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

Hepatic adenoma.

Malignant lesions of the liver

Hepatocellular carcinoma (HCC) - most common malignant liver primary in adults.
Hepatoblastoma - malignant liver primary in children.
Intrahepatic cholangiocarcinoma (ICC).^[3]
Combined hepatocellular carcinoma and intrahepatic cholangiocarcinoma (CHC).

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 resolution micrograph of SCD (medscape.com).

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:

Nodular regenerative hyperplasia - lacks: compressed rim of cells, central portal tract.^[4]

High-grade hepatocellular dysplasia

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

General

"Bader" version of low-grade dyplasia.

Microscopic

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

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

DDx:

Image:

Series of liver micrographs including high grade dysplasia (radiographics.rsna.org).

Benign hepatic neoplasms

Bile duct hamartoma

A. B.
C. D.

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:

Similar to pancreatic mucinous cystadenoma.

Cavernous hemangioma

A. B.
C. D.

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:

Small round cell tumours.
- Neuroblastoma.
Teratoma.
Hepatocellular carcinoma - separated based on histomorphology alone.

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.
    - May mimic hepatocellular carcinoma histologically.^[15]
  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

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

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. B.
C. D.
E. F.

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.

Cholangiocarcinoma

AKA bile duct carcinoma.^[18]

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
B
C
D
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.
B.
C.
D.
E.
F.
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. 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 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.

References

↑ STC. S.30-37, 19 Jan 2009.
↑ 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.
↑ 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.
↑ ^4.0 ^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.
↑ URL: http://www.mda-sy.com/vb/showthread.php?p=5083&langid=1. Accessed on: 16 February 2012.
↑ ^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.
↑ STC S.32, 19 Jan 2009.
↑ STC - 19 Jan 2009. (???)
↑ 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.
↑ 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.
↑ URL: http://emedicine.medscape.com/article/986802-overview. Accessed on: 29 November 2009.
↑ 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.
↑ URL: http://emedicine.medscape.com/article/986802-diagnosis. Accessed on: 11 February 2011.
↑ URL: http://emedicine.medscape.com/article/986802-diagnosis. Accessed on: 11 February 2011.
↑ 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.
↑ ^16.0 ^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.
↑ .
↑ URL: http://www.cancer.org/cancer/bileductcancer/detailedguide/bile-duct-cancer-what-is-bile-duct-cancer. Access on: 23 May 2013.
↑ 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.

[1] STC. S.30-37, 19 Jan 2009.

[pmid16982109-2] 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.

[pmid19212669-3] 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.

[Ref_DCHH170-1-4] 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.

[pmid9401407-6] 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. (???)

[pmid20698207-9] 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.

[Ref_PBoD923-10] 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.

[emed_hepatoblastoma-11] URL: http://emedicine.medscape.com/article/986802-overview. Accessed on: 29 November 2009.

[pmid9544889-12] 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.

[pmid16647953-16] 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.

[Ref_PCPBoD8_212-19] 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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[19]

@@ Line 1: / Line 1: @@
+[[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]].
@@ Line 17: / Line 18: @@
 ===Malignant lesions of the liver===
 *[[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).
+===Lesions that arise in a non-cirrhotic liver===
+Hepatocellular:
+*[[Hepatic adenoma]].
+*[[Fibrolamellar hepatocellular carcinoma]].
+*[[Focal nodular hyperplasia]].
+Other:
+*[[Metastasis]].
+*[[Cholangiocarcinoma]].
+*[[Liver hemangioma]].
 ===Tabular comparison===
@@ Line 50: / Line 62: @@
 ====Hepatic tumours====
+Benign:
+{| class="wikitable sortable"
+! 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+ (???)
+| -
+| [http://radiographics.rsna.org/content/24/6/1719/F8.expansion.html gross (rsna.org)]
+|-
+| [[Focal nodular hyperplasia]]
+| central scar, large vessels, usu. well-circumscribed
+| large arteries, unpaired arteries, bile duct proliferation
+|
+| usu. diagnosed by imaging
+| [http://radiographics.rsna.org/content/24/1/3/F1.expansion.html gross (rsna.org)]
+|-
+| [[Hepatocellular adenoma]]
+| subcapsular, well-circumscribed
+| loss of portal tracts, nuclear glycogenation
+| reticulin - liver plate thickness <= 3
+| background not cirrhotic, assoc. [[OCP]]
+| [http://www.mda-sy.com/up//uploads/images/mda-sy-d768fd265c.jpg gross (mda-sy.com)<ref>URL: [http://www.mda-sy.com/vb/showthread.php?p=5083&langid=1 http://www.mda-sy.com/vb/showthread.php?p=5083&langid=1]. Accessed on: 16 February 2012.</ref>]
+|}
+Malignant:
 {| class="wikitable sortable"
 ! Entity
@@ Line 61: / Line 105: @@
 | multiple, white lesions
 | variable, usu. tubular (glandular) with pseudostratified hyperchromatic nuclei
-| CK7-, CK20-, HepPar-1-, CK19-
+| CK7-, [[CK20]]+ (colorectal), HepPar-1-, [[CK19]]-
 | [[colorectal carcinoma]] most common
-| [http://commons.wikimedia.org/wiki/File:Secondary_tumor_deposits_in_the_liver_from_a_primary_cancer_of_the_pancreas.jpg gross (WC)]
+| [[Image:Secondary_tumor_deposits_in_the_liver_from_a_primary_cancer_of_the_pancreas.jpg | thumb| center| 150px| Metastases. (WC)]]
-|-
-| [[Hepatocellular adenoma]]
-| gross
-| loss of portal tracts, glycogenation
-| reticulin - liver plate thickness <= 3
-| background not cirrhotic
-| [http://www.mda-sy.com/up//uploads/images/mda-sy-d768fd265c.jpg gross (mda-sy.com)<ref>URL: [http://www.mda-sy.com/vb/showthread.php?p=5083&langid=1 http://www.mda-sy.com/vb/showthread.php?p=5083&langid=1]. Accessed on: 16 February 2012.</ref>]
 |-
 | [[Hepatocellular carcinoma]]
-| gross
+| poorly circumscribed, +/-necrosis, +/-hemorrhage
-| loss of portal tracts, glycogenation
+| loss of portal tracts, unpaired arteries, +/-nuclear atypia
-| reticulin - liver plate thickness <= 3
+| reticulin - liver plate thickness > 3
-| background not cirrhotic
+| background often cirrhotic
-| [http://commons.wikimedia.org/wiki/File:Hepatocellular_carcinoma_1.jpg gross (WC/Ed Uthman)]
+| [[Image:Hepatocellular_carcinoma_1.jpg |thumb|center|150px| 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
+| [[Image:Cholangiocarcinoma.png |thumb|center|150px| Cholangiocarcinoma. (WC)]]
+|}
 =Dysplasia of the liver=
@@ Line 92: / Line 135: @@
 Features:<ref>STC S.32, 19 Jan 2009.</ref>
 *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 cell change'').
+**Name derived from the fact that there is also an entity that was called ''large cell dysplasia'' (AKA ''large liver cell dysplasia'',<ref name=pmid9401407>{{Cite journal  | last1 = Szczepański | first1 = W. | title = Liver cell dysplasia in liver cirrhosis and hepatocellular carcinoma. | journal = Pol J Pathol | volume = 48 | issue = 3 | pages = 147-57 | month =  | year = 1997 | doi =  | PMID = 9401407 }}</ref> and ''large cell change'').
 *Increased [[NC ratio]] - "more blue".
 *Mild nuclear and cytoplasmic hyperchromatism.
@@ Line 103: / Line 146: @@
 *[http://www.medscape.com/viewarticle/515219_3 Low resolution micrograph of SCD (medscape.com)].
-==Low grade dysplasia==
+==Low-grade hepatocellular dysplasia==
-===Microscopy===
+*Generally referred to as ''low-grade dysplasia'' as the context is usually clear.
+===Microscopic===
 *Uniform cells - "noticeably different from normal".<ref>STC - 19 Jan 2009. (???)</ref>
 **Changes in nuclear size, irregular nuclear contour and/or changes in cytoplasm staining.
@@ Line 116: / Line 160: @@
 *[[Nodular regenerative hyperplasia]] - lacks: compressed rim of cells, central portal tract.<ref name=Ref_DCHH170-1>{{Ref DCHH|170-1}}</ref>
-==High grade dysplasia==
+==High-grade hepatocellular dysplasia==
-*"Bader" version of low grade dyplasia.
+*Generally referred to as ''high-grade dysplasia'' as the context is usually clear.
+===General===
+*"Bader" version of ''[[Low-grade hepatocellular dysplasia|low-grade dyplasia]]''.
+===Microscopic===
 Features - in addition to those of low grade dysplasia:<ref name=Ref_DCHH170-1>{{Ref DCHH|170-1}}</ref>
 *Liver plate >2 cells thick.
@@ Line 124: / Line 171: @@
 *Basophilic cytoplasm.
-Micrograph:
+DDx:
+*[[Low-grade hepatocellular dysplasia]].
+*[[Hepatocellular carcinoma]].
+Image:
 *[http://radiographics.rsna.org/content/22/5/1023.figures-only Series of liver micrographs including high grade dysplasia (radiographics.rsna.org)].
 =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==
+:''Should '''not''' be confused with [[bile duct hamartoma]].''
+{{Main|Bile duct adenoma}}
 ==Hepatic adenoma==
 *[[AKA]] ''hepatocellular adenoma'', abbreviated ''HCA''.
+{{Main|Hepatic adenoma}}
+==Hepatobiliary mucinous cystadenoma==
+*[[AKA]] ''biliary cystadenoma''.
 ===General===
-*Grow under the influence of sex hormones.
+*Benign neoplasm.
-**Associated with OCP use - may regress with discontinuation.
+**May transform into a malignancy.<ref name=pmid20698207>{{Cite journal  | last1 = Yu | first1 = J. | last2 = Wang | first2 = Y. | last3 = Yu | first3 = X. | last4 = Liang | first4 = P. | title = Hepatobiliary mucinous cystadenoma and cystadenocarcinoma: report of six cases and review of the literature. | journal = Hepatogastroenterology | volume = 57 | issue = 99-100 | pages = 451-5 | month =  | year =  | doi =  | PMID = 20698207 }}</ref>
-**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>
+*Cystic spaces lined by a mucinous epithelium (simple columnar epithelium with a clear cytoplasm).
-*Cords of cells upto 3 cells thick.<ref>STC S.19, 19 Jan 2009.</ref>
+*Surrounding dense ovarian like stroma.
-*Cells may have cytoplasmic clearing due to glycogen or be pale - '''obvious if seen'''.
-*Vascular - large arteries, dilated thin-walled veins.
-Negatives:
+DDX:
-*No bile ducts.
+[[Biliary Intraductal Papillary Neoplasm]]
-*No portal tracts.
+*no surrounding ovarian stroma
-*No cirrhosis!  If cirrhosis is present it isn't a hepatic adenoma - '''important'''.
+*Intraductal - connects with the biliary tree lumen.
-Images:
+Note:
-*[http://commons.wikimedia.org/wiki/File:Hepatic_adenoma_low_mag.jpg Hepatic adenoma (WC)].
+*Similar to [[pancreatic mucinous cystadenoma]].
-*[http://commons.wikimedia.org/wiki/File:Hepatic_adenoma_low_mag_reticulin.jpg Hepatic adenoma - reticulin (WC)].
-*[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)].
-DDx:
+==Cavernous hemangioma==
-*Well-differentiated HCC.<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.
-====Subclassification====
+A. [[File:1 CAV 1 680x512px.tif|Fibrous foci with increased spaces, hepatocyte focus with nonspecific fibrotic bridge (40X).]]
-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>
+B. [[File:2 CAV 1 680x512px.tif|Cavernous hemangioma with flat, non-atypical endothelium (200X).]]
-#Inflammatory hepatic adenoma.
+<br>
-#Hepatocyte nuclear factor 1 alpha-mutated hepatic adenoma.
+C. [[File:3 CAV 1 680x512px.tif|Tortuous bile ducts/ductules, not to be considered generalized in presence of mass (200X).]]
-#*Inactivating mutation.
+D. [[File:4 CAV 1 680x512px.tif|Tortuous bile ductsductules, not to be considered generalized in presence of mass (200X).]]
-#Beta-catenin-mutated hepatic adenoma
-#*Activating mutation.
-#Unclassified hepatic adenoma.
-Note:
-*Beta-catenin is considered an oncogene.
-===IHC===
+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.
-*AFP -ve. (???)
-*HNF1alpha +ve/-ve.
-*Beta-catenin +ve/-ve.
 =Malignant hepatic neoplasms=
@@ Line 191: / Line 238: @@
 Associations:
-*Beckwith-Wiedemann syndrome.<ref name=pmid9544889>{{cite journal |author=DeBaun MR, Tucker MA |title=Risk of cancer during the first four years of life in children from The Beckwith-Wiedemann Syndrome Registry |journal=J. Pediatr. |volume=132 |issue=3 Pt 1 |pages=398–400 |year=1998 |month=March |pmid=9544889 |doi= |url=}}</ref>
+*[[Beckwith-Wiedemann syndrome]].<ref name=pmid9544889>{{cite journal |author=DeBaun MR, Tucker MA |title=Risk of cancer during the first four years of life in children from The Beckwith-Wiedemann Syndrome Registry |journal=J. Pediatr. |volume=132 |issue=3 Pt 1 |pages=398–400 |year=1998 |month=March |pmid=9544889 |doi= |url=}}</ref>
 *[[Familial adenomatous polyposis]].
 Clinical:
+*Usually present with hepatomegaly.
 *High AFP.<ref>URL: [http://emedicine.medscape.com/article/986802-diagnosis http://emedicine.medscape.com/article/986802-diagnosis]. Accessed on: 11 February 2011.</ref>
@@ Line 204: / Line 252: @@
 **Immature fibrous tissue, osteoid or cartilage.
-Images:
+DDx:
-*[http://commons.wikimedia.org/wiki/File:Hepatoblastoma_-_2_-_very_high_mag.jpg Hepatoblastoma - very high mag. (WC)].
+*[[Small round cell tumours]].
-*[http://commons.wikimedia.org/wiki/File:Hepatoblastoma_-_high_mag.jpg Hepatoblastoma - high mag. (WC)].
+**[[Neuroblastoma]].
+*[[Teratoma]].
+*[[Hepatocellular carcinoma]] - separated based on histomorphology alone.
+====Images====
+<gallery>
+Image:Hepatoblastoma_-_2_-_very_high_mag.jpg | Hepatoblastoma - very high mag. (WC/Nephron)
+Image:Hepatoblastoma_-_high_mag.jpg | Hepatoblastoma - high mag. (WC/Nephron)
+</gallery>
 ====Subtypes====
@@ Line 215: / Line 271: @@
 **# Macrotrabecular pattern.
 **#* May mimic [[hepatocellular carcinoma]] histologically.<ref>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 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.</ref>
-**# Small cell undifferentiated pattern
+**# Small cell undifferentiated pattern.
+**#* Poor prognosis.
 ** Mixed epithelial and mesenchymal type:
 **# With teratoid features.
 **# Without teratoid features.
+===IHC===
+*Alpha-fetoprotein +ve.
+*Hepatocyte specific antigen +ve esp. in fetal component.<ref name=pmid16647953>{{Cite journal  | last1 = Halász | first1 = J. | last2 = Holczbauer | first2 = A. | last3 = Páska | first3 = C. | last4 = Kovács | first4 = M. | last5 = Benyó | first5 = G. | last6 = Verebély | first6 = T. | last7 = Schaff | first7 = Z. | last8 = Kiss | first8 = A. | title = Claudin-1 and claudin-2 differentiate fetal and embryonal components in human hepatoblastoma. | journal = Hum Pathol | volume = 37 | issue = 5 | pages = 555-61 | month = May | year = 2006 | doi = 10.1016/j.humpath.2005.12.015 | PMID = 16647953 }}</ref>
+*Beta-catenin +ve (cytoplasmic and nuclear).<ref name=pmid16647953/>
 ==Hepatocellular carcinoma==
-*Commonly abbreviated ''HCC''.
+*Abbreviated ''HCC''.
+{{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===
-Clinical:
+*Rare
-*Serum AFP elevated - in approx. 50% of patients.<ref>{{Ref GLP|588}}</ref>
+*Highest incidence in Far Eastern countries
-*Treatments: RFA (radiofrequency ablation), ethanol ablation, liver resection, liver transplant.<ref name=emed_hcc>[http://emedicine.medscape.com/article/282814-overview http://emedicine.medscape.com/article/282814-overview]</ref>
+*Association with hepatolithiasis and clonorchiasis
-*Mean survival at time of diagnosis ~6 months.<ref name=emed_hcc/>
+*Between 50 and 70 years of age
+*Slight male predominance
-Epidemiology:
+*Intermittent abdominal pain
-*Highest where prevalence of hepatitis B virus (HBV) is high.<ref name=Ref_PBoD924>{{Ref PBoD|924}}</ref>
+*Acute cholangitis
-*HCC generally arises in the setting of [[cirrhosis]].
+*Jaundice
-**Cirrhosis may be regressed and therefore not appreciated.
-HCCs '''without''' cirrhosis:
+*Biliary counterpart of [[pancreatic intraductal papillary mucinous neoplasm]]
-*Hepatitis B virus.<ref name=Ref_PBoD924>{{Ref PBoD|924}}</ref>
+*Biliary counterpart of [[intracholecystic papillary neoplasm]] (gall bladder)
-*Hemochromatosis.
+*Construct consumes some cases of biliary cystadenoma/cystadenocarcinoma, biliary papilloma/papillomatosis, intraductal growth type of cholangiocarcinoma and papillary carcinoma of the extrahepatic bile duct.
-*Fibrolamellar HCC.
-Risk factors:<ref name=Ref_PBoD924>{{Ref PBoD|924}}</ref><ref name=pmid18333156>{{cite journal |author=Leong TY, Leong AS |title=Epidemiology and carcinogenesis of hepatocellular carcinoma |journal=HPB (Oxford) |volume=7 |issue=1 |pages=5–15 |year=2005 |pmid=18333156 |pmc=2023917 |doi=10.1080/13651820410024021 |url=}}</ref>
+===Radiology===
-*Chronic alcoholism.
+*Bile duct dilatation
-*[[Hepatitis C]] virus (HCV) - chronic infection.
+*Intraductal masses
-*[[Hepatitis B]] virus (HBV) - chronic infection.
-*Aflatoxins (food contaminant - mould).<ref name=emed_hcc/>
-*Hereditary tyrosinemia.
-*[[Hereditary hemochromatosis]].
 ===Gross===
-Features:<ref name=Ref_PBoD925>{{Ref PBoD|925}}</ref>
+*Singular, or occasionally multiple, polypoid masses extending into the lumen of a dilated bile duct
-*Unifocal, multifocal or diffusely infiltrative.
+*Or multilocular well-defined cystic mass containing mucinous fluid
-**Tumours are multifocal in approx. 50% of cases;<ref name=pmid17696722>{{cite journal |author=Yusuf MA, Badar F, Meerza F, ''et al.'' |title=Survival from hepatocellular carcinoma at a cancer hospital in Pakistan |journal=Asian Pac. J. Cancer Prev. |volume=8 |issue=2 |pages=272–4 |year=2007 |pmid=17696722 |doi= |url=}}</ref><ref name=pmid11676064>{{cite journal |author=Sharieff S, Burney KA, Ahmad N, Salam A, Siddiqui T |title=Radiological features of hepatocellular carcinoma in Southern Pakistan |journal=Trop Doct |volume=31 |issue=4 |pages=224–5 |year=2001 |month=October |pmid=11676064 |doi= |url=}}</ref> some authors have suggested it is upto 75% of cases.<ref name=emed_hcc/>
+*Granular or papillary mucosa
-*Pale in relation to surrounding liver or green (due to bile secretion).
+*Communication with bile duct may be difficult to confirm
 ===Microscopic===
-Requirements:<ref>Adapted from STC (19 Jan 2009).</ref>
+*Papillary or villous growth within the lumen of an intra or extrahepatic bile duct
-*Architectural changes.
+*Papillary fronds with fine vascular cores
-**Liver plate more than 3 cells thick - '''key feature'''.
+*Epithelium types
-**Loss of reticulin scaffold - incomplete loss is considered significant.
+**Pancreatobiliary
-**CD34+ staining cells, suggesting loss of epithelial cells that form the sinusoids.
+**Intestinal - marked mucin secretion
-**Loss of structures seen in a normal liver lobule (bile ductules, portal triad).
+**Gastric
-**Invasion of the portal tract - useful in well-diff. lesions.<ref name=pmid19177576>{{Cite journal  | last1 = Kojiro | first1 = M. | last2 = Wanless | first2 = IR. | last3 = Alves | first3 = V. | last4 = Badve | first4 = S. | last5 = Balabaud | first5 = C. | last6 = Bedossa | first6 = P. | last7 = Bhathal | first7 = P. | last8 = Bioulac-Sage | first8 = P. | last9 = Brunt | first9 = EM. | title = Pathologic diagnosis of early hepatocellular carcinoma: a report of the international consensus group for hepatocellular neoplasia. | journal = Hepatology | volume = 49 | issue = 2 | pages = 658-64 | month = Feb | year = 2009 | doi = 10.1002/hep.22709 | PMID = 19177576 | url = http://onlinelibrary.wiley.com/doi/10.1002/hep.22709/pdf }}</ref>
+**Oncocytic types
+*Dysplasia
+**High or low grade
+**Marked variation in histologic grade between different regions of individual tumors
-Additional findings:<ref>Adapted from STC (19 Jan 2009).</ref>
+*Common association with invasive cholangiocarcinoma
-*Nuclear changes.
+**Tubular adenocarcinoma
-**Increased NC ratio - '''key feature''' if present.
+**Mucinous (colloid) carcinoma (often in association with the intestinal type).
-**Nuclear hyperchromasia.
-**Abnormal nuclear contour.
-**Mitoses.
-*Cytoplasmic changes.
-**Cytoplasmic hyperchromasia, clearing or lighter staining.
-Varied architecture - may be:<ref>{{Ref GLP|590-1}}</ref>
+====DDX====
-*Pseudoglandular - can be confused with adenocarcinoma.
+*[[Biliary Mucinous Cystic Neoplasm]]
-*[[Trabecular]].
+***Epithelium is surrounded by a distinct ovarian-like stroma.
-*Fibrolamellar.
-*Solid.
-Notes:
+====Photos====
-*HCC with trabecular morphology has some resemblance to normal liver - but has extra cells.
+<gallery>
-*Fibrolamellar - better prognosis, classically in young adults.
+Image:BileDuct IntraductalPapillaryNeoplasm LP CTR.jpg|Bile Ducts - Intraductal Papillary Neoplasm - Low power (SKB)
-*Stroma is usually scant.<ref>{{Ref GLP|591}}</ref>
+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>
-ASIDE:
+A. [[File:1 papillary cbd aca 1 680x512px.tif| Intraductal papillary neoplasm of common bile duct with associated invasive carcinoma.]]
-*''[[Trabecula]]'' = ''little beam''.
+B. [[File:2 papillary cbd aca 1 680x512px.tif| Intraductal papillary neoplasm of common bile duct with associated invasive carcinoma.]]
+<br>
-Images:
+C. [[File:3 papillary cbd aca 1 680x512px.tif| Intraductal papillary neoplasm of common bile duct with associated invasive carcinoma.]]
-*[http://commons.wikimedia.org/wiki/File:Hepatocellular_carcinoma_low_mag.jpg HCC - low mag. (WC)].
+D. [[File:4 papillary cbd aca 1 680x512px.tif| Intraductal papillary neoplasm of common bile duct with associated invasive carcinoma.]]
-*[http://commons.wikimedia.org/wiki/File:Hepatocellular_carcinoma_intermed_mag.jpg HCC - intermed mag. (WC)].
+<br>
+E. [[File:5 papillary cbd aca 1 680x512px.tif| Intraductal papillary neoplasm of common bile duct with associated invasive carcinoma.]]
-====Fibrolamellar hepatocellular carcinoma====
+F. [[File:6 papillary cbd aca 1 680x512px.tif| Intraductal papillary neoplasm of common bile duct with associated invasive carcinoma.]]
-*Abbreviated ''fibrolamellar HCC'', ''FL-HCC'', and ''FHCC''.
-=====General=====
-*Rare variant.
-*Classically afflicts younger patients.
-**Mean age at onset ~27 years in one study.<ref name=pmid16475212>{{Cite journal  | last1 = Stipa | first1 = F. | last2 = Yoon | first2 = SS. | last3 = Liau | first3 = KH. | last4 = Fong | first4 = Y. | last5 = Jarnagin | first5 = WR. | last6 = D'Angelica | first6 = M. | last7 = Abou-Alfa | first7 = G. | last8 = Blumgart | first8 = LH. | last9 = DeMatteo | first9 = RP. | title = Outcome of patients with fibrolamellar hepatocellular carcinoma. | journal = Cancer | volume = 106 | issue = 6 | pages = 1331-8 | month = Mar | year = 2006 | doi = 10.1002/cncr.21703 | PMID = 16475212 }}</ref>
-*Individuals usually do '''not''' have the classic risk factors for HCC, i.e. no [[cirrhosis]], no hepatitis.<ref name=pmid16475212/>
-Clinical:
-*AFP usu. not elevated.<ref name=pmid16475212/>
-=====Microscopic=====
-Features:<ref>{{Ref GLP|595-6}}</ref>
-*Large polygonal tumours cells with:
-**Graunular eosinophilic cytoplasm.
-**Low NC ratio.<ref>STC. 6 December 2010.</ref>
-*Layered dense collagen bundles.
-Images:
-*[[WC]]:
-**[http://commons.wikimedia.org/wiki/File:Fibrolamellar_hepatocellular_carcinoma_-2-_intermed_mag.jpg FHCC - intermed. mag. (WC)].
-**[http://commons.wikimedia.org/wiki/File:Fibrolamellar_hepatocellular_carcinoma_-2-_very_high_mag.jpg FHCC - very high mag. (WC)].
-====Sclerosing HCC====
-Features:
-*Fibrosis. (???)
-Notes:
-*Seen in non-cirrhotic livers.
-===Grading===
-Edmondson-Steiner grading system:<ref name=pmid13160935>Primary carcinoma of the liver: a study of 100 cases among 48,900 necropsies. EDMONDSON HA, STEINER PE. Cancer. 1954 May;7(3):462-503. PMID 13160935.</ref><ref name=macsween5th>{{Ref MacSween|783}}</ref>
-*Well-differentiated.
-**Some say "it cannot be diagnosed on biopsy,"<ref>AP. 28 May 2009.</ref> as it cannot be reliably differentiated from a regenerative nodule.
-*Moderately differentiated.
-**Round, regular nuclei, some hyperchromatism, nucleoli present, increase NC ratio.
-*Poor differentiated.
-**Very prominent nucleoli, pronounced nuclear irregularity.
-*Undifferentiated.
-**Anaplastic giant cells.
-Simplified description - based on MacSween:<ref name=macsween5th/>
+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).
-*Well-differentiated = cytologically near normal.
-*Moderate = looks like a cancer, small nucleoli.
-*Poor = bad cancer, raisin-like (irregular) nuclear membrane, large nucleoli (~1/3 of nucleus).
-*Undifferentiated = death on a slide, huge cells (3-4x the size of other cells).
-===IHC===
+Notes -
-*CD34 +ve sinusoids; sinusoids in normal liver are CD34 -ve.
+*Reflect on the known marked variation in histologic grade between different regions of individual tumors when rendering an opinion on a small biopsy specimen.
-*HepPar-1 +ve; may be neg. in high grade tumours.
+*Consider the possibility of an invasive component and submit tissue generously.
-*AFP +ve; may be neg. even if the serum AFP is elevated.
-*CK18 +ve.<ref>AP. 28 May 2009.</ref>
-*Glypican-3 +ve (cytoplasmic, granular cytoplasmic or membranous).<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>
-Image:
+See also:
-*[http://www.nature.com/modpathol/journal/v20/n1s/fig_tab/3800682f12.html#figure-title HCC - HepPar-1 (nature.com)].<ref name=pmid17486052>{{Cite journal  | last1 = Goodman | first1 = ZD. | title = Neoplasms of the liver. | journal = Mod Pathol | volume = 20 Suppl 1 | issue =  | pages = S49-60 | month = Feb | year = 2007 | doi = 10.1038/modpathol.3800682 | PMID = 17486052 }}</ref>
+PubCan [http://www.pubcan.org/printicdotopo.php?id=5755]
 ==Cholangiocarcinoma==
-===General===
+*[[AKA]] ''bile duct carcinoma''.<ref>URL: [http://www.cancer.org/cancer/bileductcancer/detailedguide/bile-duct-cancer-what-is-bile-duct-cancer http://www.cancer.org/cancer/bileductcancer/detailedguide/bile-duct-cancer-what-is-bile-duct-cancer]. Access on: 23 May 2013.</ref>
-*Malignancy of the biliary tree.
+{{Main|Cholangiocarcinoma}}
-*May be intrahepatic, i.e. ''intrahepatic cholangiocarcinoma'' (abbreviated ''ICC''), or extrahepatic.
-====Epidemiology====
+==Hepatic angiosarcoma==
-*Rare - approximately 1/5 the incidence of HCC.<ref>{{Ref GLP|608}}</ref>
-*More common among asians.
-Risks:
-*Infection - liver flukes (endemic to Southeast Asia):
-**''Clonorchis sinensis'' ([[AKA]] ''Opisthorchis sinensis''<ref name=Ref_PBoD926>{{Ref PBoD|926}}</ref>).<ref name=pmid18420495>{{Cite journal  | last1 = Park | first1 = do H. | last2 = Son | first2 = HY. | title = Images in clinical medicine. Clonorchis sinensis. | journal = N Engl J Med | volume = 358 | issue = 16 | pages = e18 | month = Apr | year = 2008 | doi = 10.1056/NEJMicm054461 | PMID = 18420495 |URL = http://www.nejm.org/doi/full/10.1056/NEJMicm054461 }}</ref>
-**''Opisthorchis viverrini''.<ref name=pmid20202771>{{cite journal |author=de Martel C, Plummer M, Franceschi S |title=Cholangiocarcinoma: Descriptive epidemiology and risk factors |journal=Gastroenterol Clin Biol |volume= |issue= |pages= |year=2010 |month=March |pmid=20202771 |doi=10.1016/j.gcb.2010.01.008 |url=}}</ref>
-*[[Caroli disease]] - rare congenital disease.<ref name=pmid17418061>{{cite journal |author=Ananthakrishnan AN, Saeian K |title=Caroli's disease: identification and treatment strategy |journal=Curr Gastroenterol Rep |volume=9 |issue=2 |pages=151–5 |year=2007 |month=April |pmid=17418061 |doi= |url=}}</ref>
-*[[Primary sclerosing cholangitis]] - may be assoc. with inflammatory bowel disease (IBD), esp. [[ulcerative colitis]] (UC).
-===Gross===
-*Classically one large mass - outline described as ''cauliflower-like''.<ref name=pmid18425077>{{Cite journal  | last1 = Nakanishi | first1 = Y. | last2 = Zen | first2 = Y. | last3 = Kawakami | first3 = H. | last4 = Kubota | first4 = K. | last5 = Itoh | first5 = T. | last6 = Hirano | first6 = S. | last7 = Tanaka | first7 = E. | last8 = Nakanuma | first8 = Y. | last9 = Kondo | first9 = S. | title = Extrahepatic bile duct carcinoma with extensive intraepithelial spread: a clinicopathological study of 21 cases. | journal = Mod Pathol | volume = 21 | issue = 7 | pages = 807-16 | month = Jul | year = 2008 | doi = 10.1038/modpathol.2008.65 | PMID = 18425077 | URL = http://www.nature.com/modpathol/journal/v21/n7/full/modpathol200865a.html }}</ref>
-**May have satellite nodules.
-Image:
-*[http://commons.wikimedia.org/wiki/File:Cholangiocarcinoma.png Cholangiocarcinoma (WC)].
-===Microscopic===
-Features:<ref name=Ref_GLP609>{{Ref GLP|609}}</ref>
-*Usually an ''adenocarcinoma'', i.e. gland forming with:
-**Cuboidal or columnar mucin producing cells, and
-**A dense fibrous (desmoplastic) stroma.
-Notes:
-*Biliary stents lead to reactive changes,<ref name=pmid3877438>{{Cite journal  | last1 = Carrasco | first1 = CH | last2 = Wallace | first2 = S | last3 = Charnsangavej | first3 = C | last4 = Richli | first4 = W | last5 = Wright | first5 = KC | last6 = Fanning | first6 = T | last7 = Gianturco | first7 = C | title = Expandable biliary endoprosthesis: an experimental study. | journal = AJR Am J Roentgenol | volume = 145 | issue = 6 | pages = 1279-81 | month = Dec | year = 1985 | doi =  | PMID = 3877438 }}</ref> these can be confused for malignancy.  One must always check whether a biliary stent was in situ at time of biopsy.<ref>STC. 2 October 2009.</ref>
-*Usually abundant desmoplasia, ergo hard to get good, i.e. diagnositic, endoluminal brushing specimens.<ref>STC. 6 December 2010.</ref>
-DDx:
-*Metastatic adenocarinoma.
-**[[Pancreatic adenocarcinoma]].
-*Fulminant hepatic [[necrosis]].
-**Bile ducts usu. left behind... look like well-differentiated adenocarcinoma.
-Images:
-*[[WC]]:
-**[http://commons.wikimedia.org/wiki/File:Cholangiocarcinoma_-_low_mag.jpg Cholangiocarcinoma - low mag. (WC)] - the image shows the typical demosplastic stroma.
-**[http://commons.wikimedia.org/wiki/File:Cholangiocarcinoma_-_high_mag.jpg Cholangiocarcinoma - high mag. (WC)] - the image shows a normal portal triad adjacent to atypical glandular cells within the interlobular septum and obvious tumour.
-*www:
-**[http://path.upmc.edu/cases/case296.html Cholangiocarcinoma & liver flukes - several images (upmc.edu)].
-**[http://path.upmc.edu/cases/case420.html Cholangiocarcinoma - several images (upmc.edu)].
-===IHC===
-Classic IHC pattern:<ref>{{Ref GLP|609}}</ref>
-*CK7 +ve.
-*CK20 +ve/-ve.
-*HepPar-1 -ve.
-*AFP -ve.<ref>STC. 6 December 2010.</ref>
-ICC vs. HCC:<ref name=pmid19173916>[Evaluation of immunohistochemical markers for differential diagnosis of hepatocellular carcinoma from intrahepatic cholangiocarcinoma] Dong H, Cong WL, Zhu ZZ, Wang B, Xian ZH, Yu H. Zhonghua Zhong Liu Za Zhi. 2008 Sep;30(9):702-5. Chinese. PMID 19173916.</ref>
-*ICC: CK19 (92.5%), MUC-1 (73.8%) +ve.
-*HCC: HepPar-1 (85.6%), CD34 (87.8%) +ve.
-HCC vs. ICC:<ref name=pmid16627262>{{cite journal |author=Lei JY, Bourne PA, diSant'Agnese PA, Huang J |title=Cytoplasmic staining of TTF-1 in the differential diagnosis of hepatocellular carcinoma vs cholangiocarcinoma and metastatic carcinoma of the liver |journal=Am. J. Clin. Pathol. |volume=125 |issue=4 |pages=519–25 |year=2006 |month=April |pmid=16627262 |doi=10.1309/59TN-EFAL-UL5W-J94M |url=}}</ref>
-*TTF-1: ~90-100% +ve (cytoplasmic) in HCC vs. ~10% in cholangiocarcinoma.
-==Angiosarcoma==
 {{Main|Angiosarcoma}}
+*[[AKA]] ''angiosarcoma of the liver''.
 ===General===
 *Liver angiosarcomas are associated with vinyl chloride exposure.<ref name=Ref_PCPBoD8_212>{{Ref PCPBoD8|212}}</ref>
@@ Line 417: / Line 375: @@
 ==Hepatic metastasis==
+{{Main|Liver metastasis}}
 *[[AKA]] ''liver metastases''.
-===General===
+*[[AKA]] ''metastatic liver disease''.
-*Metastases are very common - often from the gastrointestinal tract, e.g. [[colorectal cancer]].
+==Hematopoietic tumors==
-**Most liver masses in are not biopsied... as a primary lesion is evident.<ref>OA. 29 November 2009.</ref>
+A [[File:1 MM 1 Covenant 680x512px.tif|One liver core was normal (Row 1 Left 40X).]]
-*Dependent on the extent of disease, [[CRC]] metastatic to the liver may be curable with a liver resection.
+<br>
-*It is important to consider [[germ cell tumour]]s in the DDx as these may be curable with chemotherapy.
+B [[File:2 MM 1 Covenant 680x512px.tif|A triad with a proliferated bile ductule, otherwise normal (Row 1 Right 400X).]]
-*Clear cell variant of HCC may be misdiagnosed as metastatic clear cell carcinoma.
+<br>
-*Interhepatic cholangiocarcinoma is an adenocarcinoma - it may look like a metastatic lesion.
+C [[File:3 MM 1 Covenant 680x512px.tif|The other core showed a mass of tumor mashed against normal liver (Row 2 Left 40X).]]
+<br>
+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).]]
 <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>
+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.
-===Microscopic===
+[[File:5 02965636298621 sl 1.png|Malignant B cell lymphoma, NOS, in a 63 year old man’s liver]]
-Features:
+[[File:5 02965636298621 sl 2.png|Malignant B cell lymphoma, NOS, in a 63 year old man’s liver]]
-*Histologic features are dependent on primary and degree of differentiation.
+[[File:5 02965636298621 sl 3.png|Malignant B cell lymphoma, NOS, in a 63 year old man’s liver]]
-The classic liver metastasis ([[colorectal carcinoma]]):
+[[File:5 02965636298621 sl 4.png|Malignant B cell lymphoma, NOS, in a 63 year old man’s liver]]
-*Gland forming columnar shaped cells with pseudostratified hyperchromatic cigar-shaped nuclei.
+[[File:5 02965636298621 sl 31.png|Malignant B cell lymphoma, NOS, in a 63 year old man’s liver]]
+[[File:5 02965636298621 sl 6.png|Malignant B cell lymphoma, NOS, in a 63 year old man’s liver]]
+<br>
+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.
-Image:
+[[File:4 89735893919405 sl 1.png| High grade B cell lymphoma involving liver]]
-*[http://commons.wikimedia.org/wiki/File:Adenocarcinoma_liver_metastasis.jpg Liver metastasis - adenocarcinoma, not obviously CRC (WC)].
+[[File:4 89735893919405 sl 2.png| High grade B cell lymphoma involving liver]]
+[[File:4 89735893919405 sl 3.png| High grade B cell lymphoma involving liver]]
-===IHC===
+[[File:4 89735893919405 sl 4.png| High grade B cell lymphoma involving liver]]
-*Metastases are typically negative for ''HepPar-1''.
+[[File:4 89735893919405 sl 5.png| High grade B cell lymphoma involving liver]]<br>
-**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>
+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=

Difference between revisions of "Liver neoplasms"

Latest revision as of 23:15, 31 January 2017

Overview

Dysplasic lesions of the liver

Neoplastic lesions

Malignant lesions of the liver

Lesions that arise in a non-cirrhotic liver

Tabular comparison

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Benign hepatic neoplasms

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Malignant hepatic neoplasms

Hepatoblastoma

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Hepatocellular carcinoma

Biliary Intraductal Papillary Neoplasm[17]

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Biliary Intraductal Papillary Neoplasm^[17]