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Biomedical subjects

Mark R Wick

Publications and source records attributed to Mark R Wick.

15 recordsLinked to original sources
PubMed2004

Evidence-based medicine, medical decision analysis, and pathology.

Recent advances in molecular pathology and other technologies such as proteomics present pathologists with the challenge of integrating the new information generated with high-throughput methods with current diagnostic models based mostly on histopathology and clinicopathologic correlations. Parallel developments in the field of medical informatics and bioinformatics provide the technical and mathematical methods to approach these problems in a rational manner. However, it remains unclear whether pathologists or other medical specialists will become primarily responsible for the development and maintenance of these multivariate and multidisciplinary diagnostic and prognostic models that are hoped to provide more accurate, individualized patient-based information. Evidence-based medicine (EBM) and medical decision analysis (MDA) are relatively new disciplines that use quantitative methods to assess the value of information, differentiate fact from myth, and integrate so-called best evidence into multivariate models for the assessment of prognosis, response to therapy, selection of laboratory tests, and other complex problems that influence individual patient care. We review from an epistemological viewpoint the current approach to information in pathology and describe some of the concepts developed by the practitioners of EBM and MDA.

Computational Biology↗
PubMed2004

Tumefactive lipedema with pseudoxanthoma elasticum-like microscopic changes.

BACKGROUND: Lipedema is a condition characterized by diffuse, bilaterally symmetrical, painful swelling of the legs and buttocks. Microscopically, there are dermal and septal edema, adipocyte degeneration, and numerous mast cells, features held in common with lipedematous alopecia. CASE REPORT: We present the case of a 60-year-old woman with a long history of bilateral leg masses with microscopic features of lipedema. In addition, elastic-fiber changes typical of pseudoxanthoma elasticum (PXE) were discovered within the subcutaneous septa in three separate specimens obtained from an affected extremity. The patient did not have other clinical findings of PXE, although there was a history of both hypertension and congestive heart failure. CONCLUSION: This tumefactive presentation of lipedema has not been previously described. Regarding the elastic-tissue abnormalities, the patient could have either a subclinical form of PXE, perhaps predisposing to lipedema, or secondary elastic-tissue changes resulting from the massive edema. If the latter is the case, then this could represent an unusual manifestation of localized acquired cutaneous PXE (calcific elastosis).

Adipose Tissue↗
PubMed2004

Proliferating pilar tumors: a clinicopathologic study of 76 cases with a proposal for definition of benign and malignant variants.

We studied proliferating pilar tumors (PPTs) to establish histologic criteria that could predict behavior. We reviewed all cases in our consultation files (1989-2000) and evaluated 76 cases with meaningful follow-up information. Histologic examination involved attention to tumor silhouette, degree of nuclear atypia, mitotic activity, necrosis, and perineurial or angiolymphatic invasion. Tumors were stratified as follows: group 1 PPTs, circumscribed silhouettes with "pushing " margins, modest nuclear atypia, and an absence of pathologic mitoses, necrosis, and invasion of nerves or vessels; group 2 PPTs, similar to group 1 but manifested irregular, locally invasive silhouettes with involvement of the deep dermis and subcutis; group 3, invasive growth patterns, marked nuclear atypia, pathologic mitotic forms, and geographic necrosis, with or without involvement of nerves or vascular structures. Recurrence occurred in none of 48 group 1 PPTs; 3 (15%) of 20 group 2 PPTs had local regrowth; 4 (50%) of 8 of group 3 PPTs recurred and/or metastasized to regional lymph nodes. The differences between groups 1 and 3 and between 2 and 3 were statistically significant (P = .0002, P < .05, respectively). It seems justifiable to regard group 1 PPTs as benign, group 2 as having potential for locally aggressive growth, and group 3 also as having metastatic potential. The latter 2 categories might be equated with low and high grades of malignancy among PPTs of the skin.

Adult↗
PubMed2004

Determination of HER-2 status and chromosome 17 polysomy in breast carcinomas comparing HercepTest and PathVysion FISH assay.

We evaluated and compared 2 HER-2 tests (immunohistochemical analysis [HercepTest, DAKO, Carpinteria, CA] and fluorescence in situ hybridization [FISH]) and assessed chromosome 17 polysomy status in relation to these tests. HER-2 status was obtained in 690 cases. The rinse step in the HercepTest before and after addition of the visualization reagent was 2 minutes in 188 cases and was increased to 5 minutes in 600 cases. HercepTest with both rinse steps was performed on duplicate slides in 98 cases. Chromosome 17 ploidy status based on FISH results was determined in 687 cases. Weak overexpression (2+) of HER-2 protein was not due to gene amplification in a majority of cases (67/76 [88%]). A small subset of breast carcinomas (19/687 [2.8%]) strongly overexpressed (3+) HER-2 protein without gene amplification. The aneuploidy rate was similar in negative and 2+ cases (60/141 [42.5%] and 12/26 [46%]), compared with 86% (18/21) in 3+ cases. The incidence of polysomy 17 in 2+ nonamplified cases (3/67 [4%]) was similar to that seen in negative cases (5.5%), in contrast with 47% (9/19) of 3+ nonamplified cases. Adding a longer rinse step to the HercepTest converted a subset (3/10 [30%]) of weakly positive cases to negative cases. Weak overexpression of HER-2 protein in a majority of cases seems to represent an artifactual staining pattern. Chromosome 17 polysomy is a major factor in strong HER-2 protein overexpression in 3+ nonamplified cases.

Aneuploidy↗
PubMed2003

Current controversies regarding the role of asbestos exposure in the causation of malignant mesothelioma: the need for an evidence-based approach to develop medicolegal guidelines.

Asbestos is a group of fibrous silicate minerals that includes two mineralogic groups: amphiboles and serpentines. While the carcinogenic role of amphiboles (eg, crocidolite and amosite) is well established, medical "experts" that tend to strongly advocate their views currently argue in medicolegal cases multiple specific issues regarding the carcinogenicity of asbestos fibers. For example, it is controversial whether chrysotile causes malignant mesothelioma (MM); what are the specific carcinogenic thresholds for amphiboles and chrysotile; what occupations are truly at risk to develop MM as a result of asbestos exposure; what is the role of chrysotile in the development of peritoneal MM; how to assign causation in individuals exposed to multiple industrial products containing variable concentrations of various asbestos fibers; and, what criteria should be used to accept causation in household exposure cases and others. The causation criteria currently acceptable in U.S. courts are surprisingly flexible and subject to variable interpretation by medical "experts." At a time where thousands of individuals are claiming causation of MM by asbestos exposure, there is a need to develop more specific causation guidelines based on scientific evidence. Evidence-based medicine has been proposed as a new approach to the study, teaching, and the practice of medicine and has been used as a process of systematically reviewing the relevant studies in the literature to assess their scientific validity and development of guidelines. This article summarizes some of the current controversies regarding the role of asbestos exposure in the causation of MM and suggests the need for future evidence-based medicine-type studies to develop causation guidelines that could be used consistently during litigation.

Animals↗
PubMed2003

Extramedullary hematopoietic proliferations, extraosseous plasmacytomas, and ectopic splenic implants (splenosis).

Hematopoietic proliferations are well known to present ectopically outside the bone marrow, either in benign or malignant form. As such, they present a distinct problem with respect to morphologic interpretation because of their uncommonality in extramedullary sites and their capacity to simulate other lesions histologically. This review considers extramedullary myeloid tumors ("granulocytic sarcoma," "erythroblastic sarcoma," "megakaryocytic sarcoma"), tumefactive extramedullary hematopoiesis, and the peculiar condition known as "splenosis," with consideration of their clinical, microscopic, and cytohistochemical chararacteristics.

Biomarkers, Tumor↗
PubMed2003

Ectopic neural and neuroendocrine neoplasms.

Although neural and neuroendocrine tissues are distributed virtually ubiquitously throughout the body, the occurrence of selected neoplasms related to those lineages is extremely uncommon in some topographic sites. This review considers the clinicopathologic characteristics of heterotopic pituitary adenomas; neuroendocrine carcinomas in non-organ-based locations; ectopic (extraneuraxial) meningiomas and gliomas; visceral neuroblastic neoplasms and primitive neuroectodermal tumors; and paragangliomas arising outside the sympathoadrenal neural network. Practical approaches to differential diagnosis are emphasized.

Biomarkers, Tumor↗
PubMed2003

Salivary-type neoplasms of the breast and lung.

Salivary-type tumors occur in multiple sites in the human body, likely related to a basic structural homology between exocrine glands in these different anatomic areas. This paper reviews these salivary gland tumor types in breast tissue and lung. Salivary-type tumors of both breast and lung are relatively uncommon in comparison to their salivary gland counterparts. This may be attributable in part to lack of familiarity with these tumors in extra-salivary sites, and in part to histologic overlap with other primary and metastatic tumor types. Recognition of these entities is improving as the clinical and pathologic features are better delineated, and tumors are more accurately classified. Prediction of malignant behavior is not always possible in these unusual sites. In some instances, such as adenoid cystic carcinoma, behavior is known to differ considerably from that of analogous primary salivary gland tumors and in other instances there are simply too few reported cases to allow for adequate prognostication. In fact, more recent papers discuss the need to consider a spectrum encompassing benign and malignant lesions, in both breast and lung. Of course, some entities show clear-cut evidence of malignancy with documented potential for metastasis, others show bland features and well-reported benign behavior, and the less well-defined entities reside between these two extremes. The molecular pathology of salivary gland tumors has been reasonably well investigated in that location; however; there are few molecular studies devoted to salivary-type tumors of the breast and lung. This represents a potential area for future growth in further clarifying these tumors and their behavior.

Adenocarcinoma↗
PubMed2002

Inflammatory pseudotumor (myofibroblastic tumor) of the heart.

Inflammatory pseudotumor (IPT) (also known as inflammatory myofibroblastic tumor) is an uncommon spindle cell lesion that was initially recognized in the lung and is now known to occur in virtually every major organ of the body. Its precise biological nature and clinical characteristics are still relatively uncertain. We report the case of a 7-month-old girl who was found to have an IPT of the right atrium. The rarity of IPT in the heart poses a diagnostic difficulty for both pediatricians and pathologists because of the clinical and morphologic overlap with other intracardiac masses in children. The differential diagnostic aspects of IPT of the heart are discussed and the literature on that lesion is reviewed.

Diagnosis, Differential↗
PubMed2002

Evaluation of surgical margins in anatomic pathology: technical, conceptual, and clinical considerations.

Virtually all anatomic pathologists are involved in the assessment of tissue margins in surgical procedures that are performed for malignant diseases. The natural tendency to view this process as uncomplicated has, in recent years, been countered by a body of literature on the biological milieu of the marginal zone. Moreover, empirical clinical information has shown that "negative" and "positive" marginal status has an imperfect correlation with risk of recurrent disease in several organ systems and in reference to various tumor types. Problems also remain regarding the optimal techniques for pathologic sampling of margins; the possible roles, if any, of adjuvant (eg, immunohistologic and "molecular") procedures for margin evaluation, and reporting motifs for selected surgical resections. This review considers conceptual data now available on surgical margins, provides a working approach to the generic assessment of marginal surfaces, and presents organ- and tumor- specific information pertaining to this area of practice.

Biomarkers, Tumor↗
PubMedDate not supplied

Predictors of lymph node metastasis in T1 breast carcinoma, stratified by patient age.

It is important to identify T1-substage breast carcinomas (BCs) which are inherently aggressive, so that these can be managed more assertively. The purpose of this study was to distinguish those T1 BCs with the potential to metastasize to axillary lymph nodes from those lacking that ability by multiparametric analysis of several clinicopathologic features. The authors studied 197 patients with invasive BC who had undergone modified radical mastectomy; 161 tumors were ductal and 26 were lobular BCs. The study group was stratified by age into two groups: </=34 years (n = 34) and 35-84 years (n = 153). Pathologic lymph node status was correlated with estrogen receptor (ER) and progesterone receptor (PR) tumor positivity, MIB-1 proliferation index, and immunoreactivity for mutant p53 protein. These factors were studied immunohistologically using standard methodology and microwave-mediated epitope retrieval. Statistical analyses employed accepted techniques. Women in this study ranged from 22 to 84 years of age; 39 (21%) had positive lymph nodes. ER-positive tumors comprised 73% of the total; similarly, 65% were PR positive. The MIB-1 index was greater than 10% in 44% of lesions, and 14% demonstrated labeling for mutant p53 protein. Using crude odds ratio data, the MIB-1 index was the only indicator found to predict lymph node metastasis significantly (p < 0.001). Moreover, even when adjustments were made for patient age, logistic regression analysis confirmed the utility of MIB-1-values of greater than 10% in this context, with a 4.4 greater likelihood of metastasis (p < 0.001). MIB-1 indices of greater than 10% are associated with a risk of lymph node metastasis from T1 BCs, independent of patient age. Hormone receptor status and immunohistologic p53 status are not predictors of nodal involvement in this specific setting.

Adult↗