Pancreas
Exocrine tumors
Ductal adenocarcinoma, NOS (not otherwise specified)

Author: Wei Chen, M.D., Ph.D. (see Authors page)
Editorial Board Member Review: Raul S. Gonzalez, M.D.

Revised: 23 October 2017, last major update October 2017

Copyright: (c) 2003-2017, PathologyOutlines.com, Inc.

PubMed Search: Ductal adenocarcinoma [title] pancreas
Cite this page: Chen, W. Ductal adenocarcinoma, NOS. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/pancreasductal.html. Accessed November 22nd, 2017.
Definition / general
Essential features
Terminology
  • Also called tubular adenocarcinoma, usual ductal adenocarcinoma (UDA)
ICD-10 coding
Epidemiology
Sites
  • Head of the pancreas: 60% - 70%; body: 5 - 15%; tail: 10 - 15%
  • Head tumors: 50% have distention of biliary tree and progressive jaundice; 85% have extension beyond pancreas at diagnosis
  • Body / tail tumors: typically larger at diagnosis since these tumors do not cause symptoms until late; 25% have peripheral venous thrombi; metastases common
  • Rarely arises from heterotopic pancreatic tissue in the gastrointestinal tract
Pathophysiology
Etiology
  • Risk factors: smoking, alcohol abuse (particularly in African Americans), obesity, high intake of dietary saturated fat, chronic pancreatitis, diabetes
  • Hereditary syndromes: Peutz-Jeghers syndrome, hereditary pancreatitis, familial atypical multiple mole melanoma (FAMMM), familial pancreatic cancer, Lynch syndrome, familial breast cancer and other Fanconi anemia genes, familial adenomatous polyposis / FAP (Bosman: WHO Classification of Tumours of the Digestive System, 4th Edition, 2010)
Clinical features
  • Back pain, weight loss, malaise, jaundice, diabetes mellitus
  • Trousseau sign: migratory thrombophlebitis in 10% due to tumor or tumor necrosis producing platelet aggregating factors and procoagulants; causes arterial and venous thrombi
  • Coexisting pancreatitis 10%
  • Metastases:
    • Local lymph nodes (microscopic metastases found in 75% with T1 / T2 disease)
    • Liver, lung, peritoneum, adrenal, bone, distal nodes
    • Supraclavicular node metastasis may be presenting symptom
    • Tumor may track along biopsy needle path
    • Metastases to ovary may simulate primary mucinous ovarian tumors (Am J Surg Pathol 1989;13:748)
Diagnosis
  • Preoperative / pretreatment by endoscopic ultrasound guided fine needle aspiration (EUS-FNA)
  • Surgical resection specimen
Laboratory
  • Serum tests: CA19-9, CEA
Radiology description
  • Hypodense mass on CT imaging in 92% of cases
  • “Double duct” sign (dilation of both the biliary and pancreatic ducts) in pancreatic head mass
Prognostic factors
Treatment
  • Most (85%) tumors are not amenable to curable surgery
  • For head / periampullary tumors: Whipple resection (subtotal pancreaticoduodenectomy), perioperative mortality ~ 2%
  • For body / tail tumors: distal pancreatectomy
  • Resect retroperitoneal nerves and nodes if stage I / II to reduce local recurrence
  • Palliative treatment includes bypass operations, chemotherapy (gemcitabine) and radiation therapy
Gross description
  • White gray, sclerotic, poorly defined mass
  • > 75% of ductal adenocarcinoma are solid tumors
  • 25% of head tumors extend to duodenal wall
  • If advanced, may be difficult to determine site of origin between pancreas, ampulla and common bile duct
  • 20% have multiple tumors
Gross images

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Various images

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Differential diagnosis

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Complete obstruction

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Large solid tumor in tail



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1.5 cm infiltrating
adenocarcinoma within
head of pancreas
Microscopic (histologic) description
  • Infiltrating well to poorly formed glandular / ductal structures surrounded by remarkably desmoplastic stroma
  • Mucin production is specific for ductal origin vs. acinar or neuroendocrine differentiation
  • Perineural invasion present in 90%, typically with better differentiated glands
  • Angiolymphatic invasion in 50%; vacular invasion may mimic PanIN (Am J Surg Pathol 2012;36:235)
  • Well differentiated: pink apical band composed of mucin granules, may appear benign but has irregular shape and distribution; desmoplasia, marked nuclear pleomorphism with nucleoli, loss of polarity, mitotic figures
  • Moderately to poorly differentiated: seen in most tumors; abortive tubular structures, deeply infiltrative growth pattern, frequent mitosis, irregular and abortive mucin production
  • TNM histologic grading system, recommended by College of American Pathologists, is based on the extent of glandular differentiation: G1=well differentiated, ( > 95% tumor composed of glands), G2=moderately differentiated (50 - 95% glands), G3=poorly differentiated ( < 49 glands), G4=no or minimal differentiation
  • Klöppel grading system: G1 (well) to G3 (poorly differentiated) based on four criteria: degree of glandular differentiation, mucin production (lower grade more mucin), mitosis ( < 5/10HPF, 6-10/10HPF, > 10/10HPF) and nuclear features (Histopathology 1985;9:841)
  • Background pancreas may show high grade PanIN, atrophic changes, chronic inflammatory infiltrate, fibrosis, ductal dilation beyond tumor mass
Microscopic (histologic) images
Scroll to see all images



Images hosted on Pathout server:

Images contributed by Wei Chen, M.D., Ph.D.
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UDA with stromal desmoplasia

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Naked tumor gland in fat

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Perineural invasion

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Tumor glands next to vessel

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Foamy gland pattern


AFIP images
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Large duct-like neoplastic structures

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Atypical duct-like structures (arrows)


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Well differentiated


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Well to moderately differentiated

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Moderately differentiated

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Poorly differentiated


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Marked variation in differentiation

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With perineural invasion

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With associated endocrine cells

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Comparison with chronic pancreatitis

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Keratin (left); Vimentin (right)



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Various images

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Various immunostains

Cytology description
  • EUS-FNA has sensitivity and specificity of > 90% and 100%, increased sensitivity with ThinPrep, brushings are 50% sensitive (repeat if inconsistent with clinical or radiologic findings (Arch Pathol Lab Med 2000;124:387)
  • Aspirates are cellular, without acinar cells, with atypical ductal cells in sheets ("drunken honeycomb"), clusters or singly; anisonucleosis (4:1 variation)
  • Signet rings cells and mitotic figures are helpful when present, but may be absent
  • Papanicolaou Society of Cytopathology's six tiered system for pancreatobiliary cytology: non diagnostic, negative for malignancy, atypical, neoplastic, suspicious and positive / malignant (Cytojournal 2014;11(Suppl 1):3)
  • Duodenal secretions are 80% sensitive in head tumors, 33% sensitive in tail tumors; ERCP juice is 50 - 85% sensitive
Cytology images

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Moderately differentiated ductal adenocarcinoma:
cells are in cohesive groups and have large,
pleomorphic nuclei and moderate cytoplasm (AFIP)
Positive stains
Negative stains
Electron microscopy description
  • Mucigen granules
Electron microscopy images

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Well differentiated
Molecular / cytogenetics description
  • Many core signaling pathways involved
  • ~10% of pancreatic cancers have a familial basis
  • Differential diagnosis
    • Ampullary adenocarcinoma: epicenter at ampulla, presence of preinvasive component at ampulla
    • Chronic pancreatitis: lobular architecture at low power with central ectatic branched ductules and clusters of round ductules surrounded by cuff of stroma (Arch Pathol Lab Med 2009;133:382)
    • Features of UDA to differentiate above (Arch Pathol Lab Med 2015;139:848):
      • UDA has anisonucleosis (4:1 variation), loss of cell polarity, perineurial invasion, individual cell infiltration, budding into lumen; has p53 mutations and loss of SMAD4 / DPC4
      • UDA has haphazard architecture and glands at abnormal locations in interlobular areas, next to vessels and "naked glands" in fat
    • Distal bile duct adenocarcinoma: epicenter at bile duct, circumferential / symmetrical involvement of the bile duct, presence of in situ component (BilIN or biliary intraductal papillary neoplasm)
    Board review question #1
      What are the currently recognized pancreatic precursor lesions for invasive ductal adenocarcinoma?

    1. Acinar cell carcinoma
    2. Intraductal papillary mucinous neoplasm (IPMN)
    3. Mucinous cystic neoplasm (MCN)
    4. Pancreatic intraepithelial neoplasia (PanIN)
    5. Solid pseudopapillary neoplasm
    Board review answer #1
    B, C and D