Case 1: Quarter 1, 2020

Case 1: Quarter 1, 2020

Clinical History

A 58-year-old male with no past medical history presenting to the emergency department with 2-month history of increasingly severe generalized abdominal pain accompanied by intermittent “stabbing sensations” with or without eating. The patient states the pain is so severe he has been unable to sleep and over the past few weeks he has noted dark stools, intermittent fevers, nights sweats, and chills. He reports an approximately 43-pound weight loss over the past few months some of which he attributes to intentional weight loss. The patient reports vomiting after eating if he lays down and only able to eat or drink while standing. Social history includes a 10 pack-year smoking history with cessation 6 months ago. He denies heavy alcohol use or history of pancreatitis.

Computed tomography with contrast of the abdomen was significant for a 10.0 x 10.0 x 7.0 cm hypoattenuating pancreatic head mass with double duct sign and encasement of the surrounding vessels. Multiple, scattered hypodense lesions were noted throughout the right hepatic lobe concerning for metastatic disease. Endoscopic findings showed an ulcerated, infiltrating mass in the duodenal bulb. Images of the duodenal biopsies are shown below.

Figure 1. H&E stain
Figure 1. H&E stain


Figure 2. H&E stain
Figure 2. H&E stain


Figure 3. H&E stain
Figure 3. H&E stain


Figure 4. H&E stain
Figure 4. H&E stain


Figure 5. CK7
Figure 5. CK7


Figure 6. CK5/6
Figure 6. CK5/6


Please Select Your Diagnosis in the Poll, Then See the Answer and the Discussion in the Links Below


What is the diagnosis of the lesion?

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Answer: Undifferentiated carcinoma, anaplastic type


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Microscopic appearance: 
This is a high-grade malignancy revealing predominantly diffuse sheet-like growth pattern, without overt glandular differentiation, with hemorrhage and necrosis. It is composed of atypical epithelioid and spindle-shaped cells intermixed with pleomorphic, multinucleated cells with bizarre nuclei.

These cells are positive for pancytokeratin, CK7, Cam 5.2, EMA (focal), CK5/6, and p63 immunohistochemical stains.

Final diagnosis:  
Undifferentiated carcinoma, anaplastic type

Undifferentiated carcinoma is one of the histologic subtypes of pancreatic ductal adenocarcinoma. Three morphological patterns of this subtype have been recognized by the current (5th edition) WHO.

Anaplastic type undifferentiated carcinoma is characterized by pleomorphic mononuclear cells admixed with bizarre-appearing giant cells with eosinophilic cytoplasm. At least 80% of the neoplasm consists of solid sheets of cells lacking gland formation and showing markedly pleomorphic nuclei. There is usually a neutrophilic inflammatory infiltrate. Keratin expression is typically present.

Sarcomatoid type undifferentiated carcinoma is characterized by spindle-shaped cells and may contain admixed heterologous elements of bone and cartilage. At least 80% of the neoplasm displays spindle cell features,with or without heterologous differentiation. A potential pitfall exists if only heterologous elements are sampled in a limited biopsy specimen, suggesting a soft tissue tumor, chondrosarcoma, or osteosarcoma. Sarcomatoid undifferentiated carcinomas with rhabdoid cells have also been described. Loss of nuclear expression of SMARC1 (INI1) is characteristic in these rare cases.

Carcinosarcoma reveals components with obvious epithelial morphology and sarcomatous elements, with or without heterologous differentiation, and requires each component to constitute 30% of the neoplasm.

Differential diagnosis:

  • Metastatic Melanoma to the small intestine is well documented and may histologically mimic undifferentiated carcinoma, anaplastic type. Morphologically, melanoma may show large pleomorphic cells with eosinophilic cytoplasm and macronuclei admixed with spindle or epithelioid cells. A panel of routine melanoma immunohistochemistry including Melan-A, HMB45, S100, and SOX10 is highly sensitive for metastatic melanoma.
  • Undifferentiated carcinoma with osteoclast-like giant cells, another histologic subtype of pancreatic ductal adenocarcinoma, is composed of neoplastic mononuclear cells, mononuclear histiocytic cells, and non-neoplastic osteoclast-like multinucleated giant cells. Heterologous elements such as bone and cartilage may be present.
  • Dedifferentiated GISTs are composed atypical spindle-shaped, epithelioid cells, and may contain large pleomorphic cells. These neoplasms are exceptionally rare and more frequently observed in patients with a history of GIST following long term tyrosine kinase inhibitor therapy. Notably, dedifferentiation typically includes a loss of KIT immunoreactivity.
  • Adenosquamous carcinoma of the pancreas comprises approximately 2% of pancreatic exocrine cancers. Squamous and glandular components may be intermixed or distinctly separate. The squamous component must comprise at least 30% of the tumor and will stain with p63, CK5/6, and high molecular weight cytokeratin.


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Case contributed by:

Adam L. Booth, MD
Anatomic and Clinical Pathology Resident, PGY-4
University of Texas Medical Branch, Galveston, TX

Nicole D. Riddle, MD
Assistant Professor, Associate Residency Program Director
University of South Florida, Tampa, FL