Check for updates
CASE REPORT
A Case of Myxoid Adrenocortical Carcinoma With 1p Deletion Identified by Whole Exome Sequencing
Naomi Sato1 İD | Naomi Oka2 | Taito Itoh3 İD | Yuko Omori3 | Yuto Yamazaki4 | Hiroyoshi Suzuki5 |
Ryoko Saito-Koyama2 | Hiroya Rikimaru6 | Kanako Sakurai7 | Sanae Midorikawa8 | Hideo Saito9 | Zenei Arihara7
Toru Furukawa3 | Yasuhiro Nakamura1º İD
1Division of Pathological Diagnosis, Tohoku Medical and Pharmaceutical University, Sendai, Miyagi, Japan | 2Department of Pathology, National Hospital Organization Sendai Medical Center, Sendai, Miyagi, Japan | 3Department of Investigative Pathology, Tohoku University Graduate School of Medicine,
Sendai, Miyagi, Japan | 4Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan | 5Department of Pathology, South Miyagi Medical Center, Shibata, Miyagi, Japan | 6Department of Radiology, National Hospital Organization Sendai Medical Center, Sendai, Miyagi, Japan | 7Department of Endocrinology and Metabolism, National Hospital Organization Sendai Medical Center, Sendai, Miyagi, Japan | 8Faculty of Human Life Science, Miyagi Gakuin Women’s University, Sendai, Miyagi, Japan | 9Department of Urology, National Hospital Organization Sendai Medical Center, Sendai, Miyagi, Japan | 1ºDivision of Pathology, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, Sendai, Miyagi, Japan
Correspondence: Yasuhiro Nakamura (yasu-naka@tohoku-mpu.ac.jp)
Received: 28 February 2025 | Revised: 27 July 2025 | Accepted: 11 August 2025
Keywords: 1p loss | adrenocortical carcinoma | myxoid adrenocortical carcinoma | whole exome sequencing
ABSTRACT
A 57-year-old male underwent an incidental left adrenal tumor resection because of malignancy concerns. The tumor dem- onstrated a heterogeneous yellowish-white color. Histological features were characterized by nuclear atypia, diffuse growth, sinusoidal invasion, and mucin deposition in most stromal regions, leading to the diagnosis of a myxoid adrenocortical carcinoma (ACC). Whole exome sequencing analysis revealed 1p deletion and other several mutations without TP53 nor CTNNB1 mutations. Following surgery and adjuvant mitotane therapy, the patient showed no recurrence at a 5-year follow-up. Myxoid ACC is an exceedingly rare tumor characterized by mucus deposits in tumor stroma with high malignant potential. Despite the identification of crucial driver gene mutations such as TP53 and CTNNB1 in ACC, the genetic background of the myxoid ACC remains unclear. This case was the first case report of myxoid ACC with a 1p deletion, which was reported to be detected in 67% of ACC and 9% of adenoma but not in hyperplasia, supporting the correlation of this aberration with tumorigenesis. In conclusion, 1p deletion may be relevant to tumorigenesis in myxoid ACC.
1 Introduction |
Adrenocortical carcinoma (ACC) is a malignant tumor origi- nating in the adrenal cortex. Adrenal tumors are relatively common, affecting 3%-10% of the population, the majority are nonfunctioning benign adrenal adenomas [1]. In contrast, it’s the incidence of ACC was 0.5-2 cases per million per year [1, 2],
while reports from Japan indicated that 1.4% of incidentally discovered adrenal tumors were malignant [2].
The World Health Organization (WHO) Classification of Tumors defines three subtypes of ACC: oncocytic, sarcomatoid, and myxoid. Myxoid ACC is characterized by abundant extra- cellular connective tissue containing Alcian-Blue (AB)-positive
Abbreviations: AB, alcian-blue; ACC, adrenocortical carcinoma; CT, computed tomography; CYP, Cytochrome P450; MRI, magnetic resonance imaging; DHEA, dehydroepiandrosterone; DNA, deoxyribonucleic acid; WES, whole exome sequencing.
Naomi Sato and Naomi Oka contribute equally to this study.
mucin [3]. Almost half of previously reported cases are nonfunctional [4].
Vatrano et al. identified CTNNB1 as the most common muta- tion in ACC, followed by TP53 [5]. It is also known that 36.8% of ACCs have a tetraploidy copy number signature [6]. However, the molecular basis of the myxoid ACC remains contentious. Vatrano et al. reported that myxoid ACC exhibited gene mutations and copy number variations similar to those found in conventional ACC, particularly with a higher prevalence of RB1, CDK4, and CDKN2A [5]. In contrast, Giordano et al. reported a case of myxoid ACC with distinct gene expression profile from conventional ACC [7].
In this report, we present a case of myxoid ACC with a 1p deletion and discuss its significance.
2 Clinical Summary |
A 57-year-old man was referred to our hospital for evaluation of a left single adrenal tumor incidentally discovered on abdomi- nal computed tomography (CT). The tumor measured 4.3 cm and exhibited homogeneous CT attenuation (25-30 Hounsfield units) without necrosis or intratumoral hemorrhage (Figure Sla). Contrast-enhanced CT scan revealed heteroge- neous enhancement of the mass. Magnetic resonance imaging (MRI) depicted high-intensity regions of the tumor on T2- weighted images. On T1-weighted gradient-echo in-phase MRI, the tumor appeared hyperintense, while on out-of-phase MRI, it appeared hypointense (Figure S1). Gadolinium-enhanced T1- weighted MRI showed enhancement of the tumor. A positron emission tomography scan with 18F-2-fluoro-D- deoxyglucose demonstrated no tracer uptake by the tumor or elsewhere in the body.
On physical examination, the patient did not exhibit any fea- tures indicative of Cushing’s syndrome but had a history of hypertension with blood pressure readings of 153/97 mmHg. Evaluation of adrenocortical hormone levels revealed normal aldosterone renin ratio, plasma adrenocorticotropin (ACTH), serum cortisol, and serum dehydroepiandrosterone sulfate (DHEA-S) levels. Overnight suppression with 1 mg dexa- methasone reduced serum cortisol from 6.7 to 10.5 µg/dL to 1.2 µg/dL, and assessment of adrenomedullary hormones in spot urine showed normal metanephrine and normetanephr- ine levels (Table 1). These endocrine findings suggested a nonfunctioning left adrenal tumor. The possibility of malig- nancy could not be ruled out because of the tumor size (> 4.0 cm). Therefore, laparoscopic left adrenalectomy was performed.
It was considered that there was the possibility of tumor spread with mucus during surgery into the abdominal cavity or surgical margins. Therefore, postoperatively, the patient was monitored with mitotane 1500 mg/day and dexamethasone 1.5 mg/day. The total amount of mitotane used for 5 years was over 2500 g with no adverse effects except for adrenocortical insufficiency. No evidence of recurrence was observed over the 5 years following surgery. There were no pre- and postoperative blood pressure changes due to a nonfunctioning tumor.
| Plasma renin activity (ng/ml/hr) | 2.2 |
| Aldosterone (pg/mL) | 131 |
| Aldosterone-renin ratio | 59.5 (<200) |
| Spot urinary metanephrine (mg/g creatinine) | 0.05 |
| Spot urinary normetanephrine (mg/g creatinine) | 0.18 |
| ACTH (pg/mL) | 39 |
| Cortisol (µg/dL) | 6.7 |
| DHEA-S (ng/ml) | 2060 (380-3130) |
| [1 mg - dexamethasone suppression test] | |
| ACTH (pg/mL) | 4.5 |
| Cortisol (mg/dL) | 1.2 |
Note: The ranges of reference values are indicated in the parentheses. Plasma aldosterone was measured by radioimmunoassay (Spac-S® aldosterone kit; Fuji Rebio Co. Ltd., Tokyo).
Abbreviations: ACTH, adrenocorticotropin; DHEA-S, Dehydroepiandrosterone sulfate.
2.1 | Pathological Findings
The tumor dimensions measured 60 x 40 x 25 mm. Macro- scopically, the mass exhibited a yellowish-white coloration with extensive mucinous appearance without necrosis (Figure 1a).
Microscopically, Alcian-Blue-positive mucin deposition was predominant in most areas of the stroma (> 90% of tumor substrate) (Figure 1b). The tumor cells displayed irregular, unequally sized atypical nuclei and eosinophilic cytoplasm. Additionally, an elevated nucleus/cytoplasm ratio and spindle- shaped appearance were found. These findings correspond to high-grade nuclear atypia because these are never seen in adenomas (Figure 1c). Tumor cells exhibited dense prolifera- tion, primarily in trabecular and alveolar pattern structures. Moreover, diffuse architecture, which is recognized by the loss or decrease of reticulin framework within the tumor foci [8], was detected in over 30% area (Figure 1d). Mitotic count was 1/50 high power fields and MIB-1 labeling index was 3% at hot spot. Capsular and diffuse sinusoidal invasion was evident in some regions (Figure le-f). Atypical mitosis and necrosis were not detected.
Regarding the scoring system of adrenocortical neoplasm, there are several systems: not only Weiss scoring system and modified Weiss system but also Reticulin algorithm, Lin-Weiss-Bisceglia system and Helsinki scoring system. Among them, especially, Reticulin algorithm is known to be useful and reproducible for the diagnosis of myxoid ACC because a high mucin deposition rate lowers the score of Weiss system and the risk for malig- nancy may be likely to be underestimated [8].
We show each score of this present case: Weiss scoring system of 5 (high nuclear atypia, diffuse architecture > 30%, clear cells ≤ 25%, capsular invasion and venous invasion); modified Weiss system of 3 (clear cells ≤ 25% and capsular invasion); Reticulin algorithm meet the criteria of malignancy (altered reticulin
a
b
c
d
e
f
framework and vascular invasion) [8]. Consequently, the tumor was diagnosed as myxoid ACC. Immunohistochemically, the tumor cells exhibited positive staining for vimentin, Melan A, and inhibin a (very focal), negative staining for AE1/AE3 and calretinin, and no overexpression of p53 (Table 2). Additionally, as for the hormone synthesis systems(Figure 2a-f), the tumor cells were diffusely positive for Steroidogenic Factor 1 (SF-1) (Figure 2a) and 17a-hydroxylase (c17) (Figure 2b) and hetero- geneously positive for 36-hydroxysteroid dehydrogenase 1 (36HSD1), 36HSD2, Cytochrome P450 family 11 subfamily B member 1 (CYP11B1) (Figure 2c), CYP21 and dehydroepi- androsterone sulfate transferase (DHEA-ST) (Figure 2d), while completely negative for CYP11B2 (Figure 2e) and 17ß-hydroxysteroid dehydrogenase 5 (17ßHSD5) (Figure 2f). These results are consistent with primary adrenocortical tumor being nonfunctional [9].
2.2 | Mutation Analysis
Genomic deoxyribonucleic acid (DNA) was extracted from formalin-fixed paraffin-embedded tissues. Whole exome sequencing (WES) was performed by Macrogen Japan Corp (Tokyo, Japan) using the SureSelect Human All Exon V6 kit (Agilent Technologies, Santa Clara, CA, USA) and the Illumina NovaSeq. 6000 platform. Sequencing reads were aligned to the human reference genome GRCh37/hg19 using the GATK Best Practices pipeline. The mean sequencing depth was 29.3 (as computed using mosdepth), with over 97% of bases achieving Q30 or higher, based on FastQC quality reports. Somatic variant calling was conducted using Mutect2 (GATK v4.3.0.0), Strelka2, and FFPolish (v0.1.0), with default parameters unless otherwise
specified. Copy number alterations were detected using CNVkit (v0.9.10) and PureCN (v2.8.1). The copy number segmentation was further analyzed with SigProfilerExtractor (version.1.1.23) for mutational signature classification. All tools were run with default parameters following respective developer guidelines unless otherwise stated. Alignment and preprocessing (including base quality score recalibration and duplicate marking) followed the GATK Best Practices workflow for somatic variant calling. Variants were annotated using the following databases: dbSNP version 151, ClinVar (20230520 release) and COSMIC v97. Variant annotation and filtering were conducted using VEP (Ensembl Variant Effect Predictor, version 109) and snpEff (version 5.1).
Copy number analysis by WES using SigProfilerExtractor revealed that a copy number signature of this present case was classified as CN2 based on COSMIC criteria (Figure 3a). Although CN2 is typically associated with tetraploid genomes, this case exhibited CN2 features localized to specific chromo- somes (e.g., chr11 and chr15), suggesting regional gains rather than whole genome doubling. In addition, WES identified a 1p deletion (Figure 3b,c).
|
3 Discussion
Myxoid ACC is an exceedingly rare malignant tumor, and its genetic profiles are largely unknown. This is the first report of a case with myxoid ACC showing a 1p deletion.
Myxoid ACC is characterized by a predominant (> 70%) myxoid component. Mixture of mucus and tumor foci in a mosaic made
| Antibody | Host | Antigen retrieval | Dilution | Clone | Source |
|---|---|---|---|---|---|
| Vimentin | Mouse | (a) | 1 | V9 | Roche |
| MelanA | Mouse | (b) | 1 | A103 | Roche |
| Inhibina | Mouse | (b) | 1 | R1 | Agilent |
| Cytokeratin (Pan-keratin) | Mouse | (c) | 1 | AE1/AE3, PCK26 | Roche |
| p53 | Mouse | (b) | 1 | DO7 | Roche |
| SF-1/Ad4BP | Mouse | (d) | 100 | N1665 | PPMX |
| c17 | Rabbit | (d) | 500 | Poly clonal | BEX |
| DHEA-ST | Goat | — | 1000 | Poly clonal | Santa Cruz |
| 17ßHSD5 | Mouse | (d) | 500 | 2E5 | Abnova |
| 36HSD1 | Mouse | — | 500 | 37-2 | Santa Cruz |
| 3ßHSD2 | Mouse | — | 2000 | 12E4 | Kyoto Univ. |
| CYP21 | Rabbit | — | 15000 | Poly clonal | Taipei |
| CYP11B1 | Rat | (e) | 70 | 2-2 | Gomes Sanchez |
| CYP11B2 | Mouse | (e) | 500 | 40-17 | Gomes Sanchez |
Note: Antigen retrieval:
(a) Solution pH9 pH9 98℃ 40 min.
(b) CC1buffer 98°C 64 min.
(c) CC1buffer 98℃ 36 min + Protease RT 3 min.
(d) Autoclave 121°C 5 min (citrate buffer pH6).
(e) Autoclave 121°C 5 min (Solution pH9).
Abbreviations: c17, 17a-hydroxylase; CYP, Cytochrome P450 family; DHEA-ST, dehydroepiandrosterone sulfate transferase; HSD, hydroxysteroid dehydrogenase; SF-1, steroidogenic factor 1.
a
b
c
d
e
f
0
it difficult to detect the presence of mucus on CT or MRI and lead to misunderstanding as lipid content. Furthermore, it is typified by trabecular or microacinar growth patterns, small and uniformly sized cells with mild nuclear atypia, and eosinophilic cytoplasm [10]. Parameters such as diffuse growth pattern and nuclear atypia, which are crucial for the Weiss criteria, may be
absent or challenging to evaluate. Actually, Sung et al. reported eight cases of myxoid ACC with varied Weiss scores ranging from 3 to 8 [11], most of which were relatively low. In addition, even the case with the highest score, a Weiss score of 8 and a WRS of 7 exhibited only 10% mucin deposition. These findings could potentially result in an underestimation of tumor
14401827, 2025, 9, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/pin. 70045 by National Library Of Medicine, Wiley Online Library on [02/04/2026]. See the Terms and Conditions (https://onlinelibrary. wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
a
Chromosome
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
22
Maximum Likelihood Copy Number
2.5 3.0
o
0
2.0
1.5
1.0
.
0.5
o
·
0.0
o
o
1
0
1000
2000
3000
4000
5000
SNV index
b
Chromosome 1
Copy Number log-ratio
1
0
01 3
-1
N
?
0
50000
100000
150000
200000
250000
Pos(kbp)
C
Maximum Likelihood Copy Number
0.0 0.5 1.0 1.5 2.0 2.5 3.0
0
50000
100000
150000
200000
250000
Pos(kbp)
malignancy risk. Despite exhibiting borderline malignancy in morphology, myxoid ACC demonstrates a poor prognosis akin to conventional ACC [3, 12]. Therefore, it is important to carefully diagnose ACC with mucin deposits. Prior investiga- tions have indicated that nearly half of myxoid ACC cases are nonfunctional [4], consistent with our study, and no discernible relationship has been established between morphology or the degree of mucin deposition and hormone-producing potential [10].
In our present case, WES revealed a 1p deletion in addition to CN2, which is common in ACC [6]. Chromosome 1p contains genes related to apoptosis, tumor suppression, DNA repair, the Wnt signaling pathway, and more. Chromosome 1p has been identified as a “hot spot” containing genes significantly involved in various processes such as DNA repair, spindle checkpoint function, and apoptosis. 1p deletions are reported to
occur at an early stage of colorectal carcinogenesis, resulting in genomic instability and tumorigenesis [13]. The initial docu- mentation of 1p deletion in ACC dates back to 1999 [14], which highlighted its occurrence in 67% of ACC and 9% of adenoma but not in hyperplasia (p = 0.0002). Furthermore, a similar association between 1p deletion and carcinogenesis was reported for other tumors. For example, colorectal cancer demonstrates more frequent 1p deletion than adenoma [13]. These phenomena suggested the association of 1p deletion with carcinogenesis and might support our hypothesis that this mutation accelerated carcinogenesis in myxoid ACC. The major driver mutations in ACC, such as CTNNB1, TP53, TERT, CDK4, ZNRF3, and RB1 [5, 15] were absent in this case despite comprehensive WES analysis. A prior study involving WES of 41 ACC cases reported that approximately a quarter of them lacked major gene mutations or copy number variations [16]. Alternatively, DNA methylation and other factors are
considered to underlie this phenomenon: for example, Wnt inhibitory factor-1 gene inactivation. CpG island methylation and so on [5, 15-19]. Eventually, ACC may exhibit diverse driver genes based on ethnicity. According to the findings of our present case, it is suggested that myxoid ACC develop via carcinogenesis pathway distinct from conventional ACC, and in some cases a 1p deletion may be involved in this pathway. Methylation analysis could be advantageous for further exploration in future.
Subsequent investigations suggested that 1p deletion is also associated with a poorer prognosis in ACC compared with adrenocortical adenoma [17, 18]. Several reasons for long sur- vival of our present case are considered as follows: the adrenal tumor was incidentally discovered in the early phase, and mi- totane administration was well tolerated for 5 years. Recently, a randomized trial has revealed that adjuvant mitotane might not be indicated in patients with low-grade located adrenal cancer [20]. However, the efficacy of mitotane treatment could not be ruled out in these ACCs, and there are too few case reports of myxoid ACC who underwent mitotane treatment to assess its efficacy in myxoid ACC [21]. This present case might contribute to the efficacy prediction of adjuvant mitotane therapy for myxoid ACC in the future.
In conclusion, we present a rare case of myxoid ACC with extensive mucin deposition. We identified a 1p deletion that might be linked to the carcinogenesis of this ACC variant without major driver mutations typically reported in ACCs. Although further investigation into the detection method of 1p deletion and the pathogenesis of ACC or the myxoid ACC focusing on this mutation is warranted, this first report of myxoid ACC with 1p deletion suggests this alteration may contribute to its tumorigenesis.
Author Contributions
All the authors have contributed significantly to the content of the manuscript. N.S., N.O. and Y.N. conceived and designed the study. N.S. and N.O. drafted the manuscript. Y.Y., H.S., R.S .- K., Y.N. assisted in the pathological diagnosis of the present case. T.I., Y.O., and T.F. assisted with the genetic experiments. H.R., K.S., S.M., H.S., and Z.A. partici- pated in the collection and review of clinical data. Y.N. supervised all studies. All the authors read and approved the final manuscript.
Ethics Statement
The experiment reported here was conducted in agreement with the Declaration of Helsinki and was approved by the Ethics Committee of Sendai Medical Center (Miyagi, Japan) and that of Tohoku University (Miyagi, Japan). Requirement of informed consent was waived.
Conflicts of Interest
The authors declare no conflicts of interest.
References
1. T. Else, A. C. Kim, A. Sabolch, et al., “Adrenocortical Carcinoma,” Endocrine Reviews 35 (2014): 282-326.
2. T. Ichijo, H. Ueshiba, H. Nawata, and T. Yanase, “A Nationwide Survey of Adrenal Incidentalomas in Japan: The First Report of Clinical and Epidemiological Features,” Endocrine Journal 67 (2020): 141-152.
3. L. A. Erickson, “Challenges in Surgical Pathology of Adrenocortical Tumours,” Histopathology 72 (2018): 82-96.
4. A. K. Lam, “Adrenocortical Carcinoma: Updates of Clinical and Pathological Features After Renewed World Health Organisation Classification and Pathology Staging,” Biomedicines 9 (2021): 175.
5. S. Vatrano, M. Volante, E. Duregon, et al., “Detailed Genomic Characterization Identifies High Heterogeneity and Histotype-Specific Genomic Profiles in Adrenocortical Carcinomas,” Modern Pathology 31 (2018): 1257-1269.
6. H. M. Nielsen, A. How-Kit, C. Guerin, et al., “Copy Number Varia- tions Alter Methylation and Parallel IGF2 Overexpression in Adrenal Tumors,” Endocrine-related Cancer 22 (2015): 953-967.
7. T. J. Giordano, D. G. Thomas, R. Kuick, et al., “Distinct Tran- scriptional Profiles of Adrenocortical Tumors Uncovered by DNA Microarray Analysis,” American Journal of Pathology 162 (2003): 521-531.
8. O. Mete, L. A. Erickson, C. C. Juhlin, et al., “Overview of the 2022 WHO Classification of Adrenal Cortical Tumors,” Endocrine Pathology 33 (2022): 155-196.
9. Y. Nakamura, Y. Yamazaki, S. J. Felizola, et al., “Adrenocortical Carcinoma,” Endocrinology and Metabolism Clinics of North America 44 (2015): 399-410.
10. R. R. de Krijger and T. G. Papathomas, “Adrenocortical Neoplasia: Evolving Concepts in Tumorigenesis With an Emphasis on Adrenal Cortical Carcinoma Variants,” Virchows Archiv 460 (2012): 9-18.
11. T. Y. Sung, Y. M. Choi, W. G. Kim, et al., “Myxoid and Sarcomatoid Variants of Adrenocortical Carcinoma: Analysis of Rare Variants in Single Tertiary Care Center,” Journal of Korean Medical Science 32 (2017): 764-771.
12. R. Z. Karim, E. J. Wills, S. W. McCarthy, and R. A. Scolyer, “Myxoid Variant of Adrenocortical Carcinoma: Report of a Unique Case,” Pathology International 56 (2006): 89-94.
13. C. Payne, C. Crowley-Skillicorn, C. Bernstein, and H. Holubec, “Molecular and Cellular Pathways Associated With Chromosome 1p Deletions During Colon Carcinogenesis,” Clinical and Experimental Gastroenterology 4 (2011): 75-119.
14. J. Zhao, E. J. M. Speel, S. Muletta-Feurer, et al., “Analysis of Genomic Alterations in Sporadic Adrenocortical Lesions,” American Journal of Pathology 155 (1999): 1039-1045.
15. C. S. Rahane, A. Kutzner, and K. Heese, “Establishing a Human Adrenocortical Carcinoma (ACC)-Specific Gene Mutation Signature,” Cancer Genetics 230 (2019): 1-12.
16. C. C. Juhlin, G. Goh, J. M. Healy, et al., “Whole Exome Sequencing Characterizes the Landscape of Somatic Mutations and Copy Number Alterations in Adrenocortical Carcinoma,” Journal of Clinical Endocrinology & Metabolism 100 (2015): E493-E502.
17. S. Zheng, A. D. Cherniack, N. Dewal, et al., “Comprehensive Pan-Genomic Characterization of Adrenocortical Carcinoma,” Cancer Cell 29 (2016): 723-736.
18. T. J. Giordano, R. Kuick, T. Else, et al., “Molecular Classification and Prognostication of Adrenocortical Tumors by Transcriptome Pro- filing,” Clinical Cancer Research 15 (2009): 668-676.
19. Y. Mitsui, H. Yasumoto, T. Nagami, et al., “Extracellular Activation of Wnt Signaling Through Epigenetic Dysregulation of Wnt Inhibitory Factor-1 (Wif-1) Is Associated With Pathogenesis of Adrenocortical Tumor,” Oncotarget 5 (2014): 2198-2207.
20. M. Terzolo, M. Fassnacht, P. Perotti, et al., “Adjuvant Mitotane Versus Surveillance in Low-Grade, Localised Adrenocortical Carci- noma (Adiuvo): An International, Multicentre, Open-Label, Rando- mised, Phase 3 Trial and Observational Study,” Lancet Diabetes & Endocrinology 11 (2023): 720-730.
21. K. Harada, M. Yasuda, K. Hasegawa, Y. Yamazaki, H. Sasano, and F. Otsuka, “A Novel Case of Myxoid Variant of Adrenocortical Carcinoma in a Patient With Multiple Endocrine Neoplasia Type 1,” Endocrine Journal 66 (2019): 739-744.
Supporting Information
Additional supporting information can be found online in the Supporting Information section. Supplemental Figure 1. Radiological Findings.
14401827, 2025, 9, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/pin. 70045 by National Library Of Medicine, Wiley Online Library on [02/04/2026]. See the Terms and Conditions (https://onlinelibrary. wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License