CHRONIC PANCREATITIS OR DUCTAL ADENOCARCINOMA? N. Volkan Adsay, \ MD

Case for discussion 67 y/o male Back pain and weight loss CT: 4.5 cm ill-defined, solid lesion in the head FNA/Core bx: Inconclusive Pancreatoduodenectomy

The dichotomy in the DDx of SOLID pancreatic tumors Schirrous/ill-defined Fleshy /demarcated Chronic pancreatitis Ductal ca. (and variants)

Solid scirrhous lesion in the pancreas: CP vs PDAC

FGP: 1) Pale/micorvesicular cytoplasm; 2) cuticle ; 3) raisonoid, hyperchromatic nuclei

Case in discussion-diagnosis Invasive ductal carcinoma (pancreatobiliarytype adenoca.) with foamy gland pattern Incidental finding: Pancreatic Intraepithelial Neoplasia

Invasive ductal adenocarcinoma (PDAC)

PDAC Epidemiology >85% of pancreatic tumors Mean age: 63 Developed >> under-developed countries Common source of carcinoma of unknown primary 5-yr survival <5%; deadliest of all cancers

Organ Cancer Annual deaths in US (2016) 1 Lung 160 K 2 Colo-rectal 51 K 3 Pancreas 41 K 4 Breast 40 K 5 Prostate 29 K

Chronic pancreatitis vs well-differentiated ductal adenocarcinoma

Foamy gland ca. Benign (non-invasive) ducts

Chronic pancreatitis (non-invasive ducts) vs (invasive ducts) ductal adenocarcinoma

I. Distribution of ductal structures: Is the process lobular or disorganized?

Lobularity (adenosis)

Organization; proper clustering and size associations: Benign

Haphazardness of ductal elements: Carcinoma

Lack of lobularity: Carcinoma

II. Abnormal localization of ductal structures: 1. Cells around the nerves?

Perineurial what?

Benign islets can wrap around nerves

Ducts in perineural space: carcinoma

Y.T s approach at Frozen Section: 1. Be liberal in calling things atypical and asking for more. 2. In the meantime, set the threshold high in giving them the diagnosis of carcinoma, especially if it is a diagnostic biopsy.

II. Abnormal localization of ductal structures: 1. Cells around the nerves? 2. The band of tissue around the ducts

Ducts in vascular spaces: Carcinoma

Ducts in vascular spaces

II. Abnormal localization of ductal structures: 1. Anything around the nerves? 2. The band of tissue around the ducts 3. Ducts next to medium-sized, thick-walled blood vessels

Duct next to a medium-sized, thick-walled vessel: CA

II. Abnormal localization of ductal structures: 1. Anything around the nerves? 2. The band of tissue around the ducts 3. Ducts next to medium-sized, thick-walled blood vessels 4. Individual glands in the adipose tissue?

Naked epithelial units in adipose tissue, what are they?

Normal islets are often seen in adipose tissue

Isolated solitary duct in adipose tissue: CA

III. Architecture of ductal structures

Benign: Smooth contours; compressed lumina CA: Irregular contours (angulated), open lumina

Large Duct Type Invasive Adenocarcinoma of the Pancreas with Microcystic and Papillary Patterns: a potential microscopic mimic of non-invasive ductal neoplasia. Mod Pathol, 2012: 439.

Irregular contours, open lumina: CA

Cribriform-vacuolated elements: Ca

IV. Luminal contents of ductal structures

Neutrophil-rich necrotic debris in the lumen

Neutrophil-rich necrotic debris in the lumen: CA

V. Stromal changes

VI. Cytomorphologic findings

1. Small, uniform cells with high N/C ratio 2. Numerous glands, but no lumen formation Benign atrophy

B9 atrophy versus Carcinoma

B9 atrophy versus Carcinoma Look for CYTOPLASMIC ACIDOPHILIA, paradoxical N/C (similar to prostate)

If glands have ATTENUATED cells: Look for GROOVEs

Nuclear irregularities and grooves Similar to tubular ca of the breast

If glands have ABUNDANT CYTOPLASM: Look for FOAMY GLAND features

Large (multicell-size) vacuoles: Carcinoma

Individual hyperchromatic cells

Individual hyperchromatic cells: Carcinoma

VI. Cytomorphologic findings Cytology at low power

56 y/o male Case in discussion Symptoms: Abdominal pain, jaundice and weight loss Imaging/Gross: Ill-defined mass involving the pancreatic head. Pancreatoduodenectomy was performed with the clinical diagnosis of pancreas cancer

Pancreas is transformed into a sclerotic mass. Rounded contour of the pancreas is preserved (not a feature of PDAC).

NO CARCINOMA is identified after extensive sampling and microscopic examination

No carcinoma!!! This is a NEGATIVE Whipple, how can that be?

PSEUDOTUMORAL PANCREATITIS Benign conditions that form a mass, mimic pancreas cancer, and lead to pancreatectomy 1. Not that uncommon: 4 % of the pancreatectomies 2. Not as risky for the patient as it used to be: Mortality of Whipple is now < 2% (in high volume institutions) 3. Both the incidence and case profile is changing with advancing technology 4. Any etiologic subgroup of CP can lead to PP; however, some entities are notorious

Common causes of pseudotumoral pancreatitis (benign lesions that clinically mimic cancer): 1. Autoimmune pancreatitis (40%) 2. Paraduodenal (groove) pancreatitis (40%) 3. Non-specific chronic fibrosing pancreatitis (10%) 4. Others/developmental/congenital lesions (10%) * The percentages reflect this speaker s personal experience

Case in discussion Rounded lobules (atrophy, intersitial fibrosis) Chronic inflammation

Periductal expansion, inflammation and sclerosis

Delicate, wavy sclerosis: characteristic

Plasma-cell rich storiform fibrosis ( inflammatory pseudotumor-like picture): Characteristic

Plasma cell-rich periductal chronic inflammation

Periphlebitis: Important sign

Markedly increased IgG4- positive plasma cells

Case - Diagnosis AUTOIMMUNE PANCREATITIS (AIP), TYPE 1 aka LYMPHOPLASMACYTIC SCLEROSING TYPE (LPSP) aka IgG4 RELATED SCLEROSING PANCREATITIS

Autoimmune Pancreatitis: Subtypes TYPE 1. Lymphoplasmacytic sclerosing type: IgG4- related TYPE 2. GEL (granulocytic epithelial lesion) associated: - Ulcerative colitis - IgG4 is often minimal

GEL -forming variant (with Granulocytic Epithelial Lesions)

Pseudotumoral Pancreatitis Common causes 1. Autoimmune pancreatitis 2. Paraduodenal ( groove ) pancreatitis 3. (NOS) 4. Others/developmental and congenital lesions

Paraduodenal pancreatitis: Pseudotumor at the accessory ampulla region of duodenal wall and pancreas

Paraduodenal Pancreatitis (groove pancreatitis)

Paraduodenal Pancreatitis: Myoadenomatosis type picture

Pseudoinfiltrative islets admixed with nerves

Paraduodenal Pancreatitis: cystic dystrophy of heterotopic pancreas Both pseudocysts and true cysts

Paraduodenal Pancreatitis Males; uncommon in females History of alcohol abuse, HTN, DM Process often centered around accessory ampulla

PSEUDOTUMORAL PANCREATITIS Benign conditions that form a mass, mimic pancreas cancer, and lead to pancreatectomy 1.Not that uncommon: >5 % of the pancreatectomies 2.Auotimmune pancreatitis and paraduodenal pancreatitis are the most common cause