Final Diagnosis -- Cholangiocarcinoma of Liver

FINAL DIAGNOSIS:   CHOLANGIOCARCINOMA ARISING IN A HCV RELATED CIRRHOTIC LIVER.

DISCUSSION:

Intrahepatic Cholangiocarcinoma:

• Adenocarcinoma arising from intrahepatic bile duct epithelial cells
• 10% of primary liver cancers
• High prevalence in southeast and eastern Asia.
• Usually age 60+ years; no gender preference; but mean age 40 years in those with primary sclerosing cholangitis or chronic inflammatory bowel disease
• Although previously thought to be not related to cirrhosis yet Japanese series suggest that HCV related cirrhosis is a major risk factor for cholangiocarcinoma in Japan (1).

Laboratory:

• Normal AFP, occasional hypercalcemia.

Gross Characteristics:

• Tends to be firmer and whiter than liver cell carcinoma because of their greater amount of fibrous tissue. Multicentricity is common (2)

Microscopic Characteristics:

• Adenocarcinoma with glandular and tubular structures, mucin production and dense desmoplasia; epithelial cells are anaplastic, cuboidal to columnar with eosinophilic cytoplasm and round central nuclei, tumor cells are heterogeneous even within the same gland but resemble bile duct cells, not hepatocytes; spread along hepatic plates, duct walls, via nerves (81% perineural)(3), but not sinusoidal; the stroma usually abundant may be circumferential around glands; associated with neutrophils; variable vascular invasion; no bile production(4).Patterns also include : signet ring, adenosquamous, osteoclast giant cell, sarcomatous, colloid, mucoepidermoid, rhabdoid, clear cell, lymphoepithelioma-like.
• Note: the finding of foci of in-situ carcinoma, dysplasia or perineural/vascular invasion would be very valuable to differentiate a primary carcinoma form a metastasis.

Helpful special stains and immunohistochemistry:

• Mucin (+)
• CK7 (+) CK20 (-)
• CEA monoclonal (+), polyclonal (+) (cytoplasmic and luminal, not canalicular).

Molecular:

• K-ras mutations (6)

Differential diagnosis:

• Clinical and radiological assessment is essential
• Hepatocellular carcinoma (tubular type):
  • Mucin (-)
  • CEA Monoclonal (-) polyclonal (+) (canalicular not cytoplasmic).
  • AFP (+) and HepPar (+)
• Metastatic GI adenocarcinoma:
  • Could be differentiated form colorectal adenocarcinoma (CK. 20(+), CK7 (-)
  • But difficult to differentiate form pancreatic or gastric adenocarcinoma
• Other metastasis ex Breast. GCDFP (+) ER (+/-)
• Epithelioid hemangioendothelioma (vascular markers+, mucin-),
• Benign bile duct proliferations (smaller, no atypia, non- infiltrating).

Prognosis:

• Poor prognosis; death usually within 6 months; 5 year survival in resectable cases is 30%.
• 50-75% metastasize to regional lymph nodes, lungs, vertebrae, adrenals, brain, elsewhere at autopsy.

REFERENCES:

1. Masahiro Kobayashi, Kenji Ikeda, Satoshi Saitoh, Fumitaka Suzuki, Akihito Tsubota, Yoshiyuki Suzuki, Yasuji Arase, Naoya Murashima, Kazuaki Chayama, Hiromitsu Kumada "Incidence of primary cholangiocellular carcinoma of the liver in Japanese patients with hepatitis C virus-related cirrhosis". Cancer ,Volume 88, Issue 11, Date: 1 June 2000, Pages: 2471-2477.
2. Suzuki M, Takahashi T, Ouchi K, Matsuno S. "The development and extension of hepatohilar bile duct carcinoma. A three-dimensional tumor mapping in the intrahepatic biliary tree visualized with the Aid of graphics computer system". Cancer, 1989, 64: 658-666.
3. Bhuiya MR, Nimura Y, Kamiya J, Kondo S, Fukata S , Hayakawa N Shinonoya S. clinicopathological studies on perineural invasion of bile duct carcinoma. Ann surg 1992, 215: 344-349.
4. Weinbren K, Mutum SS. "Pathological aspects of cholangiocarcinoma. J Pathol 1983, 139: 217-238.
5. Nakajima T, Kondo Y. Well differentiated choangiocarcinoma diagnostic significance of morphological and immunohistochemical parameters. Am Jsurg Pathol 1989,13: 569-573.
6. Tada M, Omata M, Ohto M. High incidence of ras gene mutation in intrahepatic cholangiocarcinoma". Cancer 1992, 69: 1115-1118.

Contributed by Ahmed Bedeir MD and Parmjeet S Randhawa, MD