CIC-rearranged sarcomas (CRS) are a group of heterogeneous tumors which mostly occur in the soft tissues of limbs and trunk, and are highly invasive with poor prognosis. Here, we describe a rare case of CRS that occurred in the left kidney with a CIC-LEUTX rearrangement.
A 45-year-old male was admitted to hospital with a dry cough for more than two months without obvious cause. Physical examination and laboratory tests revealed no notable abnormality. The CT scan demonstrated a mass in the left kidney and multiple nodules in both lungs. The percutaneous core needle biopsy showed similar histomorphology and immunophenotype of small round cell malignant tumors. Genetic test revealed a CIC-LEUTX gene fusion.
We present a rare primary renal CRS with multiple pulmonary metastases, and LEUTX is confirmed as the fusion partner of CIC gene for the first time in a renal case.

目的： 探讨CIC重排肉瘤（CRS）的临床病理学特征、鉴别诊断及预后。 方法： 收集山东省肿瘤医院2020年12月至2022年5月诊治的6例CRS的临床病理资料，观察其组织形态学特征、免疫表型、分子遗传学特征，并结合文献分析。 结果： 6例患者中男性3例，女性3例，发病年龄3~58岁（平均年龄32.8岁）。软组织3例，子宫2例，肺1例。镜下观察，肿瘤由弥漫片状的未分化性圆细胞构成，呈结节状生长；细胞异型明显，细胞核呈空泡样，部分细胞核仁明显，核分裂象多见；胞质透亮或呈弱嗜酸性；局灶瘤细胞呈梭形、上皮样或横纹肌样形态；肿瘤内可见地图样坏死及间质黏液变性。免疫表型：CD99局灶阳性（5/6）、WT-1核阳性（4/6）、Fli-1阳性（4/6）、ERG阳性（3/6）、cyclin D1阳性（6/6）；其中1例CIC-NUTM1基因融合肿瘤显示NUT核弥漫阳性。INI1表达未缺失（6/6）。荧光原位杂交检测结果：6例患者均显示CIC基因重排。其中，二代测序显示存在CIC-NUTM1基因融合的患者，CIC和NUTM1分离探针均显示阳性。术后随访3~21个月，1例因病死亡，5例带瘤生存。 结论： CIC重排肉瘤是一种罕见的高级别圆细胞未分化肉瘤，独特的组织学特征、免疫表型及特征性的融合基因有助于诊断和鉴别诊断。与其他未分化小圆细胞肉瘤相比，其恶性程度更高，生存期更短。.

目的： 探讨原发于消化道CIC重排肉瘤的临床病理学特征。 方法： 回顾性分析2例原发于消化道的CIC重排肉瘤，包括病理学形态、免疫表型、遗传学特征及生存预后，并复习相关文献。 结果： 2例均为男性，年龄分别为44岁和54岁；肿瘤分别位于小肠和直肠，直径8.0 cm和9.0 cm。低倍镜下肿瘤呈分叶状或结节状，可见纤维性间隔和大片坏死。高倍镜下瘤细胞小至中等大，圆形或卵圆形，核形不规则，可见核分裂象，部分可见核仁。免疫组织化学显示2例均弥漫表达WT1，灶性表达CD99，Ki-67阳性指数分别为50%、70%。采用断裂分离探针荧光原位杂交（FISH）检测发现2例均有CIC基因断裂。2例分别于术后半个月、6个月发生远处转移，转移部位包括肺、腹腔及盆腔；1例于术后1个月死亡，1例存活。 结论： 发生在消化道的CIC重排肉瘤，组织病理学形态与尤因肉瘤较相似，免疫组织化学常表达WT1和CD99，确诊需借助FISH检测，患者预后较差。.

A 16-year-old male was admitted to the hospital for weakness of both lower extremities. Magnetic resonance imaging revealed an intraspinal extramedullary subdural mass at the thoracic 9 level. Microscopically, the tumor cells were small to medium sized and round to ovoid in shape. They were distributed in diffuse sheets or showed nodular appearance. The nucleus of the tumor had mild-to-moderate atypia, with vesicular chromatin and prominent nucleoli. A smaller proportion of tumor cells demonstrated rhabdoid morphology. Focal myxoid stromal change was present, in which tumor cells exhibited spindle shapes. Approximately two mitoses were counted per 10 high-power fields. No necrosis was observed. The tumor cells were focal positive for CD99; multifocal positive for WT1; diffuse positive for nestin, synaptophysin, and D2-40; partial positive for GFAP; focal positive for desmin and SSTR2; and scattered positive for S-100 protein. The Ki-67 labeling index was approximately 20%. Genetic testing revealed CIC-LEUTX gene fusion. Considering the patient\'s history, clinical data, pathological findings and genetic findings, we rendered a rare tumor named CIC-rearranged sarcoma with CIC-LEUTX gene fusion.

原发于婴儿心脏的恶性肿瘤极为罕见，该文报道1例发生于婴儿心脏的CIC重排肉瘤。患儿女，11个月，因纳差12 d，气短3 d、加重1 d入院。影像学检查示右心室占位、心包积液；手术大部分切除肿瘤。镜下肿瘤细胞呈巢片状分布，由圆形、卵圆形细胞及少量胖梭形细胞构成，胞质透亮或嗜酸性，核形不规则，部分核仁突出，核分裂象易见，伴地图状坏死；免疫组织化学CD99斑块状阳性，Fli1、WT1弥漫阳性；荧光原位杂交检测示CIC断裂重排，EWSR1未见重排。.

Objective: To investigate the clinicopathological, immunohistochemical and molecular features of small round cell sarcoma (SRCS) of the bone and soft tissue, and to compare the diagnostic value of different techniques. Methods: Seventy-two cases of SRCS of the bone and soft tissue diagnosed at People\'s Hospital, Peking University from January 2016 to March 2020 were recruited and retrospectively analyzed for pathological morphology, immunophenotype and fluorescence in situ hybridization (FISH) data. Next generation sequencing (NGS) was performed on 13 difficult cases. Results: In the study cohort, the patients ranged in age from 4-55 years, with a male predominance. The most Ewing\'s sarcomas and osteosarcomas occurred in the bone, while CIC-rearranged sarcomas, BCOR-rearranged sarcoma, synovial sarcoma, extraskeletal myxoid chondrosarcoma and FUS-NFATc2 rearranged sarcoma occurred in soft tissue. Histologically, all cases were composed predominantly of small round cells. Most cases were positive for vimentin and CD99, and showed a variable reactivity for neurogenic markers. Muscle marker and epithelial marker were negative for most cases. Combined with clinical features, histopathologic findings, immunophenotype, FISH and NGS, we diagnosed 46 Ewing sarcomas, 14 osteosarcomas, 3 CIC-rearranged sarcomas, 1 BCOR-rearranged sarcoma, 1 synovial sarcoma, 1 clear cell soft tissue sarcoma, 1 extraskeletal myxoid chondrosarcoma, 1 FUS-NFATc2 rearranged sarcoma, and 4 undifferentiated small round cell sarcomas. Conclusions: SRCS of bone and soft tissue is a group of malignant mesenchymal tumors based on morphological features. Most cases can be diagnosed with a combination of clinical characteristics, morphological features and immunohistochemical phenotype, while some cases require such further tests as FISH and NGS technologies, and NGS can be useful in diagnosing and categorizing SRCS.
目的： 探讨骨及软组织小圆细胞肉瘤的病理形态学表现、免疫表型、分子遗传学特征及不同检测技术的诊断价值。 方法： 收集北京大学人民医院2016年1月至2020年3月72例原发于骨及软组织的小圆细胞肉瘤，对其病理形态学表现、免疫组织化学表型及荧光原位杂交（FISH）检测结果进行回顾性分析，并对其中13例疑难病例行二代测序检测。 结果： 本组病例年龄分布在4~55岁，以男性为主，其中尤文肉瘤及小细胞骨肉瘤好发于骨组织，以长骨多见，BCOR重排肉瘤、CIC重排肉瘤、滑膜肉瘤及骨外黏液样软骨肉瘤好发于软组织；病理形态均以弥漫浸润的小圆细胞为主，免疫组织化学染色显示，几乎所有病例均表达波形蛋白和CD99，不同程度地表达神经源性标志物，上皮源性标志物和肌源性标志物表达率低；结合临床特点、形态学、免疫组织化学染色、FISH或二代测序检测诊断尤文肉瘤46例、骨肉瘤14例及透明细胞软组织肉瘤1例；经二代测序诊断3例CIC重排肉瘤及BCOR重排肉瘤、滑膜肉瘤、骨外黏液样软骨肉瘤和FUS-NFATc2融合肉瘤各1例；另有4例经FISH及二代测序检测未发现特异性分子改变，诊断为未分化小圆细胞肿瘤。 结论： 骨及软组织的小圆细胞肉瘤大部分病例结合临床、病理形态表现及免疫表现可以诊断，部分病例需借助FISH、二代测序等分子检测手段协助诊断，其中二代测序检测技术，可为此类肿瘤提供更为精确的分类及诊断。.

小圆细胞肉瘤是指光镜下形态近似的原始或较原始的小圆细胞组成的组织发生和生物学行为不同的一组恶性肿瘤。发生于骨与软组织的小圆细胞肿瘤分类比较繁杂，造成诊断困难。随着免疫组织化学及分子检测技术的发展，人们对这类肿瘤的认识有了显著提高，新近的WHO骨与软组织肿瘤分类系统将这一类肿瘤分为：尤文肉瘤、EWSR1基因与非ETS家族成员融合的圆形细胞肉瘤、伴CIC重排的肉瘤、伴BCOR基因改变的肉瘤以及未分化/未分类圆形细胞肉瘤。本文将介绍该类肿瘤分类的进展及诊断要点。.

Objective: To investigate the clinicopathologic features, immunophenotype and prognosis of CIC-rearranged sarcoma (CRS). Methods: The clinical and pathological data of 10 cases of CRS diagnosed between January 2017 and December 2018 at the Department of Pathology,Fudan University Shanghai Cancer Center were analyzed. Immunohistochemical study and fluorescence in situ hybridization (FISH) were performed. The literature was reviewed. Results: There were five males and five females with a mean age of 28 years (range, 5 to 63 years). Eight tumors developed in the somatic soft tissues, including trunk (n=3),head and neck (n=3),and extremities (n=2). One case each arose in the small intestine and the occipital lobe. The average size was 4.9 cm (range,1.5-8.0 cm). Microscopically,all cases were composed of small to medium-sized round, oval to short spindled cells, showing nodular or lobular architecture, or were arranged in sheets. Compared with Ewing sarcoma, tumor cells of CRS usually showed irregular nuclear outline, coarse chromatin with prominent nucleoli and brisk mitotic activity. Necrosis was present in four cases with one showing geographic necrosis. Immunohistochemically, tumor cells usually showed focal or patch staining of CD99 (9/10),diffuse and strong nuclear expression of WT1 in half cases (2/4),and a high Ki-67 index (median 70%). By FISH, nine cases demonstrated convincing break-apart signal of CIC gene. Follow-up data available in seven cases (mean 12.1 months); of these two patients died of disease (2/7), whereas one patient was alive with unresectable recurrent tumor,the remaining four patients were alive with no evidence of disease. Five patients (5/7) experienced local recurrence and two patients (2/7) developed metastasis. The mean and median intervals to recurrence/metastasis were eight months and four months, respectively. Conclusions: CRS is the most common type of EWSR1-negative small round cell sarcoma (SRCS). Although it has clinical and pathological overlapping features with Ewing sarcoma,the prognosis is comparatively poor. Focal or patch staining of CD99 but diffuse staining of WT1 in a case of small RCS should raise the possibility of CRS. FISH assay is required for the final diagnosis.
目的： 探讨CIC重排肉瘤（CIC-rearranged sarcoma，CRS）的临床病理学特征、免疫表型和预后。 方法： 回顾性分析复旦大学附属肿瘤医院病理科2017年1月至2018年12月间诊断的10例CRS的临床病理学资料，行免疫组织化学检测和荧光原位杂交检测，并复习相关文献。 结果： （1）男性5例，女性5例，平均年龄28岁（范围5~63岁）。8例发生于软组织，包括躯干3例、头颈部3例和下肢2例；分别发生于小肠和大脑枕叶各1例。肿瘤平均直径4.9 cm（范围1.5~8.0 cm）。（2）镜下由结节状、分叶状或片状分布的小至中等大圆形、卵圆形或短梭形细胞组成。核形不规则，常可见核仁。核分裂象易见。4例内可见坏死，其中1例显示大片地图状坏死。（3）免疫表型：9例表达CD99（9/10），其中8例为灶性或斑驳状表达，1例呈弥漫阳性。2例弥漫性表达WT1（2/4），Ki-67阳性指数70%（范围30%~90%）。（4）采用断裂分离探针荧光原位杂交（FISH）检测显示9例有CIC基因重排，1例可能存在CIC基因重排。（5）7例获得随访结果，平均随访12.1个月，5例发生局部复发；2例发生远处转移，发生复发/转移的平均和中位时间分别为8个月和4个月。2例患者死亡，1例带瘤生存，4例无瘤生存。 结论： CRS是EWSR1阴性小圆细胞肉瘤中最常见的一种类型，在临床表现和病理学上与骨外尤因肉瘤非常相似，但预后相对较差。对CD99灶性阳性但WT1弥漫阳性的小圆细胞肉瘤需考虑CRS的可能性，确诊需经FISH检测。.

A unique feature in several non-CNS-tumors is the overexpression of heat shock protein 70 (Hsp70, HSPA1A) in the cytosol, but also its unusual plasma membrane expression and release. Although in gliomas, cytosolic Hsp70 levels are not associated with histological grading, the role of membrane bound and released Hsp70 is still completely unknown. Membrane bound as well as cytosolic Hsp70 can be detected in viable tumor cells with the monoclonal antibody (mAb) cmHsp70.1. Herein, we analysed membrane bound Hsp70 levels in primary and secondary gliomas of different grades and on isolated glioma subpopulations (endothelial cells, CD133-positive cells, primary cultures) by immunohistochemistry and flow cytometry using cmHsp70.1 mAb. Extracellular Hsp70 was determined by a commercial Hsp70 sandwich ELISA (R&D) in plasma samples of glioblastoma patients and healthy volunteers. We found an overexpression of Hsp70 in primary glioblastomas compared to low-grade, anaplastic, or secondary gliomas as determined by immunohistochemistry. Especially in flow cytometry, a strong plasma membrane Hsp70 expression was only observed in primary but not secondary glioblastomas. Within the heterogeneous tumor mass, CD133-positive tumor-initiating and primary glioblastoma cells showed a high membrane Hsp70 expression density, whereas endothelial cells, isolated from glioblastoma tissues only showed a weak staining pattern. Also in plasma samples, secreted Hsp70 protein was significantly increased in patients harbouring primary glioblastomas compared to those with secondary and low grade glioblastomas. Taken together, we show for the first time that cytosolic, membrane bound and extracellular Hsp70 is uniquely overexpressed in primary glioblastomas.

Desmoplastic small round cell tumor is a highly aggressive neoplasm that generally involves the peritoneum and pelvis of young patients. Only rare cases occur outside the abdomen. We report a case presenting as a primary submandibular gland tumor in a 24-year-old man. Histologically, although there were irregular tumor islands lying in an abundant desmoplastic stroma, there were also areas comprising large cellular islands with scanty stroma in between, raising the differential diagnosis of various salivary gland carcinomas. The tumor cells were medium sized, with hyperchromatic nuclei and moderate amounts of cytoplasm. The diagnosis of desmoplastic small round cell tumor was confirmed by the presence of a polyphenotypic immunoprofile (positive for cytokeratin, desmin, and neuron-specific enolase) and the characteristic EWS-WT1 gene fusion. Although rare, desmoplastic small round cell tumor has to be considered in the differential diagnosis of poorly differentiated neoplasms of the salivary gland, especially in young patients.