Faculty Bibliography

Translational regulation is critical in cancer development and progression. Translation sustains tumor growth and development of a tumor vasculature, a process known as angiogenesis, which is activated by hypoxia. Here we first demonstrate that a majority of large advanced breast cancers overexpress translation regulatory protein 4E-BP1 and initiation factor eIF4G. Using model animal and cell studies, we then show that overexpressed 4E-BP1 and eIF4G orchestrate a hypoxia-activated switch from cap-dependent to cap-independent mRNA translation that promotes increased tumor angiogenesis and growth at the level of selective mRNA translation. Elevated levels of 4E-BP1 trigger hypoxia inhibition of cap-dependent mRNA translation at high-oxygen levels and, with eIF4G, increase selective translation of mRNAs containing internal ribosome entry sites (IRESs) that include key proangiogenic, hypoxia, and survival mRNAs. The switch from cap-dependent to cap-independent mRNA translation facilitates tumor angiogenesis and hypoxia responses in animal models

Objective: While the use of fine needle aspiration (FNA) in the diagnosis of gastrointestinal stromal tumours (GISTs) is well-established, it can be difficult to predict the prognosis of GIST based on morphology alone. The objective of the current study was to determine if expression of bcl-2, Ki-67 and p53 correlated with the outcome of GISTs based on cytological material. Methods: Cell-blocks from 14 GISTs diagnosed by FNA were retrieved. Immunostaining was performed with antibodies against bcl-2, Ki-67 and p53. All cytological diagnoses were confirmed by positive immunostaining with c-kit and/or subsequent histological evaluation. Positivity for bcl-2, Ki-67 and p53 was defined as the presence of >= 10% cytoplasmic staining, >= 5% nuclear staining and >= 5% nuclear staining respectively. Results: The 14 patients consisted of seven males and seven females with a mean age of 58 years. The average follow-up interval was 46 months. Six had a benign course and eight developed recurrences/metastases. Thirteen (93%) cases showed positive staining for bcl-2. Positive Ki-67 and p53 staining was noted in one (7%) and seven (50%) cases respectively. The difference in staining for p53 between aggressive and non-aggressive GISTs was statistically significant. No statistically significant difference was noted for bcl-2 staining or Ki-67 labelling index between the two groups. Conclusions: According to our observations, p53 immunostaining may be useful in predicting the outcome of GIST diagnosed by FNA; Ki-67 and bcl-2 are not useful as prognostic markers for GIST in FNA specimens

Fine-needle aspiration cytology (FNAC) of the head and neck region is well accepted as a diagnostic procedure in the adult population. FNAC in the pediatric population is gaining acceptance as clinicians add this technique to the diagnostic armamentarium. An experience with FNAC of the head and neck region in the pediatric population is described from 2 large inner-city hospitals. Eighty-five cases were retrieved from patients age <18 years. In 52 cases, clinical or surgical follow-up was obtained and among these cases the specificity and sensitivity of FNA was 93% and 100%, respectively. The high specificity of FNAC allows the clinician to be confident of malignancy in a clinically suspicious lesion of the head and neck in a pediatric patient. Cancer (Cancer Cytopathol) 2007. (c) 2007 American Cancer Society.

We report a case of an intraparenchymal leiomyoma of the breast with description of the radiologic, histopathologic, and immunohistochemical findings. To the best of our knowledge, this is the first case of an intraparenchymal leiomyoma of the breast diagnosed by core needle biopsy and the 22nd case described in the literature. In addition, we review the literature on this uncommon breast neoplasm

The use offine-needle aspiration biopsy or percutaneous core needle biopsy to diagnose breast lesions has increased during the past few decades. Although the benefits of these procedures are well known, controversies remain about the management of certain categories of breast lesions detected by these methods. This article discusses the management issues in categories of breast lesions, including papillary lesions, atypical lobular hyperplasia and lobular carcinoma in situ, and mucinous lesions diagnosed by the preoperative techniques of aspiration or core biopsy

CDX-2 is a homeobox gene, which encodes a transcription factor that plays a vital role in the development and differentiation of intestinal epithelial cells. Recent studies showed that CDX-2 protein expression by immunohistochemistry (IHC) has a high predictive value for confirming the diagnosis of colorectal adenocarcinoma (ACA). The differentiation of primary pulmonary ACA from metastatic colorectal ACA can be extremely challenging on fine-needle aspiration (FNA). The results of immunostains for TTF-1, CK 7, and CK 20 may be controversial in the differential diagnosis. In this study, we evaluated the clinical utility of CDX-2 in lung FNA specimens. Cell blocks from 41 primary lung and 20 colorectal ACAs metastatic to the lungs were retrieved. Cell block sections were immunostained with a CDX-2 monoclonal antibody. Sensitivity and specificity of CDX-2 for colorectal ACA was 75 and 100%, respectively. All five cases negative for CDX-2 were moderately to poorly differentiated colorectal ACAs. Our study confirms that CDX-2 is a highly useful immunohistochemical marker for the differentiation of primary pulmonary ACA from colorectal ACA metastatic to the lungs in FNA specimens. Of diagnostic importance is the loss of CDX-2 immunoreactivity in poorly differentiated colorectal ACAs. Diagn. Cytopathol. 2006;34:191-195. (c) 2006 Wiley-Liss, Inc

PURPOSE: To retrospectively review the imaging and histologic findings in patients in whom a benign papillary lesion was diagnosed at core-needle breast biopsy. MATERIALS AND METHODS: This retrospective study was approved by the institutional review board at each institution; patient consent was not required. The study was HIPAA compliant. The authors reviewed the findings from 42 patients (age range, 26-76 years; mean age, 54.3 years) with 43 benign papillary lesions diagnosed at core-needle biopsy. Thirty-six (84%) of the 43 lesions were surgically excised, and seven (16%) were followed up with long-term imaging. The authors assessed the radiographic findings, the histologic findings at core-needle biopsy, and the findings at subsequent surgical excision or imaging follow-up. Statistical analysis was performed on a per-patient basis and included the Blyth-Still-Casella procedure to construct exact 95% confidence intervals (CIs) and the Fisher exact test. RESULTS: At core-needle biopsy, lesions were diagnosed as papilloma (n = 29), sclerosing papilloma (n = 8), and benign papillary lesions not otherwise specified (n = 6). For the 36 lesions that were surgically excised, histologic follow-up showed no residual lesion in 10, intraductal papilloma in 14, intraductal papillomatosis in two, papilloma with adjacent foci of atypical ductal hyperplasia (ADH) in eight, and well-differentiated papillary ductal carcinoma in situ (DCIS) in two. Mammographic follow-up in the remaining seven lesions revealed stable calcifications in five (at 28-55 months) and no residual lesion in two (at 26-29 months). In nine of the 42 patients (21%), the diagnosis was upgraded to either ADH or DCIS (exact two-sided 95% CI = 11.4%, 36.4%). CONCLUSION: The results strongly suggest that papillary lesions diagnosed as benign at core-needle biopsy should be surgically excised because a substantial number of lesions were upgraded to ADH and DCIS at excision

BACKGROUND: Breast masses occur in men far less commonly than women and are infrequently subjected to fine-needle aspiration (FNA) biopsy. Papillary lesions of the male breast are rare and are comprised of a spectrum of lesions ranging from papillary hyperplasia in gynecomastia to invasive papillary carcinoma. The following study describes the cytomorphology of papillary breast lesions in 11 men. The patients ranged in age from 23 to 78 years old and each presented with an unilateral subareolar or periareolar breast mass that varied in size from 0.5 to 3 cm. Two patients presented with bloody nipple discharge. METHODS: Archival material (8-year period) from FNA biopsies of papillary lesions of the male breast was reviewed. The reviewed cases were correlated with appropriate clinicopathologic follow-up. RESULTS: The smears had variable cellularity but all showed papillary clusters of mammary epithelial cells with and without fibrovascular cores. Single epithelial cells with a high nuclear-to-cytoplasmic ratio and eccentric nuclei were seen in all smears; however, these were more numerous in cases of adenocarcinoma. Hemosiderin-laden macrophages were present in all cases. Nipple discharge was seen only in the 2 benign lesions. All adenocarcinomas occurred in older men. CONCLUSIONS: The only cytologic criteria that differentiated benign from malignant papillary lesions were marked cellularity and the presence of abundant 3-dimensional clusters. To the best of the authors' knowledge, the current series is the largest in the English literature to date that examines the cytomorphologic features of papillary breast lesions in men