Texture image analysis in differentiating malignant from benign adrenal cortical tumors in children and adults.

OBJECTIVE: To investigate the possible role of chromatin texture parameters, nuclear morphology, DNA ploidy and clinical functional status in discriminating benign from malignant adrenocortical tumors (ACT). PATIENTS AND METHODS: Forty-eight cases of clinically benign (n=40) and clinically malignant (n=8) ACT with a minimum of 5-years' follow-up were evaluated for chromatin texture parameters (run length, standard deviation, configurable run length, valley, slope, peak and other 21 Markovian features that describe the distribution of the chromatin in the nucleus), nuclear morphology (nuclear area, nuclear perimeter, nuclear maximum and minimum diameter, nuclear shape), and DNA ploidy. Nuclear parameters were evaluated in Feulgen-stained 5 mum paraffin-sections analyzed using a CAS 200 image analyzer. RESULTS: Since ACTs present different biological features in children and adults, patients were divided into two groups: children (< or = 15 years) and adults (>15 years). In the group of children DNA ploidy presented a marginal significance (p=0.05) in discriminating ACTs. None of the parameters discriminated between malignant and benign ACT in the adult group. CONCLUSION: ACTs are uncommon and definitive predictive criteria for malignancy remain uncertain, particularly in children. Our data point to DNA content evaluated by image analysis as a new candidate tool for this challenging task. Texture image analysis did not help to differentiate malignant from benign adrenal cortical tumors in children and adults.

Molecular profiling of isolated histological components of Wilms tumor implicates a commom role for the Wnt signaling pathway in kidney and tumor development

Wilms tumor (WT), a tumor composed of three histological components - blastema (BL), epithelia and stroma - is considered an appropriate model system to study the biological relationship between differentiation and tumorigenesis. To investigate molecular associations between nephrogenesis and WT, the gene expression pattern of individual cellular components was analyzed, using a customized platform containing 4,608 genes. WT gene expression patterns were compared to genes regulated during kidney differentiation. BL had a closer gene expression pattern to the earliest stage of normal renal development. The BL gene expression pattern was compared to that of fetal kidney (FK) and also between FK and mature kidney, identifying 25 common deregulated genes supposedly involved in the earliest events of WT onset. Quantitative RT-PCR was performed, confirming the difference in expression levels for 13 of 16 genes (81.2%) in the initial set and 8 of 13 (61.5%) in an independent set of samples. An overrepresentation of genes belonging to the Wnt signaling pathway was identified, namely PLCG2, ROCK2 and adenomatous polyposis coli (APC). Activation of the Wnt pathway was confirmed in WT, using APC at protein level and PLCG2 at mRNA and protein level. APC showed positive nuclear immunostaining for an independent set of WT samples, similarly to the FK in week 11. Lack of PLCG2 expression was confirmed in WT and in FK until week 18. Taken together, these results provided molecular evidence of the recapitulation of the embryonic kidney by WT as well as involvement of the Wnt pathway in the earliest events of WT onset.

Hepatoblastoma and liver development: a study of cytokeratin immunoexpression in twenty-nine hepatoblastoma

Hepatoblastomas (HBs) recapitulate liver development. It is possible that HBs result from malignant transformation of hepatic precursor cells, and they may reflect a blockage in normal development. Here we study the expression of cytokeratins (CKs) in order to delineate the immunoprofile and relationship with liver development, as well as vimentin and alphafetoprotein (AFP), of HBs. Immunohistochemistry was performed in a tissue microarray (TMA) containing representative areas of 18 HBs (fetal and/or embryonal and/or mesenchymal); we also reviewed 11 cases not included in the TMA. No cases stained for CKs 1, 5/6, 7, 10, 13, 15, 16, 20, and 34betaE12. CK8 stained 73.07% of fetal, 50% of embryonal, and 18% of mesenchymal areas. CK18 stained 100% of epithelial areas. CK19 staining was intense and diffuse in 100% of embryonal samples, but it was weaker in fetal areas (66.66%). AE1 stained epithelial areas in all cases, and it stained 29.41% of mesenchymal areas. AE3 stained 84.61% of embryonal and 60% of fetal components. AE1/AE3 showed stronger staining in embryonal (100%) than in fetal areas (76.92%). Vimentin staining was strong in embryonal (66.66%) and mesenchymal (84.61%) components but weak in fetal areas (8%). Alphafetoprotein was positive in only 20% of fetal and 70% of embryonal areas. Our results support the hypothesis that immunoexpression of HBs follows the stages of normal liver development. Embryonal areas look less differentiated, expressing vimentin and biliary epithelium CKs, whereas fetal areas display a more developed phenotype, similar to that of mature hepatocytes. These data aid in understanding the ontogenesis of HBs and may be used in histopathological diagnosis

p53 as a prognostic factor in adrenocortical tumors of adults and children.

Mutations of the tumor suppressor gene p53 have been considered to be important determinants in several kinds of human cancer. Accumulation of p53 protein has been reported to correlate with more aggressive clinical behavior in some neoplasms. The role of p53 expression in adrenal cortical tumors (ACT) has not been elucidated but some studies have suggested its correlation with malignant behavior. Our objective was to determine if there is a correlation between the expression of immunoreactive p53 and the biological behavior of ACT. Fifty-seven ACT (21 from children and 36 from adults) were evaluated for p53 expression by immunohistochemistry in formalin-fixed paraffin-embedded tissue and analyzed in terms of outcome. The p53 parameter was utilized semiquantitatively. Tumors were classified as p53 negative when no positivity was observed, or when only few cells showed weak positivity (0/1+) and scored as p53 positive when there was a diffuse and strong nuclear positivity (2+/3+). In children, p53 positivity was associated with clinically malignant ACT and p53 negativity was associated with clinically benign ACT (P = 0.026). In adults' ACT, p53 positivity had an effect on disease-free survival (P<0.001) and also correlated with Weiss score, with a cutoff = 4 (P = 0.04). p53 expression was related to the clinical behavior of ACT in both children and adults and these findings seem to support a role for p53 in ACT progression.

p53 as a prognostic factor in adrenocortical tumors of adults and children

Mutations of the tumor suppressor gene p53 have been considered to be important determinants in several kinds of human cancer. Accumulation of p53 protein has been reported to correlate with more aggressive clinical behavior in some neoplasms. The role of p53 expression in adrenal cortical tumors (ACT) has not been elucidated but some studies have suggested its correlation with malignant behavior. Our objective was to determine if there is a correlation between the expression of immunoreactive p53 and the biological behavior of ACT. Fifty-seven ACT (21 from children and 36 from adults) were evaluated for p53 expression by immunohistochemistry in formalin-fixed paraffin-embedded tissue and analyzed in terms of outcome. The p53 parameter was utilized semiquantitatively. Tumors were classified as p53 negative when no positivity was observed, or when only few cells showed weak positivity (0/1+) and scored as p53 positive when there was a diffuse and strong nuclear positivity (2+/3+). In children, p53 positivity was associated with clinically malignant ACT and p53 negativity was associated with clinically benign ACT (P = 0.026). In adults' ACT, p53 positivity had an effect on disease-free survival (P<0.001) and also correlated with Weiss score, with a cutoff = 4 (P = 0.04). p53 expression was related to the clinical behavior of ACT in both children and adults and these findings seem to support a role for p53 in ACT progression

Immunohistochemical detection of p53 protein expression as a prognostic indicator in Wilms tumor.

BACKGROUND: Mutations of the tumor suppressor gene p53 are commonly found in several kinds of human cancer. In some types of neoplasms, accumulation of p53 protein has been reported to correlate with more aggressive clinical behavior. The role of p53 expression in Wilms tumors (WT) is not clear yet, but most studies have confirmed its correlation with anaplasia and advanced stage disease. PROCEDURE: Ninety-seven WT were evaluated for p53 expression by immunohistochemistry in formalin-fixed paraffin-embedded tissue and correlated with outcome. Tumors were classified as p53-Negative (p53-N) when no positivity was observed or only few cells showed weak positivity (0/1+) and p53-Positive (p53-P) when there was a diffuse and strong nuclear positivity (2+/3+). RESULTS: p53-P was detected in 13 out of 97 tumors and was associated with disease relapse (39 vs.17%; P = 0.06) but not with anaplasia. Among p53-N patients only 5% had metastatic disease compared with 31% of the p53-P sample. (P = 0.038). Overall survival was 94% for patients with p53-N vs. 85% for patients with p53-P at 1 year (P = 0.34). CONCLUSIONS: p53 expression in Wilms tumor detected by immunohistochemistry seems to be associated with advanced disease and relapse.

Immunohistochemical detection of p53 protein expression as a prognostic factor in Wilms tumor

Mutations of the tumor suppressor gene p53 are commonly found in several kinds of human cancer. In some types of neoplasms, accumulation of p53 protein has been reported to correlate with more aggressive clinical behavior. The role of p53 expression in Wilms tumors (WT) is not clear yet, but most studies have confirmed its correlation with anaplasia and advanced stage disease. Ninety-seven WT were evaluated for p53 expression by immunohistochemistry in formalin-fixed parafin-embedded tissue and correlated with outcome. Tumors were classified as p53-Negative (p53-N) when no positivity was observed or only few cells showed weak positivity (0/1+) and p53-Positive (p53-P) when there was a diffuse and strong nuclear positivity (2+/3+). p53-P was detected in 13 out of 97 tumors and was associated with disease relapse (39 vs.17%; P = 0.06) but not with anaplasia. Among p53-N patients only 5% had metastatic disease compared with 31% of the p53-P sample. (P = 0.038). Overall survival was 94% for patients with p53-N vs. 85% for patients with p53-P at 1 year (P = 0.34). p53 expression in Wilms tumor detected by immunohistochemistry seems to be associated with advanced disease and relapse.

[Hepatic hemangioma] / Hemangioma hepático.

OBJECTIVE: To describe a case of a congenital hepatic hemangioma treated with surgery. METHODS: We report the case of a 6-day-old boy who presented a giant hepatic hemangioma, and describe its evolution. RESULTS: The child developed hemodynamic instability secondary to consumption coagulopathy and respiratory failure. The image studies were inconclusive. He was submitted to surgery with complete resection of the tumor. Pathology confirmed it was hemangioma. The child was discharged after 15 days and is well, without symptoms. CONCLUSIONS: Hepatic hemangiomas should be treated conservatively, with surgery reserved for intractable cardiac failure and/or refractory consumptive coagulopaty.

Abdominal recurrence of osteogenic sarcoma: a case report.

PURPOSE: Nonpulmonary metastases from osteogenic sarcoma are rare. A patient had a localized osteogenic sarcoma of the left femur which recurred in the abdomen, a previously unreported metastatic site. PATIENT AND METHODS: An 18-year-old boy was treated for osteosarcoma. He had abdominal pain, vomiting, weight loss, and symptoms of intestinal obstruction at the time of relapse. RESULTS: The patient had diffuse widespread intraabdominal osteogenic sarcoma as the only site of initial recurrence. Abdominal computerized tomography revealed ascites and calcified masses on the hepatic and peritoneal surfaces. Laparoscopic visualization of the abdomen showed hemorrhagic ascites and multiple calcified tumor on the peritoneum, diaphragm, and liver. A biopsy of a representative lesion confirmed the diagnosis of osteogenic sarcoma. The patient died from progressive disease. CONCLUSION: As the initial treatment for patients with osteogenic sarcoma is intensified, the pattern of metastases may change. Unusual sites of recurrence such as in this patient may become more prevalent. A clinical presentation of an acute abdomen in a patient previously treated for osteogenic sarcoma should prompt suspicion of intraabdominal recurrence.

Primary malignant epithelial tumors of the liver in children: a study of DNA content and oncogene expression.

Primary malignant epithelial tumors of the liver (PMETL) are rare in the pediatric age group, and very little is known about their biology as compared with adult tumors. The prognostic value of the DNA contents measured by image analysis and expression of oncogene c-erb2 and tumor suppressor gene p53 were studied in 30 cases of PMETL in children, including 24 with hepatoblastomas (HB) and 6 with hepatocellular carcinomas (HCC). p53 overexpression was detected in 12 out of 26 cases (46.0%), or in 3 of 5 HCC and 9 of 21 HB cases. A relatively high concordance of staining was observed with the two antibodies used (clone DO7, Dako and clone DO1, Santa Cruz Biotechnology). c-erb-B2 did not yield the characteristic membrane staining in any of the 27 cases in which reliable staining was obtained. However, 1 out of 4 patients with HCC and 1 of 23 with HB revealed strong granular cytoplasmic staining in several neoplastic cells. Interestingly, these were two of the three aneuploid multiploid cases. DNA histograms of 13 out of 29 cases (54.8%) were classified as DNA aneuploid (5/6 HCC and 8/23 HB): nine were hyperdiploid, one was hypodiploid (1HB), and three were multiploid (2HB and 1HCC). In the HB group, DNA aneuploidy was strongly associated with embryonal histological areas, suggesting that a disturbance in the process of cell differentiation is associated with marked genetic aberrations. Only the group of HB was submitted to univariate analysis of survival by the Kaplan-Meier method for age (< 24 months vs. > or = 24 months), sex, preoperative chemotherapy (yes vs. no), residual disease (metastasis, and/or unresectable tumor), p53 expression by immunohistochemistry (positive vs. negative), and DNA ploidy (diploid vs. aneuploid). Only residual disease at the time of diagnosis (P < 0.017) and preoperative chemotherapy (0.030) were found to be negatively correlated with biological behavior, estimated as overall survival. DNA aneuploidy tumors (P < 0.125) and male patients (P = 0.123) showed a trend toward a more aggressive clinical behavior, although the difference was not statistically significant. Combining DNA ploidy and residual disease, patients were categorized into three groups: group I, patients with no adverse prognostic factors, i.e., diploid tumors without residual disease; group II, patients with only one adverse prognostic factor, i.e., aneuploid tumor or residual disease; and group III, patients with both adverse factors, aneuploid tumors and residual disease at time of diagnosis. A log-rank test comparing the three survival curves showed a statistically significant difference between them (P < 0.003). Although the series of cases is small, the results of this study highlight the importance of including DNA ploidy in the protocols designed for HB in children by international cooperative groups.

Abdominal recurrence of osteogenic sarcoma: a case report

Nonpulmonary metastases from osteogenic sarcoma are rare. A patient had a localized osteogenic sarcoma of the left femur which recurred in the abdomen, a previously unreported metastatic site. An 18-year-old boy was treated for osteosarcoma. He had abdominal pain, vomiting, weight loss, and symptoms of intestinal obstruction at the time of relapse. The patient had diffuse widespread intraabdominal osteogenic sarcoma as the only site of initial recurrence. Abdominal computerized tomography revealed ascites and calcified masses on the hepatic and peritoneal surfaces. Laparoscopic visualization of the abdomen showed hemorrhagic ascites and multiple calcified tumor on the peritoneum, diaphragm, and liver. A biopsy of a representative lesion confirmed the diagnosis of osteogenic sarcoma. The patient died from progressive disease. As the initial treatment for patients with osteogenic sarcoma is intensified, the pattern of metastases may change. Unusual sites of recurrence such as in this patient may become more prevalent. A clinical presentation of an acute abdomen in a patient previously treated for osteogenic sarcoma should prompt suspicion of intraabdominal recurrence.