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Composite Adenomatoid Tumor and Myelolipoma of Adrenal Gland: Report of 2 Cases

February 13, 2008

By Timonera, Elizabeth R Paiva, Maria Emilia; Lopes, Jose Manuel; Eloy, Catarina; van der Kwast, Theodore; Asa, Sylvia L

Adenomatoid tumor and myelolipoma are benign, hormonally inactive tumors that are often incidental findings in the adrenal glands. Myelolipoma is more common than adenomatoid tumor in this location but both are rare, and as yet, the pathogenesis of both remains unclear.We report 2 cases of composite adenomatoid tumor and myelolipo-ma, incidentally found in the adrenal gland on investigation for other diseases. To our knowledge, composite ade- nomatoid tumor and myelolipoma of adrenal gland has not been previously reported. (Arch Pathol Lab Med. 2008;132:265-267)

Adenomatoid tumor (AT) and myelolipoma are distinct benign, hormonally inactive tumors of the adrenal gland. Adenomatoid tumor is composed of mesothelium-lined tubules and is extremely rare in the adrenal gland.1,2 At least 26 cases have been reported so far3 ; 1 case was associated with adrenal cortical hyperplasia.4 Myelolipo- ma, composed of adipose tissue and hematopoietic cells, resembles bone marrow but is phenotypically different in that myelolipoma contains very rare myeloid precursor cells, more megakaryocytes are seen, and the cellularity does not correlate with age.5 Adenomatoid tumor and my-elolipoma are often small and asymptomatic; however, some myelolipomas can grow, with a maximum reported size of 34 cm, and cause pressure symptoms, rupture, and hemorrhage.3,6-8 Myelolipoma has been associated with endocrine disorders such as Cushing syndrome,9 congenital adrenal hyperplasia,10 and hyperaldosteronism11 or with other tumors such as ganglioneuroma12 and Hodgkin lymphoma. 13 The pathogenesis of AT and myelolipoma is still unclear and as far as we know, the tumors have not been reported to occur together as a composite tumor. We report 2 cases of composite AT and myelolipoma.

REPORT OF 2 CASES

Clinical Histories and Radiology

Case 1. A 47-year-old previously healthy man was referred for the investigation of incidental adrenal masses that were identified during a computerized tomography scan performed for di- verticulitis. Magnetic resonance imaging was done and confirmed the presence of a 5.6 x 5.3 x 2.7-cm mass in the right adrenal gland that was interpreted as a predominantly lipid-poor adenoma with fat in the inferior aspect, and a 1.5-cm nodule in the left adrenal gland that was radiologically consistent with an adenoma. He was also found to have diffuse hepatosteatosis and a splenule (accessory spleen). Results of serum cortisol and 24 hour urine collection for cortisol and adrenaline metabolites were normal. A laparoscopic right adrenalectomy was performed. The postsurgical recovery was uneventful.

Case 2. A 52-year-old obese man was investigated for persistent hypertension (150/100 mm Hg) of 3 months’ duration that was difficult to control with pharmacotherapy. The urinary van- illylmandelic acid, catecholamine, metanephrine, and cortisol levels were normal, however. Computerized tomography scan and magnetic resonance imaging of the abdomen showed a 2-cm mass in the right adrenal gland, and the patient underwent a laparoscopic right adrenalectomy. His postoperative course was uneventful.

Gross and Microscopic Findings

The right adrenal gland of the first patient weighed 64 g and contained a well-circumscribed mass that measured 7.0 x 5.8 x 3.8 cm. The tumor was solid with a variegated yellow and tan cut surface and focal yellow speckled areas.

The right adrenal gland of the second patient weighed 36 g and measured 7.5 x 4.5 x 2.0 cm. Within the gland there was a well- circumscribed heterogeneous cystic and solid mass with hemorrhagic areas (Figure 1); the nodule measured 5.5 x 1.5 x 1.2 cm. There was a rim of cortical tissue at the periphery.

Both adrenal tumors were composed of a mixture of elements with different appearances surrounded by compressed cortical tissue. The tumor consisted of adrenal cortical tissue and scattered aggregates of lymphocytes with occasional follicle formation (Figure 2). There were islands of adipose and hematopoietic tissues resembling mature bone marrow (Figure 3). Myeloid, ery-throid, and lymphoid cells and megakaryocytes were present, but precursor myeloblasts were not seen. A prominent component was composed of anastomosing tubules and cystic spaces lined by flat or plump epithelioid cells with scant eosinophilic cytoplasm and round to oval fairly uniform nuclei without atypia or mitotic activity (Figure 4). These epithelioid lining cells of the AT showed strong immunoreactivity for D2-40 antibody and calre-tinin (Figures 5 and 6) and weak reactivity for cytokeratin 5/6 (not shown).

COMMENT

A composite tumor consisting of AT and myelolipoma in the adrenal gland to our knowledge has not been previously described in the literature. The cases that we report represent the first 2 cases of this unusual association. The uniqueness of this tumor is emphasized by the fact that both AT and myelolipoma of adrenal gland are rare, and at the moment, the pathogenesis of both is unclear and considered controversial.

Adenomatoid tumor is common in the genital tracts of both male and female patients but is extremely rare in the adrenal gland.1,2 Among the 26 cases reported, the majority occurred in men.3 Myelolipoma is more common in the adrenal gland and is found in 0.08% to 0.2% of autopsy cases; it is extremely rare in extra- adrenal sites.5,10 The pathogenesis of AT and myelolipoma is speculative, and the reason why these tumors occur in the adrenal is unclear because they arise from tissues that are presumably foreign to that gland.

With the use of immunohistochemistry and electron microscopy, it was found that ATs are indeed mesothelial in nature, and it has been suggested that some of the early reported cases of lymphangioma of the adrenal gland were actually ATs.3,4 Because the adrenal gland is not lined by mesothelium, it has been proposed that AT in the adrenal gland is caused by mesothelial inclusions yielding a para- adrenal or intra-adrenal AT; this is consistent with the close embryologic relationship between adrenal gland and mullerian tract and explains both heterotopic adrenal cortical tissue in the periovarian regions and conceivably an AT in the adrenal gland.2- 4,7

Myelolipoma is more clearly understood than AT, perhaps because it is more common than AT, and therefore there are more existing cases to analyze and explain the disease. Bone marrow embolization, embryonic primitive mesenchymal cells, dysregulation of hematopoietic cell apoptosis, and adrenal cortical metaplasia in response to stimuli are proposed etiologies of adrenal myelolipoma; the last is currently the most accepted theory.5,14-17 Stimuli such as necrosis, infections, and stress have been known to induce myelolipoma. In fact, myelolipomatous change was induced in the adrenal glands of rat by injecting necrotic tumor and adrenocorticotrophic hormone.5 This theory provides a plausible explanation for the coexistence of other disease conditions in 63% of adrenal myelolipo-mas. 10 Among the reported coexisting conditions with myelolipoma are hypertension, obesity, diabetes mellitus, nonfunctioning adrenal adenoma, Cushing syndrome, congenital adrenal hyperplasia, cardiovascular disease, nephrolithiasis, primary aldosteronism, Cushing disease, pheochromocytoma, hypogonadism, polycystic ovary disease, Carney complex,10 and acquired immunodeficiency syndrome.18 Recent studies have drawn attention to the possible clonality of myelolipoma, with the demonstration of a balanced translocation between 3q25 and 21p1115 and nonrandom X inactivation in most tumors.5

The significance of composite AT and myelolipoma in the adrenal gland is poorly understood at present. Understanding this phenomenon can perhaps clarify some of the issues that are currently controversial regarding the pathogenesis of AT and myelolipoma.

CONCLUSION

Adenomatoid tumor and myelolipoma are rare tumors of the adrenal gland with unclear pathogenesis. Increased awareness of the existence of a composite tumor can improve the recognition and diagnosis of this lesion that could perhaps lead to a better understanding of the pathogenesis of AT and myelolipoma.

We acknowledge the Kansas Histopathology Club and its coordinator, Ivan Damjanov, MD, PhD, who forged this collaboration between the Instituto de Patologia e Imunologia da Univer-sidade do Porto, Hospital S Joao, Porto, and the University Health Network, University of Toronto.

References

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2. Garg K, Lee P, Ro JY, Qu Z, Troncoso P, Ayala AG. Adenomatoid tumor of the adrenal gland: a clinicopathologic study of 3 cases. Ann Diagn Pathol. 2005; 9:11-15.

3. Hamamatsu A, Arai T, Iwamoto M, Kato T, Sawabe M. Adenomatoid tumor of the adrenal gland: case report with immunohistochemical study. Pathol Int. 2005;55:665-669.

4. Chung-Park M, Yang JT, McHenry CR, Khiyami A. Adenomatoid tumor of the adrenal gland with micronodular adrenal cortical hyperplasia. Hum Pathol. 2003;34:818-821.

5. Bishop E, Eble JN, Cheng L, et al. Adrenal myelolipomas show nonrandom X-chromosome inactivation in hematopoietic elements and fat: support for a clon-al origin of myelolipomas. Am J Surg Pathol. 2006;30:838-843.

6. Yildiz L, Akpolat I, Erzurumlu K, Aydin O, Kandermir B. Giant adrenal my-elolipoma: case report and review of the literature. Pathol Int. 2000;50:502-504. 7. Isotalo PA, Keeny GL, Sebo TJ, Riehle DL, Cheville JC. Adenomatoid tumor of the adrenal gland: a clinicopathologic study of five cases and review of the literature. Am J Surg Pathol. 2003;27:969-977.

8. Patel VG, Babalola OA, Fortson JK, Weaver WL. Adrenal myelolipoma: report of a case and review of the literature. Am Surg. 2006;72:649-654.

9. Armand R, Cappola AR, Horenstein RB, Drachenberg CB, Sasano H, Pa-padimitriou JC. Adrenal cortical adenoma with excess black pigment deposition, combined with myelolipoma and clinical Cushing’s syndrome: a case report and review of the literature. Int J Surg Pathol. 2004;12:57-61.

10. Rodriguez-Vallejo F, Gomez-Perez FJ. Two siblings with untreated CYP21 deficiency and giant myelolipomas: case report and review of the literature. Endocrinologist. 2006;16:172-178.

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12. Merchant SH, Herman CM, Amin MB, Ro JY, Troncoso P. Myelolipoma associated with adrenal ganglioneuroma. Arch Pathol Lab Med. 2002;126:736- 737.

13. Hagspiel KD. Manifestation of Hodgkin’s lymphoma in an adrenal mye-lolipoma. Eur Radiol. 2005;15:1757-1759.

14. Meyer A, Behrend M. Presentation and therapy of myelolipoma. Int J Urol. 2005;12:239-243.

15. Chang KC, Chen PI, Huang ZH, Lin YM, Kuo PL. Adrenal myelolipoma with translocation (3:21) (q25; p11). Cancer Genet Cytogenet. 2002;134:77-80.

16. Carranza-Lira S, Jimenez L, Quiroz E, Kofman-Alfaro S, Zenteno JC. 46, XY Agonadism associated with adrenal adenoma/ myelolipoma: report of a case analyzing Y chromosome-specific sequences. Gynecol Endocrinol. 2003;17:429- 432.

17. Sakaki M, Izaki H, Fukumori T, Taue R, Kishimoto T, Kanayama HO. Bilateral adrenal myelolipoma associated with adrenogenital syndrome. Int J Urol. 2006;13:801-802.

18. Angeles-Angeles A, Reyes E, Munoz-Fernandez L, Angritt P. Adenomatoid tumor of the right adrenal gland in a patient with AIDS. Endocr Pathol. 1997;8: 59-64.

Elizabeth R. Timonera, MD; Maria Emilia Paiva, MD; Jose Manuel Lopes, MD, PhD; Catarina Eloy, MD; Theodore van der Kwast, MD, PhD; Sylvia L. Asa, MD, PhD

Accepted for publication September 11, 2007.

From the Department of Pathology, University Health Network, University of Toronto, Ontario (Drs Timonera, van der Kwast, and Asa); the Department of Pathology, Hospital S Joao, Porto, Portugal (Drs Paiva and Eloy); and the Medical Faculty, Instituto de Patologia e Imunologia da Universidade do Porto and Hospital S Joao, Porto, Portugal (Dr Lopes).

The authors have no relevant financial interest in the products or companies described in this article.

Reprints: Sylvia L. Asa, MD, PhD, Department of Pathology, University Health Network, 200 Elizabeth St, 11th Floor, Toronto, Ontario, Canada M5G 2C4 (e-mail: sylvia.asa@uhn.on.ca).

Copyright College of American Pathologists Feb 2008

(c) 2008 Archives of Pathology & Laboratory Medicine. Provided by ProQuest Information and Learning. All rights Reserved.




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