Primary Gastric Non-Hodgkin Lymphoma as Second AIDS-Defining Malignancy in a Patient under HAART
- 1. Division of HIV/AIDS, Muñiz Hospital, Argentina
- 1. Department of Medicine, University of Buenos Aires, Argentina
- 2. Medical Director, Pavlosky Hematology Center, Argentina
- 3. National Academy of Medicine, Histopathology Laboratory, Argentina
Primary gastric non-Hodgkin lymphoma is a severe complication during the clinical course of human immunodeficiency virus infection. Clinical presentation includes symptoms associated with the upper digestive tract and “B” symptoms (fever, night sweats and weight loss). Endoscopic findings can reveal polypoid, ulcero-infiltrative or ulcer lesions. Multiple biopsy smears are necessary to determine histopathological subtypes. Diffuse large B cell lymphoma (DLBCL) is the most common histopathological subtype in HIV/AIDS patients followed by Burkitt’s lymphoma and plasmablastic lymphoma. Chemotherapy plus highly active antiretroviral therapy is the best treatment to achieve a complete remission with prolonged survival in this kind of patients.
Here we present an HIV seropositive patient who developed a primary gastric DLBCL as second AIDS-defining neoplasm during HAART therapy and after three years of successfully controlling HIV-viral load. Patient presented with a past history of anal squamous cell carcinoma several years before and gastro esophageal reflux disease treated for a long time with omeprazole. He presented with epigastric pain, nausea and dyspepsia. Upper gastrointestinal endoscopy showed erosive gastritis and a large gastric ulcer at the minor gastric curvature. Microscopy examination and immunohistochemistry of the biopsy smears of the large ulcer biopsy confirm the diagnosis of primary gastric DLBCL. He was treated with HAART plus chemotherapy with a complete remission for a time of three years.
Corti M, Pavlosky A, Narbaitz M (2020) Primary Gastric Non-Hodgkin Lymphoma as Second AIDS-Defining Malignancy in a Patient under HAART. Ann Clin Pathol 7(1): 1154.
• Primary gastric lymphoma; Diffuse large B cell
lymphoma; AIDS; HIV
Non-Hodgkin lymphoma (NHL) is a common complication of the disease caused by the human immunodeficiency virus (HIV). The involvement of the digestive tract, from the oral cavity to the anus region, is very frequent [1,2]. One of the most common characteristic of AIDS-associated NHL is the extranodal compromise at the time of diagnosis. Gastrointestinal tract (GIT) is the most commonly site of primary extranodal lymphomas, including 40% to 50% of all cases [3-6].
In the GIT, stomach is the most frequent site of involvement (50% to 88%) followed by the small intestine (14% to 38%) and the colon (10% to 20%) [4-7,8]. GIT involvement is also frequent in HIV-infected patient’s account 15% to 75% of all cases [9-11].
Here we present a patient infected with HIV who developed a primary gastric NHL during highly active antiretroviral therapy (HAART) with immune reconstitution and undetectable viral load. Patient was treated with the same scheme of HAART plus chemotherapy with a prolonged survival and a complete remission of the lymphoproliferative disorder.
A 64-year-old man with a large history of HIV infection and under HAART presented with unspecific abdominal symptoms of a month of evolution. The patient referred episodic epigastric pain, postprandial fullness, nausea, eructation and breathe odor. He denied history of fever and night sweats but the clinical manifestations were associated with a weight loss of 5 kg. The patient had history of a numerous episodes of H. pylori infection and erosive/ulcerative gastritis. He was treated in all episodes with different antimicrobial regimens. Six years before, on antiretroviral treatment, with undetectable viral load and immunological reconstitution, he was diagnosed with intra-anal squamous cell carcinoma associated with HPV-16. He was treated with HAART plus chemotherapy based on Nigro’s scheme plus tridimensional radiotherapy with a complete remission and without relapse during 10 years.
Her physical examination revealed no abdominal findings, no hepatomegaly, no splenomegaly and no lymphadenopathy. Laboratory tests were normal including LDH levels. The CD4- T-cell count was 173 cells/uL and the plasma viral load was undetectable. Upper gastrointestinal endoscopy was done and showed erosive/ulcerative gastritis at the gastric roof and body. Additionally, a large gastric ulcer at the minor gastric curvature was observed (Figure 1). Several biopsy smears were taken and revealed a chronic and active gastritis with H. pylori infection positive. Microscopy examination of the biopsy smears of the large ulcer biopsy showed a dense proliferation of atypical lymphoid cells, of median and large-sized, eosinophilic cytoplasm and one or various nucleoli infiltration of submucosa and muscularis propriety (Figures 2 and 3). Immunohistochemistry revealed that neoplastic cells were positive for CD20 (Figure 4), BcL2 (+) with negative CD3 (Figure 5) and a Ki67 proliferation index of 30% (Figure 6). Cytokeratin was also negative. Final histopathological diagnosis was primary gastric diffuse large B cell lymphoma (DLBCL). Thorax and abdominal tomography scan to determine clinical stage were normal. Bone marrow biopsy was done to stage the disease and was negative to atypical lymphoid infiltration. He was treated with the same scheme of HAART based on tenofovir plus emtricitabine, dolutegravir and darunavir boosted with ritonavir. Additionally, he received 6 cycles of chemotherapy based on CHOP plus rituximab. Also, he received trimethoprim-sulfamethoxazole as primary prophylaxis for Pneumocystis jiroveci; granulocyte colony stimulating factor, fluconazole and levofloxacin in each cycle.
After 3 years of complete remission the patient developed a new primary gastric DLBCL currently under chemotherapy and antiretroviral treatment.
Several recent studies have been reported an increased incidence of both Hodgkin lymphoma and NHL in AIDS patients. These patients, infected with HIV, are at high risk to develop NHL. The risk of NHL is 100 to 300-fold higher in HIV infected patients in comparison with the general population , being this the second most frequent malignancy following Kaposi´s sarcoma . Primary gastrointestinal NHL is a distinct clinic-pathological entity. Lymphomas represent only the 2% to 5% of all gastric malignant tumors. The increase in the incidence of primary gastric lymphoma (PGL) in the last decades is related with the increase in the number of immunodeficiency patients, especially those with HIV infection. Hernandez JA et al , detected 15 patients with PGL in a series of 76 patients with HIV-AIDS-related NHL. NHL of extranodal sites, as the digestive tract, is considered as primary when the extranodal compromise is equal or greater compared with the nodal involvement . More than 90% of PGNHL are of B-cell phenotype and generally is not associated with peripheral adenopathy . Clinical findings include abdominal pain, epigastric pain, early satiety, nausea, vomiting, gastrointestinal bleeding and B symptoms as fever, weight loss and night sweets. Generally, the endoscopic findings include thickening of gastric folds, tumor lesions, polypoid lesions, ulcerative lesions or the combination of these [2,16]. Fontes Rezende et al , in a series of 243 HIV-seropositive patients evaluated with upper digestive endocopic detected 6 patients (2,5%) with PGL. The endoscopic findings include the involvement of gastric body in all cases, with compromise of the fundus in 3 cases and also the gastric antrum in 2 others.
Histopathological biopsy smears must be classified according with the Real and WHO classification . Ann Arbor classification with Mussohoff modification is used to the staging of gastric lymphomas in I to IV stadiums. The IIA include gastric lymphomas with proximal lymphatic nodules involvement and IIB when the neoplasm also infiltration the distal nodal lymphatic .
Generally, AIDS-associated NHL are a high grade lymphomas including DLBCL, Burkitt´s lymphoma (BL) and plasmablastic lymphoma (PBL), as most frequent subtypes and which are considered as an AIDS-defining illnesses . These patients are associated with a rapid progression of neoplasm disease, frequent extranodal initial manifestations, poor prognosis and a short survival after diagnosis .
In the stomach, it is possible to show other type of lymphomas, named as mucosa-associated lymphoid tissue (MALT) lymphoma. MALT lymphoma is a low grade marginal zone B-cell lymphoma strongly associated with Helicobacter pylori infection in his pathogenesis. MALT lymphoma can occur at different extranodal sites as the GIT. Within de gastric NHL, MALT lymphoma include around 60% and most of them has a better prognosis and regressed after H. pylori eradication treatment alone. Localized gastric DLBCL do not regress with the H. pylori treatment and eradication and need 4 to 6 cycles of chemotherapy .
Actually, the best treatment of NHL in AIDS patients is based on the combination of highly active antiretroviral therapy (HAART) plus chemotherapy [22,23]. The survival of patients with AIDS-related NHL is significantly longer compared with the pre-HAART era, with high rates of complete remission and prolonged response to HAART, as we can see in our patient [14,15]. Prolonged survival is significantly associated with achievement of a complete remission and a good virological response to HAART . In comparison with a median survival of 7 months after NHL diagnosis in the pre-HAART era, the survival is prolonged in the post-HAART period [25,26]. HAART plus high intensity multi-agent chemotherapeutic regimens including the anti-CD20 monoclonal antibody rituximab is associated with a high remission rate in HIV associated-NHL . The role of surgery is limited to cases of obstruction or uncontrollable bleeding. The spontaneous remission of aggressive lymphomas as DLBCL is extremely rare. Gattiker et al , in a retrospectively review of 209 cases of aggressive lymphomas including 69 cases of DLBCL showed no case of spontaneous remission of DLBCL. Watari et al , reported 2 cases of remission of gastric DLBCL without any treatment. Finally, Sugiyama et al , published a case of gastric DLBCL with a large spontaneous remission for 10 years. Also, in the setting of HIV infection, it is possible to show a complete remission of NHL associated with HAART . In this stage, is possible that the immune reconstitution based on HAART can play a role in the tumor remission without chemotherapy.
In conclusion, HIV-positive patients have a high risk to develop lymphomas, especially NHL. Nevertheless, the risk has dropped gradually in the HAART era, especially in those with undetectable viral load and immune restoration.
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