Key Words

Chronic lymphocytic leukemia; Hodgkin’s disease; Richter syndrome transformation

Introduction

Chronic lymphocytic leukemia (CLL) is a chronic lymphoid hemopathy defined by accumulation of monoclonal B-cell lymphocytosis in the blood, bone marrow and secondary lymphoid organs. In the most cases, it has a chronic course. In 3 to 10% of cases, there is a transformation into Richter syndrome, which most often corresponds to a transformation into diffuse large B-cell lymphoma.The transformation into Hodgkin’s disease is observed In in 0.5 to 2.3% of cases [1].

The authors report a particular case of CLL transformed into Hodgkin’s disease Variant of Richter’s Syndrome with review of the literature.

Case Report

This is a 76-year-old male patient, followed for CLL Binet stage B, in symptomatic patients, the illness begins with the onset of hepatomegaly and fatigue. He was initially treat with RFC (Rituximab, Cyclophosphamide, Fludarabine) poorly tolerated and then Rituximab / Chloraminophene. One year later, clinical examination revealed splenomegaly with cervical and axillary adenopathies and he received combination chemotherapy. In April 2016, the patient was hospitalized for alteration general condition. The hemogram showed bicytopenia with leukoneutropenia (WBC 3.5 G / L, PNN 900G / L) and normocytic normochromic anemias : (Hb 9g/dl, 82fl VGM, 28 pg TCMH, 32 G / dl, reticulocytes scount at 50,000 / mm³). The bone marrow aspirate smear showed invasion of marrow by 60% of polymorphous cell population made up of large cells with double and multiple nuclei and fine chromatin with mirror-like aspects and agranular basophilic cytoplasm with vacuoles (Fig. 1).

This invasion necessitated an osteomedullary biopsy(BOM), which showed tumor proliferation whose morphological appearance and immunohistochemical profile was in favor of Diffuse Large B-Cell Lymphoma (CD20-, CD79a +, CD30+, Tdt -) (Figure 3) with the presence of binucleated cells reminiscent of Hodgkin cells or Reed-Sternberg cells (Figure 2). The BOM concluded that it was a Hodgkin’s type of Richter’s syndrome. The evolution was marked by the death of the patient in clinical picture of infectious complications with aggravation of the tumor syndrome.

Discussion

Approximately 2-8% of LLC transform into lymphoma high grade called Richter’s syndrome [1].The most frequent histological type is diffuse large cell lymphoma, which has the same clonal origin as LLC in 50% of the cases [2]. It corresponds to a diffuse proliferation of neoplastic large B lymphoid cells (CD20 +, CD79a +).Other histological types have also been described: lymphoblastic lymphoma [3], hairy cell leukemia [6] and T-cell lymphoma [4, 5, 7].

The transformation of CLL into Hodgkin’s disease is very rare. Opinions on the reality of this transformation are still controversial. Indeed, according to the literature, only 88 cases were recorded over a period of 28 years [3, 4]. The study of the clonal relationship between CLL and Hodgkin’s disease would rather have a prognostic value.

The Richter Syndrome is clinically characterized by the rapid aggravation of the tumor syndrome, the appearance of pain, the alteration of the general state and the symptoms of brain compression [11].

Two different types of prognosis are described in Hodgkin’s type of Richter’s syndrome [8,9, 10]:

Type 1: corresponds to the transformation of CLL into the Hodgkin disease, with a prognosis identical to the Richter syndrome. Histologically, there is an association of LLC (CD20 +, CD79a +, CD5 + and CD23 + cells) with Reed-Sternberg cells expressing CD30, CD15 and the LMP latency protein of EBV (Epstein-Barr virus) are dispersed. This type 1 corresponds to our case. This type 1 corresponds to our case.

Type 2: better prognosis; It corresponds to the co-existence of LLC and typical Hodgkin’s disease or the onset of a classical Hodgkin’s disease as a second cancer (de novo) in a patient bearing a known CLL.

Several studies have investigated the clonal relationship between CLL and Hodgkin’s disease. In the Hodgkinian Richter syndrome, the studies performed on Reed-Sternberg cells revealed a clonal immunoglobulin heavy chain gene rearrangements variable regions which would confirm the clonal relationship with the cells of the LLC. This criterion would be poor prognosis. [5,11, 12 ].

In Hodgkin’s Disease Variant of Richter’s Syndrome, and in the absence of this clonality, the EBV serology is more frequently found positive than in classic Hodgkin’s disease. In this case the prognosis is better [1,15 ].

These data show the important pathogenic role of EBV infection in this entity. The immunosuppression related in particular to fludarabine used in the treatment of CLL would be at the cause of this infection and would increase the risk of transformation of the Richter syndrome into Hodgkin’s disease [12, 13, 14]. This would imply the use of specific antiviral treatments in the therapeutic arsenal [9, 10].

Hodgkin and Reed-Sternberg cells scattered in a background of otherwise typical (×400)

Fig. 1: Hodgkin and Reed-Sternberg cells scattered in a background of otherwise typical (×400)

Infiltrate made of Reed-Sternberg cells. (x400)

Fig. 2: Infiltrate made of Reed-Sternberg cells. (x400)

Hodgkin and Reed-Sternberg cells immunophenotype: anti-CD79a antibody (×400)

Fig. 3: Hodgkin and Reed-Sternberg cells immunophenotype: anti-CD79a antibody (×400)

Conclusion

Hodgkin’s disease Variant of Richter’s Syndrome is a rare entity that corresponds to the transformation of CLL into Hodgkin’s disease. The study of the clonal relationship between these two pathologies has a particularly prognostic value: the transformation of the CLL into Hodgkin’s disease of poor prognosis and the co-existence of CLL and Hodgkin’s disease with a better prognosis and often associated with the Epstein-Barr virus.