Biomedical subjects

M R Wick

Publications and source records attributed to M R Wick.

At least 217 records · Page 12Linked to original sources

PubMed1988

Recognition of malignant melanoma by monoclonal antibody HMB-45. An immunohistochemical study of 200 paraffin-embedded cutaneous tumors.

Antibodies to S-100 protein have been used widely as markers of malignant melanoma, despite abundant evidence that they are non-specific for this neoplasm. Hence, alternatives to these reagents are desirable in diagnostic dermatopathology. We evaluated the characteristics of a new monoclonal antibody (HMB-45) which does have putative specificity for melanoma, and compared it with a polyclonal anti-S-100 reagent in immunohistochemical staining of 67 melanomas of the skin and 133 non-melanomatous cutaneous neoplasms. All specimens were formalin-fixed and paraffin-embedded, and were studied with the avidin-biotin-peroxidase complex technique. HMB-45 labelled 62 of 67 melanomas, while anti-S-100 recognized all tumors of this type. On the other hand, S-100 also was expressed by 15 of the non-melanocytic neoplasms, all 133 of which were HMB-45-negative. The only cases of melanoma that were missed by the latter reagent were of the spindle-cell type. Hence, HMB-45 was 100% specific and 93% sensitive, relative to a diagnosis of malignant melanoma in paraffin sections. Epithelioid and small-cell neoplasms are reliably recognized by this antibody, but it would appear that spindle-cell melanomas must be detected by other immunohistochemical means.

Antibodies, Monoclonal↗

PubMed1988

Reactive and malignant "angioendotheliomatosis": a discriminant clinicopathological study.

In order to determine whether or not phenotypic differences existed between reactive angioendotheliomatosis (RAE) and malignant angioendotheliomatosis (MAE), we studied the histological and immunohistochemical features of 4 and 8 cases of these lesions, respectively. Antibodies to leukocyte common antigen (LCA), specialized B- and T-lymphocytic determinants, Factor VIII-related antigen (FVIIIRAG), blood group isoantigens A, B, and H (BGI), epithelial antigens, vimentin, and actin; and Ulex europaeus I lectin (UEL) were utilized. Cutaneous lesions in all cases of MAE were part of a disseminated, fatal, intravascular cellular proliferation, with highly atypical cytological features. Because one of the patients in this group had cardiac valvular vegetations at autopsy, this case had been reported previously as representative of RAE. However, the latter example, as well as all others of MAE, stained strongly for LCA, B-cell antigens, and vimentin in tumor cells. FVIIIRAG was seen focally in 6 cases, in cells entrapped in platelet-fibrin thrombi; however, UEL binding and reactivity for BGI were uniformly absent. Conversely, RAE was typified by a cytologically-bland intravascular proliferation, with actin-positive, perivascular, pericytic cuffs. All 4 patients in this group had cutaneous involvement only, and the lesions tended to be self-resolving. One had pulmonary tuberculosis, but evidence for an underlying infection was absent in the remainder of RAE cases. Immunohistologically, RAE displayed universal reactivity for FVIII-RAG, BGI, UEL, and vimentin, and negativity for LCA in intravascular cells. Neither MAE nor RAE showed the presence of epithelial determinants. These data indicate that MAE and RAE are clinicopathologically distinct entities, showing lymphoid and endothelial features, respectively. Because of the phenotypic properties of the former condition, it would appear advisable to substitute the term "intravascular lymphomatosis" for "malignant angioendotheliomatosis".

Adolescent↗

PubMed1988

A reassessment of "chordoid sarcoma". Ultrastructural and immunohistochemical comparison with chordoma and skeletal myxoid chondrosarcoma.

The relationship of "chordoid sarcoma" (CS) to chordoma and myxoid chondrosarcoma has been debated for several years. In order to reassess this issue, we studied 5 CS, 5 chordomas, and 3 skeletal myxoid chondrosarcomas ultrastructurally and immunohistochemically. By electron microscopy, CS demonstrated smooth cellular outlines, macular intercellular junctions, and cytoplasmic inclusions of matrix-like material. Chordomas displayed a closely similar fine structural appearance, but in addition contained small, membrane-bound, glycogen-containing inclusions. Skeletal myxoid chondrosarcomas resembled CS, except that the former lesions had spiculated cell membranes and lacked intercellular junctions. Immunohistochemically, all CS cases expressed vimentin and lacked cytokeratin (CK). Leu 7 and S100 protein were seen in four cases each of CS, and three of these tumors demonstrated diffuse or focal reactivity for epithelial membrane antigen (EMA). Similar phenotypic features were seen in chordomas, except that all of them stained diffusely for CK, as well as EMA. Skeletal myxoid chondrosarcomas expressed vimentin, S100, and Leu 7 uniformly, but were devoid of epithelial markers. In aggregate, these data support the classification of "chordoid sarcoma" as a form of chondrosarcoma, but reveal that it may exhibit an "epithelial" antigen in some cases.

Adult↗

PubMed1988

So-called sclerosing hemangiomas of lung. An immunohistochemical study supporting a respiratory epithelial origin.

Sclerosing hemangiomas are benign pulmonary neoplasms. They were initially believed by Liebow and Hubbell to be of endothelial origin; however, subsequent ultrastructural studies have suggested an alveolar pneumocyte and mesothelial derivation. Using a panel of various antibodies on eight cases, the authors found that sclerosing hemangiomas expressed cytokeratin (seven cases), epithelial membrane antigen (seven cases), carcinoembryonic antigen (five cases), vimentin (seven cases), surfactant apoprotein (eight cases), and Clara cell antigen (five cases). These results support the hypothesis that sclerosing hemangiomas represent an epithelial tumor showing simultaneous bronchiolar epithelial and alveolar pneumocyte differentiation.

Adult↗

PubMed1988

Immunohistochemical analysis of soft tissue sarcomas. Comparisons with electron microscopy.

Soft tissue sarcomas are capable of causing diagnostic bewilderment for the surgical pathologist, because of their diversity of differentiation and overlapping histologic appearances. Immunohistochemical studies provide a means whereby this confusion can be resolved in many cases, and electron microscopy also may play a useful role in this process. This overview presents a summary of results of these 2 adjuvant modalities of pathologic analysis, as applied to the spectrum of malignant soft tissue neoplasms.

Humans↗

PubMed1988

Lymphoepithelioma-like carcinoma of the skin.

Carcinomas histologically resembling nasopharyngeal lymphoepithelioma have been identified in the salivary gland, thymus, tonsil, and uterine cervix. Five patients with similar tumors primary in the skin are described. The patients ranged in age from 50 to 81 yr. Four neoplasms were situated on the head, and one was located on the shoulder. Microscopically, they were concentrated in the mid- and deep dermis and lacked connections with epidermis. The pattern was of multiple nodules, smaller irregular islands, and cords. The uniform tumor cells had moderate amounts of lightly eosinophilic cytoplasm and vesicular nuclei with one or two prominent nucleoli. A lymphoid infiltrate was intimately associated with each neoplasm and obscured the malignant epithelium in one. Neither squamous nor glandular differentiation was present, but all tumors exhibited intracytoplasmic mucin. Immunohistochemistry was positive for cytokeratin (5 of 5; diffuse) and epithelial membrane antigen (4 of 5; 3 diffuse, 1 focal). Focal reactivity was also noted for carcinoembryonic antigen (1 of 5), neuron-specific enolase (1 of 5), and vimentin (1 of 5). S100 protein, leukocyte common antigen, Factor VIII-related antigen, prostate-specific antigen (males), Leu M1, and salivary amylase reactivity were absent. One patient developed local recurrence and metastases after 39 mo and was dead of disease at 57 mo. The remaining four were free of disease after 46, 27, 25, and 6 mo of follow-up. The diagnosis of lymphoepithelioma-like carcinoma of the skin is based on microscopic findings and exclusion of occult malignancy. The tumor can be confused with a lymphoid infiltrate and is differentiated from Merkel cell carcinoma primarily on cytologic grounds. The neoplasm may be of adnexal origin.

Aged↗

PubMed1988

Detailed studies on expression and function of CD19 surface determinant by using B43 monoclonal antibody and the clinical potential of anti-CD19 immunotoxins.

Extensive immunologic surface marker analyses and binding competition assays demonstrated that B43 monoclonal antibody (MoAb) is a new member of the CD19 cluster that recognizes the same surface epitope as several other anti-CD19 MoAbs. We used B43 MoAb to test for CD19 expression on neoplastic cells from 340 leukemia and 151 malignant lymphoma patients and on nonneoplastic cells in normal lymphohematopoietic and nonlymphohematopoietic tissues. Our study more than doubles the total number of cases with classified hematologic malignancies that have been examined for CD19 antigen expression. The data presented confirm that CD19 is the most reliable B lineage surface marker and support our view that this B lineage-restricted surface determinant may be an important functional receptor. Our findings provide unique and direct evidence that (a) CD19 is expressed on leukemic B lineage lymphoid progenitor cells freshly obtained from B lineage acute lymphoblastic leukemia patients but not on normal myeloid, erythroid, megakaryocytic, or multilineage bone marrow progenitor cells; (b) ligation of CD19 with B43 MoAb induces sustained increases in [Ca2+]i when crosslinked and inhibits high-molecular weight B cell growth factor (HMW-BCGF)-induced proliferation of activated B cells without affecting their low-molecular weight B cell growth factor (LMW-BCGF) response; therefore CD19 may be a unique signal receptor; (c) HMW-BCGF and LMW-BCGF augment expression of CD19, which suggests that CD19 and BCGF receptors may be under coordinate regulatory control; (d) approximately two million B43 MoAb molecules per cell can be bound to target B lineage lymphoma cells with a Ka of 1.9 x 10(8)/mol/L; (e) CD19 can undergo B43 MoAb-induced internalization; and (f) the opportunity is thus provided for using anti-CD19 MoAb to deliver toxins to B lineage neoplastic cells for more effective treatment of high-risk leukemia/lymphoma patients.

Antibodies, Monoclonal↗

PubMed1988

Immunohistochemical diagnosis of sinonasal melanoma, carcinoma, and neuroblastoma with monoclonal antibodies HMB-45 and anti-synaptophysin.

The efficacy of two new monoclonal antibodies with cell lineage-restricted reactivity (HMB-45 [melanocytes] and anti-synaptophysin [neuroepithelial cells]) was compared with that of "traditional" antibody panels in the delineation of malignant melanoma (MM) of the sinonasal region, nasopharyngeal carcinoma (NPC), and olfactory neuroblastoma (ONBL). HMB-45 recognized all of eight melanomas and stained one of five neuroblastomas, but failed to label any of 12 cases of NPC. All examples of ONBL were stained by anti-synaptophysin; other tumors were nonreactive with this reagent. A panel of antibodies to cytokeratin, vimentin, epithelial membrane antigen, and S100 protein was also effective in discriminating between MM, NPC and ONBL. These results suggest that HMB-45 and anti-synaptophysin are comparable in utility to more extended antibody panels in the diagnosis of sinonasal malignancies, but only if used in combination with one another.

Adult↗

PubMed1987

Leu-7 in small cell neoplasms. An immunohistochemical study with ultrastructural correlations.

In an effort to delineate the distribution of the Leu-7 antigen in small cell neoplasms, 283 paraffin-embedded examples of such tumors were studied immunohistochemically. These included 125 malignant lymphomas, 94 neuroendocrine carcinomas, 13 adenocarcinomas, 14 squamous carcinomas, four malignant melanomas, six neuroblastomas, four nephroblastomas (Wilms' tumors), six primitive neuroectodermal neoplasms, three "Askin" tumors, ten Ewing's sarcomas, and four embryonal rhabdomyosarcomas. Histologic diagnoses were verified by the use of electron microscopic study or independent immunostains. Overall, 44% of small cell neuroendocrine carcinomas expressed Leu-7, whereas nonendocrine carcinomas were uniformly nonreactive for this determinant. All neuroblastomas yielded immunopositivity, as did three primitive neuroectodermal tumors, three rhabdomyosarcomas, two "Askin" tumors, one nephroblastoma, one Ewing's sarcoma, and one malignant melanoma. None of the small cell lymphomas were Leu-7 positive. These results suggest that Leu-7 is a specific neuroendocrine marker in cases of small cell carcinoma, but its sensitivity is lower than that of other "endocrine" determinants. Reactivity patterns for Leu-7 in other small cell tumors demonstrate no specificity for any given line of cellular differentiation. However, the shared expression of this antigen by neuroblastomas, neuroectodermal tumors, Ewing's sarcomas, and Wilm's tumors contributes further to the hypothesis that these neoplasms may be related histogenetically.

Antigens, Differentiation, T-Lymphocyte↗

PubMed1987

Thymoma. A clinicopathologic review.

The clinical and pathologic features of 283 patients with thymoma treated at the Mayo Clinic (147 female and 136 male; ages 16 years to 90 years; mean, 52 years) were examined. Forty-six percent of the patients had myasthenia gravis and 10% had other paraneoplastic phenomena. The tumors were locally invasive at operation in 32%, including 6% with metastasis to lung or pleura. Intrathoracic recurrence was noted postoperatively in 15% of those who had total excision and distant metastasis developed in 3% of patients. Thirteen percent died of their thymomas and 16% died of myasthenia. Overall 5-year survival was 67% and 10-year survival was 53%. Poor prognostic factors included presence of tumor-related symptoms, large tumor size, local invasion or metastasis in initial operation, and predominantly epithelial histologic features. Although true thymomas are composed of cytologically benign elements, they show a propensity for local invasion and intrathoracic recurrence. They rarely metastasize outside the thorax.

Adolescent↗

PubMed1987

Epithelioid sarcoma and epithelioid hemangioendothelioma: an immunocytochemical and lectin-histochemical comparison.

Epithelioid sarcoma (ES) and epithelioid hemangioendothelioma (EH) both occur preferentially in the soft tissues, and may be confused with one another microscopically. We compared 8 examples of each tumor immunohistochemically, using formalin-fixed tissue, the ABC method, unconjugated Ulex europaeus I agglutinin (UEA), rabbit antibody to UEA, and monoclonal antibodies to epithelial membrane antigen (EMA), cytokeratin (CK), factor VIII-related antigen (FVIIIRAG), and blood group isoantigens A, B, and H (BGI). Six of 8 cases of ES, and 7 of 8 epithelioid hemangioendotheliomas bound UEA; similarly, 6 of 8 ES cases were reactive for BGI, as were 4 of 8 examples of EH. All epithelioid sarcomas were positive for CK, and 7 displayed EMA, whereas these antigens were lacking in EH. Conversely, 5 of 8 cases of EH contained FVIIIRAG, which was absent in all examples of ES. These findings underscore the nonspecificity of UEA-binding and BGI-expression as markers of endothelial differentiation. Moreover, they suggest that sole reliance upon these immunohistologic reactants for the identification of vascular tumors may result in diagnostic error. Inasmuch as ES and EH differ in biological behavior, such a mistake would be significant. Thus, we advocate the inclusion of immunostains for EMA, CK, and FVIIIRAG in the evaluation of histologically-similar cases of epithelioid sarcoma and epithelioid hemangioendothelioma.

Blood Group Antigens↗

PubMed1987

Dedifferentiated chondrosarcoma of bone. An immunohistochemical and lectin-histochemical study.

Ten cases of dedifferentiated chondrosarcoma (DCS) were immunohistochemically and histochemically compared with 12 de novo malignant fibrous histiocytomas, 10 osteoblastic osteosarcomas, 9 conventional chondrosarcomas, and 4 fibrosarcomas (all of bone or soft tissues), in order to discern similarities and differences in the immunophenotypes of these neoplasms. All cases of DCS and malignant fibrous histiocytoma were reactive for alpha-1-antichymotrypsin, and several examples of both tumor types bound peanut agglutinin, and expressed positivity for alpha-1-antitrypsin and lysozyme. None of these four cellular markers was observed in de novo osteosarcoma and fibrosarcoma; in addition, conventional chondrosarcoma lacked all of them except for peanut agglutinin receptors. S100 protein reactivity and binding of wheat germ agglutinin were detectable in conventional chondrosarcomas and in rare cells of the anaplastic components of primary DCS, but not in malignant fibrous histiocytoma arising ab initio and the other sarcomas. These results suggest the evolution of a second neoplastic cellular clone in DCS, with primitive morphological and phenotypic characteristics.

Adult↗

PubMed1987

Thyrocalcitonin-containing cells in the Di George anomaly.

The Di George syndrome is an anomaly characterized by the complete or partial absence of derivatives of the third and fourth pharyngeal pouches often associated with defective development of the third, fourth, and sixth aortic arches leading to absence or hypoplasia of the thymus and parathyroid glands and to cardiovascular anomalies. The fifth pharyngeal pouch, often considered a part of the fourth pouch, gives rise to the ultimobranchial body (UB), which becomes incorporated into the thyroid gland and is thought to be the source of thyroid C cells. Robinson suggested that complete or partial absence of the UB should be considered a part of the Di George anomaly. To substantiate this theory, the thyroid glands of 11 patients with the Di George syndrome and 11 age-matched control infants were examined immunohistochemically using the immunoperoxidase technique for presence or absence of thyrocalcitonin (TC)-containing cells. Only three of 11 patients with the Di George syndrome had TC-containing cells in their thyroid glands (27 per cent), and nine of 11 control infants had these cells (82 per cent). It is concluded that thyroid C cell deficiency is present in most patients with Di George anomaly, suggesting a relationship between these cells and development of derivatives of the third through fifth visceral pouches. Furthermore, there is a spectrum of deficiency of thyroid C cells in these individuals comparable with the spectrum of partial to complete absence of third and fourth pharyngeal pouch derivatives regarding thymus and parathyroid glands. Immunostaining for TC of the lungs of all infants with the Di George syndrome and control infants revealed similar numbers of thyrocalcitonin-containing cells in both groups. Asynchronous development of thyroid and lung thyrocalcitonin-containing cells in those with the Di George syndrome favors the theory that the latter develop independently of derivatives of the third through fifth visceral pouches. This study further supports a neural crest origin of the Di George anomaly and strengthens the concept that the Di George anomaly is a neurocristopathy.

Calcitonin↗

PubMed1987

Small cell neuroendocrine carcinoma of the colon and rectum: clinical, histologic, and ultrastructural study and immunohistochemical comparison with cloacogenic carcinoma.

In an effort to provide immunocytochemical data that would be useful in distinguishing between small cell epithelial tumors of the anorectal region, 10 cases of neuroendocrine small cell colorectal carcinoma (NSCCC) and five cases of cloacogenic carcinoma (CC) were studied with antibodies to cytokeratin, epithelial membrane antigen (EMA), chromogranin, blood group isoantigens (BGI), carcinoembryonic antigen (CEA), Leu-M1, Leu-7, leukocyte common antigen (LCA), S-100 protein, neurofilaments (NF), neuron-specific enolase (NSE), serotonin, and 14 neuropeptides. The diagnoses for all 15 tumors were verified ultrastructurally. Among the antigenic determinants considered, reactivity for low- and medium-molecular-weight cytokeratin, EMA, NSE, and NF was seen in the majority of NSCCCs, whereas the CCs were positive for all cytokeratin classes, BGI, EMA, and CEA. In addition, Leu-M1, Leu-7, and chromogranin were each expressed in three cases of NSCCC. None of the other antisera yielded positive results in tumors of either type. All 10 patients with NSCCC died of their tumors within 11 months of clinical presentation, while four of the five CCs proved fatal, with an average survival of 28 months. One of the patients with CC was free of disease 31 months after diagnosis. These data suggest that an immunocytochemical panel, consisting of antibodies to high-molecular-weight cytokeratin, BGI, CEA, NSE, and NF (and possibly Leu-7 and chromogranin as well), is capable of distinguishing between NSCCC and CC in problematic cases. Although tumors of both types are aggressive, it is possible that the survival statistics for both may be improved through more accurate diagnostic classification.

Adult↗

PubMed1987

Hepatoblastoma: an immunohistochemical and ultrastructural study.

The ultrastructural and immunohistochemical features of 19 hepatoblastomas were examined to evaluate the phenotypic expressivity of this solid embryonic neoplasm of childhood. Electron microscopy confirmed the embryonal and fetal characteristics of the neoplastic hepatocytes, but in addition, cells with features intermediate between these two cell types were identified. Dense bundles of collagen corresponding to the osteoid-like material by light microscopy surrounded nests of cells; the cells within this matrix stained for epithelial membrane antigen and vimentin and focally for cytokeratin, and they showed ultrastructural features of epithelial cells. The two cases of small cell hepatoblastoma reacted positively for vimentin and cytokeratin; the remaining 17 cases were immunoreactive for cytokeratin and alpha-fetoprotein, and some also for alpha 1-antitrypsin, ferritin, and vimentin. A histogenetic scheme based on our findings is proposed to explain the divergent morphologic features of this neoplasm.

Carcinoembryonic Antigen↗

PubMed1987

Placental-like alkaline phosphatase reactivity in human tumors: an immunohistochemical study of 520 cases.

Placental-like alkaline phosphatase (PLAP) activity has been reported in various human neoplasms of both somatic and germ cell types. The expression of PLAP was examined with a polyclonal antibody and the immunoperoxidase technique in formalin-fixed, paraffin-embedded sections of 37 germ cell neoplasms and 483 somatic tumors. The expression of keratin and epithelial membrane antigen (EMA) was concurrently assessed to determine whether these stains were helpful in distinguishing germ cell neoplasms from somatic tumors that might mimic them microscopically. All germ cell lesions were reactive for PLAP, but so were 62 somatic carcinomas, usually in female müllerian, intestinal, and lung cancers and less often in carcinomas of the breast and kidney. PLAP-reactive somatic tumors exhibited EMA and keratin positivity in the absence of prior protease digestion, whereas germ cell neoplasms failed to do so. Malignant mesotheliomas were nonreactive for PLAP, as were carcinomas of the nasopharynx, adrenals, liver, pancreas, stomach, prostate, and urinary bladder. PLAP is a highly sensitive but nonspecific immunohistologic marker of germ cell differentiation. However, non-protease-enhanced stains for keratin and EMA allow separation of germ cell and somatic carcinomas, despite their shared capacity for PLAP expression. In somatic neoplasms, PLAP immunoreactivity might be of potential use in predicting possible primary sources for metastatic tumors of unknown origin.

Alkaline Phosphatase↗

PubMed1987

Epithelioid sarcoma. An immunohistochemical study.

The immunohistochemical findings in 14 epithelioid sarcomas, neoplasms of uncertain histogenesis, indicate that they react with antibodies against cytokeratin, epithelial membrane antigen, and vimentin. All cases were nonreactive for leukocyte common antigen, myoglobin, and Factor VIII-related antigen. These results point to the fact that epithelioid sarcoma expresses phenotypic characteristics more often associated with epithelioid neoplasms, rather than the mesenchymal profile of most soft tissue sarcomas. One explanation for this observation is that epithelioid sarcoma is in fact a carcinoma originating in the deep soft tissues. On the other hand, the pluripotential mesoderm has a known embryonic capacity to differentiate into epithelium and, therefore, it is plausible that epithelioid sarcoma is a mesenchymally derived neoplasm. Aside from histogenetic considerations, epithelioid sarcoma may be confused with a number of other neoplastic and granulomatous processes. Differential immunohistochemical stains are useful in selected instances wherein light and electron microscopic findings are diagnostically equivocal.

Adolescent↗

PubMed1987

Malignant peripheral nerve sheath tumor. An immunohistochemical study of 62 cases.

Malignant peripheral nerve sheath tumor (MPNST) commonly presents a diagnostic challenge and may resemble a variety of other soft tissue neoplasms microscopically. The authors have examined 62 examples of MPNST immunohistochemically, using antibodies to S-100 protein, myelin basic protein (MBP), and Leu-7, all of which are potential neural markers. Sixty-eight percent of all cases expressed at least one of these three determinants, representing a higher rate of immunoreactivity than that seen for single nervous system antigens in previous studies. Conjoint reactivity for S-100/Leu-7, S-100/MBP, and MBP/Leu-7 was seen in 34%, 34%, and 24% of cases, respectively. This coexpression of antigens is important, because none of them in isolation is immunospecific for nerve sheath tumors. In addition, stains for epithelial membrane antigen were reactive in two epithelioid tumors in this series, and eight spindle-cell neoplasms demonstrated desmin positivity. Analyses for cytokeratin, carcinoembryonic antigen, and Factor VIII-related antigen were negative in all cases. These results indicate an overlap between the immunocytochemical attributes of malignant peripheral nerve sheath tumors and other soft tissue sarcomas and emphasize the desirability of assessing multiple neural markers in such cases.

Antigens↗