Molavi Chapter 10 - Pancreas Flashcards
A normal pancreatic lobule
A central duct with a well-differentiated cuboidal ductal epitheium is seen in the center with surrounding nests of acini composed of wedge-shaped cells with granular pink and purple cells.
Ways to differentiate chronic pancreatitis from adenocarcinoma
- Chronic pancreatitis (A) vs adenocarcinoma (B)
- On low power, chronic pancreatitis has preserved lobular architecture (central duct with peripheral acini) while adenocarcinoma is haphazardous.
- Incomplete lumina (luminal spaces not symmetrically surrounded by nuclei) and luminal necrosis suggest adenocarcinoma
- Cellular features of hyperchromatic, irregularly shaped nuclei, mitoses, necroses, and the 4:1 rule all suggest adenocarcinoma
- Both processes may have a desmoplastic-like stroma
Residual islets of Langerhans in chronic pancreatitis
The morphology becomes destorted, but the cells preserve their small, round, dense, and regular nuclei.
PanIN
Pancreatic intraepithelial neoplasia
Comes in three grades:
- PanIN-1: May overap with hyperplastic or reactive changes. Tall, mucinous cells resembling endocervix.
- PanIN-2: Increasing nuclear crowding, enlargement, and atypia, similar to tubular adenoma in the colon.
- PanIN-3: High-grade nuclei with loss of polarity, frequent mitoses, and loss of mucinous differentiation. Carcinoma in-situ.
Intraductal papillary mucinous neoplasm
Mucin-producing neoplasm arising from the main pancreatic duct or a secondary duct. Ducts are usually dilated as they are full of neoplasm and abundant mucin. Main ddx is mucinous cystic neoplasm (where the ducts are not connected to the lesion). 30% of high-grade IPMNs are associated with invasive adenocarcinoma.
This IPMN is low-grade. Characterized by tall, papillary fronds with fibrovascular cores covered with mucinous cells showing features similar to PanIN-2. Gross pathology is extremely helpful in the diagnosis to establish continuity with a duct vs not.
Invasive pancreatic ductal adenocarcinoma
The most common form of infiltrating adenocarcinoma in the pancreas. Usually arises in the pancreatic head and invades adjacent structures prior to becoming clinically apparent.
Perineural and perivascular invasion are common. Anisonucleosis, sometimes within a single gland, is a helpful feature (4:1 rule, seen here).
Variants include adenosquamous, colloid/mucinous, hepatoid, medullary, signet ring-cell, undifferentiated/anaplastic, and undifferentiated with osteoclast-like giant cells.
Order of genetic changes in progression to pancreatic adenocarcinoma
Mucinous cystic neoplasm
Almost always occurs in middle-aged women, usually in the pancreatic tail.
Classically characterized by multilocular cysts that do not communicate with the main ductal system. Neoplastic epithelium lines the cysts and have a rim of ovarian-type stroma.
Come in two grades: Low-grade (like PanIN-1 or -2), and high-grade (like PanIN-3, carcinoma in-situ). 1/3 of MCNs have an associated invasive carcinoma, which would be termed “invasive adenocarcinoma arising in association with a mucinous cystic neoplasm.”
Serous cystadenoma
In the pancreas (unlike the ovary) these are almost always microcystic. Grossly they have a central scar, with small, clear fluid-filled cysts lined by cuboidal cells radiating outward. Cells have clear cytoplasm (due to glycogen) and dark, small, uniform, round nuclei.
Serous cystadenocarcinomas exist but are extremely rare.
Pancreatic solid-pseudopapillary neoplasm
Unusual, distinctive tumors in the ddx of cystic lesions in young women. They are malignant, but typically indolent.
They start out solid, but may undergo central necrosis and appear at least partially cystic on imaging. They are characteristically poorly cohesive. When individual cells undergo degeneration, only the tumor cells along fibrovascular septa remain, hence “pseudopapillary” growth pattern. The nuclei are small, oval, bland, and grooved with neuroendocrine-type chromatin. Cells are often plasmacytoid with inversed polarity.
These tumors are CD10 postive and how nuclear labeling of beta catenin.
Pancreatic pseudocyst
The definition of pseudocyst is “lacking an epithelial lining.”
A walled-off area of fat necrosis and granulation tissue containing high levels of pancreatic enzymes that is not usually mistaken for malignancy, either clinically or microscopically. Most pseudocysts are actually extrapancreatic.
Acinar cell carcinoma
Rare tumor that occurs in older adults, usually male.
The appearance is that of nodules and sheets of densely-packed amphophilic (purple) cells with uniform, round nuclei. Growth may be trabecular, nested, or acinar (arranged around tiny lumina). Prominent nucleoli are often seen and are a clue to the diagnosis.
Usually positive for trypsin and chymotrypsin, like benign acinar cells.
Pancreatic neuroendocrine neoplasm
Basically just carcinoid-like neuroendocrine tumors of the pancreas. Well-circumscribed, cellular. Neoplastic cells tend to form nests or trabeculae. Smooth round to oval nuclei, salt-and-pepper chromatin, pink-to-purple cytoplasm.
Stains positive for synaptophysin, chromogranin, CD56, as well as any peptides that they may be producing if functional.
Some are functional and produce clinical syndromes related to the hormone secreted, however the majority are nonfunctional.
Importantly, with these tumors, lack of atypia is not an indication of good behavior – tumors may appear bland and then be found metastatically. Prognosis depends upon tumor’s mitotic rate.
Smad signaling overview
Ligands bind and cross-link type I and type II RTKs ⇒ Transphosphorylation, RTK activation ⇒ Activated RTKs recruit receptor SMADs (R-SMADs) via C-termianl serine phosphorylation ⇒ R-SMADs are phosphorylated and activated ⇒ activated R-SMADs recruit SMAD4, the common co-SMAD ⇒ P-R-SMAD-SMAD4 complex translocates to the nucleus and associated with transcription factors to elicit a transcriptionsl response
SMAD6 and SMAD7 inhibit RTK-mediated phosphorylation of R-SMADs
Smurf1 and Smurf2 are E3 ubiquitin ligases that target R-SMADs for degradation.
SMAD4 and pancreatic adenocarcinoma
SMAD4 is commonly inactivated in pancreatic adenocarcinoma (50% of cases)
Pancreatoblastoma
Usually a pediatric tumor.
Very histologically similar to acinar cell carcinoma, except with the addition of squamous nests and occasionally neuroendocrine and ductal components. Squamous nests will have characteristic nuclear pseudoinclusions of biotin in many cases.
If you see squamous differentiation in the pancreas in what appears to be an acinar cell carcinoma in an adult, think of this diagnosis.
