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Biomedical subjects

Barbara A Centeno

Publications and source records attributed to Barbara A Centeno.

9 recordsLinked to original sources

Pathology of liver metastases.

BACKGROUND: The liver is the most frequent site of metastatic disease, and metastatic disease to the liver is far more common than primary liver carcinoma in the United States. Pathologic evaluation of biopsy samples is key to establishing a correct diagnosis for patient management. Morphologic and immunoperoxidase studies, which are the standard for pathologic practice, accurately classify most tumors. Subclassification of carcinoma of unknown primary remains problematic. METHODS: The author reviewed the literature for articles pertaining to liver biopsy, diagnosis of specific tumor types, utility of immunohistochemical markers, and microarray and proteomic analysis. RESULTS: Sampling of liver lesions is best accomplished by combining fine-needle aspiration and needle core biopsy. Many malignancies have distinct morphologic and immunohistochemical patterns and can be correctly subclassified. Adenocarcinoma of unknown primary remains enigmatic since current immunohistochemical markers for this differential diagnosis lack specificity. Microarray analysis and proteomic analysis of tumors can provide distinct gene or protein expression profiles, respectively, for tumor classification. These technologies can be used with fine-needle aspiration and needle core biopsy samples. CONCLUSIONS: Most metastatic malignancies in the liver may be correctly diagnosed using standard morphology and immunohistochemical techniques. However, subtyping of some carcinomas and identification of site of unknown primary remains problematic. New technologies may help to further refine our diagnostic capabilities.

Biopsy, Needle↗

Somatostatin receptor profiling in hepatic metastases from small intestinal and pancreatic neuroendocrine neoplasms: immunohistochemical approach with potential clinical utility.

BACKGROUND: The expression of somatostatin receptors (SSTRs) on endocrine tumor (ET) cells forms the basis for somatostatin analog treatment of patients with SSTR-positive, hormonally active ETs. In patients with SSTR-negative ETs, the clinical response is generally absent or suboptimal, while nonfunctioning ETs with SSTR positivity show a variable response to such therapy. METHODS: We retrospectively studied SSTR subtype expression in hepatic metastases from 14 adult patients with primary endocrine carcinomas (ECAs) of the small intestine and pancreas and compared SSTR subtype expression among the primary and metastatic ECAs. Polyclonal antibodies against the 5 SSTR subtypes were used on formalin-fixed, paraffin sections from each primary and metastatic ECA. Both qualitative and semiquantitative evaluation of the stained ECA sections was carried out. RESULTS: Eleven (61%) of 18 hepatic metastases from small intestinal and pancreatic ECAs were positive for SSTR-1, 15 (83%) for SSTR-2, 13 (72%) for SSTR-3, 10 (56%) for SSTR-4, and 15 (83%) for SSTR-5. Among 11 hepatic ECA metastases from small intestinal ECAs (carcinoids), 7 (63%) expressed SSTR-1, 9 (81%) expressed SSTR-2, 8 (72%) expressed SSTR-3, 6 (54%) expressed SSTR-4, and 10 (91%) expressed SSTR-5. Of 7 hepatic ECA metastases from pancreatic ECAs, 4 expressed SSTR-1, 6 expressed SSTR-2, and 5 expressed SSTR-3 and SSTR-5 each. We also observed the immunohistochemical evidence of heterogeneity of expression of various SSTR subtypes in the primary enteropancreatic ECAs and their hepatic metastases. CONCLUSIONS: SSTR subtype expression needs to be correlated to somatostatin analog therapy. Immunohistochemical profiling of various SSTR subtypes as a part of routine surgical pathologic analysis of enteropancreatic ETs may become a useful predictor of responsiveness of ETs to various SSTR analogs.

Adult↗

Classification of human tumors using gene expression profiles obtained after microarray analysis of fine-needle aspiration biopsy samples.

BACKGROUND: Gene expression profiling using gene-discovery, high-density microarray technologies is a powerful tool. One potential application is the development of tumor classifiers that predict the site of origin. For this technology to be relevant, however, it must be applicable to tumor biopsy samples, which most often are fine-needle aspiration biopsy (FNAB) samples. METHODS: Surgically resected tumors were sampled by FNAB using different gauge needles. A portion of the excised tumor was also collected. RNA samples were extracted using standard techniques and the quality and quantity of the RNA samples were measured for each sample. Thirteen representative FNAB samples and two representative tissue samples were submitted for microarray analysis and then subjected to a tumor classifier. RESULTS: Fourteen of 18 samples analyzed for quantity and quality of RNA yielded an adequate amount of RNA (> 1 microg total RNA). Tumor type contributed to the RNA yield because one of the four inadequate samples was retrieved from a patient with lobular carcinoma of the breast and the other three samples were retrieved from patients with retroperitoneal sarcomas. Of the 13 samples submitted for microarray analysis, 9 were classified correctly as to tumor type using a tissue-based tumor classifier. CONCLUSIONS: The authors demonstrated that FNABs reproducibly obtained an adequate amount of RNA for microarray analysis when a standardized collection procedure was used. Furthermore, the samples generated interpretable gene expression profiles that could be matched accurately with a tumor classifier established on tissue specimens. The current study showed that FNAB produced adequate material for microarray analysis when utilizing a standardized collection procedure.

Biopsy, Fine-Needle↗

Modes of benign mechanical transport of breast epithelial cells to axillary lymph nodes.

The status of axillary lymph nodes is a key prognostic indicator available for the management of patients with breast cancer. Sentinel lymph node (SLN) evaluation as a predictor of lymph node status has led to increased use of ancillary methods, principally immunohistochemistry, to increase the sensitivity of the SLN biopsy. So-called "occult" micrometastases detected by such methods have led to speculation that some may have reached the SLNs by benign mechanical transport (BMT) rather than a metastatic process. We review evidence suggesting two potential modes of BMT: lymphatic transport of epithelial cells displaced by biopsy of the primary breast tumor and by breast massage-assisted SLN localization. The biopsy techniques under most scrutiny include fine needle aspiration and large-gauge core biopsy. The evidence implicating breast massage prior to SLN biopsy as a mode of BMT has been supported by statistical analysis; however, no method of distinguishing massage-associated cells in SLNs from true occult micrometastases is available. The significance of small epithelial clusters in SLNs is currently unknown. Thus, deviation from current biopsy and SLN-localizing practices is unwarranted.

Axilla↗

Diagnosis of pancreatic cystic neoplasms: a report of the cooperative pancreatic cyst study.

BACKGROUND & AIMS: Cysts of the pancreas display a wide spectrum of histology, including inflammatory (pseudocysts), benign (serous), premalignant (mucinous), and malignant (mucinous) lesions. Endoscopic ultrasonography (EUS) may offer a diagnostic tool through the combination of imaging and guided, fine-needle aspiration (FNA). The purpose of this investigation was to determine the most accurate test for differentiating mucinous from nonmucinous cystic lesions. METHODS: The results of EUS imaging, cyst fluid cytology, and cyst fluid tumor markers (CEA, CA 72-4, CA 125, CA 19-9, and CA 15-3) were prospectively collected and compared in a multicenter study using histology as the final diagnostic standard. RESULTS: Three hundred forty-one (341) patients underwent EUS and FNA of a pancreatic cystic lesion; 112 of these patients underwent surgical resection, providing a histologic diagnosis of the cystic lesion (68 mucinous, 7 serous, 27 inflammatory, 5 endocrine, and 5 other). Receiver operator curve analysis of the tumor markers demonstrated that cyst fluid CEA (optimal cutoff of 192 ng/mL) demonstrated the greatest area under the curve (0.79) for differentiating mucinous vs. nonmucinous cystic lesions. The accuracy of CEA (88 of 111, 79%) was significantly greater than the accuracy of EUS morphology (57 of 112, 51%) or cytology (64 of 109, 59%) (P < 0.05). There was no combination of tests that provided greater accuracy than CEA alone (P < 0.0001). CONCLUSIONS: Of tested markers, cyst fluid CEA is the most accurate test available for the diagnosis of mucinous cystic lesions of the pancreas.

Biomarkers, Tumor↗

Benign mechanical transport of breast epithelial cells to sentinel lymph nodes.

The evaluation of sentinel lymph nodes (SLNs) for the presence of malignant epithelial cells is essential to the staging of breast cancer patients. Recently, increased attention has focused on the possibility that epithelial cells may reach SLNs by benign mechanical means, rather than by metastasis. The purpose of this study was to test the hypothesis that pre-SLN biopsy breast massage, which we currently use to facilitate the localization of SLNs, might represent a mode of benign mechanical transport. We studied 56 patients with invasive and/or in situ ductal carcinoma and axillary SLNs with only epithelial cells and/or cell clusters (< or =0.2 mm in diameter and not associated with features of established metastases) detected predominantly in subcapsular sinuses of SLNs on hematoxylin and eosin- and/or anti-cytokeratin-stained sections. No patient had an SLN involved by either micro- or macro-metastatic carcinoma. Epithelial cells and cell clusters, < or =0.2 mm in size and without features of established metastases, occurred more frequently in the SLNs of patients who underwent pre-SLN biopsy breast massage (P < 0.001, chi2 test). The latter finding supports the hypothesis that pre-SLN biopsy breast massage is a mode of benign mechanical transport of epithelial cells to SLNs.

Breast Neoplasms↗

Comparison of human papillomavirus DNA prevalence in atypical squamous cells of undetermined significance subcategories as defined by the original Bethesda 1991 and the new Bethesda 2001 Systems.

CONTEXT: The new Bethesda System 2001 (TBS 2001) minimized the subclassification of atypical squamous cells of undetermined significance (ASCUS). OBJECTIVE: The primary goal of this study was to determine the impact of the new subclassification on the accuracy of Papanicolaou (Pap) test diagnosis by examining the prevalence of human papillomavirus (HPV) DNA in different ASCUS subcategories, as defined by the new TBS 2001 versus the original TBS 1991. The second goal was to identify specific morphologic features of atypical squamous cells that are more frequently associated with HPV detection. DESIGN: Consecutive cases of ThinPrep Pap tests were retrospectively reviewed by a panel of pathologists to obtain consensus diagnoses. The study group consisted of ASCUS cases; the positive control group consisted of low- and high-grade squamous intraepithelial lesions (LSILs and HSILs, respectively); and the negative control group consisted of cases "negative for intraepithelial lesion or malignancy." All ASCUS cases were subclassified according to TBS 1991 into the following categories: favor reactive (ASCUS-R), favor LSIL (ASCUS-L), favor HSIL (ASCUS-H), and not otherwise specified (ASCUS-NOS). In a separate review, ASCUS cases were subclassified according to TBS 2001 into the following categories: atypical squamous cells of undetermined significance (ASC-US) and atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H). Furthermore, morphologic ASCUS subtypes were recorded (atypical mature, immature, parakeratotic, and atrophic cells); in addition, individual morphologic features of atypical cells were recorded. Broad- spectrum HPV DNA amplification and genotyping was performed using short PCR fragment (SPF 10) polymerase chain reaction/Line Probe assays. RESULTS: In cases classified according to TBS 1991, HPV was detected in 32% of negative, 49% of ASCUS, and 93% of LSIL/HSIL cases. On the second review, using the diagnostic categories of TBS 2001, which eliminated the ASCUS-;R category, the number of ASCUS cases decreased by 45%. The prevalence of HPV DNA in ASCUS cases downgraded to the negative category was 38%, which was not significantly different from HPV prevalence in negative cases as diagnosed under TBS 1991. Furthermore, HPV was detected in 56% of ASC-US and 71% of ASC-H cases. The prevalence of HPV in different morphologic subtypes of ASCUS was not significantly different, and none of the 8 individual morphologic features of atypical cells were more frequently associated with HPV detection. CONCLUSION: Elimination of the ASCUS-R category in TBS 2001 resulted in a significant decrease in the number of ASCUS diagnoses. Downgraded cases had a relatively low prevalence of HPV DNA. It is expected that TBS 2001 will increase specificity of the Pap test without compromising its sensitivity.

Adolescent↗

Pancreatic tissue sampling guided by EUS, CT/US, and surgery: a comparison of sensitivity and specificity.

BACKGROUND: Needle aspiration of the pancreas is performed to differentiate pancreatic malignancy, focal chronic pancreatitis, and metastasis to the pancreas. Biopsies may be directed by using EUS, CT, US, or surgery. This study retrospectively compared the accuracy of EUS-guided, CT/US-guided, and surgical tissue sampling of the pancreas over a 5-year period. METHODS: The records of patients undergoing pancreatic tissue sampling were reviewed for a final clinical diagnosis based on the results of cytology, histology, and clinical history. The sensitivity, specificity, and accuracy of each technique were calculated. RESULTS: One hundred forty-nine tissue samples (68 EUS-guided, 70 CT/US-guided, 11 surgical) from 128 patients were compared. There was no significant difference in accuracy rates for EUS (76.4%), CT/US (81.4%), and surgically guided (81.8%) specimens. EUS was used when masses were smaller (2.6 +/- 0.1 cm) as compared with CT/US (3.4 +/- 0.2 cm, p < 0.001) and surgery (2.9 +/- 0.4 cm, p = 0.49). In univariate analyses, factors associated with greater accuracy regardless of technique were as follows: (1) older age, (2) larger size of the mass, and (3) participation by a cytologist during the procedure. A subsequent multivariate logistic regression analysis, in which the examination of the effect of each factor controls for the effect of each of the other factors, found that only older age was a significant predictor of accuracy. CONCLUSION: EUS-guided tissue sampling of pancreatic masses is as accurate as CT/US-guided sampling and surgical biopsies.

Age Factors↗

Role of cytology in the diagnosis of cystic and intradcutal papillary mucinous neoplasms.

Cytology may provide valuable information and is diagnostic in many cases, but it is limited by sampling difficulties. Performance of mucin stains and analysis of the cyst fluid for tumor markers, as described in the article on histology of cystic neoplasms elsewhere in this issue, increase detection of MCNs and IPMNs; however, as with any other laboratory test, the results of the cyst fluid cytologic analysis need to be assessed in light of the clinical and radiologic findings, particularly when the cytology is not completely diagnostic.

Biopsy↗