ASIAN SURGICAL ASSOCIATION FOUNDED 1976
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Asian Journal of Surgery
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Asian Journal of Surgery
Letter to Editor
Primary adrenocortical carcinoma with mutation in the CDKN2A gene
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Keywords: Adrenocortical carcinoma Mutation CDKN2A Cell cycle Urology
To the editor,
Adrenocortical carcinoma (ACC), a rare endocrine malignancy, accounting for 0.2% of all cancer deaths.1 Their prognosis is poor. And there are few effective treatment options. Through preventing cell cycle, CDKN2A, could restrain CDK4 and control proliferation of cells.2 The inactivation of CDKN2A leads to uncontrolled tumor growth.2 Here, we present an ACC case associated with CDKN2A mutation.
A 46-year-old woman presented with space-occupying lesion on the right adrenal gland for seven days. Seven days before admis- sion, Ultrasound revealed the adrenal was hypoechoic (3.4× 2.6 cm). CT demonstrated space-occupying lesion, consid- ering to be ACC (Fig. 1A). She underwent laparoscopic right adrenal tumor resection. Three months later, she was re-examined of MRI demonstrated periadrenal infiltration, suggesting the tumor
recurred (Fig. 1B). The tumor was measured 4.0 x 3.5 x 2.5 cm in size. Postoperative pathological analysis revealed ACC. The results of genetic testing showed that the patient had CDKN2A gene mutation.
ACC is an extremely rare endocrine malignancy with poor prog- nosis, and the incidence rate is about 1.5-2 cases per million people annually, and ACC with CDKN2A mutation is even rarer.1 The chief complaints are caused by increased glucocorticoid and androgen. The growth of tumor may lead to abdominal, flank pain, abdominal fullness, and early satiety. Since most cases are diagnosed at advanced stage, the prognosis is extremely poor.
We performed CT, MRI, endocrine examination, genetic and gene expression profile analysis to detect ACC. Accordingly, the tu- mor could be found by physical examination.3
Due to the ease of implementation, physical examination should be performed as a routine examination. Ultrasonography can reveal large adrenal masses.3 CT is more suitable to detect smaller tumors due to its non-invasiveness and high sensitivity.
The patient underwent laparoscopic right adrenal tumor resec- tion. However, the tumor recurred. Accordingly, even ACC patients received primary radical resection, recurrence is still common. Considering the malignant potential, surgical resection should be considered if the tumor is larger than 3 cm. We recommend resect the entire adrenal gland, even the entire unilateral kidney if necessary.
A
B
2021-08-07
A
XIAN YOU HOSF2021-11-29
FJ/Xiayou County general Hospital
082853. 450
Abdomen 5mm (SureStart)
CT-2107 : 54: 42. 767000
02胸部-重建
CT-276370
匿名
F
SE 4/8 IM 7/37
SE 3/6
F 046Y
10€IM 54/58
HFS
DFOV 35.2CM
AquiliorDFOV 35. 3CM
1095577
SOMATOM go. Fit
MAG 1. 49
MAG 1. 49
R
R
9CM
SFOV 50. 0CM
SFOV 50. 1CM
KV 120
KV 120
mA 280
mA 103
TI 0.5
TI 0.4
LOCA -GT 0. 0
LOCA -1013. 09
FC13
5. (Br40f\3
5. 0/0. 0
Body 5. 0 HFS
W:150 L:4胸部 5. 00 Br40 S3 HFS
W: 350 L: 45
CDKN2A and CDK4 are components of the cell cycle.4 CDK4 gene amplification and CDKN2A deletions were frequent copy number alterations in ACC.4 CDK4 encodes G1-S phase cyclin-dependent ki- nase. The compound consisted by CDK4 and the D-type cyclins con- trol passage through the G1 phase of the cell cycle. The CKD4 inhibitor is a suppressor of proliferation.2 CDKN2A can encode the tumor suppressor protein p16 and p14ARF. P16 is a CDK4 inhib- itor and p14ARF is a stabilizer of p53.5 Therefore, CDKN2A inhibits tumor proliferation by inhibiting CDK4 through p16.
In conclusion, ACC is an extremely rare endocrine malignancy. The case with poor prognosis, is an example of the disease spec- trum and act as a reminder that physical examination revealing an abdominal mass and CT showing space-occupying lesion on the adrenal gland and periadrenal infiltration, may consider for ACC, and radical surgery may be required.
Funding
This work was supported by grants from Xi’an Municipal Bureau of Science and Technology Foundation (22YXYJ0121).
Declaration of competing interest
There are no conflicts of interest regarding the publication of this article.
Acknowledgements
Not applicable.
References
1. Kebebew E, Reiff E, Duh QY, Clark OH, McMillan A. Extent of disease at
presentation and outcome for adrenocortical carcinoma: have we made prog- ress? World J Surg. 2006;30:872-878.
2. Serrano M, Hannon GJ, Beach D. A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4. Nature. 1993;366:704-707.
3. Bonfig W, Bittmann I, Bechtold S, et al. Virilising adrenocortical tumours in chil- dren. Eur J Pediatr. 2003; 162:623-628.
4. De Martino MC, Al Ghuzlan A, Aubert S, et al. Molecular screening for a person- alized treatment approach in advanced adrenocortical cancer. J Clin Endocrinol Metab. 2013;98:4080-4088.
5. Dominguez-Brauer C, Brauer PM, Chen YJ, Pimkina J, Raychaudhuri P. Tumor suppression by ARF: gatekeeper and caretaker. Cell Cycle. 2010;9:86-89.
Changming Dong
Department of Urology, First Hospital of China Medical University, No.155 Nanjing North Road, Shenyang, 110001, Liaoning, China
Pengyu Hui*, Liang Zheng
Department of Urology, The Second Affiliated Hospital of Xi’an Medical University, No. 167 Fangdong Street, Xi’an, 710038, Shaanxi, China
Yanping Huang
Department of Urology, Affiliated Hospital of Yangzhou University, Yangzhou University, No. 368 Hanjiang Street, Yangzhou, 225000, Jiangsu, China
* Corresponding author. Department of Urology, The Second Affiliated Hospital of Xi’an Medical University, No. 167 Fangdong Street, Baqiao District, Xi’an, Shaanxi, 710038, PR China. E-mail address: xipengyu2004@126.com (P. Hui).
28 March 2023 Available online 24 April 2023