Imaging Spectrum of Granulomatous Diseases of the Abdomen and Pelvis

Abstract

A granuloma is a compact organization of mature macrophages that forms because of persistent antigenic stimulation. At the microscopic level, granulomas can undergo various morphologic changes, ranging from necrosis to fibrosis, which along with other specialized immune cells define the appearance of the granulomatous process. Accordingly, the imaging features of granulomatous diseases vary and can overlap with those of other diseases, such as malignancy, and lead to surgical excisions and biopsy. However, given the heterogeneity of granulomas as a disease group, it is often hard to make a diagnosis on the basis of the histopathologic features of granulomatous diseases alone owing to overlapping microscopic features. Instead, a multidisciplinary approach is often helpful. Radiologists need to be familiar with the salient clinical manifestations and imaging findings of granulomatous diseases to generate an appropriate differential diagnosis.

^©RSNA, 2021

SA-CME LEARNING OBJECTIVES

After completing this journal-based SA-CME activity, participants will be able to:

• ■ Recognize clinical manifestations and imaging findings of granulomatous diseases of the abdomen and pelvis.

• ■ Describe various pathologic entities that granulomas may mimic.

• ■ Implement a multidisciplinary team approach to reach an accurate diagnosis of the granulomatous disease.

Introduction

Granulomatous diseases can pose a diagnostic dilemma at imaging simply because of their systemic manifestations and multiorgan involvement, with potential to mimic multiple other disease entities, including malignancy. A granuloma is a mass-forming lesion that develops because of chronic inflammation evoked by poorly degradable or unknown antigens. The human immune system responds to persistent antigenic stimulation and creates a protective barricade of activated macrophages, Langerhans cells, and lymphocytes. Granulomatous disorders include a gamut of pathologic entities with protean clinical manifestations and outcomes (1). A pathologist’s approach to granulomas identified in biopsy specimens is based primarily on etiologic differences and the presence of a foreign body giant cell reaction. The latter variety, also known as immune granulomas, is then further divided into necrotizing and nonnecrotizing granulomas (2).

There have been numerous attempts to classify granulomas, mainly on the basis of histopathologic and etiologic features; however, classifying these diseases is difficult and often confusing. Ultimately, clinical, imaging, and histopathologic correlations with multidisciplinary team input often help in reaching a diagnosis (2). In this article, we review various granulomatous entities that affect the abdomen and pelvis and highlight their pertinent imaging features by using multimodality diagnostic tools for the general radiologist.

Pathophysiologic Features of Granuloma Formation

Inflammation is the rudimentary means by which the immune system mounts a defense against pathogens and foreign antigens. In addition, this process allows the body to repair any tissue that is damaged during the eradication of the foreign antigen. Chronic inflammation typically develops over weeks and is characterized by the recruitment of more specialized immune cells, mainly macrophages. Certain antigens can cause specialized chronic inflammation, also known as granulomatous inflammation, that results from cell-mediated immunity (2,3). These antigens can be infectious or noninfectious, and at times the inciting agent remains unidentified (3). The initial encounter with a phagocyte results in elimination of the foreign antigen. However, failure to eradicate that stimulus may promote granuloma formation (Fig 1).

Figure 1.

Diagram illustrates the simplified version of granuloma formation in sarcoidosis. A, Antigen triggers the mast cells to release tissue necrosis factor (TNF), which in turn activates the neutrophils in the bloodstream, which then activate the monocytes. B, Tissue macrophages take the antigen and release tissue necrosis factor alpha, which initiates upregulation of activation and adhesion molecules. C, Activated macrophages produce chemokine ligands (monocyte chemoattractant protein 1 [MCP-1], chemokine [C-C motif] ligand 20 [CCL20], C-X-C motif chemokine ligand 10 [CXCL10], C-X-C motif chemokine ligand 16 [CXCL16]) by means of stimulation of both tissue necrosis factor alpha and natural killer (NK) cell–derived interferon gamma (IFN-γ), thereby attracting Th1 and type 17 T-helper (Th1/17) cells, monocytes, regulatory T cells (Tregs), and B cells. D, The interferon gamma produced by local natural killer cells and gamma delta T (γδT) cells further activates resident tissue histiocytes and dendritic cells. E, Activated antigen-loaded dendritic cells then migrate to peripheral lymph nodes via the lymphatic channels. F, The dendritic cell produces interleukin-12 (IL-12) and presents antigen to the naïve CD4 T cell. Under the influence of interleukin-12, naïve T cells mature into Th1 cells. Activated Th1 cells then produce interleukin-2 (IL-2), which expands the T-cell population. Then, these Th1 cells traffic to sites of inflammation and aid in the formation of granuloma by maturing macrophages. Over the course of days, mature granuloma, along with other cells, is formed if antigen persists.

Although macrophages are the predominant cells involved in granulomatous inflammation, certain T-cell subtypes, particularly type 1 T-helper (Th1) cells, mediate most cascades. Th1 cells secrete interferon gamma and other cytokines, which then convert macrophages to active tissue macrophages (also called epithelioid histiocytes), making them more effective in killing intracellular antigens. Epithelioid cells can then fuse together to form multinucleated giant cells, a hallmark of granulomas (4).

As granulomas mature, they can develop either necrosis or fibrosis (4). At histopathologic analysis, central necrosis is seen with certain types of granulomatous infections, including Mycobacterium tuberculosis, whereby necrosis develops owing to uncontrolled infection and tissue necrosis factor dysregulation and is often caseous (ie, cheese like) (4). At imaging, the necrosis usually manifests as an area of central liquefaction with peripheral enhancement.

Long-standing dysregulated inflammation driven by fibrotic cytokines (predominantly interleukin-4 and interleukin-13) feeding into tumor growth factor–β1 fibrotic pathways leads to tissue fibrosis and is predominantly mediated by the type 2 T-helper cell pathway (5). Fibrosis can help sequester the offending agent but often leads to end-organ damage such as hepatic cirrhosis in schistosomiasis (4). Angiogenesis led by vascular endothelial growth factor A can result in dysregulated neovascularization in fibrotic scars (4). At imaging, fibrotic inflammation usually results in a physiologic alteration such as urinary obstruction due to ureteral tethering from retroperitoneal fibrosis. Another special pathologic process known as xanthogranuloma can result in a specific group of disorders (histiocytoses) that at histologic analysis demonstrate an abundance of lipid-laden macrophages or foamy histiocytes with CD68-positive staining (6).

Granulomatous Disorders of the Abdomen and Pelvis

Granulomas have not been uniformly categorized into a strict taxonomy scheme, and existing classifications can be confusing. Granulomas are commonly classified on the basis of infectious and noninfectious stimulating antigens. Some have categorized them according to their morphology—specifically, whether the necrosis is apparent or there is epithelioid transformation. Other classifications are based on whether the macrophage turnover in granuloma is high versus low (1,2,4,5). For simplification, we have classified granulomas on the basis of their causal mechanism into infectious, noninfectious, and foreign-body granulomas.

Since foreign body granulomas often have an identifiable cause through the patient’s history and a nidus of large nonphagocytizable particles such as sutures, they are not reviewed in detail in this article because they are often not a diagnostic dilemma (1,2). However, xanthogranulomatous disorders are a separate entity and are discussed because of their unique granulomatous features at both imaging and histopathologic analysis.

Granulomatous Infections

Infections are the most common cause of disseminated granulomatous disease. Owing to advances in molecular diagnostics, there is continued discovery of the inciting agents of granulomatous infections previously classified as idiopathic. One such example is Whipple disease, a granulomatous infection caused by Tropheryma whippelii (5). Granulomatous infections are caused by any infectious organism. These organisms can act both as foreign bodies and as antigens for immunologic responses and result in granuloma formation.

Granulomas related to various infections can have different immunoregulatory mechanisms that govern their formation and resolution and hence may have different imaging appearances. Common infections that either lead to granulomas or demonstrate a histiocytic response within the abdomen and pelvis are discussed and further summarized in Table 1.

Table 1:

Granulomatous Infections

Bacterial Granulomatous Infections

Granulomatous infections related to bacteria are usually caused by intracellular bacteria. Human cells are able to differentiate the bacteria from host cells and thereby direct the intracellular machinery to clear the infection. However, some intracellular bacteria have adapted to the human intracellular environment such that they can survive for long periods and incite a granulomatous response (3). The imaging findings of some of the bacterial granulomatous infections, notably M tuberculosis, are described in the following section.

M tuberculosis.—Abdominal tuberculosis (TB) can involve many facets of the abdomen and pelvis, including the peritoneum, solid viscera, hollow viscera (eg, bladder and bowel), and lymph nodes. It comprises 5% of all TB cases worldwide (7), and up to 15% of these cases can involve concurrent pulmonary TB. Isolated abdominal TB can be challenging to diagnose. Tuberculous peritonitis manifests in three forms: wet type (>90% cases), dry type, and fixed fibrotic type (8). A rare morphologic form, encapsulating sclerosing peritonitis or “cocoon abdomen,” also has been described (8).

With wet-type tuberculous peritonitis, US, CT, and MRI may depict free or loculated ascites (7). US may reveal debris or fibrin strands within the ascites, implying an exudative cause (7,8). At CT, the ascites may be high in attenuation, ranging between 20 HU and 45 HU, owing to high protein and cellular content (7,8). Smooth peritoneal thickening and enhancement are present in nearly all patients with peritoneal TB (9).

With dry-type tuberculous peritonitis, there can be omental caking and peritoneal thickening that can mimic carcinomatosis; however, omental nodularity is exceedingly rare in TB (7). Caseous low-attenuation lymphadenopathy can help suggest the diagnosis; however, Whipple disease, metastatic disease, and pyogenic infection can have central necrosis and mimic low-attenuation caseous lymphadenopathy (7,8).

With the fixed fibrotic type of tuberculous peritonitis, there are matted bowel loops with omental caking and sometimes loculated ascites. The matted and thickened bowel loops usually demonstrate adjacent stellate mesenteric thickening. Strict classification is rarely applicable owing to overlapping imaging features, as shown in Figure 2. A definitive diagnosis requires ascitic fluid analysis and potentially omental or peritoneal biopsy, with demonstration of acid-fast bacilli (8).

Figure 2.

Tuberculous peritonitis in a 28-year-old man with abdominal pain and bloating of 4 weeks’ duration. Axial CT image shows bilateral renal atrophy, with caliectasis secondary to renal TB (arrow). Also note the loculated ascites (*), with smooth thickening and enhancement of the peritoneum consistent with encapsulated peritonitis of TB (cocoon abdomen).

The most common site of TB involvement in the gastrointestinal tract is the ileocecum, followed by the jejunum and colon (8). Common morphologic features are ulcers and erosions, with fistulas and sinus tracts (bowel-bowel and bowel-adjacent organs) seen during the later stages. At small-bowel follow-through fluoroscopy, the acute stage of ileocecal TB may involve thickening and gaping of the ileocecal valve, with narrowing of the terminal ileum and resultant hypermotility of the cecum. In the chronic stages of TB, the ileocecal valve becomes fixed and incompetent owing to fibrosis and a narrowed terminal ileum; this finding is also known as the Stierlin sign (8). The cecum may appear conical and truncated, and it may pull away from the right iliac fossa. At CT, there is marked circumferential thickening of the terminal ileum and cecum, and the wall thickness can measure up to 3 cm (8). An asymmetrically thickened ileocecal valve and terminal ileum are usually associated with hypoattenuating mesenteric adenopathy greater than 1 cm, and other luminal strictures can be seen (7,8).

Hepatosplenic TB is most often miliary owing to disseminated pulmonary TB and is commonly micronodular (nodules measuring <2 mm). The macronodular pattern is due to hematogenous spread via the portosystemic circulation from adjacent abdominal viscera (7,8).

Disseminated TB can affect almost any organ, with the genitourinary system most commonly involved. Granulomatous prostatitis appears as a complication of bacillus Calmette-Guérin immunotherapy administered for bladder cancer. The pattern can be diffuse, nodular, or cystic with a mural nodule; the diffuse pattern is the most common. Granulomatous prostatitis has a propensity for the peripheral zone and thus can mimic prostate adenocarcinoma in morphology and location. T2-weighted MR images show hypointense nodules in the peripheral zone that may or may not enhance and can mimic malignancy (Fig 3). Basically, any lesion scored higher than Prostate Imaging Reporting and Data System (PI-RADS) category 3 warrants a recommendation for tissue diagnosis; however, widening of the prostatic urethra can be a useful clue in differentiating granulomatous bacillus Calmette-Guérin immunotherapy–related prostatitis from malignancy (9).

Figure 3.

Granulomatous prostatitis in a 63-year-old man with a history of bacillus Calmette-Guérin immunotherapy for nonmuscle invasive bladder cancer. Transaxial MR images of a Prostate Imaging Reporting and Data System (PI-RADS) category 5 lesion (arrows) in the right posterior peripheral zone show hypointensity at T2-weighted (A) and apparent diffusion coefficient (B) imaging, enhancement at contrast-enhanced imaging (C), and type 3 perfusion kinetics at perfusion map imaging (D).

Atypical Mycobacterial Infections.—Mycobacterium avium-intracellulare complex (MAC) and related nontuberculous atypical mycobacteria can cause a variety of granulomatous infections, with MAC being the most common organism. In immunocompetent hosts, MAC most often infects the lungs. In contrast, disseminated infection may manifest in immunocompromised hosts, especially patients with AIDS (10). Abdominal involvement with MAC is rare and most often results from disseminated infection in AIDS. At CT, multiple enlarged, usually markedly hypoattenuating (sometimes with soft-tissue attenuation) lymphadenopathies in conjunction with hepatosplenomegaly and diffuse jejunal wall thickening are seen (11). Ascites is rarely present with MAC. Disseminated infection in patients who do not have AIDS usually signifies an underlying immune deficiency or immunosuppression. In immunocompetent patients, MAC infection can mimic malignancy and warrants a tissue specimen–based diagnosis (Fig 4a) (11).

Figure 4a.

Atypical mycobacterial infections. (a) Axial CT image in a 27-year-old man with AIDS and disseminated MAC who was found to have bulky lymphadenopathy shows internal areas of hypoattenuation (yellow outline), a typical finding of disseminated MAC. (b) Cholangiopancreatographic images in a 70-year-old woman with obstructive jaundice, in whom abdominal MRI (not shown) demonstrated circumferential soft tissue narrowing the common hepatic artery, with perihilar nodular soft-tissue thickening of the right hepatic duct. Endoscopic retrograde cholangiopancreatographic image (left) shows the tight mid-duct stricture (blue arrow), with correlating findings (white arrow) on the coronal MR cholangiopancreatographic image (right). Also note the mild intrahepatic biliary dilatation (yellow arrows). (c) Axial (left) and coronal (right) contrast-enhanced CT images of the abdomen and pelvis in a 56-year-old man who presented with a left-sided iliofemoral mass show a large fluid collection–abscess involving the left iliopsoas muscle (*), with extension into the anterior (white arrow) and posterior (yellow arrow) muscle compartment of the thigh. The abscess was aspirated under imaging guidance; final microbiologic findings were consistent with MAC infection.

Figure 4b.

Atypical mycobacterial infections. (a) Axial CT image in a 27-year-old man with AIDS and disseminated MAC who was found to have bulky lymphadenopathy shows internal areas of hypoattenuation (yellow outline), a typical finding of disseminated MAC. (b) Cholangiopancreatographic images in a 70-year-old woman with obstructive jaundice, in whom abdominal MRI (not shown) demonstrated circumferential soft tissue narrowing the common hepatic artery, with perihilar nodular soft-tissue thickening of the right hepatic duct. Endoscopic retrograde cholangiopancreatographic image (left) shows the tight mid-duct stricture (blue arrow), with correlating findings (white arrow) on the coronal MR cholangiopancreatographic image (right). Also note the mild intrahepatic biliary dilatation (yellow arrows). (c) Axial (left) and coronal (right) contrast-enhanced CT images of the abdomen and pelvis in a 56-year-old man who presented with a left-sided iliofemoral mass show a large fluid collection–abscess involving the left iliopsoas muscle (*), with extension into the anterior (white arrow) and posterior (yellow arrow) muscle compartment of the thigh. The abscess was aspirated under imaging guidance; final microbiologic findings were consistent with MAC infection.

Figure 4c.

Atypical mycobacterial infections. (a) Axial CT image in a 27-year-old man with AIDS and disseminated MAC who was found to have bulky lymphadenopathy shows internal areas of hypoattenuation (yellow outline), a typical finding of disseminated MAC. (b) Cholangiopancreatographic images in a 70-year-old woman with obstructive jaundice, in whom abdominal MRI (not shown) demonstrated circumferential soft tissue narrowing the common hepatic artery, with perihilar nodular soft-tissue thickening of the right hepatic duct. Endoscopic retrograde cholangiopancreatographic image (left) shows the tight mid-duct stricture (blue arrow), with correlating findings (white arrow) on the coronal MR cholangiopancreatographic image (right). Also note the mild intrahepatic biliary dilatation (yellow arrows). (c) Axial (left) and coronal (right) contrast-enhanced CT images of the abdomen and pelvis in a 56-year-old man who presented with a left-sided iliofemoral mass show a large fluid collection–abscess involving the left iliopsoas muscle (*), with extension into the anterior (white arrow) and posterior (yellow arrow) muscle compartment of the thigh. The abscess was aspirated under imaging guidance; final microbiologic findings were consistent with MAC infection.

Catscratch Disease.—Catscratch disease is caused by infection with Bartonella henselae. Other human manifestations include bacillary angiomatosis and peliosis in patients who have AIDS. At histopathologic analysis, a key finding of catscratch disease is necrotizing granuloma with microabscesses surrounded by histiocytes, lymphocytes, and dense fibrosis. These microabscesses are often stellate-shaped bacteria that usually can be demonstrated by using Warthin-Starry stain (12). Abdominal manifestations appear in a disseminated form (5%–10%), whereby multiple nodules appear in the liver and spleen. These nodules are hypoechoic at US (Fig 5) and hypoattenuating at CT. Spleen or liver enlargement may be present (12,13).

Figure 5.

Disseminated bartonellosis in a 17-year-old adolescent boy. Gray-scale US image of the liver shows multiple hypoechoic masses (arrows) consistent with disseminated bacillary angiomatosis. Similar lesions were seen in the spleen (not shown).

Actinomycosis.—Actinomycosis is caused by organisms of the genus Actinomyces. A close relative is another gram-positive aerobic organism, Nocardia (14). Both Actinomyces and Nocardia behave like fungi in their growth patterns and cause fungus-like invasive indolent infections. Actinomycosis has an association with long-standing indwelling intrauterine contraceptive devices. Any pelvic inflammatory disease associated with intrauterine device use should raise suspicion for actinomycosis. These infections are locally invasive and destroy fascial planes extending into the adjacent viscera or abdominal wall. In addition, they can mimic malignancy and have been reported to cause Fitz-Hugh and Curtis syndrome (14).

Spirochetes.—Spirochetes are long coiled bacteria that cause various human diseases, including syphilis, yaws, leptospirosis, Lyme disease, and relapsing fever. Among these, syphilis and leptospirosis tend to involve the abdomen more commonly. Syphilis is caused by Treponema pallidum, and the infection is characterized by chancroid at the site of primary inoculation (primary syphilis). Abdominal manifestations are usually seen with secondary syphilis; however, rarely, the site of primary inoculation can be oral or rectal mucosa infected during oral or anal sex. Rectal syphilis can mimic rectal cancer, and patients who participate in high-risk sexual behavior (such as men who have sex with men) should be screened for rectal syphilis (15). Approximately 25%–50% of individuals can have coexistent HIV and syphilis infections.

Although the true prevalence of anorectal syphilitic chancre is underreported, this lesion is the third most common cause of symptomatic anorectal infections among homosexual men after herpes simplex infection and gonorrhea (15). Widespread syphilitic vasculitis can lead to end-organ inflammation in various viscera. Aneurysmal aortic dilatation can develop with syphilitic aortitis, which is commonly described in the ascending aorta but can also involve other aortic segments (16).

Fungal Granulomatous Infections

Gastrointestinal and genitourinary fungal infections (ie, mycoses) are most commonly the result of disseminated disease and usually caused by primary invasive fungal pathogens, including Histoplasma capsulatum, Coccidioides immitis, Blastomyces dermatitidis, and Paracoccidioides brasiliensis. Secondary mycotic organisms, which most often cause opportunistic infections, include Candida and Aspergillus species, Cryptococcus neoformans, Pneumocystis jirovecii, and Mucorales (14). Granuloma formation occurs in immunocompetent individuals, in whom the infection results in epithelioid cell granulomas, with central coagulative necrosis most often seen in the lungs.

Histoplasmosis and coccidioidomycosis are the main granulomatous mycoses in immunocompetent individuals (17). Fungal granulomas involving the abdomen are rare, as these infections usually result in lung granulomas after the spores are inhaled. Rarely, the infection disseminates and may result in granuloma formation in other parts of the body. The most common manifestation of coccidioidomycosis is peritonitis that can mimic TB or malignancy. Infections of the other abdominal organs are rarely reported (18). Fungal peritoneal involvement by Candida species can also occur via contiguous spread, especially in patients undergoing peritoneal dialysis or after the leakage of enteric contents. It manifests as peritoneal thickening and enhancement, and omental stranding with or without nodularity (14).

Fungi, most commonly H capsulatum and Candida species, can enter the portal venous system and infiltrate the liver and spleen. In histoplasmosis, infection of the macrophages occurs and then circulates to other reticuloendothelial cells and results in granuloma formation with an abundance of macrophages and lymphocytes and infrequent necrosis. During the initial phases of infection, hepatosplenomegaly and hypoattenuating lymphadenopathy may be seen at imaging (Fig 6a). The predilection for the reticuloendothelial system manifests as calcifications in the setting of healed histoplasmosis within the liver, spleen, lymph nodes, and adrenal glands (19).

Figure 6a.

Fungal infections in three patients. (a) Axial contrast-enhanced chest (left) and abdominal (right) CT images in a 39-year-old woman with disseminated histoplasmosis show numerous miliary nodules (circle) and hypoattenuating liver lesions (arrows), which were sampled at biopsy and found to be consistent with histoplasmosis. (b) Axial T2-weighted MR image (left) and retrograde urethrogram (right) in a 60-year-old man with subacute disseminated histoplasmosis show focal disruption with a fluid collection (yellow arrows) in the region of the membranous urethra that demonstrates communication (white arrows) with the rectum (*).(c) Transaxial CT images in a 46-year-old woman with disseminated coccidioidomycosis show a necrotic mass (white arrow) in the splenic hilum, with multiple soft-tissue abscesses (blue arrows).

Candidal granulomas mimic catscratch granulomas owing to the presence of a central abscess with surrounding histiocytes and fibrous scars that manifest as discrete microabscesses at imaging (20). Fungal abscesses are usually subcentimeter hypoattenuating or hypoechoic foci at CT and US, respectively. At MRI, they are usually diffusion restricting and demonstrate T2 hyperintensity with central T1 hypointensity.

At US, four distinct patterns of hepatic candidiasis are described according to various stages of granulomatous inflammation leading to fibrosis. The first pattern is that of central echogenicity surrounded by a hypoechoic halo (“bull’s-eye”). The second pattern is that of a peripheral hypoechoic rim surrounding an echogenic wheel with a central hypoechoic region (“wheel-within- a-wheel”). The third pattern consists of homogeneous hypoechoic nodules, and the fourth pattern, echogenic scars (14,19).

Renal or bladder involvement by granulomatous fungal infections can mimic pyelonephritis or cystitis at imaging, or it may consist of discrete abscesses and pseudotumors resulting from a granulomatous response. Chronic infections may result in renal scarring, caliectasis, hydronephrosis, and fistula formation in the skin and adjacent organs (21) (Fig 6b).

Figure 6b.

Fungal infections in three patients. (a) Axial contrast-enhanced chest (left) and abdominal (right) CT images in a 39-year-old woman with disseminated histoplasmosis show numerous miliary nodules (circle) and hypoattenuating liver lesions (arrows), which were sampled at biopsy and found to be consistent with histoplasmosis. (b) Axial T2-weighted MR image (left) and retrograde urethrogram (right) in a 60-year-old man with subacute disseminated histoplasmosis show focal disruption with a fluid collection (yellow arrows) in the region of the membranous urethra that demonstrates communication (white arrows) with the rectum (*).(c) Transaxial CT images in a 46-year-old woman with disseminated coccidioidomycosis show a necrotic mass (white arrow) in the splenic hilum, with multiple soft-tissue abscesses (blue arrows).

Renal involvement can manifest clinically as renal failure due to granulomatous interstitial nephritis. A fungus ball may cause obstructive uropathy that, despite having a masslike configuration, does not demonstrate granulomatous inflammation.

Genital involvement can manifest as an abscess or pseudotumors from a granulomatous response to fungal antigen. Prostatic involvement with or without epididymal involvement is most commonly described and can manifest as nodules or abscess. In the absence of epididymal involvement, these nodules can mimic prostate adenocarcinoma when they lack central necrosis within the granuloma (21). On MR images, these granulomas can appear as discrete hypointense nodules with restricted diffusion and dynamic contrast enhancement (22,23). At voiding cystourethrography, dilatation and elongation of the inframontane urethra that differentiate infection from benign prostatic hypertrophy or prostate adenocarcinoma have been described (24). These infections can involve the prostatic urethra and may result in fistula formation in the adjacent organs (21).

Bilateral adrenal fungal infection can cause adrenal insufficiency that can be masslike. Subcutaneous abscesses, phlegmons, and sinus tracts that ensue from spread from the adjacent lymph nodes, bones, and joints can be seen with coccidioidomycosis (Fig 6c) and often require surgical débridement (25).

Figure 6c.

Fungal infections in three patients. (a) Axial contrast-enhanced chest (left) and abdominal (right) CT images in a 39-year-old woman with disseminated histoplasmosis show numerous miliary nodules (circle) and hypoattenuating liver lesions (arrows), which were sampled at biopsy and found to be consistent with histoplasmosis. (b) Axial T2-weighted MR image (left) and retrograde urethrogram (right) in a 60-year-old man with subacute disseminated histoplasmosis show focal disruption with a fluid collection (yellow arrows) in the region of the membranous urethra that demonstrates communication (white arrows) with the rectum (*).(c) Transaxial CT images in a 46-year-old woman with disseminated coccidioidomycosis show a necrotic mass (white arrow) in the splenic hilum, with multiple soft-tissue abscesses (blue arrows).

Other Infections

Another important trematode infection is schistosomiasis (also called bilharziasis). Larvae from the intermediate host, a snail, penetrate the human skin, the definitive host, when it is exposed to infected water. The larvae then travel to the circulation, where they lay eggs in the mesenteric circulation or perivesical venous plexus, depending on the species. The initial response to the larvae is type 1 immunity (usually directed toward clearing the organism); however, as the eggs are laid, there is a shift toward type 2 immunity (commonly seen with helminthic infections and assists with resolution of cell-mediated inflammation), which eventually results in granuloma formation (26). These eggs can be shed into the feces or urine, but the ones that get trapped result in an inflammatory response, which may be seen as intense inflammation at imaging (eg, periportal echogenicity in hepatic schistosomiasis). As the immune system lays the barricade to form a granuloma, fibrosis results to protect the host from toxic egg products (27).

As granulomas mature, calcifications develop in response to dead ova. At imaging, both fibrosis and calcifications imply chronic and/or healed infection (28). Two major abdominal forms of schistosomiasis are hepatosplenic and genitourinary schistosomiases. In hepatosplenic schistosomiasis, eggs deposited in the portal venules lead to periportal fibrosis, cirrhosis, and portal hypertension. With Schistosoma mansoni infection, portal venous wall thickening and increased echogenicity lead to the bull’s-eye pattern or clay pipe stem pattern (Fig 7a) (29). The region of periportal fibrosis can be hypoattenuating at CT, with marked contrast enhancement. With Schistosoma japonicum infection, septal and capsular calcifications can develop and lead to an appearance resembling the carapace of a turtle, referred to as the “turtle-back” sign (29). In contrast, calcifications are not common with S mansoni infection; however, affected patients are usually at greater risk for hepatocellular carcinoma (30).

Figure 7a.

Schistosomiasis in two patients. (a) Gray-scale US images in a 35-year-old Egyptian man with hepatic schistosomiasis show portal venules (arrows) with hyperechoic thickened walls, resulting in the clay pipe stem pattern of periportal fibrosis. CT performed a year later (not shown) depicted liver fibrosis that was presumably related to S mansoni infection, given the bull’s-eye appearance of the portal vein. (b) Transaxial soft-tissue–window CT images of the liver (left) and bladder (right) in a 76-year-old Iraqi woman with schistosomiasis (treated with praziquantel) show a calcified hepatic mass (yellow arrow), indicating liver and bladder involvement. Also note the bladder wall calcifications (black arrow), which indicate prior urinary schistosomiasis.

Genitourinary schistosomiasis is most often caused by Schistosoma hematobium infection, which is endemic to the Middle East and Africa. Although bladder involvement is most common, ureteral involvement is reported in 65% of cases, with the earliest changes seen at excretory urography and characterized by distal ureteral dilatation in the acute phase and stricturing in the chronic phase (31). Ureteral strictures most often occur in the intravesical segment or 2–5-cm distal ureter. Linear-pattern calcifications appear circumferential on axial CT images; this finding is considered to be pathognomonic (28). Urinary bladder involvement during the acute phase of infection can manifest as nodular thickening and later becomes contracted and fibrotic, with a thickened wall and calcifications (Fig 7b). When mass lesions are present, they may be caused by localized granuloma formation or squamous cell carcinoma (28).

Figure 7b.

Schistosomiasis in two patients. (a) Gray-scale US images in a 35-year-old Egyptian man with hepatic schistosomiasis show portal venules (arrows) with hyperechoic thickened walls, resulting in the clay pipe stem pattern of periportal fibrosis. CT performed a year later (not shown) depicted liver fibrosis that was presumably related to S mansoni infection, given the bull’s-eye appearance of the portal vein. (b) Transaxial soft-tissue–window CT images of the liver (left) and bladder (right) in a 76-year-old Iraqi woman with schistosomiasis (treated with praziquantel) show a calcified hepatic mass (yellow arrow), indicating liver and bladder involvement. Also note the bladder wall calcifications (black arrow), which indicate prior urinary schistosomiasis.

Noninfectious Granulomatous Conditions

Granulomatous Vasculitides

Granulomatous vasculitis is a term used to describe vasculitides that share features of necrotizing granulomatous inflammation restricted to the blood vessels. Pathologists often cannot make a definitive diagnosis on the basis of morphology alone; thus, the clinical presentation and the distribution based on imaging findings are more characteristic (32).

On the basis of the 2012 International Chapel Hill Consensus Conference revised nomenclature (33), granulomatous vasculitides can be divided into large-vessel (giant cell arteries and Takayasu arteritis); medium-vessel (mainly polyarteritis nodosa [PAN], which may sometimes be granulomatous); and small-vessel (mainly antineutrophil cytoplasmic antibody [ANCA]–associated vasculitis) vasculitides (Table 2).

Table 2:

Granulomatous Vasculitides

Giant Cell Arteritis.—GCA is the most common chronic systemic vasculitis that exclusively affects patients older than 50 years, with an average onset in those aged 70–80 years (34). GCA most commonly involves the thoracic aorta and its branches, but it can involve the abdominal aorta and its branches as well (34). At histopathologic analysis, arterial intimal thickening with transmural inflammatory cells and frank destruction of the arterial wall by necrosis may be seen.

CT is 73% sensitive and 85% specific for the diagnosis of large-vessel GCA (35). CT images commonly show a thickened arterial wall with late contrast enhancement within the vessel wall, making a portal venous phase or further delayed–contrast phase useful. Complications such as ectasia, aneurysms, and stenoses also can be seen. MRI and MR angiography yield findings similar to those at CT and CT angiography (35). Avidity at FDG PET/CT can be used to assess for inflammation. Standardized uptake values correlate with acute-phase reactants and serum interleukin-6 levels and thus may correlate with disease activity (35).

Takayasu Arteritis.—Takayasu arteritis is a chronic granulomatous vasculitis of unknown cause with a predilection for women younger than 40 years, and it is prevalent among Asian persons. The pathogenesis is poorly understood but involves cell-mediated immune mechanisms that result in chronic granulomatous inflammation similar to GCA (36,37).

Takayasu arteritis has a subacute onset, which often results in a delayed diagnosis. Vascular complications at diagnosis include aneurysms, stenoses, occlusions, and, rarely, dissection. Constitutional symptoms such as fever, fatigue, and weight loss are similar to those of GCA (36,37). Asymmetric, often diminished peripheral pulses characterize this condition as a “pulseless” arteritis, which leads to peripheral end-organ damage such as gangrene or limb claudication (36–38). Arterial stenoses result in audible bruits and discrepant blood pressures (systolic blood pressure, >10-mm Hg difference) between the extremities (36). Abdominal aortic stenosis manifests during the pulseless phase of Takayasu arteritis, affecting the abdomen, with smooth tapering of the aortic caliber; it is one of the important differential diagnoses of midaortic syndrome. Renal artery stenoses can cause malignant (severe) hypertension owing to activation of the renin-angiotensin cascade. Narrowing of the coronary ostia can lead to angina pectoris. Similarly, mesenteric vessel involvement can cause mesenteric ischemia (38).

Polyarteritis Nodosa.—PAN is a systemic necrotizing granulomatous vasculitis that tends to affect medium- to small-sized arteries (larger than arterioles). PAN is usually idiopathic, but in one-third of cases, hepatitis B surface antigen is positive. The disease manifests in the 6th decade of life, with a male predominance, and tends to affect people of European ancestry (39).

In addition to hepatitis B virus, other associated infections, including HIV, are implicated in the pathogenesis of PAN (33,39). At the 2012 Chapel Hill conference (33), PAN was defined as a “necrotizing arteritis of medium or small arteries without glomerulonephritis or vasculitis in arterioles, capillaries, or venules, and not associated with ANCA.” At histopathologic analysis, PAN manifests as necrotizing vasculitis of interlobar and arcuate renal arteries at branch points, with aneurysmal dilatation, fibrinoid necrosis, and neutrophilic infiltration of the vessel walls, often with thrombosis. In later stages, rare granulomas can be seen (32).

The most common sites of PAN involvement in the abdomen are the renal arteries (in 90% of affected patients). Other relatively common involved vascular beds include the gastrointestinal tract, liver, spleen, and pancreas (39).

Imaging, including catheter angiography, CT angiography, and MR angiography, can be used to make the diagnosis in the appropriate clinical context (39–41). A positive conventional abdominal angiography examination is one of the American College of Radiology criteria for the diagnosis of PAN, and findings of multiple small aneurysms are pathognomonic. However, occlusions are more common in patients with a diagnosis of PAN. Aneurysms are usually multiple (≥10 in one visceral circulation), measure 2–5 mm, and predominantly arise at the branching points of visceral arteries. With advances in imaging, early changes of vasculitis that can be missed at invasive catheter angiography are readily detectable at CT angiography and MR angiography (39–41).

Because the kidney is the most commonly affected organ, it may demonstrate end-organ damage manifesting with a striated nephrogram from renal infarcts, potentially mimicking pyelonephritis (39–41). Patients may be found to have spontaneous perirenal and subcapsular hematomas (Wunderlich phenomenon). Hydronephrosis can ensue from detrusor muscle spasm, with vesicoureteral reflux or fibrosis at the ureterovesical junction. As in the kidneys, in the liver, pancreas, spleen, and gallbladder, there may be complications of end-organ damage when these organs are involved by PAN (39).

With PAN, the jejunum is the most commonly involved segment of the bowel. Nonspecific segmental bowel wall thickening can be seen. In some cases of chronic involvement, resultant fibrotic strictures may cause small-bowel obstruction owing to the underlying to evolving vasculitis. Rarely, bowel hemorrhage or perforation can develop (39).

ANCA-associated Vasculitides.—ANCA-associated vasculitis, or ANCA-positive vasculitis, is a rare group of small- to medium-vessel vasculitides that includes GPA, eosinophilic GPA, and microscopic polyangiitis. These vasculitides are characterized by ANCA positivity and manifest with focal necrotizing, crescentic, pauci-immune glomerulonephritis at histopathologic analysis (42). Of note, microscopic GPA is distinguishable from GPA and eosinophilic GPA by the absence of granuloma formation but the presence of necrotizing vasculitis at histopathologic analysis (43). The gastrointestinal tract can be involved in 20%–50% of cases of eosinophilic GPA and 5%–11% cases of GPA (44).

GPA, formerly known as Wegener granulomatosis, is characterized by granulomatous necrotizing vasculitis involving the upper and lower respiratory tract, combined with glomerulonephritis. Abdominal manifestations of GPA are rare and involve the gastrointestinal luminal tract. Abdominal pain is the most common symptom, followed by nausea, vomiting, diarrhea, and hematochezia (44,45). In contrast to their presence in the pulmonary tract, granulomas are rarely identified in the gastrointestinal tract at histopathologic analysis (44,45).

At imaging, multifocal or diffuse bowel wall thickening, abnormal wall enhancement, mesenteric vascular engorgement, and ascites are seen. These affected segments can cause ulcers, submucosal edema, hemorrhage, ileus, ischemia, and obstruction. Rarely, GPA can manifest as acute abdomen with intestinal ischemia or perforation (43–45).

Venous thromboembolic events occur at a higher frequency in patients with ANCA-associated vasculitis, and these patients can have splanchnic venous thromboembolism, with the highest risk among older men who have previously experienced a venous thromboembolic event or stroke with motor deficit (43–45). Other splenic findings that may be seen at imaging include splenomegaly. The frequency of splenic infarction is probably underreported, and imaging, particularly contrast-enhanced MRI, can depict early findings of splenic infarction (Fig 8). Rarely, GPA can manifest as a mass lesion and mimic a neoplasm (46). Genitourinary involvement is reported in less than 1% of cases and can manifest with prostatitis (most common), renal masses, genital ulcers, and epididymo-orchitis (47).

Figure 8.

Necrotizing granuloma and GPA in a 45-year-old woman with fulminant hepatic failure who was transferred from an outside hospital. Coronal (top left) and axial (top right, bottom left and right) CT images of the chest, abdomen, and pelvis with intravenous contrast material show portal vein thrombus (black arrow) with a transient hepatic attenuation difference in the liver parenchyma, as well as splenic vein thrombosis with splenic infarction (white arrow). Necrotic iliac chain lymph nodes (orange arrow) and scattered cavitary pulmonary nodules (blue arrow) are seen, and an initial diagnosis of necrotizing vasculitis was suggested. Histopathologic findings confirmed a diagnosis of necrotizing granuloma, and further workup revealed GPA.

Eosinophilic GPA, formerly known as Churg-Strauss syndrome, has a clinical presentation nearly similar to that of GPA. At imaging, the gastrointestinal involvement may manifest as a halo sign owing to submucosal edema creating a striated bowel wall appearance with diffuse mucosal enhancement. Other associated findings include ascites, omental thickening, and centrally necrotic mesenteric lymph nodes (48). Rare mesenteric microaneurysms have been described with eosinophilic GPA at subtraction angiography (49).

Immune-mediated Granulomas

Sarcoidosis.—Sarcoidosis is a systemic granulomatous disease of unknown cause that is characterized histopathologically by the formation of nonnecrotizing granulomas. With a slight predilection for African American women, sarcoidosis has a global incidence of one to 40 cases per 100 000 persons annually (50). Although the cause is not entirely clear, persistent antigenic stimuli result in the recruitment of macrophages, which along with other immune cells result in granuloma formation (Fig 1). Sarcoidosis has a propensity to affect any abdominal organ, but commonly involved viscera include the stomach, liver, spleen, peritoneum, and kidneys (50).

There is symptomatic hepatic involvement in 5%–20% of cases of sarcoidosis (50). Long-standing hepatic sarcoidosis can lead to portal hypertension and cirrhosis (51). US depicts an enlarged liver with heterogeneous echotexture. Innumerable small hypoechoic nodules correspond to the granulomas present in a fraction of patients (51,52). At CT, these nodules are often hypoattenuating compared with the background liver parenchyma (51). At MRI, the same nodules are usually hypointense on T1- and T2-weighted images, but they may require biopsy because their imaging findings overlap with those of other nodular processes such as infection and metastatic disease (51,53) (Fig 9). When coalesced hepatic granulomas are larger, they are hyperintense on T2-weighted MR images, and on dynamic contrast-enhanced MR images, there is often minimal enhancement (54).

Figure 9.

Biopsy-proven sarcoidosis in a 49-year-old woman. A, Coronal contrast-enhanced chest CT image shows the classic pattern of sarcoidosis: hilar and mediastinal lymphadenopathy (arrows). B, Axial contrast-enhanced chest CT image shows peribronchovascular consolidation with tiny satellite nodules (arrow) (so-called “galaxy” sign). C, Axial contrast-enhanced abdominal CT image shows confluent lymphadenopathy (arrows) in the gastrohepatic and para-aortic region. D, Coronal abdominal half-Fourier single-shot turbo spin-echo MR image shows splenomegaly, with multiple hypointense sarcoid granulomatous nodules.

Sarcoid granulomas grow along the portal tracts, which at imaging demonstrate a T2-hypointense zone in the periportal region. This zone is also known as the “T2 halo” sign, which was originally reported with primary biliary cholangitis or cirrhosis, and autoimmune hepatitis (54). Splenic involvement is characterized by splenomegaly in 25%–60% of cases of sarcoidosis (51) and may be accompanied by parenchymal and hepatic nodules. Pancreatic involvement is rare and usually results from extension of peripancreatic lymphadenopathy. Other findings can mimic pancreatitis or pancreatic mass and warrant biopsy for a definitive diagnosis (51).

Sarcoidosis can involve a gastrointestinal lumen, most notably the esophagus, stomach, or duodenum; however, this is uncommon (55). Although endoscopy is the standard for diagnosis, gastrointestinal fluoroscopy may reveal nodular mucosa with thickened rugae, aphthous ulcers, and polypoidal filling defects (55). When fibrosis ensues, strictures can develop and result in bowel obstruction. Peritoneal involvement is extremely rare; it manifests as ascites, peritoneal stranding, thickening, and nodularity and can mimic peritoneal carcinomatosis or TB at imaging (51).

Much like hilar and mediastinal adenopathy in the chest, sarcoidosis can result in multistation lymph nodes in the abdomen and pelvis in 30% of patients (51). It tends to involve upper abdominal nodes and can be FDG avid at PET, potentially mimicking a neoplastic process (51,54).

Crohn Disease.—Inflammatory bowel disease is a chronic inflammatory condition of the gastrointestinal tract that comprises two clinical entities: Crohn disease and ulcerative colitis. Crohn disease is caused by an inability of macrophages to clear the inciting insult, resulting in chronic inflammation and granuloma formation (55).

CT enterography and MR enterography are mainstays for imaging Crohn disease, as these examinations can be used to delineate mesenteric changes as well as extraluminal disease complications. Depending on the chronicity of disease, imaging is used to detect acute inflammation, abscesses, stenoses, and fistula formation (56–58). In the abdomen and pelvis, extraintestinal manifestations can include primary sclerosing cholangitis, fatty liver disease, autoimmune hepatitis, cirrhosis, acute cholecystitis, hepatic abscesses, pancreatitis, and renal stones (59).

Xanthogranulomatous Processes of the Abdomen and Pelvis

Xanthogranulomatous processes are rare conditions that are histopathologically characterized by abundant lipid-laden (foamy) macrophages or histiocytes (xanthoma cells) (6). Infection or inflammation, among other causes, can lead to this aggressive inflammatory response. Xanthogranulomatous cholecystitis and xanthogranulomatous pyelonephritis are two conditions that result from infection or inflammation (60–64). Although involvement of other organs in the abdomen and pelvis is rare, xanthogranulomatous processes can affect nearly every organ. Non–Langerhans cell histiocytoses are a subset of xanthogranulomatous disease. These histiocyte proliferation diseases include entities such as Erdheim-Chester disease (ECD), Rosai-Dorfman disease, and juvenile xanthogranuloma (6). The salient features of these xanthogranulomatous processes are summarized in Table 3.

Table 3:

Xanthogranulomatous Processes

Xanthogranulomatous Pyelonephritis

Xanthogranulomatous pyelonephritis is a rare condition resulting from a chronically obstructing infected calculus. There is a chronic but incomplete immune response that results in granulomatous inflammation, eventually leading to destruction of the renal parenchyma and replacement by lipid-laden macrophages (6). The most commonly isolated bacteria are Proteus mirabillis and Escherichia coli (6).

Contrast-enhanced CT demonstrates hypoattenuating blown-out calyces replacing the renal parenchyma and cortical thinning, resulting in the classic “bear paw” sign, as well as a centrally located calculus (60,61) (Fig 10). The blown-out calyces may represent dilated calyces or renal parenchyma filled with pus, debris, or hemorrhage. Despite nephromegaly, there is a paradoxical contraction of the renal pelvis around the staghorn calculus. Hypoattenuation of the renal pelvis represents an extensive inflammatory process rather than hydronephrosis (6,61). Focal xanthogranulomatous pyelonephritis is commonly caused by an obstructed duplicated upper- or lower-pole moiety and hence can mimic abscess or neoplasm at imaging (6,60,61). Xanthogranulomatous pyelonephritis may result in surrounding perinephric inflammation and extrarenal extension of abscess into the psoas muscles, paraspinal muscles, and spleen (6,60).

Figure 10.

Axial contrast-enhanced CT image of the abdomen and pelvis in a 46-year-old woman with xanthogranulomatous cholecystitis shows a staghorn calculus. The portion of the calculus shown (arrowhead) has blown-out calyces (white *) within the enlarged left kidney. There is surrounding extensive stranding (orange arrow) with a renocutaneous fistula (white arrow), and an abscess (yellow *) is seen in the left back muscles.

Xanthogranulomatous Cholecystitis

Xanthogranulomatous cholecystitis most commonly occurs in females during their 5th and 6th decades of life and is believed to occur after the rupture or occlusion of Rokitansky-Aschoff sinuses or a small mucosal ulceration with subsequent intravasation of inspissated bile into the gallbladder wall. This results in an aggressive inflammatory response, with macrophages phagocytosing the biliary lipids in the bile and thereby forming xanthoma cells (6,62).

US images may show hypoechoic nodules in the gallbladder wall or hypoechoic bands surrounding the gallbladder. The hypoechoic nodules range from 3 to 20 mm and represent abscesses, xanthogranulomas, or both (6,62). There may be hyperechoic pericholecystic fat with increased vascularity, representing surrounding inflammatory change. Rarely, US images may show focal or masslike thickening, with resultant intra- and/or extrahepatic biliary ductal dilatation (6). CT and MRI findings are similar to those at US, with mural nodules that are hypoattenuating at CT (Fig 11) and T1-hypointense and T2-hyperintense at MRI. The T2 signal intensity is lower than the signal intensity of bile, and there is signal dropout at out-of-phase imaging relative to the signal intensity at in-phase imaging.

Figure 11.

Coronal contrast-enhanced CT image of the abdomen and pelvis in a 56-year-old woman with xanthogranulomatous cholecystitis shows a markedly thickened gallbladder wall (yellow arrow) with intramural low-attenuation nodules or bands (straight white arrows). The mucosa (curved arrow) is continuous and enhancing. Also note the associated bile duct dilatation (black arrow).

An important imaging feature of xanthogranulomatous cholecystitis is the presence of a continuous enhancing gallbladder mucosa (63). Gallstones with diffuse gallbladder wall thickening and a continuous mucosal line are highly suggestive of xanthogranulomatous cholecystitis (6,63). The intact mucosal line verifies that intramural nodules are truly in the wall and not involving the mucosa or extending into the lumen. This feature is also crucial to distinguishing xanthogranulomatous cholecystitis from gangrenous cholecystitis (64). The differential diagnosis also includes adenomyomatosis and gallbladder carcinoma. CT features that favor xanthogranulomatous cholecystitis over gallbladder cancer include diffuse gallbladder wall thickening, a continuous mucosal line, intramural hypoattenuating nodules, absence of intrahepatic biliary ductal dilatation, and absence of liver invasion (62–64). Complications of xanthogranulomatous cholecystitis include gallbladder perforation, abscess, fistulization to the duodenum or skin, invasion into the liver or colon, and Mirizzi syndrome (6).

Erdheim-Chester Disease

ECD is a rare noninherited multisystem non–Langerhans cell histiocytosis that mainly affects middle-aged to older adults, with a slight male predominance. There are a variety of presenting symptoms owing to multisystem involvement. Histopathologically, ECD is characterized by focal fibrosis with foamy histiocyte infiltration. The histiocytes stain positive for CD68 and negative for S-100, CD1a, and Birbeck granules (6,65).

In the abdomen, retroperitoneal xanthogranulomatosis is characterized by a thick soft-tissue rind that may encase the kidneys and ureters, leading to obstruction as well as encasement of the aorta (65). The perirenal soft-tissue rind has the pathognomonic “hairy kidneys” appearance (Fig 12), which at MRI is that of diffusion restriction (65). Aortic involvement manifests as circumferential soft-tissue encasement that may extend into branch vessels such as the mesenteric and renal arteries. Intense FDG avidity due to glucose transport receptors makes FDG PET useful in evaluating the extent of disease but not in distinguishing this process from malignancy. This retroperitoneal involvement can lead to ureteral obstruction and renal failure, with management consisting of ureteral stent placement and systemic therapy with corticosteroids or immunosuppressive agents (6,65).

Figure 12.

ECD in a 65-year-old man. Axial fused attenuation-corrected PET image of the abdomen (left) and corresponding contrast-enhanced CT image (right) show FDG-avid perinephric infiltration (arrow), giving a hairy kidneys appearance, a pathognomonic imaging sign of ECD.

Rosai-Dorfman Disease

Rosai-Dorfman disease, also called sinus histiocytosis with massive lymphadenopathy, is a rare benign non–Langerhans cell histiocytosis that typically affects children and young adults. Histologically, the disease is characterized by histiocytes that phagocytize adjacent cells (emperipolesis) (6,66). The histiocytes are strongly immunopositive for S100, positive for CD68, and negative for CD1a and factor XIIIa (6).

Clinically, Rosai-Dorfman disease typically manifests as massive painless cervical lymphadenopathy, fever, elevated sedimentation rate, and/or mild anemia (6,66). Less commonly, lymphadenopathy occurs in the retroperitoneum, mediastinum, axilla, or inguinal chains. Extranodal disease in the abdomen and pelvis is extremely rare and most commonly involves the liver and retroperitoneum (66). In the retroperitoneum, it can manifest as infiltrative soft tissue that surrounds the aorta, kidneys, and ureters (Fig 13). Another manifestation in solid viscera can be multiple hypoattenuating or hypoechoic hypovascular lesions mimicking metastatic disease or disseminated infection (66).

Figure 13a.

Biopsy-proven extranodal Rosai-Dorfman disease in two patients. (a) Axial contrast-enhanced CT images of the abdomen in a 51-year-old woman show a mass circumferentially encasing the aorta (white arrow) without narrowing. Two other masses (yellow arrows) are seen in the subcutaneous fat and interpolar region of the right kidney. (b) Transaxial MR images of the pelvis in a 50-year-old man show a T2-hypointense spiculated lesion (dashed outline) in the mesorectal fat (white arrow) abutting the rectum (blue arrow), which demonstrates avid contrast enhancement.

Figure 13b.

Biopsy-proven extranodal Rosai-Dorfman disease in two patients. (a) Axial contrast-enhanced CT images of the abdomen in a 51-year-old woman show a mass circumferentially encasing the aorta (white arrow) without narrowing. Two other masses (yellow arrows) are seen in the subcutaneous fat and interpolar region of the right kidney. (b) Transaxial MR images of the pelvis in a 50-year-old man show a T2-hypointense spiculated lesion (dashed outline) in the mesorectal fat (white arrow) abutting the rectum (blue arrow), which demonstrates avid contrast enhancement.

Juvenile Xanthogranuloma

Juvenile xanthogranuloma is a rare benign non–Langerhans cell histiocytosis that affects the skin and is typically self-limiting. It manifests in the first 2 decades of life. Histopathologic analysis reveals benign-appearing histiocytes with or without lipid-laden multinucleated histiocytes (ie, Touton giant cells) (67).

Clinically, juvenile xanthogranuloma typically manifests as circumscribed cutaneous lesions that usually regress spontaneously after a few years. Although extremely rare, extracutaneous sites of involvement below the diaphragm include the liver, spleen, pancreas, gastrointestinal tract, and urogenital tract, with the liver being the most common site (68). Imaging findings are nonspecific (Fig 14), and the diagnosis is typically made on the basis of dermal findings (6,69,70). The majority of these masses (80%) occur as a single lesion, and most patients who are found after presentation to have multiple masses are infants (71). At imaging, hepatosplenomegaly can be seen with or without discrete nodules (70). The nodules can have a central area of low attenuation with no enhancement or rim enhancement following contrast material administration. They can be iso- to hypointense on T1-weighted MR images, with high signal intensity on water-sensitive MR images (69,70).

Figure 14.

Biopsy-proven juvenile xanthogranuloma in a 3-month-old boy. Axial T1-weighted nonenhanced (left) and gadolinium-enhanced (right) MR images show circumferential masslike soft tissue and skin thickening (arrows) surrounding the corpus cavernosa and corpus spongiosum. This mass has diffuse enhancement on the contrast-enhanced image. Dermoscopic and histopathologic findings were consistent with juvenile xanthogranuloma.

Conclusion

Granulomatous diseases are a clinically diverse group of conditions and can mimic various other disease processes. It is often hard to make a diagnosis on the basis of histopathologic findings alone. Therefore, a multidisciplinary approach with use of the imaging findings discussed herein may guide the radiologist in making an appropriate diagnosis of granulomatous disorder.