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M R Wick

Publications and source records attributed to M R Wick.

At least 55 records · Page 3Linked to original sources
PubMed1998

Lymphoid lesions of the gastrointestinal tract: a histologic, immunophenotypic, and genotypic analysis of 49 cases.

The diagnosis of gastrointestinal (GI) lymphoid infiltrates can be challenging when based only on conventional microscopic assessment. When marked cytologic atypia is present, a diagnosis of malignant neoplasm is readily made; however, the distinction between a low-grade malignant neoplasm and a reactive process is much more difficult. If unfixed tissue is available, immunohistologic or genotypic methods that are usually aimed at defining B-lymphocytic monotypism can be applied. However, paraffin-embedded tissue has generally been deemed unsuitable for these techniques. We assessed the value of a panel of immunohistochemical stains and a seminested polymerase chain reaction (PCR) for the analysis of lymphoid infiltrates in routinely processed GI biopsy specimens from 49 archival cases, including morphologically benign, indeterminate, and overtly malignant lesions. Clinical outcome was used as the retrospective diagnostic standard; end points were death (of lymphomatous disease or otherwise) and clinical evidence of lymphoma. According to light microscopic criteria, 19 cases were classified as benign, 17 as malignant, and 13 as atypical. Immunophenotyping correctly identified 28 of 31 benign and 14 of 18 malignant lesions (7 cases had an indeterminate immunoprofile). Genotypic analysis correctly identified 12 of 18 malignant and 29 of 31 benign lesions, but spurious monoclonal bands were produced by PCR amplification of 2 of the latter 31 cases. No single technique exists for correct categorization of all paraffin-embedded specimens of GI lymphoid infiltrates. We recommend a sequential approach to the use of available diagnostic modalities.

Antigens, CD↗
PubMed1998

Immunohistologic differential diagnosis of basal cell carcinoma, squamous cell carcinoma, and trichoepithelioma in small cutaneous biopsy specimens.

The distinction between squamoid basal cell carcinoma and basaloid squamous cell carcinoma (or between BCC and trichoepithelioma variants) is usually made readily on the basis of defined histological criteria. However, these differential diagnoses occasionally can pose difficult morphological problems. The stated distinctions are clinically important because the risk of progressive disease is significantly higher with squamous carcinoma of the skin than with basal cell carcinoma (BCC), and a trichoepithelioma misinterpreted as BCC burdens the patient with an inaccurate diagnosis that may result in inappropriate surgery. Recent reports have suggested that reactivity with the monoclonal antibody Ber-EP4 is capable of separating histologically similar basal cell and squamous carcinomas, and that the expression of bcl-2 or CD34 antigen is able to distinguish BCC from trichoepithelioma. However, corroborative studies of these contentions are few in number. In order to investigate the usefulness of the stated immunostains in the above-cited differential diagnoses, the authors analyzed 45 basal cell carcinomas and 22 squamous carcinomas, as well as 36 trichoepitheliomas. The monoclonal antibodies Ber-EP4, My10 (CD34), and anti-bcl-2 were applied to formalin-fixed paraffin sections in all cases, using a standard avidin-biotin-peroxidase complex method. Most BCCs demonstrated strong, diffuse cytoplasmic labeling with Ber-EP4 and anti-bcl-2. In contrast, the squamous carcinomas were uniformly negative for the former marker and only focally reactive for the latter in four examples. 'Peripheral' bcl-2 staining of trichoepitheliomas was noted in 24 of 33 of the immunoreactive tumors, but the remainder were marked diffusely and similarly to most BCCs. Among the latter, immature trichoepitheliomas were diffusely reactive for this marker in 6 of 8 cases. Labeling of epithelium for CD34 failed to discriminate between any of the tumor types under evaluation, whereas staining of peritumoral stroma was characteristic of the majority of trichoepitheliomas and more than one-third of metatypical basal cell carcinomas. These data support the suggestion that Ber-EP4 and bcl-2 are useful in the separation of BCC from squamous carcinomas. Nevertheless, they also serve to caution against reliance upon bcl-2 and CD34 immunostains in attempting to distinguish BCC from trichoepithelioma in histologically enigmatic cases. There is currently no certain method other than conventional microscopy that can be applied successfully to the latter problem.

Antibodies, Monoclonal↗
PubMed1998

Peripheral pulmonary adenocarcinomas with bronchioloalveolar features: immunophenotypes correlate with histologic patterns.

Peripheral pulmonary adenocarcinomas (PPAs) often demonstrate a bronchioloalveolar component, with or without glandular differentiation. PPAs can be nondescript, mucinous, or show features of Type II pneumocytes. Particularly, mucinous lung carcinomas can resemble gastrointestinal metastases. Previous reports suggested that patterns of keratins 7 (K7) and 20 (K20) differ in pulmonary tumors versus enteric metastases. These studies, however, often failed to specify the precise morphotypes of PPA. Thus, we undertook this evaluation of PPAs with different histologic images. Thirty-nine cases were retrieved from institutional files; all were confirmed as primary tumors by clinicopathologic and radiographic review. Cases were classified as Type I (mucinous) bronchioloalveolar carcinoma (BAC1); Type II (nonmucinous) bronchioloalveolar carcinoma (BAC2); conventional PPA with BAC1-like areas (PPA1); or conventional PPA with BAC2-like foci (PPA2). Immunostains were performed for K7, K20, carcinoembryonic antigen, CA19-9, tumor-associated glycoprotein-72, surfactant apoprotein-A, and the c-erbB-2 peptide. BAC1 and PPA1 failed to express surfactant apoprotein-A, and BAC2 also consistently lacked K20, whereas 28% of PPA2 lesions were labeled for K20. All of the other determinants, however, were seen in variable proportions in each subgroup of PPA. Primary BAC1 and PPA1 resembled enteric adenocarcinomas immunophenotypically; on the other hand, BAC2 demonstrated a pattern of protein expression similar to that of Type II pneumocytes. PPA2s are a diverse group of neoplasms, and a subset of PPA2 does show K20 reactivity, as would be expected in metastatic enteric carcinomas. Thus, immunohistochemical data on PPAs must be interpreted carefully and only in clinicopathologic context. With respect specifically to primary pulmonary mucinous tumors, there still seems to be no uniformly reliably marker that will always allow the exclusion of metastatic enteric tumors.

Adenocarcinoma↗
PubMed1997

Underlying pathology in mammary Paget's disease.

BACKGROUND: Management of patients with mammary Paget's disease is controversial; recent recommendations range from primary radiotherapy to modified radical mastectomy. This review correlates associated breast findings with disease stage and outcome to help guide evaluation and treatment. METHODS: Retrospective review of clinical, mammographic and pathologic data from 38 women with mammary Paget's disease treated between 1979 and 1995 was performed. Mastectomies were performed on all but two patients with the entire breast and lymph nodes evaluated for histopathologic evidence of carcinoma. RESULTS: Underlying carcinoma (ductal carcinoma in situ and/or invasive ductal cancer) was found in most patients (92%) even when no palpable mass was evident (85%); this carcinoma is often multifocal (73%). Mammography fails to identify the underlying disease in many patients with no palpable mass and multifocal underlying disease (64%). Patients with Paget's disease and a palpable mass have a much greater incidence of invasive cancer, multifocal lesions, and positive lymph nodes, and have worse survival. CONCLUSIONS: Although some patients with Paget's disease might be well treated by breast conservation therapy, many patients have underlying multifocal carcinoma (including invasive cancer), which can be inapparent by examination and mammography. Selecting candidates with disease amenable to complete excision without mastectomy is problematic.

Adult↗
PubMed1997

Clinical-pathologic analysis of 40 patients with large cell neuroendocrine carcinoma of the lung.

BACKGROUND: The identification, classification, and appropriate treatment of patients with pulmonary carcinomas demonstrating neuroendocrine differentiation remains controversial. METHODS: Patients undergoing resection of lung cancer at Washington University since 1986 were reviewed to identify all large cell neuroendocrine carcinomas. Cases were segregated into large, small, or mixed cell categories, and graded as moderate ("atypical carcinoid") or poorly differentiated (all higher grade lesions). All patients' charts were reviewed and referring physicians contacted to ascertain cancer treatment after resection and follow-up status. RESULTS: Forty patients were identified with large cell neuroendocrine carcinoma: 8 moderate and 32 high-grade. Average follow-up was 19.8 months. Stage distribution was as follows: I, 25; II, 6; III, 6; and VI, 3. Fifteen patients have no evidence of disease, 15 are dead of disease, and 6 are alive with disease. Five-year survival of the stage I patients is 18%; all-stage 5-year survival is 13%. Of the 15 patients who died of their disease, 80% had stage I or II disease. Postoperative chemotherapy, radiation therapy, or both were given to 9 of 26 patient in stage I, with six deaths (67%). Six of 17 patients (35%) with stage I disease died after no postoperative intervention. CONCLUSIONS: Large cell neuroendocrine carcinomas identified by histologic examination have a remarkably poor prognosis even in very early stage disease. Adjuvant therapy did not improve survival.

Aged↗
PubMed1997

Expression of alpha(v)beta3 integrin is less frequent in ovarian epithelial tumors of low malignant potential in contrast to ovarian carcinomas.

Ovarian tumors of low malignant potential (LMPs) histologically lack invasion and have excellent prognosis in contrast to invasive carcinomas. Integrins are heterodimeric adhesion molecules thought to play a role in cell migration and tumor progression. The alpha(v)beta3 integrin in particular mediates melanoma invasion in vitro and promotes neoplastic angiogenesis, facilitating breast cancer metastasis. In addition, alpha(v)beta3 expression has been detected in ovarian cancer cell lines and in a limited number of human ovarian cancer samples. The distribution pattern of this integrin in LMPs is not known. We examined tissue sections from 19 LMPs and 31 ovarian carcinomas for alpha(v)beta3, in addition to alpha5beta1 and alpha2beta1 integrins, which have been shown to be expressed in ovarian cancer cell lines. Variable immunoreactivities of alpha5beta1 and alpha2beta1 were detected in both LMPs and ovarian carcinomas. Most (74.2%) ovarian carcinomas were alpha(v)beta3 positive, whereas only 36.8% of LMPs were positive, which is statistically significant (P = .009). These results establish the distribution pattern of alpha2beta1, alpha5beta1, and alpha(v)beta3 integrins in LMPs. The biological significance of the less frequent expression of alpha(v)beta3 in LMPs compared with carcinomas of the ovary needs further elucidation.

Adult↗
PubMed1997

Genital angiomyofibroblastoma. Comparison with aggressive angiomyxoma and other myxoid neoplasms of skin and soft tissue.

Angiomyofibroblastoma (AMFB) of the genital region is a relatively recently described tumor of the superficial soft tissues with a marked preference for female patients. Three cases of AMFB were reviewed, two of which involved adult men. To further elucidate the pathologic features of AMFB, these three cases were compared with 10 cases of aggressive angiomyxoma (AA), a salient diagnostic alternative, and 28 cases of other myxoid tumors that may show morphologic similarities to these neoplasms. Conventional histologic and immunohistochemical features of AMFBs were compared with those of AA, myxoid leiomyoma, myxoid leiomyosarcoma, myxoid liposarcoma, myxoid malignant fibrous histiocytoma, myxoid neurofibroma, and myxoid malignant peripheral nerve sheath tumor. The ultrastructure of two of the three AMFBs also was analyzed. Genital AMFBs were circumscribed, partially myxoid proliferations that demonstrated considerable variation in cellular density. Neoplastic elements were bland cytologically and showed both fusiform and epithelioid profiles, with a tendency to concentrate around intralesional blood vessels. Mitotic activity and necrosis were absent, and the vessels assumed an arborizing configuration and were venule or capillary sized. In contrast, all other tumor types evaluated were infiltrative, cytologically atypical, or both. All AMFBs showed immunoreactivity for vimentin, desmin, actin, and estrogen receptor protein. These results were shared by most examples of AA and smooth muscle tumors as well, but were not seen in any other neoplasms in this study. Electron microscopic findings in cases of AMFB supported the presence of myofibroblastic differentiation in the tumor cells. These results indicate that conventional morphologic analysis is paramount in the recognition of genital AMFB but that immunohistology may be helpful in a limited context in excluding other differential diagnoses. They also support the conclusion that AMFB, AA, and superficial smooth muscle tumors have similar morphotypes and immunohistologic attributes regardless of their origin in men or women.

Angiomyoma↗
PubMed1997

Sarcomatoid carcinomas of the lung: a clinicopathologic review.

Sarcomatoid carcinomas (SC) of the lung are the most common pulmonary neoplasms that exhibit a composition by spindled or pleomorphic tumor cells. As such, many of them may be confused easily with true sarcomas diagnostically unless special immunohistological or ultrastructural analyses are performed. Reactivity is expected for keratin, epithelial membrane antigen, or collagen type IV in the sarcomalike elements in SC, although it may be focal. Electron microscopy often shows the presence of junctional complexes between tumor cells, with or without pericellular basal lamina and cytoplasmic skeins of intermediate filaments. Current terminological preferences are such that several formerly used terms--including "spindle-cell carcinoma," "pulmonary blastoma," "squamous cell carcinoma with pseudosarcomatous stroma," "pseudosarcoma," and "carcinosarcoma"--are now encompassed by the more generic designation of "sarcomatoid carcinoma." The clinical course of patients with this neoplasm is aggressive, with an overall 5-year survival rate approximating 20%.

Carcinosarcoma↗
PubMed1997

Assessment of clonality in cutaneous lymphoid infiltrates by polymerase chain reaction analysis of immunoglobulin heavy chain gene rearrangement.

Determination of the biologic potential of cutaneous lymphoid infiltrates may be difficult by standard histologic or immunohistologic examination. The polymerase chain reaction (PCR) has been used to document clonal rearrangements of the immunoglobulin heavy chain gene in paraffin-embedded fixed tissues. To explore the value of PCR in evaluation of cutaneous lymphoid infiltrates, 93 archival nonmycotic lymphoid lesions (28 small or mixed lymphocytic lymphomas, 15 large cell lymphomas, 40 benign infiltrates, and 10 with atypical features) were analyzed. These cases had been previously immunophenotyped on paraffin sections, and clinical follow-up from 7 to 20 years was gathered. DNA products were generated using a seminested PCR technique, separated by 5% polyacrylamide gel electrophoresis, stained with ethidium bromide, and visualized under UV light. Cases with a 100- to 120-base pair band were scored as positive. Of the 28 small or mixed cell lymphomas, 23 had a B-cell immunophenotype or consisted of a mixture of B and T cells; of these, seven (30%) demonstrated a monoclonal pattern, and three (13%) were indeterminate. Twelve large cell cases were B-cell or mixed; five (42%) of these were positive for a monoclonal band, while four (33%) were indeterminate. None of five T-cell small cell or three T-cell large cell lymphomas demonstrated a monoclonal band. In contrast, 39 of the 40 benign cases were T-cell predominant or mixed lesions. Nevertheless, 18 of these 40 cases on initial testing suggested possible monoclonality. Six were indeterminate, and 12 demonstrated apparent monoclonal bands, of which four were reproducible on repeat testing. No histologic or clinical features of lymphoma were present in 17 of these 18 cases, suggesting that they represent false-positive results. Most of the latter lesions showed sparse perivascular infiltrates, with very few B cells. This suggests that amplification of the immunoglobulin heavy chain gene from a small number of lymphocytes may produce a monoclonal band. In summary, PCR may provide adjunct information about clonality in selected lymphoid skin lesions, but is rather insensitive in this setting. Such data must be carefully considered in the context of the histologic, immunohistologic, and clinical findings, particularly when assessing sparse infiltrates, because of the potential for false-positive results.

B-Lymphocytes↗
PubMed1997

Clear cell tumors of unknown nature and origin: a systematic approach to diagnosis.

Not infrequently, surgical pathologists encounter malignant neoplasms composed of clear cells, the sources and natures of which are indeterminate on the basis of conventional morphological study. In this context, it is frustrating that tumors of completely dissimilar lineage can show strikingly similar microscopic appearances; moreover, anatomic location provides few if any definitive clues to the likely final diagnosis in many cases of clear cell neoplasia. Because of these factors, it is necessary to systematically pursue the same approach to the pathological assessment of clear cell tumors, routinely considering not only clinical and radiologic details but also the possible application of immunohistology, electron microscopy, and cytogenetics. This review provides algorithmic schemes by which such techniques can be applied, as well as their potential drawbacks and limitations.

Adult↗
PubMed1997

Clear cell neoplasms of the endocrine system and thymus.

Clear cell tumors of the endocrine system and thymus are rare lesions with which surgical pathologists have only infrequent contact. As a result, these neoplasms may be misinterpreted and incorrectly classified. This review considers the histological, immunohistochemical, and ultrastructural features of clear cell pituitary adenomas, parathyroid tumors, pancreatic endocrine neoplasms, adrenocortical proliferations, and thymic malignancies. Emphasis is placed throughout on differential diagnosis with microscopically-similar lesions. Clear cell endocrine tumors and thymic lesions manifest a variety of potential lineages, including examples with epithelial, neural, germ cell, and lymphoid differentiation. Because of the wide differences in behavior and recommended treatment in this group, accuracy in diagnosis is essential.

Adenocarcinoma, Clear Cell↗
PubMed1997

Clear cell tumors of the alimentary tract and abdominal cavity.

Clear cell neoplasms of the abdominal organs are represented by a variety of epithelial and mesenchymal neoplasms, of varying malignant potential. Several varieties of clear cell carcinomas, including those with tubulopapillary, hepatoid, colloid, or neuroendocrine features, have been described, as well as several benign epithelial neoplasms. These epithelial tumors have been reported in the gastrointestinal hollow viscera, as well as the liver, pancreas, and biliary tract. A second major consideration is the mesenchymal-derived gastrointestinal stromal tumors, which also may feature clear cells, and comprise a spectrum of biological behavior. Miscellaneous lesions include clear cell variants of melanoma and mesothelioma. This review includes histological details of the various entities, as well as important histochemical, immunohistological, and ultrastructural features. Pertinent differential diagnostic points are stressed, including distinction of the primary clear lesions from relevant metastatic neoplasms.

Abdominal Neoplasms↗
PubMed1997

Absence of TP53 alterations in pheochromocytomas and medullary thyroid carcinomas.

The role of the TP53 gene in the development of inherited and sporadic pheochromocytomas and medullary thyroid carcinomas (MTC) has not been clarified because of conflicting reports and limitations in the assays used to detect mutations. To determine the frequency of TP53 alterations in these tumors, 22 pheochromocytomas and 29 MTCs were screened for loss of heterozygosity (LOH) on 17p with four markers. Single-strand-conformation-variant (SSCV) analysis of exons 4-9 of the TP53 gene was performed in 20 of the pheochromocytomas and in 22 of the MTCs. The expression of p53 was determined by immunohistochemistry in 19 pheochromocytomas and in 17 MTCs using two antibodies (D01 and D07) on frozen and paraffin-embedded tissues. Four of the 22 pheochromocytomas and none of the MTCs showed LOH on 17p. No mutations were detected in any of the tumors screened by SSCV analysis. Immunohistochemical staining of frozen and paraffin-embedded tumor sections did not show p53 overexpression in any of the tumors examined. Our findings indicate that mutations in the TP53 gene are an uncommon event in the tumorigenesis of pheochromocytomas and medullary thyroid carcinomas.

Adrenal Gland Neoplasms↗
PubMed1997

Clear cell neoplasms and pseudoneoplastic lesions of the central nervous system.

Mass lesions of the central nervous system (CNS) that may assume a clear cell appearance are diverse in nature. Primary conditions in this category include oligodendroglioma, hemangioblastoma, germinoma (seminoma), clear cell and chordoid meningioma, pleomorphic xanthoastrocytoma, and lipid-rich glioblastoma. These proliferations usually can be identified by attention to clinical presentation, topographic location, radiographic details, and histological nuances. Occasionally, however, electron microscopy or immunohistological analysis may be necessary. A recommended panel of reagents for the evaluation of clear cell primary CNS lesions include antibodies to glial fibrillary acidic proteins, S-100 protein, epithelial membrane antigen, vimentin, keratins, placental-like alkaline phosphatase, and synaptophysin. This article reviews the salient clinicopathologic attributes of such proliferations, elaborates a practical approach to their diagnosis, and discusses important differential diagnostic considerations. The latter include malformative lesions, infarcts, inflammatory conditions, and secondary lymphomas, carcinomas, and melanomas.

Alkaline Phosphatase↗
PubMed1996

Attenuation of rat lung isograft reperfusion injury with a combination of anti-ICAM-1 and anti-beta2 integrin monoclonal antibodies.

Four different combinations of monoclonal antibodies against rat ICAM-1, CD-11a, and CD-18 were utilized to determine the relative importance of LFA-1, Mac-1, and ICAM-1 in a rat model of severe lung allograft reperfusion injury. Negative control animals were given phosphate buffered saline (the carrier solution for the antibodies), while positive control animals were rendered neutropenic by the administration of a polyclonal mouse IgG. Antibodies were given with the donor lung flush, prior to left lung graft reperfusion, or both. Isolated graft function was determined 24 hr after implantation by arterial blood gas (ABG), and after sacrifice the native and transplanted lungs underwent bronchoalveolar lavage for alveolar protein quantitation, cell count and differential, and myeloperoxidase assay. Additionally, whole lung homogenates were assayed for myeloperoxidase activity. We found that the combination of anti-ICAM-1 (1 mg/kg) added to the donor lung flush, and anti-CD11a, anti-CD18, and anti-ICAM-1 (2 mg/kg i.v. of each) given to the recipient prior to reperfusion, resulted in significantly improved lung graft pAO2 by ABG, and decreased alveolar protein, cell count, and myeloperoxidase activity compared with control animals. Improvement was less than that seen in the neutropenic recipients, however. We conclude that LFA-1, Mac-1, and ICAM-1 are all important adhesion molecules in lung allograft reperfusion injury--yet even with antibody blockade of all three there are additional mechanisms allowing for neutrophil influx into the lungs.

Animals↗