The patient's current presentation was characterized by an insidious onset of epigastric pain that radiated to her back over the previous 3 months. On examination, left upper quadrant tenderness and epigastric fullness were noted without a palpable mass. CT revealed a large, bilobed, hypodense, infiltrating mass lesion in the neck of the pancreas and possibly 2 separate lesions measuring approximately 2.7 cm × 1.9 cm and 3.2 cm × 2.1 cm, respectively, that completely encased the superior mesenteric vein, left renal vein, and superior mesenteric artery (Figure 1). The patient's carcinoembryonic antigen level measured 7 ng/mL (normal, 0–3 ng/mL), and her CA 19-9 level measured 1,022 U/mL (normal, <37 U/mL). She was referred for endoscopic ultrasound (EUS) to obtain more definitive imaging and tissue diagnosis via EUS-guided fine-needle aspiration (FNA). EUS revealed multiple lymph nodes (up to 12 mm in size) in the peripancreatic space and 2 distinct lesions within the pancreas: a 30-mm heterogeneous mass in the pancreatic neck and a 35-mm hypoechoic mass within the body of the pancreas (Figure 2). Direct smears prepared from FNA samples of the peripancreatic node revealed only normal lymphoid cells; surprisingly, samples of the body and the neck of the pancreas were positive for squamous-cell carcinoma (Figure 3). Combined fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET)/CT imaging demonstrated an intense FDG uptake corresponding to the pancreatic mass lesions (Figure 4). Metastasis to the retroperitoneal lymph nodes and the left supraclavicular node was suggested by moderate and intense FDG-avid activity, respectively. Repeat core biopsies of the pancreas revealed squamous-cell carcinoma with cytoplasmic keratinization and marked nuclear atypia (Figure 5). Immunohistochemical staining revealed that the tumor was strongly positive for CK5/6 and p16 but negative for CK7 and CK20. In situ hybridization testing for human papillomavirus was negative.

Due to the rarity of pancreatic squamous-cell carcinoma, slides from the patient's earlier total colectomy specimen were pulled and reviewed. Interestingly, foci within that tumor were suggestive of the squamous differentiation found in the pancreatic tumor (Figure 6). Additionally, the colonic malignancy was positive for p16 and negative for high-risk human papillomavirus. Given the low incidence of primary pancreatic squamous-cell carcinoma and the similar immunophenotype of the 2 tumors, the patient was thought to most likely have pancreatic metastasis from a primary colonic lesion, rather than a de novo lesion. At the time of this case report's submission, the patient had completed 2 cycles of palliative chemotherapy involving gemcitabine hydrochloride (Gemzar, Lilly), docetaxel (Taxotere, Sanofi Aventis), and capecitabine (Xeloda, Hoffmann La Roche), and her most recent CA 19-9 measurement was 29 U/mL.

A typical diagnostic approach for pancreatic lesions includes a contrast-enhanced abdominal CT scan, FNA of the pancreatic lesion under EUS or CT guidance, and, if indicated, either resection or palliative bypass.3 Unfortunately, only 2% of pancreatic tumors that require operation are resectable, as patients typically present at an advanced stage.3 The prognosis of metastatic disease to the pancreas is poor; the mean survival rate after diagnosis is 8.7 months.3 Among the 27 patients with metastatic lesions of the pancreas who were reviewed by Roland and colleagues, 20 patients died within 1 year of diagnosis.2 Ultimately, pancreatic metastasis is a preterminal event, and efforts for surgical care must be balanced against a limited life expectancy.2

The colon is one of the most common sites for primary tumors that are metastatic to the pancreas.2 Although colorectal cancer (CRC) is the third most commonly diagnosed type of cancer and the second leading cause of cancer-related death in the United States, colorectal squamous-cell carcinoma and adenosquamous-cell carcinoma continue to be diagnostic rarities.5,6 The infrequency of these tumors is further highlighted by the End Results Group, which found that combined pure squamous and mixed adenosquamous cancer accounted for 0.1% of the 60,193 CRC cases that were reviewed.6,7 However, it should be noted that the relative incidence of colorectal squamous-cell carcinoma is higher in patients with UC (1.7%).8,9

Both pure squamous-cell carcinoma of the bowel and squamous elements in adenosquamous-cell carcinoma of the colon behave more aggressively than their glandular counterparts.10 However, the mechanism that gives rise to either squamous or adenosquamous-cell carcinoma within the colon remains poorly understood to date. Nonetheless, several pathogenic theories have been proposed.6 One theory suggests that uncommitted, or basal, cells proliferate in response to mucosal injury.6,11 Proliferation may eventually lead to an adenosquamous, pure squamous, or mixed tumor.11,12 Another theory proposes that squamous metaplasia of glandular epithelium may be the sequela of chronic inflammation.6,9 Although not all case reports of these cancers have noted chronic irritation or inflammation, inflammatory changes may explain the relatively higher incidence of adenosquamous or squamous carcinomas in individuals with UC.9,13

Other researchers have proposed squamous differentiation of adenomas or adenocarcinomas as a cause of squamous-cell carcinoma. Williams and coworkers suggested that squamous differentiation may arise within adenomas; indeed, squamous differentiation with metastatic potential may be an explanation for our patient's disease.14 Williams and associates have established diagnostic criteria for primary squamous-cell carcinoma of the colon, all of which were fulfilled in our case.14 These criteria are: Metastasis from another site to the bowel must be ruled out; a squamouslined fistulous tract must not involve the affected bowel, as this may be a source of squamous-cell carcinoma; squamous-cell carcinoma of the anus with proximal extension must be excluded; and squamous-cell carcinoma must be confirmed by histologic analysis.14,15

The rarity of colorectal squamous-cell carcinoma complicates the establishment of an accurate prognosis and increases the difficulty of treatment selection.4,15,16 Copur and colleagues report that etoposide and 5-fluorouracil are an effective combination therapy in these patients.17 Juturi and coworkers suggest that a combination of cisplatin, 5-fluorouracil, and leucovorin may be a possible treatment for patients with metastatic colorectal squamous-cell carcinoma.16 Miyamoto and colleagues believe that surgical resection is a better first-line treatment approach for colorectal squamous-cell carcinoma.15 Although the role of adjuvant chemotherapy or radiation remains unknown, adjuvant treatment may be considered if the patient has a good performance status.15