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J C Manivel

Publications and source records attributed to J C Manivel.

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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↗

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↗

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↗

Placental alkaline phosphatase immunoreactivity in testicular germ-cell neoplasms.

We analyzed the sensitivity of a polyclonal antibody to placental alkaline phosphatase (PLAP) in labelling testicular germ-cell neoplasms, by utilizing the peroxidase-antiperoxidase technique. The immunoreactivity of 89 germ-cell tumors for PLAP was as follows: 98% of cases with seminomatous elements were PLAP-positive; 97% of embryonal carcinomas and 85% of endodermal sinus tumors also showed reactivity. Cytotrophoblastic cells were focally immunoreactive in one of two cases with choriocarcinomatous elements. Staining for PLAP was strongest and most diffuse in seminomas. Intratubular germ-cell neoplasia (ITGCN) or carcinoma in situ was present in 53 (84%) of 63 specimens that had adjacent seminiferous tubules available for evaluation; PLAP was demonstrated in 98% of these. In addition, the germ-cell elements in 11 gonadoblastomas were immunoreactive for PLAP. One of 17 cases of undescended testes had ITGCN that was also strongly immunoreactive, but the remaining 16 cases were negative. Five dysgenetic gonads without ITGCN were studied, and one was immunoreactive for PLAP. Three testicular biopsy specimens from infertile men without ITGCN were PLAP-negative. Our findings indicate that PLAP is a highly sensitive marker for seminomas, for the majority of embryonal carcinomas and endodermal sinus tumors of the testis, and for ITGCN.

Alkaline Phosphatase↗

Intermediate trophoblast in germ cell neoplasms.

One-hundred-twenty-four germ cell tumors and 11 gestational choriocarcinomas were assessed immunohistochemically for the presence of the following placental markers: human chorionic gonadotrophin, human placental lactogen, and pregnancy-specific beta-1 glycoprotein, and for the expression of cytokeratin. A total of 40 cases contained syncytial trophoblastic cells, large mononuclear cells, or both. These cases included all gestational choriocarcinomas and choriocarcinomatous foci in 11 mixed germ cell tumors, 14 embryonal carcinomas, and four seminomas. Syncytial trophoblastic cells reactive for cytokeratin were identified in all choriocarcinomas, 12 embryonal carcinomas, and two seminomas. Human placental lactogen-reactive syncytial trophoblastic cells were observed in nine gestational choriocarcinomas, 10 choriocarcinomatous foci in mixed germ cell tumors, four embryonal carcinomas, and one seminoma. Pregnancy-specific beta-1 glycoprotein-reactive syncytial trophoblastic cells were seen in 10 gestational choriocarcinomas, all choriocarcinomatous foci in mixed germ cell tumors, 11 embryonal carcinomas, and one seminoma. Cytotrophoblasts, as expected, were identified only in choriocarcinomas. Cytokeratin-reactive cytotrophoblast was seen in all gestational choriocarcinomas and 10 choriocarcinomatous foci in mixed germ cell tumors. Human chorionic gonadotrophin-reactive cytotrophoblast was observed in two gestational choriocarcinomas and three choriocarcinomatous foci in mixed germ cell tumors. Cytotrophoblast was uniformly nonreactive for human placental lactogen and pregnancy-specific beta-1 glycoprotein. Cytokeratin-reactive large mononuclear cells were observed in 10 gestational choriocarcinomas, all choriocarcinomatous foci in mixed germ cell tumors, five embryonal carcinomas, and three seminomas. Human placental lactogen-reactive large mononuclear cells were identified in nine gestational choriocarcinomas, seven choriocarcinomatous foci in mixed germ cell tumors, one embryonal carcinoma, and one seminoma. Pregnancy-specific beta-1 glycoprotein-reactive large mononuclear cells were present in 10 gestational choriocarcinomas, 10 choriocarcinomatous foci in mixed germ cell tumors, two embryonal carcinomas, and two seminomas. Because of morphologic and immunohistochemical similarities of large mononuclear cells with intermediate trophoblast of the normal placenta and gestational trophoblastic neoplasms, we propose that the large mononuclear cells in gonadal and extragonadal germ cell neoplasms are equivalent to the intermediate trophoblast.

Choriocarcinoma↗

Immunoreactivity for Leu-7 in neurofibrosarcoma and other spindle cell sarcomas of soft tissue.

Monoclonal antibodies to Leu-7 have been reported to recognize a constituent of myelin-associated glycoprotein. Because of this, the authors studied 20 cases of neurofibrosarcoma (NFS), 7 of leiomyosarcoma (LMS), 3 of fibrosarcoma (FS), 8 of malignant fibrous histiocytoma (MFH), 5 of monophasic spindle cell synovial sarcoma (MSS), 5 of neurilemmoma, and 5 of neurofibroma for Leu-7 reactivity, to determine its utility in differential diagnosis. Selected examples of each tumor type were also studied ultrastructurally. Leu-7 was compared with the expression of S-100 protein, myelin basic protein, desmin, cytokeratin, and epithelial membrane antigen in the 43 neoplasms. Fifteen examples of NFS, 2 of LMS, and 2 of MSS were Leu-7+; 2 neurofibromas and 4 neurilemmomas also demonstrated reactivity with this antibody. In contrast, all cases of FS and MFH were Leu-7-. Synovial sarcomas could be effectively separated from NFS by reactivities for cytokeratin and epithelial membrane antigen in the former, but not the latter, lesions. However, LMSs and NFSs demonstrated significant immunocytochemical overlap, including shared positivity for S-100, desmin, and myelin basic protein in several cases. These results suggest that Leu-7 has restricted utility in immunohistochemical diagnosis, and must be utilized only in concert with other antigens. Moreover, it would appear that in selected instances, smooth-muscle and neurogenic sarcomas must be separated on the basis of clinical, histopathologic, and ultrastructural features alone.

Adolescent↗

Synovial sarcoma: ultrastructural study and immunohistochemical analysis by a combined peroxidase-antiperoxidase/avidin-biotin-peroxidase complex procedure.

To analyze the purportedly epithelial features of synovial sarcoma, the antigenic profiles of 20 of these neoplasms (including 12 of the monophasic type) were studied by three different immunohistochemical techniques, and the results were correlated with ultrastructural observations in 10 cases. All of the biphasic tumors were immunoreactive for the epithelial markers epithelial membrane antigen (EMA) and cytokeratin (CK) and also had ultrastructural features of epithelial differentiation. In contrast, only one of five monophasic tumors had electron microscopic features suggestive of epithelial differentiation, but eight of the 12 were immunoreactive for CK or EMA by a procedure combining the peroxidase-antiperoxidase and avidin-biotin-peroxidase complex methods. It is concluded that synovial sarcoma, including the monophasic variant, is a mesenchymal tumor with epithelial features. Immunohistochemical studies are more sensitive than ultrastructural analysis for documenting epithelial differentiation.

Adult↗

Epithelioid sarcoma and isolated necrobiotic granuloma: a comparative immunocytochemical study.

Epithelioid sarcoma (ES) occasionally may be confused, both clinically and histologically, with isolated necrobiotic granulomas (ING), leading to misdiagnosis and potential mismanagement of these conditions. We studied 11 cases of ES and 11 of ING (6 examples of deep granuloma annulare and 5 of rheumatoid nodule) immunohistochemically, in an attempt to determine whether they could be diagnostically separated by such means. Monoclonal antibodies to cytokeratin polypeptides (CK), epithelial membrane antigen (EMA), and leukocyte common antigen (LCA) were applied to formalin-fixed, paraffin-embedded sections in each case, using the avidin-biotin-peroxidase complex technique. All ES cases stained positively for CK, and 6 expressed EMA, while examples of ING were non-reactive for these antigens. Conversely, the large epithelioid histiocytic cells in cases of ING were immunoreactive with anti-LCA, whereas no case of ES displayed this determinant in tumor cells. In the latter lesions, reactive peritumoral inflammatory cells were LCA-positive, but were readily distinguished from neoplastic cells on morphological grounds, as well as by their negativity with anti-CK and anti-EMA. Based on these data, it is concluded that immunohistologic stains for epithelial and hematopoietic antigens are valuable in the conclusive diagnostic separation of epithelioid sarcoma and necrobiotic granulomas.

Adolescent↗

Dedifferentiated chondrosarcoma: an ultrastructural study of two cases, with immunocytochemical correlations.

The clinicopathologic features of two cases of dedifferentiated chondrosarcoma (DCS) are presented, in which anaplastic components showed the electron microscopic features of malignant fibrous histiocytoma, as well as immunoreactivity for alpha-1-antitrypsin and alpha-1-antichymotrypsin. Rare cells also displayed S100 protein in high-grade areas of the primary tumors, but a pulmonary metastasis lacked this determinant. These findings could be interpreted as reflecting a retained potential for primitive chondrogenesis in primary DCS, which may be lost in its metastases. In all other respects, this tumor appears to assume the morphological and immunocytochemical attributes of a fibrohistiocytic neoplasm.

Bone Neoplasms↗

Endovascular papillary angioendothelioma of childhood: a vascular lesion possibly characterized by "high" endothelial cell differentiation.

Two cases of endovascular papillary angioendothelioma (EPA) of the skin were studied immunohistochemically to assess the expression of endothelial, leukocytic, and epithelial determinants by these lesions. The tumor cells in both cases were labeled by antibodies to Factor VIII-related antigen, vimentin, and blood group isoantigens; they also bound Ulex europaeus I agglutinin. On the other hand, immunoreactivity for epithelial membrane antigen, Leu-M1, HLA-DR (Ia-like antigen), and leukocyte common antigen (LCA) was not observed. Stromal and intravascular lymphocytes were labeled intensely with antibodies to LCA and HLA-DR and were intimately associated with papillary configurations of proliferating intravascular tumor cells. These results confirm the endothelial nature of EPA and suggest that the cells of this lesion may differentiate toward "high" endothelial cells, which have been shown to interact functionally with circulating lymphocytes.

Cell Differentiation↗

Testicular sex cord-stromal tumors in children: clinicopathologic study of sixteen children with review of the literature.

Sex cord-stromal tumors of the pediatric testis present diagnostic and therapeutic challenges. This study examines the clinicopathologic features of 16 testicular sex cord-stromal tumors from children less than 18 years of age. Four juvenile granulosa cell tumors and five tumors of Sertoli or incomplete differentiation in this study had high mitotic rates and/or sarcomatoid areas that suggested malignancy, but none of these children developed recurrence or metastases. Some of these tumors had been initially misdiagnosed as yolk sac tumors or rhabdomyosarcomas because of the presence of areas superficially resembling these neoplasms. These morphologic pitfalls have received little attention in the literature. Even incompletely differentiated sex cord-stromal tumors have at least focal areas characteristic of juvenile granulosa or Sertoli cell differentiation. In addition, immunohistochemical negativity for alpha-fetoprotein, muscle specific actin, and desmin are useful for ruling out yolk sac tumor and rhabdomyosarcoma. Four patients had Leydig cell tumors and three had large cell calcifying Sertoli cell tumors. Children with Leydig cell tumors are not at risk for metastasis, but children with large cell calcifying Sertoli cell tumors are at risk for endocrine syndromes as illustrated by one of our cases. The differential diagnosis of these tumors is also discussed.

Adolescent↗

Plasmacytoma of the thoracic spine with intracellular amyloid and massive extracellular amyloid deposition.

A 65-year-old woman presented with back pain and a lytic destructive lesion of T-11. Fine-needle aspiration biopsy revealed a granulomatous reaction with unusual signet ring type cells and vacuolated histiocytes. Subsequent resection of the lesion revealed a fibrohistiocytic reaction with extensive amyloid deposition. Immunoperoxidase stains confirmed monotypic kappa light-chain staining. Ultrastructural examination of paraffin-embedded tissue confirmed extracellular amyloid deposition. A unique feature of this case was the finding of intracellular amyloid; the unusual signet ring cells were shown to be plasma cells with intracellular amyloid, and the vacuolated histiocytes also contained amyloid.

Aged↗

Fine needle aspiration cytology, immunocytochemistry and electron microscopy of fibromatosis of the breast. Report of two cases.

Two cases of primary fibromatosis of the breast are described. The lesions were suspected to be carcinomas both clinically and mammographically. Fine needle aspiration (FNA) yielded bland-appearing isolated spindle cells associated with small groups of benign ductal cells and lymphocytes. Immunoperoxidase staining performed on the original FNA smears showed positivity for vimentin and muscle-specific actin only in the spindle cells and for cytokeratin only in the epithelial cells. Electron microscopy study of one case demonstrated the ultrastructural characteristics of well-differentiated fibroblasts and myofibroblasts.

Adult↗

Primary multilobated T-cell lymphoma of the breast diagnosed by fine needle aspiration cytology and immunocytochemistry.

The fine needle aspiration (FNA) cytologic, immunocytochemical and ultrastructural findings of a primary multilobated T-cell lymphoma arising in the breast of a 61-year-old woman are described. Large pleomorphic multilobated malignant cells were primarily identified as lymphomatous in origin and phenotypically as T-cells by a selected panel of monoclonal antibodies applied to the original smears obtained by FNA biopsy. This appears to be the second report of a multilobated lymphoma arising in the breast and the first with a T-cell phenotype in this anatomic site.

Antibodies↗

Fine needle aspiration cytology and immunocytochemical characterization of the histiocytes in sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman syndrome).

A fine needle aspiration (FNA) biopsy of an enlarged lymph node in a three-year-old boy who had asymptomatic cervical and submandibular lymphadenopathy showed large histiocytes with abundant pale, eosinophilic cytoplasm containing well-preserved lymphocytes and occasional plasma cells and granulocytes. These features were consistent with a diagnosis of sinus histiocytosis with massive lymphadenopathy (SHML). Immunophenotypic study of the histiocytes, performed on the FNA smears and on paraffin-embedded sections, showed reactivity for S-100 protein and alpha-1-antichymotrypsin and negativity for lysozyme. These features, which are characteristic of SHML, demonstrate the reliability of FNA cytology in making the diagnosis of this disorder.

Biomarkers↗

Primary osteogenic sarcoma and osteogenic metaplastic carcinoma of the breast. Immunocytochemical identification in fine needle aspirates.

Pleomorphic spindle cells, osteoclastlike giant cells and plaques of osteoidlike material were the cytologic features observed in fine needle aspirates of the breast tumors from two patients. This cytologic pattern suggested a diagnosis of osteogenic sarcoma, a rare neoplasm in the breast. Immunoperoxidase staining performed on the original smears showed reactivity for vimentin in both cases. One tumor was also positive for epithelial membrane antigen (EMA); reactivity for this marker revealed the metaplastic nature of the sarcomatous cells in this tumor, suggesting a diagnosis of metaplastic carcinoma. Histologically, both tumors showed a sarcomatous pattern, with osteoid and chondroid formation, with no evidence of epithelial differentiation. Polyclonal and monoclonal antibodies against epithelial and mesenchymal markers used in tissue sections confirmed the immunophenotypes identified cytologically. Based on the immunochemical findings, the final diagnoses were osteogenic sarcoma of the breast in one case and osteogenic metaplastic carcinoma of the breast in the second case. Both patients died of metastatic disease within one year. These cases (1) show the reliability and accuracy of the immunoperoxidase method in making a differential diagnosis of ambiguous cytologic patterns in fine needle aspirates, (2) support the occurrence of a true osteogenic sarcoma of the breast (comparable to its skeletal counterpart) and (3) demonstrate that metaplastic carcinomas may closely simulate sarcomas of the breast, morphologically as well as biologically. Immunochemical staining techniques play an important role in the differential diagnosis of these neoplasms.

Antigens, Neoplasm↗

Atypical lymphocytes in spinal fluid resembling posttransplant lymphoma in a cardiac transplant recipient. A case report.

The interpretation of atypical leukocytes in the cerebrospinal fluid (CSF) poses diagnostic problems. We present a case of a heart transplant patient whose CSF contained highly atypical lymphocytes that were originally interpreted as "suspicious for lymphoma." Because the patient was clinically thought to have disseminated zoster, he was treated with acyclovir, and the atypical infiltrate resolved. This case exemplifies the extreme difficulty of interpreting cerebrospinal fluid in immunosuppressed patients who are at risk of developing posttransplant lymphoproliferative disorders.

Cell Nucleus↗