Canine heartworm mimicking pulmonary metastasis in a liver transplant candidate

Surgical Rounds®, February 2008, Volume 0, Issue 0

Bindi Naik-Mathuria, Resident in General Surgery, Michael E. DeBakey Department of Surgery; Christine O'Mahony, Assistant Professor, Division of Abdominal Transplant and Hepatobiliary Surgery, Michael E. DeBakey Department of Surgery; John A. Goss, Professor and Chief, Division of Abdominal Transplant and Hepatobiliary Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX

Bindi Naik-Mathuria, MD

Resident in General Surgery

Michael E. DeBakey Department of Surgery

Christine O'Mahony, MD

Assistant Professor

Division of Abdominal Transplant and Hepatobiliary Surgery

Michael E. DeBakey Department of Surgery

John A. Goss, MD

Professor and Chief

Division of Abdominal Transplant and Hepatobiliary Surgery

Michael E. DeBakey Department of Surgery

Baylor College of Medicine

Houston, TX

ABSTRACT

Introduction: Dirofilaria immitis, better known as canine heartworm, can infect humans and cause a pulmonary lesion (human pulmonary dirofiliariasis) that can be easily mistaken for a malignant tumor on imaging studies.

Results and discussion: A patient with a history of hepatocellular carcinoma underwent a computed tomography scan of the chest to screen for cancer as part of his liver transplantation workup. A pulmonary nodule was visualized that resembled metastatic disease. Biopsy of the lesion identified it as a granuloma caused by a dead heartworm located within a small pulmonary vessel. The authors describe this patient's case, review the literature, and discuss D immitis infection in both healthy and immunocompromised patients.

Conclusion: Although D immitis is typically benign in humans, it is uncertain how the parasite reacts in patients who are immunocompromised. These patients require close and prolonged monitoring for signs of active infection.

Dirofilaria immitis, or canine heartworm, is a parasite that sometimes infects humans. It can cause a pulmonary lesion (human pulmonary dirofiliariasis) that resembles a malignant tumor on radiographic studies. We report the case of a patient who underwent computed tomography (CT) scanning to screen for metastatic disease as part of his liver transplant workup and was discovered to have a pulmonary nodule suggestive of metastasis. The mass could not be biopsied due to its location and had to be surgically removed. Histopathology revealed D immitis infection. Removing the worm is considered sufficient treatment in healthy individuals. It is unclear whether the same is true for immunocompromised patients, and they require close follow-up.

CASE REPORT

A 53-year-old white man with alcohol-induced liver cirrhosis complicated by hepatocellular carcinoma was admitted to the hospital to undergo chemoembolization of the liver tumor and final evaluation for liver transplantation. He had smoked heavily for more than 30 years and quit just 2 months prior to this hospital admission. The patient was a native of Texas, and he had never lived outside of the United States.

His medical history included bleeding esophageal varices but no accompanying respiratory symptoms, such as shortness of breath, recent cough, or hemoptysis. The patient's only reported symptom was chronic fatigue, secondary to his end-stage liver disease. His laboratory values on admission showed elevated hepatic enzymes, thrombocytopenia, hypoalbuminemia, and coagulopathy, findings that are consistent with end-stage liver disease. The only evidence of infection in this patient was a mononuclear cell count mildly elevated to 15% (normal, <14%).

Chest radiographs showed no abnormalities. CT scanning, however, revealed a peripherally based pulmonary nodule measuring 12 mm in maximal diameter adjacent to the left atrium (Figure 1). The patient's hepatocellular carcinoma aroused suspicion that the nodule could be a metastatic lesion. Metastasis would exclude the patient from the liver transplant list. Percutaneous biopsy of the pulmonary nodule was planned to confirm metastatic disease but was not possible because of its proximity to the right atrium. Instead, a wedge lung resection was performed using video-assisted thoracoscopic surgery. The nodule was yellow-tan, calcified, and necrotic, resembling a granuloma. Histopathologic analysis identified several nonviable structures within an area of central necrosis, consistent with a diagnosis of D immitis (Figure 2). No malignant cells were noted, and bacterial and fungal cultures were negative. Excision of the mass is considered adequate treatment and no further measures were taken.

DISCUSSION

Practice

Point

Humans are "accidental" hosts, who acquire the worms after being bitten by infected mosquitoes.

D immitis is a filarial nematode whose primary host is the dog. Mature female parasites release microfilaria into the host's blood stream, and mosquitoes transmit these to secondary hosts. After transmission, the microfilaria reside in subcutaneous tissue and muscle sheaths and then migrate via the capillaries to the right heart. There, the worms are thought to reach sexual maturity within 6 months, at which time they propagate, beginning the cycle again.1 In dogs, the worms can live in the heart and the vascular tree. They are known to cause pulmonary, cerebral, hepatic, and extremity infarcts and serious vena caval thrombosis.2 Humans are "accidental" hosts, who acquire the worms after being bitten by infected mosquitoes. Although it is commonly thought that D immitis cannot survive in humans and the worms die within subcutaneous skin tissue, the worms occasionally migrate to the right ventricle, where they perish. They are subsequently embolized to small and medium pulmonary arteries, causing thrombosis and pulmonary infarction from a granulomatous reaction.1 The granulomatous reaction is self-limiting and thought to result from toxins that the dead worm releases.3

Presentation and diagnosis

In humans, D immitis infection typically presents as a spherical, subpleural nodule that measures 1 to 3 cm in diameter. The nodule is often discovered as a "coin lesion" on a routine chest radiograph or during autopsy.3 Ninety-five percent of cases involve a solitary lesion.1 Fewer than 100 cases of human D immitis infection have been reported in the United States.3 Although the majority of these cases were confined to the Eastern seaboard, the Gulf of Mexico, and the Mississippi River valley, the number of reported cases has increased over the past few decades and the geographics spread now encompasses most states. This increase likely results from uncontrolled infection in dogs.2

Most patients are asymptomatic, but cough, chest pain, eosinophilia, hemoptysis, and fever have been reported.1,3 The observance of a solitary pulmonary nodule often propagates further investigation to rule out primary or metastatic malignancy. Fine-needle biopsy has confirmed the diagnosis in a few cases, but most reports describe using open excisional biopsy via thoracotomy to evaluate the nodule.

Lack of a reliable, commercially available serologic test makes preoperative diagnosis difficult, but experimental indirect hemagglutination and enzymelinked immunosorbent assay (ELISA) for specific antibody detection have been shown to be successful.2 In one case report, positive emission tomography scanning showed hypermetabolic activity, which suggested an infectious or inflammatory etiology.4 CT scans typically demonstrate high attenuation centrally and peripheral ground-glass attenuation. Although these findings suggest a pulmonary infarction, they do not definitively differentiate these lesions from malignant ones.5

Treatment and the immunocompromised host

Practice

Point

Most patients are asymptomatic, but cough, chest pain, eosinophilia, hemoptysis, and fever have been reported.

The pulmonary nodule in humans infected with D immitis results from a dead worm, and it is therefore thought that immunocompetent hosts do not require treatment beyond excision.2 Our patient's orthotropic liver transplantation leaves him immunosuppressed and he will require prolonged, close follow-up. The presence of a pulmonary nodule of D immitis origin raises concern that a patient could have an underlying infection that may manifest itself if the patient is immunocompromised.

Most worms isolated in human tissue have been underdeveloped, which suggests that the human environment is not conducive to propagation of the parasitic cycle; however, exceptions have been reported. One case involved a gravid form of the parasite found in an immunocompromised patient suffering from lymphoid leukemia.6,7 A few reports have described extrapulmonary locations of D immitis that include the index finger, eyes, peritoneal cavity, and even the heart and vena cava.8-11 If the parasitic cycle were to be propagated in immunocompromised humans, the consequences could prove just as severe as they are for dogs. While the treatments available for dogs may be useful for humans, these agents are hepatotoxic and nephrotoxic and would not be ideal choices for a liver transplant patient.

CONCLUSION

D immitis infection is rare in humans, and there is currently no serologic test available to assist in its diagnosis. Even after a diagnostic test has been developed, clinicians should continue to report heartworm acquisition in humans to increase awareness of the possible manifestations of this condition.

Disclosure

The authors have no relationship with any commercial entity that might represent a conflict of interest with the content of this article and attest that the data meet the requirements for informed consent and for the Institutional Review Boards.

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