The recent advent of targeted cancer therapy has led to widespread implementation of molecular testing such as next-generation sequencing. Companion diagnostics are very important for predicting response to and adverse events for specific chemotherapeutic agents. Liquid-based cytology (LBC) allows immunohistochemistry, fluorescence in situ hybridization, and polymerase chain reaction to be performed. In our laboratory, two feasibility studies were done to validate the use of LBC materials. First, cytological materials were obtained from surgical specimens of 40 lung adenocarcinomas (ADC) and fixed using CytoRich^TM Red. Twenty cases (50%) were positive for epidermal growth factor receptor (EGFR) mutation. Anaplastic lymphoma kinase gene rearrangement and c-ros oncogene 1 gene rearrangements were each identified in one case (2.5%) with companion diagnostics. Second, the Cobas^TM EGFR Mutation Test ver. 2 was performed on each sample (LBC, formalin-fixed paraffin-embedded tissue or plasma) obtained by bronchoscopic examination from the 20 ADC with positive immunohistochemistry results. EGFR mutations were identified in eight cases (40%) using LBC, seven cases (35%) using formalin-fixed paraffin-embedded samples and four cases (20%) using plasma. These results suggest that LBC would be suitable for use in subtyping and molecular testing in clinical practice.

Objective : The primary site of cancer was estimated by ascites cytology and immunohistochemical staining by the cell block method (CB), and the time until a treatment plan could be decided for the cancer of unknown primary (CUP) was examined.

Study Design : This was a retrospective analysis of ascites cytology and CB in a total 5 patients who underwent ascites cytology for the diagnosis of CUP between January 2017 and April 2018. Immunohistochemical staining was performed in cases with a positive ascites cytology. The treatment policy for each case, the interval (in days) to decision about the treatment policy, the prognosis, etc., were examined.

Results : The predicted diagnosis was ovarian cancer in 4 of the 5 cases, and colon cancer in the remaining 1 case. The period from the first visit to our department to decision on the treatment plan was 7-13 days (average, 10.6 days).

Conclusion : CB is useful, minimally invasive tool for rapid prediction of the primary site of cancer in cases of CUP.

Objective : To determine the clinical significance of atypical glandular cells (AGC), we evaluated the results of histologic examination in patients who showed AGC on cytology screening for uterine cancer.

Study Design : A retrospective study was conducted of cases with AGC detected on conventional Pap smears between April 2011 and March 2016. The results revealed correlations between the histologic diagnoses and cytologic diagnoses when the AGC-positive cases were divided into the following 5 subcategories : AGC of endocervical origin, favor neoplasm (EC, FN) ; AGC of endcervical origin, not otherwise specified (EC, NOS) ; AGC of endometrial origin, NOS (EM, NOS) ; AGC-FN ; AGC-NOS.

Results : Of the 232 patients with AGC, 58 cases (25.0%) were detected to have precancerous and malignant lesions. Among the 111 patients with EC, FN or EC, NOS, there were 3 patients with CIN3, 1 with invasive squamous cell carcinoma, 10 with AIS and 7 with invasive cervical adenocarcinoma. Among the 103 patients with EM, NOS, 1 patient had atypical endometrial hyperplasia, 23 had endometrial carcinoma and 2 had ovarian carcinoma. Among the 34 patients with EC, FN and AGC-FN, 17 had precancerous or malignant lesions.

Conclusion : Detection of AGC could be predictive of precancerous or malignant lesions. AGC subcategorization is important for adequate management of the patients. Patients with EC should be followed up with endocervical sampling, and patients with EM should be followed up with endometrial sampling.

Objective : We investigated the nucleic acid quality in sodium alginate cell blocks (CBs) prepared from liquid-based cytology (LBC) specimens, and evaluated the impact of long-term storage of the LBC-CBs on the nucleic acid quality.

Study Design : We analyzed the nucleic acid quality in LBC-CBs prepared from effusion fluid in 19 patients with lung or ovarian cancer between January and March 2020. The impact of long-term storage of the LBC-CBs on the nucleic acid quality was also analyzed.

Results : The cytological findings of the LBC-CBs were satisfactory and the CB area was related to the DNA quantity (r=0.808). In regards to the impact of long-term storage, the DNA integrity number (DIN) could be calculated in 16 of the 19 cases (84.2%) and the DNA quality was relatively good. The length of time that the samples had been stored (days) prior to preparation of the LBC-CBs had no significant effect on the DIN (r=−0.176), whereas long-term sample storage (years) was associated with some deterioration of the DNA quality (p<0.001).

Conclusion : The nucleic acid quality in LBC-CBs was excellent, and if an adequate amount of DNA is collected, it could be possible to use samples prepared by this method for a variety of genetic tests.

Background : Metaplastic breast carcinoma is rare. We present a case of histologically diverse metaplastic breast carcinoma diagnosed by fine-needle aspiration cytology.

Case : A woman in her 70s was incidentally detected to have a mass in the C-portion of her left breast during a medical checkup. Fine-needle aspiration cytology revealed abundant cell clusters, including atypical polygonal cells with epithelial connections and atypical spindle cells. There appeared to be a transition between the polygonal and spindle cells. In addition, we observed atypical cell clusters surrounded by a hyaline-like substance. Based on the results of immunocytochemical analysis of the aspiration specimen, we diagnosed the patient as having metaplastic breast carcinoma. Histopathological examination showed a mixture of squamous cells and spindle cells, and the lesion was diagnosed as a mixed-type metaplastic breast carcinoma.

Conclusion : Immunocytochemical evaluation is useful for the diagnosis of mixed-type metaplastic breast carcinoma.

Background : In patients with ovarian cancer, cancer cells may be found in endometrial cytology samples by transfer of tumor cells through the fallopian tube. However, there are few reports of such an occurrence in cases with ovarian borderline tumors. We report a case of ovarian serous borderline tumor diagnosed by endometrial cytology and treated by laparoscopic salpingo-oophorectomy.

Case : A woman in her 50s was admitted to our hospital for positive endometrial cytology. Endometrial cytology revealed a few atypical cell clusters with psammoma bodies among atrophic endometrial cell clusters. Transvaginal ultrasound, CT and MRI revealed no tumor in the pelvic cavity, including the uterus and ovaries. Therefore, laparoscopic salpingo-oophorectomy was performed for the purpose of diagnosis. A small amount of surrounding ascites fluid was found to contain atypical cells similar to those observed on endometrial cytology. Initially, the tumor components were not observed histologically, but after extensive microscopic examination of specimen blocks, a small surface papillary lesion, approximately 1 mm in size, was identified in the right ovary, which was diagnosed as a serous borderline tumor with psammoma bodies.

Conclusion : In some cases of ovarian serous borderline malignancy, endometrial cytology may be useful for early detection of the primary focus.

Background : We report the urinary cytologic findings of a case of adenocarcinoma exhibiting gastric differentiation.

Case : A 40-year-old woman presented with postrenal acute renal failure and was diagnosed by magnetic resonance imaging as having a tumor of the posterior wall of the bladder, in addition to the OHVIRA (obstructed hemivagina and ipsilateral renal anomaly) syndrome. Urinary cytology showed mildly overlapping clusters of atypical glandular cells in an inflammatory background. Cell clusters with orange to yellowish intracytoplasmic mucin, cell clusters with pinkish to orange mucin on the apical surface, and small clusters of cuboidal cells with distinct cell borders and clear cytoplasm were identified. Cervical cytology showed the same cytologic findings, although the imaging tests showed no evidence of uterine tumor. Histological examination of the bladder tumor showed invasive adenocarcinoma exhibiting a serrated appearance, but no component of urothelial carcinoma. On immunohistochemistry, the tumor cells were focally positive for M-GGMC-1 and MUC6. Based on the findings, the tumor was diagnosed as adenocarcinoma of the bladder exhibiting gastric differentiation.

Conclusion : When mildly overlapping clusters of glandular cells with distinct cell borders, clear cytoplasm, and bland nuclei are identified on urinary cytology, gastric-type adenocarcinoma should be considered in the differential diagnosis.