Adrenocortical carcinoma presenting with extensive striae: A case report and literature review
Ayse Ozden®, Zerrin Orbako, Ebru Sener01, Gozde Doymus02, Hakan Doneray®
Departments of Pediatric Endocrinology, 1Pathology and 2Pediatrics, Atatürk University School of Medicine, Erzurum, Turkey
Correspondence to: Ayse Ozden, E-mail: ayshedaphne@yahoo.com
Abstract
Adrenocortical tumors are rare tumors in childhood. Virilization is the most common symptom, but about 5.5% of patients may also present with isolated Cushing’s syndrome. A girl 15 years and 8 months of age presented with complaints of striae on her legs, acne for 2 weeks, and amenorrhea for 2 months. On physical examination, extensive striae were observed on her legs and abdomen. On hormonal investigation, her adrenocorticotropic hormone level was <5 pg/ml, cortisol was 35.4 µg/dl. Her hypercortisolism raised suspicion of Cushing’s syndrome. Adrenal MRI revealed a right adrenal mass approximately 9 cm in diameter. Pleural metastasis was detected and the patient was diagnosed as having stage 4 adrenocortical carcinoma. Despite treatment, she died 9 months after diagnosis. Our case followed an aggressive clinical course and was unique due to the presence of extensive striae without pronounced virilization or Cushingoid symptoms.
Keywords:
Adrenocortical carcinoma, adrenocortical tumor, Cushing’s syndrome, striae
Introduction
Adrenal tumors are very common, affecting 3-10% of the population. The majority of these are small, benign, nonfunctioning adrenocortical adenomas. In contrast, adrenocortical carcinomas (ACC) are rare tumors with poor prognosis.[1] Malignancy should be investigated for all adrenal lesions, including those detected incidentally in imaging studies.[2]
In the USA, the incidence of ACC is estimated to be 1-2 per million per year. The global incidence of ACC in children is 0.2-0.3 per million per year, although a rate as high as 2.9-4.2 per million per year was reported in southern Brazil. This high rate was attributed to the high frequency of the low-penetrance p.R337H allele of the tumor protein 53 (TP53) gene.[1] A quarter of all TP53 mutations may be de novo. Therefore, TP53 mutation should be investigated in children with ACC even in the absence
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of family history.[1] Most ACCs are sporadic, but some may be associated with a genetic defect. Individuals with Li-Fraumeni syndrome, Beckwith-Wiedemann syndrome, multiple endocrine neoplasia type 1, and familial adenomatous polyposis have an increased risk for ACC.[3]
Unlike in adults, 90% of ACCs in children are endocrine-functional. ACC usually presents with virilization and Cushing’s syndrome, and occasionally with feminization and hyperaldosteronism.[3]
Here, we present a 15-year-old girl with pronounced striae and secondary amenorrhea who was diagnosed with Cushing’s syndrome and adrenocortical tumor despite exhibiting no marked Cushingoid symptoms.
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How to cite this article: Ozden A, Orbak Z, Sener E, Doymus G, Doneray H. Adrenocortical carcinoma presenting with extensive striae: A case report and literature review. Indian J Cancer 2025;62:548-51.
Submitted: 05-Feb-2024 Accepted: 21-Apr-2025
Revised: 06-Apr-2025 Published: 07-Mar-2026
Case Presentation
A girl 15 years and 8 months of age presented with complaints of striae on her legs, acne for the past 2 weeks, and amenorrhea for the past 2 months. She did not report any marked changes in weight. The patient had been menstruating for 3 years and used to have regular periods. Her personal medical history was unremarkable and there was no family history of pathology except for lung cancer in her grandfather. On physical examination, her body weight was 52 kg (-0.3 standard deviations [SD]), her height was 156.5 cm (-0.5 SD) and her BMI was calculated as 21.3 (50th percentile). Her blood pressure was within normal limits at 112/69 mmHg (90th percentile: 122/78 mmHg). Extensive striae were observed on her legs and abdomen [Figure 1]. Her Ferriman- Gallwey score was 7, and she did not have clitoromegaly.
In laboratory studies, her white blood cell count was 8890/mm3, hemoglobin was 16.3 g/dL, and platelet count was 300000/mm3. Blood biochemistry analysis results included fasting blood glucose: 105 mg/dL (60-100 mg/dL), blood urea nitrogen: 8.8 mg/dL, creatinine: 0.6 mg/dL, sodium: 145 mEq/L (135-145 mmol/L), potassium: 2.8 mEq/L (3.5-4.5 mmol/L), calcium: 8.5 mg/dL, phosphorus: 2.9 mg/dL, aspartate transaminase: 21 U/L, alanine transaminase: 23 U/L, lactate dehydrogenase: 577 U/L (1-247 U/L), and hemoglobin A1c: 6%.
Hormonal investigations showed adrenocorticotropic hormone (ACTH): < 5 pg/mL (10-35 pg/mL), cortisol: 35.4 µg/dL (6.7-22.6 µg/dL), prolactin: 23 ng/ml (3.3- 26.7 ng/ml), thyroid-stimulating hormone: 0.3 plU/L (0.6-3.7 ulU/L), free thyroxine (fT4): 0.7 ng/dL (0.7-1.1 ng/dL), follicle-stimulating hormone: 0.04 mlU/mL (3.8-8.7 mlU/mL), luteinizing
hormone: < 0,1 mlU/mL (2.1-10.8 mlU/mL), 17-OH progesterone: 7.34 ng/ml (0.2-2.3 ng/ml), dehydroepiandrosterone sulfate (DHEA-S): 431 µg/dL (50-321 µg/dL), androstenedione: 6.6 ng/ml (0.75-3.1 ng/ml), and total testosterone: 0.53 ng/ml (0.07- 0.48 ng/mL). The patient had borderline hypernatremia and hypopotassemia, with a normal aldosterone level of 11.2 ng/dL (2-22 ng/dL). Catecholamine levels were normal in 24-hour urine analysis. The del 17p13 (TP53) gene deletion was not detected.
Based on hypercortisolism, we proceeded with the differential diagnosis of Cushing’s syndrome. A nocturnal cortisol measurement to assess diurnal cortisol rhythm was high, at 26.6 ug/dl (>7 ug/dl), and circadian rhythm disorder was suspected. Her free cortisol level in 24-hour urine was also high, at 757.4 µg/24 hours (50-190 µg/24 hours). Cortisol level measured at 08:00 am after 1 mg dexamethasone suppression test was high, at 30 µg/dl (>1.8 g/dl). The impaired diurnal cortisol rhythm and lack of response to 1 mg dexamethasone suppression supported the diagnosis of Cushing’s syndrome.
According to Cushing’s syndrome algorithm published in the 2008 Endocrine Society guidelines the patient’s low ACTH level suggested adrenal gland pathology.[4]
Adrenal ultrasound revealed a hypoechoic, heterogeneous mass 9 x 5 cm in size with internal perfusion and lobular contour in the right adrenal gland. Adrenal MRI revealed an 84 x 53 mm enhancing mass in the right adrenal gland with
heterogeneous density and containing a hemorrhagic focus, as well as bilateral minimal pleural effusion in both hemithoraces. The patient’s MRI images are shown in Figure 2.
MRI findings of a mass with an irregular border, heterogeneous enhancement, a necrotic component, and no color change between in-phase and out-of-phase images (persistent enhancement) primarily suggested adrenal carcinoma and pleural metastasis.
The patient underwent laparoscopic right adrenalectomy and a mass weighing 210 g was removed. On histopathological examination, 13- 15 mitoses were counted per 50 high-power fields (HPF) in sections stained with hematoxylin and eosin (H and E). Although atypical mitosis was not detected, the findings were considered consistent with ACC due to the observation of perineural and lymphovascular invasion. Immunohistochemical staining was positive for inhibin and calretinin but negative for chromogranin and synaptophysin. The Ki-67 proliferation index was 8-10%. With a Weiss score of 5/9, a Wieneke score of 4/9, and a Ki-67 proliferation index of 8-10%, the pathologic diagnosis was ACC. The histopathological images of the adrenal mass removed from the patient are shown together in Figure 3.
Perineural invasion
Lymphovascular invasion
Adipose tissue invasion
Necrosis
The patient’s cortisol level decreased to 18 ug/dL on the first postoperative day but returned to 30 µg/dL at 1 month. A follow-up MRI scan was obtained to check for residual tumor and recurrence. A 29 x 13 mm non-enhancing lesion showing no diffusion restriction was detected in the right adrenal gland.
Our patient was classified as stage 4 due to the presence of distant metastasis at presentation. Nine months after diagnosis, she was admitted for thoracic surgery due to bilateral pleural effusion and pleural metastasis and subsequently died.
Discussion
Adrenocortical tumors (ACT) are extremely rare, accounting for 0.2% of all childhood tumors and 5-6% of all adrenal tumors.[5] Unlike in adults, approximately 90% of ACCs in children exhibit endocrine function.[6] Virilization is the most common presentation. However, isolated Cushing’s syndrome can also be seen in 5.5% of patients.[6] In childhood, the most common sign of Cushing’s syndrome is weight gain with insufficient vertical growth.[4] Although our patient did not exhibit the signs primarily associated with Cushing’s syndrome, such as obesity, moon facies, and hypertension, the marked striae and amenorrhea were indicative symptoms.
ACCs exhibit a bimodal age distribution, with the first peak in early childhood (around the age of 3) and the second peak at around 40-50 years.[4] However, our patient’s age was not within these ranges.
Among radiologically detectable masses of all sizes, 1 in every 1500 lesions is identified as adrenal carcinoma, and among tumors larger than 5-7 cm, about 7% are diagnosed as ACC.[7] In another study, the mean tumor size of ACCs was reported to be 10 cm, with 95% being larger than 5 cm, while in a surgical series, the prevalence of ACC among incidentalomas was found to be 2% if the tumor diameter was smaller than 4 cm, 6% at tumor diameters of 4-6 cm, and 25% if tumor diameter was larger than 6 cm.[8] Our patient’s tumor was measured as 9 cm in diameter based on radiological imaging.
In a Brazilian study of 13 children with ACC, all patients had symptoms of hypercortisolism, all of the girls exhibited signs of virilization, and acne was observed in 69.2% of the patients.[9] Similarly, our patient had pronounced striae, acne, and menstrual irregularity consistent with hypercortisolism. Our patient had an FGS score of 7, with no significant hair growth or clitoromegaly and only slightly elevated androgen levels.
ACC in children presents with hypercortisolism and virilization rather than Cushingoid symptoms.[6]
In 2016, Narumi et al. reported the case of a 9-year-old girl with ACC who showed no virilization or hyperandrogenemia but presented with the clinical symptoms of Cushing’s syndrome.[6] In this article, Narumi et al. noted that an investigation of 5 patients with isolated Cushing’s syndrome who were diagnosed with ACC revealed that all had high DHEA-S and testosterone levels. Although our patient also exhibited symptoms of hypercortisolism, there was no virilization, and her DHEA-S and total testosterone levels were only slightly elevated.
Our patient’s serum sodium level was at the upper limit of the normal range and she had hypopotassemia. Her aldosterone level, measured to check for hyperaldosteronism, was normal. This was attributed to the hypercortisolism. In addition, our patient had a high hemoglobin A1c level (6%). She also exhibited impaired glucose tolerance, with a fasting blood glucose level of 105 mg/dl and a non-fasting blood glucose level of 150 mg/dL. Postoperatively, there was an improvement in her blood glucose levels and hypopotassemia.
It can be very difficult to distinguish benign ACTs from ACC in children. Difficulties in diagnosing ACC have led to the emergence of multi-parameter scoring systems. The authors stated that the Ki-67 index and p53 can be helpful tools in distinguishing ACCs from adenomas.[5] A retrospective study of 41 children with ACC, presented to the Mayo Clinic, demonstrated that the Wieneke index is a more accurate scoring system for predicting clinical outcomes in young children.[3] Suspicion of ACC is recommended for tumors with a Weiss score of ≥3, while according to the Wieneke system, scores of 2 or lower are regarded as benign, 3 as suspicious, and 4 or higher as malignant.[5,9] Our patient had a Weiss score of 5 and Wieneke score of 4. Therefore, both scoring systems indicated malignancy in our patient.
The most important markers suggesting the presence of malignancy are shown to be capsular and venous invasion, followed by a high mitotic rate.[5] Our patient had capsular, perineural, and lymphovascular invasion and a mitotic rate of 13-15 mitoses per 50 HPF.
In a study by Das et al., 86% of ACC patients were positive for P53 overexpression. A p53 deletion was not detected in our patient. The frequency of P53 mutation is high in Brazil, but the rate in Turkey is unknown.[5] Gupta et al. reported that the presence of metastasis at the time of ACC diagnosis was an independent prognostic factor for survival.[3] Favorable prognostic indicators were age less than 4 years, presence of virilization alone, tumor size under 10 cm, tumor volume less than 200 cm3, low tumor grade, absence of metastatic disease, and surgery
quality.[3] The prognostic outlook for our patient was poor because she was over the age of 4 and had Cushingoid symptoms, pleural metastasis at the time of diagnosis, and a high Ki-67 index.
Conclusion
Although our patient did not exhibit the signs primarily associated with CS, such as obesity, moon facies, and hypertension, the marked striae were indicative symptoms.
Because there are few reported cases of pediatric ACC, there is limited information about its clinical features and treatment. We sought to contribute to the literature with this report on the unique clinical features of this aggressive case of ACC in our patient, who presented with striae but no apparent virilization or Cushingoid symptoms.
Informed consent
Written consent was obtained from the mother for the study.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
ORCID iDs
Ayse Ozden: https://orcid.org/0000-0002-3625-2387
Zerrin Orbak: https://orcid.org/0000-0002-1847-9844 Ebru Şener: https://orcid.org/0000-0002-0632-3527
Gozde Doymuş: https://orcid.org/0000-0002-8284-8456
Hakan Doneray: https://orcid.org/0000-0002-9774-3649
References
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2. Almeida MQ, Bezerra-Neto JE, Mendonça BB, Latronico AC, Fragoso MCBV. Primary malignant tumors of the adrenal glands. Clinics (Sao Paulo) 2018;73(Suppl 1):e756s.
3. Gupta N, Rivera M, Novotny P, Rodriguez V, Bancos I, Lteif A. Adrenocortical carcinoma in children. A clinicopathological analysis of 41 patients at the Mayo Clinic from 1950 to 2017. Horm Res Paediatr 2018;90:8-18.
4. Lodish MB, Keil MF, Stratakis CA. Cushing’s syndrome in pediatrics. An update. Endocrinol Metab Clin North Am 2018;47:451-62.
5. Das S, Sengupta M, Islam N, Roy P, Datta C, Mishra PK, et al. Weineke criteria, Ki-67 index and p53 status to study pediatric adrenocortical tumors: Is there a correlation? J Pediatr Surg 2016;51:1795-800.
6. Narumi H, Hasegawa S, Waki K, Fukuda K, Ohnishi Y, Ichimura T, et al. Non-androgen secreting adrenocortical carcinoma in preadolescence: A case repor tand literature review. J Pediatr Endocrinol Metab 2016;29: 1313-7.
7. Stratakis CA. Cushing syndrome caused by adrenocortical tumors and hyperplasias (corticotropin- independent cushing syndrome). Endocr Dev 2008; 13: 117-32.
8. Schteingart DE, Doherty GM, Gauger PG, Giordano TJ, Hammer GD, Korobkin M, et al. Management of patients with adrenal cancer: Recommendations of an international consensus conference. Endocrine-Related Cancer 2005; 12 667-80.
9. Monteiro NML, Rodrigues KES, Vidigal PVT, Oliveira BM. Adrenal carcinoma in children: Longitudinal study ın minas gerais Brazil. Rev Paul Pediatr 2019;37:20-6.