Primary Gastric Non-Hodgkin Lymphoma as Second AIDS-Defining Malignancy in a Patient under - HAART
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Bringing Excellence in Open Access
Annals of Clinical Pathology
Case Report *Corresponding author
Marcelo Corti, Division of HIV/AIDS, Infectious Diseases
Primary Gastric Non-Hodgkin F. J. Muñiz Hospital, Puán 381, 2°floor, Buenos Aires,
Argentina, Email: marcelocorti@fibertel.com.ar
Lymphoma as Second AIDS-Defining
Submitted: 01 September 2020
Accepted: 14 September 2020
Published: 15 September 2020
Malignancy in a Patient under ISSN: 2373-9282
Copyright
© 2020 Corti M, et al.
HAART OPEN ACCESS
Keywords
Marcelo Corti1*, Astrid Pavlosky2, and Marina Narbaitz3
• Primary gastric lymphoma; Diffuse large B cell
1
Division of HIV/AIDS, Muñiz Hospital, Argentina lymphoma; AIDS; HIV
1
Department of Medicine, University of Buenos Aires, Argentina
2
Medical Director, Pavlosky Hematology Center, Argentina
3
National Academy of Medicine, Histopathology Laboratory, Argentina
Abstract
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.
INTRODUCTION CASE REPORT
Non-Hodgkin lymphoma (NHL) is a common complication A 64-year-old man with a large history of HIV infection and
of the disease caused by the human immunodeficiency virus under HAART presented with unspecific abdominal symptoms
(HIV). The involvement of the digestive tract, from the oral of a month of evolution. The patient referred episodic epigastric
cavity to the anus region, is very frequent [1,2]. One of the most pain, postprandial fullness, nausea, eructation and breathe
odor. He denied history of fever and night sweats but the
common characteristic of AIDS-associated NHL is the extranodal
clinical manifestations were associated with a weight loss of 5
compromise at the time of diagnosis. Gastrointestinal tract (GIT)
kg. The patient had history of a numerous episodes of H. pylori
is the most commonly site of primary extranodal lymphomas, infection and erosive/ulcerative gastritis. He was treated in all
including 40% to 50% of all cases [3-6]. episodes with different antimicrobial regimens. Six years before,
In the GIT, stomach is the most frequent site of involvement on antiretroviral treatment, with undetectable viral load and
(50% to 88%) followed by the small intestine (14% to 38%) and immunological reconstitution, he was diagnosed with intra-
anal squamous cell carcinoma associated with HPV-16. He was
the colon (10% to 20%) [4-7,8]. GIT involvement is also frequent
treated with HAART plus chemotherapy based on Nigro’s scheme
in HIV-infected patient’s account 15% to 75% of all cases [9-11].
plus tridimensional radiotherapy with a complete remission and
Here we present a patient infected with HIV who developed without relapse during 10 years.
a primary gastric NHL during highly active antiretroviral therapy Her physical examination revealed no abdominal findings,
(HAART) with immune reconstitution and undetectable viral no hepatomegaly, no splenomegaly and no lymphadenopathy.
load. Patient was treated with the same scheme of HAART Laboratory tests were normal including LDH levels. The CD4-
plus chemotherapy with a prolonged survival and a complete T-cell count was 173 cells/uL and the plasma viral load was
remission of the lymphoproliferative disorder. undetectable. Upper gastrointestinal endoscopy was done and
Cite this article: 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.
Corti M, et al. (2020)
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Bringing Excellence in Open Access
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 Figure 2 Histology with H-E stain on the biopsy (×100) showing
HAART based on tenofovir plus emtricitabine, dolutegravir and diffuse infiltration of submucosa and muscularis propria by lymphoid
darunavir boosted with ritonavir. Additionally, he received 6 neoplasm.
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.
DISCUSSION
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 [11], being this the
second most frequent malignancy following Kaposi´s sarcoma
[12]. 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 Figure 3 H-E (x 400) showing large atypical lymphoid cells with
lymphoma (PGL) in the last decades is related with the increase in indented vesicular type of nucleus, prominent nucleoli, with scanty
the number of immunodeficiency patients, especially those with eosinophilic cytoplasm and atypical mitosis.
HIV infection. Hernandez JA et al [13], 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 [14]. More than 90% of PGNHL are of
B-cell phenotype and generally is not associated with peripheral
adenopathy [13]. 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 [2], 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.
Figure 1 Endoscopic findings at initial diagnosis showed a large Histopathological biopsy smears must be classified
ulcerated lesion at the minor gastric curvature (white arrow). according with the Real and WHO classification [17]. Ann Arbor
Ann Clin Pathol 7(1): 1154 (2020)
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Corti M, et al. (2020)
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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
[18].
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 [19]. These patients
are associated with a rapid progression of neoplasm disease,
frequent extranodal initial manifestations, poor prognosis and a
short survival after diagnosis [20].
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
Figure 6 Ki 67 showed a high proliferation index.
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 [21].
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 [24]. 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
Figure 4 Immunohistochemical staining revealed large atypical a high remission rate in HIV associated-NHL [27]. The role of
lymphoid cells positive by CD20 antibody. surgery is limited to cases of obstruction or uncontrollable
bleeding. The spontaneous remission of aggressive lymphomas
as DLBCL is extremely rare. Gattiker et al [28], 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 [29], reported 2 cases of remission of gastric DLBCL
without any treatment. Finally, Sugiyama et al [30], 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 [31]. 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.
REFERENCES
Figure 5 Negative immunohistochemical staining of lymphoma cells
1. Corti M. HIV/AIDS and Cancer: The Hidden Epidemic. Clin Oncol.
by CD3 antibody.
2019; 4: 1622-1623.
Ann Clin Pathol 7(1): 1154 (2020)
3/4
Corti M, et al. (2020)
Central
Bringing Excellence in Open Access
2. Fontes Rezende RF, Mantelmacher M, da Costa Ferreira S, Hyppólito A Proposal from the International Lymphoma Study Group. Blood.
EB, Machado AA, Ardengh JC, et al. Clinical, endoscopic and prognostic 1994; 84: 1361-1392.
aspects of primary gastric Non-Hodgkin’s lymphoma associated with
18. Carbone PP, Kaplan HS, Musshoff K, DW Smithers, M Tubianaet al.
acquired immunodeficiency syndrome. Bras J Infect Dis. 2009; 13: 2-4.
Report of the committee on Hodgkin´s Disease Staging Procedures.
3. Zucca E, Rogero OE, Bertoni F, Cavalli F. Primary extranodal non- Cancer Res. 1971; 31: 1860-1861.
Hodgkin’s lymphomas. Part I: gastrointestinal, cutaneous and
19. Corti M, De Dios Soler M, Baré P, María F Villafañe, Miguel De
genitourinry lymphomas. Ann Oncol. 1997; 8: 727-737.
Tezanos Pinto, Raúl Perez Bianco, et al. AIDS related lymphomas:
4. Galindo F, Fernández Marty P, Kogan A, Díaz S, Barugel ME, Dos Santos histopathological subtypes and association with Epstein Barr and
R. Linfomas de intestino delgado y cirugía. Rev Argent Cirug. 1996; human herpes virus type-8. Medicina (Buenos Aires). 2010; 70: 151-
70: 157-167. 158.
5. Thieblemont C, Bastion Y, Berger F, Rieux C, Salles G, Dumontet 20. Akanmu, A S. AIDS-associated malignancies. Afr J Med Med Sci. 2006;
C, et al. Mucosa-associated lymphoid tissue gastrointestinal and 35: 57-70.
nongastrointestinal lymphoma behavior. Analysis of 108 patients. J
21. Nakamura S, Sugiyama T, Matsumoto T, Iijimo K, Ono S, Tajika M,
Clin Oncol. 1997; 15: 1624-1630.
et al. Long term clinical outcome of gastric MALT lymphoma after
6. Nakamura S, Matsumoto T, Lida M, Yao T, Tsuneyoshi M. Primary eradication of Helicobacter pylori: a multicentre cohort follow up
gastrointestinal lymphoma in Japan: A clinicopathologic analysis of study of 420 patients in Japan. Gut. 2012; 61: 507-513.
455 patients with special reference to the time trends. Cancer. 2003;
22. Vaccher E, Spina M, di Gennaro G, R Talamini, G Nasti, O Schioppa, G
97: 2462-2473.
Vultaggio, et al. Concomitant CHOP chemotherapy and highly active
7. Boddie AW, Mullins JD, West G, Bouda D. Extranodal lymphoma: antiretroviral therapy in patients with HIV-related non-Hodgkin´s
surgical and other therapeutic alternatives. Curr Probl Cancer. 1982; lymphoma. Cancer. 2001; 91: 155-163.
6: 1-63.
23. Ratner L, Lee J, Tang S, F Hamzeh, B Herndier, D Scadden, et al.
8. Danzig JB, Brandt LJ, Reinus JF, Klein RS. Gastrointestinal malignancy Chemotherapy for human immunodeficiency virus-associated non-
in patients with AIDS. Am J Gastroenterol 1991; 86: 715-718. Hodkin´s lymphoma in combination with highly active antiretroviral
therapy. J Clin Oncol. 2001; 91: 2171-2178.
9. Heise W, Arastéh K, Mostertz P, P Mostertz, J Skörde, W Schmidt, C
Obst, et al. Malignant gastrointestinal Lymphomas in patients with 24. Wolf T, Brodt HR, Fichtlscherer S, Mantzsch K, Hoelzer D, Helm
AIDS. Digestion. 1997; 58: 218-224. EB, et al. Changing incidence and prognostic factors of survival in
AIDS-related non-Hodgkin′s lymphoma in the era of highly active
10. Levine A.M. Lymphoma in acquired immunodeficiency syndrome.
antiretroviral therapy (HAART). Leuk Lymph. 2005; 46: 207-215.
Semin Oncol. 1990; 17: 104-112.
25. Chow KU, Mitrou PS, Geduldig K, Helm EB, Hoelzer D, Brodt HR.
11. Hodgkin and Non-Hodgkin lymphomas. In: Edge SB, Byrd DR,
Changing incidence and survival in patients with AIDS-related non-
Compton CC, et al. (Edn). AJCC Cancer Staging Manual. 7thedn, New
Hodgkin´s lymphoma in the era of highly active antiretroviral therapy
York, NY: Springer, 2010.
(HAART). Leuk Lymphoma. 2001; 41: 106-116.
12. Cornejo-Juárez P, Volkow-Fernández P, Avilés-Salas A, Calderón-
26. Hoffmann C, Wolf E, Fatkenheuer G, Buhk T, Stoehr A, Plettenberg A, et
Flores E. AIDS and non-Hodgkin´s lymphoma. Experience at an
al. Response to highly active antiretroviral therapy strongly predicts
oncological center in Mexico. Rev Invest Clin. 2008; 60: 375-381.
outcome in patients with AIDS-related lymphoma. AIDS. 2003; 17:
13. Hernández JA, Navarro JT, Ribera JM, Sancho JM, Vaquero M, Sirera 1521-1529.
G, et al. Primary gastrointestinal lymphoma in patients infected with
27. Bustamante-Bernal M, Galvis J, Matos D, Sosa O, Syed SH, Padilla
HIV: Study of 15 cases in a series of 76 patients with non-Hodghkin’s
O, et al. Burkitt´s Lymphoma of the rectosigmoid and the stomach
limphoma and HIV infection. Med Clin (Barc). 1999; 112: 222-224.
presenting as hematochezia. Am J Case Rep. 2016; 15: 89-92.
14. D’Amore F, Christensen BE, Brincker H, N T Pedersen, K Thorling, J
28. Gattiker HH, Wiltshaw E, Galton DA. Spontaneous regression in non-
Hastrup, et al. Clinico-pathological features and prognostic factors in
Hodgkin’s lymphoma. Cancer. 1980; 45: 2627-2632.
extranodal extranodal non-Hodgkin’s lymphomas. Eur J Cancer. 1991;
27: 1201-1208. 29. Watari J, Saitoh Y, Fujiya M, Nakamura K, Inaba Y, Okamoto K, et
al. Spontaneous remission of primary diffuse large B-cell gastric
15. Atalay C, Kanlioz M, Demir S, Pak I, Altinok M. Primary gastrointestinal
lymphoma. J Gastroenterol. 2005; 40: 414-420.
tract lymphomas. Acta Chir Belg 2003; 103: 616-620.
30. Sugiyama T, Arita K, Shinnob E, Nakajima T. Spontaneous remission
16. Arista NJ, Jimenez A, Keirns C, Larraza O, Larriva J. The role of endoscopy
of diffuse large B cell lymphoma in the stomach and the continuation
biopsy in the diagnosis of gastric lymphoma: A morphological and
of remission for 10 years. Case Rep Gastroenterol. 2018; 12: 699-703.
immunohistochemichal eter aisal. Hum Pathol. 1991; 22: 339-348.
31. Khan F, Bauer F, Gazi G, Bilgrami S. Regression of large B-cell non-
17. Harris NL, Jaffe ES, Stein H, P M Banks, J K Chan, M L Cleary, et al. A
Hodgkin´s lymphoma of stomach with HAART: Case report and
Revised European-American Classification of Lymphoid Neoplasms:
review. Leuk Lymphoma. 2006; 47: 750-754.
Cite this article
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.
Ann Clin Pathol 7(1): 1154 (2020)
4/4
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