intrahepatic cholangiocarcinoma
Definition: Adenocarcinoma arising from intrahepatic bile duct epithelial cells.
Synopsis
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.
Laboratory:
Normal AFP, occasional hypercalcemia.
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:
- glandular pattern
- tubular pattern
- adenosquamous pattern
- mucoepidermoid pattern
- sarcomatous pattern
- colloid pattern
Variants
- intrahepatic clear cell cholangiocarcinoma
- signet ring cells
- osteoclast giant cells
- rhabdoid
- clear cell
- lymphoepithelioma-like pattern
Special stains
Mucin (+)
Immunohistochemistry
CK7 (+)
CK20 (-)
CEA monoclonal (+), polyclonal (+) (cytoplasmic and luminal, not canalicular)
Gene mutations
KRAS (Ki-ras) mutations
Differential diagnosis
hepatocellular carcinoma (tubular type) [Mucin (-) , CEA Monoclonal (-) polyclonal (+) (canalicular not cytoplasmic), AFP (+) and HepPar (+)]
metastatic GI adenocarcinoma:
- metastatic colorectal adenocarcinoma [CK20(+), CK7 (-) ]
- pancreatic adenocarcinoma
- gastric adenocarcinoma
metastasis mammary cvarcinoma [GCDFP (+) ER (+/-)]
epithelioid hemangioendothelioma [vascular markers+, mucin-]
benign bile duct proliferations [smaller, no atypia, non- infiltrating]
Differential diagnosis
The finding of foci of in-situ carcinoma, dysplasia or perineural/vascular invasion can be very valuable to differentiate a primary carcinoma form a metastasis.
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.
Variants
intrahepatic cholangiocarcinoma metastatic to the ovary (#18043033#)
See also
cholangiocarcinomas
References
Khunamornpong S, Siriaunkgul S, Suprasert P, Pojchamarnwiputh S, Na Chiangmai W, Young RH. Intrahepatic cholangiocarcinoma metastatic to the ovary: a report of 16 cases of an underemphasized form of secondary tumor in the ovary that may mimic primary neoplasia. Am J Surg Pathol. 2007 Dec;31(12):1788-99. PMID: #18043033#