LIs) of MCM 7 (cutoff value 20.0%; sensitivity 100%; specificity 100%), geminin (cutoff value 4.5%; sensitivity 88.0%; specificity 70.0%), topo IIα (cutoff value 11.0%; sensitivity 88.0%; specificity 92.0%) and Ki-67 (cutoff value 15.3%; sensitivity 78.0%; specificity 79.0%) of malignant mesothelioma cells were significantly higher than those of reactive mesothelial cells. Conclusion: LIs of MCM 7, geminin and topo IIα can be reliable tools for the differential diagnosis of reactive mesothelial cells and malignant mesothelioma cells.

Cytological significance of abnormal squamous cells in urinary cytology.

The aim of this study was to evaluate the significance of abnormal squamous cells (ASCs) in urinary cytology to clarify whether finding of ASCs could improve diagnostic accuracy. A total of 3,812 urine specimens were reviewed. We focused on three parameters of ASCs, necrotic debris, and ASC clusters, and linked them to histological diagnosis and clinical information. ASCs were identified in 34 (0.9%) specimens from 21 different patients. The incidence of ASCs was higher in females than in males. The 34 urine specimens were categorized as voided urine (16 cases), bladder‐catheterized urine (17 cases), and bladder‐washed fluid (1 case). Six (28.6%) of 21 patients were histologically diagnosed as having combined urothelial carcinoma and squamous cell carcinoma (SCC). Eight patients (38.1%) were histologically diagnosed as having SCC originating from sites other than the urinary tract; those urine specimens showed ASCs that were likely to have been exfoliated from malignant lesions. Necrotic debris and ASC clusters were identified in 12 specimens (35.3%) from 11 patients and 4 specimens (11.8%) from 4 patients, respectively, from a total of 34 specimens. Our results indicate that a great amount of care is needed for cytological diagnosis when attempting to recognize ASCs in urine specimens because ASCs were identified in not only SCC of the bladder but also in carcinoma or nonmalignant lesions of nonurinary tracts. Necrotic debris was found not only in patients who had malignant bladder tumors but also in those who had malignant lesions in locations other than the bladder. Diagn. Cytopathol. 2012.

Immunohistochemical, molecular, and clinicopathological analyses of urothelial carcinoma, micropapillary variant.

The prognosis of urothelial carcinoma, micropapillary variant (MPV), of the bladder has been shown to be worse than that of the conventional urothelial carcinoma (UC). However, it remains to be clarified why the MPV is more aggressive. We therefore here focused on the correlation between clinical features and histological, immunohistochemical and molecular findings for eight MPV and 35 UC, evaluating expression of MUC1, Ki‐67, p53, CD147, CD34, D2‐40, and extracellular matrix proteins. The Ki‐67 labeling index was significantly higher in UC than in MPV but densities of venous and lymphatic tumor emboli were significantly higher in the MPV cases and lymph node metastasis was more frequent, with a poorer prognosis. Tenascin‐C and fibronectin also showed significantly greater expression in MPV than in UC at the epithelial–mesenchymal interfaces. Direct sequencing showed point mutations of KRAS exon 1 in three MPV with significantly more frequency compared to UC. Occupation rate of the MPV area in the tumor showed significant inverse correlation with overall survival. Thus our histopathological findings provide clues to explaining why prognosis is poorer in the MPV than UC.

Adequacy evaluation of endometrial cytology using Thinlayer specimens

目的: 子宮内膜細胞診において, Thinlayer 標本と従来の塗抹標本 (Conventional 標本) の診断成績を比較し, Thinlayer 標本の特性を明らかにする.方法: 内膜組織診とエンドサイトによる内膜細胞診を同一日に施行した 96 例を対象とした. 塗抹後のエンドサイトから Thinlayer 標本を作製し, 従来の診断基準で Thinlayer 標本も診断した. 組織診の結果を基に, 両細胞診標本の感度および特異度を求め, 細胞塗抹量, 鏡検時間, 細胞像について検討した.成績: Conventional 標本の感度/特異度は 87.0%/89.4%, Thinlayer 標本は 73.9%/70.2%であり, 後者が低かったがいずれも有意差は認めなかった. Thinlayer 標本は重積性が軽減され, 背景の赤血球や炎症細胞が大きく減少していた. 鏡検時間は Thinlayer 標本で有意に短縮された. しかし Conventional 標本とは異なる細胞像を示す傾向があった.結論: Thinlayer 標本による内膜細胞診標本は Conventional 標本と同程度の感度/特異度であり, Thinlayer 標本の特性を十分理解したうえで臨床応用は可能と思われる.目的: 子宮内膜細胞診において, Thinlayer 標本と従来の塗抹標本 (Conventional 標本) の診断成績を比較し, Thinlayer 標本の特性を明らかにする.方法: 内膜組織診とエンドサイトによる内膜細胞診を同一日に施行した 96 例を対象とした. 塗抹後のエンドサイトから Thinlayer 標本を作製し, 従来の診断基準で Thinlayer 標本も診断した. 組織診の結果を基に, 両細胞診標本の感度および特異度を求め, 細胞塗抹量, 鏡検時間, 細胞像について検討した.成績: Conventional 標本の感度/特異度は 87.0%/89.4%, Thinlayer 標本は 73.9%/70.2%であり, 後者が低かったがいずれも有意差は認めなかった. Thinlayer 標本は重積性が軽減され, 背景の赤血球や炎症細胞が大きく減少していた. 鏡検時間は Thinlayer 標本で有意に短縮された. しかし Conventional 標本とは異なる細胞像を示す傾向があった.結論: Thinlayer 標本による内膜細胞診標本は Conventional 標本と同程度の感度/特異度であり, Thinlayer 標本の特性を十分理解したうえで臨床応用は可能と思われる.

Basement Membrane–like Substance in Cytologic Diagnosis in Clear Cell Adenocarcinoma of the Minor Salivary Gland of the Palate

BACKGROUND Clear cell adenocarcinoma (CCA) of the minor salivary gland accounts for < 1% of all tumors of the salivary gland. CASE A 32-year-old woman with a history of papillary carcinoma of the thyroid 1 year earlier complained of pain on the left side of the neck. After a detailed examination, the patient underwent the resection of a tumor located at the palate. Imprint cytology of the tumor revealed cohesive tumor cells of uniform size containing an abundant clear cytoplasm and round nuclei with extra but fine granular chromatin and conspicuous nucleoli. A basement membrane-like substance (BMS) was stained in light green with Papanicolaou staining and was positive for laminin with immunohistochemical staining. Histopathologic analysis confirmed the trabecular or nest-like arrangement of the cells with the clear cytoplasm and BMS substance surrounded by tumor cells, which were positive for laminin and AE1 immunohistochemically. CONCLUSION Although CCA of the palate is extremely rare, an accurate cytologic diagnosis can be made if the characteristic findings of CCA, including BMS, are imaged.

Discriminant Analysis between Malignant Mesothelioma and Reactive Mesothelium Using Nuclear Three-Dimensional Analysis Is Useful for Morphologically Suspicious Cases

Objective: Morphological discrimination between malignant mesothelioma (MM) and reactive mesothelium (RM) is often difficult. Stereological analysis of nuclear luminance using centrifuged smear samples from coelomic fluid and discriminant analysis based on Mahalanobis distance may help to more accurately discriminate between MM and RM. In the present study, discriminant analysis was conducted on cytological specimens using the auto-smear method in a blinded manner with regard to histological results. Study Design: Coelomic fluid samples of 28 cases, cytologically diagnosed using the auto-smear method, were analyzed to determine pixel counts, the number of focus layers, 3-dimensional variation in the coefficient of variation of nuclear luminance between the focus layers as well as roundness in about 30-50 atypical cell nuclei per case. These measurements were employed to determine malignancy based on Mahalanobis distance. Results: Discrimination rates were as high as 91.7% for MM and 82.7% for RM. The discrimination rates of MM with histology were >80% in 8 of 10 suspicious cases with the initial cytology. Conclusion: Our method allowed accurate discrimination between MM and RM and provides a useful alternative for the diagnosis of suspicious cases where morphological diagnosis of malignancy is difficult.