CAMTA-1 Expression in 24 Cases of Hepatic Epithelioid Hemangioendothelioma in a Single Institute: Diagnostic Utility for Differential Diagnosis from Hepatic Angiosarcoma

Abstract

Background/Aim: Epithelioid hemangioendothelioma (EHE) of the liver is an uncommon vascular tumor with variable clinical courses ranging from stable disease to fatal outcome. EHE can mimic epithelioid angiosarcoma, which has a more aggressive behavior, especially in a small biopsy sample. EHEs are known to have the WWTR1-CAMTA1 fusion gene, and nuclear expression of CAMTA1 by immunohistochemistry (IHC) has been reported in about 90% of EHEs in multiple organs. Our study aimed to validate the diagnostic utility of CAMTA1 expression in EHEs, especially in the liver. Patients and Methods: IHC was performed using anti-CAMTA1 antibody in 34 tumors (24 hepatic EHEs and 10 angiosarcomas). In CAMTA1-negative EHEs, TFE3 IHC was performed. Results: Of the 24 hepatic EHEs, 22 (91.6%) showed nuclear staining for CAMTA1. One of two CAMTA1negative cases showed TFE3 positivity. The other case was negative for TFE3. Meanwhile, all 10 angiosarcoma cases had no CAMTA1 expression. Conclusion: CAMTA1 is a highly sensitive and specific marker for diagnosis of hepatic EHE. It is helpful for differentiation of hepatic EHE and angiosarcoma, especially in small biopsy samples.

Hepatic Angiosarcoma: Clinicopathologic Study With an Investigation of ROS1 Gene Rearrangements

“…The median survival period was 5 months. The overall prognosis of PHA is dismal, compared to hepatic hemangioendothelioma with a mortality rate of 25% (13). Recently, the ROS1 fusion genes with GOPC/FIG (6) and CEP85L (7) have been reported in angiosarcomas.…”

Pediatric vascular tumors of the liver: Review from the pathologist’s point of view

“…Histologically (Figure 6 ), EHEs are relatively distinctive from the normal liver parenchyma and are composed of nests, cords, strands or single infiltrative epithelioid cells set in a myxohyaline stroma. The cells in HEH are epithelioid with eosinophilic cytoplasm and frequently show intracytoplasmic vacuoles (so-called “blister cells”)[ 20 , 28 ]. Occasionally, there are tufts or papillary projections into the vessels.…”

“…In this setting, the distinction between EHE and HA can be difficult for a pathologist, especially in small liver biopsies. Usually EHE shows nuclear calmodulin-binding transcription activator1 (CAMTA1) expression, which can be very helpful in the differential diagnosis with HA since this is a highly specific and sensitive marker for EHE with a CAMTA1 rearrangement (Figure 6 )[ 28 ]. EHE also stains for ERG, CD31, CD34, factor VIII and podoplanin (D2-40)[ 15 , 20 , 28 ].…”

“…Usually EHE shows nuclear calmodulin-binding transcription activator1 (CAMTA1) expression, which can be very helpful in the differential diagnosis with HA since this is a highly specific and sensitive marker for EHE with a CAMTA1 rearrangement (Figure 6 )[ 28 ]. EHE also stains for ERG, CD31, CD34, factor VIII and podoplanin (D2-40)[ 15 , 20 , 28 ]. Nuclear positivity for transcription factor E3 (TFE3) is seen in most cases of EHE, irrespective of an underlying TFE3 rearrangement[ 20 , 28 ].…”

“…EHE also stains for ERG, CD31, CD34, factor VIII and podoplanin (D2-40)[ 15 , 20 , 28 ]. Nuclear positivity for transcription factor E3 (TFE3) is seen in most cases of EHE, irrespective of an underlying TFE3 rearrangement[ 20 , 28 ]. A small subset of EHE expresses pan-cytokeratin or cytokeratin 8/18 (CK8/18)[ 20 ].…”