hepatic metastases uscap 2 hepatic metastases • common, multiple per day • image guided...

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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


• Image guided (ultrasound, CT)

–Nearly half with adequacy assessment

Hepatic Metastases




• Suspected/known primary site

–Confirm, obtain ancillary predictive studies

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Hepatic Metastases




• Suspected/known primary site

–Confirm, obtain ancillary predictive studies

• Unknown primary site

–Broader evaluation; ddx includes liver primary

Hepatic Metastases


• 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)


• Metastatic adenocarcinoma c/w CRC

• Kras, nras, braf assays wildtype


• 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.


• 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).


• Adenocarcinoma


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Unknown Primary• Undifferentiated large cell malignancy

• Oncocytic large cell malignancy

• Small cell carcinoma/undifferentiated large cell neuroendocrine


• 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.



• 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


• 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

hepatic metastases uscap 2 hepatic metastases • common, multiple per day • image guided...

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