Primary signet ring cell carcinoma of the pancreatic head: A case report.

Pancreatic SRCC is a rare, aggressive tumor. Given limited evidence and the risk of side effects, physicians may elect to withhold chemotherapy in select patients, with the exception of neoadjuvant chemotherapy use to facilitate resectability.

INTRODUCTION

Signet ring cell carcinoma (SRCC) is a very rare and aggressive tumor of the pancreas and constitutes <1% of all pancreatic cancers. Signet ring cell histology is most commonly seen in cancers arising from the stomach (35%‐45%),1 and less frequently from the colon and rectum (0.1%‐2.6%),2 gallbladder (2.5%‐5.5%),3 and breast (2%‐4.5%).4 According to the World Health Organization (WHO), SRCC is classified as an adenocarcinoma with more than 50% of cells demonstrating signet ring cell morphology.5 We report a case of resectable SRCC located in the head of the pancreas.

CASE REPORT

The patient is a 79‐year‐old woman who presented with jaundice, loss of appetite, and an unintentional 70‐pound weight loss over the previous two to three months. Laboratory tests revealed elevations in total bilirubin (6.3 mg/dL), alkaline phosphatase (600 U/L), and CA‐19‐9 (334 U/mL). A pancreatic protocol, triple‐phase CT scan of the abdomen and pelvis (Figure 1) revealed dilation of the common bile and pancreatic ducts, and a hyperdense mass measuring 2.5 × 2.2 × 1.9 cm and involving the head of the pancreas. The mass was abutting superior mesenteric vein for <180° without any contour irregularity. She subsequently underwent endoscopic retrograde cholangiopancreatography (ERCP), with stenting of the bile duct. Endoscopic ultrasound (EUS) with fine needle aspiration (FNA) resulted in cytology consistent with adenocarcinoma (Figure 2). The Medical Oncology team evaluated the patient, but found her to be a poor candidate for neoadjuvant chemotherapy. The mass was resectable by National Comprehensive Cancer Network (NCCN) guidelines, and she underwent a laparotomy and pancreaticoduodenectomy. Final pathology revealed a 4.0 × 3.5 × 2.0 cm mass in the pancreatic head. Microscopic examination showed poorly differentiated adenocarcinoma, with signet ring cell morphology seen in 70% of cells and ductal adenocarcinoma in the remaining 30% (Figure 3). All margins were uninvolved by either invasive carcinoma or high‐grade intraepithelial neoplasia. Distal pancreatic resection margin was at least 2.0 cm from invasive carcinoma. Three out of eighteen regional lymph nodes examined were positive for metastases. Pathological stage was pT2, pN1, and pM0 (AJCC TNM staging).

Figure 1

CT scan of the abdomen showing mass in the head of the pancreas and dilated common bile duct

Figure 2

EUS showing mass in the head of the pancreas

Figure 3

Microscopy of the lesion showing signet ring cell histology

OUTCOME AND FOLLOW‐UP

The patient tolerated the procedure well and without complication. Postoperatively, she experienced delayed gastric emptying and poor oral intake, which resolved spontaneously. Adjuvant chemotherapy was discussed with the patient, but she refused. She was discharged to a subacute rehabilitation center. There were no other surgical or medical complications. At her five‐month follow‐up appointment, she was doing well, maintaining her weight, and tolerating a regular diet. A CT abdomen/pelvis with IV and oral contrast performed at six months postoperatively demonstrated a 6‐mm hypoattenuating lesion in segment 5 of the liver, which was too small to categorize. This likely represents the subcentimeter cyst identified in the anterior right liver lobe on MRI performed preoperatively. Surveillance will continue with history and physical exam and CT scans every 3‐6 months for the first two years postoperatively, followed by every 6‐12 months as clinically indicated.

DISCUSSION

Signet ring cell carcinoma is a mucin producing neoplasm which represents <1% of all pancreatic cancers. The neoplastic epithelial cells contain intracellular mucin associated with little or no extracellular mucin. The volume of intracellular mucin is enough to compress the nucleus against the periphery of the cell, giving the classic signet ring appearance. The presence of intracellular mucins in cancer cells is known to play a role in carcinogenesis and tumor invasion.6

The ErbB2/ErbB3 complex is constitutively activated in many signet ring cell carcinomas. The heterodimeric conformation of these receptor tyrosine kinases then activates the PI3K (phosphoinositide 3 kinase) pathway and MEK1. Activation of MEK1, along with the p38 MAP kinase pathway (a downstream target of PI3K), results in the dissociation of cells in SRCC. PI3K also increases the secretion of mucin, Muc4, which in turn activates ErbB2. A positive feedback loop is formed between ErbB2/ErbB3‐Muc4–ErbB2/ErbB3, thus facilitating the dispersed phenotype of signet ring cells.7

From available case reports in the literature,8, 9, 10, 11, 12, 13, 14, 15, 16 the age at diagnosis of pancreatic SRCC ranged from 61 to 88 years. Mausam Patel et al,17 in their population‐based study, reported the mean age to be 66.6 years. The most commonly reported symptoms included abdominal pain and painless, progressive jaundice. Our finding of pancreatic SRCC in the head of the pancreas is concordant with other published case reports, revealing this to be a more common location than the pancreatic body or tail.

Radiologically, pancreatic SRCC may have a variable presentation. These tumors can be seen on CT scan of the abdomen as a discrete hyperdense (as in our case) or hypodense lesion in the pancreas.11 Case reports describe findings on CT which range from showing no significant changes10to identification of a diffuse tissue mass involving the pancreas.8 Sakai T. et al reported a case of pancreatic SRCC detected as main pancreatic duct dilation, found primarily in the pancreatic body, with multiple mural nodules identified on CT scan.9

The presentation of pancreatic SRCC may be delayed, whereby the tumor has spread to surrounding structures making it unresectable at the time of initial diagnostic evaluation. Radojkovic et al10 reported the case of a borderline resectable tumor on presentation of a 67‐year‐old female patient. In Nauta et al’s16 report, a 71‐year‐old male patient had an unresectable tumor because of invasion around the portal vein. Chow et al reported the case of an 88‐year‐old female patient who had a very aggressive course and died 20 days after the onset of symptoms. Postmortem examination showed tumor in the head of the pancreas and invading the liver, with multiple hepatic metastases.15

Fewer than 10 cases of pancreatic SRCC have been reported in the literature, the majority of which were either diagnosed upon autopsy or unresectable at presentation. Chemotherapy was given for patients considered for potential curative resection. Given the limited available evidence for the role of chemotherapy in pancreatic SRCC and the risk of side effects, physicians may elect to withhold chemotherapy in select patients. Borderline resectable disease should still be considered for neoadjuvant chemotherapy to facilitate potential resectability.

CONFLICT OF INTEREST

None of the authors have any forms of conflicts of interest.

Consent: Appropriate consent was obtained from the patient.

Guarantor: Srinivas Kavuturu.

AUTHOR CONTRIBUTION

DA: made substantial contributions to the conception and design of the case report, performed a literature review, and was involved in drafting the manuscript. LR: made substantial contributions to conception of the case report, literature review, and drafting of the manuscript. MH: made substantial contributions to the conception of the case report, and was involved in drafting the manuscript and revising it critically for important intellectual content. SK: cared for the patient and performed her surgery, made substantial contributions to conception of the case report, and was also involved in drafting and editing the manuscript.

ETHICAL APPROVAL

This case report was approved by the institute's Institutional Review Board as per its policy.