• Architecture: Sheets, small clusters (gland-like formation) and single cells
• Background: Dirty necrosis 
• Columnar cells with nuclear palisading in the larger sheets
• Increased N:C ratios
• Ovoid to elongated nuclei 
• Prominent nucleoli
• Coarse chromatin pattern
• Moderate nuclear pleomorphism

The presence of glandular formations, significant nuclear atypia, necrosis and atypical singly occurring cells point to a most likely diagnosis of adenocarcinoma. A pure pre-invasive primary lesion such as a neoplastic mucinous cyst (IPMN and MCN) is less likely, due to the presence of necrosis and single malignant cells; as well as the absence of background mucin. 

The main differential diagnosis would thus be primary ductal vs metastatic adenocarcinoma. 

Other primary tumours of the pancreas including acinar cell carcinoma and solid pseudopapillary neoplasms are unlikely due to the presence of overtly malignant features and  significant nuclear atypia. 

The clinical history would thus be important in the diagnostic workup.

The cell block shows glandular and sometimes cribriform structures lined by malignant glandular epithelium composed of tall columnar cells with elongated vesicular nuclei and prominent nucleoli. There is associated luminal necrosis.

The tumour cells are CK7- CK20+ CDX2+ SATB2+, highly suggestive of colorectal type adenocarcinoma.

Metastatic adenocarcinoma of likely colorectal origin

Based on the cytologic features alone, the clues suggestive of enteric differentiation include:

1. Peripheral palisading of nuclei  
2. Tall columnar cellular morphology with elongated nuclei 
3. Presence of dirty necrosis

Bear in mind that adenocarcinoma from various visceral sites can exhibit enteric differentiation and the following can assist in suggesting a colorectal origin:

1. Clinical correlation
   • The clinical history of previous colorectal adenocarcinoma and the presence of multiple metastatic lesions can be helpful. In this instance, there was a history of previously resected  colorectal adenocarcinoma.
2. Immunophenotype: CK7- CK20+ CDX2+ SATB2+
   • While none of these markers alone can confidently predict a colorectal origin, a combination will provide the highest sensitivity and specificity
   • A relatively new IHC in the scene is SATB2, with initial studies showing promise as an exclusive marker for colorectal adenocarcinoma
   • However, recent studies (one of the more recent cited below), have shown that SATB2 may rarely be expressed in adenocarcinoma of other visceral sites, particularly in the upper GI tract 
   • Nevertheless, SATB2 is still more specific than CDX2 for identifying colorectal adenocarcinoma and its rarity of expression in pancreatic ductal adenocarcinoma makes this marker useful in this setting

Simona De Michele, MD, Helen E Remotti, MD, Armando Del Portillo, MD, PhD, Stephen M Lagana, MD, Matthias Szabolcs, MD, Anjali Saqi, MD, MBA, SATB2 in Neoplasms of Lung, Pancreatobiliary, and Gastrointestinal Origins, American Journal of Clinical Pathology, Volume 155, Issue 1, January 2021, Pages 124–132, https://doi.org/10.1093/ajcp/aqaa118