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Biomedical subjects

Mark R Wick

Publications and source records attributed to Mark R Wick.

At least 19 recordsLinked to original sources
PubMed2005

Intercellular junctions in Ewing sarcoma/primitive neuroectodermal tumor: additional evidence of epithelial differentiation.

Ewing sarcoma/primitive neuroectodermal tumor (ES/PNET) has recently been shown to frequently express cytokeratins, suggesting partial epithelial differentiation. Older ultrastructural studies have documented primitive cell-cell junctions in ES/PNET, reportedly resembling poorly formed desmosomes. Recently, paraffin-reactive antibodies have become available to proteins found in a variety of intercellular junctions indicative of epithelial differentiation, including tight junctions, desmosomes and adherens junctions. We examined intercellular junction protein expression in a large number of genetically confirmed ES/PNET. Formalin-fixed, paraffin-embedded sections from 23 primary and seven recurrent or metastatic cases of genetically confirmed ES/PNET were immunostained for claudin-1 and occludin (tight junction structural proteins), zonula occludens-1 (ZO-1, tight junction linker protein), desmoglein 1/2 (desmosomal adherens protein), desmoplakin (desmosomal structural protein) and E-cadherin (epithelial adherens junction protein), using steam heat-induced epitope retrieval and the Dako Envision system. Cases with >5% positive cells were scored as 'positive'. Normal colonic epithelium and skin served as external positive controls. Claudin-1 was expressed by 19 of 30 specimens (63%), ZO-1 was expressed by 15 of 29 specimens (51%), and occludin was expressed by three of 28 specimens (11%). In 28 specimens all three tight junction markers were evaluable. In all, 15 samples (54%) expressed only one tight junction marker, and 10 samples (36%) expressed two tight junction markers. No case expressed all three tight junction markers. Desmoglein was expressed in one of 30 (3%) samples. Desmoplakin was expressed in two of 28 (7%) samples. E-cadherin was negative in all cases. Our data suggest that many of the previously described cell-cell junctions in ES/PNET are poorly formed tight junctions, given the high frequency of claudin-1 and ZO-1 expression. This may underestimate the true frequency of tight junction protein expression in ES/PNET, as there are at least 20 different claudins and other ZO proteins. These tight junctions are almost certainly abnormal, given the absence of occludin expression in most cases. Desmosomal and adherens junction protein expression was rare to absent. Our findings provide additional evidence that ES/PNET frequently show partial epithelial differentiation.

Bone Neoplasms↗
PubMed2005

Localized malignant mesothelioma.

Localized malignant mesotheliomas are uncommon sharply circumscribed tumors of the serosal membranes with the microscopic appearance of diffuse malignant mesothelioma but without any evidence of diffuse spread. Little is known about their behavior. We report 23 new cases. The mean age at presentation was 63 years, and the sex ratio was approximately 2:1 (male/female). Twenty-one tumors were pleural and 2 were peritoneal. Sixteen tumors reproduced microscopic patterns of diffuse epithelial mesotheliomas, 6 had mixed epithelial and sarcomatous patterns, and 1 was purely sarcomatous. After surgical excision of the tumor, 10 of 21 patients with follow-up data were alive without evidence of disease from 18 months to 11 years after diagnosis. Patients who died had developed local recurrences and metastases, but none had diffuse pleural spread. Localized malignant mesotheliomas should be separated from diffuse malignant mesotheliomas because of their localized presentation, quite different biologic behavior, and far better prognosis.

Adult↗
PubMed2005

Cutaneous melanocytic lesions: selected problem areas.

Cutaneous melanocytic proliferations are diverse morphologically, and their behavioral attributes may be difficult to discern with certainty. As a consequence, diagnostic anatomic pathologists regularly encounter problems in the interpretation of such lesions. This review considers several selected issues in that subject area, including proliferative congenital nevi, architecturally disordered (dysplastic) nevi, morphologic variants of Spitz nevus, atypical lentiginous melanocytic proliferations, nevoid melanoma, diagnostically deceptive histologic variants of melanoma, "epidermotropic" metastases of melanoma, and the relationship of melanoma microstages to tumor growth phases.

Cell Proliferation↗
PubMed2005

Sporadic medullary carcinoma of the colon: a clinicopathologic comparison with nonhereditary poorly differentiated enteric-type adenocarcinoma and neuroendocrine colorectal carcinoma.

We studied 68 sporadic colorectal carcinomas (CRCs) with medullary features (MCRCs) and compared them with 35 poorly differentiated purely "enteric" CRCs (ECRCs) and 15 purely neuroendocrine carcinomas (NECs) of grades II and III, all in patients lacking a family history of CRC. Potential clinicopathologic differences between the study groups were assessed. MCRCs were significantly more common in the ascending colon than were ECRCs, but there was no significant dissimilarity to NECs. ECRCs occurred more often in the rectosigmoid than MCRCs or NECs. MCRCs arose in older patients, and a marked sex difference also was noted. Despite an infiltrative growth pattern, MCRC was less likely than ECRC to manifest with stage III or IV disease, but there was no stage-related difference from NECs. Although the histologic images of MCRCs were evocative of neuroendocrine differentiation, chromogranin positivity and synaptophysin reactivity in that group did not differ meaningfully from that of ECRCs but was dissimilar to the 100% labeling of NECs. p53 immunolabeling was similar in the 3 tumor groups. Follow-up data in the study cases showed that 5-year mortality was 40% (27/68) for MCRC, 59% (19/32) for ECRC, and 93% (14/15) for NEC. Medullary CRC seems to be a distinct clinicopathologic variant of CRC, which does not have a neuroendocrine lineage. The biologic behavior of MCRC was better than that of ECRC or NEC.

Adenocarcinoma↗
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↗
PubMed2004

Hyperpigmented scar due to minocycline therapy.

A 20-year-old woman presented with a heavily pigmented scar on the left lower abdomen following excision of a benign compound nevus. Reexcision showed an organizing scar with pronounced hemosiderinlike pigment deposition and no residual melanocytic lesion. Results of further histopathologic workup showed positive staining with both Perls stain for iron and Fontana-Masson stain. These findings led to further questioning of the patient, which revealed a history of minocycline therapy--information that had not been provided during her initial evaluation. Hyperpigmented scars may result from minocycline ingestion. We present a review of the literature, with particular regard to the possible mechanisms of minocycline hyperpigmentation and the differential diagnosis of hyperpigmented scars.

Abdomen↗
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↗