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An Unusual Lesion Presenting as Cholangiopathy
ELECTRONIC CLINICAL CHALLENGES AND IMAGES IN GI 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58
Grace Elta and Robert J. Fontana, Section Editors
An Unusual Lesion Presenting as Cholangiopathy Q2
Tossapol Kerdsirichairat1 and Juan Carlos Manivel2 1 Division of Gastroenterology, Department of Medicine, University of Michigan, Ann Arbor, Michigan; 2Department of Pathology, University of Minnesota and Minneapolis Veterans Affairs Medical Center, Minneapolis, Minneapolis
Question: A 75-year-old man presented with gradual-onset painless jaundice and right upper quadrant pain for 3 weeks. He was afebrile, with mild right upper quadrant tenderness, without Murphy’s sign. Laboratory tests were pertinent for an aspartate aminotransferase of 142 U/L, an alanine aminotransferase of 142 U/L, alkaline phosphatase of 461 U/L, and direct/total bilirubin of 3.5/9.3 mg/dL. Magnetic resonance cholangiopancreatography showed intrahepatic biliary dilatation with right hepatic duct strictures and nonvisualization of the proximal common hepatic and central common bile ducts, replaced with vague enhancement (Figure A, arrow shows right hepatic duct strictures). Further investigations were significant for negative CA 19-9, CA-125 of 125 U/mL (normal, 0-30), and normal gamma immunoglobulin subclasses. Endoscopic ultrasonography showed marked thickening of the extrahepatic bile duct up to the hilum without definite mass lesion. Endoscopic retrograde cholangiopancreatography (ERCP) revealed a very small distal bile duct (Figure B), about 4 mm, with diffuse stenosis from the upper common duct, extending into the right hepatic duct. Left duct system was mildly dilated. This was treated with plastic biliary stent to the segment III (Figure C). Biopsies (Figure D) of the ampulla and the bile duct showed frequent immunoglobulin (Ig)G4-positive plasma cells (30 cells per high-power field). Steroid was initiated for possible IgG4-associated cholangitis (IAC). At 10 days after the index ERCP, he had worsening nausea and vomiting without worsening laboratory tests. ERCP and esophagogastroduodenoscopy showed narrowing of the duodenal bulb and the proximal second portion of the duodenum. Biopsies of the duodenum and the bile duct showed nonspecific inflammatory changes without evidence of Gastroenterology 2016;-:e1–e3 DIS 5.4.0 DTD YGAST60089 proof 26 February 2016 3:25 am ce
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ELECTRONIC CLINICAL CHALLENGES AND IMAGES IN GI 117 118 119 120 121 122 123 124 125 126 127 128 129 130 131 132 133 134 135 136 137 138 139 140 141 142 143 144 145 146 147 148 149 150 151 152 153 154 155 156 157 158 159 160 161 162 163 164 165 166 167 168 169 170 171 172 173 174
malignancy. Over a 4-week follow-up after the index ERCP, he developed worsening clinical gastric outlet obstruction. Computed tomography of the abdomen (Figure E) revealed an ill-defined mass lesion (arrow) at the gastric antrum, measuring 3.7 2.6 cm. What is the final diagnosis explaining both IAC and clinical gastric outlet obstruction? See the Gastroenterology web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI.
Q1
Conflicts of interest The authors disclose no conflicts. © 2016 by the AGA Institute 0016-5085/$36.00 http://dx.doi.org/10.1053/j.gastro.2015.10.015
e2 DIS 5.4.0 DTD YGAST60089 proof 26 February 2016 3:25 am ce
175 176 177 178 179 180 181 182 183 184 185 186 187 188 189 190 191 192 193 194 195 196 197 198 199 200 201 202 203 204 205 206 207 208 209 210 211 212 213 214 215 216 217 218 219 220 221 222 223 224 225 226 227 228 229 230 231 232
ELECTRONIC CLINICAL CHALLENGES AND IMAGES IN GI 233 234 235 236 237 238 239 240 241 242 243 244 245 246 247 248 249 250 251 252 253 254 255 256 257 258 259 260 261 262 263 264 265 266 267 268 269 270 271 272 273 274 275 276 277 278 279 280 281 282 283 284 285 286 287 288 289 290
Answer to: Image 2: Gastroduodenal Signet Ring Cell Carcinoma Presenting as Immunoglobulin G4–Associated Cholangitis
Repeat ERCP/endoscopic ultrasonography revealed thickening of the prepyloric antrum, and proximal duodenum without obvious mass, and diffuse sclerosis of the bile duct especially the right hepatic duct and markedly dilated left duct. Duodenal biopsies eventually revealed poorly differentiated signet ring cell carcinoma (Figure F, G, red circles). At 2 months, he developed new-onset symptomatic pleural effusion and ascites. Cytology analysis of the fluids showed adenocarcinoma. He died under hospice care at 2 months after the initial presentation. IAC is a new entity of cholangiopathy and IgG4-related disease, described as dense infiltration of IgG4-positive plasma cells and extensive fibrosis in the bile duct wall. Prior study proposed that a bile duct biopsy specimen showing inflamed mucosa with many IgG4-positive plasma cells (>10 cells per high power field), and no malignant cells provides histologic support for a diagnosis of IAC.1 However, a more recent study revealed that IgG4-positive plasma cells may be found within and around cancerous nests to various degrees in malignant processes, particularly in extrahepatic cholangiocarcinoma. As a result, the presence of IgG4-positive cells is not considered a histologic hallmark exclusive of IAC.2 The significance and mechanisms of IgG4 reactions in cancers are still unknown. It has been proposed that carcinoma cells could induce IgG4 reactions by direct or indirect production of interleukin-10. The usefulness of ERCP in diagnosing IAC remains limited, with low sensitivity (42%-51%), although with good specificity (88%-90%). According to previously published data, lower common bile duct strictures and segmental or long strictures with prestenotic dilatation are more common in IAC, compared with primary sclerosing cholangitis.3 This case represents an example of signet ring cell carcinoma of the stomach and duodenum that presented as IAC on both endoscopic and histopathologic findings. These could represent separate concurrent disease processes; in this patient, the latter could result from immune dysregulation secondary to occult malignancy.
References 1. 2. 3.
Ghazale A, Chari ST, Zhang L, et al. Immunoglobulin G4–associated cholangitis: clinical profile and response to therapy. Gastroenterology 2008;134:706–715. Harada K, Shimoda S, Kimura Y, et al. Significance of immunoglobulin G4 (IgG4)-positive cells in extrahepatic cholangiocarcinoma: molecular mechanism of IgG4 reaction in cancer tissue. Hepatology 2012;56:157–164. Kalaitzakis E, Levy M, Kamisawa T, et al. Endoscopic retrograde cholangiography does not reliably distinguish IgG4associated cholangitis from primary sclerosing cholangitis or cholangiocarcinoma. Clin Gastroenterol Hepatol 2011; 9:800–803.
e3 DIS 5.4.0 DTD YGAST60089 proof 26 February 2016 3:25 am ce
291 292 293 294 295 296 297 298 299 300 301 302 303 304 305 306 307 308 309 310 311 312 313 314 315 316 317 318 319 320 321 322 323 324 325 326 327 328 329 330 331 332 333 334 335 336 337 338 339 340 341 342 343 344 345 346 347 348
Grace Elta and Robert J. Fontana, Section Editors
An Unusual Lesion Presenting as Cholangiopathy Q2
Tossapol Kerdsirichairat1 and Juan Carlos Manivel2 1 Division of Gastroenterology, Department of Medicine, University of Michigan, Ann Arbor, Michigan; 2Department of Pathology, University of Minnesota and Minneapolis Veterans Affairs Medical Center, Minneapolis, Minneapolis
Question: A 75-year-old man presented with gradual-onset painless jaundice and right upper quadrant pain for 3 weeks. He was afebrile, with mild right upper quadrant tenderness, without Murphy’s sign. Laboratory tests were pertinent for an aspartate aminotransferase of 142 U/L, an alanine aminotransferase of 142 U/L, alkaline phosphatase of 461 U/L, and direct/total bilirubin of 3.5/9.3 mg/dL. Magnetic resonance cholangiopancreatography showed intrahepatic biliary dilatation with right hepatic duct strictures and nonvisualization of the proximal common hepatic and central common bile ducts, replaced with vague enhancement (Figure A, arrow shows right hepatic duct strictures). Further investigations were significant for negative CA 19-9, CA-125 of 125 U/mL (normal, 0-30), and normal gamma immunoglobulin subclasses. Endoscopic ultrasonography showed marked thickening of the extrahepatic bile duct up to the hilum without definite mass lesion. Endoscopic retrograde cholangiopancreatography (ERCP) revealed a very small distal bile duct (Figure B), about 4 mm, with diffuse stenosis from the upper common duct, extending into the right hepatic duct. Left duct system was mildly dilated. This was treated with plastic biliary stent to the segment III (Figure C). Biopsies (Figure D) of the ampulla and the bile duct showed frequent immunoglobulin (Ig)G4-positive plasma cells (30 cells per high-power field). Steroid was initiated for possible IgG4-associated cholangitis (IAC). At 10 days after the index ERCP, he had worsening nausea and vomiting without worsening laboratory tests. ERCP and esophagogastroduodenoscopy showed narrowing of the duodenal bulb and the proximal second portion of the duodenum. Biopsies of the duodenum and the bile duct showed nonspecific inflammatory changes without evidence of Gastroenterology 2016;-:e1–e3 DIS 5.4.0 DTD YGAST60089 proof 26 February 2016 3:25 am ce
59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116
ELECTRONIC CLINICAL CHALLENGES AND IMAGES IN GI 117 118 119 120 121 122 123 124 125 126 127 128 129 130 131 132 133 134 135 136 137 138 139 140 141 142 143 144 145 146 147 148 149 150 151 152 153 154 155 156 157 158 159 160 161 162 163 164 165 166 167 168 169 170 171 172 173 174
malignancy. Over a 4-week follow-up after the index ERCP, he developed worsening clinical gastric outlet obstruction. Computed tomography of the abdomen (Figure E) revealed an ill-defined mass lesion (arrow) at the gastric antrum, measuring 3.7 2.6 cm. What is the final diagnosis explaining both IAC and clinical gastric outlet obstruction? See the Gastroenterology web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI.
Q1
Conflicts of interest The authors disclose no conflicts. © 2016 by the AGA Institute 0016-5085/$36.00 http://dx.doi.org/10.1053/j.gastro.2015.10.015
e2 DIS 5.4.0 DTD YGAST60089 proof 26 February 2016 3:25 am ce
175 176 177 178 179 180 181 182 183 184 185 186 187 188 189 190 191 192 193 194 195 196 197 198 199 200 201 202 203 204 205 206 207 208 209 210 211 212 213 214 215 216 217 218 219 220 221 222 223 224 225 226 227 228 229 230 231 232
ELECTRONIC CLINICAL CHALLENGES AND IMAGES IN GI 233 234 235 236 237 238 239 240 241 242 243 244 245 246 247 248 249 250 251 252 253 254 255 256 257 258 259 260 261 262 263 264 265 266 267 268 269 270 271 272 273 274 275 276 277 278 279 280 281 282 283 284 285 286 287 288 289 290
Answer to: Image 2: Gastroduodenal Signet Ring Cell Carcinoma Presenting as Immunoglobulin G4–Associated Cholangitis
Repeat ERCP/endoscopic ultrasonography revealed thickening of the prepyloric antrum, and proximal duodenum without obvious mass, and diffuse sclerosis of the bile duct especially the right hepatic duct and markedly dilated left duct. Duodenal biopsies eventually revealed poorly differentiated signet ring cell carcinoma (Figure F, G, red circles). At 2 months, he developed new-onset symptomatic pleural effusion and ascites. Cytology analysis of the fluids showed adenocarcinoma. He died under hospice care at 2 months after the initial presentation. IAC is a new entity of cholangiopathy and IgG4-related disease, described as dense infiltration of IgG4-positive plasma cells and extensive fibrosis in the bile duct wall. Prior study proposed that a bile duct biopsy specimen showing inflamed mucosa with many IgG4-positive plasma cells (>10 cells per high power field), and no malignant cells provides histologic support for a diagnosis of IAC.1 However, a more recent study revealed that IgG4-positive plasma cells may be found within and around cancerous nests to various degrees in malignant processes, particularly in extrahepatic cholangiocarcinoma. As a result, the presence of IgG4-positive cells is not considered a histologic hallmark exclusive of IAC.2 The significance and mechanisms of IgG4 reactions in cancers are still unknown. It has been proposed that carcinoma cells could induce IgG4 reactions by direct or indirect production of interleukin-10. The usefulness of ERCP in diagnosing IAC remains limited, with low sensitivity (42%-51%), although with good specificity (88%-90%). According to previously published data, lower common bile duct strictures and segmental or long strictures with prestenotic dilatation are more common in IAC, compared with primary sclerosing cholangitis.3 This case represents an example of signet ring cell carcinoma of the stomach and duodenum that presented as IAC on both endoscopic and histopathologic findings. These could represent separate concurrent disease processes; in this patient, the latter could result from immune dysregulation secondary to occult malignancy.
References 1. 2. 3.
Ghazale A, Chari ST, Zhang L, et al. Immunoglobulin G4–associated cholangitis: clinical profile and response to therapy. Gastroenterology 2008;134:706–715. Harada K, Shimoda S, Kimura Y, et al. Significance of immunoglobulin G4 (IgG4)-positive cells in extrahepatic cholangiocarcinoma: molecular mechanism of IgG4 reaction in cancer tissue. Hepatology 2012;56:157–164. Kalaitzakis E, Levy M, Kamisawa T, et al. Endoscopic retrograde cholangiography does not reliably distinguish IgG4associated cholangitis from primary sclerosing cholangitis or cholangiocarcinoma. Clin Gastroenterol Hepatol 2011; 9:800–803.
e3 DIS 5.4.0 DTD YGAST60089 proof 26 February 2016 3:25 am ce
291 292 293 294 295 296 297 298 299 300 301 302 303 304 305 306 307 308 309 310 311 312 313 314 315 316 317 318 319 320 321 322 323 324 325 326 327 328 329 330 331 332 333 334 335 336 337 338 339 340 341 342 343 344 345 346 347 348