Malignant peripheral nerve sheath tumors of the skin.
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Diagnosis, Differential↗
Biomedical subjects
M R Wick
Publications and source records attributed to M R Wick.
Pulmonary blastoma. An immunohistochemical analysis with comparison with fetal lung in its pseudoglandular stage.
Pulmonary blastomas are believed to be mixed epithelial and mesenchymal tumors that recapitulate the developing lung at 10-16 weeks gestation. The authors compared nine blastomas with ten fetal lungs in the pseudoglandular stage of development with a panel of antibodies to various lung antigens to evaluate immunophenotypic homology. Both blastomas and embryonal lungs showed expression of cytokeratin, epithelial membrane antigen, and carcinoembryonic antigen in their epithelial elements, and both contained scattered chromogranin-positive neuroendocrine cells. Rare surfactant-producing and Clara cell antigen-elaborating cells were identified in both groups. The mesenchymal components of blastomas and fetal lung showed smooth muscle, myofibroblastic, and blastematous differentiation. The blastematous elements demonstrated vimentin and keratin coexpression in four cases, providing some support for the contention that pluripotential blastema may give rise to the epithelial and mesenchymal elements of the distal lobule.
Adult↗
Definition of method sensitivity.
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Immunohistochemistry↗
Morphologic diversity in malignant melanomas.
A review was conducted of 335 malignant melanomas to identify variant morphologic patterns that might be confused with other tumors. In all, 27 predominantly amelanotic neoplasms with unusual histologic features were selected for additional study. These included nine with an adenoid or pseudopapillary pattern, seven small cell neoplasms, five with prominent myxoid stroma, four with a hemangiopericytoma-like appearance, and two composed of neoplastic cells with a signet-ring configuration. A diagnosis of melanoma was confirmed in all cases by Fontana-Masson strains for melanin pigment, electron microscopic examination, or the results of immunohistochemical analyses for cytokeratin, vimentin, S-100 protein, and the HMB-45 antigen. One tumor was associated with a congenital hairy melanocytic nevus, five were vulvovaginal lesions, four arose in the sinonasal tract, and one occurred in the rectum. Four of the specified microscopic patterns were observed in both primary and secondary neoplasms; the two signet-ring cell melanomas were recurrent lesions. The authors conclude that malignant melanomas may assume the histologic guise of adenocarcinomas, small cell carcinomas, and sarcomas, in a variety of tissue sites. Special studies designed to detect melanocytic differentiation are therefore appropriate in diverse differential diagnostic settings.
Adolescent↗
Expression of "myelomonocytic" antigens in mesotheliomas and adenocarcinomas involving the serosal surfaces.
Because of the demonstrated efficacy of Leu-M1 as a discriminant between malignant epithelioid mesothelioma (MEM) and adenocarcinomas involving the serosal surfaces (ACSs), the authors assessed the reactivities of related "myelomonocytic" antigens in this context. Paraffin sections from 41 MEMs and 43 ACSs (pulmonary, "serous surface papillary," and metastatic mammary adenocarcinomas) were evaluated for their expression of Leu-M1, LN1, LN2, and the Mac 387 antigen. Diagnoses were based in each case on the results of conventional histologic and electron microscopic examinations. Leu-M1 was detected only in minute foci of three peritoneal MEMs and was absent entirely in pleural mesotheliomas. Conversely, 38 of 43 ACSs expressed this marker. Three cases of peritoneal MEM and one pleural mesothelioma were multifocally LN2 positive, as were 39 of 43 ACSs. LN1 was the most frequently expressed antigen in MEM, being observed in 18 such tumors (10 pleural; 8 peritoneal); it was also detected in 37 of 43 ACSs. Mac 387 failed to label any of the neoplasms assessed in this series. These results demonstrate similar patterns of "myelomonocytic" antigen expression by diverse ACS and a general absence of Leu-M1 and LN2 in MEM. LN1 and the Mac 387 antigen appear to have no additional value when compared with Leu-M1 and LN2 in the immunohistochemical evaluation of serosal neoplasms.
Antigens, Neoplasm↗
Cutaneous adnexal carcinomas with divergent differentiation.
Adnexal carcinomas of the skin are rare lesions that encompass multiple histologic patterns. The authors have identified seven neoplasms in this category that showed combined morphologic features of at least two appendegeal tissues. Two manifested pilar and sebaceous differentiation, three showed pilar, sebaceous, and sudoriferous features, and two had sweat glandular and sebaceous characteristics. All tumors arose in the skin of the head and neck; four patients were men and three were women (age range, 21-84 years). One lesion had been present for 25 years with progressive enlargement over the last 3, and another two had slowly expanded over 1-2 years; the duration of growth for the remaining cases was uncertain. Follow-up revealed that six patients were free of disease for at least 1 year after complete excision. In the seventh case, complete excision was performed, but follow-up was not available. Immunohistochemical analysis showed reactivity for keratin and epithelial membrane antigen in each case. Carcinoembryonic antigen was seen in four tumors, and amylase was present in three; none expressed vimentin, S100 protein, or gross cystic disease fluid protein-15. It is concluded that mixed cutaneous adnexal carcinomas are recognizable entities that appear to have little potential for aggressive growth. Immunohistochemical studies may serve as adjuncts to conventional microscopy in the definition of cellular lineages pursued by such neoplasms.
Adult↗
Primary malignant lymphoma arising in postmastectomy lymphedema. Another facet of the Stewart-Treves syndrome.
In rare cases, primary malignant lymphomas may arise in the soft tissues. Only one previous case has arisen in the context of chronic lymphedema. Because of the clinical appearance of such lesions, which resemble violaceous nodular or plaquelike tumors, they may be confused clinically with lymphedema-associated angiosarcomas occurring after radical mastectomy (Stewart-Treves syndrome). Furthermore, the histologic appearance of some lymphomas and angiosarcomas may also be similar. We studied two women with primary postmastectomy lymphedema-related malignant lymphoma in the soft tissues of the upper arm. These tumors arose 11 and 30 years, respectively, after radical removal of ductal mammary carcinomas. Histologically, one neoplasm mimicked metastatic carcinoma or epithelioid angiosarcoma; whereas the other was initially confused with a variety of pathologic entities, including vasculitis, epithelioid hemangioma, and malignant fibrous histiocytoma. The lymphoid nature of both lesions was confirmed by immunoreactivity for leukocyte common antigen in addition to the B-lymphocyte marker, L26. Conversely, vascular and epithelial determinants were absent. One patient's disease pursued an indolent course; she died of unknown causes but with no evidence of lymphoma at last follow-up. The second patient is currently in remission on chemotherapy. Awareness of the existence of lymphedema-related malignant lymphoma and familiarity with methods used for its distinction from epithelioid vascular sarcomas should prevent unnecessary surgery.
Aged↗
HLA-DR (Ia-like) reactivity in tumors of bone and soft tissue: an immunohistochemical comparison of monoclonal antibodies LN3 and LK8D3 in routinely processed specimens.
Recent studies of Class II histocompatibility antigen expression in bone and soft tissue sarcomas have suggested that malignant fibrous histiocytoma (MFH) may express HLA-DR, whereas histologically similar pleomorphic, epithelioid, and spindle cell malignant neoplasms generally do not. To test whether these observations are reproducible in the differential diagnosis of soft tissue sarcomas, anti-HLA-DR antibodies LK8D3 and LN3 were applied to formalin-fixed, paraffin-embedded sections of MFH, neurofibrosarcoma (NFS), leiomyosarcoma (LMS), synovial sarcoma (SS), fibrosarcoma (FS), angiosarcoma (AS), Kaposi's sarcoma (KS), chondrosarcoma (ChS), "dedifferentiated" chondrosarcoma (DChS), osteosarcoma (OS), epithelioid sarcoma (ES), and clear cell sarcoma (CCS; malignant melanoma of soft parts). The only consistent difference in Class II antigen expression was seen in the group of neoplasms composed of large polygonal cells. Among the latter lesions, four of six clear cell sarcomas were labeled by LK8D3 or LN3, but none of 12 epithelioid sarcomas were reactive. Otherwise, a diversity of tumors in other morphologic categories expressed Class II antigens, with no clear diagnostic patterns. These results may be of use in the diagnostic separation of large cell epithelioid tumors of soft tissue, but neither LN3 nor LK8D3 appears to be helpful in the identification of other sarcomas.
Antibodies, Monoclonal↗
A clinicopathologic and immunohistochemical analysis of 53 cases of medulloblastoma with emphasis on synaptophysin expression.
Synaptophysin (SYN) has been identified as an integral membrane glycoprotein of presynaptic vesicles in neurons and neuroendocrine cells, and as a marker for medulloblastoma and other neuronal tumors. SYN expression was studied with a monoclonal antibody (MAb) by the immunoperoxidase technique in 53 medulloblastomas. The expression of neuron-specific enolase (NSE), Leu-7 (LEU), S-100 protein (S100), glial fibrillary acidic protein (GFAP), neurofilament protein (NF), vimentin (VIM), cytokeratin (CKER), and desmin (DES) was also assessed with antisera and MAbs. SYN reactivity was present in 94% of tumors, whereas reactivity with other markers of neuronal differentiation was also observed: NSE (100%) and LEU (83%). Regarding the intermediate filament proteins, 38% of the cases were reactive for VIM, 21% for GFAP, and 9% for DES; none expressed NF or CKER. Eight percent were reactive for S100. Among the 53 cases, the male-female ratio was 1:3; 80% of DES-positive tumors occurred in females. The mean age was 10.5 yr, (60% diagnosed in the first decade; peak age incidence between 5 and 10 yr). Five tumors were discovered in patients older than 20 yr of age. Follow-up showed that 40% of patients developed a recurrence and 47% of patients died of tumor. No statistically significant relationship was demonstrated between patterns of immunoreactivity and prognosis. We conclude that SYN is a useful marker for medulloblastomas, indicating that this tumor is a primitive neuronal-neuroblastic neoplasm. However, it is but one of several immunophenotypic markers expressed by the medulloblastoma.
Adolescent↗
Benign fibrous histiocytoma of the skin with potential for local recurrence: a tumor to be distinguished from dermatofibroma.
We studied eight patients with benign fibrous histiocytoma (BFH) of the skin that differed, morphologically and biologically, from ordinary dermatofibroma (DF) and compared their tumors with a consecutive series of 141 DF. The patients ranged in age from 13 to 49 yr. Their lesions consisted of cutaneous nodules, 2 cm or less in size, that had been present for less than 1 yr. Seven were located on an extremity. Three of six patients (50%) who could be followed had recurrences 2, 5, and 8 mo following excision of their tumors. Microscopically, seven of the eight cutaneous BFH (CBFH) involved both dermis and subcutis. Five were distinctly multinodular. Subcutaneous involvement and/or multinodularity were present in each case. Fibroblastic and histiocytic cells were arranged in a monotonous storiform pattern throughout most or all of each lesion. There was moderate nuclear variability, but pleomorphism was absent. Several of the tumors contained sparse inflammatory, multinucleate, and foam cells and hemosiderin deposits. Vascularity was prominent. We believe that the multinodular architecture of CBFH and its involvement of both dermis and subcutis usually allow distinction from DF. The latter is uninodular, centered in the dermis, and exhibits only minor subcutaneous extension. Most DF lack the diffuse, well developed storiform appearance of CBFH. Local recurrence further distinguishes CBFH from DF, which rarely recurs. Rather than representing an aberrant form of DF, the clinical and microscopic features of CBFH suggest that it is closely related to, if not identical with, BFH of other tissues and organs.
Adolescent↗
Mesenchymal chondrosarcoma. An immunohistochemical study.
Mesenchymal chondrosarcoma is an uncommon small-cell neoplasm of bone and soft tissue, the chondrogenic nature of which has been generally accepted. However, the phenotypic attributes of the small-cell population in this neoplasm have not been well characterized, and its relationship to "precartilage mesenchyme" remains unclear. In an attempt to address this issue, we performed an immunohistochemical analysis of nine cases, using antibodies to vimentin, S100 protein, Leu-7 antigen, neuron-specific enolase, synaptophysin, desmin, muscle-specific actin, cytokeratin, and epithelial membrane antigen, and the avidin-biotin-peroxidase complex (ABC) method. The small cells of mesenchymal chondrosarcoma failed to express S100 protein, whereas all components of the tumors (small cells, lacunar chondroblasts, and chondroid matrix) stained for Leu-7 antigen in six cases. Neuron-specific enolase was identified in the small cells of four cases and in the lacunar cells of seven. None contained desmin, actin, cytokeratin, epithelial membrane antigen, or synaptophysin. The immunophenotype of mesenchymal chondrosarcoma resembled that of embryonic cartilage and thus did not contradict the premise that this tumor was the neoplastic counterpart of fetal chondroid tissues. However, immunohistologic studies are not overly helpful in the differential diagnosis between mesenchymal chondrosarcoma and other small round cell lesions.
Adolescent↗
Methods in pathology. Immunophenotype of hairy cell leukemia in paraffin sections.
The immunophenotype of hairy cell leukemia (HCL) was investigated using 20 routinely fixed paraffin-embedded tissue sections (12 bone marrows, six spleens, one liver, one lymph node) from 12 patients known to have this disease. A panel of antibodies was used, including anti-leukocyte common antigen (anti-LCA), B-lineage antibodies (LN2, MB2, L26), T-lineage reagents (MT1, UCHL1), monocytic (anti-cathepsin B) and myelomonocytic (anti-lysosyme, Mac 387) antibodies, and other less lineage-specific markers (anti-S-100, anti-alpha-1-antichymotrypsin (anti-alpha 1-ACT), anti-alpha 1-antitrypsin (anti-alpha 1-AT), anti-vimentin). Anti-LCA stained hairy cells in seven of the 12 bone marrows and consistently recognized hairy cells in the spleen, liver, and lymph nodes. Hairy cells generally reacted with B-lineage antibodies and were not labeled by T-lineage markers. No reactivity was noted with myelomonocytic antibodies, anti-S-100, anti-alpha 1-ACT, or anti-alpha 1-AT. Vimentin was expressed in the majority of cases. Tartrate-resistant acid phosphatase reactivity was demonstrated in three of the 20 routinely processed tissue sections. These data suggest that immunohistochemical studies of hairy cell leukemia in routinely processed tissue may be useful in diagnostic hematopathology and surgical pathology.
Acid Phosphatase↗
Mediastinal cysts and intrathoracic thyroid tumors.
Benign cysts of the mediastinum are thought to be predominantly congenital in origin. Hence, a thorough understanding of their clinicopathologic characteristics is facilitated by knowledge of the embryologic development of the intrathoracic organs, as outlined in this review. Pertinent radiological and pathologic features of these lesions are also discussed. In addition, ectopic thyroid tissue may give rise to mediastinal masses. The salient attributes of these tumors are considered as well.
Bronchogenic Cyst↗
Unconventional lymphocytes involved in rejection of xenogeneic heart grafts.
In this report, the efficacy of cyclosporine A and two monoclonal antibodies, anti-L3T4 and anti-Lyt-2.2, was assessed on first-set rejection of cardiac xenografts. Neither cyclosporine nor anti-Lyt-2.2 monoclonal antibody prolonged the survival of heart xenografts. Anti-L3T4 enhanced acceptance of rat hearts transplanted to C57BL/6 mice 5-fold relative to that observed in control recipients; it did not, however, prolong acceptance of hamster hearts transplanted to mice. Histologic analysis indicated that the cellular infiltrate within rejected hearts was composed of greater than 95% lymphocytes; of these, greater than 99% were Thy-1- and sIg-. These results suggest that rejection of xenogeneic hearts is mediated by unconventional lymphoid cells. This is discussed in the context of whether rejection of allografts and xenografts occur by similar or dissimilar mechanisms.
Animals↗
Localization of cathepsin B in normal and hyperplastic human prostate by immunoperoxidase and protein A-gold techniques.
Cathepsin B, a lysosomal cysteine protease, was localized in normal prostate and benign prostatic hyperplasia (BPH) using immunoperoxidase and protein A-gold techniques. Our objective was to determine whether cathepsin B was involved in the prostatic epithelium affected by nodular hyperplasia. All samples were collected immediately after prostatectomy. Immunohistochemical studies showed that the enzyme was expressed in the supranuclear cytoplasm of columnar cells and in numerous basal cells of normal and BPH acini. The strongest localization of cathepsin B occurred in acinar basal cells; hence, it is possible that cathepsin B could be useful as a marker for such cellular elements. Stromal macrophages showed reaction products, but lymphocytes and neutrophils did not. In both normal and hyperplastic glands, the enzyme was localized by gold particles in lysosomes, secretory granules, and vacuoles of columnar epithelial acinar cells. Immunoelectron microscopic study also showed the presence of cathepsin B in the heterochromatin (condensed chromatin) and nuclear membranes of columnar and basal cells, but not in euchromatin or nucleoli. At present, the function of cathepsin B in the nuclei of basal and columnar cells remains unknown. However, the cathepsin B in the cytoplasmic compartment might be associated with the lysosomal function of the cells. The role of cathepsin B as a marker for basal cell participation in the development of prostatic lesions should be studied further.
Cathepsin B↗
Undifferentiated small round-cell tumors of childhood: the immunocytochemical demonstration of myogenic differentiation in fine-needle aspirates.
The recognition of myogenic differentiation is not always possible using routine light or electron microscopic techniques. In this article, we describe our experience with two small round-cell neoplasms occurring in young children, each of which exhibited an undifferentiated light microscopic appearance. In both cases, myogenic features were revealed by immunocytochemical methods applied to fine-needle aspiration (FNA) biopsies. Each was immunoreactive for desmin and vimentin and failed to react with antibodies to leukocyte-common antigen. Moreover, formalin-fixed tissue sections of one case were negative for cytokeratin and epithelial membrane antigen. Sporadic reactivity for neuron-specific enolase and Leu-7 antigen was observed in occasional cells in FNA specimens, but synaptophysin was not identified. The rapidity of the method and the reliability of the immunocytochemical findings, when compared with routine cytologic evaluation, emphasize the diagnostic utility of immunocytochemical analysis when FNAs of pediatric soft-tissue tumors are obtained.
Actins↗
Gross cystic disease fluid protein-15 as a marker for breast cancer: immunohistochemical analysis of 690 human neoplasms and comparison with alpha-lactalbumin.
The identification of metastatic carcinoma of the breast may be difficult in the absence of a previous history of breast cancer. Various immunophenotypic markers have been introduced to aid in this process. A monoclonal antibody directed at a 15-kilodalton (kd) gross cystic disease fluid protein (GCDFP-15) was applied immunohistochemically to paraffin sections of 105 breast cancers and 585 nonmammary malignancies in order to assess its value in this context. In addition, GCDFP-15 was compared with another putative mammary epithelial marker, alpha-lactalbumin (ALA), with respect to sensitivity and specificity for a diagnosis of breast carcinoma. Overall, the rates of specificity and sensitivity and the predictive value of a positive result for GCDFP-15 were 95%, 74%, and 74%, respectively. Corresponding statistical parameters for ALA were 50%, 50%, and 23%. A consistent congruency between the reactivity patterns of primary and metastatic breast cancers was noted for GCDFP-15 but not for ALA. Besides mammary carcinomas, the major tumor types that expressed GCDFP-15 were carcinomas of the salivary glands, sweat glands, and prostate. Since the latter three types of lesions are unlikely to be diagnosed as metastatic breast cancer, statistical indices were recalculated after exclusion of these three tumor types. Following this exclusion, the adjusted rate of specificity of GCDFP-15 and the predictive value of a positive result for a diagnosis of metastatic carcinoma of the breast were each 99%. In contrast, predictive parameters for ALA were not altered. These results show that GCDFP-15 is a specific marker for breast cancer and is superior to ALA in this respect.
Adenocarcinoma↗
Immunophenotypic analysis of sinonasal non-Hodgkin's lymphomas.
A panel of paraffin effective antibodies recognizing B cells and T cells (LN-2, MB1, L26, MT1, UCHL1, kappa, lambda) was used to characterize the immunophenotypes of 26 sinonasal non-Hodgkin's lymphomas. Seventeen tumors were stage I, five were stage II, one was stage III, and three were stage IV. Nine lymphomas were classified morphologically as large cell, six were large cell immunoblastic, six were small cleaved cell, two were mixed small and large cell, two were small noncleaved cell, and one was lymphoblastic. None were follicular. Twenty-two lymphomas had a B cell immunophenotype, three were T cell neoplasms, and one was immunoreactive only for MT1. This predominance of sinonasal lymphomas with a B cell immunophenotype in patients residing in the United States contrasts with the almost exclusive occurrence of T cell sinonasal lymphomas in Chinese patients living in Hong Kong and Japanese patients residing in regions of Japan that are nonendemic for human T cell leukemia virus-1.
Adolescent↗