Hepatic Adenoma and Focal Nodular Hyperplasia: Differential Diagnosis and Treatment

The diagnosis of benign hepatic tumors as hepatic adenoma (HA) and focal nodular hyperplasia (FNH) remains a challenge for clinicians and surgeons. The importance of differentiating between these lesions is based on the fact that HA must be surgically resected and FNH can be only observed. A series of 23 female patients with benign liver tumors (13 FNH, 10 HA) were evaluated, and a radiologic diagnostic algorithm was employed with the aim of establishing preoperative criteria for the differential diagnosis. All patients were submitted to surgical biopsy or hepatic resection to confirm the diagnosis. Based only on clinical and laboratory data, distinction was not possible. According to the investigative algorithm, the diagnosis was correct in 82.6% of the cases; but even with the development of imaging methods, which were used in combination, the differentiation was not possible in four patients. For FNH cases scintigraphy presented a sensitivity of 38.4% and specificity of 100%, whereas for HA the sensitivity reached 60% and specificity 85.7%. Magnetic resonance imaging, employed when scintigraphic findings were not typical, presented sensitivities of 71.4% and 80% and specificities of 100% and 100% for FNH and HA, respectively. Preoperative diagnosis of FNH was possible in 10 of 13 (76.9%) patients and was confirmed by histology in all of them. In one case, FNH was misdiagnosed as HA. The diagnosis of HA was possible in 9 of 10 (90%) adenoma cases. Surgical biopsy remains the best method for the differential diagnosis between HA and FNH and must be performed in all doubtful cases. Surgical resection is the treatment of choice for all patients with adenoma and can be performed safely. With the evolution of imaging methods it seems that the preoperative diagnosis of FNH may be considered reliable, thereby avoiding unnecessary surgical resection.     

Benign liver tumors

With widespread use of ultrasonography, fortuitous discovery of benign tumors of the liver raises the question of surgical management in a large number of young subjects. In order to obtain certain diagnosis and determine appropriate management, avoiding unnecessary surgery for asymtomatic tumors with a benign evolution or inversely delaying surgical treatment of malign lesions, the surgeon must be aware of the different features of benign tumors, their expected course, and the capacity of imaging techniques to provide positive diagnosis. Diagnosis: The most frequent benign tumors found in the liver are hemangiomas or angiomas. Lesions measuring less than 3 cm are often fortuitous discoveries at ultrasonography,: a typical homogeneous hyperechogenic zone is sufficient for diagnosis. There are two situations where diagnosis can be difficult: atypical hypoechogenic or large remodeled lesions, hepatopathy in the context of a malignant disease. Certain diagnosis can generally be achieved with MRI. Cystic lesions of the liver are generally biliary cysts. Ultrasonography is the examination of choice and is usually sufficient for diagnosis. In certain cases there is a differential diagnosis with a young hydatid cyst or a cystadenoma although cystadenomas are very rare tumors usually observed in symptomatic middle-aged women. In case of atypical images, cystic or necrotic malignant tumor should also be entertained as a possible diagnosis. Liver cell tumors include adenomas and focal nodular hyperplasia (FNH). Adenomas related to estrogen-progestogen treatment can lead to two potentially fatal complications (intratumor or intraperitonial hemorrhage or more rarely degeneration to hepatocellular carcinoma), justifying systematic resection. FNH is on the contrary ten times more frequent than adenoma; observed independently of hormone replacement therapy, it does not lead to complications and does not require treatment. It is crucial to establish the diagnosis of noninvasive FNH in order to avoid unnecessary surgery. MRI provides 80% and 95% specificity. If the imaging work-up evidences an atypical FNH and/or a non-tumor anomaly, histological proof is needed. As the performance and risk of percutaneous biopsy remain to be assessed, we prefer laparoscopic large needle biopsy with extemporaneous pathology examination. Imaging cannot provide positive diagnosis of adenoma. Treatment: The rule is abstention from surgery for confirmed diagnosis of angioma, biliary cyst or asymptomatic FNH, irrespective of the size. For symptomatic patients, it is essential to establish positive diagnosis initially and determine the relationship between the signs and symptoms and the tumor before deciding on adapted surgery (fenestration, enucleation, hepatectomy). Surgery may be necessary for cystadenomas, adenomas or cases of doubtful diagnosis, keeping in mind the risk of morbidity and mortality associated with hepatic surgery for benign tumors.     

Diagnose und Differenzialdiagnose benigner Lebertumoren und tumorähnlicher Läsionen

Benign liver tumors and tumor-like lesions cover a broad spectrum of differential diagnoses, varying from dysontogenetic cysts to pseudolesions. Focal nodular hyperplasia, adenoma and regenerating nodules play a major role in clinical practice. Based on imaging findings, these lesions can be classified as cystic or solid, solitary or multiple, and hyper- or hypovascular. Haemangioma, FNH, steroid-associated adenoma, cystadenoma and echinococcus cysts can be reliably diagnosed using imaging techniques. The same is true for pseudolesions, which are found in particular on dynamic computed tomography. Other entities such as adenoma in cirrhotic livers, angiomyolipoma, regenerating nodules or Echinococcus alveolaris cannot be safely diagnosed by imaging and require biopsy. Morphological and functional characteristics of the most common lesions in the different imaging modalities will be discussed. Where possible, a diagnostic strategy will be presented.     

Benign and solid tumors of the liver: relationship to sex, age, size of tumors, and outcome

From 1983 through 1997, our center diagnosed 130 cases of benign neoplasms: 27 with focal nodular hyperplasia (FNH), 25 with hepatic adenoma, 71 with cavernous hemangioma, and seven with mixed tumors of different diagnoses. Most often these lesions were seen in females [female-to-male ratio (f/m): 5.5/1]. Hepatic adenomas and mixed tumors were seen exclusively in females and FNH predominantly in females (f/m: 26/1). Hemangiomas, however, were not uncommon in men (f/m: 52/19) relative to the other tumors (P < 0.001). Furthermore patients with hemangioma were older (mean age: 49 years) whereas patients with hepatic adenoma, FNH, and mixed tumors were often younger (mean age: 33, 35, and 44 years respectively; P < 0.004). Oral contraceptive steroid use was related by 21 of 25 patients (84%) with hepatic adenoma, 22 of 26 (85%) females with FNH, five of seven (71%) females with mixed tumors, and 10 of 52 (19%) patients with hemangioma. Ninety-five of the 130 patients (73%) had one or more symptoms. There was no statistically significant correlation between symptoms and the size of the lesion, the final diagnosis, and whether there were solitary or multiple masses. Three of 25 (12%) with hepatic adenoma presented with rupture, and one of 27 (4%) with FNH had such a consequence. None of the hemangiomas presented with rupture or progressed to such a state. One patient with hepatic adenoma (4%) had a focus of malignancy. Surgical removal of benign tumors was performed in 82 of 130 patients (63%), and there was one operative mortality (1.2%) in a patient who had a caudate lobe FNH. The types of surgical procedures included segmentectomy (62%), lobectomy (34%), and trisegmentectomy (4%). In two of 84 patients who had undergone laparotomy resection was not technically possible. Resection is recommended in all cases of hepatic adenoma because of fear of rupture or associated focus of malignancy. FNH was not observed to undergo a malignant transformation and will rarely rupture. Surgery is only recommended for symptomatic hemangioma, and size of the lesion is not a criterion for excision.     

Spontaneous rupture of hepatic focal nodular hyperplasia--a rare cause of acute intraabdominal bleedingf

Benign hepatic mass lesions are rare. Haemangioma, focal nodular hyperplasia and hepatocellular adenoma represent the most common ones. For the reason of serious clinical complications and potential malignant transformation of hepatic adenoma, surgical resection is the therapy of choice. Unlike adenoma focal nodular hyperplasia is mostly asymptomatic and rarely causes severe complications. We report on a spontaneous rupture and life-threatening intraperitoneal haemorrhage of a large, asymptomatic FNH, where surgical resection was indicated. Within three month after hepatic resection and after termination of oral contraceptives almost complete regeneration of liver tissue and dramatic regression of a second FNH lesion was apparent. Although haemorrhage of hepatic FNH is extremely rare, this case highlights the small risk of rupture in large lesions.     

Magnetic resonance imaging of hepatic neoplasms.

Excellent diagnostic images of the liver can now be obtained with magnetic resonance imaging (MRI) because of new imaging techniques. The flow void phenomenon allows excellent anatomic detail of the liver. Morphologic features, comparison of tumor signal to normal parenchymal signal, and tumor behavior in various pulse sequences help to define liver tumors. The MRI characteristics of primary hepatomas, cavernous hemangiomas, hepatic cysts, liver adenomas, and focal nodular hyperplasia are among the hepatic lesions described. In most instances, MRI helps in differential considerations and in some cases will provide a specific diagnosis.     

Extra-axial cavernous hemangiomas involving the dural sinuses

Extra-axial cavernous hemangiomas are rare lesions previously associated with unacceptable mortality and morbidity rates that precluded surgical resection. The authors analyze the clinical presentation, surgical results, and histology of eight intrasinus cavernous hemangiomas: six located in the cavernous sinus, one in the petrosal sinus, and one in the torcula. Magnetic resonance imaging is the best radiographic test for surgical planning. Successful tumor removal was achieved in six cases with no mortality and low morbidity. In the remaining two patients, only subtotal resection was achieved because of massive hemorrhage in one and the misdiagnosis of a pituitary adenoma leading to a transsphenoidal approach in the other. For hemangiomas arising within the cavernous sinus, extradural removal of the sphenoid bone facilitated preservation of the neurovascular structures. Since the clinical and histological characteristics of these lesions are distinct from intra-axial cavernous hemangiomas, a more appropriate term may be "sinus cavernoma" to indicate that these lesions are primarily intrasinus in origin.     

肝脏局灶性结节增生的诊断和治疗(附21例报告)

目的：探讨肝脏局灶性结节增生(focal nodular hyperplasia，FNH)的诊断和治疗经验。方法：回顾性分析两所医院1996年4月至2001年4月5年间收治并经病理证实的21例FNH的临床、影像学和病理学资料。结果：FNH术前正确诊断率较低(19．0％)，该病多见于中、青年(50岁以下占81．O％)，多无症状(57．1％)，多无乙型肝炎病毒感染(95．2％)，肝功能和AFP检查均正常(100％)；彩色多普勒检查发现80．0％(12／15)的病灶有血管通过，66．7％(10／15)的病灶血流丰富；CT动态扫描增强后60．0％(9／15)早期显著强化，60．0％(9／15)强化均匀；MRI检查强化后64．3％(9／14)早期明显强化，57．1％(8／14)信号均匀，35．7％(5／14)的病灶出现中央疤痕。本组行手术切除20例，1例未经任何治疗。结论：FNH在临床和影像学上均有一定特征，综合分析临床与多种影像学资料可提高正确诊断率。诊断FNH明确者不需外科治疗。     

Diagnostic Approach to Hepatic Mass Lesions and Role of Immunohistochemistry

This review provides an overview of various hepatic mass lesions and a practical diagnostic approach, including most recent immunohistochemical stains used in clinical practice. A wide variety of benign and malignant lesions present as hepatic masses, and the differential diagnosis varies. In cirrhotic liver, the commonest malignant tumor is hepatocellular carcinoma (HCC), which needs to be differentiated from macroregenerative nodules, dysplastic nodules, and other tumors. The differential diagnosis of lesions in noncirrhotic liver in younger patients includes hepatic adenoma (HA), focal nodular hyperplasia (FNH), HCC, and other primary hepatic neoplasms and metastases. In older populations, metastases remain the most common mass lesions.     

Enucleation of giant hemangiomas of the liver. Technical and pathologic aspects of a neglected procedure.

Cavernous hemangiomas are the most common benign tumors of the liver. Giant cavernous hemangiomas, defined as those larger than 4 cm in diameter, can reach enormous proportions. Newer imaging modalities, although often demonstrating characteristic features that strongly suggest the diagnosis, should not be augmented by biopsy because of the risk of hemorrhage. Elective surgical resection may be indicated for symptomatic giant lesions and for those with an atypical appearance where the diagnosis is in doubt. Between October 1986 and May 1991, we treated 10 patients with giant hemangiomas by enucleation or enucleation plus resection. Median operative blood loss was 800 mL (range, 200 to 3000 mL). One patient required reoperation for control of postoperative hemorrhage. Detailed pathologic examination has demonstrated an interface between hemangiomas and the normal liver tissue that allows enucleation. Enucleation is an underused procedure that if carefully performed allows resection of giant hemangiomas with a reduced blood loss and the preservation of virtually all normal hepatic parenchyma.     

Hepatic cysts: diagnosis and management

Cystic lesions of the liver are common and usually benign. The most frequent lesion is simple hepatic cyst: typical imaging findings make their diagnosis easy and they require no treatment. Complicated hepatic cysts (i.e., compression, hemorrhage, infection) have more variable imaging findings making diagnosis more difficult; they may evoke other diagnoses. Asymptomatic hepatic cysts do not require any treatment or follow-up. Symptomatic cysts may benefit from simple follow-up or may be treated by laparoscopic fenestration or alcohol sclerotherapy. The differential diagnosis of complicated hepatic cysts includes cystadenoma, cystadenocarcinoma, hydatid cyst, or cystic metastasis; surgical resection is usually indicated for these lesions.     

Splenic cysts and tumors: diagnosis and management

Cysts and tumors of the spleen are rare and are often discovered fortuitously. They are most often asymptomatic but may present with abdominal pain in the left upper quadrant. Splenic cysts are far more common than solid lesions; true cysts must be differentiated from pseudocysts of the pancreas and from cystic degeneration following splenic contusion or infarction. Cysts may be congenital (epidermoid cysts), infectious (abscess or hydatid cyst), or neoplastic (lymphangioma or angioma with tumor necrosis). Diagnosis can usually be established with the clinical context and imagery (ultrasound, CT, MRI). Surgery should be avoided for angiomas and pseudocysts. Spleen-conserving surgery is indicated for large symptomatic epidermoid cysts. Splenectomy is often required for hydatid cysts and tumors. Of the solid tumors, hemangiomas and lymphangiomas often have a characteristic fleshy appearance. For other solid tumors, whether benign or malignant, imaging may give some clues to the diagnosis, but diagnostic certitude often requires pathologic examination of the piece. Needle biopsy is contraindicated because of the risk of bleeding. Resection should be as limited as possible in order to avoid the risks of total splenectomy (overwhelming sepsis, thrombosis).     

Telangiectatic variant of hepatic adenoma: clinicopathologic features and correlation between liver needle biopsy and resection

Telangiectatic hepatic adenoma (THA) is a benign neoplasm treated by resection. The role of liver needle biopsy in identifying THA before resection has not been evaluated. We identified 55 patients who have undergone resection for hepatic adenoma (HA), THA, or focal nodular hyperplasia (FNH) after needle biopsy. Needle biopsies and resections were evaluated for the following: (1) abortive portal tracts; (2) sinusoidal dilatation; (3) ductular reaction; (4) inflammation; (5) aberrant naked vessels; (6) nodules, fibrous septa, and/or central stellate scar. THA diagnosis was made if the lesion had the first 4 criteria and lacked criterion 6. Most patients (36 of 55), including patients with THA (12 of 16), had multiple lesions (0.2 to 14.4 cm). Patients with THA showed no difference in age, body mass index, prevalence of diabetes or glucose intolerance, or presence of oral contraceptive (OCP) use from patients with HA or FNH, but patients with THA had longer periods of OCP use than patients with HA. Thirty-one percent of THAs had tumor hemorrhage. Of sampled THAs, 27% showed steatosis compared with 76% of sampled HAs (P<0.05). All resected HAs and FNHs were correctly diagnosed on needle biopsy. Of 14 patients with resected THA, 3 histologic patterns were noted on needle biopsy: (1) All THA criteria and naked vessels were present in 6 patients (43%). (2) Consistent with HA: naked vessels only were present in 4 patients (29%). (3) Suggestive of THA: some but not all THA criteria were present in 4 patients (29%). No needle biopsy of a THA was misdiagnosed as FNH. Although evaluation of resection specimens is the gold standard for diagnosis of THA, liver needle biopsy is a useful diagnostic tool that leads to adequate treatment.     

肝脏局灶性结节性增生20例的诊断和治疗

目的 探讨肝脏局灶性结节性增生（Focal nodular hyperplasia,FNH）的诊断和治疗。方法 回顾性分析本所1996年5月至1999年5月经手术和病理学检查证实的20例FNH的临床、影像、手术及病理学资料。结果 80％（16／20）FNH为45岁以下青壮年,70％（14／20）无症状,AFP均为阴性,15％有肝炎感染证据。85％（11／13）在彩色超声见到特征性的粗大中央血管（1－3mm);CT动态扫描75％（12／16）早期显著增强,MRI检查83％（10／12）增强后早期明显强化,20例病人共28个FNH病灶,93％（26／28）病灶小于5cm、无包膜,20例均经手术切除病灶,无手术死亡及严重并发症。结论 FNH在临床及影像学上有一定特征,如能在术前获明确诊断则可密切随访、暂不手术。     

Focal nodular hyperplasia and hepatic adenoma: current diagnosis and management

Benign liver tumors are common lesions that can be classified into cystic and solid lesions. Cystic lesions are the most frequent; however, they rarely represent a diagnostic or therapeutic challenge. In contrast, solid lesions are more difficult to characterize and management remains controversial. The wide availability and use of advanced imaging modalities, including ultrasonography, computed tomography, and magnetic resonance imaging have led to increased identification of incidental liver masses. Although some of these incidentally discovered masses are malignant, most are benign and must be included in the differential diagnosis. In this article we review FNH and HA. Its etiology, biological behavior, diagnosis, and treatment will be highlighted.     

肝脏局灶性结节性增生的影像学研究

目的：探讨肝脏局灶性结节性增生的诊治经验。
方法：回顾性分析31例FNH患者的临床表现、影像学检查、诊断及治疗方法等临床资料。
结果：全组31例中25例（80.6%）为40岁以下青壮年,23例（74.2%,23/31）无明显症状,HbsAg阳性1例,肝功能,AFP,CA19-9等肿瘤标记物均在正常范围内。单发肿瘤27例,4例为2个病灶。病灶多位于Ⅳ,Ⅴ,Ⅷ肝段。病灶大小0.5~15.0 cm。FNH术前诊断符合率分别为：彩超3.2%（1//31）,CT 32.1%（9/28）,MRI 20.0%（2/10）,肝动脉造影0（0/3）。术前诊断正确3例（9.7%）,误诊为肝癌13例（41.9%）,肝腺瘤4例（12.9%）,肝血管瘤2例（6.5%）,诊断不明9例（29.0%）。手术切除29例,2例经皮穿刺活检及影像学检查等确诊后予保守治疗。随访时间8个月至6.5年,29例术后均无复发。未手术2例,随访时间18~53个月,均健在,肿块大小无明显变化。
结论：FNH患者往往无临床症状,对影像学检查结果进行综合分析,是提高FNH正确诊断率的有效方法。怀疑FNH者,可经皮穿刺活检协助诊断,对于诊断明确、无症状的FNH,可定期观察,无需治疗。     

Diagnosis,management, and outcomes of 115 patients with hepatic hemangioma

BACKGROUND: Hepatic hemangiomas are congenital vascular malformations and are the most common benign hepatic tumors. Because the use of cross-sectional imaging has increased, benign hepatic tumors, especially hemangiomas, are encountered more frequently, so clinicians should be familiar with the most appropriate diagnostic tests, management, and outcomes of patients with hepatic hemangioma. STUDY DESIGN: All patients with a primary diagnosis of hepatic hemangioma referred for surgical evaluation at our institution between January 1992 and December 2000 were identified from a prospective database. Demographics, presentation, tumor characteristics, diagnostic studies, surgical procedures, and outcomes were analyzed. RESULTS; Of 115 patients in the study, nearly half were asymptomatic. In symptomatic patients, abdominal pain or discomfort was the most common presenting symptom. At our institution, the diagnosis of hemangioma was established by ultrasonographic studies in 57% of patients tested, by CT scan in 73%, and by MRI in 84%. In patients with large tumors considered for resection, direct angiography or, more recently, CT angiography, confirmed the diagnosis in 27 of 29 patients (93%). Enucleation was performed in 31 (60%) of the 52 patients who underwent surgical resection; 63 patients were observed. Postoperative complications occurred in 13 patients (25%), and there were no perioperative deaths. Of the patients with symptoms before resection, 96% had resolution of symptoms after operation. CONCLUSIONS: Hepatic hemangioma can be diagnosed in most patients using noninvasive studies, particularly MRI. Hepatic hemangiomas can be removed safely if patients become symptomatic or when malignancy cannot be excluded. CT angiography can be a valuable preoperative study in patients with large tumors, and enucleation is the procedure of choice. In asymptomatic or minimally symptomatic patients, hepatic hemangiomas usually have a benign course and can be observed.     

肝切除术在肝脏良性肿瘤治疗中的价值

目的 探讨肝切除术治疗肝脏良性肿瘤（benign liver tumors,BLT)的价值及其特点。方法 回顾性分析我院1994年1月至2001年6月用肝切除术治疗的37例肝脏良性肿瘤病人的临床资料，其中肝海绵状血管瘤29例，肝细胞腺瘤、右肝错构瘤和肝脏平滑肌瘤各2例，右肝上皮样血管内皮瘤和肝脏局灶性结节性增生各1例。结果 全组共行各种肝叶切除术26例（左外叶切除15例、右后叶切除或部分切除5例、右半肝切除3例、右前叶部分切除2例、左半肝切除1例），瘤体局部切除术11例。9例术中预置全肝血流阻断带，2例应用自体血回输。3例术后分别发生右侧胸腔积液、切口和膈下感染等并发症。无手术死亡，37例全部治愈。结论 对于多数有症状、体积较大或怀疑恶变之肝脏良性肿瘤，肝切除术是主要的治疗手段，而且安全有效；借助术中或术后病理检查可明确诊断；术中应用全肝血流阻断和自体血回输可提高困难手术的安全性，且不必担心有癌细胞扩散的危险。     

Giant cavernous liver hemangiomas: effect of operative approach on outcome

HYPOTHESIS: The choice of operative technique for resection of giant cavernous hepatic hemangiomas has an effect on outcome. DESIGN: Case series. SETTING: Tertiary hepatobiliary surgery-liver transplantation service.Patients and INTERVENTIONS: Fifty-two adult patients who underwent resection of symptomatic hepatic hemangiomas (38 [73%] in the right lobe; average diameter, 10.9 cm) by means of lobectomy or enucleation, with or without Pringle inflow occlusion. MAIN OUTCOME MEASURES: Blood transfusion, morbidity, mortality, and length of hospitalization. RESULTS: Patient age and sex and the size of hemangiomas were similar for patients who underwent lobectomy and enucleation. Right-lobe lesions were more often treated by enucleation, and inflow occlusion was used more frequently; transfusion requirements and length of hospitalization were similar for both techniques. Complications were more frequent after lobectomy. There were no deaths. In the latter years of the series, enucleation was used in 22 (63%) and inflow occlusion in 24 (69%) of 35 patients. CONCLUSIONS: Outcome is related to the operative approach used for resection of giant cavernous liver hemangiomas. Although lobectomy and enucleation are curative, enucleation offers greater preservation of normal hepatic parenchyma and fewer complications and is the preferred technique for suitable lesions.     

Intraperitoneal hemorrhage in a patient with hepatic focal nodular hyperplasia

Focal nodular hyperplasia (FNH) is a common benign liver tumor that is often confused with hepatic adenoma. Despite the benign course of both lesions, hepatic adenomas are associated with rupture and bleeding, and suggested management often includes prophylactic surgical resection. FNH lesions are thought to not rupture or bleed, and traditional management does not include resection. We report the case of a woman with FNH who presented with intraperitoneal hemorrhage after the rupture of a FNH lesion. Only six previous documented cases of hemoperitoneum associated with FNH have ever been reported. This report reviews all previously recorded cases of FNH lesions that have resulted in intraperitoneal hemorrhage. We suggest that although FNH is a benign lesion and intervention is typically unnecessary, the potential for rupture requiring surgical resection should always be considered.