Massive hemorrhage and infarction complicating focal nodular hyperplasia of the liver

Abstract

Background

Spontaneous infarction or hemorrhage of focal nodular hyperplasia (FNH) has rarely been reported in the literature.

Case outline

A 43-year-old woman presented with upper abdominal pain and anemia. CT scan showed an enormous perihepatic hematoma. Trisegmentectomy successfully dealt with the problem.

Conclusion

Although conservative management of FNH is often adopted, this case illustrates that these lesions can undergo massive bleeding.

Introduction

Focal nodular hyperplasia (FNH) is a hepatic lesion that most frequently affects otherwise healthy women of reproductive age. The nature of FNH has variably been described as neoplastic, reactive or hamartomatous; the predilection for young adult women suggests that hormones, especially estrogen, may be important in its pathogenesis ¹,²,³. Alternatively, FNH may represent a hyperplastic response to a pre-existing vascular anomaly ⁴.

Clinically, FNH must be distinguished from other mass-forming lesions in the liver. The major differential diagnoses in patients of this age and gender are hepatic adenoma and the fibrolamellar variant of hepatocellular carcinoma, although the latter is rare. Hepatic adenoma is epidemiologically associated with oral contraceptive (OC) use and has a tendency to undergo catastrophic intralesional hemorrhage, making prompt diagnosis and intervention essential. By contrast, FNH has an inconstant correlation with OCs, and hemorrhagic complications are reportedly rare ¹,². Expectant management has therefore been recommended when the diagnosis is certain ⁵,⁶.

We describe the clinical, radiologic, and histomorphologic features of a case of FNH complicated by massive intralesional hemorrhage and infarction in a woman who had taken OCs for many years.

Case report

A 43-year-old white female presented with a 3-hour history of dull, nonradiating pain in the right upper quadrant of the abdomen. She denied any constitutional symptoms or history of trauma. The patient was gravida 2, para 2. She had undergone tubal ligation 3 years earlier and had been taking oral contraceptives for 15 years before that time.

Physical examination showed a woman in obvious discomfort, lying in a fetal position. She was afebrile and anicteric. The blood pressure was 150/80, heart rate 90/min and respirations 15/min. The right upper quadrant and epigastrium were moderately tender but there was no sign of peritonitis. No mass or organomegaly were palpable. Rectal examination was normal and the stool was negative for blood. The extremities were warm and well perfused.

Admission laboratory studies revealed the following: white blood cells count (WBC) 6, 7/10 9/L, hemoglobin 9.5 g/dl, hematocrit 27%. Electrolytes, blood urea nitrogen (BUN), creatinine and amylase were normal. Total bilirubin was 1.8 mg/dl (normal 0.2±1.3 mg/dl), with a normal direct bilirubin of 0.4 mg/dl (normal 0±0.4). While the alkaline phosphatase was normal at 110 U/L (normal 38 ±126), AST and ALT were elevated at 155 U/L (normal 15±46) and 129 U/L (normal 7±56), respectively. PT was slightly increased at 15.1 s, PTT was normal at 27 s.

A working diagnosis of biliary colic prompted an abdominal sonogram, which revealed a large hematoma along the right side of the liver, a normal gall bladder, and a nondilated biliary tree. Computed tomography (CT) showed a subcapsular hematoma measuring 16×15×7 cm along the lateral margin of the right hepatic lobe (Figure 1). No free intraperitoneal fluid was seen.

Figure 1. .

CT with intravenous contrast shows a huge subcapsular hematoma in the right lobe of the liver. Note that no focal lesions are identified in the liver.

The patient was thought to have a hepatic adenoma complicated by massive hemorrhage and she was taken to the operating room for laparotomy. No free intraperitoneal blood was encountered, but there was a large subcapsular hematoma involving the entire right lobe of the liver and extending to segment 4. A trisegmentectomy was performed in the usual fashion, using a clamp-and-crush technique to divide the hepatic parenchyma. Blood loss was estimated at 2000 ml, and half of this was autotransfused. She received an additional 2000 ml crystalloid intra-operatively. Urine output was adequate and the patient remained stable throughout the procedure.

The postoperative course was uncomplicated, and she was discharged in stable condition on the fifth postoperative day. She remained well during the ensuing 18 months of follow-up.

Pathologic findings

The resected right hepatic lobe contained a subcapsular intraparenchymal hemorrhagic mass measuring 6.0×5.5×4.5 cm. Focally, there was a peripheral 0.7-cm rim of slightly yellow tissue. Although there was no capsule, subtle differences in tissue texture made it possible to distinguish the lesion from the surrounding hepatic tissue, which appeared congested but non-cirrhotic. There was no recognisable ‘central scar’, although this may have been obscured by extensive hemorrhage.

Microscopic examination showed a large blood clot that had undergone near-total hemorrhagic necrosis in the centre of the mass and this obscured the histomorphology of the lesion. Numerous sections of the centre of the lesion, as well as its interface with adjacent liver, were stained with hematoxylin and eosin (H & E); a reticulin stain was used to highlight the underlying architecture. H & E-stained sections of non-necrotic liver at the periphery of the lesion confirmed that there was no capsule; there was a large hematoma at the centre (Figure 2). While the interface with surrounding liver tissue was subtle on the H & E-stained sections, a reticulin stain showed the lesion to have a pushing margin and an architecture that was distinctly different from the adjacent liver, yet typical of FNH ⁷ (Figure 3). At the margin, there were small preserved nodules of hepatocytes that appeared to be cytologically normal. There were numerous central venules and a few preserved fibrous septa containing proliferating bile ductules (Figure 4). There was no bile stasis in the lesion, although there was some steatosis consistent with the grossly observed pale yellow color.

Figure 2. .

Focal nodular hyperplasia. Expansile proliferation of hepatocytes with a central hematoma (arrow). No capsule is seen. Original magnification, ×4; hematoxylin and eosin stain.

Figure 3. .

Focal nodular hyperplasia. There is a pushing margin (arrows) with compression of adjacent normal hepatic parenchyma. Although there is a distinctly different reticulin pattern, there is no capsule. Original magnification, ×200; reticulin stain.

Figure 4. .

Focal nodular hyperplasia. A septum of loose, inflamed fibrous tissue contains proliferating bile ductules. Original magnification, x200; hematoxylin and eosin stain.

Discussion

Focal nodular hyperplasia, a benign hepatic lesion, can occur in either sex and at any age, but is most frequently seen in adult women of reproductive age ⁶,⁸,⁹. Classically, FNH occurs in an otherwise normal liver and forms a multinodular nonencapsulated mass with pushing margins and a central fibrous scar that contains numerous blood vessels sprouting from a central feeding vessel ⁴,⁸. Variants include a multifocal distribution, which occurs in 20% of cases ⁵,⁶. Examples with a typical microscopic morphology but without a grossly evident central scar are another variation. In this case, we could not see a central scar, although it may have been obscured by hemorrhage.

Microscopically, FNH is formed by a confluent mass of many small nodules of benign-appearing hepatocytes partially or completely surrounded by fine bands of fibrous tissue containing proliferating bile ductules and vessels. While lacking a capsule, it grows in an expansile manner and compresses the adjacent hepatic parenchyma which may (as in this case) exhibit a pattern of sinusoidal congestion ⁴,⁷,⁸. Although the central scar is not always grossly evident in FNH, these microscopic features are invariable and distinguish the lesion from hepatic adenoma and carcinoma. These latter neoplasms consist of a uniform population of hepatocytes only; bile ductules and portal triads are never seen ⁷,⁸.

We believe that this patient had FNH with massive hemorrhage, a complication more frequently described in hepatic adenoma. In contrast to FNH, adenomas have a well-defined capsule, consist of hepatocytes only, lack proliferating bile ductules and usually exhibit bile stasis because there is no connection with the biliary system.

The etiology of FNH is unclear. While the demographic features suggest that sex hormones may have a role in the development or progression of FNH, oral contraceptives are much more clearly associated with hepatic adenoma. Some investigators have speculated that the primary lesion of FNH is a vascular abnormality that induces a reactive hyperplasia of hepatocytes and bile ducts ⁴. Associated hepatic hemangiomas are seen in 14–23% of cases ⁶,¹⁰,¹¹, and other associated vascular anomalies have also been described ¹². A recent study using modern molecular biology techniques has shown that most cases of FNH are due to a monoclonal proliferation of hepatocytes, a feature shared with hepatic adenoma and carcinoma ¹³. This finding suggests that the proliferative stimulus affects a single ‘path’ of tissue-determined stem cells that have a common lineage, but it does not distinguish whether FNH is reactive or neoplastic in nature ¹⁴. Benign behavior is the rule for cases that are correctly diagnosed on the basis of the criteria originally outlined by Edmondson ¹⁵ and similarly described by others ¹,².

Before embarking on definitive treatment, it is important to distinguish FNH from other mass lesions of the liver. Hepatic adenoma, hemangioma, the fibrolamellar variant of hepatocellular carcinoma and metastatic tumors can all occur in young adults; hemangioma and FNH are the commonest of these lesions ¹,⁵,⁹. With combined used of clinical presentation, ultrasound, CT scan, and nuclear scintigraphy (i.e. 99mTc-sulfur colloid scan), an accurate diagnosis can be made in 70–100% of cases ⁵,¹⁰,¹⁶.

The most unusual pathological aspect of the example of FNH described in this report was the large intralesional hematoma and near-total coagulative necrosis, features much more commonly seen in hepatic adenoma. Partial infarction has been described in a few cases of unequivocal FNH ¹,⁷,¹⁷,¹⁸. This case demonstrates that FNH, like hepatic adenoma, can occur in an otherwise healthy young adult without a prior history of malignancy or liver disease and can present with the acute onset of abdominal symptoms due to intralesional hemorrhage and infarction.

Conservative management of FNH has been recommended if the clinical picture and needle biopsy findings are consistent with the diagnosis ⁵,⁶. Onset of symptoms, enlargement, change in consistency, or bleeding are indications for active management. Resection of benign liver tumors is safe and is associated with a mortality rate lower than 1% ⁵,⁹,¹⁰. This fact is particularly true with FNH, which can often be excised by a wedge resection because of its frequently peripheral location. For unresectable FNH or when resection is contraindicated, embolisation may result in involution ¹⁹.

In conclusion, FNH is a benign, highly vascularised pseudotumor. When its diagnosis is clearly established and serial examinations do not demonstrate much growth, expectant management is generally safe. On the other hand, conservative management is not completely without risk as these tumors may rupture.