Myelolipoma: An Unusual Surgical Lesion of the Adrenal Gland
MARK J. NOBLE, MD,* DROGO K. MONTAGUE, MD, AND HOWARD S. LEVIN, MD
The clinical and pathologic features of three cases of surgically removed myelolipoma of the adrenal gland are presented. As with 18 previously reported cases, the lesions were found in obese, middle-aged persons; two of three had chronic, systemic disease (vasculitis and lymphoma, sustained hypertension). The only symptom possibly attributable to the neoplasm was nonspecific abdominal pain, and each lesion was identified by inferior renal displacement on intravenous urography. As computed tomography becomes widely available, the authors expect more myelolipomas to be detected that require surgical exploration, since there are no satisfactory, specific radiographic criteria to differentiate adrenal mye- lolipoma from adrenocortical carcinoma.
Cancer 49:952-958, 1982.
M OST REPORTS on myelolipoma of the adrenal gland involve lesions found incidentally at autopsy. These are generally unilateral, asymptomatic, benign neoplasms containing hematopoietic and fatty elements, and they are always hormonally inactive. With several hundred described in the world literature,1 they are a rare but well-recognized finding at postmortem exam- ination.
Most adrenal myelolipomas are ≤5 mm in diameter, and it is only when a myelolipoma becomes large that it might cause symptoms or be detected by radiography. There are only 18 reported cases of surgical removal of an adrenal myelolipoma,t and it is unusual for a large one to be found in a clinical setting.1-17
A review of our surgical and pathologic records dis- closed three recent cases in which operative intervention was undertaken for adrenal myelolipoma. We report our findings to increase awareness of this lesion and to prevent radical surgery in its treatment.
Case Reports
Case 1
A 52-year-old white woman was admitted to the Cleveland Clinic for evaluation of numbness and pain in her right hand
From the Departments of Urology and Pathology, The Cleveland Clinic Foundation, Cleveland, Ohio.
Address for reprints: Drogo K. Montague, MD, Department of Urology, Cleveland Clinic Foundation, Cleveland, OH 44106.
* Present address: University of Kansas Medical Center, Depart- ment of Urology, Kansas City, KS 66103.
Accepted for publication February 9, 1981.
t A nineteenth myelolipoma is excluded as a “surgical” lesion.18 It was an incidental finding after palliative adrenalectomy for breast carcinoma and was only 2 mm in diameter.
and right foot. She had a history of Raynaud’s phenomenon in the right arm, hypertension diagnosed four years before admission, and gross hematuria within the past year thought to be caused by a urinary tract infection. Physical examination revealed blood pressure of 100/70 mm Hg, marked obesity, and decreased radial and pedal peripheral pulses bilaterally.
Because of the hematuria, an intravenous pyelogram was done, which revealed the presence of a 6 cm left suprarenal mass. A computed tomographic scan (CT) disclosed a solid mass involving the left adrenal gland. Arteriography and ve- nography showed the mass to be hypovascular.
Endocrinologic evaluation included morning and evening serum cortisols, serum catecholamines, and 24-hour urinary vanillyl mandelic acid, metanephrines, free cortisol, 17-hy- droxysteroid, and 17-ketosteroid determinations. All of these tests were within normal limits.
Because of recent weight loss and concern that the left ad- renal mass represented a carcinoma, the patient was operated on, and a gray, discrete, well-encapsulated, left adrenal mass was resected along with an adherent spleen. Frozen section of the resected mass was interpreted as an infarcted adreno- cortical adenoma. The surgically resected specimen consisted of an adrenal gland measuring 5.8 × 5.0 × 2.6 cm. It contained a 4.4 cm nodule, which on transection had a thin 2.0 mm yellow surface overlying a partly hemorrhagic, partly fibrous gray mass. On microscopic examination, immediately beneath the adrenal cortex, within mature fat was an area of hema- topoietic tissue with abundant erythroid elements, recogniz- able granulocytic elements, and megakaryocytes (Fig. 1). Hemosiderin deposition was present in the hematopoietic foci. No capsule separated the cortex from this tissue. Elsewhere, beneath the cortex there was organizing fibrinohemorrhagic tissue with extensive fibrosis indicating previous infarction of the myelolipoma. Focally, at the junction of fibrous tissue and overlying cortex were areas of mature lymphocytes. A separate muscle biopsy specimen taken from the rectus abdominus re-
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vealed multifocal perivascular lymphocytic infiltration and focal vasculitis. The patient recovered uneventfully and was discharged on the eighth postoperative day to be treated with systemic steroids.
Three years after surgery, the patient was found to have a lymphoma in the neck, and she died approximately ten months after systemic chemotherapy was begun. There was no evi- dence that her myelipoma recurred.
Case 2
A 53-year-old obese white woman was referred to the Cleve- land Clinic for further evaluation of bilateral calcified adrenal masses. The patient was well until one month before admission, when she noted episodes of sharp, intermittent epigastric pain, as well as low anterior chest pain radiating to the right upper quadrant. The patient denied hematuria or other genitourinary symptoms. A purified protein derivative (PPD) test was pos- itive before admission, and there was a history of labile hy- pertension for five years. The patient had a subtotal thyroid- ectomy for adenomatous goiter in the past and was on standard thyroid replacement medication.
Serum cortisol determinations before admission revealed normal diurnal variation, and an intravenous urogram dem- onstrated downward displacement of the left kidney and bi- lateral calcified suprarenal masses. Gallbladder series revealed one large gallstone, and angiograms showed an avascular left adrenal mass. Ultrasound showed a solid mass.
On admission to the Cleveland Clinic, blood pressure was 130/90 mm Hg, and some irregularity was noted in the thyroid region on physical examination. The remainder of the ex- amination showed no abnormality. Bilateral adrenal veno- grams denoted a normal right adrenal gland and a large, avascular mass in the left adrenal gland. Preoperative serum
cortisols and 24-hour urine determinations for 17-ketoste- roids and hydroxycorticosteroids, metanephrines, normeta- nephrines, and vanillyl mandelic acid were at normal levels. Plasma aldosterone levels were normal throughout the inferior vena cava. Multiple urine cultures were negative for acid fast bacilli. Serum creatinine value was 0.8 mg/dl; complete blood count was normal. The patient underwent exploratory lapa- rotomy with resection of a yellow, well-encapsulated left ad- renal mass. The frozen section indicated that it was benign. The mass weighed 145 g, measured 8.3 × 6.5 X 3.0 cm, and was encapsulated by a thin transparent membrane. The ad- renal gland was recognizable as an attenuated structure over the convex surface of the specimen beneath which was a ho-
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mogeneous, soft, yellow-white mass (Fig. 2). On microscopic section, the periphery of the adrenal gland contained adre- nocortical tissue varying from normal thickness to a thin at- tenuated strip of two to three cells (Fig. 3). Immediately sub- jacent to the cortex was a mass composed largely of mature adipose cells with a variable amount of collagen. Scattered through the fatty tissue were foci of hematopoietic tissue con- taining erythroid, lymphoid, and occasional granulocytic and megakaryocytic elements (Fig. 4). A small amount of collag- enous tissue focally demarcated the adrenal cortex-myeloli-
poma interface. The patient’s course was without complica- tion, and she was discharged on the ninth postoperative day. She is healthy and without evidence of recurrent myelolipoma three years after surgery.
Case 3
A 43-year-old white man was referred to the Cleveland Clinic for evaluation of hypertension. He had a long history of mild hypertension (diastolic range of 90-100 mm Hg, and three weeks before admission was found to have markedly elevated blood pressure of 250/130 mm Hg. Blood pressure control was poor with therapeutic doses of hydrochlorothiazide and prazosin hydrochloride. An intraveous urogram indicated the presence of a left suprarenal mass (Fig. 5). On admission to the Cleveland Clinic, the patient’s physical examination showed no abnormality except for blood pressure of 210/130 mm Hg. Admission laboratory studies including complete blood count, SMA profile, and urinalysis showed no abnor- mality. Measurements of plasma cortisol, aldosterone, and catecholamine levels were within normal limits, as were 24- hour urinary determinations of aldosterone and metane- phrines. Chest x-ray and renal scan also showed no abnor- mality. Computed tomography of the abdomen revealed a low- density mass in the left adrenal gland (Fig. 6). Aortogram and selective left renal arteriogram were normal (Fig. 7), but a left adrenal venogram revealed splaying of the branches of the inferior adrenal vein with irregularity suggesting pooling of contrast and abnormal vascularity (Fig. 8). Blood pressure remained constant during arteriography and venography.
Because of the possibility of an adrenal carcinoma, abdom- inal exploration was performed, and a smooth, well-encap- sulated left adrenal mass was resected. Frozen section of the resected mass indicated that it was benign, and no further surgery was performed. The specimen was a soft resilient mass measuring 7.5 × 7.5 × 5.0 cm. Its surface was smooth and
glistening, varying from brown to yellow to black. Abundant fibroadipose tissue was attached to the surface. The flattened adrenal gland measured 2.5 × 4.5 × 0.5 cm and was recog- nizable on the surface. On section, the mass had a septate lobular pattern and varied from red to yellow. On microscopic section, the entire mass was circumscribed by normally ap- pearing adrenocortical tissue. The interface of cortex and un- derlying tissue was continuous in many areas. Elsewhere, col- lagenous tissue was present at the junction. The myelolipoma comprised abundant mature adipose tissue with varying amounts of collagen, sometimes substantially replacing the fatty tissue. Within the fatty mass was considerable hema- topoietic tissue, principally of erythroid and lymphoid type. Megakaryocytic and granulocytic elements were much less frequent (Fig. 9). Scattered hematopoietic nests, principally composed of mature lymphocytes, were present in overlying adrenal cortex. The patient had an uneventful postoperative recovery, and his blood pressure was unchanged from preop- erative levels. Two years postoperatively, the patient remains well with no evidence of recurrence of his neoplasm.
Discussion
There have been four recent reports of surgically re- moved adrenal myelolipomas, including thorough dis- cussions of this lesion.
Table 1 is expanded from the table in the article by Desai et al.13 and compares the findings in the 21 re- ported patients with surgically removed adrenal mye- lolipomas (including the present series of three cases). The patients’ ages ranged from 41 to 72 years, with a mean of 52 years. Ten of the 21 lesions were left-sided, including all three of our cases, and 12 of 21 patients had histories of hypertension. Thirteen of 21 patients were men, most were overweight, and their primary symptom was pain, hematuria, or hypertension. While in some cases abdominal pain might be ascribed to the mass, it is doubtful that the hematuria or hypertension in any of the patients was related to the myelolipoma. Since the majority of large myelolipomas in the liter- ature were reported as incidental autopsy findings, even large myelolipomas are probably asymptomatic. It is, therefore, not surprising that all 21 reported surgical cases were diagnosed by noting inferior renal displace- ment on intravenous urography, rather than by history, physical examination, or other laboratory findings. Probably, a larger proportion of asymptomatic myelo- lipomas will be diagnosed in living patients rather than at autopsy now that CT of the abdomen is often used to evaluate nonspecific elusive abdominal pain.
Adrenal mylolipoma is relatively avascular on angio- graphic examination.1,12,13 This was true of our three patients, except for the adrenal venogram on one patient (Case 3), which was thought by the radiologist to dem- onstrate tumor vascularity. All but the case reported
by Boudreaux et al.’ (Table 1) demonstrated no en- docrinologic function. Boudreaux’s patient had congen- ital adrenal hyperplasia with a persistently elevated level of 24-hour urinary 17-ketosteroids after surgical removal of the tumor. The implication is that the en- docrinologic abnormalities may have been secondary to hyperplastic adrenal cortex, and the myelolipoma was a separate and coincident lesion.1
Although a biochemically nonfunctioning radiolucent solid adrenal mass (by computed tomography) with no neovascularity (on angiography) might be an adrenal myelolipoma, we disagree with Desai et al.,13 who feel this is the most likely diagnosis. We have had more than 15 lesions meeting the above criteria at the Cleve- land Clinic alone, which turned out to be avascular, nonfunctional, adrenocortical carcinomas, a far more
| Age (yr.) | Sex | Side | Body habitus | Blood pressure (mm Hg) | Presenting symptoms | Urologic disease | Specimen (g) | Maximum diameter of measurement (cm) | |
|---|---|---|---|---|---|---|---|---|---|
| Dyckman and Freedman | 47 | M | Rt. | - | 116/94 | Pain | - | 1100 | 16 |
| Parsons and Thompson | 51 | F | Rt. | Obese | 140/90 | Pain | - | 1250 | 25 |
| Figueroa and Tedeschi | 61 | F | Rt. | - | - | Pain | - | ? | ? |
| Engelking et al. | 63 | M | Rt. | Obese | - | Hematuria | Renal cancer | ? | 10 |
| Newman and Silen | 41 | M | Lt. | Robust | 140/90 | Pain | - | ? | 18 |
| Whittaker | 57 | F | Lt. | Obese | 154/98 | Pain and | - | ? | 7 |
| microhematuria | |||||||||
| Tulcinsky et al. | 53 | M | Rt. | Well nourished | 190/120 | Hematuria | Calculus | 850 | 20 |
| Olsson et al. | 44 | M | Lt. | Obese | 180/90 | Hematuria | Calculus | 440 | - |
| Gee et al. | 43 | M | Rt. | Obese | 180/126 | Hypertension | - | 312 | 7.5 |
| Rubin et al. | 49 | M | Rt. | Well developed | 155/100 | Pain | - | 50 | 6 |
| Snearly et al. | 46 | F | Lt. | Obese | 120/70 | Pain | - | 140 | 8 |
| Desai et al. | 54 | M | Lt. | Obese | 130/70 | Microhematuria | No cause found | 360 | 10.5 |
| Boudreaux et al. | 57 | M | Lt. | Obese | - | Pain | CAH*, testis tumor | 5900 | 24 |
| Bosniak et al. | 43 | F | Rt. | - | Elevated | Hypertension | - | ? | |
| Behan et al. | 47 | F | Rt. | Obese | - | Pain, mass | - | ? | 11 |
| Behan et al. | 55 | M | Lt. | - | - | Dysuria | - | ? | 6 |
| Scheible et al. | 72 | M | Rt. | - | - | ? | - | ? | 6 |
| Ayyat et al. | 47 | F | Rt. | Obese | 170/95 | Pain | - | ? | 7 |
| Noble et al. | 57 | M | Lt. | Obese | 100/70 | Hematuria | - | ? | 6 |
| Noble et al. | 52 | F | Lt. | Obese | 130/90 | Pain | ? | 145 | 8 |
| Noble et al. | 43 | M | Lt. | Well nourished | 210/130 | Hypertension | - | ? | 8 |
* Congenital adrenal hyperplasia.
t Modified from Table 1 in the review of Desai et al.13
common lesion.19 Myelolipoma is sufficiently rare that it was not recorded in the differential diagnosis of any of the 21 reported cases (Table 1) before surgery. At present, there do not appear to be diagnostic radio- graphic criteria specific for myelolipoma of the adrenal gland.
Although Selye and Stone20 have demonstrated mye- lolipomatous changes in the adrenal glands of rats after injection of crude hormonal extracts of the testes, pi- tuitary gland, and thyroid gland, the etiology of mye- lolipoma of the adrenal gland in the human remains obscure. Two of our three patients had long-standing systemic disease (vasculitis and lymphoma, hyperten- sion). In Case 1, lymphoma may have been present at adrenalectomy and muscle biopsy. Several other re- ported cases also disclosed the presence of a systemic disease. Most patients were described as well nourished or obese. Whether these factors favor the development of such lesions remains unclear. No known endocrino- pathy produces adrenal myelolipoma in humans.
The most striking feature of all 21 reported cases (Table 1) is that patients generally were studied for possible malignant neoplasm, and in most cases, a lesion was found at exploration that did not appear to be malignant. In our three cases, a smooth surface with apparent encapsulation of the adrenal mass raised a question on the advisability of radical surgery. Frozen section of the resected mass was performed to help de-
cide whether to proceed surgically. When each frozen section was interpreted as benign, it was felt that ex- cision of the adrenal gland constituted adequate sur- gery, and no attempt was made to perform concomitant nephrectomy or regional lymphadenectomy. In each case, retrospective analysis confirms a correct decision. In none of our three cases (or those in the literature with follow-up) did recurrence or other problems de- velop after several years. This confirms that adrenal resection is curative.
The three reported cases demonstrate the usual pa- thology of surgically resected myelolipoma of the ad- renal gland. The masses were similar in size, color, and appearance to those in previously reported cases and had a similar microscopic appearance. Two of the three cases contained abundant hematopoietic elements (Cases 1 and 3), whereas Case 2 contained abundant fat and sparse hematopoietic tissue. One myelolipoma was ex- tensively infarcted (Case 1). There was evidence of peri- vascular lymphocytic infiltration and focal vasculitis in a muscle biopsy performed at the same time, although no evidence of vasculitis was seen in the adrenal gland specimen. In all three cases, the myelolipomatous tis- sues were in juxtaposition with adrenal cortical tissue. In some areas, fibrous tissue was interposed between the two elements (Fig. 4), whereas elsewhere no capsule or pseudocapsule was present. Although others have found adrenocortical cells within the substance of the myelolipoma, the adrenal cortex and the myelolipoma were discrete in these three cases. This does not preclude myeloid mataplasia within the substance of the adrenal cortex or choristomatous differentiation as possible etiologies of the lesion. The admixture of adrenocortical tissue and myelolipomatous tissue in a reported case of a patient with congenital adrenocortical hyperplasia1 suggests that the massive cortical hyperplasia stimu- lated the growth of adipose tissue and hematopoietic tissue. Irrespective of the myelolipoma’s origin, none of these or other reported cases have behaved malig- nantly.
Summary
Three cases of surgically resected large adrenal mye- lolipomas are presented. As with the 18 previously re- ported cases, these patients tend to be obese and often have a systemic disease. Most adrenal myelolipomas are asymptomatic, and therefore even large ones are more often found at autopsy than in a clinical setting. The only symptom that might be consistently attributable to this neoplasm is abdominal pain, often nonspecific.
All surgically removed myelolipomas of the adrenal gland were detected initially by intravenous urography, and we predict that as CT continues to be used for
evaluation of vague, nonspecific abdominal complaints, more of these lesions will be detected before autopsy.
A large, nonfunctional, relatively avascular adrenal mass is more likely to be an adrenocortical carcinoma than a myelolipoma. Although the morphologic ap- pearance of a myelolipoma may vary from area to area, frozen section at the time of surgery should indicate the correct diagnosis or at worst, a benign lesion (infarct or lipoma). The histopathologic appearance in no way resembles a malignant lesion. Because of this, frozen section evaluation of large adrenal masses following simple adrenalectomy should preclude unnecessary, ad- ditional surgery (regional lymphadenectomy, nephrec- tomy) in cases of myelolipoma.
ADDENDUM
As our article was going to press, two additional reports of surgically resected adrenal myelolipomas have appeared (1. Ishikawa H, Tach- ibana M, et al. Myelolipoma of the adrenal gland. J. Urol 1981; 126:777-779. 2. Fernandez-Sanz J, Galera H, et al. Adrena! mye- lolipoma simulating a retroperitoneal malignant neoplasm. J Urol 1981; 126:780-782). Both patients were male and had nonspecific abdominal pain. One had hypertension, the other had chronic pan- creatic disease, and in both, the lesions were sizable enough to produce abnormalities on excretory urography. Neither functioned endocri- nologically. Although CT scanning revealed a predominance of fat, concern for malignancy warranted surgery in each instance.
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