Spindle Cell Research Articles

A Case Report On Unusual Mediastinal Mass

A 28-year-old female, a known case of neurofibromatosis 1, presented to the respiratory medicine department with complaints of breathlessness and cough for 2 weeks’ duration. Clinical examination revealed right-sided moderate pleural effusion. Computed tomography (CT) chest revealed a large anterior mediastinal mass with chest wall infiltration. Histopathology showed neoplasm with epithelioid cells, arranged as sheets and interlacing spindle cells with a moderate amount of eosinophilic cytoplasm and inconspicuous nucleoli. Histopathological examination of excised specimen showed a malignant peripheral nerve sheath tumor with rhabdomyoblastic differentiation also known as malignant triton tumor. After palliative chemotherapy, later on follow-up, CT-guided biopsy from right side chest wall lesion also showed the same. Because of this rare presentation, we are reporting this case.

Soft tissue vascular tumor-like lesions in adults: imaging and pathological analysis pitfalls per ISSVA classification

ObjectivesTo compare the magnetic resonance imaging (MRI) and Doppler ultrasound (DUS) findings with the pathological findings of soft tissue vascular tumors (STVTs) according to the 2018 ISSVA (International Society for the Study of Vascular Anomalies) classification to differentiate vascular tumors from vascular malformations.MethodsThis retrospective study included patients with STVTs who underwent contrast-enhanced MRI and pathological analysis at our hospital between 2010 and 2020. The presumptive diagnosis based on the on-site imaging and histological analysis was compared with imaging and histological analysis conducted off-site utilizing the ISSVA criteria.ResultsThis study included 31 patients with 31 vascular tumors located in the head and neck (n = 3), trunk (n = 2), and extremities (n = 26). The off-site pathological analysis confirmed benign vascular tumors in 54.8% of cases (non-involuting congenital hemangioma: 35.5%; epithelioid hemangioma: 13%; pyogenic granuloma: 3%; and spindle cell hemangioma: 3%). Based on the off-site histological analysis, 25.8% were reclassified as having a vascular malformation whereas three had other benign lesions. Only phleboliths were associated with a vascular malformation (p = 0.03). The concordance between off-site MRI and pathological findings was fair (k = 0.3902 (0.0531–0.7274)), whereas that between on-site and off-site pathological analyses was poor (k = −0.0949 (−0.4661 to 0.2763)).ConclusionBenign vascular tumors have non-specific imaging features on imaging with some overlap with atypical vascular malformations. Therefore, histological analysis is recommended. Imaging and pathological analyses should be performed in accordance with the ISSVA classification to minimize inter-observer discrepancies.Critical relevance statementImaging features of benign vascular tumors on MRI are non-specific, leading to discrepancies with pathological findings and potential overlap with atypical vascular malformations. Imaging and histological analyses should be performed in accordance with ISSVA guidelines to improve patient management.Key PointsThe imaging features of benign vascular tumors are non-specific.Histological analysis is recommended for soft tissue vascular tumors in adults.Analyses of soft tissue vascular tumors should be performed in accordance with ISSVA guidelines.Graphical

Clinicopathological and molecular characteristics of NTRK-rearranged spindle cell neoplasms in the gastrointestinal tract

Objective: To investigate the clinicopathological, immunophenotypic and molecular genetic characteristics, and differential diagnosis of NTRK-rearranged spindle cell neoplasms (NTRK-RSCNs) in the gastrointestinal tract. Methods: Two NTRK-RSCNs diagnosed at the Department of Pathology of the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China and one case diagnosed at Zhengzhou Central Hospital, Zhengzhou, China from 2019 to 2022 were collected. The clinical data, histopathology, immunophenotypes and prognosis were analyzed. Fluorescence in situ hybridization (FISH) and next-generation sequencing (NGS) were used to detect NTRK gene rearrangements, while relevant literature was also reviewed and discussed. Results: Two patients were male and one was female, with the age of 17, 47 and 62 years, respectively. The tumors were located in the duodenum, ascending colon and descending colon, respectively. The tumors were protuberant masses with gray and rubbery sections. Their maximum diameter was 2.5, 5.0 and 10.0 cm, respectively. Histologically, the tumors invaded mucosa, intrinsic muscle and serosal adipose tissue. Tumor cells consisted of spindle or oval shaped cells with monotonous morphology and arranged in bundles or stripes pattern. Spindle cells were mildly to moderately atypical, with slightly eosinophilic cytoplasm and inconspicuous nucleoli. Necrosis and mitotic figures were observed in one high-grade tumor. All tumors expressed CD34, S-100 and pan-TRK in varying degrees. FISH analysis showed that NTRK1 gene was break-apart in 1 case and NTRK2 gene break-apart in 2 cases. NGS technologies showed LMNA::NTRK1 fusion in one case, STRN::NTRK2 fusion in another case. All patients recovered well after the surgery without recurrence at the end of the follow-up. Conclusions: NTRK-RSCN is rarely diagnosed in the gastrointestinal tract and has significant variations in morphology. It overlaps with various other mesenchymal tumors which should be considered as differential diagnoses. Be familiar with the features of histological morphology in combination with immunophenotype and molecular genetic characteristics can not only help diagnose NTRK-RSCNs, but provide therapeutic targets for clinical treatment.

ALK-Rearranged Renal Cell Carcinoma: A Multi-Institutional Study of 9 Cases With Expanding the Morphologic and Molecular Genetic Spectrum

ALK-rearranged renal cell carcinoma (ALK-RCC) is rare, molecularly defined RCC subtype in the recently published fifth edition of World Health Organization classification of tumors. In this study, we described 9 ALK-RCCs from a clinicopathologic, immunohistochemical, and molecular genetic aspect, supporting and extending upon the observations by previous studies regarding this rare subgroup of RCC. There were 6 male and 3 female patients with ages ranging from 14 to 59 years (mean, 34.4 years). None of the patients had sickle cell trait. The diagnosis was based on radical or partial nephrectomy specimen for 8 patients and on biopsy specimen for 1. Tumor size ranged from 2.5 to 7.2 cm (mean, 2.8 cm). Follow-up was available for 6 of 9 patients (6-36 months); 5 had no tumor recurrence or metastasis and 1 developed lung metastasis at 24 months. The patient was subsequently treated with resection of the metastatic tumor followed by crizotinib-targeted therapy, and he was alive without tumor 12 months later. Histologically, the tumors showed a mixed growth of multiple patterns, including papillary, solid, tubular, tubulocystic, cribriform, and corded, often set in a mucinous background. The neoplastic cells had predominantly eosinophilic cytoplasm. Focally, clear cytoplasm with polarized nuclei and subnuclear vacuoles (n = 1), and pale foamy cytoplasm (n = 1) were observed on the tumor cells. The biopsied tumor showed solid growth of elongated tubules merging with bland spindle cells. Other common and uncommon features included psammomatous microcalcifications (n = 5), rhabdoid cells (n = 4), prominent intracytoplasmic vacuoles (n = 4), prominent chronic inflammatory infiltrate (n = 3), signet ring cell morphology (n = 2), and pleomorphic cells (n = 2). By immunohistochemistry, all 9 tumors were diffusely positive for ALK(5A4) and 4 of 8 tested cases showed reactivity for TFE3 protein. By fluorescence in situ hybridization analysis, ALK rearrangement was identified in all the 9 tumors; none of the tested tumors harbored TFE3 rearrangement (0/4) or gains of chromosomes 7 and 17 (0/3). ALK fusion partners were identified by RNA-sequencing in all 8 cases analyzed, including EML4 (n = 2), STRN (n = 1), TPM3 (n = 1), KIF5B (n = 1), HOOK1 (n = 1), SLIT1 (n = 1), and TPM1(3′ UTR) (n = 1). Our study further expands the morphologic and molecular genetic spectrum of ALK-RCC.

Case report: Para-testicular spindle cell lipoma suspected of well-differentiated liposarcoma

Spindle cell lipoma is a relatively rare benign tumor that can occur in the posterior neck, shoulder, and upper back. Herein, we present a case of intrascrotal spindle cell lipoma in a 71-year-old male who presented with a mass in the left scrotum that had developed over 2 years. Contrast-enhanced computed tomography (CT) revealed a 5.7cm mass accompanying enhanced solid components. Magnetic resonance imaging (MRI) showed a heterogeneous signal intensity. Therefore, a well-differentiated liposarcoma derived from the spermatic cord was suspected; therefore, the patient underwent radical inguinal orchidectomy with high ligation of the spermatic cord. Histopathological examination revealed mature adipocytes and bland-spindle cells. Immunohistochemically, the tumor cells were positive for CD-34 and negative for CDK4, MDM2, and p16. These findings indicated a spindle cell lipoma. Surgical margins were negative. Three months after surgery, no relapse was observed. This case underscores the rarity of para-testicular spindle cell lipoma. While CT and MRI play crucial roles in disease diagnosis, they may not detect all lesions. To prevent overtreatment, it’s essential to also consider pre-surgical examinations and intraoperative findings.

Analysis of demographic and socioeconomic factors in biphasic synovial sarcoma using data from the National Cancer Database.

e23524 Background: Synovial sarcoma, a rare type of soft tissue sarcoma, can be classified into two subtypes - biphasic and spindle cell. Of the two, biphasic synovial sarcoma (BSS) has a better 5-year survivorship; however, 35% of patients diagnosed with BSS die within 5 years. Despite past controversy, adjuvant chemotherapy has been found to improve overall survival for patients with stage III BSS. The National Cancer Database (NCDB) was examined to discover the demographics of individuals diagnosed with BSS. Methods: The 2004-2020 NCDB was analyzed to conduct a retrospective cohort analysis. Patients with a histologically confirmed diagnosis of BSS (ICD-O-3 code 9043) were included (N = 92). Demographic factors like age, sex, race, Hispanic origin, insurance status, educational attainment, distance from facility, facility type, and Charles/Deyo score were evaluated using descriptive statistics and incidence trends were interpreted with regression analysis. Results: Ninety-two biphasic synovial sarcoma cases sampled between 2004 and 2020 revealed an average age at diagnosis of 47.3 years (SD = 19.9, range = 5–87), with males being more likely to be diagnosed (58%). The patients reside at an average of 42 miles from treatment facilities (SD = 108.56, range = 0.3–800.6). Primary disease sites varied, including the lower lobe of the bronchus or lung (12%), upper lobe (11%), and long bones (11%). Diagnosis frequency (2004–2020) showed minimal variation (R^2 = 0.007). Palliative care was not received in 95% of cases, and 41% of patients did not undergo a surgical procedure at the primary site. In patients who received surgery, residual tumor absence post-resection was noted in 56% of patients. Primary treatments included chemotherapy (48%) and radiation therapy (42%), with an average tumor size of 65.2 mm (SD = 42.8, range = 9–195 mm). Notably, 74% survived beyond 90 days post-surgery, with a thirty-day mortality rate of 2%. Patients survived an average of 8.5 years post-diagnosis. Facility-wise, 37% were in academic/research programs. Privately insured patients constituted 60%, with 51% of all patients residing in metropolitan areas of 1 million or more. Conclusions: This analysis addresses a critical knowledge gap, offering insights into the demographics and socioeconomic factors affecting the diagnosis and treatment of Biphasic Synovial Sarcoma (BSS). The average age of BSS diagnosis is 47.3 years with males being predominantly affected, consistent with earlier case reports. BSS patients showed diverse geographic distribution. Survival beyond 90 days post-surgery was high. Chemotherapy and radiation therapy were common treatments. Unique findings include a majority residing in metropolitan areas, and non-academic program treatments. This study underscores the necessity for further research to grasp the impact of these factors on BSS diagnosis, treatment, and overall survival.

Spindle cell rhabdomyosarcoma: A study of demographics and socioeconomic factors using NCDB.

e23539 Background: Spindle cell rhabdomyosarcoma (SC-RMS) is a rare malignancy characterized by elongated spindle cells displaying eosinophilic and fibrillar cytoplasm, resembling smooth muscle fibers. SC-RMS is primarily diagnosed in children with particular involvement of the nasopharynx, parotid gland, nasal cavity, and paratesticular regions. Though surgical resection and chemotherapy are the current recommendations, definitive treatment guidelines remain unestablished. Because SC-RMS is a novel cancer type, evaluating the diagnostic trend of the disease has the potential to provide valuable insights into its epidemiology. An analysis of the National Cancer Database (NCDB) was conducted to identify the demographic factors associated with patients who have been diagnosed with SC-RMS. Methods: A retrospective cohort analysis of the 2004–2020 NCDB, using ICD-O-3 code 8912/3, included patients with a histologically-confirmed diagnosis of SC-RMS (N = 132). Demographic factors (age, sex, race, Hispanic status, educational attainment, insurance status, facility type, distance from facility, and Charles/Deyo score) were analyzed by descriptive statistics and incidence trends were interpreted in regression analysis. Results: A total of 132 patients with a confirmed diagnosis of SC-RMS were identified, with a declining incidence of diagnoses per year (R² = 0.4507). The average age of diagnosis was 33.9 years (SD = 27.2, Range = 1-90). SC-RMS was more commonly observed among males (63%), with a majority of patients being non-Hispanic (87%) and White (74.2%). The top primary site was the testis (20%). Most patients (83%) had a Charlson/Deyo comorbidity score of 0. The majority (69%) of patients received surgery as their primary treatment. Most patients were privately insured (49%) and resided in metropolitan areas with a population greater than 1 million (48%). More (29%) patients were in the highest quartile of income earners of $74,063 or greater. Patients were treated most often at an academic/research program (19%) or comprehensive community care program (12%). Patients lived an average of 68.2 miles (SD = 267.9, Range = 0.6 - 2403.1) from the treatment facility. Conclusions: To the best of our knowledge, this is the first NCDB analysis on SC-RMS. Our analysis revealed that the majority of SC-RMS patients were young males with primary involvement of the testis, supporting previous studies. Analysis of the socioeconomic factors of SC-RMS patients revealed that more patients were privately insured, resided in densely populated metropolitan areas, and were part of the top quartile of income earners. Further research is supported to better understand the impact of socioeconomic factors on diagnosis, treatment options, and overall mortality rates associated with SC-RMS.

The effectiveness of adjuvant therapy in adult patients with spindle cell/sclerosing rhabdomyosarcoma: A single-center retrospective study.

e23550 Background: In recent years, the WHO classification of soft tissue tumours has classified spindle cell/sclerosing rhabdomyosarcoma (RMS) as a novel subtype of RMS. However, the prognosis and standard treatment modalities for operable spindle cell/sclerosing RMS patients remain unclear. This study aims to investigate the effectiveness and influencing factors of postoperative adjuvant therapy in adult patients with spindle cell/sclerosing RMS. Materials and Methods: This single-center retrospective study enrolled adult patients with spindle cell/sclerosing RMS who underwent surgery and subsequent adjuvant therapy at West China Hospital, Sichuan University, from August 2014 to March 2023. The included patients initially underwent surgical excision, followed by one of the adjuvant treatments: radiotherapy, chemotherapy, or a combination of radiotherapy and chemotherapy. Disease-Free Survival (DFS) and Overall Survival (OS) were calculated for the included patients in this study. Univariate analysis and multivariate COX regression were conducted to determine prognostic factors. Results: This study included a total of 17 patients diagnosed with spindle cell/sclerosing RMS. Among them, 10 (58.8%) patients received postoperative adjuvant chemoradiotherapy, while 7 (41.2%) patients underwent postoperative chemotherapy alone. 12 (70.6%) patients received chemotherapy following the VAC regimen, and 5 (29.4%) patients received non-VAC chemotherapy. The prognosis analysis indicates that the median DFS was not reached, with a 1-year DFS rate of approximately 87.8% and a 2-year DFS rate of approximately 52.4%. The median OS was not reached, with a 1-year OS rate of 100% and a 2-year OS rate of approximately 92.9%. Univariate analysis shows that compared to undergoing non-R0 resection, undergoing R0 surgical resection significantly improves patient DFS (P = 0.02). Compared to no postoperative radiotherapy, receiving postoperative prophylactic radiotherapy significantly improved both DFS (P = 0.01) and OS (P = 0.02). In contrast, using VAC as adjuvant chemotherapy did not significantly increase DFS and OS compared to non-VAC regimens (P = 0.83 and 0.57, respectively). Multivariate Cox regression analysis demonstrated that the receipt of postoperative prophylactic radiotherapy independently predicted DFS (P = 0.03). Conclusions: In adult patients with spindle cell/sclerosing RMS, R0 resection, when compared with non-R0 resection, delays disease recurrence but does not enhance overall survival. Long-term outcomes may be improved in patients who receive postoperative adjuvant radiotherapy. However, choosing a VAC regimen as adjuvant chemotherapy may not contribute to an improved long-term prognosis when compared with a non-VAC regimen. Keywords: adjuvant therapy, spindle cell, sclerosing, rhabdomyosarcoma, effectiveness

Epidemiology of undifferentiated sarcomas: A rare entity.

e23571 Background: Undifferentiated Sarcomas (USar), previously known as malignant fibrous histiocytomas, are a group of rare and diverse malignant tumors of mesenchymal origin with a prevalence of 0.08-1 per 100,000. These are aggressive tumors with often high-grade morphology. The diagnosis is made by exclusion of other sarcoma entities upon bone marrow biopsy (criteria listed below). Undifferentiated sarcomas are of four major types, i.e. Pleomorphic, Epithelioid, spindle and round cells. The exact etiology of these sarcomas remains obscure, although many signaling pathways with various genetic alterations may be implicated in their development. The goal of this epidemiologic study is to assist in better understanding of this lesser known aggressive malignancy. Methods: The data was collected from Surveillance, Epidemiology and End Result database Research Plus Data, 17 Registries, Nov 2022 Sub (2000-2020). We extracted undifferentiated sarcoma cases diagnosed between 0-90 years of age, using the ICD Code 8805/3. The analysis was stratified age, gender, race, & primary site labeled. The analysis was further completed by comparing survival using the Log-rank test (GraphPad Prism). Results: A total of 1680 cases of USar were identified, which were diagnosed between 2000 and 2020. Median age of diagnosis was 59.5 years. 50.54% were males and 49.46% were females. Of these cases, ~64.05% were Caucasians, ~15.18% Hispanics, ~10.48% Asians or Pacific Islanders, ~9.35% Black, and < 1% were Alaskan natives/American Indian and Non-Hispanics of unknown race. Further survival curves were compared based on gender, race and organ system. The average months of survival (MoS) based on gender showed no statistical significance (p value 0.6077). MoS calculated for Whites (28), Blacks (16), Asian & Pacific islanders (1), Alaskan natives & American-Indians (15), & Hispanics (21) (p value < 0.0001). MoS based on involved organ system were compared for: head/face/neck (18), GI tract (10), respiratory tract (4), heart/mediastinum/pleura (9), skin & soft tissue (51), bone (32), breast (30), GU (19), CNS (26), gynecological tract (12) and male reproductive system (29) (p < 0.0001). Conclusions: Undifferentiated Sarcoma accounts for less than 1% of all adult tumors. Only 1680 cases were found in the past twenty years, rendering it one of the rarest seen malignancies. Of the reported data, USar was most commonly observed in Caucasians. Comparing the survival curves also showed that there was no difference in survival based on gender. The highest MoS was seen in undifferentiated sarcomas of skin and soft tissues while respiratory tract tumors had the lowest average survival time. More research and analysis is warranted to understand this lesser known malignancy given its extremely low incidence.

A retrospective, descriptive analysis of a single-center experience with patients with metaplastic breast cancer.

e13173 Background: Metaplastic breast cancer (MpBC) is a subtype of breast cancer (BC) that is commonly triple negative (TN) and chemotherapy (CT) resistant. Despite CT resistance, standard of care therapy is administered according to receptor status, regardless of metaplastic histology. Randomized data regarding optimal treatment of this rare histologic subtype are lacking. Methods: This was a retrospective analysis of MpBC patients (pts) treated at Miami Cancer Institute (MCI) between 2017 and 2021. Pts were identified using COTA real-world Analytics, an analytics platform enabling rapid investigation of longitudinal real-world data. Pt demographics, pathologic characteristics, staging, treatment, and survival outcomes were collected and analyzed. Results: 46 pts with MpBC were identified. Median age at diagnosis was 60.5 years, and 83.7% were post-menopausal. 84.8% were White, 10.9% were Black, and 54.3% were Hispanic (all White). 80.4% (n=37) had TNBC (ER < 1% and HER2 negative by ASCO CAP guidelines). 13.0% of pts (n=6) had spindle cell morphology and these pts had numerically lower 5-yr overall survival (OS) compared to those with non-spindle cell morphology; (83.3%; 95% CI 53.5%-100% vs 91.7%; 95% CI 82.7%-100%). Of 21 pts (45.7%) who underwent germline genetic testing, a pathogenic variant was detected in 2 (9.5%); (BRCA2, PALBB2). At diagnosis, 93.5% (n=43) had early-stage disease, 2.2% (n=1) had de novo metastatic breast cancer (MBC), 2 were unknown. Of the early-stage pts, 12 (27.9%) had stage 1, 19 (44.1%) stage 2, and 6 (14.0%) stage 3 BC. Of 43 pts with treatment records available, 34 (79.1%) received CT and 20 (46.5%) received anthracycline-based CT in the early-stage setting. Of those who received CT, 50% (n=17) were treated in the neoadjuvant setting, and 2 pts (11.8%) achieved pathologic complete response (pCR). Median distant recurrence free survival (DRFS) and OS were not reached in the overall cohort. Two-year OS was 90.5% (95% CI 81.6%-99.4%) and two-year DRFS was 78.9% (95% CI 66.6%-91.2%). Of the 43 pts with early-stage MpBC at diagnosis, 11 (25.6%) developed MBC with lung as the most common site of metastasis. Only 15.2% (n=7) of tumors underwent somatic mutation analysis and 71.4% (5/7) were PIK3CA-mutated. Of the pts who developed MBC, median progression-free survival with cytotoxic chemotherapy was 9.0 months (95% CI 5.0-13.0). Conclusions: MpBC represents an aggressive phenotype of BC and optimal guidance regarding treatment is lacking. Consistent with published literature, a high proportion of MpBC in this study were TN (>80%). Our dataset represents the largest cohort to date of Hispanic pts with MpBC. Despite the poor outcomes historically reported with MpBC, median DRFS and OS were not reached in this cohort, with short follow up. Further prospective randomized data on the optimal treatment of MpBC is warranted and a larger multi-institution review is planned.

Better Local Disease Control With Mastectomy in Metaplastic Breast Carcinoma: Findings of a Retrospective Cohort.

Metaplastic breast cancer (MBC) is a rare type of breast carcinoma with clinicopathological differences. The prognosis and treatment strategies for MBC are usually conflicting. In this study, we aim to present the clinicopathologic features, treatment strategies, and prognosis of our MBC patients. In our retrospective study, 18 metaplastic breast cancer patients treated in our institution between January 2005 and December 2022 were evaluated. Demographic and clinicopathological characteristics, surgical and systemic treatment options, locoregional recurrences, distant metastases, and overall survival (OS) of the MBC patients were retrieved from the patient files. All patients were female; the median age was 54.42 ± 12.37 years. Most of the patients (n = 15, 83.33%) presented with palpable masses. Tumors were mostly triple-negative, with a high grade and a high Ki‑67 proliferation index. Spindle cell carcinoma and MBC with mesenchymal differentiation were the most common subtypes. Most of the patients underwent mastectomy (n = 11, 61.11%); breast-conserving surgery (BCS) was performed on seven (38,88%) patients. Lymph node positivity was detected in six of 18 patients (33.33%). Fewer patients (n = 4, 22.22%) received neoadjuvant chemotherapy. While local recurrence developed in two out of seven patients (28.57%) who underwent BCS, there was no local recurrence in patients who had mastectomy. The OS time varied according to tumor size and the presence of lymph node metastases (p <0.001; p = 0.005). Metaplastic breast cancer is genetically heterogeneous and resistant to conventional treatment strategies. Mastectomy is still the surgical treatment method that is performed more frequently and provides better local control for patients with metaplastic breast cancer.

Effect of screening with a pan-TRK immunohistochemistry-based algorithm on NTRK fusion detection rates.

e15135 Background: Rearrangements in the NTRK1, NTRK2, and NTRK3 genes are clinical actionable and predictive of response to TRK kinase inhibitors in solid tumors. Their detection in clinical practice is a priority, but their low prevalence (0.25-1%) poses a diagnostic challenge. In this study, we describe our immunohistochemical-based and cost-effective approach for NTRK rearrangements detection. Methods: We implemented a comprehensive NTRK testing approach at a reference center that combined clinical criteria (e.g., iodine therapy-resistant thyroid cancer); molecular biomarkers (e.g., non-small-cell lung carcinoma negative for driver alterations, colorectal carcinoma with deficient MMR and/or microsatellite instability); and histopathological criteria (identifying tumor subtypes associated with NTRK fusions, such as breast secretory carcinoma). Automated immunohistochemistry (Ventana BenchMark ULTRA IHC/ISH System) using the antibody pan-TRK (Ventana, EPR17341) was used as a screening tool. Positive results were confirmed through molecular techniques, including Next Generation Sequencing, NGS (Oncomine Focus Assay, Thermo Fisher, based on DNA and RNA) and/or FISH (NTRK3 break-apart probe, Zytovision). Results: We evaluated 172 patients (99 female/73 male), with a mean age of 52 years (SD 23.8). Eighteen (18) patients with neoplasms expressing TRK proteins were identified. Confirmatory studies using NGS identified fusions in 7 cases. In instances of poor RNA quality, FISH techniques (NTRK3) were employed, confirming the findings in an additional 3 patients. Overall prevalence of NTRK fusions was 5.8%. Histological types included the following tumor types: Thyroid carcinoma, 4 patients (one medullary and 3 papillary carcinomas, two of them in the pediatric population); soft tissue sarcomas, 3 patients (2 corresponding to infantile fibrosarcoma and a soft tissue provisional entity, "NTRK-rearranged spindle cell neoplasm”); secretory carcinoma of the breast, one patient; secretory carcinoma of the salivary gland, one patient; colorectal carcinoma, one patient, with a deficient MMR phenotype. NTRK3 gene fusions were found in 10 patients, (6 fusions with ETV6 detected by NGS and 3 detected by FISH), and NTRK1 fusion in 1 case (fusion with LMNA detected by NGS). The positive predictive value of pan-TRK immunohistochemistry as a screening tool was 0.55. Conclusions: In our experience, the comprehensive screening approach based on morphological and clinical/ molecular inclusion criteria, along with the use of immunohistochemical techniques (pan-TRK antibody), significantly enhances the detection rate of NTRK fusions (5.8% vs. 0.25-1%). Additionally, FISH provides a valuable tool in samples with poor RNA quality. This approach allows for a reduction in the impact of costly testing, such as NGS, on the healthcare system.

Randomized phase III trial of neo-adjuvant and adjuvant chemotherapy vs adjuvant chemotherapy alone for localized soft tissue sarcoma (NACLESS, JCOG2102).

TPS11589 Background: Soft-tissue sarcomas (STS) are a rare malignant tumor. Adjuvant perioperative chemotherapy has been investigated for high-risk patients due to the poor overall survival (OS) for surgery. A meta-analysis revealed that adjuvant chemotherapy (AC) with doxorubicin plus ifosfamide (AI) significantly prolonged OS with an absolute risk reduction of 11%. However, the optimal timing for surgery and number of courses of chemotherapy are still controversial. In Europe, Italian sarcoma group and the Spanish sarcoma group reported on the non-inferiority of three courses of neoadjuvant chemotherapy (NAC) + surgery without AC, compared to three courses of NAC + surgery + two courses of AC. On the other hand, even in the same Europe, the latest report on perioperative chemotherapy with AI from Germany was a trial of surgery + AC. Furthermore, adjuvant chemotherapy itself remains skeptical in other countries such as the US, UK, and Canada. No investigation has been made into whether chemotherapy/surgery are better to initiate treatment with. In Japan, the standard treatment is three courses of NAC with AI, surgery, and two of AC with AI. However, in JCOG1306, NAC was discontinued in 12 of 70 (17.1%) patients due to high toxicity. Only one patient (1.4%) became partial response after NAC, whereas six patients (8.6%) had disease progression during NAC. Of the 65 patients eligible for limb-sparing surgery at enrollment, three (4.6%) underwent limb amputation. Upfront surgery followed by three courses of AC was considered the most promising treatment, it avoided extended surgery and reduced toxicity while maintaining an OS equivalent to the standard treatment. The aim of this trial is to optimize the balance between the survival benefit of perioperative chemotherapy, reduce toxicities, and risks of extended surgery. Methods: This is a multicenter two-arm open-label randomized phase III trial. Patients are randomly assigned to standard (three courses of NAC, surgery, and two of AC) or experimental (surgery and three courses of AC) arms with AI comprising doxorubicin (30 mg/m2, days 1, 2) and ifosfamide (2 g/m2, days 1–5). Major inclusion criteria were (1) spindle cell STS; (2) T2-4N0M0 (UICC/AJCC 8th edition) and deeply located; (3) resectable tumors in the extremities or trunk; (4) age, 16–70 years; (5) ECOG performance status of 0–1; (6) no history of chemotherapy/radiotherapy; and (7) sufficient bone marrow function. To evaluates the non-inferiority in OS (margin: hazard ratio of 1.61) with power of 70% and one-sided alpha of 10%, 224 patients will be enrolled from 39 institutions in Japan. We began this study on November 16, 2022, and 27 of 224 patients have been enrolled as of January 7, 2024. Clinical trial information: jRCTs031220446 .

Pediatric Neurotrophic Tyrosine Receptor Kinase-rearranged Neoplasm Resembling a Vascular Malformation

Pediatric neurotrophic tyrosine receptor kinase-rearranged spindle cell neoplasms are soft tissue neoplasms whose behaviors are not well understood. We provide a case presentation of such a tumor sharing features of a vascular malformation. Our patient is an 11-year-old female referred for a lesion clinically and radiologically concerning for a vascular tumor or malformation. Upon excision, next-generation sequencing revealed a laminA-neurotrophic tyrosine receptor kinase 1 fusion. Neurotrophic tyrosine receptor kinase-rearranged spindle cell neoplasms represent an emerging entity in children now being diagnosed with a variety of techniques including immunohistochemistry, fluorescence in situ hybridization, and next-generation sequencing. Consideration for this tumor should be in the differential diagnosis of vascular skin lesions with unusual features on physical examination.

Overall survival in soft tissue sarcomas (STS) in Hispanic vs non-Hispanic White patients: Single center experience.

e23526 Background: Racial, ethnic, and socioeconomic factors have been implicated in the variability of survival rates among soft tissue sarcoma (STS). These disparities are multifactorial and may reflect differences in disease biology, access to care, treatment responses, and others. In situations where different racial groups have equitable access to healthcare, healthcare disparities can decrease, and survival gaps can narrow. Differences in survival in STS in racial minorities have been poorly studied. Recognizing the potential impact of such disparities, our study thereby contributes to the ongoing discourse on healthcare equity in STS outcomes. Methods: We conducted a retrospective analysis of 30 STS patients, stratifying them into Hispanic (H) and non-Hispanic white (NHW) groups at Dignity Health Cancer Institute in Phoenix, Arizona. The Mann-Whitney U test was chosen to compare survival distributions, given the non-normal distribution of our sample. Survival analysis was performed using the Kaplan-Meier method, and the log-rank test was applied to determine statistical significance. All analyses were executed in GraphPad Prism software. Results: Our cohort comprised 13 (43%) NHW and 17 (57%) H patients. The mean ages were 57.2 years for NHW and 48.9 years for H, with a balanced gender distribution across groups. The most common subtypes of STS in NHW were liposarcoma (n = 3, 23.1%), and spindle cell carcinoma (n = 2,15.4%). Comparatively, the most common subtypes of STS in H were liposarcoma (n = 5, 29.4%) and leiomyosarcoma (n = 3, 17.6%). All patients were diagnosed with Stage 4 STS. Treatment modalities differed marginally, with NHW patients undergoing more surgical interventions, while H patients were more frequently administered chemotherapy. Median overall survival from the start of first-line therapy was 412 days for NHW and 500 days for H patients. Despite the longer median overall survival observed in Hispanics, the intergroup difference did not reach statistical significance (P = 0.68). Conclusions: The similar survival times between H and NHW STS patients at our institution may hint at an equitable provision of care across racial demographics in a relatively controlled single-center experience. However, the trend of extended survival in the Hispanic group, while not statistically confirmed, raises questions that merit further inquiry. This study serves as a preliminary exploration into racial disparities in STS, advocating for larger-scale research with more diverse patient populations. Further studies are essential to understand these findings and identify and optimize factors contributing to narrowing the survival gap in minorities, with the goal of enhancing STS prognosis for all racial groups.

Detection of TROP2: Ushering in a new choice in the treatment of patients with special types of invasive breast cancer.

1106 Background: TROP2 has become an attractive new therapeutic target in breast cancer (BC). TROPiCS-02 trial shows that the sacituzumab govitecan(SG) which is the TROP2 ADC drug can significantly benefit the survival of patients with TNBC and HR+/HER2- BC, and the 2023 ASCO guideline recommends that TROP2 detection is not necessary before the SG treatment. However, less than 5% BC patients of special subtype were included in clinical trials, and the TROP2 expression of them is not yet known. The aim of our study is to compare the expression of TROP2 in different special types of BC, and provide reference for targeted treatment of these patients. Methods: We retrospectively retrieved tissues from 383 patients diagnosed with special type of BC and undergoing surgical resection at our institution from 2018 to 2023. Including metaplastic carcinoma (MBC), mucinous carcinoma (MC), adenoid cystic carcinoma, cribriform carcinoma, carcinoma with apocrine differentiation, neuroendocrine carcinoma and tubular carcinoma. Classify them as TNBC or HR+/HER2- BC. Applying H-score to evaluate the TROP2 expression, H-score&lt;100, 100~200, and 201~300 classified as low, moderate and high expression. Results: Expression of TROP2 is higher in tubular and cribriform carcinoma, while in MBC and MC is significantly lower (χ2=66.756, P&lt;0.001) (Table). Low expression of TROP2 is associated with low clinical staging ( P&lt;0.05), no lymph node metastasis ( P&lt;0.05), and high-grade tumor infiltrating lymphocytes ( P&lt;0.05). Moreover, TROP2 had the lowest expression in MBC, with a median H-score of 45. There are 78.13% (43/55) cases showed H-score&lt;100, with 27.3% (15/55) of cases showing no expression of TROP2 at all. It is worth noting that MBC is highly invasive and has a poor prognosis, but the expression level of TROP2 is very low in mesenchymal cells, while in squamous differentiated tumor tissue, the expression level of TROP2 is high, and the overall H-Score score is low ( P&lt;0.001). Conclusions: This study is the first preliminary study on the TROP2 expression in special types of breast cancer. Although the current ASCO guideline recommends not testing TROP2, but our study shows it is pretty low or even not expressed in MBC and MC. Notably, the lack of expression in the mesenchymal and spindle cell subtypes may be highly indicates that they lack epithelial tumor cells expressing TROP2 as vectors, resulting in the inability to exert the therapeutic effect of ADC, we suggest routine testing of TROP2. [Table: see text]

Myofibroblastic sarcoma: A study of demographic and socioeconomic factors.

e23545 Background: Myofibroblastic sarcoma is a type of non-rhabdomyosarcoma soft tissue sarcoma originating from spindle cells of mesenchymal origin with myofibroblastic differentiation. First described in 1998, there is little known about the prognostic factors of this rare and relatively new cancer. This typically non-metastasizing tumor is primarily found in the head, neck, or extremities. Treatment focuses on tumor excision, and the 5-year overall survival of low-grade myofibroblastic sarcoma cancer is 72%. This study analyzed data from the National Cancer Database (NCDB) to understand how demographic factors contribute to the treatment and prognosis of myofibroblastic sarcoma. Methods: A retrospective cohort analysis was conducted on demographic factors of patients with confirmed myofibroblastic sarcoma (ICD-8825-3) using the NCDB from 2004-2020. Regression analysis was used to study trends of patient age, sex, race, education, insurance status, distance from facility, and Charles/Deyo score within this population. Results: A total of 111 patients (N = 111) were identified in the database with a confirmed diagnosis of myofibroblastic sarcoma from 2004 to 2020 with an increasing frequency of diagnoses per year (R^2 = 0.6283). The average age of diagnosis was 47.3 (SD = 24.17, range = 0 - 90 years). Although Myofibroblastic sarcoma appeared throughout the body, the most prominent sites were the long bones of the lower limb and associative joints (6%) followed by the uterus (5%). The majority of patients were white (83%), non-Hispanic (86%), and female (63%). A higher percentage of patients lived in metropolitan areas with a population greater than 1 million (58%) compared to smaller metropolitan, urban, or rural counties (42%). Most of the patients were treated at an academic/research program (30%) followed by a comprehensive community cancer program (21%). More facility locations were based in the Pacific (15%) and the Middle Atlantic (11%) regions. The primary payer at diagnosis was private insurance/managed care (44%) followed by Medicare (32%) and Medicaid (19%). Few patients (5%) received palliative care. Conclusions: To the best of our knowledge, this is the first NCDB analysis on Myofibroblastic sarcoma. Based on our dataset, Myofibroblastic sarcoma tends to occur in the long bones of the lower limb and associative joints which differed slightly from what we found in previous reports, which described the head and neck as the two areas of highest prevalence. This is the first time the socioeconomic factors have been described in the literature: these patients are more likely to be non-Hispanic, female individuals, living in smaller towns. This study offers insight on how much further investigation is required to better understand the impact of demographic and socioeconomic factors on early diagnosis and treatments.

Clear cell and non-clear cell renal cell carcinoma in young adults: clinicopathological features, survival outcomes and prognostic factors.

Renal cell carcinoma (RCC) is infrequent among young adults. Few studies reported the outcome of RCC in young adults by pathological subtypes. The purpose of this study was to explore the clinicopathological features, survival outcomes and prognostic factors of young adult patients with clear cell (CCRCC) and non-clear cell renal cell carcinoma (NCCRCC). This study included young adult patients aged 18-40years who were diagnosed as renal cell carcinoma (RCC) between 2012 and 2022 at Peking University Third Hospital. All patients underwent either partial nephrectomy or radical nephrectomy, and some received adjuvant therapy. A comparative analysis was performed to investigate the differences in clinicopathological characteristics between the cohort of CCRCC and NCCRCC. Kaplan-Meier survival analysis was utilized to plot survival curves for young adults with RCC. The univariate and multifactorial prognostic analyses were conducted using the log-rank test and COX proportional hazards model. A total of 300 RCC patients aged 18-40years were performed, of which 201 were diagnosed with CCRCC (67%) and 99 were diagnosed with NCCRCC(33%). The NCCRCC included 29 cases (9.7%) of chromophobe RCC, 28 cases (9.3%) of MiT family translocation RCC, 22 cases (7.3%) of papillary RCC, 11 cases (3.7%) of low malignant potential multifocal cystic RCC, and 6 cases of unclassified RCC (2.0%), 2 cases of mucinous tubule and spindle cell carcinoma (0.7%), and 1 case of FH-deficient RCC (0.3%).The mean age was 33.4±6.1years old. The overall and progression free 5-year survival rate was 99.1 and 95.3%, respectively. The NCCRCC cohort demonstrated a statistically significant decrease in progression-free survival (PFS) rate when compared to the CCRCC cohort (p<0.001). There was no statistically significant difference observed in overall survival (OS) (p=0.069). Pathological stage was a significant independent predictor for OS (p=0.045). Pathological stage and nuclear grade were both independent predictors for PFS (p=0.020; p=0.005). The clinical and pathological features of young adults diagnosed with CCRCC exhibit notable distinctions from those of NCCRCC patients. The survival outcome was significantly influenced by the pathological stage, while both the nuclear grade and pathological stage had a significant impact on tumor progression. This study offered significant contributions to the understanding of the clinicopathological characteristics and prognostic determinants of renal cell carcinoma (RCC) in young adults.

Spindle Cell Neoplasm

Spindle neoplasm an uncommon variant of benign lipomatous tumor, occurs mostly in the posterior neck or the shoulder  It contains well circumscribed &amp; no aggressive subcutaneous mass  Spindle cell neoplasm may be traced to epithelial, mesenchymal &amp; odontogenic  Latin (AE1/AE3, K1), K1, K18, and EMA appear to be the most sensitive/reliable epithelial spindle cell neoplasms.  Spindle cell neoplasms can be benign or malignant. Under a microscope, the neoplasm is composed of adipocytes flat cells and long, thin spindle cells. In a spindle cell lipoma, the adipocytes are surrounded by spindle cells.  The diagnosis test includes immunohistochemistry and fluorescence in site hybridization (FISH) to confirm the diagnosis and to include other tumors that can look like a spindle cell lipoma. If a spindle cell neoplasm is large or uncomfortable, it can be removed.

Histomorphological Development Study of Cecum in Local Awassi Sheep Fetuses (Ovis Aris): Prenatal Periods

This study was conducted at Al-Qasim Green University/College of Veterinary Medicine, Anatomy and Histology Branch. The experiment was designed to study the cecum of Awassi sheep fetuses: prenatal periods. Samples (30 male and female samples) were collected from healthy females uterine and divided according to age groups into four groups by crown rump length formula (CRL) for the prenatal stage. In the first age group (50-55), the cecum was in the process of development, as it was not distinguished visually. In the second age group (70-75 days), it was a small protrusion located between the ileum and the beginning of the ascending colon. With advancing age, the third group, which includes two ages in the third trimester of pregnancy, we found that the cecum was completely formed in (100-105) days and at (130-140) days of gestation. Also, upon histological study, we found that the wall of the cecum consists of four layers, as in the rest of the parts of the digestive system, and is lined with an epithelial layer surrounded by a layer of connective tissue. It is supportive of the epithelial tissue. We also found tunica submucosa constantly devolving with age, as it is mesenchymal cells in the first stage of intrauterine life and begin to transform into connective tissue with the presence of fibers and collagen (tunica submucosa) as a result of these cells transforming into spindle cells to form the inner muscle layer, as well as tunica muscularis externa. The latter is surrounded by loose connective tissue that contains a few collagen and elastic fibers surrounded by mesothelial cells (tunica serosa) that contain blood vessels to support development in the inner layers.