Keratin immunoreactivity in melanoma of soft parts (clear cell sarcoma)

Seven of 24 soft tissue melanomas were shown to express keratins using antibodies CAM 5.2, LP34 and MNF116. No clinical or histological differences were seen in these seven cases when compared with the 17 keratin negative cases.     

Genetic and genetic expression analyses of clear cell sarcoma of the kidney

Clear cell sarcoma of the kidney (CCSK) represents a significant diagnostic and clinical challenge. In search of diagnostically useful or biologically significant genetic abnormalities, we screened 30 CCSKs from the National Wilms Tumor Study Group. Genetic gains and losses were analyzed using comparative genomic hybridization; loss of heterozygosity at 11p15 was studied using microsatellite analysis. Loss of imprinting (LOI) was studied using allele-specific expression or methylation analysis at the ApaI polymorphic site for IGF2, AluI and RsaI sites for H19, and Cfo I site for SNRPN. Comparative genomic hybridization analysis revealed quantitative abnormalities in only 4 of 30 CCSKs. Two showed gain of 1q, one also showed loss of 10q, and the other also showed loss of terminal 4p. The other two cases demonstrated chromosome 19 loss and chromosome 19p gain, respectively. All 22 cases informative for 11p15 showed retention of both alleles. Of 14 CCSKs informative for IGF2, six showed biallelic expression; all three CCSKs informative for H19 exhibited monoallelic expression. The normal imprint pattern was present in all six CCSKs analyzed for SNRPN methylation. These data demonstrate an absence of consistent genetic gains or losses in CCSKs using these methods. The high frequency of LOI for IGF2 in CCSKs (43%) is comparable to that reported in Wilms tumors. The retention of imprinting at the SNRPN and H19 loci confirm that LOI is not a ubiquitous epigenetic change. This suggests that IGF2, a potent growth factor, may play a role in the development or progression of CCSK.     

Perivascular epithelioid cell sarcoma (malignant PEComa) of the ileum

Epithelioid angiomyolipoma (AML) is the prototype of a heterogeneous group of lesions characterized by the presence of HMB-45 positive cells with clear cytoplasm, perivascular distribution, and combined myomelanocytic features, so-called perivascular epithelioid cells (PECs). These lesions are being increasingly referred to as PEComas. PEComas have been reported at diverse anatomic sites, but mainly in the abdominopelvic cavity and rarely in parenchymatous organs, skin, and soft tissues. Gastrointestinal (GI) PEComas are exceptionally rare, with less than 10 cases documented so far. Rare examples of PEComas with pleomorphic histology could have been misinterpreted as unusual variants of carcinoma or sarcoma. To make a contribution to the differential diagnosis of difficult-to-classify pleomorphic GI sarcomas, we report on a malignant pleomorphic neoplasm with features of PEComa involving the terminal ileum in a 63-year-old woman. Fourteen months after resection of the primary tumor, a huge abdominopelvic recurrence was successfully resected, but no distant metastases were detected. The differential diagnosis and malignancy criteria of GI PEComas will be discussed.     

Primary clear cell sarcoma of the ileum

Clear cell sarcoma or malignant melanoma of soft tissue is a high-grade sarcoma with melanocytic differentiation, essentially involving tendons and aponeuroses of distal extremities in young adults. Visceral locations are exceptional and only 8 cases involving the gastrointestinal tract are reported in the literature. We present a case of an ileal clear cell sarcoma discovered in a 26-year-old woman. Moreover, we emphasize on the diagnosis difficulties of this rare type of sarcoma, characterized by the specific translocation t(12;22)(q13;q12).     

Cytogenetic findings in clear cell sarcoma of tendons and aponeuroses. Malignant melanoma of soft parts

Cytogenetic analyses of clear cell sarcomas from two patients are reported. Clonal numerical and structural abnormalities were detected in both specimens, with specific involvement of chromosomes 2 and 22 in each.     

Mismatch repair protein expression and microsatellite instability: a comparison of clear cell sarcoma of soft parts and metastatic melanoma.

Clear cell sarcoma of soft parts is a rare soft tissue malignancy that shows phenotypic overlap with cutaneous melanoma but can be distinguished by the presence of a t(12;22) translocation. Microsatellite instability (MSI), a variation in the lengths of short repeat DNA segments in the genome, has been implicated in melanoma tumorigenesis, but is rare or absent in clear cell sarcoma. Defects in the mismatch repair (MMR) enzyme complex correlate with MSI in some tumor types, allowing the use of immunohistochemistry for the MMR proteins hMLH1 and hMSH2 to predict the presence of MSI. To determine if the association between MMR defects and MSI extends to clear cell sarcoma, we compared a group of nine clear cell sarcomas to 11 metastatic melanomas on the basis of MSI and the expression of MMR proteins. MSI was studied using fluorescence-based multiplexed PCR of five loci. Immunohistochemistry was evaluated on formalin-fixed paraffin-embedded tissue for hMLH1, hMHS2 and hMSH6. MSI was present in only 1/9 (11%) clear cell sarcoma case and in 8/11 (73%) melanoma cases. Immunostaining for hMLH1 and hMSH2 was preserved in all the clear cell sarcomas but loss of immunostaining for one or both proteins was seen in 6/11 melanomas (55%). hMSH6 was detected in 7/9 (78%) clear cell sarcomas and 10/11 (91%) of melanomas. Clear cell sarcoma and metastatic melanoma differed significantly with respect to the presence of MSI (P=0.010) and staining for hMLH1 and/or hMSH2 (P=0.014) but not hMSH6 (P=0.57). Mismatch repair, and consequently genomic instability may contribute to tumorigenesis in melanoma but not clear cell sarcoma. Immunostaining for hMLH1 and hMSH2 and MSI analysis may be helpful in the differential diagnosis of large soft tissue or visceral malignancies with melanocytic differentiation.     

Intracranial metastasis from clear cell sarcoma of the kidney--a case report.

Childhood kidney tumors seldom metastasize into the cranial cavity unless it is a special histological variant. We report a 4-year-old boy with multiple intracranial metastases in the left parietotemporal and right cerebellar area from primary clear cell sarcoma of the kidney without evidence of bony metastases. Metastatic tumor revealed nests of uniformly polygonal cells with clear cytoplasm demarcated by delicate fibrovascular arcades. Tumor cells were positive for vimentin and negative for cytokeratin, S-100 protein, desmin, and myoglobin. Cellular proliferation rate measured by PCNA, and Ki-67 was not significantly different between primary tumor mass and metastatic brain lesion. Expression of p53 oncoprotein was not evident in both lesions. These findings suggested that the relapse and metastasis of clear cell sarcoma of the kidney was probably due to regrowth of micro-metastases which were present at an early stage of disease.     

Ultrastructure of the Ewing's sarcoma family of tumors

Specimens of 47 tumors diagnosed by routine light microscopy as Ewing's sarcoma of bone, and 5 similar soft tissue tumors (extraskeletal Ewing's sarcomas), were examined by transmission electron microscopy. Immunohistochemical stains were performed on all the tumors, and pre-therapy and post-therapy specimens from 5 of the patients were compared. Cell and nuclear areas were assessed in 41 cases by cytomorphometry by using low-magnification electron micrographs. DNA ploidy was determined by static cytometry on 51 of the tumors. None of the methods revealed differences between the bone and soft tissue tumors. The ultrastructural spectrum extended imperceptibly from the typical forms to markedly irregular variants, and was much broader than could be anticipated from the light microscopy. Neural features were observed but they were not common. Comparison of the Ewing's sarcomas with a group of other small round cell tumors (rhabdomyosarcoma, neuroblastoma, small cell carcinoma) using the same techniques showed that they have similar cell and nuclear areas despite the obvious differences in their immunophenotypes and ultrastructure. The collective findings are in keeping with the currently favored view that Ewing's sarcoma and peripheral primitive neuro-ectodermal tumor are the extremes in a morphologic continuum within which neural differentiation ranges from absent to prominent.     

MUM-1/IRF4在滤泡性淋巴瘤中的表达及意义

目的 检测MUM-1/IRF4在滤泡性淋巴瘤中的表达,并探讨其在滤泡性淋巴瘤中表达的生物学意义.方法 应用组织芯片和免疫组织化学SP法检测98例滤泡性淋巴瘤中MUM-1/IRF4及CD10、bcl-6、bcl-2、Ki-67的表达,对MUM-1/IRF4在不同级别滤泡性淋巴瘤中的表达及与其他几个相关蛋白标志物表达的关系进行统计学分析.结果 (1)MUM-1/IRF4在滤泡性淋巴瘤中的表达率为39.8%(39/98),CD10为62.2%(61/98),bcl-6为80.6%(79/98),bcl-2为87.8%(86/98),Ki-67高表达(≥25%)的阳性率为50.0%(49/98);(2)MUM-1/IRF4主要在高级别滤泡性淋巴瘤中表达,与分级(r=0.628,P=0.000)和Ki-67(r=0.473,P=0.000)的表达呈正相关;(3)MUM-1/IRF4与CD10的表达呈负相关(r=-0.597,P=0.000),与bcl-6和bcl-2的表达无相关性.结论 MUM-1/IRF4在高级别滤泡性淋巴瘤中显著性高表达,MUM-1/IRF4阳性病例肿瘤细胞增殖活性高,提示其进展快,预后差,MUM-1/IRF4强阳性有助于高级别滤泡性淋巴瘤的诊断.

Abstract：

Objective To study the expression of MUM-1/IRF4 and its significance in follicular lymphoma. Methods Ninety-eight cases of follicular lymphoma were enrolled into the study. They were graded according to the 2008 WHO criteria. The expression of MUM-1/IRF4 protein and other markers (CD10, bcl-6, bcl-2 and Ki-67) was studied using tissue microarray and immunohistochemistry. Results Amongst the 98 cases studied, there were 24 grade 1 cases, 30 grade 2 cases, 26 grade 3A cases and 18 were grade 3B cases. The rates of expression of MUM-1/IRF4, CD10, bcl-6, bcl-2 and Ki-67 ( ≥25% )were 39. 8% ( 39/98 ), 62.2% ( 61/98 ), 80. 6% ( 79/98 ), 87. 8% ( 86/98 ) and 50. 0% ( 49/98 ),respectively. MUM-1/IRF4 predominantly expressed in high-grade follicular lymphoma and showed a significantly positive correlation with lymphoma grade ( r = 0. 628, P = 0. 000 ) and Ki-67 index ( r = 0. 473,P = 0.000). MUM-1/IRF4 expression had a significantly negative correlation with CD10 expression (r = -0. 597, P = 0. 000), but no correlation with bcl-6 and bcl-2 expression. Conclusions MUM-1/IRF4 expression is significantly higher in high-grade follicular lymphoma, indicating that these cases have a high proliferative activity, more aggressive behavior and poorer prognosis. MUM-1/IRF4, when strongly expressed, is another helpful marker for the diagnosis of high-grade follicular lymphoma.     

MicroRNA expression differentiates between primary lung tumors and metastases to the lung

For surgical pathologists, distinguishing whether a pulmonary neoplasm is primary or metastatic can be challenging, and current biomarkers do not always aid lung tumor classification. The tissue-associated expression of microRNA likely explains the remarkable finding that many tumors can be classified based solely on their microRNA expression signature. Here we show that microRNAs can serve as biomarkers for lung tumor classification. Using microRNA microarray data generated from 76 formalin-fixed, paraffin-embedded (FFPE) samples of either primary lung cancer or metastatic tumors to the lung, we have identified a set of microRNAs expressed differentially between these two groups. This set includes hsa-miR-182, which was most strongly over-expressed in the lung primary tumors, and hsa-miR-126, which was over-expressed in the metastatic tumors. The differential expression of this set of microRNAs was confirmed using qRT-PCR on a set of 54 samples. In light of our data, microRNA expression should be considered as a potential clinical biomarker for surgical pathologists faced with discerning the tumor type of an inscrutable lung neoplasm.