We present a series of characteristic cases involving patients with indeterminate adrenal lesions. These cases encompass a broad spectrum of adrenal pathologies, illustrated using various imaging modalities, with final confirmation through histopathological examination.

Adenomas

• Lipid-Rich Adenomas: Approximately 70% of adrenal adenomas contain high intracellular lipid content, resulting in low attenuation values (≤10 HU) on NNCT. They are typically homogeneous with smooth contours and do not require further evaluation.
  

  Fig 5: A 52-year-old woman with a left adrenal gland incidentaloma. (A) Non-contrast-enhanced CT shows a left adrenal mass with an attenuation value of <10 HU. (B) Contrast-enhanced CT, obtained 60 seconds after intravenous contrast administration, demonstrates homogeneous enhancement of the left adrenal mass. (C) Contrast-enhanced CT, obtained 15 minutes after intravenous contrast administration, confirms that the washout protocol test meets the criteria for an adenoma. (D) Axial in-phase and (E) out-of-phase images from chemical shift imaging show the left adrenal mass with intermediate to low signal intensity and signal dropout in the out-of-phase image. All findings indicate a lipid-rich tumor, consistent with a benign adenoma. No further investigation is required.
• Lipid-Poor Adenomas: The remaining 30% of adenomas lack sufficient intracellular lipid, rendering them indistinguishable from malignant lesions on NCCT. Contrast-enhanced CT with washout analysis or chemical shift MRI can be employed. Adenomas typically show rapid contrast washout, with RPW values greater than 50% at 15 minutes post-contrast administration. Although lipid poor adenomas contain only small amounts of microscopic fat, it is sufficient to produce a signal drop in OP images relative to IP images, a result of the chemical shift artifact.Αρχή φÏŒρμαςΤέλος φÏŒρμας
  

  Fig 6: 75-year-old man with left adrenal gland incidentaloma. (A) Axial in-phase image obtained as part of chemical shift imaging demonstrating a 5,2 cm left adrenal mass with low signal intensity and central high signal heterogeneity. (B) Axial out of phase image obtained as part of chemical shift imaging shows lack of loss of signal intensity, with ASR 1,045 and SI-index 6,67%. The adrenal mass was resected, and the pathological specimen confirmed a lipid poor adenoma.
• Atypical Adenomas: Lesions that exhibits any of the following:

• Calcifications
  

  Fig 7: 60-year-old man with right adrenal gland incidentaloma. Non-contrast-enhanced CT demonstrating a 3,5 cm right adrenal inhomogeneous mass with an attenuation value of 40 HU. The lesion demonstrates a hyperdense area of around 2 cm in diameter with small calcifications. Due to the indeterminate imaging phenotype 18-FDGPET/CT was performed with weak diffuse FDG uptake without focal differentiation in the mass under evaluation. Consequently, right adrenalectomy was performed. The histological report described a benign adrenal cortical neoplasm, consisting of 15% of cells with lipid poor cytoplasm, indicating lipid poor adenoma, with an organized hematoma with evidence of chronicity of a maximum diameter in the central position of the neoplasm.
• Hemorrhage
• Necrosis
• Size exceeding 4 cm

Adrenocortical Carcinoma

ACCs are rare but aggressive malignancies that often present as large (>4 cm), heterogeneous masses with irregular borders. They may exhibit areas of necrosis, hemorrhage, and calcifications. ACCs typically have higher attenuation values on non-contrast CT, as they very rarely may have small areas of macroscopic fat, but often have microscopic fat and very uncommonly demonstrate absolute or relative CT washout in the adenoma range. At the time of diagnosis most of the tumors are spread to adjacent organs, and regional lymph nodes. When microscopic fat is present, these lesions exhibit signal loss on IP and OP imaging. Increased T2 signal intensity and lesion heterogeneity are valuable diagnostic indicators. They are also associated with genetic syndromes (MEN I, Lynch, Li-Fraumeni).

Fig 8: 29-year-old woman with mild hyperandrogenism. (A) Non-contrast-enhanced CT demonstrating a 9,5 cm left adrenal mass with peripheral calcifications and an attenuation value of 35 HU in contact with the upper pole of the left kidney. (B) Contrast-enhanced CT obtained 60 s following administration of intravenous contrast. The right adrenal mass demonstrates heterogeneous enhancement due to the presence of central avascular areas. (C) Axial and (D) coronal T2 MR images demonstrating a heterogenous left adrenal mass with a central high signal area. The adrenal mass was resected and the pathological specimen confirmed a oncocytic adrenocortical carcinoma, an unusual histopathological variant of adrenocortical carcinoma with few reported cases in the literature.

Pheochromocytoma

Pheochromocytomas are uncommon tumors that develop in the adrenal medulla. They are typically larger than 3 cm at the time of diagnosis. These catecholamine-secreting tumors often present as well-defined, heterogeneous masses due to areas of hemorrhage, necrosis, or cystic change, with unenhanced CT density greater than 10 HU. The classic "light bulb sign", refers to homogeneous high signal intensity on T2-weighted images. They are highly vascular, leading to significant enhancement; however, usually demonstrate delayed washout. Pheochromocytomas are often referred to as "imaging chameleons", as they can resemble various other tumor types thus, biochemical evaluation is crucial for accurate diagnosis. In IP and OP sequences, these lesions do not exhibit signal loss. On T1 and T2 imaging, they exhibit a characteristic "salt and pepper" appearance due to vascular flow voids and microhemorrhages.

Fig 9: 60-year-old woman with left adrenal gland incidentaloma. (A) Non-contrast-enhanced CT demonstrating a 2,2 cm left adrenal mass with an attenuation value of 35 HU. (B) Contrast-enhanced CT obtained 60 s following administration of intravenous contrast demonstrates mild enhancement. The wash out protocol test did not meet the criteria for adenoma. (C) Non-contrast-enhanced CT obtained 7 months after the initial shows no changes regarding the size of the lesion. Nevertheless the patient underwent a full hormonal workout, which showed high levels of plasma-free metanephrines and urinary fractionated metanephrines, indicating pheochromocytoma. The adrenal mass was resected and the pathological specimen confirmed the diagnosis of phaeochromocytoma.

Fig 10: 38-year-old woman with hypertension crisis episodes, accompanied by headache, dizziness, and sweating. Non-contrast-enhanced CT demonstrating a 7,5 cm heterogenous right adrenal mass with an attenuation value of 31 HU. The patient underwent a full hormonal workout, which showed high levels of plasma-free metanephrines and urinary fractionated metanephrines, indicating pheochromocytoma. The adrenal mass was resected, and the pathological specimen confirmed the diagnosis of phaeochromocytoma.

Fig 11: 38-year-old man with hypertension crisis episodes, accompanied by headache, dizziness, nautea and sweating. (A) Coronal T2 Fat Saturation MR demonstrating a ~3 cm left adrenal mass with high signal and (B) T1 MR + gadolinium images demonstrating mild enhancement. (C) Coronal in-phase and (D) out of phase images obtained as part of chemical shift imaging don’t show loss of signal intensity. The patient underwent a full hormonal workout, which showed high levels of plasma-free metanephrines and urinary fractionated metanephrines, indicating pheochromocytoma. The adrenal mass was resected and the pathological specimen confirmed the diagnosis of phaeochromocytoma.

Metastases

Adrenal metastases are typically bilateral. May present with variable imaging features, including irregular margins and heterogeneous enhancement. In patients with a known primary malignancy, especially lung or breast cancer, the presence of adrenal masses should raise suspicion for metastatic disease. Metastases generally do not exhibit rapid contrast washout, with RPW values <50%. Hypervascular areas may contain microscopic fat, leading to signal loss on IP and OP imaging. Increased T2 signal intensity and lesion heterogeneity are valuable diagnostic indicators.

Fig 12: 66-year-old man with history of colon adenocarcinoma 3 years prior. (A) Contrast-enhanced CT demonstrating a 5 cm right adrenal mass with heterogenicity and an attenuation value of 33 HU, in the non-contrast enhanced CT . (B) Fused axial PET-CT image demonstrating high 18F-FDG uptake especially in the periphery of the lesion. Due to the history of malignancy of the patient, biopsy was performed. Histological examination revealed low-grade intestinal-type adenocarcinoma with immunomorphological features of colon adenocarcinoma metastasis.

Other Rare Entities

• Black Adenoma: Rare, benign tumors from the zona reticularis, appearing dark due to lysosomal lipofuscin. They mimic malignancy on imaging and typically present with hormone hypersecretion syndromes like Cushing’s.
  

  Fig 13: 50-year-old woman with left flank pain. (A) Non-contrast-enhanced CT demonstrating a 2,4 cm left adrenal mass with an attenuation value of 35 HU. (B) Contrast-enhanced CT obtained 60 s following administration of intravenous contrast. The left adrenal mass demonstrates heterogeneous enhancement due to the presence of small avascular - cystic areas. The wash out protocol test did not meet the criteria for adenoma. (C) Axial in-phase and (D) out of phase images obtained as part of chemical shift imaging demonstrating the left adrenal mass with intermediate signal intensity, show lack of drop of signal. (E) Fused axial PET-CT image demonstrating 18F-FDG uptake in the adrenal (SUV max: 6,7). All the above indicate less tumor lipid content but higher tissue density and blood supply, features suspicious of pheochromocytoma, interstitial tumors, and malignancy. The adrenal mass was resected, and the pathological specimen confirmed a black adenoma – a rare adrenal cortical tumor with black or dark brown color on cut sections, due to the presence of lipofuscin, a lysosomal material.
• Adrenocortical Oncocytoma: Extremely rare adrenal tumors, with or without function, with no specific imaging characteristics and indefinite diagnostic criteria and biological behavior.
  

  Fig 14: 70-year-old woman with left adrenal gland incidentaloma. (A) Non-contrast-enhanced CT demonstrating a 3,7 cm left adrenal mass with mild heterogeneity, punctuate calcifications and an attenuation value of 33 HU, in contact with the left kidney. (B) Fused axial PET-CT image demonstrating weak diffuse 18F-FDG uptake. Due to the indeterminate imaging left adrenalectomy was performed. The histological report described an adrenocortical oncocytoma, an extremely rare tumor of the adrenal gland.
• Ganglioneuroma: Rare neurogenic tumors usually present as well-defined, homogeneous masses. On MRI, they may show low signal intensity on T1-weighted images and high signal intensity on T2-weighted images.
  

  Fig 15: 38-year-old man with left adrenal gland incidentaloma. (A) Non-contrast-enhanced CT demonstrating a 5,6 cm triangular left adrenal mass with calcifications and attenuation value of 36 HU. (B) Contrast-enhanced CT obtained 15 mins following administration of intravenous contrast. The left adrenal mass demonstrates peripheral contrast uptake without contrast washout (C) Fused axial 18F-FDG PET-CT image demonstrating weak diffuse FDG uptake. (D) Fused coronal 68 Ga-DOTATE PET-CT image demonstrating no 68 Ga-DOTATE uptake. Due to the indeterminate imaging left adrenalectomy was performed. The histological report described a ganglioneuroma, a rare and benign tumor of the autonomic nerve fibers.
• Liposarcoma: Malignant tumors of mesenchymal origin that can arise from any fat containing region and carry a poor prognosis.
  

  Fig 16: 67-year-old woman with right adrenal gland incidentaloma. (A) Axial T2 MR and (B) T2 Fat Saturation MR images demonstrating a ~7 cm heterogenous lobulated mass with few signs of macroscopic fat. (C) Axial in-phase and (D) out of phase images obtained as part of chemical shift imaging don’t show loss of signal intensity. All the above indicate tumor with macroscopic lipid content. The adrenal mass was resected, and the pathological specimen confirmed a liposarcoma, a rare mesenchymal malignant neoplasm.