Hepatic metastases USCAP 2 Hepatic Metastases • Common, multiple per day • Image guided...
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Transcript of Hepatic metastases USCAP 2 Hepatic Metastases • Common, multiple per day • Image guided...
3/23/2017
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Metastatic Disease of the Liver: A common sense approach to a
common problem
Lawrence Burgart
Allina Health
University of Minnesota
Minnesota Gastroenterology
Minneapolis/St. Paul, MN
Disclosure of Relevant Financial Relationships
USCAP requires that all planners (Education Committee) in a position to
influence or control the content of CME disclose any relevant financial
relationship WITH COMMERCIAL INTERESTS which they or their
spouse/partner have, or have had, within the past 12 months, which relates to
the content of this educational activity and creates a conflict of interest. Dr. Burgarthas nothing to disclose.
Temporary metastasis to Haridwar, India
Hepatic Metastases
• Common, multiple per day
Hepatic Metastases
• Common, multiple per day
• Image guided (ultrasound, CT)
–Nearly half with adequacy assessment
Hepatic Metastases
• Common, multiple per day
• Image guided (ultrasound, CT)
–Nearly half with adequacy assessment
• Suspected/known primary site
–Confirm, obtain ancillary predictive studies
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Hepatic Metastases
• Common, multiple per day
• Image guided (ultrasound, CT)
–Nearly half with adequacy assessment
• Suspected/known primary site
–Confirm, obtain ancillary predictive studies
• Unknown primary site
–Broader evaluation; ddx includes liver primary
Hepatic Metastases
• Common, multiple per day
• Image guided (ultrasound, CT)–Nearly half with adequacy assessment
• Suspected/known primary site–Confirm, obtain ancillary predictive studies
• Unknown primary site–Broader evaluation; don’t forget liver primary
• Therapeutic resections, CRC–Therapeutic response evaluation
Hepatic Metastases ‐ Adequacy
• Touch prep of US or CT needles
• Cytotechnologist where available
• Regional hospitals, scheduled when pathologist present for lab management
• Diff‐Quik stain
Multiple masses, suspected unusual primary
Hepatic Metastases ‐ General
• Common primary sites
–Colorectal and upper GI
–Pancreatobiliary
– Lung
–Breast
• Less common primary sites
–Everything happens…
–Melanoma, GYN, GU, soft tissue, hematolymphoid, etc
72 year old woman
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Clinical Information Critical(and, anything can happen)
• 12 yrs ago, parotid tumor
• Resected, locally extensive, Rad Rx
• 5 yrs ago, local recurrence, add’lresection
• 1.5 yrs ago, local recurrence
• 0.5 yrs ago liver masses, one large, several small
72 year old woman
Metastatic acinic cell carcinoma
Suspected / known primary site
• Confirmation, definitive therapy
• Ancillary predictive studies
–Anticipated and unanticipated
–Conserve tissue!!
Suspected / known primary siteExample #1
• 47M, morbid obesity, T2 diabetes
• ED for 2 weeks left lower back pain
• CT, sigmoid colon thickening and multiple liver masses
• Liver biopsy was elected
• Plan for neoadjuvant chemotherapy
47M, AdCA with necrosis 47M, “normal” background liver
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47M, classic histology DNA MMR only IHC performed
DNA MMR intact (MLH1)
Suspected / known primary siteExample #1
• Metastatic adenocarcinoma c/w CRC
• Kras, nras, braf assays wildtype
Suspected / known primary siteExample #2
• 89F, weight loss, cough, 30 pk‐yr smoker
• 5.3 cm necrotic lung mass, extending into mediastinum
• 4.9 cm liver mass suspicious for met
• Image guided liver biopsy
89F S16-77497
Necrosis
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S16-77497
Small amount of tumor
S16-77497
Strongly TTF1 positive
Suspected / known primary siteExample #2 FMP system for ancillary studies
Example #2• DIAGNOSIS• Liver Non‐small cell lung carcinoma (NSCLC), favor adenocarcinoma
• COMMENT• Immunostains were performed on this case. The results follow, and support the above interpretation.
• TTF1: Positive• p40: Negative
• **LUNG ANCILLARY TESTING PROTOCOL**• Case number: Sxx‐xxxxxx Patient name: xxxxxx xxxxxx
• HISTOLOGIC TYPE• Non‐small cell lung carcinoma (NSCLC), favor adenocarcinoma• STAGE IV STATUS• Histologically proven stage IV disease• TISSUE BLOCK AVAILABLE FOR ANCILLARY TESTING• A1• COMMENT• This patient’s sample meets Allina Lung Cancer Committee criteria* for reflex EGFR, ALK, ROS1, and PDL1 (for pembrolizumab
(Keytruda) eligibility) testing. EGFR, ALK, ROS1, and PDL1 testing will be performed and results will be communicated in addenda. There is no need to call to order EGFR, ALK, ROS1, and PDL1 testing. If there is a need for ancillary tests other these, please call 612‐863‐4670 (option 2).
•• *Allina Lung Cancer Committee EGFR, ALK, ROS1, and PDL1 reflex testing criteria: • Stage IV disease (histologically proven or clinically suspicious)• Adenocarcinoma or TTF‐1 positive adenosquamous cell carcinoma.
Suspected / known primary siteExample #2b
• 71F, extensive perirectal abscess, sepsis
• Hospitalized, sequential imaging
• Large RML lung mass, multiple liver masses
• Image guided liver biopsy
S17‐5512
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S17‐5512 S17‐5512
TTF1
Suspected / known primary siteExample #2b
• **LUNG ANCILLARY TESTING PROTOCOL** Case number: Sxx‐xxxxxx Patient name: xxxx xxxxxxx
HISTOLOGIC TYPE Small cell carcinoma
STAGE IV STATUS Histologically proven stage IV disease
TISSUE BLOCK AVAILABLE FOR ANCILLARY TESTING A1
COMMENT This patient’s sample does NOT meet Allina Lung Cancer Committee criteria* for reflex EGFR,
ALK, ROS1, or PDL1 (for pembrolizumab (Keytruda) eligibility) testing. The block identified above will be stored in pathology for 10 years for possible future ancillary testing. If you would like ALK, EGFR, or any other ancillary tests in the future, please call 612‐863‐4670 (option 2).
*Allina Lung Cancer Committee EGFR, ALK, ROS1, and PDL1 reflex testing criteria: Stage IV disease (histologically proven or clinically suspicious) Adenocarcinoma or TTF‐1 positive adenosquamous cell carcinoma for EGFR, ALK, ROS1, and PDL1 Squamous cell carcinoma or NSCLC, favor squamous cell carcinoma for PDL1.
Suspected / known primary siteExample #3
• 75F, ductal breast CA 2 years earlier
• Stage IIA, ER+, HER2 amplified
• Now develops 5.5 cm liver mass
75F 75F
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75F
ER negative
75F
HER2 3+ positive
Known Primary, final points
• Conserve tissue– Consider splitting cores into separate cassettes
–Minimize IHC, get history, compare
• Comment on background liver tissue, or “no background liver tissue present”
Unknown Primary
• Metastases to cirrhotic liver?
• Metastasis versus cholangiocarcinoma
• Broad workup issues, based on original histologic impression
• Review clinical record carefully
Unknown primary siteExample #1
• 62M, alcoholic cirrhosis, ascites, anasarca, SOB, thrombocytopenia
• Imaging notes multiple liver masses
62M cirrhosis
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62M cirrhosis S17-2406
S17-2406 Unknown primary siteExample #1
• 62M, alcoholic cirrhosis, ascites, anasarca, SOB, thrombocytopenia
• Imaging notes multiple liver masses• IHC:
– Positive: Chromogranin, synaptophysin, cdx2– Negative: Hepar
Unknown Primary
• Undifferentiated large cell malignancy
• Oncocytic large cell malignancy
• Small cell carcinoma/undifferentiated large cell neuroendocrine
• Well differentiated neuroendocrine carcinoma
• Adenocarcinoma
• Spindle cell lesion or overt hematopoietic neoplasm: See other conference!
Unknown Primary• Undifferentiated large cell malignancy:• Cytokeratin cocktail (AE1/AE3/Cam 5.2), CD45, S100, HMB45, CD117, synaptophysin.
Others based on individual features and/or initial immunohistochemistry. May be useful to optimize tissue utilization by pre‐cutting additional unstaineds for immunohistochemistry.
• Oncocytic large cell malignancy:• Cytokeratin cocktail (AE1/AE3/Cam 5.2), Hepar, arginase, S100, HMB45, CD117,
synaptophysin, inhibin.
• Small cell carcinoma/undifferentiated large cell neuroendocrine:• Cytokeratin cocktail (AE1/AE3/Cam 5.2), TTF1, CK7, CK20, synaptophysin,
chromogranin. Consider anorectal squamous carcinoma (aka cloacagenic carcinoma).
• Well differentiated neuroendocrine carcinoma
• Adenocarcinoma
• Spindle cell lesion or overt hematopoietic neoplasm: See other conference!
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Unknown Primary• Undifferentiated large cell malignancy
• Oncocytic large cell malignancy
• Small cell carcinoma/undifferentiated large cell neuroendocrine
• Well differentiated neuroendocrine carcinoma
• Adenocarcinoma:• CK7, CK20, cdx2 &/or CDH17, TTF1. If woman, GATA3, estrogen
receptor. Some use CK17 & CK19 as an adjunct for cholangiocarcinoma (negative & positive, respectively, in many cases) versus metastasis. When the primary is likely upper GI or pancreatobiliary, there is typically a comment regarding likelihood of specific primary site. Of note, cholangiocarcinoma often presents with multiple masses.
• Spindle cell lesion or overt hematopoietic neoplasm: See other conference!
Unknown primary siteExample #2
• 72F, f/u high grade invasive urothelial CA– 5 years ago, treated by TURB & chemo– Imaging shows 4.5 cm liver lesion, gastrohepaticLNs
• EUS FNAB, liver mass and LN• Cystoscopy and CT => normal bladder
72F 72F
72F
CDX2
72F
CK20
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72F
CK7
72F
GATA3
Unknown primary siteExample #2
• 72F, f/u high grade invasive urothelial CA– 5 years ago, treated by TURB & chemo– Imaging shows 4.5 cm liver lesion, gastrohepatic LNs
• EUS FNAB, liver mass and LN• Cystoscopy and CT => normal bladder• Normal upper, lower endoscopy• CPC most c/w cholangiocarcinoma
Therapeutic Resection, CRC
• Confirm CRC• Evaluate margins• Evaluate chemorads effect• Chemotherapy ass’d liver injury
Therapeutic Resection, CRCTRG
• Tumor Regression Grade:TRG1‐ Absence of tumor cells, replaced by fibrosisTRG2‐ Rare scattered tumor cells, abundant fibrosisTRG3‐ Significant residual tumor, predominant fibrosisTRG4‐ Tumor cells predominating over fibrosisTRG5‐ Almost exclusively tumor cells without fibrosis
Annals of Oncology 2007;18:299‐304
Case 1
TRG4
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Case 1
TRG4
Case 2
TRG2
Case 2
Fibrosis
Case 3
TRG1
Case 3
TRG1
Case 4
TRG3
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Therapeutic Resection, CRCTNI
• Tumor Thickness at Tumor‐Normal Interface:"The focus in which the maximum contiguous tumor cell thickness was observed at the TNI {perpendicular to TNI in mm} was measured by a ruler. This focus was composed of uninterrupted layers of tumor cells without admixed fibrotic stroma, acellular mucin, or nonneoplastic liver parenchyma."
Am J Surg Pathol 2010;34:1287‐94
Case 2, TRG 2
TNI 1.5
Case 4, TRG2
TNI 0
Radiologic response ‐ RECIST
Journal of Surgical Oncology 2016;113:456–462
Pathologic response ‐ TRG
Journal of Surgical Oncology 2016;113:456–462
Pathologic response ‐ untreated
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Therapeutic Effect, LiverCALI
Sinusoidal dilatation:SOS 0‐ absentSOS 1‐mild (centrilobular involvement limited to one‐third of the lobular surface)SOS 2‐moderate (centrilobular involvement limited to two‐thirds of the lobular surface)SOS 3‐ severe (complete centrilobular involvement)
Nodular Regenerative Hyperplasia:NRH 0‐ absentNRH 1‐ nodules present but indistinctNRH 2‐ nodules present but only occasionally distinctNRH 3‐ nodules distinct in most examined areas
Fatty Liver Disease:Steatosis %Grade steatohepatitis (Brunt 0‐3)Stage steatohepatitis (Brunt 0‐4) Annals of Oncology 2004;15:460‐6
Ann Surg 2013;258:731‐42
Therapeutic Resection, CRC
• Confirm CRC• Evaluate margins• Evaluate chemorads effect• Chemotherapy ass’d liver injury
F17‐315 F17‐315
F17‐315
Cytokeratin
F17‐315
CD45 (CD20)
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F17‐315
CD138
F17‐315
Kappa ISH
F17‐315
Lambda ISH