: A Morphologic and Immunohistochemical Study of 13 Cases. Miyamoto H, Montgomery EA, Epstein JI. Am J Surg Pathol. 2010 Mar 4. PMID: 20216379
Departments of *Pathology daggerOncology double daggerOrthopedics section signUrology, The Johns Hopkins University School of Medicine, Baltimore, MD.
Paratesticular fibrous pseudotumor is a rare intrascrotal fibrous proliferation for which numerous synonyms have been proposed. Immunohistochemical staining was done in 13 cases identified by a database search (2000 to 2008) at our institution. All men (19 to 75 y old, mean 41.9 y) presented with scrotal masses, 6 patients also had hydroceles. Six men were treated by orchiectomy, whereas the remaining 7 men underwent excisional biopsy. Histologically, lesions were subdivided into 3 types: (1) "plaque-like" consisting of dense fibrous tissue with clefts without significant inflammation identical to a pleural plaque (5 cases); (2) "inflammatory sclerotic" with dense fibrous tissue containing lymphocytes (diffusely or aggregates or germinal centers), plasma cells, and an increased capillary network (6 cases); and (3) "myofibroblastic" consisting of reactive looking tissue-culture-like spindle cells with numerous capillaries and sparse chronic inflammation (2 cases). Stains for smooth muscle actin were positive in 11/13 (84.6%) cases, whereas desmin was positive in 4/13 (30.8%) cases. Stains for cytokeratin AE1/AE3, calretinin, and CD34 were positive in 7/13 (53.8%), 6/13 (46.2%), and 7/13 (53.8%) cases, respectively. All cases were negative for beta-catenin and ALK-1. Ki-67 showed a proliferation index of <1% in all but 2 cases, which had 5% labeling. Although there were 3 distinct histologic patterns seen in paratesticular fibrous pseudotumors, their immunohistochemical profile had overlapping features. Paratesticular fibrous pseudotumor looks histologically distinct from fibromatosis and inflammatory myofibroblastic tumor (IMT) seen in other organs, an assertion supported by negative stains for beta-catenin and ALK-1, respectively. However, as not all IMTs react with ALK and we had only 2 cases with a myofibroblastic appearance, we cannot definitively exclude the possibility that this subtype of paratesticular fibrous pseudotumor is related to IMT. Although this lesion has different histologic patterns, presently it is not warranted to split it into 3 separate entities as all share the same clinical presentation, are biologically benign, and lack consistent immunohistochemical differences.
PMID: 20216379
http://www.humpath.com/paratesticular-fibrous-pseudotumor
Saturday, March 13, 2010
Friday, March 12, 2010
ETS Gene Aberrations in Atypical Cribriform Lesions of the Prostate
: Implications for the Distinction Between Intraductal Carcinoma of the Prostate and Cribriform High-grade Prostatic Intraepithelial Neoplasia. Han B, Suleman K, Wang L, Siddiqui J, Sercia L, Magi-Galluzzi C, Palanisamy N, Chinnaiyan AM, Zhou M, Shah RB. Am J Surg Pathol. 2010 Mar 8. PMID: 20220513
Am J Surg Pathol. 2010 Mar 8. [Epub ahead of print]
ETS Gene Aberrations in Atypical Cribriform Lesions of the Prostate: Implications for the Distinction Between Intraductal Carcinoma of the Prostate and Cribriform High-grade Prostatic Intraepithelial Neoplasia.
Han B, Suleman K, Wang L, Siddiqui J, Sercia L, Magi-Galluzzi C, Palanisamy N, Chinnaiyan AM, Zhou M, Shah RB.
*Michigan Center for Translational Pathology daggerDepartment of Pathology section signHoward Hughes Medical Institute parallelDepartment of Urology paragraph signComprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI double daggerDepartment of Anatomic Pathology, Cleveland Clinic, Cleveland, OH.
BACKGROUND: Atypical cribriform lesions (ACLs) of the prostate consist of cribriform glands lined with cytologically malignant cells with partial or complete basal cell lining. It may represent cribriform "high-grade prostatic intraepithelial neoplasia" (HGPIN) or "intraductal carcinoma of the prostate" (IDC-P), which is almost always associated with clinically aggressive prostate carcinoma (PCa). Distinction between these 2 lesions has profound clinical significance, especially on needle biopsies. However, there are lesions that do not fully satisfy the criteria for IDC-P yet are worse than typical HGPIN and are difficult to distinguish based on morphologic criteria alone. METHODS: To better understand the biologic and molecular basis of distinction between cribriform HGPIN and IDC, we used break-apart fluorescence in-situ hybridization assay to assess ETS gene aberrations, a specific and commonest molecular alteration involving PCa, in a cohort of 16 isolated ACL, presumed to be an isolated cribriform HGPIN, and 45 carcinoma-associated ACL (ACL-PCa) on radical prostatectomy specimens, presumed to be spectrum of IDC-P. The latter was further divided into 2 groups: group A with marked nuclear atypia (nuclear size 6xnormal or larger) and/or comedonecrosis (n=21) and group B that did not fulfill these criteria (n=24). RESULTS: Overall, ERG rearrangement was absent (0 of 16) in isolated cribriform HGPIN, whereas present in 75% (36 of 48) of IDC-P, of which 65% (23 of 36) were through deletion and 35% (13 of 36) through insertion. Notably, 17% (6 of 36) of the IDC-P showed duplication of ERG rearrangement in combination with deletion of 5'-ERG. Hundred percent (34 of 34) of the IDC-P showed concordance of ERG rearrangement status with adjacent invasive carcinoma. There was no difference between the 2 groups of IDC-P lesions regarding prevalence of ERG rearrangement (group A 79% vs. group B 74%) and EDel2+ (20% vs. 15%). No case with ETV1, ETV4, or ETV5 rearrangement was identified. CONCLUSIONS: Our molecular data suggest that isolated cribriform HGPIN and IDC-P are biologically distinct lesions. Majority of ACL-PCa most likely represent intraductal spread of PCa. There is a significant overlap between IDC-P and HGPIN at the lower grade morphologic spectrum. ERG break-apart fluorescence in-situ hybridization assay provides insight into understanding the molecular basis of cribriform HGPIN and IDC-P and has potential clinical implications in their distinction on needle biopsies.
PMID: 20220513
Am J Surg Pathol. 2010 Mar 8. [Epub ahead of print]
ETS Gene Aberrations in Atypical Cribriform Lesions of the Prostate: Implications for the Distinction Between Intraductal Carcinoma of the Prostate and Cribriform High-grade Prostatic Intraepithelial Neoplasia.
Han B, Suleman K, Wang L, Siddiqui J, Sercia L, Magi-Galluzzi C, Palanisamy N, Chinnaiyan AM, Zhou M, Shah RB.
*Michigan Center for Translational Pathology daggerDepartment of Pathology section signHoward Hughes Medical Institute parallelDepartment of Urology paragraph signComprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI double daggerDepartment of Anatomic Pathology, Cleveland Clinic, Cleveland, OH.
BACKGROUND: Atypical cribriform lesions (ACLs) of the prostate consist of cribriform glands lined with cytologically malignant cells with partial or complete basal cell lining. It may represent cribriform "high-grade prostatic intraepithelial neoplasia" (HGPIN) or "intraductal carcinoma of the prostate" (IDC-P), which is almost always associated with clinically aggressive prostate carcinoma (PCa). Distinction between these 2 lesions has profound clinical significance, especially on needle biopsies. However, there are lesions that do not fully satisfy the criteria for IDC-P yet are worse than typical HGPIN and are difficult to distinguish based on morphologic criteria alone. METHODS: To better understand the biologic and molecular basis of distinction between cribriform HGPIN and IDC, we used break-apart fluorescence in-situ hybridization assay to assess ETS gene aberrations, a specific and commonest molecular alteration involving PCa, in a cohort of 16 isolated ACL, presumed to be an isolated cribriform HGPIN, and 45 carcinoma-associated ACL (ACL-PCa) on radical prostatectomy specimens, presumed to be spectrum of IDC-P. The latter was further divided into 2 groups: group A with marked nuclear atypia (nuclear size 6xnormal or larger) and/or comedonecrosis (n=21) and group B that did not fulfill these criteria (n=24). RESULTS: Overall, ERG rearrangement was absent (0 of 16) in isolated cribriform HGPIN, whereas present in 75% (36 of 48) of IDC-P, of which 65% (23 of 36) were through deletion and 35% (13 of 36) through insertion. Notably, 17% (6 of 36) of the IDC-P showed duplication of ERG rearrangement in combination with deletion of 5'-ERG. Hundred percent (34 of 34) of the IDC-P showed concordance of ERG rearrangement status with adjacent invasive carcinoma. There was no difference between the 2 groups of IDC-P lesions regarding prevalence of ERG rearrangement (group A 79% vs. group B 74%) and EDel2+ (20% vs. 15%). No case with ETV1, ETV4, or ETV5 rearrangement was identified. CONCLUSIONS: Our molecular data suggest that isolated cribriform HGPIN and IDC-P are biologically distinct lesions. Majority of ACL-PCa most likely represent intraductal spread of PCa. There is a significant overlap between IDC-P and HGPIN at the lower grade morphologic spectrum. ERG break-apart fluorescence in-situ hybridization assay provides insight into understanding the molecular basis of cribriform HGPIN and IDC-P and has potential clinical implications in their distinction on needle biopsies.
PMID: 20220513
Friday, March 5, 2010
High-resolution array CGH of metanephric adenomas: lack of DNA copy number changes
Szponar A, Yusenko MV, Kovacs G. Histopathology. 2010 Jan;56(2):212-6. PMID: 20102400
Laboratory of Molecular Oncology, Medical Faculty, Ruprecht-Karls-University, Heidelberg, Germany.
AIMS: Previous karyotyping and fluorescence in situ hybridization analysis of metanephric adenomas (MAs) has yielded controversial data. The aim of this study was to detect small genomic alterations, if any, specific to MAs by applying high-resolution oligoarrays.
METHODS AND RESULTS: DNA extracted from paraffin blocks of six metanephric adenomas was hybridized onto Agilent oligoarrays with approximately 43,000 in situ synthesized 60-mer oligonucleotide probes that span coding and non-coding sequences with an average spatial resolution of approximately 35 kb. None of the metanephric adenomas showed DNA copy number changes. To confirm our results, DNA extracted from the paraffin block of a chromophobe renal cell carcinoma (RCC) was simultaneously hybridized to one of the four arrays on the same slides as an internal control. The chromophobe RCC showed loss of several chromosomes but no alteration was seen in MAs. We have confirmed the negative results by dye-swap and sex mismatch hybridization experiments.
CONCLUSIONS: Our high-resolution oligoarray analysis indicates that metanephric adenomas lack DNA copy number alterations. This finding may help to differentiate between metanephric adenomas from Wilms' tumour and papillary renal cell adenoma with overlapping phenotype.
PMID: 20102400
humpath.com #6815
Laboratory of Molecular Oncology, Medical Faculty, Ruprecht-Karls-University, Heidelberg, Germany.
AIMS: Previous karyotyping and fluorescence in situ hybridization analysis of metanephric adenomas (MAs) has yielded controversial data. The aim of this study was to detect small genomic alterations, if any, specific to MAs by applying high-resolution oligoarrays.
METHODS AND RESULTS: DNA extracted from paraffin blocks of six metanephric adenomas was hybridized onto Agilent oligoarrays with approximately 43,000 in situ synthesized 60-mer oligonucleotide probes that span coding and non-coding sequences with an average spatial resolution of approximately 35 kb. None of the metanephric adenomas showed DNA copy number changes. To confirm our results, DNA extracted from the paraffin block of a chromophobe renal cell carcinoma (RCC) was simultaneously hybridized to one of the four arrays on the same slides as an internal control. The chromophobe RCC showed loss of several chromosomes but no alteration was seen in MAs. We have confirmed the negative results by dye-swap and sex mismatch hybridization experiments.
CONCLUSIONS: Our high-resolution oligoarray analysis indicates that metanephric adenomas lack DNA copy number alterations. This finding may help to differentiate between metanephric adenomas from Wilms' tumour and papillary renal cell adenoma with overlapping phenotype.
PMID: 20102400
humpath.com #6815
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