HIV/AIDS

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 Small hypodense nodules may be microabscesses

image Larger hypodense lesions might be infectious, but AIDS-related lymphoma should be considered
image Pneumocystis may result in tiny calcifications
• Biliary tree

image Cholangitis or acalculous cholecystitis caused by opportunistic infections
• Stomach, small bowel, and large bowel

image Wall thickening raises concern for opportunistic infection, which can involve any segment of GI tract
image Mural thickening of esophagus suggests esophagitis, often due to candidiasis, CMV, or HSV
image Proctitis in homosexual men related to sexual activity may be due to Neisseria gonorrhoeae, Chlamydia, or HSV
image Focal mass-like wall thickening in GI tract should raise concern for malignancy (lymphoma, Kaposi sarcoma)
• Lymph nodes

image Mild generalized lymphadenopathy (usually < 1.5 cm) is typically reactive and may be 1st clue to HIV infection
image More significant adenopathy (> 1.5 cm) suggests opportunistic infection or AIDS-related lymphoma
image AIDS-related lymphoma may be associated with discrete lesions in liver/spleen or focal mass in GI tract
• Kidney

image Bilateral large kidneys (↑ echogenicity on US) with urothelial thickening due to HIV nephropathy

PATHOLOGY

• Infections more common in HIV patients even with CD4 > 200, although risk ↑ substantially with lower CD4 counts
• Incidence of AIDS-defining malignancies (AIDS-related non-Hodgkin lymphoma, Kaposi sarcoma) has dramatically ↓ with antiretroviral therapy
image
(Left) Coronal volume-rendered CECT in an AIDS patient with low CD4 count demonstrates diffuse thickening of the small bowel with surrounding ascites. The bowel appeared similar on several subsequent studies, and this was found to be infection with MAI.

image
(Right) Axial CECT in an HIV-positive patient presenting with 3 weeks of fever, diarrhea, and weight loss shows multiple sites of low-attenuation lymphadenopathy image involving retroperitoneal and mesenteric nodes. Biopsy confirmed MAI.
image
(Left) Axial CECT shows innumerable small hypodense foci in the spleen and, more subtly, in the liver. Both the liver and spleen are enlarged.

image
(Right) Axial CECT in the same patient demonstrates multiple low-density enlarged lymph nodes image. This constellation of findings was found to represent disseminated mycobacterial infection.

TERMINOLOGY

Abbreviations

• Acquired immune deficiency syndrome (AIDS)
• Human immunodeficiency virus (HIV)

Synonyms

 

Definitions

• Abdominal opportunistic infections and neoplasms resulting from HIV/AIDS-related immunodeficiency

IMAGING

General Features

• Best diagnostic clue

image Multiple focal hepatic or splenic lesions in patient with known AIDS
image Necrotic mesenteric nodes in patient with AIDS

– Mycobacterium avium-intracellulare (MAI)
• Location

image Can affect visceral organs, gastrointestinal tract, genitourinary tract, and lymph nodes
image Retroperitoneal nodes and masses
• Size

image Variable: Ranges from microabscesses (< 1 cm) to large masses due to lymphoma or Kaposi sarcoma
• Morphology

image Bulky hepatic or GI tract masses from AIDS-related lymphoma

Imaging Recommendations

• Best imaging tool

image CECT
• Protocol advice

image IV and oral contrast

CT Findings

• Liver

image Liver may appear nodular and cirrhotic due to strong demographic overlap of HIV and chronic viral hepatitis
image Small hypodense nodules scattered throughout liver suggests microabscesses (often due to Mycobacterium avium-intracellulare  [MAI], tuberculosis, histoplasmosis, Candida, Pneumocystis, etc.)
image Liver may appear globally enlarged without focal lesions due to infiltrative infections (e.g., MAI)
image Pneumocystis (and rarely CMV or MAI) can result in multiple tiny calcifications throughout liver

– Calcifications do not signify inactive disease
image Liver involved in up to 1/4 of patients with AIDS-related lymphoma with hypodense nodules of variable size
• Biliary tree  

image Cholangitis caused by opportunistic infections

– Intrahepatic and extrahepatic biliary strictures with papillary stenosis: Bile ducts may appear thickened and enhancing
– Bile ducts may have beaded appearance very similar to primary sclerosing cholangitis
image Acalculous cholecystitis due to opportunistic infections (e.g., CMV, Cryptosporidium)

– Thickened gallbladder with pericholecystic fluid and stranding
• Spleen

image Splenomegaly in up to 3/4 of AIDS patients without infection or tumor
image Small tiny hypodense foci (microabscesses) usually due to disseminated infection (e.g., Candida, MAI, tuberculosis, coccidioidomycosis, Pneumocystis, etc.)
image Larger hypodense lesions might still be infectious, but AIDS-related lymphoma should also be considered
image Small calcifications (similar to liver) from Pneumocystis
• Stomach, small bowel, and large bowel

image Bowel wall thickening, mucosal hyperemia, and fat stranding surrounding bowel should always raise concern for infection (including opportunistic infections)

– CMV-related ulcerations of bowel may lead to GI tract perforation (one of the most common reasons for emergent abdominal surgery in AIDS patients)
image Most opportunistic infections can involve any segment of GI tract (Cryptosporidium, CMV, MAI, tuberculosis, microsporidium, Clostridium difficile, amebiasis, etc.)

– Difficult to predict pathogen based on distribution, but some organisms have predisposition for certain locations

image CMV and TB tend to involve ileum
image Giardia, microsporidium tend to involve proximal small bowel
image Colon infections often due to CMV, C. difficile, Campylobacter, amebiasis, Salmonella, and Shigella
image Mural thickening of esophagus suggests esophagitis, often due to candidiasis, CMV, or herpes simplex
image Proctitis in homosexual men due to sexual activity may be due to Neisseria gonorrhoeae, chlamydia, or HSV
image Focal mass-like wall thickening anywhere in GI tract should raise concern for malignancy (AIDS-related lymphoma, Kaposi sarcoma)

– Lymphoma associated with intussusceptions
• Lymph nodes

image Mild generalized lymphadenopathy (< 1.5 cm) is usually reactive and may be 1st clue to HIV infection

– May persist for years in absence of symptoms (i.e., persistent generalized lymphadenopathy)
image More significant adenopathy (> 1.5 cm) suggests opportunistic infection (MAI, tuberculosis) or AIDS-related lymphoma/Kaposi sarcoma

– Necrotic mesenteric nodes from MAI or tuberculosis
– Hyperenhancing lymph nodes in Kaposi sarcoma
image AIDS-related lymphoma may be associated with discrete lesions in liver/spleen or focal mass in GI tract

– GI tract most common extranodal site of involvement (75%), most often involving colon, ileum, and stomach
• Kidney

image Bilateral large kidneys with urothelial thickening due to HIV nephropathy
image Focal hypodense lesions could reflect infection (tuberculosis, MAI, fungus) or AIDS-related lymphoma
image Calcifications may be present in setting of Pneumocystis (similar to liver and spleen) or rarely MAI/CMV
• Pancreas

image Opportunistic infections can cause acute pancreatitis and pancreatic duct strictures (e.g., CMV, Cryptococcus, etc.)
• Lungs: Pneumocystis pneumonia (PCP), tuberculosis

Ultrasonographic Findings

• Kidney

image HIV nephropathy: Normal sized or enlarged kidneys with increased echogenicity (kidney > liver)

– May be associated with urothelial thickening in pelvis/intrarenal collecting system
– Parenchymal heterogeneity and loss of corticomedullary differentiation
image Increased resistive index from renal failure
image Hyperechoic foci or calcifications without posterior acoustic shadowing due to Pneumocystis, MAI, or CMV
• Gallbladder

image GB wall thickening may be reactive due to hepatitis or secondary to opportunistic acute acalculous cholecystitis
image Wall thickening and dilation of extrahepatic &/or intrahepatic bile ducts due to AIDS cholangiopathy
• Liver

image Opportunistic infections present as small hypoechoic nodules (microabscesses) scattered throughout liver
image Pneumocystis may result in small hypoechoic nodules or tiny echogenic foci
• GI tract

image Mural thickening of cecum due to CMV colitis
• Lymph nodes

image Necrotic nodes most often due to MAI or tuberculosis

Radiographic Findings

• Radiography

image Splenomegaly may be perceptible on plain radiographs
image ERCP: Distal common bile duct (CBD) strictures or multiple intrahepatic strictures

Fluoroscopic Findings

• Upper GI

image Esophageal ulcers from cytomegalovirus (CMV) esophagitis
image Diffuse mucosal edema from candidiasis

MR Findings

• Hepatic and GI tract lymphomas

image Low signal on T1WI, high signal on T2WI

DIFFERENTIAL DIAGNOSIS

Lymphoma Unrelated to HIV/AIDS

• Nodal involvement more common, unlike AIDS, where extranodal involvement is disproportionately common
• AIDS-related lymphoma often aggressive with widespread dissemination, whereas non-AIDS related lymphoma may present with early stage disease confined to nodes

Biliary Hamartomas

• Multiple small cystic lesions scattered throughout liver
• May mimic hepatic microabscesses, but patients are asymptomatic without signs of infection

Sarcoidosis

• May present with multiple small hypodense lesions in liver and spleen (mimicking microabscesses)
• Upper abdominal adenopathy frequently present, and may be mistaken for HIV-related adenopathy
• Mediastinal and hilar lymphadenopathy, characteristic lung disease, and lack of symptoms may allow distinction

Castleman Disease

• Angiofollicular hyperplasia of lymph nodes associated with herpes virus 8
• Either solitary or multicentric
• Hypervascular lymph nodes on CECT
• Predilection for left paraaortic nodes

PATHOLOGY

General Features

• Etiology

image HIV results in immunodeficiency through infection and lysis of CD4(+) T cells
image HIV-infected patients have an increased risk of developing malignancies, particularly when coinfected by Epstein-Barr virus, herpesvirus, or papillomavirus

– Incidence of AIDS-defining malignancies (AIDS-related non-Hodgkin lymphoma, Kaposi sarcoma) has dramatically ↓ with antiretroviral therapy
– Risk of other malignancies, which are often atypically aggressive and occur at younger ages than normal, still higher in HIV patients
– Non-Hodgkin lymphoma

image AIDS-defining malignancy (usually CD4 count < 100) that includes several types of lymphoma, including diffuse large B-cell and Burkitt lymphoma
image Strong tendency to arise in extranodal sites (especially GI tract), involve unusual locations, and present with advanced disease
image Median survival < 6 months
– Kaposi sarcoma

image Low-grade soft tissue sarcoma of vascular origin associated with HHV-8 infection
image Infections more common in HIV patients even with CD4 counts > 200, although risk increases substantially with lower CD4 counts

– Many different AIDS-defining infections, including disseminated MAI, tuberculosis, Pneumocystis infection, recurrent bacterial pneumonias, persistent Cryptosporidium infection, chronic HSV, etc.

image Most occur when CD4 count < 200, but can rarely occur at higher CD4 counts
– Abdominal disorders account for up to 2/3 of hospital admissions in HIV patients
• Associated abnormalities

image Opportunistic infections
image Kaposi sarcoma, lymphoma, or leukemia

Staging, Grading, & Classification

• Extranodal lymphoma in liver is stage 4

Gross Pathologic & Surgical Features

• Kaposi sarcoma

image Reddish-purple patches on skin
image Visceral organ involvement in 75% of patients
image Reddish irregular masses in periportal distribution in liver
• Lymphomas

image Usually extranodal and high-grade B-cell lymphomas or Burkitt lymphoma
image 50% of lymphoma patients have liver, GI tract, or splenic involvement
image Multifocal white to tan nodules within liver
• Associated opportunistic infections

image CMV and C ryptosporidium cause biliary infections and strictures
image MAI leads to multiple microabscesses in liver and spleen with necrotic nodes

Microscopic Features

• High-grade lymphomas e.g., B cell or Burkitt
• Malignant spindle cells with slit-like vascular spaces in Kaposi sarcoma

CLINICAL ISSUES

Presentation

• Most common signs/symptoms

image Acute HIV infection may resemble mononucleosis, with fever, headaches, and body aches
image Many patients with chronic HIV infection asymptomatic when effectively treated with antiretrovirals

– Skin abnormalities and mild constitutional symptoms possible even without immunosuppression
image Patients with advanced HIV/AIDS and immunosuppression may experience symptoms related to opportunistic infections (diarrhea, cough/shortness of breath, abdominal pain, etc.)

– Some patients experience wasting syndrome with profound weight loss and chronic diarrhea
– Odynophagia and dysphagia due to esophageal involvement
• Other signs/symptoms

image Patients with low CD4 counts frequently pancytopenic (anemia, thrombocytopenia, and lymphopenia)
image Generalized lymphadenopathy and splenomegaly common even in absence of active infection
• Clinical profile

image Clinical profile varies from country to country

– HIV in developing world spread primarily by vaginal sex (small proportions due to IV drug abuse and perinatal transmission)
– HIV in USA disproportionately associated with IV drug abuse and homosexual sexual contact

Demographics

• Age

image Primarily adults, but perinatal transmission possible
• Gender

image Worldwide most cases in heterosexuals, with F > M
• Epidemiology

image > 35 million affected worldwide
image 27% of AIDS patients have Kaposi sarcoma
image Renal involvement with AIDS in 6-11% of patients

Natural History & Prognosis

• Multiple opportunistic infections and AIDS-related tumors unless antiretroviral drugs used to suppress HIV
• AIDS defined as CD4 < 200 or development of AIDS-defining illness (either infection or malignancy)

Treatment

• Antiretroviral drugs to preserve immune status
• Antibiotics for bacterial infections and antiviral drugs for CMV infection

DIAGNOSTIC CHECKLIST

Consider

• Possibility of AIDS-related lymphoma when confronted by lymphadenopathy and bulky masses in liver or GI tract

Image Interpretation Pearls

• MAI and tuberculosis are often associated with necrotic lymphadenopathy
• Kaposi sarcoma associated with hypervascular retroperitoneal nodes and periportal liver lesions

image
(Left) Sagittal ultrasound demonstrates a normal-sized right kidney image, which is markedly echogenic, compatible with the patient’s known HIV nephropathy. Unlike other forms of chronic renal failure, the kidneys in HIV nephropathy are often normal in size or enlarged.
image
(Right) Transverse ultrasound demonstrates innumerable tiny calcifications in the spleen of an HIV patient, representing the sequelae of the patient’s known prior Pneumocystis infection.
image
(Left) Coronal CECT in an AIDS patient demonstrates diffuse mass-like wall thickening and aneurysmal dilatation of a loop of small bowel image in the left lower quadrant with internal enteric contrast image. Note the extensive lymphadenopathy image more superiorly. These findings are compatible with the patient’s biopsy-proven AIDS-related non-Hodgkin lymphoma.

image
(Right) Axial CECT in an AIDS patient demonstrates extensive mesenteric lymphadenopathy image found to represent AIDS-related non-Hodgkin lymphoma.
image
(Left) Axial CECT in an AIDS patient illustrates multiple hepatic masses image, including a mass with internal hemorrhage image, which were proven to be non-Hodgkin lymphoma. An unusual feature in this case is the mild obstruction of the intrahepatic bile ducts image.

image
(Right) Longitudinal ultrasound in a patient with AIDS demonstrates a large hypoechoic mass image. Biopsy revealed this to represent AIDS-related B-cell non-Hodgkin lymphoma.
image
Axial CECT in a 34-year-old man with a history of AIDS and weight loss reveals multifocal hypodense masses image in the liver and spleen.

image
Axial CECT in the same patient demonstrates the multifocal hypodense masses image, these seen in the abdominal nodes. These findings were found to reflect non-Hodgkin lymphoma.
image
Axial CECT in a 36-year-old man who presented with a history of AIDS demonstrates widespread thoracoabdominal lymphadenopathy image, with many of the nodes having a hyperdense (hypervascular) appearance characteristic of involvement by Kaposi sarcoma.
image
Axial CECT in the same patient illustrates the thoracoabdominal lymphadenopathy image of this patient.
image
Axial NECT shows multiple calcified granulomas image within the left kidney, due to healed infection with Pneumocystis carinii.
image
Axial CECT shows a hypodense mass image in the kidney with multiple enlarged abdominal nodes image in a patient with AIDS-related lymphoma.
image
Ultrasound in an AIDS patient demonstrates a hypoechoic mass image in the spleen. The imaging findings on ultrasound are nonspecific, but this was biopsied and shown to represent non-Hodgkin lymphoma.
image
Coronal CECT in an AIDS patient with CD4 < 100 demonstrates extensive retroperitoneal lymphadenopathy image, found to represent AIDS-related non-Hodgkin lymphoma.
image
Sagittal ultrasound demonstrates a mildly enlarged, markedly echogenic right kidney in a patient with known HIV nephropathy. Unlike other forms of chronic renal failure, the kidneys in HIV nephropathy are often normal in size or enlarged.
image
Axial CECT in an AIDS patient with a very low CD4 count demonstrates a necrotic lymph node image in the right upper quadrant. This was found to be chronic MAI infection.
image
Longitudinal power Doppler ultrasound of the lower abdomen in a 33-year-old man with a known history of AIDS and a 2-month history of abdominal and pelvic pain and weight loss shows a large hypoechoic mass image just anterior to the bladder, with prominent internal flow.
image
Transverse power Doppler ultrasound in the same patient illustrates a prominent feeding vessel to the mass. Biopsy revealed Burkitt lymphoma, a common subtype in AIDS patients.
image
Longitudinal ultrasound in an AIDS patient with liver dysfunction shows innumerable small echogenic foci image within the liver. These are healed, calcified granulomas that have resulted from hepatic infection with Mycobacterium avium complex.
image
Axial CECT in a 36-year-old man with AIDS shows widespread thoracoabdominal lymphadenopathy image, with many of the nodes having a hyperdense (hypervascular) appearance that is characteristic of involvement by Kaposi sarcoma.

SELECTED REFERENCES

1. Tonolini, M, et al. Mesenterial, omental, and peritoneal disorders in antiretroviral-treated HIV/AIDS patients: spectrum of cross-sectional imaging findings. Clin Imaging. 2013; 37(3):427–439.

 

Yang, J, et al. AIDS-Related Non-Hodgkin Lymphoma: Imaging Feature Analysis of 27 Cases and Correlation with Pathologic Findings. Asian Pac J Cancer Prev. 2014; 15(18):7769–7773.

Lee, WK, et al. CT appearances of abdominal tuberculosis. Clin Radiol. 2012; 67(6):596–604.

Aris, F, et al. AIRP best cases in radiologic-pathologic correlation: Mycobacterium avium-intracellulare complex enteritis. Radiographics. 2011; 31(3):825–830.

Tonolini, M, et al. Acute HIV-related gastrointestinal disorders and complications in the antiretroviral era: spectrum of cross-sectional imaging findings. Abdom Imaging. 2013; 38(5):994–1004.

Kehagias, I, et al. A rare case of intussusception leading to the diagnosis of acquired immune deficiency syndrome: a case report. J Med Case Reports. 2009; 3:61.

Nunweiler, CG, et al. The imaging features of nontuberculous mycobacterial immune reconstitution syndrome. J Comput Assist Tomogr. 2009; 33(2):242–246.

Sriaroon, C, et al. Diffuse intra-abdominal granulomatous seeding as a manifestation of immune reconstitution inflammatory syndrome associated with microsporidiosis in a patient with HIV. AIDS Patient Care STDS. 2008; 22(8):611–612.

Symeonidou, C, et al. Imaging and histopathologic features of HIV-related renal disease. RadioGraphics. 2008; 28:1339–1354.

Knysz, B, et al. Non-Hodgkin’s lymphoma as a rare manifestation of immune reconstitution disease in HIV-1 positive patients. Postepy Hig Med Dosw (Online). 2006; 60:547–551.

Slaven, EM, et al. The AIDS patient with abdominal pain: a new challenge for the emergency physician. Emerg Med Clin North Am. 2003; 21(4):987–1015.

Wang, NC, et al. Intussusception as the initial manifestation of AIDS associated with primary Kaposi’s sarcoma: a case report. J Formos Med Assoc. 2002; 101(8):585–587.

Bernabeu-Wittel, M, et al. Etiology, clinical features and outcome of splenic microabscesses in HIV-infected patients with prolonged fever. Eur J Clin Microbiol Infect Dis. 1999; 18(5):324–329.

Sud, A, et al. Epstein-Barr virus induced non-Hodgkin’s lymphoma as a presenting manifestation of acquired immune deficiency syndrome. J Assoc Physicians India. 1999; 47(4):442–443.

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