Endocr Pathol (2007) 18:103–105 DOI 10.1007/s12022-007-0019-3
Myelolipoma with Adrenocortical Adenoma: An unusual Combination that can Resemble Carcinoma Nabeel Al-Brahim & Sylvia Asa
Published online: 3 July 2007 # Humana Press Inc. 2007
Abstract Myelolipoma is a benign tumor that occurs in the adrenal gland and rarely in extra-adrenal sites. Commonly, it is diagnosed as an incidental finding. However, some reports indicate synchronous occurrence with other lesions including adrenocortical carcinoma. It has very rarely been reported to occur in association with adrenocortical adenoma. In this paper, we report three cases of adrenal myelolipoma associated with adrenocortical adenoma; in all three patients, the radiological appearance resembled adrenocortical carcinoma. These cases emphasize the importance of this combination as a pitfall in the correct diagnosis and management of patients with adrenal masses.
adipose tissue intermixed with hematopoietic cells. In the adrenal glands, it is usually an incidental finding because it is not associated with hormone excess syndromes. There are several reports of myelolipoma occurring synchronously with other lesions including adrenal cortical adenoma [5], ganglioneuroma [6], carcinoma [7], or pheochromocytoma [8] with or without endocrine dysfunction [9, 10]. In this report, we describe three cases of ML within adrenocortical adenoma. These lesions were large and associated with a heterogenous appearance on radiologic evaluation, resulting in a preoperative diagnosis of adrenal cortical carcinoma.
Keywords adenoma . adrenal . carcinoma . myelolipoma Case Reports Introduction
Clinical Features
Myelolipoma (ML) is a benign tumor that commonly occurs in the adrenal glands. It also occurs in extra-adrenal sites including mediastinum [1], the presacral region [2], renal hilum [3], and stomach [4]. Microscopically, it is characterized by mature
Case 1 An 82-year-old woman presented with right-sided abdominal pain. There were no other associated symptoms. The patient underwent abdominal ultrasound, and a left adrenal mass was found. The mass measured 9 cm and had a heterogeneous appearance. This heterogeneity was suspicious for adrenocortical carcinoma. There was no clinical history to suggest endocrine dysfunction, and all hormone levels in blood and urine were within the normal range. The patient underwent left adrenalectomy.
S. Asa Department of Pathology, University Health Network and Toronto Medical Laboratories, University of Toronto, Toronto, Canada S. Asa Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada N. Al-Brahim (*) Department of Pathology, Farwania Hospital, P.O. Box 3313, Salmiya 22034, Kuwait e-mail:
[email protected]
Case 2 A 71-year-old man underwent abdominal ultrasound as part of a routine annual examination, and a left adrenal mass was discovered. He had a history of hypothyroidism and nodular hyperplasia of the prostate. Magnetic resonance imaging (MRI) was performed and confirmed a heterogeneous, enhancing mass that measured 4.5 cm in diameter in the left adrenal gland. Peripheral calcification was noted on computed
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tumor composed of large, clear, and compact cells with no atypia (Fig. 2). There was no evidence of capsular or vascular invasion after examining the capsules thoroughly. Within the tumors, there was a component of myelolipoma composed of mature adipose tissue and hematopoietic cells showing trilineage differentiation. In all three cases, this was scattered within the tumor and was associated with areas of hemorrhage; the myelolipomas comprised from 20 to 50% of the tumor mass, and the hemorrhage represented a significant component so that, overall, 50 to 75% of the tumors were composed of non-adenomatous tissue. In case 2, there was atrophy of the adjacent adrenal cortex. Fig. 1 MRI identifies a large irregular mass with marked heterogeneity. The features were considered to represent adrenocortical carcinoma
Discussion tomography (CT) scan. These features were suspicious for adrenocortical carcinoma, and the patient underwent left adrenalectomy. Adrenal function was within normal limits. Case 3 A 54-year-old woman presented with cushingoid habitus including central obesity with moon facies, hypertension, and diabetes. Endocrine testing demonstrated high urinary free cortisol levels and a suppressed plasma adrenocorticotropic hormone (ACTH). The MRI revealed a 5.7-cm heterogeneous right adrenal mass (Fig. 1) abutting the inferior vena cava (IVC). Due to the size and close relation to the IVC, the patient underwent right adrenalectomy.
Pathological Findings Gross Appearance Case 1 The adrenal weighed 239 g. On section, there was a well-circumscribed mass that measured 10×8.5×5.7 cm. The cut surface was variegated with firm tan areas, yellow areas, and foci of hemorrhage. There was focal calcification.
Myelolipoma is a benign tumor of the adrenal gland. It is usually discovered incidentally, but some patients present with complications like hemorrhage that can give rise to local symptoms. Commonly, myelolipoma presents as an isolated finding in the adrenal. However, others can occur within or synchronously with other tumors. In this series, three cases of myelolipoma occurred within adrenocortical adenoma. The three cases were suspicious radiologically, as the variegated and inhomogeneous appearance was suggestive of adrenocortical carcinoma. In a review of the imaging features of adrenal masses, Lerttumnongtum et al. [11] described the CT appearance of adrenocortical carcinoma as a heterogeneous mass with central areas of attenuation because of necrosis. Peripheral enhancement is commonly seen. In addition, calcification was described in 30% of cases. Lockhart et al., in their review [12], described similar features of adrenocortical carcinoma in addition to the presence of local extension to lymphatics, the renal vein, and the IVC.
Case 2 The adrenal weighed 153 g and contained a circumscribed mass that measured 10×10×4.5 cm. The cut surface was smooth and solid and varied from gray to yellow in color. Case 3 The adrenal weighed 109.2 g. and contained an orange–yellow–gray tumor mass that measures 7.7×5.8× 4.2 cm. The tumor had a thick well-defined capsule with a rim of normal adrenal gland.
Microscopic Appearance The microscopic appearance in the three cases was similar. All three adrenals contained a well-differentiated adrenocortical
Fig. 2 Section demonstrates combined myelolipoma and adenoma (H&E, ×40)
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Similar features of heterogeneity because of hemorrhage and necrosis were present in our three cases. Case 2 also demonstrated peripheral calcification. In case 3, the tumor was abutting the IVC. Therefore, these radiological features are not pathognomonic for adrenocortical carcinoma, and the radiologists and surgeons should be aware of this possibility to avoid over-diagnosing malignancy without a tissue diagnosis. Myelolipoma is usually a well-circumscribed mass with yellow to brown color because of the predominant fat component. Radiologically, it is characterized by the presence of fat on MRI with an intensity similar to abdominal fat. Enhancement may also occur due to vascularity of the hematopoietic component. Hemorrhage and necrosis can be seen [12]. These features were present in our cases. However, the pitfall is that these features occurred with a rim of adrenocortical tumor that suggested the radiological diagnosis of adrenocortical carcinoma. The pathogenesis of myelolipoma is controversial. There were several hypotheses to explain the presence of localized hematopoietic cells. One theory implicated endocrine dysfunction after a report of transdifferentiation of adrenocortical cells to hematopoietic cells after injection with corticotrophin [13]. Another explanation was that the presence of hemorrhage and necrosis may stimulate the migration of hematopoietic cells to the adrenal [14]. These explanations suggest that ML is a reactive change rather than a neoplasm. All three of our cases had associated hemorrhage, consistent with this theory. Chang et al. [15] studied a case of adrenal ML and found that 45% of analyzed metaphases contained the balanced translocation t (3;21) (q25;p11) and concluded that adrenal ML is a true neoplasm rather than a reactive change. Because the t(3;21) translocation has been described in acute myeloid leukemia, myelodysplastic syndromes, and chronic myeloid leukemia, it was suggested that ML has a myeloid origin [15]. A recent study by Bishop et al. [16] demonstrated nonrandom inactivation of the X-chromosome in the hematopoietic cells and fat of 8 of 11 myelolipomas, further supporting the neoplastic nature of this lesion. In this short series, we report three cases of ML within adrenocortical adenoma with hemorrhage. All three cases were misdiagnosed as adrenocortical carcinoma on radiology. It is important to be aware of this combination as a
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pitfall in the correct diagnosis and management of patients with adrenal masses.
References 1. Franiel T, Fleischer B, Raab BW, Fuzesi L. Bilateral extradrenal myelolipoma. Eur J Cardio-thorac Surg 26:1220–2, 2004. 2. Mariappan MR, Fadare O, Ocal IT. Pathologic quiz case. A 74year-old man with an incidental retroperitoneal tumor found at autopsy. Presacral myelolipoma. Arch Pathol Lab Med 128:591–2, 2004. 3. Talwalkar S, Shaheen S II. Extra-adrenal myelolipoma in the renal hilum. A case report and review of the literature. Arch Pathol Lab Med 130:1049–52, 2006. 4. Le Bodic MF, Mussini-Montpellier J, Magois JY, Le pere J. Myelolipoma of the stomach. Arch Anat Pathol (Paris) 22:119–22, 1974 [in French]. 5. Manassro F, Pomara G, Rappa F, Cuttano M, Crisci A, Selli C. Adrenal myelolipoma associated with adenoma. Int J Urol 11:326–8, 2004. 6. Merchant SH, Herman CM, Amin MB, Ro JY, Troncoso P. Myelolipoma associated with adrenal ganglioneuroma. Arch Pathol Lab Med 126:736–7, 2002. 7. Sun X, Ayala A, Castro CY. Adrenocortical carcinoma with concimetant myelipoma in a patient with hyperaldestronism. Arch Pathol Lab Med 129:e144–7, 2005. 8. Ukimura O, Inui E, Ochiai A, Kojima M, Watanabe H. Combined adrenal myelolipoma and pheochromocytom. J Urol 154:1470, 1995. 9. Hisamatsu H, Sakai H, Tsuda S, Shigematsu K, Kanetake H. Combined adrenal adenoma and myelolipoma in a patient with Cushing’s syndrome: a case report and review of the literature. Int J Urol 11:416–8, 2004. 10. Mastuda T, Abe H, Takase M, Arakawa A, Masturmoto T, Fujima M, Suda K. Case of combined adrenal cortical adenoma and myelolipoma. Pathol Int 54:725–9, 2004. 11. Lerttumnongtum P, Muttarak M, Visrutarama P, Ya-in C. Imaging features of adrenal masses. Australas Radiol 48:107–13, 2004. 12. Lockhart ME, Kevin Smith J, Kenney PJ. Imaging of adrenal masses. Eur J Radiol 41:95–112, 2002. 13. Selye H, Store H. Hormonally induced transformation of adrenal into myloid tissue. Am J Pathol 26:211–33, 1950. 14. Masugi Y, Kameyama K, Aiba M, Mukai M, Hara S, Ohigashi T et al. Non-functional adrenocortical adenoma with extensive degeneration. Pathol Int 53:241–5, 2003. 15. Chang KC, Chen P, Huang Z, Lin Y, Kuo P. Adrenal myelolipoma with translocation (3;21) (q25;p11). Cancer Genet Cytogenet 134:77–80, 2002. 16. Bishp E, Eble JN, Cheng L, Wang M, Chase D, Orazi A, O’Mally P. Adrenal myelolipoma show non random x-chromosome inactivation in hematopiotic element and fat: support for clonal origin of myelolipomas. Am J Surg Pathol 30:838–43, 2006.
