Pseudocirrhosis secondary to chemotherapy of breast cancer liver metastases

Clinical History

A young female with history of G3 invasive ductal breastadenocarcinoma with bone, liver and pleural metastases at diagnosis, underwent serial follow-up CT studies during prolonged chemotherapy with several regimens (5FU+epirubicin+cyclophosphamide, paclitaxel, tamoxifen and capecitabine). Persistent mild abnormalities of liver enzymes (peak alanine-aminotransferase 95 U/l). No other risk conditions for liver disease.

Imaging Findings

At baseline, initial CT (Fig.1) detected right-sided malignant pleural effusion with pleural masses, multiple skeletal lytic lesions, and marked liver enlargement compared to the patient's body habitus disseminated with innumerable hypovascular metastases, which measured up to 5 cm in size.
After 4 months, follow-up CT (Fig.2) showed decreasing pleural effusion, decreased number, size and enhancement of liver metastases consistent with a positive therapeutic response.
Further follow-up CT studies (Figs.3 and 4) showed resolved pleuropulmonary changes at the right lung base; progressive decrease of hepatomegaly and regression of treated liver metastases, plus appearance and progressive development of band-shaped nonenhancing areas interpreted as confluent fibrosis causing focal capsular retraction.
Ultimately, nearly two years after initial diagnosis, CT (Fig.5) confirmed liver shrinkage with multifocal capsular retraction (arrowheads) and bulging contours of spared parenchymal regions (including caudate lobe hypertrophy) characteristic of pseudo-cirrhosis. The patient is doing well without clinical, imaging and laboratory signs of neoplastic recurrence.

Discussion

Due to the growing use of antineoplastic therapies, chemotherapy-related liver complications are nowadays relatively common, and may range from asymptomatic steatosis to acute hepatitis or chronic liver impairment. Hepatocellular injury is generally indicated by increasing serum levels of liver enzymes, in advanced cases by impaired synthesis and jaundice; alternatively liver changes are often detected by imaging studies obtained during oncologic follow-up [1-4].
Pseudocirrhosis is a radiologic term which refers to the progressive development of diffuse morphologic liver changes secondary to chemotherapy, which closely resemble macronodular cirrhosis at imaging, in patients without previous or concurrent chronic liver disease. Pseudocirrhosis may occur with metastases that decrease, coalesce or increase in size during treatment, and represents the extreme and widespread manifestation of capsular retraction developing adjacent to treated lesions. The majority of cases were encountered after gemcitabine administration for advanced breast cancer, occasionally in patients with pancreatic, thyroid, esophageal and gastrointestinal tumours. The pathogenesis is still unclear but probably involves chemotherapy-induced ischemic atrophy followed by secondary regenerative hyperplasia (RH) in regions with preserved blood flow. Histological studies revealed diffuse transformation of the liver parenchyma into RH nodules, without the typical “bridging” fibrosis of usual cirrhosis. Laboratory assays generally reveal normal or mildly increased serum transaminases, preserved synthetic function, decrease or normalisation of tumour markers [5-8].
As in this typical case, pseudocirrhosis is generally detected at serial CT studies, and progresses rapidly compared with true cirrhosis: changes initially appear within the first 6 months and fully develop a median 15 months after chemotherapy. The characteristic imaging features include multifocal flattening or concavity of the normally convex hepatic contour adjacent to treated metastases which typically shade off, progressive development of retractile regions of confluent fibrosis, segmental volume loss, and caudate lobe enlargement. Pseudocirrhosis often hampers the interpretation of CT studies and assessment of treatment response [1-5].
The differential diagnosis of pseudocirrhosis includes other more or less common forms of chemotherapy-related liver damage, and alternative causes of hepatic distortion, capsular retraction and shrinkage [9, 10].
Recognizing and correctly diagnosing pseudocirrhosis as a post-treatment complication rather than true cirrhosis is important, since it may lead to discontinuation or modification of chemotherapy in order to prevent further liver damage and progression to portal hypertension with splenomegaly, ascites and porto-systemic collaterals [3-8].

Differential Diagnosis List

Final Diagnosis

Pseudocirrhosis after chemotherapy for metastatic breast carcinoma.

URL:	https://www.eurorad.org/case/14164
DOI:	10.1594/EURORAD/CASE.14164
ISSN:	1563-4086