Usefulness of on-site cytology of liver tumor biopsy in specimen sampling for cancer genomic profiling test.

AIM: Appropriate sample selection with a tumor fraction ≥20% without necrosis contamination is required for successful cancer genomic profiling (CGP). Rapid on-site evaluation (ROSE) is performed to assess adequate sampling. METHOD: This retrospective study included 54 patients who underwent CGP using liver tumor biopsy specimen with ROSE. RESULT: The sampling success rate (98.1%) was higher than the previously reported 77.5%-88.9%. ROSE was performed once in 51 patients and twice in three patients; for those undergoing ROSE twice, the first ROSE was negative for malignancy, or showed few tumor cells with necrotic cell contamination, while the second ROSE obtained from another location showed abundant malignant cells. In these patients, the CGP was successful using the second specimen, though the first sample did not meet the required criteria for CGP test. CONCLUSION: Performing ROSE during liver tumor biopsy may be useful for CGP test sampling because ROSE prevents sampling errors and contributes to adequate sampling.

Primary Epithelioid Rhabdomyosarcoma of the Liver: Case Report of an Unusual Histological Variant.

Rhabdomyosarcoma (RMS) is a soft tissue tumor with striated muscle cell differentiation. It mostly occurs in children. While it can affect any part of the body, it commonly involves the urogenital organs, head and neck including the parameninges and orbit, and limbs. We describe an adult case of primary epithelioid RMS of the liver. A 71-year-old man presented with a 5.6 cm liver mass. Tumor histology revealed diffuse proliferation of small epithelioid cells and focal spindle cells. The tumor cells were immunohistochemically positive for myogenin (positive ratio 30%), desmin, Myo D1, and CD56. The tumor weakly expressed MDM2 and did not express CDK4. This suggested that dedifferentiated liposarcoma with a rhabdomyosarcomatous component was unlikely. There was no fusion gene of PAX3-FKHR or PAX7- FKHR to indicate alveolar RMS by RT-PCR. Subsequently, RNA Pan-Cancer Targeted sequencing was performed for 1385 genes revealed a single base substitution (c.742C>T) in TP53 that changes an amino acid (p.Arg248Trp). No fusion gene was found. No other primary RMS lesions were detected aside from the liver lesion. The tumor was diagnosed as a primary epithelioid RMS of the liver. His RMS already metastasized to the lymph nodes of the entire body. The patient declined further therapy and died one year later. This was the first case report of a primary epithelioid RMS of the liver.

Detection of pagetoid urothelial intraepithelial neoplasia extending to the vagina by cervical screening cytology: a case report with renewed immunochemical summary.

BACKGROUND: Pagetoid spread of urothelial carcinoma (UC) to the lower genital tract is quite a rare and diagnostically challenging condition. Pagetoid urothelial intraepithelial neoplasia extending to the vagina is difficult to diagnose, especially in remote recurrences without symptomatic or macroscopic lesions typical to Paget disease. However, its identification by cervical screening cytology is important because UC is often characterized by a long history of relapse. CASE PRESENTATION: A 68-year-old Japanese postmenopausal woman developed brown vaginal discharge after radical cystectomy for bladder cancer (high-grade UC, pT2a pN0 cM0 [Union for International Cancer Control, 8th edition]) concomitant with focal in-situ UC in the urethra. She had a history of left renal pelvis UC, which was surgically removed 9 months before the radical cystectomy. Gynecologic examination of the lower genital tract was unremarkable although cervical screening cytology demonstrated severely atypical cells with pleomorphism repeatedly. Cervical colposcopy and diagnostic conization revealed no cervical neoplasm. In retrospect, immunocytochemical p16/Ki-67 dual staining for the previous cervical screening was negative for p16 labeling, and the neoplastic cells were positive for cytokeratins 7 and 20, p63, and GATA binding protein 3. No high-risk human papillomavirus genotype was identified by an automated DNA chip system using liquid-based cytology samples. Eleven months post-cystectomy, punch biopsy of the vulva and vagina confirmed intraepithelial UC in the juxtaposed squamous epithelium with pagetoid spread demonstrating positivity for specific urothelial markers: uroplakins II and III and thrombomodulin. Concurrent invasive malignancy was ruled out, and CO2 laser vaporization of the vulvar and vaginal lesion was performed. The patient remained alive without evidence of invasive malignancy for 14 months after the radical cystectomy for bladder cancer. CONCLUSIONS: To detect recurrent pagetoid urothelial intraepithelial neoplasia with pagetoid spread in the lower genital tract, pathologists should recognize the history of prior UC with special attention to absence of p16 labeling in cervical cytology as a pointer to the diagnosis of urothelial cancer. Using further biopsy and immunohistochemical confirmation of UC relapse, investigation to rule out invasive malignancies and careful follow-up throughout the patient's lifetime is recommended.

Correlation between Ultrasound Findings of Tumor Margin and Clinicopathological Findings in Patients with Invasive Ductal Carcinoma of the Breast.

BACKGROUND: Breast ultrasound findings regarding tumor margins are crucial in judging whether a tumor is malignant or benign. However, the relationships between the margins and clinicopathological characteristics remain largely unknown. In this study, we examined the clinicopathological characteristics of patients with invasive ductal carcinoma whose ultrasound images showed either well-defined and rough or indistinct margins. METHODS: Of all consecutive patients diagnosed with invasive ductal carcinoma at the Division of Breast and Endocrine Surgery of Tottori University Hospital from January 2012 to December 2014, 122 patients whose ultrasound images showed either "well-defined and rough" or "indistinct" tumor margins were included in this study. Mammography and ultrasound images taken at the initial examination were reviewed. Patients were divided into two groups based on ultrasound findings of the tumor margins: the "well-defined and rough group" and the "indistinct group." The relationships among ultrasound findings, mammography findings and clinicopathological findings were investigated in the two groups. RESULTS: The well-defined and rough group was more likely to contain solid-tubular carcinoma, while the indistinct group was more likely to contain scirrhous carcinoma. The MIB-1 index was higher in the well-defined and rough group than in the indistinct group. Additionally, the proportion of patients with nuclear grade 3, estrogen receptor-negative/progesterone receptor-negative, and triple-negative breast cancer was greater in the well-defined and rough group than in the indistinct group. CONCLUSION: Invasive ductal carcinomas with well-defined and rough margins on ultrasound were likely to be malignant and proliferative than those with indistinct margins.

EEG Power Spectrum Analysis in Children with ADHD.

BACKGROUND: Attention deficit disorder/hyperactivity disorder (ADHD) is a pathological condition that is not fully understood. In this study, we investigated electroencephalographic (EEG) power differences between children with ADHD and healthy control children. METHODS: EEGs were recorded as part of routine medical care received by 80 children with ADHD aged 4-15 years at the Department of Pediatric Neurology in Tottori University Hospital. Additionally, we recorded in 59 control children aged 4-15 years after obtaining informed consent. Specifically, awake EEG signals were recorded from each child using the international 10-20 system, and we used ten 3-s epochs on the EEG power spectrum to calculate the powers of individual EEG frequency bands. RESULTS: The powers of different EEG bands were significantly higher in the frontal brain region of those in the ADHD group compared with the control group. In addition, the power of the beta band in the ADHD group was significantly higher in all brain regions, except for the occipital region, compared with control children. With regard to developmental changes, the power of the alpha band in the occipital region showed an age-dependent decrease in both groups, with slightly lower power in the ADHD group. Additionally, the intergroup difference decreased in children aged 11 years or older. As with the alpha band in the occipital region, the beta band in the frontal region showed an age-dependent decrease in both groups. Unlike the alpha band, the power of the beta band was higher in the ADHD group than in the control group for children of all ages. CONCLUSION: The observed intergroup differences in EEG power may provide insight into the brain function of children with ADHD.

Contrast-Enhanced Ultrasonography in Evaluation of the Therapeutic Effect of Chemotherapy for Patients with Liver Metastases.

BACKGROUND: The therapeutic effect of chemotherapy for liver metastases is currently determined by changes in tumor diameter depicted on computed tomography (CT) and magnetic resonance imaging, but it cannot accurately determine if there is central necrosis. Furthermore, due to the risk of radiation exposure and high cost, frequent examination using these methods places a heavy burden on patients. Meanwhile, real-time observation of blood flow and vessel morphology within tumors has become possible by contrast-enhanced ultrasonography (CEUS). However, use of CEUS in evaluating the therapeutic effect of anticancer chemotherapy has rarely been investigated. This study investigated whether changes in the time-intensity curve (TIC) of CEUS are useful indicators of the therapeutic effect of chemotherapy. METHODS: Five patients with liver metastases who had undergone CEUS before and after chemotherapy were included in this study. The TIC of each time point was prepared to examine whether the following five TIC parameters serve as indicators of the therapeutic effect of chemotherapy: peak intensity, time to wash-in, time to peak intensity, slope of wash-in, and area under the curve. In each parameter, rate of change (ROC) was calculated by the expression [(values before chemotherapy minus those after chemotherapy)/those before chemotherapy × 100(%)]. RESULTS: (i) Among the five TIC parameters tested, ROC of the slope of wash-in and the area under the curve reflected the therapeutic effect of chemotherapy better than the remaining three parameters. (ii) TIC parameters after one cycle of chemotherapy were examined in two of five patients, and changes in the slope of wash-in and the area under the curve were in good agreement with the computed tomography findings indicative of the therapeutic effect after the fourth chemotherapy cycle. CONCLUSION: The findings of this study suggest that ROC of the slope of wash-in and the area under the curve of the TIC are useful in evaluating the therapeutic effect of chemotherapy. Furthermore, there is a possibility that TIC analysis may enable early prediction of the therapeutic effect.

Microcalcification of Tumor is a Predictor of Response to Neoadjuvant Chemotherapy for Invasive Breast Carcinoma.

BACKGROUND: In recent years, neoadjuvant chemotherapy (NAC) is often performed for patients with unresectable breast carcinoma or without indication of breast conserving therapy. However, it is currently difficult to predict response to NAC with diagnostic imaging of breast carcinoma. In this study, we investigated imaging findings that could serve as a predictor of the response to NAC for patients with invasive breast carcinoma. METHODS: Twenty-six patients with invasive breast carcinoma who received NAC at the Division of Breast and Endocrine Surgery of Tottori University Hospital between January 2010 and May 2014 were retrospectively investigated. Their imaging findings from mammograms and ultrasonograms were reviewed. The association between findings on mammograms and ultrasonograms captured before NAC and response to treatment after NAC was examined. RESULTS: Of the 26 patients with invasive breast carcinoma, 19 (73%) responded well to treatment and 7 (27%) did not. Most notably, all 10 patients who had microcalcifications on mammogram responded well to treatment (53% of responders), and all patients who did not respond to treatment had no microcalcifications (P < 0.05). Of these 10 patients, 9 (90%) had microcalcifications of comedo type and one (10%) had non comedo type. As a distribution, 8 of the 10 (80%) had a clustered type of microcalcifications and the remaining 2 (20%) had a segmental type of them. CONCLUSION: Microcalcifications of tumor observed in mammogram (particularly comedo type) could be a predictor of response to NAC for patients with invasive breast carcinoma.