Keywords pseudocirrhosis - liver - metastasis - transitional cell carcinoma - chemotherapy
- complications - portal vein thrombosis.
Case Presentation
We present a case of a 72-year-old patient with metastatic transitional cell carcinoma
(TCC). His medical history was significant for ischemic heart disease, with a previous
myocardial infarction, benign prostatic hyperplasia and past smoking. A noncontrast
CT scan obtained at a different hospital, following a car accident in July 2018, detected
a mass between the stomach and the liver and diffuse retroperitoneal and mesenteric
lymphadenopathy, with no obvious primary tumor. Subsequent biopsy from the abdominal
mass and a para-aortic lymph node revealed urothelial carcinoma. A subsequent PET/CT
scan ([Fig. 1A ]
[B ]; G.E. healthcare PET/CT scanner, Discovery 710, year of production– 2016; neck-chest-abdomen-pelvis
CT with intravenous injection of ultravist 370, 85 mL, and PET acquisition using F-18
FDG with activity of 8 mCi; slice thickness of 2.5 mm; radiation dose– 11.55 mGy)
found numerous metastatic lesions in the liver and bones in addition to the aforementioned
widespread lymphadenopathy. The primary tumor could not be localized in the PET/CT
scan. Bone marrow biopsy was consistent with chronic lymphocytic leukemia.
Fig. 1 (A , B ) Axial images of portal venous phase CT scan of the abdomen, demonstrating hepatic
metastases. (C , D ) Coronal view and axial view: First PET-CT scan in the venous phase, demonstrating
multiple FDG-avid hepatic metastases. FDG, fluorodeoxyglucose.
Following six cycles of gemcitabine and cisplatin chemotherapy, which were initiated
in July 2018, a gradual decrease in size and attenuation of the liver metastases was
seen on CT to their complete resolution in March 2019 ([Fig. 2A ]
[B ]; Philips Medical Brilliance ICT Scanner, year of production– 2015; noncontrast upper
abdomen scan and postcontrast scan of the chest, abdomen and pelvis with IV injection
of ultravist 370, 85 mL; slice thickness of 2 mm; radiation dose 18/1 mGy). The response
in the liver and lymph nodes was followed by disease progression with new brain metastases.
Fig. 2 (A , B ) First CT scan in the venous phase after six cycles of chemotherapy demonstrate near
resolution of the hepatic metastases (axial and coronal views).
In July 2019, the patient presented to the emergency department complaining of abdominal
pain. An elevation of liver enzymes prompted an ultrasound scan which demonstrated
ascites and a small liver with lobular borders and a nonuniform texture. The portal
vein was measured 15 mm with a very slow flow of 12 cm/second. No portal thrombus
was detected. The hepatic veins demonstrated a monophasic flow.
Further evaluation with a quadriphase CT scan ([Fig. 3A ]
[E ]; G.E. healthcare CT scanner, Lightspeed VCT, year of production– 2006; upper abdomen
before and after IV injection of ultravist 370, 85 mL, in the arterial phase followed
by a scan of the chest, abdomen and pelvis in the venous phase and a delayed scan
of the upper abdomen; slice thickness of 2.5 mm for the arterial and venous phases
and 3.75 mm for the noncontrast and delayed phases; radiation dose– 79.91 mGy) showed
a heterogeneous and nodular liver parenchyma with lobular contours. The portal vein
diameter measured 18 mm, thereby demonstrating portal venous hypertension. Ascites
in moderate quantity were also noted. Considering the previous metastases to the liver,
these findings are consistent with pseudocirrhosis. A new hypodense filling defect
in the right main portal vein and its tributaries, with near complete obstruction.
The filling defect did not demonstrate postcontrast enhancement, supporting a bland
thrombus. A repeat ultrasound scan ([Fig. 3F ]; Siemens, ACUSON S2000, version VC25, year of production– 2012) shortly thereafter
demonstrated a portal vein thrombus with no color flow on Doppler scan. This again
supports a bland tumor. No biopsy was performed to the liver. It is worth mentioning
that the ascitic fluid was sampled and revealed malignant epithelial cells.
Fig. 3 (A–F ) CT scan in the venous phase, axial and coronal views; (F ) Doppler US scan. (A–C ) Nodular liver with lobular margins and ascites. (D, E ) Portal venous thrombosis. (F ) Portal venous thrombosis without color flow on US scan.
The patient passed away approximately 10 days following the quadriphase CT scan.
Discussion
Pseudocirrhosis describes the development of diffuse hepatic nodularity and segmental
volume loss, following chemotherapeutic treatment for hepatic metastases.[1 ]
[2 ] These changes cause capsular retraction and enlargement of the caudate lobe in a
similar manner to cirrhosis.[3 ] Even though pseudocirrhosis may induce portal hypertension and liver failure, it
does not share the feature of loss of synthetic function with proper cirrhosis.[3 ] Capsular retraction may evolve rapidly over 1 to 3 months.[4 ]
The underlying mechanisms for this phenomenon have not yet been adequately elucidated,
although it is believed to result from shrinkage of tumor with scarring and nodular
regeneration of uninvolved liver parenchyma.[4 ] Fennesy et al found that pseudocirrhosis occurred more frequently in patients with
larger metastases. They also demonstrated that capsular retraction occurs with an
increase in the dimensions of a subjacent metastasis, possibly owing to local distortion
of the liver parenchyma by fibrosis and tumor infiltration.[5 ]
Interestingly, pseudocirrhosis has been found mainly in patients with metastatic breast
carcinoma.[4 ]
[6 ] Pseudocirrhosis has also been sporadically reported in patients with other metastatic
malignancies such as cancers of the digestive system (esophageal, stomach colon, pancreas,),
thyroid and small-cell lung.[7 ]
[8 ]
[9 ]
[10 ]
[11 ]
[12 ] Certain lymphoma types may masquerade as pseudocirrhosis secondary to desmoplastic
reaction to tumor cells infiltrating the liver parenchyma.[13 ]
Portal vein thrombosis occurs in up to 26% of patients with cirrhosis, more commonly
among those with more severe liver disease.[14 ]
[15 ] In a review of the literature, we found only one case of portal vein thrombosis
in pseudocirrhosis due to recurrent breast cancer.[16 ]
The differential diagnosis in our patient includes pseudocirrhosis, true cirrhosis,
nodular regenerative hyperplasia, and drug-induced liver disease. Cirrhosis results
from disruption of the hepatic architecture secondary to regenerating nodules and
fibrosis, leading to a nodular liver contour and capsular retraction.[17 ] In nodular regenerative hyperplasia (NRH), small regenerative nodules develop in
the liver with scarce fibrosis secondary to altered blood flow.[18 ] The etiology is variable, ranging from systemic conditions to drugs such as chemotherapeutic
agents (most commonly azathioprine). Symptomatic portal hypertension is not very common
in NRH. Imaging of drug-induced liver injury is often nonspecific with heterogeneous
enhancement of the liver parenchyma, periportal edema and ascites.[19 ]
The constellation of nodular liver with capsular retraction and portal hypertension,
with its complications in a patient with previous metastatic liver disease, treated
with chemotherapy strongly favors the working diagnosis of pseudocirrhosis. We suggest
this as the first known occurrence of pseudocirrhosis, following treatment of transitional
cell carcinoma metastatic to the liver.
In addition, to our knowledge, portal vein thrombosis has not been described in patients
with pseudocirrhosis. In our view, it resulted in a similar manner as in true cirrhosis;
hence, the slow blood flow in the portal vein in combination with a hypercoagulable
state predisposed to its occurrence in our patient.
