Pancreas Case presentations [Read-Only]

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Interesting Cases of Pancreatic Masses

HARVARDMEDICAL SCHOOL

MASSACHUSETTS GENERALPHYSICIANS ORGANIZATION

Martha Bishop Pitman, MDProfessor of PathologyHarvard Medical SchoolDirector of Cytopathology

Massachusetts General HospitalBoston, MA

Case 1

A 76 year old asymptomatic man was found to have a multiloculated cyst in the pancreatic tail. Approximately 1mL of p pp yslightly thin, slightly bloody fluid was removed. A cystospin was made of the cells and the supernatant was sent for CEA and amylase.

Case 1: EUS ReportA 3.5 cm well defined multiloculated, lobulated cystic mass was noted in the pancreatic tail. The cyst wall was not well visualized and the septations were thick.

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Case 1

Case 1

Case 1

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Case 1

Case 1: Cyst Fluid Analysis

Amylase = 20 U/L

CEA = 0 5 ng/mlCEA = 0.5 ng/ml.

Case 1

Cytology Diagnosis: •Satisfactory for Evaluation•Neoplastic: BenignNeoplastic: Benign•Nonmucinous cyst fluid with low amylase (20•U/L) and CEA (0.5 ng/ml.) consistent with•serous cystadenoma.

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Serous Cystadenoma

Shark Core Biopsy

Moray Microforceps Biopsy

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Serous Cystadenoma

PAS dPAS

Case 1: Teaching Points• SCA produce nonmucinous fluid

– Usually bloody or clear

• Hemosiderin-laden macrophages act as a t k t t th di isurrogate marker to suggest the diagnosis

• Epithelium is fragile and may not survive processing by smearing

• SCA have low amylase and CEA

Case 2

A 64 year old woman being worked up for esophageal stricture is noted to have a cystic mass in the uncinate process. An y pEUS-FNA is scheduled.

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Case 2: EUS ReportThe body and tail of the pancreas is very atrophic. In the uncinate process, there is a fairly well circumscribed round cystic mass with thick cyst wall measuring about 30 X 20

A i t d ti f ll tmm. Aspirates are productive of yellow cyst fluid; cyst fluid CEA and amylase are assessed.

Case 2

Case 2

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Case 2


CEA = 6 mg/mLAmylase = 65 U/L

Case 2: Molecular Analysis

• KRAS wild type

• GNAS wild type

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Case 2: CB

Case 2: chromogranin

Case 2: synaptophysin

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Case 2

Cytological Diagnosis•Satisfactory for Evaluation•Neoplastic: Other•Cystic neuroendocrine tumor

Case 2: Teaching Points• cPanNETs mimic primary pancreatic cysts• The cells of PanNET fall into the HGA

category due to the small cell size and the abnormal chromatinU ll th d i f t f th ll• Usually the endocrine features of the cells are apparent

• Cytology is THE test to diagnose cPanNETs: CEA and amylase are low and molecular analysis is negative

Morales-Oyarvide V, Yoon WJ, Ingkakul T, Forcione DG, Casey BW, Brugge WR,Fernández-Del Castillo C, Pitman MB. Cystic pancreatic neuroendocrine tumors: Thevalue of cytology in preoperative diagnosis. Cancer Cytopathol. 2014

Case 2: Teaching Points• If the diagnosis is indeterminate use the

ATYPICAL category, not the SUSPICIOUS category– Atypical is to Neoplastic as Suspicious is to Positive

• Similar for other neoplasms in the “Other”• Similar for other neoplasms in the Other category

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Case 3

A 54 year old woman was found to have a cyst in the pancreatic body following resolution of a bout of pancreatitis that pbrought her to the ER.

Case 3: EUS ReportA 25 mm cyst was identified in the pancreatic body. There was a single compartment without septae. The outer wall of the lesion was thick. There was a small mural nodule.

Case 3

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Case 3


Amylase = 409 U/L

CEA = 5165 ng/mL.g


KRAS mutant

GNAS mutant

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Case 3Cytological Diagnosis

•Satisfactory for Evaluation

•Neoplastic: Other

•Mucinous cyst with high grade atypia•Mucinous cyst with high-grade atypia consistent with IPMN with at least high-grade dysplasia. See note.

Case 3: IPMN-branch duct type with high-grade dysplasia

Case 3: Teaching Points

• Cytology is the best test for determining cyst grade

• Distinguishing between low and high-grade is sufficient for patient management

• Intermediate-grade dysplasia is best placed with low-grade but features overlap with HGD.

• HGD cells are smaller than a 12 duodenal enterocyte, have abnormal chromatin and high N/C ratio; necrosis is often present

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Case 4

An 84 year old female was found to have a 2.6 cm cyst in the body/tail of the pancreas during evaluation of her Barrett’s gesophagus. An FNA was performed. 1 mL of thin, clear fluid was submitted for cytology and biochemical testing.

Case 4: EUS ReportA 2.6 cm anechoic cyst was noted in the body-tailof the pancreas. There were no septations and the wall was thin. There was no associated mass lesion. A connection to the main pancreatic duct was visualized.


Amylase = 111,153 U/L y ,

CEA = 56 ng/mL.

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Case 4

Case 4

Case 4

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Case 4Cytological Diagnosis

• Satisfactory for Evaluation

• Negative for Malignancy

• Mucoid cyst fluid; no high-grade epithelialy ; g g p

cells present. See note.Note: There appears to be extracellular mucin but its source is

unclear and CEA is not elevated above our cut off level of 192 ng/mL to support a neoplastic mucinous cyst. Benign appearing mucinous epithelium is present, the distinction from gastric contamination is not possible.

Case 4: Follow-up

-In this elderly, asymptomatic woman with low-risk imaging that supports the diagnosis of an IPMN and low-risk cytology, conser ati e obser ation as recommendedconservative observation was recommended-Follow-up at one year showed no growth

Case 4: Teaching Points• Aspiration of pancreatic cysts serves two

main purposes:– Determining if the cyst is mucinous

• Definitive criteria may not be present- choice between ND and negative, and correlation with clinical and imaging helps to determine which is best for the patient

– Determining if the cyst is high-risk by cytology, e.g. if there is HGA present

• HGA = HGD or adenocarcinoma

• No HGA + low-risk imaging = 99% NPVWu RI, Yoon WJ, Brugge WR, Mino-Kenudson M, Pitman MB.Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) contributes to a triple-negative test in preoperative screening of pancreatic cysts. Cancer Cytopathol. 2014; 122:412-419.

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Case 5A 62 year old female is worked up for acute onset of abdominal pain. Ultrasound shows a markedly dilated pancreatic duct with sharp tapering in the pancreatic head where a 2 cm round cystic mass ispancreatic head where a 2 cm round cystic mass is identified. EUS with FNA was performed.

Case 5: EUS Report

A round hypoechoic, calcified and cystic mass is identified in the pancreatic head measuring 16 mm by 20 mm The endosonographic borders are well-defined. An intact interface is seen between the mass at the adjacent structures suggesting a lack of invasion. Diagnostic needle aspiration for fluid is performed into the cystic component of the mass and into the mass itself. The amount of brown-yellow fluid collected is 4 ml The fluid is sent forThe amount of brown yellow fluid collected is 4 ml. The fluid is sent for biochemical and molecular analysis.


CEA = 35 mg/mLAmylase = 65,549 U/LKRAS mutantGNAS mutant

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Case 5:cyst

Case 5:cyst

Case 5: mass TP

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Case 5:mass TP

Case 5:mass CB

Case 5:mass CB

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Case 5:mass CB-ki-67

Case 5:mass CB-SMAD4

Case 5

Diagnosis:•Satisfactory for Evaluation•Positive for Malignancy•Adenocarcinoma consistent withAdenocarcinoma consistent with IPMN with invasive carcinoma. See note.

•Note: The cyst is mucinous by CEA elevation and KRAS/GNAS mutations, the GNAS mutation supporting an IPMN. The cyst epithelium is low-grade but the associated mass is diagnostic of adenocarcinoma, supported by a brisk ki-67 positivity and loss of nuclear SMAD4 staining.

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PDAC

Case 5: Teaching Points•Aspiration of both the cyst and associated mass is required for accurate diagnosis.•A cyst may not show significant atypia whereas the mass will show adenocarcinoma

•Although these components of a single mass lesion may have discordant results, the overall result of themay have discordant results, the overall result of the FNA is what counts

•This type of case should be considered a TP in studies•A low CEA does not exclude a mucinous cyst•GNAS mutations support the diagnosis of IPMN•Cytology is the best test for grading the cyst/mass•PDAC may be deceptively bland- the cytoplasm is the biggest clue to diagnosis!!

Case 6

A 45 year old male was found to have a mass in the pancreatic tail during work-up for non-specific abdominal pain.p p p

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Case 6: EUS ReportEUS showed a 1.5 cm round, well-defined solid and cystic mass with a heterogenous echotexture in the pancreatic tail; 3cc of thick cyst fluid obtainedthick cyst fluid obtained


CEA = 235 mg/mLAmylase = 237 U/L


• KRAS WT

• GNAS WT

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Case 6

Case 6

Case 6

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Case 6

Keratinous debris mimicking desiccated mucin

Case 6

Cytological Diagnosis:

Evaluation limited by scant cellularityEvaluation limited by scant cellularity

Negative for Malignancy

Lymphoepithelial Cyst

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• Rare; 4:1 M:F; mean 56 years

• thick cheesy keratinous debris may cause the cyst to appear solid on imaging

• Recognition of keratinous debris is the key• Recognition of keratinous debris is the key to diagnosis

• Elevated CEA a pitfall!

Case 7

A 68 year old female presented to the emergency room for acute abdominal pain



about 1 week following a dental procedure. A CT scan showed a ~3cm cyst in the

pancreatic head. The patient was referred to a gastroenterologist.

Case 7: Clinical History

• No history of alcohol abuse

• No history of pancreatitis

• Sudden onset of abdominal pain



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Case 7:EUS Performed 36 x 26 mm cyst in the pancreatic head

~10 cc of thin purulent fluid was obtained. Cultures sent; no other CFA performed. Cytology = neutrophils only.A gram stain showed gram positive cocci in pairs and chains. and culture grew abundant Rothia Dentocariosa. 1 month of antibiotics was prescribed.

Repeat EUSpersistent cyst 30 x 25mm

12 cc of opaque, thin, yellow fluid obtained.

Cytospin of cyst fluid- whole mount image

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Case 7

Case 7

Case 7

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Case 7

Case 7

Case 7: Diagnosis

Neoplastic: Other

Mucinous cyst with high-grade epithelial atypia consistent with branch-duct yp

intraductal papillary mucinous neoplasm with at least high-grade dysplasia.

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.

IPMN, branch-duct type, with focal high-grade dysplasia. No invasion identified

Case 7


• Clinical presentation– Benign appearing BD-IPMN infected from dental

procedure

• No high risk imaging features• Small, no mural nodule, no associated dilated MPD

• CFA: Biochemical– very elevated CEA supporting a mucinous etiology

• Cytology– HGA (suspicious) Resect

Case 8

• A 56 year old man presents with abdominal pain. CT shows an 8 cm solid, partially cystic mass in the pancreatic head An FNA is performed- smears andhead. An FNA is performed smears and cellblock are made.

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Case 8

Case 8

Case 8

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Case 8

Case 8

Case 8

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Case 8

Case 8

Beta-catenin

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Beta-catenin

CD10

CD56

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Case 8:Diagnosis

• Satisfactory for Evaluation

• Neoplastic: Other

• Solid-pseudopapillary Neoplasm

Case 8: Teaching Points• SPN do occur in males (4-7%) with the same age mean and range

as females- Mean age 30-35; Range 8-85

• Frequent pseudopapillary pattern – Formed by separation of vascular cores with adherent cells

– Typically thin walled vessels in cores

• >95% cured by resection95% cu ed by esect o– Most recurrences or metastases associated with atypical features

– Rare non-atypical cases may metastasize • May occur years later

– Most common metastatic sites • Liver

• Peritoneum / omentum

• Local lymph nodes involved rarely

• Neoplastic: Other interpretation category rather than Malignant in the PSC PB terminology system

Case 9A 72 year old female is found incidentally to have a vague, questionable mass in the pancreatic body. The pancreas otherwise was normal An EUS FNA ofotherwise was normal. An EUS-FNA of the mass is performed. Direct smears fixed in alcohol are stained with a Papanicolaou stain. No EUS report was available as the case was sent to me in consultation.

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Case 9

Case 9

Case 9

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Case 9

Case 9

Case 9

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Case 9

Cytological Diagnosis:Satisfactory for EvaluationNegative for MalignancyNegative for MalignancyBenign pancreatic tissue.

Acinar Tissue is often confused with NET

Case 9: Teaching Points• “negative” is an appropriate interpretation

category when imaging does not indicate a definitive mass lesion

• “nondiagnostic” is the more appropriate category when imaging clearly defines a mass lesion

• Misdiagnosis of normal acinar tissue as NET is a significant pitfall.– Mixture of ductal epithelium and “?acinar/lesional?”

tissue is a clue to it being pancreatic acinar epithelium– If uncertain, and NET is a possibility, use “atypical”

category

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Case 10

A 50 year old asymptomatic man is found to have a 1.5 cm round mass in the tail of the pancreas.

Case 10: EUS1.5 cm round well-circumscribed solid mass consistent with aneuroendocrine tumor

Case 10

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Case 10

Case 10

Case 10

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Case 10

Case 10

Case 10: synaptophysin

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Case 10: chromogranin

Case 10: CD8

Diagnosis

Negative

Splenule (Accessory spleen)

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• Splenule mimic NETs on images

• Cytologically, splenules mimic NETs or lymph node

CD8 i di ti IHC t i l ith• CD8 is diagnostic IHC stain along with negative endocrine markers

Helpful ResourcesChapter 3: Tissue handling and processing, including cellblock technique (collodian bag)

Chapter 4: Ancillary Studies

Chapter 7: Cystic Lesions

Algorithm for interpretation

Helpful ResourcesAppendix A: Template for signing out pancreatic cysts

Appendix B:

Mucinous Etiology

AbsentNon-viscous and CEAc and

-KRAS/GNAS

PresentViscous or CEAc or

+KRAS/GNAS

m grad

e b

Serous CystadenomaLymphoepithelial cyst

GI contaminate in Pseudocyst

Mucinous cystic neoplasm with low-intermediate grade dysplasiaIntraductal papillary mucinous

neoplasm with low-intermediate grade dysplasia

Colloid carcinoma

Cystic neuroendocrine tumorSolid-pseudopapillary tumorCystic acinar cell carcinoma

Mucinous cystic neoplasm with high-grade dysplasia or invasive

carcinomaIntraductal papillary mucinous

neoplasm with high-grade dysplasia or invasive carcinoma

Colloid carcinomaCystic ductal adenocarcinoma

Ep

ithel

ium

High‐grade a

Low‐g

a small cell with high nuclear to cytoplasmic ratio and abnormal chromatin and/or nuclear membranesb large cells with low nuclear to cytoplasmic ratio and moderate to abundant cytoplasm, often mucinousc Cut‐off value of 192 ng/ml has an accuracy of ~80% for detecting a mucinous cyst

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Pancreas Case presentations [Read-Only]