Progressive transformation of germinal centers (PTGC) is a benign reaction pattern in lymph nodes. The lesion of PTGC is composed of large nodules in which one or more germinal centers is infiltrated, to varying degrees, by mantle zone B cells. Progressive transformation of germinal centers can be the predominant change that prompts lymph node biopsy, but usually is a focal change most often associated with reactive follicular hyperplasia (RFH). Progressive transformation of germinal centers also can be associated with lymphomas, most often nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL), but rarely other types of Hodgkin and non-Hodgkin lymphoma.

Progressively transformed germinal centers, progressively transformed follicular centers.

The true frequency of PTGC is difficult to determine because most studies rely on referral material. Data from the Kiel Lymph Node Registry identified PTGC in 30 of 820 (3.5%) cases of nonspecific lymphadenitis (1). In most patients, PTGC is not associated with lymphomas (1,2). It has been recognized, however, that PTGC can develop in a small subset of lymphoma patients, most commonly NLPHL. In a review of 50 patients with PTGC at M.D. Anderson Cancer Center, five patients (10%) had concurrent NLPHL, 15 patients (30%) had a history of Hodgkin lymphoma (of all types), and the remaining patients had no history or subsequent Hodgkin lymphoma (3). In NLPHL patients, PTGC can involve different lymph nodes [five of 206 (2%)] (4) or the same lymph node involved by NLPHL [31 of 171 (18%)] (5).

Although originally described by Muller-Hermelink and Lennert in 1975 (6), the etiology and pathogenesis of PTGC remain unknown. Mitoses are scarce in PTGC, suggesting that the increased small lymphocytes in the germinal centers of PTGC probably enter via migration rather than proliferation (4). Various hypotheses have been proposed to explain the origin of PTGC: a pre-neoplastic stage of NLPHL (4,7,8); one of the possible destinies of the follicular center (9); and premature arrest at an early transition stage between primary and secondary follicles because of incomplete blastic transformation of B cells (10).

Progressive transformation of germinal centers most often presents as localized lymphadenopathy but can also occur as a generalized process (11,12,13). In localized cases, PTGC is typically detected in a single, asymptomatic, enlarged lymph node. Cervical lymph nodes are most commonly affected, in approximately 50% of cases, followed by axillary or inguinal lymph nodes (12). PTGC more often affects males than females and in most studies from Western countries involves young men with a median age of 28 years in one review (12). However, in one study from Japan elderly (>60 years) patients were affected in approximately 30% of cases (14). Approximately 20% of cases of PTGC occur in children (2). Recurrent PTGC may involve the same or different lymph node groups (1,2,3). Recurrence is more common in children than adults, and multiple recurrences are also more common in children (2,12). Rarely, patients with PTGC present with generalized lymphadenopathy or with involvement of multiple lymph node groups. The histologic findings in these cases are florid (13). Progressive transformation of germinal centers is rarely found in lymph nodes from patients with human immunodeficiency virus infection, even in those cases with florid RFH (3).

In most patients, PTGC does not predict the development of Hodgkin lymphoma, nor does PTGC have any relationship to Hodgkin lymphoma (1,2,5). In some patients with PTGC, usually of localized type, PTGC may precede, arise with, or follow the diagnosis of Hodgkin lymphoma, mostly NLPHL, with rare cases of classical Hodgkin lymphoma (nodular sclerosis or mixed cellularity) or non-Hodgkin lymphoma (1,3). The interval between PTGC and Hodgkin lymphoma has been as long as 13 years in one patient who initially had PTGC and subsequently developed NLPHL (8).