Recurrent and novel fusions detected by targeted RNA sequencing as part of the diagnostic workflow of soft tissue and bone tumours.

The identification of gene fusions has become an integral part of soft tissue and bone tumour diagnosis. We investigated the added value of targeted RNA-based sequencing (targeted RNA-seq, Archer FusionPlex) to our current molecular diagnostic workflow of these tumours, which is based on fluorescence in situ hybridisation (FISH) for the detection of gene fusions using 25 probes. In a series of 131 diagnostic samples targeted RNA-seq identified a gene fusion, BCOR internal tandem duplication or ALK deletion in 47 cases (35.9%). For 74 cases, encompassing 137 FISH analyses, concordance between FISH and targeted RNA-seq was evaluated. A positive or negative FISH result was confirmed by targeted RNA-seq in 27 out of 49 (55.1%) and 81 out of 88 (92.0%) analyses, respectively. While negative concordance was high, targeted RNA-seq identified a canonical gene fusion in seven cases despite a negative FISH result. The 22 discordant FISH-positive analyses showed a lower percentage of rearrangement-positive nuclei (range 15-41%) compared to the concordant FISH-positive analyses (>41% of nuclei in 88.9% of cases). Six FISH analyses (in four cases) were finally considered false positive based on histological and targeted RNA-seq findings. For the EWSR1 FISH probe, we observed a gene-dependent disparity (p = 0.0020), with 8 out of 35 cases showing a discordance between FISH and targeted RNA-seq (22.9%). This study demonstrates an added value of targeted RNA-seq to our current diagnostic workflow of soft tissue and bone tumours in 19 out of 131 cases (14.5%), which we categorised as altered diagnosis (3 cases), added precision (6 cases), or augmented spectrum (10 cases). In the latter subgroup, four novel fusion transcripts were found for which the clinical relevance remains unclear: NAB2::NCOA2, YAP1::NUTM2B, HSPA8::BRAF, and PDE2A::PLAG1. Overall, targeted RNA-seq has proven extremely valuable in the diagnostic workflow of soft tissue and bone tumours.

The Role of Methylation Analysis in Distinguishing Cellular Myxoma from Low-Grade Myxofibrosarcoma.

Cellular myxoma is a benign soft tissue tumor frequently associated with GNAS mutation that may morphologically resemble low-grade myxofibrosarcoma. This study aimed to identify the undescribed methylation profile of cellular myxoma and compare it to myxofibrosarcoma. We performed molecular analysis on twenty cellular myxomas and nine myxofibrosarcomas and analyzed the results using the methylation-based DKFZ sarcoma classifier. A total of 90% of the cellular myxomas had GNAS mutations (four loci had not been previously described). Copy number variations were found in all myxofibrosarcomas but in none of the cellular myxomas. In the classifier, none of the cellular myxomas reached the 0.9 threshold. Unsupervised t-SNE analysis demonstrated that cellular myxomas form their own clusters, distinct from myxofibrosarcomas. Our study shows the diagnostic potential and the limitations of molecular analysis in cases where morphology and immunohistochemistry are not sufficient to distinguish cellular myxoma from myxofibrosarcoma, particularly regarding GNAS wild-type tumors. The DKFZ sarcoma classifier only provided a valid prediction for one myxofibrosarcoma case; this limitation could be improved by training the tool with a more considerable number of cases. Additionally, the classifier should be introduced to a broader spectrum of mesenchymal neoplasms, including benign tumors like cellular myxoma, whose distinct methylation pattern we demonstrated.

Navigating diagnostic challenges-distinguishing malignant melanoma and clear cell sarcoma of soft tissues: a case report and review of the literature.

BACKGROUND: Within the spectrum of melanocytic-differentiated tumors, the challenge faced by pathologists is discerning accurate diagnoses, with clear cell sarcoma of soft tissues standing out as a rare and aggressive neoplasm originating from the neural crest. Accounting for 1% of all soft tissue sarcomas, clear cell sarcoma of soft tissues poses diagnostic complexities, often misidentified owing to its phenotypic resemblance to malignant melanoma. This chapter delves into the intricacies of clear cell sarcoma of soft tissues, its epidemiology, characteristic manifestations, and the imperative need for a comprehensive diagnostic approach involving immunohistochemical and molecular analyses. CASE PRESENTATION: A compelling case unfolds as a 25-year-old male from Morocco, initially misdiagnosed with malignant melanoma, experiences tumor recurrence on the second toe. With no history of trauma or familial neoplasia, the patient's clinical journey is explored, emphasizing the importance of detailed clinical examinations and radiological assessments. The chapter elucidates the histopathological findings, immunohistochemical spectrum, and the correlation between clinical parameters and diagnostic inference, ultimately leading to metatarsal amputation. This clinical vignette highlights the multidimensional diagnostic process in soft tissue neoplasms, emphasizing the synergistic role of clinical, radiological, and histopathological insights. CONCLUSION: The diagnostic challenges inherent in melanocytic-differentiated tumors, exemplified by the rarity of soft tissue clear cell sarcoma, underscore the essential role of an integrated diagnostic approach. This concluding chapter emphasizes the perpetual collaboration required across pathology, clinical medicine, and radiology for nuanced diagnostic precision and tailored therapeutic strategies. The rarity of these soft tissue malignancies necessitates ongoing interdisciplinary engagement, ensuring the optimization of prognosis and treatment modalities through a comprehensive understanding of the diagnostic intricacies presented by clear cell sarcoma of soft tissues.

[Detection of EWSR1 gene rearrangement by fluorescence in situ hybridization in bone and soft tissue tumors: clinical application evaluation and atypical signal analysis].

Objective: To investigate the clinical application of EWSR1 gene rearrangement by fluorescence in situ hybridization (FISH) in bone and soft tissue tumors and to analyze the cases with atypical signal pattern. Methods: The cases detected for EWSR1 gene rearrangement by FISH in Beijing Jishuitan Hospital, Capital Medical University from 2014 to 2021 were collected, and the value of detecting EWSR1 gene rearrangement for diagnosing bone and soft tissue tumors was analyzed. The cases with atypical positive signals were further analyzed by next generation sequencing (NGS). Results: FISH using EWSR1 break-apart probe kit was successfully performed in 97% (205/211) of cases, 6 cases failed. Four of the 6 failures were due to improper decalcification, 1 case due to signal overlap caused by thick slices, and 1 case due to signal amplification and disorder. EWSR1 gene rearrangements were positive in 122 cases (122/205, 59%), atypical positive signal in 8 cases (8/205, 4%), and negative in 75 cases (75/205, 37%). In cases testing positive, the percentage of positive cells ranged from 34% to 98%, with 120 cases (120/122, 98%) showing a positive cell percentage greater than 50%. Among the 205 successfully tested cases, 156 cases were histologically diagnosed as Ewing's sarcoma, of which 110 were positive (110/156, 71%), 7 were atypical positive (7/156, 4%), and 39 were negative (39/156, 25%). Nine cases were histologically diagnosed as clear cell sarcoma of soft tissue, of which 6 were positive (6/9), 1 was atypical positive (1/9), and 2 were negative (2/9). Five cases were histologically diagnosed as extraskeletal myxoid chondrosarcoma, of which 2 were positive (2/5) and 3 were negative (3/5). Three cases were histologically diagnosed as angiomatoid fibrous histiocytoma, of which 2 were positive (2/3) and 1 was negative (1/3). Two cases were histologically diagnosed as myoepithelioma of soft tissue, of which 1 was positive (1/2) and 1 was negative (1/2). One case was histologically diagnosed as olfactory neuroblastoma with a positive result. The 29 other tumor cases including osteosarcoma, synovial sarcoma, and malignant melanoma and others were all negative. Basing on histology as the standard for diagnosis and considering atypical positive cases as negative, comparing with the 29 cases of other tumors as control group, the sensitivity for diagnosing Ewing's sarcoma through the detection of EWSR1 gene rearrangement was 71%, and the specificity was 100%; the sensitivity for diagnosing clear cell sarcoma of soft tissue was 67%, and the specificity was 100%; the sensitivity for diagnosing extraskeletal myxoid chondrosarcoma was 40%, and the specificity was 100%; the sensitivity for diagnosing angiomatoid fibrous histiocytoma was 67%, and the specificity was 100%; the sensitivity for diagnosing myoepithelioma of soft tissue was 50%, and the specificity was 100%; the sensitivity for diagnosing olfactory neuroblastoma was 100%, and the specificity was 100%. Four of 8 cases with atypical positive signals analyzed by NGS showed EWSR1 rearrangement, including EWSR1::FLI1 in one case of Ewing sarcoma, EWSR1::NFATC2 in one case of EWSR1::NFATC2-rearranged sarcoma, EWSR1::ATF1 in one case of clear cell sarcoma of soft tissue and EWSR1::NR4A3 in one case of extraskeletal myxoid chondrosarcoma. Conclusions: Detection of EWSR1 rearrangement by FISH is of utmost significance in the diagnosis of bone and soft tissue tumors. Cases with atypical positive signals should be further scrutinized, correlating with their histomorphology and verifying by NGS if necessary.

Establishing biomarkers for soft tissue sarcomas.

INTRODUCTION: Soft tissue sarcomas (STS) are a rare and diverse group of tumors. Curative options are limited to localized disease, with surgery being the mainstay. Advanced stages are associated with a poor prognosis. Currently, the prognosis of the patient is based on histological classification and clinical characteristics, with only a few biomarkers having entered clinical practice. AREAS COVERED: This article covers extensive recent research that has established novel potential biomarkers based on genomics, proteomics, and clinical characteristics. Validating and incorporating these biomarkers into clinical practice can improve prognosis, prediction of recurrence, and treatment response. Relevant literature was collected from PubMed, Scopus, and clinicaltrials.gov databases (November 2023). EXPERT OPINION: Currently, defining prognostic markers in soft tissue sarcomas remains challenging. More studies are required, especially to personalize treatment through advanced genetic profiling and analysis using individual tumor and patient characteristics.

Well-differentiated liposarcomas and dedifferentiated liposarcomas: Systemic treatment options for two sibling neoplasms.

Well-differentiated liposarcomas (WDLPS) and dedifferentiated liposarcomas (DDLPS) account for 60 % of all liposarcomas, reflecting the heterogeneity of this type of sarcoma. Genetically, both types of liposarcomas are characterized by the amplification of MDM2 and CDK4 genes, which indicates an important molecular event with diagnostic and therapeutic relevance. In both localized WDLPS and DDLPS of the retroperitoneum and the extremities, between 25 % and 30 % of patients have local or distant recurrence, even when perioperatively treated, with clear margins present. The systemic treatment of WDLPS and DDLPS remains a challenge, with anthracyclines as the gold standard for first-line treatment. Several regimens have been tested with modest results regarding their efficacy. Herein we discuss the systemic treatment options for WDLPS and DDLPS and review their reported clinical efficacy results.

Utility of LEF1 to differentiate desmoid fibromatosis from its histologic mimics.

Diagnosis of desmoid-type fibromatosis (DF) may be challenging on biopsy due to morphologic overlap with reactive fibrosis (scar) and other uniform spindle cell neoplasms. Evaluation of nuclear ß-catenin, a surrogate of Wnt pathway activation, is often difficult in DF due to weak nuclear expression and high background membranous/cytoplasmic staining. Lymphoid enhancer-factor 1 (LEF1) is a recently characterized effector partner of ß-catenin which activates the transcription of target genes. We investigated the performance of LEF1 and ß-catenin immunohistochemistry in a retrospective series of 156 soft tissue tumors, including 35 DF, 3 superficial fibromatosis, and 121 histologic mimics (19 soft tissue perineurioma, 8 colorectal perineurioma, 4 intraneural perineurioma, 26 scars, 23 nodular fasciitis, 6 low-grade fibromyxoid sarcomas, 6 angioleiomyomas, 5 neurofibromas, 5 dermatofibrosarcoma protuberans, 3 low-grade myofibroblastic sarcomas, 3 synovial sarcomas, 3 inflammatory myofibroblastic tumors, 2 schwannomas, and 1 each of Gardner-associated fibroma, radiation-associated spindle cell sarcoma, sclerotic fibroma, dermatofibroma, and glomus tumor). LEF1 expression was not only seen in 33/35 (94%) of DF but also observed in 19/23 (82%) nodular fasciitis, 7/19 (37%) soft tissue perineurioma, 2/3 (66%) synovial sarcoma, and 6/26 (23%) scar, as well as in 1 radiation-associated spindle cell sarcoma. The sensitivity and specificity of LEF1 IHC for diagnosis of DF were 94% and 70%, respectively. By comparison, ß-catenin offered similar sensitivity, 94%, but 88% specificity. Positivity for LEF1 and ß-catenin in combination showed sensitivity of 89%, lower than the sensitivity of ß-catenin alone (94%); however, the combination of both LEF1 and ß-catenin improved specificity (96%) compared to the specificity of ß-catenin alone (88%). Although LEF1 has imperfect specificity in isolation, this stain has diagnostic utility when used in combination with ß-catenin.

Endobronchial solitary fibrous tumors: An enigma for diagnosis.

Solitary fibrous tumors (SFTs) are rare mesenchymal neoplasms constituting less than 2% of all soft tissue tumors. They typically originate in the thoracic cavity, mainly in the pleura, but can also occur in other various sites such as lung parenchyma, pericardium, and bronchus. In this study, a 49-year-old non-smoking female with a history of allergies presented to our pulmonary clinic with a chronic cough. An explorative bronchoscopy revealed an intrabronchial mass in the left superior bronchi, and a 68 Ga-DOTATOC positron emission computed tomography suggested a carcinoid tumor. Subsequent pulmonary segmentectomy unveiled a well-circumscribed polypoid lesion diagnosed as a low-grade bronchus SFT through histopathological and immunohistochemical assessments. The patient was asymptomatic after surgical excision and showed no other lesion during the 6-month follow-up. The endobronchial location of SFT is uncommon, with only a few reported cases in the literature, underscoring the necessity of considering various differential diagnoses, including carcinoid, mucoepidermoid carcinoma, endobronchial pleomorphic adenoma, hamartoma, leiomyoma, and metastasis, depending on location and imaging features. This report underscores the importance of careful histological and immunohistochemical evaluation in understanding and appropriately stratifying the risk associated with polypoid lesions.

[A hard subcutaneous swelling: not always as malignant as it seems]. / Een harde onderhuidse bult.

BACKGROUND: Nodular fasciitis is a rare, benign soft tissue tumor in young adults on the arms or trunk. CASE DESCRIPTION: A 24-year-old woman with previous pretibial melanoma in situ presented with a painless, rapidly growing subcutaneous hard swelling on the right forearm since two weeks. Ultrasound showed a subcutaneous, irregularly shaped, vascularized mass, suspicious for malignancy. Three days later, the swelling had subsided spontaneously. A new ultrasound showed a smaller, oval, sharply demarcated lesion with an inflammatory aspect. Histopathological-immunohistochemical examination of a biopsy showed a spindle cell lesion consisting of (myo)fibroblasts with some erythrocyte extravasation, consistent with nodular fasciitis. Three months later the nodule was resolved spontaneously without treatment. CONCLUSION: Nodular fasciitis should be included in the differential diagnosis in case of hard, fast-growing, subcutaneous bumps in young adults. By ultrasound, it is difficult to differentiate from a malignant soft tissue tumor. A biopsy is necessary to confirm the diagnosis with certainty.

Soft tissue tumours of the penis. The 30-year Istituto Nazionale Tumori di Milano experience.

Objective: Small series and individual cases of penile soft tissue tumours are reported in the literature: these are rare tumours that represent less than 5% of all penile tumours. Methods: Penile soft tissue tumours were collected from the archive of the Department of Pathology at the Istituto Nazionale dei Tumori of Milan between January 1990 and October 2021. All available medical records were retrieved and reviewed to obtain clinical information. Results: Our series refers to the 30-year experience of highlighting the heterogeneity in the presentation and microscopic features of these rare sarcomas. 18 penile soft tissue tumours are described, 4 benign and 14 malignant. The mean age at diagnosis was 58.2 years (range 24-96 years) and 53.6 years among malignancies (range 24-89). The most frequent histotype was Kaposi's sarcoma (nr = 4) and very unusual histotypes were observed, namely low-grade fibromyxoid sarcoma, synovial sarcoma, proximal type epithelioid sarcoma and the first reported case of dedifferentiated liposarcoma of the penis. Conclusions: Among sarcomas of the genitourinary tract, tumours of the soft tissues of the penis are the rarest. Penile sarcomas can present at a young age. Kaposi's sarcoma in HIV-negative patients has a favorable outcome, while deep sarcomas have an aggressive behavior and poor prognosis.

Right Thigh Mass Metastasis from Lung Cancer Mimicking Primary Soft Tissue Sarcoma: A Case Report.

BACKGROUND Soft tissue metastases (STMs) are less common than bone metastases and sometimes misdiagnosed as primary soft tissue malignancies. Skin, lungs, and breast are the most common primary lesions of STMs and rarely the presenting symptoms. We present an STM from lung adenocarcinoma that became a presenting symptom in nonsmoking woman. CASE REPORT A 47-year-old woman presented to our hospital with a painful mass in her right thigh and weight loss of 10 kg for 4 months. Femoral radiograph revealed a lesion suggestive of bone sarcoma. However, magnetic resonance imaging (MRI) showed it was more likely a primary soft tissue sarcoma. A small mediastinal mass was noticed on preoperative chest radiograph, and the patient denied any symptoms except the mass in the right thigh. Our clinicopathological conference team decided to perform a biopsy of mediastinal and right thigh masses. Histopathology examinations confirmed the right thigh mass as soft tissue metastasis from mediastinal mass, confirmed as lung adenocarcinoma. We treated the patient with palliative care with zoledronic acid and gefitinib. At the 6-month follow-up, the patient's symptoms significantly improved, and MRI showed a marked size reduction. CONCLUSIONS Diagnosis of STM can be difficult when presenting as the primary manifestation. Failure to identify promptly can lead to rapid disease progression and unfavorable prognosis. Failure to diagnose primary malignancy during biopsy occurs in approximately 28% of cases. This report has the potential to facilitate the avoidance of unnecessary procedures and highlight the importance of using a multidisciplinary approach in managing cases with malignancy.

Primary soft tissue sarcoma breast with multiphenotypic differentiation.

Primary soft tissue sarcomas of the breast are rare aggressive neoplasms. These often are misdiagnosed with other more common neoplasms like fibroepithelial malignancies, namely phyllodes tumour and metaplastic carcinoma. Being uncommon, chances of being misdiagnosed are higher leading to early mortality. A multidisciplinary team incorporating surgery, pathology, chemotherapy and radiotherapy is required to formulate an approach to primary soft tissue sarcoma. Generally, these tumours may show single or dual phenotype; we present one rare case report showing multiphenotypic differentiation.

DDIT3-amplified or low-polysomic pleomorphic sarcomas without MDM2 amplification: Clinicopathological review and immunohistochemical profile of nine cases.

Several high-grade pleomorphic sarcoma cases that cannot be classified into any existing established categories have been reported. These cases were provisionally classified into undifferentiated pleomorphic sarcoma (UPS). Some dedifferentiated liposarcoma (DDLS) cases may also have been classified into the UPS category due to the absence of MDM2 amplification or an atypical lipomatous tumor/well-differentiated liposarcoma component. We retrieved and reviewed 77 high-grade pleomorphic sarcoma cases, initially diagnosed as UPS in 66 cases and DDLS in 11 cases. Fluorescence in situ hybridization (FISH) analyses of DDIT3 and MDM2 were performed for available cases. Of the cases successfully subjected to DDIT3 FISH (n = 56), nine (7 UPS and 2 DDLS) showed DDIT3 amplification but no MDM2 amplification. Two UPS cases showed both telomeric (5') and centromeric (3') amplification of DDIT3 or low polysomy of chromosome 12, whereas 5 UPS and 2 DDLS cases showed 5'-predominant DDIT3 amplification. Histopathologically, all cases showed UPS-like proliferation of atypical pleomorphic tumor cells. Immunohistochemically, only one case showed focal nuclear positivity for DDIT3, supporting the previous finding that DDIT3 expression was not correlated with DDIT3 amplification. All three cases with focal MDM2 expression involved 5'-predominant amplification, two of which showed DDLS-like histological features. The majority of cases (7/9) showed decreased expression in p53 staining, suggesting that DDIT3 amplification regulates the expression of TP53 like MDM2. From a clinicopathological perspective, we hypothesize that DDIT3-amplified sarcoma, especially with 5'-predominant amplification, can be reclassified out of the UPS category.

The utility of FISH analysis in the diagnosis of BCOR-rearranged sarcomas.

BACKGROUND: A BCL6 corepressor (BCOR) gene alteration is a genetic signature of rare subsets of sarcomas. The identification of this alteration has recently contributed to the definition of new entities in the current WHO (2020) classification of soft tissue and bone tumours. We retrospectively examined cases of BCOR-rearranged sarcoma (BRS) to assess the reliability of the BCOR FISH analysis using an IVD (in vitro diagnostic) probe. METHODS: We investigated and compared the molecular diagnostic strategies and features by collecting 17 data from patients with a BCOR gene rearrangement detected using quantitative-Reverse Transcription-Polymerase Chain Reaction (qRTPCR), Next-Generation Sequencing (NGS) and Fluorescence in situ hybridization (FISH). RESULTS: We describe fourteen BCOR::CCNB3 sarcomas, one spindle cell sarcoma with a novel BCOR::MAML1 fusion, one spindle cell sarcoma with a novel BCOR::AHR fusion, and one ossifying fibromyxoid tumour with a BCOR::ZC3H7B fusion. FISH analysis of all, except one, BCOR::CCNB3 sarcoma, showed a FISH break-apart pattern with mild signal separation. The MAML1::BCOR sarcoma showed large-space split signals, while in the two patients with AHR::BCOR and ZC3H7B::BCOR fusions, no BCOR rearrangement was observed using FISH. CONCLUSIONS: Our study indicates that BCOR FISH analysis using an IVD probe, may be useful to detect the presence of a BCOR rearrangement, including both translocations and inversions; however, negative results, in some cases, can occur.

What is the diagnostic accuracy of fluorescence-guided surgery for margin assessment in appendicular bone and soft tissue tumors? - A systematic review of clinical studies.

BACKGROUND: Fluorescence-guided surgery (FGS) is a novel technique to successfully assess surgical margins intraoperatively. Investigation and adoption of this technique in orthopaedic oncology remains limited. METHODS: The PRISMA guidelines were followed for this manuscript. Our study was registered on PROSPERO (380520). Studies describing the use of FGS for resection of bone and soft tissue sarcomas (STS) on humans were included. Diagnostic performance metrics (sensitivity, specificity, positive predictive value [PPV], negative predictive value [NPV] and accuracy) and margin positivity rate were the outcomes assessed. RESULTS: Critical appraisal using the Joanna Brigs Institute checklists showed significant concerns for study quality. Sensitivity of FGS ranged from 22.2 % to 100 % in three of the four studies assessing his metrics; one study in appendicular tumors in the pediatric population reported 0 % sensitivity in the three cases included. Specificity ranged from 9.38 % to 100 %. PPV ranged from 14.6 % to 70 % while NPV was between 53.3 % and 100 %. The diagnostic accuracy ranged from 21.62 % to 92.31 %. Margin positivity rate ranged from 2 % to 50 %, with six of the seven studies reporting values between 20 % and 50 %. CONCLUSIONS: FSG is a feasible technique to assess tumor margins in bone and STS. Reported performance metrics and margin positivity rates vary widely between studies due to low study quality and high heterogeneity in dying protocols. LEVEL OF EVIDENCE: Level III, diagnostic study.

Current updates in sarcoma biomarker discovery: emphasis on next-generation sequencing-based methods.

Soft tissue sarcomas comprise a heterogeneous group of neoplasms. Although soft tissue malignancies make up only 2% of adult cancers, classification based on histomorphology presents a diagnostic challenge. Characterisation of soft tissue sarcomas by molecular analysis is rapidly evolving to improve diagnostic accuracy and develop targeted therapies. This review highlights the advances in molecular techniques, including current next-generation sequencing-based assays (fusion detection by RNA sequencing, targeted/whole exome sequencing, microRNA profiling), as well as emerging methods (liquid biopsies, DNA methylation profiling, single-cell molecular profiling and next-generation immunohistochemistry) for future clinical applications.

Thoracoscopic Wedge Resection for Low-Grade Fibromyxoid Sarcoma (Evans Tumor) with Massive Calcification and Originating from the Lung: A Rare Case in an Unexpected Location.

We encountered a rare case of low-grade fibromyxoid sarcoma, which is generally known as Evans tumor, with massive calcification originating from the lung. The patient was a 22-year-old man with Duchenne muscular dystrophy who was referred for a detailed investigation of an intrathoracic tumor with massive calcification. Although our preoperative diagnosis was a solitary fibrous tumor originating from the mediastinum or diaphragm, intraoperative thoracoscopy revealed the tumor arising from the left lower lobe without adhesion to the other organs. Considering his medical history, we aimed to preserve lung function and chose wedge resection, which completely removed the tumor. Based on the pathological findings, the tumor was diagnosed as low-grade fibromyxoid sarcoma with massive calcification originating from the lung. Although extremely rare, this tumor should be considered as a differential diagnosis for a solitary lung mass with massive calcification in young adults.

CIC-Rearranged Sarcoma.

CIC-rearranged sarcoma is a rare type of small round cell sarcoma. The tumors often affect the deep soft tissues of patients in a wide age range. They are highly aggressive, respond poorly to chemotherapy, and have a worse outcome than Ewing sarcoma. CIC-rearranged sarcoma has characteristic and recognizable histology, including lobulated growth, focal myxoid changes, round to epithelioid cells, and minimal variation of nuclear size and shape. Nuclear ETV4 and WT1 expression are useful immunohistochemical findings. CIC fusion can be demonstrated using various methods; however, even next-generation sequencing suffers from imperfect sensitivity, especially for CIC::DUX4.