References
1. Van Poppel H. Efficacy and safety of nephron-sparing surgery. Int. J. Urol. 2010; 17: 314-26.
2. Campbell SC, Novick AC, Belldegrun A et al. Guideline for management of the clinical T1 renal mass. J. Urol. 2009; 182: 1271-9.
3. Nabi G, Cleves A, Shelley M. Surgical management of localised renal cell carcinoma. Cochrane Database Syst. Rev. 2010; (3): CD006579.
4. Van Poppel H, Becker F, Cadeddu JA et al. Treatment of localised renal cell carcinoma. Eur. Urol. 2011; 60: 662-72.
5. Huang WC, Levey AS, Serio AM et al. Chronic kidney disease after nephrectomy in patients with renal cortical tumours: a retrospective cohort study. Lancet Oncol. 2006; 7: 735-40.
6. Haber GP, Gill IS. Laparoscopic partial nephrectomy: contemporary tech- nique and outcomes. Eur. Urol. 2006; 49: 660-5.
7. Reifsnyder JE, Ramasamy R, Ng CK et al. Laparoscopic and open partial nephrectomy: complication comparison using the Clavien system. JSLS 2012; 16: 38-44.
Jane E. Theodore,* MBBS
Jason Paterdis, ¡ MBBS, FRACS
*Department of Surgery, Princess Alexandra Hospital, Brisbane, Queensland, Australia and ¡Department of Surgery, Queen Elizabeth II Jubilee Hospital, Brisbane, Queensland, Australia
doi: 10.1111/ans.12420
Recurrent hyperaldosteronism after adrenalectomy: an indication for careful radiologic and histologic re-evaluation
Functioning adrenocortical carcinomas (ACC) are rare tumours with a poor prognosis.1,2 Aldosterone-producing adenomas (Conn’s syn- drome) are a more common indication for adrenalectomy and recur- rent hyperaldosteronism is generally attributable to unrecognized, benign, bilateral disease. We report a case of ACC originally mas- querading as recurrent Conn’s syndrome to highlight the fallibility of existing diagnostic scoring systems and to alert clinicians to the possibility of malignant tumour recurrence.
A 77-year-old man with a history of treated prostate cancer and osteoporosis presented with progressive hypertension and hypoka- laemia. Apart from hypertension (160 mmHg), physical examination was unremarkable. He required four antihypertensive agents and oral potassium supplementation. Further investigation revealed a serum aldosterone of 978 pmol/L (normal: 100-950), a plasma renin activity of 0.2 and an aldosterone : renin ratio of 220 (non-resolution on saline loading). Urinary catecholamines, free cortisol and dehydroepiandrosterone were normal. Abdominal computed tomog- raphy (CT) scanning demonstrated a 27-mm heterogeneous lesion within the right adrenal gland (arterial phase Hounsfield units: 50), which was thought to represent an aldosterone-producing adrenal adenoma. Selective venous sampling was not undertaken given a normal left adrenal gland.
A transperitoneal laparoscopic adrenalectomy was performed without complication. Histopathology showed a well-circumscribed 28-mm adenoma; with no significant atypia, necrosis or invasive features (Fig. 1). Local excision was complete and no evidence of metastatic prostate cancer was present. IGF-2 immunohisto- chemistry was negative, the Ki-67 score was 2% and the Weiss score was 2. Hypokalaemia resolved, and blood pressure control improved significantly within the first post-operative week. At 6 months, he was normokalaemic, required only one antihypertensive and aldosterone/renin biochemistry was normal.
Two years following surgery, imaging for an unrelated complaint revealed small, nodular soft tissue masses within the right adrenal fossa. This was thought to represent post-surgical change only and biochemistry remained normal (aldosterone: 460 pmol/L). Subse-
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6
quent difficulty with progressive hypertension and hypokalaemia 6 months later prompted additional investigation and showed recur- rence of primary hyperaldosteronism (aldosterone : renin ratio: 410). An abdominal CT showed progression of nodular tissue in the right adrenal fossa (Fig. 2). Concerns regarding the possibility of malignant disease initiated positron emission tomography scanning, which confirmed disease localized to the adrenal fossa. Resection involved a radical retroperitoneal lymph node dissection. Hyperten- sion control improved again post-operatively.
Histologic examination confirmed the presence of multiple nodules of tumour, which now demonstrated an invasive growth pattern (Fig. 3). This indicated a Weiss score of 3, and therefore a diagnosis of ACC. The possibility of benign recurrent disease with pseudoinvasion secondary to tumour rupture and surgical field con- tamination was considered. However, given extensive soft tissue
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invasion, the absence of tumour spillage at the index operation, and the subtle, albeit concerning histology in the initial adenoma, the diagnosis of ACC was preferred.
Adjuvant therapy with external beam radiotherapy and mitotane was commenced. There has been no evidence of recurrent disease (clinically, biochemically or radiologically) at the most recent review, however, the prognosis remains guarded.
Several different systems have been proposed to differentiate adenoma form carcinoma in this setting.1,3,4 The most widely employed system is the Weiss criteria with its various modi- fications.1,3,4 Using the Weiss criteria, tumours are assessed for the presence of nine histological features. In 1984, the presence of four or more features was considered to reflect malignancy. This was
modified to three or more criteria in 1989 when the metastatic potential of some ‘benign’ tumours was recognized.4
In the present case, the initial tumour was assigned a Weiss score of 2 on the basis of diffuse architecture and eosinophilic cell type and would not have qualified as a carcinoma using any of the other proposed systems. Despite this, the disease recurred locally with an infiltrative growth pattern (Weiss score: 3).
There are several case reports of tumours that are histologically benign by Weiss and other criteria that subsequently metastasize and behave in a malignant fashion.5 However, the infiltrative growth pattern of the recurrence and the low-grade, but discernible atypia in the original tumour, favoured this to be a recurrent low-grade ACC initially misdiagnosed as an adrenal adenoma.
Lastly, recurrence of completely excised, organ confined disease is difficult to explain. It can only be assumed that local micro- metastatic disease was present at the index resection that ultimately resulted in recurrence.
This case illustrates that although the Weiss criteria and other systems used to distinguish adrenal carcinomas from adenomas are generally reliable, they are not infallible. The potential for apparently ‘benign’ adenomas to recur or metastasize should be considered in the setting of recurrent hyperaldosteronism after adrenalectomy for Conn’s syndrome.
References
1. Allolio B, Fassnacht M. Clinical review: Adrenocortical carcinoma: clini- cal update. J. Clin. Endocrinol. Metab. 2006; 91: 2027-37.
2. Seccia TM, Fassina A, Nussdorfer GG et al. Aldosterone-producing adrenocortical carcinoma: an unusual cause of Conn’s syndrome with an ominous clinical course. Endocr. Relat. Cancer 2005; 12: 149-59.
3. Aubert S, Wacrenier A, Leroy X et al. Weiss system revisited: a clinico- pathologic and immunohistochemical study of 49 adrenocortical tumors. Am. J. Surg. Pathol. 2002; 26: 1612-9.
4. Weiss LM, Medeiros LJ, Vickery AL Jr. Pathologic features of prognostic significance in adrenocortical carcinoma. Am. J. Surg. Pathol. 1989; 13: 202-6.
5. Tan HS, Thai AC, Nga ME, Mukherjee JJ. Development of ipsilateral adrenocortical carcinoma sixteen years after resection of an adrenal tumour causing Cushing’s syndrome. Ann. Acad. Med. Singap. 2005; 34: 271-4.
Justin S. Gundara,* MBBS (Hons) Anthony J. Gill,; MD, FRCPA Anthony Glover,* FRACS Katherine Benson,¿ FRACP Roderick Clifton-Bligh, § PhD, FRACP Sarah Roxburgh, {[ PhD, FRACP Mark Sywak,* MMed (Clin Epi), FRACS *Department of Surgery, University of Sydney Endocrine Surgical Unit, ¡Department of Anatomical Pathology, Royal North Shore Hospital, University of Sydney, St Leonards, ¿Department of Endocrinology, Concord Repatriation General Hospital, and Departments of §Endocrinology and IRenal Medicine, Royal North Shore Hospital, University of Sydney, Sydney, New South Wales, Australia doi: 10.1111/ans.12433