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Sydney D Finkelstein

Publications and source records attributed to Sydney D Finkelstein.

At least 19 recordsLinked to original sources
PubMed2007

Analysis of loss of heterozygosity in atypical and negative bile duct brushing cytology specimens with malignant outcome: are "false-negative" cytologic findings a representation of morphologically subtle molecular alterations?

CONTEXT: Conventional cytologic evaluation of bile duct brushings for neoplasia has high specificity but relatively low sensitivity. OBJECTIVE: The aim of this pilot study was to examine whether K-ras mutations and loss of heterozygosity for multiple microsatellite markers in bile duct brushings would contribute to the detection of malignancy in cases initially reported as "negative" or "atypical." DESIGN: Bile duct brushing specimens with a negative or an atypical cytologic result (9 cases) had a benign result on the surgical pathology specimen, and 9 additional negative or atypical cases demonstrated adenocarcinoma on the resected surgical specimen. Cells from representative cytopathology and histology slides were microdissected and analyzed for K-ras mutations and for loss of heterozygosity with a panel of 15 polymorphic markers on chromosomes 1p, 3p, 5q, 9p, 9q, 10q, 17p, and 22q. RESULTS: Among cytology cases with malignant outcome, loss of heterozygosity or K-ras mutation was detected in 8 (88.8%) of 9 cases. In the corresponding 9 surgical pathology specimens with adenocarcinoma, K-ras mutations and/or allelic losses were detected in all (100%). Loss of heterozygosity or K-ras mutation was not detected in cytology cases that had a benign surgical outcome. The fractional allelic loss of these 9 cytology specimens ranged from 0 to 0.25 (mean, 0.14). This compared with the fractional allelic loss ranging from 0.15 to 0.42 (mean, 0.27) for the corresponding surgical specimens. CONCLUSIONS: This pilot study suggests that low-level fractional allelic loss or K-ras mutation in the negative/atypical cytology samples with malignant outcome is a representation of morphologically subtle molecular alterations.

Adenocarcinoma↗
PubMed2006

Analysis of loss of heterozygosity for tumor-suppressor genes can accurately classify and predict the clinical behavior of mucinous tumors arising from the appendix.

BACKGROUND: Pseudomyxoma peritonei is a rare heterogenous clinical syndrome with a variable clinical course. On the basis of the hypothesis that cumulative mutational damage can predict biological aggressiveness, we evaluated the utility of integrated histopathology and molecular analysis for patients with pseudomyxoma peritonei syndrome. METHODS: Tissue specimens from 23 mucinous appendiceal tumors were analyzed. DNA samples from multiple sites were analyzed for loss of heterozygosity by using a panel of 15 allelic loss microsatellite markers and K-ras-2 point mutational damage. The fractional mutational rate (FMR), determined as the number of mutated markers divided by the total number of informative markers, was calculated by using the six most informative markers and the K-ras-2 gene. Kappa statistics were calculated to test the association between FMR and the histopathologic classification. RESULTS: Our study included 6 female and 17 male patients with a mean age of 53.6 years and a mean survival of 43.9 months. We found an association between tumor loss of heterozygosity markers and histopathologic classification (P < .05). In addition, there was also an association between the FMR and pathological classification as well as between the FMR and survival (P < .05). An FMR less than .25 indicated low-grade disease, an FMR of .25 to .50 indicated intermediate grade, and an FMR greater than .5 indicated a high-grade tumor. CONCLUSIONS: Mutational profiling of accumulated allelic loss and point mutational damage correlated strongly with histopathologic definitions of pseudomyxoma peritonei disease and helped to predict the prognosis of these patients. FMR, along with histopathology, offers a comprehensive classification of these rare tumors.

Adenocarcinoma, Mucinous↗
PubMed2006

Determination of sequential mutation accumulation in pancreas and bile duct brushing cytology.

Neoplastic progression is characterized by clonal expansion of tumor cells associated with accumulation of mutational damage. The timing of mutation acquisition could be of value in distinguishing preneoplastic conditions from early and advanced cancer as well as characterizing tumor aggressiveness and treatment response. Using quantitative methods applied to microdissected cell clusters selected according to cytomorphologic features, we sought to demonstrate the feasibility and efficacy for determining the time and course of mutation accumulation in pancreatobiliary cytology specimens. In all, 40 pancreatic duct and 21 biliary brushing cytology specimens were retrieved from the cytology database. Xylene-resistant markings were placed on the slide underside and coverslips removed. Clusters of benign, atypical and malignant cells were manually microdissected and DNA extracted. Mutations (allelic imbalance) (loss of heterozygosity) were quantitatively determined for a broad panel of 15 markers (1p, 3p, 5q, 9p, 10q, 17p, 17q, 21q, 22q) as well as point mutation in K-ras-2 using PCR/capillary electrophoresis. Time course was based on earlier mutations having a higher proportion of mutant DNA for a particular marker. The descending frequency of detectable mutational involvement in pancreatic cytology was K-ras-2 point mutation (58%), 3p25-26 and 17q21 (35%), 5q23 (33%), 1p36 (28%), followed by the remaining molecular markers. The descending frequency of mutational content in bile duct cytology was 17p13, 1p36, 3p25-26, and 5q23 followed by remaining molecular markers. K-ras-2 point mutation was not seen in bile duct specimens. While there was overlap in the spectrum of mutational markers in pancreatic duct and biliary brushing cytology, the temporal profile was significantly different (P<0.001). Pancreatic and biliary neoplasia progression involves distinct subset of accumulated defined mutations. Determination of timing of the mutational damage in cytologic material could be incorporated in the work-up and help in making a more definitive diagnosis of malignancy in pancreatobiliary cytology specimens.

Biliary Tract Neoplasms↗
PubMed2006

K-Ras and microsatellite marker analysis of fine-needle aspirates from intraductal papillary mucinous neoplasms of the pancreas.

Preoperative diagnosis of pancreatic cystic lesions is difficult despite the combination of cytomorphology, radiographic imaging characteristics, and fluid tumor markers such as carcinoembryonic antigen. Intraductal papillary mucinous neoplasms (IPMNs) represent a subset of preinvasive pancreatic cystic neoplasms and are associated with accumulated genetic mutations, especially K-ras and tumor suppressor genes such as p53. Application of molecular techniques to cyst fluid obtained by endoscopic ultrasound guided fine-needle aspiration (EUSFNA) may contribute to preoperative assessment. Sixteen patients with pancreatic cystic lesions had cyst fluid obtained by preoperative pancreatic EUSFNA or intraoperative aspiration. All patients subsequently underwent surgical resection of the pancreas and IPMN was documented in all (6 adenomas, 6 borderline tumors, and 4 carcinomas). DNA was extracted from the cyst fluids and mutational analysis for K-ras point mutations and loss of heterozygosity (LOH) analysis using a preselected panel of genomic loci were performed. LOH was observed in 3 of 4 carcinomas as compared to 4 of 11 adenomas and borderline lesions (1 was QNS). LOH and K-ras mutations were both acquired in 2 of 4 carcinomas and in 1 of 12 adenoma/borderline lesions. Although the study is small, molecular analysis for LOH and K-ras mutations is useful in the preoperative evaluation of cystic pancreatic lesions. Increasing degree of neoplasia appears to correlate with increased genetic abnormality using a panel of selected genomic markers.

Adenocarcinoma, Mucinous↗
PubMed2006

Microdissection genotyping analysis of the effect of intraarterial cytoreductive chemotherapy in the treatment of lacrimal gland adenoid cystic carcinoma.

PURPOSE: To investigate the feasibility of integrating molecular analysis into standard histopathology for lacrimal gland adenoid cystic carcinoma (ACC), and to gain insights into the molecular pathogenesis of this tumor and its response to intraarterial cytoreductive chemotherapy (IACC) that is of clinical use. DESIGN: A retrospective, comparative case series. METHODS: setting: Institutional. patient population: Nine consecutive patients with lacrimal gland ACC were treated with IACC, followed by orbital exenteration and chemoradiotherapy. This case series was compared with a series of seven patients treated by conventional local therapies. intervention procedure: Gene analysis was performed on microdissected tissue samples. Mutational allelotyping targeting nine genomic loci was performed with 15 polymorphic microsatellite markers situated in proximity to known tumor suppressor genes serving as markers for the presence of gene deletion. main outcome measure: A fractional mutation index was used to compare the acquired mutational load between different tumors having nonidentical patterns of microsatellite informativeness. RESULTS: Allelic imbalance (loss of heterozygosity [LOH]) for microsatellite markers at 1p36 was the single most common site affected by imbalance in this series, followed by LOH in temporal sequence involving 9p21, 22q12, 10q23, and 9q22. CONCLUSIONS: Microdissection genotyping holds promise as a clinical tool in integrating molecular analysis into standard histopathology to advance the understanding of lacrimal gland ACC tumorigenesis. A unique time course for temporal mutation acquisition in ACC is proposed, consisting of 1p36 loss first. Allelic loss for microsatellite markers at 1p36 may be a common as well as an early event in ACC formation and progression.

Adult↗
PubMed2006

Endoscopic ultrasound fine needle aspirate DNA analysis to differentiate malignant and benign pancreatic masses.

OBJECTIVES: Accurate diagnosis of malignant and benign pancreatic masses can be challenging, potentially delaying treatment for cancer and subjecting patients with benign disease to unnecessary surgery. Endoscopic ultrasound fine needle aspirate (EUS-FNA) of pancreatic masses remains inconclusive in a subset of patients. The role of EUS-FNA molecular analysis in this context is studied. METHODS: Patients with benign pancreatic masses (6 cases, 4 autoimmune pancreatitis, 2 focal chronic pancreatitis) and malignant pancreatic masses (15) with inconclusive cytology (5 cases) and positive cytology (10 controls) were selected. All cases had definitive pathology. Representative cells were microdissected from each EUS-FNA sample and subjected to PCR for analysis of 16 microsatellite allele loss markers situated at 1p, 3p, 5q, 9p, 9q, 10q, 17p, 17q, 21q, and 22q. Loss of heterozygosity analysis used fluorescent capillary electrophoresis for quantitative determination of allelic imbalance. k-ras-2 point mutation analysis was also performed. Mean fractional mutation rate (FMR) was calculated and compared for each group. RESULTS: All malignant cases carried multiple mutations (FMR 0.50), regardless of positive cytology (FMR 0.52) or suspicious cytology (FMR 0.47) (p = NS). Five of the 6 benign cases carried no mutations whereas 1 case of autoimmune pancreatitis and coexisting PanIN lesions exhibited a k-ras mutation (FMR 0.01). The mean FMR for the malignant and benign samples was significantly different (p < 0.0001). CONCLUSIONS: Broad panel microsatellite loss and k-ras point mutation analysis can be reliably performed on EUS-FNA samples from pancreatic masses and improves the diagnostic accuracy. Furthermore, it accurately differentiates between malignant and benign pancreatic masses.

Adult↗
PubMed2006

Microdissection-based allelotyping: a novel technique to determine the temporal sequence and biological aggressiveness of colorectal cancer.

Pathologic staging in colorectal adenocarcinoma (CA) is based on the concept that the timing of metastatic tumor spread is directly related to the depth of the primary tumor invasion. To evaluate the temporal sequence of CA metastasis, we performed microdissection mutational profiling at multiple microscopic sites of primary and metastatic CA specimens. Twenty-one cases of CA were selected from fixed-tissue archives. Primary tumors were microdissected at the deepest point of invasion. Comparative mutational profiling for different genomic loci [1p36(CCM = cutaneous malignant melanoma], 3p26(OGGI = 8 oxoguanine DNA glycosylase), 5q23 (APC, MCC = mutated in colorectal cancer), 9p21(p16/CDKN2A = cyclin-dependent kinase 2A), 10q23(PTEN = phosphatase and tensin homolog [mutated in multiple advanced cancers 11), 12p12(K-ras-2 point mutation), 17p13(TP53), 18q25(DCC= deleted in colorectal cancer) was carried out on each microdissected tissue target using microsatellite loss of heterozygosity determination or DNA sequencing. All primary and metastatic sites of CA manifested acquired mutational change in 18 to 91 per cent of the genomic markers. In 15/21 (71%) cases, metastatic sites lacked a specific allelic loss seen in the corresponding primary tumor, indicating that the metastasis occurred before maximal depth of primary invasion. This was further supported by discordant mutational profiles between primary and secondary tumors, requiring divergent clonal evolution. This is the first report describing the temporal sequence and significance of sequential mutational acquisition in clinical tissue specimens with potential implications for a new molecular pathology approach to classify human cancer.

Adenocarcinoma↗
PubMed2005

Molecular staging of lymph nodes from patients with esophageal adenocarcinoma.

PURPOSE: This study was designed to evaluate molecular markers for the detection of micrometastasis in esophageal adenocarcinoma, define algorithms to distinguish positive from benign lymph nodes and to validate these findings in an independent tissue set and in patients with p(N0) esophageal adenocarcinoma. EXPERIMENTAL DESIGN: Potential markers were identified through literature and database searches. All markers were analyzed by quantitative reverse transcription (QRT)-PCR on a limited set of primary tumors and benign lymph nodes. Selected markers were further evaluated on a larger tissue set and classification algorithms were generated for individual markers and combinations. Algorithms were statistically validated internally as well as externally on an independent set of lymph nodes. Selected markers were then used to identify occult disease in lymph nodes from 34 patients with p(N0) esophageal adenocarcinoma. RESULTS: Thirty-nine markers were evaluated, six underwent further analysis and five were analyzed in the external validation study. Two markers provided perfect classification in both the screening and validation sets, although parametric bootstrap analysis estimated 2% to 3% optimism in the observed classification accuracy. Several marker combinations also gave perfect classification in the observed data sets, and estimates of optimism were lower, implying more robust classification than with individual markers alone. Five of thirty-four patients with esophageal adenocarcinoma had positive nodes by multimarker QRT-PCR analysis and disease-free survival was significantly worse in these patients (P = 0.0023). CONCLUSIONS: We have identified novel QRT-PCR markers for the detection of occult lymph node disease in patients with esophageal adenocarcinoma. The objective nature of QRT-PCR results, and the ability to detect occult metastases, make this an attractive alternative to routine pathology.

Adenocarcinoma↗
PubMed2005

Neoadjuvant imatinib in gastrointestinal stromal tumor of the rectum: report of a case.

Gastrointestinal stromal tumors are rare tumors of the gastrointestinal tract. Gastrointestinal stromal tumors involving the rectum are uncommon. We describe a case of a 43-year-old female with a gastrointestinal stromal tumor of the rectum who declined abdominoperineal resection. Neoadjuvant treatment with imatinib decreased her tumor size, permitting sphincter-sparing transanal excision. She had no evidence of disease for 24 months postoperatively until she recurred with lung metastases. Microdissection genotyping of the recurrent lesion revealed a deletion in exon 11. Further mutational analysis showed that her metastatic lesion was concordant with her primary rectal lesion, suggesting that systemic micrometastasis was previously present at initial diagnosis. Deletion in exon 11 predicts for response with imatinib treatment and is associated with a longer event-free and overall survival. Current studies are underway that may help us optimize the treatment for patients with gastrointestinal stromal tumors.

Antineoplastic Agents↗
PubMed2005

Microdissection-based mutational genotyping of serous borderline tumors of the ovary.

Mutational changes in a number of genetic foci were studied in 12 serous borderline tumors (SBTs) of the ovary including 2 with a micropapillary pattern. The analysis was focused on chromosomal regions that have not been previously studied in these tumors. The findings were correlated with the morphology and the FIGO stage of the tumors. Six of the tumors were stage I, one was stage II, and five were stage III. Loss of heterozygosity analysis in each tumor was performed with a panel of 12 polymorphic markers on chromosomes 1p, 5q, 9p, 9q, 10q, and 17p. The ovarian tumors displayed allelic losses most frequently on 1p (83.3%), 9q (70%), and 17p (41.7%). In the extraovarian implants, allelic losses on 1p, 9q, and 17p were present in 66.7%, 75%, and 66.7% of cases respectively. In five of six cases, allelic losses were 88% concordant between multiple tumor sites. Only one case of stage III tumor displayed a discordant pattern of allelic loss at different tumor sites. Cumulative allelic losses did not show a statistically significant difference in stage I vs. higher stage disease. The pattern and cumulative allelic loss in the two cases with micropapillary architecture was similar to that of the other tumors. We report a high frequency of allelic loss on 1p and 9q that has not been previously reported in SBTs. Morphologically heterogenous areas including benign-appearing, typical borderline, and micropapillary areas had a similar pattern of allelic loss. Although the majority of SBTs seem to be monoclonal, a minor subset may be multiclonal in origin.

Adult↗
PubMed2004

Clonal selection of adenocarcinoma of the lung as determined by loss of heterozygosity.

Although the most frequently altered oncogenes and tumor suppressor genes in non-small cell lung carcinoma (NSCLC) have been recognized, the exact mechanisms responsible for the progression and phenotypic expression of carcinoma, particularly adenocarcinoma of the lung are uncertain. Fifty-six cases of adenocarcinoma of the lung (11 bronchioloalveolar carcinoma [BAC], 25 stage 1, 20 stage 2) and paired 19 lymph node metastases (LNM) of stage 2 adenocarcinomas were analyzed for loss of heterozygosity (LOH). Analysis included a panel of 14 polymorphic microsatellite markers located on 1p, 3p, 5q, 9p, 10q, and 17p. LOH on chromosomes 1p (P = 0.0209) and 17p (P = 0.0274) was more frequently present in stage 1 adenocarcinomas than in BAC. There was no significant difference between BAC, stage 1 and stage 2 adenocarcinoma in the frequency of LOH at individual chromosomal arms. The pattern of LOH in LNM of stage 2 adenocarcinoma was similar to the primary tumor. Overall fractional allelic loss (FAL) was significantly different between BAC and stage 1 invasive adenocarcinoma (P = 0.0013), and it was significantly higher in stage 1 adenocarcinoma than in stage 2 adenocarcinoma (P = 0.0062) and their LNM (P = 0.0001). Stage 2 adenocarcinomas showed significantly higher overall FAL than their LNM (P = 0.022). Our study failed to identify a single target gene responsible for progression of lung adenocarcinoma. A trend towards lower overall FAL in advanced stage tumors and in their metastases suggests that clonal selection may play a role in lung adenocarcinoma progression.

Adenocarcinoma↗
PubMed2004

Molecular profiling of primary and metastatic neoplasms in the lung using cytologic material obtained by fine-needle aspiration: report of two cases.

Two cases are presented in which molecular analyses of cytologic material obtained by fine-needle aspiration were helpful in establishing relationships between morphologically similar neoplasms in the same patient. For appropriate clinical management, it is important to ascertain whether the tumors represent independent primaries or metastases. Alcohol-fixed cytologic material prepared as cell blocks and formalin-fixed paraffin-embedded tissue were microdissected and analyzed for allelic loss of heterozygosity at multiple preselected genetic loci. The first case illustrates a 69-yr-old man with multiple intrapulmonary nodules involving the upper and lower lobes of the left lung. Genomic analysis showed that the neoplasms in the left upper and lower lung lobes were independent primaries, because the loss of heterozygosity (LOH) patterns were substantially different. By contrast, the second case is that of a 58-yr-old man with a right thyroid nodule and multiple pulmonary tumors. LOH analysis confirmed that a sampled pulmonary tumor represented a metastasis from the thyroid primary, as similar LOH patterns involving locus D9S252 were observed on comparison of the thyroid and pulmonary neoplasms. These cases illustrate the practical diagnostic utility of genomic analysis using cytologic material in the assessment of primary and metastatic malignancies.

Aged↗
PubMed2004

Microdissection genotyping of archival fixative treated tissue for Gaucher disease.

The genetic diagnosis of Gaucher disease by molecular methods is complicated by the existence of a highly homologous transcribed pseudogene (96% identity) that is found in close proximity to the true gene on chromosome 1q21. In addition, the pseudogene sequence can mimic disease-causing mutations in the true gene. Selective polymerase chain reaction (PCR) amplification of the true gene can be accomplished in extracted DNA from fresh-frozen samples by designing oligonucleotide primers to hybridize to defined regions that are not present in the pseudogene. This standard molecular approach, which entails amplification of relatively long segments of intact DNA, is not feasible in archival, paraffin-embedded, solid-tissue specimens in which the negative effects of chemical fixation result in DNA strand scission and breakdown of nucleic acid. A novel approach, specifically created for use with archival, fixative-treated tissue specimens, was developed for detection and characterization of common mutations of Gaucher disease. Three separate robust PCR reactions were formulated, 2 for selective amplification of portions of only the true gene exons 2 and 9, with a third reaction targeting exon 10, wherein both the true and pseudogene were coamplified. In the latter, DNA sequencing was used to determine the presence of true and pseudogene allele content in addition to identification of base sequence alterations. This method, requiring a single, 4-microm-thick histologic section, was successfully applied to archival paraffin block tissue specimens that had been in storage for up to 75 years. It was capable of accurately genotyping common Gaucher disease mutations as well as discovering a novel mutation and genetic polymorphism. We recommend our approach when only fixative-treated tis sue is available for molecular genotyping.

DNA Primers↗
PubMed2004

Loss of heterozygosity reveals non-VHL allelic loss in hemangioblastomas at 22q13.

Hemangioblastomas (HBs) are low-grade (World Health Organization grade I/IV) central nervous system (CNS) tumors that frequently contain VHL (3p26) mutations. They occur sporadically and in von Hippel Lindau (VHL) disease. Encoded pVHL aids degradation of hypoxia-inducible factors (HIFs) in the presence of normal oxygen levels. HBs provide an in vivo view of HIF effects within a CNS tumor. Typically, HBs are cystic tumors containing a mural nodule formed by noninvasive, vacuolated stromal cells that are embedded in a network of capillaries. Nine HBs, consecutively resected from 8 patients at our institution during a recent 2-year time span, were evaluated for additional losses of tumor suppressor genes. Non-VHL microsatellites studied for loss of heterozygosity (LOH) are near tumor suppressor genes lost in gliomas, pituitary adenomas, several CNS tumors on 22q, neurofibromatosis 1, and colon carcinomas (13, 2, 2, 1, and 2 markers for each, respectively). LOH in the region of 3p21.3-3p26.3 occurred in 3 of 8 HBs informative for at least 1 marker (D3S1539, D3S2303, or D3S2373). By using 2 markers (D22S417 and D22S532) for 22q13.2, LOH was found in 5 of 8 informative HBs. All 3 HBs with allelic losses near VHL also showed LOH at 22q13.2. No consistent losses were found with markers for 1p34, LMYC, 5q21, 5q32, 9p21, 10q23, 17p13, and 19q13. LOH for the 22q13.2 region in HBs suggests that the loss of another tumor suppressor gene is involved in the pathogenesis of HBs in addition to VHL. Absence of LOH for glioma markers is consistent with the low-grade behavior of HBs.

Adult↗
PubMed2004

Comparison of mutational changes in involved N1 lymph nodes with those in primary tumors in stage II non-small cell lung cancer: a pilot study.

OBJECTIVES: Surgical resection is the standard treatment for stage II non-small cell lung cancer, but recurrence rates approach 60%. This study compared mutational changes in involved lymph nodes and primary tumors from patients with stage II non-small cell lung cancer to determine whether risk factors for recurrence could be identified. METHODS: Forty patients with resected stage II non-small cell lung cancer (excluding T3 N0 disease) were studied. Microdissection was performed on primary tumors and lymph nodes. Analysis was performed across 9 genomic loci by using polymerase chain reaction amplification. The ratio of fractional allelic loss between involved lymph nodes and primary tumors was used to stratify patients into high-risk (fractional allelic loss ratio of >or=1) and low-risk (fractional allelic loss ratio of <1) groups. RESULTS: The median age of the patients was 68 years (range, 42-85 years). Median follow-up was 30 months. Fractional allelic loss was greater in patients with squamous carcinomas compared with that in adenocarcinomas, but survival was similar (35 vs 39 months). The median survival was 35 months in high-risk patients and was not reached in low-risk patients (P =.3). Disease-free survival was 24 months in high-risk patients and was not reached in low-risk patients (P =.35). In the subset with adenocarcinoma (n = 18), median survival was 24 months in the high-risk group; no deaths occurred in low-risk patients (P =.01). Also, disease-free survival was 14 months in high-risk patients and was not reached in the low-risk patients (P =.05). CONCLUSIONS: Squamous cancers demonstrate greater mutational changes than adenocarcinomas; this does not affect outcome. The patients with low-risk adenocarcinomas demonstrated superior outcomes compared with those of other patients. These results should be confirmed in larger studies.

Adult↗
PubMed2004

Role of liver transplantation for hepatobiliary malignant disorders.

The role of liver transplantation for hepatobiliary malignant disorders remains controversial and will remain so until several crucial issues are resolved, the main difficulty being the shortage of organ donors. Furthermore, a consensus needs to be reached within the transplantation community on the tumour stage at which each disorder is too advanced to be salvaged by liver transplantation. Despite these limitations, there are generally accepted criteria that define when transplantation can, and should, be offered for hepatobiliary malignant disorders.

Biliary Tract Neoplasms↗
PubMed2004

Gliosarcoma with epithelial differentiation: immunohistochemical and molecular characterization. A case report and review of the literature.

Few reported cases of gliosarcomas or glioblastomas with epithelial-like areas exist. Most cases were originally diagnosed as metastatic carcinoma. Focal expression of glial fibrillary acidic protein has helped characterize these tumors as having a glial origin. We report a case of gliosarcoma with multifocal, extensive areas of well-differentiated carcinoma; demonstrating squamous and glandular differentiation. The expression of glial fibrillary acidic protein and epithelial phenotype were mutually exclusive. We performed extensive immunohistochemical analyses and comparative genotypic analysis using microdissection to secure representative glial and epithelial components. Loss of heterozygosity was analyzed with a panel of 12 polymorphic microsatellite markers designed to indicate allelic loss and situated in proximity to known tumor suppressor genes located on chromosomes 1p, 9p, 10q, 17p and 19q. We found comparable patterns of acquired allelic loss between the glial and carcinomatous components, strongly supporting the monoclonal origin of this neoplasm. This case represents an extreme form of phenotypic divergence in a malignant glioma, and constitutes a difficult diagnostic challenge. This heterogeneity reflects the potential for a range of phenotypic expression in malignant gliomas that needs to be recognized. We suggest microdissection genotyping as a molecular technique to better characterize these tumors.

Aged↗