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DOI: 10.1148/radiol.2211001754
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(Radiology. 2001;221:117-121.)
© RSNA, 2001

Gastrointestinal Imaging

Diffuse Desmoplastic Breast Carcinoma Metastases to the Liver Simulating Cirrhosis at MR Imaging: Report of Two Cases1

Alessandra B. Nascimento, MD 2, Donald G. Mitchell, MD, Raphael Rubin, MD and Eric Weaver, MD

1 From the Departments of Radiology (A.B.N., D.G.M.) and Pathology (R.R., E.W.), Thomas Jefferson University Hospital, 132 S 10th St, 1096 Main Bldg, Philadelphia, PA 19107. Received November 3, 2000; revision requested December 23; revision received March 16, 2001; accepted April 9. Address correspondence to D.G.M. (e-mail: donald.mitchell@mail.tju.edu).


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 Case Reports
Discussion
 REFERENCES
 
Two patients with breast carcinoma, without a prior diagnosis of liver lesions, had proved desmoplastic hepatic metastases that resembled cirrhosis at magnetic resonance (MR) imaging. The cirrhotic appearance of the livers may have resulted from the hepatotoxic effects of chemotherapy and/or hepatic infiltration by the metastatic tumor itself. Despite its high soft-tissue contrast, MR imaging may fail to depict extensive metastases from breast carcinoma, especially when they simulate other diseases (eg, cirrhosis). Correlation of MR imaging findings with clinical history is mandatory.

Index terms: Breast neoplasms, metastases, 00.32 • Liver, MR, 761.121411, 761.121412 • Liver neoplasms, metastases, 761.33


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
Case Reports
Discussion
 REFERENCES
 
Hepatic metastases from breast carcinoma can occasionally simulate cirrhosis anatomically, especially after systemic chemotherapy has been administered. We report two proved cases of treated breast carcinoma metastatic to the liver that resembled cirrhosis at magnetic resonance (MR) imaging and discuss the possible causes for the findings.


   Case Reports
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 ABSTRACT
 INTRODUCTION
 Case Reports
Discussion
 REFERENCES
 
Case 1
Breast carcinoma had been diagnosed in a 62-year-old woman 13 years ago. She had been treated with left mastectomy, perioperative radiation therapy, and chemotherapy, initially with fluoxymesterone. Four years ago, the patient received docetaxel and doxorubicin hydrochloride for bone metastasis. Abdominal computed tomography (CT) performed 2 years ago showed no evidence of liver metastases. Recently, the patient noted fluid retention during a period of 4–5 months, with worsening lower-extremity swelling and increasing abdominal girth. At paracentesis, 2.5 L of yellow-brown fluid was removed, and this was negative for amylase, lipase, and infection. She had no abdominal pain, fever, chills, chest pain, or shortness of breath.

Physical examination findings included a soft, nontender abdomen distended with ascites and edema in the abdominal wall and lower leg. There was no hepatosplenomegaly. Laboratory data revealed a total bilirubin level of 3.2 mg/dL (55 µmol/L) (normal range, 0.3–1.0 mg/dL [5–17 µmol/L]), direct bilirubin level of 1.4 mg/dL (24 µmol/L) (normal range, 0.1–0.3 mg/dL [2–5 µmol/L]), aspartate aminotransferase level of 80 U/L (normal range, 0–42 U/L), and alanine aminotransferase level of 46 U/L (normal range, 0–48 U/L). Results of serologic tests for hepatitis B and C were negative.

Ultrasonography (US) of the abdomen showed no focal liver lesions and no bile duct dilatation. There was reversal of flow in the main, left, and right portal veins, which was suggestive of advanced portal hypertension. MR imaging of the abdomen showed no focal liver lesions, and the findings were consistent with a grossly cirrhotic liver. The spleen was slightly enlarged and was 15 cm long. There were small retroperitoneal, periumbilical, and esophageal varices (Fig 1).



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  		Figure 1. Case 1. (A) Coronal single-shot fast spin-echo MR image ({infty}/100 [repetition time msec/echo time msec]), (B) transverse single-shot fast spin-echo MR image ({infty}/186), and (C) transverse dynamic fast spoiled gradient-echo MR image in the portal phase (8/1.5, 90° flip angle) show decreased hepatic volume and lobulated contour. There is mild enlargement of the caudate lobe (arrow in A) but no focal lesions. In C, varices (arrow) are seen medial to the spleen. (D) Specimen from liver biopsy (Masson trichrome stain; original magnification, x2,000) shows sinusoidal spread of metastatic breast carcinoma cells (small arrows) and desmoplastic reaction (blue). The large arrow indicates an island of residual hepatic parenchyma.

 
Repeat paracentesis yielded gross blood but no evidence of peritonitis. Subsequently, the patient developed signs and symptoms of hepatic encephalopathy. Results of transjugular liver biopsy revealed poorly differentiated adenocarcinoma with a dense scirrhous reaction. Small nodules of parenchyma were dispersed among the tumor deposits, producing a lobulated appearance (Fig 1). The patient died 1 month later.

Case 2
A 46-year-old African-American woman was treated for a left breast carcinoma with radiation therapy and chemotherapy (doxorubicin hydrochloride, Adriamycin; Pharmacia & Upjohn, Kalamazoo, Mich). Three years later, she noticed a mass in her right breast. Right sentinel node biopsy was performed, and seven of seven nodes were malignant. The patient received 20 weeks of therapy with paclitaxel (Taxol; Bristol-Myers Squibb, Princeton, NJ) and 3 weeks of therapy with docetaxel (Taxotere; Aventis Pharmaceuticals, Bridgewater, NJ), and she underwent bone marrow transplantation. Serial CT scans showed no focal liver lesions (Fig 2).



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  		Figure 2. Case 2. Transverse CT scan obtained during the portal venous phase shows a normal hepatic contour and no focal lesions.

 
Five years after the initial diagnosis, the patient was hospitalized for nausea, vomiting, and increasing abdominal size. A diagnosis of disseminated intravascular coagulopathy was made. She received transfusions of platelets, cryoprecipitate, and packed red blood cells and was treated with heparin. Results of physical examination revealed jaundice, crackles at the lung bases, a tender distended abdomen with signs of ascites, and 2+ pitting lower-extremity edema. Laboratory values at admission included a white blood cell count of 33 x 109/L (normal range, 4.3–10.8 x 109/L); neutrophil count, 85% (normal range, 45%–74%); lymphocyte count, 51% (normal range, 16%–41%); hemoglobin level, 8.6 g/dL (normal range, 12–16 g/dL); hematocrit level, 25.4% (0.25) (normal range, 37%–48% [0.37–0.48]); and platelet count, 27 x 109/L (normal range, 130–400 x 109/L). The total bilirubin level was 7.2 mg/dL (123 µmol/L) (normal range, 0.3–1.0 mg/dL [5–17 µmol/L]); direct bilirubin level, 2.2 mg/dL (38 µmol/L) (normal range, 0.1–0.3 mg/dL [2–5 µmol/L]); aspartate aminotransferase level, 222 U/L (normal range, 0–42 U/L); alanine aminotransferase level, 49 U/L (normal range, 0–48 U/L); prothrombin time, 20.4 seconds (normal range, 11.8–15.0 seconds); and partial thromboplastin time, 56 seconds (normal range, 27–39 seconds). Results of serologic tests for hepatitis B and C were negative.

CT scans of the thorax, abdomen, and pelvis were negative for focal liver lesions, portal vein thrombosis, biliary dilatation, and enlarged lymph nodes. They did, however, show bilateral pleural effusions. US scans of the lower extremities were negative for thrombosis. Findings at MR imaging of the abdomen performed on the same date as US were consistent with cirrhosis and portal hypertension, including variceal formation (Fig 3). There was no evidence of dilated bile ducts or focal liver lesions. Ascites, anasarca, and bilateral pleural effusions were seen. Results of liver biopsy showed diffuse metastatic involvement by a mucin-secreting, poorly differentiated adenocarcinoma. Numerous signet-ring cells and abundant tumor fibrosis were present with persistence of scattered islands of parenchyma (Fig 2). The patient developed encephalopathy 1 week after admission and died 1 month later.



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  		Figure 3. Case 2. (A) Transverse fast spin-echo MR image (4,000/102) obtained 9 months after the image shown in Figure 2 shows decreased volume in the right hepatic lobe and slight enlargement of the caudate lobe (arrows). (B) Transverse nonenhanced, (C) arterial-phase, and (D) portal-phase spoiled gradient-echo dynamic MR images (1.5/200) show ascites but no focal hepatic masses or abnormal areas of enhancement. (E) Histologic specimen (Masson trichrome stain; original magnification, x200) shows infiltration of liver by breast carcinoma with extensive sinusoidal spread and desmoplastic reaction (blue). Islands of residual hepatic parenchyma (arrow) are present. (F) High-power photomicrograph (hematoxylin-eosin stain; original magnification, x1,000) shows signet-ring features of metastatic breast carcinoma.

 

   Discussion
TOP
 ABSTRACT
 INTRODUCTION
 Case Reports
Discussion
REFERENCES
 
In both cases, MR imaging showed livers with decreased volume, lobular margins, diffuse heterogeneity, and caudate enlargement without visible focal lesions. These findings help support the diagnosis of cirrhosis in most patients (1–4). In fact, both patients had encephalopathy and signs of portal hypertension. At histologic examination, both livers were diffusely infiltrated by poorly differentiated adenocarcinoma, with associated desmoplastic reaction, which produced architecture similar to that of cirrhosis.

The pathogenesis of the cirrhotic appearance of livers in metastatic breast cancer is not clearly understood, but it may result from the hepatotoxic effects of systemic chemotherapy (5–8) and/or hepatic infiltration by the metastatic tumor itself (9–13). It is not possible to establish tumor metastasis as the sole cause of the cirrhosislike appearance of the livers in our patients because they had also been treated with chemotherapy. Perhaps both mechanisms were involved.

The liver injury caused by chemotherapy commonly causes transient increases in the serum levels of hepatic enzymes (14). A combination of agents, however, may cause enhanced toxicity. At autopsies of 11 patients who received 6-mercaptopurine and doxorubicin hydrochloride in the treatment of refractory leukemia, liver tissue showed intrahepatic cholestasis, hepatocellular necrosis, leukemic infiltration, or fatty change (8). CT scans in 22 patients who received 5-fluorouracil and doxorubicin hydrochloride, often in combination with methotrexate, tamoxifen, and/or cyclophosphamide (Cytoxan; Bristol-Myers Oncology, Princeton, NJ) in the treatment of hepatic metastases from breast carcinoma showed findings described as "pseudocirrhosis" (6). Retraction of the liver capsule with a lobular margin was noted on all images. In six of seven patients, the pathologic findings showed residual tumor as well as nodular regenerative hyperplasia, without substantial fibrosis (6). In another study (5), serial CT scans obtained in 27 patients with breast carcinoma metastatic to the liver who had received systemic and/or hepatic arterial infusion of chemotherapeutic agents showed morphologic changes that were considered to be due to chemotherapy, because the previous lesions had either been stable or disappeared. The hepatic changes included fatty metamorphosis, localized atrophy with regional contour changes, areas of low attenuation, and findings consistent with cirrhosis in four patients. Our two cases differ from those in the previous studies in two important aspects. First, there were no previous findings suggestive of hepatic metastases. Second, biopsy showed diffuse parenchymal replacement by viable tumor and dense fibrosis with a histologic architecture resembling that of cirrhosis.

There are few reports in the literature about a cirrhosislike appearance of liver metastases from breast carcinoma in patients who had not previously undergone chemotherapy, and the appearance has consisted of diffuse hepatic infiltration by tumor, predominantly intrasinusoidal, with complete distortion of the normal lobular pattern and widespread replacement by fibrous tissue. To the best of our knowledge, Cracium et al (11) described the first case in 1931, followed by Micolonghi et al (9), Wegener (12), and Amtrup (10). Although both of our patients had undergone chemotherapy, the histologic findings resembled those reported by these authors. It is possible that liver metastases were present but undetected and that they were suboptimally treated with chemotherapy, progressing eventually to diffuse infiltration.

Other authors (15–17) have reported a cirrhotic appearance of the liver, with associated metastatic nodules—usually related to breast carcinoma—identified at gross inspection. Hepatic metastases have been cited as a cause of portal hypertension; the most common malignancy involved is breast cancer (15,17,18), although a case of melanoma has also been reported (13). In these instances, if MR imaging were available, multifocal metastases with vascular obstruction might have been detected. In our cases, the possibility of preexisting cirrhosis was considered unlikely because of the lack of suggestive clinical and historical data. There is also evidence that a cirrhotic liver is relatively protected from developing metastases (19).

In one of our patients, CT showed no evidence of focal liver lesions. US failed to show focal lesions in both patients. Diffuse metastases should be considered in the proper clinical setting when imaging findings—whether obtained with US, CT, or MR imaging—are suggestive of cirrhosis.

In conclusion, despite its high soft-tissue contrast, MR imaging may fail to depict extensive metastases in patients who have undergone treatment for breast carcinoma, especially when they simulate diseases such as cirrhosis. Although there were no specific features to help recognize this pattern of metastasis, it is important to know its existence and to recognize the importance of correlation with clinical history.


   FOOTNOTES
 
2 Current address: Blumenau, Santa Catarina, Brazil. Back

Author contributions: Guarantors of integrity of entire study, A.B.N., D.G.M.; study concepts and design, A.B.N., D.G.M.; literature research, A.B.N.; clinical studies, D.G.M.; data acquisition, A.B.N.; data analysis/interpretation, A.B.N., D.G.M.; manuscript preparation, A.B.N.; manuscript definition of intellectual content and revision/review, all authors; manuscript editing and final version approval, A.B.N., D.G.M.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 Case Reports
Discussion
 REFERENCES
 

  1. Ito K, Mitchell DG, Gabata T, Hussain SM. Expanded gallbladder fossa: simple MR imaging sign of cirrhosis. Radiology 1999; 211:723-726.[Abstract/Free Full Text]
  2. Mitchell DG, Lovett KE, Hann HWL, Ehrlich S, Palazzo J, Rubin R. Cirrhosis: multiobserver analysis of hepatic MR imaging findings in a heterogeneous population. J Magn Reson Imaging 1993; 3:313-321.[Medline]
  3. Siegelman ES, Mitchell DG, Outwater E, Munoz SJ, Rubin R. Idiopathic hemochromatosis: MR imaging findings in cirrhotic and precirrhotic patients. Radiology 1993; 188:637-641.[Abstract/Free Full Text]
  4. Goldberg HI, Moss AA, Stark DD, et al. Hepatic cirrhosis: magnetic resonance imaging. Radiology 1984; 153:737-739.[Abstract/Free Full Text]
  5. Shirkhoda A, Baird S. Morphologic changes of the liver following chemotherapy for metastatic breast carcinoma: CT findings. Abdom Imaging 1994; 19:39-42.[CrossRef][Medline]
  6. Young ST, Paulson EK, Washington K, Gulliver DJ, Vredenburgh JJ, Baker ME. CT of the liver in patients with metastatic breast carcinoma treated by chemotherapy: findings simulating cirrhosis. AJR Am J Roentgenol 1994; 163:1385-1388.[Abstract/Free Full Text]
  7. Schreiner SA, Gorman B, Stephens DH. Chemotherapy-related hepatotoxicity causing imaging findings resembling cirrhosis. Mayo Clin Proc 1998; 73:780-783.[Abstract]
  8. Minow RA, Stern MG, Casey JH, et al. Clinico-pathologic correlation of liver damage in patients treated with 6-mercaptopurine and adriamycin. Cancer 1976; 38:1524-1528.[CrossRef][Medline]
  9. Micolonghi T, Pineda E, Stanley MM. Metastatic carcinomatous cirrhosis of the liver: report of a case in which death followed hemorrhage from esophageal varices and hepatic coma. AMA Arch Pathol 1958; 65:56-62.[Medline]
  10. Amtrup F. Metastatic carcinomatous liver cirrhosis. Dan Med Bull 1971; 18:46-48.[Medline]
  11. Cracium EC, Aslan A, Caffé L. Cirrhose atrophique néoplasique secondaire. Ann Anat Pathol 1931; 8:1089-1112.
  12. Wegener F. Metastatisch-krebsige leberzirrhose. Acta Hepatosplenol 1961; 8:14-24.
  13. Vivas S, Linares A. Diffuse liver metastasis mimicking cirrhosis in a patient with choroid melanoma. J Hepatol 1999; 30:726.[CrossRef][Medline]
  14. Perry CP. Chemotherapeutic agents and hepatotoxicity. Semin Oncol 1992; 19:551-565.[Medline]
  15. Borja ER, Hori JM, Pugh RP. Metastatic carcinomatosis of the liver mimicking cirrhosis: case report and review of the literature. Cancer 1975; 35:445-449.[CrossRef][Medline]
  16. Breitfellner G, Dirschmid K. Leberzirrhose infolge metastasierung bei mammakarzinom: sogenannte metastatisch-karzinomatöse zirrhose. J Suisse Med 1977; 107:241-243.
  17. Castleman B, McNeely BU. Case records of the Massachusetts General Hospital: case 38. N Engl J Med 1966; 9:491-496.
  18. Hyun BH, Singer EP, Sharrett RH, Plainfield NJ. Esophageal varices and metastatic carcinoma of liver: a report of three cases and review of the literature. Arch Pathol 1964; 77:292-298.[Medline]
  19. Seymour K, Charnley RM. Evidence that metastasis is less common in cirrhotic than normal liver: a systematic review of post-mortem case-control studies. Br J Surg 1999; 86:1237-1242.[CrossRef][Medline]



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