Received: February 17, 2018 | Accepted: August 20, 2018 | Published: September 3, 2018
OBM Hepatology and Gastroenterology 2018, Volume 2, Issue 3, doi:10.21926/obm.hg.1803009
Academic Editor: Tatsuo Kanda
Recommended citation: Yonat S, Amir D, Menahem B, Yaakov BZ, Eliyau B, Shimon S, Alian D, Kalman P, Yoav L. An Unusual Case of Signet Ring Cell Cholangiocarcinoma: Case Report and a Review of Literature . OBM Hepatol Gastroenterol 2018;2(3):009; doi:10.21926/obm.hg.1803009.
© 2018 by the authors. This is an open access article distributed under the conditions of the Creative Commons by Attribution License, which permits unrestricted use, distribution, and reproduction in any medium or format, provided the original work is correctly cited.
Cholangiocarcinoma (CC) is a mucin-producing adenocarcinoma that arises from bile duct epithelium . It is an uncommon adenocarcinoma with poor prognosis (5-year survival is less than 5%) and most patients initially present with an advanced disease . Cholangiocarcinomas are grouped by their anatomic site of origin in a descending order: hilar (65%), peripheral (30%), and intrahepatic (5%). Diagnosis is made by biopsy, usually obtained via endoscopic retrograde cholangiopancreatography (ERCP) .
Signet ring cell (SRC) cholangiocarcinoma is an extremely rare variant, with only 11 cases reported to date (Table 1). All of these cases described a localized mass, usually in the extrahepatic biliary tract. To the best of our knowledge, ours is the first reported case of a diffuse SRC cholangiocarcinoma, with no distinct mass on imaging studies. Furthermore, the patient we describe had an extremely short survival compared with other reported cases, with only 3 weeks separating first symptoms from death.
Table 1 Review of the reported cases of signet ring cell cholangiocarcinoma.
Abbreviations - M= male, F= female, N/A= not applicable, CBD= common bile duct, EUS= Enpdoscopic Ultra Sound, ERCP= Endoscopic Retrograde Cholangioscopy, F/U= follow up, PPPD=Pylorus-preserving pancreaticoduodenectom , PD= pancreaticoduodenectom
A 69-year-old male Ashkenazi Jew, was admitted for jaundice and abdominal pain. Blood chemistry analysis revealed the following: total bilirubin 4.8 mg/dl, aspartate aminotransferase (AST) 305 IU/L(N<40),alanine transaminase (ALT)374 IU/L (N<70), alkaline phosphatase (ALP) 571 IU/L (N<150), gamma-glutamyl transferase (GGT) 1925 IU/L (N<73),and cancer antigen 125 (CA 125)45.9 U/ml(N<35).Serum electrolytes, carbohydrate antigen (CA)19-9, creatinine, and amylase levels were normal. Abdominal computed tomography (CT) showed a mild dilatation of intrahepatic bile ducts, mainly in the right lobe, and a dilated gallbladder containing gall stones (Figure 1). No other abnormality was found. Endoscopic ultrasound (EUS) showed strictures of the left hepatic duct, and proximal bifurcation of the common hepatic duct and common bile duct (the right hepatic duct could not be visualized). Needle biopsies were taken from the proximal common bile duct (CBD) and from an enlarged lymph node in the porta hepatis (Figure 2).
Figure 1 Computed tomography (CT) shows no evidence of tumor in the stomach. (A) Body of stomach (B) Pylorus of stomach(C) Gallstones.
Figure 2 Endoscopic Ultra Sound. (A) Portal vein (B) Needle biopsies taken from common bile duct (C) Enlarged lymph node.
The biopsies showed a poorly differentiated signet ring adenocarcinoma (Figure 3). The tumor was at least stage IIIB (T1-3, N1, M0) according to the TNM classification of malignant tumors. An ERCP was also performed and showed multiple primary sclerosing cholangitis (PSC)-like strictures and beadings in the intrahepatic bile ducts (Figure 4).
Figure 3 Core needle biopsy from the common bile duct, H&E staining X400. Arrows show signet ring cells.
Figure 4 Endoscopic Retrograde Cholangioscopy. (A) Gall stones in the gallbladder (B) Stricture of the common biliary duct (C) Segmental intra hepatic dilatation (D) Poorly-filling intrahepatic ducts.
Attempted plastic stent insertion to the left system failed twice, and a metallic uncovered stent was inserted into the distal right system. Colonoscopy results were normal.
SRCs are signet ring-shaped cells that tend to infiltrate the organ wall diffusely, thickening it . It presents mainly in the stomach but may also present in other organs: colorectal, prostate, bladder, and others . Regardless of its location, SRC carcinoma carries a poorer prognosis then non-SRC carcinomas because of higher prevalence of peritoneal carcinomatosis, lymph node invasion at initial diagnosis, and lower R0 resection rate due to its infiltrative character . This rule also applies to SRC biliary carcinoma; median survival in unresectable non-SRC cholangiocarcinoma is 5-15 months and 18-33 months after R0 resection, compared to 6 months in SRC cholangiocarcinoma.
The incidence of SRC gastric carcinoma is increasing, especially in western countries, despite the decreasing overall incidence of gastric cancer . The incidence of signet ring cell colorectal carcinoma is increasing as well . SRC carcinoma of the biliarytract, first described in 1999, is extremely rare with only eleven cases described thus far. Nevertheless, a clear trend of increasing incidence and increasing awareness can be seen: 0.14 cases per year between 1999-2006, one case per year between 2007-2014, and then increasing to two cases per year in 2015-2016. The main demographic and clinical data are summarized in Table 1. Asian extraction is predominant with 50% males, and all patients were admitted for jaundice.
Our case is unique because of two reasons. First, a very rapid downhill course and a short period of time between onset of symptoms and death occurred; only 3 weeks compared with a median survival of 6 months. Secondly, all cases of SRC cholangiocarcinoma reported so fardescribed a tumor mass: in seven cases the mass was localized to the CBD, in three other cases the mass was in the bifurcation of the hepatic ducts, and one was of unknown origin. In contrast, SRCs in other organs such as the stomach, colon, breast etc., tend to spread diffusely in the organ, not creating a distinct mass. In our patient as well, no mass was observed on CT. ERCP raised the suspicion of malignant involvement of the mid-CBD, infiltrating diffusely into both left and right hepatic ducts. This was later histologically confirmed.
To the best of our knowledge this is the first description of diffuse SRC cholangiocarcinoma, characterized by a short survival. As the incidence of SRCs in general as well as the incidence of SRC cholangiocarcinoma seem to be on the rise, more cases will be encountered. If our observation is confirmed, then perhaps the least invasive workup should be taken in patients with SRC pathology in biopsies.
YS wrote the first draft.
SY and YL wrote the later versions.
DA was a senior surgeon caring for the patient.
BH M was the head of the surgical team caring for the patient.
BZ Y was the radiologist interpreting the CT scans.
BE was the pathologist interpreting the biopsy.
SS was head of the pathological laboratory and coordinated the pathological workup.
DA, A gastroenterologist, performed the endoscopic US study of the patient.
PK, A gastroenterologist performed the ERCP study of the patient.
All authors read and approved the final draft.
The authors have declared that no competing interests exist.
cholangiocarcinoma=CC, signet ring cell=SRC, common bile duct=CBD, endoscopic retrograde cholangiopancreatography= ERCP