Primary pancreatic squamous cell carcinoma with duodenal invasion: Literature review and a case report

Abstract

Pancreatic squamous cell carcinoma (PSCC) is a rare pancreatic exocrine tumor. Pancreas does not contain squamous cells, which further makes it a rare tumor. However, several theories have explained histogenesis and mechanism of carcinogenesis. PSCC is very rare, has a poor prognosis and an aggressive nature with limited survival time. We report a 76-year-old African American man with multiple chronic comorbidities who presented with new-onset nausea, vomiting, and abdominal pain. His work-up revealed anemia, and CT scan imaging showed a locally advanced pancreatic body and tail mass with splenic artery encasement and stomach and duodenal obstruction. The tumor caused a mass effect on surrounding structures, namely displacement of the celiac axis, splenic flexure of colon, and distal transverse colon. After discussion with a multidisciplinary hepatopancreaticobiliary tumor board, we elected to proceed for a subtotal pancreatectomy, splenectomy, side to side gastrojejunostomy and a palliative tumor resection. Pathology report confirmed an invasive, moderately differentiated SCC of the pancreas, with direct invasion of duodenum, perineural and lymphovascular invasion, positive peripancreatic soft tissue margin, and 5/24 lymph nodes were positive for metastasis. Immunohistochemistry showed positivity for p40, CK5/6, and CK7, consistent with squamous differentiation. This case aims to shed light on this rare tumor in the differential diagnosis of the pancreatic masses and adds to the growing evidence. It highlights a vigilant clinical evaluation, multidisciplinary approach, and literature review of this rare tumor type.

Introduction

Pancreatic cancer is the third leading cause of cancer-related deaths worldwide [1,2]. Histologically, pancreatic tissue consists of exocrine and endocrine tissues. The exocrine tissue is responsible for producing digestive enzymes which assist food digestion, while the endocrine tissue consists of islets of Langerhans which produce hormones like insulin and glucagon to regulate blood sugar level. The most common pancreatic neoplasm is ductal adenocarcinoma that originates from the exocrine tissue, and it accounts for approximately 85% of all pancreatic neoplasms [1,2]. Additional less common pancreatic tumors include pancreatic neuroendocrine tumors, acinar cell carcinomas, pancreatoblastomas, solid-pseudopapillary tumors, cystic neoplasms of the pancreas, intraductal papillary mucinous tumors, pancreatic lymphoma, and metastatic lesions of the pancreas [1,2].

Pancreatic squamous cell carcinoma (PSCC) or pancreatic adenosquamous carcinoma (PASC) are rarer tumors of the pancreas. PSCC accounts for approximately 1% of pancreatic tumors and predominates in male gender with an age onset of approximately 62 years [3,4]. It is an aggressive tumor with a very poor prognosis and survival [5]. Typically, patients with pancreatic cancer present with constitutional symptoms, such as anorexia, weight loss, abdominal pain, and back pain [4]. Less common symptoms include a palpable epigastric mass, jaundice, elevated blood sugar, compressive symptoms, and upper gastrointestinal bleeding [2]. Diagnostic measures include full blood work-up, tumor markers (CA-19.9 and CEA), genetic analysis, computed tomography (CT), magnetic resonance imaging (MRI), Positron Emission Tomography (PET), and gastrointestinal endoscopy [2,[4], [5], [6.]]. Histologic biopsy assessment and immunohistochemical analysis are confirmatory tools [2,4,7]. Fine or core-needle biopsy specimens can be retrieved through the guidance of CT scan, endoscopic ultrasound (EUS), or laparoscopic tissue sampling. Treatment modalities include operation, chemotherapy, and/or radiotherapy.

Case presentation

A 76-year-old African American man with a past medical history of chronic obstructive pulmonary disease (COPD), essential hypertension, atrial fibrillation and moderate aortic stenosis presented with persistent nausea, vomiting, and abdominal pain. His family history was positive for hyperlipidemia. His alcohol intake included 4 times monthly beer intake with a 45 pack-years smoking history. Additionally, he had a positive recreational drug usage, namely marijuana. Physical examination revealed epigastric tenderness without head, neck, or cutaneous lesions. Laboratory work-up revealed mild anemia, with a hemoglobin of 11.5 g/dL (reference range, 13.1-16.8 g/dL), and hematocrit of 34.9% (reference range, 38.2-48.4%). In the emergency department, the patient underwent CT Scan without contrast which revealed a large pancreatic mass in the body and tail of pancreas vs gastric GIST with obstruction of the fourth portion of the duodenum and gastric distention).

Esophagogastroduodenoscopy (EGD) demonstrated obstruction of the distal duodenum and biopsies were performed (Fig. 1). The lesion could not be crossed endoscopically, nor a wire could go through, hence, an endoscopic metallic stent placement was not feasible. Endoscopic ultrasound (EUS), contrast-enhanced computed tomography (CT) (Fig. 2), and magnetic resonance imaging (MRI) (Fig. 3) revealed a large infiltrative mass from the pancreatic body and tail with invasion of the fourth portion of duodenum. It also encased the splenic artery, displaced the celiac axis, compressed the colonic splenic flexure, and distal transverse colon. A staging CT scan with chest, abdomen, and pelvis showed no evidence of distant metastatic disease.

Fig. 1.

(A) Endoscopic images demonstrate a large volume of bilious gastric fluid containing fibrous debris, (B) and an obstructing ulcerated lesion in the fourth portion of the duodenum with active oozing and features suggestive of tumor erosion or pressure necrosis.

Fig. 2.

(A) Axial CT image demonstrates a large infiltrative mass of the pancreatic body and tail that measures 85 mm transversely and 53.6 mm anteroposteriorly, invading the fourth portion of the duodenum. (B) Coronal CT image shows the mass with a craniocaudal diameter of 91 mm, which encases the splenic artery, displaces the celiac axis, and has caused marked duodenal dilatation of 66 mm, along with mass effect on the colonic splenic flexure and distal transverse colon.

Fig. 3.

(A) Axial MRI illustrates a heterogeneous mass centered in the distal pancreatic body and tail, with a 53 mm in anteroposterior dimension. (B) Coronal MRI demonstrates the same lesion with transverse and craniocaudal dimensions of 79 mm and 69 mm, respectively. The mass circumferentially encases the fourth portion of the duodenum and proximal jejunum near the ligament of Treitz, which results in a severe upstream duodenal dilatation of up to 51 mm in diameter.

Cardiovascular assessment indicated patient to be an intermediate surgical risk (ISR) (Definition of ISR: Major adverse cardiac events, namely heart attack, cardiac arrest, or cardiac death of approximately <5% within 30 days). Multidisciplinary hepatobiliary conference discussion weighed palliative bypass vs resection based on the locally advanced stage. An open approach was selected to perform subtotal pancreatectomy, splenectomy, and side to side gastrojejunostomy. A large locally advanced pancreatic mass was identified with duodenal and peripancreatic extension without other appreciable intraabdominal masses. The above procedure was performed, and the patient tolerated the procedure well. He was discharged home in a stable condition. Histopathological examination of the distal pancreatectomy and splenectomy specimen revealed a moderately differentiated (SCC) extensively involved the pancreatic parenchyma, with extension into a 12.8 cm cystic mass arising from the pancreatic tail (Fig. 4A-D).

Fig. 4.

(A) Retrieved pancreatic specimen with the solid tumor greatest dimension of 10.1 cm. (B) Low power photomicrograph shows intersection of squamous cell carcinoma with​ normal pancreatic parenchyma. (C) High-power photomicrograph shows typical histologic features of squamous cell​ carcinoma including keratinization (Arrow). (D) High-power photomicrograph shows typical histologic features of squamous cell carcinoma, including keratinization (arrow). (E) Immunohistochemical stain for the squamous marker p40 demonstrates a positive nuclear immunoreactivity within tumor cells.

The solid tumor component measured approximately 10.1 cm in greatest dimension. The carcinoma invaded the fourth portion of the duodenum and infiltrated the peripancreatic adipose tissue with a positive soft tissue margin, while the pancreatic neck margin was negative. Pathological evaluation classified the tumor as pT3 pN2 G2 R2. Immunohistochemical analysis demonstrated diffuse nuclear p40 positivity and cytoplasmic immunoreactivity for CK5/6 and CK7, which confirms a squamous differentiation (Fig. 4E). Focal intracytoplasmic mucin was identified on mucicarmine stains within the cyst wall epithelium. Due to the nature of the patient’s presenting symptoms of obstruction and inability to place a duodenal stent, the team moved forward with staging CT scans and surgery to relieve the obstruction and create a surgical bypass. Inpatient PET scan was not available and thus completed postoperatively. Outpatient PET/CT scan showed no metastatic hyperactivity 2 weeks postoperatively except around the operative site (Fig. 5).

Fig. 5.

Axial (A) and coronal (B) PET/CT images obtained after distal pancreatectomy and splenectomy, which show an intensely hypermetabolic mass of 5.9 × 4.3 cm in the left upper quadrant. The mass causes obstruction at the duodenojejunal junction with upstream dilation of the duodenal C-loop, which suggests residual disease, with no nodal or distant metastases.

Discussion

Pancreatic adenocarcinoma is the most common primary malignancy, and it arises from the pancreatic exocrine ductules [1,2]. Conversely, pancreatic squamous cell carcinoma (PSCC) is a rare pancreatic tumor which is roughly around 1% of the pancreatic tumors with male predominance [3,4]. The squamous cell carcinoma (SCC) originates from the epithelial lines of the ductules. Histologically, the pancreatic parenchyma is free from squamous cells, however, the carcinogenesis has been explained by several theories. One of the mechanisms is squamous metaplasia of the pancreatic ductules in the presence of chronic inflammation, such as chronic pancreatitis, which causes SCC via tissue differentiation [2]. Furthermore, other proposed mechanisms include malignant differentiation of multipotent stem cells, malignant transformation of aberrant or ectopic squamous cells, pre-existing adenocarcinoma differentiation to SCC, collision tumor theory, and metastasis from other organs, such as head, neck, lungs, cervix, and esophagus [2,6,7].

In this case, immunohistochemical analysis demonstrated diffuse nuclear p40 positivity and cytoplasmic immunoreactivity for CK5/6 and CK7, which confirms a squamous differentiation. However, focal intracytoplasmic mucin was reported on mucicarmine stain within the cyst wall epithelium. Although a definitive adenocarcinomatous component was not observed in this case, these findings raise the possibility of an adenosquamous carcinoma or malignant transformation within a squamous-lined cystic lesion. This falls into the WHO classification of a pure squamous cell carcinoma of the pancreas. There is no specific risk factor linked to SCC, however, common risk factors of pancreatic adenocarcinoma can induce SCC formation, such as chronic pancreatitis, smoking, and alcohol intake [2,3]. The patient risk factors included daily alcohol intake with heavy smoking. Genetically, there is no confirmed mutation attributed to PSCC, however, BRCA2 germline mutation has been reported in the literature in addition to rare reports of family history of pancreatic cancer [[8], [9], [10]].

Clinically, the pancreatic SCC often presents with nonspecific symptoms such as abdominal pain, back pain, nausea, weight loss, jaundice, and obstructive features, however, it could rarely present with bleeding ulcer or pancreatic pseudocyst. Our patient presented with signs and symptoms of duodenal obstruction, a complication that is less frequently described in the literature [11,12]. PSCC is characterized radiologically by a peripheral contrast enhancement [6]. The absolute therapeutic modality is still unknown, however, the operability and a lower stage of presentation are good indicators for a longer survival [8,13]. It is highly malignant with a 5-year survival rate of less than 1%. It also has a very poor response to chemotherapy and radiotherapy [3,4]. Surgical resection is the preferred treatment modality for resectable lesions. However, it is frequently diagnosed in an advanced stage which requires only palliative therapy [14,15]. After resection and PET/CT findings, the patient was offered palliative radiation to the surgical bed along with 5-fluorouracil (5-FU), leucovorin, ironotecan/Camptosar, and oxaliplatin. The patient underwent palliative radiation (incomplete, only 2 sessions) with 5-FU, however, the patient did not move forward with systemic chemotherapy. Table 1 includes numerous PSCC cases reported in English literature with frequent local invasion, and it also includes the demographic characteristics, clinical presentation, imaging, pathology, treatment modalities, and outcomes. As seen in the table chart, this patient had an identical poor prognosis with the mortality of 3 months postoperatively. This summary reinforces the variability of presentation, tumor aggressiveness, survival limitation, and therapeutic approaches which range from chemotherapy, radiotherapy, palliative measures and/or a more extensive resection. In this case report, we performed subtotal pancreatectomy, splenectomy, and side to side gastrojejunostomy due to the advanced local disease with resolution of the duodenal obstruction.

Table 1.

Published Primary PSCC case reports with their clinical presentation, local effects, therapeutic modalities, pathological findings, and outcomes.

Study	Age /Sex	Presentation	Location/Size	Local effect	Metastasis	Pathology	Treatment	Outcome
Kubota et al. [16]	73/Female	Fatigue + low appetite + jaundice	(Head)/8 cm	Stomach + gastroduodenal artery + superior mesenteric vein	None	Keratinization, focal mucin pools without tubular or papillary architecture. SCC originated from pre-existing mucinous cystadenocarcinoma	Pancreaticoduodenectomy	Discharged from hospital free from symptoms
Ikeda et al. [17]	79/Male	N.A	N.A	Gastric ulcer fistula	Lymph node	SCC	Chemotherapy	Improved
Soliman et al. [18]	62/Female	Abdominal pain + vomiting	N.A	Distal duodenal obstruction + gastric fistula	Liver	N.A	Chemotherapy + self-expandable metal stent for fistula + bypass bowl obstruction	Died 3 mo later due to tumoral adverse events
Zhang et al. [13]	64/Female	Epigastric pain + hematochezia + weight loss	(Body)/7 cm	Celiac trunk + posterior wall of the gastric body + retroperitoneal lymph nodes enlargement	None	Well-differentiated SCC characterized by clouds of squamous cells with keratin pearls	Chemoradiation + targeted therapy	Died of tumor progression to liver and hemorrhagic shock after 8 mo
Taibi et al. [19]	72/Female	Jaundice	(Head)/2.2 * 1.7 cm	Biliary and pancreatic ductal dilatation + transverse colon adherence + perineural neoplastic invasion	None	Confirmed SCC (T2N0M0R0)	Whipple procedure + transverse colectomy + manual anastomosis + chemotherapy	Complete remission at 26 mo follow-up
Qiu et al. [20]	64/Male	Abdominal distension	(Body)/5.4 * 5.2 cm	None	None	Abnormal cell mass with immunophenotype consistent with SCC (CK+, p40+, p63+, CK7−). Ki-67 proliferation index 30%.	Pseudocyst drained and surgery, radiotherapy, and chemotherapy were refused	Died 3 mo after diagnosis due to liver metastasis and multiple organ failure
Marak et al. [21]	47/Female	Epigastric pain	(Body + tail) /3.2 * 5.2 * 4 cm	Jejunal loop + splenic artery encasement	None	Intraparenchymal tumor nest, keratin pearl, and clear cell change	Chemotherapy	Follow-up CT scan showed increase in the size and extension of the lesion
Choi et al. [12]	56/Male	DM + upper GI bleeding	(Body)/9.4 × 7.2 × 8.3 cm	Gastric invasion	Liver	Positive for p40 and CK 5/6 and negative for CK 20, CK 7, and CDX-2	Palliative radiotherapy + chemotherapy	Died 14 wk later due to sepsis
Wang et al. [22]	70/Male	Abdominal pain	(Body + tail)	Peripancreatic tissue + spleen	None	Poorly differentiated SCC, pT4N0M0, R0 resection, negative margins, p40+, p63+, GATA3 protein -ve, Ki-67 40%.	Radical pancreatosplenectomy + partial gastrectomy + left adrenalectomy + peripancreatic lymph node dissection + jejunostomy	Liver and stomach metastasis after 2 mo. Died at 7 mo due to liver failure
Fatah et al. [present case], 2026	76/Male	Abdominal pain + nausea + vomiting	(Body + tail)/8.5 × 5.36 × 10.1 cm	Duodenum + Splenic artery + celiac axis + splenic flexure + transverse colon	Lymph node	Keratinization, p40 positive, pT3 pN2 G2 R2, SCC	Pancreatectomy + splenectomy + gastrojejunostomy	Underwent palliative radiation & 5-FU. Died 3 mo later without systemic chemotherapy.

Conclusion

Primary pancreatic SCC is a rare tumor category among pancreatic tumors due to the absence of squamous cells in the pancreatic histology. It is an aggressive neoplasm with a poor prognosis. This case adds to the growing evidence of this rare tumor type, and it showcases the importance of evaluation by a multidisciplinary team. It requires a high index of suspicion, timely diagnosis, and an effective treatment plan with close monitoring which is of paramount importance. Reporting of such cases is essential for a better understanding of the nature, carcinogenesis, and proper management modalities for a long-term improved survival and prognosis.

Patient consent

We hereby confirm that a written consent and agreement was obtained from the patient for the case report.