5/23/2014

Mesenchymal Tumors MESENCHYMAL TUMORS OF THE LIVER: Focus on Vascular Tumors WHAT’S NEW AND UNUSUAL
Benign and the “Probably Benign”
Newly-described and variant lesions (MY PERSPECTIVE)
Malignant
Distinction of benign/low grade lesions from Angiosarcoma
CURRENT ISSUES IN ANATOMIC What is NOT Angiosarcoma PATHOLOGY Focus on Angiomyolipoma: Problem MAY 23, 2014 variants that still lead to diagnostic errors
Epithelioid, inflammatory, trabecular Linda Ferrell, MD, UCSF

VASCULAR TUMORS Cavernous Hemangioma Variants The Benign and Probably Benign HEMANGIOMA VARIANTS VASCULAR MALFORMATIONS

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Cavernous Hemangioma (CH) Cavernous Hemangioma

Not true arterial Incidental (Autopsy Giant CH, with organized or venous finding thrombosis and sclerosis architecture

No organized muscle bundles No elastic laminas Not capillary-like

Cavernous Hemangioma: Sclerosis within Cavernous Hemangioma What is often “not seen”….

Sclerosis of
Hemangioma-like vessels (HLV) in thrombosed, ischemic zones adjacent liver commonly seen with giant with scar CH formation.
Ref: Kim GE, Thung SN, Tsui WMS, Ferrell LD. Hepatic Cavernous Hemangioma: Under-Recognized Associated Histologic Features. Liver Int'l, 26:334-38, 2006. “Neo-vessels”
Low mitotic/proliferative rate <5% Recanalized
Present in almost 80% (16/19) of CH >5 cm channels
Retain composition of vascular walls in CH

2 5/23/2014

Cavernous Hemangioma-like vessels in Giant Cavernous Hemangioma adjacent liver

Giant Cavernous Hemangioma Giant Cavernous Hemangioma

Explant, right Left Lobe: lobe Smaller, irregularly 38 yr old shaped CHs and woman, in liver transitional areas failure. with HLVs admixed with liver

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“Metatastatic” and “Invasive” Giant Cavernous Hemangioma Cavernous Hemangioma

Lesion extending into hilum around Right Lobe CH Left lobe HLV Omental Lesion arteries, nerves and ducts

Nerve Duct Artery

Cavernous Hemangioma Variant Vascular Malformations

Diagnoses: Giant Cavernous Hemangioma and
Hereditary Hemorrhagic Telangiectasia Cavernous Hemangiomatosis
CH-like vessels throughout liver, involving (HHT) arterial-venous malformations hilum
also known as Osler-Weber-Rendu
Lung, spleen, omentum involved with CH-like lesions
Other Arterial and Venous Malformations Problematic cavernous hemangioma variants and other benign mimics: with similar features A Mattis, S Fischer, H Makhlouf, W Tsui, S Cho, L Ferrell. Poster at USCAP Mar 2010, published Mod Pathol Supple 1, 2010.
(may or may not be HHT)

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Vascular Malformations Vascular Malformations

Contributors and co-authors of 2 abstracts :
Cho S, Paradis V, Pai R, Bioulac-Sage P, Alves V, Souza T, Spectrum: Early or mild lesions can look Makhlouf H, Schirmacher P, Evason K, Ferrell L. Early, mild much different than advanced or Histopathologic Features of Extensive Hepatic Vascular severe lesions probably primarily Malformations. Mod Path 23 (Supple 1):352A, 2010. To due to thrombosis and ischemic Late, severe
Cho S, Wanless I, Sempoux C, Paradis V, Pai R, Thung S, effects Bioulac-Sage P, Balabaud C, Makhlouf H, Schirmacher P Alves V, Souza T, Evason K, Ferrell L. FNH-Like Lesions and Glutamine Synthetase Expression in the Liver in Hereditary Hemorrhagic Telangiectasia. Mod Path, 24 (Supple 1):358A, 2011.

Vascular Malformations: Vascular Malformations: Early Lesions or Mild Involvement More Severe or Advanced Lesions

Periportal fibrosis, Elastochrome Periductal fibrosis (as early Thrombosis within vessels and Extension of lesions into sinusoids stain ischemic lesion) sinusoids

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Vascular Malformations Vascular Malformations: Severe sinusoidal changes More Severe or Advanced Lesions

Hemangioma-like changes, Cavernous hemangioma-like extensive sinusoidal dilation transformationn

Small Vessel Hemangioma Small Vessel Hemangioma

Small channels, thin walls, Rare Small vascular channels with thin Only focal fibrotic areas walls bland nuclei (no wide walls as in CH)
Bland endothelial cells with low Newly proliferative rate <10% (CH <5%) described
Intermediate tumor cell density
Irregular “infiltrative” growth pattern at border
abnormal liver architecture mimics HCC
scaffolding effect mimics angiosarcoma

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Small Vessel Hemangioma Small Vessel Hemangioma

Small channels with thin walls, no Center of lesion, bland Edge of lesion, with organized muscle Low Mib1 (Ki-67) rate endothelial cells altered cell plate width

Small Vessel Hemangioma Small Vessel Hemangioma

Small vessel hepatic hemangioma (SVH): Exact outcome not Edge of lesion, trichrome Edge of lesion, reticulin definitive, so now recommending excision and followup.
Differentiation from angiosarcoma: AS has higher proliferative rate (>15%) and subset + for P53 and GLUT1, but negative in small vessel hemangioma

References
Gill R, Sempoux C, Makhlouf H, Thung S, Alves V, Ferrell L. Small Vessel Hepatic Hemangioma Variant in Adult Liver. Mod Pathol 25(Supple 2): 413A, 2012.
Gill R, et al. GLUT-1 expression in adult hepatic vascular neoplasms. Mod Pathol 26(Supple 2): 2013.

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Epithelioid Hemangioendothelioma

Malignant Vascular Tumors Epithelioid Hemangioendothelioma

Epithelioid Hemangioendothelioma Epithelioid Hemangioendothelioma

Elastochrome stain*, Angiosarcoma- like pattern of scaffolding growth Central vein invasion central vein invasion

*Elastochrome: trichrome plus EVG stain; highlights vein wall elastic fibers

8 5/23/2014

Angiosarcoma

Angiosarcoma
Most aggressive form of vascular malignancy
Highest proliferative rate
Epithelioid or spindle cell forms
Cystic and/or solid
Known for the typical feature of “scaffolding” growth pattern

Angiosarcoma Angiosarcoma

Epithelioid pattern High MiB1 (Ki-67) rate

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Angiosarcoma Angiosarcoma

Scaffolding growth pattern CD34 and expanded along sinusoids sinusoidal growth Cystic change Congestion Necrosis Sinusoidal growth

Angiosarcoma (higher magnification) Angiosarcoma

Cystic change Scaffolding (upper right) pattern of growth Congestion surrounds Necrosis hepatocytes Sinusoidal growth

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Angiosarcoma Angiosarcoma

Scaffolding Scaffolding pattern of pattern of growth growth with surrounds fibrosis of cell hepatocytes plate areas

Angiosarcoma Angiosarcoma: Highlights

High proliferative rate and cytologic atypia Sinusoidal growth
results in - Early pattern of growth typically along sinusoids anastomosing (scaffold-like); Atypical endothelial cells, dilated channels and sinusoids pseudopapillary
- Later pattern of growth can be pseudopapillary to pattern solid; irregularly-shaped blood filled spaces
- Lacks the stromal prominence of epithelioid hemangioendothelioma, but overlapping cases may be seen

11 5/23/2014

Undifferentiated (Embryonal) Sarcoma

Typically younger patients; tumor of uncertain etiology What else is NOT angiosarcoma Can be cystic due to necrosis/degeneration with irregular edges!! (Pattern similar to angiosarcoma scaffolding) Immunohistochemistry Undifferentiated (Embryonal)
Reactive with alpha-1-antitrypsin, alpha-1- antichymotrypsin, Sarcoma of the Liver vimentin
Occasional cytokeratin positivity
Some CD10 and p53 positivity
Negative hepatocyte-Ab, muscle, S-100 and CD34
Ref: Kiani B, Ferrell LD, Qualman S, Frankel WL. Immunohistochemical Analysis of Embryonal Sarcoma of the Liver. Applied Immunohistochem Mol Morphol 14:193-7, 2006.
Glypican-3 can be positive in giant cells (personal observation)

Undifferentiated (Embryonal) Sarcoma Undifferentiated (Embryonal) Sarcoma

Cystic areas common Related to extensive necrosis (right upper area)

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Undifferentiated sarcoma, tumor edge Undifferentiated Embryonal Sarcoma with growth along sinusoids

PASD + globules Also Alpha-1-antitrypsin + Problem with Literature Search
Int J Surg Pathol. 2012 Jun;20(3):297-300. Embryonal (undifferentiated) sarcoma of the liver with peripheral angiosarcoma differentiation….
THIS IS NOT THE CORRECT DIAGNOSIS as per three expert consultants
Authors got confused about peripheral growth

Problem Case

Angiomyolipoma  37-year-old woman  11 cm pedunculated Problem variants mass Epithelioid, Trabecular, and  No cirrhosis or other Inflammatory risk factors for HCC  Mass noted during routine gynecologic exam, no symptoms

13 5/23/2014

HCA, HCC? Reticulin Stain

Reticulin Stain: too much loss for HCA HCC or Not?

14 5/23/2014

Keratin and HMB-45 Angiomyolipoma, epithelioid variant

Ref: Tsui WMS, et al. Hepatic Angiomyolipoma: Delineation of Unusual Morphological Variants. Amer J Surg Pathol, 23:34-48, 1999.

Angiomyolipoma Angiomyolipoma

Classic Epithelioid Cells Spindle Cells features:

Fat, Epithelioid, Spindle cells

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Problem Case: Angiomyolipoma Trabecular Angiomyolipoma

HMB-45: stains stronger SMA: usually stains on epithelioid cells spindle cells HMB-45

Problem case: Problem case: Angiomyolipoma Inflammatory Angiomyolipoma Inflammatory and Trabecular

Focal dense to scattered diffuse T-cell infiltrate Case with both inflammatory and “trabecular” background

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Problem case: Angiomyolipoma, Angiomyolipoma, Mixed variant Inflammatory and Trabecular

HMB-45 SMA Fatty areas Trabecular areas

Angiomyolipoma, Mixed variant Angiomyolipoma, Mixed variant

Inflammatory areas, 10x HMB-45 Inflammatory foci with absent staining (SMA only rare + cell, not shown)

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SPECIAL THANKS TO ALL WHO HAVE CONTRIBUTED TO THE REFERENCED STUDIES: WE WOULDN’T HAVE THIS DATA WITHOUT THESE COLLABORATION

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