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.

Does Bladder Cancer Subtype Influence Pathologic Complete Response (pCR) and Pelvic Diffusion-Weighted Magnetic Resonance Imaging (DW-MRI) Response Evaluation After Neoadjuvant Chemotherapy? Pathological Perspective.

INTRODUCTION: We aimed to provide a pathological perspective on the management of muscle-invasive bladder cancer (MIBC) by correlating the prechemotherapy transurethral resection of bladder tumor findings and postchemotherapy radiologic evaluation with final radical cystectomy (RC) findings. MATERIALS AND METHODS: This retrospective study included 79 MIBC patients treated with neoadjuvant chemotherapy (NAC) and RC. Pelvic diffusion-weighted magnetic resonance imaging (DW-MRI) and pathologic reports were retrieved from our institutional database. All pathology slides were reviewed based on diagnostic criteria with high interobserver reproducibility. RESULTS: Pathologic complete response (pCR) was confirmed in 32 patients (40.5%). The concordance and discordance between MRI and RC findings occurred in 68.3% and 31.7% of cases, respectively. The 21.5% of cases that were clinical CR (cCR) on MRI actually achieved pCR on RC specimens and 46.8% of cases that were non-cCR on MRI were actually non-pCR on RC specimens. In 19.0% of cases, RC findings were pCR, but MRI demonstrated residual tumor and the opposite was 12.7%. The greatest discrepancy between the 2 methods (75%, 3/4) was for the plasmacytoid subtype. Plasmacytoid histology was the most common histological subtype identified in RC specimens after NAC, followed by micropapillary and squamous histologies. CONCLUSIONS: We found that all cases with plasmacytoid and micropapillary subtypes, and squamous differentiation did not show pCR. In particular, the largest discrepancy between MRI findings and RC pathology after NAC was seen in the plasmacytoid subtype. An accurate pathologic diagnosis based on strict criteria to identify histological subtypes of MIBC is necessary for proper treatment.

Invasive urothelial carcinoma with chordoid features or abundant myxoid stroma: A reappraisal of morphologic spectrum and risk stratification based on molecular classification.

Urothelial carcinoma (UC) with myxoid stroma or chordoid features is a rare diagnosis. We retrospectively collected data from 17 cases of diagnosed UC with myxoid stroma, mucin production, or chordoid features. We aimed to investigate the molecular subtypes of this neoplasm and to assess subtype correlations with clinical outcomes. Immunohistochemical (IHC) staining with a panel composed of markers for basal subtypes (CK5/6, CK14, and CD44) and luminal subtypes (GATA3, FOXA1, and CK20) was performed. Morphologically, all cases included an at least partial conventional UC component, with the first histologic pattern, named as "typical", characterized by a small- or medium-sized tumor cell nest. The second histologic pattern, named as "chordoid", was characterized by tumor cells with cording that mimic extra-skeletal myxoid chondrosarcoma or chordoma, and the third histologic pattern, named as "sarcomatoid", was characterized by non-cohesive spindle tumor cells with a mucin-producing or myxoid stroma background. The "typical" cases showed [CK5/6- CK14- CD44-] [GATA3 + FOXA1 + CK20-] IHC results and was classified as lumina subtype. The "chordoid" cases showed [CK5/6 + CK14 + CD44-] [GATA3- FOXA1- CK20-] IHC results and was classified as basal subtype, and the "sarcomatoid" cases showed [CK5/6- CK14- CD44+] [GATA3- FOXA1- CK20-] IHC results and was "not classified". All pT3 cases and all cases with lymph node (LN) metastasis belonged to the "sarcomatoid" pattern. All patients who had metastasis or died showed the "chordoid" or "sarcomatoid" morphology. Our findings suggest that UC with myxoid stroma/chordoid features shows characteristic expression of luminal and basal markers and different prognosis according to the morphologic pattern spectrum.

Application of The Paris System in neobladder washing cytology: Comparison between the original diagnosis and correlation with histopathology.

BACKGROUND: In urinary diversion after radical cystectomy, the incidence of recurrent urothelial carcinoma (UC) in upper urinary tract or urethra are reported in 2%-17% of the patients. Urine cytology plays a pivotal role in detecting the recurrence of UC. However, cytologic diagnosis in urinary diversion including neobladder is often challenging due to significant degenerative changes and necro-inflammatory background. Since the proposal of The Paris System (TPS) for reporting cytology, the utility of TPS in urinary diversion specimen has not been studied yet. The objective of this study is to evaluate the diagnostic usefulness of TPS compared with the original diagnosis and correlate with the matched histopathological results. METHODS: Urinary diversion cytology specimens with concurrent or subsequent biopsy or resection at EUMC in recent 16 years (from January 2002 to December 2018) are retrospectively reviewed and reclassified according to TPS criteria. The TPS categories and the original diagnoses were compared and correlated with follow-up histology. RESULTS: Concurrent or subsequent biopsy or resection within a 6-month period was available in 45 cases from 28 patients. When applying TPS, the rate of atypical and suspicious categories decreased by 13.4% and 11.1%. Using TPS increased the value of sensitivity, NPV, and accuracy to 93.75%, 93.75%, and 90.91%, respectively. CONCLUSION: Application of TPS reduced the rate of indeterminate diagnoses and moreover, improved the sensitivity and accuracy of urinary diversion cytology. Therefore, we believe that diversion urine cytology diagnosis according to TPS is useful to screen patients for detection of recurrence in routine clinical practice.

The Effect of Complete Prostate Examination of Radical Cystoprostatectomy Specimen on the Final Stage of Urothelial Carcinoma of the Urinary Bladder and the Detection of Prostate Cancer.

CONTEXT.­: The prostate sampling methods for radical cystoprostatectomy (RCP) specimens may affect pathologic results. OBJECTIVE.­: To investigate the impact on the tumor stage and clinicopathologic features according to the prostate sampling method for RCP specimens. DESIGN.­: From 2016 to 2017, the prostate in RCP was minimally and conventionally embedded (group 1, n = 98). From 2017 to 2018, it was completely embedded (group 2, n = 102). RESULTS.­: Group 2 was more likely to have prostatic ducts or acini involvement by urothelial carcinoma in situ component (27% versus 10%, P = .002) and prostate involvement (30% versus 13%, P = .003) than group 1. Although there were cases with prostatic stromal invasion in group 2 (14% versus 7%, P = .13), this was not statistically significant. In all, 6 cases were upstaged by subepithelial prostatic stromal invasion through intraurethral extension according to the 8th edition of the American Joint Committee on Cancer (AJCC) staging system. Tumor location and the presence of concurrent carcinoma in situ were strongly associated with prostate involvement of urothelial carcinoma. Prostatic adenocarcinoma (PA) was incidentally identified in 47 cases (23.5%). Incidental PA and clinically significant PA were more often identified in group 2 than group 1 (38% versus 8%, P < .01 and 15% versus 6%, P = .048, respectively). CONCLUSIONS.­: A complete prostate examination in RCP specimens can be suggested, since the final pathologic stage can be changed through a thorough prostate examination especially in accord with the AJCC staging manual 8th edition. In addition, the complete prostate analysis could detect more incidental and clinically significant PA.

A multicenter study of interobserver variability in pathologic diagnosis of papillary breast lesions on core needle biopsy with WHO classification.

BACKGROUND: Papillary breast lesions (PBLs) comprise diverse entities from benign and atypical lesions to malignant tumors. Although PBLs are characterized by a papillary growth pattern, it is challenging to achieve high diagnostic accuracy and reproducibility. Thus, we investigated the diagnostic reproducibility of PBLs in core needle biopsy (CNB) specimens with World Health Organization (WHO) classification. METHODS: Diagnostic reproducibility was assessed using interobserver variability (kappa value, κ) and agreement rate in the pathologic diagnosis of 60 PBL cases on CNB among 20 breast pathologists affiliated with 20 medical institutions in Korea. This analysis was performed using hematoxylin and eosin (H&E) staining and immunohistochemical (IHC) staining for cytokeratin 5 (CK5) and p63. The pathologic diagnosis of PBLs was based on WHO classification, which was used to establish simple classifications (4-tier, 3-tier, and 2-tier). RESULTS: On WHO classification, H&E staining exhibited 'fair agreement' (κ = 0.21) with a 47.0% agreement rate. Simple classifications presented improvement in interobserver variability and agreement rate. IHC staining increased the kappa value and agreement rate in all the classifications. Despite IHC staining, the encapsulated/solid papillary carcinoma (EPC/SPC) subgroup (κ = 0.16) exhibited lower agreement compared to the non-EPC/SPC subgroup (κ = 0.35) with WHO classification, which was similar to the results of any other classification systems. CONCLUSIONS: Although the use of IHC staining for CK5 and p63 increased the diagnostic agreement of PBLs in CNB specimens, WHO classification exhibited a higher discordance rate compared to any other classifications. Therefore, this result warrants further intensive consensus studies to improve the diagnostic reproducibility of PBLs with WHO classification.

Clinical Significance of Variable Histomorphologic Findings Related to Mucosal Inflammation in Negative Appendectomy.

The aim of the study was to investigate the clinical significance of various histomorphologic findings related to mucosal inflammation in negative appendectomy. We reviewed histopathologic findings of 118 negative appendectomies and correlated them with the appendicitis inflammatory response (AIR) score and appendiceal diameter. Among 118 patients with negative appendectomy, 94 (80%), 73 (78%) and 89 (75%) patients displayed mucosal inflammation, high neutrophil score (neutrophil count ≥10/5 high power field and surface epithelial flattening, respectively. Out of 118 patients with negative appendectomy, mucosal inflammation, high neutrophil score and surface epithelial flattening were associated with higher risk group according to the appendicitis inflammatory response (AIR) score (p < 0.05, respectively). In addition, mucosal inflammation, high neutrophil score and surface epithelial flattening were frequently detected in 118 negative appendectomies, compared with 24 incidental appendectomies (p < 0.05, respectively). In an analysis of 77 negative appendectomy patients with appendiceal diameter data available, increased appendiceal diameter was positively correlated with luminal inflammation, high neutrophil score and surface epithelial flattening (p < 0.05, respectively). In conclusion, mucosal inflammation, high neutrophil score and surface epithelial flattening in negative appendectomy may be relevant to patients' signs and symptoms, especially in cases with no other cause of the abdominal pain.

Diagnostic value of urine cytology in detecting histologic variants of urothelial carcinomas in the urinary bladder: Cytopathologic correlation of 72 cases.

BACKGROUND: Precise identification of histologic variants in urothelial carcinoma (UC) is important because some histologic types have a poor prognosis and clinical management varies. Urine cytology is used for bladder cancer screening, but the cytomorphologic features of histologic variants have not been well described. In the current study, we evaluate the effectiveness of urine cytology in detecting histologic variants of UC in the urinary bladder. METHODS: Seventy-two urine cytology specimens from patients diagnosed with high-grade UCs by radical cystectomy were retrospectively reviewed and correlated with histopathologic findings of subsequent radical cystectomy specimens. RESULTS: Of 72 total cases, 24 (33%) cases showed six histologic variants in corresponding surgical specimens, including squamous differentiation (13 cases), plasmacytoid variant (3 cases), micropapillary variant (3 cases), sarcomatoid variant (3 cases), giant cell variant (1 case), and glandular differentiation (1 case). Histopathology and cytomorphology were well correlated in 13 cases (54%), with squamous differentiation in 11 of 13 cases (85%), micropapillary features in 1 out of 3 cases (33%), and spindle cell/sarcomatoid features in 1 of 3 cases (33%). Furthermore, mucosal involvement by histologic variants, not amount of histologic variant, was related to high concordance rates between cytology and histology diagnosis. CONCLUSIONS: The morphologic features of some histologic variants of high-grade UCs, such as squamous differentiation, micropapillary variant, and sarcomatoid variant, are partially reflected on urine cytology. In addition, mucosal involvement by histologic variants was associated with a higher detection rate of histologic variants in urine cytology.

Histologically confirmed distant metastatic urothelial carcinoma from the urinary bladder: a retrospective review of one institution's 20-year experience.

BACKGROUND: Urothelial carcinoma (UC) accounts for roughly 90% of bladder cancer, and has a high propensity for diverse differentiation. Recently, certain histologic variants of UC have been recognized to be associated with unfavorable clinical outcomes. Several UC studies have also suggested that tumor budding is a poor prognostic marker. Distant metastasis of UC after radical cystectomy is not uncommon. However, these metastatic lesions are not routinely confirmed with histology. METHODS: We investigated the histopathologic features of 13 cases of UC with biopsy-proven distant metastases, with a special emphasis on histologic variants and tumor budding. RESULTS: Lymph nodes (6/13, 46%) were the most common metastatic sites, followed by the lung (4/13, 31%), liver (4/13, 31%), and the adrenal gland (2/13, 15%). The histologic variants including squamous (n=1), micropapillary (n=4), and plasmacytoid (n=1) variants in five cases of UC. Most histologic variants (4/5, 80%) of primary UCs appeared in the metastatic lesions. In contrast, high-grade tumor budding was detected in six cases (46%), including one case of non-muscle invasive UC. Our study demonstrates that histologic variants are not uncommonly detected in distant metastatic UCs. Most histologic variants seen in primary UCs persist in the distant metastatic lesions. In addition, high-grade tumor budding, which occurs frequently in primary tumors, may contribute to the development of distant metastasis. CONCLUSIONS: Therefore, assessing the presence or absence of histologic variants and tumor budding in UCs of the urinary bladder, even in non-muscle invasive UCs, may be useful to predict distant metastasis.

Double cocktail immunostains with high molecular weight cytokeratin and GATA-3: useful stain to discriminate in situ involvement of prostatic ducts or acini from stromal invasion by urothelial carcinoma in the prostate.

BACKGROUND: Distinguishing prostatic stromal invasion (PSI) by urothelial carcinoma (UC) from in situ UC involving prostatic ducts or acini with no stromal invasion (in situ involvement) may be challenging on hematoxylin and eosin stained sections. However, the distinction between them is important because cases with PSI show worse prognosis. This study was performed to assess the utility of double cocktail immunostains with high molecular weight cytokeratin (HMWCK) and GATA-3 to discriminate PSI by UC from in situ UC involvement of prostatic ducts or acini in the prostate. METHODS: Among 117 radical cystoprostatectomy specimens for bladder UCs, 25 cases showed secondary involvement of bladder UC in prostatic ducts/acini only or associated stromal invasion and of these 25 cases, seven cases revealed equivocal PSI. In these seven cases with equivocal PSI, HMWCK, and GATA-3 double immunohistochemical stains were performed to identify whether this cocktail stain is useful to identify the stromal invasion. RESULTS: In all cases, basal cells of prostate glands showed strong cytoplasmic staining for HMWCK and UC cells showed strong nuclear staining for GATA-3. In cases with stromal invasion of UC, GATA-3-positive tumor cells in the prostatic stroma without surrounding HMWCK-positive basal cells were highlighted and easily recognized. Among seven equivocal cases, two cases showed PSI and five in situ UC in the prostate. In two cases, the original diagnoses were revised. CONCLUSIONS: Our study suggested that HMWCK and GATA-3 double stains could be utilized as an adjunct method in the distinction between PSI by UC from in situ UC involving prostatic ducts or acini.

Clinicopathologic study of 60 cases of urothelial neoplasms with inverted growth patterns: Reclassification by international consultation on urologic disease (ICUD) recommendations.

BACKGROUND: Most urothelial neoplasms of the bladder show an exophytic papillary pattern, but some show an inverted growth pattern. In 2004, the World Health Organization (WHO) released a detailed histologic classification system for papillary urothelial neoplasms, but not for inverted forms. The International Consultation on Urologic Disease (ICUD) recommendations of 2012 are applicable to inverted/endophytic papillary lesions as follows: 1) inverted papilloma (IP), 2) inverted papillary urothelial neoplasm of low malignant potential (IPUNLMP), 3) inverted papillary urothelial carcinoma, low grade, non-invasive (IPUCLG-NI), 4) inverted papillary urothelial carcinoma, high grade, non-invasive (IPUCHG-NI), 5) inverted papillary urothelial carcinoma, high grade, invasive (IPUCHG-I). However, only atypical cellular morphology was considered for classification in the 2012 ICUD recommendations, and data to support to validate this new grading system are lacking. METHODS: Sixty cases of inverted urothelial papillary tumors were classified into 5 categories according to 2012 ICUD and 2016 WHO/ISUP recommendations to evaluate their clinical, pathological, and immunohistochemical characteristics. Two subgroups were defined as subgroup 1, IP and IPUNLMP, and subgroup 2, IPUCLG-NI, IPUCHG-NI, and IPUCHG-I. Clinical features (age, sex, history of urothelial carcinoma, smoking history, size, and multifocality) and histologic features (nuclear pleomorphism, mitotic count, mitosis level, apoptosis, luminal necrosis, trabecular thickening, anastomosing trabeculae, hypercellularity, loss of polarity, peripheral palisading, palisading with central streaming, and discohesiveness) were evaluated. Immunohistochemical stains for CK20, CD44, P53, p16, Ki-67, cyclin D1 and c-erbB2 were performed. RESULTS: A total of 60 cases were classified as 10 cases of IP, 29 cases of IPUNLMPs, 15 cases of IPUCLG-NI, 4 cases of IPUCHG-NI, and 2 cases of IPUCHG-I. Compared to subgroup 1, subgroup 2 showed larger tumor size, more nuclear irregularity, higher mitotic count (hot spot and per 10 high power fields), more upper level mitosis (>1/2), and more frequent apoptosis, luminal necrosis, surface papillary component, trabecular thickening, anastomosing irregular trabeculae, hypercellularity, loss of polarity, peripheral palisading with central streaming, and discohesiveness, and absence of umbrella cells and urothelial eddies. CK20, Ki67, and c-erbB2 were the only markers that were differently expressed in the two subgroups, with more expression in subgroup 2. CONCLUSIONS: The 2012 ICUD recommendations are valid to classify inverted papillary urothelial tumors. However, other histologic features besides atypical cellular morphology should also be considered to distinguish subgroup 1 and subgroup 2 inverted papillary urothelial tumors.

Human Epidermal Growth Factor Receptor 2-Subtype Invasive Ductal Carcinoma Recurring as Basal-Human Epidermal Growth Factor Receptor 2-Subtype Squamous Cell Carcinoma.

Squamous cell carcinoma of the breast and its subtype, basal-human epidermal growth factor receptor 2 (HER2) phenotype, are very rare. Herein, we report a patient who developed recurrence of squamous cell carcinoma of the breast with basal-HER2 subtype 6 years after the initial diagnosis of invasive ductal carcinoma of the HER2 subtype. To the best of our knowledge, recurrence of invasive ductal carcinoma in the form of metaplastic squamous cell carcinoma of basal-HER2 subtype has not been reported previously. We present a pathological perspective of our experience.

Feasibility of Classification of Triple Negative Breast Cancer by Immunohistochemical Surrogate Markers.

INTRODUCTION: Recently, Burstein et al identified 4 stable molecular subtypes of triple negative breast cancer (TNBC) by mRNA profiling: luminal androgen receptor (LAR), mesenchymal (MES), basal-like immune-activated (BLIA), and basal-like immune-suppressive (BLIS) types. The purpose of this study was to assess the feasibility of immunohistochemistry (IHC) surrogate panel in classifying the TNBC molecular subtypes using a large cohort of TNBC retrieved from a single institution. MATERIALS AND METHODS: IHC for androgen receptor [AR], claudin-3, E-cadherin, cytokeratin 5/6 [CK5/6], epidermal growth factor receptor [EGFR], indoleamine 2,3-dioxygenase 1 [IDO1], and Forkhead box C1 [FOXC1] were performed using the tissue microarray constructed from 200 TNBC samples. RESULTS: The 200 TNBCs were classified as LAR (AR+, n = 22; 11.0%), MES (claudin 3- and/or E-cadherin-, n = 23; 11.5%), basal-like (CK5/6+ and/or EGFR+, n = 85; 42.5%), mixed (n = 60; 30%), and unclassifiable type (n = 10; 5%). LAR type was associated with older patient age, apocrine histologic features, low density of stromal tumor-infiltrating lymphocytes (TIL), and low Ki-67 labeling index. MES type was associated with tumor cell discohesiveness and metaplastic features. Basal-like type was associated with younger patient age, high histologic grade, high stromal TIL density, and high Ki-67 labeling index. Basal-like TNBCs were further classified as BLIA (IDO1+ and FOXC1-, n = 27) or BLIS type (IDO1- and FOXC1+, n = 11). BLIS type was associated with large tumor size and low stromal TIL density, which had the worst prognostic outcome among 4 subtypes. CONCLUSION: The IHC surrogate panel may define TNBC subtypes with distinct clinicopathologic characteristics and prognostic significance.

Gastric Metastasis as the First Presentation One Year Before Diagnosis of Primary Breast Cancer.

BACKGROUND Metastasis to the stomach can be found as the first presentation of breast cancer, although it is very rare. The authors report an unusual case of metastasis to the stomach as the first presentation of breast cancer, which had a good prognosis. CASE REPORT A 51-year-old female underwent radical subtotal gastrectomy and chemotherapy because of gastric cancer with distant metastasis. At the time of diagnosis of gastric cancer, she had a negative result from routine mammography. One year later, a newly detected lesion on routine mammography was confirmed as breast cancer. Initial diagnosis of gastric cancer was changed to metastatic carcinoma from breast cancer through immunohistochemistry after bilateral mastectomy. After the completion of chemotherapy, she is currently receiving treatment with letrozole, without recurrence for 66 months. CONCLUSIONS Considering metastasis from breast cancer might be needed when unusual presentation of gastric cancer is observed even though gastric cancer is still one of the most common malignancies in Korea. Immunohistochemical analysis is helpful for diagnosis. Surgery for metastatic carcinoma of the stomach could be another option for treatment.

14-3-3ζ Overexpression is Associated with Poor Prognosis in Ovarian Cancer.

PURPOSE: 14-3-3ζregulates cell signaling, cell cycle progression, and apoptosis, and its overexpression is associated with disease recurrence and poor clinical outcomes in some solid tumors. However, its clinicopathological role in ovarian cancer is unknown. Our goal was to investigate whether 14-3-3ζis associated with ovarian cancer prognosis. MATERIALS AND METHODS: We examined 14-3-3ζexpression by immunohistochemistry in ovarian cancer tissues obtained from 88 ovarian cancer patients. The examined tissues were of various histologies and stages. 14-3-3ζexpression was also analyzed by western blot in seven ovarian cancer cell lines and a primary ovary epithelial cell line. Cell viability was measured using an MTS-based assay following cisplatin treatment. RESULTS: Among the ovarian cancer samples, 53.4% (47/88) showed high 14-3-3ζexpression, and 14-3-3ζoverexpression was positively correlated with more advanced pathologic stages and grades. 14-3-3ζoverexpression was also significantly associated with poor disease-free survival (DFS) and overall survival (OS) of ovarian cancer patients. Median DFS and OS were 1088 and 3905 days, respectively, in the high 14-3-3ζexpression group, but not reached in the low 14-3-3ζexpression group (p=0.004 and p=0.033, log-rank test, respectively). Downregulating 14-3-3ζby RNA interference in ovarian cancer cells led to enhanced sensitivity to cisplatin-induced cell death. CONCLUSION: 14-3-3ζoverexpression might be a potential prognostic biomarker for ovarian cancer, and the inhibition of 14-3-3ζcould be a therapeutic option that enhances the antitumor activity of cisplatin.

Pitfalls of Frozen Section Diagnosis for Paraganglioma: A Clinicopathologic Analysis and Review of the Literature.

Few paraganglioma (PG) cases include frozen section diagnoses, and therefore, the accuracy of frozen section diagnosis for PG remains unknown. To better understand the histologic characteristics and pitfalls of frozen section findings for PG, 15 PG cases with frozen section diagnoses were selected from 12 articles through PubMed (1984-2015). In addition, we included 3 cases of PG for which intraoperative consultations were requested during a 5-year period (2012-2016) in 2 hospitals. Seven PGs were from the thyroid; 2 from the pancreas; 4 from the mediastinum, retroperitoneum, or mesentery; 1 from the middle ear; and 4 from the urinary bladder (UB). Out of 18 PGs, correct diagnoses were rendered in only 2 cases, and no thyroid or UB PGs were correctly diagnosed on intraoperative consultation. Thyroid PGs were frequently misdiagnosed as medullary thyroid carcinomas (4/7, 57%) and UB PGs were frequently misdiagnosed as malignancies.

Evaluation of Ki-67 Index in Core Needle Biopsies and Matched Breast Cancer Surgical Specimens.

CONTEXT: - The Ki-67 index is strongly prognostic and is used as a surrogate marker to distinguish luminal A from luminal B breast cancer types. OBJECTIVE: - To investigate differences in Ki-67 index between core needle biopsy samples and matched surgical samples in breast cancer. DESIGN: - We included patients with invasive breast cancer who did not receive neoadjuvant therapy. A total of 89 pairs of core needle biopsies and surgical specimens were collected, and the Ki-67 index was assessed in hot spot areas using an image analyzer. We applied a 14% Ki-67 index to define low versus high groups. RESULTS: - The Ki-67 index was significantly higher in core needle biopsies than in surgical specimens ( P < .001), with a median absolute difference of 3.5%. When we applied 14% as a cutoff, 16 of 89 cases (18%) showed discrepancy. Thirteen cases showed a high Ki-67 index in core needle biopsies but a low Ki-67 index in surgical samples. There were 10 cases (11.2%) that showed discordant luminal A/B types between core needle biopsy and the matched surgical specimen. The reasons for the discordance were poor staining of MIB1 accompanied by fixation issues and intratumoral heterogeneity of the Ki-67 index. CONCLUSIONS: - A significant difference in the Ki-67 index between core biopsy and surgical specimens was observed. Our findings indicate that it may be better to perform the Ki-67 assay on the core needle biopsy and the surgical specimen than on only one sample.

Lymphedema Associated With Primary Amyloidosis: A Case Study.

We reported on a 60-year-old man presenting lymphedema of both lower extremities and scrotum for 3 years with unknown cause. We took a computed tomography scan of the lower extremities as a follow-up. There were diffuse subcutaneous edema in both lower extremities and multiple enlarged lymph nodes along the para-aortic and bilateral inguinal areas. For further evaluation, biopsy of an enlarged inguinal lymph node was taken, yielding a diagnosis of primary amyloidosis. A treatment of chemotherapy for amyloidosis was recommended for him. To our knowledge, this is the first report of lymphedema presenting with primary amyloidosis in Asia. This case suggests that primary amyloidosis could be one of the differential diagnoses in patients with lymphedema in the lower extremities.

Value of imaging study in predicting pelvic lymph node metastases of uterine cervical cancer.

PURPOSE: To evaluate the diagnostic accuracy of computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography/computed tomography (PET/CT) in predicting pelvic lymph node (LN) metastases in patients with cervical cancer. MATERIALS AND METHODS: From January 2009 to March 2015, 114 patients with FIGO stage IA1-IIB uterine cervical cancer who underwent hysterectomy with pelvic lymphadenectomy and took CT, MRI, and PET/CT before surgery were enrolled in this study. The criteria for LN metastases were a LN diameter ≥1.0 cm and/or the presence of central necrosis on CT, a LN diameter ≥1.0 cm on MRI, and a focally increased FDG uptake on PET/CT. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy for pelvic LN metastases were estimated. RESULTS: The sensitivity, specificity, PPV, NPV, and accuracy for detection of pelvic LN metastases were 51.4%, 85.9%, 41.3%, 90.1%, and 80.3% for CT; 24.3%, 96.3%, 56.3%, 86.8%, and 84.6% for MRI; and 48.6%, 89.5%, 47.4%, 90.0%, and 82.9% for PET/CT, respectively. The sensitivity of PET/CT and CT was higher than that of MRI (p=0.004 and p= 0.013, respectively). The specificity of MRI was higher than those of PET/CT and CT (p=0.002 and p=0.001, respectively). The difference of specificity between PET/CT and CT was not statistically significant (p=0.167). CONCLUSION: These results indicate that preoperative CT, MRI, and PET/CT showed low to moderate sensitivity and PPV, and moderate to high specificity, NPV, and accuracy. More efforts are necessary to improve sensitivity of imaging modalities in order to predict pelvic LN metastases.