| Adrenocortical carcinoma |
| Classification and external resources |
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Micrograph of an adrenocortical carcinoma (left of image – dark blue) and the adrenal cortex it arose from (right-top of image – pink/light blue). Benign adrenal medulla is present (right-middle of image – gray/blue). H&E stain.
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| ICD-10 |
C74.0 |
| ICD-9 |
194 |
| ICD-O: |
M8370/3 |
| OMIM |
202300 |
| MedlinePlus |
001663 |
| eMedicine |
ped/41 |
| MeSH |
D018268 |
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.[1][2] Adrenocortical carcinoma has a bimodal distribution by age, with cases clustering in children under 5, and in adults 30–40 years old.[1] Adrenocortical 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%.[1]
Contents
- 1 Signs and symptoms
- 2 Pathophysiology
- 3 Diagnosis
- 3.1 Laboratory findings
- 3.2 Radiology
- 3.3 Pathology
- 3.4 Differential Diagnosis
- 4 Treatment
- 5 Prognosis
- 6 References
- 7 External links
Signs and symptoms
Adrenocortical carcinoma may present differently in children and adults. Most tumors in children are functional, and virilization is by far the most common presenting symptom, followed by Cushing's syndrome and precocious puberty.[1] 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 catecholamines has been reported in adrenocortical cancers.[3] Non-functional tumors (about 40%, authorities vary) usually present with abdominal or flank pain, or they may be asymptomatic and detected incidentally.[2]
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.[1][2][4]
Pathophysiology
The main etiologic factor of adrenocortical cancer is unknown. Families with Li–Fraumeni syndrome have increased risk. The p53, retinoblastoma protein (RB) tumor suppressor genes 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.[5]
Diagnosis
Laboratory findings
Hormonal syndromes should be confirmed with laboratory testing. Laboratory findings in Cushing syndrome include increased serum glucose (blood sugar) and increased urine cortisol. 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
Radiology
Radiological studies of the abdomen, 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 scans are routinely performed to look for metastases to the lungs and bones respectively. These studies are critical in determining whether or not the tumor can be surgically removed, the only potential cure at this time.[2]
Pathology
Gross of a large adrenal cortical carcinoma.
Cell block preparation from a fine-needle aspiration biopsy of a large ACC shows tumor cells with compact, eosinophilic cytoplasm and a mild degree of nuclear pleomorphism.
Adrenal tumors are often not biopsied prior to surgery, so diagnosis is confirmed on examination of the surgical specimen by a pathologist. 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 adenomas.[3] 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
Differential diagnosis includes:[citation needed]
- Adrenocortical adenoma
- Renal cell carcinoma
- Adrenal medullary tumors
- Hepatocellular carcinoma
Treatment
The only curative treatment is complete surgical 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.[1]
Chemotherapy regimens typically include the drug mitotane, an inhibitor of steroid synthesis which is toxic to cells of the adrenal cortex,[6] as well as standard cytotoxic drugs. A retrospective analysis showed a survival benefit for mitotane in addition to surgery when compared to surgery alone.[7]
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[8]), comparing these two regimens.
Prognosis
ACC, generally, carries a poor prognosis[9] and is unlike most tumours of the adrenal cortex, which are benign (adenomas) 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%.[9]
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+.[citation needed]
References
- ^ a b c d e f edited by Vincent T. DeVita, Samuel Hellman, Steven A. Rosenberg (2005). Cancer: principles & practice of oncology. Philadelphia: Lippincott-Raven. ISBN 0-7817-4865-8.
- ^ a b c d Savarese, Diane MF; Lynnette K Nieman (2006-08-08). "Clinical presentation and evaluation of adrenocortical tumors". UpToDate Online v. 15.1. UpToDate. Retrieved 2007-06-05.
- ^ a b Richard Cote, Saul Suster, Lawrence Weiss, Noel Weidner (Editor) (2002). Modern Surgical Pathology (2 Volume Set). London: W B Saunders. ISBN 0-7216-7253-1.
- ^ Kasper DL, Braunwald E, Fauci AS, Hauser SL, Longo DL, Jameson JL. Harrison's Principles of Internal Medicine. New York: McGraw-Hill, 2005. ISBN 0-07-139140-1
- ^ Kufe D (2000). Benedict RC, Holland JF, ed. Cancer medicine (5th ed.). Hamilton, Ont: B.C. Decker. ISBN 1-55009-113-1. OCLC 156944448.
- ^ Laurence L. Brunton, editor-in-chief; John S. Lazo and Keith L. Parker, Associate Editors (2006). Goodman & Gilman's The Pharmacological Basis of Therapeutics, 11th Edition. United States of America: The McGraw-Hill Companies, Inc. ISBN 0-07-142280-3.
- ^ Terzolo M, Angeli A, Fassnacht M et al. (June 2007). "Adjuvant mitotane treatment for adrenocortical carcinoma". N. Engl. J. Med. 356 (23): 2372–80. doi:10.1056/NEJMoa063360. PMID 17554118.
- ^ http://www.firm-act.org
- ^ a b Allolio B, Fassnacht M (2006). "Clinical review: Adrenocortical carcinoma: clinical update". J Clin Endocrinol Metab 91 (6): 2027–37. doi:10.1210/jc.2005-2639. PMID 16551738. Free Full Text.
External links
- www.endotext.org article
- Cancer.Net: Adrenal Gland Tumor
- AdrenalCancerSupport.org Reference Information for Patients
- The Pawan Motwani Adrenal Cortical Cancer Foundation
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Glandular and epithelial neoplasms (ICD-O 8010-8589)
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| Epithelium |
Papilloma/carcinoma
(8010-8139) |
- Small cell carcinoma
- Combined small cell carcinoma
- Verrucous carcinoma
- Squamous cell carcinoma
- Basal cell carcinoma
- Transitional cell carcinoma
- Inverted papilloma
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|
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| Glands |
Adenomas/
adenocarcinomas
(8140-8429) |
| Gastrointestinal |
- tract: Linitis plastica
- Familial adenomatous polyposis
- pancreas
- Insulinoma
- Glucagonoma
- Gastrinoma
- VIPoma
- Somatostatinoma
- Cholangiocarcinoma
- Klatskin tumor
- Hepatocellular adenoma/Hepatocellular carcinoma
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| Urogenital |
- Renal cell carcinoma
- Endometrioid tumor
- Renal oncocytoma
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| Endocrine |
- Prolactinoma
- Multiple endocrine neoplasia
- Adrenocortical adenoma/Adrenocortical carcinoma
- Hurthle cell
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| Other/multiple |
- Neuroendocrine tumor
- Adenoid cystic carcinoma
- Oncocytoma
- Clear cell adenocarcinoma
- Apudoma
- Cylindroma
- Papillary hidradenoma
|
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Adnexal and
skin appendage (8390-8429) |
- sweat gland
- Syringocystadenoma papilliferum
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Cystic, mucinous,
and serous (8440-8499) |
| Cystic general |
- Cystadenoma/Cystadenocarcinoma
|
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| Mucinous |
- Signet ring cell carcinoma
- Mucinous cystadenoma / Mucinous cystadenocarcinoma
- Mucoepidermoid carcinoma
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| Serous |
- Ovarian serous cystadenoma / Pancreatic serous cystadenoma / Serous cystadenocarcinoma / Papillary serous cystadenocarcinoma
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Ductal, lobular,
and medullary (8500-8549) |
| Ductal carcinoma |
- Mammary ductal carcinoma
- Pancreatic ductal carcinoma
- Comedocarcinoma
- Paget's disease of the breast / Extramammary Paget's disease
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| Lobular carcinoma |
- Lobular carcinoma in situ
- Invasive lobular carcinoma
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| Medullary carcinoma |
- Medullary carcinoma of the breast
- Medullary thyroid cancer
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| Acinar cell (8550-8559) |
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| Other |
| Complex epithelial (8560-8589) |
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- See also
- Template:Epithelium and epithelial tissue
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Tumors: endocrine gland neoplasia (C73–C75/D34–D35, 193–194/226–227)
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Pancreas/
islets of Langerhans |
- neuroendocrine tumors/islet cell carcinoma: α: Glucagonoma
- β: Insulinoma
- δ: Somatostatinoma
- G: Gastrinoma
- VIPoma
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Hypothalamic/
pituitary axes
+parathyroid |
| Pituitary |
- Pituitary adenoma: Prolactinoma
- ACTH-secreting pituitary adenoma
- GH-secreting pituitary adenoma
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| Thyroid |
- Thyroid cancer (malignant): epithelial cell carcinoma
- Papillary
- Follicular/Hurthle cell
- parafollicular cell
- Anaplastic
- Lymphoma
- Squamous cell carcinoma
- Benign: Thyroid adenoma
- Struma ovarii
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| Parathyroid |
- Parathyroid adenoma
- Parathyroid carcinoma
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| Adrenal tumor |
- adrenal cortex
- Adrenocortical adenoma
- Adrenocortical carcinoma
- adrenal medulla
- Pheochromocytoma
- Neuroblastoma
- see also: Paraganglioma
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| Gonads |
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| Pinealoma |
- Pinealoblastoma
- Pineocytoma
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| MEN |
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noco (d)/cong/tumr, sysi/epon
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proc, drug (A10/H1/H2/H3/H5)
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