Case report: Heterotopic intrarenally located adrenocortical oncocytoma.

The clinical case of a 65-year-old woman with an incidentally detected left-sided mass in the upper renal pole is presented. A functional adrenal tumor was excluded. The mass was removed retroperitoneoscopically. The perioperative period was uneventful. The histopathological examination revealed a heterotopic intrarenal adrenocortical oncocytoma. Adrenal oncocytic neoplasms are very rare, with, to the authors' knowledge, only 159 described cases so far. Most cases are non-functioning adenomas that can reach a considerable size. Only 10 heterotopic adrenal oncocytomas have been described (three retroperitoneal and seven intraspinal cases). Although the intrarenal adrenal rest is the most frequently appearing variant of adrenal heterotopia, to the best of our knowledge, this report is the first description of an intrarenally growing adrenocortical oncocytic adenoma. In addition to retroperitoneally located oncocytomas, this case could be interesting for urological practice because there are no diagnostic features which could provide a secure preoperative diagnosis of an adrenal oncocytic neoplasm and its malignant variant. Generally accepted indications for surgery of adrenal masses have to be respected. The definitive pathologic diagnosis is in most cases surprising because of its rarity. Benign adrenal oncocytic neoplasms do not require any adjuvant treatment. The oncocytic variant of adrenocortical carcinoma generally has a poor prognosis.

Case report

A 65-year-old Caucasian woman with a history of arterial hypertension underwent an ultrasound examination of the kidneys performed by her general practitioner in 2012. A left-sided suprarenal mass measuring about 5 cm was detected. The physical examination showed no palpable masses in the abdomen, and the peripheral lymph nodes were not enlarged. A 3-T magnetic resonance imaging (MRI) of the adrenal glands presented a heterogeneously enhancing mass measuring 48×48×33 mm in the left apical renal pole in contact with the adrenal gland ( Figure 1). The findings seemed to suggest the presence of a renal cell carcinoma. A differential diagnosis of pheochromocytoma had also been considered. Enlarged intra- or retroperitoneal lymph nodes were not detectable in the MRI. Catecholamines and metanephrines, aldosterone-renin ratio and serum cortisol before and after inhibition were within normal range in a 24 hour-urine sample analysis. Thus, a functional adrenal tumor could be excluded.

Figure 1.

Mass in the left upper renal pole (T2-weighted MR image) with a size of 48×48×33 mm having a diffusely heterogeneous structure.

The patient underwent a retroperitoneoscopic exploration. A round shaped 4.5 cm exophytic mass of the upper renal pole was excised retroperitoneoscopically in the fashion of a renal mass enucleation applying the zero-ischemia technique. Intraoperatively, the mass had a very thin, poorly defined pseudo-capsule which was adhering to the renal parenchyma caudally and to the macroscopically inconspicuous adrenal gland medially. The adrenal gland was removed en bloc with the mass ( Figure 2). No judgement could be made regarding the origin of the tumor. The postoperative recovery period was uneventful. Histopathological examination (haematoxyline-eosin) of the specimen revealed an oncocytic adrenocortical adenoma that arose from the heterotopic intrarenal adrenal tissue ( Figure 3).

Figure 2.

Specimen with adjacent part of left adrenal gland after retroperitoneoscopically performed tumor enucleation.

Figure 3.

Histopathology section showing diffuse proliferation of oncocytes (Haematoxyline-eosin staining, magnification 200×).

The follow-up of this patient (approximately 2 years by the date of article submission) was uneventful. No additional treatment was necessary.

Discussion

Oncocytic neoplasms of the adrenal glands are extremely rare. A PUBMED search up to December 2013 uncovered only 159 cases of adrenocortical oncocytomas since the first description of this tumor in adrenal in 1986 [17]. Most of the papers describe only single patient case reports.

Oncocytic neoplasms or oncocytomas are mostly benign tumors which commonly occur in the kidneys, thyroid, parathyroid, pituitary and salivary glands [1, 2] and rarely in the respiratory tract [3, 4], choroid plexus [5] and adrenal glands. Oncocytic neoplasms of the adrenal glands, with, to the authors’ knowledge, only 159 previously described cases, are an extremely rare phenomenon. Most of these tumors were discovered as incidental findings on CT or MRI as non-functional adrenal masses. Various malignant potential can be determined in 20% of adrenocortical oncocytic neoplasms [6]. Oncocytomas arising from the heterotopic adrenocortical tissue have been described in only 10 case reports, seven cases were located intraspinally [7– 13] and three cases in the retroperitoneum [14– 16]. An oncocytic adenoma arising from heterotopic intrarenal adrenocortical tissue was not suspected in the preoperative assessment of this case because this entity has not been described previously. However, in addition to retroperitoneally located oncocytomas, this should be considered in the future as a differential diagnosis in cases presenting with an intrarenal or retroperitoneal mass.

This paper contains the first report on an oncocytic adenoma arising from the heterotopic intrarenal located adrenal tissue. Heterotopic adrenal tissue or adrenal rest presented mostly by cortical structures is more frequently located in the kidney. Other sites such as the celiac trunk, epididymis, spermatic cord, ovary, broad ligament, liver capsule, gallbladder, pancreas and spleen are rare [18].

Oncocytic neoplasms are mostly encapsulated masses with a brown or yellow surface on cut-section. The radial scar can be absent. Oncocytic neoplasms microscopically consist of so called oncocytes, large cells with rich eosinophilic granulations due to the high concentration of mitochondria. The Weiss criteria [19], which are commonly used in the histological diagnosis of adrenocortical malignancies, are not applicable to adrenocortical oncocytic neoplasms because all tumors have eosinophilic tumor cytoplasm, diffuse architecture and nuclear atypia. The modified Lin-Weiss-Bisceglia system differentiates between major, minor and definitional criteria for malignancy [6]. None of these criteria is present in benign adrenal oncocytic neoplasms. Masses with uncertain malignant potential demonstrate the presence of one to four minor criteria (>10 cm or >200g, necrosis, capsular invasion or sinusoidal invasion) in absence of major criteria (mitotic rate >5 mitoses per 50 high-power fields, any atypical mitoses or venous invasion). In adrenal oncocytic carcinomas any of the major criteria could be present.

There are no specific criteria on both computed tomography and MRI and MRI with chemical shift subtraction for adrenal oncocytic neoplasm and its malignant variant [20]. The bulk size cannot be used as a reliable criterion to estimate the risk of malignancy.

Eighty-three percent of adrenal oncocytic neoplasms are non-functioning masses [21]. In rare cases, an adrenal oncocytic neoplasm can produce catecholamines, cortisol or testosterone [21].

The therapeutic standard is a minimally invasive adrenalectomy. In cases of a large mass, infiltration of surrounding structures, and lymph node bulks, an open surgery approach should be chosen.

Today, there are no recommendations for the follow-up of benign adrenal oncocytic neoplasms. Only one local recurrence of a neoplasm that was originally diagnosed as benign has been described and fulfilled the criteria of uncertain malignant potential [21]. The oncocytic variant of adrenocortical carcinoma has a poor prognosis, with a postoperative recurrence rate of 75%, and a tumour-related mortality of 40% in a small group of 24 patients with a median follow-up of 21 months (range: 1 – 180 months) [21]. An adjuvant or palliative chemotherapy with mitotane can be administered in patients with adrenocortical carcinomas with beneficial effects [22], but there is no evidence of efficacy when applied to oncocytic variant.

Conclusion

To the authors’ knowledge, this case report presents the first description of a heterotopic intrarenally located adrenocortical oncocytoma. Although being a rare location, this case is worth mentioning, given the challenging situation with regard to the diagnostics and differentiation from the potentially aggressive malignant lesions. Taking in account the absence of radiological criteria of a benign character, this tumor should be considered and treated as a malignant lesion, although a minimally invasive approach should be chosen when possible. The definitive pathologic diagnosis is in most cases surprising because of the rarity of this type of neoplasm and radiological appearance mimicking renal cell carcinoma or adrenal carcinoma. Benign adrenal oncocytic neoplasms do not require any adjuvant treatment.

Informed consent

Written informed consent for the publication of clinical details and clinical images was obtained from the patient.

This is a report of a very interesting case of a heterotopic intrarenal adrenocortical oncocytoma.

As the authors stated this may be the first reported case in the literature.

The major concern is the appearance of the mass in relation to the kidney at figure 1, exactly at the location of left adrenal gland. The authors stated that they performed a retroperitoneoscopical enucleation and, intraoperatively, the mass had a very thin, poorly defined pseudo-capsule which was adhering to the renal parenchyma as well as to the macroscopically inconspicuous adrenal gland.

These observations raise the possibility that this mass was in fact arising from the adrenal gland itself and not from a heterotopic location within the kidney. A tumor of 4.5 cm located intrarenally would be difficult to enucleate without interfering with any renal parenchyma and therefore vascular structures - causing bleeding.

The provided histopathological figure displays only diffuse sheets of oncocytic cells without any evidence any surrounding renal tissue.

I would recommend a repeat discussion with the pathologist to see if this not really an adrenal oncocytoma, which would be still a rare entity, albeit with more than 50 cases reported in the literature.

I have read this submission. I believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.

Dear Professor Turkeri,

Thank you for your evaluation.

Indeed, this tumor arose from the renal parenchyma and in fact left adrenal was intact and had no continuous contact to the tumor.

We have discussed your concerns with the pathologist and in the revised version of the article we will provide a pathology slice, where the nearby renal parenchyma and normal adrenal cells could be seen direct by the tumor, making the final diagnosis undoubtful.

With best wishes,

Konstantin Goding, Nicole Bang and Yuri Tolkach

The authors report a heterotopic adrenal oncocytoma in a 65 year-old lady with essential hypertension. A routine ultrasound detected a 5 cm adrenal mass, however, MRI showed a 4.8 x 4.8 x 3.3 cm mixed intensity upper polar renal mass. Features were not suggestive of a malignant tumour. Urinary and blood work up excluded a functioning adrenal adenoma. The oncocytoma was removed retroperitoneoscopically with the zero-ischemia technique.

It is a well written report, however, I have the following observations on the current submission:

The sequence of the work up is not clear: was the MRI done first; or were urinary catecholamines and metanephrines, aldosterone-renin ratio and serum cortisol determined first? In the latter case, why was a pheochromocytoma suspected when neither the clinical manifestations nor imaging (MR) suggested a pheochromocytoma?

The authors have rightly noted that the imaging characteristics of benign and malignant oncocytoma are not clearly described in the current literature - they were entertaining a diagnosis of an RCC pre-operative. Did the authors consider doing a biopsy prior to surgical intervention?  It would be pertinent to mention indications for biopsy in such a situation, and discuss its merits and demerits.

I have read this submission. I believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.

Dear Dr. Ather,

Thank you for you valuable comments.

With regard to the first point: hormonal evaluation was done after MRI investigation to exclude the probability of hormone-producing tumor, while the tumor was located very close to the adrenal, though the probability was indeed very small. It was done according to the local guidelines.

Concerning the second point, based on contemporary evidence it is hard to discuss the necessity of biopsy both in adrenal and renal tumors. We did not consider this diagnostic modality. In our opinion, in this case there was no place for the biopsy.

With kind regards,

Konstantin Godin, Nicole Bang and Yuri Tolkach