Variant Of Pancreatic Ductal Adenocarcinoma Research Articles

Clinical and Genomic Characterization of Pancreatic Ductal Adenocarcinoma with Signet-Ring/Poorly Cohesive Cells

Signet-ring cell (SRC)/poorly cohesive cell carcinoma is an aggressive variant of pancreatic ductal adenocarcinoma (PDAC). This study aimed to clarify its clinicopathologic and molecular profiles based on a multi-institutional cohort of 20 cases.The molecular profiles were investigated using DNA and RNA sequencing. The clinicopathologic parameters and molecular alterations were analyzed based on survival indices and using a validation/comparative cohort of 480 conventional PDAC patients.The primary findings were as follows: (1) clinicopathologic features: SRC carcinomas are highly aggressive neoplasms with poor prognosis, and the lungs are elective metastatic sites; (2) survival analysis: a higher SRC component was indicative of poorer prognosis. In particular, the most clinically significant threshold of SRC was 80%, showing statistically significant differences in both disease-specific and disease-free survival; (3) genomic profiles: SRC carcinomas are similar to conventional PDAC with the most common alterations affecting the classic PDAC drivers KRAS (70% of cases), TP53 (55%), SMAD4 (25%), and CDKN2A (20%). EGFR alterations, RET::CCDC6 fusion gene, and microsatellite instability (3 different cases, 1 alteration per case) represent novel targets for precision oncology. The occurrence of SMAD4 mutations was associated with poorer prognosis; (4) pancreatic SRC carcinomas are genetically different from gastric SRC carcinomas: CDH1, the classic driver gene of gastric SRC carcinoma, is not altered in pancreatic SRC carcinoma; (5) transcriptome analysis: the cases clustered into 2 groups, one classical/exocrine-like, and the other squamous-like; and (6) SRC carcinoma-derived organoids can be successfully generated, and their cultures preserve the histologic and molecular features of parental SRC carcinoma.Although pancreatic SRC carcinoma shares similarities with conventional PDAC regarding the most important genetic drivers, it also exhibits important differences. A personalized approach for patients with this tumor type should consider the clinical relevance of histologic determination of the SRC component and the presence of potentially actionable molecular targets.

Large Duct Pancreatic Ductal Adenocarcinoma: A Morphological Variant of Pancreatic Ductal Adenocarcinoma With Distinct CT and MRI Characteristics.

To investigate the imaging characteristics of large duct pancreatic ductal adenocarcinoma (LD-PDAC) on computed tomography (CT) and magnetic resonance imaging (MRI). Thirty-five patients with LD-PDAC (63.2 ± 9.7 years) were retrospectively evaluated. Tumor morphology on CT and MRI (predominantly solid mass vs. solid mass with prominent cysts vs. predominantly cystic mass) was evaluated. Additionally, the visibility, quantity, shape (oval vs. branching vs. irregular), and MRI signal intensity of neoplastic cysts within the LD-PDAC were investigated. The radiological diagnoses rendered for LD-PDAC in radiology reports were reviewed. LD-PDAC was more commonly observed as a solid mass with prominent cysts (45.7% [16/35] on CT and 37.1% [13/35] on MRI) or a predominantly cystic mass (20.0% [7/35] on CT and 40.0% [14/35] on MRI) and less commonly as a predominantly solid mass on CT (34.3% [12/35]) and MRI (22.9% [8/35]). The tumor morphology on imaging was significantly associated with the size of the cancer gland on histopathological examination (P = 0.020 [CT] and 0.013 [MRI]). Neoplastic cysts were visible in 88.6% (31/35) and 91.4% (32/35) of the LD-PDAC cases on CT and MRI, respectively. The cysts appeared as branching (51.6% [16/35] on CT and 59.4% [19/35] on MRI) or oval shapes (45.2% [14/35] on CT and 31.2% [10/35] on MRI) with fluid-like MRI signal intensity. In the radiology reports, 10 LD-PDAC cases (28.6%) were misinterpreted as diseases other than typical PDAC, particularly intraductal papillary mucinous neoplasms. LD-PDAC frequently appears as a solid mass with prominent cysts or as a predominantly cystic mass on CT and MRI. Radiologists should be familiar with the imaging features of LD-PDAC to avoid misdiagnosis.

Efficacy of chemotherapy for patients with metastatic or recurrent pancreatic adenosquamous carcinoma: A multicenter retrospective analysis

Background/objectivesPancreatic adenosquamous carcinoma (PASC) is a rare variant of pancreatic ductal adenocarcinoma (PDAC). The usual treatment for metastatic or recurrent PASC is systemic chemotherapy in accordance with the PDAC treatment strategy. This study aimed to investigate the efficacy of chemotherapy, especially the benefit of recent combination therapies, in patients with metastatic or recurrent PASC. MethodsWe conducted a multicenter retrospective analysis of 116 patients with metastatic or recurrent PASC treated with first-line chemotherapy between April 2001 and December 2017 at 24 Japanese institutions. ResultsCombination chemotherapies included gemcitabine + nab-paclitaxel (GnP, n = 28), fluorouracil/leucovorin + irinotecan + oxaliplatin (FFX, n = 10), gemcitabine + S-1 (GS, n = 10), and others (n = 9). Monotherapies included gemcitabine (n = 51) and S-1 (n = 8). The median overall survival (OS) was 6.5, 7.3, and 4.3 months for the whole cohort, the combination therapy group, and the monotherapy group, respectively. Multivariate analysis indicated that combination therapy showed a better trend in OS than monotherapy (hazard ratio = 0.68; 95% confidence interval, 0.38–1.20). GnP or FFX were selected in 58.7% of patients after FFX was approved in Japan, and revealed a median OS, median progression-free survival, and objective response rate of 7.3 months, 2.8 months, and 26.9% in GnP and 7.2 months, 2.3 months, and 20.0% in FFX respectively. ConclusionsThis study suggests that combination therapy may be more effective than monotherapy. GnP and FFX showed similar and clinically meaningful efficacy for patients with metastatic or recurrent PASC.

Genomic characterization of undifferentiated sarcomatoid carcinoma of the pancreas

Undifferentiated sarcomatoid carcinoma (USC) of the pancreas is a rare but especially aggressive variant of pancreatic ductal adenocarcinoma (PDAC), composed of at least 80% of sarcomatoid cells. This study aimed to elucidate its clinicopathological and molecular features. The study cohort included 10 patients with pancreatic USC. Clinicopathological parameters were determined for each patient. The molecular profile was investigated using next-generation sequencing (NGS). Histologically, all tumors were hypercellular neoplasms with spindle-shaped or sarcomatoid cells. All patients showed vascular and perineural invasion. Most patients had a poor prognosis. NGS showed important similarities with conventional PDAC, including frequent alterations in the classic PDAC drivers, KRAS (100% of cases), TP53 (90%), and CDKN2A (60%). There were also some important distinctions from conventional PDAC: 1) SMAD4, a typical PDAC driver gene, was mutated in only one case (10%); 2) Another distinctive molecular feature was the recurrent KRAS amplification (30% of cases), which is very rare in conventional PDAC. It has been previously reported in another subtype of pancreatic undifferentiated carcinoma, the rhabdoid variant, and may be a key event leading to the acquisition of an undifferentiated phenotype in a subgroup of cases; 3) Lastly, in two different cases, we detected two potentially actionable targets, not belonging to the typical PDAC molecular landscape, such as MCL1 amplification and POLQ mutation. Our study sheds light on this rare tumor type, which shows aggressive biological behavior and few druggable alterations. The most distinctive molecular features of pancreatic USC are the paucity of SMAD4 alterations and recurrent KRAS amplification.

A phase II trial of the super-enhancer inhibitor Minnelide™ in advanced refractory adenosquamous carcinoma of the pancreas.

Adenosquamous carcinoma of the pancreas (ASCP) is a very rare and highly aggressive variant of pancreatic ductal adenocarcinoma, accounting for 0.5-4% of all pancreatic cancer cases in the USA. Current data indicate that epigenetic changes and MYC overexpression lead to squamous transdifferentiation of pancreatic tumor cells and development of ASCP. Minnelide™, an oral anti-super-enhancer drug that inhibits MYC expression in preclinical models of ASCP, has demonstrated safety in a phase I study. We describe the design for a phase II, open-label, single-arm trial of Minnelide in patients with advanced refractory ASCP.

“Pure” hepatoid tumors of the pancreas harboring CTNNB1 somatic mutations: a new entity among solid pseudopapillary neoplasms

Hepatoid tumors (HTs) represent a rare group of neoplasms that are histologically similar to hepatocellular carcinoma but arise outside the liver. The current World Health Organization classification recognizes the hepatoid morphology of pancreatic tumors only as a possible variant of pancreatic ductal adenocarcinoma (PDAC). Here, we describe two cases of “pure” HT of the pancreas showing common features and characterized by indolent biological behavior. These tumors were roundish nodules with pushing borders, hyaline globules, and pure hepatoid histology; they were diffusely positive for β-catenin and LEF1 on immunohistochemistry. At next-generation sequencing, both neoplasms harbored only one pathogenic somatic mutation that affected the CTNNB1 gene at exon 3 and showed a loss of heterozygosity on chromosomes 18 and 21. By integrating macroscopic and microscopic features, along with their molecular profiles, we advocate that such tumors represent a distinct entity from PDAC and should be considered a new variant of solid pseudopapillary neoplasms. The recognition of this new neoplastic category may have immediate implications not only for tumor taxonomy but also for clinical practice.

Pancreatic body cancer presenting with dysphagia and palpable abdominal mass being mistaken for gastric gastrointestinal stromal tumor: "Case report".

Introduction and importanceBody and tail pancreatic cancers account for one third of pancreatic ductal adenocarcinomas (PDACs). Dysphagia is an extremely rare manifestation of pancreatic cancer that may follow direct invasion of primary pancreatic cancer to esophagus. Pancreatic cancer can be confused with either pancreatic or peripancreatic lesions like gastrointestinal stromal tumors (GISTs) on diagnostic computed tomography (CT) scans. Undifferentiated pancreatic cancer, which is a rare variant of pancreatic ductal adenocarcinoma rarely, present with palpable abdominal mass. The aim of this case report is to show the rare presentation of this deadly malignancy with dysphagia and palpable abdominal mass which was mistaken on CT scan for gastric gastrointestinal stromal tumor.Presentation of the caseA 60 years old male farmer presented with progressive dysphagia to solid food of 3 months duration. He has no history of smoking, diabetes or alcohol intake. Physical examination showed hard epigastric mass with poorly defined borders. Imaging suggested gastrointestinal stromal tumor found to be primary pancreatic body cancer at laparotomy. Biopsy later confirmed undifferentiated pancreatic cancer.DiscussionThe presentation of pancreatic ductal adenocarcinoma is nonspecific. Presence of clinical symptoms indicates advanced disease. Pancreatic body cancer has poor prognosis due to late presentation of the disease as compared to its counter pancreatic head cancer. CT scan has 85% diagnostic accuracy.ConclusionBoth surgeons and radiologists should be familiar with common and uncommon CT scan findings of pancreatic ductal adenocarcinoma as this can avoid unnecessary invasive investigation or treatment.

Abstract PO-054: A phase II trial of the super-enhancer inhibitor Minnelide in advanced refractory adenosquamous carcinoma of the pancreas (ASCP)

Abstract Background: Adenosquamous carcinoma of the pancreas (ASCP) is a very rare and highly aggressive variant of pancreatic ductal adenocarcinoma (PDA), accounting for 0.5-4% of all pancreatic cancer cases in the US. Current data indicates that epigenetic changes and Myc overexpression lead to squamous transdifferentiation of pancreatic tumor cells and development of ASCP. Minnelide is an oral anti-super-enhancer drug that inhibits Myc expression in preclinical models of ASCP. Oral Minnelide has been previously tested in the clinic where a Phase I study determined a recommended phase 2 dose of 2 mg/day. Major toxicities included neutropenia and sepsis. We hypothesize that Minnelide will be safe and effective in patients with advanced ASCP. Methods: This Phase II open label, single arm study being conducted at the NIH Clinical Center in Bethesda, MD (NCT04896073) will enroll up to 25 evaluable participants with advanced ASCP that has been previously treated. Eligibility criteria include: histologically confirmed ASCP (≥30% malignant squamous component), presence of metastatic, recurrent, or locally advanced unresectable disease, and progression or intolerance ≥1 prior systemic treatment for advanced disease. All participants will self-administer Minnelide at 2mg PO daily on days 1-21 of each 28-day cycle, for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Restaging scans will be performed every 8 weeks. Optional biopsies will be requested at baseline, mid-cycle 1 and at time of progression. The primary objective is to determine the antitumor activity of Minnelide by evaluating the disease control rate. Secondary objectives are determination of drug safety in this patient population, progression free survival, and overall survival. Exploratory objectives include assessment of Minnelide effect on tumor cell epigenetics, Myc expression and immune cell populations using on-treatment tumor biopsy tissues. Changes in circulating tumor DNA and circulating immune cell populations upon treatment will also be evaluated. A Simon optimal two-stage phase II trial design will be used. If 3 of the first 12 patients experience disease control, then enrollment will continue up to 25 evaluable participants. If ≥8 of 25 participants experience disease control this would rule out an unacceptably low clinical benefit of 20% in favor of 40% (α = 0.1, β = 0.2). This trial opened for accrual in July 2021. Citation Format: Nebojsa Skorupan, Mehwish I. Ahmad, Seth M. Steinberg, Jane B. Trepel, Derek Cridebring, Haiyong Han, Daniel D. Von Hoff, Christine Alewine. A phase II trial of the super-enhancer inhibitor Minnelide in advanced refractory adenosquamous carcinoma of the pancreas (ASCP) [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2021 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2021;81(22 Suppl):Abstract nr PO-054.

Invasive Large Duct Type Pancreatic Adenocarcinoma: A Diagnostically Challenging Entity

Abstract Introduction/Objective Large duct type invasive pancreatic adenocarcinoma is a morphological variant of pancreatic ductal adenocarcinoma that poses a radiologic and pathologic diagnostic challenge as it closely mimics other non- invasive neoplasms, including mucinous cystic neoplasms and intraductal papillary mucinous neoplasms (IPMN). We report a case of large duct type invasive adenocarcinoma that on radiology closely mimics an IPMN. Methods/Case Report The case id that of a 73-year-old male presenting with weight loss and chronic diarrhea. Abdominal imaging revealed features suggestive of main duct IPMN with possible side branch extension into the pancreatic head. Endoscopic retrograde cholangiopancreatography showed a bile duct stricture that was stented and biopsied, revealing mucinous material with neoplastic cells. A Whipple procedure was performed, revealing a 3.3 cm, tank-pink, papillary lesion in the pancreatic head, that is partially cystic with mucinous contents, and displaying exophytic extension into the main pancreatic duct. Microscopically, the lesion consists of a high-grade IPMN involving the main pancreatic duct with side branch extension, and associated with invasive adenocarcinoma, the majority of which is of the large duct type, showing irregularly distributed large ducts with jagged edges and surrounding desmoplasia, with intra-luminal mucinous material and neutrophils. The lining cells show focal pseudo-stratification and bland cytology. Foci of conventional type invasive adenocarcinoma, clusters of invasive tumor cells, and peri-neural invasion are also identified. Post- procedure, the patient underwent chemotherapy with marked symptomatic improvement. Results (if a Case Study enter NA) NA Conclusion Large duct type invasive adenocarcinoma of the pancreas can closely mimic non-invasive pancreatic neoplasms, posing diagnostic challenges that require identification of subtle features to achieve the correct diagnosis and guide treatment.

Abstracts and Case Studies for the College of American Pathologists 2021 (CAP21) Annual Meeting

Abstracts and Case Studies for the College of American Pathologists 2021 (CAP21) Annual Meeting

Use of ring-enhancement and focal necrosis to differentiate pancreatic adenosquamous carcinoma from pancreatic ductal adenocarcinoma on CT and MRI

PurposeTo assess the ability of the ring-enhancing sign and focal necrosis to diagnose adenosquamous carcinoma (ASqC), a variant of pancreatic ductal adenocarcinoma (PDAC), on MRI and CT. MethodsThe following features of ASqC and conventional PDAC were evaluated on CT and MRI: tumor size, location, margins, borders (non-exophytic, exophytic), and T1 signal intensity. Two readers, blinded to histopathology results, rated their confidence in detecting ring-enhancement and focal necrosis (FN) on a 5-point Likert scale on both MRI and CT. Inter-reader agreement was assessed with Cohen's kappa (k). ResultsA total of 24 patients were included: eight patients with treatment naïve and histologically proven ASqC (six women, mean age: 63, range: 40–75) and 16 patients with PDAC (eight women, mean age: 67, range: 47–83). Statistically significant differences between ASqC and PDAC were seen in tumor size, location, presence of FN, and ring enhancement (p = 0.01–0.037). The readers were more confident in depicting the key differentiating feature ring-enhancement in ASqC on MRI compared to CT (confidence 1.71 ± 0.49 vs. 0.88 ± 0.35, p = 0.017) with moderate inter-reader agreement (k = 0.46 and 0.5, respectively). FN showed substantial inter-reader agreement on MR and moderate agreement on CT (k = 0.67 and 0.5, respectively). ConclusionsCompared to CT, MRI depicts ring-enhancement in ASqC with greater reader confidence and FN in ASqC with higher inter-reader agreement. The concurrent presence of these two imaging features should raise high suspicion for ASqC.

Pancreatic undifferentiated carcinoma with osteoclast-like giant cells curatively resected after pembrolizumab therapy for lung metastases: a case report

BackgroundTherapy targeting programmed death-1 or programmed death-1 ligand-1 (PD-1/PD-L1) has been developed for various solid malignant tumors, such as melanoma and non-small-cell lung cancer (NSCLC), but this approach has little effect in the treatment of pancreatic cancer. Pancreatic undifferentiated carcinoma with osteoclast-like giant cells (UCOGC) is a rare pancreatic malignancy having unique morphology and is considered a variant of pancreatic ductal adenocarcinoma (PDAC). Although UCOGC has been reported to have better prognosis than conventional PDAC, the optimal treatment for UCOGC with distant metastases has not been determined.Case presentationA 66-year-old man was initially diagnosed with NSCLC with multiple intrapulmonary metastases and abdominal lymph node metastasis in the tail of the pancreas, and bronchial biopsy and diagnostic imaging were performed. Pathologic examination of the lung showed poorly differentiated adenocarcinoma cells expressing epithelial marker and PD-L1. Therefore, pembrolizumab monotherapy for NSCLC was given. The pulmonary lesions shrank markedly and were in complete remission after 8 months of anti-PD-1 therapy, though no therapeutic effect was observed in the pancreatic site. Distal pancreatectomy was then performed, and histopathological examination showed that the tumor was UCOGC originating from the pancreas. The histologic findings of the resected specimen mimicked those of the lung biopsy specimen, leading to the final assessment that the lung tumors were metastatic foci that migrated from the UCOGC, and only the metastatic lesions benefited from pembrolizumab therapy.ConclusionImmune checkpoint inhibitors have limited therapeutic effects on primary lesions of pancreatic cancer, but they may exert antitumor effects on pulmonary metastases of UCOGC.

Efficacy of chemotherapy for patients with unresectable or recurrent pancreatic adenosquamous carcinoma: A multicenter retrospective analysis.

647 Background: Pancreatic adenosquamous carcinoma (PASC) is a rare variant of pancreatic ductal adenocarcinoma (PDAC). Although unresectable or recurrent PASC is usually treated by systemic chemotherapy, there are few reports which show the efficacy of chemotherapy. The aim of this study was to evaluate the efficacy of chemotherapy for patients (pts) with unresectable or recurrent PASC. Methods: We collected data retrospectively from 24 Japanese institutions. The selection criteria were as follows: 1) histologically or cytologically proven PASC (non-surgical specimens were eligible if squamous cell carcinoma (SCC) was detected), 2) unresectable or recurrent disease treated with 1st line chemotherapy between April 2001 and December 2017. Results: This study included 138 pts with median age of 66 years (range: 36-85). About 60% of pts were diagnosed with biopsy and only SCC was detected in 13.0% of pts. Median overall survival (mOS) was 6.7 months (M), median progression free survival (mPFS) was 2.8 M, and the 1-year survival rate (1YSR) was 26.7%. For the 102 metastatic or distal recurrent pts with PS of 0-1, patient characteristics were as follows: ≥76 years old, 9 (8.8%); PS of 0, 39 (38.2%); number of metastatic sites ≥2, 25 (24.5%). The treatment efficacies (The objective response rates(%)/mPFS(M)/mOS(M)/1YSR(%)) of the 5 major regimens were Gemcitabine(GEM) (n=45, 4.4%/2.2M/4.8M/28.1%), GEM+nab-PTX (n=24, 29.2%/2.9M/7.6M/23.1%), GEM+S-1 (n=9, 11.1%/5.1M/9.9M/25.4%), FOLFIRINOX (n=7, 14.3%/2.5M/7.5M/14.3%), and S-1 (n=7; 28.6%/2.6M/5.0M/28.6%), respectively. One patient with liver metastasis underwent conversion surgery after GEM+nab-PTX and achieved long survival. CRP ≥3.0mg/dl, CA19-9 ≥1000 U/ml, residual primary site, and monotherapy had a significant correlation with poor survival in multivariate analysis. Conclusions: Although combination chemotherapy regimens such as FOLFIRINOX and GEM+nab-PTX are now available, the prognosis of metastatic PASC remains poor. Development of more effective treatment options is required.

Dissecting the presence of malignant squamous cells in pancreatic cytopathology: A case series.

The presence of malignant squamous cells in pancreatic cytopathology is a rare phenomenon that results either from a primary or a metastatic process. Pancreatic adenosquamous carcinoma (PASC) represents the most common variant of pancreatic ductal adenocarcinoma and is associated with a dismal prognosis. Within the period of 2013-2018, the archives of "Hygeia and Mitera Hospital" were searched for pancreatic cytopathology-related diagnoses that included the interpretation of "malignant squamous cells present." All fine needle aspirations (FNAs) of pancreatic lesions, including liver metastases in patients with known pancreatic primaries, were retrieved along with their relevant clinical information. Five pancreatic and two liver FNAs acquired from a total of six patients were reexamined. None of these patients had any documented history of primary squamous malignancy elsewhere. All pancreatic and one of the two liver FNAs showed malignant squamous cells, identified based on either morphology or immunochemistry. The other liver FNA represented a metastatic deposit which comprised of only a glandular component, whereas the associated pancreatic FNA exhibited both squamous and glandular counterparts. Most cases characteristically showed necrosis and keratinization. Of interest, two cases revealed the presence of tumor-associated giant cells. In conclusion, the presence of malignant squamous cells in pancreatic FNAs could mean the presence of PASC, especially when there is no documented history of a primary malignancy and a complete clinical and imaging workup has been performed. Immunochemistry on cell block material could help to confirm squamous differentiation in the absence of overt keratinization.

PD-1, PD-L1, and CD163 in pancreatic undifferentiated carcinoma with osteoclast-like giant cells: expression patterns and clinical implications

Undifferentiated carcinoma with osteoclast-like giant cells (UCOGC), a variant of pancreatic ductal adenocarcinoma (PDAC), has a striking genetic similarity to PDAC but a significantly improved overall survival. We hypothesize that this difference could be due to the immune response to the tumor, and as such, we investigated the expression of PD-1, PD-L1, and CD163 in a series of UCOGC. To this aim, 27 pancreatic UCOGCs (11 pure and 16 PDAC-associated), 5 extrapancreatic tumors with osteoclast-like giant cells and 10 pancreatic anaplastic carcinomas were immunostained using antibodies against PD-1, PD-L1, and CD163. In pancreatic UCOGCs, PD-L1 was expressed in neoplastic cells of 17 (63%) of 27 cases, more often in cases with an associated PDAC (P = .04). Expression of PD-L1 was associated with poor prognosis, confirmed by multivariate analysis: patients with PD-L1-positive UCOGCs had a risk of all-cause mortality that was 3 times higher than did patients with PD-L1-negative UCOGCs (hazard ratio, 3.397; 95% confidence interval, 1.023-18.375; P = .034). PD-L1 expression on tumor cells was also associated with aberrant P53 expression (P = .035). PD-1 was expressed on rare lymphocytes in 12 UCOGCs (44.4%), mainly located at the tumor periphery. CD163 was expressed on histiocytes, with a diffuse and strong staining pattern in all UCOGCs. Extrapancreatic tumors with osteoclast-like giant cells showed very similar staining patterns for the same proteins. Anaplastic carcinomas have some similarities to UCOGCs, but PD-L1 has no prognostic roles. Our results may have important implications for immunotherapeutic strategies in UCOGCs; these tumors may also represent a model for future therapeutic approaches against PDAC.

Pancreatic undifferentiated carcinoma with osteoclast-like giant cells is genetically similar to, but clinically distinct from, conventional ductal adenocarcinoma.

Undifferentiated carcinoma of the pancreas with osteoclast-like giant cells (UCOGC) is currently considered a morphologically and clinically distinct variant of pancreatic ductal adenocarcinoma (PDAC). In this study, we report clinical and pathological features of a series of 22 UCOGCs, including the whole exome sequencing of eight UCOGCs. We observed that 60% of the UCOGCs contained a well-defined epithelial component and that patients with pure UCOGC had a significantly better prognosis than did those with an UCOGC with an associated epithelial neoplasm. The genetic alterations in UCOGC are strikingly similar to those known to drive conventional PDAC, including activating mutations in the oncogene KRAS and inactivating mutations in the tumor suppressor genes CDKN2A, TP53, and SMAD4. These results further support the classification of UCOGC as a PDAC variant and suggest that somatic mutations are not the determinants of the unique phenotype of UCOGC. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Fine-Needle Aspiration Biopsy Diagnosis of Oncocytic Carcinoma of the Pancreas

Oncocytic carcinoma of the pancreas is a very rare variant of pancreatic ductal adenocarcinoma. Fine-needle aspiration biopsy reports of this tumor are exceptionally rare. We report the case of a 65-year-old female patient who presented with a mass in the head of the pancreas. The mass was sampled by fine-needle aspiration biopsy on 2 separate occasions, and both samples were diagnosed as oncocytic carcinoma of the pancreas. The patient underwent a Whipple resection, and histopathologic examination of the resection specimen showed an invasive oncocytic carcinoma arising from intraductal oncocytic papillary neoplasm with high-grade dysplasia. Here we discuss the cytologic and histological features, differential diagnoses, utility of ancillary studies, and the recently updated knowledge about this rare entity.

Clinical Characteristics of Adenosquamous Carcinoma of the Pancreas

Adenosquamous carcinoma of the pancreas (ASC) is a variant of pancreatic ductal adenocarcinoma (PDAC), but the prognosis remains unclear. The purpose of this study was to clarify the prognosis of ASC using a matched case-control design. We evaluated clinical characteristics of ASC treated between 2001 and 2011 in our institution. As controls, PDAC cases matched with ASC cases for sex, age, pretreatment Eastern Cooperative Oncology Group performance status, location, initial therapy and American Joint Committee on Cancer TNM staging for pancreatic cancer were also evaluated. Of the 914 cases of pancreatic neoplasm, 28 cases (3.06%) of ASC were identified, and 56 cases of PDAC were matched as controls. Median overall survival (OS) was significantly worse for ASC (8.38 months) than for PDAC (15.75 months; hazard ratio [HR], 1.94; 95% confidence interval, 1.07-3.51; P = 0.026). Of the 22 unresected cases, median OS was again significantly worse for ASC (4.67 months) than for PDAC (12.36 months; HR, 2.39; 95% confidence interval, 1.27-4.51; P = 0.007). These results demonstrate that ASC is more aggressive than PDAC.

FOLFIRINOX as First-Line Treatment for Unresectable Acinar Cell Carcinoma of the Pancreas: A Case Report

Pancreatic acinar cell carcinoma (ACC) is a rare, aggressive variant of pancreatic ductal adenocarcinoma. Surgery is the only curative treatment option and protocols for palliative chemotherapies in this context are not standardized yet. We reported a 63-year-old white male patient who had painless jaundice, weight loss, elevated bilirubin, and a mass of the pancreatic head as well as liver metastasis. Core biopsy revealed the diagnosis of ACC. Therapy with FOLFIRINOX resulted in a significant decrease of the primary tumor and regressiveness of a liver metastasis after chemotherapy. Our report suggests that pancreatic ACC treated by FOLFIRINOX is well tolerated and might be superior to other single chemotherapies in this rare tumor disease.

Clinical Characteristics and Overall Survival in Patients with Anaplastic Pancreatic Cancer

Anaplastic pancreatic cancer (APC) is a rare undifferentiated variant of pancreatic ductal adenocarcinoma with poor overall survival (OS). The aim of this study was to evaluate the clinical outcomes of APC compared with differentiated pancreatic ductal adenocarcinoma. We conducted a retrospective review of all patients treated at the Mayo Clinic with pathologically confirmed APC from 1987 to 2011. After matching with control subjects with pancreatic ductal adenocarcinoma, OS was evaluated using Kaplan-Meier estimates and log-rank test. Sixteen patients were identified with APC (56.3% male, median age 57 years). Ten patients underwent exploration of whom eight underwent pancreatectomy. Perioperative morbidity was 60 per cent with no mortality. The median OS was 12.8 months. However, patients with APC who underwent resection had longer OS compared with those who were not resected, 34.1 versus 3.3 months (P = 0.001). After matching age, sex, tumor stage, and year of operation, the median OS was similar between patients with APC and those with ductal adenocarcinoma treated with pancreatic resection, 44.1 versus 39.9 months, (P = 0.763). Overall survival for APC is poor; however, when resected, survival is similar to differentiated pancreatic ductal adenocarcinoma.