Figure 1. Figure 1. Radiographic and Pathological Features of Malignant Hymenolepis nana. Anteroposterior and axial CT scans in Panels A and B, respectively, show the presence of lung nodules. Panel C shows a biopsy specimen from a cervical lymph node containing firm, solid masses. Panel D shows small, atypical cells in an air-dried lymph-node touch preparation stained with Diff-Quik. Hematoxylin and eosin staining of a lymph-node histologic section shows invasive, irregular nests of proliferative cells (asterisk) in Panel E, monomorphic cellular features and multinucleated syncytia (arrowheads) on a higher-power field in Panel F, and cytologic atypia with occasional large, pleomorphic nuclei and multiple nucleoli (arrowheads) in Panel G. The transmission electron micrograph in Panel H shows ribosome-rich cytoplasm with scattered mitochondria (arrowhead) and a nucleus with a conspicuous central nucleolus (asterisk). Scale bars correspond to 1 cm in Panel C, 10 μm in Panels D through G, and 1 μm in Panel H.

In January 2013, a 41-year-old man in Medellín, Colombia, presented with fatigue, fever, cough, and weight loss of several months’ duration. He had received a diagnosis of HIV infection in 2006 and was nonadherent to therapy; the most recent CD4 cell count was 28 per cubic millimeter, and the viral load was 70,000 copies per milliliter. Stool examination revealed H. nana eggs and Blastocystis hominis cysts. Computed tomographic imaging showed lung nodules ranging in size from 0.4 to 4.4 cm (Figure 1A and 1B), as well as liver and adrenal nodules and cervical, mediastinal, and abdominal lymphadenopathy. Excisional biopsy of a cervical lymph node and core-needle biopsy of the lung were performed. The Centers for Disease Control and Prevention (CDC) was initially consulted by means of telediagnosis, with digital images sent to the Web-based DPDx diagnostic laboratory; paraffin-embedded tissues were subsequently submitted to the CDC. The patient received three doses of albendazole as empirical treatment, and antiretroviral medications were reinstated. The disease progressed, and a second cervical lymph-node biopsy was performed in April 2013, with fresh tissue sent to the CDC for evaluation.

The lymph nodes were grossly abnormal, solid, nodular masses (Figure 1C), from which a touch preparation showed small, atypical cells with scant cytoplasm and prominent nucleoli (Figure 1D). Histologic examination showed effacement of normal architecture by irregular, crowded nests of small, atypical cells (Figure 1E). Syncytia containing atypical nuclei were present at the periphery of the nests (Figure 1F). The individual cells had scant cytoplasm and measured 5 to 6 μm in diameter (slightly smaller than a human red cell), with nuclei that were approximately 2 to 3 μm in diameter. Occasional cells were markedly enlarged, with pleomorphic nuclei containing multiple nucleoli (Figure 1G). Mitotic figures, angiolymphatic invasion, and necrosis were also observed. Similar cells were present in the sample from the core-needle biopsy of the lung (see Fig. S1 in the Supplementary Appendix, available with the full text of this article at NEJM.org). Transmission electron microscopy showed that the cytoplasm was ribosome-rich and contained scattered mitochondria (Figure 1H). Other than syncytia formation, no feature of differentiation, including formation of microvilli, was seen (Fig. S2 in the Supplementary Appendix). Immunohistochemical staining of these cells was negative for human cytokeratin and vimentin (often expressed in cancer cells), as well as for free-living amebas.

This case posed a diagnostic conundrum. The proliferative cells had overt features of a malignant process — they invaded adjacent tissue, had a crowded and disordered growth pattern, and were monomorphic, with morphologic features that are characteristic of stem cells (a high nucleus-to-cytoplasm ratio) — but the small cell size (<10 μm in diameter) suggested infection with an unfamiliar, possibly unicellular, eukaryotic organism. Infection with a plasmodial slime mold (phylum, Amoebozoa; class, Myxogastria) was considered because of the prominent syncytia formation. Although many cestode tissues are syncytial — notably, their tegument — a tapeworm infection was initially considered less likely because of the primitive appearance of the atypical cells, the complete absence of architecture that was identifiable as tapeworm tissue, and the rarity of previously reported cases of invasive cestodiasis.2,3

During our laboratory investigations, the lesions of the lung, liver, and adrenal glands remained stable, but the lymph nodes (particularly in the neck) increased to a maximum of 5 cm in diameter, and over the course of 4 months, the patient’s clinical condition deteriorated. The patient was receiving tenofovir for the treatment of HIV infection and amphotericin B for histoplasmosis, and renal failure developed. The patient declined hemodialysis, and the delivery of palliative care was begun in May 2013. A molecular diagnosis was provided 72 hours before he died, and specific treatment was not attempted. A postmortem examination was not performed. Before he died, the patient provided written informed consent for studies to be performed and for publication of the results.