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Surgical Treatment of Adrenal Myelolipoma

Original Article

Introduction

Adrenal myelolipomas are rare benign tumors com-

posed of maturated adipose tissue and hematopoietic

cells. In most cases they are small and asymptomatic.

Discovered incidentally by ultrasound or computed to-

mography examination, they are classified as “adrenal

incidentalomas” and follow the corresponding indica-

tions for surgical removal.

Materials and methods

We present 6 patients within a prospective study

who were performed retroperitoneal endoscopic

adrenalectomy (REA) between June 2007 and Janu-

ary 2010 at the Second Surgical Department of UM-

HAT ”Alexandrovska”, Sofia, on the occasion of adrenal

gland myelolipoma. Five of the patients had unilateral

pathology and one - bilateral. In the patient with bilat-

eral pathology we performed a two-stage procedure

– REA on the first stage and conventional contralateral

adrenalectomy on the second.

The demographic characteristic of patients is pre-

sented in Table 1.

SURGICAL TREATMENT OF ADRENAL MYELOLIPOMAG. Todorov1, Ts. Lukanova1, M. Georgiev2

1Second Surgical Department, Medical University, Sofia2Department of Urology, Medical University, Sofia

Key words: endoscopic adrenalectomy, adrenal tumors, myelolipomaContact details: G. Todorov, Second Surgical Department, Medical University, 1 Sv. Georgi Sofiiski Blvd. – 1431, e-mail: g_todorov63@abv.bg

Abstract: Objective: To evaluate the potential of different surgical techniques in the treatment of rare tumors of the adrenal

glands.

Material and methods: We present 6 patients within a prospective study who underwent retroperitoneal endoscopic

adrenalectomy (REA) between June 2007 and January 2010 at the Second Surgical Department of UMHAT ”Alexandrovska”,

Sofia, on the occasion of adrenal gland myelolipoma.

Results: REA was carried out in 5 patients, while in one with bilateral myelolipomas - REA was performed followed by

a conventional contralateral adrenalectomy on the 2nd stage. The mean operative time for endoscopic surgery was 70 min

- (60’-90’), with an average intraoperative blood loss of 50 ml. There were no intraoperative and postoperative complica-

tions.

Conclusions: Myelolipomas are rare diseases of the adrenal glands, most often discovered incidentally in imaging diag-

nostics. The indications for their surgical treatment follow those of the incidentalomas. Mini-invasive techniques performed

by experienced endocrine and laparoscopic team are an effective and feasible way for their removal.

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J Clin Med. 2010; 3(3):24-30

Patients went through

the following examinations:

- clinical (including BMI),

- paraclinical (including precise adrenal hormonal

status for exclusion of subclinical Cushing-syndrome

and “occult” pheochromocytoma)

- imaging (standard ultrasound examination of ab-

dominal organs and retroperitoneal areas and contrast

computed tomography, if necessary - MRI) in order to

confirm the diagnosis, assess the malignant potential

of the formation and implement appropriate preop-

erative preparation.

Within the prospective study, we evaluated and

analyzed age, sex, BMI, size and location of tumor,

operative time, intraoperative and postoperative com-

plications, and postoperative hospital stay. Clinical

symptoms and relapse of the disease were tracked

during the follow-up period.

Results

In four patients the “adrenal tumor formation” was

detected incidentally during examinations on other

occasions. In one patient, the diagnosis myelolipoma

was suspected in the CT scan. One of the women had

been operated in another clinic on occasion of “chron-

ic calculous cholecystitis” eight years earlier. The per-

formed conventional cholecystectomy simultaneously

had revealed a tumor formation in the right adrenal

gland (25/25 mm preoperative CT size, intraoperative

- 50/60 mm), so a biopsy had been carried out. There

had not been total extirpation of the gland because

of proximity to vena cava inferior, difficult access and

benign macroscopic feature of the formation. The his-

tological examination of the material had indicated

a presence of “adrenal myelolipoma”. The formation

had been monitored in dynamics by nuclear magnetic

resonance with a noticed increase in size while main-

taining structural characteristics and normal size and

structure of the left adrenal gland. Eight years later

that patient manifested also hormonal secretion with

elevated levels of aldosterone and rennin triple tested

in upright position and within normal potassium lev-

els. The functional activity and the size of the forma-

tion required surgical intervention. The identified for-

mations in the other two patients were between 8-10

cm in size and hormonally inactive.

The analysis focuses on the characteristics of the

tumor formations - their size and location (Table 2),

clinical symptoms and comorbidity and CT - features.

(Table 3)

All patients had accompanying diseases - obesity

class I-II and arterial hypertension. Dyslipidemia within

metabolic syndrome was found in one female patient,

in two there was thyroid gland pathology – struma

nodosa and Hashimoto’s thyroiditis. One of the men

had been operated in the past with brain cyst and

nephro-and ureterolithiasis in the left.

CT-scans were carried out in all patients, including

MRI for the woman with 8-year follow up of the my-

elolipoma. In that woman’s case the mass of the right

adrenal gland was described as hyperintense, with

inhomogeneous intralesional structure, originating

from the adrenal gland, with rounded shape, benign

macromorphological characteristics and dimensions

68.3/49.2 mm, visibly enlarged compared to previ-

ous MRI examinations. The formation was with highly

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expansive cranial growth, and in its development it

pressed, without infiltrating v.c. inferioris, reduced the

pararenal space to the right, and pushed the right

kidney in the caudal direction. In STIR (sequence with

fat suppression), the lesion is presented with distinct

hyperintense signal characteristic, suggesting reduced

fat contents. The CT-characteristics of the myelolipo-

ma-like tumor formation are presented in Table 3,

while the CT image of the bilateral myelolipomas - in

Figure 1.

“Hand-assisted” retroperitoneal endoscopic adrena-

lectomy was carried out in two of the patients with

unilateral pathology. The patient with bilateral inci-

dentalomas underwent a two-stage procedure - the

first stage was total retroperitoneoscopic adrenalec-

tomy on the right, and the second - left lumbotomy

with adrenalectomy because of previous surgery in

the area – pyelolithotomy and ureterolithotomy, on

the occasion of nephrolithiasis, which considering the

10-cm size and the corresponding malignant poten-

tial, was evaluated as contraindication for mini-invasive

procedure.

The mean operative time of the endoscopic surger-

ies was 70 min - (60’-90’), with an average intraopera-

tive blood loss of 50 ml. In one case, we succeeded

to perform subtotal adrenalectomy with preservation

of apparently unchanged parenchyma of the adrenal

gland. The other required the removal of the entire

gland. Extirpation of the specimen was accomplished

by the use of “Endo-bag”, with skin excision expanded

whenever required by the size of the tumor. There

were no intraoperative and postoperative complica-

Surgical Treatment of Adrenal Myelolipoma

CT-image - a tumor formation in the right adrenal gland area, with transversal dimensions 54/74 mm; density is fat-equivalent - 60-90 HU; a capsule with irregular thickness; density does not change a�er application of contrast material

Postoperative view of the removed specimen and its macroscopic characteristics

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J Clin Med. 2010; 3(3):24-30

tions. Conventional adrenalectomy was performed

through lumbotomy and resection of the XII rib, while

intraoperatively were revealed multiple adhesions of

the renal capsule to the peritoneum and lumbar mus-

cle. The adrenal tumor formation was also accreted to

the tail of the pancreas. Verticalization and oral intake

in retroperitoneoscopic operations began on the 6th

postoperative hour; the mean postoperative stay was

2 days. With the conventional access this stay was ex-

tended to 6 days.

The histological diagnosis in all patients was “adrenal

myelolipoma”.

The follow up of the patients includes clinical, ul-

trasound and hormonal examinations on the 1st, 6th

and 12th postoperative months. There are no records

of recurrence or changes in the contralateral gland in

patients with unilateral pathology on the 12th month

of the follow-up. In the female patient with renin

overproduction, there was no such problem on the

6th month of the follow-up within normal potassium

levels. The man with bilateral adrenalectomy was ad-

ministered hormone replacement therapy.

Discussion

Adrenal myelolipomas are rare benign tumors com-

posed of fatty connective tissue and hematopoietic ele-

ments in different proportions. No malignant potential

of these lesions is reported in literature. Myelolipomas

are most often incidental findings (incidentalomas) of

imaging diagnostics, performed on another occasion.

They constitute about 3% of all primary adrenal tumors,

and their incidence in autopsies is 0.06% to 0.2%.1 Their

approximate share of the “incidentalomas” is 7-15%.15 My-

elolipomas are found among people aged 25-65 years,

most often affecting those aged 50-60 years2. The right

adrenal gland is more frequently involved than the left

(ratio 3:2.1) and the bilateral myelolipomas are rare.14

Our patients were in the age range 39-65 years and the

ratio right: left adrenal gland was respectively - 1.3:1. In

one case there was bilateral myelolipoma.

Far back in 1866, while exploring questions about the

biochemistry and cytology of the adrenal gland, Arnold3

reported the possibility that blood cells available from

ectopic tissue elements of bone marrow may develop

in the adrenal gland. For the first time, Gierke in 1905

represented a histological evidence of bone marrow in

the adrenal gland.4 Researchers of that time discussed

the presence of heterotopic bone tissue in the adre-

nal gland as a “pre-myeloma”. The name “myelolipoma”

was introduced in 1929 by Oberling to describe this ect-

opy.5 Etiopathogenesis of this disease remains unclear.

Experimental myeloid transformation in the adrenal

gland was induced by subcutaneous injection of extract

of anterior pituitary and metiltestosteron.19 Currently,

there are various theories about the origin and devel-

opment of the adrenal myelolipomas - development of

clusters of mesenchymal stem cells, bone marrow em-

boli, extramedullary hemopoiesis6, as the most widely

accepted is the theory of metaplasia of the reticuloen-

dothelial cells of capillaries as a result of stressful stimuli

- infection, ischemia, necrosis.7 Nonrandom inactivation

of the X-chromosome is established in these tumors,

suggesting their clonal origin and consequently the

presence of a single precursor for the fatty and myeloid

cell elements.8 Myelolipomas are morphologically dif-

ferent from normal bone marrow, showing differences

in cellular composition, cellularity and structure of the

stromal component.8

Myelolipomas originate in the adrenal cortex and

their surface is composed by pseudo-capsule of the

compressed zona glomerulosa and zona fasciculata.2

Yet in 1930, Soos9 classified the myelolipomas into two

categories:

Figure 1. CT image of bilateral myelolipomas

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Type I - tumor formations with yellow-orange color

and predominance of fatty connective tissue, non-

abundant presence of myeloid elements, large quantity

of erythroblasts.

Type II - tumor formations dark red, red-brown in

color, with predominance of bone marrow compo-

nent in which myeloid prevail the erythroblastic ele-

ments.

Myelolipomas are most often incidental findings of

imaging diagnostics performed on other occasions and

are asymptomatic. .

In most cases, the ultrasonography examination shows

suprarenal lesion with a heterogeneous structure, con-

taining hyperechogenic and hypoechogenic loci, corre-

lating respectively with the fat and hematopoietic ele-

ments. Calcifications can also be identified. Abdominal

radiography or intravenous urography can demonstrate

in some cases x-rays negative tumor mass in the adrenal

zone, dislocating the kidney caudally.

On computed tomography scan the myelolipomas

present different percentage of fatty tissue scattered

among low-density hematopoietic elements (usually

with a density 20-30 HU), which are often referred to as

soft tissue elements. MRI is sometimes necessary to es-

tablish the origin of the tumor and to compare the sig-

nal intensity of the formation to that of the liver in order

to distinguish malignant from benign lesion.17

Bone marrow elements are often isointense with

spleen. According to some authors, the presence of fat

density in an adrenal tumor formation on a CT scan

is virtually pathognomonic for mielolipoma18 and there

is no need for further diagnostics.10,11 However, others

suggest the opposite – the presence of fat tissue in

the formation may not be pathognomonic for myelol-

ipoma for two reasons - first - other rare diseases, such

as lipomas and liposarcoma contain such tissue, and

second – there are described cases of adrenal lipomas

and adrenocortical carcinomas, containing small areas

of fat tissue.20,21 We observed histologically confirmed

adrenal lipoma and adenolipoma in our operative ma-

terial, which gives us no reason to suggest “myelolipo-

ma” diagnosis only by imaging examination.

Differential diagnosis includes adrenal liposarcoma,

renal angiomyelolipoma, retroperitoneal lipomas and

others. With the significant predominance of myeloid

tissue, calcifications and hemorrhagic areas, the fatty

component may remain unrecognized. Although most

myelolipomas are presented as isolated adrenal masses,

myelolipoma fields have been described in association

with other pathological changes in the adrenal gland

as adrenocortical hyperplasia, adrenocortical adeno-

mas, adrenocortical carcinomas and endocrinological

dysfunctions, including Addison’s Disease, Conn’s syn-

drome, 21-hydroxylase deficiency, 17-hydroxylase defi-

ciency and ectopic corticotropic production.12 In one of

our cases, there was a hormonal hypersecretion featur-

ing elevated levels of aldosterone and renin in triple

upright position testing, which was normalized on the

sixth month after the operation within normal potas-

sium levels and persistent hypertension. We considered

this abnormal hormonal production as part of the pre-

sented pathology, as the contralateral gland showed no

imaging changes in the follow-up.

The clinical manifestation of myelolipomas may be

acute abdominal pain and hemorrhagic shock due to

rupture and hemorrhage from the formation, or ab-

dominal discomfort as a result of their large size. Spon-

taneous hemorrhage is more typical for tumors with

predominantly myeloid components.16

Comorbidity of myelolipomas with obesity and hyper-

tension are often reported, as in some cases the sug-

gested reason for the hypertension is the compression

of the renal artery.22,23 In our study, one of the female

patients had had a 5-year history of hypertension, and

on the postoperative follow-up the dosage of the ACE-

inhibitor taken as systemic therapy, was reduced, and

the diuretic therapy - stopped. Association with chole-

lithiasis, however, is rare, as the most probable discussed

cause is an accidental coincidence.13 In our case, the

conventional cholecystectomy is the reason for diagnos-

ing myelolipoma in one of the patients. Associated ma-

lignant pathology, such as renal cell cancer23, colon can-

cer2 etc. and simultaneous adrenal and extra-adrenal

myelolipomas have been described.24

Surgical treatment is the main therapeutic approach in

symptomatic and complicated lesions. Symptomatic tu-

Surgical Treatment of Adrenal Myelolipoma

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J Clin Med. 2010; 3(3):24-30

mors, growing in size, greater than 4 cm tumors, show-

ing areas of hemorrhage or necrosis tumors, as well

as those suspected for malignancy, should be removed

surgically. Conventional or endoscopic access may be

chosen depending on the size. Various techniques are

described - conventional and mini-invasive. Our opin-

ion is that when appropriate size is present, mini-in-

vasive technique is feasible for the treatment of these

tumors. In our material there are no intra-or postopera-

tive complications. Advantages, such as lesser hospital

stay, faster recovery and return to normal physical and

social activity at this stage of development of surgical

science and technology are indisputable. As described

by other authors, the laparoscopic approach may have

great results in smaller lesions (between 6-8 cm). Con-

ventional classical methods also have their indications

- both transabdominal and lumbar. Laparotomies using

subcostal or posterior access are also described.25 There

are also opposing views that surgery should not be “lib-

eralized” through using translumbar or endoscopic ac-

cesses.26 Regardless of access, strict postoperative follow-

up is mandatory. There is no described malignancy of

that pathology in literature. The 8-year follow-up period

of one of our patients, has shown no malignization, de-

spite the increase in size and expansive growth on the

imaging diagnostics. The increase in size and suspected

malignancy in imaging examinations, considering the

absence of exact criteria for imaging diagnosis of “mye-

lolipoma”, impose the same principles for removal, such

as the ones in adrenal incidentalomas.

Conclusion

Myelolipomas are rare diseases of the adrenal

glands, most often discovered incidentally in imaging

diagnostics. The indications for their surgical treatment

follow those of the incidentalomas. Mini-invasive

techniques, preformed by experienced endocrine and

laparoscopic team are an effective and feasible way for

their removal.

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