Spontaneous retroperitoneal haemorrhage in a young adult

Abstract

We report a rare case of a primary adrenal cortical malignancy presenting with spontaneous retroperitoneal haemorrhage in a young adult. To the best of our knowledge, this is the thirteenth such case to be reported in the English literature.

Background

In the absence of trauma, retroperitoneal haemorrhage is commonly caused by a ruptured aneurysm of the abdominal aorta or its branches or anticoagulant therapy. Rarely, a primary adrenal cortical neoplasm presents with spontaneous retroperitoneal haemorrhage. We report one such rare presentation of an adrenocortical neoplasm.

Case presentation

A 21-year-old woman was referred to us with a history of sudden onset of pain in the left loin for 1 day and generalised weakness. There was no history of trauma, fever, haematuria, urinary symptoms or any known medical illness. On examination, the patient had severe pallor and tachycardia (120/min), but her blood pressure was maintained at around 126/80 mm Hg. The patient had mild abdominal distension and guarding over the left lumbar region. The left renal angle was tender.

Investigations

Haematological investigation revealed severe anaemia (haemoblobin 5.4 g/dL) with decreased haematocrit (16%) and neutrophilic leukocytosis (13 200/mm³). The coagulation profile, as well as the serum amylase and lipase levels, was normal. Routine urine examination revealed 6–8 pus cells/high power field (HPF) and absence of RBC. The urinary pregnancy test was negative.

Transabdominal ultrasound (US) showed ascites and a large heterogeneous echogenic space occupying lesion (SOL) (9.5 cm×11.8 cm) between the left kidney and spleen abutting both viscera. Absence of internal vascularity was suggestive of a haematoma. A US-guided aspiration from the lesion (a procedure not recommended in the literature), performed before the patient was referred to us, showed altered blood. We performed a contrast-enhanced CT scan of the abdomen which showed a left-sided perirenal collection suggestive of haematoma (figure 1) with ascites and left-sided pleural effusion. The collection displaced the left kidney and the spleen. Possible differential diagnoses included a ruptured splenic or renal vascular aneurysm, an arteriovenous malformation or an adrenal vascular lesion. Conservative treatment with packed RBC transfusion was advised initially. A CT angiography showed a huge, vascular, well-defined solid mass with internal haemorrhage and fat globules in the left suprarenal region with surrounding haematoma extending in the left perinephric space, left paracolic gutter and pelvis, suggestive of angiomyolipoma of the left adrenal with haemorrhage. A functional adrenal neoplasm was ruled out by normal levels of serum potassium, aldosterone and 24 h urinary cortisol and metanephrines.

Figure 1.

Contrast-enhanced CT scan of the abdomen showing a left-sided perirenal collection (arrow).

Treatment

An open left adrenalectomy was performed 2 weeks after presentation. An 8 cm×6 cm sized mass (figure 2), densely adherent to the diaphragm, was found on exploration via a left subcostal incision. After mobilisation of the splenic flexure and the spleen, the mass with the haematoma was dissected from the superior surface of the left kidney (figure 3) and removed en bloc with a cuff of adherent diaphragm. The diaphragmatic rent was closed with interrupted Vicryl sutures. The mass (8 cm×6 cm×4 cm), weighing 180 g, was encapsulated and well-circumscribed (figure 4). The cut surface was greyish yellow with areas of haemorrhage and cystic degeneration.

Figure 2.

Intraoperative picture: left adrenal mass with haematoma (arrow).

Figure 3.

Mass being dissected off the left kidney (arrow indicates tumour mass).

Figure 4.

Resected specimen.

Outcome and follow-up

Postoperative recuperation was uneventful. Histological examination of the resected specimen showed round or polygonal tumour cells with hyperchromatic nuclei, nuclear polymorphism and abundant eosinophilic cytoplasm in a hyalinised stroma (figure 5). Other features were occasional mitotic figures, focal capsular invasion (figure 6), areas of haemorrhage and infarction and focal collections of foamy macrophages and pigment containing histiocytes. There was no vascular invasion. The pericapsular area showed normal adrenal tissue. Reactive lymphadenitis was present. Immunohistochemistry revealed lesional positivity for cytokeratin, synaptophysin and melan-A and negativity for epithelial membrane antigen (EMA), chromogranin A, S-100 and inhibin (figure 7). This was consistent with a diagnosis of an adrenocortical neoplasm of uncertain malignant potential.

Figure 5.

Oval to polygonal cells with vesicular nuclei and mitotic figures (H&E ×40).

Figure 6.

Focal capsular invasion ( H&E ×10).

Figure 7.

Immunohistochemistry.

The patient is doing well during follow-up. A follow-up CECT scan performed postoperatively does not show any evidence of residual locoregional disease or metastasis. She has been referred to the Medical Oncology Unit for consideration of adjuvant therapy.

Discussion

Common aetiologies of spontaneous retroperitoneal haemorrhage in adults include trauma, coagulopathy or anticoagulation therapy, ruptured aneurysm of the aorta, splenic or renal artery and an arteriovenous malformation.¹ Infrequently, the source may be an adrenal haemorrhage (AH), which may be predisposed by trauma, surgery, severe stress or sepsis. Rarely, AH results from a ruptured adrenal neoplasm.

Adrenal angiomyolipomas are rare benign adrenal neoplasms, derived from perivascular epithelioid cells (PEComas). They account for 0.5% of primary adrenal tumours. An abundance of elastin-poor vessels within the tumour makes them prone to haemorrhage. Spontaneous haemorrhage can also occur in the retroperitoneum. Asymptomatic angiomyolipomas less than 4 cm in size can be followed up annually with US or CT scan. However, a symptomatic lesion or lesions >4 cm should be treated by surgery or selective arterial embolisation as they are more predisposed to rupture (tumour size in our case was ∼9×11 cm on preoperative imaging).²

AH from a malignant primary adrenal neoplasm is rarer still. In a retrospective study of 217 patients of AH admitted in the Mayo Clinic College of Medicine from 1976 to 2001, only 14 were associated with adrenal malignancy. Of these, only 4 (1.8% of all cases of AH) had a primary adrenal neoplasm; the remaining 10 had adrenal metastases.³

Adrenocortical carcinoma (ACC) is a rare malignancy with an annual incidence of 1–2/million.^{4 5} It is common in the fifth decade of life and in children less than 5 years.⁴ Presentation in young adults, as in our case, is rare. Both sexes are affected equally. These tumours are usually large (9–13 cm) at the time of presentation with extra-adrenal spread. Half of these tumours are functional, commonly presenting with Cushing's syndrome and virilisation.⁵ Non-functioning tumours present commonly with abdominal pain or pressure symptoms, or less frequently with haematuria, varicocele, palpable abdominal mass or symptoms due to metastasis like malaise, fever and dyspnoea. Adrenal masses may be detected incidentally on imaging for a different pathology. They are called ‘incidentaloma’.

Spontaneous retroperitoneal haemorrhage is a rare presentation of ACC. To the best of our knowledge, this is the 13th such case to be reported in the English literature of primary adrenal cortical malignancy presenting with spontaneous retroperitoneal haemorrhage.^{1 3 6–9} A report from the Centre for Postgraduate Medical Education, Warsaw, mentions 180 patients of adrenal carcinoma, including only four who had retroperitoneal haemorrhage as the presenting feature.⁶

A contrast-enhanced CT scan is the investigation of choice, which typically reveals a heterogeneous mass with irregular margins, central necrosis, extra-adrenal infiltration and high attenuation. Liver and lung metastases are common, and are associated with poor prognosis. There was no evidence of such metastasis in our case. Fine-needle aspiration (FNA) of a suspected ACC is not recommended because of the anticipated tumour spill. In suspected cases of pheochromocytoma, FNA is contraindicated.¹⁰

Patients with intratumoural haemorrhage usually do not present with haemorrhagic shock. Initially, they can be managed conservatively and investigated prior to surgery,³ as was done for our patient. An interval of about a week allows organisation of the haematoma and results in better surgical outcome. However, presentation with haemorrhagic shock may necessitate emergency laparotomy without a formal CT scan and invariably results in suboptimal oncological clearance. There are reports of angioembolisation of bleeding adrenal vessels, but this may cause alteration of the histology and make the diagnosis difficult.^{7 11} In our patient, a selective angioembolisation followed by a repeat imaging study after re-absorption of the haematoma, in the form of a positron emission tomography-CT scan, might have given us a clue to the possibility of a malignant adrenal neoplasm. However, this was not possible because of the lack of facility for angioembolisation in our hospital.

Complete surgical excision results in about 5-year survival rates of 40–50%. This may necessitate en bloc resection of adjacent organs or removal of tumour thrombus from the inferior vena cava under cardiopulmonary bypass.¹² There is level IV evidence¹³ to suggest that locoregional lymphadenectomy improves tumour staging and leads to a favourable oncological outcome. Incomplete excision is associated with median survival of less than a year. In our patient, an en bloc resection of the tumour with the adherent part of the diaphragm was performed. Also, as noted above, there was no evidence of locoregional residual disease on a follow-up CT scan indicating complete tumour removal. Large tumour size and intratumoural haemorrhage, as found in our case, are poor prognostic factors.¹⁴ Dissemination of tumour cells during the vascular accident has been proposed to be responsible for extensive local invasion and metastasis, resulting in poor prognosis.⁶

The role of mitotane as adjuvant therapy for ACC is controversial and has been under evaluation in several randomised clinical trials.¹⁵ A recent retrospective study on 177 patients has shown longer recurrence free survival in patients treated with adjuvant mitotane therapy.¹⁶ Mitotane is not effective in improving survival in patients with retroperitoneal haemorrhage. As a result, newer therapies viz, targeted therapy with Epidermal Growth Factor Receptor Inhibitors, Insulin-like Growth Factor-1 Receptor Inhibitor antiangiogenic factors and tyrosine kinase inhibitors, as well as individualised therapy based on molecular biology of the tumour, are under evaluation.¹⁷

Learning points.

• Spontaneous retroperitoneal haemorrhage can be a rare presentation of an adrenal cortical neoplasm.

• This possibility should be kept in mind, especially in patients with a diagnosis of a perirenal haematoma on imaging.

• In a haemodynamically stable patient, conservative management should be performed at least for a week to allow the haematoma to organise, for better oncological outcome.