Immunopathology of malignant mesothelioma.

The pathologic diagnosis of malignant mesothelioma is difficult because the disease is rare and because it has many morphologic variants. This chapter emphasizes practical aspects of the pathologic features and of the differential diagnosis of malignant mesothelioma.

Phenotype of bile ducts and infiltrating lymphocytes in graft-versus-host disease.

When graft-versus-host (GVH) disease affects the liver, it is characteristically the bile ducts which are involved, infiltrated by lymphocytes. To characterize this process further, and to determine whether there were any antigenic changes in the bile ducts, we stained 9 liver biopsies involved by GVH disease, 10 non-GVH biopsies that had a prominent portal lymphocytic component, and 8 biopsies taken incidentally at surgery for noninflammatory liver disease with epithelial membrane antigen, AE-3, AE-1, a keratin cocktail, keratin 19, CD45RO (UCHL-1), CD43 (Leu-22), CD20 (L26), vimentin, and LN-3. The infiltrating lymphocytes were T cells (CD45RO+, CD43+, CD20-) which variably expressed LN-3. The bile ducts were positive for the keratin cocktail, AE-1, AE-3, and keratin-19, but only occasionally positive for EMA and LN-3. There was no significant difference in the staining patterns of either the bile duct cells or lymphocytes between the three groups. With the antibodies that we used, there does not appear to be a significant difference in the antigenic phenotype of the bile ducts in GVH as compared to normal or reactive livers.

Splenic involvement by aggressive malignant lymphomas of B-cell and T-cell types. A morphologic and immunophenotypic study.

To determine whether there are any consistent morphologic differences between B-cell and T-cell aggressive non-Hodgkin's lymphomas of the spleen, the authors analyzed 16 spleens involved by mixed cell (1 case) or large cell (15 cases) lymphomas. Immunologic data were derived from cell suspensions or frozen tissue in each case. Five cases had a T-cell phenotype, and 11 were B-cell. Morphologic features favoring a T-cell phenotype included epithelioid histiocytic reactions, confinement of the lymphomas to the splenic T-zones (periarteriolar lymphoid sheath and marginal zone), and clear cell or polymorphous cytologic features. Features favoring a B-cell phenotype included multiple discrete nodules in the white pulp, large coalescent tumor nodules in association with small lymphocytic lymphoma, and large non-cleaved or immunoblastic plasmacytoid cytologic characteristics. Four cases were unusual because most neoplastic large cells were distributed diffusely or formed only small aggregates in the red pulp without definite tumor masses or nodules involving the white pulp. Because of this distribution and the frequently encountered erythrophagocytosis by benign-appearing histiocytes, these cases resembled malignant histiocytosis. A T-cell phenotype was predicted for all four cases; however, only one case, a lymphoma with polymorphous cytologic characteristics, was of T-cell lineage. The other three cases were of B-cell lineage. The authors' results indicate that in most instances the B-cell or T-cell nature of aggressive splenic lymphomas is predictable from the distributional and cytologic features. As in lymph nodes, there are cases for which the morphologic characteristics of B-cell and T-cell lymphomas are indistinguishable.

Angiotropic (intravascular) large cell lymphoma. A clinicopathologic study of seven cases with unique clinical presentations.

The authors recently reported the antigenic phenotypes of three cases of so-called "malignant angioendotheliomatosis" and suggested that angiotropic large cell lymphoma (ALCL) is a more appropriate designation for this disease. The authors now report an additional seven cases of ALCL with unique clinical presentations. One patient presented with prostate enlargement, the second with lytic bone lesions and thickened nasal sinus mucosa, the third had diffuse myalgia, the fourth had dyspnea and pulmonary infiltrates, the fifth had gangrene of the lower extremities, total-body skin involvement, and pancytopenia, the sixth had a lesion of the foreskin mimicking squamous cell carcinoma, and the seventh had a mediastinal mass. In all cases histologic features were characteristic of ALCL with, in two cases, extravascular spread into soft tissue. Immunohistologic studies showed a B-cell phenotype in five cases and a T-cell phenotype in one case. Two patients received combination chemotherapy using established treatment protocol for large cell lymphoma, and remain in complete clinical remission and two patients are responding clinically to combination chemotherapy. Two patients died shortly after receiving combination chemotherapy. One patient has only recently been diagnosed as having ALCL and no long-term follow-up is available. These data indicate that, although ALCL affects predominantly the central nervous system and skin, unusual clinical presentations may occur, and patients with ALCL may respond to combination chemotherapy for large cell lymphoma.

Detection of immunoglobulin light-chain mRNA in lymphoid tissues using a practical in situ hybridization method.

The identification of immunoglobulin protein in routinely fixed and paraffin-embedded sections using antibodies combined with immunoperoxidase or similar techniques of detection is often problematic. We developed an in situ hybridization methodology for the identification of light-chain mRNA that is applicable to formalin-fixed, paraffin-embedded tissues, using either radiolabeled or biotinylated oligonucleotide probes based on the kappa and lambda light-chain gene-constant regions. Reactive plasma cells can be consistently identified in reactive lymphoid tissues, and a monotypic pattern of light-chain mRNA restriction was seen in each of eight cases of multiple myeloma/plasmacytoma. Immunoblasts and germinal center cells also are labeled in reactive lymphoid tissues. Using 355-labeled probes, 29 of 93 cases (30%) of non-Hodgkin's lymphomas had detectable light-chain mRNA, while 19% of non-Hodgkin's lymphomas were positive using biotinylated probes.

Antigenic phenotype of Langerhans cell histiocytosis: an immunohistochemical study demonstrating the value of LN-2, LN-3, and vimentin.

In order to determine the antigenic phenotype of the proliferating cells in Langerhans cell histiocytosis (LCH), we studied 15 such examples by using formalin- and B5-fixed, paraffin-embedded tissues. We used a panel of antibodies that are known to react with lymphocyte- and histiocyte-associated antigens. These included LN-1, LN-2, and LN-3 monoclonal antibodies (MoAbs), MoAbs to leukocyte common antigen (LCA), Leu-M1 antigen, vimentin, and epithelial membrane antigen (EMA), as well as polyclonal antibodies to lysozyme and S100 protein. The antigens encountered most frequently in LCH cells were S100 protein (93% of cases), vimentin (86%), and those detected by LN-2 (80%) and LN-3 (82%). Lysozyme was detected focally in two cases and diffusely in one case. The LCH cells were negative for LN-1, LCA, Leu-M1, and EMA. There was only one specimen in which S100 protein was not demonstrated; in this case, LN-3, vimentin, and T6 on frozen section were positive. The phenotype of LCH cells is similar to that of Langerhans' cells and interdigitating histiocytes. Our results demonstrate the value of using a panel of antibodies, including anti-vimentin MoAb, LN-2, and LN-3 for the immunophenotypic diagnosis of LCH in addition to an antibody to S100 protein.

S-100 immunoreactivity in primary and metastatic carcinoma of the breast: a potential source of error in immunodiagnosis.

Immunoreactivity for S-100 protein, typically a marker for malignant melanoma and neural-derived tumors, was observed in neoplastic cells of 57 of 68 cases (84%) of formalin-fixed, paraffin-embedded primary and/or metastatic carcinoma of the breast of various histologic types. The extent of S-100 immunoreactivity varied, with only a minor proportion of positive tumor cells noted in some cases. An awareness of this staining profile for S-100 protein, particularly in metastatic poorly differentiated neoplasms with unknown primaries, is imperative for accurate immunohistochemical interpretation. Using a panel of reagents which includes antibodies to keratin proteins and epithelial membrane antigen, the epithelial nature of S-100-positive carcinomas may be readily defined. Tumor cells in all cases of primary and metastatic carcinoma of the breast evaluated in this study exhibited strong staining for both of these tissue markers. To preclude misinterpretation of tumor type due to anomalous staining patterns for a specific antibody, eg, S-100 protein, a panel of antibodies is recommended for assessment of metastatic poorly differentiated tumors.

Angiosarcoma of the bladder: a case report.

We report a case of angiosarcoma of the bladder. Numerous cases of hemangioma of the bladder have been reported previously but only 3 cases of angiosarcoma have been published. In our case immunoperoxidase staining for factor VIII antigen was useful in substantiating the diagnosis of angiosarcoma.