Outcomes of the Bethesda system for reporting thyroid cytopathology in community- vs. institution-performed cytology.

OBJECTIVES: Despite the important role of the community in the assessment and risk stratification of patients with thyroid nodules, evidence-based data on the Bethesda System for Reporting Thyroid Cytopathology (BSRTC) performance in community clinics is lacking. We aim to evaluate BSRTC performance of aspirations taken in community clinics compared with primary referral center. METHODS: Patients who underwent thyroid surgery between 2013 and 2018 at our institution were divided according to the fine needle aspirations (FNA) settings: community FNA (cFNA) vs. institutional FNA (iFNA). Demographics, BSRTC results and final pathology were collected. Diagnostic values were calculated for BSRTC categories (sensitivity, specificity, positive predictive value [PPV], and negative predictive value [NPV]), and were compared between the groups. RESULTS: A total of 268 nodules were included in the study; 77% (207) cFNA and 23% (61) iFNA. Patients in the community were younger (51.7 ± 15.1 vs. 56.6 years±14.8, p = 0.03) and with less epidemiology risk factors for thyroid cancer (1.9% vs 13.1%, p < 0.001). cFNA malignancy rate for BSRTC I-VI was 0%, 6.4%, 11.8%, 32.1%, 91.6% and 93.8% respectively. Best sensitivity was found for BSRTC III-VI in both groups (88% and 83%, cFNAs and iFNAs, respectively). Overall best performance was obtained for BSRTC V-VI for both groups (cfNA: 85%, 97%, 93%, 94% and 93%; iFNAs: 81%, 100%, 100%, 87% and 91%, for sensitivity, specificity, PPV, NPV and accuracy, respectively). CONCLUSIONS: Community-performed FNAs demonstrate acceptable BSRTC distribution and malignancy rates, comparable with a primary referral academic hospital. This supports the universality of the BSRTC 2017 and its recommendations also in the community.

Positive Correlation of Thyroid Nodule Cytology with Molecular Profiling-a Single-Center Experience.

Despite several reports on the association between molecular profiling, aggressive histology, and clinical outcomes, the association between mutation expression and pre-operative cytology is yet to be demonstrated. Therefore, we performed a retrospective, single-center study, including all patients who underwent molecular profiling of thyroid nodules in Bethesda System for Reporting Thyroid Cytopathology (BSRTC) categories III to VI, between 2018 and 2019. Medical records were reviewed to collect demographics, cytology results according to BSRTC, final pathology (presence of malignancy and its type, as well as presence of aggressive features, including extrathyroidal extension, positive neck lymph nodes, and multifocality), and the identified genetic variants stratified by risk levels, according to the 2015 ATA guidelines. We supplemented this analysis with a systematic review to identify the variant distributions across the literature. We included data on 55 nodules from 48 patients for the final analysis. A significant positive correlation was found between BSRTC categories and the mutation risk level, shown by an increase in the intermediate to high-risk mutation rate in the higher BSRTC categories (Rs = 0.660, p ≤ 0.001). A significant positive correlation was also found between mutation risk levels and the presence of malignancy and aggressive tumor features (Rs = 0.637, p < 0.001 and Rs = 0.459, p = 0.006, respectively). This novel positive and significant correlation between BSRTC categories and the mutation risk level provides additional insight to aid clinicians in the interpretation of BSRTC results and may contribute to the discussion of appropriate management of thyroid nodule with patients.

Outcomes of the Bethesda system for reporting thyroid cytopathology: Real-life experience.

OBJECTIVE: The 2017 revised Bethesda System for Reporting Thyroid Cytopathology (BSRTC) included new malignancy rates for each category as well as new management recommendations. Here, we evaluate the malignancy rate and test performance for BSRTC categories in a middle-sized institution outside the United States (US). DESIGN: Retrospective single centre case series with chart review. PATIENTS: All patients who underwent thyroid surgery with a preoperative BSRTC between the years 2010 and 2018 at our institution. MEASUREMENTS: In order to assess the malignancy rate for each BSRTC, all medical records were reviewed to collect demographics, nodule's size, BSRTC and final pathology. RESULTS: Three hundred and sixty-four patients were included, with an overall malignancy rate of 34.3%. The malignancy rate for BSRTC categories I-VI was as follows: 13.3%, 5.1%, 25.0%, 24.4%, 91.3% and 95.2%, respectively. The most sensitive test was when BSRTC III-VI were evaluated (91%). Overall best performance (sensitivity, specificity, PPV, NPV and accuracy) was obtained when BSRTC V-VI were grouped together with a substantial decrease when adding BSRTC III-IV (90%, 97%, 94%, 95%, 95% vs, respectively, 91%, 73%, 62%, 95%, 79%, respectively). CONCLUSIONS: Despite differences from the reported 2017 BSRTC malignancy rates, we demonstrated that the revised 2017 BSRTC management recommendations for thyroid nodules are also valid in smaller non-US centre, supporting its use globally.

Metastatic carcinoma occurring in a gastric hyperplastic polyp mimicking primary gastric cancer: the first reported case.

Hyperplastic polyps of the stomach are regarded as benign. However, in rare cases they may contain incipient primary carcinomas. To our knowledge, breast carcinoma metastatic to a gastric hyperplastic polyp has not yet been reported. We describe the case of a 69-year-old woman to whom a gastric polyp was endoscopically excised. The patient had previously undergone a right mastectomy for mixed, invasive ductal and lobular carcinoma 5 years earlier. Histological sections from the gastric lesion showed typical features of hyperplastic polyp with foci of poorly differentiated adenocarcinoma including signet ring cells infiltrating the lamina propria. The histologic findings were consistent with a primary gastric cancer. However, the carcinoma cells were immunopositive for estrogen and progesterone receptors and GATA3 and negative for CDX2, Hep Par 1, and MUC5AC. E-cadherin showed membranous reactivity in some of the carcinoma cells while in others it was negative. Accordingly, metastatic mixed, lobular and ductal breast carcinoma was diagnosed. We conclude that metastatic adenocarcinoma mimicking primary gastric cancer can be rarely encountered in hyperplastic gastric polyps.

Hepatocyte antigen (Hep Par 1) is helpful in distinguishing between inflamed and architecturally altered ileal and colonic mucosa.

In chronic inflammatory states, the ileal mucosa may flatten, whereas the colonic mucosa may develop a villiform surface. Accordingly, pathologic biopsies labeled by the endoscopist as "ileocolic" or "ileocecal" may generate confusion or uncertainty as to their specific origin. To facilitate distinguishing between architecturally altered ileal and colonic mucosae, we assessed the hepatocyte paraffin 1 (Hep Par 1) antibody, reported to react with normal and metaplastic small bowel epithelium but not with normal colonic epithelium, in 25 ileal biopsies (10 normal and 15 pathologic), 25 colonic biopsies (10 normal and 15 pathologic), and 20 samples labeled as "ileocecal" or "ileocolic" in which the organ of origin could not be definitely established because of mucosal inflammation and distortion. The latter group included 8 cases diagnosed as being of "probable ileal origin," 7 cases diagnosed as being of "probable colonic origin," and 5 cases diagnosed as "uncertain." Diffuse granular cytoplasmic Hep Par 1 expression was detected in all normal and pathologic ileal mucosal biopsies, whereas all colonic biopsies were negative or focally reactive. Cases of "probable ileal origin" were diffusely positive (granular cytoplasmic pattern), whereas those of "probable colonic origin" were negative or focally reactive. Two of the "uncertain" cases expressed Hep Par 1, whereas 3 were negative, thus supporting their ileal and colonic derivation, respectively. In conclusion, Hep Par 1 is diffusely expressed by pathologic ileal mucosa, being negative or only focally positive in pathologic colonic mucosa. Accordingly, it represents a valuable tool for recognizing the tissue source in problematic ileocolonoscopic biopsies.

Utility of MIB-1 (Ki-67) in evaluating diminutive colorectal polyps with cautery artifact.

CONTEXT: Accurate interpretation of colorectal polyp histology is essential in the decision-making process during treatment and surveillance following polypectomies. However, interpretation of diminutive colorectal polyps removed by thermal electrocoagulation (hot biopsy technique) is often problematic as a result of cautery artifact. OBJECTIVE: To evaluated the usefulness of the proliferation marker MIB-1 (Ki-67) as an aid in the differential diagnosis of diminutive colorectal polyps with cautery artifact, as adenomatous and nonadenomatous polyps display different patterns of epithelial proliferation. DESIGN: Seventy-five diminutive colorectal polyps with extensive cautery artifact displaying at least the upper portions of 3 adjacent crypts with the corresponding surface epithelium were evaluated and immunolabeled with MIB-1. They included 25 cases in which a definitive or presumptive diagnosis could not be reached (indeterminate polyps), 25 cases diagnosed as compatible with adenomatous polyp, and 25 cases diagnosed as compatible with nonadenomatous polyp. RESULTS: MIB-1 immunoreactivity was well preserved in the cauterized areas. Among indeterminate polyps, MIB-1 stained upper crypts and surface epithelium in 14 cases (adenomatous polyp staining pattern) and revealed minimal or absent staining in these areas in 11 cases (nonadenomatous polyp staining pattern). All cases diagnosed as compatible with adenomatous polyp displayed the adenomatous polyp staining pattern. In contrast, all cases diagnosed as compatible with nonadenomatous polyp revealed the nonadenomatous polyp staining pattern. CONCLUSIONS: Immunoreactivity for MIB-1 may be used as a beneficial adjunctive test to help diagnose diminutive colorectal polyps with extensive cautery artifact.

Expression of the intestinal marker Cdx2 in secondary adenocarcinomas of the colorectum.

CONTEXT: Secondary adenocarcinomas of the large bowel can closely mimic primary tumors. The differentiation of secondary from primary adenocarcinomas of the colorectum, however, is important because their clinical management and prognosis are different. Immunostaining with the nuclear transcription factor Cdx2, expressed in normal intestinal epithelia and colorectal adenocarcinomas, could be of potential diagnostic use. OBJECTIVE: To investigate the diagnostic value of Cdx2 immunoexpression in distinguishing primary from common forms of secondary colorectal adenocarcinomas. DESIGN: Cdx2 immunoexpression was analyzed in 20 primary colorectal adenocarcinomas and in 34 secondary colorectal adenocarcinomas and their corresponding primary tumors. All secondary tumors were diagnosed through endoscopic biopsies and included 8 cases of ovarian (4 serous, 2 mucinous, and 2 endometrioid), 6 of mammary (4 lobular and 2 ductal), 4 of gastric (2 intestinal and 2 diffuse), 4 of pulmonary, 4 of pancreatic (ductal), 3 of prostatic, 3 of colorectal, and 2 of endometrial origin. RESULTS: Cdx2 was expressed in normal colorectal epithelium, in primary colorectal adenocarcinomas (20/20 cases), in secondary adenocarcinomas of colorectal (3/3) and gastric (3/4) origin, and in metastatic ovarian mucinous adenocarcinomas (2/2). In contrast, no Cdx2 immunoreactivity was observed in secondary colorectal tumors of ovarian (serous and endometrioid), mammary, pancreatic, pulmonary, prostatic, and endometrial origin. CONCLUSION: Cdx2 immunostaining may be useful in discriminating primary colorectal carcinomas from frequent types of secondary colorectal adenocarcinomas of nongastrointestinal origin. We suggest including Cdx2 in any antibody panel put together to distinguish between primary and secondary epithelial colorectal malignancies.

Expression of the intestinal marker Cdx2 in the columnar-lined esophagus with and without intestinal (Barrett's) metaplasia.

Barrett's esophagus is diagnosed when goblet cells are found in the lower esophageal mucosa. However, the distribution of these cells is patchy and they may not represent the earliest marker of intestinal metaplasia. Cdx2 is a transcription factor whose expression in normal tissues is restricted to intestinal-type epithelium. Its distribution in the columnar-lined esophagus with and without intestinal metaplasia has been seldom studied. We evaluated Cdx2 expression in lower esophageal biopsies from 90 patients with endoscopic diagnosis of short segment Barrett's esophagus, including 45 consecutive cases showing intestinal metaplasia (goblet cells present in hematoxylin eosin and/or Alcian blue stains) and 45 consecutive cases without goblet cells. 25 samples of cardiac-type mucosa without intestinal metaplasia biopsied from the stomach served as controls. All cases with intestinal metaplasia revealed Cdx2 reactivity in goblet cells and adjacent nongoblet columnar cells. Dysplastic foci, seen in five cases from this group, were Cdx2 positive. In the group without goblet cells, Cdx2 was focally expressed by columnar cells in 17 (38%) cases. All control cases were Cdx2 negative. Strips of Alcian blue-positive nongoblet columnar cells ('columnar blues') were observed in 11 (24%) of the cases without intestinal metaplasia. All these foci were Cdx2 negative. In conclusion, Cdx2 is a highly sensitive marker for Barrett's esophagus. It is also expressed in a significant minority of cases of columnar-lined esophagus without goblet cells, suggesting that it may detect intestinal phenotypic modifications in the absence of goblet cells. Accordingly, Cdx2 immunostaining could help identify patients with Barrett's metaplasia in cases where no goblet cells are visible in biopsies from the columnar-lined esophagus. Finally, lack of Cdx2 expression in the 'columnar blues' suggests that these cells are not diagnostic of intestinal metaplasia.

The value of Cdx2 immunostaining in differentiating primary ovarian carcinomas from colonic carcinomas metastatic to the ovaries.

Histologic differentiation of primary ovarian carcinoma from colonic carcinoma metastatic to the ovary may be difficult. Cytokeratin 7 (CK7) and cytokeratin 20 (CK20) immunostaining is usually used, but these markers lack specificity for ovarian and intestinal epithelium, and overlapping results have been reported. Cdx2 is a transcription factor whose expression in normal tissues is limited to the intestinal epithelium. It is also expressed in the vast majority of colonic carcinomas and in a sizeable proportion of cases of gastric, pancreatobiliary, and ovarian mucinous carcinomas. We evaluated Cdx2, CK7, and CK20 expression in 50 ovarian carcinomas (15 serous, 20 mucinous, and 15 endometrioid), 15 colonic carcinomas metastatic to the ovaries, and 20 primary colonic carcinomas. The extent (1-25%/1+, 26-75%/2+, >75%/3+) and intensity (weak/1+, strong/2+) of staining were recorded semiquantitatively. All primary and metastatic colonic carcinomas had diffuse (3+) strong Cdx2 reactivity. All serous and endometrioid tumors were Cdx2 negative, whereas mucinous carcinomas had 1+ or 2+ immunoreactivity. All ovarian carcinomas had strong diffuse CK7 staining, whereas all colonic carcinomas were negative for CK7. CK20 stained diffusely and strongly all primary and metastatic colonic carcinomas and was 1+ or 2+ in all mucinous carcinomas, in 67% of serous carcinomas, and in 33% of endometrioid carcinomas. In conclusion, 1) Cdx2 is a highly sensitive (100%) marker for colonic carcinoma metastatic to the ovary; 2) Cdx2 is more specific than CK20 as it is not expressed by serous and endometrioid carcinomas; and 3) a limited panel of Cdx2 and CK7 helps in distinguishing colonic carcinomas metastatic to the ovaries (Cdx2+/CK7-) from primary ovarian serous (Cdx2-/CK7+), endometrioid (Cdx2-/CK7+), and mucinous (Cdx2+/CK7+) carcinomas.

CD10 is helpful in detecting occult or inconspicuous endometrial stromal cells in cases of presumptive endometriosis.

BACKGROUND: Previous studies have shown that CD10 is a marker for normal, ectopic, and neoplastic endometrial stromal cells. However, its value in confirming a diagnosis of presumptive endometriosis has not been extensively studied. OBJECTIVE: To assess the reactivity of CD10 in a series of cases of presumptive endometriosis and to establish the potential usefulness of this antibody in confirming the diagnosis. DESIGN: We studied hematoxylin-eosin sections and immunoreactivity of CD10 in 20 cases diagnosed as "suspicious for," "suggestive of," or "compatible with" endometriosis as well as in 12 cases of lesions that may be confused with endometriosis (3 endosalpingioses, 3 mesothelial hyperplasias, 3 ovarian follicular cysts, and 3 hemorrhagic corpora lutea). RESULTS: Routine sections from cases of presumptive endometriosis showed glands lacking a distinct cuff of endometrial stromal cells because of atrophy or because of changes secondary to hemorrhage, inflammation, fibrosis, and/or cystic dilatation. In a few cases, the distinction between endometrial and ovarian stroma could not be assessed with certainty. CD10 immunostaining confirmed the diagnosis in 17 (85%) of the cases, as it strongly stained endometrial stromal cells that were not apparent on hematoxylin-eosin sections. All sections from lesions that may simulate endometriosis were CD10-. CONCLUSION: CD10 is helpful in detecting occult or inconspicuous ectopic endometrial stromal cells and in distinguishing endometriosis from its potential mimickers. We recommend its use to confirm or exclude the presence of endometrial stromal cells in cases of presumptive endometriosis and in lesions that may be mistaken for this entity.