Giant adrenal myelolipoma: when trauma and oncology collide

Abstract

Three patients presented some decades after severe traumatic injury with atypical bowel symptoms which were caused by a giant myelolipoma of the adrenal gland. The aetiology of this rare, benign and generally asymptomatic tumour is virtually unknown at present and several hypotheses have been devised. This report describes a possible association between high-energy trauma and the development of giant myelolipomas, further contributing to the hypothesis that severe systemic stress could be an aetiological factor in the development of an adrenal myelolipoma.

Background

Adrenal myelolipoma is a rare benign tumour of the adrenal gland and is composed of fatty and haematopoietic tissues. These tumours are usually found incidentally during routine radiological investigations and nearly always asymptomatic. Most tumours are small and unilateral right sided, but cases of bilateral and giant myelolipomas have been reported.^1–3 The exact aetiology remains unclear and differentiation between other tumours such as adrenal cortical or medullary neoplasms, adenoma, lipoma, angiomyelolipoma and liposarcoma is difficult to make (table 1).

Table 1.

Differential diagnosis of adrenal mass

	Benign	Malign
Hormonally active	Feochromocytoma Ganglioneuroma Adenoma Nodular hyperplasia	Ganglioneuroblastoma Neuroblastoma Adrenal cortical carcinoma Metastasis (eg, breast, kidney, lung, melanoma, etc)
Hormonally inactive	(Angio) Myelolipoma Lipoma Lymphoma Haemangioma Neurofibroma Haematoma/haemorrhage Cysts Teratoma Granuloma Infectious (tuberculosis/fungus/echinococcosis)	Angiosarcoma Liposarcoma Leiomyosarcoma Malignant schwannoma Adrenal cortical carcinoma Metastasis (eg, breast, kidney, lung, melanoma, etc)
Pseudo-adrenal mass
Radiological artefact Lymph gland Accessory spleen Pancreatic or stomach tumour Vascular malformation

Current literature shows a possible correlation between congenital adrenal hyperplasia, Cushing syndrome, hypertension, obesity, cholelithiasis, diabetes mellitus and haematological abnormalities and the development of adrenal myelolipoma.^{4 5} We report three patients with the presentation of a giant myelolipoma after a high-energy trauma in the past.

Case presentation

Case 1

A 60-year-old man presented with a sudden onset of abdominal pain, dysuria and haematuria after a previous period of chronic dull aching on the left side of his lower back with radiating pain to his left shoulder and loin. His medical history stated a car accident 23 years earlier in which the patient suffered several injuries including pulmonary contusion, multiple right-sided rib fractures, retroperitoneal haematoma, hepatic rupture and a lumbar spine fracture. In addition, he was overweight and had cholecystolithiasis.

Recent ultrasonography showed a right-sided retroperitoneal suprarenal mass. Additional CT showed a non-homogenous bilateral tumour mass which consisted predominantly of fatty tissue, most probably of mesenteric origin (figure 1). The laboratory findings showed no abnormal adrenal hormonal activity.

Figure 1.

Bilateral non-homogeneous mass composed of fatty and non-fatty tissues.

An explorative laparotomy was performed wherein two retroperitoneal masses were resected en bloc with the adrenal glands without injury to the kidneys. Histopathological examination of the right mass (8.5 cm) revealed a tumour which consisted completely of fat cells and the left mass (12 cm) a tumour consisting of mature fat and haematopoietic cells. The diagnosis of adrenal myelolipoma was made. The hospital stay was further uneventful and the patient recovered completely.

Case 2

A 43-year-old man presented with a dull pain in the right-upper abdominal quadrant, haematuria and weight loss for the past few months. His medical history stated a motorcycle accident 21 years earlier in which the patient suffered multiple right-sided rib fractures, multiple lumbar spinal fractures, pulmonary, pancreatic, hepatic and right renal contusion and a large retroperitoneal haematoma between the inferior vena cava and the right kidney. An emergency laparotomy was performed in which a massive retroperitoneal haematoma was seen with no signs of active bleeding or adrenal injury.

Given the current symptoms a CT scan was made which revealed a 20 cm large right-sided retroperitoneal mass with close relation to the liver (figure 2) as well as a mild hydronephrosis of the right kidney (figure 3). The laboratory findings showed no abnormal adrenal hormonal activity.

Figure 2.

The tumour compromises the right kidney and causes mild hydronephrosis.

Figure 3.

Both pictures showing a close relation to the liver. In patient 2 (left picture) a partial liver resection was performed but investigation of the specimen showed no involvement of the liver. In patient 3 (right picture) both tumour as gallbladder were removed.

After an inconclusive biopsy an explorative laparotomy was performed and the tumour was excised en bloc with the adrenal gland and segment V and VI of the liver. Histopathological examination showed a large encapsulated mass of 21×21 cm which consisted of mature fat cells and haematopoietic elements with haemorrhagic and necrotic parts with iron deposition (figure 4). There was no ingrowth in the liver. These findings matched the diagnosis adrenal myelolipoma. The hospital stay was further uneventful and the patient recovered completely.

Figure 4.

Microscopic view of the adrenal mass. (A) Normal adrenal cortical cells, (B) mature adipocytes, (C) haematopoietic cells, including erythroblasts, myeloid cells and megakaryocytes and (D) iron deposits.

Case 3

A 48-year-old man presented with dyspepsia with bloating, belching and pyrosis for the past few months. His medical history stated a severe trauma 27 years earlier in which the patient suffered right-sided rib fractures, a pneumothorax and thoracic spine fractures.

With regard to current symptoms the patient was analysed by an internist who performed ultrasonography to exclude cholecystolithiasis. This showed, in addition to cholecystolithiasis, a right-sided adrenal mass, suspicious for adrenal incidentaloma. The patient was referred to our hospital and an additional CT scan showed a 11.5 cm mass with a density equal to fat and a narrow relation to the liver (figure 3). Again, laboratory findings showed no abnormal adrenal hormonal activity.

A laparotomy was performed and the tumour was resected en bloc with the adrenal gland combined with a cholecystectomy. Histopathological examination showed a 14 cm mass composed of mature fat cells and haematopoietic cells, suspicious for myelolipoma. Again the specimen contained haemorrhagic parts and iron depositions (figure 5). The gallbladder showed mild reactive inflammation, appropriate to the diagnosis cholecystolithiasis. The hospital stay was further uneventful and the patient recovered completely.

Figure 5.

Macroscopic view of the adrenal mass in patient 3. Signs of haemorrhage are seen in the central part of the tumour. On the left (arrow) normal adrenal tissue is visible.

Outcome and follow-up

All patients had an uneventful hospital stay and recovered completely. Outpatient check afterwards showed complete relief of bowel symptoms.

Discussion

Our case series contributes to the hypothesis of a relationship between high-energy trauma and the development of adrenal myelolipoma. This relationship is important because it can provide guidance at an early diagnostic stage. When patients have a medical history of a high-energy trauma, an adrenal myelolipoma should certainly be considered.

Gierke⁶ was the first to describe a tumour of the adrenal cortex which consisted of mature adiposites and haematopoietic cells in 1905. In 1929, Oberling⁷ introduced the term myelolipoma. It is a rare, benign and hormonally inactive tumour, incidentally found during autopsies. The exact incidence is unknown but based on autopsy studies estimated at 0.2%.⁴ However, through improving radiological imaging techniques myelolipomas are increasingly reported as incidental findings and can be as high as 10%.^{2 4}

Adrenal myelolipoma has been associated with congenital adrenal hyperplasia, Cushing syndrome, hypertension, obesity, cholelithiasis, diabetes mellitus and haematological abnormalities in previous reports.^{4 5} However, the complete aetiology of myelolipoma remains unknown. The most consistent theory is differentiation of undifferentiated mesenchymal cells to myeloid and lipoid tissues. The presence of adrenal haematopoietic tissue can be explained embryonically because the adrenal cortex and bone marrow originate from the same mesenchymal tissues. This cell differentiation can hypothetically be activated by systemic stress from chronic illness, necrotic tissue or high-energy trauma.⁸ This theory is supported by animal studies where myelolipomatous changes were seen after injecting necrotic tissues in rats.⁹ Furthermore, recent studies have shown significant changes in bone marrow haematopoiesis after severe trauma.^{10 11} Other theories include bone marrow embolisms, extramedullary haematopoiesis and bone marrow metaplasia. The patients in our report had experienced major traumas which could have caused direct or indirect adrenal injury by inducing systemic stress.

Traumatic adrenal injury is seen in less than 5% of blunt abdominal trauma and is a sign of severe trauma because of its retroperitoneal location within Gerota's fascia.¹² There are various theories about the mechanism of traumatic adrenal injury. First, acute rise of intra-adrenal venous pressure due to compression of inferior cava vena during abdominal impact could cause adrenal injury. This could explain why the right gland is involved more often, because it drains directly into the inferior vena cava whereas the left gland drains into the renal vein. Second, the adrenal gland is crushed between the spine and other surrounding organs like the spleen or liver. And finally, adrenal injury could be caused by a deceleration force which tears the adrenal arterioles. The extent of the injuries in our patients, combined with the pathological finding of iron pigments supports these theories of a possible traumatic adrenal injury, leading to differentiation of myelolipomatous adrenal tissue over time.

The presentation of adrenal myelolipoma is usually asymptomatic. A small percentage of patients presents with abdominal symptoms, flank pain or haematuria. Even life-threatening haemorrhagic shock has been described in myelolipomas larger than 10 cm.⁸ The symptoms appear to be caused by mechanical compression or tumour necrosis or haemorrhage. Two patients in this report presented with symptomatic tumours, the third patient had symptoms that most likely were caused by cholecystolithiasis.

CT is considered the best imaging technique/modality to confirm the diagnosis.^{13 14} On CT it is visible as a well-circumscribed mass composed of predominantly fatty tissue with foci of myeloid tissue and gives a range of attenuation from −30 to −115 Hounsfield units (HU). After contrast administration enhancement is seen in the myeloid parts of the tumour. In case of haemorrhage some parts show higher or lower HU depending on the age of the bleeding and may also contain calcification deposits. Owing to this variability, making a reliable diagnosis is often difficult. As a differential diagnosis, retroperitoneal liposarcoma, adrenal adenoma, adrenal carcinoma or metastasis and retroperitoneal lipoma should also be considered (table 1). Fine needle biopsy is not useful in the workup of incidentally discovered adrenal masses and can be potentially hazardous in terms of bleeding and tumour rupture.¹⁵

The treatment of adrenal incidentaloma remains controversial. Most reports suggest surgical resection in case of symptomatically or hormonally active adrenal tumours and tumours over 4–6 cm in size because of a strong correlation with malignancy.^{4 16–18} However, myelolipomas are hormonally inactive and commonly larger than 6 cm. In general there is no relationship between the size of the tumour and symptoms or risk of life-threatening haemorrhage.^{4 16 19 20} Instead of depending on size, the treatment of adrenal myelolipoma should be individualised based on the clinical course, radiological features and histopathological findings. Conservative management could be advocated in asymptomatic patients with a tumour <10 cm. In those cases regular follow-up after 1–2 years is advised due to the risk of interval growth.^{4 16} Surgery should be considered the gold standard in symptomatic patients’ disease and when the diagnosis is unclear.

This study has some limitations that need to be addressed. First, none of the patients had a CT scan during trauma care since a CT scan was not a standard imaging technique in the early 80s. Therefore, the adrenal myelolipoma could already have been present at the time of trauma. However, one patient received an emergency laparotomy which showed no adrenal injury or abnormal masses. Also, the ultrasonography performed during trauma screening showed no signs of adrenal injury in the two remaining patients. First it is important to emphasise that ultrasound can only detect lesions >2 cm and mainly right-sided adrenal masses. Second, although very unlikely, the iron pigments and necrosis seen on pathological examination could have been caused by spontaneous haemorrhage rather than traumatic adrenal injury.

In conclusion, high-energy trauma could be considered an important factor in the development of adrenal myelolipoma. More case series or retrospective cohort studies of patients with adrenal myelolipomas are needed to clarify this association. A previous medical history of a severe trauma can provide guidance at an early diagnostic stage when confronted with patients with an adrenal mass. Watchful waiting is an option provided when life-threatening diagnoses are excluded.

Learning points.

• High-energy trauma could be considered a factor in the development of adrenal myelolipoma.

• The presentation of adrenal myelolipoma is usually asymptomatic.

• Conservative therapy is advocated in patients with asymptomatic adrenal myelolipoma <10 cm.