Vascular neoplasms of the skin: a current perspective.
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Hemangioendothelioma↗
Biomedical subjects
M R Wick
Publications and source records attributed to M R Wick.
The first six years' experience with the Pathology Residents' In-Service Examination, 1983-1988.
Data derived from the 1983-1988 administrations of the American Society of Clinical Pathology Residents In-Service Examination (PRISE) are presented. Data indicate an increase in participation by U.S. and Canadian pathology residency training programs (from 55% in 1983 to approximately 90% in 1988). Demographic data reflect an increase in the proportion of foreign medical graduates (from 24.8% in 1983 to 32.8% in 1988) in U.S. training programs with concomitant decrease in proportion of U.S. medical graduates (from 74.8% to 61.5%, respectively). Canadian residents comprise approximately 5% of the test population. Response surveys from residents and program directors indicate a high degree of satisfaction with the PRISE. In 1988 40.6% of all program directors thought that the PRISE satisfied their objectives very well, and 56% thought that objectives were met satisfactorily. For residents the corresponding rates were 21.2% and 70.7%. Trends in resident group performance in each subspecialty area of pathology, and the implications for residency training are discussed.
Adult↗
Technologic anarchy?
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Medical Laboratory Science↗
Pleuropulmonary blastoma. The so-called pulmonary blastoma of childhood.
The authors studied 11 pediatric intrathoracic neoplasms that share clinicopathologic features and constitute a specific tumor in children. These neoplasms were intrapulmonary, mediastinal, or pleural-based masses. A common histologic feature was the presence of small, primitive cells with blastematous qualities separated by an uncommitted stroma. Focal rhabdomyosarcomatous, chondrosarcomatous, and liposarcomatous differentiation was observed. Epithelial components had bland cytologic features and probably represented entrapped benign epithelium and/or mesothelium. The prognosis for these patients was grave; seven patients died of their disease 5 months to 2 years after diagnosis. Two patients have survived disease-free for 10 and 12 years after diagnosis. Two recent cases are alive 14 and 32 months after diagnosis. This neoplasm constitutes a distinct entity which has been reported in the literature as pulmonary blastoma in children. It differs from pulmonary blastoma in adults because of its variable anatomic location, primitive embryonic-like blastema and stroma, absence of a carcinomatous component, and potential for sarcomatous differentiation. The designation of pleuropulmonary blastoma is suggested by the authors for these intrathoracic neoplasms of childhood rather than pulmonary blastoma for histogenetic and anatomic reasons. The clinicopathologic features, immunophenotypic and ultrastructural characteristics, possible histogenesis, and differential diagnosis of these neoplasms from other thoracopulmonary tumors in children serve as the basis for this report.
Child↗
Immunohistochemistry of germ cell and trophoblastic neoplasms.
The immunoprofiles of 121 germ cell and trophoblastic neoplasms were defined, using a battery of antibodies against cytokeratin (CK), vimentin (VIM), epithelial membrane antigen (EMA), placental alkaline phosphatase (PLAP), S-100 protein, leukocyte common antigen (LCA), UCHL-1, LN-2, carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), chromogranin A, Leu-7, alpha-fetoprotein (AFP), alpha-1-antitrypsin (AAT), and the beta subunit of human chorionic gonadotropin (BHCG). In addition to 85 neoplasms of testicular origin, the cases included eight ovarian germ cell tumors and 28 extragonadal neoplasms. All tissues had been subjected to formalin fixation and paraffin embedding. Similar immunoreactivity patterns were seen in gonadal and extragonadal neoplasms, gestational and nongestational choriocarcinomas, components of mixed germ cell tumors and their pure counterparts, and metastatic and primary lesions. Placental alkaline phosphatase was a sensitive marker of germ cell differentiation, and expression of this marker in the absence of EMA appeared to be a staining pattern unique to germ cell tumors. Both LCA and S100 were absent in neoplastic germ cells, and thus were useful in differentiating these tumors from malignant lymphoma and malignant melanoma, respectively. Cytokeratin was helpful in distinguishing seminomas/dysgerminomas from nonseminomatous germ cell tumors, although 10% of seminomas showed focal or diffuse cytokeratin reactivity. Finally, 75% of all germ cell neoplasms displayed NSE, calling the specificity of this determinant into question.
Alkaline Phosphatase↗
Congenital adrenal hypoplasia and selective absence of pituitary luteinizing hormone: a new autosomal recessive syndrome.
Congenital hypoplasia of the adrenal glands (CHA) is a rare condition, particularly in the absence of a central nervous system (CNS) anomaly. Two major types of CHA have been described in the setting of an apparently normal CNS and pituitary: a cytomegalic type usually with X-linked recessive inheritance and a miniature adult type that, when hereditary, is an autosomal recessive trait. Glycerol kinase deficiency (GKD) is an X-linked recessive trait, and it may be associated with CHA and adrenal insufficiency, presumably because of deletion of adjacent X-linked loci. We report on three sibling infants, one male and two females, with normal CNS and lethal CHA of the miniature adult type, selective absence of pituitary LH; two of the infants also had glycerol kinase (GK) activity that was decreased but not in the GKD range. Restriction fragment length polymorphism (RFLP) analysis of X chromosome markers located at Xp21-p22 was carried out on the maternal grandfather, both parents, two of three affected infants, and a living normal brother. The results excluded the X-linked type of this disorder associated with GKD in this family. Autosomal recessive inheritance is most likely.
Adrenal Glands↗
Relationship of prostatic acid phosphatase localization in human prostate by a monoclonal antibody with the Gleason grading system.
Prostatic acid phosphatase (PAP) was localized in human prostate with a monoclonal antibody prepared against PAP isoenzyme II to determine patterns of its expression in normal, hyperplastic (BPH), and cancerous glands. The monoclonal antibody reacted with both isoenzymes II and IV in immunoblot studies. Formalin-fixed, paraffin-embedded tissue was used from patients who had not been treated with hormones or chemotherapy. In normal glands and BPH, there was marked variation in the intensity of PAP staining in morphologically otherwise similar epithelial cells. There was similar heterogeneity of staining in the adenocarcinomas. Rough quantification of the intensity patterns in the clinical groups indicated a slight shift to more intense staining in BPH and well-differentiated carcinomas but a progressive decline in the PAP staining in the moderately and poorly differentiated tumors. This decrease in intracellular staining with decreasing differentiation is not inconsistent with the clinical observation that serum levels of acid phosphatase generally increase with higher grade and disseminated tumors, since the enzyme is simply more accessible to the circulatory system in those cases. The same decrease may explain the few disseminated tumors that are not associated with elevated serum levels.
Acid Phosphatase↗
Circumferential nodulocystic keratopathy. A case report.
An apparently unique type of corneal nodular keratopathy is presented. The keratopathy was characterized by large, circumferentially bilaterally located, cystic nodules just inside the limbus. No epithelial cell or collagenous degeneration nor evidence of chronic inflammatory process was found on histopathologic examination of a biopsy of a nodule. Proteinaceous material was present between the epithelial cell basement membrane and collagenous stroma. There was no antecedent history of keratitis or uveitis. The patient was known to have inflammatory bowel disease (regional ileitis) and rheumatoid arthritis with ankylosing spondylitis. However, the corneal lesions could not definitely be associated with any of these disorders. This case does not correspond with any previously described corneal disorders. We have termed it circumferential nodulocystic keratopathy, which best describes its clinical and histologic features.
Albumins↗
Immunophenotyping of hematopoietic malignancies in paraffin sections.
Immunophenotyping of hematopoietic malignancies is usually accomplished in frozen sections or cell suspensions. To determine whether this procedure was also feasible in paraffin sections, we performed a double-blind immunoperoxidase study of 65 hematopoietic tumors whose phenotypes had been determined previously in fresh tissue. A selected antibody panel was used, including anti-LN2, UCHL-1, anti-cathepsin B, anti-Leu M1, anti-MB2, and anti-MT1. A correct phenotype was obtained on paraffin sections in 95% of cases. All 31 B-cell malignancies were properly classified, showing reactivity for LN2 and MB2. In 14 of 15 T-cell hematopoietic malignancies, all cells reacted with anti-MT1 and/or UCHL-1; the 1 case negative for these antigens was misdiagnosed as a B-cell tumor because of misinterpreted LN2 reactivity in benign histiocytes. Four of 5 true histiocytic neoplasms were positive for cathepsin B and LN2 but lacked other antigens; the fifth case was wrongly considered a B-cell proliferation because only bland histiocytes displayed cathepsin B. Only 1 of 7 Hodgkin's lymphomas was misdiagnosed (as a T-cell tumor); in the other 6 cases, Reed-Sternberg cells were reactive for LN2 and LEU M1. Five of 6 extramedullary myeloid leukemias also stained for LN2, MT1, and LEU M1. One showed LN2, MB2, and MT1; this case was classified as a B-cell neoplasm and indeed represented a pre-B-cell transformation of chronic myelogenous leukemia. These results show that the specified panel of antibodies may be useful for immunophenotyping of hematopoietic neoplasms when only paraffin sections are available for analysis. However, it cannot supplant traditional cell-marker studies of hematopoietic tumors because of its lesser accuracy.
Antibodies, Monoclonal↗
Neuroendocrine neoplasms of the thymus.
Neuroendocrine tumors of the thymus bear many similarities to "carcinoids" and "oat-cell carcinomas" in other organs, and are clinicopathologically distinct from thymomas, thymic seminomas, and other primary tumors of this gland. They are associated with Cushing's syndrome or multiple endocrine neoplasia in 35% of cases, and are often locally aggressive. Approximately 30-40% of patients have distant metastases of their tumors that ultimately result in fatality, since the response of thymic neuroendocrine neoplasms to irradiation and chemotherapy is poor. Ultrastructural studies and immunohistochemical stains for chromogranin, protein gene product 9.5, and synaptophysin are effective tools for the diagnosis of thymic carcinoid and oat-cell carcinoma.
Diagnosis, Differential↗
The use of proteolysis with ficin, for immunostaining of paraffin sections. A study of lymphoid, mesenchymal, and epithelial determinants in human tissues.
In order to maximize staining, modifications of immunostaining methods have included proteolytic enzyme digestion of tissue. The authors performed a study of the effect of ficin in 110 paraffinized specimens, including tonsil, lymph nodes, benign vascular and nerve sheath tumors, and various carcinomas and sarcomas. This agent was compared with pepsin and bromelain, as alternative proteases. A panel of monoclonal and polyclonal antibodies was used, with and without previous digestion by ficin, pepsin, and bromelain. A score was assigned to each stain, based on the number and intensity of reactive cells. Ficin enhanced staining markedly in immunostains with antibodies to keratin and Factor VIII-related antigen (F8RAG). Conversely, it abolished staining for LN-2 (a lymphoid marker) and weakened reactivity for S-100 in nerve sheath tumors. Bromelain produced similar results, except that it enhanced S-100. Pepsin was comparatively less active than ficin and bromelain overall but did produce the greatest amplification of vimentin staining in sarcomas. Digestion with any of the three enzymes failed to influence reactivities of leukocyte common antigen, UCHL-1 (a lymphoid marker), alpha-1-antichymotrypsin, carcinoembryonic antigen, epithelial membrane antigen, and blood group isoantigens. These results may reflect a dissimilar recognition of peptide targets in some antigenic proteins, by ficin, bromelain, and pepsin. Hence, one enzymatic agent is unlikely to produce optimal staining for all determinants. With this proviso, however, ficin appeared to be the best general enhancer for antigens known to require vigorous digestion (e.g., keratin; F8RAG) for optimal reactivity in paraffin sections.
Cysteine Endopeptidases↗
Transitional cell carcinoma of the urinary bladder with pseudosarcomatous stroma.
An 84-year-old man who complained of hematuria had transurethral resection of a large polypoid tumor in the urinary bladder. Pathologic examination showed an invasive, moderately differentiated transitional cell carcinoma with numerous atypical mesenchymal cells in its stroma. The latter cells failed to stain immunohistochemically for epithelial markers and were interpreted as reactive or pseudosarcomatous in nature. Transitional cell carcinomas with pseudosarcomatous stroma should be distinguished from bladder tumors with a neoplastic spindle cell component such as sarcomatoid carcinomas and carcinosarcomas.
Aged↗
Paul Ehrlich: the prototypic clinical pathologist.
The well-defined scientific roles of Paul Ehrlich are reviewed in context with modern concepts and practices in immunology.
Allergy and Immunology↗
Sarcomatoid carcinoma of the urinary bladder. A clinicopathologic analysis of 12 cases and review of the literature.
Twelve carcinomas of the urinary bladder with a prominent component of spindle-shaped cells (sarcomatoid carcinomas) that arose in patients from 60 to 83 (average, 71.5 years) years of age are reported. The seven male and five female patients typically complained of hematuria. Seven tumors were sessile and five were polypoid. On microscopic examination, the malignant spindle cells merged with in situ transitional cell carcinoma or various forms of invasive carcinoma, including transitional cell carcinoma (11 cases), adenocarcinoma (2 cases), squamous cell carcinoma (2 cases), and small cell undifferentiated carcinoma (2 cases). Immunocytochemical stains were performed in 11 cases; the spindle cells stained for cytokeratin, epithelial membrane antigen, and vimentin. Limited follow-up in this series does not allow for conclusions concerning differences in behavior between sarcomatoid carcinoma and conventional transitional cell carcinoma of similar grade and stage. However, the typically deep invasion of the former tumors and their histologic features indicate that they are highly aggressive neoplasms.
Aged↗
Spindle-cell and pleomorphic neoplasms of the skin. A clinicopathologic and immunohistochemical study of 30 cases, with emphasis on "atypical fibroxanthomas".
Atypical fibroxanthoma belongs to the family of spindle-cell and pleomorphic neoplasms of the skin. The lineage of differentiation of this tumor and the means whereby it can be diagnostically separated from other similar morphologic entities have been controversial. In order to address these issues, the authors studied 30 spindle-cell and/or pleomorphic cutaneous tumors, including atypical fibroxanthomas (AFXs), superficial malignant fibrous histiocytomas (MFHs), dermatofibrosarcoma protuberans (DFSPs), sarcomatoid squamous-cell carcinomas (SCCs), spindle-cell malignant melanomas (MMs), and leiomyosarcomas, (LMSs). These cases were analyzed using a panel of eight antibodies and the immunoperoxidase technique. AFXs were reactive for vimentin, alpha-1-antichymotrypsin (AACT), alpha-1-antitrypsin (AAT), and cathepsin-B (CB) but failed to display cytokeratin (CK), epithelial membrane antigen (EMA), S-100 protein, and desmin. MFHs and DFSPs exhibited immunophenotypic profiles that were nearly identical to that just described. In contrast, SCCs were typified by positivity for CK and EMA; MMs exhibited uniform reactivity for S-100 protein; and LMSs contained desmin in four of five cases. A surprising result was the expression of S-100 by LMSs. Also, all tumors displayed at least one of the three proteolytic enzymes assessed in this study (AAT, AACT, and CB), demonstrating the relative diagnostic nonspecificity of these determinants. It is concluded that AFXs are "fibrohistiocytic" neoplasms, with substantial morphologic and immunohistochemical similarity to MFHs. The immunohistochemical classification of spindle-cell and pleomorphic tumors of the skin necessitates the use of antibody panels to assess the presence of markers that are characteristic of each diagnostic group.
Adolescent↗
Spindle-cell proliferations of the urinary tract. An immunohistochemical study.
In order to define the immunohistochemical features of spindle cell proliferations of the urinary tract, we studied 18 lesions of this type with a panel of antibodies to epithelial and mesenchymal determinants. Histologically, 13 cases showed features that were not conclusively those of either spindle cell carcinoma or sarcoma, three contained overtly epithelial areas, and two were classified as "postoperative spindle cell nodules" (PSCN). Nine tumors in the indeterminate group and three with focally overt carcinomatous growth stained for cytokeratin and epithelial membrane antigen (EMA) and were classified as carcinomas. Eleven of these coexpressed vimentin, but desmin and muscle-specific actin were undetectable. The four remaining indeterminate neoplasms expressed desmin and muscle-specific actin as well as vimentin, but they lacked epithelial markers; these were categorized as leiomyosarcomas. Both PSCN were reactive for cytokeratin with each of three separate monoclonal antibody preparations. Desmin, actin, and vimentin were also observed in such lesions, but EMA was not. Because spindle cell proliferations may be difficult to interpret in routinely stained tissue sections, the additional information provided by immunohistochemical studies is helpful in establishing a diagnosis and separating biologically disparate lesions.
Carcinoma↗
Aggressive papillary middle-ear tumor. A clinicopathologic entity distinct from middle-ear adenoma.
A 29-year-old woman had a middle-ear mass that resulted in hearing loss and seventh-nerve palsy. The tumor invaded the petrous bone, the mastoid, at least one semicircular canal, and then extended into the posterior fossa. Microscopically, it consisted of complex, interdigitating papillae lined by uniform, cuboidal to low columnar cells. The cells resembled the epithelium of the normal middle ear and middle-ear adenoma, but the papillary architecture distinguished this neoplasm from the latter, nonpapillary tumors. Papillary middle-ear tumors are locally invasive. We propose the term "aggressive papillary middle-ear tumor" (APMET). Nine other examples of APMET have been reported under various diagnostic terms. All have been locally destructive with frequent intracranial invasion. Although none of the tumors has metastasized, one patient died of uncontrolled local disease. For this reason, APMET must be distinguished from nonpapillary middle-ear tumors.
Adenocarcinoma↗
Primary cutaneous leiomyosarcoma. A histological and immunohistochemical study of 9 cases, with ultrastructural correlation.
Leiomyosarcoma (LMS) of dermal and subcutaneous tissues is an uncommon neoplasm. In order to analyze the specialized pathologic features of this tumor, we undertook a histological, ultrastructural, and immunohistochemical study of 9 superficial LMS, including 7 dermal lesions and 2 subcutaneous neoplasms. These were compared with 12 examples of "deep" extracutaneous LMS. Metastases to the skin from two of the latter neoplasms were also examined. Immunohistochemistry was found to be a useful diagnostic adjunct to light microscopic and ultrastructural studies in that all LMS coexpressed vimentin and desmin, regardless of site, and 90% also expressed muscle-specific actin. Variable expression of cathepsin B and myelin basic protein was noted in 8 and 10 tumors, respectively, whereas none contained cytokeratin. Weak cytoplasmic positivity for epithelial membrane antigen was seen in 1 dermal and 3 extracutaneous LMS. Of 7 dermal LMS, 4 contained S-100 protein, whereas this determinant was found in only 1 of 12 extracutaneous tumors. Conversely, Leu 7 reactivity was present in 7 of 12 extracutaneous LMS, but only 2 of 9 superficial lesions. Review of clinical features confirmed that subcutaneous LMS is capable of aggressive behaviour, whereas dermal LMS was more likely to behave in an indolent fashion. However, one example of dermal LMS exhibited aggressive local recurrences and distant metastasis, ultimately leading to the death of the patient. Therefore, careful clinical followup is indicated in all cases.
Adult↗