Sensitive and Specific Immunohistochemical Diagnosis of Human Alveolar Echinococcosis with the Monoclonal Antibody Em2G11

Abstract

BackgroundAlveolar echinococcosis (AE) is caused by the metacestode stage of Echinococcus multilocularis. Differential diagnosis with cystic echinococcosis (CE) caused by E. granulosus and AE is challenging. We aimed at improving diagnosis of AE on paraffin sections of infected human tissue by immunohistochemical testing of a specific antibody.Methodology/Principal FindingsWe have analysed 96 paraffin archived specimens, including 6 cutting needle biopsies and 3 fine needle aspirates, from patients with suspected AE or CE with the monoclonal antibody (mAb) Em2G11 specific for the Em2 antigen of E. multilocularis metacestodes. In human tissue, staining with mAb Em2G11 is highly specific for E. multilocularis metacestodes while no staining is detected in CE lesions. In addition, the antibody detects small particles of E. multilocularis (spems) of less than 1 µm outside the main lesion in necrotic tissue, liver sinusoids and lymphatic tissue most probably caused by shedding of parasitic material. The conventional histological diagnosis based on haematoxylin and eosin and PAS stainings were in accordance with the immunohistological diagnosis using mAb Em2G11 in 90 of 96 samples. In 6 samples conventional subtype diagnosis of echinococcosis had to be adjusted when revised by immunohistology with mAb Em2G11.Conclusions/SignificanceImmunohistochemistry with the mAb Em2G11 is a new, highly specific and sensitive diagnostic tool for AE. The staining of small particles of E. multilocularis (spems) outside the main lesion including immunocompetent tissue, such as lymph nodes, suggests a systemic effect on the host.

Unconventional Maturation of Dendritic Cells Induced by Particles from the Laminated Layer of Larval Echinococcus granulosus

“…Recently, abundant particulate LL-derived materials have been detected in tissue sections from patients infected by E. multilocularis (26). These particles can be found millimeters away from the LL itself, including in lymph nodes draining the infected organ.…”

Echinococcus vogeliin Immigrant from Suriname to the Netherlands

“…Immunohistochemistry with monoclonal antibody Em2G11 raised against an E. multilocularis laminated layer antigen (Em2) ( 6 ) showed a faint and patchy pattern of the laminated layer in the E. vogeli lesion (Figure). Neither the previously described typical complete staining of the laminated layer as found in E. multilocularis larvae nor the entire absence of staining as described for E. granulosus metacestodes ( 7 ) was seen in the E. vogeli lesion. The typical staining of small particles of E. multilocularis , characteristically seen adjacent to E. multilocularis (spems) vesicles ( 7 ), was completely absent in this specimen.…”

“…Neither the previously described typical complete staining of the laminated layer as found in E. multilocularis larvae nor the entire absence of staining as described for E. granulosus metacestodes ( 7 ) was seen in the E. vogeli lesion. The typical staining of small particles of E. multilocularis , characteristically seen adjacent to E. multilocularis (spems) vesicles ( 7 ), was completely absent in this specimen. Immunohistochemical examination with a monoclonal antibody against echinococcal cytoskeleton protein EM10 ( 8 ) showed staining of the germinal layer and protoscolices of E. multilocularis and E. granulosus larvae but only partial staining of the protoscolices of E. vogeli larvae.…”

Autochthonous human alveolar echinococcosis in a Hungarian patient

“…In particular, histology revealed fragments of slender (<1 mm) and PAS-positive laminated layer, as well as abundant necrosis and tubular growth pattern which are characteristic conventional histological criteria for diagnosis of AE (Fig. 2a, b) [6]. Western blot (Ldbio Diagnostics, France) serology were negative to E. multilocularis, 5 and 9 months after surgery.…”

“…Being aware of the very low incidence of human AE in Hungary, we decided to make a histopathological reevaluation before the initiation of the recommended adjuvant parasitostatic therapy [7]. An independent pathologist confirmed the diagnosis of hepatic AE infection on histological slides from the original paraffin block using immunohistochemical staining with the monoclonal antibody Em2G11 [6]. Since positive staining with this antibody is highly specific for a glycoprotein of the laminated layer of E. multilocularis, an AE was diagnosed (Fig.…”