Radiology examination as a diagnostic aid in presentations with wide differential diagnoses: Case report of new Hodgkin’s lymphoma on a background of poorly controlled HIV

Hodgkin’s lymphoma and disseminated Mycobacterium avium complex (MAC) infection share similar clinical features; both may affect human immunodeficiency virus (HIV)-positive individuals. We discuss a patient with poorly controlled HIV-infection presenting with chest sepsis, dyspnoea and weight loss. Whilst the initial working diagnosis was that of MAC infection, pathology results had not met diagnostic criteria. Lymph node biopsy instead revealed classical Hodgkin’s lymphoma. We discuss the role of radiological examination in cases of diagnostic uncertainty.


Introduction
Hodgkin's lymphoma (HL) and disseminated Mycobacterium avium complex (MAC) infection are seen in patients who are human immunodeficiency virus (HIV)-positive. They often share similar clinical features such as fever, night sweats, lymphadenopathy, anaemia and weight loss. It may be difficult to distinguish these conditions clinically; mycobacterial cultures may only aid diagnosis after several weeks of incubation. Radiological imaging is therefore important to aid accurate, timely diagnosis and guide biopsy. We present a case illustrating a diagnostic dilemma in a patient presenting with poorly controlled HIV.

Case report
A 55-year-old man presented to the Accident and Emergency Department with a 2-month history of dyspnoea (acutely worsening over 2 days preceding admission), cough productive of purulent sputum, fever and weight loss. He was known to be HIV-positive (genotype-2, diagnosed 1991) but had been non-compliant with antiretroviral medication (Truvada, Darunavir and Ritonavir) for 2 years. Additional background included a history of depression, subdural haematoma, recurrent bacterial chest infections and drug abuse (daily heroin smoker).
On examination, he was unkempt, cachectic and dehydrated. He was septic but maintaining normal oxygen saturations on room air. Cardiovascular and neurological examinations were unremarkable. He was tachypnoeic and crepitations were auscultated at the right lung base. His abdomen was non-tender with palpable hepatosplenomegaly. Right-sided anterior cervical and right-sided inguinal lymphadenopathy was palpated.
A chest radiograph demonstrated right basal opacification. Computerised tomography of the chest abdomen and pelvis (CT-CAP) revealed patchy air space opacification at the left oblique fissure, left lower and right lower lobes, paraseptal and central lobular emphysema and bibasal atelectasis (Figures 1 and 2). Hepatosplenomegaly was confirmed and free fluid was evident throughout the abdomen and pelvis ( Figure 3). Multiple enlarged lymph nodes (up to 1.8 cm diameter) were visualised throughout the thorax, abdomen and pelvis (Figures 4 and 5).
Hodgkin's lymphoma and disseminated Mycobacterium avium complex (MAC) infection share similar clinical features; both may affect human immunodeficiency virus (HIV)-positive individuals. We discuss a patient with poorly controlled HIV-infection presenting with chest sepsis, dyspnoea and weight loss. Whilst the initial working diagnosis was that of MAC infection, pathology results had not met diagnostic criteria. Lymph node biopsy instead revealed classical Hodgkin's lymphoma. We discuss the role of radiological examination in cases of diagnostic uncertainty. Notably, one sputum culture subsequently grew Mycobacterium intracellulare; following this, another sputum culture grew Mycobacterium mucogenicum. Neither organism was grown on subsequent sputum samples. Neither of two mycobacterial blood cultures nor a lymph node mycobacterial culture showed any growth on final reporting. At least two sputum cultures positive   for the same organism or one positive culture from a 'sterile' site (such as blood, lymph nodes or bone marrow) are required to diagnose atypical mycobacterial infection. 1,2 The positive sputum cultures were therefore not considered significant.

Discussion
The patient presented our multi-disciplinary team with a diagnostic challenge. Given his clinical presentation including low CD4 count, mycobacterial infection was felt to be the most likely diagnosis. However, radiological imaging highlighted significant, widespread lymphadenopathy throughout the thorax, abdomen and pelvis, which was later confirmed by tissue diagnosis to be HL.
Hodgkin's lymphoma is more prevalent in HIV-positive individuals, and is often aggressive with B symptoms at presentation; it is associated with EBV-positivity. 3 Interestingly, unlike other malignancies, its incidence has not decreased with the introduction of highly active antiretroviral therapy, although overall and progression-free survival has improved. CT-PET is superior to conventional CT for staging. However, biopsy is essential to confirm diagnosis. 4 MAC (M. avium and M. intracellulare) accounts for up to 85% of infectious causes of abdominal lymphadenopathy in acquired immunodeficiency syndrome (AIDS). 5 Whilst M. avium is common in disseminated MAC, M. intracellulare is a more important respiratory pathogen. MAC lung disease may present as either apical fibrocavitary disease or nodular and bronchiectatic changes (right middle lobe or lingula). The disease course is often indolent and it may be difficult to distinguish environmental contamination from clinically relevant infection. Consequently, bronchial lavage or biopsy is often required to aid diagnosis. 6 Mycobacterium mucogenicum is typically seen in catheterrelated and post-traumatic skin infections. It rarely causes respiratory tract infection, and positive sputum cultures are often because of environmental contamination. 7 Widespread homogenous lymphadenopathy may be a feature of both MAC and HL; however, lymphadenopathy is often massive in HL (> 3 cm diameter). 5 Hepatosplenomegaly is commoner in MAC than in HL. 5 HL tends to be seen with a CD4 count around 240 cells/μL 4 ; in contrast, disseminated MAC is typically found with CD4 < 50 cells/μL. 1 HIV-2 tends to be less virulent with lower rates of progression to AIDS than in HIV-1; there are many differences in the behaviour of the virus and the consequent effects on the immune system that may explain this. The HIV-2 virus has a lower replication efficiency than HIV-1 and varies in its use of co-receptors. There are also differences in the levels and activity of the viral proteins Tat and Nef, which are thought to lead to a reduced rate of de novo T-cell infection and less immune activation (immune activation is strongly predictive of disease progression) in HIV-2 compared with HIV-1 infection. 8 In HIV-2 infection, there are increased levels of CD4+CD25+ regulatory T-cells, an increased ability to replace infected CD4+ T-cells, and less T-cell apoptosis than in HIV-1 infection. 8 Our patient, however, had poorly controlled, progressive HIV-2. This was likely because of his poor compliance with medication: he had stopped taking antiretrovirals on multiple occasions in the past and developed multiple resistances; his CD4 count had varied from 81 cells/μL -370 cells/μL over the previous 12 years.

Conclusion
HL and MAC present similarly in HIV-positive patients.
Although the level of immunocompromise at which they present can differ, both represented feasible differential diagnoses in this case. In these situations, radiological assessment is essential in interpreting the clinical picture, guiding biopsy and, ultimately, achieving a confirmed diagnosis.

Ethical consideration
No patient identifiable information has been presented. Written consent has been obtained from the patient prior to publication; a copy of the consent form has been provided.