hand out pancreatic cytology sarajevo 2016-06-18 out pancreatic... · pancreatic cytology ... •...
TRANSCRIPT
2016-06-16
1
PANCREATIC CYTOLOGY
Mehmet Akif Demir, MD
Clinical Pathology and Genetics
Sahlgrenska University Hospital Gothenburg-Sweden
Papanicolau Society of Cytopathology5 Commities and their publications in 2014
• Adler D, Schmidt CM, Al-Haddad M, et al. Clinical evaluation, imaging studies, indications for cytologic study, and preprocedural requirements for duct brushing studies and pancreatic FNA: The Papanicolau Society of Cytopathology recommendations for pancreatic and biliary cytology. Diagnostic Cytopathology, 2014;42(4):325-332
• Brugge W, DeWitt J, Klapman JB. Techniques for cytologic sampling of pancreatic and bile duct lesions. Diagnostic Cytopathology, 2014; 42(4):333-337
• Pitman MB, Centeno BA, Ali SZ, et al. Standardized terminology and nomenclature for pancreatobiliary cytology: The Papanicolau Society of Cytopathology Guidelines. Diagnostic Cytopathology 2014;42(4):338-350.
• Layfield LJ, Ehya H, Fille AC et al. Utilisation of ancillary studies in the cytologic diagnosis of biliary tract and pancreatic lesions: The Papanicolau Society of Cytopathology Guidelines for Pancreatobiliary Cytology. 2014 Diagnostic Cytopathology, 42(4):351-362
• Kurtycz DFI, Field A, Tabatabai L, et al. Post-brushing and fine needle-aspiration biopsy follow-up and treatment options for patients with pancreatobiliary lesions: The papanicolau Society of Cytopathology Guidelines. Cytojournal 2014; 11(Suppl 1):5. Published online 2014 Jun 2. doi: 10.4103/1742-6413.133356
Other references
• Pitman MB, Layfield LJ. Guidelines for pancreaticobiliary cytology from the Papanicolau Society of Cytopathology: a review. Cancer Cytopathol 2014;122:399-411.
• Layfield LJ, Dodd L, Factor R, Schmidt RL. Malignancy risk associated with diagnostic categories defined by the Papanicolau Society of Cytopathology Pancreatobiliary Guidelines. Cancer Cytopathology 2014;122:420-427.
Benefits of a common nomenclature
• Standardization of nomenclature
• Unifies reporting of disease categories
• Contributes to evaluation of interobserver variability
• Improves intraobserver reproducibility
• Better aligns patient management options with interpretations
• Improves patient care
• Universally understanding by clinicians and pathologists
• ”Statistics” (economical aspects)
Categories
General tiered System in Cytology PSC suggestion for PB cytology
Nondiagnostic I. Nondiagnostic
Negative (Benign) II. Negative
Atypical III. Atypical
Suspicious IV. Neoplastic
-Benign
-Other
V. Suspicious
Positive VI. Positive/Malignant
Management
• Malignant ………………………..surgery
• Premalignant
• Low-intermediate grade………observation with repeat sampling
• Hig grade …………………………….surgery
• Neoplasm…………………………..surgery or observation
• Benign………………………………..medical management
• Endocrine tumors………………. surgery, chemotherapy, observation
Clinical information
• Patient age, gender
• Symptoms
• Anamnesis (important details that may effect diagnosis)
2016-06-16
2
Radiological information
• Localisation of the lesion in the pancreas
• Characteristics of the lesion• Size, growth pattern (rounded, infiltrative)
• Solid or cystic (unilocular, multilocular, solid with cystic component, thickness of the wall, calcifications)
• Vascularisation
• Cyst contents: thin, thick, mucinous, viscous, water-clear, brown,…
• NEEDLE TRACT!!! EUS Via?• Esophagus?
• Gastric wall?
• Duodenum?
Ancillary tests
• CEA
• AMYLASE
• Molecular analyses: KRAS, GNAS
• Immunocytochemistry & Immunohistochemistry (cell-block)
Differential Diagnostic Approach
SOLID
• Chronic pancreatitis
• Ductal adenocarcinoma
• Acinar cell carcinoma
• Pancreatic endocrine neoplasm
• Solid pseudopapillary tumor
• Pancreatoblastoma
• Metastasis
CYSTIC
• Pseudocyst
• Serous cyst
• Mucinous cyst (MCN, IPMN)
• Cystic degeneration of typicallysolid tumors
• Rare cystic lesions• Simple cysts
• Lymphoepthelial cyst
• Peripancreatic cysts
Important!
• DO NOT DIAGNOSE AS ”TUMOR” IF THERE IS NO RADIOLOGIC MASS LESION!!!
• NO MASS LESION: MOST PROBABLY NORMAL ACINAR CELLS/FRAGMENT, NOT ACINAR CELL CARCINOMA OR NEUROENDOCRINE TUMOR!!!
NormalNormal
2016-06-16
3
Contamination !!!
• Gastric
• Intestinal
• Contamination or a component of the tumor?
Gastric contamination, cell-block
Duodenal contamination
Cystic lesions
• Direct smears
• Other analyses on fresh undiluted cyst fluid
• CEA
• Molecular
• Cytomorphologic
• Cytospin
• Cellblock
http://www.radiologyassistant.nl/en/p4ec7bb77267de/pancreas-cystic-lesions.html
2016-06-16
4
Amylase & CEA
• Amylase levels
• High levels associated with pseudocysts
• May be increased in IPMN and LEC
• Not increased in serous cysts and MCN
• Elevated CEA: in favour of mucinous cyst
• Cannot distinguish IPMN from MCN
• No correlation with malignancy
• May be increased in duplication cysts, lymphoepithelial cysts
Molecular tests
• KRAS• supports a neoplastic mucinous cyst
• Cannot distinguish IPMN and MCN
• Does not contribute grading
• GNAS• supports IPMN over MCN
• No correlation with grade
• RNF43• Supports a mucinous cyst
• Does not distinguish IPMN and MCN
• 3p deletions• 3p25, VHL gene, and other 3p deletions supports Serous Cystic Adenoma (SCA)
• CTNNB1 (Beta-catenin) deletion• Support Solid Pseudopapillary Neoplasm (SPN)
Suggested Categories (Papanicolau Society ofCytopathologists)
• I. NONDIAGNOSTIC
• II. NEGATIVE
• III. ATYPIA
• IV. NEOPLASTIC
• BENIGN
• OTHER
• SUSPICIOUS FOR MALIGNANCY
• POSITIVE/MALIGNANT
I. Nondiagnostic
• A specimen that provides no diagnostic or useful information aboutthe lesion sampled.
• Criteria• Preparation artifact
• Obscuring artifact
• Gastrointestinal epithelium only
• Normal pancreatic tissue elements in the setting of a clearly defined mass by imaging
• Acellular aspirates of a solid mass or pancreatobiliary brushing
• Acellular aspirate of a cyst without evidence of a mucinous etiology (thickmucin, elevated CEA or KRAS mutation)
II: Negative
• Definition: A sample that contains adequate cellular and/or extracellular tissue to evaluate or define a non-neoplastic lesion thatis identified on imaging.
• Includes the presence of normal pancreatic tissue in the appropriateclinical setting such a vague fullness on imaging and no distict masslesion.
(Benign pancreas, Chronic pancreatitis, Autoimmune pancreatitis, pseudocyst, lymphoepithelial cyst, accessory spleen)
III. Atypical
• Definition: Cells with cytoplasmic, nuclear, or architectural features not consistent with normal or reactive cellular components of the pancreas or bile ducts, and insufficient features to classify them as a neoplasm or suspicious for a high grade malignancy.
• The findings do not explain a lesion identified on imaging studies
• Follow-up evaluation is warranted.
2016-06-16
5
Atypical
• Mild-moderate cellular atypia, NOS
• Mucinous/ductal epithelium with mild-moderate nuclear atypia (from a solid lesion or not clearly from a mucinous cyst)
• PanIN
• GI contamination with atypia
• Ductal atypia in bile duct samples
IV. Neoplastic
• Benign
• Other
IV. Neoplastic: Benign
• Definition: Cytological specimen sufficientlycellular and representative, with or without the context of clinical, imaging, and ancillary studies, to be diagnostic of a benign neoplasm.
• SCA (Serous cystadenoma)• Sparse cellularity
• Clean or bloody background
• Flat sheets and loose clusters
• Bland cuboidal cells
• Clear, finely vacuolated or granular cytoplasm with indistinct borders
• Associated hemosiderin-laden macrophages
• Low CEA; low amylase
• No KRAS mutation
IV. Neoplastic: Other
• Definition: A neoplasm that is either premalignant such as IPMN or MCN with low, intermediate or high grade dysplasia, or a solid-cellular neoplasmsuch as well-differentiated PanNET or SPN
• PanNET
• SPN
• Mucinous cyst (IPMN or MCN), not otherwise specified
• Mucinous cyst (IPMN or MCN), with low-grade atypia
• Mucinous cyst (IPMN or MCN) with high-grade atypia
• GIST
WHO 2010 classification of the primary neuroendocrine tumors of the gastrointestinal system
• NET G1 (carcinoid) (Neuroendocrine Tumor Gr-1)
• NET G2 (Neuroendocrine Tumor Gr-2)
• NEC (Neuroendocrine Carcinoma, large cell or small cell type)
• MANEC (Mixed Adenoneuroendocrine Carcinoma)
• Hyperplastic and preneoplastic lesions.
• NETs usually show local metastases but NECs are usually much more aggressive tumors and can show widespread metastases
2016-06-16
6
PanNET
• Almost the same classification and grading system as in gastrointestinal system
• “Pancreatic small cell NECs may not express neuroendocrine markersand this does not preclude the diagnosis so long as alternative diagnostic considerations are excluded”.
• NET usually p53(-), NEC usually p53(+)
• NET can be positive for CD99. t(11;22) translocation can be helpful in differential diagnosis of PNET.
ENETS (European Neuroendocrine Tumor Society) grading*
• G1
• mitotic count <2/10HPF and/or
• Ki 67 index 2≤ %
• G2
• mitotic count 2-20/10HPF and/or
• Ki67 index 3-20
• G3
• mitotic count >20/10HPF and/or
• Ki67 index >20
• Mitotic count in at least 50HPFs
• Ki 67 index as a percentage of 500-2000 cells counted in areas of strongest nuclear labelling (hot spots)
ENETS (European Neuroendocrine Tumor Society) gradinG
High Ki67 in FNA but about 1% in
surgical biopsy ??? 5 months interval
between biopsy & FNAC
Hot-spots and nucleolar ”hot-
spots”. How can we standardize
Ki-67 counting in cytology?
Cyto Ki67 Cyto Ki67
CASE: Scull base neuroendocrine tumour /lymph node FNAC…
IHC-panel for PanNET/NEC
• Chromogranin-A
• CK8/18
• Gastrin
• Glukagon
• Insulin
• Ki67
• Pancreatic Polypeptid
• Somatostatin
• Synaptophysin
• (Trypsin)
• (Beta-cathenin)
Case: Pancreas EUSPanNET
2016-06-16
7
GASTRIN
SYNAPTOPHYSIN
CK 8/18
CHROMOGRANIN AZES
Case-pancreas tumor: SCPPN
Onlymucin: Category?
Category?
Case:pancreas MCN?
CEA
Whipple: PanIN-I-II, IPMN borderline, kr pancreatit, squa metap
2016-06-16
8
Case: Cytologically lowgrade MCN/IPMN?Whipple: PanIn-II
V: Suspicious for malignancy
• Definition:
• A specimen is suspicious for malignancy when some but not all of the criteria of a specific malignant neoplasm are present, mainly pancreatic adenocarcinoma.
• The cytological features raise strong suspicion for malignancy, but the findings are qualitatively and/or quantitatively insufficient for a conclusive diagnosis.
VI: Positive/Malignant
• Definition: Unequivocal display of malignant cytologiccharacteristics
• Adenocarcinoma of the pancreatobiliary ducts, and variants
• Acinar cell carcinoma
• High-grade neuroendocrine carcinoma (small and large cell type)
• Pancreatoblastoma
• Lymphoma
• Metastases
Acinar cell carcinoma
Acinar cell carcinoma
TrypsinTrypsinTrypsinTrypsin (!!!positive in normal cells also)
Cell-block
Cytospin
2016-06-16
9
IHCC-panel for GIST
• ASMA
• CD34
• C-KIT
• DESMIN
• DOG-1
• Ki-67
• S100
C-kit
CD34
DOG-1
Ki-67
CASEOld man with a3 cm tumorin the pacreaticcorpus
Renal Cell Carcinoma metastasis
CD10
VIMENTIN
CARBA
Hvala Hvala Hvala Hvala vamvamvamvam punopunopunopuno nanananapažnjipažnjipažnjipažnji....