Newly detected hepatic nodules during follow-up of cancer survivors receiving chemotherapy may pose a diagnostic dilemma. We investigated a series of hepatic focal nodular hyperplasia (FNH) diagnosed by either typical MRI features and follow-up or pathology in cancer survivors.

This retrospective study evaluated 38 patients with tumours who developed new hepatic FNH after cyclophosphamide-based (n = 19) and oxaliplatin-based (n = 19) chemotherapies. The main tumour types were breast cancer (n = 18) and colorectal cancer (n = 17). MRI findings, clinical features, and temporal evolution of all target hepatic lesions (n = 63) were reported. In addition, the two chemotherapy drug groups were compared.

The median interval between chemotherapy completion and FNH detection was 30.4 months (12.9, 49.4). Six patients underwent biopsy or surgery, while the remaining patients were diagnosed based on typical MRI features and long-term follow-up. Among the patients, 60.5% (23/38) presented with multiple nodules and 63 target lesions were detected. The median size of target lesions was 11.5 mm (8.4, 15.1). The median follow-up time was 32.5 months (21.2, 48.6), and 15 patients experienced changes in their lesions during the follow-up period (11 increased and 4 decreased). The cyclophosphamide-based treatment group had a younger population, a greater proportion of females, and a shorter time to discovery than the oxaliplatin-based chemotherapy group (all p ≤ 0.016).

FNH may occur in cancer survivors after cyclophosphamide- or oxaliplatin-based chemotherapy. Considering a patient's treatment history and typical MRI findings can help avoid misdiagnosis and unnecessary invasive treatment.

When cancer survivors develop new hepatic nodules during follow-up, clinicians should think of the possibility of focal nodular hyperplasia in addition to liver metastasis, especially if the cancer survivors were previously treated with cyclophosphamide or oxaliplatin.

Cancer survivors, after chemotherapy, can develop hepatic focal nodular hyperplasia. Cyclophosphamide and oxaliplatin are two chemotherapeutic agents that predispose to focal nodular hyperplasia development. Focal nodular hyperplasia occurs at shorter intervals in patients treated with cyclophosphamide.

Focal nodular hyperplasia (FNH) of the liver is a rare benign lesion that may be related to the vascular and hepatic damage induced by completion of tumor therapy and a reaction to localized vascular abnormality. The aim of this study was to analyze the clinical course in pediatric solid tumor patients with FNH.

We analyzed thirty-two patients with pediatric solid tumors who received multiagent chemotherapy (15 advanced neuroblastomas, 7 hepatoblastomas, 5 rhabdomyosarcomas, 2 nephroblastomas, 1 rhabdoid tumor of the kidney, 1 clear cell sarcoma of the kidney and 1 pancreatoblastoma). All of them had been previously treated at our hospital, and have been alive for over 3 years without recurrence.

FNH lesions were discovered in three (9.4%) of 32 patients, and were neuroblastoma (NB) stage 4. All 3 patients received induction chemotherapy and high-dose alkylating agents, and developed grade 3 (National Cancer Institute Common Toxicity Criteria; NCI-CTC) liver dysfunction during completion of tumor therapy without veno-occlusive disease. Two of the 3 patients received the same induction chemotherapy and high doses of alkylating agents with total body irradiation for cytoreductive agents prior to peripheral blood cell transplantation. FNH lesions in both female patients who received estrogen replacement therapy after completion of tumor therapy have expanded and are increasing.

FNH appears to be a late complication of iatrogenic disease in NB stage 4 patients. The therapeutic agents for NB stage 4 and estrogen replacement therapy should be considered as risk factors for the development of FNH.

Focal nodular hyperplasia (FNH) of the liver is rare in children, and it is usually diagnosed through a biopsy of the liver or hepatectomy. The authors report a case of a 10-year-old girl with multiple focal nodular hyperplasia lesions of the liver after the completion of tumor therapy for advanced neuroblastoma, and review the usefulness of the combination of power Doppler ultrasonography (US) and superparamagnetic iron oxide (SPIO) enhanced magnetic resonance imaging (MRI) for the diagnosis of FNH without a biopsy of the liver or hepatectomy.

Hepatocellular carcinoma (HCC) is increasing in incidence in many countries, and is the most common cause of death in patients with cirrhosis. With regular surveillance, small early HCC lesions can be identified. An algorithm has been developed that allows for diagnosis of these lesions. Very early HCC lesions have high cure rates with appropriate treatment. If all these factors are in place most HCCs can be cured.

Hepatic hemangioma and focal nodular hyperplasia are both frequently observed benign lesions of the liver. Whereas hepatic hemangioma is the most frequent benign liver tumor in children, focal nodular hyperplasia occurs predominantly in adult patients. Concomitance of both entities has been described in adults, suggesting a similar pathogenesis. We report on a 6-month-old child with a continuously shrinking hepatic hemangioma after interventional therapy and a growing hepatic mass 5 years later, which emerged as focal nodular hyperplasia at the site of the former hemangioma. Diagnostic and therapeutic strategies regarding this patient are discussed. The present case supports the theory that these two entities may share a similar pathomechanism.

Described herein is the case of an 8-year-old boy who developed a hepatic nodular lesion after having received anti-neoplastic therapy for nephroblastoma. Histological examination of the excised specimen indicated a disordered arrangement of hepatic components with hemangioma-like features. This case was diagnosed as a variant of focal nodular hyperplasia. It is speculated that this hepatic lesion is a late complication of treatment for nephroblastoma and might develop from congenital malformative area of the liver.

Thanks to ultrasonography, computed tomography, and nuclear magnetic resonance, not only symptomatic but also asymptomatic liver tumours are discovered more frequently than before. Focal nodular hyperplasia (FNH) is one such tumour, most frequently an asymptomatic tumour of the liver, which predominantly appears in women during the generative period, who have taken oral contraceptives for several years. We present a 27-year-old woman, who has never taken either oral contraceptives or other hormones, in whom a left lobe liver tumour was unexpectedly discovered during a routine investigation performed for psychiatric complaints. The tumour, removed by left lateral bisegmentectomy (segments II and Ill), was composed of two tumoural nodes: 70x58x47 mm and 20x20x20 mm, the bigger one of which had a light grey central stellate scar. Histology revealed a focal nodular hyperplasia. The postoperative recovery was uneventful and the patient stayed symptom free for more than three years after surgery.

This report describes the use of superparamagnetic iron oxide-enhanced magnetic resonance imaging to diagnose fibronodular hyperplasia of the liver in a 12-year-old girl.

The association between hepatic hemangioma (HH) and focal nodular hyperplasia (FNH) or the association between FNH and hepatic adenoma (HA) has been reported. The authors report a case in which FNH, HH, and HA simultaneously appear in the liver. A 25-year-old woman was admitted to the Department of Surgery of the University of Catania (Italy), after presenting pain in the right hypocondrium. No therapy with oral contraceptives, no pregnancy and no abnormalities of the laboratory tests were found. Ultrasonography and computed tomography scans revealed four masses with the characteristics of HH, HA, FNH, and a hydatid cyst located, respectively, in segments II, IV, IV, and V of the liver. The surgical procedures performed were hemangioma and adenoma enucleation and en bloc resection of the FNH, hydatid cyst and gallbladder. No complications were recorded in the postoperative period and the patient was discharged from the hospital after 1 week. A pathological examination confirmed the preoperative diagnosis. To the best of our knowledge, the association of HH, FNH, and HA has never been reported. A common pathogenesis has clearly been demonstrated for hepatocytes and other cell types. The simultaneous presence of these three different kinds of tumor suggest that HH, FNH and HA could be the different expression of the same malformative anomaly.

Focal nodular hyperplasia (FNH) of the liver is a benign hepatic lesion relatively common in women. No studies specifically designed to describe the presentation and imaging findings in males have been published.

The aims of this study were: (a) to describe the clinical and imaging findings in 18 men with FNH, and (b) to compare these data with those observed in 216 women with FNH observed during the same nine year period.

According to a final diagnosis of FNH assessed either by pathological examination or by magnetic resonance (MR), the medical charts of 18 men with FNH observed at our institution were reviewed. In order to compare clinical and MR presentations, the files of 216 women with a total of 291 FNH lesions, investigated during the same nine year period, were reviewed.

Eighteen FNH lesions, with a mean diameter of 37.5 mm, were demonstrated in the 18 male patients. A total of 291 lesions with a mean diameter of 63.4 mm were comparatively demonstrated in 216 female patients. Mean age at diagnosis was significantly higher in men (p<0.01) and mean FNH size was significantly smaller in men (p<0.001). Surgery was more frequently performed in men (72.2%) than in women (16.7%) (p<0.001).

Our data indicate that FNH is rare in men and that the lesions are smaller and more often atypical than those in women.

This article focuses on the origin, diagnosis, and management of focal benign lesions of the liver. The most common lesions include cavernous hemangioma, focal nodular hyperplasia, hepatic adenoma, and nodular regenerative hyperplasia. A number of less frequent occurring lesions are also discussed. In general, the common lesions can be diagnosed by radiologic imaging, but occasionally biopsies are required, and surgical removal is often needed.

Focal nodular hyperplasia of the liver is a lesion characterized by a well-circumscribed region of hyperplastic liver parenchyma and contains a stellate fibrous scar. The lesion is thought to be because of liver-cell hyperplasia that is caused by focal circulatory disturbances. We describe here a pediatric case of this lesion that provided direct histopathologic evidence of circulatory disturbances. We identified arterial and portal thrombi, as well as recanalization of arteries in the nodule. Hepatic necrosis was also seen in the lesion. We speculate that thrombosis of the hepatic artery and/or portal vein was the cause of hepatic necrosis and that reperfusion following hepatic arterial recanalization resulted in nodule formation. Although there was no stellate scar present in our case, the presence of bile ductular proliferation at the periphery of the nodule was helpful in distinguishing this lesion from adenoma and hepatocellular carcinoma. The early stage of nodular formation may explain the lack of a stellate scar in our case. The patient was treated earlier with actinomycin D and vincristine following surgical excision of Wilms' tumor. It is possible that such chemotherapy contributed to thrombosis in our case.

We report the first case of an Echinococcal cyst and focal nodular hyperplasia, two usually isolated hepatic lesions, in direct contiguity. The patient presented with right upper quadrant pain and subsequent imaging studies found a cystic and solid lesion. These studies suggested that this lesion was an hepatic adenoma, which had bled forming a hematoma. Pathological examination of the surgical resection showed Echinococcus multilocularis with contiguous focal nodular hyperplasia. Because focal nodular hyperplasia is a benign hepatic lesion the etiology of which is thought to be abnormal arterial blood flow, we postulate that the parasitic hepatic infection by E. multilocularis may have incited the formation of this contiguous hepatic lesion.

Atypical histologic variants of focal nodular hyperplasia have been reported and are sometimes difficult to recognize. To characterize the morphologic spectrum of focal nodular hyperplasia, we studied 305 lesions surgically resected from 168 patients. Clinicomorphologic correlations were established by statistical analyses. The patients included 150 women and 18 men (sex ratio, 8:1; median age, 38 years). One hundred twenty-eight (76.2%) patients had solitary lesions, and 40 (23.8%) had 2 to 30 lesions. All 305 lesions measured 1 mm to 19 cm in diameter. Only 49% of these lesions had one to three macroscopic scars. Histologically, 245 (80.3%) lesions were of classical form, and 60 (19.7%) lesions were nonclassical. The latter were classified as focal nodular hyperplasia of telangiectatic form (47 lesions), of mixed hyperplastic and adenomatous form (five lesions), and with atypia of large cell type (eight lesions). Several benign or malignant tumors were found in association with these lesions. This large retrospective series of focal nodular hyperplasia shows the relative incidence of its classical and nonclassical forms. The absence of a central scar could explain the difficult preoperative diagnosis of some of the cases. The morphologic diagnostic criteria in this study require further prospective evaluation.

Malignant vascular neoplasms of the liver are uncommon. We report the case of a young woman who developed an epithelioid hemangioendothelioma of the liver associated with multiple focal nodular hyperplasias and hepatic cavernous hemangiomas. Such an unusual association is probably not fortuitous and could support the theory that focal nodular hyperplasia is a reaction to an abnormal vascular supply rather than a true neoplasm.

Congenital absence of portal vein (CAPV) is a rare vascular malformation: all 16 cases up to now reported are associated with other congenital anomalies and with benign or malignant hepatic neoplasms. Our report concerns a girl with a complex malformative syndrome consisting of CAPV, nodular tumor-like hyperplasia of the liver, and multicystic kidney dysplasia. CAPV was diagnosed by angiography, showing the splenic vein and superior mesenteric vein joined to form a "common trunk" directly entering the inferior vena cava above the liver. The liver maintained the normal lobular architecture, but immunohistochemical and ultrastructural observations revealed abnormalities of the hepatocyte membranes and diffuse capillarization of the sinusoids. In this paper, we present the relationship between the tissue modification and the lobular microcirculation changes due to CAPV, with exclusive perfusion of arterial blood flow.

There is uncertainty regarding the role, if any, of oral contraceptive steroids in the development of focal nodular hyperplasia of the liver. A case of focal nodular hyperplasia of the liver diagnosed by scintigraphy in a 33-year-old woman is presented. The lesion regressed in a dramatic way after oral contraceptive discontinuation. This case report suggests that oral contraceptives may influence the natural history of focal nodular hyperplasia of the liver, and that a trophic effect on the liver lesion is quite possible.

A case of multiple focal nodular hyperplasia of the liver occurring in a 22-year-old woman with musculoskeletal hemihypertrophy and anomalous vascular supply to the liver is described. The patient had Klippel-Trénaunay-Weber syndrome and abdominal pain and tender massive hepatomegaly. Visceral angiography showed marked dilatation of the celiac axis and both the main trunk and peripheral branches of the hepatic artery. Large abdominal veins drained from the dome of the liver into the hepatic veins. The vascular anomalies were evident on contrast-enhanced computed tomography and magnetic resonance imaging. Multiple focal nodular hyperplasia was confirmed by laparoscopic liver biopsy. The findings in this patient support the concept that multiple focal nodular hyperplasia characteristically occurs in a syndromic form and is induced by an irregular arterial supply in the liver, with localized hyperfusion that leads to nodular areas of hepatocyte hyperproliferation.

The chronic dietary administration of hexachlorobenzene (HCB) to rats for a year or more results in the formation of liver tumours described as hepatocellular carcinomas, hepatomas or haemangiomas. The hepatotoxicity of HCB, which is greatest in hamsters and rats, gives rise to peliosis and necrosis with haemosiderosis. This pattern of hepatotoxicity indicates vascular damage, which through haemosiderosis could increase not only the toxic effect of HCB to hepatocytes but also its tumourogenic potential. The present study confirmed vascular damage by the identification of widespread fibrin deposits in the livers of rats chronically exposed to HCB, using an antibody to rat fibrin. Based on our study we suggest that the formation of hepatomas and haemangiomas with elements of peliosis (cystic blood-filled cavities) could be explained by the compensatory hyperplastic responses to hepatocellular necrosis and by the simultaneous loss of hepatocellular cords. The accumulation of iron in the liver would strongly potentiate the development of hepatic tumours, as has been found in HCB and polychlorinated biphenyl-treated mice with iron overload. The implications of this non-genotoxic mechanism of hepatoma formation for the assessment of human health risk are discussed.

We report a case of acetaminophen-induced liver necrosis in a 14-year-old girl. At autopsy, a 9 cm subcapsular nodule was present in the right lobe of the liver which showed distinct zonation: a central greyish white area of fibrolamellar carcinoma with a peripheral fleshy, tan-coloured rim ranging from 1 to 2 cm in thickness. This peripheral zone consisted of nodular, hyperplastic parenchyma resembling the changes seen in focal nodular hyperplasia, and stood out from the adjacent necrotic parenchyma. The sparing of this zone from the deleterious effects of acetaminophen provides indirect evidence of a predominantly arterial rather than portal blood supply to this region. The arterial supply was most probably derived from the tumour vasculature and may explain the parenchymal hyperplasia sometimes reported adjacent to a fibrolamellar carcinoma. Awareness of this phenomenon is essential when evaluating a needle biopsy, as sampling of this region may lead to a false negative diagnosis.

A retrospective analysis of the results of ultrasound (US), computed tomography (CT), and magnetic resonance imaging (MRI) of 24 cases (28 lesions) of proven focal nodular hyperplasia (FNH) is presented. While US exhibited nonspecific features, CT frequently showed characteristic features: hypodensity on precontrast scans (69%), transient immediate enhancement after bolus injection (96%), and homogeneity (85%). A scar was noted in 31% of the cases. The typical MR triad of isointensity on T1- and/or T2-weighted (T2-WI), homogeneity, and a scar which shows hyperintensity on T2-WI was seen in only 12% of our cases. The most common finding was homogeneity (94%). In two cases the scar was hypointense on T2-WI. To our knowledge, this finding has not been described before. We conclude that the features of FNH, although fairly constant, are at times indistinguishable from those of other hepatic tumors, such as hepatic adenoma (HA), fibrolamellar hepatocellular carcinoma (FLHCC), small hepatocellular carcinoma, and a hyperplastic nodule. Therefore, a multimodality approach is essential for the correct diagnosis in order to prevent unnecessary surgery.

Adenomatous hyperplasia (AH), a hyperplastic parenchymal nodule, is detected most often through radiological and pathological observations in chronic advanced liver disease. AH can be classified into two categories: ordinary type or macroregenerative nodule (MRN) type I, and atypical type or MRN type II. Characteristically, both types contain portal tracts with portal veins and biliary elements. Ordinary AH may represent a large regenerative nodule with limited growth potential. Atypical AH shows slightly cellular and structural atypia, altered phenotypic expression, and increased proliferative activity compared to the surrounding liver. Histologic differentiation of atypical AH from well-differentiated hepatocellular carcinoma (HCC) is controversial, and generally accepted diagnostic criteria are still lacking. Atypical AH occasionally contains overt malignant foci. Histological observations and portography show that nodules of AH are supplied by portal venous blood. While AH nodules appear to be hypoperfused according to arteriographic studies, atypical AH contains small arterial branches which are abundant in contrast to the surrounding liver. The data obtained so far indicate that atypical AH may be a hepatocellular neoplasm which belongs nosologically to a gray area of neoplasm, in which overt HCC is likely to develop. It is clinically recommended that atypical AH is treated as "malignant" because of the occasional inclusion of HCC foci. For its treatment, percutaneous ethanol injection is becoming popular.

Morphological features of lesions conforming to the description of solitary necrotic nodules of the liver were compared with liver haemangiomata and necrotic tumour metastases in the liver. An origin in haemangiomata is confirmed for most of the lesions studied, although the necrotic nodule may represent the end stage of a variety of lesions. These lesions are usually benign, although necrotic nodules are often mistaken for liver metastases. A reticulin stain is useful in assessing the lesions.