Scientific letter
An unusual cause of fulminant hepatic failure: Metastatic infiltration by infiltrating ductal carcinoma of the breast
Una causa inusual de fallo hepático fulminante: infiltración metastásica por carcinoma ductal infiltrante de mama
Francisco Javier Pardilla Moraledaa,
, Rosario Serrano Pardob, Lourdes del Campo del Valc, Luisa García-Bueya
Corresponding author
a Servicio de Aparato Digestivo, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid, Madrid, Spain
b Servicio de Anatomía Patológica, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid, Madrid, Spain
c Servicio de Radiodiagnóstico, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid, Madrid, Spain
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Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid, Madrid, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Una causa inusual de fallo hepático fulminante: infiltración metastásica por carcinoma ductal infiltrante de mama" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1072 "Ancho" => 1995 "Tamanyo" => 347267 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">A) Invasion of the liver by invasive ductal carcinoma (haematoxylin-eosin). B) Immunohistochemistry with GATA3 expression. C) Immunohistochemistry with CK19 expression. D) CT with intravenous contrast, arterial phase. Thickening of the skin and nodular lesions on the left breast. E) and F) Portal phase. Hypodense lesions distributed throughout the liver parenchyma, hepatomegaly, ascites.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Acute liver failure is defined as the sudden and severe deterioration of liver function, in the form of coagulopathy and encephalopathy, in patients without previous liver disease. It is a rare condition, with an incidence of fewer than 10 cases per million population per year. Causes include invasion of the liver by a malignant neoplasm, although it is very rare for acute liver failure to occur.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,2</span></a></p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Case report</span><p id="par0010" class="elsevierStylePara elsevierViewall">This was a 50-year-old woman with no relevant medical history except for 10 cigarettes and 40 g of alcohol per day. She came to the accident and emergency department with a month-long history of right mechanical low back pain, associated with slight abdominal distension. Physical examination revealed only frank mucocutaneous jaundice.</p><p id="par0015" class="elsevierStylePara elsevierViewall">Laboratory tests showed haemoglobin 12.2 g/dl, leucocytes 14.24 thousand/mm<span class="elsevierStyleSup">3</span>, platelets 86 thousand/mm<span class="elsevierStyleSup">3</span>, neutrophils 10.89 thousand/mm<span class="elsevierStyleSup">3</span>, INR 2.23, prothrombin activity 33%, creatinine 0.9 mg/dl, sodium 126 mEq/l, potassium 4.6 mEq/l, total bilirubin 12.8 mg/dl, GOT/AST 373 U/l, GPT/ALT 110 U/l, GGT 183 U/l, LDH 890 U/l and alkaline phosphatase 316 U/l. Ascitic fluid showed leucocytes 123 mm<span class="elsevierStyleSup">3</span>, glucose 89 mg/dl, protein 1 g/dl, albumin 0.5 g/dl and a serum-ascites albumin gradient of 1.8 g/dl.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Hepatotoxins, hepatotropic viruses, spontaneous bacterial peritonitis and other infectious foci were ruled out. Autoimmunity showed IgG 2250 mg/dl, IgA 750 mg/dl and IgM 845 mg/dl, with negative ANA, AMA, anti-LKM-1 and anti-SLA.</p><p id="par0025" class="elsevierStylePara elsevierViewall">Abdominal ultrasound showed hepatomegaly with lobulated contours and very heterogeneous echotexture, patent portal vein, recanalisation of the umbilical vein and moderate ascites.</p><p id="par0030" class="elsevierStylePara elsevierViewall">Despite supportive treatment (albumin expansion, systemic corticosteroids and antibiotic therapy), the patient deteriorated, both clinically and analytically, with worsening of coagulopathy, acute kidney injury, hyponatraemia and grade I encephalopathy.</p><p id="par0035" class="elsevierStylePara elsevierViewall">As acute on chronic liver failure was suspected, a transplant centre was contacted. Pathology examination of transjugular liver biopsy revealed “liver parenchyma invaded by malignant epithelial neoplasm. Immunohistochemistry: CK7+; CK20−; CK19+; TTF-1-; glypican 3-; arginase 1-; GATA-3+, oestrogen and progesterone receptors negative, c-erbB2 not assessable. Findings consistent with liver invasion by carcinoma of mammary origin” (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). Ascitic fluid cytology was negative for malignancy.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0040" class="elsevierStylePara elsevierViewall">Computerised axial tomography showed multiple focal liver lesions in both lobes, consistent with metastasis, as well as alterations in the left breast suggestive of malignancy (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). Mammography showed a left breast nodule suspicious for malignancy with skin thickening in relation to oedema and/or inflammatory carcinoma, without suspicious lymph nodes (BI-RADS 5).</p><p id="par0045" class="elsevierStylePara elsevierViewall">Progress continued to be poor, and as liver transplantation was impossible due to massive metastatic invasion, the patient died 10 days after admission.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Discussion</span><p id="par0050" class="elsevierStylePara elsevierViewall">We have presented a case of fulminant hepatic failure, most commonly caused worldwide by hepatotropic virus infections, and by drug toxicity specifically in the West. Less common are ischaemic hepatitis, autoimmune hepatitis, Wilson’s disease or massive tumour invasion.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,2</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">After lymphatic involvement, the liver is the organ most frequently affected by haematogenous spread of solid malignancies, sometimes causing massive intrasinusoidal invasion. The main primary tumours which metastasise to the liver are colorectal carcinoma, breast carcinoma, melanoma, neuroendocrine tumours, lung carcinoma and gastric carcinoma.<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3,4</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">In cases of liver involvement due to breast carcinoma, the metastatic pattern usually consists of discrete nodules, with diffuse metastatic invasion and acute liver failure being rare. However, diffuse metastatic invasion is the form most commonly associated with acute liver failure.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">This clinical case reminds us that tumour invasion can be a cause of acute liver failure and, although uncommon, it should be considered in the differential diagnosis in patients without evidence of viral hepatitis or consumption of hepatotoxic drugs and with non-specific findings in imaging tests, particularly if there is a history of cancer. In addition, it can behave as a “pseudocirrhosis”, in which the desmoplastic reaction induced by the invasive cancer leads to collagenisation of the liver parenchyma, resulting in hepatocyte atrophy, which induces acute liver failure and signs of portal hypertension.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">It is therefore necessary to maintain a high index of suspicion, and in these cases a pathology study is required to reach a definitive diagnosis,<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> although in patients with heterogeneous livers on ultrasound it is important to perform other imaging tests beforehand, preferably with contrast.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Ethical considerations</span><p id="par0075" class="elsevierStylePara elsevierViewall">This work did not involve the use of human subjects, as the information has simply been obtained in a completely anonymous manner from a patient’s medical records following the protocols of our work centre on the publication of patient data.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Funding</span><p id="par0080" class="elsevierStylePara elsevierViewall">No funding was received for this study.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Conflicts of interest</span><p id="par0085" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:7 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Case report" ] 2 => array:2 [ "identificador" => "sec0015" "titulo" => "Discussion" ] 3 => array:2 [ "identificador" => "sec0020" "titulo" => "Ethical considerations" ] 4 => array:2 [ "identificador" => "sec0025" "titulo" => "Funding" ] 5 => array:2 [ "identificador" => "sec0030" "titulo" => "Conflicts of interest" ] 6 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:1 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1072 "Ancho" => 1995 "Tamanyo" => 347267 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">A) Invasion of the liver by invasive ductal carcinoma (haematoxylin-eosin). B) Immunohistochemistry with GATA3 expression. C) Immunohistochemistry with CK19 expression. D) CT with intravenous contrast, arterial phase. Thickening of the skin and nodular lesions on the left breast. E) and F) Portal phase. 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