Unusual sequence of lymphoid disorders: Follicular lymphoma subsequent to Hodgkin lymphoma and transformed into diffuse large B-cells non Hodgkin lymphoma

To the Editor

Although Hodgkin lymphoma (HL) can develop in patients with B-cell follicular lymphoma (FL) [1], [2], especially after treatment, and some cases of coexisting histological features of HL and FL (composite lymphoma) [3–5] has been described, the truly occurrence of a FL following a HD [6], as recently observed by us, has been very rarely reported so far. Indeed, we recently encountered an unusual sequence of lymphoid tumors in the same patient; indeed, after a long lasting recovery from a classical HL, he presented a FL subsequently evolved in a diffuse large B-cells lymphoma (DLBCL). A 67-year-old man kept under our attention with malaise and generalized superficial and deep lymphadenopathies. His past medical history was remarkable. Indeed, from 6 years before he had been affected by an Ann Arbor stage IIIA mixed cellularity classical HD. Therefore, the patient had been treated with six cycle of ABVD chemotherapy (doxorubicin, bleomycin, dacarbazine and vinblastine) achieving a complete remission (CR). Therefore, he was regularly followed-up, durably maintaining the CR until the admission. Moreover, in the meantime, he had suffered from a mellitus diabetes, hypertension and severe ischemic cardiomyopathy complicated by two acute myocardial infarctions, for which four coronary artery bypass grafting have been performed. Moreover, he had been affected by muscle-invasive cancer of the bladder that had been surgically removed. A comprehensive work up, including an excision superficial node biopsy, a whole TC scan, and a trephine bone marrow biopsy, demonstrated a stage IV B-cell non-Hodgkin lymphoma, showing combined follicular and diffuse growth pattern (FL, grade 3). Given the poor patient's general conditions and the severe cardiovascular comorbidities, he received rituximab as single agent, achieving a good partial remission. Ten months later, being the patient on maintenance rituximab, he presented with a massive right inguinal adenopathy that was surgically removed. A histological diagnosis of DLBCL was made. To date, the patient is receiving a non anthracycline-containing chemotherapy as salvage treatment. The present case illustrates an unusual sequential occurrence of Hodgkin's lymphoma, follicular lymphoma and diffuse large B-cell lymphoma in the same patient, arising as histopathologically independent tumors, as confirmed by a careful re-classification of the three distinct lymphoma entities performed by a certified and skilled haematopathologist. The development of a FL following recovery from HL, given their same origin by the germinal centre [7], may raise the debate as to whether it has been due to a clonal evolution or as the chance occurrence of a second and unrelated lymphoid malignancy which finally progressed into a DLBCL. Unfortunately, studies addressing clonal relationship between three lymphoma subtypes have not been performed, for which the questions about the tumor origin, and the mechanism of the neoplastic transformation remained unresolved. However, in the only one previously reported case of FL developed to HL 2 years apart, a common origin of the tumor cells of two neoplasias from a common precursor deriving from germinal center B cell has been demonstrated [6]. Therefore, in conclusion, the sequence of different lymphoid disorders observed by us may be related to a unique disease entity evolved by a progressive transformation until the final development of a more aggressive disorder.