CC BY-NC-ND 4.0 · Avicenna J Med 2022; 12(04): 182-185
DOI: 10.1055/s-0042-1756675
Case Report

Aldosterone-Secreting Large Oncocytic Neoplasm of the Adrenal Gland with Borderline Potential

Maher Alshaheen
1   Department of Internal Medicine, Bahrain Specialist Hospital, Manama, Kingdom of Bahrain
,
Krishanu Das
2   Department of Urology and Andrology, Bahrain Specialist Hospital. Manama, Kingdom of Bahrain
,
Mary Jean
3   Department of Pathology, Bahrain Specialist Hospital, Manama, Kingdom of Bahrain
,
4   Department for Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany
› Author Affiliations
Funding None.
 

Abstract

Adrenal oncocytomas are rare tumors that are mostly benign and non-functional although they may be hormonally active and can exhibit a borderline or malignant potential. We present a case of a 40-year-old female patient with known hypertension who presented with abdominal discomfort. Radiologic investigations showed a large mass on the left adrenal gland. In the hormonal study, an aldosterone-secreting tumor was identified. After laparoscopic resection, the histological assessment of the 12-cm mass showed an oncocytic neoplasm with borderline characteristics. The laboratory results returned to normal and the hypertensive disease improved. The patient was doing well after 14 months of follow-up. This is the seventh documented case of aldosterone-secreting oncocytoma, the first borderline tumor of this type, and the largest reported tumor so far.


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Introduction

Adrenocortical oncocytic neoplasms are rare tumors that are characterized by the presence of oncocytes.[1] The majority of these tumors are non-functional, but they may be associated with hormonal secretion, causing a variety of adrenal hormonal syndromes.[2] Although most tumors are benign, borderline and malignant variants were described.[3] In this article, we describe the seventh documented case of aldosterone-secreting oncocytoma, the first borderline tumor of this type, and the largest reported tumor so far.


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Case Report

A 40-year-old female patient presented to her general practitioner with increasing abdominal discomfort in the left hypochondrium over a few months. Her medical history included arterial hypertension for around 8 years, which was treated with amlodipine 5 mg once daily. On ultrasonography, the general practitioner found a mass between the spleen and the left kidney. The patient was referred to our center for further study. On computed tomography, the mass was consistent with an adrenal tumor ([Fig. 1]).

Zoom Image
Fig. 1 (A) Coronal, (B) transverse, and (C) sagittal sections of the computed tomography of the abdomen in the arterial phase of contrast enhancement. A large inhomogeneous lesion with cystic components can be seen in the left upper quadrant of the abdomen. The lesion abuts and compresses both the spleen and the upper pole of the left kidney (B and C). There is no evidence of local invasion, other masses, regional lymphadenopathy, or metastases to the parenchymal organs.

We initiated a comprehensive laboratory workup. Pheochromocytoma, Cushing's syndrome, and androgen-secreting tumors were excluded ([Table 1]). The results showed low plasma renin relative to the normal plasma aldosterone with elevated aldosterone to renin ratio (ARR). We established the diagnosis of an aldosterone-secreting adrenal tumor and made the indication of surgical treatment.

Table 1

Serum laboratory results

Laboratory assay

Patient's results

Reference range

Creatinine, mg/dL

0.67

0.5–0.9

Blood urea nitrogen, mg/dL

14.9

5–50

Sodium, mmol/L

138

135–145

Potassium, mmol/L

3.89

3.5–5.1

Chloride, mmol/L

104.4

98–107

Adrenalin, ng/L

76

< 82

Noradrenalin, ng/L

460

< 499

Metanephrine, ng/L

50

< 90

Normetanephrine, ng/L

96

< 126

Cortisol (at 4 am), nmol/L

490.6

171–536

Cortisol (at 4 pm), nmol/L

260.6

64–327

Testosterone, ng/mL

0.051

0.084–0.481

DHEA-S, µg/dL

66.51

35.4–256

Aldosterone, ng/dL

14.7

1.2–35

Renin, ng/dL

0.22

0.26–2.8

ARR

67.8

< 19

Abbreviations: ARR, aldosterone to renin ratio; DHEA-S, dehydroepiandrosterone sulfate.


The operation was performed laparoscopically through a transperitoneal approach using three ports. The specimen was extracted through a Pfannenstiel incision ([Fig. 2]). The patient was discharged home on the second postoperative day.

Zoom Image
Fig. 2 Gross examination of the specimen. (A) The nodular mass measures 12 × 9 × 6 cm and weighs 329 g. (B) The cut section shows solid grayish areas as well as soft hemorrhagic spaces in between.

The histopathologic study showed an oncocytic adrenocortical neoplasm of uncertain malignant potential. The immunohistochemical tests showed a positive melan A and Ki67 with a score of 3%, whereas calretinin, chromogranin, S-100, and inhibin were all negative ([Fig. 3]).

Zoom Image
Fig. 3 Microscopic examination of the tumor with the hematoxylin and eosin (H&E) stain (upper row) and with immunostaining (lower row). (A) The mass is well-circumscribed with no capsular invasion (original magnification x40). (B) The tumor cells are arranged in a diffuse and sinusoidal pattern (original magnification x100). (C) Close-up of oncotic cells showing the abundant eosinophilic cytoplasm with hyperchromatic nuclei and prominent nucleoli. Mitotic activity equals 2 to 3 per 50 high power fields (original magnification x400). The immunohistochemistry was positive for melan A (D), positive for Ki67 with a score of 3% (E), and negative for chromogranin (F).

One week postoperatively, the hormonal profile showed a significant decrease in ARR from 67.8 to 22, and the maintenance dose of amlodipine could be reduced to 2.5 mg daily. One year postoperatively, ARR was normal at 3.8. After 14 months of follow-up, the patient was well with no signs of local or distant recurrence.


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Discussion

Adrenocortical oncocytic neoplasms are rare tumors that include oncocytoma, oncocytic neoplasm of uncertain malignant potential, and oncocytic carcinoma.[1] The hallmark of these tumors is the presence of oncocytes, which are polygonal cells with abundant granular eosinophilic cytoplasm.[4] These tumors predominate in females and occur more often on the left side.[1] Most adrenal oncocytomas are benign and up to 70% are nonfunctional.[2] The differential diagnosis includes mainly adrenal adenomas in addition to gangliomas, gangliocytic paragangliomas, and lipomas.[5]

Some adrenal oncocytic neoplasms are hormonally active. Reported associations include pheochromocytoma, Cushing's syndrome, and hyperandrogenism.[1] [6] However, aldosterone-secreting oncocytoma is a very rare variant,[7] and there are only six documented cases in the literature, with this case being the seventh. [Table 2] presents a review of all described cases.

Table 2

Reported cases of aldosterone-secreting oncocytic tumors of the adrenal gland

No.

Authors

Year

Country

Gender

Age

(y)

Side

Size (cm)

Symptoms

Surgery

Classification

Follow-up

1

Ali and Raphael[5]

2007

Canada

M

25

R

8.5

Hypertension

NA

Malignant

NA

2

Mete and Asa[6]

2009

Canada

F

72

L

1.4

Hypertension

L

Benign

NA

3

Wong et al[2]

2010

Australia

M

22

L

5.5

Asymptomatic

NA

Benign

ANED at 108 months

4

Duregon et al[1]

2011

Italy

F

66

R

5

NA

NA

Benign

NA

5

Duregon et al[1]

2011

Italy

F

40

R

4

NA

NA

Benign

NA

6

Akin et al[10]

2014

Turkey

M

11

R

4.5

Metabolic

L

Benign

NA

7

Alshaheen et al

2022

Bahrain

F

40

L

12.0

Pain and hypertension

L

Borderline

ANED at 14 months

Abbreviations: ANED, alive with no evidence of disease; F, female; L, laparoscopic adrenalectomy; L, left; M, male; NA, not available; R, right.


Our patient was previously considered to have essential hypertension but without a proper workup. This stresses the importance of investigating secondary causes in every patient with hypertension.[8] Hypokalemia was long considered a sine qua non for the diagnosis of aldosterone-secreting adrenal tumors, but most patients show normal potassium levels.[8] The preoperative aldosterone level was also in the normal range and the diagnosis was based on the elevated aldosterone to renin ratio (ARR). A saline infusion test was not performed because it would not have influenced the treatment decision.

Elevated aldosterone levels are not a prerequisite for the diagnosis of aldosteronoma. Stowasser et al found that plasma aldosterone was less than 15 ng/dL in 36% of 74 patients who were diagnosed with primary aldosteronism based on an ARR greater than 30.[8] The other two observations that confirm the hormonal nature of the tumor in this patient are the gradual return of the ARR to the normal range and the improvement of hypertension during follow-up. A recent meta-analysis revealed that ARR has a sensitivity of 89% and a specificity of 96% at cut-offs ranging from 26.35 to 59.66, which suggests that ARR is an effective and convenient screening tool for primary aldosteronism.[9]

In the absence of local invasion, the malignancy potential of adrenal oncocytomas is determined based on the modified Lin–Weiss–Bisceglia (LWB) scoring system. Tumors are classified into benign, borderline, or malignant according to major or minor criteria. The major criteria include a mitotic rate > 5 per 50 high power fields, atypical mitoses, or venous invasion. The minor criteria are size > 10 cm or weight > 200 g, microscopic necrosis, capsular invasion, or sinusoidal invasion. The tumor is considered malignant if it shows one major criterion, borderline if it shows one or more minor criteria, and benign if it does not show any major or minor criteria.[3] The tumor in our case measured 12 cm and weighed 329 g. There was no vascular invasion, and the mitotic activity equaled 2 to 3 per 50 high power fields. Accordingly, this tumor is the first described aldosterone-secreting oncocytoma with borderline potential. Interestingly, the Ki67-score as one of the immunohistochemical tests is considered the single most important factor for predicting the recurrence after R0 resection of adrenocortical carcinoma and it equaled 3% in our case, which is associated with a favorable prognosis.[4]

The tumor presented in this case is the largest aldosterone-secreting oncocytoma described so far. As shown in [Table 1], five of the seven reported aldosterone-secreting oncocytomas were benign. In their literature review, Wong et al reported three cases of recurrence out of 47 borderline oncocytomas over a median follow-up of 96 months.[2] Our patient was doing well after 14 months, and further follow-up is planned over the next 5 years.


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Conclusion

Adrenal oncocytomas are rare tumors that are usually diagnosed after the surgical resection of an adrenal neoplasm. The histological diagnosis requires the differentiation of these tumors from adrenal adenomas. Based on the major and minor criteria of the modified Lin–Weiss–Bisceglia scoring system, these tumors are classified into benign, borderline, or malignant. As in other adrenal tumors, laparoscopic adrenalectomy is feasible for large oncocytomas after the exclusion of local invasion in the preoperative imaging.


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Conflict of Interest

None declared.

Patient Consent

Written informed consent was obtained from the patient and is available on request.


Authors' Contributions

K.D. operated on the patient and wrote the first draft. M.A. was involved in the diagnostic work-up and follow-up, collected the clinical data, and edited the manuscript. M.J. examined the specimen and contributed to the pathologic details of the work. M.F.S. researched the documented cases, organized the figures and tables, and edited the discussion. All authors reviewed and approved the final manuscript before submission.



Address for correspondence

Mhd Firas Safadi, MD, FHEA
Department for Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Technische Universität
Fetscherstraße 74, 01307 Dresden
Germany   

Publication History

Article published online:
15 September 2022

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Zoom Image
Fig. 1 (A) Coronal, (B) transverse, and (C) sagittal sections of the computed tomography of the abdomen in the arterial phase of contrast enhancement. A large inhomogeneous lesion with cystic components can be seen in the left upper quadrant of the abdomen. The lesion abuts and compresses both the spleen and the upper pole of the left kidney (B and C). There is no evidence of local invasion, other masses, regional lymphadenopathy, or metastases to the parenchymal organs.
Zoom Image
Fig. 2 Gross examination of the specimen. (A) The nodular mass measures 12 × 9 × 6 cm and weighs 329 g. (B) The cut section shows solid grayish areas as well as soft hemorrhagic spaces in between.
Zoom Image
Fig. 3 Microscopic examination of the tumor with the hematoxylin and eosin (H&E) stain (upper row) and with immunostaining (lower row). (A) The mass is well-circumscribed with no capsular invasion (original magnification x40). (B) The tumor cells are arranged in a diffuse and sinusoidal pattern (original magnification x100). (C) Close-up of oncotic cells showing the abundant eosinophilic cytoplasm with hyperchromatic nuclei and prominent nucleoli. Mitotic activity equals 2 to 3 per 50 high power fields (original magnification x400). The immunohistochemistry was positive for melan A (D), positive for Ki67 with a score of 3% (E), and negative for chromogranin (F).