Clinical Analysis of 10 AIDS Patients with Malignant Lymphoma

Introduction

Acquired Immunodeficiency Syndrome (AIDS) patients often develop opportunistic infections and malignant tumors because of their low immune function. Studies found that 3.3% of newly diagnosed AIDS patients had non-Hodgkin’s lymphoma (NHL) ^[1]. Most of these patients were in the middle or late stages of the disease when they saw a doctor. Thus, monotherapy is often ineffective ^[2]. The most effective method is combined treatment. This study summarizes and analyzes the clinical data and treatment of 10 AIDS patients with malignant lymphoma.

Patients and Methods

Results

Pathology results and clinical stage

Please see Table 2 and Figure 1.

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Table 2.

Patients’ pathology results and clinical stage.

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Figure 1.

A: Case 10 (narrow intestinal lumen 35-40 cm from the anus). Four miliary colonic tissue samples were collected, one of which showed active chronic inflammation. A heterocyst can be seen in the other three pieces. B: Case 7 (punctate smear of cervical lymph nodes). A large quantity of dysplastic lymphoblasts indicated diffuse large B cell lymphoma. Immunohistochemistry: CD20(+), CD3(-), CD10(-), MUM-1(-), Bcl-6(- ), Ki-67(-), Lambda(±), Kappa(±). C: Case 6 (punctate smear of lymph nodes). Cellular degeneration was obvious. Small quantities of dyskaryotic cells, and sometimes nuclear division figures were observed. D: Case 5 (galactophore puncture cell mass). Burkitt’s lymphoma. Immunohistochemistry: CD56(-),CK AE1/3(-), LCA(CD45)(+), CD3(-), CD20(+), CD10(+), Mum-1(-), Bcl-6(-), ki-67 (diffuse+). E: Case 2 (lower part of stomach), two miliary fundus glands from gastric mucosal tissues. Large quantities of atypical lymphocytes infiltrated into the mucosa, indicating non-Hodgkin’s diffuse large B cell lymphoma. Immunohistochemistry: tumor cell Bcl-6(+), CD10(+), CD20(+), CD3(-), CK AE1/3(-), Ki-67(+), Mum-1(+). F: Case 1 (left axillary lymph node). Needle aspiration cell mass: most active hyperplastic lymphocytes were active mother cells. Combined with immunohistochemistry, the lesion was diagnosed as Burkitt’s lymphoma. Immunohistochemistry: Bcl-6(+), CD10(+), CD20(+), CD3(-), Ki-67(+), Mum-1(-). G: Case 4. Fine-needle aspiration cytology: a single allotype macrolymphocyte indicated lymphoma. Combined with the immunohistochemistry result, the lesion was diagnosed as diffuse large B cell lymphoma. Immunohistochemistry: CK AE1/3(-), CD20(+++).

Discussion

AIDS-related lymphomas (ARLs) occur mainly among more advanced AIDS patients. The CD4⁺ cell count in the peripheral blood is often lower than 100/μL. Therefore, the occurrence of lymphoma is related mainly to the degree and duration of the defect in the immune function of patients^[3]. Studies have shown that ARLs occur within 4 months to 27 months for AIDS patients ^[4]. In this study, the CD4⁺ cell count in 8 patients was less than 200/μL. Further examination proved this finding.

Studies show that 95% of ARLs are from B cells ^[5], which are mostly highly malignant lymphomas, such as Burkitt’s lymphoma (BL), which accounts for 60%. The others are moderately malignant lymphomas, which mainly include diffuse large B cell lymphomas (DLBCLs) ^[6]. Low-grade malignant lymphomas are rare. In the current study, 7 patients had DLBCL and 3 had BL. The data seems inconsistent because of the limited research data. Nevertheless, our results show that NHL develops from B cells.

ARL has several clinical manifestations. At the onset, B cell symptoms are common. At least 80% of patients are already in the stage IV at the onset of ARL, which is different from those among patients with the same type of lymphoma but without HIV infection. The latter is characterized mainly by painless enlargement of superficial lymph nodes. Only a small number of patients have B symptoms at onset during early clinical stages ^{[7, 8]}. Seven patients had fever. Lymph nodes involvement occurred in 5 patients and extranodal involvement occurred in 5 patients, all of whom were in stage II E to stage IV. Lesions in the gastrointestinal tract, liver, and lung are the most common extranodal lesions of ARL. On the other hand, lesions rarely occur in the adrenal glands, breast, and the brain. In this report, invasion was observed in the gastrointestinal tract, the liver, the lungs, pancreas, the adrenal glands, breast, and the brain, which indicated that the patients were already in the middle or late stage of lymphoma.

The results of the EBV antibody examination were negative in 7 cases. Considering patients’ poor immune status, no further EBV-DNA examination was performed. For EBV-related lymphadenitis, whether the lymphoma was related to EBV infection could not be determined based on one case of lymph node pathology. The study showed that many ARLs were related to EBV infection and that the relationship between them was related to the type of lymphoma ^{[9, 10]}. Data also showed that 79% of immunoblast or large cell lymphoma cases are positive for EBV and only 40% of Burkitt’s lymphomas are positive for EBV. In this study, 70% of the patients had DLBCL and only 30% were Burkitt’s lymphomas.

Before highly active antiretroviral treatment (HAART) was applied in clinical practice, chemotherapy in small dosages was always used for the treatment of ARL to avoid the toxicity of chemotherapeutic drugs. The 2-year survival rate was about 10% ^{[9, 11]}. After HAART was applied widely in 1996, the immune function of patients could be restored, thus, ARL patients could endure chemotherapy at standard dosages without the amplification of untoward effects ^{[12, 13]}. However, whether HAART should be used in chemotherapy synchronously is still under debate. Many scholars believe that the application of HAART in the process of chemotherapy is safe and effective ^{[14, 15]}. In this study, 6 patients chose chemotherapy. Three cases underwent chemotherapy after HAART was applied, 1 underwent HAART and chemotherapy at the same time, and 2 underwent chemotherapy 1 or 2 times without HAART. Four patients did not undergo chemotherapy whereas 2 of them chose to be treated with HAART. Two of the 3 patients treated with HAART and subsequent chemotherapy are now in remission, whereas 1 died of a recrudescent tumor. The patient treated with HAART and chemotherapy at the same time left hospital without follow-up. One of the 2 patients who chose to be treated with HAART alone left the hospital without follow-up whereas the other patient died. The 2 patients who underwent chemotherapy only 1 to 2 times also died. The 2 patients who did not undergo any treatment died. These results indicate that although ARL patients have bad prognosis with a high death rate, HAART in combination with chemotherapy at the standard dosage produces better prognosis than simple chemotherapy. The studies about this aspect have more data to be accumulated for further deep investigation.

The complications which developed among patients during chemotherapy included bacterial and mycotic infections at different locations, tuberculosis, and bone marrow depression, hemorrhage of the digestive tract, and renal dysfunction. These complications indicate that chemotherapeutic drugs cause further injury to the immune function of AIDS patients, resulting in the occurrence of various opportunistic infections. The bone marrow depression caused by chemotherapeutic drugs is another reason for the multi-site infections. In addition, the toxicities of chemotherapeutic drugs to the liver and kidney injure important visceral organs and affect the prognosis of patients. Timely anti-infective and symptomatic treatments are the key factors for chemotherapy. However, the overall prognosis of patients is not very optimistic. In this report, 3 patients died of chemotherapeutic complications, whereas 3 died of lymphoma.

In summary, AIDS related lymphoma, a common malignant tumor, always occurs among advanced AIDS patients. The most dominant type of lymphoma is NHL from B cells. Although AIDS related lymphoma presents various types of clinical manifestations, it is often indicated by invasion of visceral organs. Patients are always in the middle and late stages of lymphoma when they consult a doctor, making effective treatment difficult. Hence, the overall prognosis of patients remains bad even when HAART treatment is used. We emphasize awareness of related diseases, as well as early detection and treatment to improve the patient prognosis.