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Benign pure androgen-secreting adrenal tumor misdiagnosed as adrenocortical carcinoma on 18F-FDG PET-CT: a rare case report
Zhan Wang1 . Jiayang Chen1 . Xiaohua Shi2 . Yi Liu1 . Wenda Wang1 . Guoyang Zheng1 . Yang Zhao1 . Yanan Li1 . Xu Wang1 . Dongxu Qiu1 . Yushi Zhang1
Received: 14 August 2024 / Accepted: 22 September 2024 / Published online: 30 September 2024 @ The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2024
Abstract
Background Adult pure androgen-secreting adrenal tumors (PASATs) are rarely reported and the malignancy of such tumor are difficult to confirm before surgery. Here we report a PASAT demonstrating extremely 18F-FDG uptake turned out to benign tumor by postoperative pathology examination.
Case presentation A 19-year-old adolescent found a tumor measuring 7.2 cm located in the right adrenal region on enhanced CT during the routine physical examination. Signs of virilization and elevated testosterone and dehydroepian- drosterone (DHEA) were verified during preoperative examination. 18F-FDG PET/CT revealed the tumor had an extremely high 18F-FDG uptake with a SUVmax reaching 42.7, which turned out to be oncocytic adrenocortical adenoma by pathological examination.
Conclusions 18F-FDG PET/CT may be limited in assessing the malignancy of PASAT.
Keywords 18F-FDG PET/CT . Pure androgen-secreting adrenal tumor . Virilization . Case report
Background
Pure androgen-secreting adrenal tumor (PASATs) is a rare tumor with only 20 cases reported in the world. Such kind of tumor arise from the most inner layer of the adrenal cortex and secret high levels of sex-hormones, leading to the virilization of the patients. The limited cases made it difficult to confirm the malignancy of the tumor before surgery and pathological examination. According to the previous researches, high FDG uptake on 18F-FDG PET/CT was positively correlated with the high Ki-67 index and overall survivals, indicating the potential malignancy of
PASATs [1]. In addition, dimeters larger than 5 cm also highly suggest a malignant tumor.
Here, we reported a PASAT, measuring up to 6.2 cm with heterogeneous enhancement on CT scan and demon- strating extremely high FDG uptake with SUVmax reaching 42.7, all of which present a malignant sign. However, the postoperative pathological result revealed an oncocytic adrenocortical adenoma with uncertain malignant potential and a low Ki-67 index of 3%. The inconsistency between preoperative imaging signs and postoperative pathology may reflect the unique pathophysiology of PASAT and give us reference for treating such kind of tumors.
These authors contributed equally: Zhan Wang, Jiayang Chen, Xiaohua Shi
☒ Yushi Zhang
1 Department of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, 100730 Beijing, China
2 Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, 100730 Beijing, China
Case presentation
During the physical examination before been admitted into university, this 19-year-old patient received an abdominal ultrasound examination on September 2023 and a hypoe- choic and uneven lesion measuring about 5.5x 3.5 cm could be observed on the right adrenal gland area. The lesion was well circumscribed with clear boundaries and regularity. The patient was later admitted into the local hospital and underwent enhanced CT scan of the adrenal glands. The images showed an oval tumor with soft tissue
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B
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density and clear boundaries in the right adrenal gland area. The tumor has a size of about 6.26 x 3.56 cm, which was obviously unevenly strengthened after enhanced scanning. The endocrine test revealed a low ACTH of 1.9 pg/ml and an extremely high dehydroepiandrosterone sulfate (DHEAS) of 1874.61 ug/dL (normal range reference 75-314 ug/dL). The patient has a history of menstrual irregularities with the frequency of half a year and period of 2 weeks.
The patient was later referred to our hospital for suspi- cion of adrenocortical carcinoma. The complete physical examination revealed obvious signs of virilization, includ- ing hirsutism and masculine body (Fig. 1A-C) and clitoral enlargement (Fig. 1D). In addition, she also has protruded laryngeal prominence and a deep voice. No signs of Cushing syndrome, including a rounded and red face, thinning of the limbs, and the back of a buffalo were observed.
The endocrine test in our hospital (as shown in Table 1) revealed an obvious elevated DHEAS (26969 ng/ml; Nor- mal range with LC-MS/MS: 830-3770 ng/ml), DHEA (22.6 ng/ml; Normal range with LC-MS/MS: lower than 13 ng/ml) and testosterone (1.93 ng/ml; Normal range with LC-MS/MS: 0.08-0.60 ng/ml). The ACTH, plasma cortisol and 24 h urine free cortisol were within the normal range. To rule out the co-existing Cushing syndrome, the low dose dexamethasone suppression test was performed and the result was negative. In addition, other hormone, including the aldosterone, renin, angiotensin II, NMN, MN, 24 h catecholamines were all within the normal reference range.
| Pre-operation | Post-operation | |
|---|---|---|
| DHEAS (NR: 830-3770 ng/ml) | 26969 | 2459 |
| DHEA (NR: < 13.0 ng/ml) | 22.6 | 8.3 |
| T (NR: 0.08-0.60 ng/ml) | 1.93 | 0.14 |
DHEAS Dehydroepiandrosterone sulfate, DHEA Dehydroepiandros- terone, T testosterone, NR normal range
No significant abnormalities were found on 131I-MIBG scanning. To further rule out the possibility of ovary dis- eases with the similar clinical manifestations, including polycystic ovary syndrome, the abdominal and pelvic MRI scan didn’t find any abnormalities.
To further check the tumor size and assess the malignant potential, the enhanced CT scan and 18F-FDG-PET/CT were applied. Enhanced CT scan revealed the tumor located in the right adrenal region and had no clear boundaries with liver, measuring 6.2 cm with heterogeneous enhancement. On PET/CT scan, the lesion shows obvious FDG uptake with a SUVmax reaching 42.7. The above evidence highly suggests the possibility of adrenocortical carcinoma Fig. 2.
Trans-laparoscopic right adrenal tumor resection was successfully performed and the tumor’s capsule was intact, suggesting a radical surgery. The tumor was ovary, brown and fish-like texture, measuring 6.5 cm and 66.7 grams (Fig. 3A, B). The postoperative pathological examination confirmed the diagnosis of oncocytic adrenocortical ade- noma with uncertain malignant potential and a low KI-67
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index of 3% (Fig. 3C-F), regardless of the Helsinki or Lin- Weiss-Bisceglia scoring system for oncocytic adrenocor- tical tumor. Postoperative endocrine test on the second day revealed that the plasma level of DHEA and DHEAS returned to normal range (as shown in Table 1).
Discussion
Pure androgen-secreting adrenal tumors are extremely rare disease and hence only few case reports or case series have been published until now. The limited cases have restricted our understanding of such kind of tumors. Due to the
tumor was soft, fish-like. The well differentiated tumor cells under low (C) and high significance (D). The IHC staining of the tumor revealed that the a-inhibin (E) was positive and a low Ki-67 (F) index of 3%
unfavorable prognosis of adrenocortical carcinoma, we must distinguish PASATs from malignant adrenocortical tumors, which is still a big challenge for clinical doctors. Here, we reported a rare PASAT with extremely high FDG uptake, which suggests the malignant potential before sur- gery, unexpected turned out to be relatively benign tumor. Our case may provide guidance for the treatment of PASAT.
PASAT is an exceedingly rare cause of high androgen secretion with women being predominant. A relevant study in 2018 included 1205 consecutive female patients with DHEAS, A4 and T measured to find out the cause of androgen excess. The result revealed that among 881 pre-
menopausal women, 303 patients had increased androgen and the adrenal-originated cause accounted for 27 cases, namely 18 CAH, 4 ACC, 3 Cushing disease and 2 adre- nocortical adenoma [2]; Another population-based cohort study in 2020 included 1287 patients with adrenal tumors, and only one case showed the symptoms of androgen- secretion [3]. Therefore, due to the rarity of PASAT, few studies have been conducted to show the benign and malignant nature of PASAT. A retrospective study in France included 801 patients with adrenal masses and the incidence of PASAT was 2.4% with 50% being malignant ☒ [4]. A meta-analysis showed that most of the patients in previous case reports were female and PASAT patients were widely distributed in all age groups with a peak age of 21-30 years old [5]. The low prevalence of PASAT in men may be due to the fact that symptoms of hyperandrogenism are more difficult to diagnose in men, resulting in some male patients being clinically ignored. Hirsutism is the most prominent clinical manifestation of PASAT. Other common symptoms due to abnormal androgen production include clitoral enlargement, menstrual dysfunction, hair loss, obe- sity, voice deepening, and acne [6]. In this case, the 19- year-old girl also showed obvious signs of virilization as described above.
Imaging diagnostic tools, including abdominal CT, MRI and 18F-FDG PET/CT, are useful in evaluating the benign and malignant nature of adrenal tumors before resection. Relevant studies have shown that18F-FDG PET/CT is highly sensitive and specific in distinguishing benign and malignant adrenal tumors [7-10]. A meta-analysis in 2011 showed that 18F-FDG PET/CT had a sensitivity of 97% and specificity of 91% for characterizing adrenal masses as malignant [7]. Additionally, a study in 2015 also showed that a sensitivity of 96.7% (95% CI 0.83-0.99) and a specificity of 83.3% (95% CI 0.55-0.95) were achieved to distinguish adrenal adenomas from malignant masses [10]. A study in 2018 indicated that hyperfunctioning adrenal tumors demonstrated higher 18F-FDG uptake than non- functional adrenal tumors, which meant that 18F-FDG PET/ CT had higher efficacy in the diagnosis of functional adrenal tumors [11]. In addition to its relevance with the diagnosis of adrenal tumors, 18F-FDG PET/CT was also found to be related to Ki-67 expression. A cohort study concerning 63 proven cases of ACC demonstrated that Ki- 67 expression was positively correlated with 18F-FDG uptake [1]. The correlation between Ki-67 expression and 18F-FDG uptake has also been similarly described in other malignant tumors, such as head and neck cancer, ovarian cancer, malignant lymphoma, and non-small cell lung cancer [12-15]. Besides the diagnosing value, a recent study also showed that higher SUVmax in 18F-FDG PET/ CT was correlated with shorter survival [16]. In summary, 18F-FDG PET/CT plays a crucial role in the comprehensive
evaluation of adrenal tumors by accurately distinguishing between benign and malignant masses, particularly bene- fiting from its sensitivity to hypermetabolic activity in functional tumors. Moreover, its ability to reflect Ki-67 expression underscores its relevance in assessing tumor aggressiveness and predicting patient outcomes. Therefore, 18F-FDG PET/CT serves not only as a diagnostic tool but also as a prognostic indicator in the management of adrenal masses.
18F-FDG PET/CT has also been used for the diagnosis of benign and malignant PASATs in several reported cases and the results were furtherly confirmed by pathological examination which indicated that 18F-FDG PET/CT was useful in the diagnosis of benign and malignant PASATs. A case report of PASAT in a postmenopausal elderly woman showed a round nodule in the left adrenal gland and the SUVmax of the nodule was only 2.56 by the result of PET/ CT. Consistently, the Pathological examination demon- strated that the PASAT was indeed a benign tumor [17]. Another case of 47-years-old female patient with PASAT also revealed low intra-tumoral metabolism by imaging result of 18F-FDG PET/CT, and histological analysis con- firmed the benign nature of the PASAT [18]. In some other cases, 18F-FDG PET/CT was also used in the diagnosis of PASAT before surgery and the results didn’t conflict with the pathological examination [19-21]. However, in this case, the tumor which demonstrated an extremely high SUVmax (42.7), finally turned out to be oncocytic adre- nocortical adenoma by pathological examination. Our case suggests that 18F-FDG PET/CT has limitations in identify- ing the malignancy of PASAT. From our perspective, while 18F-FDG PET/CT can provide valuable information in diagnosing PASATs, particularly by assessing metabolic activity, its findings should be interpreted cautiously. We consider that the evaluation of a PASAT patient needs to be multifaceted, a thorough endocrine workup is also neces- sary in addition to basic imaging examination, and the final determination of benign or malignant nature still heavily relies on pathological examination after surgical resection. Our case reminded readers that when PASATs demon- strated extremely high FDG uptake, the diagnosis of ACC should be cautious. Maybe more researches about the relationship between the SUVmax on 8F-FDG PET/CT and the malignancy of PASAT should be carried out in the future, so as to better stratify the patients before surgery.
In summary, we reported a rare case of PASAT demonstrating extremely high 18F-FDG uptake turned out to benign tumor by postoperative pathology examination. Our case demonstrates that false-positive results on 18F-FDG PET-CT objectively exist and the accuracy of 18F-FDG PET/CT in determining benignity or malignancy of adrenal masses, especially in PASAT requires further study. We encourage clinicians to record and report more cases and
hope that in the future, well-designed studies could be conducted to further evaluate the diagnosing value of 18F-FDG PET/CT in pure androgen-secreting adrenal tumors.
Author contributions Z.W. prepared the figures and wrote the manuscript text; J.C. wrote the text of discussion part; X.S., Y.L., W.W., G.Z., Y.Z., Y.L., X.W., and D.Q. jointly prepared the materials; All authors reviewed the manuscript.
Funding National High Level Hospital Clinical Research Funding (Grant Number: 2022-PUMCH-B-010); Postdoctoral Fellowship Pro- gram of CPSF (Grant Number: GZC20230301).
Compliance with ethical standards
Conflict of interest The authors declare no competing interests.
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