Objectives Multi-institutional studies are required for the validation of the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC). Methods A total of 1,560 fine-needle aspirations of the salivary glands were retrieved from two institutions for a 12-year period. The diagnoses were reclassified based on the MSRSGC. Risk of malignancy (ROM) for each category was calculated based on 694 histologic follow-up cases. Results The ROM for each category was: 18.3% for nondiagnostic, 8.9% for nonneoplastic, 37.5% for atypia of undetermined significance (AUS), 2.9% for benign neoplasm, 40.7% for salivary gland neoplasm of uncertain malignant potential (SUMP), 100% for suspicious for malignancy, and 98.3% for malignant. The sensitivity, specificity, positive predictive rate, and negative predictive rates were 89%, 99%, 98%, and 96%, respectively. Conclusions The results of the current study are in keeping with the MSRSGC. The indeterminate categories of AUS and SUMP showed intermediate ROMs at 37.5% and 40.7%, respectively.

There is a distinction in the cytologic diagnosis between noninvasive and invasive FVPTC. The invasive subtype was diagnosed by FNA as suspicious for PTC or PTC in nearly 75% of cases, while only one (4%) case for the noninvasive subtype was diagnosed as suspicious for PTC (P < .05).

BACKGROUND. Early cytologic detection and treatment of high‐grade squamous intraepithelial lesion (HSIL) is critical to cervical cancer prevention. The term atypical squamous cells (ASC), cannot exclude HSIL (ASC‐H) was introduced in 2001 in the Bethesda System (TBS 2001) to define changes suggestive, but not diagnostic, of HSIL in the absence of unequivocal squamous intraepithelial lesion (SIL). Previous studies showed that women with ASC‐H cytology are at an increased risk of harboring underlying histopathologic HSIL. TBS 2001, however, did not address the significance of finding ASC‐H changes in a background of unequivocal low‐grade SIL (LSIL). There may be a tendency for cytologists to lump these changes with either LSIL or HSIL, depending on their level of comfort. In their laboratory, the authors have referred to these changes as “LSIL, cannot exclude HSIL” (LSIL‐H). METHODS Between July 2001 and July 2003, all Papanicolaou (Pap) tests that were obtained by using the ThinPrep technique were retrieved from the computer data base at the authors' institution. All categories of squamous cell abnormalities, including LSIL‐H, were evaluated for their incidence and follow‐up diagnoses of HSIL and more severe lesions (HSIL +). All patients had a minimum of 2 year follow‐up by biopsy and cytology (range, 2–4 years). RESULTS LSIL‐H comprised 0.15% (n = 194) of all Pap tests (n = 129,911) that were evaluated during the study period. Follow‐up biopsy was available on 59 patients (30.4%), which showed HSIL + in 40.7% of patients. This rate of associated HSIL + differed significantly from that of LSIL (13%; P < .001) and HSIL (74%; P < .001), but was similar to that of ASC‐H (44.6%). CONCLUSIONS The results from this study showed that patients with cytologic diagnoses of LSIL‐H had an intermediate risk of harboring histopathologic HSIL +. This risk was similar to ASC‐H but fell between the low risk associated with ACS‐US and LSIL and the high risk associated with HSIL cytologic diagnoses. The authors believe that LSIL‐H should be considered as a distinct cytologic diagnostic interpretation and should be separated from LSIL and HSIL. Although LSIL‐H does not represent a unique biologic entity, it has clinical usefulness because of its high positive predictive value for HSIL + lesions. Cancer (Cancer Cytopathol) 2006; 108:. © 2006 American Cancer Society.

The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) has provided a set of uniform diagnostic terminology including benign (B), atypia of undetermined significance (AUS), follicular neoplasm (FN), suspicious for malignancy (SM), malignancy (M), and nondiagnostic (ND) for the interpretation of thyroid fine-needle aspiration (FNA). We applied this terminology on our 1,382 thyroid aspirates in a community practice setting, which included 539 cases of B (39%), 376 cases of AUS (27.2%), 116 cases of FN (8.4%), 37 cases of malignant (2.7%), 36 cases of SM (2.6%), and 278 cases of ND (20.1%). Two hundred twenty-one cases (16%) of thyroid FNA had corresponding follow-up thyroidectomies. Each diagnostic category represented a unique association with risk of malignancy and risk of neoplasm. Based on histologic follow-up, the risk of neoplasm (including benign and malignant neoplasm) was B 14%, AUS 44%, FN 67%, SM 77%, and M 100% and the risk of malignancy was B 3%, AUS 6%, FN 22%, SM 56%, and M 100%. The classification and follow-up recommendation of TBSRTC are appropriate for each category. Both B and AUS are low-risk lesions with low probability of malignancy. FN predicts a higher rate for neoplasm but an intermediate rate for malignancy while SM carries a high risk for malignancy.

Objective To study the level of high‐sensitivity C‐reactive protein (hsCRP) and its relationship with disease activity, damage, and cardiovascular risk factors in patients with systemic lupus erythematosus (SLE). Methods Consecutive patients who fulfilled ≥4 American College of Rheumatology criteria for SLE who did not have a concurrent infection were recruited. Blood was assayed for hsCRP level, and disease activity, organ damage of SLE, and cardiovascular risk factors were assessed. Linear regression analyses were performed for the relationship between hsCRP levels, SLE activity, damage, and cardiovascular risk factors. Results In total, 289 patients were studied (94% women, mean ± SD age 39.0 ± 13.1 years, and mean ± SD SLE duration 7.8 ± 6.7 years). The mean ± SD Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score was 4.9 ± 5.6 and clinically active SLE was present in 122 patients (42%). The mean ± SD hsCRP level was 4.87 ± 12.7 mg/liter, and 28 patients with active SLE (23%) had an undetectable hsCRP level (<0.3 mg/liter). The linear regression analyses revealed a significant correlation between hsCRP level and musculoskeletal disease (β = 0.21), hematologic disease (β = 0.19), active serositis (β = 0.46), and clinical SLEDAI score (β = 0.24) after adjusting for age, sex, body mass index, serum creatinine, and the use of various medications (P < 0.005 for all). hsCRP levels correlated significantly with anti–double‐stranded DNA titer (β = 0.33, P < 0.001) but did not correlate with complement C3 (β = −0.07, P = 0.26). An hsCRP level >3 mg/liter was significantly associated with male sex, long‐term smoking, diabetes mellitus, a higher atherogenic index, and a history of arterial thrombosis. hsCRP levels correlated significantly with pulmonary and endocrine damage scores. Conclusion hsCRP was detectable in 77% of SLE patients with clinically active disease and correlated with SLEDAI scores, particularly in serositis and in the musculoskeletal and hematologic systems. Elevated hsCRP levels in SLE were associated with certain cardiovascular risk factors and a history of arterial thromboembolism.

The cytologic diagnosis of follicular variant of papillary thyroid carcinoma (FVPTC) can be extremely challenging and may be associated with false negative diagnoses. The purpose of this study was to determine the minimal cytologic criteria needed to identify FVPTC. We examined sixty-nine fine-needle aspiration (FNA) cases, processed with Diff-Quik and Papanicolaou stains, that were either diagnostic or suspicious of FVPTC. All cases had histologic confirmation. These cases included 29 FVPTC, 18 classic papillary thyroid carcinoma (PTC), 17 follicular neoplasm (6 adenomas, 10 carcinomas, 1 neoplasm NOS), 2 lymphocytic thyroiditis and 3 nodular goiter. Seven of the most commonly cited cytomorphologic features, including flat syncytial sheets, nuclear enlargement, fine chromatin, nuclear grooves, nuclear pseudoinclusions, and amount of colloid and cytoplasm, were evaluated. A diffuse distribution of fine chromatin, nuclear grooves, and colloid was seen more often in FVPTC than in follicular neoplasm (p<0.01). The combination of flat/syncytial sheets, nuclear enlargement, and fine chromatin was observed in all our cases of FVPTC, and is therefore considered a sensitive marker in detecting FVPTC. Logistic regression analysis revealed colloid to be the only positive predictor in favor of FVPTC over classic PTC.

Specific criteria for the diagnosis of fine-needle aspiration (FNA) of Hürthle Cell Carcinoma (HCC) have rarely been discussed in the literature. A retrospective review of 35 FNA cases with the diagnosis of Hürthle cell lesion or Hürthle cell neoplasm was performed. In each case, there was a subsequent surgical excision. The FNA specimens were divided according to histologic diagnoses as HCC (12 cases), Hürthle cell adenoma (HCA) (14 cases), and benign nonneoplastic Hürthle cell lesions (BNHCL) (9 cases). Each case was examined using a semiquantitative scoring system for the following 11 features: presence or absence of colloid, lymphocytes, and transgressed blood vessels (each scored 0 or 1); the percentage of nuclear enlargement, small cell dysplasia, large cell dysplasia, nuclear crowding, and cellular dyshesion (each scored 0-3); and age, gender, and size of lesion. When diagnosed by FNA as either Hürthle cell neoplasm or Hürthle cell lesion, males were much more likely to have malignant tumors than females. Statistically significant cytologic features that favored malignant (HCC) over benign lesions (HCA and BNHCL) included small cell dysplasia, large cell dysplasia, nuclear crowding, and cellular dyshesion. The presence of colloid and lymphocytes favored a benign lesion. Nuclear enlargement and large tumor size are significantly more common in neoplasms than BNHCL.

Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer with lack of predictive biomarkers. We conducted a study to assess DNA damage repair (DDR) gene mutations as a predictive biomarker in PDAC patients treated with FOLFIRINOX. Indiana University Simon Cancer Center pancreatic cancer database was used to identify patients with metastatic PDAC, treated with FOLFIRINOX and had tissue available for DNA sequencing. Baseline demographic, clinical, and pathologic information was gathered. DNA isolation and targeted sequencing was performed using the Ion AmpliSeq protocol. Overall survival (OS) analysis was conducted using Kaplan-Meier, logistic regression and Cox proportional hazard methods. Multivariate models were adjusted for age, gender, margin status, CA 19-9, adjuvant chemotherapy, tumor and nodal stage. Overall, 36 patients were sequenced. DDR gene mutations were found in 12 patients. Mutations were seen in BRCA1 ( = 7), BRCA2 ( = 5), PALB2 ( = 3), MSH2 ( = 1), and FANCF ( = 1) of all the DDR genes sequenced. Median age was 65.5 years, 58% were male, 97.2% were Caucasian and 51.4% had any family history of cancer. The median OS was near significantly superior in those with DDR gene mutations present vs. absent [14 vs. 5 months; HR, 0.58; 95% confidence interval (CI), 0.29-1.14; log-rank = 0.08]. Multivariate logistic (OR, 1.47; 95% CI, 1.04-2.06; = 0.04) and Cox regression (HR, 0.37; 95% CI, 0.15-0.94; = 0.04) showed presence of DDR gene mutations was associated with improved OS. In a single institution, retrospective study, we found that the presence of DDR gene mutations are associated with improved OS in PDAC patients treated with FOLFIRINOX.