Highlights from the 7th Oncological Pathology Conference 'Pathological Anatomy in the context of the National Cancer Law: An overview of the Latin American experience', 15, 22 and 23 July 2022, Trujillo, Peru.

The seventh session of the Oncological Pathology Conference (JoPaO) entitled 'Pathological Anatomy in the context of the National Cancer Law: An overview of the Latin American experience', was held virtually on July 15, 22 and 23. Peru was the headquarters for this event, where 17 national and international professors of high academic standing participated. They interacted in a multidisciplinary context through talks with national panellists and the general public. The recent promulgation of the 'National Cancer Law' fosters the development of discussion forums to analyse the national realities and uphold continuous learning about experiences in other Latin American countries with successful cancer programmes, in which pathology holds a principal role. The topics addressed during this JoPaO included the exchange of Latin American cancer management experiences, an emphasis on investments in and the development of strategic plans to improve care, the use of new technologies, laboratory quality control, and the need to advance scientific research.

Undifferentiated carcinoma with osteoclast-like giant cells of the pancreas diagnosed by endoscopic ultrasound guided biopsy.

Undifferentiated pancreatic carcinoma with osteoclast-like giant cells is a rare tumour that has been published under a wide variety of names, including pleomorphic carcinoma, giant cell carcinoma, sarcomatoid carcinoma and carcinosarcoma, among others. For these reasons and its low frequency, the reports of these tumours are scarce and frequently lead to confusion with other entities which present with giant cells. We present the case of a patient with obstructive jaundice and a mixed cystic and solid pancreatic mass, accompanied by multiple hepatic lesions. The histological study of the material obtained by endoscopic ultrasound guided biopsy demonstrated a proliferation of atypical epithelioid cells, accompanied by a spindle cell component with marked pleomorphism and numerous osteoclast-like giant cells. The epithelioid component showed positive immunostaining with cytokeratin cocktail and cytokeratin 7. The spindle cell component showed coexpression of cytokeratins and vimentin. The osteoclast-like giant cells were positive for CD68. Protein p53 was overexpressed in both epithelial and spindle cell neoplastic components, and was negative in the giant cells. These findings permitted the diagnosis of undifferentiated carcinoma of the pancreas with osteoclast-like giant cells. This case outlines the effectiveness of endoscopic ultrasound-guided biopsy and the importance of morphological and immunohistochemical examination in the diagnosis of different types of pancreatic tumours, especially when they are in advanced stages and are not suitable for surgical treatment.

Childhood liver tumors in Argentina: Incidence trend and survival by treatment center. A report from the national pediatric cancer registry, ROHA network 2000-2015.

BACKGROUND: Information on the epidemiology of pediatric liver tumors in Latin America is limited. PURPOSE: To describe the incidence of liver tumors in a pediatric registry in Argentina according to geographic region, national trends over 16 years, and survival related to stage, age, sex, and care center. METHODS: Newly diagnosed liver tumors cases are registered in the Argentine Pediatric Oncology Hospital Registry (ROHA) with an estimated coverage of 91% of national cases. Age-standardized incidence rate per millon (ASR) was calculated based on the National Vital Statistics Reports. Five-year overall survival (OS) was estimated using the Kaplan-Meier method. The log-rank test was used to compare subgroup survival. RESULTS: Two hundred seven cases of hepatoblastoma (HB) and 73 of hepatocellular carcinoma (HCC) were identified. ASR of liver tumors was 1.8/million (95% confidence Interval [CI], 1.6-2.0) per year. ASR was 1.4 (1.2-1.6) for HB and 0.4 (0.3-0.5) for HCC. For HB, the highest incidence was found in the northwest region including the Altiplano. OS was 60.4% (53.4-66.8) for HB and 36.1% (25.2-47.2) for HCC. Five-year survival rate of children with metastatic HB treated at liver transplant hospitals (LTH) was 54.2% (30.3-73.0) compared to 13.3% (2.2-34.6) for those seen at other hospitals (OH) (P = .02), while for HCC this rate was 46.3% (30.7-60.6) at LTH compared to 17.5% (3.1-41.9) at OH (P = .01). CONCLUSIONS: The incidence rate of pediatric liver tumors was stable over the 16-year study period. Patients may benefit if at treatment initiation they are evaluated jointly with LTH specialists to define treatment strategies.

Identification of Factors Affecting Tacrolimus Trough Levels in Latin American Pediatric Liver Transplant Patients.

Tacrolimus is the cornerstone in pediatric liver transplant immunosuppression. Despite close monitoring, fluctuations in tacrolimus blood levels affect safety and efficacy of immunosuppressive treatments. Identifying the factors related to the variability in tacrolimus exposure may be helpful in tailoring the dose. The aim of the present study was to characterize the clinical, pharmacological, and genetic variables associated with systemic tacrolimus exposure in pediatric liver transplant patients. De novo transplant patients with a survival of more than 1 month were considered for inclusion and were genotyped for cytochrome P450 3A5 (CYP3A5). Peritransplant clinical factors and laboratory covariates were recorded retrospectively between 1 month and 2 years after transplant, including alanine aminotransferase (ALT), aspartate aminotransferase, hematocrit, and tacrolimus predose steady-state blood concentrations collected 12 hours after tacrolimus dosing. A linear mixed effect (LME) model was used to assess the association of these factors and the log-transformed tacrolimus dose-normalized trough concentration (logC0/D) levels. Bootstrapping was used to internally validate the final model. External validation was performed in an independent group of patients who matched the original population. The developed LME model described that logC0/D increases with increases in time after transplant (ß = 0.019, 95% confidence interval [CI], 0.010-0.028) and ALT values (ß = 0.00030, 95% CI, 0.00002-0.00056), whereas logC0/D is significantly lower in graft CYP3A5 expressers compared with nonexpressers (ß = -0.349, 95% CI, -0.631 to -0.062). In conclusion, donor CYP3A5 genotype, time after transplant, and ALT values are associated with tacrolimus disposition between 1 month and 2 years after transplant. A better understanding of tacrolimus exposure is essential to minimize the occurrence of an out-of-range therapeutic window that may lead to adverse drug reactions or acute rejection.

Colorectal Adenoma Risk Is Increased among Recently Diagnosed Adult Celiac Disease Patients.

BACKGROUND: The association between celiac disease and colorectal neoplasia has been previously studied, but the question whether recently diagnosed celiac patients show an increased colorectal adenoma prevalence remains unanswered. AIMS: To compare the prevalence of colorectal adenomas between adult patients with a recent diagnosis of celiac disease versus healthy controls. MATERIALS AND METHODS: A retrospective case-control study was undertaken. Patients with a diagnosis of celiac disease at an age of 45 years or more who undertook colonoscopy six months before or six months after the initiation of a gluten-free diet were enrolled as cases. Asymptomatic subjects undertaking screening colonoscopy were recruited as controls in a 2 : 1 fashion. The prevalence of colorectal adenomas and the prevalence of advanced adenomas were compared between groups. RESULTS: 57 celiac disease patients and 118 controls were enrolled. There was a greater prevalence of female patients among the celiac group, with no significant differences in terms of age. There were more obese patients among controls and a higher proportion of tabaquism among celiac patients. Adenoma prevalence was significantly higher among celiac patients (47.37% versus 27.97%, p = 0.01). Advanced adenoma detection was not different between groups. CONCLUSION: Adult patients with a recent diagnosis of celiac disease have an increased prevalence of colorectal adenomas.

Minimal Disseminated Disease in Nonmetastatic Retinoblastoma With High-Risk Pathologic Features and Association With Disease-Free Survival.

IMPORTANCE: Fatal metastatic relapse may occur in children with retinoblastoma and high-risk pathologic features (HRPFs). Minimal dissemination (MD) may be an additional tool for risk estimation. The use of cone-rod homeobox (CRX) transcription factor messenger RNA for MD evaluation in metastatic retinoblastoma was previously reported, but no data in nonmetastatic cases with HRPFs are available. OBJECTIVES: To evaluate whether MD is detectable in patients with nonmetastatic retinoblastoma and to assess its prognostic effect on disease-free survival (DFS). DESIGN, SETTING, AND PARTICIPANTS: This single-institution cohort study of patients with nonmetastatic retinoblastoma and HRPFs used prospectively defined inclusion criteria and a sampling strategy to procure bone marrow (BM) and cerebrospinal fluid (CSF) samples from May 1, 2007, through October 31, 2013. Median follow-up was 38 months (range, 8-89 months). Survival analysis was closed in December 2015, and no further updates were made after that point. INTERVENTIONS: The study evaluated CRX messenger RNA by quantitative polymerase chain reaction in BM and CSF at diagnosis and follow-up. In 14 patients, GD2 synthase was used instead of CRX for CSF evaluation. Patients were treated under uniform guidelines. MAIN OUTCOMES AND MEASURES: Metastatic relapse. RESULTS: The study included 96 children (median age at study inclusion, 26 months; range, 1-168 months; 46 male [47.9%]; 50 female [52.1%]) with nonmetastatic retinoblastoma and HRPFs (isolated massive choroidal invasion in 14, postlaminar optic nerve invasion in 51 [26 with concomitant massive choroidal and 13 with scleral invasion], 12 with scleral invasion without postlaminar optic nerve invasion, and 7 with tumor at the resection margin of the optic nerve) were evaluated at the time of primary or secondary enucleation. Minimal dissemination was detected in 9 patients (7 BM samples and 2 CSF samples) and was associated with extension beyond the resection margin of the optic nerve and scleral involvement, but only the former was independently associated (adjusted odds ratio, 57.0; 95% CI, 4.8-678.2; P = .001). In addition, MD occurred in 8 of the 43 International Intraocular Retinoblastoma Classification group E eyes with glaucoma (18.6%) and in 8 of 80 (10%) and 1 of 16 children (6.3%) who underwent primary or secondary enucleation, respectively. Children with MD had a 3-year DFS of 0.78 compared with 0.98 in those without MD (95% CI for the difference in DFS, 0.17-0.23; P = .004). CONCLUSIONS AND RELEVANCE: These findings identified a high-risk population of children with retinoblastoma and HRPFs with MD. Because the number of events was small, these results, which suggest that children with International Intraocular Retinoblastoma Classification group E retinoblastoma and glaucoma have a higher risk of MD at diagnosis, should not be considered definitive at this time.

Hepatic metastasis of thymoma: case report and immunohistochemical study.

Thymomas are rare tumours characterised by their slow growth and capacity to invade directly by contiguity. While distant dissemination is infrequent, all sub-types of thymoma have the capacity to metastasise to extrathoracic organs. We present here the case of a female patient with a liver mass discovered 13 years after the removal of a mediastinal thymoma and after ten years from thyroidectomy for papillary carcinoma. The histopathological study showed that the lesion contained an epithelial component, which was immunohistochemically positive for pankeratin. It was accompanied by numerous small lymphocytes testing positive for TdT, CD3, CD4, CD5, CD8, CD99, and CD43. The result was consistent with hepatic metastatic thymoma sub-type B1, according to the World Health Organisation classification (WHO). Our case highlights the importance of morphological and immunohistological examinations in the differential diagnosis of visceral masses in patients with a history of thymoma. Given the infrequency of its metastasis and the increased risk of developing other primary tumours that these patients have, these studies play a significant role.

[Tufting enteropathy: a case report, histopathological methodology, and differential diagnoses]. / Enteropatía en penacho: reporte de un caso, metodología de estudio de la biopsia y diagnósticos diferenciales.

Tufting enteropathy (TE), previously known as intestinal epithelial dysplasia, is a rare congenital enteropathy characterized by refractory diarrhea in the neonatal period. It presents clinical and histological heterogeneity and may be associated with birth defects and punctuate keratitis. The causative gene(s) have not yet been identfied making prenatal diagnosis unavailable. Although there are milder phenotypes most require parenteral nutrition for prolonged periods with the risk of complications. TE becomes an indication for intestinal transplantation. We report the case of a 4-month-old male, born full term with a normal weight. The parents consulted because of severe malnutrition and chronic watery diarrhea. Duodenal and rectal biopsy was negative. Because of poor tolerance gastroclysis was changed to parenteral nutrition. The infant had several catheter-related infections and died at 13 months from catheter-associated complications. Histopathological autopsy was performed. The material was fixed in paraffin and studied with routine techniques. PAS and immunohistochemistry for CD10 were performed. We observed villous atrophy with intestinal epithelial dysplasia and disorganization on the surface of epithelial cells resembling tufts in jejunal and ileal tissue. The objective of this study was to present a rare case of neonatal enteropathy, especially TE, describe the methodology used to study the biopsy, and discuss the differential diagnoses. TE is a rare neonatal enteropathy that is difficult to diagnose and manage. Children in whom TE is suspected should be referred to specialized pediatric centers, with the option of intestinal transplantation.

Immunoreactivity of the 14F7 Mab raised against N-Glycolyl GM3 Ganglioside in retinoblastoma tumours.

INTRODUCTION: The identification of molecules expressed selectively on the surface of retinoblastoma cells would allow applying targeted therapies. The Ganglioside, N-Glycolyl-GM3 (NeuGc-GM3), is an attractive candidate, as it has been detected in other paediatric neuroectodermic tumours, and it is not expressed in human normal tissues. The 14F7 antibody recognizes specifically the ganglioside NeuGc-GM3. PURPOSE: To characterize the expression of NeuGc-GM3 in retinoblastoma cell lines and in retinoblastoma tumours using the 14F7 monoclonal antibody. METHODS: We studied WERI-Rb1 and Y79 cell lines, 24 retinoblastoma primary tumours from unilateral and bilateral cases and two bone marrow biopsies from metastatic retinoblastoma. Tumours were classified into three groups: non-invasive (n = 13), invasive (n = 9) and metastatic (n = 2). Three eyes enucleated because of non-tumoural conditions were used as controls. Cell lines and tumour sections were studied by immunohistochemistry using the 14F7 antibody. NeuGc-GM3 expression was evaluated by analysing the percentage of positive tumoural cells and the staining intensity. These parameters were analysed comparatively among the three groups. RESULTS: Both retinoblastoma cell lines showed immunoreactivity to NeuGc-GM3 but WERI-Rb1 presented higher intensity than Y79. All the tumours studied showed strong immunoreactivity to NeuGc-GM3 with no significant differences among groups. In both bone marrow specimens, NeuGc-GM3 immunoreactivity was observed in retinoblastoma cells. In bilaterally enucleated cases, NeuGc-GM3 immunoreactivity was not altered before and after chemotherapy. Non-tumoural retinas were negative. CONCLUSIONS: NeuGc-GM3 is highly expressed in retinoblastoma cell lines, tumours and metastatic cells to the bone marrow, and it is not detectable in control eyes. There were no significant differences in the immunoreactivity to 14F7 among tumours from different disease stages. Its immunoreactivity did not change after chemotherapy.

[Rhabdomyosarcoma of the biliary tree. Case report]. / Rabdomiosarcoma de la vía biliar. Presentación de un caso.

We present a girl 21 months old with recurrent jaundice. Initially she presented fever of unknown origin but jaundice, white coloured stools and pruritus were observed 10 days later. She underwent endoscopic retrograde cholangiopancreatography with sphincterotomy; symptoms dissapeared. One month later, symptoms came back and, suspecting choledochal cyst the patient underwent endoscopic retrograde cholangiopancreatography for diagnostic confirmation and for placement of a biliary stent. The material obtained was sent for histopathology study and embryonal rhabdomyosarcoma of the biliary tree was diagnosed. The patient started chemotherapy following EpSSGRMS 2005 protocol. There was no evidence of metastasis. She completed treatment and to the day of this report she is free of illness.

Rabdomiosarcoma de la vía biliar: Presentación de un caso / Rhabdomyosarcoma of the biliary tree: Case report

Se presenta el caso de una paciente de 21 meses con ictericia recurrente. La consulta inicial se había realizado debido a la aparición de febre de origen desconocido, pero después de 10 días se observó ictericia, acolia y prurito. Se efectuó una colangipancreatografía retrógrada endoscópica con esfnterotomía amplia, con lo que se logró la desaparición de los síntomas. Un mes más tarde, estos reaparecieron, por lo que, con sospecha de que se trataba de un quiste del colédoco, se realizó una nueva colangipancreatografía retrógrada endoscópica para confrmar el diagnóstico y colocar un stent para drenaje de la vía biliar. El material obtenido en el estudio se envió a anatomía patológica y se diagnosticó rabdomiosarcoma embrionario de la vía biliar. Se inició tratamiento con quimioterapia según el protocolo EpSSGRMS 2005. La niña no presentaba metástasis en el momento del diagnóstico. Completó el tratamiento y hasta la fecha de redacción de este trabajo, se encontraba libre de enfermedad.

We present a girl 21 months old with recurrent jaundice. Initially she presented fever of unknown origin but jaundice, white coloured stools and pruritus were observed 10 days later. She underwent endoscopic retrograde cholangiopancreatography with sphincterotomy; symptoms dissapeared. One month later, symptoms came back and, suspecting choledochal cyst the patient underwent endoscopic retrograde cholangiopancreatography for diagnostic confrmation and for placement of a biliary stent. The material obtained was sent for histopathology study and embryonal rhabdomyosarcoma of the biliary tree was diagnosed. The patient started chemotherapy following EpSSGRMS 2005 protocol. There was no evidence of metastasis. She completed treatment and to the day of this report she is free of illness.

Inflammatory myofibroblastic tumor of the lung in children: anaplastic lymphoma kinase (ALK) expression and clinico-pathological correlation.

The inflammatory myofibroblastic tumor (IMT) is a rare neoplastic lesion with a high incidence in children and young people, and may arise in lungs, soft tissue, or viscera. It is recognized as a borderline tumor with the possibility to recur, undergo malignant transformation, and metastasize. IMT is composed of fascicles of bland myofibroblastic cells admixed with an inflammatory infiltrate consisting of lymphocytes, plasma cells, and eosinophils. We reviewed pulmonary IMT diagnosed at Garrahan Hospital in Buenos Aires, Argentina, during 12 years and examined the clinical, laboratory, and pathological features as well as molecular genetics. Eight pediatric cases were evaluated with a male-to-female ratio of 5:3 and a median age of 6 years at diagnosis. The most common lung localization was the upper lobe. All cases underwent surgical excision and no local recurrences were found. Five out of eight patients, including two cases with metastatic/multifocal lesions in the central nervous system (CNS), are alive and disease free after a median follow-up of 30 months. Anaplastic lymphoma kinase (ALK) expression was negative in all pulmonary samples by immunohistochemistry (IHC), however, rearrangement for ALK locus by fluorescence in situ hybridization was found in one lung and in two CNS samples. These findings may reflect higher sensitivity of the molecular biologic procedure compare to traditional IHC practice. In our pediatric experience, 25% of patients with lung IMT developed CNS lesions; therefore we consider that CNS screening in these patients should be considered, at diagnosis and later during follow up.

Detection of N-glycolyl GM3 ganglioside in neuroectodermal tumors by immunohistochemistry: an attractive vaccine target for aggressive pediatric cancer.

The N-glycolylated ganglioside NeuGc-GM3 has been described in solid tumors such as breast carcinoma, nonsmall cell lung cancer, and melanoma, but is usually not detected in normal human cells. Our aim was to evaluate the presence of NeuGc-GM3 in pediatric neuroectodermal tumors by immunohistochemistry. Twenty-seven archival cases of neuroblastoma and Ewing sarcoma family of tumors (ESFT) were analyzed. Formalin-fixed, paraffin-embedded tumor samples were cut into 5 µm sections. The monoclonal antibody 14F7, a mouse IgG1 that specifically recognizes NeuGc-GM3, and a peroxidase-labeled polymer conjugated to secondary antibodies were used. Presence of NeuGc-GM3 was evident in 23 of 27 cases (85%), with an average of about 70% of positive tumors cells. Immunoreactivity was moderate to intense in most tumors, showing a diffuse cytoplasmic and membranous staining, although cases of ESFT demonstrated a fine granular cytoplasmic pattern. No significant differences were observed between neuroblastoma with and without NMYC oncogene amplification, suggesting that expression of NeuGc-GM3 is preserved in more aggressive cancers. Until now, the expression of N-glycolylated gangliosides in pediatric neuroectodermal tumors has not been investigated. The present study evidenced the expression of NeuGc-GM3 in a high proportion of neuroectodermal tumors, suggesting its potential utility as a specific target of immunotherapy.

Detection and characterization of N-glycolyated gangliosides in Wilms tumor by immunohistochemistry.

Gangliosides are glycolipids present on the cell surface. The N-glycolylated ganglioside NeuGc-GM3 has been described in some neoplasms, such as breast carcinoma and melanoma, but is usually not detected in normal human cells. Our aim was to evaluate the presence of NeuGc-GM3 in Wilms tumor by immunohistochemistry. Postchemotherapy tumors were grouped into different histologic subtypes considering the main preserved component. Formalin-fixed, paraffin-embedded tumor samples were cut into 5-microm sections. The monoclonal antibody 14F7, a mouse IgG1 that specifically recognizes NeuGc-GM3, and a peroxidase-labeled polymer conjugated to secondary antibodies were used. Sections from breast carcinoma were employed as positive controls. Presence of NeuGc-GM3 was evident in 22 of 25 (88%) cases. The staining was stronger in the epithelial component, with a membrane pattern and cytoplasmic diffusion. The stromal component expressed cytoplasmic NeuGc-GM3 in cells with rhabdomyoblastic differentiation. Tubules of adjacent renal tissue were also positive, but no expression of NeuGc-GM3 was detected in nontumoral fetal kidney. Until now, the expression of N-glycolylated gangliosides in pediatric solid tumors has not been investigated. The present study evidenced the expression of NeuGc-GM3 in a high proportion of Wilms tumors, suggesting its potential utility as a specific target of immunotherapy.

Diffuse hyperplastic perilobar nephroblastomatosis.

Nephroblastomatosis is a rare preneoplastic lesion defined as the presence of diffuse or multifocal nephrogenic rests. They are divided into 4 categories: perilobar, intralobar, combined, and universal. The aim of this report is to describe a case of diffuse hyperplastic perilobar nephroblastomatosis. A 1-year-old boy presented with an abdominal mass on the left side. Computed tomography scan showed a homogeneous, isointense enlarged left kidney. A fine needle aspiration cytology was reported as Wilms tumor. After chemotherapy, the left kidney was excised. Nephrectomy specimen presented a thick cortical rim of hyperplastic nephrogenic tissue, well delineated from preserved renal parenchyma without pseudocapsule. Nephroblastomatosis is a rare condition affecting renal parenchyma. Diagnosis is based on imaging studies, such as ultrasound, computed tomography scan, and magnetic resonance imaging. Fine needle aspiration cytology is of limited value. Therapeutic management is controversial. Chemotherapy is used preoperatively, and surgical excision may be an alternative for refractory cases.

Mortality risk score in liver transplantation: changes over time in its predicting power.

UNLABELLED: Since the onset of our liver transplantation program in 1992, 362 transplants were performed in 338 children. A risk score for predicting mortality was designed and implemented over time. The description of a method utilized to design the risk score, changes in mortality rate over 12 yr and the analysis of factors that might have influenced these changes are presented and discussed in this paper. PATIENTS AND METHODS: Cox regression analysis was applied to a retrospective sample of 110 patients with liver cirrhosis, transplanted between 1992 and 2000. A risk score was prepared using beta coefficients of the two significant variables related to survival time: age (1.08, p=0.02) and bilirubin levels (0.93, p=0.03), and two groups were identified: low- and high-risk score. The score was applied in two consecutive samples: 2000-2002 and 2002-2004. RESULTS: In the first sample (1992-2000), we found 69 and 41 as low- and high-risk patients, with a median survival time of 93.13 and 2.93 months (p=0.0001). In the 2000-2002 sample, a median survival time of 41.7 and 2.33 months (p=0.03) was found for low- and high-risk groups, respectively. In the third sample (2002-2004), there was a remarkable decrease in mortality in the high-risk group (n=29) and the score did not discriminate between high- and low-risk groups (p=0.35). CONCLUSION: A scoring system to identify risk levels in liver transplantation patients is an operative and powerful tool during a given period of time but it has to be updated as risk factors will vary following the team's learning curve.

Alagille syndrome: cutaneous manifestations in 38 children.

The Alagille syndrome is one of the most common inherited disorders causing chronic liver disease during childhood. During the 1990s, 38 children with Alagille syndrome were evaluated at two pediatric centers in Buenos Aires, Argentina. Characteristic clinical, humoral, and cutaneous features were analyzed. The average age of diagnosis was 29 months old (range of between 2 months and 15 years). Cholestasis was evident in 92% of patients during the neonatal period. Family antecedents related to the syndrome were found in 18.5% of the patients. Peculiar facies developed in 85% of patients. Chronic cholestasis and pruritus were observed in all of the patients and jaundice was evident in 78%. Eighty-four percent of the patients had heart disease (pulmonary stenosis, intraauricular communication, intraventricular communication), 76% of them showed growth retardation, and vertebrae abnormalities were found in 63%. Embryotoxon appeared in 76% of patients, and renal disturbances in 21%. Eleven children (28%) had xanthomas, in the neck, elbows, palms, helixes, inguinal area, gluteus, and knees. The earliest findings appeared in the first months of life, and the latest at 5 years of age. The xanthomas located in the folds had a stony aspect. Cholesterol levels ranging from 220 to 1600 mg percentage (mg%) were demonstrated in all of the children with xanthomas. Liver transplantation was performed in seven of the patients (18.4%). Two of them died after this operation. The disappearance of xanthomas after transplantation was remarkable in all of the patients.