Histopathologic image-based deep learning classifier for predicting platinum-based treatment responses in high-grade serous ovarian cancer.

Platinum-based chemotherapy is the cornerstone treatment for female high-grade serous ovarian carcinoma (HGSOC), but choosing an appropriate treatment for patients hinges on their responsiveness to it. Currently, no available biomarkers can promptly predict responses to platinum-based treatment. Therefore, we developed the Pathologic Risk Classifier for HGSOC (PathoRiCH), a histopathologic image-based classifier. PathoRiCH was trained on an in-house cohort (n = 394) and validated on two independent external cohorts (n = 284 and n = 136). The PathoRiCH-predicted favorable and poor response groups show significantly different platinum-free intervals in all three cohorts. Combining PathoRiCH with molecular biomarkers provides an even more powerful tool for the risk stratification of patients. The decisions of PathoRiCH are explained through visualization and a transcriptomic analysis, which bolster the reliability of our model's decisions. PathoRiCH exhibits better predictive performance than current molecular biomarkers. PathoRiCH will provide a solid foundation for developing an innovative tool to transform the current diagnostic pipeline for HGSOC.

Prognostic Significance of ARID1A Expression Patterns Varies with Molecular Subtype in Advanced Gastric Cancer.

Background/Aims: AT-rich interactive domain 1A (ARID1A) is frequently mutated in gastric cancer (GC), especially Epstein-Barr virus (EBV)-associated and microsatellite instability high GC. The loss of ARID1A expression has been reported as a poor prognostic marker in GC. However, the relationships between ARID1A alteration and EBV-associated and microsatellite instability high GC, which are known to have a favorable prognosis, has hampered proper evaluation of the prognostic significance of ARID1A expression in GC. We aimed to analyze the true prognostic significance of ARID1A expression by correcting confounding variables. Methods: We evaluated the ARID1A expression in a large series (n=1,032) of advanced GC and analyzed the relationships between expression pattern and variable parameters, including clinicopathologic factors, key molecular features such as EBV-positivity, mismatch repair protein deficiency, and expression of p53 and several receptor tyrosine kinases including human epidermal growth factor receptor 2, epidermal growth factor receptor, and mesenchymal-epithelial transition factor. Survival analysis of the molecular subtypes was done according to the ARID1A expression patterns. Results: Loss of ARID1A expression was found in 52.5% (53/101) of mutL homolog 1 (MLH1)-deficient and 35.8% (24/67) of EBV-positive GCs, compared with only 9.6% (82/864) of the MLH1-proficient and EBV-negative group (p<0.001). The loss of ARID1A expression was associated only with MLH1 deficiency and EBV positivity. On survival analysis, the loss of ARID1A expression was associated with worse prognosis only in MLH1-proficient and EBV-negative GC. Multivariate analysis revealed that both loss of ARID1A and decreased ARID1A expression were independent worse prognostic factors in patients with advanced GC. Conclusions: Only in MLH1-proficient and EBV-negative GC, the loss of ARID1A expression is related to poorer prognosis.

Additional Excision Biopsy in Patients With Atypical Ductal Hyperplasia at Ultrasound-guided Vacuum-assisted Breast Biopsy.

BACKGROUND/AIM: We conducted this single-center, retrospective study to identify predictors of upgrading to malignancy and to discuss the necessity of additional excision biopsy in patients who were diagnosed with atypical ductal hyperplasia (ADH) at ultrasound (US)-guided vacuum-assisted breast biopsy (VABB) based on our 18-year, single-center experience. PATIENTS AND METHODS: The current study was conducted in a total of 12,160 patients who were evaluated at our medical institution during an 18-year period between January of 2003 and December of 2020. We included the patients who were diagnosed with ADH at US-guided VABB using the Mammotome® (Devicor Medical Products, Inc., Cincinnati, OH, USA). We therefore included a total of 114 patients (n=114) with ADH in the current study. RESULTS: Of 114 eligible patients, 36 underwent additional excision biopsy and the remaining 78 did not. Of these 36 patients, 15 were found to have an upgrading to malignancy at a rate of upgrading of 41.7%. These include 7 cases (46.6%) of low-grade ductal carcinoma in situ (DCIS), 3 cases (20.0%) of intermediate grade DCIS, 1 case (6.7%) of microinvasive DCIS, 3 cases (20.0%) of multifocal lobular carcinoma in situ, and 1 case (6.7%) of mucinous carcinoma. Finally, only suspicious microcalcification on mammography was a significant predictor of upgrading to malignancy (p=0.023). CONCLUSION: An additional excision biopsy is recommended to reduce the rate of upgrading to malignancy in patients who were diagnosed with ADH through a US-guided VABB.

CDX-1/CDX-2 Expression Is a Favorable Prognostic Factor in Epstein-Barr Virus-Negative, Mismatch Repair-Proficient Advanced Gastric Cancers.

Background/Aims: Caudal type homeobox (CDX)-1 and -2 are reportedly involved in the development and progression of gastric cancer (GC). Although there are several reports on the prognostic significance of CDX-2 expression in GC, it remains controversial. In this study, we sought to validate the prognostic value of CDX-1 and -2 expression according to the histologic and molecular subtypes of GC. Methods: In total, 1,158 cases of advanced GC were investigated using immunohistochemical staining and tissue microarrays for CDX-1 and -2 expression, and survival analysis was performed according to different histological and molecular subtypes. Results: Of the 915 GCs with CDX-1 expression, 163 (17.8%) were Epstein-Barr virus (EBV)-positive or mismatch repair deficient (MMR-d), and the remaining 752 (82.2%) were EBV-negative or MMR-proficient (MMR-p). Of the 1,008 GCs with CDX-2 expression, 177 (17.5%) were EBV-positive or MMR-d, and the remaining 831 (82.5%) were EBV-negative or MMR-p. In the EBV-positive and MMR-d groups, CDX expression had no relationship with patient outcomes. In the EBV-negative and MMR-p groups, 404 (53.7%) and 523 (62.9%) samples were positive for CDX-1 and CDX-2 expression, respectively. Survival analysis demonstrated that CDX-1 and CDX-2 expression in all patients was correlated with favorable outcomes in terms of overall survival (multivariate analysis; p=0.018 and p=0.028, respectively). In the subgroup analysis, CDX-1 expression and CDX-2 expression were associated with favorable outcomes in EBV-negative and MMR-p intestinal (p=0.015 and p=0.010), and mixed and diffuse-type (p=0.019 and p=0.042) GCs, respectively. Conclusions: The expression of CDX-1 and CDX-2 is a favorable prognostic factor in EBVnegative, MMR-p advanced GC.

Perivascular Stem Cell-Derived Cyclophilin A Improves Uterine Environment with Asherman's Syndrome via HIF1α-Dependent Angiogenesis.

Asherman's syndrome (AS) is characterized by intrauterine adhesions or fibrosis resulting from scarring inside the endometrium. AS is associated with infertility, recurrent miscarriage, and placental abnormalities. Although mesenchymal stem cells show therapeutic promise for the treatment of AS, the molecular mechanisms underlying its pathophysiology remain unclear. We ascertained that mice with AS, like human patients with AS, suffer from extensive fibrosis, oligo/amenorrhea, and infertility. Human perivascular stem cells (hPVSCs) from umbilical cords repaired uterine damage in mice with AS, regardless of their delivery routes. In mice with AS, embryo implantation is aberrantly deferred, which leads to intrauterine growth restriction followed by no delivery at term. hPVSC administration significantly improved implantation defects and subsequent poor pregnancy outcomes via hypoxia inducible factor 1α (HIF1α)-dependent angiogenesis in a dose-dependent manner. Pharmacologic inhibition of HIF1α activity hindered hPVSC actions on pregnancy outcomes, whereas stabilization of HIF1α activity facilitated such actions. Furthermore, therapeutic effects of hPVSCs were not observed in uterine-specific HIF1α-knockout mice with AS. Secretome analyses of hPVSCs identified cyclophilin-A as the major paracrine factor for hPVSC therapy via HIF1α-dependent angiogenesis. Collectively, we demonstrate that hPVSCs-derived cyclophilin-A facilitates HIF1α-dependent angiogenesis to ameliorate compromised uterine environments in mice with AS, representing the major pathophysiologic features of humans with AS.

Increased Expression of the Matrix-Modifying Enzyme Lysyl Oxidase-Like 2 in Aggressive Hepatocellular Carcinoma with Poor Prognosis.

Background/Aims: Lysyl oxidase-like 2 (LOXL2), a collagen-modifying enzyme, has been implicated in cancer invasiveness and metastasis. Methods: We evaluated the expression of LOXL2 protein, in addition to carbonic anhydrase IX (CAIX), keratin 19, epithelial cell adhesion molecule, and interleukin 6, in 105 resected hepatocellular carcinomas (HCCs) by immunohistochemistry. Results: LOXL2 positivity was found in 14.3% (15/105) of HCCs, and it was significantly associated with high serum α-fetoprotein levels, poor differentiation, fibrous stroma, portal vein invasion, and advanced TNM stage (p＜0.05 for all). Additionally, LOXL2 positivity was significantly associated with CAIX (p=0.005) and stromal interleukin 6 expression (p=0.001). Survival analysis of 99 HCC patients revealed LOXL2 positivity to be a poor prognostic factor; its prognostic impact appeared in progressed HCCs. Furthermore, LOXL2 positivity was shown to be an independent predictor of overall survival and disease-specific survival (p＜0.05 for all). Interestingly, co-expression of LOXL2 and CAIX was also an independent predictor for overall survival, disease-specific survival, disease-free survival, and extrahepatic recurrence-free survival (p＜0.05 for all). Conclusions: LOXL2 expression represents a subgroup of HCCs with more aggressive behavior and is suggested to be a poor prognostic marker in HCC patients.

Recurrence Rates and Characteristics of Phyllodes Tumors Diagnosed by Ultrasound-guided Vacuum-assisted Breast Biopsy (VABB).

BACKGROUND/AIM: Recently, the development of ultrasonography (US)-guided vacuum-assisted breast biopsy (VABB) has enabled the excision of benign breast tumors with normal surrounding breast tissues; thus, complete excision is possible without residual tumor tissue. We sought to identify the clinicopathological characteristics and recurrence rates of benign phyllodes tumors diagnosed by US-guided VABB. PATIENTS AND METHODS: Data from 11,221 US-guided VABBs performed at the Gangnam Cha Medical Center over 12 years were analyzed. Eighty-three lesions were diagnosed as benign phyllodes tumors; 67 with >24 months of follow-up data were investigated. All lesions were excised using an 8-gauge probe without residual tissue; patients underwent follow-up US every 3-6 months. RESULTS: Five patients (7.46%) experienced local recurrence during a mean follow-up period of 27.8 months; no distant metastases occurred. The mean tumor size was 3.0 cm in the recurrence group and 1.87 cm in the non-recurrence group (p=0.05). CONCLUSION: Benign phyllodes tumors excised and diagnosed using VABB showed a low recurrence rate during the follow-up period; thus, these tumors, particularly those <3 cm, can be safely monitored with ultrasonography instead of performing immediate re-excision.

Clinicopathological Analysis of Ultrasound-guided Vacuum-assisted Breast Biopsy for the Diagnosis and Treatment of Breast Disease.

BACKGROUND/AIM: To evaluate the usefulness and safety of vacuum-assisted breast biopsy (VABB) for breast lesion diagnosis and treatment. PATIENTS AND METHODS: Clinical and histopathological data of 8,748 patients, who underwent 11,221 VABB procedures were analyzed. RESULTS: Most patients (58.2%) were <40 years old. Most lesions (39.6%) were 0.6-1.0 cm in diameter while 3.2% were ≥3.0 cm; fibroadenomas were the most common (46.6%). Eight (14% of 57) cases of atypical ductal hyperplasia were underestimated. The positive predictive values (PPVs) of breast imaging reporting and data system (BI-RADS) ultrasound category were 0.6%, 3.4%, 34.8%, 66.2%, and 93.8% for category 3, 4a, 4b, 4c, and 5 lesions, respectively. The mean number of core specimens was 9.5±8.8; the mean procedure time was 3.4±2.7 min. No residual lesions were found in 94.4% of the 7,480 patients. CONCLUSION: VABB could replace ultrasound-guided core biopsy and surgical excisional biopsy for the diagnosis of breast disease and the treatment of benign breast lesions.

Additional Targeted Biopsy in Clinically Suspected Prostate Cancer: Prospective Randomized Comparison between Contrast-Enhanced Ultrasound and Sonoelastography Guidance.

Our aim was to improve the detection of prostate cancer by evaluating whether contrast-enhanced ultrasound (CEUS) or sonoelastography (SE) is more helpful in guiding targeted biopsy (TB) performed before systematic biopsy (SB). A total of 52 patients suspected of having prostate cancer were prospectively included and randomly assigned to either the CEUS or SE group. Different, independent radiologists performed TB and twelve-core SB. Within each group, cancer detection rates based on core number were compared between SB and TB. We evaluated the effect of TB on core-based cancer detection rates between the CEUS and SE groups. Cancer detection was higher in overall TB cores 16.4% (28/171) than SB cores 11.4% (71/624) in both groups. In the SE group, TB cores revealed higher cancer detection than did SB cores from 4.49% (14/312) to 12.86% (9/70) (p = 0.01). Compared with CEUS, SE may improve detection rates when considering additional TB guidance methods.

Repeat Targeted Prostate Biopsy under Guidance of Multiparametric MRI-Correlated Real-Time Contrast-Enhanced Ultrasound for Patients with Previous Negative Biopsy and Elevated Prostate-Specific Antigen: A Prospective Study.

OBJECTIVES: To prospectively determine whether multi-parametric MRI (mpMRI) - contrast-enhanced ultrasound (CEUS) correlated, imaging-guided target biopsy (TB) method could improve the detection of prostate cancer in re-biopsy setting of patients with prior negative biopsy. METHODS: From 2012 to 2014, a total of 42 Korean men with a negative result from previous systematic biopsy (SB) and elevated prostate-specific antigen underwent 3T mpMRI and real-time CEUS guided TB. Target lesions were determined by fusion of mpMRI and CEUS. Subsequently, 12-core SB was performed by a different radiologist. We compared core-based cancer detection rates (CaDR) using the generalized linear mixed model (GLIMMIX) for each biopsy method. RESULTS: Core-based CaDR was higher in TB (17.92%, 38 of 212 cores) than in SB (6.15%, 31 of 504 cores) (p < 0.0001; GLIMMIX). In the cancer-positive TB cores, CaDR with suspicious lesions by mpMRI was higher than that by CEUS (86.8% vs. 60.5%, p= 0.02; paired t-test) and concordant rate between mpMRI and CEUS was significantly different with discordant rate (48% vs. 52%, p=0.04; McNemar's test). CONCLUSION: The mpMRI-CEUS correlated TB technique for the repeat prostate biopsy of patients with prior negative biopsy can improve CaDR based on the number of cores taken.

Rapid Reticulin Fiber Staining Method is Helpful for the Diagnosis of Pituitary Adenoma in Frozen Section.

Approximately 90% of neoplasms found in the sellar region are adenoma of the pituitary gland. The use of frozen sections for the diagnosis of pituitary adenomas has an accuracy of 90% and is useful in evaluating complete tumor removal. However, it is sometimes difficult to diagnose pituitary adenomas using frozen sections because of the small sample size and marked artifact, and the contiguity of the pituitary adenoma with normal pituitary gland tissue. In this study, we evaluated the use of our modified reticulin stain to make correct decision in frozen section with reduced stain time and investigated the objective diagnostic criteria of pituitary adenoma with reticulin stain. We used Gomori's silver impregnation methods to stain reticulin fibers in frozen pituitary gland sections of 36 samples from 24 patients. We modified the conventional staining method by reducing the overall staining time. We diagnosed pituitary lesion according to our interpretation criteria and compared the results to those of the conventional method and findings of hematoxylin and eosin-stained slides. Reticulin fiber staining of normal adenohypophysis outlines the supporting stroma around the blood vessels and shows regular of the gland meshwork interconnecting the capillaries. In contrast, reticulin fiber staining of the adenomatous tissue shows loss of meshwork or frequent fragmentation. Our modified reticulin stain is more rapid than the established method and shows similar levels of accuracy. Independent evaluation by two pathologists showed discrepancies in diagnosis in four out of 36 cases with modified reticulin stain. Our rapid modified reticulin staining method for frozen sections may be useful as a diagnostic tool for pituitary adenomas and can complement routine hematoxylin and eosin staining.

Differences between the clinical and histopathological tumor stages in breast cancer diagnosed using vacuum-assisted breast biopsy.

The present study aimed to determine the difference between the clinical tumor stage (T stage) based on pre-operative ultrasound and the histopathological T stage subsequent to surgery in vacuum-assisted breast biopsy (VABB)-diagnosed breast cancer. Tumor sizes measured ultrasonography (USG) and histologically were retrospectively calculated and analyzed using paired t-tests in 209 patients diagnosed with breast cancer using VABB. The patients were classified into two groups, consisting of breast imaging reporting and data system (BI-RADS) category 4a or below, who underwent complete resection by VABB, and BI-RADS category 4b or above, who underwent incisional biopsy by VABB. The histopathological tumor size was found to be smaller compared with the USG-determined size in 92.3% of pT1a, 75.5% of pT1b, 44.2% of pT1c, 47.7% of pT2 and 0% of pT3 cases. Furthermore, the histopathological tumor size was smaller compared with the USG-determined size in 62.8% of cases classified as BI-RADS category 3-4a and in 53.7% of cases classified as BI-RADS category 4b-5. The smaller the primary tumor at the time of diagnosis by VABB, the higher the likelihood of pathological underestimation on post-operative histopathological assessment compared to pre-operative USG.

Metabolic differences in estrogen receptor-negative breast cancer based on androgen receptor status.

This study investigated the relationship between steroid hormone receptor signaling and cellular metabolism in tumorigenesis by examining the expression of metabolic proteins with respect to androgen receptor (AR) and human epidermal growth factor receptor-2 (HER-2) status in estrogen receptor-negative (ER-) breast cancer. ER- breast cancer cases (n = 334) were selected from a microarray analysis, including those that were AR+ and AR- (n = 127 and 207, respectively) and HER-2+ and HER-2- (n = 140 and 194, respectively). The expression of proteins involved in glycolysis, glutaminolysis, and mitochondrial and intermediary (i.e., serine/glycine) metabolism was determined by immunohistochemistry and correlated with AR and HER-2 status. The expression of several proteins involved in glycolysis, glutaminolysis, and serine/glycine metabolism was higher (p < 0.01) in the AR- than in the AR+ group. In the former, the expression of the glycolytic protein carbonic anhydrase (CA)IX was associated with a shorter disease-free survival period (p = 0.029) and overall survival rate (p = 0.001). In a multivariate Cox analysis, immunoreactivity for CAIX (hazard ratio 15.89, 95 % confidence interval (CI) 1.820-131.6; p = 0.010) was an independent factor in predicting the survival of the AR+ group. In conclusion, differential expression patterns of metabolism-related proteins were noted in ER- breast cancer according to AR status. These findings highlight the link between hormone receptor signaling and metabolic pathways whose dysregulation could underlie breast tumorigenesis.

Expression levels of serine/glycine metabolism-related proteins in triple negative breast cancer tissues.

To evaluate the expression levels of serine/glycine metabolism-related proteins (PHGDH, PSAT, PSPH, SHMT, and GLDC) in six different subtypes of triple negative breast cancer (TNBC) patients and gain insight into their implications. Formalin-fixed, paraffin-embedded tissues from 129 TNBC patients were assembled into tissue microarrays. Immunohistochemical staining was performed for serine/glycine metabolism-related proteins (PHGDH, PSAT, PSPH, SHMT, and GLDC) and surrogate immunohistochemical markers (CK5/6, EGFR, claudin 3, claudin 4, claudin 7, E-cadherin, STAT1, interleukin-8 [IL-8], AR, and GGT-1) for identifying the molecular subtype of TNBC. TNBC subtype classifications included the following: basal-like (CK5/6-positive and/or EGFR-positive), molecular apocrine (AR-positive and/or GGT-1-positive), claudin-low (claudin 3-, claudin 4-, claudin 7-negative and/or E-cadherin-negative), immune-related (IL-8-negative and stromal STAT1-positive), mixed (features from two or more of the four subtypes), and null (no features from any of the four subtypes). Tissues from basal marker-positive patients showed increased expression levels of tumoral PHGDH compared with those from basal marker-negative patients (p = 0.029); lack of stromal SHMT1 expression was significantly correlated with T stage (p = 0.016). Multivariate Cox analysis revealed that a lack of stromal SHMT1 expression was an independent prognostic factor for predicting a shorter disease-free survival period (hazard ratio 4.002, 95 % confidence interval [CI] 1.077-14.83, p = 0.038); furthermore, a lack of tumoral PHGDH expression was predictive of a shorter overall survival rate (hazard ratio 3.053, 95 % CI 1.002-9.305, p = 0.050). In conclusion, the most abundantly expressed serine/glycine metabolism-related protein in basal-like TNBC tissues was tumoral PHGDH, and expression levels of stromal SHMT1 and tumoral PHGDH were inversely correlated with clinical prognostic factors. Also, this study is the first to assess serine/glycine relationships at the protein level in regards to clinical outcomes.

A biphasic tumor consisting of pilocytic astrocytoma with an anaplastic solitary fibrous tumor component in the pineal region: a case report and literature review.

Here we report a case of a biphasic tumor consisting of pilocytic astrocytoma with anaplastic solitary fibrous tumor component in the pineal region. The majority of the tumor showed typical histologic features of pilocytic astrocytoma. A minor part of the tumor showed marked proliferation of short spindle cells around vessels. These spindle cells showed CD34 and CD99 immunoreactivity. From a review of the literature, we found that only one similar case has been reported. Contrary to the reported case, our case showed anaplastic features of solitary fibrous tumor histology.

Urinary decoy cell grading and its clinical implications.

BACKGROUND: Examination of urine for decoy cells (DCs) is a useful screening test for polyomavirus (PV) activation. We explored the significance of the amount of DCs in persistent shedding, PV nephropathy and acute rejection. METHODS: A case-controlled study was performed in 88 renal allograft patients who had DCs detected at least once in four or more urine samples. RESULTS: Fifty one patients were classified into the high-grade shedding group (HG) and 37 patients into the low-grade shedding group (LG) according to DC shedding (≥10 or <10 DCs/10 high power field [HPF]). DC shedding of more than three consecutive months was significantly more prevalent in the HG as compared with their LG counterparts (p<0.0001). Urinary DCs were present for more than one year in 29.4% of the HG and 8.1% of the LG. Real-time polymerase chain reaction for PV was higher in both urine (51.4% vs. 11.1%) and plasma (9.1% vs. 0%) of the HG than the LG. The prevalence of PV nephropathy was higher in the HG than the LG (p=0.019). However, there was no significant difference in the prevalence of acute rejection. CONCLUSIONS: Shedding of ≥10 DCs/10 HPF is associated with sustained shedding, polymerase chain reaction positivity and PV nephropathy, but not a predictor of acute rejection.

Optimal combination of immunohistochemical markers for subclassification of non-small cell lung carcinomas: A tissue microarray study of poorly differentiated areas.

BACKGROUND: Recently, studies have been reported on the optimal immunohistochemical markers for subclassification of non-small cell lung carcinoma (NSCLC). The main pitfall in subclassification of NSCLC is small specimen with poorly differentiated area. In this study, we added newly proposed markers (e.g., napsin A, SOX2) to conventional markers (p63, TTF-1, CK5/6, and CK7) and evaluated optimal combination for subtyping of NSCLC, primarily focusing on the poorly differentiated area. METHODS: Eighty two resected NSCLCs with poorly differentiated areas were classified based on histologic findings. After histologic review, only poorly differentiated areas were selected and tissue microarrays were constructed to simulate small biopsy conditions. A total of 36 adenocarcinomas (ADCs), 38 squamous cell carcinomas (SQCCs), and 8 large cell carcinomas were included. All specimens were stained with TTF-1, napsin A, CK7, p63, CK5/6, and SOX2. RESULTS: With respect to ADC, TTF-1 was positive in 19 of 36 cases (53%) and napsin A was in 25 of 36 (69%). Both markers were specific for ADC (100% and 98%, respectively). With TTF-1 and napsin A in combination, sensitivity increased to 75%. CK7 was sensitive (92%) but not specific marker (76%) for ADC. With respect to SQCC, p63 was positive in 35 of 38 cases (92%) and CK5/6 was in 23 (61%). Both markers were specific for SQCC (both 93%). With p63 and CK5/6 in combination, sensitivity increased slightly to 95%, but specificity was lower at 91%. SOX2 was specific (100%) but not sensitive marker (53%) for SQCC. Combinations did not substantially increase the diagnostic performance. CONCLUSION: A simple panel of napsin A, TTF-1, and p63 can be sufficient to reliably subclassify poorly differentiated areas of NSCLC.

Langerhans cell histiocytosis in endoscopic biopsy: marked pinching artifacts by endoscopy.

Various diseases should be considered when evaluating a suprasellar mass. Diabetes insipidus has been reported as the primary manifestation in a patient with Langerhans cell histiocytosis involving the hypothalamopituitary axis (HPA) and can be helpful for the diagnosis. The use of endoscopic biopsy for suprasellar masses has increased. However, as it is difficult to make a diagnosis with endoscopic biopsy because of the many artifacts, pathologists must be careful. Langerhans cell histiocytosis involving the HPA as solitary lesions is rare. We report the eighth case that provides neurologists, radiologists, and pathologists with various implications.

Detection of sexually transmitted infection and human papillomavirus in negative cytology by multiplex-PCR.

BACKGROUND: The aim of this study was to determine the prevalence of human papillomavirus (HPV) and 15 species that cause sexually transmitted infections (STIs) in negative cytology. In addition, we compared the diagnostic performance of multiplex polymerase chain reaction (PCR) with widely available techniques used to detect HPV. METHODS: We recruited 235 women of reproductive age who had negative cytology findings in a liquid-based cervical smear. STIs were identified by multiplex PCR, and HPV genotypes by multiplex PCR, hybrid capture 2, and DNA microaray; discordant results were analyzed by direct sequencing. RESULTS: Approximately 96.6% of patients with negative cytology results were positive for pathogens that cause STIs. The pathogens most frequently detected were Gardnerella vaginalis, Ureaplasma urealyticum. The incidence of HPV in negative cytology was 23.3%. Low-risk HPV infection was significantly correlated with Chalmaydia trachomatis, and high-risk HPV infection was significantly correlated with Group ß streptococcus. The analytical sensitivities of the multiplex PCR and DNA microarray were higher than 80%, and the analytical specificity was nearly 100% for all tests. CONCLUSIONS: Multiplex PCR yielded results that most of patients with negative cytology were positive for pathogens that cause STIs, and were more similar to that of DNA microarray, than that of hybrid capture 2 in terms of analytical sensitivity and prediction value of HPV infection.