Binford Dammin 2016 Companion Meeting

Parasitic Infections of the Lung and Infectious Mimics Bobbi Pritt, MD, MSc, DTM&H Mayo Clinic

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Dr. Pritt has no conflicts of interest to disclose. Parasites in the lung • Variety of protozoa, helminths and, rarely, arthropods • Most common protozoan pulmonary diseases: • Malaria lung • Amebiasis (amebic lung abscess) • Toxoplasmosis • Most common helminthic diseases: • • • • • •

Pulmonary parasitic Syndromes • Loeffler syndrome • Transient syndrome associated with migration of , Strongyloides stercoralis, and larvae through lungs • Fever, malaise, cough, wheezing, dyspnea ~15 days after infection • Blood eosinophilia – 1500 cells/µL • Tropical pulmonary eosinophilia • Immune hyperresponsiveness to microfilariae of and that become trapped in the lungs • Slow onset, paroxysmal nocturnal cough, asthma-like attacks, fever, malaise, rarely dyspnea, • Blood eosinophilia - >3000 cells/µL • Serious; if untreated, leads to progressive pulmonary fibrosis and respiratory failure

Role of the Pathologist

• Many of these infections and syndromes are diagnosed by traditional laboratory assays • There are a number of parasites that are not infrequently seen in cytology and histopathology preparations Case #1

• 67 yo American male with known COPD and recent increase in productive cough • Lives in Tennessee; no travel history outside of the U.S. • Solitary nodule noted on chest radiograph • The nodule was resected H&E, 20x H&E, 100x Diagnosis? Dirofilariasis Dirofilariasis

• Usually caused by Dirofilaria immitis (the dog heart worm) • Less commonly caused by D. repens • (round worm) • Dogs are the natural host • Commonly seen in regions where there are numerous stray dogs that are not de-wormed. • American southeast How is Dirofilaria transmitted?

A. Ingestion of eggs in fecally-contaminated soil B. Ingestion of larvae in undercooked meat C. Penetration of intact skin by larvae in soil D. Bite from an infected mosquito

Clinical and radiologic features

• Most patients have mild symptoms and don’t seek treatment • Solitary pulmonary nodule (coin lesion) may be noted later on imaging • Cough, chest pain, hemoptysis • Peripheral eosinophilia in only ~10%

Gross features

• Well-defined area of coagulation necrosis with normal surrounding lung • Worm may be seen in region of necrosis (100-350 µm diameter) Histologic features

• Caseous-like necrosis • Surrounding rim of fibrosis • Granulomatous inflammation which may include eosinophils • Internal lateral ridges underlying lateral chords are usually preserved Ridged cuticle

Internal lateral ridges Differential Diagnosis

100 µm

Aspirated food material – seeds, nuts, plants material Differential Diagnosis - continued

• Large areas of coagulation necrosis with surrounding granulomatous inflammation should prompt consideration of dirofilariasis • Perform special stains for mycobacteria and fungi • Perform deeper sections to look for a worm, 100-350 µm diameter: diagnostic for Dirofilaria sp. • Other roundworms in the lung: • Primarily larvae (much smaller; no internal organs) • Not associated with large areas of coagulation necrosis Name a round worm that can life- threatening pulmonary disease • Strongyloides stercoralis • Primarily infects the small intestine • A low level of autoinfection occurs during normal infection: larvae penetrate bowel wall, enter blood stream, and migrate to the lungs. There they break out into the alveoli, migrate up the bronchi and trachea, and are swallowed to reach the intestine again. • In the immunocompromised host, autoinfection increases to cause HYPERINFECTION Filariform larvae (stage found in the lungs) have a subtly-notched tail Histologic features

• Larvae may not have an associate immune response • Usually alveolar hemorrhage and mixed inflammatory infiltrate • Larvae: 400-700 µm length; 10-20 µm diameter • Secondary bacterial pneumonia is common

Differential Diagnosis

Curschmann spirals – inspissated mucus coils Differential diagnosis of roundworm larvae in the lungs • Intestinal : Strongyloides stercoralis, Ascaris lumbricoides, hookworm larvae • All 3 cause transient migration during early stage infection; associated with Loeffler syndrome. Only S. stercoralis causes hyperinfection with massive numbers of larvae. Larvae will also be found in stool. • Clinical presentation and subtle morphologic features can distinguish them (e.g. notched tail of Strongyloides, lateral alae of Ascaris). • Microfilariae in tropical pulmonary eosinophilia • Degenerating worms found in eosinophilic abscesses • Larvae causing visceral migrans (Toxocara spp., ) • Usually in children; larvae have lateral alae Case #2

• 52 year old Mexican woman with asthma • Presented with increased dyspnea and productive cough • Sputum was obtained for microbiology and cytology

Pap, 1000x Pap, 1000x Pap, 1000x Pap, 600x Diagnosis? Ciliocytophthoria (a.k.a. detached ciliary tufts) and degenerated respiratory epithelial cells Ciliocytophthoria/DCTs

• Mimic of flagellate parasites • Commonly seen in respiratory specimens, especially in inflammatory states (e.g. asthma) • Often motile on wet preparations • Have been mistaken as trophozoites of Trichomonas tenax, Balantidium coli, or the free-living amebae Object/organism Size (µm Distinguishing Morphologic Features diameter) Detached ciliary tufts 5-15 Cilia present in a dense mat, attached to a terminal plate; cilia beat in a rhythmic motion without propelling the object forward Trichomonas tenax 5-15 4 apical flagellae Balantidium coli 40-200 Free-living amebae (e.g. 15-60 No flagellate form; only Naegleria fowleri Acanthamoeba spp., (trophozoit has a flagellate form in nature (not Balamuthia mandrillaris) es) humans) Balantidium coli trophozoites

Detached ciliary tufts Case #3

• Woman • No travel history outside of the United States

• Pleural peel H&E, 20x H&E, 40x H&E, 100x H&E, 400x H&E, 1000x Diagnosis? Paragonimiasis Paragonimiasis

• Caused by and other • The only helminth that preferentially infects the lung • Trematode (fluke, a leaf-like flat worm) • Widespread in parts of Asia; also in Mexico, Central America and the United States (P. kellicotti) • Due to ingesting raw or undercooked crustaceans (e.g. crayfish, crabs)

Gross features

• 1 or more cystic cavities • 1-3 cm diameter • Commonly near/communicating with large bronchioles • Wall of cavity is thin, up to several mm thickness • Each cavity contains 1-2 flukes in mucinous/necrotic fluid • Flukes are 7-12 mm long, “coffee-bean” or “lemon” shape Histopathologic features

• Adults may be seen within cystic cavities with eosinophilic and granulomatous inflammation • Area around the cyst often has retained eggs

Eggs

• Yellow-brown • Birefringent wall

• Shouldered operculum • Associate with acute and granulomatous inflammation Differential Dx

• Eggs of spp. • No operculum • Not birefringent • Usually contain a nucleated larval form Parasites ‘commonly’ seen in lungs in pathology specimens Protozoa Helminths • Entamoeba histolytica • Dirofilaria immitis (amebiasis) • • Toxoplasma gondii • Paragonimus westermani • Free-living amebae (rare) • Schistosoma spp. • Plasmodium falciparum (rare; • Strongyloides stercoralis autopsy) • ()