Adrenocortical carcinoma
| Adrenocortical carcinoma | |
|---|---|
| Other names | Adrenal cortical carcinoma,adrenocorticocarcinoma,adrenal cortical cancer,adrenal cortex cancer |
 | |
| Micrographof 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. | |
| Specialty | Oncology |
Adrenocortical carcinoma(ACC) is an aggressivecanceroriginating in thecortex(steroid hormone-producing tissue) of theadrenal gland.
Adrenocortical carcinoma is remarkable for the manyhormonal syndromesthat can occur in patients with steroid hormone-producing ( "functional" ) tumors, includingCushing's syndrome,Conn syndrome,virilization,andfeminization.Adrenocortical carcinoma has often invaded nearby tissues ormetastasizedto distant organs at the time of diagnosis, and the overall5-year survival rateis about 50%.[1]
Adrenocortical carcinoma is a rare tumor, with incidence of one to two per million population annually.[2][3][4][5][6]It has a bimodal distribution by age, with cases clustering in children under 5 and in adults 30–40 years old.[5]The widely usedangiotensin-II-responsivesteroid-producingcell lineH295Rwas originally isolated from a tumor diagnosed as adrenocortical carcinoma.[7][8]
Signs and symptoms
[edit]Adrenocortical carcinoma may present differently in children and adults. Most tumors in children are functional, andvirilizationis by far the most common presenting symptom(s), followed byCushing's syndromeandprecocious puberty.[5]Among adults presenting with hormonal syndromes, Cushing's syndrome alone is most common, followed by mixed Cushing's and virilization (glucocorticoidandandrogenoverproduction).FeminizationandConn syndrome(mineralocorticoidexcess) occur in less than 10% of cases. Rarely,pheochromocytoma-like hypersecretion ofcatecholamineshas been reported in adrenocortical cancers.[9]Nonfunctional tumors (about 40%, authorities vary) usually present with abdominal or flank pain, varicocele, and renal vein thrombosis[10]or they may be asymptomatic and detected incidentally.[6]
All patients with suspected ACC should be carefully evaluated for signs and symptoms of hormonal syndromes. For Cushing's syndrome (glucocorticoid excess), these includeweight gain,muscle wasting,purple lines on the abdomen, a fatty "buffalo hump"on the neck, a"moon-like" face,and thinning, fragile skin. Virilism (androgen excess) is most obvious in women, and may produceexcess facial and body hair,acne,enlargement of theclitoris,deepening of the voice, coarsening of facial features,cessation of menstruation.Conn syndrome (mineralcorticoid excess) is marked byhigh blood pressure,which can result inheadacheandhypokalemia(low serum potassium, which can in turn produce muscle weakness, confusion, andpalpitations), low plasmareninactivity, and high serumaldosterone.Feminization (estrogenexcess) is most readily noted in men, and includesbreast enlargement,decreasedlibido,andimpotence.[5][6][11]
Pathophysiology
[edit]The main etiologic factor of ACC is unknown, although families withLi–Fraumeni syndrome,caused by an inherited inactivation mutation inTP53,have increased risk. Several genes have been shown to be recurrently mutated, includingTP53,CTNNB1,MEN1,PRKAR1A,RPL22,andDAXX.[12][13]ThetelomerasegeneTERTis often amplified whileZNRF3andCDKN2Aare often homozygously deleted.[13]The genesh19,insulin-like growth factor II (IGF-II), andp57kip2are important for fetal growth and development. They are located on chromosome 11p. Expression of theh19gene is markedly reduced in both nonfunctioning and functioning adrenal cortical carcinomas, especially in tumors producingcortisolandaldosterone.Also, a loss occurs of activity of thep57kip2gene product in virilizing adenomas and adrenal cortical carcinomas. In contrast,IGF-IIgene expression has been shown to be high in adrenal cortical carcinomas. Finally,c-mycgene expression is relatively high in neoplasms, and it is often linked to poor prognosis.[14]
Bilateral adrenocortical tumors are less common than unilateral. The majority of bilateral tumours can be distinguished according to size and aspect of the nodules:primary pigmented nodular adrenocortical disease,which can be sporadic or part ofCarney complex,and primary bilateral macro nodular adrenal hyperplasia.[citation needed]Metastasisis most commonly to theliverandlung.[15]
Diagnosis
[edit]Laboratory findings
[edit]Hormonal syndromes should be confirmed with laboratory testing. Laboratory findings in Cushing syndrome include increasedserum glucose(blood sugar) and increased urinecortisol.Adrenal virilism is confirmed by the finding of an excess of serumandrostenedioneanddehydroepiandrosterone.Findings in Conn syndrome includelow serum potassium,low plasma renin activity, and high serum aldosterone. Feminization is confirmed with the finding of excess serum estrogen.[citation needed]
Imaging
[edit]Radiological studies of theabdomen,such asCT scansandmagnetic resonance imagingare useful for identifying the site of the tumor, differentiating it from other diseases, such asadrenocortical adenoma,and determining the extent of invasion of the tumor into surrounding organs and tissues. On CT, it shows heterogeneous appearance due to necrosis, calcifications, and haemorrhage. After contrast injection, it shows peripheral enhancement. Invasion of adjacent structures such as kidney, vena cava, liver, and retroperitoneal lymph nodes are also common.[16]
On MRI, it shows low intensity on T1-weighted images, and high T2 signal with strong heterogeneous contrast enhancement and slow washout. Haemorrhagic areas may show high T1-signal.[16]
Pathology
[edit]
Adrenal tumors are often not biopsied prior to surgery, so diagnosis is confirmed on examination of the surgical specimen by apathologist.Grossly, ACCs are often large, with a tan-yellow cut surface, and areas ofhemorrhageandnecrosis.Onmicroscopic examination,the tumor usually displays sheets of atypical cells with some resemblance to the cells of the normaladrenal cortex.The presence ofinvasionandmitotic activityhelp differentiate small cancers fromadrenocortical adenomas.[9] Several relatively rare variants of ACC include:[citation needed]
- Oncocytic adrenal cortical carcinoma
- Myxoid adrenal cortical carcinoma
- Carcinosarcoma
- Adenosquamous adrenocortical carcinoma
- Clear cell adrenal cortical carcinoma
Differential diagnosis
[edit]
Differential diagnosis includes:[citation needed]
Adrenocortical carcinomas are most commonly distinguished fromadrenocortical adenomas(their benign counterparts) by the Weiss system,[2]as follows:[18]
| Characteristic[18] | Score |
|---|---|
| High nuclear grade (enlarged, oval to lobated, with coarsely granular to hyperchromatic chromatin and easily discernible, prominent nucleoli)[19] | 1 |
| More mitoses than 5/50 high power fields | 1 |
| Atypical mitoses | 1 |
| Eosinophilic cytoplasm in >75% of tumor cells | 1 |
| Diffuse architecture of >33% of tumor | 1 |
| Necrosis | 1 |
| Venous invasion | 1 |
| Sinusoidal invasion (no smooth muscle in wall) | 1 |
| Capsular invasion | 1 |
Total score indicates:[18]
- 0-2: Adrenocortical adenoma
- 3: Undetermined
- 4-9: Adrenocortical carcinoma
Treatment
[edit]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 therenal veinorinferior vena cava.The 5-year survival rate after successful surgery is 50–60%, but unfortunately, many patients are not surgical candidates. A 2018 systematic review suggests thatlaparoscopic retroperotenial adrenalectomyappears to reduce late morbidity, time to oral fluid or food intake and time to ambulation when compared to laparoscopic transperitoneal adrenalectomy, however there is uncertainty about these effects due to very low-quality evidence.[20]For outcomes such as all-cause mortality, early morbidity, socioeconomic effects, and operative and postoperative parameter, the evidence is uncertain about the effects of either interventions over the other.[20]
Radiation therapyandradiofrequency ablationmay be used forpalliationin patients who are not surgical candidates.[5]Minimally invasive surgical techniques remain controversial due to the absence of long-term data, with a particular concern for rates of recurrence and peritoneal carcinomatosis.[citation needed]
Chemotherapyregimens typically include the drugmitotane,an inhibitor of steroid synthesis, which is toxic to cells of theadrenal cortex,[4][21]as well as standard cytotoxic drugs. A retrospective analysis showed a survival benefit for mitotane in addition to surgery when compared to surgery alone.[22]
The two most common regimens arecisplatin,doxorubicin,etoposide(EDP) + mitotane, andstreptozotocin+ mitotane. The FIRM-ACT trial demonstrated higher rates of response and longer progression-free survival with EDP + mitotane than with streptozotocin + mitotane.[23]
Prognosis
[edit]ACC, generally, carries a positive prognosis,[24]with an overall5-year survival rateof about 50%.[1]Five-year disease-free survival for a complete resection of astageI–III ACC is about 30%.[24]The most important prognostic factors are age of the patient and stage of the tumor. Poor prognostic factors include mitotic activity, venous invasion, weight of 50 g or more, diameter of 6.5 cm or more, Ki-67/MIB1 labeling index of 4% or more, and p53 positive.[citation needed]
In its malignancy, adrenocortical carcinoma is unlike most tumours of the adrenal cortex, which arebenign(adenomas) and only occasionally causeCushing's syndrome.[citation needed]
References
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- ^Fassnacht M, Dekkers OM, Else T, Baudin E, Berruti A, de Krijger R, et al. (October 2018)."European Society of Endocrinology Clinical Practice Guidelines on the management of adrenocortical carcinoma in adults, in collaboration with the European Network for the Study of Adrenal Tumors".European Journal of Endocrinology.179(4): G1–G46.doi:10.1530/EJE-18-0608.hdl:2318/1650497.PMID30299884.
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- ^Wang T, Rainey WE (March 2012)."Human adrenocortical carcinoma cell lines".Molecular and Cellular Endocrinology.351(1): 58–65.doi:10.1016/j.mce.2011.08.041.PMC3288152.PMID21924324.
- ^Gazdar AF, Oie HK, Shackleton CH, Chen TR, Triche TJ, Myers CE, et al. (September 1990)."Establishment and characterization of a human adrenocortical carcinoma cell line that expresses multiple pathways of steroid biosynthesis".Cancer Research.50(17): 5488–5496.PMID2386954.
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- ^Cheungpasitporn W, Horne JM, Howarth CB (August 2011)."Adrenocortical carcinoma presenting as varicocele and renal vein thrombosis: a case report".Journal of Medical Case Reports.5:337.doi:10.1186/1752-1947-5-337.PMC3160386.PMID21806824.
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- ^abAssié G, Letouzé E, Fassnacht M, Jouinot A, Luscap W, Barreau O, et al. (June 2014). "Integrated genomic characterization of adrenocortical carcinoma".Nature Genetics.46(6): 607–612.doi:10.1038/ng.2953.PMID24747642.S2CID13089427.
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- ^James Norman (16 February 2023)."Diseases of the Adrenal Cortex: Adrenal Cancer".EndocrineWeb.Updated on: 04/14/16
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