Routine Pathological Diagnosis Research Articles

Tailoring pretext tasks to improve self-supervised learning in histopathologic subtype classification of lung adenocarcinomas

Lung adenocarcinoma (LUAD) is a morphologically heterogeneous disease with five predominant histologic subtypes. Fully supervised convolutional neural networks can improve the accuracy and reduce the subjectivity of LUAD histologic subtyping using hematoxylin and eosin (H&E)-stained whole slide images (WSIs). However, developing supervised models with good prediction accuracy usually requires extensive manual data annotation, which is time-consuming and labor-intensive. This work proposes three self-supervised learning (SSL) pretext tasks to reduce labeling effort. These tasks not only leverage the multi-resolution nature of the H&E WSIs but also explicitly consider the relevance to the downstream task of classifying the LUAD histologic subtypes. Two tasks involve predicting the spatial relationship between tiles cropped from lower and higher magnification WSIs. We hypothesize that these tasks induce the model to learn to distinguish different tissue structures presented in the images, thus benefiting the downstream classification. The third task involves predicting the eosin stain from the hematoxylin stain, inducing the model to learn cytoplasmic features relevant to LUAD subtypes. The effectiveness of the three proposed SSL tasks and their ensemble was demonstrated by comparison with other state-of-the-art pretraining and SSL methods using three publicly available datasets. Our work can be extended to any other cancer type where tissue architectural information is important. The model could be used to expedite and complement the process of routine pathology diagnosis tasks. The code is available at https://github.com/rina-ding/ssl_luad_classification.

Abstract 5642: Validation of a novel multiplex immuno-fluorescence panel for the spatial analysis of the tumor microenvironment

Abstract IHC counterparts. Subsequently, the panel was transferred on a multi-organ TMA including several tumoral and non-tumoral specimens, showing robust performance across multiple tissue types. The protocol was optimized to achieve high staining quality for all 13 markers in terms of signal specificity Investigation of the tumor microenvironment (TME) by multiplex immunofluorescence (mIF) has accelerated the understanding of the spatial immune context in tumors. mIF has proven to be a powerful technique for the identification of new potential biomarkers and therapeutical targets. Despite increased application of mIF assays to characterize the TME, state-of-the art protocols remain technically challenging. Manual execution and use of dedicated reagents render them lengthy and costly. Moreover, their reproducibility is often questioned together with their transferability between different tissue types. Here, we show the development and validation of an Immuno-Oncology (IO) Core Panel of 13 clinically relevant biomarkers to enable spatial analysis of the immune TME on the COMET™ platform across various tissue types. Formalin-fixed paraffin-embedded human tissue sections from tonsil and a 24-cores multi-organ tissue microarray (TMA) were stained using the IO Core Panel from Lunaphore on the COMET™ platform by fully automated sequential immunofluorescence (seqIF™), which consists of cycles of staining, imaging, and elution. The panel allows for simultaneous detection of CD3, CD4, CD8, CD45, FoxP3, PD1, PD-L1, CD11c, CD20, CD56, CD68, aSMA and Ki-67 by indirect immunofluorescence using unlabeled primary antibodies and Alexa Fluor™ Plus secondary antibodies. The 13-plex IO Core panel was initially developed and validated on tonsil as positive control tissue. To compare immunofluorescent (IF) and immunohistochemistry (IHC) staining patterns, the sections retrieved from COMET™ after seqIF™, were stained by a histology facility with standard IHC established for routine pathological diagnosis. All markers demonstrate accurate detection with specific IF staining, comparably to gold-standard, sensitivity, ratio to background and dynamic range. The repeatability and reproducibility of the automated IO Core Panel on the COMET™ platform was verified by day-to-day tests on one platform and tests among multiple platforms, respectively. Our study demonstrated the robustness of the validated IO Core Panel across multiple tissue types with highly specific and reproducible results. The marker detection with standard indirect immunofluorescence on the COMET™ instrument allows for future, rapid expansion and customization of the panel including additional primary antibodies towards the need of the individual underlying scientific question. Citation Format: François Rivest, Victor de Gautard, Vytautas Navikas, Saska Brajkovic, Bastian Nicolai. Validation of a novel multiplex immuno-fluorescence panel for the spatial analysis of the tumor microenvironment. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5642.

Impact of digital pathology implementation in Reunion Island

In recent decades, the major scientific advances in oncology have complexified anatomic pathology practice. Collaboration with local and national pathologists is essential for ensuring a high-quality diagnosis. Anatomic pathology is undergoing a digital revolution that implements whole slide imaging in routine pathologic diagnosis. Digital pathology improves diagnostic efficiency, allows remote peer review and consultations (telepathology), and enables the use of artificial intelligence. The implementation of digital pathology is of particular interest in isolated territories, facilitating access to expertise and therefore to specialized diagnosis. This review discusses the impact of digital pathology implementation in French overseas territories, particularly in Reunion Island.

The DNA integrity number and concentration are useful parameters for successful comprehensive genomic profiling test for cancer using formalin-fixed paraffin embedded tissue.

The acquisition of high-quality biospecimens and the appropriate handling of these materials are indispensable for successful clinical sequencing. We developed a cancer clinical sequencing system targeting 160 cancer genes: PleSSision-Rapid. Through the PleSSision-Rapid system, we have analyzed DNA quality evaluated by DIN (DNA integrity number) with 1329 formalin-fixed paraffin embedded (FFPE) samples including 477 prospectively collected tissues for genomic test (P) and 852 archival samples after routine pathological diagnosis (A1/A2). As a result, the samples with more than DIN 2.1 was 92.0% (439/477) in prospectively collected sample (P), while it was 85.6% (332/388) and 76.7% (356/464) in two types of archival samples (A1/A2). We performed the PleSSision-Rapid sequence using the samples with over DIN 2.1 and DNA concentration >10 ng/μL with which we were able to construct a DNA library, and the probability of sequence success was almost equivalent during all types of specimen processing, at 90.7% (398/439) in (P), 92.5% (307/332) in (A1) and 90.2% (321/356) in (A2), respectively. Our result indicated the clinical benefit to prepare the prospective collection of FFPE materials for indisputable clinical sequence, and that DIN ≥ 2.1 would be a solid parameter for sample preparation of comprehensive genomic profiling tests.

MMP14 expression levels accurately predict the presence of extranodal extensions in oral squamous cell carcinoma: a retrospective cohort study

BackgroundExtranodal extension (ENE) is an adverse prognostic factor for oral squamous cell carcinoma (OSCC), and patients with OSCC along with ENE require neck dissection. In this study, we developed a novel ENE histology-based pathological predictor using MMP14 expression patterns in small biopsy specimens.MethodsA total of 71 surgically resected tissue, 64 dissected lymph node (LN), and 46 biopsy specimens were collected from 71 patients with OSCC. Immunohistochemical analyses of total MMP14 expression in the tumour nest and cancer-associated fibroblasts (CAFs) were performed using the MMP14 co-scoring system (high- or low-risk). The association analysis of MMP14 expression in metastatic LNs was performed with respect to the presence and absence of ENE. Clinicopathological analyses and multivariate examinations were performed to assess the risks of metastasis and ENE presence. The predictive value of ENE and the impact of ENE and MMP14 expression on 5-year overall survival were examined.ResultsHigh-risk MMP14 expression was detected in metastatic LN specimens with ENE. MMP14 expression in tumour nests and CAFs and its overexpression at the tumour–stromal interface significantly correlated with the presence of ENE. The MMP14 co-scoring system was an independent risk predictor for ENE, with sensitivity, specificity, and accuracy of over 80% in biopsy samples; patients with a high risk in the MMP14 co-scoring system had significantly worse prognoses in both resections and biopsies.ConclusionThe MMP14 co-scoring system accurately predicted ENE presence and poor prognosis via immunohistochemical evaluation of small biopsies. This system is a simple, accurate, and inexpensive immunohistochemical approach that can be used in routine pathological diagnosis for effective treatment planning.

Deep learning based registration of serial whole-slide histopathology images in different stains

For routine pathology diagnosis and imaging-based biomedical research, Whole-slide image (WSI) analyses have been largely limited to a 2D tissue image space. For a more definitive tissue representation to support fine-resolution spatial and integrative analyses, it is critical to extend such tissue-based investigations to a 3D tissue space with spatially aligned serial tissue WSIs in different stains, such as Hematoxylin and Eosin (H&E) and Immunohistochemistry (IHC) biomarkers. However, such WSI registration is technically challenged by the overwhelming image scale, the complex histology structure change, and the significant difference in tissue appearances in different stains. The goal of this study is to register serial sections from multi-stain histopathology whole-slide image blocks. We propose a novel translation-based deep learning registration network CGNReg that spatially aligns serial WSIs stained in H&E and by IHC biomarkers without prior deformation information for the model training. First, synthetic IHC images are produced from H&E slides through a robust image synthesis algorithm. Next, the synthetic and the real IHC images are registered through a Fully Convolutional Network with multi-scaled deformable vector fields and a joint loss optimization. We perform the registration at the full image resolution, retaining the tissue details in the results. Evaluated with a dataset of 76 breast cancer patients with 1 H&E and 2 IHC serial WSIs for each patient, CGNReg presents promising performance as compared with multiple state-of-the-art systems in our evaluation. Our results suggest that CGNReg can produce promising registration results with serial WSIs in different stains, enabling integrative 3D tissue-based biomedical investigations.

The outcomes of Tiantan first-aid protocol on critically ill patients with primary central nervous system lymphoma

Objective: To examine the outcomes of Tiantan first-aid protocol on critically ill patients with primary central nervous system lymphoma (PCNSL). Methods: The clinical data of 18 patients with PCNSL who were treated according to Tiantan first-aid protocol at Department of Neurosurgery,Beijing Tiantan Hospital, Capital Medical University from November 2019 to December 2021 were retrospectively analyzed. There were 9 males and 9 females, aged (56.9±11.1)years (range: 29 to 77 years). The median Karnofsky performance status(KPS) score at admission was 40 (range: 20 to 60). Three patients were mild coma, 3 were lethargy and 12 were conscious. The mean midline shift was 0.7 cm (range: 0 to 1.8 cm). After admission, all patients were treated according to the plan of rapid biopsy, rapid routine pathology and rapid salvage chemotherapy. The treatment procedures, clinical and radiographic outcomes, KPS score and adverse reactions of patients after chemotherapy were collected. Results: All of the 18 patients completed the first-aid treatment. The median duration from admission to the biopsy was 1 day (range: 0 to 5 days), from biopsy to routine pathological diagnosis was 1 day (range: 1 to 4 days) and from routine pathology to salvage chemotherapy was 1 day (range: 0 to 4 days). All the patients were pathologically confirmed with diffuse large B cell lymphoma, 1 patient was double-hit lymphoma. Seventeen patients underwent clinical remission and 1 died of cardiac dysfunction. The successful salvage rate was 17/18. Radiologically, complete remission was observed in 1 case, partial remission in 16 cases, and stable disease in 1 case. The median KPS score at discharge was 60 (range: 30 to 80). The mild gastrointestinal, hematological and hepatic adverse effects were observed after chemotherapy. Conclusion: Tiantan first-aid protocol is effective for critically ill patients with PCNSL, which has the merit to be popularly used and improved.

A deep learning model for breast ductal carcinoma in situ classification in whole slide images

The pathological differential diagnosis between breast ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) is of pivotal importance for determining optimum cancer treatment(s) and clinical outcomes. Since conventional diagnosis by pathologists using microscopes is limited in terms of human resources, it is necessary to develop new techniques that can rapidly and accurately diagnose large numbers of histopathological specimens. Computational pathology tools which can assist pathologists in detecting and classifying DCIS and IDC from whole slide images (WSIs) would be of great benefit for routine pathological diagnosis. In this paper, we trained deep learning models capable of classifying biopsy and surgical histopathological WSIs into DCIS, IDC, and benign. We evaluated the models on two independent test sets (n= 1382, n= 548), achieving ROC areas under the curves (AUCs) up to 0.960 and 0.977 for DCIS and IDC, respectively.

Polypeptide-GalNAc-Transferase-13 Shows Prognostic Impact in Breast Cancer.

Simple SummaryThe knowledge of the molecular mechanisms underlying breast tumorigenesis has allowed the identification of an increasing number of biomarkers, which have been correlated with cancer prognosis or used as predictors for specific treatment responses, thus improving the ability to individualize therapy. Protein O-glycosylation is dysregulated in breast cancer cells. Abnormal O-glycans have functional importance in cell adhesion, invasion, and metastasis. Polypeptide N-acetylgalactosaminyltransferases (GalNAc-Ts) family enzymes regulate the initial steps of mucin type O-glycosylation and may be responsible for the altered glycosylation observed in cancer. Previous reports have related GalNAc-T13 expression to cancer aggressiveness. In the present work, we produced a specific monoclonal antibody against GalNAc-T13 which is capable of recognizing this enzyme on formalin-fixed tissues. We observed a significant higher expression of this enzyme in metastatic samples compared with the corresponding primary tumors. Significantly, a high GalNAc-T13 score was associated with worse patient survival rates, thus supporting its prognostic potential.Breast cancer is a public health concern and is currently the fifth cause of mortality worldwide. Identification of different biological subtypes is essential for clinical management; therefore, the role of pathologists is essential and useful tools for immunohistochemistry diagnosis are needed. Polypeptide-GalNAc-transferases are emerging novel biomarkers related to cancer behavior and GalNAc-T13, correlated with aggressiveness in some tumors, is an interesting candidate. Few monoclonal antibodies reacting with native proteins, and not affected by fixation and paraffin embedding, have been reported. The aim of this work was to develop a useful monoclonal antibody anti-GalNAc-T13 and to assess its potential significance in breast cancer diagnosis. We evaluated 6 human breast cancer cell lines, 338 primary breast tumors and 48 metastatic lymph nodes and looked for clinical significance correlating GalNAc-T13 expression with patients’ clinical features and survival. We found high GalNAc-T13 expression in 43.8% of the cases and observed a significant higher expression in metastatic lymph nodes, correlating with worse overall survival. We hypothesized several possible molecular mechanisms and their implications. We conclude that GalNAc-T13 may be a novel biomarker in breast cancer, useful for routine pathological diagnosis. Elucidation of molecular mechanisms related to aggressiveness should contribute to understand the role of GalNAc-T13 in breast cancer biology.

A novel break site of EML4-ALK report and a rare PRKAR1A-ALK report analyzed by different ALK detection platforms in non-small cell lung cancer patients.

Backgrounddetection of anaplastic lymphoma receptor tyrosine kinase gene (ALK) rearrangements in patients with non‐small‐cell lung cancer (NSCLC) has become a routine pathological diagnosis worldwide.Methodsthere are three major conventional diagnostic methods for ALK fusions: fluorescent in situ hybridization (FISH); immunohistochemistry (Ventana IHC (D5F3)); and polymerase chain reaction (PCR). Next‐generation sequencing (NGS) technology as is a new tool for ALK status detection with great potential. These four methods are highly consistent in detecting ALK status (coincidence rate >96%). However, discrepancies in ALK status have been found in some patients among these methods, which causes confusion for clinicians.Results and conclusionin this study, we analyzed two patients whose ALK statuses were not consistent using these four methods. We explored the potential reasons for deviation of the test results and found a novel EML4‐ALK break site, which had been not described previously.

Tumor–stroma ratio is a crucial histological predictor of occult cervical lymph node metastasis and survival in early-stage (cT1/2N0) oral squamous cell carcinoma

Occult cervical lymph node metastasis is a significant prognostic factor in patients with early-stage (cT1/2N0) oral squamous cell carcinoma (OSCC). The aim of this study was to investigate the potential value of the tumor–stroma ratio (TSR) as a histological predictor of occult cervical metastasis and survival in early-stage OSCC. This retrospective study included 151 patients who underwent excision of the primary lesion and elective neck dissection from 2013 to 2017. The clinicopathological features of the tumor, risk factors associated with occult neck metastasis, and prognostic factors for overall survival (OS) and disease-free survival (DFS) were studied. A significant correlation of TSR (P = 0.009) was found with occult neck metastasis in the multivariate logistic regression model. Multivariate Cox proportional hazards regression analysis showed that the TSR (P = 0.002) and perineural invasion (P = 0.011) were associated with OS. Occult neck metastasis (P = 0.032) was associated with DFS. These findings indicate that assessment of the TSR might be useful in prognostication for early-stage OSCC patients. Moreover, the TSR is effective in allowing an accurate evaluation of the risk of occult neck metastasis, and this may be easily applicable in the routine pathological diagnosis and clinical decision-making for elective neck dissection.

Progesterone Receptor Expression in Meningiomas: Pathological and Prognostic Implications.

BackgroundThe progesterone receptor (PR) is variably expressed in most meningiomas and was found to have prognostic significance. However, the correlation with patient age, tumor location, time to recurrence, and pattern of regrowth has scarcely been discussed.MethodsA surgical series of 300 patients with meningiomas is reviewed. The PR expression was classified as: 0. absent; 1. low (<15%); 2. moderately low (16–50%); 3. moderately high (51–79%); 4. high (≥80%). The PR values were correlated with the patient age and sex, meningioma location, WHO grade, Ki-67 MIB1, recurrence rate, pattern of recurrence (local-peripheral versus multicentric diffuse), and time to recurrence.ResultsThe PR expression has shown lower rate of high expression in the elderly group (p = 0.032) and no sex difference (including premenopausal versus postmenopausal women), higher expression in medial skull base and spinal versus other locations (p = 0.0036), inverse correlation with WHO grade and Ki67-MIB1 (p < 0.0001). Meningiomas which recurred showed at initial surgery higher rates of low or moderately low PR expression than the non-recurrent ones (p = 0.0004), whereas the pattern of regrowth was not significant. Higher rates of PR values ≥80% were found in cases with time to recurrence >5 years (p = 0.036).ConclusionThe higher PR expression in medial skull base meningiomas, the significant correlation with the time to recurrence, the lack of difference of PR expression between premenopausal and postmenopausal women and between local-peripheral versus multicentric-diffuse recurrences are the most relevant unreported findings of this study. The rate of PR expression must be included in the routine pathological diagnosis of meningiomas because of its prognostic significance.

Haemolymphangioma of the small bowel mesentery in adults: two case reports and a literature review

BackgroundHaemolymphangioma arising from the small bowel and its mesentery is extremely rare in the clinical setting. To date, only 8 cases of small bowel haemolymphangioma have been reported, and there have been no previously reported cases of haemolymphangioma in the small bowel mesentery (PubMed). The formation of this tumour is mostly congenital, but the exact mechanism is still unclear. As a benign tumour, the presentation of the disease may vary from a simple well-defined cystic lesion to an aggressive ill-defined lesion mimicking malignancy. However, there are no typical symptoms, and preoperative diagnosis is difficult.Case presentationWe present two cases of haemolymphangioma in the small bowel mesentery in a 54-year-old man and a 52-year-old woman. Both of them came to the hospital due to an abdominal mass. In the first case, a cystic teratoma in the left abdominal area was considered after abdominal plain computed tomography (CT) and magnetic resonance imaging (MRI) scans. After taking an enhanced CT scan, a lipoma was considered based on the images. In the second case, cystic masses of the left upper and middle abdomen were observed on abdominal ultrasonography. An abdominal plain CT scan showed an irregular low-density mass in the left upper and middle abdomen. With an enhanced CT scan, haemolymphangioma was considered based on the images. After complete surgical removal, the masses were found to originate from the small bowel mesentery and had not invaded into the peripheral lymphatic tissue. In case 1 in this study, the routine pathology diagnosis was lymphangioma, while in case 2, the diagnosis was haemangioma. The final diagnosis was confirmed to be haemolymphangioma by immunohistochemistry in both cases. No recurrence was evident during 4 months of follow-up. We review the previous case reports of haemolymphangioma in the abdominal cavity and discuss their clinical features, diagnosis, treatment and prognosis.ConclusionsThe clinical manifestations of abdominal haemolymphangiomas can vary for both location and size. Abdominal CT examination has important clinical value for haemolymphangioma in the abdominal cavity. The final diagnosis of haemolymphangioma depends on a postoperative pathological examination. In addition, postoperative regular follow-up is necessary.

A standardized pathological proposal for evaluating microvascular invasion of hepatocellular carcinoma: a multicenter study by LCPGC.

Microvascular invasion (MVI) is a key pathological factor that severely affects the postoperative prognosis of patients with hepatocellular carcinoma (HCC). However, no MVI classification schemes based on standardized gross sampling protocols of HCC are available at present. 119 HCC specimens were sampled at multiple sites (3-, 7-, and 13 points) for the optimum MVI detection rate. 16,144 resected HCCs were graded as M0, M1 or M2 by adopting three-tiered MVI grading (MVI-TTG) scheme based on the seven-point sampling protocol (SPSP). Survival analyses were performed on 2573 patients to explore the advantages of MVI-TTG. The MVI detection rate determined by SPSP was significantly higher than that determined by the 3-point sampling method (34.5% vs. 47.1%, p = 0.048), but was similar to that determined by the 13-point sampling method (47.1% vs. 51.3%, p = 0.517). Among 16,144 resected HCCs, the proportions of M0, M1 and M2 specimens according to SPSP were 53.4%, 26.2% and 20.4%, respectively. Postoperative survival analysis in 2573 HCC patients showed that the 3-year recurrence rates in M0, M1 and M2 MVI groups were 62.5%, 71.6% and 86.1%, respectively (p < 0.001), and the corresponding 3-year overall survival (OS) rates were 94.1%, 87.5% and 67.0%, respectively (p < 0.001). M1 grade was associated with early recurrence, while M2 grade was associated with both early and late recurrence. MVI-TTG had a larger area under the curve and net benefit rate than the two-tiered MVI grading scheme for predicting time to recurrence and OS. SPSP is a practical method to balance the efficacy of sampling numbers and MVI detection rates. MVI-TTG based on SPSP is a better prognostic predictor than the two-tiered MVI scheme. The combined use of SPSP and MVI-TTG is recommended for the routine pathological diagnosis of HCC.

A method to obtain reproducible Ki-67 indices in lung adenocarcinoma.

Proliferative activity, evaluated from the Ki-67 index, is a strong prognostic factor in lung adenocarcinoma (LADC). Here, we optimised a procedure to measure the Ki-67 index and establish the best cut-off value. We examined 342 stage I LADCs for the immunohistochemical expression of Ki-67 using different antibodies, MIB1 and SP6. The results revealed the superior specificity of SP6; therefore, SP6 was used in subsequent analyses. Slides were scanned with a virtual slide system. Using software, tumour cells were counted in a whole tumour. Thereafter, the tumour was evenly subdivided into 0.25-mm2 tiles. The frequency of positive cells was counted in each tile of an invasive area or the whole tumour. We calculated the number of tumour cells required to produce a 95% confidence interval (CI) <0.05. Additionally, we calculated coverage probabilities (CP) using two different methods, counting any number or 200 cells per tile. The results showed that we could meet our goal by counting 2000 cells from 10 random tiles (200 cells each) in invasive areas. We successfully developed an optimal procedure for determination of the Ki-67 labelling index using an SP6 antibody, which provided CP>70% and CI of <0.05 in more than 90% of cases. Furthermore, we identified an optimal cut-off value of 0.12 with an alternative of 0.15, based on disease recurrence. This procedure and the cut-off values may be used in the routine pathological diagnosis of LADC.

Gastric cancer nodal tumour-stroma ratios influence prognosis.

This study showed that nodal tumour-stroma ratio (NTSR) is an independent prognostic factor for overall and disease-free survival of patients with gastric cancer. Both relative stroma-rich primary tumour-stroma ratio (PTSR) and NTSR were independent negative prognostic factors for overall survival in gastric cancer. This study supports assessment of tumour-stroma ratio in the routine pathological diagnosis of gastric cancer. validated in node-positive disease.

AUTOPHAGIC MYOPATHIES / MYOFIBRILLAR MYOPATHIES / DISTAL MYOPATHIES / POMPE DISEASE: P.17 Screening for Pompe disease using muscle section in Japan

Pompe disease (PD) is an autosomal recessive glycogen storage disease due to deficiency of acid alpha-glucosidase (GAA). As enzyme replacement therapy is available, any patient should not be overlooked. However, late-onset PD (LOPD) cases can often clinically show nonspecific limb-girdle phenotype and sometimes pathologically lack pathognomonic vacuolar changes. Although we have reported acid-phosphatase-positive globular inclusion in myofibers as a diagnostic marker, still PD cases may be overlooked on routine muscle pathology diagnosis as the inclusion may not always be obvious.

The correlation between ultrasonographic features, bFGF, and the local invasiveness of thyroid papillary carcinoma.

The present study aimed to investigate the correlation between ultrasonographic features, basic fibroblast growth factor (bFGF), and the local invasiveness of papillary thyroid carcinoma (PTC).A total of 350 samples of thyroid nodules were collected. Routine ultrasonography was performed before the operation and routine pathological diagnosis and bFGF detection were performed after the operation.’These 350 samples of thyroid nodules included 90 samples of nodular goiter, 36 samples of focal thyroiditis, and 224 samples of PTC. A total of 326 thyroid nodules were examined for bFGF. The results revealed that the difference in the expression of bFGF between the benign and malignant groups was statistically significant (P < .05) and the difference in the positive expression of bFGF between the invasive and non-invasive PTC groups was statistically significant (P < .05).Whether the shape of PTC is regular or not and whether there is micro-calcification in PTC and other ultrasonographic features, the size and location of the lesions and the age of the patient help make a preliminary prediction of local invasiveness before the operation. Postoperative detection of bFGF is helpful for further risk assessments of PTC.

Combination of KRAS and SMAD4 mutations in formalin-fixed paraffin-embedded tissues as a biomarker for pancreatic cancer.

Formalin‐fixed paraffin‐embedded (FFPE) tissues used for routine pathological diagnosis are valuable for cancer genomic analysis; however, the association between mutation status derived from these specimens and prognosis in pancreatic ductal adenocarcinoma (PDAC) remains unclear. We analyzed 50 cancer‐related gene mutations including driver genes in PDAC, using next‐generation sequencing (NGS) to clarify the association between gene mutations and prognosis. DNA was extracted from FFPE tissues obtained from 74 patients with untreated resectable PDAC who underwent surgery at our institution between 2013 and 2018. Fifty of the 74 patients with DNA extracts from FFPE samples suitable for NGS were analyzed. The prevalence of driver gene mutations was as follows: 84% for KRAS, 62% for TP53, 32% for SMAD4, and 18% for CDKN2A. There were no cases of single SMAD4 mutations; its rate of coincidence with KRAS or TP53 mutations was 30% and 2%, respectively. The combination of KRAS and SMAD4 mutations resulted in significantly shorter relapse‐free survival (RFS; median survival time [MST], 12.3 vs. 28.9 months, P = .014) and overall survival (OS; MST, 22.3 months vs. not reached, P = .048). On multivariate analysis, the combination of KRAS and SMAD4 mutations was an independent prognostic factor for RFS (hazard ratio [HR] 4.218; 95% confidence interval [CI], 1.77‐10.08; P = .001) and OS (HR 6.730; 95% CI, 1.93‐23.43; P = .003). The combination of KRAS and SMAD4 mutations in DNA obtained from FFPE tissues is an independent poor prognostic factor in PDAC.

From This Month's Histopathology

From This Month's Histopathology