Challenges in the diagnosis and management of vitreoretinal lymphoma - Clinical and basic approaches.

Vitreoretinal lymphoma (VRL) is a subtype of diffuse large B-cell lymphoma and is sight- and life-threatening in the vast majority of patients. Lymphoma cells infiltrate the vitreous body and/or subretinal space and exhibit clinical signs of vitreous opacities and creamy white subretinal lesions. Although the intraocular signs can serve as clues to suspect VRL, they are nonspecific and may be misdiagnosed as uveitis. Histopathological evidence of malignant cells on vitreous biopsy, for instance, is the gold standard for diagnosis of VRL; however, cytological examination of the vitreous often results in a low success rate owing to the small quantity and poor quality of tissues and cells in the sample. Recent advancements in immunological, molecular, and gene analyses using intraocular samples have made it possible to accurately diagnose VRL. As for the management of VRL, local treatments with irradiation and/or intravitreal injections of anti-tumor agents (methotrexate or rituximab) are effective in suppressing intraocular VRL lesions. However, the effect of systemic chemotherapy, with or without brain irradiation, on preventing central nervous system involvements remains controversial. In this review article, we discuss the following concepts based on previous literature and our unpublished results: current ocular imaging examinations such as optical coherence tomography and fundus autofluorescence; immunological, molecular, and gene expression characterization of intraocular biopsies with special attention to flow cytometry; immunoglobulin gene rearrangement assays that use the polymerase chain reaction test; cytokine assays; gene mutations (MYD88, CD79B); and current local and systemic treatments of VRL.

Simultaneous Presentation of Waldenström's Macroglobulinemia and MYD88 Gene Mutation with Multiple Myeloma.

Waldenström's macroglobulinemia (WM) and multiple myeloma (MM) are two distinct forms of mature hematologic B-cell malignancies. A missense somatic mutation in MYD88 gene (MYD88L265P) has been found in hematologic B-cell malignancies. The simultaneous presentation of Waldenström's macroglobulinemia and MYD88 mutation with multiple myeloma in the same patient is very rare and only a few cases have been reported in the literature.

Primary Type3 (Non-ABC, Non-GCB) Subtype of Extranodal Diffuse Large B-Cell Lymphoma of the Thyroid Bearing No MYD88 Mutation by Padlock Probe Hybridization.

Primary extranodal malignant lymphoma of the thyroid is a rare entity composed of mostly neoplastic transformation of germinal center-like B cells (GCB) or memory B cells. Other B-cell-type malignancies arising primarily in the thyroid have rarely been described. Immunohistochemical examination of autopsied primary malignant lymphoma of the thyroid in an 83-year-old Japanese female revealed the presence of a non-GCB subtype of diffuse large B-cell lymphoma (DLBCL) without the typical codon 206 or 265 missense mutation of MYD88. The lack of the highly oncogenic MYD88 gene mutation, frequently observed in DLBCL of the activated B-cell (ABC) subtype, and the detection of an extremely aggressive yet local clinical phenotype demonstrated that the present case was an exceptional entity of the type3 (non-GCB and non-ABC) subtype.

CD79B and MyD88 gene mutation in primary testicular diffuse large B cell lymphoma / 临床与实验病理学杂志

Purpose To explore the mutation of CD79B and MyD88 in primary testicular diffuse large B cell lymphoma and their significance.Methods Histopathologic features were observed in 15 cases of primary testicular diffuse large B cell lymphoma and immunophenotype was analyzed by immunohistochemical staining (IHC).Sanger sequencing was used to detect CD79B Y196 and MyD88 L265 mutation in these cases.The relationship between CD79B,MyD88 mutation and the clinicopathological features was analyzed.Results Immunophenotypically,15 cases were non germinal center B cell type.CD79B (Y196) mutation was detected in 4 cases (26.7％).For MyD88,L265 mutation was found in 7 cases (46.7％).CD79B and MyD88 mutations were found in 3 cases.The followup information was obtained in 8 patients.No association was found between CD79B,MyD88 mutation and outcome of patients.Conclusion Primary testicular diffuse large B cell lymphoma of non germinal center B cell type is a rare aggressive B cell lymphoma with poor prognosis and poor response to chemotherapy.CD79B,MyD88 gene mnutation was detected in Chinese patients with frequency of 26.7％ and 46.7％ respectively.It is possible for molecular targeted therapy of the primary testicular diffuse large B cell lymphoma on the basis of high frequency of CD79B and MyD88 gene mutation.