Liver nodules resembling focal nodular hyperplasia after hepatic venous thrombosis

We report the case of focal nodular hyperplasia-like nodular hepatic lesions, that developed in the liver of a 35-year-old Caucasian female who required orthotopic liver transplantation for Budd-Chiari syndrome. The rapid development of focal nodular hyperplasia-like lesions in a severe hepatic vascular disorder and in the absence of cirrhosis may represent an additional argument in favor of the vascular origin of focal nodular hyperplasia. The pathogenesis of the nodules is not clear, but pathological arterialization of the liver in hepatic vein thrombosis may be a candidate mechanism.     

Clinicopathological features of focal nodular hyperplasia-like nodules in 130 cirrhotic explant livers

OBJECTIVES: Focal nodular hyperplasia-like nodules (FNH-like nodules) are focal lesions occurring in liver cirrhosis and are morphologically very similar to classical FNH in an otherwise normal liver. They are sometimes misdiagnosed as hepatocellular carcinoma (HCC) on imaging because both types of lesions show arterial-phase enhancement. Although the morphological, immunohistochemical, and imaging features of FNH-like nodules are well-known, their pathogenesis and role in hepatocarcinogenesis have not been studied in detail. Therefore, we performed a detailed pathological evaluation of 130 cirrhotic explant livers and correlated these data with the clinical features of the patients. METHODS: All cirrhotic explant livers were uniformly sliced at 5-mm intervals and all detected focal lesions were microscopically classified according to internationally accepted criteria. The obtained data regarding FNH-like nodules were then correlated with other pathological findings and with clinical data obtained during pretransplant evaluation and recorded in a database. RESULTS: FNH-like nodules were present in 15% of patients and their small size (75% of cases < 1 cm) appears to preclude detection by imaging in almost all cases. The presence of esophageal varices and pretransplant treatment with chemoembolization were independently and significantly associated with the presence of FNH-like nodules. There were no associations between FNH-like nodules on the one hand and low-grade dysplastic nodules, high-grade dysplastic nodules, and HCCs on the other hand. CONCLUSIONS: The clinicopathological features of FNH-like nodules support the hypothesis that vascular alterations in liver cirrhosis play an important role in their pathogenesis and that FNH-like nodules do not have an increased risk of malignant transformation.     

Multiple focal nodular hyperplasia

Focal nodular hyperplasia (FNH) is a benign lesion of the liver which usually presents with one or two localizations. We report a patient with history of resection of a biliary cyst, and who had been taking oral contraceptives for the past 18 years, who had multiple localizations of FNH (more than 30 lesions). The largest lesion measured 10.5 × 11 × 12 cm. The imaging characteristics of our patient were atypical. A central scar could be demonstrated only in the largest lesion, in an eccentric location. In the other lesions, no scar formations could be detected. Futhermore, imaging characteristics suggested that several of the lesions contained fat. This was confirmed by biopsy. The patient had an associated inflammatory syndrome which could not be otherwise explained. The patient was advised to stop taking the oral contraceptives. Follow-up after 2 years showed that the lesions were unchanged; the inflammatory syndrome persisted. Multiple localizations of FNH are very rare. Sometimes they are associated with malformations in other organs (vascular malformations and neoplasia, mostly of the brain). Often they occur as isolated cases, however. Usualy their prognosis seems to be good. (Received Jan. 14, 1998; accepted May 22, 1998)     

Oestrogen hormone receptors in focal nodular hyperplasia

Background

The role of hormones in focal nodular hyperplasia (FNH) has been investigated with conflicting results.

Objective

The aim of this study was to evaluate oestrogen and progesterone receptor immunohistochemical expression in FNH and surrounding normal liver (control material).

Methods

Biopsy materials from FNH and control tissue were investigated using an immunostainer. Receptor expression was graded as the proportion score (percentage of nuclear staining) and oestrogen receptor intensity score.

Results

Study material included tissue from 11 resected FNH lesions and two core biopsies in 13 patients (two male). Twelve samples showed oestrogen receptor expression. The percentage of nuclear oestrogen receptor staining was <33% in eight FNH biopsies, 34–66% in two FNH biopsies, and >67% in both core biopsies. The better staining in core biopsies relates to limitations of the staining technique imposed by the fibrous nature of larger resected FNH. Control samples from surrounding tissue were available for nine of the resected specimens and all showed oestrogen receptor expression. Progesterone receptor expression was negligible in FNH and control samples.

Conclusions

By contrast with previous studies, the majority of FNH and surrounding liver in this cohort demonstrated oestrogen receptor nuclear staining. The implications of this for continued oral contraceptive use in women of reproductive age with FNH remain uncertain given the lack of consistent reported growth response to oestrogen stimulation or withdrawal.     

The pathogenesis of focal nodular hyperplasia of the liver

Abstract   The pathogenesis of focal nodular hyperplasia is poorly understood. The lesion has been reported adjacent to many other focal hepatic lesions suggesting this is a nonspecific reaction to injury. Recent evidence suggests that arterio-venous shunt formation may trigger a positive feedback loop that includes hepatocellular hyperplasia.     

Cholestatic features in focal nodular hyperplasia of the liver

Twenty specimens of focal nodular hyperplasia were studied with special attention to the histological features of chronic cholestasis (grouped under the headings of cholestasis, cholate-stasis and signs of ductular reabsorption). In all specimens, evidence was found for one or more features of cholestasis and cholate-stasis. Signs of ductular reabsorption were less constant, and apparently varied according to the developmental stage of the lesion. The cholestatic features emphasize the bile secretory capacity of the lesional parenchyma, and are apparently due to the lack of real bile ducts in the portal tract equivalents of the lesional tissue. Evidence is presented that the "ductular component" in FNH is not due to proliferation of pre-existing ductules, but rather derives from ductular metaplasia of liver cell plates in zone 1 equivalents. This metaplastic development of a ductular network may serve the function of reabsorbing the biliary constituents produced by the lesional parenchyma, leading to periductular inflammation and progressive fibrosis, thus producing an equivalent of biliary fibrosis and biliary cirrhosis.     

Hepatocellular carcinoma in a patient with focal nodular hyperplasia

BackgroundFocal nodular hyperplasia is an uncommon liver tumour that typically requires no therapeutic intervention.Case outlineA 43-year-old woman with a 20-year history of oral contraceptive use presented with symptomatic bilateral liver masses. Biopsy revealed hepatocellular carcinoma in the right hemiliver and focal nodular hyperplasia in the left hemiliver.At operation,the patient was noted to have multiple liver nodules bilaterally, and all intraoperative biopsies were consistent with focal nodular hyperplasia including a biopsy taken from the region that demonstrated carcinoma preoperatively. Because of the earlier biopsy results and the patient''s preoperative symptoms, a right hemihepatectomy was performed. Final pathology revealed hepatocellular carcinoma directly adjacent to an area of focal nodular hyperplasia, as well as multiple other areas of hyperplastic liver tumour.DiscussionAlthough focal nodular hyperplasia is believed to be benign, few studies have followed patients with this tumour beyond three years. Longer-term follow-up studies are needed to determine the natural history of focal nodular hyperplasia, potentially focussing on a subset of patients with either diffuse tumours or prolonged oral contraceptive use.     

Pictures of focal nodular hyperplasia and hepatocellular adenomas

This practical atlas aims to help liver and non liver pa-thologists to recognize benign hepatocellular nodules on resected specimen. Macroscopic and microscopic views together with immunohistochemical stains illustrate typical and atypical aspects of focal nodular hyperplasia and of hepatocellular adenoma, including hepatocel-lular adenomas subtypes with references to clinical and imaging data. Each step is important to make a correct diagnosis. The specimen including the nodule and the non-tumoral liver should be sliced, photographed and all different looking areas adequately sampled for par-affin inclusion. Routine histology includes HE, trichrome and cytokeratin 7. Immunohistochemistry includes glu-tamine synthase and according to the above results ad-ditional markers such as liver fatty acid binding protein, C reactive protein and beta catenin may be realized to differentiate focal nodular hyperplasia from hepatocel-lular adenoma subtypes. Clues for differential diagnosis and pitfalls are explained and illustrated.     

Lymphoid nodules and nodular lymphoid hyperplasia in bone marrow biopsies

Out of 2,474 bone marrow biopsies we have observed 330 cases (13.3%) with presence of lymphoid nodules (LN). LN were frequent in old age (24.6% over 80 years), in females (17%) and in some diseases, such as rheumatoid arthritis and systemic lupus erythematosus (73.7% of the cases), partial aplasia (34%), hypersplenism (30.4%), hemopoietic dysplasia (25%), chronic renal failure (20.4%), polycythemia vera (20.2%), idiopathic thrombocytopenic purpura (18.8%), acute leukemia (17.7%). Nodular lymphoid hyperplasia of the bone marrow was found especially in systemic autoimmune diseases (26.3%), hypersplenism (9.8%), preleukemia (7.3%) and acute leukemia (4.2%). The presence of excessive medullary LN could indicate a bone marrow microenvironment damage, possibly of autoimmune origin.     

克隆性分析技术在肝脏局灶性结节性增生诊断中的应用

目的:探讨整个肝局灶性结节性增生(FNH)病变及各结节的克隆性,以阐明其本质,同时比较其与肝细胞腺瘤(HA)鉴别的克隆性组成方法:女性肝脏标本3例共4个FNH病灶．在病变区和非病变区取组织提取基因组DNA,余标本制备石蜡切片,HE染色,应用显微切割技术分离其中3个FNH内的小结节状病变,提取基因组DNA,经甲基化敏感的HpaⅡ或Hha Ⅰ消化,巢式PCR扩增磷酸甘油酸激酶(PGK)和雄激素受体(AR)基因．应用Bst Ⅺ酶切和琼脂糖凝胶电泳显示PGK基因的单核苷酸多态性; 应用变性聚丙烯酰胺凝胶电泳显示AR基因的 CAG重复序列长度多态性．2例HA和4例HCC 作为肿瘤参照．结果:2例HA及4例HCC均为单克隆性．4个 FNH病变,直径1．5-5．3 cm,但缺乏特征性的中央星状瘢痕,结果均显示为多克隆性病变;其中的61个结节性病变中,56个呈变异肝细胞结节(NAH)形态,5个为普通再生结节．克隆性分析结果显示,56个NAH样病变中,除4个未扩增成功外,52个NAH中有21个(40．4％)显示X 染色体失活嵌合性丢失,提示为肿瘤性病变; 其中1例FNH的14个单克隆结节中,有2个与其他病变失活带型不一致,提示在同一FNH中; 存在着不同起源的NAH样病变．5个普通肝细胞增生结节及病变周围肝组织均为多克隆组成．结论:FNH是由无数个NAH构成的,其整个病变是多克隆性,但其中某些结节已经是肿瘤性增生．克隆性检测有助于其与HA的鉴别,而且所取样本必须是病变的整个切面或其大部分．     

肝脏局灶性结节性增生的诊治:附5例病例报告

目的讨论肝脏局灶性结节性增生的诊治特点。方法总结我科自1999年7月至2005年7月所收治的5例肝脏局灶性结节性增生病例,结合1994年至2005年国内有关文献,分析病史、实验室检查、影像学检查及治疗效果。结果本组5例病人均无自觉症状,肝功能、AFP正常,均行肝部分切除手术,病理诊断证实为肝脏局灶性结节性增生,术后转归良好。结论肝脏局灶性结节性增生发病机制尚不清楚,联合应用多种影像学检查有助于明确诊断;对诊断不明确病例仍应手术探查。