Trastuzumab Emtansine–Associated Porto-Sinusoidal Vascular Disorder: Clinical Features and Outcomes from Published Cases

Introduction: Ado-trastuzumab emtansine (T-DM1) is a targeted agent for human epidermal growth factor receptor 2 (HER2)-positive breast cancer, which combines the anti-tumor activity of trastuzumab with the cytotoxic effect of DM1, a microtubule inhibitor. Although T-DM1 has improved outcomes in patients with HER2-positive breast cancer, portal hypertension may occur during treatment in the absence of overt cirrhosis on liver biopsy. These clinical and pathological features are consistent with porto-sinusoidal vascular disorder (PSVD). This study aimed to summarize the reported clinical, biochemical, imaging, histological, therapeutic, and prognostic features of T-DM1-associated PSVD. Methods: PubMed and Web of Science were searched for published cases of T-DM1-associated PSVD. Given the evolving terminology of PSVD, related terms, including non-cirrhotic portal hypertension and nodular regenerative hyperplasia, were also included in the search strategy. If the patient has a recorded history of T-DM1 exposure and the liver biopsy results meet PSVD criteria, the case is included regardless of whether there is clinical, endoscopic, or imaging evidence of portal hypertension. Cases without liver biopsy or with features suggestive of overt cirrhosis were excluded. Patient-level data were extracted and descriptively summarized, including demographic characteristics, clinical manifestations, biochemical indicators, imaging examination results, liver biopsy results, treatment methods, and prognosis. Unreported data were considered missing values and were not imputed. Results: Seven eligible articles comprising eight patients were identified. All patients were female, with a mean age of 60.38 years and a median age of 62.50 years. The interval from T-DM1 initiation to PSVD diagnosis ranged from 6 to 30 months. When reported, the mean interval from treatment initiation to symptom onset was 18.3 months. Thrombocytopenia and splenomegaly were observed in 7 of 8 patients. Mild elevations in alanine aminotransferase and aspartate aminotransferase were observed in all patients. Liver biopsy showed thinned and disorganized hepatic plates accompanied by nodular regeneration of hepatocytes in six patients. Clinical improvement was observed after discontinuation or modification of T-DM1 in most cases. Conclusions: T-DM1-associated PSVD is a rare but clinically significant complication that may develop months after treatment initiation. It commonly presents with thrombocytopenia, splenomegaly, gastrointestinal bleeding, or mild liver biochemical abnormalities in the absence of overt cirrhosis. Early recognition of unexplained platelet decline, splenic enlargement, or portal hypertension-related findings during T-DM1 therapy may facilitate timely diagnosis and individualized management. Withdrawal or modification of the suspected drug may contribute to clinical improvement, although further studies are needed to clarify the mechanism and optimal management strategy.