The Experts below are selected from a list of 1710 Experts worldwide ranked by ideXlab platform
Karuna Garg - One of the best experts on this subject based on the ideXlab platform.
-
prospective detection of germline mutation of fumarate hydratase in women with uterine smooth muscle tumors using pathology based screening to trigger genetic counseling for hereditary Leiomyomatosis renal cell carcinoma syndrome a 5 year single institutional experience
The American Journal of Surgical Pathology, 2019Co-Authors: Joseph T Rabban, Emily Chan, Julie Mak, Charles Zaloudek, Karuna GargAbstract:Pathology-based screening of uterine smooth muscle tumors (uSMT) for morphology suggestive of fumarate hydratase deficiency (FH-d morphology) has been proposed as a method to identify women at increased risk for hereditary Leiomyomatosis renal cell carcinoma (HLRCC) syndrome. For 5 years our clinica
-
Uterine smooth muscle tumors with features suggesting fumarate hydratase aberration: detailed morphologic analysis and correlation with S-(2-succino)-cysteine immunohistochemistry
Modern Pathology, 2014Co-Authors: Carolina Reyes, Yevgeniy Karamurzin, Norma Frizzell, Karuna Garg, Daisuke Nonaka, Ying-bei Chen, Robert A SoslowAbstract:Rare, sporadic uterine leiomyomas arise in the setting of severe metabolic aberration due to a somatic fumarate hydratase mutation. Germline mutations account for the hereditary Leiomyomatosis and renal cell carcinoma syndrome, which predisposes for cutaneous and uterine leiomyomas and aggressive renal cell carcinomas. Altered fumarate hydratase leads to fumarate accumulation in affected cells with formation of S -(2-succino)-cysteine, which can be detected with the polyclonal antibody. High levels of these modified cysteine residues are found characteristically in fumarate hydratase-deficient cells but not in normal tissues or tumors unassociated with hereditary Leiomyomatosis and renal cell carcinoma syndrome. We hypothesized that S -(2-succino)-cysteine-positive leiomyomas, indicating fumarate hydratase aberration, have morphologic features that differ from those without S -(2-succino)-cysteine positivity. Hematoxylin and eosin-stained slides of uterine smooth-muscle tumors were prospectively analyzed for features suggesting hereditary Leiomyomatosis and renal cell carcinoma syndrome, such as prominent eosinophilic macronucleoli with perinucleolar halos, yielding nine cases. Germline genetic testing for fumarate hydratase mutations was performed in three cases. A detailed morphological analysis was undertaken, and S -(2-succino)-cysteine immunohistochemical analysis was performed with controls from a tissue microarray (leiomyomas (19), leiomyosarcomas (29), and endometrial stromal tumors (15)). Of the nine study cases, four had multiple uterine smooth muscle tumors. All cases had increased cellularity, staghorn vasculature, and fibrillary cytoplasm with pink globules. All cases had inclusion-like nucleoli with perinuclear halos (7 diffuse, 1 focal). All showed diffuse granular cytoplasmic labeling with the S -(2-succino)-cysteine antibody. Two of three tested patients had germline fumarate hydratase mutations. Only one leiomyoma from the tissue microarray controls was immunohistochemically positive, and it showed features similar to other immunohistochemically positive cases. Smooth-muscle tumors with fumarate hydratase aberration demonstrate morphological reproducibility across cases and S -(2-succino)-cysteine immuno-positivity. Although the features described are not specific for the germline fumarate hydratase mutation or the hereditary Leiomyomatosis and renal cell carcinoma syndrome, their presence should suggest fumarate hydratase aberration. Identifying these cases is an important step in the diagnostic workup of patients with possible hereditary Leiomyomatosis and renal cell carcinoma.
Robert A Soslow - One of the best experts on this subject based on the ideXlab platform.
-
Uterine smooth muscle tumors with features suggesting fumarate hydratase aberration: detailed morphologic analysis and correlation with S-(2-succino)-cysteine immunohistochemistry
Modern Pathology, 2014Co-Authors: Carolina Reyes, Yevgeniy Karamurzin, Norma Frizzell, Karuna Garg, Daisuke Nonaka, Ying-bei Chen, Robert A SoslowAbstract:Rare, sporadic uterine leiomyomas arise in the setting of severe metabolic aberration due to a somatic fumarate hydratase mutation. Germline mutations account for the hereditary Leiomyomatosis and renal cell carcinoma syndrome, which predisposes for cutaneous and uterine leiomyomas and aggressive renal cell carcinomas. Altered fumarate hydratase leads to fumarate accumulation in affected cells with formation of S -(2-succino)-cysteine, which can be detected with the polyclonal antibody. High levels of these modified cysteine residues are found characteristically in fumarate hydratase-deficient cells but not in normal tissues or tumors unassociated with hereditary Leiomyomatosis and renal cell carcinoma syndrome. We hypothesized that S -(2-succino)-cysteine-positive leiomyomas, indicating fumarate hydratase aberration, have morphologic features that differ from those without S -(2-succino)-cysteine positivity. Hematoxylin and eosin-stained slides of uterine smooth-muscle tumors were prospectively analyzed for features suggesting hereditary Leiomyomatosis and renal cell carcinoma syndrome, such as prominent eosinophilic macronucleoli with perinucleolar halos, yielding nine cases. Germline genetic testing for fumarate hydratase mutations was performed in three cases. A detailed morphological analysis was undertaken, and S -(2-succino)-cysteine immunohistochemical analysis was performed with controls from a tissue microarray (leiomyomas (19), leiomyosarcomas (29), and endometrial stromal tumors (15)). Of the nine study cases, four had multiple uterine smooth muscle tumors. All cases had increased cellularity, staghorn vasculature, and fibrillary cytoplasm with pink globules. All cases had inclusion-like nucleoli with perinuclear halos (7 diffuse, 1 focal). All showed diffuse granular cytoplasmic labeling with the S -(2-succino)-cysteine antibody. Two of three tested patients had germline fumarate hydratase mutations. Only one leiomyoma from the tissue microarray controls was immunohistochemically positive, and it showed features similar to other immunohistochemically positive cases. Smooth-muscle tumors with fumarate hydratase aberration demonstrate morphological reproducibility across cases and S -(2-succino)-cysteine immuno-positivity. Although the features described are not specific for the germline fumarate hydratase mutation or the hereditary Leiomyomatosis and renal cell carcinoma syndrome, their presence should suggest fumarate hydratase aberration. Identifying these cases is an important step in the diagnostic workup of patients with possible hereditary Leiomyomatosis and renal cell carcinoma.
-
Uterine smooth muscle tumors with features suggesting fumarate hydratase aberration: detailed morphologic analysis and correlation with S-(2-succino)-cysteine immunohistochemistry.
eScholarship University of California, 2014Co-Authors: Garg Karuna, Reyes C, Karamurzin Y, Frizzell N, Nonaka D, Chen Y-b, Robert A SoslowAbstract:Rare, sporadic uterine leiomyomas arise in the setting of severe metabolic aberration due to a somatic fumarate hydratase mutation. Germline mutations account for the hereditary Leiomyomatosis and renal cell carcinoma syndrome, which predisposes for cutan
Ying-bei Chen - One of the best experts on this subject based on the ideXlab platform.
-
leiomyoma with bizarre nuclei a morphological immunohistochemical and molecular analysis of 31 cases
Modern Pathology, 2017Co-Authors: Ying-bei Chen, Jennifer A Bennett, Britta Weigelt, Sarah Chiang, Pier Selenica, Ann Bialik, Anne M Schultheis, Raymond S Lim, Vicente MoralesoyarvideAbstract:Leiomyomas associated with hereditary Leiomyomatosis and renal cell carcinoma syndrome and leiomyomas with bizarre nuclei often show overlapping morphological features, in particular cells with prominent eosinophilic nucleoli, perinucleolar halos, and eosinophilic cytoplasmic inclusions. Although hereditary Leiomyomatosis and renal cell carcinoma syndrome is defined by fumarate hydratase (FH) germline mutations, resulting in S-(2-succino)-cysteine (2SC) formation, it is unknown whether leiomyomas with bizarre nuclei show similar alterations. In this study, we evaluated the morphology and FH/2SC immunoprofile of 31 leiomyomas with bizarre nuclei. DNA from tumor and normal tissues from 24 cases was subjected to massively parallel sequencing targeting 410 key cancer genes. Somatic genetic alterations were detected using state-of-the-art bioinformatics algorithms. No patient reported a personal history of renal neoplasia or cutaneous leiomyomas, but one had a family history of renal cell carcinoma while another had a family history of uterine leiomyomas. Aberrant FH/2SC expression was noted in 17 tumors (16 FH-negative/2SC-positive, 1 FH-positive/2SC-positive). On univariate analysis, staghorn vessels, eosinophilic cytoplasmic inclusions, diffuse distribution of prominent eosinophilic nucleoli with perinucleolar halos, and an 'alveolar pattern of edema' were associated with an abnormal immunoprofile, but only staghorn vessels remained significant on multivariate analysis. Massively parallel sequencing analysis (n=24) revealed that 13/14 tumors with aberrant FH/2SC immunoprofile harbored somatic FH somatic genetic alterations, including homozygous deletions (n=9), missense mutations coupled with loss of heterozygosity (n=3), and a splice site mutation (n=1), whereas no somatic FH mutations/deletions were found in tumors with normal immunoprofile (n=10; P<0.0001). Leiomyomas with bizarre nuclei with normal FH/2SC staining pattern more frequently harbored TP53 and/or RB1 alterations than those with aberrant FH/2SC immunoprofile (60 vs 14%; P=0.032). These data demonstrate that leiomyomas with bizarre nuclei are morphologically and genetically heterogeneous and that hereditary Leiomyomatosis and renal cell carcinoma syndrome-related morphological features, abnormal FH/2SC staining, and somatic FH mutations/deletions can be seen in a subset of sporadic tumors.
-
Uterine smooth muscle tumors with features suggesting fumarate hydratase aberration: detailed morphologic analysis and correlation with S-(2-succino)-cysteine immunohistochemistry
Modern Pathology, 2014Co-Authors: Carolina Reyes, Yevgeniy Karamurzin, Norma Frizzell, Karuna Garg, Daisuke Nonaka, Ying-bei Chen, Robert A SoslowAbstract:Rare, sporadic uterine leiomyomas arise in the setting of severe metabolic aberration due to a somatic fumarate hydratase mutation. Germline mutations account for the hereditary Leiomyomatosis and renal cell carcinoma syndrome, which predisposes for cutaneous and uterine leiomyomas and aggressive renal cell carcinomas. Altered fumarate hydratase leads to fumarate accumulation in affected cells with formation of S -(2-succino)-cysteine, which can be detected with the polyclonal antibody. High levels of these modified cysteine residues are found characteristically in fumarate hydratase-deficient cells but not in normal tissues or tumors unassociated with hereditary Leiomyomatosis and renal cell carcinoma syndrome. We hypothesized that S -(2-succino)-cysteine-positive leiomyomas, indicating fumarate hydratase aberration, have morphologic features that differ from those without S -(2-succino)-cysteine positivity. Hematoxylin and eosin-stained slides of uterine smooth-muscle tumors were prospectively analyzed for features suggesting hereditary Leiomyomatosis and renal cell carcinoma syndrome, such as prominent eosinophilic macronucleoli with perinucleolar halos, yielding nine cases. Germline genetic testing for fumarate hydratase mutations was performed in three cases. A detailed morphological analysis was undertaken, and S -(2-succino)-cysteine immunohistochemical analysis was performed with controls from a tissue microarray (leiomyomas (19), leiomyosarcomas (29), and endometrial stromal tumors (15)). Of the nine study cases, four had multiple uterine smooth muscle tumors. All cases had increased cellularity, staghorn vasculature, and fibrillary cytoplasm with pink globules. All cases had inclusion-like nucleoli with perinuclear halos (7 diffuse, 1 focal). All showed diffuse granular cytoplasmic labeling with the S -(2-succino)-cysteine antibody. Two of three tested patients had germline fumarate hydratase mutations. Only one leiomyoma from the tissue microarray controls was immunohistochemically positive, and it showed features similar to other immunohistochemically positive cases. Smooth-muscle tumors with fumarate hydratase aberration demonstrate morphological reproducibility across cases and S -(2-succino)-cysteine immuno-positivity. Although the features described are not specific for the germline fumarate hydratase mutation or the hereditary Leiomyomatosis and renal cell carcinoma syndrome, their presence should suggest fumarate hydratase aberration. Identifying these cases is an important step in the diagnostic workup of patients with possible hereditary Leiomyomatosis and renal cell carcinoma.
Carolina Reyes - One of the best experts on this subject based on the ideXlab platform.
-
Uterine smooth muscle tumors with features suggesting fumarate hydratase aberration: detailed morphologic analysis and correlation with S-(2-succino)-cysteine immunohistochemistry
Modern Pathology, 2014Co-Authors: Carolina Reyes, Yevgeniy Karamurzin, Norma Frizzell, Karuna Garg, Daisuke Nonaka, Ying-bei Chen, Robert A SoslowAbstract:Rare, sporadic uterine leiomyomas arise in the setting of severe metabolic aberration due to a somatic fumarate hydratase mutation. Germline mutations account for the hereditary Leiomyomatosis and renal cell carcinoma syndrome, which predisposes for cutaneous and uterine leiomyomas and aggressive renal cell carcinomas. Altered fumarate hydratase leads to fumarate accumulation in affected cells with formation of S -(2-succino)-cysteine, which can be detected with the polyclonal antibody. High levels of these modified cysteine residues are found characteristically in fumarate hydratase-deficient cells but not in normal tissues or tumors unassociated with hereditary Leiomyomatosis and renal cell carcinoma syndrome. We hypothesized that S -(2-succino)-cysteine-positive leiomyomas, indicating fumarate hydratase aberration, have morphologic features that differ from those without S -(2-succino)-cysteine positivity. Hematoxylin and eosin-stained slides of uterine smooth-muscle tumors were prospectively analyzed for features suggesting hereditary Leiomyomatosis and renal cell carcinoma syndrome, such as prominent eosinophilic macronucleoli with perinucleolar halos, yielding nine cases. Germline genetic testing for fumarate hydratase mutations was performed in three cases. A detailed morphological analysis was undertaken, and S -(2-succino)-cysteine immunohistochemical analysis was performed with controls from a tissue microarray (leiomyomas (19), leiomyosarcomas (29), and endometrial stromal tumors (15)). Of the nine study cases, four had multiple uterine smooth muscle tumors. All cases had increased cellularity, staghorn vasculature, and fibrillary cytoplasm with pink globules. All cases had inclusion-like nucleoli with perinuclear halos (7 diffuse, 1 focal). All showed diffuse granular cytoplasmic labeling with the S -(2-succino)-cysteine antibody. Two of three tested patients had germline fumarate hydratase mutations. Only one leiomyoma from the tissue microarray controls was immunohistochemically positive, and it showed features similar to other immunohistochemically positive cases. Smooth-muscle tumors with fumarate hydratase aberration demonstrate morphological reproducibility across cases and S -(2-succino)-cysteine immuno-positivity. Although the features described are not specific for the germline fumarate hydratase mutation or the hereditary Leiomyomatosis and renal cell carcinoma syndrome, their presence should suggest fumarate hydratase aberration. Identifying these cases is an important step in the diagnostic workup of patients with possible hereditary Leiomyomatosis and renal cell carcinoma.
Daisuke Nonaka - One of the best experts on this subject based on the ideXlab platform.
-
Uterine smooth muscle tumors with features suggesting fumarate hydratase aberration: detailed morphologic analysis and correlation with S-(2-succino)-cysteine immunohistochemistry
Modern Pathology, 2014Co-Authors: Carolina Reyes, Yevgeniy Karamurzin, Norma Frizzell, Karuna Garg, Daisuke Nonaka, Ying-bei Chen, Robert A SoslowAbstract:Rare, sporadic uterine leiomyomas arise in the setting of severe metabolic aberration due to a somatic fumarate hydratase mutation. Germline mutations account for the hereditary Leiomyomatosis and renal cell carcinoma syndrome, which predisposes for cutaneous and uterine leiomyomas and aggressive renal cell carcinomas. Altered fumarate hydratase leads to fumarate accumulation in affected cells with formation of S -(2-succino)-cysteine, which can be detected with the polyclonal antibody. High levels of these modified cysteine residues are found characteristically in fumarate hydratase-deficient cells but not in normal tissues or tumors unassociated with hereditary Leiomyomatosis and renal cell carcinoma syndrome. We hypothesized that S -(2-succino)-cysteine-positive leiomyomas, indicating fumarate hydratase aberration, have morphologic features that differ from those without S -(2-succino)-cysteine positivity. Hematoxylin and eosin-stained slides of uterine smooth-muscle tumors were prospectively analyzed for features suggesting hereditary Leiomyomatosis and renal cell carcinoma syndrome, such as prominent eosinophilic macronucleoli with perinucleolar halos, yielding nine cases. Germline genetic testing for fumarate hydratase mutations was performed in three cases. A detailed morphological analysis was undertaken, and S -(2-succino)-cysteine immunohistochemical analysis was performed with controls from a tissue microarray (leiomyomas (19), leiomyosarcomas (29), and endometrial stromal tumors (15)). Of the nine study cases, four had multiple uterine smooth muscle tumors. All cases had increased cellularity, staghorn vasculature, and fibrillary cytoplasm with pink globules. All cases had inclusion-like nucleoli with perinuclear halos (7 diffuse, 1 focal). All showed diffuse granular cytoplasmic labeling with the S -(2-succino)-cysteine antibody. Two of three tested patients had germline fumarate hydratase mutations. Only one leiomyoma from the tissue microarray controls was immunohistochemically positive, and it showed features similar to other immunohistochemically positive cases. Smooth-muscle tumors with fumarate hydratase aberration demonstrate morphological reproducibility across cases and S -(2-succino)-cysteine immuno-positivity. Although the features described are not specific for the germline fumarate hydratase mutation or the hereditary Leiomyomatosis and renal cell carcinoma syndrome, their presence should suggest fumarate hydratase aberration. Identifying these cases is an important step in the diagnostic workup of patients with possible hereditary Leiomyomatosis and renal cell carcinoma.
