Diagnostic Dilemmas: A Multi-Institutional Retrospective Analysis of Adrenal Incidentaloma Pathology Based on Radiographic Size

Introduction/Background Adrenal incidentalomas (AIs) are masses >1 cm found incidentally during radiographic imaging. They are present in up to 4.4% of patients undergoing CT scan, and incidence is increasing with usage and sensitivity of cross-sectional imaging. Most result in diagnosis of adrenal cortical adenoma, questioning guidelines recommending removal of all AIs with negative functional workup. This retrospective study analyzes histological outcome based on size of non-functional adrenal masses. Material and Methods 10 years of data was analyzed from two academic institutions. Exclusion criteria included patients with positive functional workups, those who underwent adrenalectomy during nephrectomy, <18 years, and incomplete records. AI radiologic and histologic size, histologic outcome, laterality, imaging modality, gender, and age were collected. T-test was used for comparison of continuous variables, and the two-sided Fisher’s exact or chi-square test were used to determine differences for categorical variables. Univariate analysis of each independent variable was performed using simple logistic regression. Results 73 adrenalectomies met the above inclusion criteria. 60 were detected on CT scan, 12 on MRI, and one on ultrasound. Eight of 73 cases resulted in malignant pathology, 3 of which were adrenocortical carcinoma (ACC). Each ACC measured >6 cm, with mean radiologic and pathologic sizes of 11.2 cm and 11.3 cm. Both radiologic and pathologic size were significant predictors of malignancy (p=0.008 and 0.011). Conclusions Our results question the generally-accepted 4 cm cutoff for excision of metabolically-silent AIs. They suggest a 6 cm threshold would suffice to avoid removal of benign lesions while maintaining sensitivity for ACC.

Autophagy-Related Proteins Are Differentially Expressed in Adrenal Cortical Tumor/Pheochromocytoma and Associated with Patient Prognosis

The aim of this research was to evaluate the expression and concomitant implications of LC3A, LC3B, beclin-1, and p62, which are key components of autophagy in human adrenal gland tumors. Tissue microarray was made for 321 cases of adrenal gland tumor (adrenal cortical adenoma (ACA): 115, adrenal cortical carcinoma (ACC): 17, and pheochromocytoma (PCC): 189). Immunohistochemical staining was performed for beclin-1, p62, LC3A, and LC3B, and the results were compared with the patients’ clinicopathologic parameters. LC3A, LC3B, beclin-1, and LC3B isolated single positive cells (ISPC) positivity rates were higher in PCC than in adrenal cortical tumor (ACT), whereas p62 positivity was lower in PCC than in ACT. The proportion of positive LC3B (ISPC) was higher in ACC than in ACA. In addition, the proportion of cells positive for p62 and LC3B (ISPC) was significantly higher in PCCs with a GAPP score of ≥3. In univariate Cox analysis, p62 positivity (p = 0.014) and the presence of p62 (ISPC) (p = 0.001) were associated with shorter disease-free survival in PCC. Moreover, p62 positivity was predictive of shorter overall survival (OS) in patients with PCC by multivariate analysis (relative risk, 6.240; 95% CI, 1.434–27.15; p = 0.015). Differences were found in the expression of autophagy-related proteins according to adrenal gland tumor types. Compared to ACT, the proportion of LC3A, LC3B, beclin-1, and LC3B (ISPC) positivity was higher in PCC, whereas p62 positivity was lower. Similarly, p62 positivity in PCC was associated with patient prognosis of OS.

Expression of Glucose Metabolism-Related Proteins in Adrenal Neoplasms

<b><i>Purpose:</i></b> The aim of this study was to investigate the expression patterns of glucose metabolism-related proteins and their clinicopathologic implications in adrenal cortical neoplasms (ACN) and pheochromocytoma (PCC). <b><i>Methods:</i></b> Immunohistochemical staining was performed to evaluate glucose metabolism-related proteins (GLUT1, CAIX, hexokinase II, G6PDH, PHGDH, and SHMT1) in 132 ACN cases (115 adrenal cortical adenoma [ACA] and 17 adrenal cortical carcinoma [ACC]) and 189 PCC cases. <b><i>Results:</i></b> Expression levels of GLUT1 in tumor cells ([T]; <i>p</i> &#x3c; 0.001), GLUT1 in stromal cells ([S]; <i>p</i> &#x3c; 0.001), G6PDH (<i>p</i> &#x3c; 0.001), and SHMT1 (<i>p</i> = 0.002) were higher in ACN than in PCC. GLUT1 (T; <i>p</i> = 0.045) and PHGDH (<i>p</i> = 0.043) levels were higher in ACC than in ACA. In a univariate analysis of ACN, GLUT1 (T; <i>p</i> = 0.017), CAIX (S; <i>p</i> = 0.003), and PHGDH (<i>p</i> = 0.009) levels were correlated with a shorter overall survival (OS). GLUT1 (T; <i>p</i> = 0.001) and PHGDH (<i>p</i> &#x3c; 0.001) were related to a shorter OS in PCC. GLUT1 (T) positivity (<i>p</i> = 0.043) in ACN predicted a poor OS in a multivariate Cox analysis. In PCC, high GAPP score (<i>p</i> = 0.026), GLUT1 (T; <i>p</i> = 0.002), and PHGDH (<i>p</i> &#x3c; 0.001) were independent prognostic factors for poor OS. <b><i>Conclusions:</i></b> The adrenal gland tumors ACN and PCC had different expression patterns of glucose metabolism-related proteins (GLUT1, G6PDH, and SHMT1), with higher expression levels in ACN than in PCC. GLUT1 and PHGDH were significant prognostic factors in these adrenal neoplasms.

Functional and non-functional types of adrenal tumors: a case series

Adrenal gland masses could be classified into functional, malignant, or benign. An adrenal cortical adenoma is one of the most common incidentalomas found with either functional or non-functional type. Pheochromocytoma is a neural crest cell origin tumor associated with catecholamine production. A classic triad of headache, sudden episodic perspiration, and tachycardia marked a pheochromocytoma. We report three patients with adrenal tumors. First, a 52-year-old woman with complaints of pain in the left flank suggests a left kidney tumor. The patient has an increased blood pressure intraoperatively. Adrenal cortical adenoma was found postoperatively. The second case is an Indonesian male 27-year-old with pain in the upper right abdomen. Intraoperative, the patient also has an escalation in blood pressure. Antihypertensive drugs are also used in this patient. Postoperatively, a pathology result of pheochromocytoma was revealed from this patient. The third case, adrenal myelolipoma, was suspected in a 48-year-old male and underwent surgery because of tumor growth. Later, a histopathological examination revealed myelolipoma of the adrenal. Management of adrenal tumor should be done individually based on each patient. In the first and second cases, blood pressure was unstable intraoperatively and was managed using several drugs, and was stable at follow-up. In the third case was no hemodynamic problem. In the case of an adrenal tumor, management tailoring should be based on the individual patient.

Cushing’s syndrome manifesting as chronic insomnia caused by adrenal cortical adenoma with incidental pituitary microadenoma: a case report

Background: Cushing’s syndrome is condition caused by excessive glucocorticoid with insomnia as one of its neuropsychiatric manifestation. Cushing’s syndrome may be caused by excessive adrenocorticotropin hormone (ACTH-dependent), for example from ACTH producing pituitary tumors, or by overproduction of cortisol by adrenocortical tumors. In this report, we presented a case with Cushing’s syndrome manifesting as chronic insomnia with adrenal cortical adenoma and pituitary microadenoma.Case presentation: A 30-year-old woman was consulted from the Neurologic Department to the Internal Medicine Department with the chief complaint of insomnia and worsening headache since 6 months prior to the admission. She had undergone head MRI and abdominal CT scan previously and was found to have both pituitary microadenoma and left adrenal mass. From the physical examination she had clinical signs of Cushing’s syndrome like Cushingoid face and purplish striae on her stomach. Midnight cortisol serum examination was done initially and showed high level of cortisol. High dose dexamethasone suppression test or DST (8 mg overnight) was later performed to help determine the main cause of Cushing’s syndrome. The result failed to reach 50% suppression of cortisol serum, suggestive that the Cushing’s syndrome was not ACTH-dependent from the pituitary but potentially from overproduction of cortisol by the left adrenal mass. Therefore, left adrenalectomy was performed and the histopathological study supported the diagnosis of adrenal cortical adenoma.Conclusion: Chronic insomnia is a very important symptoms of Cushing’s syndrome that should not be neglected. The patient had both microadenoma pituitary and left adrenal mass thus high dose DST test (8 mg overnight) needed to be performed to differentiate the source of Cushing’s syndrome. The result showed only little suppression therefore the pituitary microadenoma was not the source of Cushing’s syndrome and more suggestive from the adrenal etiology.

Case Report on Anastomosing Haemangioma: An Unusual Vascular Tumor in Kidney

Anastomosing haemangioma is a rare benign vascular neoplasm, which may mimic angiosarcoma histologically. We here present a case of anastomosing haemangioma arising from the kidney. This patient presented with a large kidney mass and adrenal mass. The clinical and radiological findings were suspicious for renal cell carcinoma with metastasis. Radical nephrectomy and adrenalectomy were thus performed. Histopathological examination and immunohistochemical studies concluded a diagnosis of anastomosing haemangioma of the kidney and concurrent adrenal cortical adenoma. It is important to differentiate this tumor from other borderline or malignant vascular neoplasms.

Adrenal-Renal Fusion with Adrenal Cortical Adenoma and Ectopic Adrenal Tissue, Presenting as Suspected Renal Mass: A Case Report

Adrenal-renal fusion with adrenal cortical adenoma is a rare anomaly with only a few cases described in the literature. Imaging-based identification of this anomaly remains a diagnostic challenge, making it difficult to differentiate upper pole renal malignancy from adrenal cortical adenoma. We describe a case of a 62-year-old woman with an upper pole cystic renal mass on imaging, who underwent robotic partial nephrectomy. Intraoperatively the renal mass was found to be an adrenal-renal fusion anomaly, with ectopic adrenal tissue. Adrenal-renal infusion of an adrenal cortical adenoma was confirmed on final pathology. Due to lack of imaging-based diagnosis, this condition should be considered in the differential for upper pole renal masses.