Hymenolepis nana is the most common human tapeworm, infecting approximately 75 million people. Most infections are asymptomatic and usually limited to the gastrointestinal tract. Muehlenbachs and colleagues report a unique case of extra-intestinal H. nana with genomic mutations that were consistent with malignancy.
The patient was a 41-year-old man diagnosed with HIV infection in 2006 who was nonadherent with antiretroviral therapy (ART). He initially presented with several months of weight loss, fatigue, fever, and cough. His CD4 count was 28/mm3 and his viral load was 70,000 copies/mL. Stool examination showed H. nana eggs and Blastocystis hominis cysts. Computed tomography scans showed multiple nodules in the lungs, adrenal glands, and liver, ranging in size from 0.4 to 4.4 cm, as well as diffuse lymphadenopathy. He underwent excisional biopsy of a cervical lymph node and needle biopsy of a lung nodule. Three doses of albendazole were prescribed, and he was restarted on ART. Over the following 4 months, the nodules in the lungs, liver, and adrenals remained stable, but the lymph nodes increased in size. He was diagnosed with histoplasmosis and treated with amphotericin B, but developed renal failure; he declined hemodialysis. Palliative care was started, and he died in May 2013.
The investigators used DNA from the cervical lymph node as well as H. nana reference-strain specimens to construct sequencing libraries. Polymerase chain reaction (PCR) assays identified H. nana DNA in the specimen, which was confirmed by immunohistochemical studies and in situ hybridization that localized cestode antigen and nucleic acid signals. The DNA from the patient’s sequence was found to have three single-nucleotide insertions consistent with a deleterious mutation. Deep sequencing from the lymph node specimen generated 10.2 million reads. When the human sequences were removed, 1.4 million reads mapped onto the H. nana reference genome. Furthermore, complex genomic rearrangement and amplification was found in the human sequences, but not in the H. nana reference sequences. Finally, insertion-site analysis revealed six insertional mutations, three of which have mammalian homologues associated with malignancy.
COMMENTARY
This report is interesting because it apparently shows that malignantly transformed cells derived from a parasite can cause cancer in a human. It is known that infections with certain pathogens (e.g., human papilloma virus, Schistosoma haematobium) can lead to the development of cancer in humans, and that transmissible cancer cells circulate in Tasmanian devils. Indeed, it is also understood that in rare cases, cancer cells can be transmitted from human to human, such as with organ transplantation or from mother to fetus. But Muehlenbachs and colleagues present evidence of direct transmission of mutations associated with cancer from H. nana, a novel finding. The pathophysiology of the malignant transformation of the tapeworm cells is uncertain. The authors theorize that the patient’s compromised immune system allowed the tapeworm to proliferate, resulting in the accumulation of somatic mutations in the H. nana stem-cell population.
An unsettling finding from this case is that the patient received albendazole, the drug of choice for tissue-invasive disease. Yet, as the authors mention, the efficacy of albendazole against clonal proliferations of tapeworm stem cells is uncertain, and there is some evidence that it is ineffective. Thus, invasive H. nana with cellular proliferations might not be treatable with currently available drugs, and is an area that needs further investigation. It seems plausible that chemotherapy drugs that work in human cancer might also be effective against cancer cells from parasites. Before this hypothesis is explored, the link between human disease and malignant transformation in a parasite needs to be replicated by independent investigators.
[Editor’s Note: As Dr. Watkins indicates, transmissible cancers have previously been identified, including not only Tasmanian devil facial tumor disease, which is transmitted among the animals by facial biting, but also canine transmissible venereal tumor. Of further interest is that a Nobel Prize in Medicine was awarded to Johannes Fibiger in 1926 for his subsequently refuted “discovery” that the nematode Spiroptera carcinoma (now called Gongylonema neoplasticum) caused gastric cancer. Although this did not represent a claim of transmissibility of malignant cells but rather a secondary effect of a parasitic infection (such as the association of bladder cancer with S. haematobium infection mentioned above), it provides an interesting background anecdote.]
The first reported case of human disease caused by parasite-derived cancer cells was discovered in a 41-year-old man with HIV infection; lung, adrenal, and liver nodules; and lymphadenopathy.
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