Liver neoplasms

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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.

Hepatic adenoma

  • AKA hepatocellular adenoma, abbreviated HCA.

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

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.

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

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

Hepatic 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

  • 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.
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  5. URL: http://www.mda-sy.com/vb/showthread.php?p=5083&langid=1. Accessed on: 16 February 2012.
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  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.
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  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.
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  18. URL: http://www.cancer.org/cancer/bileductcancer/detailedguide/bile-duct-cancer-what-is-bile-duct-cancer. Access on: 23 May 2013.
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