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Biomedical subjects

John R Goldblum

Publications and source records attributed to John R Goldblum.

At least 19 recordsLinked to original sources
PubMed2006

Clostridium difficile-associated pouchitis.

Pouchitis is the most common long-term sequela of ileal pouch-anal anastomosis (IPAA) following total proctocolectomy. No single pathogen is identified as being solely responsible for the pathogenesis of the disease. Here we describe a case of Clostridium difficile-associated pouchitis that was successfully treated with ciprofloxacin and tinidazole. Diagnosis and management of a patient with medically refractory pouchitis associated with Clostridium difficile infection is described. A 63-year-old male with underlying ulcerative colitis and IPAA presented with increased stool frequency and seepage for 2 months, which partially responded to oral metronidazole. While on the antibiotic therapy, pouch endoscopy was performed and showed severe pouchitis. Assays for Clostridium difficile toxins in stool specimens were positive. He was treated with a 4-week course of ciprofloxacin 500 mg BID and tinidazole 500 mg TID. His symptoms resolved within several days from the initiation of therapy. A repeat pouch endoscopy at week 5 showed a complete resolution of mucosal inflammation of the pouch, while tests for Clostridium difficile toxins became negative. Clostridium difficile-associated pouchitis is rare. However, Clostridium difficile infection should be excluded in patients with chronic refractory pouchitis.

Anti-Infective Agents↗
PubMed2006

Critical diagnoses (critical values) in anatomic pathology.

Similar to critical values in clinical pathology, occasional diagnoses in surgical pathology and cytology may require urgent contact of the physician to facilitate rapid intervention or treatment. However, there are no established critical value (critical diagnosis) guidelines in anatomic pathology. As discussed herein, the Association of Directors of Anatomic and Surgical Pathology (ADASP) believes that establishing anatomic pathology critical diagnosis guidelines represents a practice improvement and patient safety initiative. The ADASP also recognizes that a generic anatomic pathology critical diagnosis guideline such as this should only be used as a template because the list needs to be customized at each individual hospital after consultation with relevant clinical services. Based on surveys of the membership of the ADASP, this document provides examples of possible critical diagnoses in anatomic pathology.

Diagnostic Errors↗
PubMed2006

A landscape effect in tenosynovial giant-cell tumor from activation of CSF1 expression by a translocation in a minority of tumor cells.

Tenosynovial giant-cell tumor (TGCT) and pigmented villonodular synovitis (PVNS) are related conditions with features of both reactive inflammatory disorders and clonal neoplastic proliferations. Chromosomal translocations involving chromosome 1p13 have been reported in both TGCT and PVNS. We confirm that translocations involving 1p13 are present in a majority of cases of TGCT and PVNS and show that CSF1 is the gene at the chromosome 1p13 breakpoint. In some cases of both TGCT and PVNS, CSF1 is fused to COL6A3 (2q35). The CSF1 translocations result in overexpression of CSF1. In cases of TGCT and PVNS carrying this translocation, it is present in a minority of the intratumoral cells, leading to CSF1 expression only in these cells, whereas the majority of cells express CSF1R but not CSF1, suggesting a tumor-landscaping effect with aberrant CSF1 expression in the neoplastic cells, leading to the abnormal accumulation of nonneoplastic cells that form a tumorous mass.

Cell Movement↗
PubMed2006

Primary intravascular synovial sarcoma: a disease of young adult women? Report of a case diagnosed by aspiration biopsy and review of the literature.

Intravascular synovial sarcoma (IVSS) is an extremely rare tumor with only four well-documented cases in the English literature. All tumors were located in large veins of the lower extremities or trunk in young women except for one case occurring in a 54-yr-old woman. We report here an additional case of IVSS arising from the superior vena cava in a 32-yr-old woman who presented with a cervical mass and superior vena cava syndrome. A fine-needle aspiration biopsy (FNAB) was performed and showed a malignant biphasic tumor with spindle cell and epithelioid components. The tumor cells were negative for CD31, CD34, factor VIII, desmin, smooth muscle actin, and S-100 protein, and had positive staining for vimentin and cytokeratin (AE1/AE3) predominantly in the spindle and epithelial components, respectively. A diagnosis of synovial sarcoma was made and confirmed in a subsequent transvascular biopsy demonstrating chromosomal translocation t(X, 18) by fluorescence in situ hybridization using a dual color, break-apart-style probe for SYT. Although clinically similar to previously reported IVSS, this is the first case arising in large veins of the upper portion of the trunk and diagnosed by FNAB.

Adult↗
PubMed2006

Molecular diagnosis of Campylobacter jejuni infection in cases of focal active colitis.

Campylobacter jejuni (CJ) is the most commonly isolated stool pathogen in the United States. Biopsy findings are typically those of focal active colitis (FAC), a nonspecific pattern usually indicating infection or adverse drug effect that is characterized by focal cryptitis and preservation of crypt architecture. We developed a molecular test for CJ that can be performed on routinely processed gastrointestinal biopsy specimens, and assessed what percentage of patients with biopsy findings of FAC have molecular evidence of CJ infection. One hundred and ten colon biopsies diagnosed as FAC were retrieved from three institutions. Polymerase chain reaction (PCR) was performed following DNA extraction; primers were designed to target a 286-bp fragment of the mapA gene that is specific to CJ. Pure genomic DNA derived from cultures served as the positive control; reagent blanks and 50 normal colon specimens served as negative controls. Nineteen percent (21/110) of the FAC biopsies were positive for CJ DNA by PCR analysis. Fourteen CJ-positive patients presented with diarrhea, 3 presented with gastrointestinal bleeding, and 3 had incidental FAC found on screening colonoscopy. Ten patients had abnormal colonoscopic findings, including erythema (4), ulcers (4), colitis (1), and hemorrhage (1). As CJ is an enteric pathogen that is not present in the gut as a commensal organism, the presence of CJ DNA suggests current or recent previous infection in these patients. CJ infection should be considered in patients with diarrhea and colon biopsies showing FAC. Furthermore, PCR analysis performed on fixed, routinely processed colon biopsies is an excellent diagnostic method for detection of this organism.

Adult↗
PubMed2006

Extragastrointestinal stromal tumors presenting as vulvovaginal/rectovaginal septal masses: a diagnostic pitfall.

Gastrointestinal stromal tumor (GIST) are the most common mesenchymal tumors of the gastrointestinal (GI) tract. Most GISTs arise in the stomach and small bowel, whereas a small number occur elsewhere in the GI tract. Rare cases are identified outside the GI tract and are collectively known as extragastrointestinal stromal tumors (EGISTs). Because of their malignant potential and recent advances in the management of GISTs with imatinib mesylate (Gleevec, Glivec), it is imperative that these tumors are correctly diagnosed. In this study, we reviewed the clinical and pathologic characteristics of 3 cases of EGIST presenting as vulvovaginal/rectovaginal septal masses that were originally misdiagnosed, presumably due to their unusual anatomic locations. The original diagnoses were leiomyoma in one case and leiomyosarcoma in 2 cases. The lesions were localized to the rectovaginal septum () or vagina () and ranged from 4 to 8 cm in diameter. All 3 lesions had a spindle cell morphology that mimicked a smooth muscle tumor. Mitotic figures numbered from 12/50 to 16/50 high power fields (HPFs; median 15). Immunohistochemistry revealed that all 3 cases were strongly positive for KIT (CD117) and CD34 and negative for smooth muscle actin, desmin, pan-cytokeratin, and estrogen receptor. KIT sequence analysis revealed oncogenic mutations in all 3 cases. The first tumor recurred at 2 years and the second tumor recurred at 10 years; the third case is too recent for meaningful follow-up. EGISTs that present as gynecologic masses are rare but may be more common than is currently recognized. Misdiagnosis may lead to inappropriate therapy because conventional chemotherapy and radiotherapy are not effective in the treatment of GISTs, whereas imatinib mesylate (Gleevec, Glivec) has a proven role in managing these tumors. Thus, it is imperative to consider EGISTs in the differential diagnosis of mesenchymal neoplasms in the vulvovaginal/rectovaginal septum.

Adult↗
PubMed2006

Variability in the diagnosis of dysplasia in ulcerative colitis by dynamic telepathology.

Telepathology (TP) is the practice of evaluating pathology cases by the digital transmission of diagnostic slides as either static pictures (static TP) or by a continuous flow of pictures from a robotic microscopy (dynamic TP). The diagnostic efficacy of dynamic TP-based consultation services has not been widely tested. Dysplasia arising in association with chronic ulcerative colitis (CUC) is, at present, the most important marker for an increased risk of malignancy in patients with this disease. However, the diagnosis of dysplasia suffers from a significant degree of intra- and interobserver variability which usually necessitates a second opinion prior to definitive treatment. Thus, it is often necessary to obtain expert consultation of potential dysplasia cases by dedicated gastrointestinal pathologists. The aim of this study was to evaluate the utility and interobserver variability of diagnosing dysplasia in CUC with the use of dynamic TP. Dynamic TP was used to evaluate digitalized images of 38 CUC cases with areas considered negative, indefinite, or positive for dysplasia (low or high grade) independently by seven pathologists. Subsequently, all cases were graded by each of the pathologists by light microscopic examination of the H&E-stained glass slides. The degree of intra- and interobserver variability was determined by Kappa statistics. Overall, there was a poor degree of interobserver agreement (K=0.32) among the seven pathologists after analysis of the cases by dynamic TP. The poorest level of agreement was in the indefinite and low-grade dysplasia categories, whereas the highest level was in the negative and high-grade dysplasia categories. Grouping together several diagnostic categories (for instance: Indefinite and low, or low- and high-grade dysplasia) had no significant effect on the level of agreement. The degree of variability in interpretation of cases by microscopic slide analysis was similar (K=0.35). After reviewing all the cases by microscopic analysis of the glass slides, the diagnosis was changed in 51% of the observations; in the majority of these (61%), the grade of dysplasia was decreased. In summary, the use of dynamic TP for consultation in CUC-associated dysplasia has a poor level of interobserver agreement, but does not differ significantly from that obtained by the evaluation of the cases by microscopic slide analysis. Diagnoses rendered by dynamic TP tend to be of a higher grade compared to that obtained by microscopic slide analysis. Thus, although dynamic TP may be used for the consultation of CUC dysplasia cases, more specific criteria are needed in the general categorization of dysplasia in CUC.

Colitis, Ulcerative↗
PubMed2005

Determination of stromal signatures in breast carcinoma.

Many soft tissue tumors recapitulate features of normal connective tissue. We hypothesize that different types of fibroblastic tumors are representative of different populations of fibroblastic cells or different activation states of these cells. We examined two tumors with fibroblastic features, solitary fibrous tumor (SFT) and desmoid-type fibromatosis (DTF), by DNA microarray analysis and found that they have very different expression profiles, including significant differences in their patterns of expression of extracellular matrix genes and growth factors. Using immunohistochemistry and in situ hybridization on a tissue microarray, we found that genes specific for these two tumors have mutually specific expression in the stroma of nonneoplastic tissues. We defined a set of 786 gene spots whose pattern of expression distinguishes SFT from DTF. In an analysis of DNA microarray gene expression data from 295 previously published breast carcinomas, we found that expression of this gene set defined two groups of breast carcinomas with significant differences in overall survival. One of the groups had a favorable outcome and was defined by the expression of DTF genes. The other group of tumors had a poor prognosis and showed variable expression of genes enriched for SFT type. Our findings suggest that the host stromal response varies significantly among carcinomas and that gene expression patterns characteristic of soft tissue tumors can be used to discover new markers for normal connective tissue cells.

Breast Neoplasms↗
PubMed2005

The gene expression profile of extraskeletal myxoid chondrosarcoma.

Extraskeletal myxoid chondrosarcoma (EMC) is a soft tissue tumour that occurs primarily in the extremities and is characterized by a balanced translocation most commonly involving t(9;22) (q22;q12). The morphological spectrum of EMC is broad and thus a diagnosis based on histology alone can be difficult. Currently, no systemic therapy exists that improves survival in patients with EMC. In the present study, gene expression profiling has been performed to discover new diagnostic markers and potential therapeutic targets for this tumour type. Global gene expression profiling of ten EMCs and 26 other sarcomas using 42,000 spot cDNA microarrays revealed that the cases of EMC were closely related to each other and distinct from the other tumours profiled. Significance analysis of microarrays (SAM) identified 86 genes that distinguished EMC from the other sarcomas with 0.25% likelihood of false significance. NMB, DKK1, DNER, CLCN3, and DEF6 were the top five genes in this analysis. In situ hybridization for NMB gene expression on tissue microarrays (TMAs) containing a total of 1164 specimens representing 62 different sarcoma types and 15 different carcinoma types showed that NMB was highly expressed in 17 of 22 EMC cases and very rarely expressed in other tumours and thus could function as a novel diagnostic marker. High levels of expression of PPARG and the gene encoding its interacting protein, PPARGC1A, in most EMCs suggest activation of lipid metabolism pathways in this tumour. Small molecule inhibitors for PPARG exist and PPARG could be a potential therapeutic target for EMC.

Adult↗
PubMed2005

Interinstitutional variability and effect of tissue fixative on the interpretation of a Barrett cytokeratin 7/20 immunoreactivity pattern in Barrett esophagus.

A unique pattern of cytokeratin (CK) 7/20 immunostaining (diffuse staining with CK7 and surface and superficial crypt staining with CK20) has been reported to be useful in differentiating Barrett esophagus (BE) from intestinal metaplasia of the stomach. However, there are conflicting results regarding the prevalence of a BE CK7/20 staining pattern in BE between different studies. Therefore, this study was performed to determine the degree of variability in interpretation of a BE CK7/20 pattern and to determine the reasons for variability when present. Esophageal and gastric mucosal biopsies from 67 patients with BE and antral intestinal metaplasia at 2 institutions were immunostained for CK7/20. All cases were evaluated for the presence of a BE CK7/20 pattern by 2 gastrointestinal pathologists from each institution, and the degree of agreement between institutions was determined. To determine the effect of tissue fixation and staining methods on the pattern of CK7/20 staining, unstained slides were exchanged between institutions, stained separately by each institution, and reexamined by all pathologists. There was excellent agreement on the presence of a BE CK7/20 staining pattern between pathologists at the same institution but only moderate agreement between pathologists at different institutions (71% overall, kappa = 0.58). Among BE cases, a BE CK7/20 staining pattern was identified in 50 (96%) of 52 cases by Cleveland Clinic Foundation pathologists but only 35 (67%) of 52 cases by Brigham and Women's Hospital pathologists. The major source of disagreement related to the interpretation of weak or variable CK7 staining of deep intestinalized mucosa in BE biopsies that were fixed in Hollande, but not those that were fixed in formalin. After the creation of a new set of criteria for a positive BE CK7/20 staining pattern, which took into account the effects of Hollande's fixative, the degree of agreement between pathologists at each of the 2 institutions was excellent (100%, kappa value = 1.0). Therefore, the CK7/20 staining pattern is influenced by the type of fixative used. Only a moderate level of interobserver agreement among pathologists regarding a BE CK7/20 pattern can be achieved if one is not aware of these effects. Nevertheless, specific criteria for interpretation of CK7/20 staining can be successfully applied between institutions and need to be developed before use of this technique in clinical practice.

Barrett Esophagus↗
PubMed2005

Clinicopathologic and molecular genetic characterization of low-grade fibromyxoid sarcoma, and cloning of a novel FUS/CREB3L1 fusion gene.

Low-grade fibromyxoid sarcoma (LGFMS) is an indolent, late-metastasizing malignant soft-tissue tumor that is often mistaken for either more benign or more malignant tumor types. Cytogenetic analyses have identified a recurrent balanced translocation t(7;16) (q32-34;p11), later shown by molecular genetic approaches to result in a FUS/CREB3L2 fusion gene. Whereas preliminary studies suggest that this gene rearrangement is specific for LGFMS, its incidence in this tumor type and the possible existence of variant fusion genes have not yet been addressed. For this purpose, a series of potential LGFMS were obtained from nine different soft-tissue tumor centres and subjected to molecular analysis as well as careful histopathologic review. Reverse transcriptase-polymerase chain reaction analysis disclosed a FUS/CREB3L2 fusion transcript in 22 of the 23 (96%) cases that remained classified as LGFMS after the histologic re-evaluation and from which RNA of sufficient quality could be extracted, whereas none of the cases that were classified as other tumor types was fusion-positive. In one of the tumors with typical LGFMS appearance, we found that FUS was fused to the CREB3L1 gene instead of CREB3L2. The proteins encoded by these genes both belong to the same basic leucine-zipper family of transcription factors, and display extensive sequence homology in their DNA-binding domains. Thus, it is expected that the novel FUS/CREB3L1 chimera will have a similar impact at the cellular level as the much more common FUS/CREB3L2 fusion protein. Taken together, the results indicate that virtually all LGFMS are characterized by a chimeric FUS/CREB3L2 gene, and that rare cases may display a variant FUS/CREB3L1 fusion.

Adolescent↗
PubMed2005

PDGF-A, PDGF-Rbeta, TGFbeta3 and bone morphogenic protein-4 in desmoplastic small round cell tumors with EWS-WT1 gene fusion product and their role in stromal desmoplasia: an immunohistochemical study.

Histologically, desmoplastic small round cell tumor is composed of the characteristic neoplastic small round cells with divergent differentiation, and distinct desmoplastic stroma. Genetically, the tumor shows a characteristic 11;22 translocation, involving the EWS gene on chromosome 22 and the WT1gene on chromosome 11 to produce an EWS-WT1 fusion gene which generates a chimeric protein functioning as a novel transcription factor that activates expression of target genes such as PDGF-A. Expression of PDGF-A, a potent growth factor for fibroblasts, has been detected in desmoplastic small round cell tumors and has been linked to the characteristic desmoplasia in these tumors. Bone morphogenic proteins, which are members of the TGFbeta superfamily play a complex role in regulating cell growth and differentiation and bone formation but have not been evaluated in desmoplastic small round cell tumors. In all, 24 desmoplastic small round cell tumors with EWS-WT1 fusion product confirmed by RT-PCR analysis were evaluated for expression of PDGF-A, PDGF-Rbeta, TGFbeta3 and bone morphogenic protein-4 by standard immunohistochemical methods with antigen retrieval on paraffin sections. Immunoreactivity was evaluated semiquantitively. Tumor-associated desmoplasia was quantified using a three-tier scale on hematoxylin- and eosin-stained sections. Desmoplastic small round cell tumors showed variable immunoreactivity with TGFbeta3 (21/24), BMP4 (14/21), PDGF-A (19/24) and PDGF-Rbeta (16/22). Less frequently, the stromal cells showed reactivity with TGFbeta3, PDGF-Rbeta and PDGF-A. Tumor-associated desmoplasia was prominent in eight, intermediate in seven and weak in nine cases. There was no correlation between tumor-associated desmoplasia and the markers tested except PDGF-A. In contrast to a previous study, our study showed that the level of PDGF-A expression inversely correlated with tumor-associated desmoplasia. Other targets of the EWS-WT1 transcription factor other than PDGF-A may be directly responsible for the prominent tumor-associated desmoplasia seen in desmoplastic small round cell tumor.

Abdominal Neoplasms↗
PubMed2005

Expression profile and molecular genetic regulation of cyclin D1 expression in epithelioid sarcoma.

Epithelioid sarcoma is a distinctive, aggressive soft tissue tumor typically presenting as a subcutaneous or deep dermal mass in the distal extremities of young adults. Molecular genetic data of well-characterized cases of epithelioid sarcoma are sparse. A recent cytogenetic study of epithelioid sarcoma by conventional metaphase comparative genomic hybridization reported recurrent gains at chromosome 11q13, a region containing many genes, including the cyclin D1 gene. Cyclin D1 is a positive cell cycle regulator that is overexpressed in a variety of neoplasms, including mantle cell lymphoma and breast carcinoma. The objective of this study was to examine cyclin D1 expression in epithelioid sarcoma. Of 24 cases evaluated, 23 (96%) displayed cyclin D1 nuclear expression using immunohistochemical evaluation. Eight cases, which expressed cyclin D1 by immunohistochemistry, were evaluated by fluorescence in situ hybridization (FISH) and RNA in situ hybridization (RISH) for amplification of the cyclin D1 gene and messenger RNA (mRNA) expression, respectively. Seven of eight cases showed a typical eusomic state. One case showed pseudoamplification due to aneusomy/polysomy. There was no evidence of cyclin D1 gene amplification or messenger RNA overexpression detected by FISH or RNA in situ hybridization analyses, respectively. Our data clearly demonstrate that cyclin D1 protein is upregulated in epithelioid sarcoma, suggesting a role for this cell cycle regulator in the pathogenesis of epithelioid sarcoma. The high level of cyclin D1 protein expression in epithelioid sarcoma appears to be regulated by translational and/or post-translational mechanisms.

Cyclin D1↗
PubMed2005

Intercellular junctions in Ewing sarcoma/primitive neuroectodermal tumor: additional evidence of epithelial differentiation.

Ewing sarcoma/primitive neuroectodermal tumor (ES/PNET) has recently been shown to frequently express cytokeratins, suggesting partial epithelial differentiation. Older ultrastructural studies have documented primitive cell-cell junctions in ES/PNET, reportedly resembling poorly formed desmosomes. Recently, paraffin-reactive antibodies have become available to proteins found in a variety of intercellular junctions indicative of epithelial differentiation, including tight junctions, desmosomes and adherens junctions. We examined intercellular junction protein expression in a large number of genetically confirmed ES/PNET. Formalin-fixed, paraffin-embedded sections from 23 primary and seven recurrent or metastatic cases of genetically confirmed ES/PNET were immunostained for claudin-1 and occludin (tight junction structural proteins), zonula occludens-1 (ZO-1, tight junction linker protein), desmoglein 1/2 (desmosomal adherens protein), desmoplakin (desmosomal structural protein) and E-cadherin (epithelial adherens junction protein), using steam heat-induced epitope retrieval and the Dako Envision system. Cases with >5% positive cells were scored as 'positive'. Normal colonic epithelium and skin served as external positive controls. Claudin-1 was expressed by 19 of 30 specimens (63%), ZO-1 was expressed by 15 of 29 specimens (51%), and occludin was expressed by three of 28 specimens (11%). In 28 specimens all three tight junction markers were evaluable. In all, 15 samples (54%) expressed only one tight junction marker, and 10 samples (36%) expressed two tight junction markers. No case expressed all three tight junction markers. Desmoglein was expressed in one of 30 (3%) samples. Desmoplakin was expressed in two of 28 (7%) samples. E-cadherin was negative in all cases. Our data suggest that many of the previously described cell-cell junctions in ES/PNET are poorly formed tight junctions, given the high frequency of claudin-1 and ZO-1 expression. This may underestimate the true frequency of tight junction protein expression in ES/PNET, as there are at least 20 different claudins and other ZO proteins. These tight junctions are almost certainly abnormal, given the absence of occludin expression in most cases. Desmosomal and adherens junction protein expression was rare to absent. Our findings provide additional evidence that ES/PNET frequently show partial epithelial differentiation.

Bone Neoplasms↗
PubMed2005

Dual-color, break-apart fluorescence in situ hybridization for EWS gene rearrangement distinguishes clear cell sarcoma of soft tissue from malignant melanoma.

Clear cell sarcoma of soft tissue (malignant melanoma of soft parts) is a soft tissue sarcoma with melanocytic differentiation that typically occurs in the tendons and aponeuroses of young adults. As demonstrated by cytogenetics and reverse-transcriptase polymerase chain reaction, between 70% and over 90% of clear cell sarcomas have a t(12;22) translocation, fusing the EWS and ATF1 genes on chromosomes 22q12 and 12q13, respectively. Identification of this translocation distinguishes clear cell sarcoma from histologic mimics, most importantly conventional malignant melanoma. We report our experience with a commercially available, dual-color, break-apart fluorescence in situ hybridization (FISH) probe, which allows detection of EWS (22q12) gene rearrangement in formalin-fixed, paraffin-embedded tissues. Histologically and immunophenotypically well-characterized cases of clear cell sarcoma (n = 10) and malignant melanoma (n = 32) were evaluated with a 22q12 dual-color, break-apart probe (Vysis, Downer's Grove, IL, USA), which spans the known common breakpoints in the EWS gene on chromosome 22 (introns 7-10). Signals from tumor cell nuclei were counted under a fluorescence microscope and the presence of red-green break-apart signals was recorded. Of the clear cell sarcoma cases, seven of 10 showed evidence of an EWS gene rearrangement with a mean of 81.6% positive cells per sample (range: 60-95%). All cases of malignant melanoma (n = 32) showed virtually absent break-apart signals in the EWS gene (less than 4% cells per case). FISH detects EWS gene rearrangement in a substantial proportion of clear cell sarcomas, with excellent specificity. Importantly, EWS FISH is negative in malignant melanoma, a clinically dissimilar tumor, which may closely mimic clear cell sarcoma histologically and immunohistochemically. As the studied probe can be utilized in routinely processed tissue, FISH provides an excellent alternative to reverse-transcriptase polymerase chain reaction in cases where fresh tissue is unavailable.

Diagnosis, Differential↗