Objective : Re-screening of smears diagnosed as negative for intraepithelial lesion or malignancy (NILM) by routine screening has been recommended to increase the accuracy of cytological diagnosis. We conducted this study to clarify the effectiveness and significance in uterine cancer screening.

Study Design : Re-screening of specimens diagnosed as NILM by routine screening revealed false-negative cases. The false-negative rate was calculated. In addition, the histologic findings of the cases with false-negative smears were compared with those of the negative smears confirmed by re-screening.

Results : We performed re-screening of 20987 cases (3.97%) out of the 528402 cases routinely diagnosed as NILM over a 7-year period. Upon re-screening, the cytologic result changed from negative to abnormal in 44 cases. Thus, the false negative rate was determined to be 0.99% and the sensitivity of routine screening was calculated to be 99.01%. The cytologic diagnoses in aforementioned 44 cases were ASC-US (16 cases), ASC-H (9 cases), LSIL (17 cases), HSIL (1 case) and ACG (1 case). Histological examnation of 41 of the 44 cases diagnosed as abnormal by re-screening revealed CIN1 in 12 cases (29.3%), CIN2 in 8 cases (19.5%) and CIN3 in 4 cases (9.8%).

Conclusion : In mass screening for uterine cervical cancer, re-screening of negative smears improves the sensitivity over that of the first screening. Re-screening may improve the sensitivity and accuracy of cytologic diagnosis, and occasionally allow detection of cervical neoplastic lesions.

Objective : An attempt was made to confirm the safety and diagnostic value of the Cervex brush^® for uterine cervical cancer screening of pregnant women.

Study Design : We conducted cancer screening using the Cervex brush^® in a total of 179 pregnant women between 2014 and 2016, and obtained 184 samples. The severity of bleeding at the time of screening was scored from (−) to (++). Five patients with abnormal cytology underwent both Cervex brush^® sampling and cotton swab sampling at the same time.

Results : In the group from which samples were obtained with the use of the Cervex brush^®, about 99% showed no bleeding or only slight bleeding within 24 hours after the sampling. The severity of bleeding was not related to the gestational duration or the cytological results. No severe obstetrical complications were encountered after the Cervex brush^® sampling. The proportion of inappropriate smears was higher for cotton swab sampling than for Cervix brush^® sampling.

Conclusion : Cervical cancer screening using a Cervex brush^® can be performed safely in pregnant women, and is a more efficient sampling method than cotton swab sampling for accurate cytological diagnosis.

Objectives : Dark 3-dimensional tissue fragments which called hyperchromatic crowded cell groups (HCG) are frequently observed in the BD SurePath (SP) liquid-based cytology (LBC). In this study, we evaluated the frequency of HCG in HSIL specimens by BD SP system.

Study Design : Cytology specimens of 250 women categorized as HSIL were assessed. They were taken from women on routine cervical check-up, collected with Cervex-Brush, and processed by BD SP LBC system. This study was approved by the ethical committee of the Jikei University School of Medicine (22-189 [6366]).

Results : The patients’ age ranged from 22 and 68 years (average 38 years). HCG were observed in 69.3% of HSIL. The cervical biopsy was performed in 206 of 250 patients (82.4%).The histology showed benign in 10 patients (atrophy in 1, immature metaplasia in 9), CIN) 1 in 43, CIN2 in 99 cases, CIN3 in 47, Microinvasive squamous cell carcinoma in 7. The diagnostic accuracy in those of lesions more than CIN2 was 74.3%, and that of more than CIN1 was 95.1%.

Conclusions : HCG were frequently present in the cytology specimens with HSIL by BD SP system. Although Abnormal are easy to find on cytological screening, we must carefully differentiate them from atrophic squamous epithelium or immature metaplastic cells.

Currently in Japan, cytology quality control (QC) guidelines state that from cytology samples that are diagnosed as negative by a cytotechnologist, 10% are arbitrarily chosen to be rescreened, while the other 90% are not further evaluated. In a previous study, we found 117 (1.19%) False Negatives (FN). This FN rate was higher than the expected value including previous studies in Japan (FN rate : 0.05%, 0.61%). As stated in the “Basic Plan to Promote Cancer Awareness” in 2012 we have a target for the cervical cancer screening rate of 50% (up from 26%). This goal will dramatically increase the number of samples and increase the workload for cytotechnologists that will in turn lead to a potentially large number of FN cytology samples which could be missed, thus leading to a higher mortality rate. The present study looked at reports on the use of an automated rescreening system for samples diagnosed as negative by a cytotechnologist. Based on our results, we found that the automated screening system could be effective for the QC rescreening of cervical cytology samples.

Background : Synovial chondromatosis is a cartilaginous neoplasm of the synovial membrane and usually diagnosed based on clinical and radiological findings. We report herein on a case of synovial chondromatosis diagnosed based on the synovial fluid cytology, which was thought to be feasible for preoperative diagnosis.

Case : A 34-year-old woman visited our hospital because of pain and swelling of the left knee from one year previously. Radiological examination showed increased synovial fluid, but no obvious findings of underlying disease. Synovial fluid cytology was performed and the smear revealed nodular clusters of chondrocytes surrounded with a chondroid matrix. The cells showed mild nuclear atypia such as anisonucleosis, binucleation, small nucleoli and high cellularity. The arthroscopic findings revealed whitish synovial tissues and a synovectomy was performed. Histological examination showed primary synovial chondromatosis.

Conclusion : Synovial fluid cytology is useful for preoperative diagnosis of synovial chondromatosis, when diagnosis based on radiologic examination is difficult.

Background : Salivary duct carcinomas (SDCs) are high-grade malignant tumors of the salivary glands that are frequently encountered in clinical practice. Herein, we report a case of SDC of the parotid gland with multiple metastases that showed sarcomatoid components.

Case : A woman in her 70’s presented to us with swellings in her left parotid and submandibular regions. Fine needle aspiration cytology revealed large clusters of malignant cells, however, the histological features could not be predicted prior to the surgery. The findings of imprint cytology from the excised tumor were consistent with SDC and the tumor was diagnosed by histopathological examination as SDC. The specimens revealed both adenocarcinomatous and sarcomatoid components, and the latter were also observed in the metastatic tumors in the submandibular gland and lymph nodes. Nine months after the initial treatment, metastatic tumors were detected clinically in the lungs and adrenals. Transbronchial scraping cytology revealed sarcomatoid cells alone.

Conclusion : When conducting cytological examinations of SDC, it is necessary to consider alterations of the cellular morphology caused by metastasis.

Background : We report a case of CN diagnosed by cerebrospinal fluid cytology.

Case : A 30-year-old female patient seen at this hospital for a blow injury to the head was found on head MRI to have a tumor measuring 43 mm in diameter in the right lateral ventricle. In the intraoperative cerebrospinal fluid cytology preparations, tumor cells were observed in clusters or singly, with pale light green cytoplasm and round nuclei with finely granular chromatin and ill-defined nucleoli, some forming rosettes, a finely fibrillated neuropil matrix. The cells were immunocytochemically positive for synaptophysin. Histologically, the tumor was composed of small round tumor cells in a sheet-like arrangement with fine capillary arcades, some forming Homer Wright-type rosettes. Immunohistochemically, the tumor cells showed positive staining for synaptophysin ; the MIB-1 labeling index was 3%. The histological diagnosis was CN, WHO grade Ⅱ.

Conclusion : In cerebrospinal fluid cytology, use of LBC and immunohistochemical staining, could allow precise diagnosis of CN.

Background : The cytopathologic features of body cavity effusion in patients with IgG4-related disease have not been well documented. We report a case clinically compatible with IgG4-related disease, in which cytological examination successfully proved the presence of IgG4-positive plasma cells in pleural effusion.

Case : Computed tomography demonstrated mild pleural thickening with bilateral pleural and pericardial effusion in a female patient in her 70 s. The serum levels of IgG and IgG4 were both elevated. Conventional cytology of the pleural effusion revealed numerous infiltrating plasma cells with small lymphocytes, but no malignant cells. Although IgG4-related disease was suspected, IgG4 positivity could not be readily demonstrated in the plasma cells, either on a cytological smear or biopsy tissues, and plasma cell neoplasia could not be excluded. Immunostaining of a cell block preparation demonstrated that more than 50% of the plasma cells were IgG4-positive, without evidence of clonal immunoglobulin light chain restriction. In addition to the clinical features, the infiltrating plasma cells in the pleural effusion were considered to be associated with IgG4-related disease.

Conclusion : Use of a cell block preparation of the pleural effusion, combined with conventional cytological evaluation, seems to be effective for diagnosis of IgG4-related disease.

Background : Small cell carcinoma (SmCC) of the uterine cervix is a rare and highly aggressive tumor, which often presents with early distant metastasis and carries a poor prognosis. Herein, we report three cases of uterine cervical SmCC.

Cases : All the patients, who were in their 50’s to 80’s, presented with irregular vaginal bleeding. Physical examination revealed a tumor mass in the uterine cervix, and cervical smears and biopsy specimens were obtained from each patient. Cytological examination showed proliferation of uniformly small tumor cells with scant cytoplasm arranged singly or in clusters in a necrotic background. Histologically, the tumor consisted of densely packed small tumor cells with scant cytoplasm and increased nuclear chromatin, admixed with focal squamous and adenocarcinoma components. Immunohistochemically, the tumor cells were positive for CD56, synaptophysin, and NSE. The tumor cells were also positive for p16, suggesting that cervical SmCC may be causally related to human papilloma virus infection. In two cases, the tumor cells were focally positive for c-kit.

Conclusion : SmCC of the uterine cervix is a rare, but clinically aggressive tumor. Therefore, precise cytological interpretation is important for early diagnosis of cervical SmCC. Positive staining for c-kit in two of our three cases indicates that the tumor may respond to molecular-targeted therapy, although further investigation is needed.

A case of prostatic ductal adenocarcinoma demonstrated in the bladder washing fluid specimen prompted us to write a case report.

An 80-year-old man presented with gross hematuria. Cytological examination of bladder wash specimens revealed tight aggregates of tall columnar cells showing a papillary structure, peripheral nuclear palisading, and glandular formation. The neoplastic cells had large round-to-oval nuclei containing conspicuous nucleoli and vesicular chromatin. Immunocytochemically, the tumor cells showed positive staining for PSA.

Prostatic ductal adenocarcinoma must be included in the differential diagnosis when atypical tall columnar cells are detected in urine/bladder wash specimens. The combination of the cytological features and positive immunocytochemical staining for PSA helps in the differential diagnosis.