Extranodal noncutaneous lymphoid hyperplasias represent a continuous spectrum of B-cell neoplasia: demonstration by molecular genetic analysis

Abstract

We investigated 16 lymphoid proliferations occurring in the ocular adnexa, salivary glands, breast, and thyroid gland and satisfying the histopathologic and immunophenotypic criteria of benign lymphoid hyperplasia for the presence of clonal rearrangements of the antigen receptor, c-myc, bcl-1, and bcl-2 genes and Epstein-Barr virus (EBV) DNA sequences. Each of these 16 extranodal, noncutaneous lymphoid neoplasms exhibited clonal immunoglobulin heavy and/or light chain and lacked T-cell receptor (TCR) beta-chain gene rearrangements. The patterns of immunoglobulin gene rearrangements included solitary and multiple barely perceptible to faint bands, solitary clear and definite bands, and solitary high-intensity bands superimposed on a background of multiple less-intense bands. Three ocular adnexal lymphoid neoplasms exhibited bcl-1 or bcl-2 gene rearrangements. None of the 16 lymphoid neoplasms contained EBV DNA sequences. Two patients developed a histopathologically confirmed malignant lymphoma in an extranodal site. None of the remaining 14 patients developed additional lymphoid neoplasms during a mean follow-up period of 30 months, despite conservative therapy. These results demonstrate that extranodal, noncutaneous lymphoid neoplasms meeting the histopathologic and immunophenotypic criteria for benign lymphoid hyperplasia frequently contain occult monoclonal and oligoclonal B-cell populations representing a continuous and progressive spectrum of B-cell neoplasia up to and including malignant lymphoma.

Immunoglobulin Gene Analysis of Cutaneous Pseudolymphoma by Polymerase Chain Reaction

“…According to Wan et aI., monoclonality was detected in 92% of cases of B cell non-Hodgkin's lymphoma and was relatively specific for this disease. On the other hand, rearrangements of immunoglobulin genes have been reported in some inflammatory and neoplastic conditions (lymphadenopathy in transplant patients (8), orbital pseudotumors (9), Sjogren syndrome (10), and so on). According to these clinical examples, demonstration of gene rearrangement by itself may not be sufficient for a diagnosis of malignancy, but it may indicate an abnormal lymphoproliferative process in which a substantial proportion of cells represent a single clone.…”

Novel therapeutic option for orbital atypical lymphoid hyperplasia

“…3,5 This has prompted the suggestion that reactive lymphoid hyperplasia is an unstable lesion leading to development of progressive clonal expansions of B-lymphocytes within the orbit with the potential to result in malignant lymphoma. 3 This is believed to be the result of an immunoregulatory defect in which T-helper cells outnumber the T-suppressor cells. 3 Most orbital adnexal tumours present with palpable mass, proptosis or ptosis.…”

“…3 This is believed to be the result of an immunoregulatory defect in which T-helper cells outnumber the T-suppressor cells. 3 Most orbital adnexal tumours present with palpable mass, proptosis or ptosis. Irrespective of the pathology, staging investigations are recommended at diagnosis as the extent of the disease is a strong determinant of prognosis.…”

“…This is well reported in literature. 3 No evidence of systemic lymphoma was detected on CT scan or bone marrow biopsy.…”

Lacrimal gland lymphoma: A cytomorphologic and immunophenotypic study

“…Studies using these methods have demonstrated that ocular adnexal lymphoid proliferations may represent a continuous spectrum of B cell lymphocyte neoplasms ranging from polymorphic lesions harboring small monoclonal B-cell lymphocyte populations to monomorphic malignant lymphomas comprised almost entirely of a single clonal B cell population. 2,3,16,17 We present here a study of six lacrimal gland lymphomas studied by fine-needle aspiration cytology, flow cytometric immunophenotyping, and gene rearrangement studies. There have been only a few cytomorphologic studies of ocular adnexal lymphoid proliferations 4-8 and no studies specifically addressing the cytologic features of lacrimal gland lymphomas.…”