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Archives of Pathology & Laboratory... Feb 2024The examination of small pancreatic biopsies is a difficult task for pathologists. This is due to the scant and fragmented material often obtained from diagnostic...
CONTEXT.—
The examination of small pancreatic biopsies is a difficult task for pathologists. This is due to the scant and fragmented material often obtained from diagnostic procedures as well as the significant overlap between different neoplastic and nonneoplastic entities. In the upcoming neoadjuvant era, biopsies could become even more important, representing the only possibility to look at the real histomorphology of tumors before chemotherapy-induced modifications.
OBJECTIVES.—
To summarize and discuss the state-of-the-art diagnostic workflow for small pancreatic biopsies, including the most important morphologic and immunohistochemical features and molecular alterations. The main diagnostic pearls and pitfalls of this challenging scenario are also discussed. The most important topics of this review are represented by: (1) pancreatic ductal adenocarcinoma, along with its main differential diagnoses, including autoimmune pancreatitis; (2) solid hypercellular neoplasms, including neuroendocrine neoplasms, acinar cell carcinoma, pancreatoblastoma, and solid pseudopapillary neoplasms; and (3) cystic lesions. Real-world considerations will be also presented and discussed.
DATA SOURCES.—
Sources included a literature review of published studies and the author's own work.
CONCLUSIONS.—
The correct diagnosis of pancreatic lesions is a crucial step in the therapeutic journey of patients. It should be based on robust, standardized, and reliable hallmarks. As presented and discussed here, the integration of morphology with immunohistochemistry, and in selected cases, with molecular analysis, represents a decisive step in this complex scenario.
PubMed: 38387616
DOI: 10.5858/arpa.2023-0426-RA -
Frontiers in Pediatrics 2022Pancreatic tumors in children are infrequently encountered in clinical practice. Their non-specific clinical presentation and overlapping imaging characteristics often... (Review)
Review
Pancreatic tumors in children are infrequently encountered in clinical practice. Their non-specific clinical presentation and overlapping imaging characteristics often make an accurate preoperative diagnosis difficult. Tumors are categorized as epithelial or non-epithelial, with epithelial tumors further classified as tumors of the exocrine or endocrine pancreas. Although both are tumors of the exocrine pancreas, solid pseudopapillary neoplasm is the most prevalent solid pancreatic tumor in children, while pancreatoblastoma is the most common malignant tumor. Insulinoma is the most common pediatric pancreatic tumor of the endocrine pancreas. Malignant tumors require a complete, often radical, surgical resection. However, pancreatic parenchyma-sparing surgical procedures are utilized for benign tumors and low-grade malignancy to preserve gland function. This review will discuss the epidemiology, pathophysiology, clinical and diagnostic characteristics, and management options associated with both common and rare solid pancreatic masses in children. We will also discuss current challenges encountered in their evaluation and treatment.
PubMed: 36507125
DOI: 10.3389/fped.2022.966943 -
Cancer Cytopathology Nov 2019Pancreatoblastoma (PBL) is a rare malignant pancreatic tumor seen predominantly in childhood, and its cytologic diagnosis remains challenging.
BACKGROUND
Pancreatoblastoma (PBL) is a rare malignant pancreatic tumor seen predominantly in childhood, and its cytologic diagnosis remains challenging.
METHODS
Twelve fine-needle-aspirations from 11 adults were analyzed.
RESULTS
In total, 6 men and 5 women (median age, 45 years; age range, 32-60 years) had tumors measuring a median 5.6 cm (range, 2.5-12 cm) located in the pancreatic head (n = 7) or tail (n = 4), including 3 with familial adenomatous polyposis (FAP)/FAP-related syndromes and 4 with metastasis at diagnosis. The median follow-up was 39.8 months (range, 0.8-348 months), and 5 patients died of disease. The original cytology diagnoses were: PBL (n = 2), neuroendocrine neoplasm (n = 2), poorly differentiated neuroendocrine carcinoma (n = 2), well differentiated neuroendocrine tumor (n = 1), poorly differentiated carcinoma (n = 2), "positive for malignancy" (n = 1), acinar cell carcinoma (n = 1), and epithelioid neoplasm with endocrine and acinar differentiation versus PBL (n = 1). Universal cytopathologic findings included hypercellularity; 3-dimensional clusters; and single, monotonous, blast-like cells that were from 1.5 to 2.0 times the size of red blood cells with high nuclear-to-cytoplasmic ratio, fine chromatin, small, distinct nucleoli, and a resemblance to well differentiated neuroendocrine tumor and poorly differentiated neuroendocrine carcinoma. Branching pseudopapillae (n = 7) and grooved nuclei (n = 3) raised the differential diagnosis of solid-pseudopapillary neoplasm, but with more atypia. Uncommon features included pleomorphism (n = 4) and numerous mitoses (n = 1). Squamoid morules were seen on smears (n = 5) or cell blocks (n = 6) in 70% of patients and were characterized by epithelioid cells with elongated, streaming nuclei, fine chromatin, absent nucleoli, and positive nuclear β-catenin (n = 6 of 8). The median Ki-67 index was 21% (range, 2%-70%), and neuroendocrine marker expression was common (100%), but acinar markers were variable (63%).
CONCLUSIONS
A combination of cytologic findings in PBL, including a predominant population of primitive blast-like cells, subtle squamoid morules, frequent neuroendocrine and variable acinar phenotype, should facilitate accurate cytologic diagnosis and distinction from common mimics.
Topics: Adenomatous Polyps; Adult; Biopsy, Fine-Needle; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Male; Middle Aged; Pancreas; Pancreatic Neoplasms; Tumor Burden
PubMed: 31581358
DOI: 10.1002/cncy.22187 -
Asian Journal of Surgery Nov 2023
Topics: Humans; Child; Pancreatic Neoplasms
PubMed: 37290981
DOI: 10.1016/j.asjsur.2023.05.104 -
Genes Dec 2023Adult pancreatoblastoma (PBL) is a rare pancreatic malignancy, with recent evidence suggesting a possible link to familial adenomatous polyposis (FAP). This study aims... (Review)
Review
BACKGROUND
Adult pancreatoblastoma (PBL) is a rare pancreatic malignancy, with recent evidence suggesting a possible link to familial adenomatous polyposis (FAP). This study aims to review the latest evidence and explore a possible association between adult PBL and FAP.
METHODS
Two independent literature reviews were conducted: (1) on PBL and FAP, and (2) on PBL in the adult population not diagnosed with FAP.
RESULTS
Out of 26 articles on PBL and FAP screened, 5 were selected for systematic review, including 1 additional case. We identified eight FAP-related PBL cases, with a median age of 40 (IQR: 34-50). Of these, seven (87%) occurred in adults. We found 65 cases of adult PBL not FAP-related; thus, 7 out of 65 cases (10.7%) of adult PBL reported in the literature are associated with a clinical diagnosis of FAP or were carriers of germline pathogenic variants (GPVs).
CONCLUSION
Data suggest a non-random association between adult PBL and FAP. Further research is essential to optimise surveillance protocols and develop more effective treatment strategies.
Topics: Adult; Humans; Adenomatous Polyposis Coli; Germ-Line Mutation; Pancreatic Neoplasms
PubMed: 38254934
DOI: 10.3390/genes15010044 -
BMJ Case Reports Apr 2020
Topics: Aged; Carcinoma, Acinar Cell; Endoscopic Ultrasound-Guided Fine Needle Aspiration; Humans; Male; Mesenteric Veins; Neoadjuvant Therapy; Pancreatic Neoplasms; Thrombosis; Tomography, X-Ray Computed; Treatment Outcome
PubMed: 32265211
DOI: 10.1136/bcr-2019-233884 -
Frontiers in Oncology 2021Pancreatoblastoma is a rare malignant epithelial neoplasm of the pancreas that mainly occurs in children and involves abnormalities in the WNT/β-catenin pathway, such...
BACKGROUND
Pancreatoblastoma is a rare malignant epithelial neoplasm of the pancreas that mainly occurs in children and involves abnormalities in the WNT/β-catenin pathway, such as mutation. However, the molecular abnormalities in adult pancreatoblastoma are not well known.
CASE PRESENTATION
An elderly man, who underwent elective distal pancreatectomy and splenectomy, was referred to our hospital with a mass in the tail of the pancreas. Histologically, the lesion revealed proliferation of clear, basophilic, and cartilaginous tumor cells with lymphatic metastasis. Each of the morphologically distinct tumor components showed different immunohistochemical patterns, indicating heterogeneous differentiation, including epithelial (both acinar and ductal), mesenchymal, and neuroendocrine differentiation. All tumor components showed nuclear expression of β-catenin and cyclin D1. Per next-generation sequencing (NGS), the clear and basophilic tumor cells shared mutations in , , and . Among the mutations, , c.1816_1817insA showed the highest frequency in both cell types, indicating that mutation was a driver mutation of the tumor. A diagnosis of PB was rendered.
SUMMARY
In conclusion, the clear and basophilic cells of the tumor were supposedly derived from the same clone and subsequently acquired additional mutations. This is the first report of clonal evolution in pancreatoblastoma.
PubMed: 34513702
DOI: 10.3389/fonc.2021.725290 -
Tumori Aug 2019Exocrine pancreatic cancers include common type pancreatic ductal adenocarcinoma and cystic neoplasms, which account for 85% and 10% of cases, respectively. The...
INTRODUCTION
Exocrine pancreatic cancers include common type pancreatic ductal adenocarcinoma and cystic neoplasms, which account for 85% and 10% of cases, respectively. The remaining 5% are rare histotypes, comprising adenosquamous carcinoma, acinar cell carcinoma, signet ring cell carcinoma, medullary carcinoma, pancreatoblastoma, hepatoid carcinoma, undifferentiated carcinoma and its variant with osteoclast-like giant cells, solid pseudopapillary carcinoma, and carcinosarcoma. Due to their low incidence, little knowledge is available on their clinical and molecular features as well as on treatment choices. The national initiative presented here aims at the molecular characterization of series of rare histotypes for which therapeutic and follow-up data are available.
METHODS
A nationwide Italian Rare Pancreatic Cancer (IRaPaCa) task force whose first initiative is a multicentric retrospective study involving 21 Italian cancer centers to retrieve histologic material and clinical and treatment data of at least 100 patients with rare exocrine pancreatic cancers has been created. After histologic revision by a panel of expert pathologists, DNA and RNA from paraffin tissues will be investigated by next-generation sequencing using molecular pathway-oriented and immune-oriented mutational and expression profiling panels constructed availing of the information from the International Cancer Genome Consortium. Bioinformatic analysis of data will drive validation studies by immunohistochemistry and in situ hybridization, as well as nanostring assays.
CONCLUSIONS
We expect to gather novel data on rare pancreatic cancer types that will be useful to inform the design of therapeutic choices.
Topics: Carcinoma, Acinar Cell; Carcinoma, Adenosquamous; Carcinoma, Pancreatic Ductal; Female; Humans; Immunohistochemistry; Italy; Male; Pancreatic Neoplasms; Retrospective Studies
PubMed: 30967031
DOI: 10.1177/0300891619839461 -
DNA Methylation Profiling Enables Accurate Classification of Nonductal Primary Pancreatic Neoplasms.Clinical Gastroenterology and... Jun 2024Cytologic and histopathologic diagnosis of non-ductal pancreatic neoplasms can be challenging in daily clinical practice, whereas it is crucial for therapy and...
BACKGROUND & AIMS
Cytologic and histopathologic diagnosis of non-ductal pancreatic neoplasms can be challenging in daily clinical practice, whereas it is crucial for therapy and prognosis. The cancer methylome is successfully used as a diagnostic tool in other cancer entities. Here, we investigate if methylation profiling can improve the diagnostic work-up of pancreatic neoplasms.
METHODS
DNA methylation data were obtained for 301 primary tumors spanning 6 primary pancreatic neoplasms and 20 normal pancreas controls. Neural Network, Random Forest, and extreme gradient boosting machine learning models were trained to distinguish between tumor types. Methylation data of 29 nonpancreatic neoplasms (n = 3708) were used to develop an algorithm capable of detecting neoplasms of non-pancreatic origin.
RESULTS
After benchmarking 3 state-of-the-art machine learning models, the random forest model emerged as the best classifier with 96.9% accuracy. All classifications received a probability score reflecting the confidence of the prediction. Increasing the score threshold improved the random forest classifier performance up to 100% with 87% of samples with scores surpassing the cutoff. Using a logistic regression model, detection of nonpancreatic neoplasms achieved an area under the curve of >0.99. Analysis of biopsy specimens showed concordant classification with their paired resection sample.
CONCLUSIONS
Pancreatic neoplasms can be classified with high accuracy based on DNA methylation signatures. Additionally, non-pancreatic neoplasms are identified with near perfect precision. In summary, methylation profiling can serve as a valuable adjunct in the diagnosis of pancreatic neoplasms with minimal risk for misdiagnosis, even in the pre-operative setting.
Topics: Humans; DNA Methylation; Pancreatic Neoplasms; Male; Female; Aged; Middle Aged
PubMed: 38382726
DOI: 10.1016/j.cgh.2024.02.007