Michael J. Kornstein

Invasive thymoma: the role of mediastinal irradiation following complete or incomplete surgical resection.

To evaluate the role of mediastinal irradiation (RT) following surgery for invasive thymomas, a clinical and pathologic review of 117 patients with the diagnosis of thymoma was completed. Fourteen cases were excluded because of the lack of histologic criteria for a thymic tumor, and the remaining 103 were classified according to a staging system as follows: stage I, completely encapsulated (43); stage II, extension through the capsule or pericapsular fat invasion (21); stage III, invasion of adjacent structures (36); and stage IV, thoracic dissemination or metastases (3). The 5-year actuarial survival and relapse-free survival rates were 67% and 100% for stage I, 86% and 58% for stage II, and 69% and 53% for stage III. No recurrences occurred among stage I patients after total resection without RT. However, eight of 21 patients with invasive (stage II or III) thymomas had mediastinal recurrence as the first site of failure following total resection without RT. The 5-year actuarial mediastinal relapse rate of 53% in this group compares unfavorably with the mediastinal relapse rate seen among stage II or III cases following total resection with RT (0%) or following subtotal resection/biopsy with RT (21%). Despite attempted salvage therapy, five of eight patients with mediastinal relapse following total resection alone died of progressive disease. No significant difference was observed in the local relapse rate, overall relapse rate, or survival between those patients undergoing biopsy and RT v subtotal resection and RT for invasive thymomas (stages II and III). Total resection alone appears to be inadequate therapy resulting in an unacceptably high local failure rate with poor salvage therapy results.

Cortical versus medullary thymomas: A useful morphologic distinction?

We have tested the hypothesis that thymomas can be classified solely on the basis of epithelial cell morphology and that this distinction is prognostically useful. One hundred thymic epithelial tumors were classified according to the morphologic resemblance to cortical or medullary thymic epithelium and to the traditional classification (lymphocytic, epithelial, mixed, and spindled). Follow-up data was obtained on 78 patients. Fifty-eight percent of the tumors were invasive. Nineteen of the invasive tumors relapsed and none of the non-invasive tumors relapsed (P less than .0001). Four of nine tumors with microscopic invasion through the capsule recurred. Statistical analysis showed no significant differences in relapse-free survival for any of the histologic categories. Ninety-four percent of the tumors studied were keratin positive and all were chromogranin negative. Carcinoembryonic antigen was negative for all but one cytologically malignant tumor; of the tumors 75% were epithelial membrane antigen positive, 80% were Leu-7 positive, and 11% were neuron specific enolase positive. Seven of 12 tumors tested expressed HLA-DR. There was no correlation between immunoreactivity and classification. The morphologic cortical/medullary distinction is conceptually attractive but appears clinically to be no more advantageous than the traditional classification.

Absence of the OKT4 epitope on blood T cells and thymus cells in a patient with thymoma, hypogammaglobulinemia, and red blood cell aplasia

Human helper/inducer T-lymphocytes that express the T4 antigen are important in the regulation of B and T cell functions. Several epitopes of the T4 molecule have now been recognized; however, the precise role of these molecules in the function of helper/inducer T cells is unclear. We studied a patient with thymoma, hypogammaglobulinemia, and red blood cell aplasia whose blood lymphocytes and thymus cells did not express the epitope recognized by OKT4 monoclonal antibody but did display the T4 epitopes recognized by OKT4A and Leu3A monoclonal antibodies. The absence of the OKT4 epitope on the patients thymus cells suggested that the abnormality occurred during early T cell differentiation. The patient had intact delayed hypersensitivity to 4/4 antigens, and his blood lymphocytes proliferated normally to phytohemagglutinin, concanavalin A, pokeweed mitogen, tetanus toxoid, and allogeneic cells. The patients T cells demonstrated augmented suppressor activity that was localized to the OKT8+ population rather than to the unusual T4 subset. Irradiation abrogated suppressor activity and rendered his T cells capable of providing help for polyclonal B cell differentiation. The data emphasize the limitations of OKT4 as the sole reagent for characterizing the subset of human helper/inducer cells and demonstrate that the expression of the T4 epitope recognized by OKT4 monoclonal antibody is not required for certain helper/inducer T cell functions in vitro and in vivo.

Immunohistology of the benign lymphoepithelial lesion in aids-related lymphadenopathy: a case report

We report a case of a benign lymphoepithelial lesion of the parotid gland in a patient with progressive generalized lymphadenopathy (PGL) related to human immunodeficiency virus. Serologic studies and immunoperoxidase studies for lymphocyte subsets, which have not previously been reported in this lesion, suggest involvement of an intraparotid lymph node by PGL rather than Sjogrens syndrome.

Phenotypic and functional analysis of lymphocytes in myasthenia gravis

Myasthenia gravis (MG) is a disease of neuromuscular transmission which is manifested clinically by muscle weakness, frequently of a profound degree. It is one of a new class of autoimmune diseases whose pathogenesis is mediated by autoantibodies directed against tissue receptors. In myasthenia, the responsible antibodies are directed against the nicotinic acetylcholine receptors (AChR) located at postsynaptic myoneural junctions. The interaction of these antibodies with AChR disrupts neuromuscular transmission. Although the pathogenesis of MG has been elucidated only within the past decade, immunologists had long been interested in this disease. MG occurs in association with other putative autoimmune disorders including rheumatoid arthritis and systemic lupus erythematosus [-reviewed in 61] and is associated with an increased incidence of an array of autoantibodies including antinuclear factor, anti-thyroglobulin and rheumatoid factor [reviewed in 62]. Other clues pointing to the immune system were provided by several lines of evidence implicating the thymus in the pathogenesis of MG. Patients frequently showed dramatic clinical improvement after thymectomy. Thymic pathologic findings were commonly observed with germinal center hyperplasia in as many as 75% of patients and lymphoepithelial thymomas in an additional 10% [16, 55]. Cells within the thymus, including myoid and epithelial cells [25, 43,128] and perhaps even thymocytes [29] were shown to express AChR. These observations, taken together, suggested that the thymus represented a potentially important focus for initiating or perhaps perpetuating the autoimmune response in MG. Despite significant advances in the characterization of antibodies to AChR (hereafter called anti-AChR) and elucidation of their immunopathogenic role in MG, a wide gap remains in the understanding of those mechanisms which are responsible for the emergence of these antibodies. In an effort to delineate such

Myasthenia gravis and primary squamous cell carcinoma of the thymus (a case report)

We detail a case of primary squamous cell carcinoma of the thymus in a patient with myasthenia gravis. The clinical course of the patient and the gross and histologic appearance of the thymus are discussed. Appropriate therapy for patients with these tumors includes resection of the tumor followed by radiation therapy and continued surveillance for recurrence. Review of the literature indicates less than 50% survival at 10 years and 22% recurrence rate at 5 years for patients with this tumor.

Diagnosis of occult meat aspiration by fiberoptic bronchoscopy

Cytologic examination of bronchial washings from a patient with a persistent localized pulmonary infiltrate revealed large numbers of striated muscle fibers. The patient died shortly after bronchoscopy, and postmortem examination provided evidence of recurrent aspiration pneumonias. Since skeletal muscle fibers are not likely to enter the tracheobronchial tree from any endogenous source, it is proposed that this unusual cytologic finding is virtually diagnostic of recent food aspiration.

Acquired hyper-IgM syndrome with necrotizing granuloma.

This article is highlighted by the finding of striking cervical lymphadenopathy in a patient with acquired hyper-IgM syndrome and the pathologic description of the involved nodes. Routine hematoxylin-eosin stains demonstrated the presence of idiopathic necrotizing granulomas in the nodal tissue, a finding not previously reported in this syndrome. Immunoperoxidase techniques were used to further characterize these granulomas and delineate the cellular composition of the nodal architecture. We found that the necrotizing granulomas consisted of a peripheral rim of Ia positive palisaded, epithelioid histiocytes and central areas of debris and scattered inflammatory cells that were T11 positive. In the uninvolved areas of the node, we observed a lack of IgG-bearing lymphocytes in germinal centers as well as an absence of IgG-containing and decreased IgA-containing plasma cells in interfollicular areas. In conjunction with these in situ observations, there was a lack of IgA and IgG immunoglobulin-secreting cell responses in pokeweed mitogen-stimulated cultures of the patients peripheral blood mononuclear cells. Unique features of this article include: (1) the association of necrotizing granulomas with the hyper-IgM syndrome and (2) the use of monoclonal antibodies to characterize the distributions of nodal lymphocytes in a patient with this disorder.

The Thymus in Myasthenia Gravis: An Immunohistologic Study

Abnormalities of the thymus have long been noted in patients with myasthenia gravis (MG).1,2,3 Morphologically, the presence of germinal centers in the medulla of the MG thymus was described by Castleman in 1949.1 Functionally, the MG thymus cells have altered immunologic activity.2,3 Recently the development of monoclonal antibodies to T cell subsets allows for the furthur investigation of the MG thymus.4 We have used such monoclonal antibodies to investigate the MG thymus in tissue sections. We have compared these results to findings obtained in studies of suspended cells from the same thymus specimens.