Background The Afirma gene expression classifier (GEC) is used to assess malignancy risk in indeterminate thyroid nodules (ITNs) classified as Bethesda category III/IV. Our objective was to analyze GEC performance at two institutions with high thyroid cytopathology volumes but differing prevalence of malignancy. Methods Retrospective analysis of all ITNs evaluated with the GEC at Memorial Sloan Kettering Cancer Center (MSK; n = 94) and Mount Sinai Beth Israel (MSBI; n = 71). These institutions have differing prevalences of malignancy in ITNs: 30–38 % (MSK) and 10–19 % (MSBI). Surgical pathology was correlated with GEC findings for each matched nodule. Performance characteristics were estimated using Bayes Theorem. Results Patient and nodule characteristics were similar at MSK and MSBI. The GEC-benign call rates were 38.3 % (MSK) and 52.1 % (MSBI). Of the GEC-benign nodules, 8.3 % (MSK) and 13.5 % (MSBI) were treated surgically. Surgical pathology indicated that all of GEC-benign nodules were benign. Of the GEC-suspicious nodules, 60.0 % (MSK) and 61.7 % (MSBI) underwent surgery. Positive predictive values (PPVs) for GEC-suspicious results were 57.1 % (95 % CI 41.0–72.3) at MSK and 14.3 % (95 % CI 0.2–30.2) at MSBI. The estimated negative predictive values (NPVs) were 86–92 % at MSK and 95–98 % at MSBI. Conclusions There were wide variations in the Afirma GEC-benign call rate, PPV, and NPV between MSBI (a comprehensive health system) and MSK (a tertiary referral cancer center), which had differing rates of malignancy in ITNs. The GEC could not routinely alter management in either institution. We believe that this assay would be expected to be most informative in practice settings where the prevalence of malignancy is 15–21 %, such that NPV >95 % and PPV >25 % would be anticipated. Knowing the prevalence of malignancy in ITNs at a particular institution is critical for reliable interpretation of GEC results.

Diagnosing malignancy in bile duct brushings is highly challenging. Seven reviewers of variable backgrounds and levels of participation in bile duct brushing sign out blindly reviewed 60 specimens (30 malignant with histologic confirmation and 30 benign (15 stented) with resection or ≥18 months of uneventful follow-up), testing the utility of 14 malignant characteristics. Eleven characteristics were statistically significantly associated with malignancy including 3-dimensional clusters (63% in malignant vs 3% in benign, odds ratio 50, P=0.0003), pleomorphism (62 vs 3, odds ratio 48, P=0.0004), 2-cell population (60% vs 3, odds ratio 44, P=0.0005), chromatin pattern (hypo/hyperchromasia) changes (70% vs 7%, odds ratio 33, P<0.0001), high nuclear-to-cytoplasmic ratio (48 vs 3%, odds ratio 27, P=0.0023), cytoplasmic vacuoles (43 vs 3%, odds ratio 22, P=0.0042), nuclear irregularity (70 vs 10%, odds ratio 21, P<0.0001), cellular discohesion (38 vs 3%, odds ratio 18, P=0.0082), hypercellularity (23% vs 0), nuclear molding (20% vs 0) and prominent nucleoli (21% vs 0). Necrosis and infiltrating inflammation were not helpful in identifying malignancy ('neutrophil cannibalism' was noted in 43% malignant); 21/30 (70%) malignant brushings had ≥3 malignant characteristics, while 23 (77%) benign brushings had none. Of 20 brushings with ≥4 characteristics, 1(5%) proved benign and showed detachment atypia, a close malignant mimicker in brushings. Identification of 3 characteristics maximized the combined sensitivity (70%), specificity (97%) and accuracy (83%), but sensitivity dropped as number of characteristics increased. Identification of 3/11 characteristics (3-dimensional clusters, pleomorphism, high nuclear-to-cytoplasmic ratio, nuclear irregularity, hypercellularity, discohesion, chromatin changes, vacuoles, prominent nucleoli, molding and 2-cell population) improves pathologists' overall performance greatly.

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Objective: Fine-needle aspiration (FNA) diagnosis of salivary gland neoplasms is often challenging. Differentiating between pleomorphic adenomas (PA) and other basaloid neoplasms, especially basal cell adenoma (BCA) and adenoid cystic carcinoma (AdCC), can be difficult in cellular aspirates. PLAG1 (PA gene 1) is a proto-oncogene, which is frequently rearranged in PAs, leading to the aberrant expression of its protein. PLAG1 IHC expression has been reported to be positive in most PAs. The aim of this study was to evaluate the sensitivity and specificity of PLAG1 to differentiate PA from other basaloid neoplasms. Study Design: Immunohistochemical evaluation of PLAG1 was performed on 125 cases (52 FNAs and 73 surgical excisions). Nuclear staining of tumor cells was scored by the intensity and percentage of positive tumor cells. A combined score of >5 was defined as positive. Results and Conclusion: The sensitivity (55%) and specificity (75%) of PLAG1 in diagnosing PA in FNAs is relatively modest thus limiting its diagnostic utility. BCAs and AdCCs showed PLAG1 false positivity, in surgical excision specimens and less so in FNAs. This may be due to limited sampling or tumor heterogeneity. Hence, PLAG1 is a modest marker for PAs in FNAs.

Context.-Literature on factors impacting bile duct brushings (BDBs) performance characteristics remain limited.Objective.-To capture the current state of daily practice with BDB sign-out.Design.-Two hundred fifty-three of 444 BDBs signed out by more than 7 cytopathologists, with histopathologic and/or clinical follow-up of at least 18 months, were examined.Results. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of malignancy detection were 35%, 100%, 100%, 58%, and 66%, respectively. When atypical, suspicious, and malignant (ASM) categories were combined, sensitivity increased (58%), specificity and PPV dropped (97%), and accuracy increased (73%). Carcinoma type (bile-duct versus pancreatic-ductal) had no effect on accuracy (P ¼ .60) or diagnostic class (P ¼ .84), nor did time of performance (first 7.5 versus latter 7.5 years, P ¼ .13). Interestingly, ThinPrep þ cell block (n ¼ 41) had higher sensitivity (61%) and lower specificity (80%) than ThinPrep only (versus 51% and 100%, respectively). Sensitivity and specificity were higher (47% and 100%) in nonstented than stented specimens (59% and 97%). Relative risk of malignancy for ''suspicious'' (2.30) and ''atypical'' (2.28) categories was lower but not very different from that of ''malignant'' category (2.41).Conclusions.-Bile duct brushings had fairly low sensitivity but high specificity and PPV with no false positives. Sensitivity almost doubled and specificity dipped minimally when ASM categories were combined, highlighting the need for better classification criteria for atypical/suspicious cases. Higher specificity, PPV, NPV, and accuracy but lower sensitivity in stented BDBs suggest that they be called malignant only when evidence is overwhelmingly convincing. (Arch Pathol Lab Med. 2018;142:863-870; doi: 10.5858/ arpa.2017-0150-OA) T he diagnosis of malignancy in the biliary tree remains a clinical and pathologic challenge, with brush cytology being the most frequently used initial diagnostic test. Cytologic diagnosis is especially challenging, as tumors are often well differentiated and thus cytologically bland.Conversely, these well-differentiated examples are closely mimicked morphologically by reactive changes in patients with primary sclerosing cholangitis, nonspecific inflammation, cholelithiasis, and stents. 1,2Most studies on bile duct brushings (BDBs) agree that the sensitivity of this modality is fairly low, although the numbers vary substantially from 6% to 64%, [3][4][5][6][7][8][9][10][11][12][13][14][15][16] and the factors implicated in the test's inaccuracies are also significantly different. These variations are presumably related to case definition (identification) as well as the setting in which the studies were performed and the different methods of specimen processing used. 3,17,18 Consequently, the relative impact of different parameters on BDB interpretation by cytopathologists remains unclear and is yet to be fully unraveled.In this study, in order to capture the current s...

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Suboptimal transfusion documentation remains problematic and is highly correlated with nonjustifiable transfusions. Newly adopted approaches to minimize blood transfusions have not improved transfusion documentation and corresponding out-of-guideline transfusions, although overall transfusions have been reduced by PA, particularly in the setting of a PBM program.

Blood transfusion is a common procedure in the hospital setting, and the safety of the blood supply has been vastly improved over