Leiomyoma of the Adrenal Gland Presenting as a Non-Functioning Adrenal Incidentaloma: Case Report and Review of the Literature
Jingmei Lin . Matthew J. Wasco · Melvin Korobkin . Gerard Doherty . Thomas J. Giordano
Published online: 16 January 2008 C Humana Press Inc. 2008
Abstract A 31-year-old woman was incidentally found to have a large right adrenal mass by computed tomography imaging and underwent a workup that included endocrino- logical evaluation and positron emission tomography imaging. Laboratory results revealed the mass to be non- functioning. Imaging studies revealed a 9-cm heteroge- neous mass that was not FDG avid. Because of concern for adrenal cortical carcinoma, the patient underwent a suc- cessful right adrenalectomy. Pathology examination dem- onstrated an 11-cm circumscribed mass consisting of uniform spindle cells without nuclear pleomorphism, necrosis, or mitotic activity. The diagnosis of leiomyoma was supported by a panel of immunohistochemical stains. Adrenal leiomyomas have been reported in the literature, although most are small and not preoperatively suspicious for malignancy. This case illustrates that benign tumors such as leiomyomas, when large and heterogeneous on imaging, can clinically mimic adrenal cortical carcinomas and should be included in the differential diagnosis of adrenal incidentalomas.
J. Lin . M. J. Wasco . T. J. Giordano Departments of Pathology, University of Michigan Health System, 1150 West Medical Center Drive, MSRB-2, C570D, Ann Arbor, MI 48109-0669, USA e-mail: Giordano@umich.edu
M. Korobkin Departments of Radiology, University of Michigan Health System, Ann Arbor, MI, USA
G. Doherty Departments of Surgery, University of Michigan Health System, Ann Arbor, MI, USA
Keywords adrenal gland · adrenal incidentaloma · leiomyoma · pathology
Introduction
The so-called adrenal “incidentalomas” are “clinically inapparent adrenal masses that are discovered inadvertently in the course of diagnostic testing or treatment for other clinical conditions that are not related to suspicion of adrenal disease” [1]. Their incidence has risen recently due primarily to increasing and improved imaging studies [2, 3]. Incidentalomas are usually small tumors, but occasional large tumors are also identified. Many incidentalomas are non-functioning with regard to their endocrinological status, but sub-clinical endocrinopathies are often present [4-7].
The majority of adrenal incidentalomas are adrenal cortical tumors (either adenomas or carcinomas) or adrenal medullary tumors (pheochromocytomas), with cortical adenoma being the predominate diagnosis [2]. However, the adrenal gland can give rise to a broad range of other tumor types. Thus, the complete differential diagnosis of adrenal incidentalomas includes a long list of rare, miscellaneous tumors. In this paper, we report a case of a patient with a large, non-functioning adrenal tumor, preoperatively concerning for adrenal cortical carcinoma, which was successfully resected. In addition, the literature of reported adrenal leiomyomas is also reviewed.
Case Report
A 31-year-old African-American woman underwent an unremarkable vaginal delivery, after which she experienced
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shortness of breath and underwent a computed tomography (CT) to rule out a pulmonary embolus. The CT scan discovered an incidental large right adrenal tumor. She was then referred to undergo an endocrinological laboratory evaluation that included serum cortisol, adrenocorticotropic hormone, renin, aldosterone, plasma fractionated free metanephrines, and 24-h urinary-free cortisol, all of which were within normal limits. Thus, the tumor was concluded to be non-functioning.
The physical examination revealed a normotensive woman without stigmata of Cushing syndrome. The remainder of the physical examination was normal.
CT imaging with contrast showed a large (9.0×7.7 cm) heterogeneous right adrenal mass with multiple areas of decreased attenuation (Fig. 1). There was no regional lymphadenopathy. Positron emission tomography (PET) with 2-[18F] fluoro-2-deoxy-D-glucose (FDG) showed background levels of tracer uptake. Radiographic differen- tial diagnosis included adrenal cortical adenoma and carcinoma and pheochromocytoma.
The patient underwent successful open right adrenalec- tomy. The tumor was adherent to the inferior surface of the right lobe of the liver superiorly, so the liver capsule was resected with the tumor. The tumor itself was removed intact without violation of the capsule. The tumor was non- adherent to the right kidney or renal vessels. The patient had an uncomplicated recovery and was discharged on postoperative day 6.
The resection specimen measured 11×9×7 cm and weighed 315 g. Gross pathologic examination revealed a solid, well-circumscribed tan mass with central hyaliniza- tion. Histologically, the tumor was composed of bland looking spindle cells in a background of marked hyaliniza- tion and fibrosis (Fig. 2a,b). The tumor compressed the adjacent normal adrenal gland (Fig. 2a). Tumor necrosis and mitotic activity were not identified. A diagnosis of leiomyoma was supported by immunohistochemical (IHC) studies (see Table 1 for IHC conditions), the results of which were smooth muscle actin, diffusely and strongly positive in the tumor cells (Fig. 2c); desmin, negative in the tumor cells with appropriate internal control; S-100,
a
b
C
d
| Antibody | Dilution | Pretreatment | Protocol | Vendor | Address |
|---|---|---|---|---|---|
| S100 | 1:250 | None | Ultraview DAB detection | Dako | Carpenteria, CA |
| Desmin | 1:40 | CC1 mild | Ultraview DAB detection | Dako | Carpenteria, CA |
| EMA | 1:50 | CC1 mild | Ultraview DAB detection | Dako | Carpenteria, CA |
| CD34 | 1:100 | CC1 mild | Ultraview DAB detection | Dako | Carpenteria, CA |
| BCL2 | 1:40 | CC1 std, amp | Ultraview DAB detection | Calbiochem | La Jolla, CA |
| SMA | 1:200 | CC1 short | Ultraview DAB detection | Sigma | St. Louis, MO |
| C-kit | 1:50 | CC1 mild | Ultraview DAB detection | Dako | Carpenteria, CA |
negative; c-kit, negative; ß-catenin, membranous staining without nuclear staining; bcl2, negative; epithelial mem- brane antigen (EMA), negative; and CD34, negative in the tumor cells with intra-tumoral vessels positive (Fig. 2d).
Literature Review
Leiomyoma of the adrenal gland is rare, with 13 cases previously reported in the literature [8-20] (summarized in Table 2). Including the current case, the age of patients with adrenal leiomyoma was broad, ranging from 2 to 72 years (average, 37 years). Adrenal leiomyoma predominated in women (9 out of 14, 64%). Left-sided tumors were more common (8 out of 14), and there were two cases of bilateral tumors. Tumor size ranged from 0.7 to 11 cm (average, 6.0 cm), and adrenal weight was between 17.8 and 315 g. The current adrenal leiomyoma was 11 cm and 315 g, which is the largest adrenal leiomyoma reported to date.
Discussion
Adrenal incidentolomas are defined as adrenal tumors discovered by imaging studies performed for another condition [1]. Over the years, they have become an increasingly significant clinical problem [2, 21], so much so that in 2002, the National Institutes of Health hosted a multidisciplinary panel on the “state-of-the-science on management of the clinically inapparent adrenal mass.” One of the recommendations of that panel [1] was that tumors larger than 6 cm be surgically resected. At the time of the panel, insufficient information on FDG-PET was available to be incorporated into the recommendations. With time, it is possible, as PET technology becomes more mainstream, that it can be factored into the management guidelines of adrenal incidentalomas.
Leiomyomas are benign tumors consisting of smooth muscle cells. They occur most frequently in the uterus and gastrointestinal tract but have been found in a wide range of
| Report | Size (cm) | Weight (g) | Age (year) | Sex | Side | Functional | Clinical associations | Reference |
|---|---|---|---|---|---|---|---|---|
| 1 | 5.5×4.5×3.5 | Un | 53 | F | Left | No | None | [8] |
| 2 | 3×3.5×3 | 17.8 | 49 | F | Left | No | AIDS(+), EBV(-) | [12] |
| 3 | 5×3.1×4.2 | Un | 65 | F | Left | No | None | [14] |
| 4 | 3.5 | Un | 35 | F | Left | Un | AIDS(+), | [19] |
| 5 | 7×5×5 | Un | 2 | M | Right | Un | AIDS(+), EBV(+) | [15] |
| 6 | 5.5×5×4.5 | 84 | 48 | F | Left | No | Hypertension | [18] |
| 7 | 9×7×6 | Un | 72 | M | Left | No | None | [13] |
| 8 | 3 | Un | 32 | M | Left | No | AIDS | [10] |
| 9 | 5×4×3 | Un | 10 | F | Left | Un | Ataxia-telangiectasia | [17] |
| 10 | L: 5; R: 3 | Un | 11 | F | Bilateral | Un | AIDS | [20] |
| 11 | L: 4×5×3.5; R: 8×5×3 | L: 24.5; R: 80.5 | 15 | M | Bilateral | No | Multiple leiomyomas involving spleen, epicardium, bilateral testicular microlithiasis and empty sella tursica | [11] |
| 12 | Un | Un | 40 | F | Right | No | None | [9] |
| 13 | 7.2 | Un | 56 | M | Right | No | None | [16] |
| 14 | 11×9×7 | 315 | 31 | F | Right | No | None | Current case |
Un unknown; R right; L left; AIDS acquired immune deficiency syndrome; EBV Epstein-Barr virus
sites including the adrenal glands [18]. The leiomyomas found in the adrenal gland are usually small tumors that are not highly worrisome for adrenal cortical carcinoma. The current case is the largest reported and because of its large size was concerning for a non-functioning adrenal cortical carcinoma.
It is not unexpected that the leiomyoma reported in this paper was not FDG-PET avid, as these benign tumors have a low proliferation rate and thus presumably do not metabolize glucose at rate high enough to be PET positive. However, there have been several reports of PET-positive leiomyomas [22-24]. Absent FDG-PET avidity was a preoperative sign that this was a benign tumor, especially as a heterogeneous adrenal tumor on CT imaging is likely to be a high-grade carcinoma that would be expected to be FDG-PET positive [25-27]. However, a negative PET study is not sufficient to unequivocally conclude a given tumor is benign and preclude surgery. An adrenal tumor of this size should be surgically resected even when non-functioning and FDG-PET negative.
It is noteworthy that many of the reported cases of adrenal leiomyomas are in patients with human immuno- deficiency virus/acquired immune deficiency syndrome (HIV/AIDS) and/or latent Epstein-Barr virus (EBV) infec- tion [15]. Among the reported cases of adrenal leiomyoma, five are from AIDS patients [10, 12, 15, 19, 20]. The association of leiomyoma and HIV/AIDS is not restricted to the adrenal gland, as these tumors have been found in various sites in both children and adults [28, 29]. Epstein- Barr virus infection has been associated with smooth muscle tumors in immunocompromised patients but not in immunocompetent patients [29]. The pathogenetic reason for this association between leiomyoma and these viral infections is unclear and needs further investigation. The HIV status of the patient presented in this paper is not known.
In summary, knowledge of the differential diagnosis of adrenal masses, including unusual and miscellaneous tumors, is crucial for optimal management. This will be particularly true should the day arrive in which imaging studies reliably permit the observation of a large, non- functioning adrenal mass. For now, all large incidentally discovered adrenal tumors will need resection, and the pathologic differential diagnosis should be expanded to include large leiomyomas such as the one reported in this paper.
References
1. NIH. NIH state-of-the-science statement on management of the clinically inapparent adrenal mass (“incidentaloma”). NIH Con- sens State Sci Statements. 19:1-25, 2002.
2. Bovio S, Cataldi A, Reimondo G, et al. Prevalence of adrenal incidentaloma in a contemporary computerized tomography series. J Endocrinol Invest 29:298-302, 2006.
3. Thompson GB, Young WF Jr. Adrenal incidentaloma. Curr Opin Oncol 15:84-90, 2003.
4. Newell-Price J, Grossman A. Adrenal incidentaloma: subclinical Cushing’s syndrome. Postgrad Med J 72:207-10, 1996.
5. Tsvetov G, Shimon I, Benbassat C. Adrenal incidentaloma: clinical characteristics and comparison between patients with and without extraadrenal malignancy. J Endocrinol Invest 30:647- 52, 2007.
6. Lee JA, Zarnegar R, Shen WT, Kebebew E, Clark OH, Duh QY. Adrenal incidentaloma, borderline elevations of urine or plasma metanephrine levels, and the “subclinical” pheochromocytoma. Arch Surg 142:870-3, 2007, (discussion 73-4).
7. Arnaldi G, Masini AM, Giacchetti G, Taccaliti A, Faloia E, Mantero F. Adrenal incidentaloma. Braz J Med Biol Res 33:1177- 89, 2000.
8. Chang TH, Lee YC, Liu CC, Huang CH, Wu WJ. Adrenal leiomyoma treated by hand-assisted laparoscopic adrenalectomy: a case report. Kaohsiung J Med Sci 22:575-9, 2006.
9. Chao CS, Zhou ZG, Liao EY. The diagnosis and management of adrenal “incidentaloma”. Zhonghua Nei Ke Za Zhi 33:395-7, 1994.
10. Dahan H, Beges C, Weiss L, et al. Leiomyoma of the adrenal gland in a patient with AIDS. Abdom Imaging 19:259-61, 1994.
11. Demirel S, Erk O, Akkaya V, et al. Multiple vascular leiomyomas involving bilateral adrenal glands, spleen, and epicardium, associated with bilateral testicular microlithiasis and empty sella turcica. J Pediatr Surg 32:1365-7, 1997.
12. Gibbs KE, White A, Kaleya R. Laparoscopic management of an adrenal leiomyoma in an AIDS patient. A case report and review of the literature. JSLS 9:345-8, 2005.
13. Goldman RL, Brodey PA. Symptomatic leiomyoma of the adrenal. Clin Imaging 18:277-8, 1994.
14. Jacobs IA, Kagan SA. Adrenal leiomyoma: a case report and review of the literature. J Surg Oncol 69:111-2, 1998.
15. Jimenez-Heffernan JA, Hardisson D, Palacios J, Garcia-Viera M, Gamallo C, Nistal M. Adrenal gland leiomyoma in a child with acquired immunodeficiency syndrome. Pediatr Pathol Lab Med 15:923-9, 1995.
16. Jurczak F, Hamy A, Paineau J, Courant O, Visset J. An unusual “incidentaloma”: adrenal leiomyoma. J Chir (Paris) 131:391, 1994.
17. Mouchet F, Ninane J, Gosseye S, et al. Leiomyoma of the suprarenal gland in a child with ataxia-telangiectasia. Pediatr Hematol Oncol 8:235-41, 1991.
18. Nishida S, Tanimura A, Takasaki S, et al. Surgically resected adrenal leiomyoma: report of a case. Surg Today 25:455-7, 1995.
19. Parola P, Petit N, Azzedine A, Dhiver C, Gastaut JA. Symptom- atic leiomyoma of the adrenal gland in a woman with AIDS. Aids 10:340-1, 1996.
20. Rosenfeld DL, Girgis WS, Underberg-Davis SJ. Bilateral smooth- muscle tumors of the adrenals in a child with AIDS. Pediatr Radiol 29:376-8, 1999.
21. Mantero F, Albiger N. A comprehensive approach to adrenal incidentalomas. Arq Bras Endocrinol Metabol 48:583-91, 2004.
22. Ak I, Ozalp S, Yalcin OT, Zor E, Vardareli E. Uptake of 2-[18F] fluoro-2-deoxy-D-glucose in uterine leiomyoma: imaging of four patients by coincidence positron emission tomography. Nucl Med Commun 25:941-5, 2004.
23. Meirelles GS, Ravizzini G, Yeung HW, Akhurst T. Esophageal leiomyoma: a rare cause of false-positive FDG scans. Clin Nucl Med 31:342-4, 2006.
24. Chura JC, Truskinovsky AM, Judson PL, Johnson L, Geller MA, Downs LS Jr. Positron emission tomography and leiomyomas:
clinicopathologic analysis of 3 cases of PET scan-positive leiomyo- mas and literature review. Gynecol Oncol 104:247-52, 2007.
25. Han SJ, Kim TS, Jeon SW, et al. Analysis of adrenal masses by 18F-FDG positron emission tomography scanning. Int J Clin Pract 61:802-9, 2007.
26. Leboulleux S, Dromain C, Bonniaud G, et al. Diagnostic and prognostic value of 18-fluorodeoxyglucose positron emission tomography in adrenocortical carcinoma: a prospective compari- son with computed tomography. J Clin Endocrinol Metab 91:920- 5, 2006.
27. Zettinig G, Mitterhauser M, Wadsak W, et al. Positron emission tomography imaging of adrenal masses: (18)F-fluorodeoxyglu- cose and the 11beta-hydroxylase tracer (11)C-metomidate. Eur J Nucl Med Mol Imaging 31:1224-30, 2004.
28. Radin DR, Kiyabu M. Multiple smooth-muscle tumors of the colon and adrenal gland in an adult with AIDS. AJR Am J Roentgenol 159:545-6, 1992.
29. Wachsberg RH, Cho KC, Adekosan A. Two leiomyomas of the liver in an adult with AIDS: CT and MR appearance. J Comput Assist Tomogr 18:156-7, 1994.