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ORIGINAL ARTICLE
Year : 2014  |  Volume : 51  |  Issue : 4  |  Page : 459-463
 

Spectrum of malignancies in human immunodeficiency virus – positive patients at a Tertiary Care Centre in South India


1 Department of Pathology, Nizam's Institute of Medical Sciences, Hyderabad, Telangana, India
2 Department of Medical Oncology, Nizam's Institute of Medical Sciences, Hyderabad, Telangana, India
3 Department of General Medicine, Nizam's Institute of Medical Sciences, Hyderabad, Telangana, India

Date of Web Publication1-Feb-2016

Correspondence Address:
T R Paul
Department of Pathology, Nizam's Institute of Medical Sciences, Hyderabad, Telangana
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0019-509X.175295

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 » Abstract 

Context: India has a very large number of patients living with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome. Opportunistic infections in these patients are commonly encountered. However, malignancies in such patients also do occur. Aim: The aim was to study the spectrum of malignancies in HIV-positive patients at a tertiary health care center. SETTINGS AND DESIGN: Retrospective study. Materials And Methods: The cases were retrieved from pathology record files at our Institute from January 2003 to December 2008. The follow-up was obtained from Medical oncology records. The morphology of each case was reviewed along with immunohistochemistry wherever done. Results: There were 61 such cases (51 males, 10 females). The age range was 7–78 years with a median of 35 years. The clinical presentation varied according to the malignancy. The largest group was non-Hodgkin lymphoma (18 nodal, 23 extra-nodal). The others included carcinoma breast (4), chronic myeloid leukemia (3), Burkitt Leukemia (2), squamous cell carcinoma anal region (2), multiple myeloma (2) and one each of miscellaneous malignancies (7). Conclusion: Malignancies in HIV positive individual occurred in younger individuals. Non-Hodgkin lymphomas, especially extra-nodal lymphomas, were the most common malignancy. There were no cases of proven Kaposi's sarcoma or invasive cervical carcinomas. There were two cases of multiple myeloma which are infrequently reported.


Keywords: Human immunodeficiency virus, lymphoma, malignancy, India


How to cite this article:
Paul T R, Uppin M S, Uppin S G, Radhika K, Prayaga A K, Sundaram C, Reddy V S, Rao D R, Rajappa S, Sreenivasan V R. Spectrum of malignancies in human immunodeficiency virus – positive patients at a Tertiary Care Centre in South India. Indian J Cancer 2014;51:459-63

How to cite this URL:
Paul T R, Uppin M S, Uppin S G, Radhika K, Prayaga A K, Sundaram C, Reddy V S, Rao D R, Rajappa S, Sreenivasan V R. Spectrum of malignancies in human immunodeficiency virus – positive patients at a Tertiary Care Centre in South India. Indian J Cancer [serial online] 2014 [cited 2019 Dec 10];51:459-63. Available from: http://www.indianjcancer.com/text.asp?2014/51/4/459/175295



 » Introduction Top


India has a very large number of persons living with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS). In the adult population, the HIV prevalence is thought to be about 0.34%.[1] Telangana/ Andhra Pradesh are few of the Southern states where HIV prevalence is very high. Though patients living with HIV/AIDS are extremely susceptible to opportunistic infections like tuberculosis and fungal infections, the risk of cancer in these patients is thought to be low.[2] Non-Hodgkins lymphoma (NHL), Kaposi sarcoma, and invasive cervical carcinoma are considered AIDS-defining malignancies [2] and are the most commonly reported malignancies in HIV/AIDS patients worldwide. However, the incidence of Kaposi sarcoma in India is very low.[3],[4],[5] In the present article, we put forward the spectrum of malignancies occurring in HIV-positive patients presenting to a Tertiary Health Care Centre in Telangana, India.


 » Materials and Methods Top


All patients, who were HIV positive and presented to the Institute and were diagnosed as having malignancies during the period 2003–2008, were included in the study.

This is a large teaching and referral hospital having medical and surgical oncology services. However, there are few specialties (like Gynecology and Dermatology) not developed as full-fledged departments.

The cases were retrieved from the pathology record files. The clinical; biochemical, imageologic details as well as follow-up were obtained from the patient's records. The morphology of each case was reviewed. As per the requirements of each case, immunohistochemistry was performed with a wide range of markers (Leukocyte common antigen, CD 20, CD 3, CD 34, CD 15, CD 30, epithelial membrane antigen, cytokeratin, alpha-fetoprotein, neuron-specific enolase, carcinoembryonic antigen, estrogen receptors, progesterone receptors, her 2 neu, CD 138, CD 117, Ki 67, CD 99, human melanoma black 45). These were done using antibodies procured from DAKO, Denmark. The antigen localization was carried out using labeled streptavidin-biotin technique. Two cases of acute leukemia had cytochemistry with myeloperoxidase, periodic acid Schiff and oil red O done on smears.


 » Results Top


During the study period, there were 61 patients of malignancies occurring in HIV-positive patients. The number of cases diagnosed per year during the study period is shown in [Graph 1][Additional file 1]. From the table, it is observed that the number of cases over a 6-years period was fairly constant.

The age and gender distribution are given in [Graph 2] [Additional file 2]. The patients ranged from 7 years to 78 years of age with a median age of 35 years. The male to female ratio was 5.1:1.

The symptoms and signs of the patients varied with the type of malignancy. Fevers of prolonged duration and lymphadenopathy were the most commonly encountered symptom and sign respectively.

The mode of transmission of the virus to the patient was known in 15 patients and not known in 46 patients, and is represented in [Table 1]. There were four children under 15 years of age who acquired the infection through vertical transmission.
Table 1: Mode of transmission of HIV infection (n=61)

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The CD 4 counts available at the time of diagnosis of the malignancy are as given in [Table 2]. The median value of the CD 4 counts was 184 cells/cmm.
Table 2: CD 4 counts at the time of diagnosis of malignancy (n=23)

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Sixteen of the 61 cases were on highly active anti-retroviral therapy (HAART), at the time of diagnosis of malignancy.

The spectrum of malignancies presenting during the study period is given in [Table 3]. Nodal and extra-nodal lymphomas accounted for the bulk of malignancies (30% and 38%, respectively). At the same time, there were no histologically proven cases of Kaposi sarcoma.
Table 3: Spectrum of malignancies in HIV/AIDS positive patients (n=61)

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The site of the lymphoid neoplasm and the histologic type is shown in [Table 4] and [Table 5], respectively [Figure 1],[Figure 2],[Figure 3],[Figure 4]. There were no cases of Hodgkins lymphoma in the study.
Table 4: Sites of lymphoid malignancies (n=45) in HIV/AIDS patients

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Table 5: Histologic types of the lymphoid malignancies (n=45) in HIV/AIDS patients

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Figure 1: (a) Plasmablastic lymphoma of oral cavity H and E ×400, (b) CD-138 strongly positive in cells

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Figure 2: (a) Small intestine showing diffuse infiltrate of lymphoid cells extending through the wall of bowel (H and E ×200), (b) The same cells on high power showing monomorphic lymphoid cells, (c) Intense cytoplasmic positivity of the cells for CD20 (Immunohistochemistry CD 20 HRP×400)

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Figure 3: Multiple myeloma (a) Multiple lytic lesions, (b) Lytic lesions in the skull, (c) Plasma cells and plasmablasts in bone marrow (Geimsa ×400)

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Figure 4: Burkitt Leukemia (Geimsa ×1000) Inset: Positivity for oil red O ×400)

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As part of staging workup after the diagnosis of lymphomas, bone marrow study was done in 27 patients, of which 10 patients showed marrow involvement by lymphoma, 16 were not involved and 1 patient showed marrow hypoplasia.

The treatment and follow-up details are given in [Table 6]. Patients with HIV and malignancies, especially NHL had a poor prognosis, even after therapy. Due to financial constraints and other family problems, a good number of patients refused therapy after diagnosis.
Table 6: Treatment/management details following diagnosis (n=61) of malignancies in HIV/AIDS patients

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 » Discussion Top


Acquired immunodeficiency syndrome defining cancers include Kaposi sarcoma, NHL, and invasive cervical carcinoma. The other malignancies are unrelated to immune deficiencies however a few of them have a higher incidence in the setting of HIV infection.[5]

We observed that nodal and extra-nodal NHLs formed the major bulk of malignancies in HIV-positive individuals. Similar reports have been published from India.[3],[4]

It is believed that cancer is not currently a common problem in HIV patients in India. [Table 1] show that there has not been a significant rise in malignancies in HIV-positive patients during the 6-years study period. High mortality from infectious diseases like tuberculosis and fungal infections has truncated survival, preventing progression to severe immunosuppression, when the risk of malignancies increases. India is emerging as a leader for more affordable regimens of HAART to control the HIV infection and drugs to treat infectious conditions. As these are being supplied to the patient almost free of cost, there would be a reduction of competing mortality and this would lead to increase of cancer as a clinical problem in the near future.[2]

The median age of presentation of malignancies in patients with HIV was 35 years, and a majority (74%) was lymphoid neoplasia. This was similar to another Indian study by Agarwal et al.[6] This indicates that in HIV positive individuals, lymphomas tend to occur at an earlier age than the general population.

There was not a single case of histologically proven Kaposi sarcoma in this series. Though there have been an occasional case reports from India [7],[8],[9],[10] of Kaposi sarcoma in HIV patients, large series of malignancies in HIV patients [3],[4] showed that this was a relatively rare malignancy here. The seroprevalence of human herpes virus-8 (HHV-8) is low in countries like India, Sri Lanka and Thailand [11] and this correlates with the fact that very few AIDS-related Kaposi sarcoma have been reported in these countries.

As reported in Indian literature,[12] lymphoid neoplasia formed the largest group and accounted for 74% of HIV – associated malignancies. There were no cases of Hodgkins lymphoma in this series. A number of cases of lymphoma had unusual and multiple sites of involvement at presentation like subcutaneous and the soft tissue lymphomas. The reasons for unusual and widespread extra-nodal disease in patients with AIDS are unknown but may relate to perturbation of various adhesion molecules.[13]

Although the precise mechanism of lymphomagenesis in the setting of HIV infection is not fully elucidated, different theories have been considered.[13] It is thought that the HIV and/or Epstein Barr virus would induce B-cell proliferation and create an environment in which mutations in critical oncogenes and tumor suppressor genes may occur along with abnormal DNA rearrangements, leading to c-myc activation, clonal selection and finally lead to the development of monoclonal B–cell lymphoma.

The HIV-associated NHLs have traditionally been classified as,[14],[15]

  • Lymphomas also occurring in immunocompetent patients


    • Burkitts lymphoma leukemia; (two each in this study)
    • Diffuse large B cell lymphoma (centroblastic and immunoblastic-33 in this study).
  • Lymphomas occurring more specifically in HIV patients


    • Primary effusion lymphoma (none in the study)
    • Plasmablastic lymphomas of the oral cavity (four cases in this study).


  • Lymphomas occurring in other immunodeficient states
    • Polymorphic B-cell lymphoma (none in the study).




Research has shown that [15] the level of host's immune deficiency selects the type of AIDS-related lymphoma that will develop in a patient. AIDS–Burkitts lymphoma and centroblastic lymphomas develop in the presence of relatively sustained CD 4 counts. AIDS-immunoblastic lymphoma and HHV-8 associated lymphoma tend to occur with marked immunodeficiency and reduced CD 4 counts. Different clinicopathologic categories of AIDS-lymphomas derive from distinct B-cell subsets and associate with different pathogenetic pathways.

In this study, of the 23 patients with CD 4 counts available at the time of diagnosis of the malignancy, three patients had counts <50/cmm; five had counts between 51 and 100/cmm and 15 had counts >100/cmm. It appears that the majority of the patients had sustained CD 4 counts.

During the study period, there was only one patient with primary central nervous lymphoma, which was HIV positive.

There were four cases of oral cavity lymphomas diagnosed as plasmablastic lymphomas which are high-grade lymphomas occurring in HIV-positive individuals.[16] They have to be differentiated from diffuse large B cell lymphomas of immunoblastic type with plasmacytic differentiation, plasma cell neoplasia, and Burkitts lymphoma. Though initially described in the oral cavity, plasmablastic lymphomas were also described in other sites such as gastrointestinal tract, lymph nodes, and other sites.[17]

There were two young male patients, who were diagnosed as multiple myeloma. One of the patients had lytic lesions in the skull. Plasma cell dyscrasias have been described in young HIV positive patients.[18],[19],[20] The presence of high-titer anti-HIV activity in the paraproteins of AIDS patients suggests that an antigen-driven process in response to HIV infection may contribute to the early development of plasma cell disorders.

There was not a single case of the patient with invasive cervical carcinoma in this series. This could be due to a referral bias as this Institute does not have a full-fledged Gynecology Department. However, the incidence of cervical carcinoma in HIV-positive patients varied in different studies.[21] It was reported to be high by Dhir et al.,[4] but not so in other studies.[22] There was little evidence that this tumor relates to HIV-induced immune deficiency. Women at high risk for sexually acquired HIV infection are also at high risk for human papillomavirus (HPV) infection (HPV-16 and 18).

Non-acquired immunodeficiency syndrome defining malignancies

There were four patients with carcinoma breast in HIV-positive patients above 45 years of age. Though some reports [23] suggested that breast cancer in HIV patients occurred at a relatively early age and was aggressive with a poor survival outcome, other reports [24] negated this. Still others [25] have suggested that the low number of carcinoma breast in HIV patients could be explained by their overall low risk (lower socio-economic status, high parity, etc.) and also the possibility that immunodeficiency may protect HIV-infected persons from developing breast cancer.

Myeloid neoplasia is rare in the background of HIV positivity.[26] There was no case of acute myelogenous leukemia in this study. There were three cases of chronic myeloid leukemia (CML) who were doing well on imatinib and HAART therapy. Reports suggest that CML may evolve more rapidly in HIV patients.[26],[27],[28] This could be due to the direct action of HIV on bloodlines or due to the immunosuppression induced by the virus. However, it was also reported that concurrent treatment with imatinib and HAART can result in appropriate control of CML and HIV infection as well as long-term survival.[28]

There were two patients with anal squamous cell carcinomas in this series. HPV appears to contribute to the anal cancer risk in India.[2],[20] An alternate hypothesis is that HIV – induced immunosuppression results in the development of anal cancer.

There was one patient with hepatocellular carcinoma; however, this patient was both HIV and hepatitis B surface antigen positive. It has been suggested that the risk of hepatoma is attributable to the hepatitis virus and not to the HIV-related immune deficiency.[5]

There were six other cases of single malignancies in the present study. All these were possibly incidental malignancies in HIV-positive individuals and occasionally reported as case reports.[29],[30]


 » Conclusions Top


Though India is in the midst of the AIDS epidemic, the risk of cancer in Indians is not high. NHL formed the largest group of malignancies in patients with HIV/AIDS. Majority of them were extra-nodal and were diffuse large B cell lymphomas. They occurred at a younger age group than the rest of the population, with a median age of 35 years. Other AIDS – defining malignancies such as Kaposi sarcoma and invasive cervical carcinomas were not encountered in this study.





 
 » References Top

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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]

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