Neighborhood and racial influences on triple negative breast cancer: evidence from Northeast Ohio.

PURPOSE: Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer (BC) with higher recurrence rates and poorer prognoses and most prevalent among non-Hispanic Black women. Studies of multiple health conditions and care processes suggest that neighborhood socioeconomic position is a key driver of health disparities. We examined roles of patients' neighborhood-level characteristics and race on prevalence, stage at diagnosis, and mortality among patients diagnosed with BC at a large safety-net healthcare system in Northeast Ohio. METHODS: We used tumor registry to identify BC cases from 2007 to 2020 and electronic health records and American Community Survey for individual- and area-level factors. We performed multivariable regression analyses to estimate associations between neighborhood-level characteristics, measured by the Area Deprivation Index (ADI), race and comparative TNBC prevalence, stage at diagnosis, and total mortality. RESULTS: TNBC was more common among non-Hispanic Black (53.7%) vs. non-Hispanic white patients (46.4%). Race and ADI were individually significant predictors of TNBC prevalence, stage at diagnosis, and total mortality. Race remained significantly associated with TNBC subtype, adjusting for covariates. Accounting for TNBC status, a more disadvantaged neighborhood was significantly associated with a worse stage at diagnosis and higher death rates. CONCLUSION: Our findings suggest that both neighborhood socioeconomic position and race are strongly associated with TNBC vs. other BC subtypes. The burden of TNBC appears to be highest among Black women in the most socioeconomically disadvantaged neighborhoods. Our study suggests a complex interplay of social conditions and biological disease characteristics contributing to racial disparities in BC outcomes.

Patients with Nonalcoholic Fatty Liver Disease Have a Low Response Rate to Vitamin D Supplementation.

Background: Hypovitaminosis D is associated with an increased severity of nonalcoholic fatty liver disease (NAFLD), but reports on the response to cholecalciferol (vitamin D3) supplementation are conflicting.Objective: The objective of this study was to determine if standard vitamin D3 supplementation is effective in NAFLD with hypovitaminosis D.Methods: Sixty-five well-characterized adults [age (mean ± SD): 51.6 ± 12.3 y] with biopsy-proven NAFLD were screened. Forty-two patients (the ratio of men to women was 13:29) had hypovitaminosis D (plasma 25-hydroxyvitamin D [25(OH)D] <30 ng/mL). An observational study was performed in NAFLD patients with hypovitaminosis D treated with 2000 IU cholecalciferol (vitamin D3) daily for 6 mo per clinical practice. Plasma 25(OH)D, hepatic and metabolic panels, and metabolic syndrome components were assessed before and after cholecalciferol supplementation. Body composition was measured by using bioelectrical impedance analysis. The primary outcome measure was plasma 25(OH)D ≥30 ng/mL at the end of the study. Secondary outcomes included change in serum transaminases, fasting plasma glucose, and insulin and homeostasis model assessment of insulin resistance (HOMA-IR). Chi-square, Student's t tests, correlation coefficient, and multivariate analysis were performed.Results: Twenty-six (61.9%) patients had nonalcoholic steatohepatitis (NASH), and 16 (38.1%) had hepatic steatosis. After 6 mo of cholecalciferol supplementation, plasma 25(OH)D ≥30 ng/mL was observed in 16 subjects (38.1%; responders) whereas the remaining 26 patients (61.9%) were nonresponders with plasma 25(OH)D <30 ng/mL. Significantly fewer (P < 0.01) patients with NASH were responders (4 of 26, 15.4%) than those with hepatic steatosis (12 of 16, 75%). Baseline fasting serum alanine aminotransferase, plasma glucose, and HOMA-IR were similar in the responders and nonresponders, but the NASH score on the liver biopsy was lower (16.5%) in the responders (P < 0.001). Nonresponders had a higher fat mass (10.5%) and lower fat-free mass (10.4%) than responders did. End-of-treatment alanine aminotransferase and HOMA-IR improved only in responders. The baseline HOMA-IR and histological NASH score were independent predictors of nonresponse to cholecalciferol supplementation.Conclusions: Daily supplementation with 2000 IU cholecalciferol for 6 mo did not correct hypovitaminosis D in the majority of patients with NASH. Further studies are needed to determine if higher doses are effective. This trial was registered at clinicaltrials.gov as 13-00153.

The development of a non-invasive model to predict the presence of non-alcoholic steatohepatitis in patients with non-alcoholic fatty liver disease.

BACKGROUND: Non-alcoholic steatohepatitis (NASH) is an advanced and aggressive form of non-alcoholic fatty liver disease (NAFLD), which remains difficult to diagnose without a liver biopsy. Hyperferritinemia has increasingly been associated with the presence of NASH. Hence, we sought to explore the relationship between ferritin and NASH and to develop a composite model based on ferritin to predict the presence of NASH. METHODS: A total of 405 patients with biopsy-proven NAFLD were enrolled in the study. Comparison was explored to assess differences between patients with and without NASH, upon which a scoring model was established using variables found to be independent predictors of NASH. RESULTS: Among all patients with NAFLD, 291 (72%) had biopsy-proven NASH, and 114 (28%) had non-NASH. Mean age was 48 ± 12 years, and 56% were female. Ferritin was significantly higher in NASH compared with non-NASH patients (184 vs 126, respectively; P < 0.001) but lacked diagnostic accuracy for predicting NASH alone (area under the curve [AUC 0.62]). The addition of other significant variables such as aspartate aminotransferase, body mass index, platelet count, diabetes, and hypertension to ferritin improved the prediction of NASH with an AUC 0.81 (95% confidence interval: 0.76-0.86). Internal validation of the model using imputed data sets demonstrated that AUC did not change materially. CONCLUSIONS: While higher ferritin was significantly associated with NASH, ferritin alone lacked diagnostic accuracy to predict NASH. However, incorporating several easily obtainable variables with ferritin allowed the construction of a novel scoring system that can be easily applied in the clinical setting to guide management of NAFLD.

Renin-angiotensin system and fibrosis in non-alcoholic fatty liver disease.

BACKGROUND & AIMS: Therapeutic options are limited for patients with non-alcoholic fatty liver disease (NAFLD). One promising approach is the attenuation of necroinflammation and fibrosis by inhibition of the renin-angiotensin system (RAS). We explored whether the risk of fibrosis was associated with the use of commonly used medications in NAFLD patients with hypertension. Specifically, we sought to determine the association between RAS blocking agents and severity of hepatic fibrosis in NAFLD patients with hypertension. METHODS: Cross-sectional study where clinical information including demographics, anthropometry, medical history, concomitant medication use, biochemical and histological features were ascertained in 290 hypertensive patients with biopsy proven NAFLD followed at two hepatology outpatient clinics. Stage of hepatic fibrosis was compared in patients with and without RAS blocker use. Other risk factors for fibrosis were evaluated from the electronic medical records and patient follow-up. RESULTS: Baseline characteristics of hypertensive patients treated with and without RAS blockers were similar except for less ballooning (1.02 vs. 1.31, P = 0.001) and lower fibrosis stage (1.63 vs. 2.16, P = 0.002) in patients on RAS blockers On multivariate analysis, advancing age (OR: 1.04; 95%CI: 1.01-1.06, P = 0.012) and presence of diabetes (OR: 2.55; 95%CI: 1.28-5.09, P = 0.008) had an independent positive association, while use of RAS blockers (OR: 0.37; 95%CI: 0.21-0.65, P = 0.001) and statins (OR: 0.52; 95%CI: 0.29-0.93, P = 0.029) had a negative association with advanced fibrosis. CONCLUSION: Hypertensive patients with NAFLD on baseline RAS blockers had less advanced hepatic fibrosis suggesting a beneficial effect of RAS blockers in NAFLD.

Double-blind randomized placebo-controlled clinical trial of omega 3 fatty acids for the treatment of diabetic patients with nonalcoholic steatohepatitis.

BACKGROUND: Nonalcoholic steatohepatitis (NASH) is common and severe in patients with diabetes mellitus. Although, there are no effective treatments for NASH in diabetic patients, preliminary reports suggest that polyunsaturated fatty acids (PUFA) may be beneficial in these patients. AIM: A prospective, randomized, double-blind placebo-controlled study (NCT 00323414) was performed in NASH patients with diabetes. Clinicaltrials.gov (NCT 00323414). SUBJECTS AND METHODS: A total of 37 patients (50.6 ± 9.8 y) with well-controlled diabetes (HbA1C<8.5%) were randomized to receive either PUFA containing eicosapentaenoic acid (2160 mg) and docosahexaenoic acid (1440 mg) daily or an isocaloric, identical placebo containing corn oil for 48 weeks under CONSORT guidelines. Clinical, demographics, biochemical laboratory tests, body composition using DEXA, and liver biopsy were performed at randomization and at the end of treatment. Liver biopsy was scored by the NASH CRN criteria. An intention-to-treat analysis was performed. RESULTS: At inclusion, sex, age, body weight, biochemical tests, glucose control, and liver histology were similar in the 2 treatment groups. There was no change in liver enzymes, body weight, or body composition during the study in either group. At the end of the treatment, hepatic steatosis and the activity score improved (P<0.05) and lobular inflammation worsened (P<0.001) with placebo but was unchanged with PUFA. At the end of the treatment, insulin resistance (serum glucose and HOMA) worsened with PUFA but not placebo. CONCLUSIONS: PUFA provided no benefit over placebo in NASH patients with diabetes. The effects of PUFA on histology and insulin resistance were inferior to placebo. These data provide no support for PUFA supplements in NASH.

Age impacts ability of aspartate-alanine aminotransferase ratio to predict advanced fibrosis in nonalcoholic Fatty liver disease.

BACKGROUND AND AIM: While histological differences have been reported between pediatric and adult nonalcoholic fatty liver disease (NAFLD), potential age-related changes in serum transaminases and liver histology remain largely unexplored. Our study sought to investigate the clinical and histological characteristics of NAFLD across age. METHODS: This was a prospective cross-sectional study of 502 biopsy-proven NAFLD patients. Clinical data were evaluated and compared among different age groups; group A (ages 18-44), B (ages 45-64), and C (≥ ages 65). RESULTS: 34.9, 56.0, and 9.1 % of the cohort were distributed among group A, B, and C, respectively. While the prevalence of nonalcoholic steatohepatitis (NASH) was comparable across age groups, the prevalence of advanced fibrosis increased with age (p = 0.000). Although the mean ALT progressively decreased with age; 87, 64, 56 U/L in group A, B, and C, respectively (p = 0.000), there was no difference in mean AST (p = 0.939) across age. The AST:ALT ratio (AAR) progressively increased from 0.7, 0.9, and 1.1 in group A, B, and C, respectively (p = 0.000). In group C, an AAR ≥ 1 was found in 74 and 40 % of patients with and without advanced fibrosis. CONCLUSION: With advancing age, ALT levels progressively declined while AST levels remained stable, leading to a higher AAR. Although higher AAR is often used as a surrogate measure of advanced fibrosis, advancing age can also contribute to increased AAR. In fact, an AAR ≥ 1 was found in significant number of elderly patients without advanced fibrosis. Consequently, an increased AAR may be a function of decreasing ALT with age in addition to progressive fibrosis.

Hypovitaminosis D is associated with increased whole body fat mass and greater severity of non-alcoholic fatty liver disease.

BACKGROUND & AIMS: Hypovitaminosis D is common in obesity and insulin-resistant states. Increased fat mass in patients with non-alcoholic fatty liver disease (NAFLD) may contribute to hypovitaminosis D. To determine the relation among plasma vitamin D concentration, severity of disease and body composition in NAFLD. METHODS: Plasma vitamin D concentration was quantified in 148 consecutive biopsy-proven patients with NAFLD (non-alcoholic steatohepatitis - NASH: n = 81; and hepatic steatosis: n = 67) and healthy controls (n = 39). NAFLD was scored using the NASH CRN criteria. Body composition was quantified by bioelectrical impedance analysis and abdominal CT image analysis. RESULTS: Plasma vitamin D concentration was significantly lower in NAFLD (21.2 ± 10.4 ng/ml) compared with healthy controls (35.7 ± 6.0 ng/ml). Higher NAFLD activity scores were associated with lower plasma concentration of vitamin D (r(2)  = 0.29; P < 0.001). Subgroup analysis among patients with NAFLD showed that patients with NASH had significantly lower (P < 0.01) vitamin D levels than those with steatosis alone (18.1 ± 8.4 vs. 25.0 ± 11.3 ng/ml). Low concentrations of vitamin D were associated with greater severity of steatosis, hepatocyte ballooning and fibrosis (P < 0.05).On multivariate regression analysis, only severity of hepatocyte ballooning was independently associated (P = 0.02) with low vitamin D concentrations. Plasma vitamin D (P = 0.004) and insulin concentrations (P = 0.03) were independent predictors of the NAFLD activity score on biopsy. Patients with NAFLD had higher fat mass that correlated with low vitamin D (r(2)  = 0.26; P = 0.008). CONCLUSIONS: Low plasma vitamin D concentration is an independent predictor of the severity of NAFLD. Further prospective studies demonstrating the impact of vitamin D replacement in NAFLD patients are required.

YB1 Is a Major Contributor to Health Disparities in Triple Negative Breast Cancer.

Triple negative breast cancer (TNBC) is the most aggressive amongst all breast cancer (BC) subtypes. While TNBC tumors represent less than 20% of all BC subtypes, they are responsible for the most BC-related deaths. More significantly, when considering TNBC incidence across all racial/ethnic groups, TNBC accounts for less than 20% of all BCs. However, in non-Hispanic black women, the incidence rate of TNBC is more than 40%, which may be a contributing factor to the higher BC-related death rate in this population. These disparities remain strong even after accounting for differences in socioeconomic status, healthcare access, and lifestyle factors. Increased evidence now points to biological mechanisms that are intrinsic to the tumor that contribute to disparate TNBC disease burdens. Here, we show that YB1, a multifunction gene, plays a major role in the TNBC disparities between African American (AA) and Caucasian American (CA) women. We show in three independent TNBC tumors cohorts, that YB1 is significantly highly expressed in AA TNBC tumors when compared to CAs, and that increased levels of YB1 correlate with poor survival of AA patients with TNBC. We used a combination of genetic manipulation of YB1 and chemotherapy treatment, both in vitro and in animal models of TNBC to show that YB1 oncogenic activity is more enhanced in TNBC cell lines of AA origin, by increasing their tumorigenic and aggressive behaviors, trough the activation of cancer stem cell phenotype and resistance to chemotherapeutic treatments.

A rare case of a non-neural granular cell tumor presenting as an enlarging right chest wall nodule in a 4-year-old male and review of the literature.

Non-neural granular cell tumor was first described in 1991 as an unusual primitive, polypoid variant of the conventional granular cell tumor. To date, this neoplasm remains a rare entity and the cell of origin is uncertain. While the histological features are similar to the conventional granular cell tumor, it represents a distinct entity that is negative for S100 and lacks true nerve sheath differentiation. Here, we describe a case of a 4-year-old male who presented with a painless, soft nodule on his right chest wall that was slowly increasing in size. The mass was excised and sent for pathologic analysis. Microscopic examination reveals spindle and epithelioid cells with vesicular nuclei and prominent granular eosinophilic cytoplasm. Immunohistochemical analysis shows negative staining for S100 and AE1/AE3/PCK26 but is positive for CD68. A diagnosis of a non-neural granular cell tumor was made. We report a rare and diagnostically challenging case in a pediatric patient.

Validity of real time ultrasound in the diagnosis of hepatic steatosis: a prospective study.

BACKGROUND/AIMS: Ultrasound is used to screen for hepatic steatosis, the most common liver disease in the United States. However, few studies have prospectively evaluated the accuracy of ultrasound to diagnose hepatic steatosis. Therefore, a double blinded prospective study was performed in consecutive patients undergoing liver biopsy to evaluate the accuracy of ultrasound to diagnose hepatic steatosis. METHODS: Real time ultrasound was performed just prior to the biopsy by a single investigator masked to the clinical diagnosis. The liver biopsy was reviewed by a pathologist masked to the clinical indication or sonographic findings. RESULTS: Of 73 consecutive patients studied, macrovesicular steatosis of any severity on biopsy was found in 46 (63%) and micro vesicular fat found in 51 (69.9%). The overall impression of the sonographer for the presence of macrovesicular hepatic steatosis of any degree had a sensitivity of 60.9% and a specificity of 100%. The sensitivity increased to 100% and the specificity to 90% when there was > or =20% of fat. The zonular distribution of the fat did not alter the diagnostic accuracy of ultrasound. Ultrasound had a poor yield in the diagnosis of microvesicular fat with an overall sensitivity of 43% and a specificity of 73%. The combination of increased echogenicity and portal vein blurring on ultrasound had the greatest sensitivity in the diagnosis of hepatic steatosis. CONCLUSION: Real time ultrasound using a combination of sonographic findings has a high specificity but underestimates the prevalence of hepatic steatosis when there is<20% fat.

Fine-needle aspiration biopsy of thyroid nodules: Is routine ultrasound-guidance necessary?

BACKGROUND: Current guidelines recommend either ultrasound-guided or palpation-guided fine-needle aspiration biopsy for evaluation of a thyroid nodule. However, it has been suggested that ultrasound-guided fine-needle aspiration biopsy should be used routinely in all patients to reduce the rate of nondiagnostic and false negative results. The purpose of this study was to determine whether any difference exists in nondiagnostic and false negative rates between the two methods of fine-needle aspiration biopsy at our institution. METHODS: A retrospective review of a prospectively maintained thyroid database was completed to determine the rates of nondiagnostic and false negative fine-needle aspiration biopsy in patients with nodular thyroid disease evaluated during the period 1990-2017. RESULTS: From 1990 to 2017, a total of 2,322 patients underwent fine-needle aspiration biopsy for evaluation of nodular thyroid disease, 1,123 (48%) underwent ultrasound-guided fine-needle aspiration biopsy and 1,199 (52%) underwent palpation-guided fine-needle aspiration biopsy. Ultrasound-guided fine-needle aspiration biopsy was nondiagnostic in 4.5% and had a 5.2% false negative rate, compared with palpation-guided fine-needle aspiration biopsy, which was nondiagnostic in 5.0% and had a 2.6% false negative rate (P = .53 and .14, respectively). CONCLUSION: The rate of nondiagnostic and false negative fine-needle aspiration biopsy results is similar whether US guidance is used or not. To minimize resource utilization, ultrasound-guided fine-needle aspiration biopsy can be used selectively for nonpalpable, predominantly cystic, or previously nondiagnostic nodules.

ThinPrep Pap tests in patients with endometrial cancer: a histo-cytological correlation.

The aim of this retrospective study was to correlate cytological diagnoses of endometrial cancers in ThinPrep Pap tests with the histological diagnoses. ThinPrep specimens from 67 patients within 12 mo of the histological diagnosis of endometrial cancer were studied. Of this study sample, 89.6% had abnormal Pap tests. Abnormal Pap tests occurred in 96.8, 68.4, and 100% of patients with grades 1, 2, or 3 endometrial cancers, respectively. Of patients with endocervical involvement, 88.9% had positive or suspicious Pap tests, compared with 41.1% without endocervical involvement (LR = 7.85, P < 0.01). Of patients with > or =50% myometrial invasion, 78.9% had positive or suspicious Pap tests, compared with 34.8% with less than 50% invasion (LR = 10.97, P < 0.01). Positive or suspicious Pap tests were found in 59.5 and 32.1% of those with tumors > or =3 cm or <3cm, respectively (LR = 4.85, P < 0.05).

Diagnostic value of the thin-layer, liquid-based Pap test in endometrial cancer: a retrospective study with emphasis on cytomorphologic features.

OBJECTIVE: To examine the diagnostic value (sensitivity and specificity of the ThinPrep Pap test in the detection of endometrial cancer and assess the morphologic features of endometrial cancer in ThinPrep tests. STUDY DESIGN: In a retrospective, case-controlled study, we identified 60 Pap slides performed within 12 months of the tissue diagnosis of endometrial carcinoma and 56 comparison slides from patients without known carcinoma. The slides were blindly reviewed by the authors without knowledge of the surgical diagnosis. An independent diagnosis was given for the tests based on 14 diagnostic criteria from the 2001 Bethesda System and 6 additional criteria proposed by the authors. RESULTS: The sensitivity of detecting endometrial carcinoma was 88.3% (95% CI 77.8-94.2%) and specificity was 87.5% (95% CI 76.4-93.8%). The positive likelihood ratio was 7.067 (95% CI 3.513-14.217) and negative likelihood ratio was 0.133 (95% CI 0.066-0.269). Enlarged nuclei and the presence of nucleoli in endometrial cells were the most reliable indicators of endometrial cancer or atypical endometrial cells. CONCLUSION: The ThinPrep Pap test has high sensitivity and specificity in detecting or suggesting the presence of endometrial cancer. Certain cytomorphologic features are helpful in distinguishing benign and malignant endometrial lesions.

Concordant clear cell "mesonephric" carcinoma of the bladder and lung adenocarcinoma with clear cell features - multiple primaries versus metastatic neoplasms: a case report.

BACKGROUND: Clear cell carcinoma of the bladder is a rare variant of urinary bladder adenocarcinoma. We report a case of a patient with clear cell carcinoma of the bladder and a concordant right upper lobe pulmonary adenocarcinoma with clear cell features, and we address the role of immunohistochemistry and cytogenetic analysis in distinguishing the two primary malignancies. CASE PRESENTATION: Our patient was a 59-year-old African American woman who presented with hematuria. Her past medical history included invasive mammary carcinoma and end-stage renal disease treated with hemodialysis. A computed tomographic urogram revealed a 3-cm polypoid bladder mass. A follow-up chest computed tomographic scan revealed a 1-cm right upper lobe nodule. The patient underwent transurethral biopsy and subsequent radical cystectomy, as well as a transthoracic core needle biopsy of the lung nodule. Histologically, the bladder tumor consisted of flat, cuboidal to columnar cells with clear or eosinophilic cytoplasm and a hobnail appearance, organized in tubulocystic and papillary patterns. The neoplastic cells were diffusely positive for α-methylacyl-coenzyme A racemase, cancer antigen 125, and cytokeratin 7; focally positive for cytokeratin 20, P53, and carcinoembryonic antigen; and negative for thyroid transcription factor 1. The lung tumor demonstrated a glandular architecture with mucin production (positive for mucin with mucicarmine and periodic acid-Schiff with diastase stain). The neoplastic cells were diffusely positive for cytokeratin 7, napsin A, and thyroid transcription factor 1, and they were negative for cytokeratin 20 and cancer antigen 125. Genetic testing of the pulmonary neoplasm demonstrated ARID2 genomic alterations. CONCLUSIONS: The presence of clear cell features in both neoplasms raised the possibility of lung metastasis from the primary bladder tumor. However, the glandular architecture of the lung neoplasm along with its distinctive immunohistochemical and genetic profiles confirmed the presence of two separate primaries.

When fine-needle aspiration biopsy cannot exclude papillary thyroid cancer: a therapeutic dilemma.

HYPOTHESIS: Clinical or cytologic factors predictive of malignancy can be identified and incorporated into a treatment algorithm for patients with a fine-needle aspiration biopsy (FNAB) specimen interpreted as "suspicious for" papillary thyroid cancer (PTC). DESIGN: Retrospective review of a prospectively maintained database. SETTING: University-affiliated tertiary care hospital. PATIENTS: Seven hundred thirty-eight patients with nodular thyroid disease evaluated between 1990 and 2004. INTERVENTIONS: Patients with an FNAB specimen suspicious for PTC were identified. The frequency of carcinoma was determined. Clinical features were reviewed. The FNAB specimens suspicious for PTC were examined in a blinded fashion to determine if specific cytologic features were important in distinguishing benign vs malignant disease. MAIN OUTCOME MEASURES: The presence of specific clinical and cytologic features was correlated with the incidence of carcinoma. A secondary outcome measure was to determine the value of frozen section examination in establishing the extent of thyroidectomy. RESULTS: Forty-five patients (7%) had an FNAB specimen suspicious for PTC; 18 (40%) of these patients had carcinoma. Prominent nuclear inclusions and/or grooves, papillary formations, and the absence of colloid were features associated with PTC (P<.05). No clinical features reliably identified malignant disease. Frozen section examination results altered treatment in 15 (56%) of 27 patients. CONCLUSIONS: An FNAB specimen suspicious for PTC is associated with a 40% incidence of carcinoma. Extensive nuclear inclusions and/or grooves, papillary formations, and the absence of colloid are predictive of carcinoma. Rare intranuclear inclusions and/or grooves alone in an otherwise benign-appearing specimen are uniformly associated with benign disease. Frozen section examination is of value in determining the extent of thyroidectomy.

Fine-needle aspiration biopsy specimen with a predominance of Hürthle cells: a dilemma in the management of nodular thyroid disease.

BACKGROUND: A fine-needle aspiration biopsy (FNAB) specimen of a thyroid nodule with a predominance of Hürthle cells usually is indicative of a Hürthle cell neoplasm, but it also may occur with nonneoplastic disease. METHODS: A prospective nodular thyroid disease database was used to identify patients with a FNAB specimen consisting of a predominance of Hürthle cells. Clinical factors were investigated and FNAB specimens were examined in a blinded fashion by a single cytopathologist to determine if there were specific factors that could be used to distinguish nonneoplastic from neoplastic disease. RESULTS: Of the 738 patients with nodular thyroid disease, 622 had a FNAB specimen. The FNAB specimen was interpreted as consistent with a Hürthle cell neoplasm in 45 (7%) patients, 7 (16%) with carcinoma, 21 (47%) with adenoma, 12 (27%) with adenomatous hyperplasia, and 5 (11%) with thyroiditis. Extensive cellularity and absent colloid were associated with neoplastic disease (P < .05). No cytologic feature reliably excluded neoplastic disease (P > .05). No significant differences in age (x +/- SD) (51 +/- 17 vs 54 +/- 17 y), sex (female/male ratio, 6/1 vs 15/2), nodule size (3.9 +/- 1.9 vs 3.4 +/- 2.0 cm), weight of excised thyroid tissue (42 +/- 27 vs 33 +/- 30 g), or functional status of the thyroid gland was observed between patients with neoplastic (n = 28, 62%) versus nonneoplastic (n = 17, 38%) disease. CONCLUSIONS: Neoplastic disease accounts for two thirds of the pathology in patients with a predominance of Hürthle cells on FNAB specimen and neither clinical nor cytologic features reliably exclude Hürthle cell adenoma or carcinoma. As a result, thyroidectomy is recommended for all patients with a thyroid nodule and a predominance of Hürthle cells on FNAB specimen.

Clinical spectrum of non-alcoholic fatty liver disease in diabetic and non-diabetic patients.

BACKGROUND: While non-alcoholic fatty liver disease (NAFLD) has been well characterised in patients with diabetes mellitus (DM), less is known about NAFLD in non-DM patients. We investigated the clinical characteristics of NAFLD patients with and without DM and accuracy of the NAFLD fibrosis score (NFS) in these two NAFLD groups. METHODS: Clinical, biochemical and histological variables were evaluated in this prospective cross-sectional study of 503 patients with biopsy proven NAFLD. Comparisons between patients with and without DM were analysed. NFS was correlated with liver histology to assess its robustness in patients with and without DM. RESULTS: There were 503 biopsy proven NAFLD patients with 48% of the cohort being diabetic. Relative to patients without DM, patients with DM were older (52 vs. 46 years, p < 0.001), with higher proportion of females (70% vs. 54%, p < 0.001), higher BMI (37 vs. 35, p = 0.009), higher prevalence of hypertension (73% vs. 44%, p < 0.001), higher prevalence of NASH (80.2% vs. 64.4%; p < 0.001) and advanced fibrosis (40.3% vs. 17.0%; p < 0.001). A considerable amount of patients without DM still had NASH (64%) and advanced fibrosis (17%). The clinical utility of the NFS differed between NAFLD patients with and without DM, with sensitivity to exclude advanced fibrosis being 90% of NAFLD patients with DM but only 58% of patients without DM. CONCLUSION: Patients with DM have more severe NAFLD based on histology. However, NASH and advanced fibrosis also occur in a considerable proportion of NAFLD patients without DM. The lower utility of the NFS in NAFLD patients without DM emphasises the heterogeneous nature of the NAFLD phenotype.

Adenomatoid tumor of the adrenal gland with micronodular adrenal cortical hyperplasia.

We report a case of an adenomatoid tumor (AT) of an adrenal gland with micronodular adrenal cortical hyperplasia (ACH). A 51-year-old man was found to have newly developed hypertension with clinical evidence of primary aldosteronism. A computerized tomogram of the abdomen revealed a solitary mass in the right adrenal gland. He underwent a right adrenalectomy for a presumptive clinical diagnosis of a solitary aldosterone-producing adrenal cortical adenoma. On histopathologic examination, the adrenal gland demonstrated an AT, diagnosed by the characteristic histological features, immunohistochemical stain results, and electron microscopic findings. The surrounding adrenal cortex showed multiple small hyperplastic cortical nodules. After the adrenalectomy, the patient's blood pressure normalized. Primary AT of the adrenal gland coexisting with micronodular ACH associated with hypertension has not been previously reported.