Progressive transformation of the germinal center of extranodal organs: a clinicopathological, immunohistochemical, and genotypic study of 14 cases.

Progressive transformation of germinal center (PTGC) usually affects the peripheral lymph nodes. Little is known about the extranodal PTGC. To clarify the clinicopathological and molecular findings of extranodal PTGC, we studied 14 such cases. Using formalin-fixed, paraffin-embedded sections, we carried out histological and immunohistochemical examinations, as well as in situ hybridization (ISH) and polymerase chain reaction (PCR). Eleven patients were female, and three were male. They were between 44 and 77 years old, with a mean age of 62 years. The large intestine (n=7) was the most frequently involved tissue, followed by skin (n=2) and subcutaneous soft tissue (n=2). Oral cavity, Waldeyer ring, and orbit were affected in one case each. Histologically, 13 cases contained both early stage PTGC and late stage PTGC. The remaining 14th case contained only late stage PTGC. Expansion of the marginal zone was identified in three cases. Immunohistochemical study demonstrated the reactive nature of the B-cells in all 14 lesions. However, PCR study revealed immunoglobulin heavy chain (IgH) gene rearrangement in one of our 14 cases. There was no development of B-cell lymphoma in one lesion with IgH rearrangement. ISH study demonstrated Epstein-Barr virus-encoded small RNA+ cells in three lesions. Compared with PTGC of the peripheral lymph node, PTGC of extranodal sites was characterized by a female predominance, an older age group, and the presence of numerous PTGC at the affected sites. However, the histological findings of extranodal PTG were similar to those of lymph node PTGC. The clinicopathological findings of the extranodal PTGCs appeared to be different from those of lymph node PTGC.

Histological variety of localized lymphoid hyperplasia of the large intestine: histopathological, immunohistochemical and genotypic findings of 16 cases.

Previous reports emphasized that localized lymphoid hyperplasia (LLH) of the large intestine is usually histologically characterized by large lymphoid follicles with striking enlarged germinal centers, and a narrow surrounding mantle zone and marginal zone (MZ). To clarify the histological varieties of LLH of the large intestine, 16 such cases have been studied. The present study demonstrated histological diversity of the LLH of the large intestine including (i) reactive follicular hyperplasia (RFH) (n=8), (ii) RFH with progressive transformation of the germinal center (PTGC) (n=3), (iii) RFH with MZ hyperplasia (n=3) and (iv) RFH with PTGC and MZ hyperplasia (n=2). Overall histomorphological findings of the present series appear quite different from previous descriptions of LLH of the large intestine. The present study showed histological variety of the LLH of the large intestine. Moreover, LLH of the large intestine should be differentiated from extranodal marginal zone B-cell lymphoma and nodular lymphocyte predominant Hodgkin lymphoma as well as follicular lymphoma. Immunohistological studies demonstrated the reactive nature of all 16 lesions. However, three cases showing RFH demonstrated immunoglobulin heavy chain gene rearrangement by polymerase chain reaction study in 12 cases examined. It remains unclear whether these three cases showing RFH could be a sign of the prelymphomatous stage (incipient follicular lymphoma) or representing merely an exaggeration of normal B-cell clonal response in the germinal centers.