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Q1: What are the findings on ultrasound and computed tomography?
Abdominal ultrasound shows multiple hypoechoic focal lesions in the spleen, some of them having central echogenic foci producing bull's eye or target configuration. Contrast enhanced computed tomography shows multiple, non-enhancing, hypodense focal areas in liver in addition to the spleen. Few of the splenic lesions demonstrate central hyperdense foci. Incidentally, a few old healed calcified foci are also seen in the liver and spleen.
Q2: What is the radiological diagnosis?
The image morphology of liver and splenic lesions in this immunocompromised patient is strongly suggestive of fungal infection.
Q3: How can the diagnosis be confirmed?
Image guided fine needle aspiration and microscopic examination of the aspirate can be done to confirm the diagnosis. An aspirate from the centre of the focal lesion is most likely to yield a positive result as the fungal elements are most abundant in these central necrotic areas. Blood and tissue cultures may be falsely negative, particularly with candidal infections. In our patient, ultrasound guided fine needle aspiration was performed. The aspirate demonstrated mycelia and budding yeast cells confirming the diagnosis of hepatosplenic candidiasis.
Fungal infections of the liver and spleen occur almost exclusively in individuals with underlying defects of host immune defence mechanism. The most commonly implicated organism isCandida albicans, but infections with other fungi such as aspergillus and cryptococcus may also occur.1 The presenting symptoms are generally non-specific, consisting of fever, pain referable to the area of involvement, tenderness on direct palpation, enlargement of liver and/or spleen, and rarely, jaundice. Usually both liver and spleen are involved, though either organ may be affected in isolation.2
Initially hepatomegaly and/or splenomegaly are present. Subsequently focal lesions develop that later spread throughout the parenchyma. They may be single or multiple. When multiple, they tend to be located adjacent to one another or may become partially confluent.3 Their size varies from 0.3 cm to 4.0 cm and they have relatively well defined borders. Five sonographic patterns of hepatosplenic candidiasis have been described.3 Pattern 1 represents an early active phase of the disease in which ultrasound demonstrates either a “wheel within wheel” (type a) or “wagon wheel” (type b) appearance. In the former appearance, the outer hypoechoic rim is formed by fibrosis while the inner hyperechoic rim is composed of the inflammatory process. In the centre of the inner hyperechoic zone, there is an area of necrosis identified as the hypoechoic nidus. In the wagon wheel appearance, echogenic radial strands are seen which imitate the spokes of a wheel. These “spokes” represent the inflammatory process, whereas hypoechoic regions between the spokes is the fibrous component. The axis of the wheel is formed by hypoechoic, necrotic nidus.
Pattern 2, manifested by the “bull's eye” or target configuration, lacks the central necrotic hypoechoic nidus. The lesion consists of the inflammatory process forming the echogenic centre, which is surrounded by fibrosis seen as the hypoechoic rim.3 Pattern 3 is characterised by a purely hypoechoic lesion. It is seen when the inflammatory process is being replaced by fibrosis.3 Later this hypoehoic lesion is transformed into a completely echogenic lesion (pattern 4) with a varying degree of posterior acoustic shadow. This sonographic appearance is produced by scar tissue with or without calcification. This echogenic lesion is usually smaller than pattern 2 or 3 lesions and may even disappear completely in the course of the healing process.3
Box 1: Various patterns of candidal infection of liver and spleen on ultrasound
Pattern 1a: wheel within wheel appearance
Pattern 1b: wagon wheel appearance
Pattern 2: bull's eye appearance/target configuration
Pattern 3: pure hypoechoic defect
Pattern 4: echogenic lesion with a varying intensity of posterior acoustic shadow
Box 2: Differential diagnosis of multiple hypodense/hypoechoic splenic and liver lesions
In acute phase of the disease, lesions of patterns 1 and 2 prevail. As disease progresses, pattern 3 lesions are identified, however, pattern 1 and 2 lesions may still be present. When pattern 4 lesions appear, pattern 1 is no longer seen and the lesions of other patterns regress in size. This is recognised late in the course of the disease.3
Fungal abscesses in liver and spleen of neutropenic patients are not always detectable on sonography, even in the presence of disseminated infection. The lesions become apparent when the neutrophil count returns to normal.4 It is important to identify pattern 1 or 2 in at least one lesion, as these appear only when the neutrophil count in a previously neutropenic patient is returning to normal and infection is active.5 This fact suggests that the inflammatory response of the host plays a part in defining the characteristic appearance.6 Pattern 3 and 4 lesions occur later in course of the disease and suggest that the infection is subsiding.5
Computed tomography may demonstrate similar appearances. Pastakiaet al reported that pattern 1 lesions were not seen on computed tomograms and pattern 2 lesions were demonstrated only occasionally.5 Pattern 3 lesions (multiple rounded areas of decreased attenuation scattered throughout the liver and spleen) were most common. Pattern 4 lesions, representing areas of calcification, were seen late in course of the disease. In our patient, no focal hepatic lesion could be detected on ultrasound, while computed tomography showed multiple pattern 3 and one pattern 2 lesion in the liver and multiple pattern 2 and 3 lesions in the spleen. Similar observation was also made by Pastakia et al. A computed tomogram is more sensitive in detecting the focal lesions; however, it is less specific as the characteristic pattern 1 and 2 lesions are demonstrated only occasionally. Periportal areas of increased attenuation seen on computed tomography are also reported which correlate pathologically with focal linear fibrosis in these immunocompromised patients.5
The usual differential diagnosis of multiple, focal lesions in liver and spleen include lymphoma, leukaemia deposits, metastasis, bacterial and fungal infection, and sarcoid. Most of these diseases give rise to non-specific focal hypoechoic lesions on sonography. Target lesions may however be seen in metastatic disease, although metastatic disease is unusual in the spleen. Deposits of lymphoma and leukaemia show rapid regression after cytostatic treatment, a fact which may help to differentiate them from the lesions of other aetiologies.6
To summarise, the detection of focal hepatic and splenic lesions with characteristic image morphology should suggest a possible underlying fungal disease in a febrile leukaemic patient. Apart from the aetiological diagnosis of fungal infection, the imaging features also provide understanding of their evolution over time.
Multiple candidal abscesses in liver and spleen in acute myeloid leukaemia.