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 Table of Contents  
CASE REPORT
Year : 2022  |  Volume : 6  |  Issue : 1  |  Page : 27-29

Neuroendocrine tumor in a patient living with human immunodeficiency virus


1 Department of Internal Medicine, Hamad Medical Corporation, Doha, Qatar
2 Department of Laboratory Medicine and Pathology, Hamad Medical Corporation, Doha, Qatar

Date of Submission25-Feb-2022
Date of Acceptance10-Jun-2022
Date of Web Publication11-Aug-2022

Correspondence Address:
Dr. Khalid Albsheer
Department of Internal Medicine, Hamad Medical Corporation, Doha
Qatar
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ljms.ljms_10_22

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  Abstract 


Neuroendocrine tumors (NETs) are epithelial neoplasms with predominant neuroendocrine differentiation, potentially arising from anywhere along the alimentary tract. We report a case of NET in a patient living with human immunodeficiency virus (HIV) (PLWH). A 58-year-old gentleman presented to the emergency department with a 2-week history of dry cough, loose motions, and fatigue; he had unintended weight loss ongoing during the past 4 months. Examination is significant for hepatomegaly (20 cm). On evaluation, a diagnosis of both HIV/AIDS and metastatic NET of gastrointestinal origin was confirmed. The chronic antigenic stimulation, cytokine dysregulation, and inflammation observed in PLWH are believed to influence the development of variety of malignancy. Hence, a high index of suspicion for neoplasms in HIV/AIDS (PLWH) regardless of their viral load or immunosuppression status is necessity when presented with red flag malignancies, especially with the overlapping symptoms of AIDS and the constitutional symptoms of cancers.

Keywords: Gastrointestinal tumor, human immunodeficiency virus, neuroendocrine tumor


How to cite this article:
Albsheer K, Alhassan Ahmed SM, Sibira RM, B. Habas EM. Neuroendocrine tumor in a patient living with human immunodeficiency virus. Libyan J Med Sci 2022;6:27-9

How to cite this URL:
Albsheer K, Alhassan Ahmed SM, Sibira RM, B. Habas EM. Neuroendocrine tumor in a patient living with human immunodeficiency virus. Libyan J Med Sci [serial online] 2022 [cited 2022 Oct 5];6:27-9. Available from: https://www.ljmsonline.com/text.asp?2022/6/1/27/353687




  Introduction Top


Neuroendocrine tumors (NETs) arise from endocrine cells and nervous systems. NETs often present as either a benign or a malignant neoplasm.[1] They occur mostly in the intestine, where are often called carcinoid tumors. They have been reported rarely from the pancreas, lung, and the rest of the body.[2] The primary site of NET is not always detectable, and it presents mostly in the liver as metastasis. Small intestinal NET was distinguished from other types of tumors during the early nineties. Carcinoid tumors are slow-growing tumors (“cancer-like” rather than truly cancerous) derived from enterochromaffin cells and very often secrete a range of hormones such as serotonin, gastrin, and others depending upon the site of origin. The WHO classifies NETs based on histological features into well-differentiated, intermediate-differentiated, and poorly differentiated tumors.[3]

Human immunodeficiency virus (HIV) is a condition in which acquired progressive failure of the immune system leads to life-threatening opportunistic infections and increased risk of certain tumors. A wide range of cancers reported in HIV/AIDS (patient living with HIV [PLWH]) includes Kaposi's sarcoma, cervical cancer, non-Hodgkin's lymphoma, as well as a number of other non-AIDS–related cancers.[4]

To our knowledge, there are no previous reports of association between the NET and defined cohorts of PLWHs in gulf countries. We therefore present this case of NET in a 58-year-old Sri Lankan male patient.


  Case Report Top


A 58-year-old Sri Lankan male who has been living in Qatar for the past 5 years, with established history of hepatitis B virus (HBV) since 2013. He presented to the emergency department with a history of intermittent fever, persistent dry cough, and intermitted episodes of watery diarrhea for 2–4 weeks. He also complained fatigue, weight loss of 15 kg, and anorexia for the last 4 months. His vital signs upon his initial presentation showed low-grade fever of 37.6, no tachypnea or tachycardia, and blood pressure of 109/69 mmHg.

On general physical examination, the patient was cachexic and pale and no lymphadenopathy or jaundice. Chest examination revealed crackles in the left lower zone with bronchial breathing, dull precaution, and increase vocal fremitus. The abdominal examination showed hepatomegaly with a liver span of 20 cm. The rest of his examination was not significant.

His basic laboratory tests showed mild leukopenia, macrocytic anemia, and decrease in absolute neutrophil count [Table 1].
Table 1: Initial laboratory investigations

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Chest X-ray was ordered and showed consolidation in the lower left lob. The patient was diagnosed with community-acquired pneumonia (CAP) and started on azithromycin. However, the atypical presentation of CAP with low-grade fever, leukopenia, along with significant weight loss, and cachexia, rose suspension of immunosuppression state, and hence, the patient was tested for HIV along with white blood cell flow cytometry. His HIV viral load was found to be 205,000 copies, CD4 + 87 [Table 2], and a diagnosis of AIDS was confirmed.
Table 2: Flow cytometry

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Viral panel (except for HIV and rhinovirus) and blood and stool cultures were negative for opportunistic organisms excluding any infectious reason for his diarrhea.

Ultrasound showed multiple liver lesions. Contrast-computed tomography (CT) abdomen showed significantly enlarged liver of 26 cm, with variable-sized focal lesions in both lobes. These findings in the liver suggested metastases that were possibly NETs in origin. Liver biopsy showed atypical cell infiltration [Figure 1]a and [Figure 1]b, and immunohistochemistry revealed neuroendocrine neoplasm grade 3 (Ki-67 about 40%) [Figure 1]c and [Figure 1]d.
Figure 1: (a and b) Liver biopsy showing that liver tissue is infiltrated by solid nests of atypical cells. The cells are medium to large, have pleomorphic, hyperchromatic nuclei, high nuclear-to-cytoplasmic ratio, and abundant atypical mitotic figures. Cytoplasm is eosinophilic to amphophilic color with finely cytoplasmic granules are identified. Nuclei are central, round-to-oval, with loss of “salt-and-pepper” chromatin. (c and d) Immunohistochemistry showing that atypical cells are positive with CKAE1/AE3, synaptophysin, and CD56. They are negative with chromogranin and TTF1. Ki-67 proliferative index is 40%. These findings diagnose neuroendocrine tumor WHO grade 3. However, it is unclear whether this represents a possible metastatic neuroendocrine tumor or represents a primary liver neuroendocrine neoplasm

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A whole-body fluorodeoxyglucose (FDG) positron emission tomography (PET) scan showed multiple hypodense liver lesions that showed mild-to-moderate FDG uptake that was consistent with metastatic disease. Ga68 scan showed that the liver has high volume of metastatic burden with highly somatostatin receptor dense tissue. The patient also had CT chest and upper and lower gastrointestinal (GI) endoscopy with random biopsies to identify the possible primary site of NET. The workup rose a possibility that the primary tumor is most likely of a duodenum (ampulla) or head of the pancreatic origin.


  Discussion Top


This case represents the first report of contemporaneous diagnosis of NET in a cohort of PLWH in the Gulf and suggests extra clinical vigilance in the diagnostic workup of these patients.

Cancer is the leading cause of death in HIV-infected persons in highly developed countries, with AIDS, and non-AIDS–related cancers account for a third of all causes of death.[5] The standard incidence ratio (SIR) of AIDS - defining cancers like: kaposi sarcoma, cervicle cancer, Non hodgkin lymphoma, etc– with exception for invasive cervical carcinoma – in PLWH has significantly decreased after in the era of highly active antiretroviral therapy (HAART) and the correlated increase in CD4 count among this population.[6],[7] However, the use of HAART has not shown any impact on the SIR of non-ADC,[7] yet the decrease in CD4+ count has been thought to influence various carcinogenic infections and hence the risk for a wide range of cancers,[8],[9] even in patients with controlled HIV viral load and preserved CD4+ counts.[6] The chronic antigenic stimulation, cytokine dysregulation, and inflammation are believed to influence the development of variety of malignancy.[6] In addition, HBV is a known oncovirus,[6] which our patient has a coinfection, and might have contributed to the pathogenesis of NET in this case.

NET of the midgut origin has rarely been reported in an association HIV, and up to date, NETs in general are not considered as virus-related cancer – with exception for Merkel cell carcinoma.[4] In a report by Lito et al.,[3] they identified four adult patients, with a mean age of 42 years (range: 37–47) infected with HIV, who developed NET with the primary lesion in the GI tract. Interestingly, they were moderately immunocompromised with a median CD4 + count of 497 cells/mm (range: 182–1100), but with chronic HIV infection (2–15 years duration). The report described their initial presenting symptoms as nonspecific, including abdominal pain, diarrhea, weight loss, and rectal bleeding. Moreover, specialized diagnostic workup was necessary to identify the tumor.

In another case, 52-year-old man who is known HIV positive since 1991 was maintained on antiretroviral therapy with emtricitabine-tenofovir and raltegravir with undetectable HIV viral load and the CD4 count of 850 cells/μL at the time of presentation. His main complaint at presentation was diplopia. Magnetic resonance imaging of the orbits revealed a mass in the left orbit with the involvement of the optic nerve. Histopathology of the mass conformed metastatic small cell carcinoma. CT scan of the chest, abdomen, and pelvis and a PET revealed multiple liver lesions and a large pancreatic tail mass. Given these findings, his final diagnosis was extrapulmonary high-grade small cell carcinoma of the pancreas (small cell is a poorly differentiated high-grade neuroendocrine carcinoma).[4]

These cases, along with our case, highlight the importance of an astute clinical vigilance of NET in PLWH. The wide range of nonspecific presenting symptoms of these malignancy can overlap with other HIV-related illnesses, and high index of suspicion for NET in the setting of HIV infection when presented with unexplained liver lesions in PLWH is needed regardless of the viral load or CD4+ status. While the cause of these lesions is diverse, identifying NET early does significantly impact the management plan fort these patients and quality of care provided for them postcancer diagnosis.

Consent statement

The patient provided verbal and written consent for the publication of this case. MRC approval was sought for the publication of the case.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that his name and initials will not be published and due efforts will be made to conceal his identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Rindi G, Klimstra DS, Abedi-Ardekani B, Asa SL, Bosman FT, Brambilla E, et al. A common classification framework for neuroendocrine neoplasms: An International Agency for Research on Cancer (IARC) and World Health Organization (WHO) expert consensus proposal. Mod Pathol 2018;31:1770-86.  Back to cited text no. 1
    
2.
Hamilton SR. Pathology and genetics of tumours of the digestive system (World Health Organization classification of tumours). Adv Anat Pathol 2000;8:355-6.  Back to cited text no. 2
    
3.
Lito P, Pantanowitz L, Marotti J, Aboulafia DM, Campbell V, Bower M, et al. Gastroenteropancreatic neuroendocrine tumors in patients with HIV infection: A trans-Atlantic series. Am J Med Sci 2009;337:1-4.  Back to cited text no. 3
    
4.
Husnain M, Park W, Ramos JC, Johnson TE, Chan J, Dasari A, et al. Complete response to ipilimumab and nivolumab therapy in a patient with extensive extrapulmonary high-grade small cell carcinoma of the pancreas and HIV infection. J Immunother Cancer 2018;6:1-5.  Back to cited text no. 4
    
5.
Yarchoan R, Uldrick TS. HIV-associated cancers and related diseases. N Engl J Med 2018;378:1029-41.  Back to cited text no. 5
    
6.
Clifford GM, Polesel J, Rickenbach M, Dal Maso L, Keiser O, Kofler A, et al. Cancer risk in the Swiss HIV Cohort Study: Associations with immunodeficiency, smoking, and highly active antiretroviral therapy. J Natl Cancer Inst 2005;97:425-32.  Back to cited text no. 6
    
7.
Clifford GM, Franceschi S. Cancer risk in HIV-infected persons: Influence of CD4+count. Future Oncol 2009;5:669-78.  Back to cited text no. 7
    
8.
Hernández-Ramírez RU, Shiels MS, Dubrow R, Engels EA. Spectrum of cancer risk among HIV-infected people in the United States during the modern antiretroviral therapy era: A population-based registry linkage study. Lancet HIV 2017;4:e495.  Back to cited text no. 8
    
9.
Goehringer F, Bonnet F, Salmon D, Cacoub P, Paye A, Chêne G, et al. Causes of death in HIV-infected individuals with immunovirologic success in a national prospective survey. AIDS Res Hum Retroviruses 2017;33:187-93.  Back to cited text no. 9
    


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