Undifferentiated carcinoma with osteoclast-like giant cells

Pancreas
Exocrine tumors / carcinomas
Undifferentiated carcinoma with osteoclast-like giant cells

Author: Claudio Luchini, M.D., Ph.D.

Topic Completed: 26 November 2019

Minor changes: 9 March 2020

Copyright: 2002-2020, PathologyOutlines.com, Inc.

PubMed Search: Undifferentiated carcinoma with osteoclast-like giant cells pancreas

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Table of Contents

Cite this page: Luchini C. Undifferentiated carcinoma with osteoclast-like giant cells. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/pancreasosteoclastic.html. Accessed May 30th, 2020.

Definition / general

Undifferentiated carcinoma of the pancreas with no glandular differentiation and with prominent infiltration by histiocytes and osteoclast-like giant cells
May be found in association with a differentiated component of pancreatic ductal adenocarcinoma

Essential features

Undifferentiated carcinoma with atypical neoplastic cells lacking gland formation
Presence of multinucleated giant cells resembling osteoclasts

Terminology

Undifferentiated carcinoma with osteoclast-like giant cells (UCOGC, UCOCGC)
Old terminology, not in use: giant cell tumor of the pancreas, osteoclastoma

ICD coding

ICD-O: 8035 / 3 - undifferentiated carcinoma with osteoclast-like giant cells
ICD-10: C25.9 - malignant neoplasm of pancreas, unspecified

Epidemiology

M:F = 0.9:1 (Am J Surg Pathol 2016;40:1203, J Pathol 2017;243:148)
Commonly presents in the sixth to seventh decades (Am J Surg Pathol 2016;40:1203, J Pathol 2017;243:148)
1.4% of all pancreatic cancers (Am J Surg Pathol 2016;40:1203)

Sites

Head of the pancreas (60 - 75% of cases), body / tail (25 - 40%) (Am J Surg Pathol 2016;40:1203, J Pathol 2017;243:148)

Pathophysiology

Unknown; a role may be played by hemorrhagic / chronic inflammatory foci with recruitment of tumor supporting macrophages within the pancreas or within a pancreatic ductal adenocarcinoma (Hum Pathol 2018;81:157)

Clinical features

Presenting symptoms include jaundice (tumors in the pancreatic head), abdominal or back pain, weight loss and nausea (Am J Surg Pathol 2016;40:1203, J Pathol 2017;243:148)

Diagnosis

CT scan and MRI are the preferred imaging modalities
Diagnosis is by biopsy or surgical resection (more difficult with cytology but may be possible, Cancer Cytopathol 2017;125:563)

Radiology description

Usually mass lesions with delayed enhancement (Am J Surg Pathol 2016;40:1203)

Radiology images

Images hosted on other servers:

Ultrasound

Prognostic factors

Presence of an associated conventional ductal adenocarcinoma component is associated with a poorer prognosis and is one of the most important prognostic moderators (Am J Surg Pathol 2016;40:1203, J Pathol 2017;243:148)
PDL1 expression by tumor cells is associated with poor prognosis (Hum Pathol 2018;81:157)

Case reports

54 year old man with a huge (28 cm) mass, for which radical resection was possible (Int Cancer Conf J 2017;6:193)
54 year old woman with a large cystic mass in the pancreas (Int J Clin Exp Pathol 2015;8:11785)
60 year old woman with upper abdominal pain (J Cancer Res Ther 2015;11:1046)
61 year old woman with long term survival after surgical resection and chemotherapy (Case Rep Gastroenterol 2016;10:472)
65 year old man with weight loss (Medicine (Baltimore) 2018;97:e13516)
68 year old woman with a prominent invasion of pancreatic ductal tree (JOP 2011;12:170)

Treatment

Surgical resection if possible, gemcitabine based chemotherapy (Case Rep Gastroenterol 2016;10:472)

Gross description

Larger than conventional ductal adenocarcinoma (J Pathol 2017;243:148)
Brownish (not whitish) and with pushing borders
Frequent cyst formation
Hemorrhage or necrosis typically present

Gross images

Contributed by Claudio Luchini, M.D., Ph.D.

Gross appearance

Images hosted on other servers:

Hemorrhagic mass

Cystic mass

Cystic mass with gastric invasion

Frozen section description

Hypercellular neoplasm with atypical cells
Multinucleated giant cells, although they cannot always be documented in small biopsy sent for frozen section (may be focal component)

Frozen section images

Contributed by Claudio Luchini, M.D., Ph.D.

Frozen section

Microscopic (histologic) description

Composed of 3 cell types:
- Mononuclear neoplastic cells, sometimes very atypical
- Mononuclear histiocytes (nonneoplastic)
- Multinucleated giant cells (osteoclast-like giant cells) (nonneoplastic)
Foci of hemorrhage and necrosis are very common
Typical involvement of the pancreatic ductal tree, sometimes with pseudopolypoid growth pattern (J Pathol 2017;243:148)
May arise in association with mucinous cystic neoplasm of the pancreas and intraductal papillary mucinous neoplasm of the pancreas (Am J Surg Pathol 2016;40:1203, World J Surg Oncol 2011;9:100, Am J Surg Pathol 2015;39:179)
Osteoid material may be found (J Pathol 2017;243:148)

Microscopic (histologic) images

Contributed by Claudio Luchini, M.D., Ph.D.

Associated conventional adenocarcinoma

Ductal tree involvement

Microhemorrhagic foci

Extensive necrotic hemorrhage

CK8 / 18+

Focal CK8 / 18+

CK8 / 18-

Cytology description

3 cell types (osteoclast-like giant cells, neoplastic cells and histiocytes) are present in most cases (~80%)
Cytology has a diagnostic value for this tumor in ~80% of cases (Cancer Cytopathol 2017;125:563)

Cytology images

Images hosted on other servers:

Romanowsky stain

Papanicolaou stain

Positive stains

Neoplastic cells:
- Cytokeratin AE1 / AE3, CK7, CK8 / 18 are usually positive but may be totally negative
- p53 in > 50% of cases
- Ki67 high proliferation index
Histiocytes:
- CD68, CD163 (Hum Pathol 2018;81:157)
Multinucleated giant cells:
- CD68, cathepsin K (Hum Pathol 2019;85:168)

Negative stains

Neoplastic cells:
- CD68, CD163, S100, CD45
Histiocytes and multinucleated giant cells:
- Cytokeratins, p53

Electron microscopy description

Neoplastic cells: abundant mitochondria, no microvilli or desmosomes (J Korean Med Sci 2005;20:516)
Multinucleated osteoclast-like giant cells: multiple nuclei with rim of chromatin, abundant mitochondria, free ribosomes, dilated empty rough endoplasmic reticulum cisternae (J Korean Med Sci 2005;20:516)

Electron microscopy images

Images hosted on other servers:

Neoplastic cell

Giant cell

Molecular / cytogenetics description

Overlaps with the genetic profile of conventional ductal adenocarcinoma, with the most common mutated genes KRAS, TP53, CDKN2A and SMAD4 (J Pathol 2017;243:148)
GLI3, a gene belonging to the hedgehog signaling pathway, may be found mutated in this tumor
The same mutation (290 M > L) affecting the gene SERPINA3 has been documented in 25% of cases in a whole exome sequencing analysis (J Pathol 2017;243:148)

Sample pathology report

Pancreas, pancreatectomy:
- Pancreatic undifferentiated carcinoma with osteoclast-like giant cells (see synoptic report)

Differential diagnosis

Undifferentiated / anaplastic carcinoma of the pancreas:
- Absence of osteoclast-like giant cells
Paraduodenal (groove) pancreatitis:
- Multinucleated giant cells may be abundant but neoplastic cells are lacking (Cytopathology 2015;26:122)
Melanoma:
- Contains melanin pigment instead of or in addition to hemosiderin
- S100+

Board review style question #1

This is an immunohistochemical slide (CK8 / 18) from a pancreatic tumor in an elderly female with jaundice. S100 was negative throughout and the multinucleated cells were CD68 positive. Which is the most likely diagnosis?

Anaplastic lymphoma
Melanoma
Pancreatitis
Primitive mesenchymal tumor of the pancreas
Pancreatic undifferentiated carcinoma with osteoclast-like giant cells

Board review answer #1

E. This is a pancreatic undifferentiated carcinoma with osteoclast-like giant cells. These tumors may be composed of neoplastic cells totally negative for cytokeratin. This finding, which is not uncommon, cannot be used to exclude this tumor entity (WHO Classification of Tumours Editorial Board: Digestive System Tumours, 5th Edition, 2019).

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