Benign Feminizing Adrenal Tumor in an Adult Male

DISCUSSION

The paucity of data describing truly benign feminizing adrenal tumors leads to difficulties in distinguishing between benign and malignant tumors. Mongiat-Artus et al postulated that any adrenal tumor secreting estrogens should be considered malignant regardless of presentation and size.⁸ However, current consensus guidelines consider the components of the Weiss score—mitotic rate, atypical mitoses, high nuclear grade, low percentage of clear cells, necrosis, diffuse architecture of tumor, capsular invasion, sinusoidal invasion, and venous invasion—as essential in distinguishing between benign and malignant.⁵ Another important aspect to consider is the proliferative indices, such as Ki-67, as these values are significantly higher in the setting of adrenocortical carcinoma vs adenoma. Beuschlein et al suggested a grading system in relation to Ki-67 in which higher Ki-67 scores are associated with higher tumor grades and worse prognoses.⁹ A Ki-67 score <10% is considered grade 1, scores between 10% and 19% are grade 2, and scores >20% are grade 3. The feminizing adrenal tumors presenting with high mitotic rates (a component of the Weiss score) were associated with a dire prognosis.⁵ We used the Weiss score and the Ki-67 score to label our case as benign and suggest that if a tumor is radiologically, macroscopically, and histopathologically diagnosed as benign with Hounsfield units, Weiss score, and Ki-67 score, the tumor should be considered benign, regardless of the patient's hormonal status.

As mentioned previously, only 2 other cases of benign estrogen-only–secreting adrenal tumors have been reported, and only 1 was in a male patient with feminizing features as in our case.^6,7 The outcome of the male patient—reported by Andía Melero et al—was not expected, as 3 years postadrenalectomy, he had a reoccurrence with metastasis and died.⁷ This patient had cellular proliferation without atypia and no capsular invasion and was diagnosed with adenoma. The histologic finding in the case begs the questions of whether the histologic appearance can be considered accurate in all cases and whether histologic appearance is more appropriate for prognosis of malignant feminizing adrenal tumors than benign feminizing adrenal tumors. Andía Melero et al suggest that even in the setting of a benign histopathologic diagnosis, the clinician should be highly suspicious of a tumor secreting estrogen.⁷ Andía Melero et al did not report a Weiss score or a Ki-67 value for their patient.

Luton et al reported a case of a benign estrogen-only–secreting adrenal tumor in a female who was in her reproductive years. The patient presented with metrorrhagia as her chief complaint, and imaging revealed a mass on her adrenal gland. After resection, the patient's ovulatory cycle returned to normal, and she had no further issues at 2-month, 15-month, and 11-year follow-up. Luton et al described the histologic findings as benign, but they did not include information on special stains or Weiss score.⁶ Despite the difference in sex, we can draw parallels in the way the tumors behaved in our patient and in the patient described by Luton et al. After excision of the tumors, both patients’ symptoms improved, and neither patient had further issues at extended follow-up. This outcome suggests that for a truly benign estrogen-only–secreting tumor, excision is the only treatment necessary.

The approach to a benign feminizing adrenal tumor is similar to the approach used for other adrenocortical tumors. Evaluation of these masses should include a workup for hypercortisolism and pheochromocytoma, along with testing for sex hormones and the adrenal intermediaries listed in Table 2. Surgical resection is considered the best treatment for feminizing adrenal tumors, with laparoscopic resection being the procedure of choice if the tumor meets the guidelines for laparoscopic resection (<10 cm and not invading local tissue or lymph nodes).⁵ Surgical resection generally results in reduced gynecomastia and the other feminizing features associated with feminizing adrenal tumors. Medical therapy with tamoxifen or aromatase inhibitors and mitotane has been reported to be successful in treatment of adrenocortical carcinoma; however, no studies have compared the efficacy between these treatments.¹⁰

Given the sentinel event after benign histopathology in the case reported by Andía Melero et al, primary care physician follow-up of these patients is imperative. Follow-up at 6 months postoperatively and yearly thereafter should include an adequate history for identifying reoccurring symptoms, a physical examination, and trending of hormonal levels.