Changes in beta-catenin expression and activation during progression of primary sclerosing cholangitis predict disease recurrence

Primary sclerosing cholangitis (PSC) is a rare, chronic, cholestatic liver disease characterized by progressive inflammation and fibrosis of the bile ducts. We have previously demonstrated the importance of Wnt/β-catenin signaling in mouse models of PSC. In this study, we wished to determine the clinical relevance of β-catenin localization in patient samples. In livers explanted from patients diagnosed with PSC, the majority (12/16; 75%) lacked β-catenin protein expression. Biopsies from patients post-transplant were classified as recurrent or non-recurrent based on pathology reports and then scored for β-catenin activation as a function of immunohistochemical localization. Despite lack of statistical significance, patients with recurrent primary disease (n = 11) had a greater percentage of samples with nuclear, transcriptionally active β-catenin (average 58.8%) than those with no recurrence (n = 10; 40.53%), while non-recurrence is correlated with β-catenin staining at the cell surface (average 52.63% for non-recurrent vs. 27.34% for recurrent), as determined by three different methods of analysis. β-catenin score and years-to-endpoint are both strongly associated with recurrence status (p = 0.017 and p = 0.00063, respectively). Finally, there was significant association between higher β-catenin score and increased alkaline phosphatase, a marker of biliary injury and disease progression. Thus, β-catenin expression and activation changes during the progression of PSC, and its localization may be a useful prognostic tool for predicting recurrence of this disease.

Thyroglobulin in lymph node fine-needle aspiration biopsy washout fluid. A tertiary center experience

Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. Most PTC secretes thyroglobulin, a useful marker in monitoring preoperative staging and postoperative progression; in addition to serum thyroglobulin, fine needle aspiration washout thyroglobulin (FNA-Tg) is also used. Our aim was to determine the cut-off value for FNA-Tg in our center and to describe major discrepancies between FNA-Tg, cytology and pathology results of the lymph nodes. Methods: We retrospectively retrieved from the electronic database of our endocrinology center all the FNA-Tg measurements between December 10, 2019 and September 2021. For each measurement we also retrieved the corresponding sex, FNAB results and the pathology reports. FNA-Tg was measured by ECLIA immunoelectro-chemiluminescent method. Results: There were 58 FNAB and FNA-Tg of suspect cervical lymph nodes in 40 patients. There were 17 cytologically benign lymph nodes of which 13 had low and 4 had high FNA-Tg; 3 non-diagnostic cytology results of which one had high FNA-Tg; 38 PTC metastases of which 6 had low and 32 had high FNA-Tg titers. The cut-off value of FNA-Tg in our center is 10 ng/ml, with a sensitivity of 86.6% (in those with pathology reports available after surgery). Conclusions: Washout TG is useful in suspicious lymph nodes and has added value to cytology in selected cases. The cut-off value of FNA-Tg in our center is 10 ng/ml, with a sensitivity of 86.6%. However, we must consider the possible false negative results that may occur in some histological types of PTC.

Comparison of Survival Between Unilocular Cystic and Purely Solid Renal Cell Carcinoma

Purpose To evaluate clinicopathologic features and survival outcomes of unilocular cystic renal cell carcinoma (cRCC) compared with purely solid renal cell carcinoma (RCC), and to evaluate the oncologic aggressiveness of unilocular cRCC. Methods The relevant data of 957 patients with sporadic unilateral RCCs underwent surgical treatment in 2 institutions from Jan 2014 to Oct 2018 were obtained. We excluded multilocular cystic renal neoplasm of low malignant potential (MCRNLMP), RCCs with multilocular cysts and necrotic RCCs. 74 unilocular cRCCs were identified by pathology reports. We performed propensity score matching (PSM) and randomly selected 148 purely solid RCCs. The clinicopathologic features and survival outcomes were compared properly. Results After PSM, age, BMI, Charlson Comorbidity Index, and postoperative Chronic Kidney Disease grade were not significantly different. Both overall survival and cancer-specific survival of unilocular cRCCs were significantly better than the purely solid RCCs by the log-rank test. Twenty-five cases of solid RCCs were in the pT3 or pT4 stage, while no pT3 or pT4 tumors were found in unilocular cRCCs. Fuhrman grade, pT stage, lymphatic metastasis and tumor diameter were found to be independent prognostic factors. Conclusion Unilocular cRCCs have a lower Fuhrman grade and pathological stage and a better prognosis compared with solid RCC. Unilocular cRCCs still probably have lymphatic metastasis at diagnosis and may have postoperative metastasis, which is different from MCRNLMP. We recommend that the diagnosis of unilocular cRCC should be reflected in pathology reports. Different subtypes of cRCC should be taken into consideration in counseling and management.

Squamous Differentiation in the Thyroid: Metaplasia, Neoplasia, or Bystander?

Background. Squamous differentiation within the thyroid is seen in a variety of settings. Squamous epithelium is non-native to the thyroid, and its debated origins span reactive metaplasia and developmental/embryologic remnants. Despite a lack of clarity as to its evolution, squamous epithelium may be associated with both neoplastic and non-neoplastic processes. Methods. Thyroid pathology reports spanning a 30-year period were reviewed for terms indicating squamous features. Associated diagnostic and clinical information was collated. Results. Four hundred and twenty seven of 17,452 (2.4%) thyroid surgical pathology cases during this period utilized terminology indicating squamous differentiation including 243 malignant (58%) and 178 benign (42%) diagnoses. There were 111 (26%) primary thyroid malignancies with squamous differentiation, 116 (28%) malignancies of non-thyroid origin including local extension from nearby cancers, and 16 (4%) malignancies of uncertain primary. Most benign lesions were non-neoplastic (84%). The minor subset representing benign neoplasia was interpreted as secondary reactive changes. Conclusion. While squamous differentiation is seen routinely in the thyroid, it is most commonly reported in malignancy. For primary thyroid malignancies reported to demonstrate a squamous component, biologically aggressive tumors were overrepresented. Available evidence suggests that multiple pathways may contribute to the presence of squamous epithelium in the thyroid including metaplasia of mature follicular cells, development from established embryonic remnants, or inception in putative, incompletely characterized stem-like cells. Our retrospective review presents an institutional landscape from which further investigation into the frequency and unique histologic and molecular context of intrathyroidal squamous differentiation as a driver or terminal event in thyroid pathophysiology.

Acute Abdomen—A Clinical Presentation of MIS-C in Children

Objective Multisystemic inflammatory syndrome in children (MIS-C) is characterized by persistent fever, systemic hyperinflammation, and multiple-organ dysfunction. There are a few reports about MIS-C presenting with acute abdomen. The aim of this study is to demonstrate the clinical characteristics and treatment options for MIS-C-related acute abdomen and appendicitis. Methods This was a retrospective study conducted between April 2020 and October 2020 in our pediatric intensive care unit in Turkey. Patients between the ages of 1 month and 18 years who presented with acute abdomen and were ultimately diagnosed with MIS-C were included. Results Seven patients with a median age of 12.5 (interquartile range 10.5–13) years were enrolled. Four were females. The most frequent symptoms were fever, abdominal pain, and vomiting. Three patients had involvement of the appendix that required surgical intervention. All pathology reports were compatible with appendicitis. The other patients also had an acute abdomen. One patient had malignant hyperthermia during induction of anesthesia, so surgery was postponed and medical management was commenced. The clinical picture regressed with immunomodulation. All patients were treated with intravenous immunoglobulin and steroids. Four patients with acute abdomens improved with immunomodulation, and surgery was not needed. Conclusion MIS-C may present with an acute abdomen. Immunomodulation should be considered instead of surgery if the clinical course is not complicated.

Multiple Idiopathic Internal Root Resorption in an Adolescent: A Case R Multiple Idiopathic Internal Root Resorption in an Adolescent: A Case Report

Internal root resorption (IRR) refers to a slow or rapid progressive resorption process that occurs in the pulp cavity of the tooth or the dentin of the root. IRR occurs as result of odontoclast action; in many cases, the pulp tissue exhibits chronic inflammation, and odontoblasts and predentin do not appear on the dentin wall near the pulp. Exact predisposing factors have not been clearly elucidated; therefore, it is difficult to identify reliable data on the prevalence of IRR because of its scarce occurrence and pathology. Reports have indicated that IRR is more common in the primary than in the permanent teeth. This case report discusses a 17-year-old girl with multiple idiopathic internal root resorptions of anterior permanent teeth in a short period of a time and its management.

Development of a Semiautomated Search Tool to Identify Grading From Pathology Reports for Tumors of the CNS and Prostate Cancers

PURPOSE This study demonstrates the functionality of semiautomated algorithms to classify cancer-specific grading from electronic pathology reports generated from military treatment facilities. Two Perl-based algorithms are validated to classify WHO grade for tumors of the CNS and Gleason grades for prostate cancer. METHODS Case-finding cohorts were developed using diagnostic codes and matched by unique identifiers to obtain pathology records generated in the Military Health System for active duty service members from 2013 to 2018. Perl-based algorithms were applied to classify document-based pathology reports to identify malignant CNS tumors and prostate cancer, followed by a hand-review process to determine accuracy of the algorithm classifications. Inter-rater reliability, sensitivity, specificity, positive predictive values (PPVs), and negative predictive values were computed following abstractor adjudication. RESULTS The high PPV for the Perl-based algorithms to classify CNS tumors (PPV > 98%) and prostate cancer (PPV > 99%) supports this approach to classify malignancies for cancer surveillance operations, mediated by a hand-reviewed semiautomated process to increase sensitivity by capturing ungraded cancers. Early detection was pronounced where 33.6% and 50.7% of malignant records retained a CNS WHO grade of II or a Gleason score of 6, respectively. Sensitivity metrics met criteria (> 75%) for brain (79.9%, 95% CI, 73.0 to 85.7) and prostate (96.7%, 95% CI, 94.9 to 98.0) cancers. CONCLUSION Semiautomated, document-based text classification using Perl coding successfully leveraged identification of WHO and Gleason grades to classify pathology records for CNS tumors and prostate cancer. The process is recommended for data quality initiatives to support cancer reporting functions, epidemiology, and research.

P-BN21 Diagnostic accuracy of transabdominal ultrasound for assessing gallbladder polyps

Background Gallbladder polyps are common findings on transabdominal ultrasound (TAUS) and their implications are not entirely clear. Current guidelines advise monitoring with serial TAUS and to offer laparoscopic cholecystectomy if criteria are met to minimise risk of malignant transformation. TAUS is easily accessible and useful at identifying gallbladder polyps, however, has limitations when differentiating between pseudopolyps and true gallbladder polyps with malignant potential. This study looks at a district general hospital’s outcomes for patients undergoing laparoscopic cholecystectomy for gallbladder polyps. Methods This retrospective study identified patients who had polyps identified on TAUS and subsequently undergone laparoscopic cholecystectomy from 2011 to 2021. We identified patients using hospital coding and subsequently assessed their pre-operative imaging and clinic letters to ensure gallbladder polyps were the reason for cholecystectomy. The size of polyp on TAUS was noted and pathology reports were assessed to determine if polyps had been correctly identified on TAUS and if these were true or pseudopolyps. Clinic letters were assessed to determine if patients were symptomatic pre-operatively. Results 66 patients were identified as having polyps pre-operatively. The size of polyp ranged from 2-19mm with a mean of 7.4mm. 39 (59%) patients were symptomatic pre-operatively. TAUS findings correlated with pathology findings of polyps in 45 (68%) patients. Of the 21 patients with no polyps on pathology: 11 had gallstones, 9 had chronic cholecystitis and 1 normal gallbladder. Of the polyps identified 44 were pseudopolyps and only 1 was a true adenoma – 39 cholesterol polyps, 3 inflammatory polyps and 2 adenomyomatosis. There was no evidence of dysplasia on the adenoma, it measured 5mm on TAUS and the patient was symptomatic. Conclusions This study highlights the limitations of TAUS in correctly identifying true polyps. The 41% of asymptomatic patients all had benign findings on pathology and likely had no benefit from surgery. Whilst TAUS is a useful method of identifying potential polyps these findings would suggest that other methods of identifying true polyps should be sought to minimise patients undergoing unnecessary surgery.

Electronic case report forms generation from pathology reports by ARGO, automatic record generator for onco-hematology

The unstructured nature of Real-World (RW) data from onco-hematological patients and the scarce accessibility to integrated systems restrain the use of RW information for research purposes. Natural Language Processing (NLP) might help in transposing unstructured reports into standardized electronic health records. We exploited NLP to develop an automated tool, named ARGO (Automatic Record Generator for Onco-hematology) to recognize information from pathology reports and populate electronic case report forms (eCRFs) pre-implemented by REDCap. ARGO was applied to hemo-lymphopathology reports of diffuse large B-cell, follicular, and mantle cell lymphomas, and assessed for accuracy (A), precision (P), recall (R) and F1-score (F) on internal (n = 239) and external (n = 93) report series. 326 (98.2%) reports were converted into corresponding eCRFs. Overall, ARGO showed high performance in capturing (1) identification report number (all metrics > 90%), (2) biopsy date (all metrics > 90% in both series), (3) specimen type (86.6% and 91.4% of A, 98.5% and 100.0% of P, 92.5% and 95.5% of F, and 87.2% and 91.4% of R for internal and external series, respectively), (4) diagnosis (100% of P with A, R and F of 90% in both series). We developed and validated a generalizable tool that generates structured eCRFs from real-life pathology reports.