Fibrolamellar carcinoma (FLC) is a rare form of carcinoma that typically affects young adults and is characterized, under the
microscope, by laminated
fibrous layers interspersed between the tumor cells. Approximately 200 new cases are diagnosed worldwide each year. FLC, also known as fibrolamellar hepatocellular carcinoma, is different from the more common hepatocellular carcinoma (HCC) in that it afflicts young people with normal liver function and no known risk factors.
Cause
A recent study showed the presence of the
DNAJB1-
PRKACA
The catalytic subunit α of protein kinase A is a key regulatory enzyme that in humans is encoded by the ''PRKACA'' gene. This enzyme is responsible for phosphorylating other proteins and substrates, changing their activity. Protein kinase A catal ...
chimeric transcript (resulting from a 400kb somatic deletion on chromosome 19) in 100% of the FLCs examined (15/15) This gene fusion has been confirmed in a second study.
[Dinh TA, Vitucci EC, Wauthier E, Graham RP, Pitman WA, Oikawa T, Chen M, Silva G, Greene KG, Torbenson MS, Reid LM, Sethupathy P (2017) Comprehensive analysis of The Cancer Genome Atlas reveals a unique gene and non-coding RNA signature of fibrolamellar carcinoma.
Sci Rep 7:44653. doi: 10.1038/srep44653]
Pathology
The histopathology of FLC is characterized by laminated fibrous layers, interspersed between the tumor cells.
Cytologically, the tumor cells have a low
nuclear to cytoplasmic ratio with abundant
eosinophilic
cytoplasm. Tumors are non-encapsulated, but well circumscribed, when compared to conventional HCC (which typically has an invasive border).
Diagnosis
Due to lack of symptoms, until the tumor is sizable, this form of
cancer is often advanced when diagnosed. Symptoms include vague abdominal pain, nausea, abdominal fullness, malaise and weight loss. They may also include a palpable
liver mass. Other presentations include
jaundice
Jaundice, also known as icterus, is a yellowish or greenish pigmentation of the skin and sclera due to high bilirubin levels. Jaundice in adults is typically a sign indicating the presence of underlying diseases involving abnormal heme meta ...
,
ascites, fulminant liver failure,
encephalopathy,
gynecomastia (males only), thrombophlebitis of the lower limbs, recurrent deep vein thrombosis,
anemia and hypoglycemia.
The usual markers for
liver disease –
aspartate aminotransferase,
alanine aminotransferase and
alkaline phosphatase
The enzyme alkaline phosphatase (EC 3.1.3.1, alkaline phosphomonoesterase; phosphomonoesterase; glycerophosphatase; alkaline phosphohydrolase; alkaline phenyl phosphatase; orthophosphoric-monoester phosphohydrolase (alkaline optimum), systematic ...
– are often normal or only slightly elevated. FLC often does not produce
alpha fetoprotein
Alpha-fetoprotein (AFP, α-fetoprotein; also sometimes called alpha-1-fetoprotein, alpha-fetoglobulin, or alpha fetal protein) is a protein that in humans is encoded by the ''AFP'' gene. The ''AFP'' gene is located on the ''q'' arm of chromosome 4 ...
(AFP), a widely used marker for conventional
hepatocellular carcinoma
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer in adults and is currently the most common cause of death in people with cirrhosis. HCC is the third leading cause of cancer-related deaths worldwide.
It occurs in t ...
. It is associated with elevated
neurotensin levels.
Diagnosis is normally made by imaging (
ultrasound,
CT or
MRI) and biopsy
Treatment
In FLC, plasma
neurotensin and serum
vitamin B12 binding globulin are commonly increased and are useful in monitoring the disease and detecting recurrence.
FLC can often be surgically removed.
Liver resection
Hepatectomy is the surgical resection (removal of all or part) of the liver. While the term is often employed for the removal of the liver from a liver transplant donor, this article will focus on partial resections of hepatic tissue and hepatopo ...
is the optimal treatment and may need to be performed more than once, since this disease has a very high recurrence rate. Due to such recurrence, periodic follow-up
medical imaging
Medical imaging is the technique and process of imaging the interior of a body for clinical analysis and medical intervention, as well as visual representation of the function of some organs or tissues (physiology). Medical imaging seeks to rev ...
(CT or MRI) is necessary.
When the tumor cannot be removed surgically or when there is distant spread, many different systemic therapies are currently being used to treat the disease. However, no standard of care currently exists for FLC. Consequently, there remains a pressing need to identify proven, effective systemic therapies for the cancer. Radiotherapy has been used but data is limited concerning its use.
The FibroFoundation has resources available o
different FLC treatment options
The survival rate for FLC largely depends on whether (and to what degree) the cancer has
metastasized, i.e. spread to the
lymph node
A lymph node, or lymph gland, is a kidney-shaped organ of the lymphatic system and the adaptive immune system. A large number of lymph nodes are linked throughout the body by the lymphatic vessels. They are major sites of lymphocytes that inclu ...
s or other organs. Distant spread (metastases), significantly reduces the median survival rate. Five-year survival rates vary between 40–90%.
Epidemiology
FLC accounts for 1–10% of primary liver cancers.
[Lafaro KJ, Pawlik TM (2015) Fibrolamellar hepatocellular carcinoma: current clinical perspectives. J Hepatocell Carcinoma 2:151–157 doi: 10.2147/JHC.S75153] It typically has a young age at presentation (20–40 years: mean age ~27 years
) when compared to conventional HCC. Unlike the more common HCC, patients most often do not have coexistent liver disease such as
cirrhosis.
History
This disease was first described by Hugh Edmondson in a 14-year-old female with no underlying liver disease.
[Edmondson HA (1956) Differential diagnosis of tumors and tumor-like lesions of liver in infancy and childhood. AMA J Dis Child 91(2):168–186] The name fibrolamellar hepatocellular carcinoma was coined by Craig et al. in 1980.
[Craig JR, Peters RL, Edmondson HA, Omata M. Fibrolamellar carcinoma of the liver: a tumor of adolescents and young adults with distinctive clinico-pathologic features. Cancer 46(2):372–379] It was not recognized as a distinct form of cancer by the WHO until 2010.
[Bosman FT (2010) World Health Organization. WHO Classification of Tumours of the Digestive System. 4th ed. Lyon: International Agency for Research on Cancer]
Additional images
Image: Fibrolamellar hepatocellular carcinoma -2- intermed mag.jpg , Intermed. mag.
Image: Fibrolamellar hepatocellular carcinoma -2- high mag.jpg , High mag.
References
External links
{{DEFAULTSORT:Fibrolamellar Hepatocellular Carcinoma
Diseases of liver
Pediatric cancers
Digestive system neoplasia
Rare cancers