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- 2010美国病理学年会摘要翻译(骨和软组织）
A Subset of
P Argani, P Illei, G Netto, J Ro, HY Cho, S Dogan, M Ladanyi, G Martignoni, S Aulmann,
SW Weiss. Johns Hopkins Medical Institutions, Baltimore, MD; Asan Medical Center, Seoul, Korea; Memorial Sloan-Kettering Cancer Center, New York, NY; University of Verona, Verona, Italy; University of Heidelberg, Heidelberg, Germany; Emory
University,
Background: Perivascular epithelioid cell neoplasms (PEComas) include the common renal angiomyolipoma, pulmonary clear cell sugar tumor and lymphangioleiomyomatosis, and less common neoplasms of soft tissue, gynecologic and gastrointestinal tracts. Recently, aberrant immunoreactivity for TFE3 protein (a sensitive and specific marker of neoplasms harboring TFE3 gene fusions) has been reported in as many as 80% of PEComas. TFE3 gene status in these neoplasms has not been systematically investigated, though a recent case report has documented a PSF-TFE3 gene fusion in an extrarenal PEComa
在PEComas中TFE3基因融合物的表达
乔治亚州亚特兰大学
背景;血管周围上皮细胞瘤（PEComas)包括普通的肾脏血管肌脂瘤，肺透明细胞瘤，淋巴管肌瘤病，普通的软组织瘤，妇产科和胃肠道方面的肿瘤。TFE3蛋白（是一种敏感而特异的TFE3基因融合物的标志物）的异常免疫反应在80%PEComas中被报告，TFE3基因的地位在这些肿瘤中没有被系统性的研究，尽管最近的一个病例报告明确指出PSF-TFE3基因融合物在肾外PEComas中出现
- there is no reason not to follow ur heart
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本帖最后由 于 2010-04-03 22:28:00 编辑
| 以下是引用njwbhuang在2010-4-3 11:15:00的发言： CD1a Immunopositivity in Perivascular Epithelioid Cell Neoplasms (PEComas): True CD1a Expression or Technical Artifact? |
CD
背景; PEComas是由免疫组织化学上表达肌源的黑色素细胞的血管周上皮样细胞构成的罕见肿瘤。PEComas与其他伴有平滑肌和黑色素细胞分化的肿瘤的区分很困难。最近研究发现PEComas常规表达CD1a，CD1a是一种郎格汉斯细胞相关的跨膜糖蛋白，参与抗原的递呈。CD1a的表达可能有助于PEComas与其相似肿瘤的区分。我们评估了CD1a在PEComas和其相似肿瘤中的表达。
设计：一共54例肿瘤（PEComas27例、平滑肌肉瘤11例、黑色素瘤10例、透明细胞肉瘤6例）分布在两个实验室进行了CD1a的检测（实验室A：31例，实验室B：23例）。9例实验室B的病例在实验室A进行了再次检验。实验室A的方法：克隆号为MTB1(1:20, Novocastra)，高温抗原修复，修复液为EDTA (pH 8.0)，检测系统为Dako先进的检测系统，背景染色弱。实验室B的方法：克隆号为MTB1(1:30, CellMarque)，在中等细胞调节器中进行抗原修复#1 (pH 8.0–9.0)，检测系统为链霉素生物素检测系统，DAB显色。CD1a结果判断为1+, 5-25%; 2+, 26-50; 3+, >51%。郎格汉氏细胞作为阳性内对照。
结果：实验室A中所有病例CD1a都为阴性，实验室B中16例（肾血管肌脂肪瘤14例、软组织PEComas1例、肺糖瘤1例）CD1a均表达阳性（+：7例、2+：7例、3+：2例）。所有非PEComas都不表达CD1a。所有阳性表达的PEComas都是细胞质着色，膜不着色。9例实验室B中CD1a表达阳性的病例在实验室A中检测时均表达阴性。
结论：我们推断PEComas并不是以一种生物学上似是而非的膜染色真正表达CD1a，而是在某些实验室可呈异常的胞质表达。仔细观察先前发表的表达CD1a的PEComas的显微照片可以看出都是细胞质染色。这种异常的免疫染色可能反映了与抗原修复和检测方法有关的一种技术误差。另外这种染色因不出现于非PEComas里，可能代表着PEComas特有抗原的交叉反应。最后我们不认为CD1a免疫组化在PEComas鉴别诊断中具有实际作用。
- 刀锋上的蚂蚁
A Subset of
P Argani, P Illei, G Netto, J Ro, HY Cho, S Dogan, M Ladanyi, G Martignoni, S Aulmann,
SW Weiss. Johns Hopkins Medical Institutions, Baltimore, MD; Asan Medical Center, Seoul, Korea; Memorial Sloan-Kettering Cancer Center, New York, NY; University of Verona, Verona, Italy; University of Heidelberg, Heidelberg, Germany; Emory
University,
Background: Perivascular epithelioid cell neoplasms (PEComas) include the common renal angiomyolipoma, pulmonary clear cell sugar tumor and lymphangioleiomyomatosis, and less common neoplasms of soft tissue, gynecologic and gastrointestinal tracts. Recently, aberrant immunoreactivity for TFE3 protein (a sensitive and specific marker of neoplasms harboring TFE3 gene fusions) has been reported in as many as 80% of PEComas. TFE3 gene status in these neoplasms has not been systematically investigated, though a recent case report has documented a PSF-TFE3 gene fusion in an extrarenal PEComa.
Design: We used a fluorescence in situ hybridization (FISH) break-apart assay to evaluate for TFE3 gene fusions in archival material from 26 PEComas. These cases included 2 previously published TFE3 immunoreactive non-renal PEComas, 12 additional non-renal PEComas (5 soft tissue, 4 abdominal, 2 uterine, 1 hepatic), and 12 renal angiomyolipomas with predominant spindle or epithelioid morphology. Results were correlated with TFE3 immunoreactivity and clinicopathologic features.
Results: Three non-renal PEComas (mean patient age 19 years) demonstrated TFE3 gene fusions by FISH; all three demonstrated strong positive (3+) TFE3 immunoreactivity. Two of these cases had adequate mRNA for RT-PCR analysis, and neither harbored a PSF-TFE3 gene fusion. In addition, a metastasis of a uterine PEComa which showed moderate positive (2+) TFE3 immunoreactivity demonstrated TFE3 gene amplification, a previously unreported phenomenon. None of the other 22 PEComas (mean patient age 54 years) demonstrated TFE3 gene alterations, though 4 demonstrated moderate positive
(2+) TFE3 immunoreactivity. All 4 PEComas with TFE3 alterations immunolabeled strongly for Cathepsin K, similar to other PEComas.
Conclusions: A subset of PEComas harbor TFE3 gene fusions. While numbers are small, distinctive features of these cases include young age, extrarenal location, absence of association with tuberous sclerosis (TS), predominant epithelioid clear cell morphology, minimal immunoreactivity for muscle markers, and strong (3+) TFE3 immunoreactivity. Despite significant morphologic overlap with other PEComas, PEComas harboring TFE3 gene fusions may represent a distinctive entity.
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Novel EWSR1-POU5F1 Fusion in Soft Tissue Myoepithelial Tumors. A Molecular Analysis of 29 Cases, Including Soft Tissue, Bone and Visceral Locations Showing Common Involvement of EWSR1 Gene
Rearrangement
CR Antonescu, L Zhang, NE Chang, BR Pawel, W Travis, AE Rosenberg, GP Nielsen, P Dal Cin, CD Fletcher. Memorial Sloan-Kettering Cancer Center, New York, NY; The Children’s Hospital of Philadelphia, Philadelphia, PA; Massachusettes General Hospital, Boston, MA; Brigham&Women’s Hospital, Boston, MA.
Background: The diagnosis of myoepithelial tumors (MET) outside salivary glands remains challenging, especially in unusual clinical presentations, such as bone or visceral locations. Few reports have indicated an EWSR1 gene rearrangement in soft tissue MET, and, in one case each, the fusion partner was identified as being either PBX1 or ZNF444. However, larger studies to investigate if these genetic abnormalities are recurrent or if restricted to the soft tissue location are lacking.
Design: 29 MET from mainly soft tissue, but also bone & visceral locations, showing classic morphologic features and supporting immunoprofile, with available tissue were included for molecular analysis. Patient age ranged from 1-70 years old. Gene rearrangements in EWSR1, PBX1 and ZNF444 were investigated by FISH. In 2 cases with EWSR1 rearrangement and frozen tissue available, 3’RACE was performed to
identify potential novel fusion partners.
Results: EWSR1 gene rearrangement by FISH was detected in 59% cases. A novel EWSR1-POU5F1 was identified in a pediatric soft tissue MET by 3’RACE and subsequently confirmed in 2 additional soft tissue tumors in young adults, but not in other locations. The presence of a EWSR1-PBX1 was seen in one soft tissue tumor, while EWSR1-ZNF444 was noted in one pulmonary MET.
Conclusions: EWSR1 gene rearrangement is a common event in MET irrespective of their anatomic location. Many of the EWSR1 negative tumors were superficial lesions, suggesting the possibility of genetically distinct groups. A subset of soft tissue MET harbor a novel EWSR1-POU5F1 fusion, which can be used as a molecular diagnostic test in difficult cases.
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CD1a Immunopositivity in Perivascular Epithelioid Cell Neoplasms (PEComas): True CD1a Expression or Technical Artifact?
WA Ahrens, AL Folpe. Carolinas Medical Center, Charlotte, NC; Mayo Clinic, Rochester, MN.
Background: PEComas comprise a family of rare neoplasms composed of morphologically distinctive perivascular epithelioid cells exhibiting a “myomelanocytic” immunophenotype. The distinction of PEComas from other tumors with melanocytic and smooth muscle differentiation can be difficult. A recent study has claimed that PEComas routinely express CD1a, a Langerhans cell-associated transmembrane glycoprotein involved in antigen presentation, and that expression of this marker may be helpful in the distinction of PEComas from various mimics. We evaluated a series of PEComas and potential mimics for CD1a expression.
Design: A total of 54 cases (27 PEComas; 11 leiomyosarcomas; 10 melanomas; 6 clear cell sarcomas) were evaluated in 2 laboratories (Laboratory A: 31 cases, Laboratory B 23 cases). Nine Laboratory B cases were retested at Laboratory A. Laboratory A methods: MTB1 clone (1:20, Novocastra), heat-induced epitope retrieval in EDTA (pH 8.0), Dako Advance detection system (Dako Corp.) with background reducing diluent.
Laboratory B methods: MTB1 clone (1:30, CellMarque), heat-induced epitope retrieval in Medium Cell Conditioner #1 (pH 8.0–9.0), streptavidin-biotin detection system with DAB chromogen. Scoring: 1+, 5-25%; 2+, 26-50; 3+, >51%. Langerhans cells served as a positive internal control in all tested cases.
Results: All Laboratory A cases were negative. 16 Laboratory B PEComas (14 renal angiomyolipomas, 1 soft tissue PEComa, 1 pulmonary clear cell “sugar” tumor) showed CD1a immunopositivity (1+: 7 cases; 2+: 7 cases; 3+: 2 cases). All non-PEComas were negative. All positive PEComas showed cytoplasmic staining only, without membranous staining. The 9 Laboratory B positive PEComas were negative when retested at Laboratory A.
Conclusions: We conclude that PEComas do not truly express CD1a in a biologically plausible membranous pattern, but may instead show aberrant cytoplasmic immunopositivity in some laboratories. Close inspection of published photomicrographs of previously reported CD1a-positive PEComas shows an identical pattern of cytoplasmic positivity. This aberrant pattern of immunopositivity likely reflects a
technical artifact related to epitope retrieval and detection methods. Alternatively, this staining could represent cross-reactivity with an epitope unique to PEComas, as it was not observed in non-PEComas. Ultimately, however, we do not believe there is a real role for CD1a immunohistochemistry in the differential diagnosis of PEComas.
