Adrenocortical carcinoma
Encyclopedia
Adrenocortical carcinoma, also adrenal cortical carcinoma (ACC) and adrenal cortex cancer, is an aggressive cancer
originating in the cortex
(steroid hormone
-producing tissue) of the adrenal gland
. Adrenocortical carcinoma is a rare tumor, with incidence of 1-2 per million population annually. Adrenocortical carcinoma has a bimodal distribution by age, with cases clustering in children under 6, and in adults 30–40 years old. Adenocortical carcinoma is remarkable for the many hormonal syndromes which can occur in patients with steroid hormone-producing ("functional") tumors, including Cushing's syndrome
, Conn syndrome, virilization
, and feminization
. Adrenocortical carcinoma has often invaded nearby tissues or metastasized
to distant organs at the time of diagnosis, and the overall 5-year survival rate is only 20-35%.
is by far the most common presenting symptom, followed by Cushing's syndrome
and precocious puberty
. Among adults presenting with hormonal syndromes, Cushing's syndrome alone is most common, followed by mixed Cushing's and virilization (glucocorticoid
and androgen
overproduction). Feminization
and Conn syndrome (mineralocorticoid
excess) occur in less than 10% of cases. Rarely, pheochromocytoma
-like hypersecretion of catecholamine
s has been reported in adrenocortical cancers. Non-functional tumors (about 40%, authorities vary) usually present with abdominal or flank pain, or they may be asymptomatic and detected incidentally.
All patients with suspected adrenocortical carcinoma should be carefully evaluated for signs and symptoms of hormonal syndromes. For Cushing's syndrome (glucocorticoid
excess) these include weight gain
, muscle wasting, purple lines on the abdomen, a fatty "buffalo hump
" on the neck, a "moonlike" face
, and thinning,fragile skin. Virilism (androgen
excess) is most obvious in women, and may produce excess facial and body hair
, acne
, enlargement of the clitoris
, deepening of the voice, coarsening of facial features, cessation of menstruation. Conn syndrome (mineralcorticoid excess) is marked by high blood pressure which can result in headache
and hypokalemia
(low serum potassium, which can in turn produce muscle weakness, confusion, and palpitations) low plasma renin
activity, and high serum aldosterone
. Feminization
(estrogen
excess) is most readily noted in men, and includes breast enlargement
, decreased libido
and impotence.
have increased risk. The p53
, retinoblastoma protein
(RB) tumor suppressor gene
s located on chromosomes 17p, 13q respectively, may be changed. The genes h19, insulin-like growth factor II (IGF-II), p57kip2 are important for fetal growth and development. They are located on chromosome 11p. Expression of the h19 gene is markedly reduced in both nonfunctioning and functioning adrenal cortical carcinomas, especially in tumors producing cortisol
and aldosterone
. There is also a loss of activity of the p57kip2 gene product in virilizing adenomas and adrenal cortical carcinomas. In contrast, IGF-II gene expression has been shown to be high in adrenal cortical carcinomas. Finally, c-myc gene expression is relatively high in neoplasms, and it is often linked to poor prognosis.
. Adrenal virilism is confirmed by the finding of an excess of serum androstenedione
and dehydroepiandrosterone
. Findings in Conn syndrome include low serum potassium
, low plasma renin
activity, and high serum aldosterone
. Feminization is confirmed with the finding of excess serum estrogen
, such as CT scans and magnetic resonance imaging
are useful for identifying the site of the tumor, differentiating it from other diseases, such as adrenocortical adenoma
, and determining the extent of invasion of the tumor into surrounding organs and tissues. CT scans of the chest
and bone scan
s are routinely performed to look for metastases
to the lung
s and bone
s respectively. These studies are critical in determining whether or not the tumor can be surgically
removed, the only potential cure
at this time.
. Grossly, adrenocortical carcinomas are often large, with a tan-yellow cut surface, and areas of hemorrhage and necrosis
. On microscopic examination
, the tumor usually displays sheets of atypical cells with some resemblance to the cells of the normal adrenal cortex
. The presence of invasion
and mitotic activity
help differentiate small cancers from adrenocortical adenoma
s.
There are several relatively rare variants of adrenal cortical carcinoma: Oncocytic adrenal cortical carcinoma, Myxoid adrenal cortical carcinoma, Carcinosarcoma, Adenosquamous adrenocortical carcinoma, Clear cell adrenal cortical carcinoma.
Differential diagnosis includes:
Adrenocortical adenoma
,
Renal cell carcinoma
,
Adrenal medullary tumors,
Hepatocellular carcinoma
.
excision of the tumor, which can be performed even in the case of invasion into large blood vessels, such as the renal vein
or inferior vena cava
. The 5-year survival rate after successful surgery is 50-60%, but unfortunately, a large percentage of patients are not surgical candidates. Radiation therapy
and radiofrequency ablation
may be used for palliation
in patients who are not surgical candidates.
Chemotherapy
regimens typically include the drug mitotane
, an inhibitor of steroid
synthesis which is toxic to cells of the adrenal cortex
, as well as standard cytotoxic drugs. A retrospective analysis showed a survival benefit for mitotane in addition to surgery when compared to surgery alone.
The two most common regimens are cisplatin
, doxorubicin
, etoposide
+ mitotane
and streptozotocin
+ mitotane
. It is unknown which regimen is better. Researchers at Uppsala University Hospital
initiated a collaboration between adrenocortical cancer specialists in Europe, USA and Australia, to conduct the first ever randomized controlled trial in adrenocortical cancer (FIRM-ACT study), comparing these two regimens.
and is unlike most tumours of the adrenal cortex, which are benign
(adenoma
s) and only occasionally cause Cushing's syndrome
. Five-year disease-free survival for a complete resection of a stage
I-III ACC is approximately 30%.
The most important prognostic factors are age of the patient and stage of the tumor.
Poor prognostic factors: mitotic activity, venous invasion, weight of 50g+; diameter of 6.5 cm+, Ki-67/MIB1 labeling index of 4%+, p53+.
Research Fellow Sachin H. Jain, Professor Michael E. Porter
, and colleagues at Harvard Business School have published an extensive business school case study documenting the care process for a single patient with adrenal cortical carcinoma, "Ledina Lushko: Navigating Health Care Delivery."
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
originating in the cortex
Adrenal cortex
Situated along the perimeter of the adrenal gland, the adrenal cortex mediates the stress response through the production of mineralocorticoids and glucocorticoids, including aldosterone and cortisol respectively. It is also a secondary site of androgen synthesis.-Layers:Notably, the reticularis in...
(steroid hormone
Steroid hormone
A steroid hormone is a steroid that acts as a hormone. Steroid hormones can be grouped into five groups by the receptors to which they bind: glucocorticoids, mineralocorticoids, androgens, estrogens, and progestogens...
-producing tissue) of the adrenal gland
Adrenal gland
In mammals, the adrenal glands are endocrine glands that sit atop the kidneys; in humans, the right suprarenal gland is triangular shaped, while the left suprarenal gland is semilunar shaped...
. Adrenocortical carcinoma is a rare tumor, with incidence of 1-2 per million population annually. Adrenocortical carcinoma has a bimodal distribution by age, with cases clustering in children under 6, and in adults 30–40 years old. Adenocortical carcinoma is remarkable for the many hormonal syndromes which can occur in patients with steroid hormone-producing ("functional") tumors, including Cushing's syndrome
Cushing's syndrome
Cushing's syndrome is a hormone disorder caused by high levels of cortisol in the blood. This can be caused by taking glucocorticoid drugs, or by tumors that produce cortisol or adrenocorticotropic hormone or CRH...
, Conn syndrome, virilization
Virilization
In biology and medicine, virilization refers to the biological development of sex differences, changes that make a male body different from a female body. Most of the changes of virilization are produced by androgens...
, and feminization
Feminization (biology)
In biology and medicine, feminization refers to the development in an organism of physical or behavioral characteristics unique to the female of the species. This may represent a normal developmental process, contributing to sexual differentiation....
. Adrenocortical carcinoma has often invaded nearby tissues or metastasized
Metastasis
Metastasis, or metastatic disease , is the spread of a disease from one organ or part to another non-adjacent organ or part. It was previously thought that only malignant tumor cells and infections have the capacity to metastasize; however, this is being reconsidered due to new research...
to distant organs at the time of diagnosis, and the overall 5-year survival rate is only 20-35%.
Signs and Symptoms
Adrenocortical carcinoma may present differently in children and adults. Most tumors in children are functional, and virilizationVirilization
In biology and medicine, virilization refers to the biological development of sex differences, changes that make a male body different from a female body. Most of the changes of virilization are produced by androgens...
is by far the most common presenting symptom, followed by Cushing's syndrome
Cushing's syndrome
Cushing's syndrome is a hormone disorder caused by high levels of cortisol in the blood. This can be caused by taking glucocorticoid drugs, or by tumors that produce cortisol or adrenocorticotropic hormone or CRH...
and precocious puberty
Precocious puberty
As a medical term, precocious puberty describes puberty occurring at an unusually early age. In most of these children, the process is normal in every respect except the unusually early age, and simply represents a variation of normal development. In a minority of children, the early development is...
. Among adults presenting with hormonal syndromes, Cushing's syndrome alone is most common, followed by mixed Cushing's and virilization (glucocorticoid
Glucocorticoid
Glucocorticoids are a class of steroid hormones that bind to the glucocorticoid receptor , which is present in almost every vertebrate animal cell...
and androgen
Androgen
Androgen, also called androgenic hormone or testoid, is the generic term for any natural or synthetic compound, usually a steroid hormone, that stimulates or controls the development and maintenance of male characteristics in vertebrates by binding to androgen receptors...
overproduction). Feminization
Feminization
Feminization can refer to:*Feminization the hormonally induced development of female sexual characteristics*Feminization a sexual or lifestyle practice where a person assumes a female role...
and Conn syndrome (mineralocorticoid
Mineralocorticoid
Mineralocorticoids are a class of steroid hormones characterised by their similarity to aldosterone and their influence on salt and water balances.-Physiology:...
excess) occur in less than 10% of cases. Rarely, pheochromocytoma
Pheochromocytoma
A pheochromocytoma or phaeochromocytoma is a neuroendocrine tumor of the medulla of the adrenal glands , or extra-adrenal chromaffin tissue that failed to involute after birth and secretes excessive amounts of catecholamines, usually noradrenaline , and adrenaline to a lesser extent...
-like hypersecretion of catecholamine
Catecholamine
Catecholamines are molecules that have a catechol nucleus consisting of benzene with two hydroxyl side groups and a side-chain amine. They include dopamine, as well as the "fight-or-flight" hormones adrenaline and noradrenaline released by the adrenal medulla of the adrenal glands in response to...
s has been reported in adrenocortical cancers. Non-functional tumors (about 40%, authorities vary) usually present with abdominal or flank pain, or they may be asymptomatic and detected incidentally.
All patients with suspected adrenocortical carcinoma should be carefully evaluated for signs and symptoms of hormonal syndromes. For Cushing's syndrome (glucocorticoid
Glucocorticoid
Glucocorticoids are a class of steroid hormones that bind to the glucocorticoid receptor , which is present in almost every vertebrate animal cell...
excess) these include weight gain
Weight gain
Weight gain is an increase in body weight. This can be either an increase in muscle mass, fat deposits, or excess fluids such as water.-Description:...
, muscle wasting, purple lines on the abdomen, a fatty "buffalo hump
Lipodystrophy
Lipodystrophy is a medical condition characterized by abnormal or degenerative conditions of the body's adipose tissue. A more specific term, lipoatrophy is used when describing the loss of fat from one area...
" on the neck, a "moonlike" face
Moon face
Moon face, or moon facies, is a medical sign where the face swells up into a rounded shape.It is often associated with Cushing's syndrome or steroid treatment , which has led to it being known as Cushingoid facies or steroid facies respectively...
, and thinning,fragile skin. Virilism (androgen
Androgen
Androgen, also called androgenic hormone or testoid, is the generic term for any natural or synthetic compound, usually a steroid hormone, that stimulates or controls the development and maintenance of male characteristics in vertebrates by binding to androgen receptors...
excess) is most obvious in women, and may produce excess facial and body hair
Hirsutism
Hirsutism or frazonism is the excessive hairiness on women in those parts of the body where terminal hair does not normally occur or is minimal - for example, a beard or chest hair. It refers to a male pattern of body hair and it is therefore primarily of cosmetic and psychological concern...
, acne
Acne
Acne is a general term used for acneiform eruptions. It is usually used as a synonym for acne vulgaris, but may also refer to:*Acne aestivalis*Acne conglobata*Acne cosmetica*Acne fulminans*Acne keloidalis nuchae*Acne mechanica...
, enlargement of the clitoris
Clitoris
The clitoris is a sexual organ that is present only in female mammals. In humans, the visible button-like portion is located near the anterior junction of the labia minora, above the opening of the urethra and vagina. Unlike the penis, which is homologous to the clitoris, the clitoris does not...
, deepening of the voice, coarsening of facial features, cessation of menstruation. Conn syndrome (mineralcorticoid excess) is marked by high blood pressure which can result in headache
Headache
A headache or cephalalgia is pain anywhere in the region of the head or neck. It can be a symptom of a number of different conditions of the head and neck. The brain tissue itself is not sensitive to pain because it lacks pain receptors. Rather, the pain is caused by disturbance of the...
and hypokalemia
Hypokalemia
Hypokalemia or hypokalaemia , also hypopotassemia or hypopotassaemia , refers to the condition in which the concentration of potassium in the blood is low...
(low serum potassium, which can in turn produce muscle weakness, confusion, and palpitations) low plasma renin
Renin
Renin , also known as an angiotensinogenase, is an enzyme that participates in the body's renin-angiotensin system -- also known as the Renin-Angiotensin-Aldosterone Axis -- that mediates extracellular volume , and arterial vasoconstriction...
activity, and high serum aldosterone
Aldosterone
Aldosterone is a hormone that increases the reabsorption of sodium ions and water and the release of potassium in the collecting ducts and distal convoluted tubule of the kidneys' functional unit, the nephron. This increases blood volume and, therefore, increases blood pressure. Drugs that...
. Feminization
Feminization
Feminization can refer to:*Feminization the hormonally induced development of female sexual characteristics*Feminization a sexual or lifestyle practice where a person assumes a female role...
(estrogen
Estrogen
Estrogens , oestrogens , or œstrogens, are a group of compounds named for their importance in the estrous cycle of humans and other animals. They are the primary female sex hormones. Natural estrogens are steroid hormones, while some synthetic ones are non-steroidal...
excess) is most readily noted in men, and includes breast enlargement
Gynecomastia
Gynecomastia or Gynaecomastia, , is the abnormal development of large mammary glands in males resulting in breast enlargement. The term comes from the Greek γυνή gyné meaning "woman" and μαστός mastós meaning "breast"...
, decreased libido
Libido
Libido refers to a person's sex drive or desire for sexual activity. The desire for sex is an aspect of a person's sexuality, but varies enormously from one person to another, and it also varies depending on circumstances at a particular time. A person who has extremely frequent or a suddenly...
and impotence.
Pathobiology
The main etiologic factor of adrenocortical cancer is unknown. Families with Li-Fraumeni syndromeLi-Fraumeni syndrome
Li-Fraumeni syndrome is an extremely rare autosomal dominant hereditary disorder. It is named after Frederick Pei Li and Joseph F. Fraumeni, Jr., the American physicians who first recognized and described the syndrome. Li-Fraumeni syndrome greatly increases susceptibility to cancer...
have increased risk. The p53
P53
p53 , is a tumor suppressor protein that in humans is encoded by the TP53 gene. p53 is crucial in multicellular organisms, where it regulates the cell cycle and, thus, functions as a tumor suppressor that is involved in preventing cancer...
, retinoblastoma protein
Retinoblastoma protein
The retinoblastoma protein is a tumor suppressor protein that is dysfunctional in the majority types of cancer. One highly studied function of pRb is to prevent excessive cell growth by inhibiting cell cycle progression until a cell is ready to divide...
(RB) tumor suppressor gene
Tumor suppressor gene
A tumor suppressor gene, or anti-oncogene, is a gene that protects a cell from one step on the path to cancer. When this gene is mutated to cause a loss or reduction in its function, the cell can progress to cancer, usually in combination with other genetic changes.-Two-hit hypothesis:Unlike...
s located on chromosomes 17p, 13q respectively, may be changed. The genes h19, insulin-like growth factor II (IGF-II), p57kip2 are important for fetal growth and development. They are located on chromosome 11p. Expression of the h19 gene is markedly reduced in both nonfunctioning and functioning adrenal cortical carcinomas, especially in tumors producing cortisol
Cortisol
Cortisol is a steroid hormone, more specifically a glucocorticoid, produced by the adrenal gland. It is released in response to stress and a low level of blood glucocorticoids. Its primary functions are to increase blood sugar through gluconeogenesis; suppress the immune system; and aid in fat,...
and aldosterone
Aldosterone
Aldosterone is a hormone that increases the reabsorption of sodium ions and water and the release of potassium in the collecting ducts and distal convoluted tubule of the kidneys' functional unit, the nephron. This increases blood volume and, therefore, increases blood pressure. Drugs that...
. There is also a loss of activity of the p57kip2 gene product in virilizing adenomas and adrenal cortical carcinomas. In contrast, IGF-II gene expression has been shown to be high in adrenal cortical carcinomas. Finally, c-myc gene expression is relatively high in neoplasms, and it is often linked to poor prognosis.
Laboratory findings
Hormonal syndromes should be confirmed with laboratory testing. Laboratory findings in Cushing syndrome include increased serum glucose (blood sugar) and increased urine cortisolCortisol
Cortisol is a steroid hormone, more specifically a glucocorticoid, produced by the adrenal gland. It is released in response to stress and a low level of blood glucocorticoids. Its primary functions are to increase blood sugar through gluconeogenesis; suppress the immune system; and aid in fat,...
. Adrenal virilism is confirmed by the finding of an excess of serum androstenedione
Androstenedione
Androstenedione is a 19-carbon steroid hormone produced in the adrenal glands and the gonads as an intermediate step in the biochemical pathway that produces the androgen testosterone and the estrogens estrone and estradiol.-Synthesis:Androstenedione is the common precursor of male and female sex...
and dehydroepiandrosterone
Dehydroepiandrosterone
5-Dehydroepiandrosterone is a 19-carbon endogenous steroid hormone. It is the major secretory steroidal product of the adrenal glands and is also produced by the gonads and the brain. DHEA is the most abundant circulating steroid in humans....
. Findings in Conn syndrome include low serum potassium
Hypokalemia
Hypokalemia or hypokalaemia , also hypopotassemia or hypopotassaemia , refers to the condition in which the concentration of potassium in the blood is low...
, low plasma renin
Renin
Renin , also known as an angiotensinogenase, is an enzyme that participates in the body's renin-angiotensin system -- also known as the Renin-Angiotensin-Aldosterone Axis -- that mediates extracellular volume , and arterial vasoconstriction...
activity, and high serum aldosterone
Aldosterone
Aldosterone is a hormone that increases the reabsorption of sodium ions and water and the release of potassium in the collecting ducts and distal convoluted tubule of the kidneys' functional unit, the nephron. This increases blood volume and, therefore, increases blood pressure. Drugs that...
. Feminization is confirmed with the finding of excess serum estrogen
Estrogen
Estrogens , oestrogens , or œstrogens, are a group of compounds named for their importance in the estrous cycle of humans and other animals. They are the primary female sex hormones. Natural estrogens are steroid hormones, while some synthetic ones are non-steroidal...
Radiology
Radiological studies of the abdomenAbdomen
In vertebrates such as mammals the abdomen constitutes the part of the body between the thorax and pelvis. The region enclosed by the abdomen is termed the abdominal cavity...
, such as CT scans and magnetic resonance imaging
Magnetic resonance imaging
Magnetic resonance imaging , nuclear magnetic resonance imaging , or magnetic resonance tomography is a medical imaging technique used in radiology to visualize detailed internal structures...
are useful for identifying the site of the tumor, differentiating it from other diseases, such as adrenocortical adenoma
Adrenocortical adenoma
A adrenocortical adenoma is a benign tumor of the adrenal cortex.It can present with Cushing's syndrome or primary aldosteronism....
, and determining the extent of invasion of the tumor into surrounding organs and tissues. CT scans of the chest
Chest
The chest is a part of the anatomy of humans and various other animals. It is sometimes referred to as the thorax or the bosom.-Chest anatomy - Humans and other hominids:...
and bone scan
Bone scan
A bone scan or bone scintigraphy is a nuclear scanning test to find certain abnormalities in bone which are triggering the bone's attempts to heal. It is primarily used to help diagnose a number of conditions relating to bones, including: cancer of the bone or cancers that have spread to the bone,...
s are routinely performed to look for metastases
Metastasis
Metastasis, or metastatic disease , is the spread of a disease from one organ or part to another non-adjacent organ or part. It was previously thought that only malignant tumor cells and infections have the capacity to metastasize; however, this is being reconsidered due to new research...
to the lung
Lung
The lung is the essential respiration organ in many air-breathing animals, including most tetrapods, a few fish and a few snails. In mammals and the more complex life forms, the two lungs are located near the backbone on either side of the heart...
s and bone
Bone
Bones are rigid organs that constitute part of the endoskeleton of vertebrates. They support, and protect the various organs of the body, produce red and white blood cells and store minerals. Bone tissue is a type of dense connective tissue...
s respectively. These studies are critical in determining whether or not the tumor can be surgically
Surgery
Surgery is an ancient medical specialty that uses operative manual and instrumental techniques on a patient to investigate and/or treat a pathological condition such as disease or injury, or to help improve bodily function or appearance.An act of performing surgery may be called a surgical...
removed, the only potential cure
Cure
A cure is a completely effective treatment for a disease.The Cure is an English rock band.Cure, or similar, may also refer to:-Film and television:* The Cure , a short film starring Charlie Chaplin...
at this time.
Pathology
Adrenal tumors are often not biopsied prior to surgery, so diagnosis is confirmed on examination of the surgical specimen by a pathologistAnatomical pathology
Anatomical pathology or Anatomic pathology is a medical specialty that is concerned with the diagnosis of disease based on the gross, microscopic, chemical, immunologic and molecular examination of organs, tissues, and whole bodies...
. Grossly, adrenocortical carcinomas are often large, with a tan-yellow cut surface, and areas of hemorrhage and necrosis
Necrosis
Necrosis is the premature death of cells in living tissue. Necrosis is caused by factors external to the cell or tissue, such as infection, toxins, or trauma. This is in contrast to apoptosis, which is a naturally occurring cause of cellular death...
. On microscopic examination
Histopathology
Histopathology refers to the microscopic examination of tissue in order to study the manifestations of disease...
, the tumor usually displays sheets of atypical cells with some resemblance to the cells of the normal adrenal cortex
Adrenal cortex
Situated along the perimeter of the adrenal gland, the adrenal cortex mediates the stress response through the production of mineralocorticoids and glucocorticoids, including aldosterone and cortisol respectively. It is also a secondary site of androgen synthesis.-Layers:Notably, the reticularis in...
. The presence of invasion
Invasion
An invasion is a military offensive consisting of all, or large parts of the armed forces of one geopolitical entity aggressively entering territory controlled by another such entity, generally with the objective of either conquering, liberating or re-establishing control or authority over a...
and mitotic activity
Mitosis
Mitosis is the process by which a eukaryotic cell separates the chromosomes in its cell nucleus into two identical sets, in two separate nuclei. It is generally followed immediately by cytokinesis, which divides the nuclei, cytoplasm, organelles and cell membrane into two cells containing roughly...
help differentiate small cancers from adrenocortical adenoma
Adrenocortical adenoma
A adrenocortical adenoma is a benign tumor of the adrenal cortex.It can present with Cushing's syndrome or primary aldosteronism....
s.
There are several relatively rare variants of adrenal cortical carcinoma: Oncocytic adrenal cortical carcinoma, Myxoid adrenal cortical carcinoma, Carcinosarcoma, Adenosquamous adrenocortical carcinoma, Clear cell adrenal cortical carcinoma.
Differential diagnosis includes:
Adrenocortical adenoma
Adrenocortical adenoma
A adrenocortical adenoma is a benign tumor of the adrenal cortex.It can present with Cushing's syndrome or primary aldosteronism....
,
Renal cell carcinoma
Renal cell carcinoma
Renal cell carcinoma is a kidney cancer that originates in the lining of the proximal convoluted tubule, the very small tubes in the kidney that filter the blood and remove waste products. RCC is the most common type of kidney cancer in adults, responsible for approximately 80% of cases...
,
Adrenal medullary tumors,
Hepatocellular carcinoma
Hepatocellular carcinoma
Hepatocellular carcinoma is the most common type of liver cancer. Most cases of HCC are secondary to either a viral hepatitide infection or cirrhosis .Compared to other cancers, HCC is quite a rare tumor in the United States...
.
Treatment
The only curative treatment is complete surgicalSurgery
Surgery is an ancient medical specialty that uses operative manual and instrumental techniques on a patient to investigate and/or treat a pathological condition such as disease or injury, or to help improve bodily function or appearance.An act of performing surgery may be called a surgical...
excision of the tumor, which can be performed even in the case of invasion into large blood vessels, such as the renal vein
Renal vein
The renal veins are veins that drain the kidney. They connect the kidney to the inferior vena cava.It is usually singular to each kidney, except in the condition "multiple renal veins".It also divides into 2 divisions upon entering the kidney:...
or inferior vena cava
Inferior vena cava
The inferior vena cava , also known as the posterior vena cava, is the large vein that carries de-oxygenated blood from the lower half of the body into the right atrium of the heart....
. The 5-year survival rate after successful surgery is 50-60%, but unfortunately, a large percentage of patients are not surgical candidates. Radiation therapy
Radiation therapy
Radiation therapy , radiation oncology, or radiotherapy , sometimes abbreviated to XRT or DXT, is the medical use of ionizing radiation, generally as part of cancer treatment to control malignant cells.Radiation therapy is commonly applied to the cancerous tumor because of its ability to control...
and radiofrequency ablation
Radiofrequency ablation
Radio frequency ablation is a medical procedure where part of the electrical conduction system of the heart, tumor or other dysfunctional tissue is ablated using the heat generated from the high frequency alternating current to treat a medical disorder...
may be used for palliation
Palliative care
Palliative care is a specialized area of healthcare that focuses on relieving and preventing the suffering of patients...
in patients who are not surgical candidates.
Chemotherapy
Chemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....
regimens typically include the drug mitotane
Mitotane
Mitotane, or o,p'-DDD, is an antineoplastic medication used in the treatment of adrenocortical carcinoma. It is an isomer of DDD and is a derivative of DDT...
, an inhibitor of steroid
Steroid
A steroid is a type of organic compound that contains a characteristic arrangement of four cycloalkane rings that are joined to each other. Examples of steroids include the dietary fat cholesterol, the sex hormones estradiol and testosterone, and the anti-inflammatory drug dexamethasone.The core...
synthesis which is toxic to cells of the adrenal cortex
Adrenal cortex
Situated along the perimeter of the adrenal gland, the adrenal cortex mediates the stress response through the production of mineralocorticoids and glucocorticoids, including aldosterone and cortisol respectively. It is also a secondary site of androgen synthesis.-Layers:Notably, the reticularis in...
, as well as standard cytotoxic drugs. A retrospective analysis showed a survival benefit for mitotane in addition to surgery when compared to surgery alone.
The two most common regimens are cisplatin
Cisplatin
Cisplatin, cisplatinum, or cis-diamminedichloroplatinum is a chemotherapy drug. It is used to treat various types of cancers, including sarcomas, some carcinomas , lymphomas, and germ cell tumors...
, doxorubicin
Doxorubicin
Doxorubicin INN is a drug used in cancer chemotherapy. It is an anthracycline antibiotic, closely related to the natural product daunomycin, and like all anthracyclines, it works by intercalating DNA....
, etoposide
Etoposide
Etoposide phosphate is an anti-cancer agent. It is known in the laboratory as a topoisomerase poison. Etoposide is often incorrectly referred to as a topoisomerase inhibitor in order to avoid using the term "poison" in a clinical setting...
+ mitotane
Mitotane
Mitotane, or o,p'-DDD, is an antineoplastic medication used in the treatment of adrenocortical carcinoma. It is an isomer of DDD and is a derivative of DDT...
and streptozotocin
Streptozotocin
Streptozotocin is a naturally occurring chemical that is particularly toxic to the insulin-producing beta cells of the pancreas in mammals...
+ mitotane
Mitotane
Mitotane, or o,p'-DDD, is an antineoplastic medication used in the treatment of adrenocortical carcinoma. It is an isomer of DDD and is a derivative of DDT...
. It is unknown which regimen is better. Researchers at Uppsala University Hospital
Uppsala University Hospital
Uppsala University Hospital in Uppsala, Sweden is a teaching hospital for the Uppsala University Faculty of Medicine and the Nursing School. Uppsala University Hospital is owned and operated by the Uppsala County Council in cooperation with the university and serves, together with Enköping...
initiated a collaboration between adrenocortical cancer specialists in Europe, USA and Australia, to conduct the first ever randomized controlled trial in adrenocortical cancer (FIRM-ACT study), comparing these two regimens.
Prognosis
ACC, generally, carries a poor prognosisand is unlike most tumours of the adrenal cortex, which are benign
Benign
A benign tumor is a tumor that lacks the ability to metastasize. Common examples of benign tumors include moles and uterine fibroids.The term "benign" implies a mild and nonprogressive disease. Indeed, many kinds of benign tumors are harmless to human health...
(adenoma
Adenoma
An adenoma is a benign tumor of glandular origin. Adenomas can grow from many organs including the colon, adrenal glands, pituitary gland, thyroid, prostate, etc. Although these growths are benign, over time they may progress to become malignant, at which point they are called adenocarcinomas...
s) and only occasionally cause Cushing's syndrome
Cushing's syndrome
Cushing's syndrome is a hormone disorder caused by high levels of cortisol in the blood. This can be caused by taking glucocorticoid drugs, or by tumors that produce cortisol or adrenocorticotropic hormone or CRH...
. Five-year disease-free survival for a complete resection of a stage
Cancer staging
The stage of a cancer is a description of the extent the cancer has spread. The stage often takes into account the size of a tumor, how deeply it has penetrated, whether it has invaded adjacent organs, how many lymph nodes it has metastasized to , and whether it has spread to distant organs...
I-III ACC is approximately 30%.
The most important prognostic factors are age of the patient and stage of the tumor.
Poor prognostic factors: mitotic activity, venous invasion, weight of 50g+; diameter of 6.5 cm+, Ki-67/MIB1 labeling index of 4%+, p53+.
Research Fellow Sachin H. Jain, Professor Michael E. Porter
Michael Porter
Michael Eugene Porter is the Bishop William Lawrence University Professor at Harvard Business School. He is a leading authority on company strategy and the competitiveness of nations and regions. Michael Porter’s work is recognized in many governments, corporations and academic circles globally...
, and colleagues at Harvard Business School have published an extensive business school case study documenting the care process for a single patient with adrenal cortical carcinoma, "Ledina Lushko: Navigating Health Care Delivery."