A 68-year-old man recently underwent a renal transplantation procedure. His renal failure was attributed to immunosuppressive therapy from a liver transplant. Shortly after the renal transplant, he developed progressive respiratory distress and sepsis. Because the patient was immunocompromised, prophylactic therapy was started with antibiotic, antifungal, and antiviral drugs. Despite therapy, the patient’s cardiopulmonary status continued to decline. CT of the chest was obtained to further investigate (Figure 1).
Post-transplant lymphoproliferative disorder
The risk of infectious syndromes in transplant recipients has traditionally been divided into three major time periods, each with varying probabilities of different microorganisms.1 These time periods include the 1st month, 1st through 6th month, and 6th through 12th month post-transplantation. In the first month post-transplant, the major effects of exogenous immunosuppression are not yet apparent. As a result, the major causes of infection in the first month post-transplant are due to pre-existing infection from the donor or recipient and infectious complications from the transplant surgery itself or hospitalization. Microorganisms in this group include vancomycin-resistant enterococci, methicillin-resistant staphylococci, Clostridium difficile, and hepatitis B and C.2
Patients are most susceptible to the effects of immunosuppression in the first through sixth months post-transplant and, therefore, are at the greatest risk for opportunistic infections such as Pneumocystis jirovecii, cytomegalovirus, Epstein-Barr virus, and tuberculosis.1 Although fungal infections such as histoplasmosis and cryptococcus most commonly occur during this period, they have been cited in the literature as being relatively uncommon unless the patient is receiving greater than normal amounts of immunosuppression, which was the case in this patient.3,4
From 6 to 12 months post-transplant, most patients have stable and reduced levels of immunosuppression. In this period, they are most susceptible to community-acquired pneumonias due to respiratory pathogens such as pneumococcus or legionella.1
Similar to other patients with prolonged hospitalizations and indwelling central venous catheters, transplant recipients are susceptible to pulmonary septic embolism, which may mimic the aforementioned infectious conditions. Organ transplant recipients are also susceptible to a large and varied group of lymphoproliferative diseases that occur after solid organ or stem cell transplantation, including lymphoid hyperplasias and malignancies, which may appear similar to infectious conditions on CT.
PTLD is the second most common type of malignancy following transplantation and tends to occur at least one year following transplant.5 Risk factors include primary Epstein-Barr infection, cytomegalovirus infection, and transplants from a seropositive donor to a seronegative donor. PTLD shares imaging characteristics of non-Hodgkin lymphoma and similarly has a variable manifestation depending on the organ involved. Although the abdomen is most commonly involved, pulmonary manifestations include pulmonary nodules and masses with homogenous soft-tissue attenuation on CT. The nodules and masses can have smooth or irregular borders. Although not typical of the condition, cases have demonstrated a ground-glass halo or central necrosis involving these lesions, mimicking the findings of pulmonary aspergillosis and septic pulmonary embolism.6
Pulmonary septic embolism is a condition in which infectious intravascular particles of thrombus containing microorganisms are embolized into the lungs via the pulmonary arterial system. Emboli may originate from many sources, but classically result from right-sided infective endocarditis from a mechanical valve or intravenous drug abuse. Infected deep venous thrombosis and infected catheters are additional potential sources. CT findings include multiple discrete nodules randomly distributed throughout the lungs that have a propensity to cavitate in various stages of evolution. Although ground-glass halos can form around the emboli, these are more typical of gram-negative septic emboli. Subpleural wedge-shaped consolidations are also a common feature secondary to infarction from occlusion of pulmonary arteries by septic emboli.7
Pulmonary cryptococcosis is a form of pulmonary fungal infection most commonly caused by Cryptococcus neoformans. Typically, the respiratory tract is the primary route for entry of the fungal spores occurring via inhalation. The infection most commonly occurs in immunocompromised patients but has the potential to affect immunocompetent patients as well. The clinical presentation can range from asymptomatic nodular disease to severe acute respiratory distress syndrome. The most common CT findings are randomly distributed nodular or mass-like opacities. The opacities in pulmonary cryptococcus are typically smooth. In addition, peribronchovascular ground-glass opacities, mediastinal lymphadenopathy, and pleural effusions are common findings. Like several other entities, the smoothly marginated opacities can demonstrate the “halo sign” and create a diagnostic dilemma.8
Angioinvasive aspergillosis is an infection caused by saprophytic airborne filamentous fungus Aspergillus species, usually Aspergillus fumigatus. It is the most severe and aggressive form of aspergillosis. It results from occlusion of small- to medium-sized pulmonary arteries by fungal hyphae. The most important risk factor is severe and prolonged neutropenia, almost always occurring in immunosuppressed patients. It is most commonly seen in graft-vs-host disease, in patients undergoing allogenic bone marrow transplantation and those with end-stage AIDS. CT findings include multiple pulmonary nodules and masses. The “halo sign” is classic for this condition and represents hemorrhage due to invasion of adjacent pulmonary vessels. Similar to septic emboli, peripheral wedge-shaped consolidations can be seen and represent hemorrhagic pulmonary infarction.9
The left upper lobe consolidation was percutaneously sampled and returned positive for Cryptococcus neoformans. The patient’s clinical symptoms improved, and imaging findings nearly completely resolved following antifungal therapy.
Despite improvements in immunosuppressive agents, infection remains a major barrier to disease-free survival following solid organ transplantation.1 When a transplant recipient presents with an infectious syndrome, early and specific diagnosis and treatment are essential to optimize clinical outcomes. As cryptococcosis is most often associated with extrapulmonary findings such as meningitis, a negative work-up for these extrapulmonary findings can create a diagnostic dilemma for clinicians. As such, it is important for clinicians to be aware of the pulmonary findings of cryptococcosis along with the other conditions discussed.
Malhotra U, Santos-Nunez G. Pulmonary Nodules Following Renal Transplant. J Am Osteopath Coll Radiol. 2020;9(2):24-25.