Patozone

General

 

If a mass is highly suspicious on imaging, should just be resected; otherwise cytology may be appropriate

- significant morbidity of surgery; not all lesions tx'd c surgery (ie lymphoma)

- FNA can be through skin or done endoscopically (more common bc allows for staging sometimes)

- up to 3% complication of acute pancreatitis

- cysts are traditionally hypocellular

- bile duct brushing best eval'd by liquid-based prep; smears can be air-dried or EtOH-fixed

- biochemical analysis can be done on cysts

 

Categories for reporting: Negative for malignant cells; Atypical cells present; Suspicious for malignancy; Neoplastic cells present; Positive for malignant cells; Nondiagnostic specimen

 

 

Normal pancreas

 

Normal pancreatic tissue has little stroma and lots of parenchyma

- exocrine tissue arranged in ducts around lobules that inc in size as approaches ampulla

-- mucinous differentiation indicative of PanIN

- acinar cells > ductal cells (opposite in bile ducts)

 

Cyto: acinar cells in grape-like clusters and isolated cells attached to fibrovascular stroma c eccentric round nuclei; evenly distributed finely granular chromatin c abundant cytoplasm and indistinct cell borders (+ SYN, CHR, CD56)

- ductal cells in evenly-spaced flat sheets (honeycomb, not usually single cells) c round nuclei; finely granular chromatin; no nucleoli and well-defined cytoplasmic borders (+ PAS-D, amylase)

- any cytoplasmic mucin is pathologic

 

 

Acute Pancreatitis

 

Caused by release of enzymes that hurt the pancreas, is rarely aspirated

- if aspirated, may see neutros, calcifications, necrotic debris and histiocytes

 

Chronic Pancreatitis

 

May mimick a neoplastic process bc forms a fibrous mass; thus if aspirated will be hypocellular c inflam and fat necrosis / calcifications, flat sheets of evenly-spaced cells that are mildly crowded, no (or rare) atypical cells, round nuclei c smooth nuclear contours, prominent (but not macro-) nucleoli, rare mits and low NC

 

IHC: (+) SMAD4 (lost in carcinoma)

- negative p53 (accumulates in carcinoma)

 

Pseudocyst

 

Usually caused by acute pancreatitis; lacks an epithelial lining (hence "pseudo-") but has an inflammatory fibrous capsule which surrounds necrotic tissue

- cyst fluid has inc amylase, CEA is low

 

 

Mucinous Cystic Neoplasm (MCN)

 

5% of pancreatic neoplasms; found in the body / tail of pancreas women in 6th decade

- uni- or (usually) multilocular cysts, no communication with pancreatic ducts

- lining epithelium has a spectrum ranging from benign, borderline and malignant

 

Lined by mucinous epitelium that is completely enclosed and has ovarian-type stroma that expresses ER/PR

- may be considered malignant if there is some degree of invasion

- the ovarian-type stroma is rarely seen in cytology

 

IHC: (+) pVHL, S100P, DPC4, MUC5AC, MUC6+/-

 

Tx: excision (irrespective of grade)

 

Px: 1/3 assoc c invasive adenoca

 

Intraductal Papillary Mucinous Neoplasm (IPMN)

 

Rare, more freq in older males, MC in head of pancreas

- radiological and clinical input is essential

- single or multiloculated ducts

Up to 5% of pancreatic tumors

- grow along pancreatic ducts making thick mucin that can block pancreatic secretions and form cysts; usually found in head of pancreas; M=F

- similar to MCN, may be invasion (MCN and IPMN cannot be distinguished by cytology)

 

Px: excellent if no invasion; otherwise grade based on depth of invasion

 

Pancreatic Intraepithelial Neoplasia (PanIN)

 

Pre-malignant mucinous changes in the pancreatic ducts

PanIN-1 = low grade atypia

PanIN-2 = moderate atypia c stratification and tufting of epithelium; polarity is maintained

PanIN-3 = severe atypia w/o invasion (confined to ducts)

 

IHC: synapto,

Pancreatic Ductal Adenocarcinoma

 

MCC pancreatic neoplasia (up to 9/10); smoking is a risk factor; seen in 7th-9th decades presenting c abd pain, jaundice, pruritis, unexplained weight loss

- most (3/4) found in pancreatic head and most are well- to moderately diff

 

Cyto: hypercellular c irreg clusters (drunken honeycomb) and single cells c strange morphology (irreg contours and chromatin distribution), inc NC, mucinous cytoplasm, marked anisonucleosis (4:1 nuclear size variation in a single sheet / group)

- the groovy nuclei are sometimes called popcorn cells; and the grooves in cells sometimes called tulip cells

- some cells c foamy cytoplasm can have deceptively low NC

 

IHC: (+) p53, PanCK, E-cadherin

- negative (nuclear) SMAD4, synapto, chromogranin, vimentin, trypsin, lipase, NSE, PR, B-catenin, a1-antitrypsin, a1-antichromotrypsin, CD10, CD56, Chymotrypsin

 

Pancreatic Neuroendocrine Tumor (PanNET or PEN)

 

Up to 2% of pancreatic tumors; generally small circumscribed lesions seen around 5th decade

- can be low or high grade (well- or poorly differentiated, respectively); though cytologic atypia doesn't correlate c malignant behavior

 

May be functional and secrete variety of hormones (insulin, glucagon, VIP, serotonin, etc)

-- insulinomas are generally b9; though up to 4/5 are considered aggressive

- rarely invade pancreatic ducts

 

Cyto: hypercellualr c single cells (bare nuclei) in pseudorosettes or small clusters c uniform, round, eccentric (plasmacytoid) nuclei and salt n peppa chromatin

 

Proliferation rate used to grade:

Low-grade = 2-10 mits / 10 hpf

Intermediate-grade = 10-20 mits / 10 hpf

High-grade = >20 mits / 10 hpf

- Ki67 may be helpful

 

IHC: (+) Pankeratin, chromogranin, synaptophysin, CD56, Islet 1, PAX8;E-cadherin, may also stain for pancreatic hormones, variable vimentin

- negative trypsin, B-catenin (can see membranous or cytoplasmic staining), lipase, a1-antitrypsin, a1-antichymotrypsin, CD10

 

Px: cytologic atypia does not correlate with malignant behavior, with the exception of high-grade small and large cell neuroendocrine tumors

- most reliable predictor is presence of invasion or mets

Acinar cell Carcinoma (ACC)

 

<2% pancreatic neoplasms; occurs around 7th decade; can be anywhere in pancreas

Resemble pancreatic acini and make pancreatic enzymes; usually solid

- can be functional, secreting lipase, amylase,

 

Cyto: hypercellular c solid-cellular pattern of monomorphic single / naked cells in non-cohesive aggregates c granules in background, round / oval nucleus c smooth contour, prominent nucleolus and delicate granular cytoplasm

 

IHC: (+)  Pankeratin, trypsin; lipase, a1-antitrypsin, a1-antichymotrypsin, weak B-catenin; usually positive for Islet 1 and PAX8, B-catenin can be membranous

 

- negative chromogranin, synaptophysin, CD56, vimentin

 

Px: poor; <10% 5-year survival

 

Solid-Pseudopapillary Neoplasm (SPN)

 

- aka Solid PesudoPapillary Tumor (SPPT)

Rare (up to 2%) in young women (around 4th decade) found throughout pancreas

 

Well-circumscribed c variable solid and cystic parts

 

Cyto: hypercellular c myxoid fibrovascular cores lined by tumor cells c finely vacuolated cytoplasm c indistinct cell borders and round nuclei c grooves and no nucleoli; hyaline globules that are PAS-D positive

 

IHC: (+) CD56, B-catenin (nuclear), KIT (CD117), CD10, vimentin, NSE, PR, a1-antitrypsin, a1-antichymotrypsin, chymotrypsin, variable Pan CK and synaptophysin

- negative E-cadherin, trypsin, lipase

 

Tx: surgery (usually curative)

 

Px: usually low malig potential, but may have invasion into structures (nerve, vessels) that suggest aggressive behavior

 

Pancreatoblastoma

 

Rare; found in young children (MCC pancreatic neoplasm in childhood)

 

Cyto: Epithelial part c syncytial groups and isolated cells that are monomorphic c moderate cytoplasm and squamoid corpuscles; also a stromal part c primitive spindly cells and occasional heterologous elements (ie cartilage)

 

IHC: (+) Pankeratin, trypsin, chromogranin, synaptophysin, CD56; weak B-catenin