Primary cutaneous large B-cell lymphoma, leg type, successfully treated with rituximab plus chemotherapy

ARTICLE

Auteur(s) : Celia Posada García¹, Ángeles Florez¹, Raquel Pardavila¹, Arancha Garcia-Cruz¹, Lourders Amador², Mónica Álvarez³, Laura María Alberte³, Manuel José Cruces¹

¹Servicio de Dermatología, Hospital Provincial de Pontevedra. CHOP, C/ Loureiro Crespo 2, Pontevedra, E-36001, Spain
²Dept of Hematology, Complexo Hospitalario de Pontevedra. Pontevedra, Spain
³Dept of Pathology, Complexo Hospitalario de Pontevedra. Pontevedra, Spain

Primary cutaneous large B-cell lymphoma, leg type (PCLBCL LT), has a poor prognosis, anthracycline-containing chemotherapy being its first line treatment [1]. During recent years rituximab therapy has also been reported, with variable but promising results [2].

We report two cases of PCLBCL LT presenting with different clinical pictures and successfully treated with rituximab plus chemotherapy.

Patient 1: an 81-year-old man with a one-month history of rapidly growing and painful necrotic ulcers on his left leg (figure 1A). A biopsy revealed a diffuse dermal and subcutaneous infiltrate of large monomorphous atypical lymphoid cells. Immunochemistry results were: CD20+, bcl 2+, CD30+, CD3- and bcl-6-. Complementary tests disclosed visceral involvement. Rituximab 375 mg/m² plus cyclophosphamide-mitoxantrone-vincristine-prednisone (CNOP) was administered every 3 weeks. Ulcers healed after 5 cycles of therapy (figure 1B). Resolution was confirmed by biopsy. Following the last cycle the patient suffered from a candidemia, which was successfully resolved with antifungal therapy.

Patient 2: a 76-year-old woman with a 2-year history of growing erythematosus tumors on her right leg (figure 1C). A biopsy showed a dense dermal infiltrate composed of median and large cells with irregular nuclei and discrete nucleoli. Immunohistochemistry lymphoid cells were CD20+, bcl-2+, bcl-6+, CD10+; and CD3-. Screening tests did not show systemic involvement. Rituximab 375 mg/m² combined with cyclophosphamide-doxorubicin-vincristine-prednisone (CHOP) was initiated every 2 weeks. Following the 5^th and 6^th cycles the patient suffered from an enterococcus cloacae bacteraemia, two pseudomembranous colitis and a respiratory tract infection. After 6 cycles, the skin lesions resolved (figure 1D). Resolution was confirmed by biopsy.

PCLBCL LT usually presents in elderly patients as erythematosus or violaceous tumors on one or both legs [1-3]. Clinically atypical variants such as chronic venous ulcer-like (patient 1) have been reported [4]. This emphasizes the importance of differential diagnosis in long-standing leg ulcers which do not heal, or those ulcers which exhibit unusual clinical features. In these cases biopsies should be performed to exclude malignancy.

The 5-year estimated survival rate of PCLBCL LT differs, depending on series, from 41% to 73% [1, 3, 5]. Location on the leg and multiple skin lesions are the strongest prognostic factors associated with a poorer prognosis [1]. Other features associated with a poor outcome are old age at onset, ulceration and positive stains for bcl-2, MUM-1 and OCT-2 [5]. Our patients were elderly and presented with multiple ulcerated skin lesions on their legs; biopsies were bcl-2 positive. The short follow-up does not allow us to confirm their theoretical poor prognosis.

Rituximab, a chimeric anti-CD20 monoclonal antibody, is currently approved in USA and Europe to treat relapsed or refractory indolent CD20+ B-cell non-Hodgkin’s lymphoma (NHL) and aggressive NHL, when combined with chemotherapy [2]. The role of rituximab in cutaneous B-cell lymphomas is still unclear. Since 2000, case reports and small series have described its use with variable responses. Some publications recommend the use of rituximab in cases of elderly patients, leg-type lymphoma, multiple skin lesions, relapsed cases and cases with no other therapies possible [6]. Combination of rituximab plus chemotherapy is not well-defined. Different studies have reported better outcomes than rituximab in monotherapy [1]. Our patients achieved excellent responses with combined therapy.

Rituximab is generally well tolerated, infusion-related events being the most frequent ones. Combination with chemotherapy is not associated with more toxicity [2]. Our patients suffered from systemic infections which were well controlled with standard treatment. These undesirable effects may be more related to chemotherapy than to rituximab.

In conclusion, rituximab represents an efficacious and well tolerated option for the treatment of PCLBCL LT. Due to the more agressive behaviour of this tumor, the association of chemotherapy with rituximab seems a better option when the patient’s general condition allows it. This combination may become a first-line treatment in the near future.

Acknowledgements

References

2 Scheinfeld N. A review of rituximab in cutaneous medicine. Dermatol Online J 2006; 27; 12: 3. Avalable from: http://www.ncbi.nlm.nih.gov/pubmed/16638371?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

3 Grange F, Beylot-Barry M, Courville P, Maubec E, Bagot M, Vergier B, et al. Primary cutaneous diffuse large B-cell lymphoma, leg type: clinicopathologic features and prognostic analysis in 60 cases. Arch Dermatol 2007; 143: 1144-50.

4 González-Vela MC, González-López MA, Val-Bernal JF, Mayorga M, Armesto S, Fernández-Llaca H. Cutaneous diffuse large B-cell lymphoma of the leg mimicking a chronic venous ulcer. Eur J Dermatol 2007; 17: 92-3.

5 Hallermann C, Niermann C, Fischer RJ, Schulze HJ. New prognostic relevant factors in primary cutaneous diffuse large B-cell lymphomas. J Am Acad Dermatol 2007; 56: 588-97.

6 Kerl K, Prins C, Saurat JH, French LE. Intralesional and intravenous treatment of cutaneous B-cell lymphomas with the monoclonal anti-CD20 antibody rituximab: report and follow-up of eight cases. Br J Dermatol 2006; 155: 1197-200.