Difference between revisions of "Liver neoplasms"

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[[Image:Secondary tumor deposits in the liver from a primary cancer of the pancreas.jpg|thumb|right|300px|Liver metastases at [[gross pathology|gross]].]]
This article examines '''liver neoplasms''' and '''pre-malignant lesions of the liver'''.  In North America, most malignant liver lesions are [[liver metastasis|metastases]].
This article examines '''liver neoplasms''' and '''pre-malignant lesions of the liver'''.  In North America, most malignant liver lesions are [[liver metastasis|metastases]].


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===Malignant lesions of the liver===
===Malignant lesions of the liver===
*[[Hepatocellular carcinoma]] (HCC) - most common malignant liver primary in adults.
*[[Hepatocellular carcinoma]] (HCC) - most common malignant liver primary in adults.
*Hepatoblastoma - malignant liver primary in children.  
*[[Hepatoblastoma]] - malignant liver primary in children.  
*Intrahepatic cholangiocarcinoma (ICC).<ref name=pmid19212669>{{Cite journal  | last1 = Shirakawa | first1 = H. | last2 = Kuronuma | first2 = T. | last3 = Nishimura | first3 = Y. | last4 = Hasebe | first4 = T. | last5 = Nakano | first5 = M. | last6 = Gotohda | first6 = N. | last7 = Takahashi | first7 = S. | last8 = Nakagohri | first8 = T. | last9 = Konishi | first9 = M. | title = Glypican-3 is a useful diagnostic marker for a component of hepatocellular carcinoma in human liver cancer. | journal = Int J Oncol | volume = 34 | issue = 3 | pages = 649-56 | month = Mar | year = 2009 | doi =  | PMID = 19212669 | url = http://www.spandidos-publications.com/serveFile/ijo_34_3_649_PDF.pdf?type=article&article_id=ijo_34_3_649&item=PDF}}</ref>
*Intrahepatic [[cholangiocarcinoma]] (ICC).<ref name=pmid19212669>{{Cite journal  | last1 = Shirakawa | first1 = H. | last2 = Kuronuma | first2 = T. | last3 = Nishimura | first3 = Y. | last4 = Hasebe | first4 = T. | last5 = Nakano | first5 = M. | last6 = Gotohda | first6 = N. | last7 = Takahashi | first7 = S. | last8 = Nakagohri | first8 = T. | last9 = Konishi | first9 = M. | title = Glypican-3 is a useful diagnostic marker for a component of hepatocellular carcinoma in human liver cancer. | journal = Int J Oncol | volume = 34 | issue = 3 | pages = 649-56 | month = Mar | year = 2009 | doi =  | PMID = 19212669 | url = http://www.spandidos-publications.com/serveFile/ijo_34_3_649_PDF.pdf?type=article&article_id=ijo_34_3_649&item=PDF}}</ref>
*Combined hepatocellular carcinoma and intrahepatic cholangiocarcinoma (CHC).
*Combined hepatocellular carcinoma and intrahepatic cholangiocarcinoma (CHC).


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*[[Metastasis]].
*[[Metastasis]].
*[[Cholangiocarcinoma]].
*[[Cholangiocarcinoma]].
*[[Hemangioma]].
*[[Liver hemangioma]].


===Tabular comparison===
===Tabular comparison===
Line 70: Line 71:
! Images
! Images
|-
|-
| Hepatic [[hemangioma]]
| [[Hepatic hemangioma]]
| similar to normal liver parenchyma, red (hemorrhagic), well-circumscribed
| similar to normal liver parenchyma, red (hemorrhagic), well-circumscribed
| spaces lined by benign endothelial cells
| spaces lined by benign endothelial cells
Line 104: Line 105:
| multiple, white lesions
| multiple, white lesions
| variable, usu. tubular (glandular) with pseudostratified hyperchromatic nuclei
| variable, usu. tubular (glandular) with pseudostratified hyperchromatic nuclei
| CK7-, [[CK20]]-, HepPar-1-, CK19-
| CK7-, [[CK20]]+ (colorectal), HepPar-1-, [[CK19]]-
| [[colorectal carcinoma]] most common
| [[colorectal carcinoma]] most common
| [[Image:Secondary_tumor_deposits_in_the_liver_from_a_primary_cancer_of_the_pancreas.jpg | thumb| center| 150px| Metastases. (WC)]]
| [[Image:Secondary_tumor_deposits_in_the_liver_from_a_primary_cancer_of_the_pancreas.jpg | thumb| center| 150px| Metastases. (WC)]]
Line 178: Line 179:


=Benign hepatic neoplasms=
=Benign hepatic neoplasms=
==Bile duct hamartoma==
A. [[File:1 BDH 1 680x512px.tif|Trichrome shows fibrous spaces with dilated ducts (20X).]]
B. [[File:2 BDH 1 680x512px.tif|Bizarre, ramifying tubules with dilatations (100X).]]
<br>
C. [[File:3 BDH 1 680x512px.tif|Bland epithelial linings (400X).]]
D. [[File:4 BDH 1 680x512px.tif|Surrounding tract with tortuous bile ducts & inflammation, likely secondary to hamartomas (200X).]]
Bile duct hamartomas. A. Trichrome shows fibrous spaces with dilated ducts. B. Bizarre, ramifying tubules with dilatations. C. Bland epithelial linings. D. Surrounding tract with tortuous bile ducts & inflammation, likely secondary to hamartomas.
==Bile duct adenoma==
==Bile duct adenoma==
:''Should '''not''' be confused with [[bile duct hamartoma]].''
:''Should '''not''' be confused with [[bile duct hamartoma]].''
Line 184: Line 195:
==Hepatic adenoma==
==Hepatic adenoma==
*[[AKA]] ''hepatocellular adenoma'', abbreviated ''HCA''.
*[[AKA]] ''hepatocellular adenoma'', abbreviated ''HCA''.
===General===
{{Main|Hepatic adenoma}}
*Grow under the influence of sex hormones.
**Associated with ''[[oral contraceptive pill]]'' (OCP) use<ref name=Ref_WMSP221>{{Ref WMSP|221}}</ref><ref name=pmid221698>{{Cite journal  | last1 = Rooks | first1 = JB. | last2 = Ory | first2 = HW. | last3 = Ishak | first3 = KG. | last4 = Strauss | first4 = LT. | last5 = Greenspan | first5 = JR. | last6 = Hill | first6 = AP. | last7 = Tyler | first7 = CW. | title = Epidemiology of hepatocellular adenoma. The role of oral contraceptive use. | journal = JAMA | volume = 242 | issue = 7 | pages = 644-8 | month = Aug | year = 1979 | doi =  | PMID = 221698 }}</ref> - may regress with discontinuation.
**May rupture in [[pregnancy]].
*Usually diagnosed by radiology.
 
===Gross===
Features:<ref>STC S.20, 19 Jan 2009.</ref>
*Often subcapsular location.
*Well circumscribed, but not encapsulated.
 
===Microscopic===
Features:
*Sheets or cords of cells with mild variation of cell and nuclear size.<ref name=Ref_PBoD923>{{Ref PBoD|923}}</ref>
*Cords of cells upto 3 cells thick.<ref>STC S.19, 19 Jan 2009.</ref>
*Cells may have cytoplasmic clearing due to glycogen or be pale - '''obvious if seen'''.
*Vascular - large arteries, dilated thin-walled veins.
 
Negatives:
*No bile ducts.
*No portal tracts.
*No cirrhosis!  If cirrhosis is present it isn't a hepatic adenoma - '''important'''.
 
DDx:
*Well-differentiated [[hepatocellular carcinoma]].<ref>SN. 29 May 2009.</ref>
**Hepatic adenoma is differentiated from ''well-differentiated HCC'' by its architecture; adenomas have cords of cells upto 3 cells thick & have preserved reticulin architecture.
*[[Focal nodular hyperplasia]].
 
====Images====
<gallery>
Image:Hepatic_adenoma_low_mag.jpg | Hepatic adenoma. (WC/Nephron)
Image:Hepatic_adenoma_low_mag_reticulin.jpg | Hepatic adenoma - reticulin. (WC/Nephron)
</gallery>
www:
*[http://www.ajronline.org/cgi/content-nw/full/182/6/1520/FIG3 Hepatic adenoma (ajronline.org)].
*[http://radiographics.rsna.org/content/22/5/1023.figures-only Series of liver micrographs including hepatic adenoma (radiographics.rsna.org)].
 
====Subclassification====
Based on molecular changes:<ref>{{Cite journal  | last1 = Katabathina | first1 = VS. | last2 = Menias | first2 = CO. | last3 = Shanbhogue | first3 = AK. | last4 = Jagirdar | first4 = J. | last5 = Paspulati | first5 = RM. | last6 = Prasad | first6 = SR. | title = Genetics and imaging of hepatocellular adenomas: 2011 update. | journal = Radiographics | volume = 31 | issue = 6 | pages = 1529-43 | month = Oct | year = 2011 | doi = 10.1148/rg.316115527 | PMID = 21997980 }}</ref><ref name=pmid21883740>{{Cite journal  | last1 = Sasaki | first1 = M. | last2 = Yoneda | first2 = N. | last3 = Kitamura | first3 = S. | last4 = Sato | first4 = Y. | last5 = Nakanuma | first5 = Y. | title = Characterization of hepatocellular adenoma based on the phenotypic classification: The Kanazawa experience. | journal = Hepatol Res | volume = 41 | issue = 10 | pages = 982-8 | month = Oct | year = 2011 | doi = 10.1111/j.1872-034X.2011.00851.x | PMID = 21883740 }}</ref>
#Inflammatory hepatic adenoma.
#*[[AKA]] ''telangiectatic adenoma''.<ref>{{Cite journal  | last1 = Maylee | first1 = H. | last2 = Harada | first2 = K. | last3 = Igarashi | first3 = S. | last4 = Tohda | first4 = G. | last5 = Yamamoto | first5 = M. | last6 = Ren | first6 = XS. | last7 = Osawa | first7 = T. | last8 = Hasegawa | first8 = Y. | last9 = Takahashi | first9 = N. | title = Case of telangiectatic/inflammatory hepatocellular adenoma arising in a patient with primary sclerosing cholangitis. | journal = Hepatol Res | volume = 42 | issue = 6 | pages = 611-8 | month = Jun | year = 2012 | doi = 10.1111/j.1872-034X.2011.00962.x | PMID = 22568458 }}
</ref>
#*Associated with obesity.{{fact}}
#Hepatocyte nuclear factor 1 alpha-mutated hepatic adenoma.
#*Inactivating mutation.
#Beta-catenin-mutated hepatic adenoma
#*Activating mutation.
#Unclassified hepatic adenoma.
 
Note:
*Beta-catenin is considered an oncogene.
 
===IHC===
*AFP -ve. (???)
*HNF1alpha +ve/-ve.
*Beta-catenin +ve/-ve.


==Hepatobiliary mucinous cystadenoma==
==Hepatobiliary mucinous cystadenoma==
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Features:
Features:
*Cystic spaces lined by a mucinous epithelium (simple columnar epithelium with a clear cytoplasm).
*Cystic spaces lined by a mucinous epithelium (simple columnar epithelium with a clear cytoplasm).
*Surrounding dense ovarian like stroma.
DDX:
[[Biliary Intraductal Papillary Neoplasm]]
*no surrounding ovarian stroma
*Intraductal - connects with the biliary tree lumen.


Note:
Note:
*Similar to [[pancreatic mucinous cystadenoma]].
*Similar to [[pancreatic mucinous cystadenoma]].
==Cavernous hemangioma==
A. [[File:1 CAV 1 680x512px.tif|Fibrous foci with increased spaces, hepatocyte focus with nonspecific fibrotic bridge (40X).]]
B. [[File:2 CAV 1 680x512px.tif|Cavernous hemangioma with flat, non-atypical endothelium (200X).]]
<br>
C. [[File:3 CAV 1 680x512px.tif|Tortuous bile ducts/ductules, not to be considered generalized in presence of mass (200X).]]
D. [[File:4 CAV 1 680x512px.tif|Tortuous bile ductsductules, not to be considered generalized in presence of mass (200X).]]
Cavernous hemangioma. A. Fibrous foci with increased spaces, hepatocyte focus with nonspecific fibrotic bridge. B. Cavernous hemangioma with flat, non-atypical endothelium. C. Tortuous bile ductules, not to be considered generalized in presence of mass. D. Tortuous bile ducts, not to be considered generalized in presence of mass.


=Malignant hepatic neoplasms=
=Malignant hepatic neoplasms=
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*Abbreviated ''HCC''.
*Abbreviated ''HCC''.
{{Main|Hepatocellular carcinoma}}
{{Main|Hepatocellular carcinoma}}
==Biliary Intraductal Papillary Neoplasm<ref>{{Cite journal  | Masayuki Ohtsuka, Hiroaki Shimizu, Atsushi Kato, et al., “Intraductal Papillary Neoplasms of the Bile Duct,” International Journal of Hepatology, vol. 2014, Article ID 459091, 10 pages, 2014. doi:10.1155/2014/459091}}</ref>==
===General===
*Rare
*Highest incidence in Far Eastern countries
*Association with hepatolithiasis and clonorchiasis
*Between 50 and 70 years of age
*Slight male predominance
*Intermittent abdominal pain
*Acute cholangitis
*Jaundice
*Biliary counterpart of [[pancreatic intraductal papillary mucinous neoplasm]]
*Biliary counterpart of [[intracholecystic papillary neoplasm]] (gall bladder)
*Construct consumes some cases of biliary cystadenoma/cystadenocarcinoma, biliary papilloma/papillomatosis, intraductal growth type of cholangiocarcinoma and papillary carcinoma of the extrahepatic bile duct.
===Radiology===
*Bile duct dilatation
*Intraductal masses
===Gross===
*Singular, or occasionally multiple, polypoid masses extending into the lumen of a dilated bile duct
*Or multilocular well-defined cystic mass containing mucinous fluid
*Granular or papillary mucosa
*Communication with bile duct may be difficult to confirm
===Microscopic===
*Papillary or villous growth within the lumen of an intra or extrahepatic bile duct
*Papillary fronds with fine vascular cores
*Epithelium types
**Pancreatobiliary
**Intestinal - marked mucin secretion
**Gastric
**Oncocytic types
*Dysplasia
**High or low grade
**Marked variation in histologic grade between different regions of individual tumors
*Common association with invasive cholangiocarcinoma
**Tubular adenocarcinoma
**Mucinous (colloid) carcinoma (often in association with the intestinal type).
====DDX====
*[[Biliary Mucinous Cystic Neoplasm]]
***Epithelium is surrounded by a distinct ovarian-like stroma.
====Photos====
<gallery>
Image:BileDuct IntraductalPapillaryNeoplasm LP CTR.jpg|Bile Ducts - Intraductal Papillary Neoplasm - Low power (SKB)
Image:BileDuct IntraductalPapillaryNeoplasm MP CTR.jpg|Bile Ducts - Intraductal Papillary Neoplasm - Medium power (SKB)
Image:BileDuct IntraductalPapillaryNeoplasm HP CTR.jpg|Bile Ducts - Intraductal Papillary Neoplasm - High power (SKB)
Image:BileDucts IntraductalPapillaryNeoplasm NonMucinousType LP PA.jpg|Bile Ducts - Intraductal Papillary Neoplasm - Low power (SKB)
Image:BileDucts IntraductalPapillaryNeoplasm OncocyticType HP PA.jpg|Bile Ducts - Intraductal Papillary Neoplasm - High power (SKB)
Image:BileDucts IntraductalPapillaryNeoplasm NonMucinousType HP2 PA.jpg|Bile Ducts - Intraductal Papillary Neoplasm - High power (SKB)
</gallery>
A. [[File:1 papillary cbd aca 1 680x512px.tif| Intraductal papillary neoplasm of common bile duct with associated invasive carcinoma.]]
B. [[File:2 papillary cbd aca 1 680x512px.tif| Intraductal papillary neoplasm of common bile duct with associated invasive carcinoma.]]
<br>
C. [[File:3 papillary cbd aca 1 680x512px.tif| Intraductal papillary neoplasm of common bile duct with associated invasive carcinoma.]]
D. [[File:4 papillary cbd aca 1 680x512px.tif| Intraductal papillary neoplasm of common bile duct with associated invasive carcinoma.]]
<br>
E. [[File:5 papillary cbd aca 1 680x512px.tif| Intraductal papillary neoplasm of common bile duct with associated invasive carcinoma.]]
F. [[File:6 papillary cbd aca 1 680x512px.tif| Intraductal papillary neoplasm of common bile duct with associated invasive carcinoma.]]
Intraductal papillary neoplasm of common bile duct with associated invasive carcinoma. A. The papillary tumor comprises mostly variably dilated acini. B. Tumor also shows areas of micropapillae. C. Some areas within the non-invasive tumor showed necrosis, with the black pyknotic nuclei amid red debris. D. Definite invasion was established low power by glands headed in perpendicular directions. E. Embedded in fibroblastic response are non-acinar walls and isolated epithelial groups. F. Also embedded in fibroblastic response are flat glands with nuclei showing loss of polarity (lack of respect for lateral intercellular borders shown by variable orientation to base of gland).
Notes -
*Reflect on the known marked variation in histologic grade between different regions of individual tumors when rendering an opinion on a small biopsy specimen.
*Consider the possibility of an invasive component and submit tissue generously.
See also:
PubCan [http://www.pubcan.org/printicdotopo.php?id=5755]


==Cholangiocarcinoma==
==Cholangiocarcinoma==
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==Hepatic metastasis==
==Hepatic metastasis==
{{Main|Liver metastasis}}
*[[AKA]] ''liver metastases''.
*[[AKA]] ''liver metastases''.
*[[AKA]] ''metastatic liver disease''.
*[[AKA]] ''metastatic liver disease''.
===General===
==Hematopoietic tumors==
*Metastases are very common - often from the gastrointestinal tract, e.g. [[colorectal cancer]]. 
A [[File:1 MM 1 Covenant 680x512px.tif|One liver core was normal (Row 1 Left 40X).]]
**Most liver masses in are not biopsied... as a primary lesion is evident.<ref>OA. 29 November 2009.</ref>
<br>
*Dependent on the extent of disease, [[CRC]] metastatic to the liver may be curable with a liver resection.
B [[File:2 MM 1 Covenant 680x512px.tif|A triad with a proliferated bile ductule, otherwise normal (Row 1 Right 400X).]]
**Peritoneal disease, i.e. a malignant peritoneal nodule, in the context of liver metastases does poorly, and is considered a contraindication to liver resection.<ref name=pmid8511077>{{Cite journal  | last1 = Elias | first1 = D. | last2 = Rougier | first2 = P. | last3 = Mankarios | first3 = H. | last4 = Fahrat | first4 = F. | last5 = Lasser | first5 = P. | title = [Resectable liver metastases and synchronous extra-hepatic sites of colorectal origin. Surgical indications]. | journal = Presse Med | volume = 22 | issue = 11 | pages = 515-20 | month = Mar | year = 1993 | doi =  | PMID = 8511077 }}
<br>
</ref>
C [[File:3 MM 1 Covenant 680x512px.tif|The other core showed a mass of tumor mashed against normal liver (Row 2 Left 40X).]]
*It is important to consider [[germ cell tumour]]s in the DDx as these may be curable with chemotherapy.
<br>
*Clear cell variant of HCC may be misdiagnosed as metastatic [[clear cell carcinoma]].
D [[File:4 MM 1 Covenant 680x512px.tif|Tumor cells showed round to ovoid nuclei without pattern and with grey cytoplasm that proved to be CD138 positive (Row 2 Right 400X).]]
*Interhepatic cholangiocarcinoma is an adenocarcinoma - it may look like a metastatic lesion.
<br>
<br>
Further reading:
Plasmacytoma appearing as a tumor mass. A. One liver core was normal. B. A triad with a proliferated bile ductule, otherwise normal. C. The other core showed a mass of tumor mashed against normal liver. D. Tumor cells showed round to ovoid nuclei without pattern and with grey cytoplasm that proved to be CD138 positive.
*{{Cite journal  | last1 = Anders | first1 = RA. | last2 = Kamel | first2 = IR. | title = Biopsy considerations in the diagnosis of hepatic masses. | journal = Clin Gastroenterol Hepatol | volume = 5 | issue = 5 | pages = 541-4 | month = May | year = 2007 | doi = 10.1016/j.cgh.2007.02.028 | PMID = 17478344 }}


===Gross pathology/radiology===
A. [[File:1 B cell lym liver 1 680x512px.tif|Apparent inflamed fibrous tract with lobular inflammatory collections in adjacent liver (Row 1 Left 40X).]]
*Multifocal or solitary.
<br>
**Classically multifocal.
B. [[File:2 B cell lym liver 1 680x512px.tif|Apparent inflamed fibrous band between two relatively hepatocyte regions (Row 1 Right 40X).]]
<br>
C. [[File:3 B cell lym liver 1 680x512px.tif|Apparent piecemeal necrosis with bile ductular proliferation (Row 2 Left 200X).]]
<br>
D. [[File:4 B cell lym liver 1 680x512px.tif|Apparent portal inflammation with unaffected interlobular bile duct (Row 2 Right 200X).]]
<br>
E. [[File:5 B cell lym liver 1 680x512px.tif|Apparent lobular infiltrate with small masse.]]
<br>
F. [[File:6 B cell lym liver 1 680x512px.tif|Proof is at high power. All cells are similar to macrophages but are too closely crowded to be macrophages. The monomorphism (one type of cell) should inspire immunohistochemical stains, which showed the patient had a B cell lymphoma.]]
<br>
B cell lymphoma mimicking hepatitis with fibrosis. A. Apparent inflamed fibrous tract with lobular inflammatory collections in adjacent liver. B. Apparent inflamed fibrous band between two relatively hepatocyte regions. C. Apparent piecemeal necrosis with bile ductular proliferation. D. Apparent portal inflammation with unaffected interlobular bile duct. E. Apparent lobular inflammation with collections a bit too large for usual lobular inflammation.  F. Proof is at high power. All cells are similar to macrophages but are too closely crowded to be macrophages. The monomorphism (one type of cell) should inspire immunohistochemical stains, which showed the patient had a B cell lymphoma.


<gallery>
[[File:5 02965636298621 sl 1.png|Malignant B cell lymphoma, NOS, in a 63 year old man’s liver]]
Image: Secondary_tumor_deposits_in_the_liver_from_a_primary_cancer_of_the_pancreas.jpg |Hepatic metastases (pancreas). (WC)
[[File:5 02965636298621 sl 2.png|Malignant B cell lymphoma, NOS, in a 63 year old man’s liver]]
</gallery>
[[File:5 02965636298621 sl 3.png|Malignant B cell lymphoma, NOS, in a 63 year old man’s liver]]
 
[[File:5 02965636298621 sl 4.png|Malignant B cell lymphoma, NOS, in a 63 year old man’s liver]]
===Microscopic===
[[File:5 02965636298621 sl 31.png|Malignant B cell lymphoma, NOS, in a 63 year old man’s liver]]
Features:
[[File:5 02965636298621 sl 6.png|Malignant B cell lymphoma, NOS, in a 63 year old man’s liver]]
*Histologic features are dependent on primary and degree of differentiation.
<br>
The classic liver metastasis ([[colorectal carcinoma]]):
Malignant B cell lymphoma, NOS, in a 63 year old man’s liver. No other specimens were available for further classification. A. Tumor expands a triad and occupies parenchymal regions. B. Bounding a bile duct, modestly sized round to reniform lymphoid cells, many without nucleoli, accompany small round lymphocytes. Some of the larger cells have clefts (arrows). C. CD3 stain shows many of the lymphoid cells are intercalated reactive T cells. D. Ki67 shows less than half the tumor cells, mostly the larger ones, are in proliferative phase, arguing against the notion of a high grade B cell lymphoma. E. CD79A establishes B cell phenotype (CD20 was also positive). F. That the tumor cells are BCL2 positive evinces B cell neoplasia. The cells were CD10, BCL6, and cyclin D1 negative, militating against mantle cell lymphoma and CLL, with no follicular origin identified.
*Gland forming columnar shaped cells with pseudostratified hyperchromatic cigar-shaped nuclei.
 
DDx:
*[[Cholangiocarcinoma]].
*[[Hepatocellular carcinoma]], pseudoglandular.<ref name=pmid2440554>{{Cite journal  | last1 = Kondo | first1 = Y. | last2 = Nakajima | first2 = T. | title = Pseudoglandular hepatocellular carcinoma. A morphogenetic study. | journal = Cancer | volume = 60 | issue = 5 | pages = 1032-7 | month = Sep | year = 1987 | doi =  | PMID = 2440554 }}</ref>
 
====Image====
<gallery>
Image:Adenocarcinoma_liver_metastasis.jpg | Liver metastasis - adenocarcinoma. (WC/Nephron)
</gallery>
 
===IHC===
*Metastases are typically negative for ''HepPar-1''.
**HepPar-1 (hepatocytes paraffin antibody 1) - labels hepatocellular mitochondria.<ref name=pmid12502967>The diagnostic value of hepatocyte paraffin antibody 1 in differentiating hepatocellular neoplasms from nonhepatic tumors: a review. Lamps LW, Folpe AL. Adv Anat Pathol. 2003 Jan;10(1):39-43. Review. PMID 12502967.</ref>
 
Note:
*If a primary is already established by pathology and the clinical impression is a metastasis, it isn't necessary to do IHC if the morphology of the lesion in the liver is compatible with the established primary.
===Sign out===
<pre>
LIVER, PORTION OF SEGMENTS 2 AND 3, RESECTION:
- METASTATIC ADENOCARCINOMA.
-- RESECTION MARGIN CLEARANCE 2 MM.
- LIVER STEATOSIS, MILD.
</pre>
 
====Micro====
The section show liver parenchyma with an invasive adenocarcinoma. The adenocarcinoma
has well formed glands with dirty necrosis.  The nuclei are appear crowded and
have an ellipsoid shape.  Focally, zones of necrosis are present. See background liver.


BACKGROUND LIVER (BASED ON H&E ONLY)<br>
[[File:4 89735893919405 sl 1.png| High grade B cell lymphoma involving liver]]
Fibrosis: not identified.<br>
[[File:4 89735893919405 sl 2.png| High grade B cell lymphoma involving liver]]
Fibrous septa: absent.<br>
[[File:4 89735893919405 sl 3.png| High grade B cell lymphoma involving liver]]
Septa with curved contours: absent.<br>
[[File:4 89735893919405 sl 4.png| High grade B cell lymphoma involving liver]]
Large droplet steatosis (% of hepatocytes): mild (20%).<br>
[[File:4 89735893919405 sl 5.png| High grade B cell lymphoma involving liver]]<br>
Ballooning of hepatocytes: not identified.<br>
High grade B cell lymphoma involving liver in a 77 year old woman. A. A band of cancer abuts fibrotic liver with steatosis. B. Cancer cells show primitive, round to ovoid, variably sized, dark nucleoli and an aberrant mitoses. Cytoplasm is scant. C. Cancer cells are CD79a positive. D. Most cancer cell nuclei were positive for Ki-67, overall about 80%. E. A minority of cancer cells are CD10 positive.
Mallory-Denk bodies: not identified.<br>
Portal inflammation: present, mild.<br>
Interface activity: not identified.<br>
Lobular necroinflammation: not identified.<br>
Ducts: present in normal numbers.<br>
Duct injury: not identified.<br>
Ductular reaction: not identified.<br>
Cholestasis: present peritumoural, otherwise absent.<br>
Terminal hepatic venules: present.<br>
Ground glass cells with routine stains: not identified.


=See also=
=See also=

Latest revision as of 23:15, 31 January 2017

Liver metastases at gross.

This article examines liver neoplasms and pre-malignant lesions of the liver. In North America, most malignant liver lesions are metastases.

This article focuses on primary malignancies of the liver, neoplastic liver lesions, and biliary malignancies. It only briefly discusses metastatic lesions. An introduction to liver pathology is in the liver article. Medical liver disease is dealt with in the medical liver disease article.

Overview

Dysplasic lesions of the liver

Types:[1]

  • "Large cell dysplasia" (AKA large cell change) - not considered a precursor for HCC, not considered a dysplasia.[2]
  • Small liver cell dysplasia (AKA small cell dysplasia).
  • Low grade dysplasia.
  • High grade dysplasia.

Neoplastic lesions

Malignant lesions of the liver

Lesions that arise in a non-cirrhotic liver

Hepatocellular:

Other:

Tabular comparison

Precursors

Features of HCC & its precursors - generated from DCHH[4] and STC:

Features SLCD Low-grade dysplasia High-grade dysplasia HCC
Plate thickness <3 cells <=2 cells <=3 cells, usu. >2 cells >3 cells
Reticulin (stain) intact chicken wire intact chicken wire intact chicken wire damaged chicken wire
Nuclear changes nuc. enlargement,
hyperchromasia		 +/- atypia (???) marked atypia +/- incr. NCR,
+/-irreg. nuc. contour
Cytoplasmic change hyperchromasia, decr. as
cell size preserved		 none (???) +/- basophilia variable (lighter vs. hyperchromasia)
Portal tracts ? loss of portal tracts loss of portal tracts loss of portal tracts
Management follow ??? follow ablate ablate/surgery

Abbreviations:

  • SLCD = small liver cell dysplasia.

Notes:

  • Large cell dysplasia:
    • Cell size ~ 2x normal, NC ratio ~ normal.
  • SLCD:
    • Cell size ~ 1/2x normal, NC ratio - increased.

Hepatic tumours

Benign:

Entity Gross Microscopic IHC/stains Other Images
Hepatic hemangioma similar to normal liver parenchyma, red (hemorrhagic), well-circumscribed spaces lined by benign endothelial cells CD31+ (???) - gross (rsna.org)
Focal nodular hyperplasia central scar, large vessels, usu. well-circumscribed large arteries, unpaired arteries, bile duct proliferation usu. diagnosed by imaging gross (rsna.org)
Hepatocellular adenoma subcapsular, well-circumscribed loss of portal tracts, nuclear glycogenation reticulin - liver plate thickness <= 3 background not cirrhotic, assoc. OCP gross (mda-sy.com)[5]

Malignant:

Entity Gross Microscopic IHC/stains Other Images
Liver metastasis multiple, white lesions variable, usu. tubular (glandular) with pseudostratified hyperchromatic nuclei CK7-, CK20+ (colorectal), HepPar-1-, CK19- colorectal carcinoma most common
Metastases. (WC)
Hepatocellular carcinoma poorly circumscribed, +/-necrosis, +/-hemorrhage loss of portal tracts, unpaired arteries, +/-nuclear atypia reticulin - liver plate thickness > 3 background often cirrhotic
HCC. (WC/Uthman)
Cholangiocarcinoma cauliflower-like outline, white, classically solitary, no cirrhosis tubular architecture and mild nuclear atypia (adenocarcinoma), desmoplastic stroma CK7+, CK19+ background usu. not cirrhotic
Cholangiocarcinoma. (WC)

Dysplasia of the liver

Small liver cell dysplasia

  • Abbreviated SLCD.
  • AKA small cell dysplasia.

General

  • Considered a precursor to HCC.
    • Frequently found in livers with HCC - when compared to livers without HCC.[6]

Microscopic

Features:[7]

  • Cells similar in size to normal hepatocytes.
    • Name derived from the fact that there is also an entity that was called large cell dysplasia (AKA large liver cell dysplasia,[6] and large cell change).
  • Increased NC ratio - "more blue".
  • Mild nuclear and cytoplasmic hyperchromatism.

Notes:

  • Normal hepatic architecture (main differentiator from HCC).
  • Remember "... blue is bad".

Micrograph:

Low-grade hepatocellular dysplasia

  • Generally referred to as low-grade dysplasia as the context is usually clear.

Microscopic

  • Uniform cells - "noticeably different from normal".[8]
    • Changes in nuclear size, irregular nuclear contour and/or changes in cytoplasm staining.
  • Loss of portal tracts.
  • Irregular margin.

Notes:

  • DCHH describes LGD as: "normal hepatocytes in plates [of normal thickness]".[4]

DDx:

High-grade hepatocellular dysplasia

  • Generally referred to as high-grade dysplasia as the context is usually clear.

General

Microscopic

Features - in addition to those of low grade dysplasia:[4]

  • Liver plate >2 cells thick.
  • Significant nuclear atypia.
  • Basophilic cytoplasm.

DDx:

Image:

Benign hepatic neoplasms

Bile duct hamartoma

A. Trichrome shows fibrous spaces with dilated ducts (20X). B. Bizarre, ramifying tubules with dilatations (100X).
C. Bland epithelial linings (400X). D. Surrounding tract with tortuous bile ducts & inflammation, likely secondary to hamartomas (200X).


Bile duct hamartomas. A. Trichrome shows fibrous spaces with dilated ducts. B. Bizarre, ramifying tubules with dilatations. C. Bland epithelial linings. D. Surrounding tract with tortuous bile ducts & inflammation, likely secondary to hamartomas.

Bile duct adenoma

Should not be confused with bile duct hamartoma.
Main article: Bile duct adenoma

Hepatic adenoma

  • AKA hepatocellular adenoma, abbreviated HCA.
Main article: Hepatic adenoma

Hepatobiliary mucinous cystadenoma

  • AKA biliary cystadenoma.

General

  • Benign neoplasm.
    • May transform into a malignancy.[9]

Microscopic

Features:

  • Cystic spaces lined by a mucinous epithelium (simple columnar epithelium with a clear cytoplasm).
  • Surrounding dense ovarian like stroma.

DDX: Biliary Intraductal Papillary Neoplasm

  • no surrounding ovarian stroma
  • Intraductal - connects with the biliary tree lumen.

Note:

Cavernous hemangioma

A. Fibrous foci with increased spaces, hepatocyte focus with nonspecific fibrotic bridge (40X). B. Cavernous hemangioma with flat, non-atypical endothelium (200X).
C. Tortuous bile ducts/ductules, not to be considered generalized in presence of mass (200X). D. Tortuous bile ductsductules, not to be considered generalized in presence of mass (200X).


Cavernous hemangioma. A. Fibrous foci with increased spaces, hepatocyte focus with nonspecific fibrotic bridge. B. Cavernous hemangioma with flat, non-atypical endothelium. C. Tortuous bile ductules, not to be considered generalized in presence of mass. D. Tortuous bile ducts, not to be considered generalized in presence of mass.

Malignant hepatic neoplasms

In North America, the most common malignant liver tumour is metastases.

Hepatoblastoma

General

  • Most common liver cancer in children.[10][11]
    • Rare in adolescents and adults.
    • Age of diagnosis usu. ~1 year old; most less than 3 years old.
  • Surgical biopsy; core needle biopsy not done as as lesion is vascular.

Associations:

Clinical:

  • Usually present with hepatomegaly.
  • High AFP.[13]

Microscopic

Features:

  • Small round cell tumour.
  • Fetal hepatocytes ~ 1:3 NC ratio, eosinophilic cytoplasm.
  • +/-Mesenchymal component
    • Immature fibrous tissue, osteoid or cartilage.

DDx:

Images

  • Hepatoblastoma - very high mag. (WC/Nephron)

  • Hepatoblastoma - high mag. (WC/Nephron)

Subtypes

  • Six histologic subtypes - that are subdivided into two groups:[14]
    • Epithelial type:
      1. Fetal pattern.
      2. Embryonal and fetal pattern.
      3. Macrotrabecular pattern.
      4. Small cell undifferentiated pattern.
        • Poor prognosis.
    • Mixed epithelial and mesenchymal type:
      1. With teratoid features.
      2. Without teratoid features.

IHC

  • Alpha-fetoprotein +ve.
  • Hepatocyte specific antigen +ve esp. in fetal component.[16]
  • Beta-catenin +ve (cytoplasmic and nuclear).[16]

Hepatocellular carcinoma

  • Abbreviated HCC.
Main article: Hepatocellular carcinoma

Biliary Intraductal Papillary Neoplasm[17]

General

  • Rare
  • Highest incidence in Far Eastern countries
  • Association with hepatolithiasis and clonorchiasis
  • Between 50 and 70 years of age
  • Slight male predominance
  • Intermittent abdominal pain
  • Acute cholangitis
  • Jaundice

Radiology

  • Bile duct dilatation
  • Intraductal masses

Gross

  • Singular, or occasionally multiple, polypoid masses extending into the lumen of a dilated bile duct
  • Or multilocular well-defined cystic mass containing mucinous fluid
  • Granular or papillary mucosa
  • Communication with bile duct may be difficult to confirm

Microscopic

  • Papillary or villous growth within the lumen of an intra or extrahepatic bile duct
  • Papillary fronds with fine vascular cores
  • Epithelium types
    • Pancreatobiliary
    • Intestinal - marked mucin secretion
    • Gastric
    • Oncocytic types
  • Dysplasia
    • High or low grade
    • Marked variation in histologic grade between different regions of individual tumors
  • Common association with invasive cholangiocarcinoma
    • Tubular adenocarcinoma
    • Mucinous (colloid) carcinoma (often in association with the intestinal type).

DDX

Photos

  • Bile Ducts - Intraductal Papillary Neoplasm - Low power (SKB)

  • Bile Ducts - Intraductal Papillary Neoplasm - Medium power (SKB)

  • Bile Ducts - Intraductal Papillary Neoplasm - High power (SKB)

  • Bile Ducts - Intraductal Papillary Neoplasm - Low power (SKB)

  • Bile Ducts - Intraductal Papillary Neoplasm - High power (SKB)

  • Bile Ducts - Intraductal Papillary Neoplasm - High power (SKB)

A. Intraductal papillary neoplasm of common bile duct with associated invasive carcinoma. B. Intraductal papillary neoplasm of common bile duct with associated invasive carcinoma.
C. Intraductal papillary neoplasm of common bile duct with associated invasive carcinoma. D. Intraductal papillary neoplasm of common bile duct with associated invasive carcinoma.
E. Intraductal papillary neoplasm of common bile duct with associated invasive carcinoma. F. Intraductal papillary neoplasm of common bile duct with associated invasive carcinoma.

Intraductal papillary neoplasm of common bile duct with associated invasive carcinoma. A. The papillary tumor comprises mostly variably dilated acini. B. Tumor also shows areas of micropapillae. C. Some areas within the non-invasive tumor showed necrosis, with the black pyknotic nuclei amid red debris. D. Definite invasion was established low power by glands headed in perpendicular directions. E. Embedded in fibroblastic response are non-acinar walls and isolated epithelial groups. F. Also embedded in fibroblastic response are flat glands with nuclei showing loss of polarity (lack of respect for lateral intercellular borders shown by variable orientation to base of gland).

Notes -

  • Reflect on the known marked variation in histologic grade between different regions of individual tumors when rendering an opinion on a small biopsy specimen.
  • Consider the possibility of an invasive component and submit tissue generously.

See also: PubCan [1]

Cholangiocarcinoma

Main article: Cholangiocarcinoma

Hepatic angiosarcoma

Main article: Angiosarcoma
  • AKA angiosarcoma of the liver.

General

  • Liver angiosarcomas are associated with vinyl chloride exposure.[19]

Microscopic

Features:

  • Atypical endothelial cells - may be subtle.

Hepatic metastasis

Main article: Liver metastasis
  • AKA liver metastases.
  • AKA metastatic liver disease.

Hematopoietic tumors

A One liver core was normal (Row 1 Left 40X).
B A triad with a proliferated bile ductule, otherwise normal (Row 1 Right 400X).
C The other core showed a mass of tumor mashed against normal liver (Row 2 Left 40X).
D Tumor cells showed round to ovoid nuclei without pattern and with grey cytoplasm that proved to be CD138 positive (Row 2 Right 400X).
Plasmacytoma appearing as a tumor mass. A. One liver core was normal. B. A triad with a proliferated bile ductule, otherwise normal. C. The other core showed a mass of tumor mashed against normal liver. D. Tumor cells showed round to ovoid nuclei without pattern and with grey cytoplasm that proved to be CD138 positive.

A. Apparent inflamed fibrous tract with lobular inflammatory collections in adjacent liver (Row 1 Left 40X).
B. Apparent inflamed fibrous band between two relatively hepatocyte regions (Row 1 Right 40X).
C. Apparent piecemeal necrosis with bile ductular proliferation (Row 2 Left 200X).
D. Apparent portal inflammation with unaffected interlobular bile duct (Row 2 Right 200X).
E. Apparent lobular infiltrate with small masse.
F. Proof is at high power. All cells are similar to macrophages but are too closely crowded to be macrophages. The monomorphism (one type of cell) should inspire immunohistochemical stains, which showed the patient had a B cell lymphoma.
B cell lymphoma mimicking hepatitis with fibrosis. A. Apparent inflamed fibrous tract with lobular inflammatory collections in adjacent liver. B. Apparent inflamed fibrous band between two relatively hepatocyte regions. C. Apparent piecemeal necrosis with bile ductular proliferation. D. Apparent portal inflammation with unaffected interlobular bile duct. E. Apparent lobular inflammation with collections a bit too large for usual lobular inflammation. F. Proof is at high power. All cells are similar to macrophages but are too closely crowded to be macrophages. The monomorphism (one type of cell) should inspire immunohistochemical stains, which showed the patient had a B cell lymphoma.

Malignant B cell lymphoma, NOS, in a 63 year old man’s liver Malignant B cell lymphoma, NOS, in a 63 year old man’s liver Malignant B cell lymphoma, NOS, in a 63 year old man’s liver Malignant B cell lymphoma, NOS, in a 63 year old man’s liver Malignant B cell lymphoma, NOS, in a 63 year old man’s liver Malignant B cell lymphoma, NOS, in a 63 year old man’s liver
Malignant B cell lymphoma, NOS, in a 63 year old man’s liver. No other specimens were available for further classification. A. Tumor expands a triad and occupies parenchymal regions. B. Bounding a bile duct, modestly sized round to reniform lymphoid cells, many without nucleoli, accompany small round lymphocytes. Some of the larger cells have clefts (arrows). C. CD3 stain shows many of the lymphoid cells are intercalated reactive T cells. D. Ki67 shows less than half the tumor cells, mostly the larger ones, are in proliferative phase, arguing against the notion of a high grade B cell lymphoma. E. CD79A establishes B cell phenotype (CD20 was also positive). F. That the tumor cells are BCL2 positive evinces B cell neoplasia. The cells were CD10, BCL6, and cyclin D1 negative, militating against mantle cell lymphoma and CLL, with no follicular origin identified.

High grade B cell lymphoma involving liver High grade B cell lymphoma involving liver High grade B cell lymphoma involving liver High grade B cell lymphoma involving liver High grade B cell lymphoma involving liver
High grade B cell lymphoma involving liver in a 77 year old woman. A. A band of cancer abuts fibrotic liver with steatosis. B. Cancer cells show primitive, round to ovoid, variably sized, dark nucleoli and an aberrant mitoses. Cytoplasm is scant. C. Cancer cells are CD79a positive. D. Most cancer cell nuclei were positive for Ki-67, overall about 80%. E. A minority of cancer cells are CD10 positive.

See also

References

  1. ↑ STC. S.30-37, 19 Jan 2009.
  2. ↑ Park, YN.; Roncalli, M. (Nov 2006). "Large liver cell dysplasia: a controversial entity.". J Hepatol 45 (5): 734-43. doi:10.1016/j.jhep.2006.08.002. PMID 16982109.
  3. ↑ Shirakawa, H.; Kuronuma, T.; Nishimura, Y.; Hasebe, T.; Nakano, M.; Gotohda, N.; Takahashi, S.; Nakagohri, T. et al. (Mar 2009). "Glypican-3 is a useful diagnostic marker for a component of hepatocellular carcinoma in human liver cancer.". Int J Oncol 34 (3): 649-56. PMID 19212669. http://www.spandidos-publications.com/serveFile/ijo_34_3_649_PDF.pdf?type=article&article_id=ijo_34_3_649&item=PDF.
  4. ↑ 4.0 4.1 4.2 4.3 Tadrous, Paul.J. Diagnostic Criteria Handbook in Histopathology: A Surgical Pathology Vade Mecum (1st ed.). Wiley. pp. 170-1. ISBN 978-0470519035.
  5. ↑ URL: http://www.mda-sy.com/vb/showthread.php?p=5083&langid=1. Accessed on: 16 February 2012.
  6. ↑ 6.0 6.1 Szczepański, W. (1997). "Liver cell dysplasia in liver cirrhosis and hepatocellular carcinoma.". Pol J Pathol 48 (3): 147-57. PMID 9401407.
  7. ↑ STC S.32, 19 Jan 2009.
  8. ↑ STC - 19 Jan 2009. (???)
  9. ↑ Yu, J.; Wang, Y.; Yu, X.; Liang, P.. "Hepatobiliary mucinous cystadenoma and cystadenocarcinoma: report of six cases and review of the literature.". Hepatogastroenterology 57 (99-100): 451-5. PMID 20698207.
  10. ↑ Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease (7th ed.). St. Louis, Mo: Elsevier Saunders. pp. 923. ISBN 0-7216-0187-1.
  11. ↑ URL: http://emedicine.medscape.com/article/986802-overview. Accessed on: 29 November 2009.
  12. ↑ DeBaun MR, Tucker MA (March 1998). "Risk of cancer during the first four years of life in children from The Beckwith-Wiedemann Syndrome Registry". J. Pediatr. 132 (3 Pt 1): 398–400. PMID 9544889.
  13. ↑ URL: http://emedicine.medscape.com/article/986802-diagnosis. Accessed on: 11 February 2011.
  14. ↑ URL: http://emedicine.medscape.com/article/986802-diagnosis. Accessed on: 11 February 2011.
  15. ↑ URL: http://www.cap.org/apps/cap.portal?_nfpb=true&cntvwrPtlt_actionOverride=%2Fportlets%2FcontentViewer%2Fshow&_windowLabel=cntvwrPtlt&cntvwrPtlt{actionForm.contentReference}=cap_foundation%2FcaseOfMonth%2FMar10%2Fmar_2010_cotm_diagnosis.html&_state=maximized&_pageLabel=cntvwr#null. Accessed on: 11 February 2011.
  16. ↑ 16.0 16.1 Halász, J.; Holczbauer, A.; Páska, C.; Kovács, M.; Benyó, G.; Verebély, T.; Schaff, Z.; Kiss, A. (May 2006). "Claudin-1 and claudin-2 differentiate fetal and embryonal components in human hepatoblastoma.". Hum Pathol 37 (5): 555-61. doi:10.1016/j.humpath.2005.12.015. PMID 16647953.
  17. ↑ .
  18. ↑ URL: http://www.cancer.org/cancer/bileductcancer/detailedguide/bile-duct-cancer-what-is-bile-duct-cancer. Access on: 23 May 2013.
  19. ↑ Mitchell, Richard; Kumar, Vinay; Fausto, Nelson; Abbas, Abul K.; Aster, Jon (2011). Pocket Companion to Robbins & Cotran Pathologic Basis of Disease (8th ed.). Elsevier Saunders. pp. 212. ISBN 978-1416054542.
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