Adenosquamous Carcinoma Of The Pancreas Research Articles

Efficacy of platinum chemotherapy agents in adenosquamous carcinoma of the pancreas.

e16317 Background: Adenosquamous carcinoma of the pancreas (ASCP) is an aggressive, infrequent subtype of pancreatic cancer that combines a glandular and squamous component and is associated with poor survival. Data regarding adjuvant therapy remain controversial. Methods: Patients with advanced PASC from 2005 to 2021 were consecutively included in this retrospective study. Overall survival (OS) and progression-free survival (PFS) were evaluated by Kaplan-Meier method. Results: Eighteen PASC patients treated surgically were included (median age, 69.3 years; males, 58.2%). All patients received adjuvant chemotherapy. Ten patients (55%) received newer platinum based regimen combination (FOLFIRINOX) and eight patients (45%) received gemcitabine-based regimens. Platinum based regimen as compared to gemcitabine regimen showed an improvement of overall response rate (42.5% and 12.3 %, p=0.001), PFS (median,10.4 versus 3.1 months, p=0.03) and OS (median, 15.8 vs 6.9 months, p=0.21).Multivariate analysis revealed that, among all patients (n=18), the following factors were independently predictive of poor survival: margin-positive resection (HR =3,15; 95% CI, 1.5-5.9; P<0.001), lymph node involvement (HR =2.9; 95% CI, 1.7 -7.5; P=0.003), and lack of inclusion of a platinum agent in the adjuvant regimen (HR =2.6; 95% CI, 1.5 -4.9; P=0.035). Conclusions: Given the rarity of ASC, optimal management remains poorly defined, particularly in the postoperative period. Therapies based on platinum chemotherapeutics may be preferable to all other chemotherapy regimens.

Abstract PR13: Single-cell mapping reveals a common origin for diverse subtypes of pancreatic cancer

Abstract The detailed understanding of the molecular basis of tumor initiation and progression is essential for the effective management and treatment of any cancer, including pancreatic cancer. To determine if the stem and progenitor cells can serve as cells of origin for pancreatic cancer, we have created a new mouse strain in which tamoxifen inducible Cre (CreERT2) is knocked into the endogenous locus encoding the stem cell regulator Musashi2 (Msi2). When crossed to a Cre-regulatable Myc transgenic (CAG-LSL-MycT58A) strain, Msi2-CreERT2 mice develop multiple pancreatic cancer subtypes: pancreatic ductal adenocarcinoma (PDAC), adenosquamous carcinoma of the pancreas (ASCP), and acinar cell carcinoma (ACC) following Myc activation in Msi2+ cells in the adult stage. A combination of single-cell genomics with computational analysis of developmental states and lineage trajectories of tumors in our model suggests that oncogenic Myc preferentially triggers the transformation of the most immature subset of Msi2+ cells, leading to the rise of a common pool of pre-cancer cells with multi-lineage potential. These pre-cancer cells subsequently take distinct fates within the same mice by activation of distinct transcriptional programs and large-scale genomic changes. Additionally, combining transcriptomic and functional genomic approaches, we have identified hyaluronan-mediated motility receptor (HMMR) as a potential novel dependency in mouse and human ASCP cells, providing a framework to develop interception strategies for this lethal disease. In summary, our study shows that multiple pancreatic cancer subtypes can arise from a common pool of Msi2+ cells and provides a powerful framework to understand and control the programs that shape divergent fates in pancreatic cancer. Citation Format: Nirakar Rajbhandari, Michael Hamilton, Tannishtha Reya. Single-cell mapping reveals a common origin for diverse subtypes of pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr PR13.

A Simple Overview of Pancreatic Cancer Treatment for Clinical Oncologists.

Pancreatic cancer (PDAC) is one of the most aggressive solid tumors and is showing increasing incidence. The aim of our review is to provide practical help for all clinical oncologists and to summarize the current management of PDAC using a simple "ABC method" (A-anatomical resectability, B-biological resectability and C-clinical conditions). For anatomically resectable PDAC without any high-risk factors (biological or conditional), the actual standard of care is represented by surgery followed by adjuvant chemotherapy. The remaining PDAC patients should all be treated with initial systemic therapy, though the intent for each is different: for borderline resectable patients, the intent is neoadjuvant; for locally advanced patients, the intent is conversion; and for metastatic PDAC patients, the intent remains just palliative. The actual standard of care in first-line therapy is represented by two regimens: FOLFIRINOX and gemcitabine/nab-paclitaxel. Recently, NALIRIFOX showed positive results over gemcitabine/nab-paclitaxel. There are limited data for maintenance therapy after first-line treatment, though 5-FU or FOLFIRI after initial FOLFIRINOX, and gemcitabine, after initial gemcitabine/nab-paclitaxel, might be considered. We also dedicate space to special rare conditions, such as PDAC with germline BRCA mutations, pancreatic acinar cell carcinoma and adenosquamous carcinoma of the pancreas, with few clinically relevant remarks.

Loss of chromosome 9p21 is associated with a poor prognosis in adenosquamous carcinoma of the pancreas.

Adenosquamous carcinoma of the pancreas (ASCP) is a rare histological subtype of pancreatic cancer with a poor prognosis and a high metastasis rate. However, little is known about its genomic landscape and prognostic biomarkers. A total of 48 ASCP specimens and 98 pancreatic ductal adenocarcinoma (PDAC) tumour specimens were sequenced to explore the genomic landscape and prognostic biomarkers. The homozygous deletion of the 9p21.3 region (including CDKN2A, CDKN2B, and MTAP) (9p21 loss) occurred in both ASCP and PDAC, and a higher frequency of 9p21 loss was observed in ASCP (12.5% vs 2.0%, P=0.022). Notably, 9p21 loss was significantly associated with poor disease-free survival (DFS) in ASCP patients (mDFS (Median DFS)=4.17 vs 7.33 months, HR (Hazard Ratio)=3.70, P=0.009). The most common gene alterations in patients with ASCP were KRAS (96%), TP53 (81%), CDKN2A (42%), SMAD4 (21%), CDKN2B (13%), and FAT3 (13%). The mutation rates of ACVR2A (6.25% vs 0%), FANCA (6.25% vs 0%), RBM10 (6.25% vs 0%), and SPTA1 (8.33% vs 1.02%) were significantly higher in ASCP than in PDAC. In conclusion, we have comprehensively described the genomic landscape of the largest cohort of ASCP patients to date and highlight that 9p21 loss may be a promising prognostic biomarker for ASCP, which provides a molecular basis for prognosis prediction and new therapeutic strategies for ASCP.

Two rare cancers of the exocrine pancreas: to treat or not to treat like ductal adenocarcinoma?

Pancreatic cancer is an aggressive malignancy with increasing incidence. Pancreatic ductal adenocarcinoma (PDAC) accounts for > 90% of pancreatic cancer diagnoses, while other exocrine tumors are much rarer. In this review, we have focused on two rare cancers of the exocrine pancreas: adenosquamous carcinoma of the pancreas (ASCP) and pancreatic acinar cell carcinoma (PACC). The latest findings regarding their cellular and molecular pathology, clinical characteristics, prognosis, and clinical management are discussed. New genetic and transcriptomic data suggest that ASCP is related to or overlaps with the basal transcriptomic subtype of PDAC. These tumors are highly aggressive and driven by activated KRAS and MYC expression. Clinical outcomes remain poor and effective treatments are limited. PACC has no morphologic or genetic resemblance to PDAC and more favorable outcomes. Early stage PACC patients have improved survival with surgical resection and patients with advanced disease benefit most from platinum- or fluoropyrimidine-containing chemotherapy. Frequency of actionable genetic mutations is high in this disease and case reports suggest good outcomes when matched therapy is given. Dedicated clinical studies examining ASCP and PACC are limited and difficult to accrue. Further research is needed to define optimal clinical management for these rare diseases.

Postoperative serum hyperamylasemia (POH) predicts additional morbidity after pancreatoduodenectomy: It is not all about pancreatic fistula

Adenosquamous carcinoma of the pancreas (ASC) is a rare malignant neoplasm of the pancreas, exhibiting both glandular and squamous differentiation. However, little is known about its imaging features. This study examined the imaging features of pancreatic ASC.We evaluated images of contrast-enhanced computed tomography (CT) and endoscopic ultrasonography (EUS). As controls, solid pancreatic neoplasms matched in a 2:1 ratio to ASC cases for age, sex and tumor location were also evaluated.Twenty-three ASC cases were examined, and 46 solid pancreatic neoplasms (43 pancreatic ductal adenocarcinomas, two pancreatic neuroendocrine tumors and one acinar cell carcinoma) were matched as controls. Univariate analysis demonstrated significant differences in the outline and vascularity of tumors on contrast-enhanced CT in the ASC and control groups (P < 0.001 and P < 0.001, respectively). A smooth outline, cystic changes, and the ring-enhancement pattern on contrast-enhanced CT were seen to have significant predictive powers by stepwise forward logistic regression analysis (P = 0.044, P = 0.010, and P = 0.001, respectively). Of the three, the ring-enhancement pattern was the most useful, and its predictive diagnostic sensitivity, specificity, positive predictive value and negative predictive value for diagnosis of ASC were 65.2%, 89.6%, 75.0% and 84.3%, respectively.These results demonstrate that presence of the ring-enhancement pattern on contrast-enhanced CT is the most useful predictive factor for ASC.

Clinical Outcome and Prognostic Factors of Pancreatic Adenosquamous Carcinoma Compared to Ductal Adenocarcinoma-Results from the German Cancer Registry Group.

Simple SummaryAbout 0.5% of pancreatic malignancies are adenosquamous carcinomas. The pathophysiology of these carcinomas is poorly understood and clinical data is sparse. We compared characteristics and prognostic factors of adenosquamous carcinoma and ductal adenocarcinoma, which represent the most common type of pancreatic cancer based on data from the German cancer registry group. Adenosquamous carcinoma showed poorer differentiation and higher frequency of blood vessel invasion indicative of a more aggressive tumor biology. Adenosquamous tumor differentiation was a strong negative prognostic factor. Survival of patients with adenosquamous carcinoma was shorter compared to patients with a ductal adenocarcinoma after surgical tumor resection. This study suggests that distinct multimodal treatment protocols should be considered for adenosquamous carcinomas of the pancreas.Background: Adenosquamous carcinoma of the pancreas (ASCP) is a rare malignancy and its pathophysiology is poorly understood. Sparse clinical data suggest that clinical outcome and overall survival is worse in comparison to common pancreatic ductal adenocarcinoma (PDAC). Methods: We evaluated clinical outcome and prognostic factors for overall survival of patients with ASCP in comparison to patients with PDAC recorded between 2000 and 2019 in 17 population-based clinical cancer registries at certified cancer centers within the Association of German Tumor Centers (ADT). Results: We identified 278 (0.5%) patients with ASCP in the entire cohort of 52,518 patients with pancreatic cancer. Significantly, more patients underwent surgical resection in the cohort of ASCP patients in comparison to patients with PDAC (p < 0.001). In the cohort of 142 surgically resected patients with ASCP, the majority of patients was treated by pancreatoduodenectomy (44.4%). However, compared to the cohort of PDAC patients, significantly more patients underwent distal pancreatectomy (p < 0.001), suggesting that a significantly higher proportion of ASCP tumors was located in the pancreatic body/tail. ASCPs were significantly more often poorly differentiated (G3) (p < 0.001) and blood vessel invasion (V1) was detected more frequently (p = 0.01) in comparison with PDAC. Median overall survival was 6.13 months (95% CI 5.20–7.06) for ASCP and 8.10 months (95% CI 7.93–8.22) for PDAC patients, respectively (p = 0.094). However, when comparing only those patients who underwent surgical resection, overall survival of ASCP patients was significantly shorter (11.80; 95% CI 8.20–15.40 months) compared to PDAC patients (16.17; 95% CI 15.78–16.55 months) (p = 0.007). ASCP was a highly significant prognostic factor for overall survival in univariable regression analysis (p = 0.007) as well as in multivariable Cox regression analysis (HR 1.303; 95% CI 1.013–1.677; p = 0.039). Conclusions: In conclusion, ASCP showed poorer differentiation and higher frequency of blood vessel invasion indicative of a more aggressive tumor biology. ASCP was a significant prognostic factor for overall survival in a multivariable analysis. Overall survival of resected ASCP patients was significantly shorter compared to resected PDAC patients. However, surgical resection still improved survival significantly.

Development and external validation of a dynamic nomogram to predict the survival for adenosquamous carcinoma of the pancreas

ObjectiveWe aimed to develop a nomogram to predict the survival and prognosis of adenosquamous carcinoma of the pancreas (ASCP).BackgroundAdenosquamous carcinoma of the pancreas (ASCP) is a relatively rare histological subtype of pancreatic exocrine neoplasms. It was reported a worse survival in ASCP than in pancreatic adenocarcinoma (PDAC). Prediction of ASCP prognosis is of great importance.MethodsHistologically confirmed ASCP patients from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) Program database were finally enrolled and divided into development and internal validation cohorts. Moreover, a multi-center cohort of 70 patients from China was registered as the external validation. A nomogram was developed based on independent predictors of ASCP determined in multivariable analysis.ResultsA total of 233 patients from SEER were finally included. Univariate and Multivariate analysis showed that tumor size, radiotherapy, chemotherapy, and lymph node ratio (LNR) were considered the independent prognostic indicators. We developed a nomogram according to these four parameters. The C index of the nomogram in the development cohort was 0.696. Through analysis of the area under the curve (AUC) of the different cohorts, we observed that the predictive efficacy of the nomogram for 1-, and 2-year overall survival (OS) were better than those of the American Joint Committee on Cancer (AJCC) TNM (8th) staging system both in the development and validation cohort. External validation confirmed that 1-year survival is 67.2% vs. 29.7%, similar to the internal cohort analysis.ConclusionThe nomogram showed good performance in predicting the survival of ASCP. It could help surgeons to make clinical decisions and develop further plans.

Survival Analysis and Prediction Model of ASCP Based on SEER Database.

BackgroundThis study aims to compare the incidence and clinical and survival characteristics of adenosquamous carcinoma of the pancreas (ASCP) and adenomatous carcinoma of the pancreas (ACP), analyze the survival factors of ASCP and construct a prognostic model.MethodPatients diagnosed with pancreatic cancer from 2000 to 2018 are selected from the SEER database. ASCP and ACP are compared in terms of epidemiology, clinical characteristics and prognosis. Cases are matched in a 1:2 ratio, and survival analysis is performed. The Cox proportional hazard model is used to determine covariates related to overall survival (OS), and an ASCP prognosis nomogram is constructed and verified by consistency index (C-index), calibration chart and decision curve analysis (DCA). The accuracy of the model is compared with that of AJCC.Stage and SEER.Stage to obtain the area under the receiver operating characteristic (ROC) curve.Resultsthe age-adjusted incidence of ACP increased significantly over time from 2000 to 2008 and from 2008 to 2018 (P < 0.05). APC was 2.01% (95% CI: 1.95–2.21) and 1.08% (95% CI: 0.93–1.25) respectively. The age-adjusted incidence of ASCP increased with time from 2000 to 2018 (P < 0.05) and APC was 3.64% (95% CI: 3.25–4.01).After propensity score matching (PSM), the OS and cancer-specific survival (CSS) of ACP are better than those of ASCP. The survival time of ASCP is significantly improved by the combined treatment of surgery + chemotherapy + radiotherapy, with a median OS of 31 months. Cox proportional hazard regression analysis shows that age, race, surgery, radiotherapy, chemotherapy and tumor size are independent factors affecting the prognosis. DCA and area under the curve (AUC) value shows that the model has good discrimination ability.ConclusionThe OS prognosis of ASCP is worse than that of ACP, and the nomogram has high accuracy for the prognosis prediction of ASCP.

Genomic landscape and clonal evolution between adenocarcinoma and squamous components in adenosquamous carcinoma of the pancreas.

e16265 Background: Adenosquamous carcinoma of the pancreas (ASCP) is a rare histological subtype of pancreatic cancer with high metastasis rate and poor prognosis, which is characterized by a variable proportion of adenocarcinoma and squamous carcinoma components with at least 30% of the tumor showing squamous differentiation. To get further insight into the tumorigenesis and progression, we profiled the genetic characterization and explored the evolutionary model of this subtype. Methods: A total of 10 patients with ASCP were enrolled. For each sample, glandular and squamous carcinoma tissues were separated by microdissection. Whole exome sequencing for 20 samples with matched peri-carcinomatous tissues were performed by next-generation sequencing. Results: Genetic profiling revealed that top 5 mutated genes of adenocarcinoma and squamous components were highly consistent including TP53 (100% vs 100%), KRAS (100% vs 90%), CDKN2A (40% vs 40%), KDM6A (20% vs 20%) and LRP1B (20% vs 20%). KEGG pathway analysis showed that PI3K-Akt, MAPK and FoxO signaling pathways were the most frequently mutated pathways in adenocarcinoma. In contrast, Apelin and Rap1 signaling pathways were highly mutated in squamous components, advocating that these pathways may play important roles in the transformation of squamous carcinomas. A higher proportion of indels were identified in adenocarcinoma than squamous components (12.1% vs 3%). The chromosome regions of 3p21.3, 9p21.3, 11p15.5, 16p13.11 and 21q22.3 were the most commonly deleted regions in the adenocarcinoma components, while losses of 1p36.21, 3p25.3, 3q13.13, 6p22.3 and 11p15.5 had been observed in the squamous components. Some of these regions had important effects on development and progression of cancer. For example, 9p21.3 had well-established impact on cell proliferation and apoptosis containing two crucial tumor suppressor genes, CDKN2A and CDKN2B. Additionally, the C &gt; T mutation was predominant among the 6 types of single nucleotide variations. Most common signatures were related to aging (Single base substitutions, SBS1), BRCA1/2 mutations and responders to platinum therapy (SBS3), and defective DNA mismatch repair (SBS6). Tumor evolution analysis showed that the glandular and squamous components shared a common origin. There were two evolutionary scenarios in the early stages of tumor evolution, with a third of nine patients ware parallel evolution and the remaining patients were linear evolution. KRAS (100%), TP53 (66.7%) and TTN (33.3%) were frequently identified as clonal mutations. Conclusions: This is the first study to elucidate the genomic alteration as well as the clonal evolution using whole-exome sequencing in ASCP patients. It provides evidence for more comprehensive understanding of pathophysiology of ASCP at genomic level, which could contribute to the amelioration for ASCP patients’ management.

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.

Adenosquamous Carcinoma of the Pancreas

Adenosquamous Carcinoma of the Pancreas

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.

Adenosquamous and squamous cell carcinoma of the pancreas: two histopathological variants of ductal adenocarcinoma

Abstract Introduction: Primary squamous cell carcinoma (SCC) and adenosquamous carcinoma of the pancreas are rare malignancies for which diagnostic and treatment strategy are challenging. In this paper we present a literature review of these tumors based on two case reports. Case presentation: In the first case, a 55-year-old male presented with an inoperable pancreatic head/body junction tumor. Endoscopic ultrasound-guided fine needle aspiration was practiced, and histopathological examination revealed a squamous cell carcinoma of the pancreas. After exclusion of any another tumor, the diagnosis of cT4N0M0-staged primary pancreatic SCC was made. The patient is under treatment with gemcitabine and oxaliplatin. The second case is represented by a 73-year-old patient in which imagistic examinations highlighted a cystic mass of the pancreatic body. Following coporeo-caudal splenic-pancreatectomy and histopathological-proved diagnosis of adenosquamous carcinoma, the patient started chemotherapy but died at 11 months after surgery. Both tumor components displayed positivity for markers which prove ductal (cytokeratin19, maspin) and squamous differentiation (p63, cytokeratin5/6) same as vimentin, as indicator of epithelial mesenchymal transition (EMT). Conclusions: SCC and adenosquamous carcinoma of the pancreas are aggressive malignancies which prognosis remains highly reserved. These tumors might be variants of ductal adenocarcinomas which are dedifferentiated through EMT phenomenon.

Importance of multimodal therapy in the management of non-metastatic adenosquamous carcinoma of the pancreas: Analysis of treatment sequence and strategy

Background: Adenosquamous carcinoma of the pancreas (ASCP) is an aggressive variant of pancreatic cancer with historically poor survival. Little is known about the optimal treatment regimen or sequence for patients with ASCP. We characterize survival outcomes stratified by treatment regimen and sequence for ASCP patients using an administrative dataset in the era of modern chemotherapeutics.

Adenosquamous Carcinoma of the Pancreas Comprise a Heterogeneous Group of Tumors With the Worst Outcome: A Clinicopathological Analysis of 25 Cases Identified in 562 Pancreatic Carcinomas Resected With Curative Intent.

Information of the clinicopathological characteristics and outcome data of patients with adenosquamous carcinoma of the pancreas (ASCAP) remains limited. This study's aim is to describe the clinical, pathological, and molecular characteristics of 25 resected ASCAPs. Of all 25 cases, patient characteristics, follow-up data, and pathological/immunohistological features were reviewed and analyzed. In this 3-institutional retrospective analysis of 562 pancreatic cancer patients, we identified 25 cases with histologically confirmed ASCAP (4.4%). Follow-up was available in 21 ASCAP and 50 pancreatic ductal adenocarcinoma control patients with a median overall survival of 8.2 and 21 months, respectively. Age, tumor size, localization in the tail, lymph node status, and resection margin seem to be the most significant factors of survival in our ASCAP cohort. In contrast to pancreatic ductal adenocarcinoma, positive expression of p63, keratins K5/14, and the epidermal growth factor receptor are a robust marker profile of these tumors. Adenosquamous carcinoma of the pancreas comprises a group of neoplasms in which stage and adverse morphological features contribute to its bad prognosis. Further work must be pursued to improve detection and treatment options to reduce mortality. Specifically, differences in biology might become a target for the development of possible therapies.

Cellular organization and histogenesis of adenosquamous carcinoma of the pancreas: evidence supporting the squamous metaplasia concept

Adenosquamous carcinoma of the pancreas (ASCAP) is characterized by conventional pancreatic ductal adenocarcinoma (PDAC) and squamous carcinoma components with at least 30% of the tumour showing squamous differentiation. To get further insight into the histogenesis of these lesions, we analysed the cellular organization of ASCAP compared to PDACs. Using Immunohistochemistry and triple immunofluorescence labelling studies for keratins, p63, p40, MUC1, MUC2, MUC5AC, Ki67, and EGFR we demonstrate that many ASCAPs contain a transitional zone between the K8/18-positive adenocarcinomatous component and the p63+ /p40+ /K5/K14+ squamous component initiated by the expression of p63 in K8/18+ adenocarcinomatous cells and the appearance of basally located p63+ K5/14+ cells. p63+ K5/14+ cells give rise to fully developed squamous differentiation. Notably, 25% of conventional PDACs without histologically recognizable squamous component contain foci of p63+ p40+ and K5/14+ cells similar to the transitional zone. Our data provide evidence that the squamous carcinoma components of ASCAPs originate from pre-existing PDAC via transdifferentiation of keratin K8/18-positive glandular cells to p63-, p40-, and keratin K5/14-positive squamous carcinoma cells supporting the squamous metaplasia hypothesis. Thus our findings provide new evidence about the cellular process behind squamous differentiation in ASCAPs.

Adenosquamous carcinoma of the pancreas

Adenosquamous carcinoma of the pancreas

Clinical presentation and outcome of adenosquamous carcinoma of the pancreas - a matched pair analysis to pancreatic ductal adenocarcinoma

Background: Adenosquamous carcinoma of the pancreas (ASCP) is a rare and aggressive subtype of pancreatic adenocarcinoma. The aim of the present study was to investigate the characteristics and outcomes of patients with ASCP in comparison to ductal adenocarcinoma of the pancreas (PDAC). Material & Methods: All patients with ASCP treated between 12/2001 and 12/2017 were identified from a prospective database. Clinicopathological and follow-up data were analyzed. A nested-case-control-study with matched-pair analysis was performed to compare overall survival of ASCP versus PDAC (1:2 matching using: pTNM, grading, R-status, localization, gender, age, s/p neoadjuvant therapy). Results: Of 3909 patients operated for pancreatic adenocarcinoma, 91 (2.3%) patients with ASCP were identified. Patients with ASCP had a lower BMI compared to patients with PDAC (23.9 vs. 24.8 kg/m2; p=0.003). Compared to PDAC, a higher proportion of ASCP tumors were located in the pancreatic tail (19% vs. 10%; p=0.04). ASCP tumors were larger (4.0 vs. 3.2 cm; p<0.001), more likely to have positive lymph nodes (88% vs. 78%; p=0.04) and more frequently showed poor differentiation (G3: 79% vs. 36%; p<0.001). There was no significant difference in overall survival between ASCP and PDAC in the matched-pair analysis (p=0.984). However, there was a trend towards shorter median survival in ASPC (10.8 vs. 15.1 months), as well as a trend towards a better 5-year survival rate in ASCP (21% vs. 10%). Conclusions: ASCP exhibits poorer differentiation and higher rates of lymph node metastases if compared to PDAC as criteria of aggressive tumor biology. Nevertheless patients with ASCP and PDAC tumors have comparable survival after surgical resection. In spite of the poor median survival, 5-year survival rates after surgical resection of about 20% can be expected. Further studies including analyses of the molecular features of ASCP are needed to better define the prognosis of this tumor.

中心嚢胞変性と厚い線維性被膜を示し，術後17年健存を得た膵腺扁平上皮癌の1例

中心嚢胞変性と厚い線維性被膜を示し，術後17年健存を得た膵腺扁平上皮癌の1例