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Squamous Cell Carcinoma of the Pancreas

Published:February 18, 2017DOI:https://doi.org/10.1016/j.amjms.2017.01.014
      Pancreatic malignancies can be divided into endocrine and exocrine processes. Of the exocrine malignancies, ductal carcinoma is the most common and can be further subclassified into adenocarcinoma, adenosquamous and squamous cell carcinoma. Squamous cell carcinoma of the pancreas is extremely rare with most of its literature presented in the form of case reports. We report a case of squamous cell carcinoma of the pancreas with an atypical presentation.
      A 61-year-old male patient with hypertension and history of seizure disorder presented to the Emergency Department with fatigue, dizziness and a 3-day history of melena, concerning for a gastrointestinal bleed. It is worth noting that he was recently evaluated by his primary care physician for symptoms of fatigue, weight loss, jaundice, right upper quadrant abdominal pain, dark urine and light-colored stool. Specifically, he noted an unintentional 18 kilogram weight loss in the last 3 months. Outpatient workup included computed tomography scans of the chest, abdomen and pelvis that demonstrated a 6.5 × 5.9 cm mass involving the pancreatic head with intrahepatic and extrahepatic biliary and pancreatic ductal dilatations and atrophy of the pancreatic body and tail, most compatible with pancreatic malignancy (Figure A). The pancreatic mass was noted to encase the gastroduodenal artery. Small lesions in the liver were also evident, suspicious for hepatic metastasis.
      FIGURE
      FIGUREA, CT scan showed a mass with greatest dimensions of 6.5 × 5.9 cm involving the pancreatic head, with intrahepatic and extrahepatic biliary and pancreatic ductal dilatations, and atrophy of the pancreatic body and tail. B, Graphical representation of the trend of the WBC counts across all hospitalizations. November 13, 2016. CT, computed tomography; WBC, white blood cell.
      Upon admission to the hospital, he was tachycardic, but was otherwise afebrile and hemodynamically stable. On physical examination, he was jaundiced with conjunctival icterus and tender to palpation in the right upper quadrant. Admission laboratory studies showed hemoglobin of 5.5 g/dL (reference range: 13.5-17.5 g/dL) and international normalized ratio of 2.2 (reference range: 0.8-1.2). Intravenous fluids, packed red blood cells, fresh frozen plasma and vitamin K were administered. Emergent esophagogastroduodenoscopy was performed, which revealed a large fungating mass invading the duodenum from the pancreas with diffuse bloody oozing. Histopathology of the biopsy revealed infiltrating squamous cell carcinoma with a positive p40 immunostain. Tumor markers, cancer antigen 19-9 and carcinoembryonic antigen were within normal limits.
      Additional laboratory studies showed white blood cells of 37.6 cells/L (reference range: 3.5-10.5 × 109 cells/L), direct bilirubin of 4.1 mg/dL (reference range: 0-0.3 mg/dL) and alkaline phosphatase of 464 U/L (reference range: 45-115 U/L). Broad-spectrum antibiotics were initiated and quickly tapered off due to a negative infectious evaluation that included a chest X-ray, urinalysis and blood cultures. Oncology did not recommend percutaneous biliary drainage for his obstructive mass, as he did not show signs and symptoms of infection. Further workup of his leukocytosis included automatic and manual differential, which showed neutrophilic predominance, and peripheral smear, which was negative for blasts. It is worth noting that he had not received any granulocyte colony-stimulating factor or corticosteroids.
      Following this procedure, he remained hemodynamically stable and was discharged home. A medical oncologist was consulted, who stated that further therapy would be palliative, not curative, and the decision was made to pursue palliative radiation as an outpatient. He underwent 2 sessions of radiation before developing complications. In the 2 months following discharge, he had 3 subsequent hospitalizations for repeat gastrointestinal bleeding and 2 for gastric outlet obstruction requiring placement of duodenal stent. These hospitalizations were complicated by persistent fevers and leukocytosis up to 106 with negative iatrogenic, infectious and hematologic workup (Figure B). He eventually passed away on hospice care within 2 months of diagnosis.
      Pure squamous cell carcinoma of the pancreas is extremely rare with an incidence of 0.5-5% of all pancreatic malignancies.
      • Beyer K.L.
      • Marshall J.B.
      • Metzler M.H.
      • et al.
      Squamous cell carcinoma of the pancreas. Report of an unusual case and review of the literature.
      A recent epidemiologic study identified 214 cases from 2000-2012 using the Surveillance, Epidemiology and End Results (SEER) database and suggested an increased incidence over this period.
      • Makarova-Rusher O.V.
      • Ulahannan S.
      • Greten T.F.
      • et al.
      Pancreatic squamous cell carcinoma: a population-based study of epidemiology, clinicopathologic characteristics and outcomes.
      Because of this rarity, it is often presumed to be a result of metastasis from another primary site. In our patient, computed tomography images and endoscopy were concerning for a pancreatic primary and did not identify other primary sources.
      Squamous cell carcinoma of the pancreas is a poorly understood phenomenon. The pathophysiology is still unknown, as the pancreas is typically devoid of squamous cells. The following have been hypothesized as the etiology of squamous cell carcinoma of the pancreas: (1) ductal cells undergo squamous metaplasia and malignant transformation due to chronic inflammation; (2) a pre-existing adenosquamous carcinoma or adenocarcinoma converts into squamous cell carcinoma; (3) primitive multipotent cells, which may differentiate into glandular or squamous cells, undergo malignant transformation.
      • Ben Kridis W.
      • Khanfir A.
      • Toumi N.
      • et al.
      Primary squamous cell carcinoma of the pancreas: a report of two cases and review of the literature.
      • Kodavatiganti R.
      • Campbell F.
      • Hashmi A.
      • et al.
      Primary squamous cell carcinoma of the pancreas: a case report and review of the literature.
      Often, additional biopsies are needed to confirm that the malignant cells are not of adenosquamous origin. In our patient, gland formation was not mentioned on histopathology; however, further samplings were not performed to exclude adenosquamous carcinoma of the pancreas.
      The clinical presentation and course of squamous cell carcinoma of the pancreas is similar to that of adenocarcinoma.
      • Beyer K.L.
      • Marshall J.B.
      • Metzler M.H.
      • et al.
      Squamous cell carcinoma of the pancreas. Report of an unusual case and review of the literature.
      Most occur in patients between 30 and 80 years old.
      • Beyer K.L.
      • Marshall J.B.
      • Metzler M.H.
      • et al.
      Squamous cell carcinoma of the pancreas. Report of an unusual case and review of the literature.
      • Brown H.A.
      • Dotto J.
      • Robert M.
      • et al.
      Squamous cell carcinoma of the pancreas.
      It is unclear whether squamous cell carcinoma shares similar risk factors to those of adenocarcinoma of the pancreas, including tobacco abuse, chronic pancreatitis and familial history—none of which were present in our patient. The most common presenting clinical findings are anorexia, weight loss and abdominal or back pain.
      • Beyer K.L.
      • Marshall J.B.
      • Metzler M.H.
      • et al.
      Squamous cell carcinoma of the pancreas. Report of an unusual case and review of the literature.
      • Brown H.A.
      • Dotto J.
      • Robert M.
      • et al.
      Squamous cell carcinoma of the pancreas.
      While our patient had similar symptoms, his clinical presentation was dictated by the anatomic distribution of the mass. Specifically, his outpatient presentation with jaundice, dark urine and light-colored stool was more consistent of a ductal obstructive process from a mass involving the pancreatic head. As the mass grew and invaded into his duodenum, his presentation evolved from melena due to a malignant bleed into intractable nausea and vomiting due to gastric outlet obstruction. Presentation with gastrointestinal bleed has been described in other case reports.
      • Aurello P.
      • Petrucciani N.
      • D’Angelo F.
      • et al.
      Squamous cell carcinoma of the pancreas presenting with upper gastrointestinal bleeding.
      Our patient had significant leukocytosis as high as 106 during subsequent hospitalizations. Further evaluation did not identify iatrogenic, infectious or hematologic etiology. Interestingly, his leukocytosis decreased after 2 sessions of radiation but eventually increased again when these palliative therapies were discontinued. It was concerning for leukemoid reaction, a reactive leukocytosis with white blood cell count exceeding 50 × 109 L. It has been reported as a paraneoplastic syndrome in tumors, including pancreatic adenocarcinoma,
      • Dos Santos M.
      • Bouhier K.
      • Dao M.T.
      Paraneoplastic leukemoid reaction in pancreatic cancer: a case report.
      and is associated with aggressive tumor growth and overall poor prognosis.
      • Dos Santos M.
      • Bouhier K.
      • Dao M.T.
      Paraneoplastic leukemoid reaction in pancreatic cancer: a case report.
      To our knowledge, this feature has never been described in association with squamous cell carcinoma of the pancreas.
      The 2 larger case series on squamous cell carcinoma have disagreed regarding its anatomic distribution within the pancreas. Brown et al
      • Brown H.A.
      • Dotto J.
      • Robert M.
      • et al.
      Squamous cell carcinoma of the pancreas.
      notes that the mass occurs with equal frequency in the pancreatic head, body or tail; however, Beyer et al
      • Beyer K.L.
      • Marshall J.B.
      • Metzler M.H.
      • et al.
      Squamous cell carcinoma of the pancreas. Report of an unusual case and review of the literature.
      noted 73% predominance in the head of the pancreas with 27% occurrence in the body or tail. Studies do concur that most patients have advanced disease at diagnosis, and therapy depends on its level of dissemination. If possible, curative resection is the best therapeutic option. For unresectable disease, management consists of systemic chemotherapy and radiation therapy. Whereas there is no standard regimen, chemotherapy options include cisplatin combinations with fluorouracil, etoposide and vinblastine and gemcitabine combinations with carboplatin and fluorouracil.
      • Kodavatiganti R.
      • Campbell F.
      • Hashmi A.
      • et al.
      Primary squamous cell carcinoma of the pancreas: a case report and review of the literature.
      Even with therapy, squamous cell carcinoma of the pancreas has a high mortality rate and overall poor prognosis. Brown et al
      • Brown H.A.
      • Dotto J.
      • Robert M.
      • et al.
      Squamous cell carcinoma of the pancreas.
      noted a median survival of 7 months in patients undergoing curative resection and 3 months in those who did not.
      In summary, squamous cell carcinoma of the pancreas is extremely rare. It is a poorly understood phenomenon with unknown pathophysiology. In addition to having a rare type of pancreatic malignancy, our patient exhibited another unusual feature of leukemoid reaction. This is the first case reported in published literature on leukemoid reaction in squamous cell carcinoma of the pancreas and illustrates the need for further investigation into squamous cell carcinoma of the pancreas.

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