Late recurrence of hepatocellular carcinoma after liver transplantation: is an active surveillance for recurrence needed?

INTRODUCTION: Liver transplantation (OLT) is considered the most efficient therapeutic option for patients with liver cirrhosis and early stage hepatocellular carcinoma (HCC) in terms of overall survival and recurrence rates, when restrictive selection criteria are applied. Nevertheless, tumor recurrence may occur in 3.5% to 21% of recipients. It usually occurs within 2 years following OLT, having a major negative impact on prognosis. The efficacy of active posttransplantation surveillance for recurrence has not been demonstrated, due to the poor prognosis of recipients with recurrences. AIM: To analyze the clinical, pathological, and prognostic consequences of late recurrence (>5 years after OLT). METHOD: We analyzed the clinical records of 165 HCC patients including 142 males of overall mean age of 58 ± 6.9 years who underwent OLT between July 1994 and August 2011. RESULTS: Overall survival was 84%, 76%, 66.8%, and 57% at 1, 3, 5, and 10 years, respectively. Tumor recurrence, which was observed in 18 (10.9%) recipients, was a major predictive factor for survival: its rates were 72.2%, 53.3%, 26.7%, and 10% at 1, 3, 5, and 10 years, respectively. HCC recurrence was detected in 77.8% of patients within the first 3 years after OLT. Three recipients (100% males, aged 54-60 years) showed late recurrences after 7, 9, and 10 years. In only one case were Milan criteria surpassed after the examination of explanted liver; no vascular invasion was detected in any case. Recurrence sites were peritoneal, intrahepatic, and subcutaneous abdominal wall tissue. In all cases, immunosuppression was switched from a calcineurin-inhibitor to a mammalian target of rapamycin inhibitor. We surgically resected the extrahepatic recurrences. The remaining recipient was treated with transarterial chemoembolization with doxorubicin-eluting beads and sorafenib. Prognosis after diagnosis of recurrence was poor with median a survival of 278 days (range, 114-704). CONCLUSIONS: Global survival, recurrence rate, and pattern of recurrence were similar to previously reported data. Nevertheless, in three patients recurrence was diagnosed >5 years after OLT. Although recurrence was limited and surgically removed in two cases, disease-free survival was poor. Thus, prolonged active surveillance for HCC recurrence beyond 5 years after OLT may be not useful to provide a survival benefit for these patients.

Pancreatic fusocellular sarcoma. The importance of endoscopic ultrasound-guided fine needle aspiration in the differential diagnosis of solid pancreatic tumors.

In the presence of a pancreatic tumor, the main diagnostic problem is to determine the benign o malignant nature of the lesion, and then to evaluate its resectability. A preoperative biopsy was usually rejected based on the fact that negative results do not exclude malignancy, that such biopsy may hamper the possibility of curative surgery because of potential seeding along the biopsy s trajectory, that surgical morbidity and mortality are low, and also because of the high diagnostic sensitivity of the various imaging techniques. Biopsy for solid pancreatic tumors was limited to irresectable tumors, and isolated cases with suspicion of tuberculosis, lymphoma or neuroendocrine tumors. Nowadays the performance of a pancreatic biopsy is becoming essential for the correct management of solid lesions, and is useful not only to establish malignancy, but also for a better knowledge of all kind of pathologies and, thus, for better therapeutic management. In this context, endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) has proven a safe technique with a low rate of complications and a diagnostic accuracy superior to other procedures, this being considered the method of choice for the study of solid pancreatic lesions. An illustrative example is the case we report in this article -a patient diagnosed of a solid, locally advanced-stage pancreatic tumor with imaging techniques (abdominal ultrasounds and EUS) under EUS-guided FNA; the procedure could establish a final diagnosis of pancreatic fusocellular sarcoma.

Sarcoma fusocelular de páncreas: importancia de la PAAF guiada por ultrasonografía endoscópica en el diagnóstico diferencial de los tumores sólidos pancreáticos / Pancreatic fusocellular sarcoma. The importance of endoscopic ultrasound-guided fine needle aspiration in the differential diagnosis of solid pancreatic tumors

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[The immunohistochemical expression of cyclin B1 is associated with higher SUV in 18F-FDG-PET in non-small cell lung cancer patients. Initial results]. / La expresión inmunohistoquímica de ciclina B1 conlleva mayores valores de SUV en la 18F-FDG-PET de pacientes con carcinomas no microcíticos de pulmón. Primeros resultados.

AIM: to study the expression of cyclin B1 and its possible relationship with the maximum SUV in FDG-PET and MIB1 expression in patients with NSCLC. MATERIALS AND METHODS: 49 patients (15 adenocarcinomas, 27 squamous cell carcinomas and 7 bronchoalveolar carcinomas) were included in this study; the immunohistochemical expression of cyclin B1 was determined using the tissue-array technique. Each PET was performed 60 minutes after the i.v. administration of 350-518 MBq of FDG on an Advance system (GE) in 2D acquisition mode. RESULTS: cyclin B1 expression was detected in 40 out of 45 cases. The SUV values were higher (p=0.04) in the cyclin B1+ cases than in the negative cases (16.4+/-8.1 vs 10.9+/-6.2). Cyclin B1 expression and SUV values were not correlated with the clinical stage. The expression of cyclin B1+ correlated positively (p<0.0001) with that of MIB1. After univariate analysis, only the cellular proliferation was a prognostic factor (p=0.037). CONCLUSIONS: our results suggest that there is a direct correlation between cyclin B1 expression and max-SUV values in the PET of NSCLC patients. When the association of cyclin B1 with positive MIB1 is also considered, our results support the role of cell proliferation in FDG uptake by the tumour.

La expresión inmunohistoquímica de ciclina B1 conlleva mayores valores de SUV en la 18F-FDG-PET de pacientes con carcinomas no microcíticos de pulmón. Primeros resultados / The immunohistochemical expression of cyclin B1 is associated with higher SUV in 18F-FDG-PET in non-sma ll cell lung cancer patients. Initial results

Objetivo: estudiar la posible correlación entre la expresión de ciclina B1, proliferación celular y la SUV máxima-18F-FDG-PET en pacientes con carcinomas no microcíticos pulmonares. Material y metodo: se incluyó a 49 pacientes (15 adenocarcinomas, 27 carcinomas escamosos y 7 carcinomas broncoalveolares) y se realizó la expresión inmunohistoquímica de ciclina B1 mediante tissue-arrays. Asimismo, analizamos la proliferación celular (MIB-1). El PET se realizó 60 min después de la administración intravenosa (i.v.) de 350-518 MBq de 18F-FDG en un PET (Advance, GE) y adquisión en 2D. Resultados: la expresión inmunohistoquímica de ciclina B1 se detectó en 40 (81,6%) casos y no se relacionó con el estadio clínico (I-II: 17/21 frente a III-IV: 23/28). Los valores de SUV fueron mayores (p = 0,04) en los casos positivos (16,4 ± 8,1) que en los negativos (10,9 ± 6,2) y no difirieron en función del estadio clínico. La expresión de ciclina B1 se correlacionó (p < 0,0001) con la de MIB1. Tras análisis univariable, la ciclina B1 y los valores SUV no fueron factores pronósticos, pero sí la proliferación celular (p = 0,037). Conclusiones: nuestros resultados muestran una relación directa entre la expresión de ciclina B1 y los valores max SUV en el PET de pacientes afectos de carcinomas no microcíticos de pulmón, lo cual, unido a la asociación de aquella con la positividad del MIB1, apoya el papel de la proliferación celular en la captación del radiofármaco por el tumor(AU)

Aim: to study the expression of cyclin B1 and its possible relationship with the maximum SUV in FDG-PET and MIB1 expression in patients with NSCLC. Materials and methods: 49 patients (15 adenocarcinomas, 27 squamous cell carcinomas and 7 bronchoalveolar carcinomas) were included in this study; the immunohistochemical expression of cyclin B1 was determined using the tissue-array technique. Each PET was performed 60 minutes after the i.v. administration of 350-518 MBq of FDG on an Advance system (GE) in 2D acquisition mode. Results: cyclin B1 expression was detected in 40 out of 45 cases. The SUV values were higher (p = 0.04) in the cyclin B1+ cases than in the negative cases (16.4 ± 8.1 vs 10.9 ± 6.2). Cyclin B1 expression and SUV values were not correlated with the clinical stage. The expression of cyclin B1+ correlated positively (p < 0.0001) with that of MIB1. After univariate analysis, only the cellular proliferation was a prognostic factor (p = 0.037). Conclusions: our results suggest that there is a direct correlation between cyclin B1 expression and max-SUV values in the PET of NSCLC patients. When the association of cyclin B1 with positive MIB1 is also considered(AU)

[The immunohistochemical expression of cyclooxygenase 2 is inversely associated with (18)F-FDG-PET SUV values in non-small-cell lung cancers. Initial results]. / La expresión inmunohistoquímica intensa de ciclooxigenasa 2 se asocia inversamente con los valores máximos de SUV en la (18)F-FDG-PET de pacientes afectados de carcinomas no microcíticos de pulmón. Relación con otros factores biológicos.

OBJECTIVE: To study the expression of COX-2 and its possible relationship with the maximum standardized uptake value (SUV) in FDG-PET, and EGFR, p16 and MIB1 expression in patients with NSCLC. MATERIAL AND METHOD: 45 patients (12 adenocarcinomas and 33 squamous cell carcinomas) were included in this study; the immunohistochemical expression of COX-2, MIB-1, p16 and EGFR was determined using tissue-array. Each PET was performed 60 minutes after the i.v. administration of 350-518 MBq of FDG on an Advance system (GE) in 2D acquisition mode. RESULTS: COX-2 expression was detected in 35 out of 45 cases, and was very significant (> ++) in 12 of them. SUV values were lower in the COX-2 > ++ cases that in the remaining cases (13.4 +/- 1.2 vs. 12.9 vs. 17.1 +/- 1.5; p = 0.059). COX-2 > ++ expression and maxSUV values were not correlated with the clinical stage. The expression of COX-2 > ++ was correlated positively with p16 (r = 0.36; p = 0.014) and negatively with MIB1 (r = -0.32; p = 0.041) expression, whereas the SUV was correlated positively with EGFR (r = 0.44; p = 0.004) and negatively with p16 (r = -0.29; p = 0.041) expression. CONCLUSIONS: Our results suggest that: a) the expression of COX-2 > ++ is often found in this kind of lung cancer and is not associated with the clinical stage; b) the maxSUVs were not related to the stage and were lower in COX-2 > ++ tumours than in the other cases; and c) the different behaviour of both parameters can be explained by their correlation with cell proliferation (MIB1), EGFR and p16 expression.

La expresión inmunohistoquímica intensa de ciclooxigenasa 2 se asocia inversamente con los valores máximos de SUV en la 18F-FDG-PET de pacientes afectados de carcinomas no microcíticos de pulmón. Relación con otros factores biológicos / The immunohistochemical expression of cyclooxygenasa 2 is inversely associated with 18F-FDG-PET SUV values in non-small cell lung cancers. Initial results

Objetivo: estudiar la expresión de COX-2 y sus posibles relaciones con el valor de captación estándar (SUV, standardized uptake value, valor de captación estándar) máximo-FDG-PET y la expresión de MIB1, p16 y receptor del factor de crecimiento epidérmico (EGFR) en pacientes afectados de carcinoma no microcítico de pulmón (CPNM). Material y método: se incluyó 45 pacientes (12 adenocarcinomas y 33 carcinomas escamosos) en los que se analizó, mediante tissue-arrays, la expresión de los factores biológicos. Los valores de SUV se obtuvieron 60 min después de la administración del radiofármaco y la imagen se efectuó en un PET Advanced System (GE). Resultados: la expresión de COX-2 se apreció en 35/45 casos, y fue muy importante (> ++) en 12. Los valores de SUV fueron menores (p = 0,059) en los casos COX-2 > ++ que en los restantes (13,4 ± 1,2 frente a 12,9 frente a 17,1 ± 1,5). La expresión de COX-2 > ++ no se correlacionó con el estadio, ni tampoco lo hizo el SUV. La expresión de COX-2 > ++ se correlacionó positivamente con la de p16 (r = 0,36; p = 0,014) y negativamente con la de MIB1 (r = -0,32; p = 0,041), mientras que la SUV lo hizo positivamente con la del EGFR (r = 0,44; p = 0,004) y negativamente con la de p16 (r = -0,29; p = 0,041). Conclusiones: a) la expresión intensa (> ++) de COX-2 se constata en el 26,6% de los CPNM y es independiente del estadio clínico; b) los valores de SUV tampoco se relacionaron con el estadio y fueron menores en los tumores COX-2++ que en el resto de casos, y c) este comportamiento diferente de ambos parámetros se podría explicar por sus distintas relaciones con la proliferación celular (MIB1) y la expresión de EGFR y p16 (AU)

Objective: To study the expression of COX-2 and its possible relationship with the maximum standardized uptake value (SUV) in FDG-PET, and EGFR, p16 and MIB1 expression in patients with NSCLC. Material and method: 45 patients (12 adenocarcinomas and 33 squamous cell carcinomas) were included in this study; the immunohistochemical expression of COX-2, MIB-1, p16 and EGFR was determined using tissue-array. Each PET was performed 60 minutes after the i.v. administration of 350-518 MBq of FDG on an Advance system (GE) in 2D acquisition mode. Results: COX-2 expression was detected in 35 out of 45 cases, and was very significant (> ++) in 12 of them. SUV values were lower in the COX-2 > ++ cases that in the remaining cases (13.4 ± 1.2 vs. 12.9 vs. 17.1 ± 1.5; p = 0.059). COX-2 > ++ expression and maxSUV values were not correlated with the clinical stage. The expression of COX-2 > ++ was correlated positively with p16 (r = 0.36; p = 0.014) and negatively with MIB1 (r = -0.32; p = 0.041) expression, whereas the SUV was correlated positively with EGFR (r = 0.44; p = 0.004) and negatively with p16 (r = -0.29; p = 0.041) expression. Conclusions: Our results suggest that: a) the expression of COX-2 > ++ is often found in this kind of lung cancer and is not associated with the clinical stage; b) the maxSUVs were not related to the stage and were lower in COX-2 > ++ tumours than in the other cases; and c) the different behaviour of both parameters can be explained by their correlation with cell proliferation (MIB1), EGFR and p16 expression. © 2008 Elsevier España, S.L. and SEMN. All rights reserved (AU)

Serum levels of keratin-18 fragments [tissue polypeptide-specific antigen (TPS)] are correlated with hepatocyte apoptosis in alcoholic hepatitis.

Apoptosis is a major feature in alcoholic hepatitis. During apoptosis, the M30 neoepitope becomes exposed after keratin-18 cleavage. The tissue polypeptide-specific antigen (TPS) is a keratin-18 fragment that is routinely used as a tumor marker. Serum TPS levels are increased in patients with alcoholic hepatitis. The aim of this study was to investigate the possible relationship of TPS levels with hepatocyte apoptosis in alcoholic hepatitis. Thirty-one patients with alcoholic hepatitis and 22 with fatty liver were included. Hepatocyte apoptosis was evaluated by M30 immunostaining. Serum TPS levels were measured by a commercial immunoassay. The apoptotic score was higher in patients with alcoholic hepatitis than in patients with fatty liver. There was a significant correlation between the apoptotic score and TPS levels. The correlation of the apoptotic score with TPS levels was stronger than with standard liver tests. Serum TPS may be a marker of apoptosis in alcoholic hepatitis.

[The autoimmune hepatitis-primary biliary cirrhosis overlap syndrome: a case report]. / Síndrome overlap hepatitis autoinmune-cirrosis biliar primaria: a propósito de un caso.

The autoimmune hepatitis-primary biliary cirrhosis overlap syndrome is an entity characterized by clinical, analytical, immunological and histological manifestations of both entities. We present the case of a 26-year-old woman with a serious acute hepatitis that fulfills the diagnostic criteria of the overlap syndrome and that showed a satisfactory response to oral corticoid therapy.

Serum cytokeratins in alcoholic liver disease: contrasting levels of cytokeratin-18 and cytokeratin-19.

Serum cytokeratin (CK) levels are widely used as tumor markers. Serum levels of CK-18, a tumor marker also known as tissue polypeptide specific antigen (TPS), are increased in patients with alcoholic liver disease. Cytokeratin-18 is the main component of Mallory bodies, a hallmark of alcoholic hepatitis, which may also contain CK-19. Serum levels of CK-18 and CK-19, a tumor marker also known as CYtokeratin FRAgment 21-1 (CYFRA 21-1) were investigated in (a) heavy drinkers with alcoholic liver disease (n=15), (b) patients with malignancy (n=22), and (c) healthy controls (n=10). Serum levels of CYFRA 21-1 (CK-19) were markedly increased in patients with malignancy, but were similar in heavy drinkers and healthy controls. In contrast, serum levels of TPS (CK-18) in heavy drinkers were higher than those of healthy controls, and even tended to be higher than those of patients with malignancy. Both CK-19 and CK-18 levels were higher in cases of alcoholic hepatitis than in cases of fatty liver. Correlation with hepatocyte CK inclusions was stronger for serum TPS (CK-18) than for CYFRA 21-1 (CK-19). In conclusion, serum CYFRA 21-1 (CK-19) and TPS (CK-18) show a different pattern of increase that could reflect the composition of the altered hepatocyte CK network in alcoholic liver disease. Their usefulness as tumor markers, particularly that of serum TPS (CK-18), may be limited in patients with alcoholic liver disease.

Breast tumor resembling the tall cell variant of papillary thyroid carcinoma: a case report.

The breast tumor resembling the tall cell variant of papillary thyroid carcinoma is a very unusual mammary carcinoma whose histologic and predominant nuclear features mimic a papillary thyroid carcinoma. We report the case of a 64-year-old woman who presented with a palpable nodule in the right breast. Fine needle aspiration disclosed abundant cellularity with isolated cells, sheets, and papillary formations of epithelial cells with nuclear grooves. Histologically, the neoplastic cells were arranged in a solid to papillary architecture, with follicular-like and cribriform areas. The cells were columnar to cuboidal with eosinophilic cytoplasm, clear chromatin, nuclear grooves, and occasional nuclear pseudoinclusions. Tumor cells were positive for cytokeratins, alpha and beta-estrogen receptors, progesterone receptor, androgen receptor, CEA, and bcl-2. We searched for BRAF mutations with negative results. Recognizing the cytologic and histologic characteristics of these peculiar mammary tumors that mimic thyroid carcinomas can avoid unnecessary clinical investigations.

Cell-cycle-associated markers and clinical outcome in human epithelial cancers: a tissue microarray study.

The development and progression of epithelial cancers are the result of an imbalance in signals promoting and inhibiting cellular proliferation and apoptosis. The aim of this study is to evaluate the expression of cell-cycle and apoptosis regulators and correlate them with clinical outcome in the most frequent carcinomas, in order to establish common prognostic biomarkers independent of cancer origin. Using tissue microarrays (TMAs), we have analysed the immuno-expression of Ki-67, Bcl-2, Bax, cyclin D1, cyclin D3, CDK1, CDK2, CDK6, p16, p21, and p27 in a series of 205 carcinomas of the large bowel, breast, lung and prostate (80, 73, 37 and 15 cases, respectively). By univariate analysis, positivity for p27, p16 and Bcl-2 was associated with better overall survival (P<0.0135, P<0.0442 and P<0.0001, respectively). The risk of mortality was 2.3-fold greater in patients without Bcl-2 expression. TMA immunohistochemical analysis identified a subset of epithelial cancers with overlapping alterations in cell-cycle checkpoints, apoptosis regulators and tumour suppressor pathways. We found that in most common epithelial cancers, regardless of origin, Bcl-2 appears to be the key biological factor influencing clinical behaviour.

Prospective histopathological analysis of hepatocellular carcinoma treated with percutaneous ethanol injection in patients on the waiting list for liver transplantation.

INTRODUCTION: Liver transplantation (LT) improves survival in selected patients suffering from hepatocellular carcinoma (HCC). Unfortunately, the long time lapse between indication and LT may cause tumor progression. Thus, percutaneous ethanol injection (PEI) has been proposed as adjuvant therapy of HCC in patients awaiting LT. The efficacy of PEI assessed using histopathological analysis of hepatectomy specimens has not been adequately evaluated. PATIENTS AND METHODS: Twenty-nine nodules of HCC in 27 patients (21 men; mean age, 58.1 +/- 7.3 years) listed for LT were treated with PEI. Pretreatment mean serum alpha-fetoprotein (AFP) was 11 +/- 13.4 ng/mL. Mean tumor diameter was 30.8 +/- 12.9 mm. Data from the explanted livers after transplantation included percentage tumor necrosis, presence of satellite and distant nodules, vascular invasion, tumor capsule, and grade of differentiation. RESULTS: Nineteen patients with 20 treated lesions underwent transplantation. The median interval PEI-LT was 3 months. Complete necrosis was observed in 13 nodules (65%). Satellite nodules were present in 10% of lesions. Previously unrecognized distant lesions were seen in 15.8% of patients. Only 1 nodule presented microscopic vascular invasion. Most HCC were well differentiated (90%), and completely encapsulated (80%). No tumor-related deaths occurred. Seventeen patients are alive and recurrence-free after a median follow-up of 15 months. CONCLUSIONS: PEI may achieve significant necrosis in cases of HCC awaiting LT. Nevertheless, previously unrecognized satellite and distant lesions may be observed. Further studies are needed to evaluate the influence of tumor necrosis on overall survival of these patients.

Doppler ultrasonography for the assessment of tumor necrosis after percutaneous ethanol injection prior to liver transplantation as adjuvant therapy of hepatocellular carcinoma.

INTRODUCTION: Percutaneous ethanol injection (PEI) is considered to be a curative treatment for hepatocellular carcinoma (HCC). The imaging technique of choice for the assessment of local response after PEI has not been well defined, but helical computerized tomography (hCT) has been recommended. The aim of this study was to assess the accuracy of Doppler ultrasonography (US) for evaluation of tumor necrosis after PEI. PATIENTS AND METHODS: Twenty-one patients with single HCC listed for liver transplantation underwent multisession US-guided PEI. Liver Doppler US was done at the 4th week after PEI. Complete response was defined as the absence of any intratumoral Doppler signal. The liver was analyzed in transplant recipients during the follow-up. Complete pathological response was defined as necrosis > or = 90% of total tumor volume. Histological and sonographic findings were compared. RESULTS: Twelve patients underwent transplantation (9 men, mean age 60 +/- 5.2 years). Nine of these (75%) showed a complete ultrasonographic response. In the explanted liver, complete necrosis was present in 6 nodules, and incomplete necrosis was seen in the remaining 6 cases. In comparison with histology, Doppler US showed values of sensitivity, specificity, positive predictive values, and negative predictive values of 50%, 100%, 100%, and 60%, respectively. Overall accuracy was 75%. CONCLUSIONS: In our series, Doppler US showed low sensitivity but high specificity in the assessment of HCC necrosis after PEI. The ultrasonographic finding of complete response requires hCT for confirmation, but the presence in Doppler US of neoplastic viable tissue is enough to indicate a further cycle of PEI.

Prolonged survival after liver transplantation for Hodgkin's disease-induced fulminant liver failure.

A 30-year-old male with a past history of nodular lymphocyte predominance Hodgkin's disease in apparent complete remission for two years received a liver transplantation because of fulminant liver failure. Histopathological examination of the explanted liver showed massive infiltration by Hodgkin's disease. In spite of a nodal recurrence of Hodgkin's disease, the patient is alive and in excellent general condition six years after liver transplantation.

Serum levels of tissue polypeptide specific antigen are correlated with hepatocyte cytokeratin expression in alcoholic liver disease.

BACKGROUND: Serum levels of the tumor marker tissue polypeptide specific antigen (TPS, cytokeratin 18 fragments) are increased in patients with alcoholic liver disease, particularly in cases of alcoholic hepatitis. Mallory bodies, characteristic of alcoholic hepatitis, are cytokeratin 8 and 18 aggregates. The study was aimed at investigating the possible relationship of serum TPS levels with hepatocyte cytokeratin expression in patients with alcoholic liver disease. METHODS: Twenty-four patients with alcoholic liver disease were studied. Immunohistochemical staining for cytokeratins 8 and 18 was performed in liver specimens by means of CAM 5.2 monoclonal antibody. The number of hepatocytes containing CAM 5.2-reactive cytokeratin inclusions was compared with serum TPS levels. MAIN RESULTS AND CONCLUSIONS: The vast majority of alcoholics (95%) showed increased (>100 units/liter) serum TPS levels. Serum TPS levels were significantly correlated with the number of hepatocyte cytokeratin inclusions. Serum TPS levels can predict hepatocyte cytokeratin expression in patients with alcoholic liver disease.

Liver-cell adenomas with heavy iron deposition.

We report 3 unusual cases of liver cell adenomas with some uncommon features, corresponding to 3 women aged 45, 37, and 41 years, respectively. The diagnosis was incidental in 2 cases, and the third presented with abdominal pain. Radiologic findings were consistent with liver-cell adenoma, but gross examination failed to reveal the lesion until 24 hours of formalin fixation in 2 cases. Histopathological examination showed a striking deposition of iron pigment. In fact, Pearl's stain was the best way to visualize the limits of the neoplasm, which were irregular (pseudo-infiltrative). There was no evidence of other architectural or cytologic features suggesting an alternative diagnosis, particularly liver-cell carcinoma. Follow-up ranged from 9 months to 6 years and all patients are free of disease.