BY LOUISE VESANEN, MSC, & AHMED RAZZIUDIN, MD
A 53-year-old woman was brought to the ED from a nursing home for hypotension and hypoxia. She appeared septic. Her blood pressure was 80/60 mm Hg, and she was pale, cyanotic, and jaundiced. The patient was nonverbal at baseline due to underlying cerebral palsy, so information about her present illness was provided by her nursing home. Recent records listed elevated alkaline phosphatase and gallstone finding on ultrasound. Physical exam demonstrated abdominal distension and tenderness on palpation of her right upper quadrant.
Initial workup included CBC, CMP, blood glucose, urinalysis, blood cultures, lactic acid, blood gases, and CT scan of the chest and abdomen/pelvis. The pertinent findings are listed in the table. A left subclavian triple lumen was inserted to administer IV fluids and norepinephrine to correct the hypotension, and she was intubated due to severe hypoxia. Sepsis was treated immediately with broad-spectrum antibiotics (vancomycin and piperacillin/tazobactam), and she was given two units of PRBC to correct the hemoglobin.
Table. Pertinent Findings from Initial Workup.
Chest CT revealed extensive areas of dense consolidation and nodularity in the right upper and lower lungs, suggesting pneumonia or atelectasis. The abdominal/pelvic CT demonstrated a phlegmon in the gallbladder fossa, which consisted of a bubbly fluid collection measuring 6.5 x 3.7 cm. (Fig. 1.) An ultrasound confirmed a 6 cm echogenic mass containing multiple cystic components, suggestive of a necrotic gallbladder. The common bile duct (CBD) was moderately dilated, measuring 7 mm.
The abdominal/pelvic CT demonstrating a phlegmon in the gallbladder fossa, which consisted of a bubbly fluid collection measuring 6.5 x 3.7 cm.
The patient was admitted to the ICU for ascending cholangitis with septic shock secondary to biliary sources. Urine and blood cultures evidenced bacteriuria and bacteremia with growth of Escherichia coli >100,000 in the urine and Klebsiella pneumonia in the blood. Amikacin was added to the patient's medications, and vancomycin was discontinued. Despite the use of antibiotics, she had persisting leukocytosis with WBC of 23,000.
The patient was scheduled for an exploratory laparoscopy to improve her status and clarify the nature of the biliary problem. She was given 1 unit of PRBC and 3 units of fresh frozen plasma due to prolonged INR before the procedure. It turned into an open surgery when the gallbladder could not be visualized due to the omentum and the right colon. The gallbladder fossa consisted of a large phlegmon and contained several yellowish stones. Surgeons performed a cholecystectomy, right hemicolectomy and ileostomy, and biopsies of the gallbladder and right colon were submitted for pathology. A cholecystectomy tube was inserted into the gallbladder area to drain the fluid. An intraoperative cholangiogram exhibited the passage of dye into the duodenum and equally into the stomach and the distal CBD. Based on the cholangiogram findings, a post-op CT was requested to evaluate possible fistula presence.
Metastasis to the Gallbladder
Gallbladder biopsy revealed infiltrating, poorly differentiated adenocarcinoma with tissue gangrene. Right colon biopsy revealed a Grade 3 tumor in pericolic fat (3 x 1.5 x 0.5 cm) identified as poorly differentiated adenocarcinoma with signet-ring cells and surface ulceration through muscle and serosa. The pathologist's findings indicated a tumor originating from the colon with metastasis to gallbladder. Prognosis at this stage was determined to be poor in light of the local advancement of disease.
Immunohistochemical stains from gallbladder and colon biopsies revealed that both tumors were positive for pancytokeratin, CK20, and CDX2. CDX2 is an intestine-specific transcription factor, which is a specific marker of gastrointestinal adenocarcinomas. The colon tumor was negative for CK7, but the gallbladder tumor revealed scattered CK7-positive cells. Mucicarmine stain visualized intracytoplasmic mucin in the colon tumor, while the gallbladder mucicarmine stain was negative. CEA value was elevated at 6.61.
A CT scan with contrast depicted irregular contrast collection in the gallbladder region, which directly communicated with the duodenum and CBD. (Fig. 2.) Contrast was also visualized within the stomach and small bowel loops. The distal CBD was further dilated, now measuring 10.2 mm. (Fig. 3.) The esophagogastroduodenoscopy confirmed an area on the duodenal wall where there appeared to be a fistula tract (Fig. 4), either cholecystoduodenal or choledochoduodenal fistula, but it could not be definitively identified.
Fig. 2. A CT scan with contrast depicted irregular contrast collection in the gallbladder region, which directly communicated with the duodenum and CBD.
Fig. 3. The distal CBD was further dilated, now measuring 10.2 mm.
Fig. 4. The esophagogastroduodenoscopy confirmed an area on the duodenal wall where there appeared to be a fistula tract.
The patient's family was informed of the diagnosis, and at that time, our patient's mother disclosed that one of her sisters died at 33 from metastatic colon cancer. In considering the patient's comorbidities, mental state, bedbound status, and family history, the physicians involved in her care decided not to pursue any active treatment and transferred her to hospice for palliative care. Sadly, our patient died in hospice one week later.
Colorectal cancer is the third most common cancer worldwide and constitutes a major public health issue globally with an estimated 1.2 million new diagnoses and more than 630,000 cancer deaths per year, amounting to nearly eight percent of all cancer-related fatalities. (Sci Rep 2016;6:29765; World J Gastroenterol 2013;19:7183.) Approximately 56 percent of patients with colorectal cancer die as a result of their cancer. (Sci Rep 2016;6:29765.) Research shows that 20 percent of patients with colorectal cancer have distant metastases at diagnosis, and this figure has remained stable for the past two decades. (Clin Exp Metastasis 2015;32:457; CA Cancer J Clin 2016;66:7.) Colorectal cancer can spread by lymphatic and hematogenous dissemination, as well as by contiguous and transperitoneal routes. The most common metastatic sites are the regional lymph nodes, liver, lungs, and peritoneum. A total of six percent of metastatic adenocarcinomas of unknown primary origin are connected to colorectal carcinoma. (J Clin Oncol 1995;13:2094.)
To our knowledge, this is the first literature report of a middle-aged woman presenting with cholecystitis, gallbladder abscess, and cholecystoenteric fistula, who was subsequently diagnosed with colon adenocarcinoma with metastasis to the gallbladder. Our patient's colon biopsy stained positive for mucicarmine and was also characterized by signet-ring cells. Occasionally, mucin accumulates intracellularly in mucinous adenocarcinomas, resulting in signet-ring cell morphology. (Mod Pathol 2008;21:1533.) Signet-ring histology is associated with dismal prognosis and higher risk of death for colon and rectum cancers, mainly due to delayed diagnosis. (Int Surg 2014;99:691; Ann Surg Oncol 2012;19:2814.)
This was the unfortunate case for our patient who had a peculiar spread of right colon cancer to the gallbladder, with consequent abscess and perforation. A study found that the most common primary tumor that metastasized to the gallbladder is gastric cancer, followed by renal cell carcinoma and hepatocellular carcinoma. (Korean J Radiol 2014;15:334.)
Gallbladder perforations are rare, with reported incidence ranging between two and 10.6 percent in patients with acute cholecystitis and cholelithiasis. (Hepatobiliary Pancreat Dis Int 2009;8:212.) Spontaneous internal biliary fistulas also represent a complication of cholelithiasis in more than 90 percent of cases, and can otherwise be attributed to peptic ulcer disease and malignancy. (Eur Radiol 1999;9:1145; Radiology 2002;224:9.) The most commonly missed opportunity for early diagnosis of colon cancer is the failure to initiate or complete the investigation of iron deficiency anemia. (Br J Surg 1993;80:1327.) Considering that this patient had a family history of colon cancer, she may have benefitted from a more thorough workup because her iron deficiency anemia was from unknown causes.
Ms. Vesanen is a third-year medical student at the University of Medicine and Health Sciences in St. Kitts. Dr. Raziuddin is an internist and emergency physician at tWeiss Memorial Hospital, Gottlieb Memorial Hospital, and Westlake Hospital, all in Illinois.