|Year : 2021 | Volume
| Issue : 4 | Page : 159-162
Aldosterone-producing adrenocortical carcinoma with unusual initial presentations: A rare disease and case report
Jen- Chieh Chen1, Tzu- Chun Wei2, Chin- Chen Pan3, Yen- Hwa Chang2, William J Huang2
1 Department of Urology, Taipei Veterans General Hospital, Taipei, Taiwan
2 Department of Urology, Taipei Veterans General Hospital; Department of Urology, College of Medicine and Shu-Tien Urological Science Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan
3 Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
|Date of Submission||30-Jun-2021|
|Date of Decision||15-Aug-2021|
|Date of Acceptance||17-Aug-2021|
|Date of Web Publication||3-Dec-2021|
Dr. Tzu- Chun Wei
Department of Urology, Taipei Veterans General Hospital, No. 201, Sec. 2, Shipai Rd., Beitou Dist., Taipei 112
Source of Support: None, Conflict of Interest: None
Aldosterone-producing adrenocortical carcinoma (APAC) is extremely rare. It is not only the rarest functional adrenocortical carcinoma (ACC) but also the most infrequent cause of primary hyperaldosteronism (PH). Furthermore, if hypertension and hypokalemia present in a patient with ACC, they are more likely secondary to overproduction of glucocorticoid, rather than PH. To our knowledge, APAC has not yet been reported in Taiwan with detailed clinical manifestations. We present a patient diagnosed with APAC due to an unusual initial presentation, predominantly right-sided varicocele, treated successfully by en bloc resection, being disease-free for 10 months. Due to the rarity and unfavorable outcomes of APAC, we report the patient's clinical course, treatment, and follow-up outcomes.
Keywords: Adrenocortical carcinoma, aldosterone-producing adrenocortical carcinoma, primary hyperaldosteronism, right-sided varicocele
|How to cite this article:|
Chen JC, Wei TC, Pan CC, Chang YH, Huang WJ. Aldosterone-producing adrenocortical carcinoma with unusual initial presentations: A rare disease and case report. J Cancer Res Pract 2021;8:159-62
|How to cite this URL:|
Chen JC, Wei TC, Pan CC, Chang YH, Huang WJ. Aldosterone-producing adrenocortical carcinoma with unusual initial presentations: A rare disease and case report. J Cancer Res Pract [serial online] 2021 [cited 2022 Aug 10];8:159-62. Available from: https://www.ejcrp.org/text.asp?2021/8/4/159/331653
| Introduction|| |
Adrenocortical carcinoma (ACC) is a rare disease, with an incidence of 0.7–2 per million population per year. The clinical presentations of ACC are varied, and the prognosis is generally poor. Approximately 50%–60% cases of ACC are functional, with the most common hormone secreted by ACC being glucocorticoid, followed by androgen. Aldosterone-producing adrenocortical carcinoma (APAC) is extremely rare, accounting for only 2.5%–5% of functional ACC. Only a few case analyses of APAC have been published worldwide, and APAC has not yet been reported in Taiwan with detailed clinical manifestations. Herein, we present a patient diagnosed with APAC due to unusual initial presentations. The clinical course, treatment, and follow-up outcomes are described.
| Case Report|| |
A 63-year-old man came to our urology clinic due to bleeding on the right scrotal skin for 2 days and a mildly enlarged right scrotum. He had been healthy without any systemic diseases except for a history of hypertension for 1 year (blood pressure around 180/100 mmHg), to which he did not pay much attention. A physical examination revealed bilateral varicoceles, with greater prominence on the right side, Grade 3. No tenderness or swelling of the right epididymis and testis was noted. Abdominal ultrasound was arranged to exclude a right intra-abdominal lesion due to predominantly right-sided varicocele, which showed a large heterogeneous mass at the right suprarenal region, measuring 12.3 cm × 9.9 cm. Contrast-enhanced computed tomography confirmed the diagnosis of a right adrenal tumor [Figure 1]. Other biochemical findings included normal serum cortisol level (10.1 μg/dL), normal adrenocorticotropic hormone concentration (<5 μU/mL), but hypokalemia (2.5 mmol/L), increased aldosterone (374 pg/mL), and serum direct renin concentration at the lower limit of normal range (3.58 pg/mL). The 24-h urine vanillylmandelic acid level was mildly high (7.82 mg/day), as were epinephrine (26.7 mcg/day), norepinephrine (141.8 mcg/day), and dopamine (444.3 mcg/day). A chest X-ray and whole-body bone scan showed no evidence of distant metastasis. Right open adrenalectomy was performed for en bloc resection [Figure 2]. Grossly, the tumor was well-defined, with a frozen section indicating free margins at both the liver and right kidney. Microscopically the tumor cells were diffusely immunoreactive for melan-A and focally positive for synaptophysin. The expressions of p53, beta-catenin, and phosphatase and tensin homolog gene were not abnormal. The Ki67 labeling index was around 18% [Figure 3]. On the basis of the Weiss system, the tumor was classified as ACC with a modified Weiss score of 3. The hypokalemia and hyperaldosteronism normalized within several days after surgery [Figure 4]. No local recurrence, lymphadenopathy, or distant metastasis has been noted during 10 months of follow-up, and biochemical results have been normal.
|Figure 1: Contrast-enhanced computed tomography indicated a large heterogeneously enhanced tumor (orange arrow) at the right suprarenal region, which most likely originated from the right adrenal gland. (a) Axial view. (b) Coronal view|
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|Figure 2: Gross appearance of the right adrenalectomy specimen. (a) A well-defined brownish tumor measuring 12 cm × 13.5 cm × 10 cm. (b) A section of the tumor showed heterogenous components with hemorrhage|
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|Figure 3: The microscopic findings and diagnostic staining for pathology. (a) Hematoxylin and eosin staining; (b) Melan-A; (c) Beta-catenin; (d) Phosphatase and tensin homolog; (e) Ki67 index is about 18%|
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|Figure 4: The serum potassium (a), aldosterone (b), and direct renin (c) levels of the patient before and after surgery|
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| Discussion|| |
We reported an extremely rare case of APAC in Taiwan with an unusual initial presentation, predominantly right-sided varicocele, who was treated successfully by en bloc resection and has remained disease-free for 10 months. To our knowledge, APAC has not yet been reported in Taiwan with detailed clinical manifestations, and this case provides our experience on its diagnosis, treatment, and follow-up outcomes. Our case also emphasizes that solitary or predominantly right-sided varicocele should warrant the consideration of a possible intra-abdominal lesion near the right renal hilum.
As previously mentioned, among functional ACC, APAC is extremely rare. Because the number of glucocorticoid-producing ACCs is far greater than that of APAC, it should be kept in mind that if hypertension and hypokalemia present in a patient with ACC, they are more likely to be secondary to the overproduction of cortisol or 11-deoxycorticosterone, rather than primary hyperaldosteronism (PH)., On the other hand, APAC is not only the rarest functional ACC but also the most infrequent cause of PH (<1%), with the most commonly reported etiology of PH being bilateral adrenal hyperplasia (60%), followed by primary adenoma (35%) and unilateral hyperplasia (2%). Several somatic mutations of aldosterone-driving genes have been identified in aldosterone-producing adenomas (APAs). However, it is still unknown whether APAC harbors similar mutations, with only one study reporting that APACs had very few mutations of APA-associated genes. Further research of the possible mechanisms causing excessive aldosterone production by APACs may help in the understanding of this extremely rare disease.
Our patient had predominantly right-sided varicocele caused by ACC. In general, about 50%–79% of ACC patients are symptomatic, and the symptoms and signs of ACC are usually associated with excess hormone production (40%–60%) or a mass effect (30%). To date, only one case of ACC presenting with right-sided varicocele has been reported. Besides ACC, the more common causes of predominantly right-sided varicocele are renal cell carcinoma, lymphoma, Wilms tumor, and aortic aneurysm.
As with ACC, the management of APAC requires a multidisciplinary team (MDT). Surgical resection remains the mainstay of treatment, and it offers the best chance of a cure as well as symptom control. According to the final pathology, our patient was diagnosed with Stage II ACC based on the American Joint Committee on Cancer (AJCC) staging system, with a 5-year survival rate ranging from 20% to 58%. However, the impact of the functional status of the tumor on survival in ACC remains controversial, and the outcomes of APAC according to AJCC staging system of ACC have not yet been assessed due to its rarity. Seccia et al. summarized the prognosis of APAC in 60 published cases from 1955 to 2005, with a median overall survival and time to either recurrence or death of 18 and 7 months, respectively.
For a nonmetastatic ACC treated by en bloc resection, adjuvant mitotane has been suggested to significantly decrease the recurrence rate and mortality. This suggestion is supported by a recent systematic review and meta-analysis. Moreover, adjuvant radiotherapy can also be considered in patients who are at high risk of local recurrence, including those with a positive surgical margin, ruptured capsule, large size, or high grade. Regarding our patient, our MDT suggested adjuvant mitotane or radiotherapy, however, he decided not to receive any adjuvant treatments after shared decision-making. He remains disease-free after more than 10 months of follow-up.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Partin AW, Campbell MF, Walsh PC, Wein Alan J. Campbell-Walsh Urology. 12th
ed. Amsterdam: Elsevier; 2021.
Else T, Williams AR, Sabolch A, Jolly S, Miller BS, Hammer GD. Adjuvant therapies and patient and tumor characteristics associated with survival of adult patients with adrenocortical carcinoma. J Clin Endocrinol Metab 2014;99:455-61.
Huang CJ, Wang TH, Lo YH, Hou KT, Won JG, Jap TS, et al.
Adrenocortical carcinoma initially presenting with hypokalemia and hypertension mimicking hyperaldosteronism: A case report. BMC Res Notes 2013;6:405.
Nanba K, Omata K, Else T, Beck PC, Nanba AT, Turcu AF, et al.
Targeted molecular characterization of aldosterone-producing adenomas in White Americans. J Clin Endocrinol Metab 2018;103:3869-76.
Mouat IC, Omata K, McDaniel AS, Hattangady NG, Talapatra D, Cani AK, et al.
Somatic mutations in adrenocortical carcinoma with primary aldosteronism or hyperreninemic hyperaldosteronism. Endocr Relat Cancer 2019;26:217-25.
Brand TC, Morgan TO, Chatham JR, Kennon WG, Schwartz BF. Adrenal cortical carcinoma presenting as right varicocele. J Urol 2001;165:503.
Cheungpasitporn W, Horne JM, Howarth CB. Adrenocortical carcinoma presenting as varicocele and renal vein thrombosis: A case report. J Med Case Rep 2011;5:337.
Seccia TM, Fassina A, Nussdorfer GG, Pessina AC, Rossi GP. Aldosterone-producing adrenocortical carcinoma: An unusual cause of Conn's syndrome with an ominous clinical course. Endocr Relat Cancer 2005;12:149-59.
Tang Y, Liu Z, Zou Z, Liang J, Lu Y, Zhu Y. Benefits of adjuvant mitotane after resection of adrenocortical carcinoma: A systematic review and meta-analysis. Biomed Res Int 2018;2018:9362108.
[Figure 1], [Figure 2], [Figure 3], [Figure 4]