Not all that shines is cancer : pulmonary cryptococcosis mimicking lymphoma in [ ( 18 ) ] F fluoro-2-deoxy-D-glucose positron emission tomography

Received on: May 23,2012 – Accepted on: Jul 17, 2012 ABSTRACT We report of a case of pulmonary cryptococcosis mimicking lymphoma in a positron emission tomography (FDG-PET) scan. A 62-year old man with diffuse large B-cell lymphoma had complete resolution of abdominal and pulmonary lesions after three cycles of rituximab-based chemotherapy (R-CHOP). However, FDG-PET showed new pulmonary nodules, suggesting active lymphoma. Chronic inflammatory granuloma was seen in the histopathological exam, with round-shaped structures compatible with fungus, later identified as Cryptococcus neoformans on culture. The lesions disappeared after 6 weeks of fluconazole therapy, and the patient could continue chemotherapy without further infectious complications.


Not all that shines is cancer: pulmonary cryptococcosis mimicking lymphoma in [(18)] F fluoro-2-deoxy-D-glucose positron emission tomography
Nem tudo o que brilha é câncer: criptococose pulmonar mimetizando linfoma na tomografia por emissão de pósitrons com [(18)] F fluoro-2-desoxi-D-glicose ] F fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) is an imaging modality based on the Warburg effect, the propensity of cancer cells to maintain elevated glycolysis in the presence of oxygen (1) .It has shown great value in distinguishing between benign and malignant lesions (2) , and has emerged as the gold standard technique for staging both Hodgkin's and aggressive non-Hodgkin's lymphomas (NHL) (3,4) .Several reports describe pitfalls in FDG-PET imaging diagnosis.Benign inflammatory/infectious lesions can have increased metabolic rates and can be misclassified as malignant lesions.Single pulmonary nodules imaging by FDG-PET may be particularly difficult to evaluate, since Mycobacterium or fungal granulomas can resemble lung cancer (5) .The standardized uptake value (SUV max), a calculated measure of contrast uptake, has been used in an attempt to differentiate the underlying etiology of such lesions.Low SUV values (up to 2.5) are seen more frequently with benign lesions and high uptake values (over 2.5) are more frequent with Not all that shines is cancer einstein.2012;10(4):502-4 malignant lesions (6) .Clinical judgment and a complete laboratory evaluation can help establishing the correct diagnosis, although biopsy is usually necessary.

CASE REPORT
A 62-year old man was referred to the institution due to weight loss, fever, abdominal pain and jaundice.Computerized tomography (CT) of the abdomen revealed 6-cm infiltrative perihepatic mass, liver nodules, splenomegaly and periaorthic enlarged lymph nodes.CT of the thorax revealed multiple pulmonary nodules and enlarged axillary, cervical and mediastinal nodes.Biopsy of the hepatic mass diagnosed CD20+ diffuse large B-cell lymphoma (DLBCL).
After three cycles of rituximab-based chemotherapy (R-CHOP), the patient complained of daily fever, up to 38ºC.Extensive laboratorial and imaging workup for infectious disease was inconclusive.FDG-PET study revealed complete resolution of previous abdominal and pulmonary lesions.However, new pulmonary nodules, up to 2.5cm large, with a SUV max of 13.6 were observed on the right posterior lobe of the lung, suggesting active lymphoma (Figure 1).
An open lung biopsy was performed to elucidate the diagnosis.A chronic inflammatory granuloma was observed in the histopathological exam with roundshaped structures compatible with fungus (Figure 2).Culture of the pulmonary tissue revealed Cryptococcus neoformans.Fluconazole (150mg daily) was started, 6 weeks later the pulmonary lesions had disappeared and the patient was asymptomatic.He was able to continue chemotherapy without further infectious complications.

DISCUSSION
Pulmonary cryptococcosis (PC) is an infectious fungal disease often seen in immunocompromised hosts.Several risk factors have been described including HIV infection, malignancies, stem cell and organ transplantation, and they are treated with glucocorticoids or tumor necrosis factor antagonists (7,8) .In the case described here, both malignancy and chronic use of glucocorticoids imposed a risk for fungal infection.
FDG-PET is very sensitive and accurate in NHL staging and reevaluation.However, it is known that immunocompromised patients may have atypical clinical presentations of infectious diseases and biopsy may be necessary for a correct diagnosis.The use of SUV for discrimination between benign and malignant disease has been extensively studied and the majority of studies establish a SUV of 2.0 to 5.0 as a rational cutoff (9) .Particularly in cryptococcosis, few reports have been conclusive.Huang et al. (6) , for example, observed a SUV max ranging from 2.2 to 11.6.In the patient studied, a SUV of 13.6 was highly suggestive of active NHL.However, with the impressive clinical and radiological response observed in other affected areas and after a judicious evaluation of the pulmonary  nodules, the different diagnosis of fungal infection was suspected.This report highlights the importance of histhopathological diagnosis before initiating/changing a treatment.

Figure 2 .
Figure 2. Histologic section from open lung biopsy showing chronic inflammatory granuloma and round-shaped structures compatible with fungus (hematoxylin-eosin, 100 X)