Toxoplasmosis complicating lung cancer: a case report

Introduction

Toxoplasma gondii infection, “toxoplasmosis”, is relatively common, and the prevalence of carrying the dormant, cystic form has been reported as 40% in Europe, 20%–50% in Africa,¹ and 10%–30% in the People’s Republic of China.^1,2 Most people who carry T. gondii are healthy, but for those with HIV or cancer toxoplasmosis can be life-threatening. Toxoplasmosis has been reported to increase the fatality rate of Hodgkin’s disease, leukemia, myeloma, melanoma, AIDS, and brain cancer.^2–12 Although toxoplasmosis is known to complicate pneumonia and other respiratory diseases,^12–20 its role in lung cancer has not been adequately described. Here, we describe a case of toxoplasmosis presenting with non-small-cell lung cancer for the purpose of making screening and treatment recommendations.

Case presentation

A 64-year-old Chinese woman was admitted to our hospital with a history of nonproductive cough (without hemoptysis) of 6 months’ duration and chest pain of 1 week’s duration. She had lived in a rural area with a cat for many years. She had no history of eating raw or undercooked foods and she was uncertain whether she had ever drunk unpasteurized goat’s milk. Her medical history was unremarkable. She did not have shortness of breath, fever or sweats, weight loss, or a history of smoking. Physical examination revealed multiple swollen lymph nodes palpable on the top of the right collarbone, without tenderness. Temperature, respiration, heart rate, and abdominal examination showed no abnormalities. Other systemic examinations were within normal limits.

The chest radiograph showed bilateral prominence and right hila adenopathy. Computed tomography scan of the lung showed space-occupying lesions in the lower right lobe confirming centrally located carcinoma. We also observed significant enlargement of the lymph nodes in the right hilar areas and mediastinum, which we considered malignant. The patient also had pneumonia in the right lung. Bronchoscopy suggested that tracheal carina was broadened; the ridge between upper right lobe and middle bronchus was widened, as was the ridge between middle right lobe and lower lobe bronchus. Bronchoscopy also showed the right posterior basal bronchus suffered from compressed bronchostenosis. Squamous carcinoma cells were found in the bronchial brushing. There was no evidence of distant metastasis. Echocardiography suggested pulmonary hypertension. Pulmonary ventilation and small-airway function were mildly blocked.

Laboratory testing demonstrated no obvious abnormality except the carcinoembryonic antigen level was at 8.21 ng/mL (reference interval: 0–5 ng/mL). Exfoliative cytology examination of the hydrothorax did not detect tumor cells. Interestingly, the Wright-stained bronchoalveolar-lavage (BAL) fluid cytology diagnosis was positive for T. gondii (Figure 1), and many crescent-shaped tachyzoites were detected in clumps around host cells (indicated by an arrow in each of Figure 1A–D). Individual elongated bodies averaged 4–7 μm in length, with a pointed anterior end and rounded posterior end; one side was slightly flattened, the other side bulged. The nucleus was situated toward the center. All of the tachyzoites were extracellular (ectocytic); no intracellular parasite was evident. Serological examination revealed that anti-T. gondii immunoglobulin (Ig) M and IgG antibodies were positive. Other lab tests were unremarkable. The leukocyte count was 5.64×10⁹/L (41.8% lymphocytes, 52.1% neutrophils, 5.3% monocytes), and liver function tests were within the normal ranges (albumin 42.8 g/L, total bilirubin 10.10 μmol/L, direct bilirubin 2.5 μmol/L, alanine aminotransferase [ALT] 7.0 IU/L, aspartate transaminase [AST] 17.0 IU/L). Serology testing for HIV was negative.

Figure 1 Wright-stained bronchoalveolar lavage fluid smears. Notes: (A–D) Arrows indicate extracellular “tachyzoites”, also known as “trophozoites”, which can be propagated within the nucleated cells. No intracellular parasites are present. Magnification ×1,000.

Upon diagnosis of lung cancer, the patient decided to forgo any kind of treatment and we subsequently lost contact with her.

Discussion

T. gondii is an obligate intracellular protozoan.¹⁵ The lifecycle of T. gondii is divided into five stages: trophozoite, cyst, schizont, gametophyte, and oocyst. Final maturation to sexual maturity occurs only in the intestines of cats. The main route of infection of T. gondii is fecal–oral transmission. It also can be transmitted to the fetus through the placenta. Generally, eosinophilia is not typical when infected with the protozoan. Clinical manifestations are complicated and atypical, and most infections are latent or acute. Differential diagnosis relies mainly on direct detection of Toxoplasma tachyzoites in BAL or by serological techniques.

Among healthy people, toxoplasmosis is generally mild and self-limiting, but among neonates and cancer patients, this opportunistic infection is serious, often fatal. Many cases of pulmonary toxoplasmosis have been described in patients with hematologic malignancies and solid tumors, but none in lung cancer, as far as we are aware.

We discovered a rare case of T. gondii infection in a lung cancer patient, with diagnosis of infection based on tachyzoites present in BAL and positive T. gondii-specific IgM antibody, and diagnosis of squamous lung cancer based on chest X-ray, bronchoscopy, and computed tomography scan.

Other investigators have described pulmonary toxoplasmosis in those with HIV or cancer,^13–20 although not in lung cancer. A French nationwide study reviewed 64 cases of BAL-confirmed pulmonary toxoplasmosis among patients with HIV infection; 30 (47%) of the 64 cases were responsive to toxoplasmosis treatment, while 24 patients (37%) died of toxoplasmosis. Israelsky and Remington, in the USA, have also reported improved outcomes resulting from treatment of T. gondii infection among immune compromised patients.⁵ They reported improvement in 68% of patients for whom the diagnosis was made early enough to begin treatment.⁵ De Salvador-Guillouët et al reported a case of severe acute primary pulmonary toxoplasmosis in an immunocompetent of 19-year-old French man with BAL-confirmed tachyzoites.¹⁴ Leal et al reported a similar case in Brazil.¹⁹ In their paper, Leal et al also reviewed nine other cases of T. gondii pneumonia. Most of these cases had positive IgM and IgG T. gondii-specific antibodies and tachyzoite in BAL fluid. Fortunately most of these patients responded to treatment and made a full recovery.

Clinicians should be aware of toxoplasmosis complicating lung cancer, as toxoplasmosis is readily treatable. Indeed, in some countries T. gondii serology is ordered routinely during examination of cancer patients, with BAL fluid being the material of choice for diagnosing pulmonary toxoplasmosis as well as lung biopsies.^16–18

We report a case of toxoplasmosis complicating squamous cell lung cancer in the People’s Republic of China. We recommend consideration of periodic monitoring of T. gondii infection in lung cancer patients in order to improve treatment and increase survival.

Acknowledgments

We would like to thank Dr Lisa Herrinton (Division of Research, Kaiser Permanente, Oakland, CA, USA) and Dr Changyu Zheng (National Institute of Dental and Craniofacial Research, National Institute of Health, Bethesda, MD, USA) for editing this manuscript. This study was funded by the Technology Development Program of Jilin Province (no 200705178).

Disclosure

The authors report no conflict of interest in this work.

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