Burkitt's lymphoma--the message from microarrays.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to Nancy Lee Harris.
Explore the source record for details and available documents.
The types of B-cell lymphoma commonly involving the spleen include splenic marginal zone lymphoma and T-cell/histiocyte-rich large B-cell lymphoma. We describe a unique case of splenic marginal zone lymphoma associated with micronodular T cell/histiocyte-rich large B-cell lymphoma in the red pulp, a combination that has not previously reported in the literature.
Cytogenetic data for T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) are scarcely available. We report here a case of THRLBCL with a near-tetraploid karyotype and complex chromosomal aberrations, without rearrangement of BCL2 or BCL6, and characterized pathologically by a variegated morphologic appearance with areas resembling nodular lymphocyte-predominant Hodgkin's lymphoma (NLPHL).
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Primary cutaneous lymphomas are currently classified by the European Organization for Research and Treatment of Cancer (EORTC) classification or the World Health Organization (WHO) classification, but both systems have shortcomings. In particular, differences in the classification of cutaneous T-cell lymphomas other than mycosis fungoides, Sezary syndrome, and the group of primary cutaneous CD30+ lymphoproliferative disorders and the classification and terminology of different types of cutaneous B-cell lymphomas have resulted in considerable debate and confusion. During recent consensus meetings representatives of both systems reached agreement on a new classification, which is now called the WHO-EORTC classification. In this paper we describe the characteristic features of the different primary cutaneous lymphomas and other hematologic neoplasms frequently presenting in the skin, and discuss differences with the previous classification schemes. In addition, the relative frequency and survival data of 1905 patients with primary cutaneous lymphomas derived from Dutch and Austrian registries for primary cutaneous lymphomas are presented to illustrate the clinical significance of this new classification.
Explore the source record for details and available documents.
The aetiology of primary B-cell lymphomas of the thymus is enigmatic. Although thymic follicular lymphoid hyperplasia (TFH) is commonly associated with myasthenia gravis (MG), lymphoma is not a complication of this condition. The present paper reports a high frequency of monoclonal B-cell populations (6 of 18 cases; 33%) in micronodular thymoma (MNT), a peculiar thymic epithelial neoplasm with a B-cell-rich stroma, while B cells were consistently polyclonal in TFH (25 cases) and other types of thymomas (15 cases) (p < 0.001). An intratumoural lymphoma could be identified in three of the six monoclonal MNTs. Sequencing of the monoclonal IgH chain revealed partially overlapping VDJ gene usage in MNT and thymic mucosa-associated lymphoid tissue (MALT) lymphomas. The neoplastic epithelium of MNTs, but not of TFH and other types of thymoma, expressed high levels of dendritic cell, T-cell, and B-cell chemoattractants, such as CCL18, CCR6, and CCL20. It is concluded that abnormal chemokine expression in an epithelial tumour, MNT, can promote the recruitment of MALT, the emergence of monoclonal B cells, and, eventually, the subsequent development of mediastinal lymphomas. More generally, the concept that expression of a 'high-risk' spectrum of chemokines due to local or genetic factors may interfere with B-cell homeostasis and may contribute to MALT lymphoma development in chronic inflammatory states is proposed.
Angioimmunoblastic T-cell lymphoma (AITCL) is a histologically distinct and relatively common subtype of T-cell lymphoma. Although the putative normal cell counterpart is a mature CD4+ T cell, the precise cell of origin remains elusive. We evaluated cases with a diagnosis of AITCL to determine the specificity and utility of CD10 coexpression, particularly by flow cytometry (FCM), in facilitating this diagnosis. Coexpression of BCL6 was also assessed. Eight AITCL cases were evaluated histologically, immunohistochemically, and by 4-color FCM. Four cases of peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), were also analyzed. The lymphoma cells in all 8 AITCL cases were CD4+, CD45RO+ T cells, with classic extrafollicular meshworks of CD21/CD23/CD35+ follicular dendritic cells. Furthermore, all cases of AITCL cases contained interfollicular CD10+ cells by immunohistochemistry, and increased coexpression of CD10 on T cells was also detected in 6 of 8 cases by FCM. CD10 coexpression was not observed in all 4 PTCL-NOS cases. Although not specific for AITCL, increased numbers of BCL6+ cells were seen in AITCL as compared with PTCL-NOS. Double immunohistochemistry performed on an AITCL case with high numbers of BCL6+ cells highlighted coexpression of BCL6 and CD4 on the same cells. The finding suggests that AITCL may be a neoplasm of (possibly intrafollicular) CD10+, BCL6+, and CD4+ memory T cells. Although our series is small, our results suggest that CD10 coexpression may be a useful discriminant, particularly if the differential diagnosis is PTCL-NOS, and demonstrate that this can be determined by FCM.
Hodgkin's lymphoma rarely involves the thyroid gland. We report the clinical and pathologic features of five cases of Hodgkin's lymphoma that presented as thyroid lesions. All five patients were females, aged 29-59 years. Three patients had a history of chronic thyroiditis and hypothyroidism and two were euthyroid. One patient had a remote history of Hodgkin's lymphoma. Imaging studies showed a 'cold' nodule (three cases) or a diffusely enlarged thyroid gland, resembling goiter or fibrosclerosing thyroiditis (two cases). Thyroid fine-needle aspiration was performed before thyroidectomy in all cases; three of these cases contained some atypical cells, raising the possibility of Hodgkin's lymphoma. Histologically, all cases were classical Hodgkin's lymphoma, nodular sclerosis subtype. The four patients with primary thyroid lymphoma had Stage IIE disease. All patients were treated with surgical excision and chemotherapy, with or without radiation therapy, and were alive after 2 months to 7 years of follow-up. A review of the English literature between 1962 and 2005 revealed 16 cases of thyroid Hodgkin's lymphoma, with a female preponderance and generally favorable outcome similar to the cases in our series. Hodgkin's lymphoma of the thyroid is rare and can mimic a primary thyroid epithelial tumor or thyroiditis clinically. Histologic diagnosis may be difficult due to marked fibrosis. Hodgkin's lymphoma should be considered in the differential diagnosis of thyroid neoplasms.
Histologic grading has been used as a guide for clinical management in follicular lymphoma (FL). Proliferation index (PI) of FL generally correlates with tumor grade; however, in cases of discordance, it is not clear whether histologic grade or PI correlates with clinical aggressiveness. To objectively evaluate these cases, we determined PI by Ki-67 immunostaining in 142 cases of FL (48 grade 1, 71 grade 2, and 23 grade 3). A total of 24 cases FL with low histologic grade but high PI (LG-HPI) were identified, a frequency of 18%. On histologic examination, LG-HPI FL often exhibited blastoid features. Patients with LG-HPI FL had inferior disease-specific survival but a higher 5-year disease-free rate than low-grade FL with concordantly low PI (LG-LPI). However, transformation to diffuse large B-cell lymphoma was uncommon in LG-HPI cases (1 of 19; 5%) as compared with LG-LPI cases (27 of 74; 36%). In conclusion, LG-HPI FL appears to be a subgroup of FL with clinical behavior more akin to grade 3 FL. We propose that these LG-HPI FL cases should be classified separately from cases of low histologic grade FL with concordantly low PI.
Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease with recognized variability in clinical outcome, genetic features, and cells of origin. To date, transcriptional profiling has been used to highlight similarities between DLBCL tumor cells and normal B-cell subtypes and associate genes and pathways with unfavorable outcome. To identify robust and highly reproducible DL-BCL subtypes with comprehensive transcriptional signatures, we used a large series of newly diagnosed DLBCLs, whole genome arrays, and multiple clustering methods. Tumors were also analyzed for known common genetic abnormalities in DLBCL. There were 3 discrete subsets of DLBCL-"oxidative phosphorylation," "B-cell receptor/proliferation," and "host response" (HR)-identified characterized using gene set enrichment analysis and confirmed in an independent series. HR tumors had increased expression of T/natural killer cell receptor and activation pathway components, complement cascade members, macrophage/dendritic cell markers, and inflammatory mediators. HR DLB-CLs also contained significantly higher numbers of morphologically distinct CD2+/CD3+ tumor-infiltrating lymphocytes and interdigitating S100+/gamma interferon-induced lysosomal transferase-positive (GILT+) CD1a-/CD123- dendritic cells. The HR cluster shared features of histologically defined T-cell/histiocyte-rich B-cell lymphoma, including fewer genetic abnormalities, younger age at presentation, and frequent splenic and bone marrow involvement. These studies identify tumor microenvironment and host inflammatory response as defining features in DLBCL and suggest rational treatment targets in specific DLBCL subsets.
Explore the source record for details and available documents.
Occurrence of an aggressive lymphoma in patients with chronic lymphocytic leukemia (CLL), clinically referred to as Richter's syndrome, occasionally manifests as a lymphoproliferation resembling Hodgkin's lymphoma (HL) and often containing the Epstein-Barr virus (EBV). Only a limited number of HL variants have been subject to informative analysis regarding their clonal relationship to the CLL, with evidence of a same clonal origin in some cases and of clonally unrelated neoplasms in other cases. In this paper, we performed a detailed pathologic, virologic, and molecular analysis of two cases of Richter's syndrome with HL features. The first case occurred in a 65-year-old man with a 5-year history of CLL as a mediastinal and supraclavicular mass histologically diagnosed as lymphocyte depleted HL with no background CLL. The second case occurred in a 78-year-old woman with a 4-year history of CLL as an inguinal mass with a composite histologic appearance comprising areas of CLL, areas of CLL with Hodgkin Reed-Sternberg cells, and areas of HL. Both patients had received fludarabine therapy. The HRS cells were CD20-/CD30+/CD15-/J-chain- in case no. 1 and CD20+/-/CD30+/CD15-/J-chain- in case no. 2. In both cases, the Hodgkin's Reed-Sternberg cells (HRS) were positive for type A EBV, and a 30-bp deletion of the LMP-1 gene was detected in case no. 2. Using microdissection and polymerase chain reaction amplification of the immunoglobulin heavy chain gene (IgH) complementarity determining region III of each cell type, we demonstrated a distinct clonal origin for the CLL cells and the HRS in both cases. These cases bring support to the hypothesis that EBV+ HL in CLL patients occurs as unrelated secondary neoplasms most likely as the result of the immune depression associated with CLL and also raise the question of a possible causal role of fludarabine.
We report the case of a 73-year-old man who presented with a 2- to 3-month history of epigastric discomfort and guaiac-positive stool. An upper gastrointestinal endoscopy revealed a diffuse erythematous nodular mucosa and submucosal thickening in the stomach. Diffuse mucosal nodularity was also found in the second portion of the duodenum. A complete workup with histologic, immunohistochemical, and molecular studies revealed 2 distinct, apparently unrelated lymphomas, namely, a gastric marginal zone B-cell lymphoma (mucosa-associated lymphoid tissue type) in a background of Helicobacter pylori gastritis and a grade 1/3 duodenal follicular lymphoma. The patient was then treated with an H pylori eradication regimen. No therapy was given for his duodenal follicular lymphoma because his symptoms were thought to be due to the gastric disease and because the duodenal lesion was small. A 6-month follow-up with upper gastrointestinal endoscopy revealed only focal biopsy scarring in the stomach and an apparently normal duodenum. The follow-up biopsies revealed significant regression of his mucosa-associated lymphoid tissue lymphoma, but persistence of his duodenal follicular lymphoma. The combination of these 2 lymphomas in the same patient and the different clinical responses to antibiotic treatment make this case unique.
BACKGROUND AND OBJECTIVES: Familial aggregation has been recognized in patients with several lymphoid neoplasms, but the genetic basis for this familial clustering is not known. Germ-line mutations in the ataxia-telangiectasia mutated (ATM) and CHK2 genes have been detected in patients with mantle cell lymphoma (MCL), suggesting a potential role of these genes in genetic predisposition to these tumors. However, no familial association has been previously recognized in MCL. DESIGN AND METHODS: To determine the possible existence of familial lymphoid neoplasms in MCL, we searched clinical records of MCL patients and identified three families in which a MCL, an acute B-cell lymphoblastic leukemia, and a lymphoplasmacytic lymphoma occurred in a first-degree relative of a MCL patient. RESULTS: The neoplasms in two daughters appeared at an earlier age and were more aggressive than that in the respective parent, suggesting that the phenomenon of anticipation may characterize familial lymphomas associated with MCL. No mutations were detected in the ATM, CHK2, CHK1, and p53 genes. INTERPRETATION AND CONCLUSIONS: Our findings suggest that inactivation of the investigated DNA damage response genes do not account for familial disease aggregation in MCL patients, although such aggregation may occur and seems to be associated with the phenomenon of anticipation.