ELECTRONIC CLINICAL CHALLENGES AND IMAGES IN GI A Rare Cause of Noncirrhotic Intrahepatic Portal Hypertension Priyanka Chugh,1 James S. Park,1,2 and Cristina H. Hajdu3 1
Department of Medicine, 2Division of Gastroenterology, 3Department of Pathology, New York University School of Medicine/ Langone Medical Center, New York, New York
Question: A 38-year-old woman with history of splenomegaly and thrombocytopenia was referred to the outpatient hepatology office after an extensive negative hematologic and infectious workup. On physical examination, the patient seemed to be comfortable with a blood pressure of 110/65 mm Hg and heart rate of 72 bpm. Her abdominal examination showed an enlarged spleen. A rectal examination revealed brown stool without melena. Laboratory evaluation revealed a white blood cell count of 4,800/mL, hemoglobin of 11.3 g/dL (baseline, 12.2 g/dL), platelets 53 103/mL (baseline, 70 103/mL), creatinine of 0.6 mg/dL, prothrombin time of 12 seconds, and International Normalized Ratio of 1.1. Electrolytes, amylase, lipase, liver chemistry tests, ceruloplasmin, and immunoglobulin levels were normal. Anti-smooth muscle antibody and antimitochondrial antibody were negative. Pertinent review of systems revealed that the patient is a current tobacco user with a 10-year pack history and a former user of intravenous heroine. Abdominal ultrasonography with Doppler revealed a diffusely heterogeneous liver parenchyma and enlarged spleen measuring 20.2 cm with a patent splenic vein (Figure A). Esophagogastroduodenoscopy demonstrated multiple columns of large esophageal varices in the lower third of the esophagus (Figure B). A colonoscopy demonstrated small to medium sized, nonbleeding rectal varices. Both studies were consistent with portal hypertension. A transjugular core liver biopsy was performed and the slides demonstrated liver cell plate atrophy alternating with hepatocellular regeneration (hematoxylin and eosin, and reticulin stains), and focal portal and pericellular fibrosis (trichrome stain). A minimal to mild inflammatory infiltrate composed of lymphocytes and clutters of macrophages containing brown granular refractive material was noted in the portal tracts without evidence of cirrhosis (Figure C, D). No significant bile duct injury, steatosis, granulomas, siderosis, or alpha1-antitrypsin globule was identified on histology. These findings were consistent with nodular regenerative hyperplasia, a condition of noncirrhotic intrahepatic portal hypertension (NCIPH). However, further inquisition of the same region under polarized light revealed multiple scattered, white, birefringent, irregular or needle-shaped material within some of the portal tracts (Figures E [arrow head], F [arrow head]). Gastroenterology 2014;147:e7–e9
ELECTRONIC CLINICAL CHALLENGES AND IMAGES IN GI What is the most likely etiology of this patient’s nodular regenerative hyperplasia? See the Gastroenterology web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI.
Conflicts of interest The authors disclose no conflicts. © 2014 by the AGA Institute 0016-5085/$36.00 http://dx.doi.org/10.1053/j.gastro.2014.04.004
e8
ELECTRONIC CLINICAL CHALLENGES AND IMAGES IN GI Answer to the Clinical Challenges and Images in GI Question: Image 4: Talc-Associated Liver Injury From Intravenous Drug Use Mineral talc is soft, hydrous magnesium silicate crystals known to have the physical characteristic of white birefringence under polarized light.1 The etiology of talc in the liver is multifactorial, resulting from intravenous drug use, blood transfusion, occupational and household exposure, and body ink.3 The patient admitted to intravenous drug use less than ten times with her last use being 2 years before her presentation. Many intravenous drug users utilize a suspension of drugs that contain talc as tablet filler, among other substances such as a cornstarch, silica, and cotton fibers. Microscopic examination is used to make the diagnosis. Mineral talc elicits a macrophage-induced inflammatory reaction compatible with a wide array of findings such as nonspecific portal inflammation, steatosis, acute hepatitis, chronic persistent hepatitis, collagen deposition, and cirrhosis under hematoxylin and eosin staining. Electron microscopy, electroninduced x-ray fluorescence microanalysis, and electron diffraction are further used to determine the elemental composition of the birefringent material. Mineral talc crystals have a sharp needle shaped appearance, referred to as “flaky pastry” under electron microscopy.1–3 The significance of this discovery in our patient has helped us to understand the constellation of her clinical findings. Splenomegaly, esophageal varices, and rectal varices in the absence of hepatic cirrhosis point toward the diagnosis of NCIPH. The portal fibrohyaline deposition initiated by talc crystals may compromise the blood flow through small portal veins, resulting in portal hypertension. Talc deposition in the liver was heterogeneous, resulting in an uneven microcirculation injury, obliteration of some small portal veins with secondary arterialization and nodular regeneration, and ensuing nodular regenerative hyperplasia. Our case illustrates for the first time nodular regenerative hyperplasia occurring in NCIPH secondary to mineral talc deposition from intravenous drug use. The treatment is aimed at reversing the initial insult to the liver and treating the sequel of injury as per well-established guidelines. Our patient was enrolled in an intensive outpatient drug rehabilitation program and placed on b-blocker therapy.
References 1. 2. 3.
Allaire GS, Goodman ZD, Ishak KG, et al. Talc in the liver tissue of intravenous drug abusers with chronic hepatitis. A comparative study. Am J Clin Pathol 1989;92:583–588. Kringsholm B, Christoffersen P. Liver pathology in fatal drug addiction. Forensic Sci Int 1982;20:141–151. Liu YC, Tomashefski J, McMahon JT, et al. Mineral-associated hepatic injury: a report of seven cases with x-ray microanalysis. Hum Pathol 1991;22:1120–1127.
e9
Department of Medicine, 2Division of Gastroenterology, 3Department of Pathology, New York University School of Medicine/ Langone Medical Center, New York, New York
Question: A 38-year-old woman with history of splenomegaly and thrombocytopenia was referred to the outpatient hepatology office after an extensive negative hematologic and infectious workup. On physical examination, the patient seemed to be comfortable with a blood pressure of 110/65 mm Hg and heart rate of 72 bpm. Her abdominal examination showed an enlarged spleen. A rectal examination revealed brown stool without melena. Laboratory evaluation revealed a white blood cell count of 4,800/mL, hemoglobin of 11.3 g/dL (baseline, 12.2 g/dL), platelets 53 103/mL (baseline, 70 103/mL), creatinine of 0.6 mg/dL, prothrombin time of 12 seconds, and International Normalized Ratio of 1.1. Electrolytes, amylase, lipase, liver chemistry tests, ceruloplasmin, and immunoglobulin levels were normal. Anti-smooth muscle antibody and antimitochondrial antibody were negative. Pertinent review of systems revealed that the patient is a current tobacco user with a 10-year pack history and a former user of intravenous heroine. Abdominal ultrasonography with Doppler revealed a diffusely heterogeneous liver parenchyma and enlarged spleen measuring 20.2 cm with a patent splenic vein (Figure A). Esophagogastroduodenoscopy demonstrated multiple columns of large esophageal varices in the lower third of the esophagus (Figure B). A colonoscopy demonstrated small to medium sized, nonbleeding rectal varices. Both studies were consistent with portal hypertension. A transjugular core liver biopsy was performed and the slides demonstrated liver cell plate atrophy alternating with hepatocellular regeneration (hematoxylin and eosin, and reticulin stains), and focal portal and pericellular fibrosis (trichrome stain). A minimal to mild inflammatory infiltrate composed of lymphocytes and clutters of macrophages containing brown granular refractive material was noted in the portal tracts without evidence of cirrhosis (Figure C, D). No significant bile duct injury, steatosis, granulomas, siderosis, or alpha1-antitrypsin globule was identified on histology. These findings were consistent with nodular regenerative hyperplasia, a condition of noncirrhotic intrahepatic portal hypertension (NCIPH). However, further inquisition of the same region under polarized light revealed multiple scattered, white, birefringent, irregular or needle-shaped material within some of the portal tracts (Figures E [arrow head], F [arrow head]). Gastroenterology 2014;147:e7–e9
ELECTRONIC CLINICAL CHALLENGES AND IMAGES IN GI What is the most likely etiology of this patient’s nodular regenerative hyperplasia? See the Gastroenterology web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI.
Conflicts of interest The authors disclose no conflicts. © 2014 by the AGA Institute 0016-5085/$36.00 http://dx.doi.org/10.1053/j.gastro.2014.04.004
e8
ELECTRONIC CLINICAL CHALLENGES AND IMAGES IN GI Answer to the Clinical Challenges and Images in GI Question: Image 4: Talc-Associated Liver Injury From Intravenous Drug Use Mineral talc is soft, hydrous magnesium silicate crystals known to have the physical characteristic of white birefringence under polarized light.1 The etiology of talc in the liver is multifactorial, resulting from intravenous drug use, blood transfusion, occupational and household exposure, and body ink.3 The patient admitted to intravenous drug use less than ten times with her last use being 2 years before her presentation. Many intravenous drug users utilize a suspension of drugs that contain talc as tablet filler, among other substances such as a cornstarch, silica, and cotton fibers. Microscopic examination is used to make the diagnosis. Mineral talc elicits a macrophage-induced inflammatory reaction compatible with a wide array of findings such as nonspecific portal inflammation, steatosis, acute hepatitis, chronic persistent hepatitis, collagen deposition, and cirrhosis under hematoxylin and eosin staining. Electron microscopy, electroninduced x-ray fluorescence microanalysis, and electron diffraction are further used to determine the elemental composition of the birefringent material. Mineral talc crystals have a sharp needle shaped appearance, referred to as “flaky pastry” under electron microscopy.1–3 The significance of this discovery in our patient has helped us to understand the constellation of her clinical findings. Splenomegaly, esophageal varices, and rectal varices in the absence of hepatic cirrhosis point toward the diagnosis of NCIPH. The portal fibrohyaline deposition initiated by talc crystals may compromise the blood flow through small portal veins, resulting in portal hypertension. Talc deposition in the liver was heterogeneous, resulting in an uneven microcirculation injury, obliteration of some small portal veins with secondary arterialization and nodular regeneration, and ensuing nodular regenerative hyperplasia. Our case illustrates for the first time nodular regenerative hyperplasia occurring in NCIPH secondary to mineral talc deposition from intravenous drug use. The treatment is aimed at reversing the initial insult to the liver and treating the sequel of injury as per well-established guidelines. Our patient was enrolled in an intensive outpatient drug rehabilitation program and placed on b-blocker therapy.
References 1. 2. 3.
Allaire GS, Goodman ZD, Ishak KG, et al. Talc in the liver tissue of intravenous drug abusers with chronic hepatitis. A comparative study. Am J Clin Pathol 1989;92:583–588. Kringsholm B, Christoffersen P. Liver pathology in fatal drug addiction. Forensic Sci Int 1982;20:141–151. Liu YC, Tomashefski J, McMahon JT, et al. Mineral-associated hepatic injury: a report of seven cases with x-ray microanalysis. Hum Pathol 1991;22:1120–1127.
e9
