Fibrolamellar carcinoma (FLC) is a rare form of carcinoma that typically affects young adults and is characterized, under the

microscope A microscope () is a laboratory instrument used to examine objects that are too small to be seen by the naked eye. Microscopy is the science of investigating small objects and structures using a microscope. Microscopic means being invisi ...

, by laminated

fibrous Fiber or fibre (from la, fibra, links=no) is a #Natural fibers, natural or Fiber#Artificial fibers, artificial substance that is significantly longer than it is wide. Fibers are often used in the manufacture of other materials. The stronge ...

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 DnaJ homolog subfamily B member 1 is a protein that in humans is encoded by the ''DNAJB1'' gene. Interactions DNAJB1 has been shown to interact with: * HSPA4 Heat shock 70 kDa protein 4 is a protein that in humans is encoded by the ''HSPA4'' ...

- PRKACA 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 Cell biology (also cellular biology or cytology) is a branch of biology that studies the structure, function, and behavior of cells. All living organisms are made of cells. A cell is the basic unit of life that is responsible for the living and ...

, the tumor cells have a low nuclear to cytoplasmic ratio with abundant

eosin Eosin is the name of several fluorescent acidic compounds which bind to and form salts with basic, or eosinophilic, compounds like proteins containing amino acid residues such as arginine and lysine, and stains them dark red or pink as a resul ...

ophilic

cytoplasm In cell biology, the cytoplasm is all of the material within a eukaryotic cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. ...

. 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 Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...

is often advanced when diagnosed. Symptoms include vague abdominal pain, nausea, abdominal fullness, malaise and weight loss. They may also include a palpable

liver The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it ...

mass. Other presentations include jaundice,

ascites Ascites is the abnormal build-up of fluid in the abdomen. Technically, it is more than 25 ml of fluid in the peritoneal cavity, although volumes greater than one liter may occur. Symptoms may include increased abdominal size, increased weight, a ...

, fulminant liver failure,

encephalopathy Encephalopathy (; from grc, ἐνκέφαλος "brain" + πάθος "suffering") means any disorder or disease of the brain, especially chronic degenerative conditions. In modern usage, encephalopathy does not refer to a single disease, but r ...

gynecomastia Gynecomastia (also spelled gynaecomastia) is the abnormal non-cancerous enlargement of one or both breasts in males due to the growth of breast tissue as a result of a hormone imbalance between estrogens and androgens. Updated by Brent Wisse ( ...

(males only), thrombophlebitis of the lower limbs, recurrent deep vein thrombosis,

anemia Anemia or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, t ...

and hypoglycemia. The usual markers for

liver disease Liver disease, or hepatic disease, is any of many diseases of the liver. If long-lasting it is termed chronic liver disease. Although the diseases differ in detail, liver diseases often have features in common. Signs and symptoms Some of the si ...

–

aspartate aminotransferase Aspartate transaminase (AST) or aspartate aminotransferase, also known as AspAT/ASAT/AAT or (serum) glutamic oxaloacetic transaminase (GOT, SGOT), is a pyridoxal phosphate (PLP)-dependent transaminase enzyme () that was first described by Arthur ...

alanine aminotransferase Alanine transaminase (ALT) is a transaminase enzyme (). It is also called alanine aminotransferase (ALT or ALAT) and was formerly called serum glutamate-pyruvate transaminase or serum glutamic-pyruvic transaminase (SGPT) and was first character ...

and alkaline phosphatase – are often normal or only slightly elevated. FLC often does not produce alpha fetoprotein (AFP), a widely used marker for conventional hepatocellular carcinoma. It is associated with elevated

neurotensin Neurotensin is a 13 amino acid neuropeptide that is implicated in the regulation of luteinizing hormone and prolactin release and has significant interaction with the dopaminergic system. Neurotensin was first isolated from extracts of bovine ...

levels. Diagnosis is normally made by imaging (

ultrasound Ultrasound is sound waves with frequencies higher than the upper audible limit of human hearing. Ultrasound is not different from "normal" (audible) sound in its physical properties, except that humans cannot hear it. This limit varies ...

, CT or

MRI Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to form pictures of the anatomy and the physiological processes of the body. MRI scanners use strong magnetic fields, magnetic field gradients, and radio waves ...

) and biopsy

Treatment

In FLC, plasma

and serum

vitamin B12 Vitamin B12, also known as cobalamin, is a water-soluble vitamin involved in metabolism. It is one of eight B vitamins. It is required by animals, which use it as a cofactor in DNA synthesis, in both fatty acid and amino acid metabolism. ...

binding globulin are commonly increased and are useful in monitoring the disease and detecting recurrence. FLC can often be surgically removed. Liver resection 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 (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 Metastasis is a pathogenic agent's spread from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, then, ...

, i.e. spread to the lymph nodes 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 Cirrhosis, also known as liver cirrhosis or hepatic cirrhosis, and end-stage liver disease, is the impaired liver function caused by the formation of scar tissue known as fibrosis due to damage caused by liver disease. Damage causes tissue rep ...

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