Case 31

A pancreatic tail mass connected with spleen. Here is the section:

>80% of section showed this morphology of glands with mucin pool

1. What's your diagnosis?

   A: Chronic pancreatitis

   B: High-grade pancreatic intraepithelial neoplasia

   C: Ductal adenocarcinoma

   D: Acinar carcinoma

   E: Solid pseudopapillary neoplasm

   F: Intraductal papillary mucinous neoplasm

   G: Colloid carcinoma

Answer

This is a case of colloid carcinoma and high grade pancreatic intraepithelial neoplasia. Colloid carcinomas are a type of adenocarcinoma where at least 80% of the cancerous cells are suspended in extracellular mucin pools. These tumors are often large, well-defined, and commonly associated with intestinal-type intraductal papillary mucinous neoplasms (IPMNs). The neoplastic epithelium forms strips, clusters, glands, and sometimes individual cells, including signet-ring cells. Colloid carcinoma cells show intestinal differentiation, with strong CDX2 and MUC2 expression, unlike conventional ductal adenocarcinomas. The presence of mucin pools and perineural invasion helps differentiate it from mucin spillage. Colloid carcinomas have a better prognosis than ductal adenocarcinomas, with a 5-year survival rate exceeding 55%.

A list of key features of these entities are summarized below:

1. Chronic pancreatitis: Organized, lobular arrangement of the duct; intact duct; contains calculi, secretory plugs; Uniform, round-oval, no mitosis, no or small nucleoli.

   
   

   

   In this section of CP, the rounded configuration of the residual lobule is retained, but there is loss of acinar parenchyma due to replacement by loose, organizing fibrosis. Islets are still present; Credit: ExpertPath, Alyssa M. Krasinskas, MD; Lisa Yerian, MD

   
   

2. Intraductal Papillary Mucinous Neoplasm: Intraductal papillary mucinous neoplasms (IPMNs) are grossly visible lesions in the pancreatic ductal system characterized by papillary formation. Microscopically, IPMNs are marked by the growth of columnar mucin-producing cells that can form flat or papillary structures, from microscopic folds to visible projections. IPMNs are classified based on the degree of cytoarchitectural atypia: low-grade (mild to moderate atypia) and high-grade (severe atypia with irregular papillae, nuclear changes, and numerous mitoses). IPMNs are further subclassified by cell differentiation into gastric, intestinal, and pancreatobiliary types. Oncocytic-type IPMN is now considered a distinct entity.

   
   

   

   WHO classification of tumor, Olca Basturk, MD

   

   WHO classification of tumor, Olca Basturk, MD

   
   

3. Pancreatic intraepithelial neoplasia (PanIN): Pancreatic intraepithelial neoplasia (PanIN) lesions are composed of cuboidal or columnar cells that produce varying amounts of mucin. These lesions are classified based on the degree of architectural and cytological atypia, into low-grade and high-grade categories. Low-grade PanIN lesions are flat or papillary, with nuclei located at the base or appearing pseudostratified, and show mild to moderate atypia. They lack significant structural changes such as cribriform patterns or micropapillae, and mitoses are rare. High-grade PanIN lesions, on the other hand, are usually micropapillary or papillary, with marked loss of cellular orientation, irregular nuclear layers, and severe cytological abnormalities. Mitoses are more frequent, and occasionally cribriform patterns or intraluminal necrosis may be seen. Low grade PanIN you still see mucin but not seen in high grade.

   
   

   

   LG-PanIN, WHO classification of tumor, Olca Basturk, MD

   
   

   

   HG-PanIN, WHO classification of tumor, Olca Basturk, MD

   
   

4. Pancreatic intraductal tubulopapillary neoplasm: ITPNs (intraductal tubulopapillary neoplasms) are characterized by nodules of closely packed tubular glands, forming large cribriform structures. These tumors typically show expression of cytokeratins, which are common markers for epithelial cells, but they lack MUC5AC expression, a mucin marker often found in other types of pancreatic neoplasms. This distinctive feature helps differentiate ITPNs from other pancreatic lesions.

   
   

   

   WHO classification of tumor, Olca Basturk, MD

   
   

   

   WHO classification of tumor, Olca Basturk, MD

5. Mucinous cystic neoplasm: Mucinous cystic neoplasms (MCNs) of the pancreas. These are grossly visible, multilocular cystic lesions, primarily occurring in female patients. MCNs do not communicate with the ductal system. Microscopically, they consist of cysts lined by cuboidal or columnar neoplastic epithelium that stains positive for mucin, with variable degrees of atypia. The lesions also contain ovarian-like mesenchymal stroma, which is typically positive for estrogen receptors (ER) and/or progesterone receptors (PR) at least focally. This combination of features helps distinguish MCNs from other pancreatic cystic lesions.

   
   

   • Mucinous Cystic Neoplasms (MCNs):

     • Typically found in women and located in the pancreas tail/body

     • Do not communicate with the duct system

     • Contain ovarian-type stroma

   • Retention Cysts:

     • Unilocular, lack atypia

     • Distinguished by location and absence of florid papillae

   • Pancreatic Intraepithelial Neoplasia (PanIN):

     • Small (<5 mm) non-invasive lesions with gastric foveolar differentiation

     • Smaller lesions may resemble small gastric-type IPMNs, but large intestinal-type IPMNs are more likely

   • Oncocytic Papillary Neoplasms:

     • Characterized by eosinophilic cytoplasm, enlarged nuclei, and complex cell proliferation

   • Incipient IPMN:

     • Lesions 0.5-1.0 cm with finger-like papillae or GNAS mutations

   • Intraductal Tubulopapillary Neoplasms:

     • Resemble pancreatobiliary-type IPMNs but have a tubular architecture and lack mucin

   • Simple Mucinous Cysts:

     • Mucin-filled cysts >1 cm, lack features of IPMNs or MCNs

References: https://tumourclassification.iarc.who.int/chapters/31/254

Case credit: UCSD Pathology

Author: Wangpan Jackson Shi, MD