Follicular lymphoid hyperplasia of the oral cavity representing progressive transformation of germinal center

Follicular lymphoid hyperplasia (FLH) of the oral cavity is a rare and poorly understood lymphoproliferative disorder. We present a case of FLH of the oral cavity presenting with progressive transformation of germinal center (PTGC). The patient was a 49-year-old Japanese woman presenting with a hard mass in the right cheek. The resected specimen contained numerous lymphoid follicles with active germinal centers and a portion of the lymphoid follicles exhibited PTGC. The PTGCs contained a few large lymphoid cells resembling lymphocytic and histiocytic Reed-Sternberg cells of nodular lymphocyte-predominant Hodgkin lymphoma. The PTGC was surrounded by groups of epithelioid cells. In situ hybridization studies demonstrated strong expression of Epstein-Barr virus (EBV)-encoded small RNA in scattered large lymphoid cells in the PTGC. Although the etiology of FLH of the oral cavity remains unclear, the present case suggests that a subset of FLH of the oral cavity appears to be an EBV-associated lymphoproliferative disorder.     

Follicular hyperplasia, follicular lysis, and progressive transformation of germinal centers. A sequential spectrum of morphologic evolution in lymphoid hyperplasia

We studied mantle B-cell and T-cell ingression in hyperplastic follicles (HFs), follicular lysis (FL), and progressive transformation of germinal centers (PTGC) in 19 paraffin-embedded, H&E-, bcl-2-, CD20-, and CD3-stained lymph nodes. We enumerated the T cells (CD3+) and mantle B cells (bcl-2+/CD3-) per 100 cells in 5 high-power fields of each entity (mean +/- SD). Compared with HF, FL had increased numbers of T cells migrating into germinal centers (39.8 +/- 10.0 vs 25.8 +/- 7.8; P < .0001). and a mild increase of mantle B cells (12.3 +/- 11.4 vs 2.1 +/- 1.6; P < .001). PTGC showed an increase of T-cell ingression compared with HF (36.5 +/- 12.1 vs 25.8 +/- 7.8; P < .0001) and more migration of mantle B cells into the follicle than FL (41.0 +/- 22.5 vs 12.3 +/- 11.4; P < .0001). T cells and mantle B cells ingress in FL and PTGC, although the mantle B-cell component predominates in the latter, suggesting that follicular hyperplasia, FL, and PTGC constitute an evolutionary spectrum in resolution of lymphoid hyperplasia with sequential ingression of T cells followed by mantle B cells. The maintenance of bcl-2 expression in mantle B cells in PTGC may cause differential diagnostic pitfalls in florid PTGC vs follicular lymphoma, particularly the so-called floral variant.     

F18 fluorodeoxyglucose uptake in progressive transformation of germinal centres

FDG-PET/CT is a widely established imaging modality for staging, restaging and monitoring therapy response in lymphoma patients. Progressive transformation of germinal centres (PTGC) is a benign condition presenting characteristically as asymptomatic lymphadenopathy. This paper presents a case of a 53-year-old man with a history of Hodgkin's disease (HD) whose F(18) FDG-PET/CT scan showed high uptake in left axillary lymph nodes (SUV 3.8). A subsequent, left axillary lymph node biopsy revealed PTGC. PTGC can present as a false positive finding on FDG-PET/CT in lymphoma patients and biopsy should be done in HD patients in clinical remission but have a positive FDG-PET/CT scan.     

Follicular dendritic cell networks of primary follicles and germinal centers: phenotype and function

Follicular dendritic cells (FDCs) were identified decades ago by their ability to retain immune complexes and more recent findings indicate that they are a source of B cell attractants and trophic factors. New imaging studies have shown that B cells closely associate with their dendritic processes during migration. Here we will review the properties of these specialized follicular stromal cells and provide an update on the requirements for their maturation into phenotypically distinct cells within germinal center light and dark zones. We will then discuss current understanding of how they help support the B cell immune response.     

Follicular lymphoma mimicking marginal zone lymphoma in lymph node: a case report

Nodal follicular lymphoma (FL) is typically composed of follicular or nodular proliferation of small cleaved lymphoid cells, presumably derived from germinal center (GC) B cells. The hallmark of FL is t(14;18)(q32;q21) chromosomal translocation, which juxtaposes anti-apoptotic gene BCL2 to immunoglobulin heavy chain (IGH) promoter. Reflecting this background, FL cells are immunohistochemically positive for BCL2 as well as GC B cell markers CD10 and BCL6. It is known that low grade B-cell lymphomas, including FL, chronic lymphocytic leukemia/small lymphocytic lymphoma, and marginal zone lymphoma, are sometimes associated with marginal zone differentiation or plasmacytic differentiation. The marginal zone differentiation obscures the morphological differences among these, providing diagnostic challenges for histopathologists. In this paper, we present a case of FL, originally mimicking marginal zone lymphoma in the axillary lymph node. Subsequent bone marrow biopsy showed paratrabecular infiltration of small to medium-sized lymphoid cells. Immunohistochemical analysis of the bone marrow biopsy together with histopathology and flow cytometry of the axillary lymph node led to a final diagnosis of FL with marginal zone differentiation in the axillary lymph node and its bone marrow infiltration. Our case illustrates and reconfirms the importance of clinicopathological correlation which leads to a correct diagnosis.     

Progressive transformation of germinal centers with and without association to Hodgkin's disease

Progressively transformed germinal centers occurred in about 3.5% of cases of chronic nonspecific lymphadenitis. They are larger than germinal centers and are composed of follicular mantle lymphocytes, small clusters of proliferating mainly medium-sized B- and T-cells, as well as an extensive network of follicular dendritic cells. Sixty-six patients with lymph node enlargement containing progressively transformed germinal centers and staging and sequential biopsies of 213 patients with Hodgkin's disease (mixed and nodular sclerosis type) were investigated with special reference to the relationship of this lesion to Hodgkin's disease. In most cases, progressively transformed germinal centers developed without any obvious signs of illness and seemed to have no association with Hodgkin's disease. The patients could be differentiated into two groups. The larger group, Group 1 (n = 55 of 66) consisted of patients showing progressively transformed germinal centers without association to Hodgkin's disease. The smaller group, Group 2 (n = 11 of 66) showed progressively transformed germinal centers obviously with association to nodular paragranuloma (Hodgkin's disease lymphocytic predominance type). Progressively transformed germinal centers preceding (n = 3), simultaneously (n = 4), and after development of nodular paragranuloma (n = 4) were found. With regard to subtypes of Hodgkin's disease other than paragranuloma, progressively transformed germinal centers also could be found in sequential biopsies of Hodgkin's disease of mixed and nodular sclerosis type. In one case, progressively transformed germinal centers preceded, in another case they occurred simultaneously in mixed type of Hodgkin's disease, and in two cases of nodular sclerosis type progressively transformed germinal centers developed after the onset of Hodgkin's disease. These findings suggest that progressively transformed germinal centers may be a result of different processes that may be occasionally related not only to nodular paragranuloma, but also in rare cases to nodular sclerosis and mixed type of Hodgkin's disease.     

A B-cell lymphoma-associated chromosomal translocation in a progressive transformation of germinal center

Progressive transformation of germinal center (PTGC) is a pattern of lymph node reactive hyperplasia. It can also be the predominant pattern in a hyperplastic lymph node known as florid PTGC. It is characterized histologically by the expansion of the mantle zone lymphocytes into both the adjacent sinusoids and germinal centers. The lymphocytes destroying the germinal centers are predominantly B cells, with a minor population of T cells. Morphologically, it can be confused with nodular lymphocyte-predominant Hodgkin disease (NLPHD) because of its nodular pattern and because of the presence of large cells that can be incorrectly identified as lymphocytic and histiocytic cells. A relationship between PTGC and NLPHD remains unclear, and many authors have suggested that PTGC can represent a precursor lesion of NLPHD. Here we report the first karyotype obtained in PTGC, in a 12-year-old boy. It shows a t(3;22)(q27;q11) translocation, probably involving the BCL6 gene. This translocation has previously been described in diffuse large B-cell lymphomas and in NLPHD with BCL6 rearrangement. This finding offers an insight into a possible tumorigenic pathway from PTGC to NLPHD. Further studies will be required to confirm this hypothesis.     

Non-endemic Burkitts's lymphoma. A B-cell tumor related to germinal centers.

To investigate the nature of non-endemic Burkitt's lymphoma, we examined neoplastic cells from eight American patients for receptors for sheep erythrocytes (E), complement (EAC), and Fc fragment of lgG (igGEA), and for surface immunoglobulins (Slg) and hydrolytic enzymes. In addition, we reviewed 47 biopsies and 17 autopsies from American patients to ascertain patterns of involvement by tumor in lymph nodes, spleens and Peyer's patches. Neoplastic cells in all cases studies bore monoclonal surface immunoglobulins of the igM class. Receptors for EAC and igGEA were identified on a minority of the cells. Little or no hydrolytic enzyme activity was demonstrable. These results indicate that, like Burkitt's lymphoma in Africans, this histologically identical tumor in American patients consists of B lymphocytes. In 10 biopsies and two autopsies, germinal centers were selectively involved by tumor, suggesting that these neoplastic cells may be related to some B lymphocytes of normal germinal centers.     

Progressive transformation of germinal centers: a clinicopathological study of 42 Japanese patients

To clarify the clinicopathological features of progressive transformation of germinal center (PTGC) unrelated to nodular lymphocyte predominant Hodgkin's lymphoma in Japanese patients, we reviewed 42 cases and compared the results with those of the United States and Germany. Our results were similar to theirs, with male predominance (M/F ratio, 3:1) and the presentation of a solitary asymptomatic enlarged lymph node in the head and neck area as the common features. However, in Japan, PTGC occurs more frequently in elderly patients. In this study, 12 (29%) of the patients with PTGC were aged 60 years or more. Thirteen patients (31%) with lymphadenopathy in the neck and head area had developed localized chronic inflammation (chronic sialoadenitis=4, chronic tonsillitis=3, infectious epidermal cyst=2) or an autoimmune disorder (hyperthyroidism=2 and bronchial asthma=2). None of the patients developed a malignant lymphoma during the follow-up period of 5 to 238 months (median 27 months). Histologically, in a single longitudinal section of the lymph node, the PTGC occupied up to 5% of the total follicles in 22 patients, 5-10% in 10, 10-20% in 7, and more than 20% in 3. In 5 (12%) patients, an association with prominent marginal zone hyperplasia was also noted. This study also indicates that nodal involvement by various low-grade B-cell lymphomas exhibiting marginal zone distribution patterns should be considered as a differential diagnosis of PTGC. Moreover, in Japan, PTGC is thought to be involved in the etiology of florid reactive follicular hyperplasia in elderly patients.     

Follicular dendritic cells restrict interleukin-4 availability in germinal centers and foster memory B cell generation

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Classical Hodgkin lymphoma occurring in clusters of nodal marginal zone B-lymphocytes in association with progressive transformation of germinal center. A case report

We present a case of a classical Hodgkin lymphoma occurring in clusters of marginal zone B-lymphocytes (MZBLs). Most lymphoid follicles possessed hyperplastic germinal centers, while a portion of the follicles exhibited a progressive transformation of the germinal center (PTGC). Clusters of MZBLs showed a perifollicular distribution. The classic Reed-Sternberg cells were found in clusters of MZBLs. A portion of the Reed-Sternberg cells were CD15+, CD20+, CD30+, CD79a+, fascin+, vimentin+, EMA-, and bcl-2-. Some Reed-Sternberg cells were surrounded by CD3+ CD45RO+ CD57-rosettes. In situ hybridization studies demonstrated strong expression of EBER in classic Reed-Sternberg cells and their variants. The overall morphological, immunohistological, and EBV findings confirmed that the present case is a classical Hodgkin lymphoma. The MZBLs were CD20+, CD79a+, sIgM+/-, sIgD-, CD5-, CD21-, CD43-, CD45RO-, and Bcl-2-. Some MZBLs had polytypic intracytoplasmic immunoglobulin. Problems arising in the differential diagnosis between lymphocyte-predominant Hodgkin lymphoma and PTGC have been described. An occasional association between MZBLs clusters and PTGC has been reported previously. This case suggests that classical Hodgkin lymphoma should be added to the differential diagnosis of PTGC.     

In situ follicular lymphoma with progressive transformation of the germinal centers confirmed by laser capture microdissection, IGH gene rearrangement analysis, and fluorescence in situ hybridization for t(14;18)

The authors report an unusual case of in situ follicular lymphoma associated with progressive transformation of the germinal centers. The patient was a 74-year-old Chinese woman with sequential lymphadenopathy in the right and left cervical regions over a period of 2 months. The first biopsy revealed in situ follicular lymphoma with progressive transformation of germinal centers, and the biopsy of the second lymph node led to a diagnosis of in situ follicular lymphoma. The immunophenotype, polymerase chain reaction amplification of the immunoglobulin heavy chain gene, and fluorescence in situ hybridization for t(14;18) were analyzed in each biopsy specimen, which showed both specimens to have t(14;18)(q32;q21) and revealed progression from polyclonality to monoclonality. These findings suggest a case of multicentric in situ follicular lymphoma and provide new insights into the pathogenesis of this disease.     

Follicular variant of peripheral T-cell lymphoma mimicking follicular lymphoma: a case report with a review of the Literature

Peripheral T-cell lymphoma (PTCL) with a follicular growth pattern is very rare. Herein, a case of follicular variant of PTCL in a 50-year-old man who complained of tonsillar and generalized lymph node swelling is reported. The resected tonsil revealed a vague nodular growth pattern of atypical cells, medium to large in size, with abundant pale cytoplasm. The lymphoma cells were CD3(+) CD4(+) CD5(+) CD8(-) CD10(+) CD56(-) CD57(-) BCL6(+) PD-1(+) CXCL13(+) and were associated with a meshwork of CD21(+) follicular dendritic cells. Molecular studies revealed clonal rearrangement of the T-cell receptor gamma chain gene but not of the immunoglobulin gene. Cytogenetic analysis disclosed a complex abnormality in 18 of 20 cells with the exclusion of t(5; 9). These findings suggest that the present case is a follicular variant of PTCL derived from follicular T-helper cells.