Spindle Cell Tumor Research Articles

Histologic Variants of Kaposi Sarcoma in the Gastrointestinal Tract: A Contemporary Multi-institutional Clinicopathologic Analysis of 46 Cases.

Kaposi sarcoma (KS) can pose diagnostic challenges in biopsy specimens. Multiple histologic variants of cutaneous KS have been described; however, the histomorphologic spectrum of gastrointestinal (GI) KS has not been systematically studied. This large series comprehensively evaluated 46 cases of KS involving the GI tract and identified 7 histomorphologic variants, some that have not been previously described. Five of them are inconspicuous but have unique morphologic patterns, including lymphangioma/lymphangiectatic-like (n=17), mucosal hemorrhage/telangiectatic-like (n=17), mucosal inflammation-like (n=15), granulation tissue-like (n=13), and mucosal prolapse-like (n=4) variants. These variants can be easily misdiagnosed or misinterpreted on routine examination if KS is not considered, and if the immunohistochemical stain for human herpesvirus-8 is not performed. The other 2 morphologic variants present as spindle cell proliferations and are the GI stromal tumor-like (n=8) and inflammatory myofibroblastic tumor-like (n=2). These variants raise a broad differential diagnosis of spindle cell tumors of the GI tract and could pose diagnostic challenges. In summary, GI KS lesions exhibit variable, often unconventional histomorphologic patterns. KS should be included in the differential diagnosis even if features of conventional KS are not seen, particularly in limited biopsies in immunocompromised patients, such as those with human immunodeficiency virus infection. Although the clinical significance of these morphologic variants is yet to be determined, they are nonetheless important from a diagnostic standpoint. Misdiagnosis and delay in appropriate management can be avoided by recognizing the morphologic diversity of GI KS and appropriately utilizing the human herpesvirus-8 immunohistochemical stain.

A RARE CASE OF A RECURRENT LEIOMYOSARCOMA OF THE BUCCAL MUCOSA

Leiomyosarcomas are rare malignant tumors that affect smooth muscle tissue. In the oral cavity, leiomyosarcomas are exceedingly rare. The diagnosis is challenging due to the overlap of morphologic findings with several spindle cell tumors. Herein, we reported a rare recurrent case of leiomyosarcoma in a 73-year-old woman presenting clinically as a painful nodule on the buccal mucosa. Microscopically, the tumor showed atypical spindle cells with elongated, blunt-ended nuclei and eosinophilic cytoplasm arranged in a fascicular pattern. Immunohistochemistry showed positivity for vimentin, α-SMA, HHF35, h-Caldesmon, and focal positivity for desmin. S-100 protein, CD34, myogenin, and pan-cytokeratin (AE1/AE3) were negative. Surgical excision followed by chemotherapy was performed. No recurrence was observed after 12 months of follow-up. Careful histopathologic analysis, supported by immunohistochemistry, is essential to ensure a correct diagnosis. Early wide surgical excision and prolonged follow-up is strongly recommended.

Solitary fibrous tumor: A rare lesion with an unusual paravertebral presentation

BackgroundSolitary fibrous tumor (SFT) is a rare spindle-cell neoplasm [1]. Although typically originating from pleura, head and neck presentation accounts for about 6–18 % and very few cases have been described in paravertebral and posterior neck spaces [2]. Both computed tomography (CT) scans and magnetic resonance imaging (MRI) help in differential diagnosis of such lesion [3]. However, only histological and immunohistochemical studies give a conclusive diagnosis: CD34, BCL-2, and in particular STAT6 stainings are strongly orientative [4]. Radical surgery with free margin excision is the first treatment option, rarely requiring adjuvant therapy [2]. Prognosis is typically good and strictly related to histological risk assessment [5]. Rare cases of local recurrence and distant metastasis have been described in literature [2]. ObjectiveThe purpose of this video is to describe the operative technique of a transcervical removal of a rare case of right paravertebral SFT. We present the diagnostic flowchart, management strategies, surgical technique and we provide anatomical dissection parallelism, which might be of interest to the readers. Materials and methodsA 59-years-old man with a one-year right cervical asymptomatic swelling was referred to our department. A contrasted MRI documented an expansive 6.5 cm capsulated lesion in the deep posterior neck spaces with diffuse contrast enhancement and inhomogeneous appearance. A core needle biopsy was performed, and the results from the initial immunohistochemical panel were not univocal showing positivity for cytokeratins AE1/AE3, PAX8, and no reactivity for CD34. A second immunohistochemical panel was then performed, displaying diffuse nuclear positivity for STAT6, which is a surrogate marker for the NAB2-STAT6 gene fusion, a specific driver mutation of SFT. Therefore, a radical excision was performed via transcervical approach (Video 1). No post-operative complications neither cranio-cervical neurological deficit occurred. ResultsIn comparison to pre-operative histopathologic study, the definitive histological examination of the whole mass revealed a more classical morphology of SFT. It was classified as an intermediate risk SFT [5]. A complete free margin excision was confirmed. After a multidisciplinary discussion, no adjuvant therapies were suggested. A six- and twelve-months radiological follow-up with MRI showed no evidence of disease. ConclusionSFT may represent a misdiagnosed entity in head and neck spaces and a correct diagnosis through immunohistochemistry is mandatory. Radical excision with free surgical margins should be pursued as adequate goal. Since SFTs show variable risk of metastatic disease, adjuvant radiotherapy should be contemplated in high-risk diseases and a clinico-radiological follow-up with MRI is required.

Diagnosis and Differentiation of Spindle Cell Tumors on the Face of Elderly Patients

Diagnosis and Differentiation of Spindle Cell Tumors on the Face of Elderly Patients

Primary Osseous Leiomyosarcoma with Vertebral and Nodal Metastasis in a Young Woman: A Rare Case Report.

Introduction. Primary leiomyosarcoma of bone is rarely described in the literature. In young patients, the clinical and radiological features may mimic relatively common tumours like osteosarcoma. Vertebral and nodal metastasis from osseous leiomyosarcoma is extremely uncommon. Case presentation. A 25-year-old female presented with progressively increasing pain and swelling of the right knee. Clinical and radiological features were suggestive of osteosarcoma. Pre-operative biopsy showed a malignant spindle cell tumour. The surgical resection specimen showed features of leiomyosarcoma of the right proximal tibia. On further evaluation, the patient was found to have an L3-L4 vertebral lesion and histopathological evaluation showed a similar tumour. After 11 months of initial presentation, the patient had axillary lymph node metastasis. Conclusion. Primary osseous leiomyosarcoma should be considered as a differential diagnosis even in young patients presenting with meta-diaphyseal expansile malignant bony lesions. Histology and ancillary studies can confirm the diagnosis.

EGFR internal tandem duplications in fusion-negative congenital and neonatal spindle cell tumors.

Next-generation sequencing (NGS) assays can sensitively detect somatic variation, and increasingly can enable the identification of complex structural rearrangements. A subset of infantile spindle cell sarcomas, particularly congenital mesoblastic nephromas with classic or mixed histology, have structural rearrangement in the form of internal tandem duplications (ITD) involving EGFR. We performed prospective analysis to identify EGFR ITD through clinical or research studies, as well as retrospective analysis to quantify the frequency of EGFR ITD in pediatric sarcomas. Within our institution, three tumors with EGFR ITD were prospectively identified, all occurring in patients less than 1year of age at diagnosis, including two renal tumors and one mediastinal soft tissue tumor. These three cases exhibited both cellular and mixed cellular and classic histology. All patients had no evidence of disease progression off therapy, despite incomplete resection. To extend our analysis and quantify the frequency of EGFR ITD in pediatric sarcomas, we retrospectively analyzed a cohort of tumors (n=90) that were previously negative for clinical RT-PCR-based fusion testing. We identified EGFR ITD in three analyzed cases, all in patients less than 1year of age (n=18; 3/18, 17%). Here we expand the spectrum of tumors with EGFR ITD to congenital soft tissue tumors and report an unusual example of an EGFR ITD in a tumor with cellular congenital mesoblastic nephroma histology. We also highlight the importance of appropriate test selection and bioinformatic analysis for identification of this genomic alteration that is unexpectedly common in congenital and infantile spindle cell tumors.

Cytomorphological spectrum of solitary fibrous tumour: revisited.

Solitary fibrous tumour (SFT) is a tumour of mesenchymal origin. Its diagnosis on cytology is challenging, owing to variation in cellularity, sparsely distributed cellular and stromal components. Cytomorphological findings for this type of tumour have rarely been described in the literature-only a few case reports and the occasional case series have been presented thus far. We present the cytomorphological features of SFT with special emphasis on immunochemical findings. We present cytological data from eight cases of histopathologically proven SFTs. The cytomorphological features, immunochemical markers and differential diagnostic entities on fine needle aspiration cytology are discussed. Fine needle aspiration was performed at various anatomical sites. Cytology smears showed variable cellularity, with tumour cells arranged in loose clusters and as singly scattered cells. Interlacing fascicles with palisading of cells was noted. The cells were predominantly spindle to elongated, having moderate cytoplasm with elongated wavy nuclei. These nuclei had fine to coarse chromatin, with inconspicuous to prominent nucleoli. There was prominent, metachromatically staining, amorphous to fibrillary, collagenous to myxoid matrix material associated with the tumour cells. Other findings included intranuclear pseudo-inclusions, multinucleated giant cells and atypical mitoses. Cytological diagnoses offered varied from 'spindle cell neoplasm' to 'spindle cell sarcoma' or 'suggestive of sarcoma'. Immunocytochemistry (ICC) performed on cell block sections showed positivity for STAT6, CD34 and Bcl-2. Cytological diagnosis of SFT can be challenging. A careful search for characteristic cytomorphological features is diagnostically helpful. The cytomorphology should be interpreted with caution, with an appropriate ICC panel, including STAT6 and CD34.

A review of solitary fibrous tumours of the orbit and ocular adnexa.

Solitary fibrous tumour (SFT) is an uncommon spindle cell tumour of mesenchymal origin characterised by NAB2-STAT6 gene fusion. Although it was first described in the pleura, it can occur in connective tissue in any part of the body, but rarely presents in the orbit and ocular adnexa. SFT, which is part of the same disease spectrum as other fibroblastic tumours such as giant cell angiofibroma, haemangiopericytoma and fibrous histiocytoma, usually presents as a painless, slow-growing mass in any age group and generally follows a benign course, with a good prognosis after complete excision. However, malignant forms rarely occur. Even for benign tumours a more aggressive clinical behaviour is possible, with relentless infiltrative local growth, frequent recurrence following surgery, and malignant transformation with the potential for metastatic spread. Careful long-term follow-up is essential. The published literature on SFTs of the orbit and ocular adnexa is reviewed, and the aetiology, clinical presentation, epidemiology, radiological features, histopathology, immunohistochemistry, risk stratification, clinical management, and prognosis are discussed, reflecting on our own experience.

The Mean ApoC1 Serum Level in Postoperative Samples from Neurosurgical Patients Is Lower than in Preoperative Samples and during Chemotherapy

Simple SummaryApolipoprotein C1 is mainly synthesized in the liver and helps in the digestion of fatty acids and in their clearance from the bloodstream. Recent reports have described the role of ApoC1 in malignant tumors of internal organs, exerting an impact on tumor growth and prognosis. Only little is known about ApoC1 in patients with diseases affecting the nervous system, so in this study, samples from neurosurgical patients were examined. A total of 219 samples from 85 patients with brain tumors was compared to 11 samples from patients undergoing non-tumor spine surgery. After drawing the blood sample, it was centrifuged to yield the serum supernatant, which was then assessed by a photometric antibody test (ELISA). The results give the concentration of ApoC1 in the probed blood in µg/mL. From a single sample, it was not possible to determine the underlying disease, such as lumbar disc herniation or brain tumor. Of note, the ApoC1 levels of glioblastoma patients fell significantly after the neurosurgical resection of the tumor and then rose again during chemotherapy. Ongoing research deals with a detailed statistical analysis to determine whether ApoC1 serum levels qualify for use as a blood biomarker for glioblastoma.Serum levels of apolipoprotein ApoC1 have been described in a number of systemic tumor entities as potential biomarkers, but little is known about ApoC1 in neurosurgical patients. A total of 230 serum samples from 96 patients were analyzed using an ELISA technique. Patient diagnoses comprised 70 glioblastomas WHO IV°, 10 anaplastic astrocytomas III°, one anaplastic oligodendroglioma III°, one oligodendroglioma II°, one diffuse astrocytoma II°, one pilocytic astrocytoma I°, and a single case of a spindle cell tumor without WHO grading, as well as 11 spinal interventions. The mean ApoC1 level of the 230 samples was 132.03 µg/mL (median 86.83, SD 292.91). In the 176 glioblastoma samples, the mean ApoC1 level was 130.0 µg/mL (median 86.23, SD 314.9), which was neither different from the whole group nor from patients with spinal interventions (215.1 μg/mL, median 63.6, SD 404.9). In the postoperative samples, the mean ApoC1 level was significantly lower (85.81 μg/mL) than in the preoperative samples (129.64 μg/mL) and in samples obtained during adjuvant chemotherapy (168.44 μg/mL). While absolute ApoC1 serum levels in a patient do not allow for the distinction between neurosurgical histological entities, future analyses will examine whether the time course of ApoC1 in an individual patient can be related to certain treatment stages.

Clinical Assessment Limitation in Extragastrointestinal Stromal Tumour of Rectovaginal Septum Diagnosis: A Case Report

Extragastrointestinal tumour of rectovaginal septum (rvGIST) is a rare malignancy that affects rectovaginal septum. We present a case of rvGIST that was initially managed as cervical eGIST based on clinical assessment. A 66-year-old woman presented with postmenopausal bleeding and constipation. Bimanual pelvic examination revealed an irregular mass occupying the vagina. CT thorax, abdomen and pelvis showed a 9.2 x 10.0 x 14.0 cm pelvic mass arising from cervix, extending superiorly to involve the uterus. The patient proceeded to undergo total abdominal hysterectomy, bilateral salpingo-oophorectomy, enucleation of rectovaginal septum mass, rectosigmoidectomy and permanent colostomy. Intraoperatively, there was a 9 x 7 cm mass arising from rectovaginal septum. Histopathological examination of surgical specimen revealed spindle cell tumour diffusely positive for CD34, CD117 and DOG1. The final diagnosis was rvGIST. In conclusion, the diagnosis of rvGIST require a combination of clinical assessment with intraoperative finding and histological assessment of the surgical specimen.

Inflammatory Myofibroblastic Tumor of the Bladder in an 8-Year-Old Girl: About a Case with Review of the Literature

Introduction: The inflammatory myofibroblastic tumor is a rare tumor. It most often occurs in the bladder in the genitourinary sphere. This benign and aggressive spindle cell tumor affects children and frequently girls. The objective of this work is to describe from a clinical case, the clinical, radiological, and histological characteristics of an inflammatory myofibroblastic tumor in an 8 years old girl. Case Presentation: An 8-year-old girl was followed for an inflammatory myofibroblastic tumor of the bladder revealed by micturition burns complicated by hematuria. She underwent an ultrasound and radiological workup demonstrating an anterior bladder parietal mass reaching the rectus abdomen is muscle. Subsequently, an excisional biopsy was performed and histological and immunohistochemical examination revealed an inflammatory myofibroblastic tumor. Discussion: Inflammatory myofibroblastic tumors of the bladder are benign tumors with aggressive features usually revealed by voiding symptoms, pelvic pain, and pelvic mass. Treatment is based on Trans urethral resection of the bladder. Anatomical pathology examination shows spindle-shaped myofibroblast and fibroblast cells, a collagenous or myxoid matrix, and inflammatory cells composed of plasma cells, lymphocytes, and eosinophils. The diagnosis is confirmed by immunohistochemistry with an expression of CAM5.2, desmin, aSMA, and vimentin and especially of Anaplasic Lymphoma Kinase (ALK). Conclusion: Rare tumor process, whose malignant potential remains unknown. Management is by conservative surgery of the bladder.

Adult NTRK-rearranged spindle cell neoplasms of the viscera: with an emphasis on rare locations and heterologous elements

AbstractNTRK-rearranged mesenchymal neoplasms mostly affect the soft tissues of pediatric patients. Given the responsiveness to selective NTRK inhibitors, it remains critical to identify those ultra-rare cases occurring in the viscera of adults. In five females and two males aged 18–53 years, we characterized visceral mesenchymal tumors harboring TPM3-NTRK1 [uterine cervix (N = 2), pleura, prostate], LMNA-NTRK1 (lung), SQSTM1-NTRK3 (heart), and NTRK3 rearrangement with unknown fusion partner (colon/mesocolon) with RNA sequencing, FISH, RT-PCR, and immunohistochemistry. The tumors exhibited spindled to ovoid/epithelioid or pleomorphic cells, often arranged in fascicles, and were low-to-intermediate-grade and high-grade in three and four cases, respectively. Keloid-like stromal collagen and perivascular hyalinization was noted in five. Adenosarcoma-like appearances were observed in two, manifesting frond-like protrusions in one cervical tumor and phyllodes-like architecture in the prostatic tumor. Abrupt high-grade transformation into pleomorphic liposarcoma was found in another cervical tumor, while the pleural tumor contained intermixed rhabdomyoblasts. Pan-TRK immunostaining was positive in all cases. All cases expressed CD34, while five were S100-positive. CDKN2A homozygous deletion with concomitant p16 loss occurred in 4/7. Whole-exome sequencing identified TP53 mutation (c.672+2T>C, involving a splice site, with concomitant protein loss) in a cervical sarcoma, limited to its heterologous liposarcomatous component. At least moderate pan-TRK immunoreactivity was present in varying proportions of potential pathologic mimics, with BCOR-positive sarcoma (56%, 5/9), undifferentiated uterine sarcoma (50%, 3/6), and spindle cell/sclerosing rhabdomyosarcoma (33%, 2/6) being among the most frequent. This underscored the unsatisfactory specificity of pan-TRK immunohistochemistry and warranted molecular confirmation in the diagnosis of adult NTRK-rearranged visceral mesenchymal neoplasms. The current report highlights the ever-expanding clinicopathologic and genetic spectrum of this entity by describing the unprecedented cardiac and pleural locations and heterologous differentiation, as well as the second NTRK-rearranged “prostatic stromal sarcoma,” while substantiating CDKN2A deletion as a frequent occurrence.

Sarcomatoid carcinoma: A rare biphasic variant of OSCC: A case report

Sarcomatoid carcinoma is a type of spindle cell neoplasm. These varieties of neoplasms comprise of a diverse collection of benign and malignant neoplasms. Sarcomatoid carcinoma, also known by various other names such as Spindle cell carcinoma, Lane’s tumor, to name a few, is an exceedingly rare and aggressive variant of squamous cell carcinoma 3, 7, 8 The variation in its nomenclature reflects the divergent interpretation of the sarcomatoid component as reactive or neoplastic, mesenchymal or epithelial.8 It accounts for

VEGF and VEGFR family members are expressed by neoplastic cells of NF1-associated tumors and may play an oncogenic role in malignant peripheral nerve sheath tumor growth through an autocrine loop

Neurofibromatosis type 1 (NF1) is a common autosomal dominant disorder. The role of angiogenesis and VEGF pathway in the pathogenesis of neurofibromas and malignant peripheral nerve sheath tumors (MPNSTs) remains poorly understood.We assessed the expression of VEGF and VEGFR family members in cohorts of plexiform neurofibromas (pNF), MPNSTs and MPNST cell lines at transcript [pNF, n = 49; MPNST, n = 34] and protein levels [pNF, n = 21; MPNST, n = 9].VEGF and VEGFR members were variably expressed in cell lines. VEGFA (p = 3.10−5), VEGFR1 (p = 0.08), and VEGFR2 (p = 2.10−4) mRNAs were overexpressed in MPNSTs in comparison with pNFs. Both VEGFA and VEGFR1 proteins were expressed by spindle tumor cells of pNFs and MPNSTs. VEGFA was expressed more in MPNSTs than in pNFs (p = 9.10−6) and a trend for VEGFR1 overexpression was observed (p = 0.06). VEGFR2 was not found at the protein level. The microvascular density was significantly reduced in MPNSTs as compared to pNFs (p = 0.0025), with no differences regarding the expression of the activated phosphorylated forms of ERK (P-ERK [p = 0.63]) and AKT (P-AKT [p = 0.41]) in endothelial cells, suggesting that VEGF-dependant angiogenesis may not be critical for MPNST oncogenesis.Altogether, these results indicate that the VEGF-VEGFR pathway may play a role in the development of pNFs and MPNSTs, independently of angiogenesis. Whether or not it drives an oncogenic autocrine/paracrine loop in neoplastic cells, participating in an increased activation of signaling pathways downstream of tyrosine kinase receptors, including VEGFRs, is a tempting hypothesis. Nevertheless, the specific targeting of angiogenesis in MPNSTs may not be sufficient to slow down tumor growth.

New molecular entities of soft tissue and bone tumors.

The advances of molecular techniques have led to the refinement of the classification of mesenchymal tumors, leading to newly introduced entities in the recently published fifth edition of the WHO Classification of Soft Tissue and Bone Tumors, which are discussed in this review. For the first time, entities are included of which the name refers to the underlying molecular alteration including round cell sarcoma with EWSR1 -non-ETS fusions, CIC -rearranged sarcoma, and sarcoma with BCOR genetic alteration. EWSR1-SMAD3 -positive fibroblastic tumor and NTRK -rearranged spindle cell neoplasm are provisionally included as 'emerging' entities based on the underlying molecular alteration, though the entity still needs to be better defined. Other newly recognized entities are not named after their molecular change, but the molecular alteration helped to delineate them from others: atypical spindle cell/pleomorphic lipomatous tumor, anastomosing hemangioma, angiofibroma of soft tissue, myxoid pleomorphic liposarcoma, and poorly differentiated chordoma. Classification of mesenchymal tumors is increasingly based on the underlying molecular changes, although this cannot be interpreted separately from clinical, morphological, and immunohistochemical characteristics.

NTRK -Rearranged Uterine Sarcomas: Clinicopathologic Features of 15 Cases, Literature Review, and Risk Stratification.

NTRK -rearranged uterine sarcomas are rare spindle cell neoplasms that typically arise in the uterine cervix of young women. Some tumors recur or metastasize, but features which predict behavior have not been identified to date. Distinguishing these tumors from morphologic mimics is significant because patients with advanced stage disease may be treated with TRK inhibitors. Herein, we present 15 cases of NTRK- rearranged uterine sarcomas, the largest series to date. Median patient age was 35 years (range: 16 to 61). The majority arose in the uterine cervix (n=14) and all but 2 were organ-confined at diagnosis. Tumors were composed of an infiltrative, fascicular proliferation of spindle cells and most showed mild-to-moderate cytologic atypia. All were pan-TRK positive by immunohistochemistry (13/13); S100 (11/13) and CD34 (6/10) were usually positive. RNA or DNA sequencing found NTRK1 (10/13) and NTRK3 (3/13) fusions with partners TPR , TPM3 , EML4 , TFG , SPECC1L , C16orf72 , and IRF2BP2 . Unusual morphology was seen in 2 tumors which were originally diagnosed as unclassifiable uterine sarcomas, 1 of which also harbored TP53 mutations. Follow up was available for 9 patients, of whom 3 died of disease. By incorporating outcome data of previously reported tumors, adverse prognostic features were identified, including a mitotic index ≥8 per 10 high-power fields, lymphovascular invasion, necrosis, and NTRK3 fusion. Patients with tumors which lacked any of these 4 features had an excellent prognosis. This study expands the morphologic spectrum of NTRK -rearranged uterine sarcomas and identifies features which can be used for risk stratification.

Undifferentiated Hepatic Sarcoma: A Rare Case

Primary hepatic undifferentiated pleomorphic sarcoma (UPS) is a rare malignant mesenchymal tumor with a nonspecific clinical and radiologic presentation. Primary hepatic UPS is often a diagnosis of exclusion made by multiple immunohistological testing that rules out hepatic, hematologic, neural, and epithelial origin. Stains for mesenchymal origin are usually the only positive stain and do not demonstrate evidence of specific mesenchymal cell differentiation. We report a case of a 56-year-old male with no significant past medical history that presented with complaint of epigastric abdominal pain of six months duration. A computed tomography (CT) scan of the abdomen and pelvis exhibited numerous hepatic masses involving right and left hepatic lobe. A CT-guided core needle biopsy discovered undifferentiated/pleomorphic sarcoma. Histomorphology showed spindle cell neoplasm without recognizable hepatic tissue. Immunohistochemistry (IHC) stains were positive for smooth muscle actin (SMA) but failed to establish a more specific histogenesis. Furthermore, IHC stains revealed spindle neoplastic cells with focal and patchy positive h-caldesmon (approximately 10-15% of neoplastic cells), and negative for desmin. Given these results, the diagnosis of undifferentiated/pleomorphic sarcoma was established. It is imperative to consider UPS in the differential diagnosis of large liver lesions without evidence of differentiation. Early identification of this rare tumor can prevent the possibility of distant metastasis and improve survival among patients.

Tyrosine kinase-altered spindle cell neoplasms with EGFR internal tandem duplications.

In this study, we present two extra-renal pediatric spindle cell neoplasms with epidermal growth factor receptor (EGFR) internal tandem duplications (ITD). Histologically, these tumors demonstrated the same histologic features seen in other tyrosine kinase-altered spindle cell neoplasms, with one case showing abundant adipose tissue with cellular fibrous septae resembling lipofibromatosis and the other case showing fascicles of spindled cells resembling infantile fibrosarcoma. There was variable expression of CD34, S100, and SMA, and all cases were negative for panTRK. This case series adds to our molecular understanding of the spectrum of tyrosine kinase-altered spindle cell neoplasms and represents the first reported examples of EGFR ITDs in extra-renal tumors. The presence of EGFR alterations in the absence of gene fusions represents a potential therapeutic target and necessitates a broader testing panel for this group of tumors.

Malignant solitary fibrous tumors: a clinicopathological and molecular genetic analysis

Objective: To explore the clinicopathological features, immunophenotype and molecular genetic characteristics of malignant solitary fibrous tumor (MSFT). Methods: Seven cases of MSFT were collected from the First Affiliated Hospital of Zhengzhou University from July 2018 to December 2020. Immunohistochemistry, RNA-based NGS and DNA-based NGS were performed. Results Among the 7 patients, there were 5 males and 2 females with a median age of 53 years (37-69 years). Two tumors located at skull base, and one in the tentorium of cerebellum, parietal occipital region, occipital area, chest and buttock respectively. The maximum diameter of the tumor was 2.5-20.0 cm. Microscopically, typical hemangiopericomatoid structures were noted; the tumor was cellular, fusiform or oval, very pleomorphic, with necrosis and high mitotic figures (>4/10 HPF). In some cases, classical solitary fibrous tumor morphology and dedifferentiated region were observed. Immunohistochemically, the tumor was positive for CD34 (6/7), STAT6 (7/7), bcl-2 (7/7), but negative for S-100 (7/7); CKpan or EMA was positive to varying degrees; mutated p53 was noted (3/7); Ki-67 positive index was more than 10%. NAB2-STAT6 gene fusion was typically detected in all the 7 cases. In 4 cases, ZNF415-FGFR1, COPG1-MET, IPO11-LRRC70_ncRNA-PLAG1 and Clorf198-CD274 (PD-L1) gene fusions were also detected. NOTCH1 mutation was found in 7 cases and TP53 mutation in 4 cases. TERT promoter mutations were not detected in all the cases. Conclusions: MSFT is rare and needs to be differentiated from many other spindle cell tumors. Especially when tumors express epithelial markers, they are easily misdiagnosed as sarcomatoid carcinoma and synovial sarcoma, etc. Immunohistochemistry and molecular detection of NAB2-STAT6 gene fusion have important diagnostic values. NOTCH1 and TP53 mutations may be associated with the progression of MSFT. Some patients have FGFR1 gene fusion and MET gene fusion, which may be potential therapeutic targets.

RARE-25. Primary Intracranial Ewing Sarcoma in a Child: Case Report

Ewing sarcoma is a rare childhood tumor which accounts for 3% of all pediatric malignancies. More so, primary intracranial involvement with meningeal attachment is even rarer, accounting for only 1% of all Ewing sarcoma. We report a case of a 5-year-old boy who presented with headache, vomiting, and left-sided weakness that rapidly progressed over a period of three months. Cranial MRI showed a 7.1 x 6.7 x 8.6 cm multilobulated, heterogeneously enhancing, mixed solid and cystic extra-axial tumor compressing the frontoparietal lobe and causing significant midline shift. It was attached to the falx and infiltrated the middle third of the superior sagittal sinus. We performed a large right frontoparietal craniotomy to excise the tumor. Because of massive bleeding from the tumor, only a subtotal resection was possible. The bone flap was left out. The patient was discharged fully awake but with right hemiplegia on the fourteenth post-op day. Histopathologic examination revealed a spindle cell neoplasm that exhibited diffuse membranous staining for CD99. Fluorescence in-situ hybridization confirmed EWSR1 gene rearrangement, consistent with Ewing sarcoma. Three months after his surgery, the patient subsequently received 56 Gy of radiation therapy. At twelve months post-op, he remains fully awake and is back in school. He has residual left hemiparesis, but with antigravity movement. A multidisciplinary team involving Pediatric Oncology, Pediatric Neurology, Neurosurgery, Pathology, Radiation Oncology, and Rehabilitation Medicine is essential for patients with rare central nervous system tumors, to maximize effective treatment strategies despite limited resources.