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BACKGROUND It has been shown previously that detection of the epithelial membrane antigen using the mouse monoclonal antibody MOC-31 has diagnostic utility in the distinction between mesothelioma and metastatic carcinoma in body fluids. The current immunohistochemical study confirmed the effectiveness of MOC-31 as a marker for adenocarcinoma from a broad range of primary sites in body fluid cytology prepared as paraffin sections of cell blocks. METHODS The authors evaluated 112 cell blocks for MOC-31 immunoreactivity, including 17 mesotheliomas, 86 metastatic adenocarcinomas from various sites, and 9 control fluids from patients with nonneoplastic conditions. RESULTS Membranous reactivity for MOC-31 was observed in 86 of 86 samples (100%) of metastatic adenocarcinoma, regardless of the specific primary site. Sixteen of 17 mesothelioma samples were negative. In all but 1 sample of adenocarcinoma, > 90% of tumor cells present showed reactivity, and the staining intensity consistently was strong. Staining of scattered, morphologically benign mesothelial cells was observed in nine samples but did not interfere with interpretation. CONCLUSIONS On the basis of the staining profile, MOC-31 represented an effective marker for metastatic carcinoma in cell block preparations and may aid in distinguishing between benign and malignant mesothelial cells in these tumors. Cancer (Cancer Cytopathol) 2006. © 2006 American Cancer Society.

BACKGROUND It has been shown that detection of the Wilms tumor susceptibility gene 1 protein (WT1) has diagnostic utility in the distinction of mesothelioma from adenocarcinoma in tissue sections of pleural tumors. This immunohistochemical study evaluates the effectiveness of WT1 as a marker for malignant mesothelioma in paraffin sections of cell block preparations derived from effusion specimens. METHODS The authors evaluated 111 cell blocks for WT1 immunoreactivity, including 14 mesotheliomas and 97 metastatic adenocarcinomas from various sites. RESULTS Nuclear reactivity for WT1 was observed in all samples of mesothelioma. However, only 22 of 97 samples (23%) of metastatic adenocarcinoma, nearly all of which were of ovarian origin (91%), exhibited nuclear reactivity for WT1. In 14 other samples (most of pulmonary derivation), WT1 staining restricted to the cytoplasm was observed for some tumor cells and was regarded as nonspecific. CONCLUSIONS Based on this staining profile, WT1 represents an effective marker for mesotheliomas in cell block preparations and can aid in its distinction from pulmonary adenocarcinoma. In assessment of effusion specimens with metastatic carcinoma, nuclear reactivity for WT1 is highly suggestive of an ovary primary tumor. Cancer (Cancer Cytopathol) 2002;96:000–000. © 2002 American Cancer Society.

BACKGROUND The involvement of the breast by lymphoma is a rare form of extralymph node lymphoma and represents either primary disease or systemic involvement. The authors hypothesized that screening mammography may influence the detection of lymphomatous involvement of the breast. METHODS All patients (n = 81 patients) who were diagnosed with lymphomatous involvement of the breast at the study institution between 1988 and 1999 were evaluated retrospectively. RESULTS Clinical information was available for 73 patients who could be classified into three major groups according to their diagnosis: primary breast lymphoma (PBL) (44%), breast involvement from disseminated disease at the time of initial diagnosis (29%), and recurrence of preexisting lymphoma to the breast (27%). The majority of PBL were of intermediate or high grade, and the majority of disseminated lymphomas involving the breast were of low grade. Lymphomatous recurrence to the breast was slightly more likely to be of intermediate grade rather than low grade. In 91% of patients, the diagnosis of lymphoma was made after the evaluation of a palpable mass. All patients who were identified after the evaluation of an abnormal screening mammogram (9%) had low-grade lymphomas. Of the 32 patients with PBL, screening mammography discovered only 1. Nineteen percent of patients with PBL also had a history of an autoimmune disorder. CONCLUSIONS These findings suggest that screening mammography has not altered substantially the detection of breast lymphoma. The clinical outcome of patients with breast lymphoma is dependent on histology and appears to parallel that of patients with lymphoma of similar histology involving other sites. Cancer 2002;94:6–13. © 2002 American Cancer Society.

Clinical and pathologic features of 24 patients with large cell lymphomas that expressed the activation antigen Ki-1 are described. Phenotypic and/or genotypic studies characterized these neoplasms as T-cell (16 cases), B-cell (six cases), or null cell (two cases) type. Males predominantly were affected. Age of patients ranged from 19 to 73 years, with a bimodal distribution, with peaks in the third and seventh decades. Lymphadenopathy was present in nearly all patients. Extranodal involvement, including skin, soft tissue, bone, central nervous system, lung, or small intestine was observed in a total of 54% of the patients, either at presentation or during the course of disease. "Prototypic" features of large cell anaplastic lymphomas were observed for eight T-cell lymphomas, with morphologic heterogeneity noted for the remainder. Eight patients, all with T-cell neoplasms (only one with prototypic morphology), have died of lymphoma (median survival, 5 months). An antecedent history of a lymphoproliferative disorder (mycosis fungoides, B-cell lymphoma, immunoblastic lymphadenopathy) was apparent in seven patients. An 8-year history of Crohn's disease occurred in one patient with a T-cell lymphoma involving small intestine. Phenotypically, loss of one or more markers was typically noted for T-cell neoplasms. Leukocyte common antigen was detected in all cases, although partial loss of immunoreactivity was noticed in some cases. Nearly all cases evaluated for Ia antigen or alpha-1-antichymotrysin were reactive. Eleven of 16 T-cell, two of six B-cell, and two null cell lymphomas expressed epithelial membrane antigen. Ki-1-positive large cell lymphomas are characterized by clinical, morphologic, and immunophenotypic heterogeneity.

To define the role of intensive combination chemotherapy in the treatment of low-grade or intermediate-grade lymphomas, the authors report results in 49 patients treated with intermediate-dose or high-dose methotrexate, bleomycin, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), cytoxan (cyclophosphamide), vincristine, and dexamethasone (m/M-BACOD) with long-term follow-up. The complete response rate was 59% (29 of 49), including 67% (eight of 12) with low-grade and 57% (21 of 37) with intermediate-grade disease. The median survival for the entire group was 81 months. The 29 complete responders had a long median survival of 131 months. Forty-five percent (13 of 29) of the complete responders, 27% of the entire group, continue in remission with a median disease-free survival of 76 months. This includes five of 19 patients with diffuse poorly differentiated lymphoma, a disease generally characterized by early relapse. Twelve patients achieved a partial response and had a shorter median survival of 53 months, whereas nonresponders survived a median of less than 5 months. Late relapse was noted in patients with low-grade and intermediate-grade disease. Age (younger than or older than 60 years) was the only predictor of long-term survival. These data indicate very long disease-free survival can be achieved in low-grade and intermediate-grade lymphomas after attaining a complete remission. Intensive doxorubicin containing chemotherapy can be considered as an option for patients with advanced low-grade lymphoma but can only be proven to be superior to single-agent chemotherapy or no initial therapy by controlled randomized trails.

The clinical, pathologic, and immunologic features of 78 cases of peripheral/post-thymic T-cell lymphomas are described. These neoplasms were extremely heterogeneous and were classified as small lymphocytic, mixed small and large cell, large cell, lymphoepithelioid cell, angiocentric, and adult T-cell leukemia/lymphoma type. Some cases revealed angioimmunoblastic or Hodgkin's-like features. These neoplasms mainly affected older adults (mean age, 57 years; median age, 60 years). Lymphadenopathy represented the most frequent clinical presentation, although most patients demonstrated both nodal (87%) and extranodal involvement (77%) during the course of disease. Sites of extranodal disease included skin/soft tissue, spleen, lung, liver, bone, gastrointestinal tract, central nervous system, peripheral blood, nasopharynx, and retrovaginal tissue. Splenomegaly at presentation was most frequently observed in lymphoepithelioid cell lymphomas. Angiocentric lymphomas involved lung. A mediastinal presentation was typically observed in young adults and associated with a poor prognosis. Patients with gastrointestinal lymphomas presented with bleeding and/or malabsorption. B symptoms were present in most cases (65%). Hypercalcemia occurred in four patients. Phenotypic studies of T-cell antigens demonstrated the loss of one or more pan-T-cell markers in eight of 47 cases evaluated. Assessment of T-cell subsets revealed a helper/inducer phenotype for nearly all immunoreactive cases. For the overall series, 32 patients died of disease (median survival time, 11.5 mo). There was a statistical difference between the combined groups of small lymphocytic and lymphoepithelioid cell types as compared with mixed and large cell types, with a poorer survival for the latter group. Angiocentric and adult T-cell leukemia/lymphoma were associated with poor survival. This series of T-cell lymphomas further documents the marked heterogeneity of this group of neoplasms as well as the poor prognosis observed for certain histologic types.

A retrospective review of 34 patients with non-Hodgkin's lymphoma and a leukemic phase was undertaken. The median survival after onset of a leukemic phase was 30 months for patients with nodular poorly differentiated lymphocytic lymphoma which was significantly longer than 19 months for diffuse poorly differentiated lymphocytic lymphoma, and 2 months for diffuse histiocytic and undifferentiated lymphoma. Clinical features of patients with diffuse histologies that contributed to a poor prognosis included advanced stage of disease as well as age. Underlying lymph node histology also defined features of the leukemic phase which included duration, peak leukocyte count, and in some instances, distinctive morphologic characteristics of circulating malignant cells. Although small sample size did not permit definitive correlations of immunological subtype and survival, heterogeneity was noted, suggesting that clearer stratification of these patients with immunologic techniques may be useful in assessing prognosis in future investigations.

A case of T-cell lymphoblastic lymphoma is described in which the patient presented with a characteristic mediastinal mass and lack of bone marrow involvement. Immunologic studies of the surface phenotype of the malignant cells in a pleural effusion with monoclonal antibodies revealed the cells to be of thymic origin and distinguished them from the surface phenotypes seen in T-cell acute lymphoblastic leukemia. Twenty-five months after presentation with lymphoma, the patient developed an acute nonlymphocytic leukemia. With the improved prognosis seen in lymphoblastic lymphoma with intensive combination chemotherapy, it is expected that more cases of subsequent acute nonlymphocytic leukemia will be seen. In view of the natural history of lymphoblastic lymphoma to develop into lymphoblastic leukemia, it is important to be alert to a complicating nonlymphocytic leukemia.

Tissues from a variety of breast lesions were incubated with 14C-testosterone (17beta-hydroxy-4-androsten-3-one). Conversion to 14C-5alpha-dihydrotestosterone (17beta-hydroxy-5alpha-androstan-3-one) and 14C-androstenedione (4-androsten-3,17-dione) was measured. Normal breast tissue showed formation of 14C-androstenedione but no formation of 14C-5alpha-dihydrotestosterone. Fibroadenomas showed a high degree of testosterone metabolism forming both 14C-androstenedione and 14C-5alpha-dihydrotestosterone. The adenocarcinomas of the breast, contrary to a previous report in the literature, showed no conversion to 14C-5alpha-dihydrotestosterone. The data suggest that formation of 5alpha-dihydrotestosterone is a predominant metabolic pathway in fibroadenoma.

The cases of thyroid carcinoma treated at this hospital during the period 1948 to 1981 were reviewed retrospectively. Nine hundred eighty-six patients with thyroid nodules were operated on. One hundred fifty-two were thyroid carcinoma (59 papillary, 36 mixed papillary-follicular, 30 follicular, 20 anaplastic, 5 medullary, and 2 Hurthle cell tumors). There was a 92% follow-up for a mean of 10 years. In the last decade, patients presented at a younger age, the female predominance was diminished, and 15% had had previous neck irradiation. Surgery consisted of total (27) or subtotal thyroidectomy (89), lobectomy or nodulectomy (24), and biopsy (12). Total thyroidectomy had an incidence of postoperative complications that was 20 times higher than that with partial thyroidectomy (P less than 0.001). Disease-related death, recurrence, and survivor status were discussed. There was no significant difference between total versus subtotal thyroidectomy. This study reaffirms the usefulness of subtotal resection and the avoidance of morbidity of more radical total thyroidectomy surgery.

Lymphocyte subpopulations have been defined for twenty-five involved lymph nodes, ten involved spleens and twenty-five uninvolved spleens of patients with Hodgkin's disease. A predominance of T lymphocytes was observed in involved lymph nodes (77 ± 3% se) and also in involved and uninvolved spleens, with splenic tumor nodules demonstrating the highest T cell values for splenic tissue (75 ± 3% se). The T cell content of involved nodes, however, did not differ significantly from that of a group of hyperplastic nodes. The percentages of T lymphocytes in splenic tumor nodules (75 ± 3% se) and in uninvolved spleens (68 ± 2% se) of patients with Hodgkin's disease were greater (p < 0.05) than those observed for the group of control spleens with traumatic rupture (54 ± 5% se). Histologically uninvolved spleens of patients with Hodgkin's disease demonstrated a higher B cell content (22 ± 2% se) than splenic tumor nodules (13 ± 2% se). The percentage of B lymphocytes observed in spleens with traumatic rupture (47% ± 6% se) was significantly greater than those observed for involved and uninvolved spleens of patients with Hodgkin's disease and those found in spleens of patients with various nonlymphoproliferative disorders. An unusual finding in these studies was the identification of IgMEA rosette forming lymphocytes which were significantly increased (p < 0.01) in nodes infiltrated by Hodgkin's disease (9.3 ± 1.6% se) as compared with a group of hyperplastic nodes (1.6 ± 0.4% se), and in splenic tumor nodules (3.7 ± 0.8% se) as compared with spleens with traumatic rupture (0.4 ± 0.3% se).

Peripheral blood from 125 patients (160 specimens) with various types of lymphoid leukemias was evaluated for B- and T-cell markers (E rosettes, C3 and Fc receptors, and surface immunoglobulin). B-cell leukemias (comprised 82% of the series and included chronic lymphocytic leukemia (69/71 cases), acute lymphocytic leukemia (1/18 cases), lymphosarcoma cell leukemia (15/18 cases), prolymphocytic leukemia (one case), plasma cell leukemia (one case), hairy cell leukemia (12/12 cases), and leukemic phase of "histiocytic" lymphoma and Waldenstrom's macroglobulinemia (one case each). Within the B-cell group, certain leukemias exhibited distinct patterns of lymphocyte surface markers. Three cases of lymphosarcoma cell leukemia revealed both T and B cell markers (E-rosette formation and monoclonal SIg). T-cell leukemias comprised 12% of the series and included chronic lymphocytic leukemia (2/71 cases), acute lymphocytic leukemia (11/18 cases), and Sezary's syndrome (2/2 cases). In eight cases of acute lymphocytic leukemia, the majority of the cells demonstrated no definable markers (non-B, non-T cell type). Ultrastructural studies, performed in selected cases, were correlated with immunologic findings. Distinctive morphologic features were observed for different variants of B- and T-cell leukemias. Neoplastic cells of T-cell leukemias revealed a greater nuclear irregularity than B-cell proliferations, as assessed by the nuclear contour index (ratio of circumference to the square root of the nuclear area). The cytoplasmic feature most predictive of immunologic cell type was abundant rough endoplasmic reticulum, suggesting plasmacytoid differentiation, observed in some B-cell proliferations.

Ultrastructural studies were performed on 40 B-cell and 14 T-cell lymphomas of non-Hodgkin's type (NHL). Most B-cell lymphomas were comprised of neoplastic cells with morphologic features compatible with a follicular center cell origin. Dendritic reticulum cells and their desmosome-associated processes, characteristic of germinal centers, were observed in all 11 cases of nodular poorly differentiated lymphocytic lymphoma and in one of two cases of nodular "histiocytic" lymphoma, but were not identified in the lymphomas with a diffuse growth pattern. Desmosomes were observed between dendritic reticulum cells and were not found between lymphoid cells. Large neoplastic cells comprising lymphomas of "histiocytic," mixed lymphocytic "histiocytic," and "undifferentiated" types were characterized ultrastructurally and immunologically as lymphoid cells. Malignant lymphomas of well and moderately well differentiated lymphocytic types (7 cases) revealed B-cell markers, and represented a distinct homogenous group of neoplasms, with electron microscopic features most closely resembling follicular cuff lymphocytes. T-cell malignancies included lymphoblastic lymphomas (3 cases), large cell ("histiocytic") lymphomas (4 cases), lymphoepithelioid cell ("Lennert's") lymphomas (2 cases), mycosis fungoides (3 cases) and diffuse poorly differentiated lymphocytic lymphomas (2 cases). A consistent finding in the T-cell proliferations was the presence of small and/or large lymphoid cells with extremely irregular and/or convoluted nuclei, which occurred in varying proportions and with variable degrees of nuclear complexity. The nuclear irregularity evident in the neoplastic T cells was distinguishable from that observed for lymphoid cells of B-cell lymphomas. In comparing the cytoplasmic features of the T- and B-cell neoplasms ultrastructurally, the only distinguishing feature was the presence of well developed granular endoplasmic reticulum with dilated cisternae, i.e., plasmacytoid features, predictive of a B cell origin.

A patient with benign lymphoepithelial lesions of the parotids who developed widespread reticulum cell sarcoma is described. Fourteen other cases of Sjogren's syndrome and/or benign lymphoepithelial lesions of the salivary glands are reviewed. Some of these cases were associated with thymoma, mac-roglobulinemia, reticulum cell sarcoma of the stomach, progressive systemic sclerosis, Hashimoto's thyroiditis, hypergammaglobulinemia, high titers of antirheumatoid factor, Raynaud's phenomenon, and adenopathy.