ONCOCYTIC ADRENOCORTICAL CARCINOMA IN A YOUNG PATIENT

Abstract

Context

Adrenocortical carcinoma (ACC) is a rare neoplasm with an aggressive course and poor prognosis. The worldwide incidence is about 0.5 to 2 cases per million population per year. Oncocytic adrenocortical carcinoma is a rare histopathological variant of ACC with only a few reported cases in the literature.

Case report

We report a case of an oncocytic variant of adrenocortical carcinoma in a 21-year-old male patient who presented with a left adrenal mass. Imaging studies confirmed a large left adrenal mass with involvement of the left renal vein and inferior vena cava. Endocrine workup showed mildly elevated serum cortisol levels.

Discussion

Oncocytic AAC is a rare histopathological variant of ACC, as well as a rare subgroup of oncocytic adrenal neoplasms Hormonally active or functioning adrenocortical carcinomas most commonly secrete cortisol whereas co-secretion of multiple steroid hormones is a rare phenomenon.

Conclusions

Surgery remains the mainstay of treatment, but most of the patients present late with large masses and eventually become unsuitable for curative resection.

INTRODUCTION

Adrenocortical carcinomas (ACCs) are rare and aggressive neoplasm with an annual incidence of 0.5-2 cases per million population and account for 0.02-0.2% of all cancer-related deaths (1-4). Approximately one per 1500 adrenal tumours is malignant, irrespective of the size of the tumour (4). The occurrence of ACC shows a bimodal distribution, one small peak in the first decade and a second large peak in the fourth to fifth decades (1,5). ACCs show a slight female preponderance with an incidence of 58.6% as compared to 41.4% in males. The reason for the increased incidence in females may be attributed to increased cigarette smoking and oral conceptive use (5). 60% of the ACCs are functional or hormone-secreting with cortisol being the most secreted hormone. Combined secretion of all adrenocortical hormones is quite rare (6-8).

CASE HISTORY

A 21-year-old male presented with abdominal discomfort and mild left flank pain from the past few weeks. On examination acne and central obesity, striae were noted. CECT abdomen showed a well-defined heterogeneously enhancing round mass in the suprarenal region measuring 9.8x9.3x9.4 cm. The diagnosis given on CECT was left adrenal mass lesion with thrombus in the left renal vein and inferior vena cava with possible differential diagnoses of adrenocortical carcinoma and atypical pheochromocytoma. On multiple occasions, the serum cortisol was found to be raised. 24-hour urinary cortisol test-120 micrograms per day. Serum cortisol morning and evening levels were 34 ug/dL and 68 ug/dL, while plasma metanephrines and nor metanephrines were 30 and 100 pg/mL. The possibility of Pheochromocytoma was ruled out, whereas serum testosterone 2.59 ng/ml and DHEA-S (Dehydroepiandrosterone) 77.65 ug/dl were within normal limits. Clinical diagnosis of suspected left adrenal lesion with Cushing syndrome was rendered. Left nephrectomy with adrenalectomy specimen was sent for histopathological examination. Gross examination showed a well-circumscribed tumour measuring 9.6x8.9x7.6 cm in the upper pole and which was arising from the adrenal gland. The cut surface of the tumour appeared tan, brown to yellow colour with a white central radial scar (Fig. 1). The rest of the tumour appears necrotic with areas of hemorrhage. The remaining adrenal gland measured 0.6x0.5 cm was seen compressed to the periphery by the tumour. Microscopic examination showed an invasive tumour arising from the adrenal cortex with tumour cells arranged in diffuse to solid pattern and nest also. Tumour cells exhibit round nuclei, conspicuous nucleoli, and abundant densely eosinophilic granular cytoplasm. Scattered large pleomorphic cells along with occasional intracytoplasmic hyaline globules were noted (Fig. 2). Extensive areas of necrosis and moderate mitotic activity (21/50 HPF) were identified. Evidence of lymphovascular space invasion, capsular invasion, infiltration into surrounding periadrenal fat and large vessel involvement (left renal vein and inferior vena cava) was present. The initial provisional histopathological report was given with three differential diagnoses i.e., an oncocytic variant of adrenocortical carcinoma, malignant pheochromocytoma, and metastatic carcinoma. Immunohistochemistry showed that tumour cells were immunoreactive to Melan-A (Fig. 3), synaptophysin (Fig. 4), and focally positive for inhibin and were negative for chromogranin (Fig. 5), Cytokeratin’s, and PAX-8. Due to the increased cortisol levels, the tumor was functional. Thus, a final histopathological diagnosis of the Oncocytic variant of functional adrenocortical carcinoma was made as per Lin Weiss Biscelgia criteria. Post-op cortisol (A) levels were 11.7ug/dL. The F18 FDG PET CT Whole Body Scan after 10 months showed no evidence of metabolically active residual/recurrent diseases.

Figure 1.

Adrenal mass with a central scar.

Figure 2.

Tumour cells with round nuclei, conspicuous nucleoli, and abundant densely eosinophilic granular cytoplasm (x40 H&E).

Figure 3.

Tumour cells are immunoreactive to Melan A (x20)

Figure 4.

Tumour cells are immunoreactive to Synaptophysin (x20).

Figure 5.

Tumour cells are immunonegative to Chromogranin (x20).

DISCUSSION

Conventional ACCs show slight female predominance with a female to male ratio of 2.5-3.5:1 (9). A study by Wajchenberg BL et al. mentioned that 45% of the adults with functional ACCs usually present with Cushing’s syndrome alone or a mixed Cushing’s and virilization syndrome with overproduction of both glucocorticoids and androgens as observed in 25% of the cases (10). Patients with functional tumours present with symptoms related to excess hormone production whereas non-functional tumours present with symptoms related to tumour burdens such as abdominal mass or flank pain. Rare clinical presentation may include an incidentally found adrenal mass detected on imaging studies (9). Imaging modalities like computed tomography (CT) and magnetic resonance imaging (MRI) can detect local invasion as well as the involvement of surrounding major vasculature. The maximum diameter of the adrenal mass may be a predictor of malignancy with a cut-off of 4cm. Most ACCs are greater than 4cm in diameter, whereas adrenal adenomas are less than 4cm (9). To detect or exclude thrombotic tumour masses in the suprarenal vein, renal vein or inferior vena cava, venography is essential in all adrenal masses that are planned for surgical resection (10).

OAC is a rare histopathological variant of ACC, as well as a rare subgroup of oncocytic adrenal neoplasms (OANs) with approximately 36 cases, reported so far in the literature (11) Although Weiss criteria are considered as the standard tool for diagnosis of adrenocortical malignancy, these oncocytic tumours should be further classified based on Lin-Weiss-Biscelgia (LWB) system to discriminate the malignant potential and to have a better prognostic classification (12). OANs are classified based on the LWB system with the following major criteria: a mitotic rate of >5 mitoses/50 hpf, and any atypical mitoses or venous invasion. The minor criteria include enormous size (>10 cm and/or>2000 g), necrosis and capsular or sinusoidal invasion. The presence of any one of the major criteria indicates malignancy (OAC), and the presence of one to four minor criteria is indicative of uncertain malignant potential, while the absence of all the major and minor criteria indicates benign mass (adrenocortical oncocytoma) (13). OACs are solitary lesions presenting in adults with no sex predilection which is different from as already stated bimodal peak of conventional ACCs (14). Grossly, adrenal oncocytic neoplasms are large, encapsulated, and well-circumscribed masses with an average diameter of 8 cm (2-20 cm). The cut surface is brown, yellow to mahogany-coloured with areas of haemorrhage and necrosis. The classic central radiating scar is not always present in OANs. The microscopy reveals cells arranged in solid, trabecular, tubular, or papillary patterns with abundant eosinophilic and granular cytoplasm. Electron microscopy reveals abundant mitochondria typical of adrenocortical cells (15). The main differential diagnoses to be considered on histopathology are the oncocytic variant of pheochromocytoma, an eosinophilic variant of chromophobe renal cell carcinoma and conventional ACC. Immunoreactivity for alpha-inhibin and Melan-A along with numerous mitochondria in the cytoplasm on electron microscopy, strongly favour the diagnosis of OAC (16). ACC and its oncocytic variant are aggressive cancer and has often invaded the surrounding tissue or metastasized to distant organs at the time of diagnosis with a 5-year survival rate of 20-35% (17). The 5-year survival rate increases to 50-60% after successful surgery, however, a large number of patients are surgically inoperable and will eventually present with relapse (18). Radiofrequency ablation and radiation therapy may be used as palliation along with chemotherapy which includes mitotane and standard cytotoxic drugs (19).

In conclusion, ACC is a rare and extremely aggressive malignant neoplasm with a poor prognosis. ACCs especially the non-functional types present late with advanced and metastatic disease. Oncocytic adrenal cortical carcinomas represent a distinct subset of adrenal neoplasms that differ from conventional ACCs on clinical as well as prognostic grounds. Complete resection remains the mainstay of treatment, especially in cases with stage I-III. The need of the hour is to develop a careful follow-up plan for such tumours with high rates of recurrence.

Conflict of interest

The authors declare that they have no conflict of interest.