Pancreas

Exocrine carcinomas

Undifferentiated carcinoma


Editorial Board Member: Wei Chen, M.D., Ph.D.
Deputy Editor-in-Chief: Raul S. Gonzalez, M.D.
Claudio Luchini, M.D., Ph.D.

Last author update: 13 February 2023
Last staff update: 13 February 2023

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PubMed Search: Undifferentiated carcinoma pancreas

Claudio Luchini, M.D., Ph.D.
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Cite this page: Luchini C. Undifferentiated carcinoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/pancreasundifferentiated.html. Accessed March 28th, 2024.
Definition / general
  • Carcinoma of the pancreas that does not show a definitive direction of differentiation
  • Under this definition, there are 4 variants: anaplastic, sarcomatoid, rhabdoid and carcinosarcoma (Mod Pathol 2015;28:248)
Essential features
  • Undifferentiated carcinoma with atypical neoplastic cells and without gland formation
  • Absence of osteoclast-like giant cells
  • Very poor prognosis
Terminology
  • Undifferentiated carcinoma of the pancreas
  • Old terminology, not in use: spindle cell carcinoma, pleomorphic carcinoma
ICD coding
  • ICD-O:
    • 8020/3 - carcinoma, undifferentiated, NOS
    • 8021/3 - carcinoma, anaplastic, NOS
  • ICD-10:
    • C25.9 - malignant neoplasm of pancreas, unspecified
Epidemiology
Sites
Pathophysiology
Clinical features
Diagnosis
Radiology description
Prognostic factors
  • Prognosis is very poor, with an average survival time of just 5 months, making it difficult to describe significant prognostic factors (J Am Coll Surg 2012;215:627)
  • Absence of osteoclast-like giant cells is important for the diagnosis of real, undifferentiated carcinoma (i.e., to avoid misdiagnosis) but is essential for the prognosis as well, since the prognosis of real, undifferentiated carcinoma is very poor, compared with that of carcinoma with osteoclast-like giant cells
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)
Treatment
Gross description
Gross images

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

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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
  • Undifferentiated carcinoma of the pancreas is a hypercellular tumor with scant stroma and scant desmoplastic reaction; this differs from conventional pancreatic ductal adenocarcinoma which has a large amount of desmoplastic stroma with few neoplastic cells / glands
    • This is a major point in the differential diagnosis between these 2 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 of > 80% highly atypical cells that have pleomorphic nuclei and lack gland formation
    • Sarcomatoid subtype is composed of > 80% atypical spindle cells, resembling a sarcoma (Int J Mol Sci 2022;23:1283, Hum Pathol 2022;128:124)
      • Rhabdoid subtype is a very rare sarcomatoid variant which is composed of large atypical cells with eosinophilic cytoplasm and eccentrically located nuclei
    • Carcinosarcoma is a subtype in which there is a mixture of roundish epithelioid cells and spindle sarcomatous cells; each component should arbitrarily constitute 30% of the neoplasm to qualify as carcinosarcoma
Microscopic (histologic) images

Contributed by Claudio Luchini, M.D., Ph.D. and AFIP
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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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Biopsy

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Details on biopsy

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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
Positive stains
Negative stains
Molecular / cytogenetics description
  • Overlaps with the genetic profile of conventional ductal adenocarcinoma
  • In the rhabdoid variant, KRAS alterations and SMARCB1 expression status define 2 subtypes, with possible translational implications (Mod Pathol 2015;28:248)
  • There is an enrichment in KRAS amplification in both rhabdoid and sarcomatoid variants, if compared with conventional ductal adenocarcinoma (Mod Pathol 2015;28:248, Hum Pathol 2022;128:124)
  • SMAD4 alterations appear as a rare molecular event in the sarcomatoid variant, if compared with conventional ductal adenocarcinoma (Hum Pathol 2022;128:124)
Sample pathology report
  • Pancreas, pancreatectomy:
    • Pancreatic undifferentiated carcinoma
  • Pancreas, biopsy / cytology:
    • Pancreatic undifferentiated carcinoma (see comment)
    • Comment: Cellular neoplasm with highly atypical cells is 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. No, immunohistochemistry is mandatory. 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 reactions seen in conventional ductal adenocarcinoma of the pancreas compare to that of undifferentiated carcinoma?

  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 carcinoma
  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 adenocarcinoma usually has much more fibrosis / desmoplasia than undifferentiated carcinoma. This is a major point in the differential diagnosis between the 2 diagnoses.

Comment Here

Reference: Undifferentiated carcinoma
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