Benign Cohort Research Articles

Pediatric rib lesions: a 13-year experience

Background Rib lesions in the pediatric population are rare but significant processes and are often neoplastic. Methods All patients with primary rib lesions evaluated by the Department of Surgery at Children's Hospital Boston from 1992 to 2005 were studied. The patient's diagnosis, sex, symptoms and their duration, radiologic evaluation, biopsy status, surgical procedure, and follow-up were assessed. Results Thirty-three patients, ages 3 to 23 years (median, 12.7 years), were evaluated. Sixteen patients (48%) had benign and 17 (52%) had malignant lesions. Within the benign cohort of 16 patients, there were 6 osteochondromas, 4 aneurysmal bone cysts, and 2 fibrous dysplasias as well as 1 of each of the following: enchondroma, periosteal chondroma, eosinophilic granuloma, and chondrophyte. Within the malignant cohort of 17 patients, 13 were diagnosed with Ewing's sarcoma, 3 with osteogenic sarcoma, and 1 with chondrosarcoma. The sex distribution for the malignant group was 11 (65%) females and 6 (35%) males. Conclusions Rib tumors are rare entities in the pediatric population. However, a significant number of rib lesions are malignant. Therefore, proper diagnosis and expeditious treatment are critical.

Breast Papillomas in the Era of Percutaneous Needle Biopsy

The significance of breast papillomas detected on core needle biopsy (CNB) remains unclear. While those associated with malignancy or atypia are excised, no clear solution exists for benign papillomas. We sought to determine the indication for surgical excision, incidence of malignancy, significance, and natural history. In this retrospective review, patients were divided into benign, atypical, or malignant cohorts based on initial results. While patients with malignant or atypical features were encouraged to undergo surgical excision, no standard recommendation was given for benign papillomas. Mammographic features, method of initial diagnosis, pathology results, and follow-up data were analyzed. Between January 1994 to December 2005, 5,257 CNBs were performed at our tertiary level medical center. 206 patients were diagnosed with 215 breast papillomas. 174 (81%) papillomas were benign, 26 (12%) were associated with atypia, and 15 (7%) were associated with malignancy. Two benign papillomas (1.1%) developed into cancer over an average of 53 months. Average follow-up of those patients not undergoing excision for benign papilloma was 41 months; we had 92 patients with greater than two year follow-up and 57 patients with greater than four year follow-up. Of patients with atypia or malignancy associated with papilloma, there was a 26% and 87% associated rate of malignancy, respectively. Benign breast papillomas diagnosed by CNB have a low risk of malignancy and do not need excision. However, they should be considered high risk lesions which require serial radiographic monitoring. Papillomas associated with atypia or malignancy should continue to be excised.

Serum Biomarkers to Differentiate Benign and Malignant Mammographic Lesions

Mammographic screening has increased detection of earlier-stage breast cancers and has decreased mortality from breast cancer. A Breast Imaging-Reporting and Data System (BIRADS) 4 classification prompts a biopsy that most often reveals benign disease. Our objective was to determine if serum protein-expression profiles could be used to differentiate between benign and malignant mammographic lesions. After IRB approval, women undergoing an image-guided biopsy for a BIRADS category 4 lesion were recruited. Serum was collected prebiopsy and labeled retrospectively after final pathology was reviewed. Serum was incubated with weak cation exchange magnetic beads and assayed in duplicate for analysis on matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) instrumentation (Bruker Daltonics). Spectra were analyzed using ClinProTools 2.0 software (Bruker Daltonics), and classifications determined using a genetic-clustering algorithm. In a 14-month period, 260 subjects were recruited into this study. Sera from 92 subjects were randomly selected to form benign (n = 46) and cancer (n = 46) cohorts. The MALDI-TOF spectra analysis yielded 273 peaks, with 14 peaks expressed differentially (p < 0.05) between the cancer and benign cohorts. A genetic algorithm model was generated, yielding a sensitivity of 88.3% and specificity of 85.8%. MALDI-TOF protein-expression profiles generated from BIRADS 4 sera could be used to distinguish between benign and malignant mammographic lesions.

Primary Hyperparathyroidism: Can Parathyroid Carcinoma Be Anticipated on Clinical and Biochemical Grounds? Report of Nine Cases and Review of the Literature

Parathyroid carcinoma (PC) mimics benign primary hyperparathyroidism (PHP), but the diagnosis of PC is seldom available at the time of the first operation. Because PC is plagued by recurrences usually beyond cure, one may wonder whether some of these could be prevented by more extensive resections initially, i.e., if the diagnosis of PC were available at that time. Over a 25-year period, 311 consecutive patients with PHP underwent operation in our department: 302 had benign disease (adenomas or hyperplasias), and 9 had PC. Several clinical parameters, serum calcium and parathyroid hormone (PTH) levels, and the weight of the parathyroid tumor removed were compared in both groups. Receiver operating characteristic curves and logistical regression analyses were used to distinguish PC from benign PHP. Eight of 9 patients with PC had symptoms, versus 238 (79%) of 302 with benign PHP (not significant). In the PC subgroup, serum calcium and PTH levels and the tumor weights of the parathyroid glands removed were significantly higher than in the benign PHP cohort, even if these three parameters were regularly flawed by low positive predictive values (14%, 20%, and 15%, respectively). Serum calcium, PTH levels, and tumor weights were significantly greater in the PC subgroup, even if not invariably in a discriminatory way. However, when PTH is <4 times the upper limit of normal and tumor weight is <1.9 g, the probability of PC is nil.

Nuclear Grooves in Normal and Abnormal Cervical Smears

To determine whether the frequency of nuclear grooves in intermediate squamous cells in cervical smears is related to inflammatory or neoplastic events. Sixty benign and 40 neoplastic, nonatrophic cervical smears, collected by conventional methods and stained by Papanicolaou stain, were selected for this study. Twenty smears of the benign cohort showed evidence of inflammation. The neoplastic cohort comprised 20 smears representative of low grade and 20 of high grade squamous intraepithelial lesion (LSIL and HSIL, respectively), with 50% in each group showing evidence of inflammation. The patients, of mixed ethnic backgrounds, were between 18 and 45 years of age. The frequency of nuclear grooves in 100 morphologically benign intermediate squamous cells were determined in each case. The results were evaluated by statistical analysis. The study established that the presence of inflammation had no impact on the frequency of nuclear grooves in benign intermediate squamous cells in either benign or neoplastic smears. When compared with benign smears, there was no increase in the frequency of nuclear grooves in LSIL. Smears of HSIL showed the highest frequency of nuclear grooves. The difference between HSIL and other groups was statistically significant (P < .01). The frequency of nuclear grooves in either normal or neoplastic smears is unrelated to inflammation. In smears with neoplastic changes, an increase in grooved nuclei occurred in HSIL. The mechanism and significance of this observation are unknown and warrant further study.

Prospective study of biliary strictures to determine the predictors of malignancy.

There have been few prospective studies regarding the investigation of biliary strictures, principally because of rapid technological change. The present study was designed to determine the sensitivity of various imaging studies for the detection of biliary strictures. Serum biochemistry and imaging studies were evaluated for their role in distinguishing benign from malignant strictures. Thirty-one patients with suspected noncalculus biliary obstruction were enrolled consecutively in the study. A complete biochemical profile, ultrasound, Disida scan and cholangiogram (endoscopic retrograde cholangiopancreatography [ERCP] or percutaneous cholangiogram) were obtained at study entry. Stricture etiology was determined based on cytology, biopsy and/or clinical follow-up at one year. Twenty-nine of 31 patients had biliary strictures, of which 15 were malignant. The mean age of the malignant cohort was 73.9 years versus 53.9 years in the benign cohort (P<0.001). Statistically significant differences between the malignant and benign groups, respectively, were as follows: alanine transaminase 235.2 versus 66.9 U/L (P=0.004), aspartate transaminase 189.8 versus 84.5 U/L (P=0.011), alkaline phosphatase 840.2 versus 361.1 U/L (P=0.002), bilirubin 317.8 versus 22.1 micromol/L (P<0. 001) and bile acids 242.5 versus 73.2 micromol/L (P=0.001). Threshold analysis using receiver operative characteristic (ROC) curves demonstrated that a bilirubin level of 75 micromol/L was most predictive of malignant strictures. Intrahepatic duct dilation was present in 93% of malignant strictures versus 36% of benign strictures (P=0.002). Common hepatic duct dilation was less discriminatory (malignant 13.5 versus benign 9.6 mm; P=0.11). Ultrasound was highly sensitive (93%) in the detection of the primary tumour in the bile duct or pancreas, or in the visualization of nodal or liver metastases. In benign disease, ultrasound failed to detect evidence of intrahepatic or extrahepatic biliary dilation in most cases. Disida scans were not able to distinguish between malignant or benign strictures and could not accurately localize the level of obstruction. The sensitivity of Disida scan for the diagnosis of obstruction was 50%. Cholangiographic characterization of strictures revealed an equal distribution of smooth (eight of 13) and irregular (five of 13) strictures in the malignant group. Ten of 13 benign strictures were characterized as smooth. Malignant strictures were significantly longer than benign ones - 30.3 versus 9.2 mm (P=0.001). Threshold analysis using ROC curves showed that strictures greater than or equal to 14 mm were predictive of malignancy (sensitivity 78%, specificity 75%, log odds ratio 11.23). A serum bilirubin level of 75 micromol/L or higher, or a stricture length of greater than 14 mm was highly predictive of malignancy in patients with a biliary stricture. Ultrasound was useful in predicting malignant strictures by detecting either intrahepatic duct dilation or by visualizing the tumour (primary or metastases). Strictures with a 'benign' cholangiographic appearance are frequently malignant. Disida scan did not add additional information. ERCP is necessary to diagnose benign strictures, which tend to be less extensive at presentation.