Objective : To improve the diagnostic accuracy of bile smear cytology, we assessed two cell-yielding procedures and their utility.
Study Design : Subjects seen between October 2008 and December 2009 found to have a biliary stricture in endoscopic retrograde cholanigiopancreatography (ERCP) underwent conventional brush sampling. Following this, the cytologist (1) cut the brush head off of the support wire, centrifuged it directly in tissue culture medium for 1 minute, at 3,000 rpm, removed the head, centrifuged the medium again, and smeared the cell pellet onto 2 glass slides. The cytologist then (2) cut remaining sheath tubing and wire into 12 cm segments, put all pieces into the centrifuge tube, centrifuged them for 1 minute at 3,000 rpm, then collected sheath tubing contents and submitted them for cytospin preparation.
Results : Final diagnoses based on surgery, biopsy, or clinical progression were evaluated for sensitivity, specificity, and accuracy. Using conventional smears alone, sensitivity was 59.5, specificity 70, and accuracy 61.5%. For conventional smears plus brush washings and sheath tubing contents, sensitivity was 73.8, specificity 100, and accuracy 78.8%.
Conclusion : Combining conventional smear procedures with the two cell-yielding procedures yielded clearly superior diagnostic accuracy.

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Objective : Upper respiratory cancer may occasionally be detected in sputum cytology. We compared cytological features of laryngeal cancer and early bronchial lung cancer detected in cytology screening.
Study Design : 8 cases of laryngeal cancer and 14 early bronchial lung cancer cases detected in cytology mass screening between 1994 and 2006 were investigated. Severely atypical and squamous cancer cells extracted from specimens were compared statistically in terms of : staining properties ; size, shape, and brightness of cytoplasm ; properties of cell borders ; nuclear number and shape ; and nuclear chromatin.
Results : Both groups showed mildly increased chromatin. Approximately 90% of cells were small- to medium-sized orange- and yellow-staining with mild nuclear atypia. Laryngeal cancer specimens had numerous orange-staining cells with no cellular brightness, while early bronchial lung cancer specimens exhibited a significantly high numbers of yellow-staining cells and cellular brightness. Receiver operating characteristic (ROC) curve analysis identified ≧84% of non bright orange-staining cells with 100% sensitivity and 100% specificity for laryngeal cancer.
Conclusions : Sputum cytology findings differed between laryngeal cancer and early bronchial lung cancer-findings suggesting that focusing on cytology features may help to detect laryngeal cancer early.

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Background : Although sputum cytology is the only way to detect early hilar lung cancer in lung cancer screening, there are also various problems. Therefore, the subcommittees concerning sputum cytology was established in each the Japan Lung Cancer Society and the Japanese Society of Clinical Cytology, and in a joint effort with the Japan Society for Respiratory Endoscopy, the investigation of these problems were reported by the committee of the three societies.
We concluded that confirming the usefulness of sputum cytology at present is the inevitable and the most important issue.
Objective : We clarified the actual situation of diagnosis for early hilar lung cancer in Japan by a questionnaire.
Subject and Methods : We sent questionnaires to authorized and associated institutes of the Japan Society for Respiratory Endoscopy, and respondents were questioned concerning the following items. The basic items were a) the number of bronchoscopies performed, b) the number of lung cancer resections, c) the number of diagnoses of new early hilar lung cancer, d) the modes of detection, e) histological type, f) treatment modalities that can be estimated in each institute from 2006 to 2007. Moreover, to the extent possible, we ask them to respond to g) the number of advanced hilar squamous cell carcinoma, h) the number of sputum cytology examinations that were found to be positive or suspected to be positive, i) the number of peripheral lung cancer detected by sputum cytology, j) the number of cancers in otorhinological field or esophageal cancers detected by sputum cytology.
Results and the Estimated Number of Diagnosis in Japan : The questionnaires were sent to 504 authorized and associated institutes of the Japan Society for Respiratory Endoscopy and returned from 308 (61.1%) of them. These institutes, in the cases of primary lung cancer resections, covered 57.1% of the field study result of the Japanese Association of General Thoracic Surgery. A total of 150 diagnosed cases of early hilar lung cancer in a year were reported. By the reported number and the covering ratio, the number of early hilar lung cancer diagnosis was estimated between 154 and 270 cases per year. Also, 4,000 cases of hilar squamous cell carcinoma in a year in Japan were estimated. Concerning the mode of detection, sputum cytology was the most numerous, accounting for 90% of squamous cell carcinomas ; however, the rate of early cancer was less than 10% of hilar squamous cell carcinoma, and moreover, there were regional differences in the detection rates.
Conclusions : The national survey of hilar lung cancer suggested that there were 4,000 patients with hilar squamous cell carcinoma at present. However, the ratio of early cancer was less than 10%, and the regional differences in the ratio of early to not early hilar squamous cell carcinoma were also suggested. Based on these, there might have been more opportunities of early diagnosis of hilar lung cancer than were actually diagnosed. Further quality control and much more sputum cytologic examinations for lung cancer screening is recommended.

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Background : Malignant ovarian germ cell tumors may occur in subjects with 46, XY pure gonadal dysgenesis (Swyer syndrome).
Case : A 22-year- old phenotypic woman undergoing pelvic tumor laparotomy was found to have a solid right ovarian tumor 12 cm in diameter and a left adnexal streak-gonad mass. The cut surface of the right ovarian tumor from the ensuing bilateral salpingo-oophorectomy showed grayish-white nodule and a solid part with hemorrhaging and necrosis. The pathological diagnosis was malignant mixed germ cell tumor consisting of dysgerminoma and choriocarcinoma. Histopathological left- ovarian findings indicated gonadoblastoma. Right ovarian tumor imprint cytology showed two characteristic findings of (i) large round atypical cells with macronucleoli and marked lymphocytic infiltration and (ii) atypical syncytiotrophoblastic cells and cytotrophoblastic cells against a bloody necrotic background. Imprint cytology suggested a mixed germ cell tumor including dysgerminoma and choriocarcinoma.
Conclusion : Imprint cytology is useful in diagnosing of malignant ovarian mixed germ cell tumors.

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Background : We report a case of endometrial carcinoma possibly arising in an endometrial polyp.
Case : A 65-year-old woman, para 2, was referred to us for postmenopausal bleeding, atypical endometrial cytology and endometrial thickening of 18 mm measured by transvaginal ultrasonography. Initial cytological examination showed atypical monolayered cohesive cell sheets with a conspicuous nucleolus. A lack of structural atypia regardless of marked cellular atypia prevented a determination from the smear of endometrial cancer. Three months later, endometrial cytology showed the same numerous atypical monolayered scanty irregular cell sheets with a more enlarged nucleolus and hyperchromatic nuclei. A strong suspicion of malignancy necessitated endometrial biopsy and overall curettage, then total hysterectomy, bilateral salpingooophorectomy, and pelvic lymphadenectomy. Histological examination confirmed the diagnosis of endometrioid adenocarcinoma, grade 2, in endometrial polyp, with partially stromal invasion confined within the polyp. No endometrial hyperplasia, no lesion in any other part of the endometrium, and no involved lymph nodes were seen. The tumor was immunonegative for p53, ER, and PgR.
Conclusions : This case of cytologically evident marked cellular atypia lacking structural atypia should alert physicians of the potentially problematic diagnosis of endometrial carcinoma.

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Background : Lobular breast neoplasms do rarely express E-cadherin, although ductal carcinoma with reduced E-cadherin expression has been reported.
Case : A 60-year-old woman admitted to treat a right breast nodule was found in fine-needle aspiration cytology to have typical lobular carcinoma features, e.g., rosary-like appearance, straight-line arrangement and intracytoplasmic tumor cell lumina. Tumor cells had large nuclei with strong atypia and coarsely granular heterogeneously distributed chromatin. These findings suggested a ductal carcinoma tumor origin. Immunohistochemically, tumor cells lacked membrane E-cadherin expression although E-cadherin was expressed in nuclei and the Golgi zone. Tumor cells did not express the CK34βE12, usually expressed in lobular neoplasms. Based on these findings, the tumor was diagnosed as invasive carcinoma with reduced E-cadherin, probably of ductal epithelial origin.
Conclusion : Cytological nucleus findings were useful in diagnosing our case of invasive breast carcinoma with reduced E-cadherin expression. The classification of such tumors, however, requires further verification.

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[in Japanese]

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The spirit of The Bethesda System maintains that inadequate specimens should not be used to make cytological diagnosis. This also applies to histological diagnosis. Suitably assessing cytological and histological specimens is step 1 in accuracy control.

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The Bethesda System revised in 2001 includes categories defining risk status rather than specific diagnosis, e. g., “atypical squamous cells” (ASC), and “atypical glandular cells of undetermined significance” (AGUS).
ASC is divided into : atypical squamous cells “of undetermined significance” (ASC-US) and atypical squamous cells that “cannot exclude high-grade squamous intraepithelial lesion (HSIL) ” (ASC-H). It has been shown that a significant number of women with ASC-US are histologically diagnosed with squamous intraepithelial lesion (SIL) including HSIL (CIN 2 or 3) in subsequent or follow-up biopsies. Several studies have shown that women with ASC-H are more likely to have HSIL in subsequent biopsy than those with ASC-US, and that postmenopausal women with ASC-H are usually associated with low-grade SIL or benign change. Non neoplastic processes that could be interpreted as ASC include reactive atypia due to inflammation, irradiation effects, atrophy, immature metaplasia, and transitional metaplasia.
Follow-up in women with AGC has shown that high-grade lesions are identified in 10% to 40% of cases, and are more often squamous than glandular. Benign endocervical glandular lesions include reactive atypia due to inflammation or irradiation, tubal or tuboendometrioid metaplasia, endometriosis, endocervical polyps, and endocervical gland hyperplasia, and Arias-Stella reaction.

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Objective : We reviewed the meaning of koilocytosis in cytology and histology in diagnosing HPV-related squamous uterine cervix lesions.
Study Design : We analyzed the frequency and differential diagnosis of koilocytosis by reexamining cytological specimens with low grade squamous intraepithelial lesions (LSIL) and histological specimens of mild dysplasia (CIN 1).
Results : Of 55 cytological LSIL cases, 23 (42%) had koilocytosis. Of the 29 CIN 1 biopsy specimen, 19 (65.5%) had koilocytosis.
Conclusions : Koilocytosis is thus useful in evaluating the effects of HPV infection and diagnosing cervical intraepithelial neoplasia. Koilocytosis is, in cytology, the most important finding for differentiating LSIL from other nonneoplastic cytological changes and HSIL.

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Objectives : We reviewed pathological problems in General Rules for Clinical and Pathological Management of Uterine Cervical Cancer based on recent HPV developments and on the Bethesda system. We propose 3 new general rules on nomenclature and definitions for dysplasia/CIS system, glandular dysplasia, and microinvasive adenocarcinoma.
Conclusions : (i) In early squamous lesion nomenclature, the CIN system (CIN1, 2, 3) is recommended instead of the dysplasia/CIS system for histological diagnosis. (ii) The definition of glandular dysplasia should be clarified. (iii) Microinvasive adenocarcinoma criteria should be improved.

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We reviewed the Cervical Cytological Diagnosis Report conforming to The Bethesda System 2001 introduced in Japan in 2009. Referencing major U. S. and Japanese guidelines, we explored aspects of this approach requiring attention in treatment choice.
1. The Bethesda System evaluation of specimen adequacy, its most important quality assurance component, makes sampling device choice of conventional Pap smears vital. The 2011 Japan guidelines for gynecological practice suggest that a brush and/or spatula be used in sampling.
2. The Bethesda System includes glandular cell abnormalities, but the new concept atypical glandular cell (AGC) requires careful handling.
3. U. S. and Japanese guidelines differ in managing cervical intraepithelial neoplasia (CIN) grade 2. Cases of CIN grade 2 that are observed in Japan are treated in U. S. Japan’s 2011 gynecological practice guidelines suggest active follow-up with treatment acceptable for cases difficult to follow-up.

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