Difference between revisions of "Hepatocellular carcinoma"

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| LMDDx      = [[cholangiocarcinoma]], occasionally [[liver metastasis]], [[High-grade hepatocellular dysplasia|high-grade dysplasia]]
| LMDDx      = [[cholangiocarcinoma]], occasionally [[liver metastasis]], [[High-grade hepatocellular dysplasia|high-grade dysplasia]]
| Stains    = reticulin (thickened liver plate)
| Stains    = reticulin (thickened liver plate)
| IHC        = CD34 +ve sinusoids, HepPar-1 +ve (usu.), AFP +ve (usu.), CK8/18 +ve, glypican-3 +ve  
| IHC        = CD34 +ve sinusoids, HepPar-1 +ve (usu.), [[AFP]] +ve (usu.), CK8/18 +ve, [[glypican-3]] +ve  
| EM        =
| EM        =
| Molecular  =
| Molecular  =
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Image:Hepatocellular_carcinoma_intermed_mag.jpg | HCC - intermed mag. (WC)
Image:Hepatocellular_carcinoma_intermed_mag.jpg | HCC - intermed mag. (WC)
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A
[[File:1 HCC 3 680x512px.tif| Hepatocellular carcinoma with fragments of liver afflicted by steatosis & with regenerative, benign fragments.]]
B
[[File:2 HCC 3 680x512px.tif| Hepatocellular carcinoma with fragments of liver afflicted by steatosis & with regenerative, benign fragments.]]
C
[[File:3 HCC 3 680x512px.tif| Hepatocellular carcinoma with fragments of liver afflicted by steatosis & with regenerative, benign fragments.]]
D
[[File:4 HCC 3 680x512px.tif| Hepatocellular carcinoma with fragments of liver afflicted by steatosis & with regenerative, benign fragments.]]
E
[[File:5 HCC 3 680x512px.tif| Hepatocellular carcinoma with fragments of liver afflicted by steatosis & with regenerative, benign fragments.]]
F
[[File:6 HCC 3 680x512px.tif| Hepatocellular carcinoma with fragments of liver afflicted by steatosis & with regenerative, benign fragments.]]
G
[[File:7 HCC 3 680x512px.tif| Hepatocellular carcinoma with fragments of liver afflicted by steatosis & with regenerative, benign fragments.]]
H
[[File:8 HCC 3 680x512px.tif| Hepatocellular carcinoma with fragments of liver afflicted by steatosis & with regenerative, benign fragments.]]
Hepatocellular carcinoma with fragments of liver afflicted by steatosis & with regenerative, benign fragments. A. Fragments of liver with crowded nuclei, consistent with hepatoma, as well as with steatosis [arrows]. B. Fragments of liver with crowded nuclei, consistent with hepatoma, as well as with larger amount of cytoplasm, consistent with regeneration [arrow]. C. The fatty liver below has aberrant-appearing nuclei, but not particularly crowded, in contrast to the fragment on top, which has crowded nuclei. D. Reticulin stain shows apparent expansion of nuclei between black lines on the fatty liver, but this may also be seen with simple steatosis; on the crowded liver note the lack of definite expansion. E. The regenerative focus shows abundant cytoplasm. F. Reticulin on this regenerative focus shows preservation of the low number of nuclei between black lines. G. This typical hepatocellular focus shows crowding, occasional acini, and basophilia, similar to the focus seen in row 2. Note that some cells show apparent steatosis. H. Reticulin on this hepatocellular focus shows loss of reticulin fibers, with more than six nuclei between several black lines (Row 4 Right 200X).
A
[[File:1 hcc 1 680x512px.tif|Fibrous bands dissect hepatocyte nodules, mostly hepatoma(Row 1 Left 20X).]]
B
[[File:2 hcc 1 680x512px.tif|The fibrous band on right bears proliferating bile ductules; acinar arrangement on left shows holes much larger than canaliculi (Row 1 Right 100X).]]
C
[[File:3 hcc 1 680x512px.tif|The tumor has cancerous nuclei; note the bile which makes for absolute diagnostic certainty [arrow] (Row 2 Left 400X).]]
D
[[File:4 hcc 1 680x512px.tif|Noncancerous hepatocytes on left can be compared with tumor cells on right. Note increased nuclear crowding & a subtle increment in cytoplasmic basophilia in tumor  (Row 2 Right 400X).]]
Hepatocellular carcinoma with acini.  A. Fibrous bands dissect hepatocyte nodules, mostly hepatoma. B. The fibrous band on right bears proliferating bile ductules; acinar arrangement on left shows holes much larger than canaliculi. C. The tumor has cancerous nuclei; note the bile which makes for absolute diagnostic certainty [arrow]. D. Noncancerous hepatocytes on left can be compared with tumor cells on right. Note increased nuclear crowding & a subtle increment in cytoplasmic basophilia in tumor.
A
[[File:1 steatohep HCC 6 680x512px.tif|Fragments of tumor at low power mimic normal hepatocyte groups without triads (Row 1 Left 20X).]]
B
[[File:2 steatohep HCC 6 680x512px.tif|Vacuoles, mostly small, occasionally become large enough to warrant “macrovesicular” [green arrows]. Note Mallory hyalin [red arrows] (Row 1 Right 400X).]]
C
[[File:3 steatohep HCC 6 680x512px.tif|Chronic inflammatory cells bound some cancer cells (Row 2 Left 400X).]]
D
[[File:4 steatohep HCC 6 680x512px.tif|Nuclear inclusions are occasionally prominent [arrows] (Row 2 Right 400X).]]
Hepatocellular carcinoma, steatohepatitic variant. A. Fragments of tumor at low power mimic normal hepatocyte groups without portal triads. B. Vacuoles, mostly small, occasionally become large enough to warrant the term “macrovesicular” [green arrows]. Note Mallory hyalin [red arrows]. D. Chronic inflammatory cells bound some cancer cells. D. Nuclear inclusions [arrows] are occasionally prominent [arrows].
[[File: HCC CL 1 sl 1.png| Hepatocellular carcinoma, clear cell variant]]
[[File: HCC CL 1 sl 2.png| Hepatocellular carcinoma, clear cell variant]]
[[File: HCC CL 1 sl 3.png| Hepatocellular carcinoma, clear cell variant]]
[[File: HCC CL 1 sl 4.png| Hepatocellular carcinoma, clear cell variant]]
[[File: HCC CL 1 sl 5.png| Hepatocellular carcinoma, clear cell variant]]
Hepatocellular carcinoma, clear cell variant. Much more difficult on biopsy than on resection is the specific identification of the clear cell variant, although it was done here. Variants are of little clinical significance apart from the fibrolamellar variant. A. Tumor fragment masses with clearing contrast with pink liver fragments. B. Tumor cell cytoplasm on the core biopsy varies, often clear, often light pink and foamy. C. PAS without diastase shows brightly positive tumor cytoplasm. D. Modestly variable, rounded nuclei show open chromatin and nucleoli. Individual pyknotic nuclei (black arrows) are insufficient as evidence of necrosis sufficient to increase grade. D. PAS with diastase shows the material is glycogen. E. At resection, the cytoplasmic clarity at low power is more impressive than on biopsy. F. The high power view of the resection specimen shows the cytoplasm is truly clear. Arrows point to Mallory bodies.
[[File:5 04760075043191 sl 1.png| Hepatocellular carcinoma arising in cirrhosis]]
[[File:5 04760075043191 sl 2.png| Hepatocellular carcinoma arising in cirrhosis]]
[[File:5 04760075043191 sl 3.png| Hepatocellular carcinoma arising in cirrhosis]]
[[File:5 04760075043191 sl 4.png| Hepatocellular carcinoma arising in cirrhosis]]
[[File:5 04760075043191 sl 5.png| Hepatocellular carcinoma arising in cirrhosis]]
[[File:5 04760075043191 sl 6.png| Hepatocellular carcinoma arising in cirrhosis]]
[[File:5 04760075043191 sl 7.png| Hepatocellular carcinoma arising in cirrhosis]]
[[File:5 04760075043191 sl 8.png| Hepatocellular carcinoma arising in cirrhosis]]
Hepatocellular carcinoma superimposed on cirrhosis in a 60 year old man. A. Dark tumor, sometimes with separate cords visible at low power (black arrow), contrasts with lightly colored regenerative nodules (green arrows) within fibrotic bands. B. Regenerative nodules are separated by a band with proliferated bile ducts, whose orientation, lacking haphazard spread, bespeaks a benign process. C. Reticulin of regenerative nodule shows two cell thick cords lacking orientation, disrupted without reason, aggregated and, at left, slighely dispersed. D. Hepatocellular carcinoma shows darker cytoplasm and more nuclei per square mm than regenerative nodules. Note the many acini, also a good sign of cancer. E. Reticulin fibers have disappeared, leaving cords with 6 or more nuclei thick in places. F. PAS D stain shows benign proliferated bile ducts, whose orientation from lower left to upper right deprives the proliferation of the haphazard nature of a cholangiocarcinoma. G. PAS-D shows the cytoplasmic digestion of glycogen in a hepatocellular carcinoma, a helpful hint at times. Note the finger like cords, the mitosis (black arrow), and the occasional acinar lumens (red arrows). H. PAS D of regenerative nodule contrasts with the image of the hepatocellular carcinoma.


===Fibrolamellar hepatocellular carcinoma===
===Fibrolamellar hepatocellular carcinoma===
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*CD34 +ve sinusoids; sinusoids in normal liver are CD34 -ve.
*CD34 +ve sinusoids; sinusoids in normal liver are CD34 -ve.
*HepPar-1 +ve; may be neg. in high grade tumours.
*HepPar-1 +ve; may be neg. in high grade tumours.
*AFP +ve; may be neg. even if the serum AFP is elevated.
*[[AFP]] +ve; may be neg. even if the serum AFP is elevated.
*CK8/18 +ve.<ref name=pmid16680226>{{Cite journal  | last1 = Stroescu | first1 = C. | last2 = Herlea | first2 = V. | last3 = Dragnea | first3 = A. | last4 = Popescu | first4 = I. | title = The diagnostic value of cytokeratins and carcinoembryonic antigen immunostaining in differentiating hepatocellular carcinomas from intrahepatic cholangiocarcinomas. | journal = J Gastrointestin Liver Dis | volume = 15 | issue = 1 | pages = 9-14 | month = Mar | year = 2006 | doi =  | PMID = 16680226 }}</ref>
*CK8/18 +ve.<ref name=pmid16680226>{{Cite journal  | last1 = Stroescu | first1 = C. | last2 = Herlea | first2 = V. | last3 = Dragnea | first3 = A. | last4 = Popescu | first4 = I. | title = The diagnostic value of cytokeratins and carcinoembryonic antigen immunostaining in differentiating hepatocellular carcinomas from intrahepatic cholangiocarcinomas. | journal = J Gastrointestin Liver Dis | volume = 15 | issue = 1 | pages = 9-14 | month = Mar | year = 2006 | doi =  | PMID = 16680226 }}</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>
*[[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>
*TTF-1 +ve cytoplasmic staining.<ref name=pmid22359993>{{Cite journal  | last1 = Mishra | first1 = M. | last2 = Morgan | first2 = V. | last3 = Hamati | first3 = AK. | last4 = Al-Abbadi | first4 = M. | title = Carcinoma of unknown primary: check the liver... thanks to TTF-1. | journal = Tenn Med | volume = 105 | issue = 1 | pages = 35-6, 40 | month = Jan | year = 2012 | doi =  | PMID = 22359993 }}</ref>
**Benign liver also has cytoplasmic staining.


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