Adrenal adenoma mimicking angiomyolipoma: A diagnostic pitfall

Abstract

Angiomyolipoma is a mesenchymal tumor that originates predominantly from perivascular epithelioid cells and is generally considered benign. It is commonly found in the kidneys and rarely in extrarenal locations. Herein, we report a case of angiomyolipoma misdiagnosed as right adrenal angiomyolipoma. A 69-year-old male was diagnosed with a space-occupying lesion in the right adrenal gland. Preoperative abdominal computed tomography showed a 38 × 28-mm non-uniformly enhanced mass in the right adrenal gland. We performed laparoscopic resection of the right adrenal mass. The procedure was successful, and the tumor was completely removed. Based on the initial postoperative pathological report, the lesion was diagnosed as an angiomyolipoma. However, after being verified and certified by a national-level pathology center, this diagnosis was determined to be incorrect. The final pathological diagnosis was adrenal adenoma. For such difficult-to-distinguish pathological diagnoses, routine immunohistochemical identification is recommended. In this case, surgical management of a 4-cm adrenal mass resulted in a favorable treatment outcome. We report this case to draw clinical attention to the therapeutic value of tumors measuring 3–4 cm.

Introduction

Angiomyolipoma (AML) is a benign tumor composed of blood vessels, smooth muscle, and adipose tissue. ¹ The male-to-female ratio is approximately 1.5. AML most commonly occurs in the kidneys, whereas extrarenal AML is rare. An adrenal origin is rare and usually asymptomatic. ² Epithelioid angiomyolipoma (EAML) is a distinct AML subtype.^3–5 It exhibits the biological behavior of borderline tumor, possesses a malignant tendency, and poses a risk of metastasis and recurrence. Only seven cases of adrenal EAML have been documented in the English-language literature.^6,7 These tumors are usually diagnosed incidentally based on imaging studies; however, larger AMLs may cause bleeding and pain. Adrenal AML is rare in clinical settings, and the limited number of studies and literature reports has restricted our understanding of the disease. Adrenal adenoma is a common adrenal tumor. Sometimes, conventional hematoxylin and eosin (H&E) staining is not sufficient to clearly distinguish them, which may lead to misdiagnosis. EAML mimicking adrenal cortical carcinoma is uncommon in clinical practice. ⁵ Immunohistochemical (IHC) staining is required for identification. However, a more fundamental diagnostic pitfall is that adrenocortical adenoma is not routinely considered in the histopathological differential diagnosis of AML due to their distinct lineage (epithelial vs. mesenchymal). This cognitive blind spot may cause pathologists to overlook adenoma when encountering an adrenal tumor with adipocytes and vascular components using conventional H&E staining. Therefore, every adrenal mass with unusual morphological features should deliberately include adrenocortical adenoma as a potential differential diagnosis, especially when IHC testing is not immediately performed. Therefore, we report this case of common adenoma misdiagnosed as a right adrenal AML to further improve our understanding of this disease.

Case report

A 69-year-old male patient was admitted to the Zhangye People's Hospital affiliated to Hexi University (Zhangye, China) in September 2025, with complaints of increased frequency and urgency of urination and difficulty in urination. The next day, the patient underwent plasma enucleation of the prostate. He had no history of surgery. The computed tomography (CT) upon admission indicated a mass shadow in the right adrenal area, with a size of approximately 38 mm × 28 mm. The inferior vena cava was compressed and pushed forward with an unclear boundary. The CT values ranged from 14 to 67 HU. An enhanced scan showed progressive and heterogeneous enhancement, with delayed CT values ranging from 34 to 110 HU (Figure 1(a) and (b)). Routine blood tests and liver and kidney function tests were performed. All electrolyte levels were within normal ranges. Routine urine tests revealed 3+ red blood cell counts and no white blood cells. Endocrinological assessment revealed the following: (a) renin level, 7.45 pg/mL (reference range: 4.2–38.15 pg/mL); (b) angiotensin I level, 0.45 ng/mL (reference range: 0.55–2.65 ng/mL); (c) angiotensin II level, 44.76 pg/mL (reference range: 24–62 ng/mL); and (d) aldosterone level, 43.02 pg/mL (reference range: 32.45–161 pg/mL). The level of cortisol was 88.77 nmol/L (reference range: <276 nmol/L) and that of adrenocorticotropic hormone (ACTH) was 1.57 pg/mL (reference range: 7.26–62.73 pg/mL). Retroperitoneal laparoscopic right adrenal space-occupying resection was performed in October 2025 (Figure 2). Postoperative pathological examination revealed a right adrenal AML (Figure 1(c) and (d)); his postoperative cortisol level was 21.5 nmol/L, and ACTH level was 11.97 pg/mL (reference range: 7.26–62.73 pg/mL). No complications were observed. Subsequently, the patient's specimen was referred to the pathologists of the National Cancer Center (Fudan University Cancer Hospital) for consultation. IHC analysis demonstrated positivity for inhibin-α and Melan-A; focal or weak positivity for vimentin, pan-cytokeratin (Ck-pan; rare and weak), calretinin, synaptophysin (Syn), and chromogranin A (CgA); a Ki-67 proliferation index (Ki67+) of 1%–2%; and negativity for human melanoma black-45 (HMB45) and smooth muscle actin (SMA). Based on the light microscopic morphology and immunohistochemistry, the lesion was diagnosed as an adrenal cortical adenoma with cystic changes. Therefore, the patient was confirmed to have a common adenoma (Figure 3). The patient was satisfied with the treatment outcome and was discharged. All participant details were removed to ensure patient privacy, and written informed consent was obtained prior to treatment. In addition, the patient signed a consent form for data publication. The reporting of this study conforms to the Case Report (CARE) guidelines. ⁸

Figure 1.

Computed tomography (CT) and hematoxylin and eosin (H&E) staining. (a) Unenhanced CT revealed a mass in the right adrenal region and (b) the lesion showed enhancement during the enhanced scan; (c) H&E staining (original magnification: 40×); and (d) H&E staining (original magnification: 100×).

Figure 2.

The tumor was completely resected during the procedure. (a) Exposed tumor, (b) exposed central adrenal vein, (c) ligated central adrenal vein, (d) postoperative wound, (e) postoperative tumor specimen, and (f) specimen section.

Figure 3.

Immunohistochemical staining results. (a) CgA, (b) Vimentin, (c) CK-Pan, (d) Inhibin-α, (e) Syn, (f) Ki-67, (g) HMB45, (h) Melan-A, and (i) SMA.

Discussion

AML is a mesenchymal tumor commonly found in the kidneys. ⁹ The second most common site for this tumor is the liver. Extrarenal AMLs are extremely rare and can occur in the retroperitoneum, adrenal glands, mammary glands, reproductive tract, pancreas, skin, omentum, and breasts.^10–12 AML of the adrenal gland is very rare. ¹³ It is a challenging diagnosis for pathologists and is often misdiagnosed as sarcomatoid carcinoma or sarcoma. Adrenal AML can be very small or can grow to a large size without being detected. Asymptomatic small tumors can be actively monitored and followed up. However, larger or symptomatic tumors that produce endocrine hormones should be removed to avoid complications or spontaneous rupture leading to bleeding. AML is classified as a perivascular epithelioid cell tumor (PEComa) based on the pathology. ¹⁴

Adrenal AML is composed of blood vessels, smooth muscle, and mature fat. On plain CT scans, a typical negative value area (−20 to −100 HU) can be observed. During enhanced scanning, the fat component shows no enhancement, whereas the vascular and smooth muscle components show mild-to-moderate enhancement.^15,16 Adrenal cortical adenomas are mainly composed of intracellular lipids and have CT values typically ranging from 0 to 10 HU, without visible low-density fat at the surface. Myeloid lipomas have a higher fat content and lower CT values; however, they lack the abnormal vascular enhancement features of AML. Pheochromocytomas, cortical carcinomas, and metastatic tumors appear as solid soft tissue masses, with CT values generally >20 HU. They often present with necrosis, cystic changes, or invasive manifestations and lack the negative CT value area of mature fat. However, in this case, the CT values were positive. Based on the CT findings alone, it is not possible to determine whether the lesion is an adenoma or another type of adrenal tumor. Therefore, CT has limited accuracy in determining the nature of the lesion; it only provides anatomical localization. AML is a benign mesenchymal tumor. Histologically, it is characterized by a mixture of mature fat tissue, thick-walled abnormal blood vessels, and smooth muscle tissue in different proportions. These three components can be distributed in an interlaced sheet-like, nest-like, or diffuse manner. The blood vessels within the tumor are mostly malformed vessels with uneven wall thickness and a lack of elastic fibers. The smooth muscle cells are mostly spindle-shaped or epithelioid, without atypia, mitotic figures, necrosis, or invasive growth. In this case, the patient did not undergo IHC testing at that time. H&E staining section revealed differentiated and mature adipocytes, dilated blood vessels, and hyaline degenerated stroma within the tumor. Therefore, the Pathology Department of Zhangye People's Hospital Affiliated to Hexi University initially diagnosed the lesion as an AML. Subsequently, we consulted the national-level pathology center (Fudan University Affiliated Cancer Hospital, China National Cancer Center) for confirmation. IHC analysis was also conducted, and the lesion was ultimately diagnosed as a common adenoma.

Adrenocortical adenoma is not typically listed in the differential diagnosis of AML from a histopathological perspective. AML is a mesenchymal PEComa epithelioid cell tumor, whereas adrenocortical adenoma is an epithelial neoplasm. They originate from different germ layers, and standard pathology textbooks seldom emphasize their morphological overlap. Consequently, when a pathologist encounters an adrenal tumor containing mature adipocytes, thick-walled vessels, and spindle cells on H&E stain, features reminiscent of AML, the possibility of an adenoma may not be actively considered. This cognitive bias is amplified when IHC testing is not requested upfront, as in this case. Second, a sampling or morphological simulation issue may contribute to the misdiagnosis. In our patient, the H&E sections showed differentiated adipocytes, dilated vessels, and hyalinized stroma within the tumor. These changes can occur in adrenocortical adenomas, particularly those exhibiting degenerative or pseudolipomatous changes, in which the entrapped adrenal fat and metaplastic smooth muscle-like areas may mimic the triphasic appearance of an AML. However, true AML would show immunoreactivity for melanocytic markers (HMB45 and Melan-A) and smooth muscle markers (SMA), none of which were present in this case. Therefore, the absence of these markers, combined with positive inhibin-α and focal calretinin, definitively excluded AML and confirmed an adrenocortical adenoma. This case highlights that even when morphological findings strongly suggest AML, adrenal adenoma should remain an important differential diagnosis. IHC staining is essential for preventing a misdiagnosis.

Adrenal myelolipoma usually presents with a clear tumor boundary, consisting of unevenly proportioned mature adipose tissue and bone marrow hematopoietic tissue. The adipocytes generally have no atypia; however, hemorrhage and calcification may be present. In contrast, adrenal hamartoma is composed of differentiated mature fat, blood vessels, and smooth muscle. Adrenal cortical carcinoma demonstrates diverse tumor cell morphology, with marked nuclear atypia, and may contain multinucleated tumor giant cells. The number of nuclear divisions varies. Necrosis is common, and it often invades the capsule or large veins. IHC staining for SF1, inhibin, and Melan-A is typically positive in adrenocortical carcinoma. Most high-grade liposarcomas are composed of mature adipose tissue and adipocyte-like cells. Some adipocytes and stroma may have atypia, with relatively thick fibrous septa, and atypical cells can be seen in the stroma. IHC staining of cyclin-dependent kinase 4 (CDK4), mouse double minute 2 (MDM2), and cyclin-dependent kinase inhibitor 2A (P16) is usually positive. Fluorescence in situ hybridization testing can detect amplification of CDK4 and MDM2 genes.

Adrenal cortical adenoma typically has a clear tumor boundary and a golden-yellow cut surface. The tumor cells are generally in the form of nests, cords, and trabeculae, composed of different proportions of two types of cells: (a) one with abundant cytoplasm and bright cells containing rich lipid droplets and (b) another with less lipid in the cytoplasm and eosinophilic dark cells. Nuclear mitotic figures are rare. Immunohistochemically, HMB45 and Melan-A are positive, S-100 is positive for fat cells, and SMA is positive for smooth muscle cells. In the present case, HMB45 and Melan-A were negative; therefore, the IHC results do not support a diagnosis of AML. Although other morphological structures support AML, this case highlights the importance of performing IHC for such patients.

With the development of imaging technology, an increasing number of incidental adrenal tumors have been reported; however, adrenal AMLs are rarely documented. The current literature mainly includes reports of individual and sporadic cases, discovered incidentally, lacking descriptive statistics for large-scale cases. Nasiroğlu Imga et al. analyzed 431 sporadic adrenal tumors from a single center over a 10-year period. ¹⁷ The mean age of the patients was 55.4 ± 11.5 years, with a mean tumor size of 25.9 ± 14.3 mm. Adenoma localization revealed 165 (38.3%) right-sided, 185 (42.9%) left-sided, and 81 (18.8%) bilateral cases. Among the functioning adrenal incidentaloma cases (23.4%), autonomous cortisol secretion, Cushing's syndrome, pheochromocytoma, and primary aldosteronism were observed in 10.4%, 5.1%, 3.9%, and 3.9% of cases, respectively. The patient in this study was incidentally diagnosed during a visit to the hospital for evaluation of prostate disease. CT revealed a space-occupying lesion in the right adrenal gland. The patient had no clinical symptoms in daily life and did not undergo a physical examination.

The distinction between adrenal AML and adrenocortical adenoma is not merely academic; it carries direct therapeutic implications. For renal or adrenal AML, asymptomatic small AMLs (<4 cm) are usually managed conservatively with active surveillance because they are benign mesenchymal tumors with very low malignant potential. Larger or symptomatic AMLs may be treated with selective arterial embolization or nephron-sparing surgery to prevent spontaneous rupture and bleeding. Complete adrenalectomy is rarely required for AML unless the tumor causes intractable pain or massive hemorrhage.^17,18 For adrenocortical adenoma, management depends on hormonal functionality and size. Functioning adenomas (e.g. cortisol- or aldosterone-producing) should be resected regardless of size. For nonfunctioning adenomas, current guidelines (e.g. those formulated by the European Society of Endocrinology) recommend surgery if the tumor is >4 cm, shows rapid growth, or exhibits suspicious imaging features, due to a low but definite risk of adrenocortical carcinoma.^19,20 In our case, the adenoma measured 38 mm (close to 4 cm) and had grown significantly over 2 years; thus, laparoscopic adrenalectomy was justified even though the tumor was nonfunctioning preoperatively. The postoperative normalization of ACTH levels further supported the benefit of resection. Therefore, misdiagnosing an adrenocortical adenoma as AML could lead to inappropriate conservative follow-up (applied to AML) while missing an indication for surgery (required for a size-growing adenoma). Conversely, misdiagnosing AML as an adenoma might prompt unnecessary adrenalectomy. Therefore, accurate pathological diagnosis using IHC staining is essential to guide correct clinical management.

In this case, the adrenal adenoma and adrenal gland were completely removed surgically. Previous studies have also shown the use of indocyanine green–assisted laparoscopic partial adrenalectomy. ¹⁴ The patient was preoperatively informed that indocyanine green was not available. The patient was also worried about the possibility of recurrence and the presence of microadenomas in the right adrenal gland. Postoperatively, the patient chose to undergo total resection and agreed to co-operate for regular follow-ups. The patient's preoperative ACTH level was 1.57 pg/mL, whereas his postoperative ACTH level was 11.97 pg/mL. This change may be related to the patient's tumor and adrenal gland removal, which may have resulted in negative feedback and caused the hormone levels to rise. Regarding the revised pathological report, we re-explained the findings to the patient and obtained their understanding. The patient's follow-up plan remained unchanged and they continued to attend regular follow-ups. This case provided several important insights. For postoperative pathological examinations of adrenal masses, IHC testing is recommended. Conventional H&E staining may lead to misdiagnosis, whereas IHC staining can improve diagnostic accuracy and help avoid such errors. This also highlights the importance of careful pathological evaluation for both clinicians and pathologists.