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Adenosquamous Carcinoma of the Pancreas

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Adenosquamous Carcinoma of the Pancreas PAPER Adenosquamous Carcinoma of the Pancreas James A. Madura, MD; Benjamin T. Jarman; Michael G. Doherty; Moo-Nahm Yum, MD; Thomas J. Howard, MD Hypothesis: Adenosquamous carcinoma of the pan- and or tail lesions had distal pancreatectomy and sple- creas is a rare but particularly virulent variant of inva- nectomy. Pathologically, all the tumors were poorly dif- sive ductal carcinoma. This review will demonstrate the ferentiated and aneuploid, and 5 of the 6 were locally aggressive biologic activity, histopathologic features, and metastatic. All but 1 patient had postoperative compli- DNA flow cytometric characteristics of this aggressive le- cations, but there were no operative deaths. One half of sion. In addition, the outcome is less favorable than in the patients received postoperative adjuvant chemo- other pancreatic neoplasms, in spite of aggressive surgi- therapy and radiation therapy. Only 1 patient is still alive cal and postoperative adjuvant therapy. at 9 months after surgery, but has known residual can- cer around his portal vein noted during palliative distal Design: A retrospective review of 6 patients treated dur- pancreatectomy. ing an 8-year period. Conclusions: Adenosquamous carcinoma of the pan- Setting: A major urban university tertiary referral creas is an uncommon variant of exocrine pancreatic neo- hospital. plasm. It is characterized by an admixture of adenoma- tous and squamous cell elements and demonstrates Patients: There were 6 patients with this unusual tu- aggressive biologic behavior. This series of 6 patients is simi- mor seen between 1990 and 1998. There were 4 men and lar to the 134 cases reported since 1907, in that survival is 2 women, all white, with a mean ± SD age of 63.5 ± 14.7 short despite aggressive surgical therapy. Few patients with years. Symptoms were similar to those in patients with this disease live more than 1 year. Aggressive therapy should more common pancreatic malignant neoplasms. be tempered by the realization of the uniform poor prog- nosis associated with this malignant neoplasm. Results: Four patients with tumors in the head of the pancreas had pancreatoduodenectomy, and 2 with body Arch Surg. 1999;134:599-603 NVASIVE DUCTAL carcinoma ac- ture. Most of the reports have been small counts for the majority of pan- series or single case reports, and, of the creatic malignant neoplasms and large autopsy or surgical tissue reviews, has a poor prognosis with the ex- only a few reports detail clinical, his- ception of a series of highly se- topathologic, and patient outcome data. Ilected patients undergoing radical surgi- Survival times have been short in those pa- cal therapy for cure. Adenosquamous tients found to have unresectable tu- carcinoma of the pancreas is an unusual mors, as well as in those who have under- variant of pancreatic neoplasm. It has been gone aggressive resection for attempted variously referred to as adenoacan- cure. The prognosis of this uncommon le- thoma, mixed squamous and adenocarci- sion appears to be even less favorable than noma, and mucoepidermoid carcinoma. the invasive ductal tumor, with only a few These tumors are histologically charac- patients surviving more than 1 year. Be- terized by adenomatous cell populations cause of its rarity, only anecdotal studies mixed with varying amounts of keratin- of adjunctive radiation or chemotherapy From the Departments of ized squamous cell elements. Major insti- are available. Surgery (Drs Madura and tutional reviews of autopsy and/or surgi- This series of 6 cases over an 8-year Howard and Messrs Jarman cal specimens suggest an incidence of period demonstrates the aggressiveness of and Doherty) and Pathology (Dr Yum), Indiana University approximately 4% of all pancreatic neo- this tumor, and its rapid course from dis- School of Medicine, plasms; however, only 134 cases have been covery to death, despite aggressive surgi- Indianapolis. reported in the accessible world’s litera- cal treatment. ARCH SURG/ VOL 134, JUNE 1999 599 ©1999 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/26/2021 PATIENTS AND METHODS Between 1990 and 1998, six patients were diag- nosed as having adenosquamous carcinoma of the pancreas and treated at the Indiana University Medi- cal Center Hospitals, Indianapolis. There were 4 men and 2 women, all white, whose mean ± SD age was 63.5 ± 14.7 years. The duration of symptoms prior to presentation was 4.3 ± 3.9 months, and symp- toms included abdominal pain and weight loss in 5 of the 6 patients, nausea and vomiting in 3 patients, and anorexia and jaundice in 2 patients. A single pa- tient with a large tumor invading the duodenum pre- sented with upper gastrointestinal tract bleeding and Figure 1. Computed tomographic scan of a patient with large anemia. Physical findings included upper abdomi- adenosquamous carcinoma of the mid-body of the pancreas. nal tenderness in 4 patients, jaundice in 2 patients with tumors in the head of the pancreas, and a pal- pable abdominal mass in 1 patient. Laboratory stud- ies were unremarkable with the exception of el- evated bilirubin and alkaline phosphatase levels in the 2 patients with jaundice and moderately el- evated serum carbohydrate antigen 19-9 (Ca 19-9) of 200 U/mL (reference value, #70 U/mL) in 1 pa- tient. Computed tomography and endoscopic ultra- sound both accurately demonstrated and localized a pancreatic mass in all 6 patients (Figure 1). Endo- scopic retrograde cholangiopancreatography was per- formed in 5 patients and demonstrated pancreatic duc- tal obstruction by tumor in the head or body, which corresponded with the tumor location on the imag- ing studies (Figure 2). Three patients had preop- erative fine-needle aspiration biopsy of the tumor mass but none of the specimens were diagnostic of adeno- squamous carcinoma. All 3 of the patients with tu- mors in the head of the pancreas underwent pancre- atoduodenectomy, and those with tumors in the body and/or tail of the pancreas were treated by distal pan- createctomy and splenectomy. Figure 2. The endoscopic retrograde cholangiopancreatogram of the patient in Figure 1, demonstrating pancreatic ductal cutoff in the mid-body of the pancreas. RESULTS atic parenchyma. Histologically, the tumors all displayed a mixture of ductal adenocarcinoma and squamous cell There were no postoperative deaths, but 5 of the 6 pa- carcinoma, with the latter comprising more than 30% of tients had postoperative complications, including 3 with the lesion. In a single case, the squamous cell component ventilator dependence and 2 with pancreatic fistulas that exceeded the glandular component by a 9:1 ratio. The ad- responded to nonoperative management. Postopera- enocarcinoma consisted of ductlike structures lined by co- tively, survival was short, with a mean ± SD survival of lumnar cells having large vesicular nuclei and prominent 5.04 ± 3.58 months. Three of the patients received ad- nucleoli. Most of these cells had pale to clear cytoplasm juvant chemoradiation therapy, but this did not result with occasional mucin vacuoles. The malignant squa- in significant prolongation of survival. One of the pa- mous cells were large and polygonal, having large hyper- tients who had previously undergone pulmonary resec- chromatic nuclei and eosinophilic cytoplasm with inter- tion for lung carcinoma committed suicide at 4 months cellular bridges and occasional squamous pearls. They were postoperatively. Four patients died of their malignancy arranged in diffuse sheets and lobules. These squamous at 1, 3, 5, and 12 months postoperatively. One patient and glandular components were for the most part inti- with known residual tumor surrounding the portal vein mately admixed (Figure 3). The tumors elicited a des- is alive at 8 months and has undergone radiation therapy moplastic response, which accounted for the firmness ap- along with gemcitabine therapy. preciated on gross examination. Four tumors were located in the head of the pan- Peripancreatic fat and neural invasion was present creas and 2 were in the body and tail. Tumor size ranged in all 6 cases. Lymphatic invasion was noted in 4 cases from 1.2 to 6.5 cm, with a mean size of 4.2 cm. Grossly, and the duodenal wall was invaded by tumor in 3 of the the lesions were firm with a light tan to yellowish color 4 tumors located in the head of the pancreas. Lymph node and merged imperceptibly with the surrounding pancre- metastases were found in 5 of the 6 patients. DNA flow ARCH SURG/ VOL 134, JUNE 1999 600 ©1999 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/26/2021 cytometry demonstrated aneuploidy in 5 patients with S-phase determination between 5.2% and 30.0% (Table 1). COMMENT Exocrine tumors of the pancreas have been classified his- tologically in several large institutional reviews.1-4 The majority of cases are recognized as invasive ductal car- cinomas. Other recognized variants include the muci- nous tumors; pleomorphic, anaplastic, and large cell types; acinar cell carcinoma; spindle cell tumors; microadeno- carcinomas; and oncocytic cancers.5 Adenosquamous and squamous cell carcinomas are recognized much less fre- quently and probably account for 1% to 4% of all re- Figure 3. Histopathologic specimen in a patient with adenosquamous ported tumors. carcinoma of the pancreas. There is desmoplastic stroma with spindly The first known report of adenosquamous carci- fibroblasts and nests of squamous cell carcinoma and a malignant glandular noma in the literature is credited to Herxheimer6 in adenocarcinoma focus in the center (hematoxylin-eosin, original 1907 in which he referred to this lesion as “cancroide.” magnification 3250). Subsequently, other authors have referred to this tumor of mixed columnar adenocarcinoma and keratin- containing squamous cell elements as mixed squamous Table 1. Histopathological Characteristics and Flow and adenocarcinoma, mucoepidermoid carcinoma, and Cytometric Data in 6 Patients With Adenosquamous adenoacanthoma. This admixed tumor has been seen Carcinoma of the Pancreas* more commonly in other organ systems, such as the lungs, esophagus, colon, stomach, salivary glands, and Nodes, Patient Tumor No.
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