JOP. J Pancreas (Online) 2019 Jan 30; 20(1):01-03.

REVIEW ARTICLE

Squamous of the Pancreas: A Review of the Literature

Joseph A. Di Como

Department of Surgery, Conemaugh Memorial Medical Center, Johnstown PA

ABSTRACT Primary squamous cell carcinoma is a particularly rare form of pancreatic , comprising approximately 1% of all pancreatic , with a reported incidence range of 0.5% to 5%. This presents a clinical challenge as diagnosis, response to treatment, prognosis and outcome are relatively poorly understood compared the relatively more common pancreatic . Primary squamous cell lack of glandular component. Clinical information relating to primary squamous cell carcinoma is scant and is derived primarily from carcinomaretrospective of studies.the pancreas Discrepancies is typically in theonly reported diagnosed incidence once other of p rimaryprimary squamous sources ofcell the carcinoma tumor are in excludedthe literature and havehistology been confirms attributed a to erroneous categorization of adenosquamous carcinoma as primary squamous cell carcinoma, possibly leading to overestimation of incidence. Analyses of the biologic behavior of primary squamous cell carcinoma from previous reports highlights its propensity to affect older individuals, presence of at diagnosis, poor response to chemotherapeutic agents and radiation therapy and an extremely short survival period. Surgical resection is the only potential curative treatment and should be considered in all primary squamous cell carcinoma patients with resectable disease.

INTRODUCTION squamous cell carcinoma of the pancreas is typically only diagnosed once other primary sources of the tumor Despite being the tenth most commonly diagnosed in the United States, remains component. Discrepancies in the reported incidence of the fourth leading cause of all cancer-related death. The SCCPare excluded in the literature and have been confirms attributed a lack to of erroneous glandular aggressive nature of this disease makes pancreatic cancer the only cancer tracked by both the American Cancer possibly leading to overestimation of incidence in some Society and the National Cancer Institute to persistently cases.categorization of adenosquamous carcinoma as SCCP [7], malignancies can be divided into endocrine and non- Analyses of the biologic behavior of SCCP from previous endocrinehave a five-year origin. survival Non-endocrine rate below malignancies10% [1]. Pancreatic of the reports highlights its propensity to affect older individuals, pancreas are of ductal and acinar origin, with ductal being presence of metastasis at diagnosis, poor response to chemotherapeutic agents and radiation therapy and an subdivided into adenocarcinoma and squamous cell ,more common with [2]. adenocarcinoma Ductal cell carcinomas accounting can forbe 90%further of pancreatic malignancies. DISCUSSIONextremely short survival period [2, 8]. The most common affecting the pancreas Primary squamous cell carcinoma (SCCP) is a are of ductal cell origin, which includes both PA and particularly rare form of pancreatic cancer, comprising approximately 1% of all pancreatic malignancies, with a reported incidence range of 0.5% to 5% from the squamous cell carcinoma of the pancreas is typically onlySCCP, diagnosed with the once vast other majority primary being sources PA [9].of the Primary tumor diagnosis, response to treatment, prognosis and outcome areliterature relatively [3, 4, poorly 5, 6, 7]. unde Thisrstood presents compared a clinical the challenge relatively as component. Discrepancies in the reported incidence of are excluded and histology confirms a lack of glandular more common pancreatic adenocarcinoma (PA). Primary SCCP in the literature have been attributed to erroneous

possibly leading to overestimation of incidence in some Received June 19th, 2018 - Accepted December 15th, 2018 categorization of adenosquamous carcinoma as SCCP [7], Keywords Carcinoma, Squamous Cell; Pancreatic Neoplasms Abbreviations PA pancreatic adenocarcinoma; SCCP primary a low incidence reported between 0.2% and 5% of all squamous cell carcinoma cases. Histopathologically confirmed cases of SCCP have Correspondence Joseph A Di Como Chief Resident, Department of Surgery Histologically SCCP like other squamous Conemaugh Memorial Medical Center pancreatic cancers [2]. 1086 Franklin Street, Johnstown Pennsylvania 15905 demonstrate keratinization with an esosinophilic Tel +973-641-8598 cytoplasm, formation of whorls or “pearls” with E-mail [email protected] intercellular bridges and epithelial cells arranged

JOP. Journal of the Pancreas - http://pancreas.imedpub.com/ - Vol. 20 No. 1 – January 2019. [ISSN 1590-8577] 1 JOP. J Pancreas (Online) 2019 Jan 30; 20(1):01-03. in irregularly shaped nests and cords. In addition, presentations with upper gastrointestinal bleeding and desmoplastic responses secondary to ductal obstruction have also been suggested as a prominent feature. Various pancreas appear to be equally affected by SCCP, with theories exist concerning the pathogenesis of SCCP. A melena have also been reported [14]. All regions of the The distribution pattern of SCCP varies, with one study in conditions such as pancreatitis, may induce squamous reportingtumors commonly 73% in the overlapping head of the multiplepancreas, regions45% in [2].the possible mechanism is that chronic inflammation, seen Hypercalcemia is another common, with up to 64% of pancreatic ducts examined metaplasia [10]. Squamous metaplasia is relatively bodymetastasis, and 23% with in a thevarying tail [15].degree of interaction between that SCCP may result from malignant transformation of parathyroidfinding reported hormone, in parathyroid SCCP without hormone-like evidence peptides, of bony squamousat autopsy metaplastic demonstrating zones this in histology the pancreatic [2], suggesting ductal prostaglandins, vitamin D-like sterols and osteoclasts as that most, if not all instances of SCCP are associated with chronicepithelium. pancreatitis. This possibility In one study is supported reported by by the Mikal finding and the Thelikely mean mechanism tumor size, [10]. as reported by Brown et al. in his review of 36 autopsy patients with SCCP was 7.8 cm, with 100 autopsies on patients with pancreatic cancer. Other approximately 95% of patients demonstrating evidence of theoriesCampbell for [11], the pancreatitisdevelopment was of SCCP discovered include inmalignant 49% of metastasis at the time of evaluation or surgery. The most change in a primitive cell capable of differentiating into commonly involved structures included, regional lymph either squamous or glandular carcinoma and malignant nodes, liver, lung and bone. This study also demonstrated that the majority of SCCP are over 4cm, and tended to be poorly differentiated and present with distant disease changeRadiological in an aberrant features squamous that havecell [2]. been reported in at presentation compared to PA. Metastatic SCCP is far differentiating SCCP from PA are the enhancement of the tumor with contrast computed tomography (CT) and “blush” patterns with angiography. These two features pancreaticmore common neoplasms than primary were metastatic SCCP [16]. and In no an primary autopsy are likely due to the hypervascular nature of SCCP. In a squamousstudy by Cubilla tumors and were Fitzgerald found. [16], Of 261these, (63.5%) 49 (11.9%) of 411 report by Fajardo et al metastasized from the lung, 12 (2.9%) from the cervix a bolus injection of intravenous (IV) contrast in a patient and 10 (2.4%) from the . Due to the tendency with SCCP demonstrated. [12], an the increased use of dynamic attenuation CT with of of any squamous found in the pancreas to be a metastatic lesion rather than a primary tumor, it is critical vascularity. Sprayregen et al that appropriate evaluation using radiological imaging, cases35 Hounsfield of SCCP Unitstumor (HU) “blushes” to 61 HU,were indicating present, increasedwith one . [13] reported that in 2 endoscopic visualization or other diagnostic modalities be some studies to conclude that these features may aid in case demonstrating hypervascularity. This finding led date, no criteria exists for a cytologic distinction between metastaticimplemented and to SCCP. identify possible primary cancers [2]. To be noted that radiological hypervascularity are seen in other conditions,differentiating including SCCP from , adenocarcinoma , [12]. It should The treatment options for SCCP are limited, with adenosquamous carcinoma, hemangiomas, angiosacroma, surgical resection, and radiotherapy with and neuoendocrine cell neoplasms of the or locally advanced at time of diagnosis, making resection high index of suspicion for SCCP as part of the differential impossiblelimited to poor in most results patients. [10, 15]. SCCP is often metastatic pancreas [12]. Regardless, the clinician should maintain a diagnosis when hypervascularity or tumor blush is Limited data suggests survival may be improved with adjuvant therapy, and differs between SCCP and PA. Katz primary squamous cell carcinoma of the pancreas have demonstrated an improvement in survival identified in a pancreatic lesion. Specific risk factors for et al with the use of chemoradiation in the palliative setting, adenocarcinoma appear to also be associated with the . [17] yet to be defined. However, the same risk factors for therapy. Different chemotherapeutic agents have been but no significant improvement was seen with adjuvant developmentAnalyses ofof SCCPthe [2].biologic behavior of SCCP from published literature highlights its propensity to affect older individuals, presence of metastasis at diagnosis, includingused, including gemcitabine combinations displaying of an cisplatin, improved 5-fluorouracil response. A poor response to chemotherapeutic agents and radiation and vinblastine, with one report [7] suggesting regimens in patients with SCCP treated with bleomycin. The mean age of 62 to 65 has been reported for patients with rarityreport ofby SCCPRavry makes [18] described the role symptomatic of chemoradiation improvement in the SCCPtherapy and an extremely short survival period [2, 8]. A management of these tumors unclear. To date no standard chemotherapy regimen has been established for SCCP and Patients with SCCP typically present with symptoms [4]. further investigation is needed identical to those of adenocarcinoma, and include abdominal pain, back pain, anorexia, weight loss, A range of median survival times has been reported for nausea, vomiting and obstructive jaundice. Uncommon SCCP from 6-16 months for patients that had undergone

JOP. Journal of the Pancreas - http://pancreas.imedpub.com/ - Vol. 20 No. 1 – January 2019. [ISSN 1590-8577] 2 JOP. J Pancreas (Online) 2019 Jan 30; 20(1):01-03. curative resection, and 0-9 months for those who did not 8. National Cancer Institute: Surveillance Epidemiology and End Results show a poor survival, Cancer Statistics Review. http://seer.cancer.gov with mean 1- and 5- year survival rates of 4.8% and 1% 9. [4]. Previously reported studies TS. 415 patients with adenosquamous carcinoma of the pancreas: a population-basedBoyd CA, Benarroch-Gampel analysis of prognosis J, Sheffield and survival. KM, Cooksley J Surg Res CD, 2012; Riall respectivelyNovel methods [10, 19, of 20, SCCP 21, detection22]. are emerging today. There are currently two reports of the role of “squamous 174:12-9.10. Brayko [PMID: CM, Doll21816433] DC. Squamous cell carcinoma of the pancreas associated with hypercalcemia. Gastroenterology 1982; 83:1297-9. cell carcinoma antigen” (SCCPAg) to diagnose and monitor et al. [PMID:11. Sears 7129033] HF, Kim Y, Strawitz J. Squamous cell carcinoma of the pancreas. elevatedthe disease. in a patient Reports with by HachiyaSCCP with [23] a value and Minamiof 14.9 U/mL 12. Fajardo LL, Yoshino MT, Chernin MM. Computed tomography that[24] indicateddeclined to that normal the serum limits levels after of complete SCCPAg wasresection notably of J Surg Oncol 1980; 14:261-5. [PMID: 7392648] the neoplasm. While more investigation is needed, these findings in squamous cell carcinoma of the pancreas. J Comput Tomogr reports suggest that the level of serum SCCPAg may be a 1988;13. Sprayregen 12:138-9. S,[PMID: Schoenbaum 3168524] SW, Messinger NH. Angiographic features of squamous cell carcinoma of the pancreas. J Can Assoc Radiol 1975; modality has been widely accepted to effectively monitor SCCPuseful to marker date. for tumor recurrence. However, no specific 26:122-4.14. Minami [PMID: T, Fukui 1158957] K, Morita Y, Kondo S, Ohmori Y, Kanayama S, et al. A case of squamous cell carcinoma of the pancreas with an initial CONCLUSION symptom of tarry stool. J Gastroenterol Hepatol 2001; 16:1077-9. SCCP is a rare and aggressive neoplasm. It commonly [PMID:15. Beyer 11595080] KL, Marshall JB, Metzler MH, Poulter JS, Seger RM, Díaz-Arias presents with metastatic disease and has more aggressive AA. Squamous cell carcinoma of the pancreas. Report of an unusual case characteristics when compared to PA. Surgical resection should be considered in any SCCP patient with resectable and16. review of the literature. Dig Dis Sci 1992; 37:312-8. [PMID: 1735353] disease that are candidates for surgery, as it appears to be in cytologic specimens from the pancreas: cytological differentialLayfield diagnosis LJ, Cramer and H, Maddenclinical implications.J, Gopez EV, Liu Diagn K. Atypical Cytopathol squamous 2001; the best option for improving survival.

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