BACKGROUND: Chordoma, a rare malignant tumor arising from notochordal tissue, usually occurs along the spinal axis. Only a few published reports of primary lung chordomas exist. Herein, we present a case of primary lung chordoma and discuss important considerations for diagnosing rare chordomas.
METHODS: We report a case of primary lung chordoma in a 39-year-old male with a history of testicular mixed germ-cell tumor of yolk sac and teratoma. Computed tomography revealed slow-growing solid lesions in the left lower lobe. We performed wedge resection for suspected germ-cell tumor lung metastasis. Histologically, large round or oval cells with eosinophilic cytoplasm were surrounded by large cells with granular, lightly eosinophilic cytoplasm. Tumor cells were physaliphorous. Immunohistochemistry was positive for brachyury, S-100 protein, epithelial membrane antigen, vimentin, and cytokeratin AE1/AE3, suggesting pulmonary chordoma. Re-examination of the testicular mixed germ-cell tumor revealed no notochordal elements. Although some areas were positive for brachyury staining, hematoxylin and eosin (HE) staining did not show morphological features typical of chordoma. Complementary fluorescence in situ hybridization (FISH) of the lung tumor confirmed the absence of isochromosome 12p and 12p amplification. Thus, a final diagnosis of primary lung chordoma was established.
CONCLUSIONS: In patients with a history of testicular mixed germ cell tumors, comparison of histomorphology using HE and Brachyury staining of lung and testicular tumors, and analyzing isochromosome 12p and 12p amplification in lung tumors using FISH is pivotal for the diagnosis of rare lung chordomas.

YAP1-KMT2A融合肉瘤是一种罕见的软组织肉瘤新亚型，好发于青壮年，形态学与硬化性上皮样纤维肉瘤（SEF）有一定程度重叠，但不表达MUC4。本例患者为34岁女性，左腋下无痛性肿块半年。肿瘤周界相对清楚，由大小形态相对一致的上皮样细胞呈小簇状、短条索状、梁状、巢状或弥漫片状分布于致密胶原化间质中，局部可见血管外皮瘤样结构和地图样坏死。瘤细胞无显著异型性，核分裂象约15个/10 HPF。瘤细胞表达上皮细胞膜抗原、CD99、cyclin D1和BCOR，MUC4阴性。荧光原位杂交显示KMT2A基因易位，二代测序显示YAP1-KMT2A基因融合。常规病理工作中，若遇到形态类似SEF，但不表达MUC4的肿瘤，要考虑到YAP1-KMT2A融合肉瘤的可能性，并行分子检测予以明确。.

BACKGROUND: CIC-rearranged sarcomas (CRS) represent a new entity of undifferentiated small round cell sarcoma belonging to the Ewing-like sarcomas family. CRS are the most common type. Fusion partners for the CIC gene include DUX4, FOXO4, and the recently recognizedNUTM1. Rare cases of CIC::NUTM1 sarcoma in pediatric patients have recently been reported in brain, kidney, bone, and soft tissues. However, such cases have not been identified in the soft tissues of the limbs.
METHODS: We reported a case of CIC::NUTM1 sarcoma located in the right upper limb of an 18-year-old man. The tumor displayed morphologic features typical of CIC::DUX4 sarcomas, with small- to medium-sized round cells, a lobular pattern, focal spindling, myxoid stroma, and patchy necrosis. The tumor diffusely expressed NUTM1, was positive for WT1cter at weak to moderate intensity, and was focally positive for CD99, while it was negative for keratins, EMA, P40, MyoD1, myogenin, NKX2.2, BCOR, and pan-TRK. Fluorescence in situ hybridization analyses revealed cleavage of the CIC and NUTM1 genes.
CONCLUSIONS: CIC::NUTM1 sarcomas represent a novel molecular variant of CRS with a preference for the central nervous system and younger pediatric persons. Its morphology and phenotype may be mistaken for NUT carcinomas, and the behavior is more progressive than other forms of CRS. For this rare and newly discovered gene fusion variant, it is necessary to integrate molecular and immunohistochemical findings with morphologic features in the diagnosis of undifferentiated neoplasms.

Follicular lymphoma (FL) is a common type of B-cell lymphoma, accounting for about 20% of all lymphomas. Although FL is primarily characterized by an indolent clinical course, histological transformation (HT) remains one of the significant challenges in managing patients with FL. Here, we present a case of FL with partial large-cell transformation due to Epstein-Barr Virus (EBV) arising in a 50-year-old Japanese woman with no known immunodeficiency. Immunohistochemical studies revealed that medium-sized FL cells expressed CD20, CD10, BCL2, and BCL6, whereas large cells were positive for CD20, and MUM1. In situ hybridization (ISH) revealed large cells to be positive for EBV-encoded small RNA (EBER) and further immunohistochemical investigation demonstrated EBER+ cells to express latent membrane protein 1 (LMP1). The Ki-67 index was about 30% in FL cells, and over 70% in large cells. Fluorescence in situ hybridization for BCL2 combined with EBER-ISH identified BCL2 rearrangement in both EBV-infected large cells and EBV-uninfected FL cells, suggesting these two components were clonally related. These findings indicate that EBV contributes to the transformation of FL. As far as the authors could find, only four previous cases of FL development to EBV-positive aggressive lymphoma have been reported. Further studies are needed to clarify the role of EBV in the HT of FL.

OBJECTIVE: Herein, we present a case of mosaic trisomy 6 detected by amniocentesis.
METHODS: Amniocentesis (G-banding) was performed at 17 weeks of gestation; the results were 47,XY,+6[3]/46,XY[12]. Fetal screening ultrasonography showed no morphological abnormalities, and the parents desired to continue the pregnancy. The infant was delivered vaginally at 39 weeks\' gestation. The male infant weighed 3002 g at birth with no morphological abnormalities. G-banding karyotype analysis performed on the infant\'s peripheral blood revealed 46,XY[20]. FISH analysis revealed trisomy signals on chromosome 6 in 1-4 out of 100 cells from the placenta. The single nucleotide polymorphism microarray of the umbilical cord blood revealed no abnormalities. Methylation analysis of umbilical cord blood revealed no abnormalities in PLAGL1. No disorders were observed at one year of age.
CONCLUSIONS: When amniocentesis reveals chromosomal mosaicism, it is essential to provide a thorough fetal ultrasound examination and careful genetic counseling to support the couples\' decision-making.

BACKGROUND: Ewing\'s sarcoma (ES) is an aggressive cancer of bone and soft tissue, most of which tend to occur in the bone. Extraosseous Ewing\'s sarcoma (EES) of the cervix is extremely rare.
METHODS: In the present work, we reported a 39-year-old cervical EES patient with a 2.5*2.1*1.8 cm tumor mass. According to previous literatures, our case is the smallest tumor found in primary cervical ES ever. The patient initially came to our hospital due to vaginal bleeding, and then the gynecological examination found a neoplasm between the cervical canal and partially in the external cervical orifice. The diagnosis of EES was confirmed below: Hematoxylin & Eosin staining (H&E) revealed small round blue malignant cells in biopsy specimens. Immunohistochemistry (IHC) showed the positive staining for CD99, NKX2.2, and FLI1. Disruption of EWSR1 gene was found by fluorescence in situ hybridization (FISH), and the EWSR1-FLI1 gene fusion was determined by next-generation sequencing (NGS). The patient received laparoscopic wide hysterectomy, bilateral adnexectomy, pelvic lymphadenectomy, and postoperative adjuvant chemotherapy and remained disease free with regular follow-up for 1 year.
CONCLUSIONS: Through a systematic review of previously reported cervical ES and this case, we highlighted the importance of FISH and NGS for the accuracy of ESS diagnosis, which could assist on the optimal treatment strategy. However, due to the rarity of the disease, there is no standard treatment schemes. Investigation on molecular pathological diagnosis and standardization of treatment regimens for cervical ES are critical to patients\' prognosis.

OBJECTIVE: This study aims to perform a prenatal genetic diagnosis of a high-risk fetus with trisomy 7 identified by noninvasive prenatal testing (NIPT) and to evaluate the efficacy of different genetic testing techniques for prenatal diagnosis of trisomy mosaicism.
METHODS: For prenatal diagnosis of a pregnant woman with a high risk of trisomy 7 suggested by NIPT, karyotyping and chromosomal microarray analysis (CMA) were performed on an amniotic fluid sample. Low-depth whole-genome copy number variation sequencing (CNV-seq) and fluorescence in situ hybridization (FISH) were used to clarify the results further. In addition, methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) was performed to analyze the possibility of uniparental disomy(UPD).
RESULTS: Amniotic fluid karyotype analysis revealed a 46, XX result. Approximately 20% mosaic trisomy 7 was detected according to the CMA result. About 16% and 4% of mosaicism was detected by CNV-seq and FISH, respectively. MS-MLPA showed no methylation abnormalities. The fetal ultrasound did not show any detectable abnormalities except for mild intrauterine growth retardation seen at 39 weeks of gestation. After receiving genetic counseling, the expectant mother decided to continue the pregnancy, and follow-up within three months of delivery was normal.
CONCLUSIONS: In high-risk NIPT diagnosis, a combination of cytogenetic and molecular genetic techniques proves fruitful in detecting low-level mosaicism. Furthermore, the exclusion of UPD on chromosome 7 remains crucial when NIPT indicates a positive prenatal diagnosis of trisomy 7.

Spitz tumour with ALK rearrangement is a recently described entity and a rare tumour. The incidence of Spitz tumour was estimated at 3.63 per 100,000 persons in American paediatric population; while there is no data in Asian population. Here we reported a case of an eleven-year-old Asian boy who presented with a left shin nodule of two months\' duration. The skin biopsy revealed a Spitz tumour with predominantly spindle cell morphology arranged in fascicles, vertically orientated nests and radial growth pattern. Junctional component, melanin pigment or Kamino bodies were not identified. Immunohistochemical study displayed homogenous cytoplasmic staining for ALK. Fluorescence in-situ hybridisation (FISH) analysis confirmed ALK rearrangement. Review of the literatures demonstrated that positive ALK immunohistochemistry may not correlate with ALK rearrangement. ALK-rearranged Spitz tumour confirmed with FISH analysis favour clinically benign behaviour despite atypical histomorphology or positive sentinel lymph node. Therefore, correlation of histomorphology, immunohistochemical stain and molecular study are important for the definitive diagnosis of this entity.

报道多系统受累的间变性淋巴瘤激酶（ALK）阳性组织细胞增生症1例。患者女，35岁。因发现左乳肿物10 d入院。镜下见乳腺组织内梭形细胞增生、交错排列，细胞核卵圆形，核分裂象罕见，胞质丰富、嗜碱或透亮，背景可见散在淋巴细胞浸润，及散在残存的脂肪细胞及乳腺导管。免疫组织化学染色显示异常增生的梭形细胞CD68、CD163、ALK阳性，广谱细胞角蛋白（CKpan）、p63、Langerin、S-100蛋白、CD34、β-catenin、结蛋白、Calponin、STAT6阴性。ALK荧光原位杂交（FISH）分离探针检测显示ALK基因有断裂。二代测序于DNA及RNA水平均检测到ALK：：KIF5B基因融合。ALK阳性组织细胞增生症是新近收录于第5版WHO造血与淋巴组织肿瘤的罕见病例，是伴有ALK：：KIF5B基因融合的独特亚型，常常伴有多系统受累，ALK抑制剂靶向治疗有效、但远期生存情况不明确。经验不足的医师容易因认识不足而误诊，因此需要充分认识其临床表现、病理特征与分子改变。.

Rhabdomyosarcoma with TFCP2-related fusions (TFCP2-RMS) is a rare entity that commonly affects young adults with a predilection for skeletal involvement. We herein report a 40-year-old female patient with TFCP2-RMS who was misdiagnosed as fibrous dysplasia or low-grade central osteosarcoma of the mandible by referring institutions. Histologically, the tumor showed dominant spindle cells and focal epithelioid cells with marked immature woven bone formation. Immunophenotypically, in addition to the characteristic expression of myogenic markers, ALK, and cytokeratins, tumor cells also unusually expressed osteogenic markers, such as MDM2 and SATB2. Through fluorescence in situ hybridization, the tumor cells showed EWSR1::TFCP2 gene fusion and no MDM2 gene amplification. This is a rare case of TFCP2-RMS, which was misdiagnosed as low-grade central osteosarcoma due to its presenting immunophenotype of MDM2 and SATB2, as well as extensive osteoid matrix formation.