Primary cutaneous B-cell lymphoma successfully treated with highly active antiretroviral therapy alone: a case report and review of the literature.

Cutaneous B-cell lymphoma (CBCL) is an unusual skin neoplasm with a great range of clinical presentations. Here, we report a case of CBCL in an AIDS patient presented as a single and nodular/ulcerative lesion in the perianal area. The patient was started on highly active antiretroviral therapy alone with a good clinical and oncological response. Two years later, the patient is asymptomatic with undetectable viral load and immune reconstitution.

Introduction

Patients with AIDS-related non-Hodgkin's lymphoma (NHL) present more frequent with extranodal involvement and high grade histopathology.[1] Also, they respond less to chemotherapy with shorter overall survival in comparison with NHL in the general population.[2] Since 1996, with the introduction and widespread use of highly active antiretroviral therapy (HAART), survival of patients with AIDS-related NHL has improved.[3]

We report the clinical characteristics and outcome of a patient with diagnosis of AIDS and primary NHL of the skin, successfully treated only with HAART.

Case Report

A 42-year-old homosexual man, seropositive for the human immunodeficiency virus (HIV), was referred to our Division of HIV/AIDS disease because he presented history of fever, weight loss and perianal pain since the last 2 months. He had no history of alcohol, illegal drugs use or tobacco consumption.

Relevant findings of physical examination included fever (38°C) and weight loss (3 kg in the last month); there were no other accompanying symptoms.

Skin examination of the perianal area showed a single, indurate and inflammatory mass of 4 × 3 cm in diameter [Figure 1]. Relevant laboratory findings were hemoglobin 12.3 g/dl, hematocrit 35.9%, leukocytes count 5 × 1000/mm3, platelets 325,000/mm3 and lactate dehydrogenase (LDH) 634 U/l. Liver function tests were normal, including alkaline phosphatase level. Serological status for hepatitis C virus was negative. Abdominal ultrasound was also normal. A sample for biopsy was taken. Histopathology examination showed the ulceration of the epidermis, and the dermis showed extended areas of ulceration and necrosis with a dense and diffuse infiltrate of lymphoid cells with large and multinucleated cells having central nuclei and various nucleoli near the basal membrane. Monoclonal antibodies demonstrated that the atypical cells showed reactivity for the antiCD20 (B-cell phenotype). The histopathology findings were consistent with the diagnosis of high-grade B-cell NHL. Computarized tomography scans of the brain, thorax, abdominal and pelvis were normal; bone marrow biopsy was negative to detect atypical cells. The CD4 T-cell count was less than 50 cell/μL and the plasma viral load was more than 500,000 copies/ml (log10 5.20).

Figure 1

A single, indurate nodular and inflammatory mass of 4 × 3 cm in diameter in perianal area

Due to the good clinical status and the localized and single skin lesion of lymphoma, we took the decision, with the oncologist, to begin treatment based only with antiretroviral drugs. The patient was treated with a regimen based on abacavir plus lamivudine plus saquinavir boosted with ritonavir. After 2 years of this treatment, the lymphoma regressed completely and the patient is in a good clinical condition and without evidence of relapse neoplasm disease. The perianal lesion was cicatrix [Figure 2]. His last CD4 T-cell count was 529 cell/μl (30%), and the plasma viral load was undetectable.

Figure 2

Remission and cicatrizing of the perianal lesion after 2 years of HAART alone

Discussion

AIDS associated B-cell lymphomas are commonly described to have atypical morphology, extranodal involvement as primary manifestation and an aggressive clinical course. The majority of HIV-related lymphomas are diffuse, large B-cell lymphomas (DLBCL). DLBCL are a heterogeneous group of NHL with distinct clinicopathological entities, including B-cell lymphomas with plasmablastic differentiation.[4] The differential diagnosis between these histopathological subtypes is made by the immunohistochemical examination with monoclonal antibodies directed against CD20, CD45, CD10, CD138, plasma cell clone, VS38c, BCL6, mib 1, kappa and lambda light chains and cyclin D1.[4]

Cutaneous involvement of NHL is uncommon in HIV-infected patients. However, cutaneous lymphoma is being encountered with more frequency in these patients. These neoplasms comprise T-cell lymphomas which include about 85% of all the cases and the remaining 15% cases are of B-cell origin.[5]

Approximately, 50–75% of AIDS-related NHL arises at extranodal sites.[6]

After the digestive tract, the skin is one of the most common sites for extranodal lymphomas in these patients. Primary cutaneous lymphomas represent 10% of extranodal NHL, and B-cell histological subtype, as in our patient, is less common than T-cell histological subtype.[7-9]

Cutaneous B-cell lymphomas (CBCL) are a specific group of NHL that have been considered as an advanced state of the neoplasm by both the European Organization for Research and Treatment of Cancer (EORTC) and the World Health Organization (WHO) classifications.[10-12]

Specific cutaneous lesions are more frequent in NHL in comparison with Hodgkin's disease. Patients with NHL showed cutaneous compromise in 15–20% of cases, and in 5% of these, skin lesions are the first manifestation of the neoplasm, as in our patient.

CBCL is uncommon and include a wide range of clinical manifestations, histopathology, immunophenotype and prognosis. Skin involvement includes single or multiple infiltrative macules, dermis papules, subcutaneous nodes, ulcerative lesions and infiltrative dermohypodermic plaques. The number of lesions, single versus multiple, is a prognostic factor in primary CBCL.[13]

Only a few cases of complete response of NHL to HAART alone have been reported. Regression of primary effusion lymphoma, plasmablastic lymphoma, primary central nervous system lymphoma and Burkitt's lymphoma has been reported after initiation of HAART.[14-18]

Sidhu et al., reported four cases of HIV-related lymphomas and reviewed eight other patients published in the medical literature, who responded rapidly and durably to HAART alone. Eight of these cases were B-cell lymphomas and only two were cutaneous lymphomas. In total, the authours reviewed 12 cases of HIV-infected patients with lymphomas, who responded to HAART, without chemotherapy.[19]

Combination chemotherapy with HAART is the gold standard to improve the prognosis and survival rates of this kind of patients.[2021] However, in patients with single skin lesions and without evidence of other localizations of the neoplasm, as in the case we reported, it is possible to achieve a good clinical, oncological and infectological response using HAART alone.

We report a patient with a complete remission of a CBCL associated only with HAART, probably related with the immune reconstitution. Our case reported here emphasizes the fact that unusual locations of NHL should be considered in AIDS patients, especially in those with severe immune suppression. Chemotherapy is certainly necessary to control the majority of HIV-related lymphomas. Further data are needed to define the attributes of lymphomas which may respond to HAART alone.[21]