Exocrine carcinomas

Undifferentiated carcinoma

Deputy Editor-in-Chief: Raul S. Gonzalez, M.D.
Claudio Luchini, M.D., Ph.D.

Last author update: 24 February 2020
Last staff update: 22 April 2022

Copyright: 2012-2022,, Inc.

PubMed Search: Undifferentiated carcinoma[TI] pancreas

Claudio Luchini, M.D., Ph.D.
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Cite this page: Luchini C. Undifferentiated carcinoma. website. Accessed August 11th, 2022.
Definition / general
Essential features
  • Undifferentiated carcinoma with atypical neoplastic cells and without gland formation
  • Absence of osteoclast-like giant cells
  • Very poor prognosis
  • Undifferentiated carcinoma of the pancreas
  • Old terminology, not in use: spindle cell carcinoma, pleomorphic carcinoma
ICD coding
  • C25.9 - malignant neoplasm of pancreas, unspecified

  • 8020/3 - undifferentiated carcinoma, NOS
  • 8021/3 - undifferentiated anaplastic carcinoma
  • An important role may be played by the process of epithelial to mesenchymal transition (Pancreas 2019;48:36)
  • Chronic inflammation with histiocytes is not a crucial mechanism as in undifferentiated carcinoma with osteoclast-like giant cells (Hum Pathol 2018;81:157)
Clinical features
Radiology description
Prognostic factors
Case reports
  • 59 year old man with undifferentiated carcinoma of the pancreas, sarcomatoid type (World J Clin Cases 2019;7:236)
  • 63 year old man with undifferentiated carcinoma of the pancreas, rhabdoid type, with multiple metastases (autopsy report) (Pathol Int 2015;65:264)
  • 64 year old woman with undifferentiated carcinoma of the pancreas, anaplastic type, associated with cystic degeneration of the lesion (World J Gastroenterol 2016;22:8631)
  • 65 year old man with undifferentiated carcinoma of the pancreas, anaplastic type, involving the ampullary region (Am J Case Rep 2019;20:597)
  • 73 year old woman with undifferentiated carcinoma of the pancreas, carcinosarcoma type (Pancreas 2017;46:1225)
Gross description
Gross images

Contributed by Claudio Luchini, M.D., Ph.D.
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Ductal adenocarcinoma
with undifferentiated

AFIP images
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Ill demarcated tumor in head of pancreas

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Extensive hemorrhagic necrosis

Frozen section description
  • Hypercellular neoplasm with atypical cells
Microscopic (histologic) description
  • Unlike conventional ductal adenocarcinoma, this tumor is composed of poorly cohesive cells (WHO Classification of Tumours Editorial Board: Digestive System Tumours (Medicine), 5th Edition, 2019)
  • These tumors are usually hypercellular and with scant stroma: indeed, differently from conventional pancreatic ductal adenocarcinoma, where there is a large amount of desmoplastic stroma with few neoplastic cells / glands, undifferentiated carcinoma of the pancreas is a hypercellular tumor, with scant stroma and scant desmoplastic reaction
    • This is a major point in the differential diagnosis between these two entities
  • Perineural invasion and vascular invasion are very common
  • Different subtypes are characterized at the histological level by different morphologic hallmarks:
    • Anaplastic subtype is a tumor composed by highly atypical cells, with pleomorphic appearance
    • Sarcomatoid subtype is composed by atypical spindle cells, resembling a sarcoma
    • Carcinosarcoma is a subtype in which there is a mixture of roundish epithelioid cells and spindle sarcomatous cells
    • Rhabdoid subtype, which some authors considered a special variant of pancreatic ductal adenocarcinoma, is composed of large cells with a eosinophilic cytoplasm and with an eccentrically located nuclei
Microscopic (histologic) images

Contributed by Claudio Luchini, M.D., Ph.D.
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Anaplastic undifferentiated carcinoma

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Massive perineural invasion

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Massive vascular invasion

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Association with ductal adenocarcinoma

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Invasion of duodenum

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Rhabdoid aspects

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Details on biopsy

AFIP images
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Spindle cell sarcomatoid features

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Pleomorphic large cells

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Engulfment of red blood cells

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Glandular differentiation

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Tumor is keratin+

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Tumor is CEA+ in glandular portions

Cytology description
  • Hypercellular neoplasm: presence of highly atypical cells
Negative stains
Molecular / cytogenetics description
  • It overlaps with the genetic profile of conventional ductal adenocarcinoma
  • In the rhabdoid variant, KRAS alterations and SMARCB1 expression status define two subtypes, with possible translational implications (Mod Pathol 2015;28:248)
Sample pathology report
  • Pancreas, pancreatectomy:
    • Pancreatic undifferentiated carcinoma
  • Pancreas, biopsy / cytology:
    • Pancreatic undifferentiated carcinoma (see comment)
      • Comment: Cellular neoplasm with highly atypical cells, consistent with undifferentiated carcinoma of the pancreas.
      • Surgical resection: percentage of the undifferentiated component; infiltration, if any, of duodenum, common bile duct, neck margin, intestinal margin and retroperitoneal margin if Whipple resection, spleen and pancreatic margin if distal pancreatectomy; vascular / perineural invasion if any; nodal metastasis (if any); pTNM staging.
Differential diagnosis
Board review style question #1

    This is a high magnification field of a tumor within the pancreas. Can the diagnosis of undifferentiated carcinoma be made based on morphology only?

  1. No, electron microscopy must be used to rule out a melanoma.
  2. No, immunohistochemistry is mandatory.
  3. No, molecular analysis is mandatory.
  4. No, special histochemical stains are mandatory.
  5. Yes, morphology only is sufficient.
Board review style answer #1
B. Morphology is the most important step for the diagnosis; however, immunohistochemistry for keratin and vimentin should be performed in most cases to rule out sarcoma, melanoma and metastasis. This is particularly true for undifferentiated carcinoma with sarcomatoid features, to avoid misdiagnosis with sarcomas and for anaplastic type, to rule out melanoma or metastases.

Comment Here

Reference: Undifferentiated carcinoma
Board review style question #2
    How do the fibrosis and desmoplastic reaction seen in in conventional ductal adenocarcinomas of the pancreas compare to that of undifferentiated carcinomas?

  1. Conventional ductal adenocarcinoma typically has more fibrosis and desmoplasia
  2. Only anaplastic type undifferentiated carcinoma shows more fibrosis / desmoplasia than conventional ductal adenocarcinoma
  3. There is always more fibrosis in undifferentiated carcinomas
  4. There is the same quantity of fibrosis in both diagnoses
  5. They are highly variable in both diagnoses
Board review style answer #2
A. Conventional ductal adenocarcinomas usually has much more fibrosis / desmoplasia than undifferentiated carcinomas. This is a major point in the differential diagnosis between the two diagnoses.

Comment Here

Reference: Undifferentiated carcinoma
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