Characterization of lymphoproliferative lesions of the conjunctiva: immunohistochemical and molecular genetic studies.

BACKGROUND: Conjunctival lymphoproliferative lesions have not been selected for independent analysis with newer immunohistochemical and molecular genetic techniques to highlight their unique profile. METHODS: Retrospective case series examined biopsies from 16 consecutive patients with conjunctival lymphoproliferative lesions. The histopathologic, immunohistochemical, and molecular genetic features were characterized, as well as the frequency of tumour type, prognostic implications, clinical features, and treatments offered. RESULTS: The diagnosis was lymphoma in 12 cases, atypical lymphoid hyperplasia (ALH) in 1 case, and reactive lymphoid hyperplasia (RLH) in 3 cases. The primary lymphomas consisted of 4 mucosa-associated lymphoid tissue lymphomas (MALTL), 1 follicular lymphoma (FL), 2 diffuse large B-cell lymphomas (DLBCLs), 1 lymphoplasmacytic lymphoma, and 1 T-cell lymphoma. Primary lymphomas were treated with radiation (n = 7), surgery (n = 1), and topical chemotherapy (n = 1). Complete remission was achieved in 8 of 9 primary lymphomas. Two cases of recurrence to the other conjunctiva were treated with radiation and both remained disease free. Secondary lymphomas included 2 DLBCL and 1 MALTL. Complete remission was seen in 2 patients after radiation plus chemotherapy, while the patient treated with chemotherapy alone was lost to follow-up. The 1 case of ALH presented bilaterally and achieved complete remission after topical chemotherapy treatments. The 3 RLH cases were surgically managed and 2 of the 3 recurred and were subsequently excised. Eleven lymphomas were of B-cell lineage by immunophenotyping. Molecular genetic studies of immunoglobulin heavy chain (IgH) gene rearrangement by polymerase chain reaction (PCR) showed clonal bands in 6 of 12 lymphomas, 1 of 3 RLH (polyclonal by immunophenotyping) and 1 ALH. BCL2-IgH [t(14;18)] rearrangement was seen in 8 of 12 cases (1 FL, 3 DLBCLs, 4 MALTLs) by real-time quantitative PCR. INTERPRETATION: Conjunctival lymphomas are predominantly B-cell type with a high prevalence of MALTL. An unexpected finding was the BCL2-IgH rearrangement seen in 4 of 5 MALTL cases in our series. The significance of this remains unclear.

Lymphoproliferative lesions of the lacrimal gland: clinicopathological, immunohistochemical and molecular genetic analysis.

BACKGROUND: Lacrimal gland lymphoproliferative disorders are usually classified as orbital adnexal tumours. Because the lacrimal gland is the only orbital structure with native lymphocytes, we examined cases with primary involvement of the gland. METHODS: The 14 cases were selected from a review of all cases in the surgical pathology files of the Ottawa Hospital between 1992 and 2003. The lesions were categorized according to the latest World Health Organization classification of tumours of lymphoid tissues. We conducted a clinical, histopathological, immunohistochemical, immunophenotypic and molecular genetic analysis of the cases. RESULTS: The 8 female and 6 male patients, aged 20 to 88 (mean 60) years, were followed for an average of 4 years (range 11 months to 13 years). All presented with supratemporal orbital swelling. The 5 primary lymphomas, of mucosa-associated lymphoid tissue (MALT), were confined to the lacrimal gland (stage IE); 1 tumour transformed to diffuse large B-cell lymphoma, necessitating chemotherapy, and the other 4 were treated with radiation. One of the 5 patients had previously had Sjögren's syndrome. The 6 secondary lymphomas (4 follicular) presented either concurrently with systemic lymphoma or up to 12 years afterwards and were treated in a variety of ways; all the patients had an orbital relapse. At the last follow-up assessment, 6 of the patients with lymphoma had no evidence of disease, 3 were alive with disease, 2 had died (1 of lymphoma, the other with no evidence of disease), and the status of 1 patient was not known. Of the 3 patients with reactive proliferations, 2 had reactive lymphoid hyperplasia (associated with Sjögren's syndrome in 1), and 1 had Rosai-Dorfman disease. All 9 lymphomas that underwent molecular genetic analysis were of B-cell lineage, and 8 had a monoclonal rearrangement in the immunoglobulin heavy-chain gene (IgH); the 9th lymphoma showed an oligoclonal rearrangement. One lymphoma showed the t(14;18) translocation, typical of follicular lymphoma; no lymphoma showed the t(11;18) translocation, commonly found in MALT lymphoma (but only 2 cases were studied). Molecular genetic analysis was performed in 2 of the cases of reactive lymphoid hyperplasia: monoclonal IgH rearrangement was detected in 1 case (the patient with Sjögren's syndrome), oligoclonal rearrangement in the other. INTERPRETATION: Lacrimal gland lymphomas are B-cell tumours that develop in older adults. Primary tumours, a hIgH proportion of which have MALT characteristics, have a favourable prognosis. Molecular genetic studies may be useful when morphologic and immunophenotypic studies give equivocal results.

Isolated pleural PTLD after cardiac transplantation.

UNLABELLED: PREAMBLE: Epstein-Barr virus infection (EBV) and immunosuppression promote emergence of posttransplant lymphoproliferative disorders (PTLD) in patients undergoing organ transplantation. OBJECTIVE: We report a case of PTLD confined to the pleura. FINDINGS: The patient was a 62-year-old male who had undergone cardiac transplant in 1993 for ischemic heart disease. Seven years later, he presented with dyspnea and bilateral pleural effusions. The CT scan revealed left sided pleural base thickening. The cytology of the pleural fluid and fine needle aspirate of the pleura was both suggestive of PTLD. However, the tissue submitted for ancillary studies did not contain the diagnostic material. A clinical decision was made to withdraw immunosuppressive therapy and start rituximab. His clinical course was complicated by Pneumocystis carinii pneumonia and he died 4 months after the diagnosis of PTLD. Autopsy revealed bilateral pleural effusions with pleural nodules involving the visceral and parietal pleura of both lungs. Immunohistochemistry demonstrated B cell lineage with kappa/lambda ratio of 1. PCR studies done on the pleural nodules (postmortem specimen) revealed the presence of EBV DNA and absence of human herpes virus 8 (HHV8) DNA. In situ hybridization revealed positive staining for EBV RNA within the neoplasm. CONCLUSION: Pleural-based PTLD is rare. Cytology in conjunction with immunophenotyping and molecular studies can be useful for a definitive diagnosis. In our case, cytology sample was suggestive of PTLD. PCR studies performed on the antemortem specimen confirmed the presence of monoclonal IgH gene rearrangement, while the postmortem specimen revealed oligoclonal IgH gene rearrangement. The change from monoclonal to oligoclonal IgH gene rearrangement suggests reversion of monoclonal to polyclonal PTLD following rituximab and CHOP therapy. We also demonstrated EBV DNA and RNA in the tumor nodules, supporting EBV-induced PTLD.