Spindle Cell Sarcoma Research Articles

A Case Report Of A Spindle Cell Sarcoma With Ntrk-3 Rearrangement And A Novel Gene Fusion Partner (Ntrk3-Eif2s2)

Abstract Casestudy A group of spindle cell tumors with characteristic morphologic features, co-expression of CD34 and S100 and recurrent gene rearrangements in RAF-1, BRAF, and NTRK has recently been described. These tumors were found to be previously labeled as malignant peripheral nerve sheath tumor, infantile fibrosarcoma or unclassified spindle cell sarcoma. We describe a case of a 25-year-old female who presented with a right thigh mass. She underwent an ultrasound-guided biopsy showing a spindle cell tumor with co-expression of CD34 and S100 and subsequently underwent resection of the mass. Gross examination showed a 7.5 cm multi-lobulated, tan-pink, hemorrhagic and fleshy mass. Histologically, the tumor was relatively well-demarcated and consisted of spindle cells with moderate to high cellularity in a patternless architecture. The spindle cells showed moderate to marked pleomorphism, pale amphophilic cytoplasm, ovoid-to-elongated nuclei with vesicular chromatin, and occasional prominent nucleoli. Areas of prominent perivascular and stromal hyalinization were seen. Mitotic activity was brisk with up to 33 mitoses per 10 high power fields. Necrosis representing approximately 5% of the mass was identified. On immunohistochemistry, the tumor cells showed strong and diffuse positivity for CD34 and S100 and were negative for SOX10, broad-spectrum cytokeratin, EMA, SMA, Desmin, STAT6, MUC4, TLE1, and H3K27me3 (retained nuclear expression). EIF2S2-NTRK3 fusion gene was detected using next generation sequencing analysis. Conclusion A few cases of NTRK3 spindle cell sarcomas, other than classic infantile fibrosarcoma, have been previously reported in the literature with fusion genes involving ETV6, EML4, and STRN, among others. A gene fusion involving NTRK3 and EIF2S2 has not been previously reported. NTRK3-fused sarcomas typically show high-grade morphology and aggressive clinical behavior. Identification of NTRK-fused sarcomas is clinically important, as these advanced tumors are potentially amenable to NTRK inhibition. In our case, patient received adjuvant post-operative radiation therapy and returned with lung metastasis 5 months after surgery.

Rare Primary Malignant Bone Sarcomas.

Simple SummaryPrimary malignant bone tumors are infrequent cancers. More than 90% of these neoplasms are classified as osteosarcomas, Ewing sarcomas or chondrosarcomas, and their clinical presentation, diagnosis, and treatment principles are well-established. The entities described in this article, are ultra-rare varieties of bone sarcomas, and there clinical and histological characteristics are not well known. Therefore, they are very difficult to be diagnosed and there is a lot of uncertainty on their treatment. Because of their rarity, it is also extremely difficult to perform clinical research on these cancers. This article creates more awareness of these very rare bone tumors. It explains how to recognize and diagnose each entity and it summarizes the medical scientific literature that is available on these cancers. Increasing awareness and clinical research for these cancers are key elements to improve the prognosis for patients with these diseases in the long term.Rare primary malignant bone sarcomas (RPMBS), other than osteosarcoma, chondrosarcoma, chordoma, and Ewing sarcoma, account for about 5–10% of primary bone tumors and represent a major diagnostic challenge. These tumors include spindle cell and round cell sarcoma entities, hemangiopericytoma-like and vascular tumors. Additionally, several histotypes, traditionally described in the soft tissues, such as myxofibrosarcoma, synovial sarcoma, and malignant peripheral nerve sheath tumor of bone, have been reported in patients with primary bone tumors. While wide surgical resection is the mainstay of local treatment, systemic therapy of these rare entities is controversial. Patients with undifferentiated spindle cell or pleomorphic high-grade tumors of bone, are usually treated with osteosarcoma-like chemotherapy, while patients with round cell and undifferentiated round cell tumors (URCTs), may respond to sarcoma treatment regimens for Ewing sarcoma patients. Studies on analogies and differences among these ultra-rare tumors have seldom been reported. This review describes relevance, clinical aspects, diagnostic procedures, staging, treatment recommendations, and current research in this composite tumor group.

Diagnostic Dilemma: Synovial Sarcoma Masked As Common Gynecological Pathologies

Study Objective Synovial sarcoma most commonly presents as a soft tissue tumor in young adults. This case report illustrates a diagnostic dilemma, in which a rare tumor was misdiagnosed on imaging on two separate occasions as common gynecological pathologies. Design N/A Setting N/A Patients or Participants N/A Interventions N/A Measurements and Main Results 45-year-old woman presented to the GynOncology clinic as a referral for management of a pedunculated leiomyoma identified on MRI. The patient was counseled on options, and agreed to placement of an intrauterine device. She re-presented two years later, and pelvic ultrasound showed that the previously identified fibroid was now believed to be a dermoid cyst; with interval increase in size, measuring 10.6 × 12.1 × 15. The patient underwent diagnostic laparoscopy, where a mass of indeterminate origin was noted; involving the round ligament, broad ligament, abdominal peritoneum, and abutting the dome of the bladder. Intraoperative frozen section returned indeterminate. Given the patient's desire for future fertility and uncertainty of malignancy, the decision was made to await final pathology before proceeding with surgical management. Pathology showed low-grade spindle-cell sarcoma with molecular features of synovial sarcoma. In two weeks time, the patient underwent a robotic-assisted total laparoscopic hysterectomy, bilateral salpingo-oophorectomy, and tumor debulking. Per the operative report, the mass that was first thought to be a pedunculated fibroid and then a dermoid cyst was an approximately 20cm retroperitoneal mass originating from the left broad ligament and occupying the entire left pelvic sidewall, pararectal space, paravesical space, and the space of Retzius and encasing the left ureter. Final pathology showed synovial sarcoma, which was confirmed with FISH results. Conclusion This case demonstrates synovial sarcoma misdiagnosed as common gynecological pathologies. This rare pathology is one that gynecologists should be aware of, as its early recognition and treatment allows for improved survival benefit with adjuvant chemotherapy.

The value of re-staging chest CT at first local recurrence of extremity and trunk soft tissue sarcoma

To determine the prevalence of pulmonary metastases on re-staging chest CT at the time of first local recurrence (LR) of trunk or extremity soft tissue sarcoma (STS). Retrospective review of all patients diagnosed with recurrent STS between May 2007 and April 2018. Data collected included patient age and sex, site of primary STS, time to LR, recurrence site, initial tumour grade, recurrent tumour grade, findings of initial staging chest CT, and prevalence of pulmonary metastases on re-staging chest CT. The study included 109 patients (males = 68, females = 41; mean age 56years, range 9-92years). The commonest tumour sub-types were myxofibrosarcoma (27.5%), undifferentiated pleomorphic/spindle cell sarcoma (20.2%), synovial sarcoma (10.1%), and malignant peripheral nerve sheath tumour (10.1%). Initial staging chest CT demonstrated pulmonary metastases in 1 of 77 (1.3%) patients for whom CT was available for review. The mean time to LR was 30.8months (range 3-224months). Pulmonary metastases were diagnosed on re-staging chest CT in 26 of 109 cases (23.9%), being commonest with grade 3 STS (36.1%). Pleomorphic sarcoma (85.7%) and undifferentiated spindle cell sarcoma (33.3%) were the 2 commonest tumour sub-types associated with pulmonary metastases at first LR. Re-staging chest CT at the time of first LR of STS identified a prevalence of 23.9% pulmonary metastases, which supports the need for chest CT at the time of LR in line with the UK guidelines for the management of bone and soft tissue sarcoma. • Pulmonary metastases were diagnosed in 1.3% of soft tissue sarcomas at presentation. • Pulmonary metastases were identified in ~ 24% of patients at first local recurrence of soft tissue sarcoma, most commonly with pleomorphic sarcoma and Trojani grade tumours. • No patient with a low-grade recurrence had pulmonary metastases.

EWSR1-PATZ1-rearranged sarcoma: a report of nine cases of spindle and round cell neoplasms with predilection for thoracoabdominal soft tissues and frequent expression of neural and skeletal muscle markers.

The knowledge of clinical features and, particularly, histopathological spectrum of EWSR1-PATZ1-rearranged spindle and round cell sarcomas (EPS) remains limited. For this reason, we report the largest clinicopathological study of EPS to date. Nine cases were collected, consisting of four males and five females ranging in age from 10 to 81 years (average: 49 years). Five tumors occurred in abdominal wall soft tissues, three in the thorax, and one in the back of the neck. Tumor sizes ranged from 2.5 to 18 cm (average 6.6 cm). Five patients had follow-up with an average of 38 months (range: 18-60 months). Two patients had no recurrence or metastasis 19 months after diagnosis. Four patients developed multifocal pleural or pulmonary metastasis and were treated variably by surgery, radiotherapy, and chemotherapy. The latter seemed to have little to no clinical benefit. One of the four patients was free of disease 60 months after diagnosis, two patients were alive with disease at 18 and 60 months, respectively. Morphologically, low, intermediate, and high-grade sarcomas composed of a variable mixture of spindled, ovoid, epithelioid, and round cells were seen. The architectural and stromal features also varied, resulting in a broad morphologic spectrum. Immunohistochemically, the following markers were most consistently expressed: S100-protein (7/9 cases), GFAP (7/8), MyoD1 (8/9), Pax-7 (4/5), desmin (7/9), and AE1/3 (4/9). By next-generation sequencing, all cases revealed EWSR1-PATZ1 gene fusion. In addition, 3/6 cases tested harbored CDKN2A deletion, while CDKN2B deletion and TP53 mutation were detected in one case each. Our findings confirm that EPS is a clinicopathologic entity, albeit with a broad morphologic spectrum. The uneventful outcome in some of our cases indicates that a subset of EPS might follow a more indolent clinical course than previously appreciated. Additional studies are needed to validate whether any morphological and/or molecular attributes have a prognostic impact.

HIGH GRADE SARCOMA WITH MYXOID FEATURES

SESSION TITLE: Medical Student/Resident Lung Cancer Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Primary pulmonary sarcomas (PPS) are a rare tumor entity in general and tend to be low grade tumors (1). Most sarcomas diagnosed in the lung are due to metastasis and follow an aggressive course (2,3,4,5). This case presents an aggressive, high grade, primary lung spindle cell sarcoma with myxoid features. CASE PRESENTATION: An 84-year-old female presented with chest pain and worsening dyspnea on exertion for two weeks. Imaging revealed a left posterior perihilar mass in her lung. The patient was stabilized and discharged with planned outpatient bronchoscopy with endobronchial ultrasound with transbronchial needle biopsy (EBUS-TBNA). Biopsies of left hilar adenopathy and the lower lobe mass were positive for malignant cells. Histologic analysis, including immunohistochemistry, revealed the tumor to be most consistent with Primary Spindle Cell Sarcoma of the lung not otherwise specified (NOS). The patient presented two weeks after the bronchoscopy with worsening dyspnea and cough. Repeat imaging of her chest revealed significant progression of the mass-like consolidation. The patient was admitted for further evaluation. She became hemodynamically unstable and required intubation with mechanical ventilation and vasopressor support. The patient’s malignancy was determined staged as IVA, M1a. The patient's clinical status continued to rapidly deteriorate. The patient and her family decided to pursue comfort cares and the patient died shortly thereafter. DISCUSSION: Primary Pulmonary Myxoid Sarcoma (PPMS) is a similar tumor entity to PPS. Histologically, PPMS is characterized by polygonal tumor or spindle cells in a myxoid stroma with some atypia (4,6). The time of symptom onset to expiration was 61 days. This case describes a tumor with both aggressive and non-aggressive characteristics. Tissue analysis of this tumor revealed no cytological atypia or necrosis. Feng et al found that tumors in the respiratory system have a poorer prognosis. Tumor size is a prognostic indicator in PPS and tumors over 5 cm had a poorer overall survival (8). This tumor at symptom onset was 8 cm. The size and location of this tumor may have contributed to its aggressiveness and prognosis. Surgical resection is the treatment of choice for PPS and PPMS (3,7,8,9). CONCLUSIONS: There have been few case reports of this type of tumor being an aggressive and high-grade tumor. Given the aggressive nature, physicians need to be aware of this entity so appropriate guidance to patients and families can be provided. Furthermore, more research needs to be done in order to better classify this type of primary sarcoma of the lung. Reference #1: 1.Prieto-Granada CN, Ganim RB, Zhang L, Antonescu C, Mueller J. Primary Pulmonary Myxoid Sarcoma: A Newly Described Entity—Report of a Case and Review of the Literature. International Journal of Surgical Pathology. 2017;25(6):518-525. doi:10.1177/1066896917706413. Reference #2: 2.Koelsche C, Tavernar L, Neumann O, et al. Primary pulmonary myxoid sarcoma with an unusual gene fusion between exon 7 of EWSR1 and exon 5 of CREB1. Virchows Archiv. 2019. doi:10.1007/s00428-019-02716-4. Reference #3: 3.Billingsley KG, Burt ME, Jara E, et al. Pulmonary Metastases From Soft Tissue Sarcoma. Annals of Surgery. 1999;229(5):602. doi:10.1097/00000658-199905000-00002. 4.Jeon YK, Moon KC, Park S-H, Chung DH. Primary pulmonary myxoid sarcomas with EWSR1-CREB1 translocation might originate from primitive peribronchial mesenchymal cells undergoing (myo)fibroblastic differentiation. Virchows Archiv. 2014;465(4):453-461. doi:10.1007/s00428-014-1645-z. 5.Von Mehren M, Randall L, Benjamin RS et al. Soft tissue sarcoma version 2.2018. The Journal of the National Comprehensive Cancer Network. 2018;16(5): 536-563. doi: 10.6004/jnccn.2018.0025 6.Thway K, Nicholson AG, Lawson K, et al. Primary Pulmonary Myxoid Sarcoma With EWSR1-CREB1 Fusion. The American Journal of Surgical Pathology. 2011;35(11):1722-1732. doi:10.1097/pas.0b013e318227e4d2. 7.Feng L, Wang M, Yibulayin F, et al. Spindle cell sarcoma: a SEER population-based analysis. Scientific Reports. 2018;8(1). doi:10.1038/s41598-018-23145-4. 8.Spraker MB, Bair E, Bair R, Connell PP, Mahmood U, Koshy M. An Analysis of Patient Characteristics and Clinical Outcomes in Primary Pulmonary Sarcoma. Journal of Thoracic Oncology. 2013;8(2):147-151. doi:10.1097/jto.0b013e318277401f. 9.Bacha EA, Wright CD, Grillo HC, et al. Surgical treatment of primary pulmonary sarcomas1. European Journal of Cardio-Thoracic Surgery. 1999;15(4):456-460. doi:10.1016/s1010-7940(99)00045-7. DISCLOSURES: No relevant relationships by Jared Alberts, source=Web Response No relevant relationships by Alheli Arce Gastelum, source=Web Response No relevant relationships by Zachary DePew, source=Web Response No relevant relationships by Paul Millner, source=Web Response No relevant relationships by Kenneth Mueller, source=Web Response

PLEURAL SPINDLE CELL NEOPLASM IN A PATIENT WITH NEUROFIBROMATOSIS TYPE I

SESSION TITLE: Fellows Disorders of the Pleura Posters SESSION TYPE: Fellow Case Report Posters PRESENTED ON: October 18-21, 2020 INTRODUCTION: A twenty-two year old male with NF1 presented with multiple pleural masses, consistent with spindle cell neoplasm. Given his history, malignant peripheral nerve sheath tumor is suspected and a rare presentation of this disease. CASE PRESENTATION: A twenty-two-year-old male with Neurofibromatosis Type 1 (NF1) presented to the Emergency Department with abdominal pain. Past medical history included malignant peripheral nerve sheath tumor (MPNST) of the left leg. Despite resection, there was local recurrence within one month and the patient subsequently received chemotherapy with ifosphamide and etoposide, radiation, and surgical resection with a below-knee amputation. A one-cm right lower lobe pulmonary nodule with mild FDG avidity was found on surveillance PET scan. An attempted biopsy was unsuccessful due to the location of the nodule. Unfortunately, the patient was lost to followup. He presented six months later with abdominal pain and dyspnea and was found to have a large right pleural effusion with pleural masses causing mediastinal shift (Figure 1). Tube thoracostomy was performed. Pleural fluid analysis showed a lymphocyte-predominant, exudative effusion. Infectious workup, including bacterial and fungal cultures and adenosine deaminase level, was negative. Cytology demonstrated only reactive mesothelial cells. Pleuroscopy was performed, and multiple pleural-based masses (Figure 2) were biopsied and found to be consistent with spindle cell neoplasm. Immunostaining was negative for neurofilament, CD34, STAT6, Bcl-2, SMA and desmin, CD117, Dog-1, Sox-10, ALK-1, beta-catenin. There was rare staining of S100 and WT-1 positivity, with further histopathological workup pending. DISCUSSION: NF1 is an autosomal dominant disorder with variable organ involvement. Mutation in the NF1 gene results in loss of function of the neurofibromin tumor suppressor protein and upregulation of RAS activity leading to increased tumorigenesis. While a benign disorder, the incidence of malignancy in patients with NF1 is increased and is estimated to be around 2-4.1% per lifetime. Malignant transformation in young adults is most often MPNST, a type of spindle cell sarcoma. Pleural involvement, while rare, is often from metastases as suspected in this case. Accurate and early diagnosis has implications for therapy but can be difficult to distinguish from other soft tissue sarcomas as there is no specific molecular signature. Immunohistochemical staining may show weak staining for S-100 protein in 50% of cases. Surgical resection is preferred in localized disease. Metastatic disease is associated with a poor prognosis, with fewer than 40% of patients surviving past one year after diagnosis. CONCLUSIONS: While a benign disease, NF1 is associated with an increased risk of malignant transformation; pleural involvement is rare but should be on the differential diagnosis of a pleural mass associated with NF1. Reference #1: Zhang Y, Chao J, Qin S. Type I neurofibromatosis with spindle cell sarcoma: A case report. World Journal of Clinical Cases 2019;7:3104-3110. Reference #2: Bethany C. Prudner Tyler Ball , Richa Rathore , and Angela C. Hirbe. Diagnosis and management of malignant peripheral nerve sheath tumors: Current practice and future perspectives. Neuro-Oncology Advances 2019; 20: 1–10 Reference #3: Evans DG, B. M., McGaughran J, Sharif S, Howard E, Moran A: Malignant peripheral nerve sheath tumours in neurofibromatosis 1. J Med Genet, 39((5)): 311-4, 2002 DISCLOSURES: No relevant relationships by Edward Bergin, source=Web Response No relevant relationships by Arista Chand, source=Web Response No relevant relationships by Joshua Malo, source=Web Response

How Are Indeterminate Pulmonary Nodules at Diagnosis Associated with Survival in Patients with High-Grade Osteosarcoma?

How Are Indeterminate Pulmonary Nodules at Diagnosis Associated with Survival in Patients with High-Grade Osteosarcoma?

Diagnostic Enigma: Spindle Cell Sarcoma of the Aorta Presenting as Pulmonary Embolism and Chronic Anaemia.

Primary aortic sarcoma is a rare and aggressive malignancy with only approximately 190 cases reported in the literature. While angiosarcoma and intimal sarcomas represent an estimated 67.7% of malignant aortic tumours, spindle cell sarcomas are even more exclusive, consisting of only 0.9% of malignant aortic tumours. Differentiated from other malignant aortic tumours, spindle cell sarcomas are of mesenchymal origin and usually express vimentin and osteopontin. Clinical presentations are variable and nonspecific, ranging from back pain, abdominal pain or elevated blood pressure, misleading to differentials like pulmonary emboli or aortic aneurysms such as in our case here. In this article, we discuss the finding of an extremely rare aortic sarcoma masquerading as a pulmonary embolism. The patient underwent surgical resection; however, the course was complicated by the development of brain metastases and intracranial haemorrhage. The literature is expanding regarding the evolution of adjuvant chemotherapy and radiation therapy in the treatment of these patients. The exact pathogenesis of spindle cell sarcomas is unknown but thought to be related to the MDM2-p53 pathway. The development of spindle cell sarcomas may be related to Li-Fraumeni syndrome, which should be on the differential for these patients. This case highlights the importance of identifying aortic sarcomas in patients who present with signs and symptoms of peripheral embolization as the diagnosis can be easily misconstrued for thrombus or aortic aneurysm, leading to a delay in proper and timely management. We herein emphasize that aortic sarcomas should be included in the clinician’s working differential due to the poor prognosis and outcomes that these aggressive tumours carry.LEARNING POINTSMalignant aortic tumours are rare and can present with a multitude of symptoms ranging from constitutional symptoms to abdominal discomfort to unexplained hypertension. Spindle cell sarcomas represent 1 of the least common malignant aortic tumours reported in the literature.Malignant aortic tumours have a poor prognosis, and of the various types of malignant aortic tumours, aortic sarcomas have a particularly poor prognosis with a 5-year survival rate of 8%.The exact pathophysiology of these malignancies is unknown but is thought to be related to the MDM2-p53 pathway and may be related to Li-Fraumeni syndrome.

Diagnosis and management of tropomyosin receptor kinase (TRK) fusion sarcomas: expert recommendations from the World Sarcoma Network.

Sarcomas are a heterogeneous group of malignancies with mesenchymal lineage differentiation. The discovery of neurotrophic tyrosine receptor kinase (NTRK) gene fusions as tissue-agnostic oncogenic drivers has led to new personalized therapies for a subset of patients with sarcoma in the form of tropomyosin receptor kinase (TRK) inhibitors. NTRK gene rearrangements and fusion transcripts can be detected with different molecular pathology techniques, while TRK protein expression can be demonstrated with immunohistochemistry. The rarity and diagnostic complexity of NTRK gene fusions raise a number of questions and challenges for clinicians. To address these challenges, the World Sarcoma Network convened two meetings of expert adult oncologists and pathologists and subsequently developed this article to provide practical guidance on the management of patients with sarcoma harboring NTRK gene fusions. We propose a diagnostic strategy that considers disease stage and histologic and molecular subtypes to facilitate routine testing for TRK expression and subsequent testing for NTRK gene fusions.

POLYOSTOTIC FIBROUS DYSPLASIA DIFFERENTIATED IN INTERMEDIATE-GRADE SPINDLE CELL SARCOMA: A CASE REPORT

A 53-year-old female patient presented with complaint of volume increase in the face with 5 months’ of evolution. Physical examination showed a right hemifacial tumor, spontaneous pain, dystopia, amaurosis, right nasal obstruction, and multinodular hardened lesions on the right upper alveolar ridge. The tomographic examination revealed hyperdense lesions in frontal bone enveloping the ethmoid bilaterally, maxillary sinus, and nasal cavity, in addition to the other long bones, which led to the diagnosis of polyostotic fibrous dysplasia. No other endocrinologic finding suggested a syndromic variant, and the rapid and progressive growth led the team to investigate the malignancy. After an angiotomographic study, intense periosteum activity and central vascularization by the external carotid artery were observed. Biopsy was chosen through the core biopsy method, in which the immunohistochemistry confirmed the differentiation in intermediate-grade spindle cell sarcoma. The proposed treatment was chemotherapy and radiotherapy, evolving to death within 3 months’ of the disease. A 53-year-old female patient presented with complaint of volume increase in the face with 5 months’ of evolution. Physical examination showed a right hemifacial tumor, spontaneous pain, dystopia, amaurosis, right nasal obstruction, and multinodular hardened lesions on the right upper alveolar ridge. The tomographic examination revealed hyperdense lesions in frontal bone enveloping the ethmoid bilaterally, maxillary sinus, and nasal cavity, in addition to the other long bones, which led to the diagnosis of polyostotic fibrous dysplasia. No other endocrinologic finding suggested a syndromic variant, and the rapid and progressive growth led the team to investigate the malignancy. After an angiotomographic study, intense periosteum activity and central vascularization by the external carotid artery were observed. Biopsy was chosen through the core biopsy method, in which the immunohistochemistry confirmed the differentiation in intermediate-grade spindle cell sarcoma. The proposed treatment was chemotherapy and radiotherapy, evolving to death within 3 months’ of the disease.

Identification of Novel Fusion Genes in Bone and Soft Tissue Sarcoma and Their Implication in the Generation of a Mouse Model.

Fusion genes induced by chromosomal aberrations are common mutations causally associated with bone and soft tissue sarcomas (BSTS). These fusions are usually disease type-specific, and identification of the fusion genes greatly helps in making precise diagnoses and determining therapeutic directions. However, there are limitations in detecting unknown fusion genes or rare fusion variants when using standard fusion gene detection techniques, such as reverse transcription-polymerase chain reaction (RT-PCR) and fluorescence in situ hybridization (FISH). In the present study, we have identified 19 novel fusion genes using target RNA sequencing (RNA-seq) in 55 cases of round or spindle cell sarcomas in which no fusion genes were detected by RT-PCR. Subsequent analysis using Sanger sequencing confirmed that seven out of 19 novel fusion genes would produce functional fusion proteins. Seven fusion genes detected in this study affect signal transduction and are ideal targets of small molecule inhibitors. YWHAE-NTRK3 expression in mouse embryonic mesenchymal cells (eMCs) induced spindle cell sarcoma, and the tumor was sensitive to the TRK inhibitor LOXO-101 both in vitro and in vivo. The combination of target RNA-seq and generation of an ex vivo mouse model expressing novel fusions provides important information both for sarcoma biology and the appropriate diagnosis of BSTS.

ATYPICAL SPINDLE CELL NEOPLASM OF THE JAW MIMICKING A BENIGN LESION—A RARE CASE REPORT

Clinical Presentation Atypical spindle cell neoplasms are extremely rare lesions, especially in the jaws, and are well known for their aggressive behavior.1 We present the case of a 58-year-old male in whom this tumor was incidentally noted on routine dental examination. The tumor resembled a benign odontogenic lesion on computed tomography (CT) and magnetic resonance imaging (MRI). Because of its propensity for metastasis, positron emission tomography (PET)/CT was performed to rule out distant metastasis. Differential Diagnosis Correlating the innocuous clinical presentation with the radiographic appearance of well-defined nature of the lesion and its paracoronal position with respect to an impacted tooth, the differential diagnosis included dentigerous cyst, other odontogenic cyst, cystic ameloblastoma, and other benign odontogenic tumor. Because of the irregular margins, we assumed the lesion could have been secondarily infected. Diagnosis and Management Histopathologic examination revealed an atypical pleomorphic spindle cell neoplasm of indeterminate origin. The patient underwent segmental mandibulectomy with radical neck dissection. Follow-up PET/CT revealed mild fluoro-2-deoxy-D-glucose (FDG) avidity in the left intraparotid lymph nodes. This could be a reactive process or recurrent/second primary tumor. A close follow-up after 3 months was recommended. Discussion Undifferentiated spindle cell sarcomas are high-grade, aggressive soft tissue sarcomas with no specific line of differentiation. To our knowledge, fewer than 30 cases have been reported. This case would be of specific interest to oral and maxillofacial radiologists because of its resemblance to a benign odontogenic lesion on CT and MRI. In conclusion, this malignancy can mimic benign lesions, and this may have significant influence on formulating the treatment plan, favoring a more conservative approach. Atypical spindle cell neoplasms are extremely rare lesions, especially in the jaws, and are well known for their aggressive behavior.1 We present the case of a 58-year-old male in whom this tumor was incidentally noted on routine dental examination. The tumor resembled a benign odontogenic lesion on computed tomography (CT) and magnetic resonance imaging (MRI). Because of its propensity for metastasis, positron emission tomography (PET)/CT was performed to rule out distant metastasis. Correlating the innocuous clinical presentation with the radiographic appearance of well-defined nature of the lesion and its paracoronal position with respect to an impacted tooth, the differential diagnosis included dentigerous cyst, other odontogenic cyst, cystic ameloblastoma, and other benign odontogenic tumor. Because of the irregular margins, we assumed the lesion could have been secondarily infected. Histopathologic examination revealed an atypical pleomorphic spindle cell neoplasm of indeterminate origin. The patient underwent segmental mandibulectomy with radical neck dissection. Follow-up PET/CT revealed mild fluoro-2-deoxy-D-glucose (FDG) avidity in the left intraparotid lymph nodes. This could be a reactive process or recurrent/second primary tumor. A close follow-up after 3 months was recommended. Undifferentiated spindle cell sarcomas are high-grade, aggressive soft tissue sarcomas with no specific line of differentiation. To our knowledge, fewer than 30 cases have been reported. This case would be of specific interest to oral and maxillofacial radiologists because of its resemblance to a benign odontogenic lesion on CT and MRI. In conclusion, this malignancy can mimic benign lesions, and this may have significant influence on formulating the treatment plan, favoring a more conservative approach.

An interesting case of spindle cell sarcoma of elbow

Spindle cell sarcomas are a group of aggressive malignant soft tissue tumors with a diverse clinical presentation. A 32 years old woman presented with a recurrent nerve sheath tumour, involving flexor carpi ulnaris and a portion of ulnar nerve. Wide local excision of the tumour was done creating a 4 cm gap defect in the ulnar nerve. Distal nerve transfer and Guyon’s canal release was done and anterior transposition of ulnar nerve to distal motor branch of ulnar nerve end to side (ETS) supercharge was done preserving motor function to the little and ring finger. Achieving negative surgical margins in primary soft tissue sarcoma is a critical for local disease control. The anatomical and functional compromise that can occur while giving adequate clearance margin for the tumor can be overcome by microsurgical techniques and neuroanastomosis with positive outcomes like preservation of function and better prognosis.

Teaching NeuroImages: Intracranial DICER1 -associated spindle cell sarcoma in a child

An 8-year-old boy presented with a 2-week history of worsening right-sided headache and left-sided jerking movements. Symptoms were associated with vomiting, photophobia, phonophobia, and diplopia but no loss of consciousness. cEEG demonstrated increased voltage on the right but no evidence of seizures. Brain MRI demonstrated a large right frontoparietal mass (figure 1). The pathologic findings were compatible with DICER1 -associated pleomorphic spindle cell sarcoma (figure 2). Recently described, DICER1 mutation predisposes individuals to development of a subgroup of tumors termed “spindle cell sarcoma with rhabdomyosarcoma-like features, DICER1 mutant” although it may present as “primary intracranial sarcoma, DICER1 -mutant.”1,2

Inflammatory myofibroblastic tumours of the thorax: Radiologic and clinicopathological correlation.

Context and Aims:Inflammatory myofibroblastic tumour (IMT) is a rare mesenchymal neoplasm with intermediate malignant potential. The aim of this study is to describe and compare the clinical presentation, computed tomography (CT) findings and anaplastic lymphoma kinase -1 (ALK-1) expression of IMT of the thorax in children and adults. We also sought to study the tumour behaviour after treatment on the follow-up imaging.Materials and Method:This is a retrospective observational study of 22 histopathologically proven cases of IMT in the thorax. The clinical parameters, CT findings, biopsy results, treatment received and follow-up were recorded. Statistical analysis was performed using Fisher's exact test.Results:IMT of the thorax had diverse imaging appearances, presenting either as large invasive lung masses with or without calcifications or as smaller endobronchial lesions. Children commonly presented with long duration fever (P = 0.02) and large invasive lung masses (P = 0.026), whereas adults presented with long duration haemoptysis (P = 0.001) and endobronchial lesions or smaller lung parenchymal lesions. Calcifications were more common in children (P = 0.007). ALK-1 was positive in 40% of children and 18.2% of adults (P = 0.547). Endobronchial lesions showed a trend for ALK-1 negativity. Patients with bronchoscopic excision had local recurrence and patients with surgical wedge resection had metastatic brain lesions as compared to those with lobectomy and pneumonectomy (P = 0.0152). A patient with unresectable lung mass had malignant transformation to spindle cell sarcoma after 9.5 years.Conclusions:Thoracic IMT presents with some distinct clinical and CT findings in adults and children. The CT findings and management options have implications for prognosis. If resectable, lobectomy is a better option than wedge resection or bronchoscopic excision for preventing local recurrence and metastasis. IMT can undergo malignant transformation.

Paratesticular Liposarcoma Mimicking Inguinal Hernia: a Case Report

Paratesticular tumors account for approximately 5% of intrascrotal mass, and mostly they arise from the spermatic cord (75%). Here, we report a paratesticular mass having a misleading presentation of irreducible inguinal hernia. A 54-year-male patient presented with complaint of right inguino-scrotal swelling for 5 years. Serum tumor markers were within normal limits. Ultrasound of scrotum reveals inguino-scrotal hernia with omental fat and bowel loop herniating out. Patient underwent right inguinal exploration with high inguinal orchidectomy. Histopathology revealed paratesticular high-grade spindle cell sarcoma, and immunohistochemistry was suggestive of paratesticular liposarcoma.

Cytologic grading of canine and feline spindle-cell sarcomas of soft tissues and its correlation with histologic grading

In humans, soft tissue spindle cell sarcomas (STSCS) grading is considered a useful parameter in determining prognosis and therapy, and it is recognized as an important prognostic factor in canine STSCS. The purpose of this study was to assess the utility and the accuracy of a cytologic grading system on fine needle aspiration cytology (FNAC) smears of canine and feline cutaneous and subcutaneous STSCS .Thirty-three cases of cytologically diagnosed STSCS were included. The smears and their tumour sections were cytologically and histologically graded, according to established methods in human oncology.Canine STSCS showed a cyto/histologic concordance in 12/20 cases (60%). Concordance was observed in 4/8 (50%) of grade 1, in 8/12 (67%) of grade 2, and in 0 cases of grade 3. Feline STSCS showed concordance in 11/13 cases (85%). Concordance was observed in 5/6 (83%) of grade 1, in 4/4 (100%) of grade 2, and in 2/3 (66.6%) of grade 3 cases. The overall concordance in the entire canine and feline population was 70%. The gradewise concordance was 65% in grade 1, 75% in grade 2, and 66% in grade 3 cases. The overall concordance is similar to that reported in humans. Although a wider population is required to strengthen our findings, these results suggest that cytologic grading of STSCSs may be a useful tool for therapeutic and prognostic evaluations in dogs and cats.

Soft tissue sarcomas: Evaluation by immunohistochemistry

Soft tissue sarcomas represent a histologically heterogenous group of malignant tumors arising from the soft tissue compartments, i.e smooth muscles, skeletal muscles, adipose tissue, blood vessels, connective tissue mesenchyme, neural tissue and other tumors of uncertain histogenesis(1). Soft tissue sarcomas are relatively rare tumors, represent less than 1% of adult malignancies based on data report from American Cancer Society (2). The crude incidence rate in Iraq for soft tissue sarcomas was 219/ 100,000 population during 2014 with male: female ratio of 1.3:1, and highest peak age between 30-34 years (3). The histological subtype and microscopic criteria are two parameters that influence the tumor grade which is the best predictor for aggressiveness. ( 2)
 Objectives:
 A retrospective evaluation of soft tissue sarcomas, using immunohistochemical study of Myosin, Desmin, Smooth muscle Actin (SMA) and Vimentin, aiming to re-evaluate the primary diagnosis and whether IHC assessment in soft tissue sarcoma is mandatory to reach a final interpretation.
 Material and Patients: 
 A total of 50 cases soft tissue sarcomas were reviewed retrospectively from case archives of histopathology department/ Central Public Health Laboratory, for the period (2011-2018). The data for these cases were collected including the age, gender, site of the tumor and the preliminary biopsy report findings. Hematoxylin& Eosin (H&E) stain and IHC staining of unstained sections from formalin-fixed, paraffin-embedded tissue were performed using SMA, Vimentin, Desmin and Myosin.
 Methods: Age and gender distribution of the 50 cases was correlated. The IHC staining performed on 5 microns paraffin sections, applying peroxidase-Antiperoxidase technique and both positive and negative control slides were included for Smooth muscle actin (SMA), clone 1A4, Desmin (clone D33), Myosin (clone 2F12.A9) and Vimentin (Clone V9). The monoclonal antibodies used were from DAKO manufacturer as ready to use monoclonal antibodies while freeze-dried antibodies used for myosin with 1:20 dilution. Negative and positive control slides were used simultaneously. The staining intensity was assessed based on the percentage of positive cells expression of the four IHC monoclonal antibodies. Negative staining reported when no stain seen. Positive (+) means up to 30% of tumor cells with antigen expression. Positive (++) interpretation given when 31-60% of tumor cells show staining reaction, while Positive (+++) interpretation reported when over 60% of tumor cells showing staining reaction.
 Results:
 The staining interpretation of the four monoclonal antibodies were confirmatory for the original diagnosis in 40% of cases, while 60% of the final diagnoses were against the original interpretation. SMA was positive in 38/50 cases (76%). Desmin was positive in 8/50 cases (20%) Vimentin was positive in 42/50 of cases (84%), Myosin was positive in 30/50 of cases (71.4%).
 The current study focus on histological re-evaluation of different types of soft tissue sarcomas (including RMS-with its subtypes), MFH-storiform, pleomorphic and myxoid subtypes), fibrosarcoma, leiomyosarcoma, alveolar soft part sarcoma and synovial sarcoma depending on immunohistochemical study. The original diagnosis have been changed after the immunohistochemistry stain from fibrosarcoma to rhabdomyosarcoma and leiomyosarcoma , Malignant fibrous histiocytoma to rhabdomyosarcoma, alveolar rhabdomyosarcoma to Malignant fibrous histiocytoma, soft tissue sarcoma to rhabdomyosarcoma , pleomorphic MFH to pleomorphic rhabdomyosarcoma. Embryonal and alveolar rhabdomyosarcoma were confirmed by IHC as so. Leiomyosarcoma was confirmed as the same in one case. Embryonal Rhabdomyosarcoma changed to leiomyosarcoma by IHC positivity for desmin. Six cases of MFH were confirmed as malignant fibrous histiocytoma after IHC. Two cases of synovial sarcoma were re-evaluated as rhabdomyosarcoma. Vimentin revealed 100% positivity in 10 cases and regarded as a sensitive marker for mesenchymal tissue but it is not specific for certain types of sarcomas. The presence of desmin diffusely throughout a tumor is an indication of myoid differentiation and the presence of either SMA or desmin focally should not necessarily be equated with myoid lineage but rather with myofibroblastic lineage, which go in the same direction with Hirofumi N. et al. (1998).(4)
 Conclusions: The co-expression of SMA and Desmin helped in the diagnosis of leiomyosarcoma (LMS). Myosin expression was helpful in the diagnosis of rhabdomyosarcoma (RMS) and alveolar soft part sarcoma (ASPS). Smooth muscle actin (SMA) and vimentin were not specific for the diagnosis of malignant fibrous histiocytoma (MFH). High grade spindle cell sarcoma express SMA only without myosin or desmin can be categorized as pleomorphic myogenic sarcoma. By applying immunohistochemical markers, 60% of soft tissue sarcomas were different from the preliminary diagnosis while 40% of cases were supportive of the original H&E diagnosis.

Beta Human Papillomavirus and Merkel Cell Polyomavirus in Skin Neoplasms

Beta Human Papillomavirus and Merkel Cell Polyomavirus in Skin Neoplasms