Double Trouble: Synchronous Small Cell Carcinoma and Adenocarcinoma of the Pancreas – Case Report Open Access

Pancreatic cancer is estimated to be 8.3% of all cancer deaths with a 5-year survival rate of 12.5% [1]. Around 90% of pancreatic cancers are classified as pancreatic ductal adenocarcinomas (PDACs) [1]. Unlike many other cancers where early detection and advancements in cancer treatments have improved survival rates, most patients with PDAC (>80%) are diagnosed at an advanced stage. This leads to a 5-year survival rate of just 11% [2]. To identify multiple primary neoplasms within one organ is uncommon as compared to occurring in different organs [3]. Synchronous lesions are seen within 2 to 6 months of the primary tumor, whereas metachronous lesions usually occur after 6 months. The overall occurrence of multiple primary neoplasm has risen given a longer lifespan, extensive use of body imaging, genetic and environmental factors [4].

A 61-year-old male with medical history of type 2 diabetes mellitus type and hypertension, a social history pertinent for tobacco use for a decade, and a BMI of 28.86 kg/m² presented with a chief complaint of bilateral flank pain and mid-abdominal discomfort of 2-day duration. The physical exam was pertinent for normal bowel sounds, soft abdomen, and mid-abdominal tenderness. The patient reported to have epigastric fullness as well as intermittent epigastric pain, night sweats, and 50 pounds weight loss for around 9 weeks prior to presentation. Work-up was notable for CT findings of bilateral non-obstructing kidney mass with left hydronephrosis and a 26 mm × 21 mm low-density area in the distal pancreas body with mild peripancreatic fat stranding. Carbohydrate antigen 19-9 level was noted to be 12,250, and lipase and liver biochemistries were normal. PET/CT scan showed low-level fluorodeoxyglucose uptake in the retroperitoneal lymph nodes in the upper abdomen predominantly in the aortocaval and left periotic distribution, highly suspicious for local nodal metastases and increased uptake in the head and body of the pancreas (Fig. 1). Endoscopic ultrasound (EUS) showed a round mass was identified in the genu of the pancreas. The mass was hypoechoic. The mass measured 12 mm by 12 mm in maximal cross-sectional diameter. The endosonographic borders were well defined (shown in Fig. 2, left), and an irregular mass was identified in the pancreatic tail and was hypoechoic. The outer margins were irregular (shown in Fig. 2, right). The patient underwent EUS-guided fine needle aspiration of both the masses and an enlarged periaortic lymph node. The pancreatic head mass was notable for poorly differentiated small- to intermediate-sized cells with focal area of tumor necrosis and associated stromal fibrotic response favoring small cell carcinoma (shown in Fig. 3), while the biopsy of the body mass demonstrated moderately differentiated adenocarcinoma (shown in Fig. 4). The periaortic lymph node showed involvement of adenocarcinoma, and INSMI1 stain was negative for the presence of small cell carcinoma. A repeat CT scan showed hypoenhancing mass involving pancreatic body consistent with known pancreatic adenocarcinoma measuring approximately 3.5 × 2.6 cm with atrophy of the upstream pancreatic tail (Fig. 5, right). A second small hypoenhancing mass involving the pancreatic neck measures 1.2 × 1.1 cm, consistent with biopsy-proven neuroendocrine carcinoma. This is located anterior to the portal vein and closely approximates the portal vein without portal vein narrowing (Fig. 5, left). The patient was not deemed a surgical candidate. He was started on modified leucovorin calcium (folinic acid), fluorouracil, irinotecan hydrochloride, and oxaliplatin (mFOLFIRINOX) for the pancreatic adenocarcinoma after completing stereotactic body radiation therapy for the small cell carcinoma. Patient completed 12 cycles of mFOLFIRINOX and switched to maintenance with folinic acid, fluorouracil, and irinotecan for 1 month after which disease progression on PET scan was noted. Patient is anticipated to start either gemcitabine and nab-paclitaxel or gemcitabine and capecitabine.

Pancreatic cancers mainly originate from the ductal epithelial cells of the exocrine pancreas and are classified as ductal adenocarcinomas (PDAC). PDAC is a highly aggressive cancer with a poor clinical outcome, limited treatment options, and no reliable methods for early detection. PDACs frequently contain activating mutations in the KRAS oncogene, which plays a crucial role in tumor initiation and progression. Inactivating mutations in tumor suppressor genes like CDKN2A/p16, TP53, and SMAD4 work in conjunction with KRAS mutations to promote the rapid growth of aggressive PDAC tumors [5]. Among all the primary pancreatic neoplasms, only 1% neoplasm primary small cell carcinoma of the pancreas (SCCP) is a rare and highly aggressive cancer with a very poor prognosis. The biological origins of SCCP remain unclear, but it is thought that these cancers may stem from totipotent stem cells within the pancreatic ductal system, which can differentiate into a variety of endocrine cells [6]. The diagnosis of SCCP is confirmed by histologic analysis of a tumor biopsy and focusing on neuroendocrine differentiation markers such as chromogranin and synaptophysin [6]. Upon review of literature, very few cases have been reported of synchronous pancreatic tumors [7‒10]. Three sporadic synchronous tumors of the pancreas were reported by Sastry et al. [3]: one at the ampullary of Vater was poorly differentiated adenocarcinoma (preoperatively), and the other two (noted upon resection of specimen) were neuroendocrine (benign) at the head of pancreas and pancreatic adenocarcinoma at the uncinate. However, to our knowledge this is the first case of synchronous small cell carcinoma and adenocarcinoma within the pancreas. Previous case reports have been reported of two or more synchronous pancreatic masses in the pancreas caused by pancreatic cancer, type 1 autoimmune pancreatitis, and sarcoidosis [11]. This case is exceptional, as primary SCCP is rare, particularly when it occurs in conjunction with pancreatic adenocarcinoma. The prognosis of both cancers is dismal. No underlying pancreatic parenchymal disease for the development of the two primary cancers in the pancreas could be identified. He was recommended to undergo chemotherapy for pancreatic adenocarcinoma and stereotactic body radiation therapy for radiosensitive small cell carcinoma. In essence, synchronous pancreatic masses are rare. A thorough evaluation with imaging modalities in conjunction with EUS-guided fine needle aspiration should be obtained when multiple tumors are present in the pancreas to make an ultimate diagnosis and to guide management.

This case that stands as a reminder about the possibility of multiple primary malignant tumors of different origins must be considered when multiple tumors are present within the pancreas.

Informed written consent was obtained from the patient for publication of the details of their medical case and any accompanying images. The CARE checklist has been completed by the authors for this case report and added as online supplementary material (for all online suppl. material, see https://doi.org/10.1159/000545467). Ethical approval is not required for this study in accordance with local or national guidelines.

The authors have no conflicts of interest to declare.

This study was not supported by any sponsor or funder.

R.J.T., M.Z., and A.C. drafted the article and provided substantial contributions to the conception of this case report; M.C. provided interpretation of the histological images. S.K. and P.C. gave final approval of the version of the article to be published. All authors agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

All data generated or analyzed during this study are included in this article. Further inquiries can be directed to the corresponding author.