Miscarriage-Related Acute Kidney Injury: A Case Report.

Background: Pregnancy-related acute kidney injury (Pr-AKI) is associated with significant maternal and fetal morbidity and mortality, with a three- to four-fold increase in perinatal mortality. Pr-AKI can arise from various obstetric complications, such as hyperemesis gravidarum, septic abortion, hypertensive disorders of pregnancy, pyelonephritis, and antiphospholipid antibody syndrome. Therefore, early diagnosis and appropriate intervention, including the identification of the underlying etiology, are important to effectively manage Pr-AKI. Therefore, we report a case of Pr-AKI after early miscarriage in a patient without hyperemesis gravidarum or septic abortion whose renal function gradually improved postoperatively for miscarriage. Case Presentation: A 34-year-old primigravid woman was referred to us for perinatal management at 6 weeks of gestation. Unfortunately, she was diagnosed with miscarriage 1 week later. The patient had no history of hyperemesis gravidarum or septic abortion; however, she developed oliguria, and her serum creatinine and blood urea nitrogen levels were abnormally increased. Consequently, she underwent a renal biopsy to evaluate renal dysfunction, which indicated tubulointerstitial damage. The patient also underwent manual vacuum aspiration for a miscarriage. Postoperatively, her urine output increased, and her renal function improved. She was determined to have experienced Pr-AKI due to her miscarriage. Conclusion: Our patient had Pr-AKI after a miscarriage in the absence of other causes. This case report highlights the presence of unknown causes of Pr-AKI, warranting further research for the development of preventive interventions.

Ovarian Mesonephric-like Adenocarcinoma Recurring With a Rhabdomyosarcoma Component: A Case Report.

Mesonephric-like adenocarcinoma (MLA) has recently been described as a tumor of the endometrium or ovaries, which, morphologically and immunohistochemically, resembles mesonephric adenocarcinoma arising mostly in the uterine cervix. Herein, we report, to our knowledge, the first case of ovarian MLA that developed into an extremely rapidly growing recurrent mesonephric-like carcinosarcoma, as confirmed by a genomic profiling test. A 51-year-old woman underwent chemotherapy with complete debulking surgery for ovarian carcinoma. Pathologically, the patient was diagnosed with stage IVB ovarian MLA. Subsequent to 15 months of complete remission, an enhanced computed tomography scan revealed a solid tumor of 10 cm diameter in the abdominal cavity. Secondary surgery was terminated with a 2 cm 2 tumor biopsy specimen collection considering perioperative complications. Histologically, the tumor consisted of short spindle cells, and immunohistochemical staining revealed a rhabdomyosarcomatous profile without an epithelial component. Despite treatment for the sarcoma, she died 3 months after the detection of the tumor. The genomic profiling of the primary ovarian carcinoma and secondary resected tumor biopsy specimens revealed an identical KRAS mutation in both. Therefore, we concluded that the ovarian MLA recurred with a rhabdomyosarcoma component.

Hypercalcemia associated with dysgerminoma and elevation of calcitriol: A case report and review of the literature.

We report on the case of a patient with dysgerminoma, a rare germ cell tumor, which showed hypercalcemia with an elevation of 1α,25-dihydroxycholecalciferol (calcitriol). A 27-year-old nulliparous woman presented with hypercalcemia during the examination of a right ovarian tumor with an elevation of calcitriol, lactate dehydrogenase, and alkaline phosphatase. Fractional excretion of calcium was elevated, and intact parathyroid hormone was suppressed. After undergoing right salpingo-oophorectomy, the patient's serum calcium and calcitriol returned to the normal range within a week. A literature search was conducted on the topic by reviewing databases for dysgerminoma showing hypercalcemia. We identified 14 patients from the literature and performed a pooled analysis, including the results of our case. However, most cases lack data that can help investigate the potential association between parathyroid hormone, parathyroid hormone-related protein, calcitriol, and phosphorus in hypercalcemia. Thus, more case reports that include additional information are required to fully elucidate the mechanism of hypercalcemia associated with dysgerminoma.

Cessation of methotrexate and a small intestinal resection provide a good clinical course for a patient with a jejunum perforation induced by a methotrexate-associated lymphoproliferative disorder: a case report.

BACKGROUND: Methotrexate (MTX) is a frequently used drug in the treatment of rheumatoid arthritis (RA), but occurrences of lymphoproliferative disorders (LPD) have been reported in patients undergoing an MTX regimen. Almost half of the patients with methotrexate-associated lymphoproliferative disorders (MTX-LPD) have extranodal lesions; moreover, although extremely rare, digestive tract perforations resulting from the extranodal lesions of MTX-LPD have also been reported. CASE PRESENTATION: We describe the case of an 81-year-old woman with RA who had been prescribed MTX at 6 mg per week for the past 11 years. She was admitted to our hospital with occasional abdominal pain and was first diagnosed with enteritis. Her abdominal pain did not improve, and a computed tomography scan showed abdominal effusion and free air in the abdominal cavity. She was diagnosed with a digestive tract perforation and underwent emergency surgery. The perforation site was identified in the jejunum, and she underwent small intestinal resection around the perforated region. The pathological findings showed an ulcer in the jejunum and infiltration of large atypical lymphocytes around the perforated region. An immunohistochemical examination revealed the expression of a cluster of differentiation 20 and latent membrane protein 1. Considering the patient's history of RA treated with MTX, she was diagnosed as having Epstein-Barr virus (EBV)-related MTX-LPD with a histological diagnosis of EBVMCU. MTX was discontinued after the surgery, and her soluble interleukin-2 receptor (sIL-2R) levels had returned to normal 1 year later. She has had a good course for the 2 years since surgery and remains asymptomatic with no recurrence of MTX-LPD, as confirmed by the sIL-2R levels. CONCLUSION: We experienced a rare case of the jejunum perforation induced by MTX-LPD. Since only a few cases have been reported of a patient with small intestinal perforation induced by MTX-LPD, further research is necessary to evaluate the clinicopathological features of MTX-LPD. The patient had disease remission after surgery and by discontinuing MTX treatment; our case did not require chemotherapy. EBV-positive patients, especially those with a pathological presentation of EBVMCU, could have a higher likelihood of remission, which could have been a factor in the present case.

Clear cell neuroendocrine tumor in the gallbladder diagnosed as a benign polyp preoperatively: a case report.

BACKGROUND: Gallbladder neuroendocrine neoplasm is a rare disease that is divided into neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs). Clear cell NETs of the gallbladder are extremely rare. We report the case of a patient with polypoid clear cell NET G1 of the gallbladder who underwent laparoscopic cholecystectomy. CASE PRESENTATION: A 10-mm pedunculated polyp in the gallbladder neck was detected on a follow-up abdominal ultrasound in a 60-year-old man with chronic hepatitis and hepatitis B without medication. Six months later, an abdominal ultrasound revealed that the tumor had enlarged to 12 mm in size. He was asymptomatic and had no abnormalities in other laboratory examinations, including the tumor markers, carcinoembryonic antigen and CA19-9. Abdominal ultrasound showed a 12-mm polyp in the neck of the gallbladder with perfusion and focal thickening of the gallbladder wall. A gallbladder stone was also seen in the fundus. An enhanced computed tomography scan and magnetic resonance imaging revealed a polypoid lesion and gallbladder stone located at the neck of the gallbladder and the fundus, respectively. Malignancy could not be excluded, and hence, a laparoscopic cholecystectomy was performed. Pathologically, a pedunculated polyp (14 × 11 × 15 mm) was observed in the neck of the gallbladder, and the polypoid lesion comprised nests or trabecular growths of clear NET cells in the lamina propria (ENETS: T1N0M0; AJCC: T1aN0M0). Immunohistochemical staining with synaptophysin, chromogranin A, and CD56 was confined to the tumor. The pathological diagnosis was clear cell NET G1 of the gallbladder. Although clear cell NET is often described as a distinct manifestation of von Hippel-Lindau disease (VHL), the patient had no past medical or family history of VHL. Until his one-and-a-half-year follow-up, the patient was doing well and without any signs of recurrence. CONCLUSION: We report an extremely rare case of gallbladder clear cell NET G1. When NET G1 is incidentally identified in a gallbladder surgical specimen, clinical information and pathological findings should be considered as references.

A case of primary clear cell hepatocellular carcinoma comprised mostly of clear cells.

Clear cell hepatocellular carcinoma (CHCC) is defined as a tumor which contains more than 50% of clear cells. However, CHCC with more than 90% of clear cells are extremely rare. We report a case of a 65-year-old woman who was found to have a solitary mass, which was histologically diagnosed as clear cell hepatocellular carcinoma composed of 90% or more clear cells. The tumor presented rim arterial phase hyperenhancement in computed tomography, magnetic resonance imaging, and computed tomography during hepatic arteriography, and was classified as LR-M category according to The Liver Imaging Reporting and Data System version 2018(LI-RADS v2018). This tumor may mimic other tumors with similar radiographic features, such as intrahepatic cholangiocellular carcinoma and metastatic tumor.

Thermal effects of the Thunderbeat™ device on the recurrent laryngeal nerve during thyroid surgery.

PURPOSE: To investigate the safety of the Thunderbeat™ (TB) device in thyroid surgery by clarifying its thermal effects on the recurrent laryngeal nerve (RLN). METHODS: We performed thyroidectomy using TB on four female pigs under general anesthesia. TB was applied 0, 1, and 2 mm from the RLN. The effects of incisions made in tissues in the vicinity of the RLN were evaluated by intraoperative neuromonitoring and pathological examination. RESULTS: The value of the neural integrity monitor (NIM) was unchanged at 2 and 1 mm, but there was loss of signal at 0 mm. The differences between 2 and 0 mm were not clear from the pathological findings. CONCLUSIONS: When using the TB device during thyroid surgery, it is recommended that it is visually kept from making any contact with the RLN.

Immunophenotypic profiles for distinguishing orbital mucosa-associated lymphoid tissue lymphoma from benign lymphoproliferative tumors.

PURPOSE: To evaluate novel immunophenotypic profiles of patients with orbital lymphoproliferative tumors. METHODS: From 2006 to 2014, surgical biopsies from consecutive patients with newly diagnosed orbital mucosa-associated lymphoid tissue (MALT) lymphoma and IgG4-related ophthalmic disease (IgG4-ROD) were collected from Tokyo Medical University Hospital. A total of 44 tumors from 44 patients were analyzed, including 21 with orbital MALT lymphoma (11 men and 10 women, mean age 67.8 ± 13.4 years) and 23 with definitive IgG4-ROD (9 men and 14 women, mean age 60.5 ± 15.1 years). Patients with secondary orbital MALT lymphoma and MALT lymphoma with IgG4-ROD were excluded. All patients were immunocompetent Asian adults. Samples were analyzed by immunohistochemistry and flow cytometric analysis. Flow cytometry was performed with the following antibodies: CD3, CD4, CD5, CD8, CD10, CD19, CD20, CD23, CD25, CD30, CD34, and CD56 lambda and kappa chains. RESULTS: Expression of CD25 and CD19 was higher in patients with orbital MALT lymphoma compared to patients with IgG4-ROD (p < 0.001). In contrast, expression of CD3, CD4, and CD23 was higher in patients with orbital IgG4-ROD compared to those with MALT lymphoma (all p < 0.01). The presence of CD23 and CD25 in the specimens was confirmed by immunohistochemistry. CONCLUSION: The present study elucidated the novel immunophenotypic features of orbital MALT and benign lymphoproliferative disorders such as IgG4-ROD. Among them, CD23 and CD25 have shown a disease-specific expression pattern.

Inhibitory effects of Kaempferia parviflora extract on monocyte adhesion and cellular reactive oxygen species production in human umbilical vein endothelial cells.

PURPOSE: The rhizome of Kaempferia parviflora (KP) is used in traditional Thai medicine. In this study, we investigated the effects of an ethanol KP extract and two of its components [5,7-dimethoxyflavone (DMF) and 5-hydroxy-3,7,3',4'-tetramethoxyflavone (TMF)] on monocyte adhesion and cellular reactive oxygen species (ROS) production in human umbilical vein endothelial cells (HUVECs), which provide an in vitro model of events relevant to the development and progression of atherosclerosis. METHODS: RAW264.7 mouse macrophage-like cells were incubated with various concentrations of KP extract or polymethoxyflavonoids and stimulated with lipopolysaccharide prior to measuring nitrite levels in the culture media. Monocyte adhesion was evaluated by measuring the fluorescently labeled human monocytic leukemia THP-1 cells that is attached to tumor necrosis factor-α (TNF-α)-stimulated HUVECs. Cellular ROS production was assessed by measuring cellular antioxidant activity using pyocyanin-stimulated HUVECs. RESULTS: KP extract and DMF reduced nitrite levels (as indicator of nitric oxide production) in LPS-stimulated RAW264.7 cells and also inhibited THP-1 cell adhesion to HUVECs. These treatments induced mRNA expression of endothelial nitric oxide synthase in TNF-α-stimulated HUVECs and downregulated that of various cell adhesion molecules, inflammatory mediators, and endothelial function-related genes. Angiotensin-converting enzyme activity was inhibited by KP extract in vitro. Furthermore, KP extract, DMF, and TMF inhibited the production of cellular ROS in pyocyanin-stimulated HUVECs. CONCLUSION: KP extract, DMF, and TMF showed potential anti-inflammatory and antioxidant effects in these in vitro models, properties that would inhibit the development and progression of atherosclerosis.

Giant insulinoma: report of a case and review of published reports.

BACKGROUND: Larger insulinomas are reportedly more likely to be malignant; however, their biological behavior has not been clearly elucidated. We here report the characteristics and treatment of a giant insulinoma with local invasion and lymph node metastasis. We also review published reports concerning the clinical features of giant insulinomas and comparing their grading with that of pancreatic neuroendocrine tumors. CASE PRESENTATION: A 71-year-old man was referred to our hospital for investigation of persistent hypoglycemia. On the current presentation, laboratory tests showed serum glucose, immunoreactive insulin, and C peptide concentrations of 45 mg/dL, 17.2 µIU/mL and 4.1 ng/mL, respectively. Dynamic magnetic resonance imaging showed a hypervascular tumor measuring 13.5 cm in the head of the pancreas. Computed tomography scanning demonstrated local invasion and lymph node involvement. He thus had Whipple's triad, which is associated with malignant insulinoma. No distant metastases having been identified, pancreaticoduodenectomy was performed. Intraoperatively, three separate tumors were identified in the pancreatic head. Pathological examination showed all three tumors were pancreatic neuroendocrine tumors; the tumor cells in the largest mass were strongly immunoreactive for insulin. The Ki-67 index was 2-5% in most parts of the largest tumor and over 20% in the poorly differentiated areas. This tumor was classified as neuroendocrine carcinoma in accordance with the 2010 World Health Organization classification of pancreatic endocrine neoplasms. He remains free of evidence of recurrence 2 years postsurgery. A review of published reports indicated that giant insulinomas are more malignant than smaller ones, and metastatic disease is found on presentation in 56% of patients with giant insulinomas; however, we were unable to identify any correlation between grade of pancreatic neuroendocrine tumor and biological behavior of giant insulinomas. CONCLUSIONS: Giant insulinomas more frequently exhibit malignant behavior, such as local invasion, lymph node involvement, and liver metastasis, than smaller ones. However, there was no relationship between grade and rate of metastases or survival in this small case series. Identification of useful biological markers is necessary.

Primary gastrointestinal stromal tumor of the liver: a case report and review of the literature.

BACKGROUND: Recently, gastrointestinal stromal tumors that have developed outside of the digestive tract have been reported. These tumors are collectively termed extra-gastrointestinal stromal tumors. Extra-gastrointestinal stromal tumors can also develop in the liver. Only eight case reports involving primary GIST of the liver have been published. We report a case and review the literature regarding this disease. CASE PRESENTATION: A 70-year-old woman with a past history of gastric cancer visited our hospital for regular inspection. With extensive radiological imaging, a computed tomography scan revealed a mass with a size of 6.8 cm in the lateral segment of the liver. (18)F-Fluoro-2-deoxyglucose positron emission tomography revealed no other malignancies except for the liver tumor. Because the lesion was suspected of being a primary malignant hepatic tumor, lateral segmentectomy was performed. The immunohistochemical analysis supported the diagnosis of gastrointestinal stromal tumors in the liver. The patient has had no evidence of recurrence during the 10-month follow-up period; imatinib chemotherapy was not administered. CONCLUSIONS: Primary hepatic gastrointestinal stromal tumors had no characteristics that distinguished them from ordinary tumors in imaging examinations. Primary gastrointestinal stromal tumors might have developed from interstitial Cajal-like cells.

Comparison between whole mount tissue preparations and virtual tissue microarray samples for measuring Ki-67 and apoptosis indices in human bladder cancer: A cross-sectional study.

Recent tissue microarray (TMA)-based studies have shown that cell proliferation- and apoptosis-related biomarkers are associated with clinical outcomes in patients with bladder urothelial carcinoma. However, little is known about the differences in these biomarker measurements between whole mount tissue preparations and TMAs. This study aimed to elucidate the discrepancy in the measurements of Ki-67 indices (KIs) and apoptosis indices (AIs) between whole mount tissue preparations and TMAs of bladder urothelial carcinoma samples.Whole mount tissue preparations for Ki-67 immunohistochemistry and terminal deoxynucleotidyl transferase dUTP nick end labeling were made from 30 patients who underwent transurethral resection of bladder urothelial carcinoma. Digital microscopy-assisted virtual TMAs, consisting of 3 small round areas (1 or 0.6 mm in diameter), were generated from the same whole mount tissue preparations. The measurement results in highly reactive areas of biomarkers were compared between the whole mount tissue preparation- and the TMA-based methods. Bland-Altman plot analysis, regression analysis, and Kendall τ were performed to investigate differences in the measurement results, systematic biases, and correlations between biomarkers.Although the Bland-Altman plot analysis demonstrated that almost all the plots were within the limits of agreement, fixed biases were detected in the 1- and 0.6-mm TMAs for the KI (0.181 and 0.222, respectively) and the AI (0.055 and 0.063, respectively). Proportional biases were also detected in the 1- and 0.6-mm TMAs for the AI (P < 0.001 and P < 0.001, respectively). Furthermore, positive correlations between KIs and AIs were observed in whole mount tissue preparations (r = 0.260, P = 0.044) and in the 1 mm TMAs (r = 0.375, P = 0.004); however, no such correlation was observed in the 0.6 mm TMAs.Our study suggests that the measurement results for certain biomarkers of bladder urothelial carcinoma obtained from TMA-based samples can be susceptible to systematic bias, and the lack of correlation between biomarkers cannot be avoided as it is in whole mount tissue preparations. Virtual TMAs can help identify systematic bias and establish a better sampling strategy prior to performing high-throughput TMAs for biomarker studies.

Hypoxia inducible factor-1 mediates upregulation of urokinase-type plasminogen activator receptor gene transcription during hypoxia in cervical cancer cells.

Hypoxia occurs during development of cervical cancer and is considered to correlate with its invasion. Hypoxia mediates tumor cells to have more invasive property in a variety of cancers. Urokinase plasminogen activator receptor (uPAR) which mediates invasion is considered to be induced by hypoxia. We sought to determine the regulators of uPAR expression during hypoxia in cervical cancer. We showed that cervical cancer cell lines, CaSki and CA, were more invasive under hypoxic condition (1% O2) than under normoxic condition (20% O2) by invasion assays. Using western blot analysis, hypoxia enhanced the endogenous hypoxia-inducible factor (HIF)-1α and uPAR protein expression. uPAR mRNA level was also upregulated by hypoxia using real-time RT-PCR. Overexpression of HIF-1α which is induced by hypoxia activated the transcriptional activity of the uPAR promoter by luciferase assays. HIF-1 protein bound the putative HIF-1 response element on the uPAR promoter using electrophoretic mobility shift analysis, and additional luciferase assays show that this is essential for uPAR transactivation by HIF-1. HIF-1 overexpression enhanced the endogenous uPAR expression and introduction of siRNA for HIF-1α diminishes uPAR expression during hypoxia. These results indicate the upregulation of uPAR by hypoxia in cervical cancer cells is mediated through HIF-1. In cervical cancer tissues, we also demonstrated that uPAR protein expression was detected in cervical cancer but not in normal cervix or cervical intraepithelial neoplasia (CIN) by immunohistopathological staining. Our results provide evidence that regulation of uPAR expression by HIF-1 represents a mechanism for cervical cancer invasion during hypoxia.

Pathological Characterization of Ovarian Cancer Patients Who Underwent Debulking Surgery in Combination With Diaphragmatic Surgery: A Cross-Sectional Study.

Despite exhaustive efforts to detect early-stage ovarian cancers, greater than two-thirds of patients are diagnosed at an advanced stage. Although diaphragmatic metastasis is not rare in advanced ovarian cancer patients and often precludes optimal cytoreductive surgery, little is known about the mechanisms and predictive factors of metastasis to the diaphragm. Thus, as an initial step toward investigating such factors, the present study was conducted to characterize the pathological status of ovarian cancer patients who underwent debulking surgery in combination with diaphragmatic surgery. This is a retrospective and cross-sectional study of patients who underwent debulking surgery in combination with diaphragmatic surgery at our institution between January 2005 and July 2015. Clinicopathological data were reviewed by board-certified gynecologists, pathologists, and cytopathologists. The rates of various pathological findings were investigated and compared by Fisher exact test between 2 groups: 1 group that was pathologically positive for diaphragmatic metastasis (group A) and another group that was pathologically negative for diaphragmatic metastasis (group B). Forty-six patients were included: 41 patients pathologically positive and 5 pathologically negative for diaphragmatic metastasis. The rates of metastasis to the lymph node (95.8% vs 20%, P = 0.001) and metastasis to the peritoneum except for the diaphragm (97.6% vs 60.0%, P = 0.028) were significantly increased in group A compared with group B. However, no significant differences between the 2 groups were found for rates of histological subtypes (high-grade serous or non-high-grade serous), the presence of ascites, the presence of malignant ascites, exposure of cancer cells on the ovarian surface, blood vascular invasion in the primary lesion, and lymphovascular invasion in the primary lesion. Our study demonstrated that metastasis to the lymph node and nondiaphragmatic metastasis to the peritoneum are significantly associated with metastasis to the diaphragmatic peritoneum, indicating that these factors may be pathological predictors of diaphragmatic metastasis in patients with ovarian cancer. However, as the data available are not sufficient to demonstrate the predictive power of these factors, a further comprehensive, large-scale study should be performed.

Establishment of successively transplantable rabbit VX2 cancer cells that express enhanced green fluorescent protein.

Morphological detection of cancer cells in the rabbit VX2 allograft transplantation model is often difficult in a certain region such as serosal cavity where reactive mesothelial cells mimic cancer cells and both cells share common markers such as cytokeratins. Therefore, tagging VX2 cells with a specific and sensitive marker that easily distinguishes them from other cells would be advantageous. Thus, we tried to establish a successively transplantable, enhanced green fluorescent protein (EGFP)-expressing VX2 model. Cancer cells obtained from a conventional VX2-bearing rabbit were cultured in vitro and transfected with an EGFP-encoding vector, and then successively transplanted in Healthy Japanese White rabbits (HJWRs) (n = 8). Besides, conventional VX2 cells were transplanted in other HJWRs (n = 8). Clinicopathological comparison analyses were performed between the two groups. The success rate of transplantation was 100% for both groups. The sensitivity and specificity of EGFP for immunohistochemical detection of VX2 cells were 84.3 and 100%, respectively. No significant differences in cancer cell morphology, tumor size (P = 0.742), Ki-67 labeling index (P = 0.878), or survival rate (P = 0.592) were observed between the two. VX2 cells can be genetically altered, visualized by EGFP, and successively transplanted without significant alteration of morphological and biological properties compared to those of the conventional model.

Cytological features of mammary analogue secretory carcinoma of salivary gland: fine-needle aspiration of seven cases.

Mammary analogue secretory carcinoma (MASC) is a recently described salivary gland neoplasm that is defined by ETV6-NTRK3 gene fusion. There have been few case reports on the cytopathologic features of MASC to date. We examined the clinicopathological and cytological features of seven cases of MASC defined by RT-PCR analysis of the ETV6-NTRK3 fusion gene. The cases occurred in three men and four women aged between 39 and 68 years, with a mean of 51.6 years. In five of these seven cases, the tumor involved the parotid gland. Histologically, all cases displayed predominantly microcystic patterns, often a mixture of follicular and papillary-cystic structures. All tumors were immunoreactive for mammaglobin, S-100 protein, and vimentin. Available fine-needle aspiration cytology smears were cellular and exhibited many loosely cohesive syncytial clusters or isolated cells. Many histiocytes, some of which contained hemosiderin pigments, and variously shaped mucinous material were evident in the background or within the epithelial clusters. The majority of cases showed small to medium-sized follicular structures with secreted materials. Papillary clusters were occasionally found. Tumor cells exhibited small to medium-sized round to oval nuclei, with a smooth contour and indistinct or small nucleoli, and vacuolated cytoplasm. No tumor cells had obvious intracytoplasmic zymogen granules. It appeared that clusters of small to medium-sized follicular and papillary configurations consisting of bland tumor cells with vacuolated cytoplasm, but lack of intracytoplasmic zymogen granules, in a mucinous or hemosiderin-laden histiocyte-rich background, were a characteristic cytological feature highly suggestive of MASC.

A retrospective study of urokinase-type plasminogen activator receptor (uPAR) as a prognostic factor in cancer of the uterine cervix.

BACKGROUND: Hypoxia occurs during the development of uterine cervical cancer and is considered to correlate with its invasion. Hypoxia promotes both the invasiveness and the metastasis of cancer cells through urokinase-type plasminogen activator receptor (uPAR) expression. The aim of this study was to evaluate the correlation between uPAR mRNA level and clinical prognostic factors of uterine cervical cancer. METHODS: We performed a retrospective review of 59 patients with cervical cancer and 9 subjects with normal cervical tissues. Total RNA was isolated from tissues of the uterine cervix surgically removed from patients. The mRNA of uPAR could be measured by real time PCR (RT-PCR). Histopathological factors such as histopathological type, cervical stromal, parametrial, lymphovascular, and uterine corpus invasions, metastasis to the pelvic lymph nodes, and pTNM stage were confirmed by two pathologists. The examined prognostic factors alongside the histopathological ones were FIGO clinical stage, hemoglobin level, serum level of SCC, and the effect on clinical outcomes. These factors were statistically evaluated by Fisher's exact test, log-rank test, and ROC analysis. Immunohistochemical staining with anti-uPAR monoclonal antibody was also performed. RESULTS: In uterine cervical cancer, overexpression of uPAR mRNA was significantly related to shorter disease-free survival (p = 0.0396). However, the other clinical prognostic and histopathological factors were not related to uPAR mRNA expression level. Immunohistochemical staining showed that positive staining for uPAR was histologically localized on the membrane of carcinoma cells. However, the staining was not very intense. CONCLUSIONS: Overexpression of uPAR mRNA may be a prognostic factor in cancer of the uterine cervix.

Relationship between the liver tissue shear modulus and histopathologic findings analyzed by intraoperative shear wave elastography and digital microscopically assisted morphometry in patients with hepatocellular carcinoma.

OBJECTIVES: Shear wave elastography is a novel noninvasive method for assessing liver fibrosis by measuring liver stiffness. This study was conducted to evaluate how pathologic changes could have an impact on measured elasticity values in both resected hepatocellular carcinomas and adjacent liver tissue. METHODS: Intraoperative shear wave elastography was performed in 7 patients who underwent liver resection at our institution; 7 hepatocellular carcinomas and adjacent liver tissue were subjected to elastographic measurements. A total of 48 circular regions of interest (ROIs; 3-8 mm in diameter) were located in the hepatocellular carcinomas (n = 37) and adjacent liver tissue (n = 11), and mean stiffness values were obtained from each ROI. All of the histologic images corresponding to the 48 ROIs after surgery were transformed into digital microscopic images by a scanning system, and histologic parameters, such as the proportions of nuclear areas, fatty areas, fibrous areas, and vessel areas, were quantitatively assessed. Relationships between the mean stiffness and the histologic parameters were investigated by the mixed effects model. RESULTS: By univariate analysis, the proportions of collagen fiber areas (P = .039), fibrous areas (P = .045), hepatocellular nuclear areas (P = .045), and nuclear areas other than hepatocellular and lymphoplasmacytic areas (P = .039) showed statistically positive associations with mean stiffness values. Multivariate analysis indicated that the proportion of collagen fiber areas was the strongest pathologic determinant of mean stiffness (P = .008), with hepatocellular nuclear areas also having a significant effect (P = .010). CONCLUSIONS: Fibrosis predictably affects elastographic estimation, but hepatocellular density (ie, hepatocellular nuclear areas) also alters elastographic assessment.

Angiolymphoid hyperplasia with eosinophilia occurring in bilateral eyelids.

BACKGROUND: Angiolymphoid hyperplasia with eosinophilia (ALHE) is an uncommon benign lesion, primarily occurring in the head and neck. ALHE arising from the ocular adnexa is rare, and the bilateral presentation is especially rare in the eyelids. CASE PRESENTATION: A 64-year-old Japanese man presented with tearing. Multiple nodules, approximately 5 mm in size, were observed in bilateral upper and lower eyelids. Surgical excisions of the both eyelids masses were performed. Histopathological examination of the excised masses demonstrated proliferated blood vessels lined by plump endothelial cells together with a lymphoid and eosinopilic infiltrate, compatible with a diagnosis of ALHE. Flow cytometry studies showed that the mass consisted of mostly CD3-positive cells. During two-year follow-up, no recurrence of the mass was observed and the patient had no subjective symptom of tearing CONCLUSION: ALHE may occur in the bilateral eyelids. The cause of ALHE remains uncertain, but our results of flow cytemetry suggest that T cells are related to the pathogenesis of this disease.

Primary large cell neuroendocrine carcinoma of the ureter.

Large cell neuroendocrine carcinoma (LCNEC) is the rarest type of urinary tract malignancy. Herein, we report a case of LCNEC that arose in the ureter of a 78-year-old Japanese man with a history of ascending colon cancer that had been excised by a right hemicolectomy. Left-sided hydronephrosis associated with the ureteral tumor was discovered during follow-up. A left nephroureterectomy combined with a partial resection of the urinary bladder was performed because atypical cells were detected using voided urine cytology. A histopathological examination revealed that the ureteral tumor contained large atypical epithelial cells of neuroendocrine morphology without a urothelial carcinomatous component. The neoplastic cells were immunohistochemically positive for synaptophysin, chromogranin A, CD56, and cytokeratins, but they were negative for uroplakin III and thyroid transcription factor-1. The Ki-67 labeling index of the neoplastic cells was 50%. Transmission electron microscopy demonstrated the presence of numerous dense granules in the cytoplasm of the neoplastic cells. The ureteral lesion was finally classified as stage III, pT3 cN0 cM0. The patient's postoperative course was uneventful without chemoradiotherapy, and LCNEC did not recur in the subsequent nine months. This case demonstrates that LCNEC can occur in the ureter, which normally does not contain neuroendocrine cells in the urothelium.