Pathology of Echinococcosis

Abstract

Infection of humans by the larval stage of the tapeworms Echinococcus granulosus sensu lato or Echinococcus multilocularis causes the life-threatening zoonoses cystic echinococcosis (CE) and alveolar echinococcosis (AE). Although cystic liver lesions are a hallmark of both diseases, course, prognosis, and patients' management decisively differ between the two. The wide and overlapping spectrum of morphologies and the limited availability of ancillary tools are challenges for pathologists to reliably diagnose and subtype echinococcosis. Here, we systematically and quantitatively recorded the pathologic spectrum in a clinically and molecularly defined echinococcosis cohort (138 specimens from 112 patients). Immunohistochemistry using a novel monoclonal antibody (mAbEmG3) was implemented, including its combined application with the mAbEm2G11. Six morphologic criteria sufficiently discriminated between CE and AE: size of smallest (CE/AE: >2/2 mm) and largest cyst (CE/AE: >25/25 mm), thickness of laminated layer (CE/AE: >0.15/0.15 mm) and pericystic fibrosis (CE/AE: >0.6/0.6 mm), striation of laminated layer (CE/AE: moderate-strong/weak), and number of cysts (CE/AE: 9/>9). Combined immunohistochemistry with mAbEm2G11 (E. multilocularis specific) and mAbEmG3 (reactive in AE and CE) was equally specific as and occasionally more sensitive than polymerase chain reaction. On the basis of these findings, we developed a diagnostic algorithm for the differential diagnosis of echinococcosis. In summary, we have not only identified the means to diagnose echinococcosis with greater certainty, but also defined morphologic criteria, which robustly discriminate between CE and AE. We expect our findings to improve echinococcosis diagnostics, especially of challenging cases, beneficially impacting the management of echinococcosis patients.

Genetic diversity of Echinococcus multilocularis and Echinococcus granulosus sensu lato in Kyrgyzstan: The A2 haplotype of E. multilocularis is the predominant variant infecting humans

“…PCR confirmed the presence of E. multilocularis in 60 out of 61 AE human patients diagnosed in Kyrgyzstan. The remnant sample was additionally confirmed as AE using immunohistochemichal-stainings with monoclonal antibodies [26]. From the 60 samples mentioned above, it was possible to amplify and acquire good quality sequences from all the three genes of interest (cob, nad2 and cox1) in 52 isolates.…”

Fast-Growing Alveolar Echinococcosis Following Lung Transplantation

“…Histological examination of tissue, showing characteristic PAS-positive metacestode layer allows for the diagnosis of AE, even if differential diagnosis with cystic echinococcosis is sometimes difficult. Thus, it should require the implementation of an immunohistochemistry assay using mAb Em2G11 staining [7,22]. AE diagnosed in the context of immunosuppression has a poor prognosis overall [3].…”

Immunohistological detection of small particles of Echinococcus multilocularis and Echinococcus granulosus in lymph nodes is associated with enlarged lymph nodes in alveolar and cystic echinococcosis

“…As seen in imaging and macroscopic analysis, the lesions of both AE and CE are characterized by metacestode proliferation. However, in CE mostly few typical cysts surrounded by the parasite laminated layer and the host tissue adventitial layer are seen, in contrast AE lesions manifest with an invasive growth pattern and multiple small alveolar structures in histological examination [9,10].…”

“…The perilesional reactive tissue consists of an inner zone of epithelioid cells, a fibrotic zone, and an outer rim of lymphocytes [13]. CE and AE are clearly distinguished histologically by the thickness of the laminated layer and a different morphology of accompanying necrosis and surrounding fibrosis [9].…”

“…Immunohistochemistry (IHC) is an important diagnostic tool supporting conventional histology, especially in small biopsy specimens not containing all the diagnostic histological features for AE and CE. Two primary antibodies against echinococcus antigens are currently available; these are the monoclonal antibody (mAb) Em2G11 and the mAb EmG3 [9,14,15]. mAb Em2G11 is specific for the mucin-type Em2 glycoprotein of E. multilocularis and recognizes AE in tissue or effusions containing the antigen [9,[14][15][16].…”