Peripheral Tumor Research Articles

Analysis of positive predictors in diagnosing lung cancer on transthoracic and transbronchial procedure

Background: Lung cancer remains the most cause of death due to cancer. Due to high mortality rate of lung cancer, early diagnosis of lung cancer plays a very important role in therapeutic management. Clinical symptoms and tumor characteristics such as size and location are found to vary in lung cancer patients. Various modalities can be used to obtain materials or samples include transthoracic and transbronchial methods. Research was conducted to analyze positive predictors of cancer between transthoracic and transbronchial procedures in lung cancer patients. Methods: This research is an analytical observational study with a cross-sectional design in using secondary data through medical records from January 2022 to December 2023. Univariate analysis presents data in the form of frequency, mean and standard deviation. Bivariate analysis was carried out using chi-square and multivariate analysis using multiple logistic regression. The measure used as a predictor is the adjusted odds ratio. Inference or conclusion is based on the 95% confident interval and p value at the alpha value limit of 0.05. The entire data process above uses SPSS 26.0 statistical software Results: The total research subjects who met the research requirements were 111 patients. The characteristics of the research subjects were symptoms of cough (n=97; 87.4%), hemoptyisis (n=51; 45.9%), breathlessness (n=104; 93.7%) and chest pain (n=87; 78.4%), mostly peripheral tumor (n=70; 63.1%) and size >3 cm (n=103; 92.8%). Logistic regression analysis showed cough symptoms and peripheral tumor location each had an adjOR value of 5.247 (95% CI 1.432-19.552; p=0.013) and adjOR 0.088 (95% CI 0.034-0.229; p=0.000) for lung cancer positivity on transbronchial procedure. On transthoracic procedure, cough symptoms and peripheral tumor location respectively had an adjOR value of 0.190 (95% CI 0.051-0.703; p=0.013) and adjOR 11.407 (95% CI 4.374-29.747; p=0.000) for lung cancer positivity. Conclusions: Cough is a positive predictor of lung cancer in transbronchial procedures. Meanwhile, peripheral tumor location is a positive predictor of lung cancer in transthoracic procedures.

TMEM158, as plasma cfRNA marker, promotes proliferation and doxorubicin resistance in ovarian cancer.

The current study aimed to identify the potential biomarker for the diagnosis of ovarian cancer within plasma cell-free RNA (cfRNA) species and to characterize their oncogenic properties. cfRNAs were isolated from the peripheral blood of ovarian cancer patients and sequenced using an NGS platform. Principal component analysis (PCA) was performed using Salmon software. Gene ontology (GO) analysis was conducted with clusterProfiler. The relative abundance of TMEM158 transcripts was determined by real-time PCR. Cell viability and proliferation was monitored using the MTT and cell counting assays, respectively. The protein levels of TMEM158 and ABCG2 were quantified by immunoblotting. We observed a clear separation of cfRNAs between ovarian cancer patients and healthy individuals. Additionally, we identified TMEM158 as the most significantly differential gene in both peripheral blood and tumor tissues. Overexpression of TMEM158 stimulated cell viability and promoted cell proliferation in ovarian cancer cells. Notably, the aberrant upregulation of TMEM158 was closely associated with doxorubicin resistance in ovarian cancer. Mechanistically, we demonstrated that TMEM158 positively regulates ABCG2 expression, which consequently contributes to drug resistance. In summary, we identified cfRNA TMEM158 as a potential diagnostic biomarker for ovarian cancer and elucidated the critical involvement of TMEM158-ABCG2 signaling axis in the development of doxorubicin resistance.

TMOD-26. GENERATION OF A CHROMOSOME 8 GAIN;NF1-/- HIPSC-DERIVED SCHWANN CELL PRECURSOR MODEL

Abstract Neurofibromatosis type 1 (NF1) is an autosomal dominant cancer predisposition syndrome caused by a germline mutation in the NF1 gene. The loss of the second copy of NF1 within Schwann cell precursors (SCPs) contributes to the formation of plexiform neurofibromas (PNs) found in 30-50% of NF1 patients. PNs can progress into malignant peripheral sheath tumors (MPNSTs), an aggressive form of cancer and a leading cause of mortality in NF1 patients. Our lab previously demonstrated frequent chromosome 8 (Chr8) gain in NF1-MPNST patient-derived xenografts (PDX) and patient tumors. To investigate Chr8 gain’s role, we created isogenic NF1-/- iPSC cell lines with and without Chr8 gain. Trisomy 8 fibroblasts were obtained and single-cell cloned to establish wildtype (WT) and Chr8 gain populations. Washington University’s Genome Engineering & Stem Cell Center (GESC@MGI) reprogrammed these cells into human induced pluripotent stem cells (hiPSCs). Using synthetic gRNA and CRISPR/Cas9, NF1 knockout lines were generated. Four iPSC cell lines were differentiated into SCPs, and cell survival and proliferation were assessed using Incucyte cell survival and CellTiter-Glo® Assay. Fluorescence in situ hybridization (FISH) and karyotyping validated the human iPSCs. qPCR revealed high expression of iPSC markers OCT3/4 and SOX2 in all iPSC lines. After differentiation, SCP markers (GAP43 and ITGA4) were upregulated in WT, NF1-/-, and Chr8 gain;NF1-/- SCP lines, demonstrating successful differentiation. Furthermore, Chr8 gain; NF1-/- SCPs displayed enhanced proliferation and increased cell survival compared to WT and NF1-/- SCPs, suggesting improved characteristics in the presence of Chr8 gain. In summary, our research provides insights into Chr8 gain and NF1 loss effects on SCP differentiation, proliferation, and survival. Understanding these molecular mechanisms may contribute to developing targeted therapies for NF1.

Adult supratentorial peripheral primitive neuroectodermal tumor with multiple metastases: a case report and literature review

BackgroundIntracranial primitive neuroectodermal tumors (PNETs) are characterized by poorly differentiated, highly malignant, aggressive small round tumor cells originating from the central and peripheral nervous systems.Case presentationA 25-year-old Chinese woman experienced sudden onset headache, vomiting, and severe anemia. Imaging examinations revealed a mass in the left parietal occipital lobe. Following microsurgery, histological confirmation revealed the tumor to be pPNET. Postoperative computed tomography (CT) showed multiple metastases in the lung, liver, and retroperitoneal lymph node. Unfortunately, she died of tumor cachexia 1 month after chemotherapy.ConclusionsDue to the rare presentation of pPNET, pPNET would be misdiagnosed without the histological diagnosis. Here, we aimed to provide clinicians with information about the treatment and relevant literature of pPNET.

Mesocolic schwannoma mimicking gastrointestinal stromal tumor: A case report and review of literature.

Schwannomas are common peripheral nerve tumors originating from Schwann cells, primarily occurring in the head and neck, limbs, and trunk. Schwannomas occurring in the mesocolon are rare and often have no specific manifestations. Abdominal schwannomas need to be differentiated from common abdominal tumors such as gastrointestinal stromal tumors. We report a case of a mesocolic schwannoma in a 59-year-old female presenting with gastrointestinal symptoms of acid reflux. At an outside hospital, gastroscopy, colonoscopy, and abdominal computed tomography scans revealed a soft tissue mass adjacent to the greater curvature of the stomach, leading to a suspicion of a gastric mesenchymal tumor. Mesocolic schwannoma. Laparoscopy was performed at our hospital. Intraoperatively, the tumor was found to be closely related to the transverse colon and was initially diagnosed as a mass originating from the transverse colon. Consequently, a resection of the mass along with the adherent portion of the transverse colon was performed. Postoperative pathology and immunohistochemistry confirmed that the tumor was a schwannoma of the mesentery and did not originate from the transverse colon. Schwannomas can be distinguished from gastrointestinal stromal tumors by immunohistochemical staining, and surgical treatment is effective for benign schwannomas.

A B7-H3–Targeted CD28 Bispecific Antibody Enhances the Activity of Anti–PD-1 and CD3 T-cell Engager Immunotherapies

Abstract T-cell activation is a multistep process requiring T-cell receptor engagement by peptide–MHC complexes (Signal 1) coupled with CD28-mediated costimulation (Signal 2). Tumors typically lack expression of CD28 ligands, so tumor-specific Signal 1 (e.g., neoepitope presentation) without costimulation may be ineffective or even induce T-cell anergy. We designed the bispecific antibody XmAb808 to co-engage the tumor-associated antigen B7-H3 with CD28 to promote T-cell costimulation within the tumor microenvironment. XmAb808 costimulation was measured by its ability to activate and expand T cells and enhance T cell–mediated cancer cell killing in cocultures of human peripheral blood mononuclear cells and cancer cells and in mice engrafted with human peripheral blood mononuclear cells and tumor xenografts. XmAb808 avidly bound cancer cells and stimulated IL2 and IFNγ secretion from T cells cocultured with cancer cells engineered to deliver Signal 1 to T cells via a surface-expressed anti-CD3 antibody. XmAb808 enhanced expression of the antiapoptotic factor Bcl-xL and CD25, promoting survival and IL2-dependent expansion of T cells coupled with increased T cell–mediated cytotoxicity in vitro. XmAb808 combined with an EpCAM×CD3 bispecific antibody to enhance target cell killing through IL2-dependent expansion of CD25+ T cells. This combination also suppressed pancreatic tumor xenograft growth in mice. Furthermore, XmAb808 combined with an anti–programmed cell death protein 1 antibody to suppress breast tumor xenograft growth in mice. XmAb808 as monotherapy and in combination with an anti–programmed cell death protein 1 antibody is currently in clinical development in patients with advanced solid tumors. Our results suggest that XmAb808 may also combine with tumor antigen–targeted anti-CD3 (Signal 1) T-cell engagers.

A Comparison of Stereotactic Radiation Therapy in Elderly Patients with Central or Peripheral Stage I-II (T1-3 N0 M0) Non-Small Cell Lung Cancer.

The objective of this study was to compare the clinical outcomes of stereotactic body radiation therapy (SBRT) in elderly patients aged 65 or older with clinical stage I-II non-small-cell lung cancer (NSCLC), specifically examining the differences between centrally located lung tumors and peripherally located lung tumors. From April 2009 to January 2020, a total of 136 patients with 136 tumors (65 central, 71 peripheral; NSCLC) at an early stage (T1-3N0M0) were treated with SBRT at a single institution. Central/peripheral location was assessed retrospectively on planning CT scans. A propensity score matching analysis was utilized to compare the two groups. In addition, the prognosis and related toxicity were compared between the two study arms. A total of 33 central tumors and 33 peripheral tumors were matched and analyzed. The results showed no significant differences in overall survival (OS) and progression-free survival (PFS) between the two groups. The 2-year OS was 71.88% (95% CI, 57.87%-89.27%) in the central lung cancer group, while it was 93.94% (95% CI, 86.14%-100.00%) in the peripheral lung cancer group (P=0.462). The 2-year PFS was 43.75% in the central lung cancer group, while it was 78.79% in the peripheral lung cancer group (P=0.279). Further subgroup analysis indicated that the location of peripheral tumor have a positive impact on OS in patients with adenocarcinoma. The occurrence of local failure, regional failure, or distant failure was comparable between central and peripheral tumors. There was no statistically significant difference in toxicity between the central and the peripheral tumor groups. The outcomes of SBRT for central tumors versus peripheral lung tumors in elderly patients with early-stage NSCLC were similar. SBRT demonstrated a similar level of safety in terms of toxicity for both central and peripheral lung tumors.

P227 Differences in immunological cell populations between peripheral blood and tumor tissue in patients with NMIBC of varied differentiation grades

P227 Differences in immunological cell populations between peripheral blood and tumor tissue in patients with NMIBC of varied differentiation grades

Neuroscience in peripheral cancers: tumors hijacking nerves and neuroimmune crosstalk.

Cancer neuroscience is anemerging field that investigates the intricate relationship between the nervous system and cancer, gaining increasing recognition for its importance. The central nervous system governs the development of the nervous system and directly affects brain tumors, and the peripheral nervous system (PNS) shapes the tumor microenvironment (TME) of peripheral tumors. Both systems are crucial in cancer initiation and progression, with recent studies revealing a more intricate role of the PNS within the TME. Tumors not only invade nerves but also persuade them through remodeling to further promote malignancy, creating a bidirectional interaction between nerves and cancers. Notably, immune cells also contribute to this communication, forming a triangular relationship that influences protumor inflammation and the effectiveness of immunotherapy. This review delves into the intricate mechanisms connecting the PNS and tumors, focusing on how various immune cell types influence nerve‒tumor interactions, emphasizing the clinical relevance of nerve‒tumor and nerve‒immune dynamics. By deepening our understanding of the interplay between nerves, cancer, and immune cells, this review has the potential to reshape tumor biology insights, inspire innovative therapies, and improve clinical outcomes for cancer patients.

Peripheral tumor necrosis factor production is a predictor for remission under adalimumab in Crohn’s disease

Peripheral tumor necrosis factor production is a predictor for remission under adalimumab in Crohn’s disease

TSPO deficiency promotes the progression of malignant peripheral sheath tumors by regulating the G2/M phase of the cell cycle via CDK1

Malignant peripheral nerve sheath tumors (MPNSTs) are highly aggressive Schwann cell-derived sarcomas that are sporadic or associated with Neurofibromatosis 1 (NF1) gene mutations. Traditional therapies are usually ineffective for treating MPNSTs, so new targets need to be identified for the treatment of MPNSTs. In the present study, the role of the mitochondrial translocator protein (TSPO) in the regulation of cell proliferation and the cell cycle in MPNSTs was investigated. TSPO expression was lower in MPNSTs than in NFs. Loss-of-function experiments revealed that TSPO deficiency promoted MPNST cell growth, migration, and invasion and influenced the cell cycle in vitro and in vivo. In addition, TSPO depletion suppressed cell apoptosis by downregulating the expression of caspase-3, caspase-8, HSP60, p27, p53, and BCL-2 and suppressed the cell cycle by upregulating CDK1, CDK2, CCNB1 and CCNA2. Furthermore, CDK1 was determined to be an upstream target of TSPO-mediated regulation via RNA-seq, qPCR, and Western blotting. Specifically, depletion of CDK1 weakened the effect of TSPO deficiency on cell proliferation and migration. More importantly, CDK1 knockdown induced significant cell cycle arrest in the G2/M phase. In summary, TSPO deficiency regulates the cell cycle in MPNSTs by targeting CDK1, which may be an effective molecular target for prognosis evaluation and treatment.

A neuromuscular clinician's guide to magnetic resonance neurography.

Magnetic resonance neurography (MRN) is increasingly used in clinical practice for the evaluation of patients with a wide spectrum of peripheral nerve disorders. This review article discusses the technical aspects of MRN highlighting the core sequences performed for clinical care. A robust, high-resolution, heavily T2-weighted fluid-sensitive sequence performed on a 3.0 Tesla magnet system remains the main workhorse MRN sequence. In specific clinical scenarios, adjunct techniques such as diffusion-weighted imaging can be added to a protocol for disease characterization. In addition, gadolinium-based contrast material can also be administered for the purposes of image optimization (suppress adjacent vascular signal) and disease characterization. Technical modifications to field of view and planes of imaging can be made based on the clinical question and discussion with the radiologist(s). On fluid-sensitive MRN sequences, a normal peripheral nerve exhibits iso- to minimally hyperintense signal relative to skeletal muscle with a predictable trajectory, preserved "fascicular" architecture, and tapered caliber from proximal to distal. Peripheral nerve abnormalities on MRN include alterations in signal, caliber, architecture, diffusion characteristics as well as enhancement and provide information regarding the underlying etiology. Although some MRN findings including nerve hyperintensity and long-segmental enlargement are nonspecific, there are certain diagnoses that can be made with high certainty based on imaging including benign peripheral nerve tumors, high-grade peripheral nerve injury, and intraneural ganglia. The purpose of this article is to familiarize a neuromuscular clinician with fundamentals of MRN acquisition and interpretation to facilitate communication with the neuromuscular radiologist and optimize patient care.

Three-Dimensional Magnetic Resonance Imaging in the Musculoskeletal System: Clinical Applications and Opportunities to Improve Imaging Speed and Resolution.

Although conventional 2-dimensional magnetic resonance (MR) sequences have traditionally comprised the foundational imaging strategy for visualization of musculoskeletal anatomy and pathology, the emergence of isotropic volumetric 3-dimensional sequences offers to advance musculoskeletal evaluation with comparatively similar image quality and diagnostic performance, shorter acquisition times, and the added advantages of improved spatial resolution and multiplanar reformation capability. The purpose of this review article is to summarize the available 3-dimensional MR sequences and their role in the management of patients with musculoskeletal disorders, including sports imaging, rheumatologic conditions, peripheral nerve imaging, bone and soft tissue tumor imaging, and whole-body MR imaging.

Oncolytic avian reovirus-sensitized tumor infiltrating CD8+ T cells triggering immunogenic apoptosis in gastric cancer.

Gastric cancer (GC) is a leading malignant disease in numerous countries, including Taiwan with limited therapeutic options. Animal viruses including oncolytic avian reovirus (ARV) have the possibility to avoid pre-existing immunity in humans, while being safe and immunostimulatory. Here, we provide a novel insight into oncolytic ARV and UV-ARV-sensitized patient's peripheral blood mononuclear cells (P-PBMCs) and tumor infiltrating lymphocytes (TILs) killing primary GC (PGC) cells through the surface TLR3 and TRAIL/DR4/DR5 immunogenic apoptosis pathway. We conducted a comprehensive study to reveal whether ARV- or UV-inactivated ARV (UV-ARV)-modulated P-PBMCs or TILs killing ARV- and UV-ARV-sensitized AGS cells and PGC cells derived from clinical patients and to investigate the regulation of surface TLR3 receptor and upstream signaling pathways. Apoptosis analysis by flow cytometry and Western blot, suppression of signal pathway by specific inhibitors, in situ proximity ligation assay (PLA), time-resolved flurometry and lactate dehydrogenase (LDH) cytotoxicity assays, and an in vitro co-culture model were established to study the interplay between ARV- and UV-ARV-sensitized P-PBMCs and TILs to kill PGC cells and their upstream pathways. Our results reveal that increased levels of DR4 and DR5 were observed in ARV and UV-ARV sensitized PGC cells through the TLR3/p38/p53 signaling pathway. Importantly, we found that the σC protein of ARV or UV-ARV interacted with surface TLR3 of CD8+ TILs, thereby triggering the TLR3/NF-κB/IFN-γ/TRAIL signaling pathway which induces immunogenic apoptosis of PGC cells. This study sheds further light on the molecular basis behind ARV oncolysis and facilitates the ARV or UV-ARV as a cancer therapeutic. The study provides novel insights into ARV- or UV-ARV-sensitized P-PBMCs and CD8+ TILs to kill PGC cells through the immunogenic apoptosis pathway. We conclude that P-PBMCs can easily be obtained from GC patients and provide a rich source as TILs to kill PGC cells.

Correlation of tumor budding with a novel and other established prognostic parameters in patients with invasive breast carcinoma.

Breast cancer is the most common malignancy among women. Established prognostic markers in breast carcinomas include tumor size, histologic grade, nodal status, lymphovascular invasion, perineural invasion, hormone receptor status, HER-2 status, and age. To correlate peripheral tumor budding (pTB) with stromal tumor-infiltrating lymphocytes (sTILs) and established prognostic factors in invasive breast carcinoma. It is a retrospective study conducted at multiple centers including a tertiary care center. 100 cases were included over a period of 2.5 years. All cases of invasive breast carcinoma (IBC) in which excision specimens with lymph node dissection were available were studied. Slides were reviewed for pTB and sTILs. Tumor budding of ≤20/10 hpf was considered low tumor budding, and >20 buds/10 hpf was considered high tumor budding. Tumor budding was correlated with age, tumor size, lymphovascular invasion, perineural invasion, tumor stage (pT, pN), stromal tumor-infiltrating lymphocytes, tumor grade, ductal carcinoma in situ, hormonal receptors, and HER2neu. Fisher exact test and Chi-square test were used. We found that high tumor budding was seen in 34 cases and low tumor budding in 66 cases. There was a statistically significant association between high tumor budding and tumor size (P = 0.007), lymphovascular invasion (P < 0.001), perineural invasion (P = 0.004), tumor staging/pT (P = 0.006), nodal staging/pN (P = 0.001), and low sTILs (P < 0.001). However, the association of high tumor budding with parameters like age (P = 0.979), histological type (P = 0.243), tumor grade (P = 0.052), DCIS (P = 0.478), and ER (P = 0.633), and PR (P = 0.544), HER2Neu status (P = 0.171) was not significant. This study suggests tumor budding score can be used as a prognostic indicator for breast cancer.

Application of multimodal intraoperative neurophysiological monitoring technology in neurofibromatosis type 1 related peripheral nerve tumor surgery

To summarize application effect and clinical experience of multimodal intraoperative neurophysiological monitoring (IONM) technology in the surgery of neurofibromatosis type 1 (NF1) related peripheral nerve tumors. A retrospective study was conducted on NF1 patients, who admitted between January 2019 and December 2023 and treated with peripheral nerve tumor resection surgery assisted by multimodal IONM technology. There were 49 males and 45 females. The age ranged from 5 to 78 years, with an average of 33.7 years. Tumor morphological classification included 71 cases of nodular type, 13 cases of diffuse type, and 10 cases of mixed type. Target tumors were distributed in craniofacial region (47 cases), neck (11 cases), trunk (12 cases), and limbs (24 cases). Preoperatively, 44 cases had no obvious neurological symptoms, while the remaining patients had neurological symptoms, including 15 cases of visual impairment, 5 cases of hearing impairment, 16 cases of somatic movement disorders, and 31 cases of somatic sensory disorders, of which 7 cases had more than one symptom. IONM plans were selected based on the relevant nerves and adjacent important structures of the target tumor, including visual evoked potential (17 cases), somatosensory evoked potential (44 cases), motor evoked potential (88 cases), and electromyogram (94 cases). All surgeries were successfully completed. Ninety-three patients underwent total/near total resection and 1 patient underwent palliative resection. Pathological examination showed 80 cases of neurofibroma and 14 cases of malignant peripheral nerve sheath tumors. Complications included 2 cases of hematoma and 3 cases of incision infection. All patients were followed up 3-61 months (median, 15 months). During follow-up, no significant changes in neurological symptoms or tumor recurrence were found. Among the patients with preoperative visual impairment, there were 14 cases with no improvement in symptoms and 1 with improvement after surgery. Among the patients with somatic movement disorders, there were 11 cases with no improvement in symptoms, 3 cases with improvement, 2 cases with aggravation, 4 newly onset cases, and 1 case with significant impact on daily life after surgery. Among the patients with somatic sensory disorders, there were 17 cases with no improvement in symptoms, 14 cases with improvement, and 13 newly onset cases. The patients with hearing impairment showed improvement after surgery. The clinical manifestations of NF1 related peripheral nerve tumors are complex. Multimodal IONM technology can provide real-time detection of nerve provocation and damage. Surgical treatment with multimodal IONM technology is safe and can reduce complications.

Outcomes of a modified technique of partial parotidectomy and novel parotid tumour position classification from a single surgeon prospective database.

Conservative parotidectomy for benign tumours reduces facial nerve palsy, without increasing local recurrence. We report a modified technique of partial parotidectomy and using a novel description of tumour position, explore relationships between tumour position and histological margins, facial nerve palsy and local recurrence. A prospectively collected single surgeon parotidectomy database was analysed, including tumour location (superficial/deep lobe; central/peripheral) and outcomes. A partial parotidectomy identified the facial nerve and the proximal portion of its branches with a macroscopically clear resection margin. Mean follow up was 5.9 years for pleomorphic adenomas. Three hundred and three patients underwent parotidectomy; 257 (84.8%) were superficial and 46 (15.2%) deep lobe. Tumour position was recorded in 291: 236 (81.1%) were peripheral tumours and 55 (18.9%) central. Histological margin involvement was similar in central and peripheral tumours, both overall and for superficial and deep lobe tumours, but was commoner in central deep lobe tumours, (P = 0.003). Temporary partial facial nerve palsy occurred in 21 (6.9%), with one permanent partial nerve palsy (0.3%). Deep lobe tumours and total parotidectomy were associated with facial nerve palsy (P = 0.01). Facial nerve monitoring reduced the risk of palsy (P < 0.01). Local recurrence of pleomorphic adenomas was uncommon, occurring in 3 (2.0%) of 151 patients. This series confirms the safety and adequacy of more conservative partial parotidectomy for benign tumours, highlighting most tumours are peripheral, but not more prone to histological margin involvement or local recurrence, and with routine intraoperative facial nerve monitoring, is achieved with low facial nerve palsy rates.

5118 When Thyroid Gland Is Not Made Of Thyroid Cells

Abstract Disclosure: A. Bulut: None. L. Ma: None. J.P. Noordzij: None. S.Y. Lee: None. Introduction: Neurofibroma is a type of peripheral nerve tumor that can arise sporadically or be a part of neurofibromatosis type 1 (NF1), a rare genetic disorder. Neurofibromas within the thyroid gland are extremely rare. Here, we present the fifth reported case of primary neurofibroma of thyroid gland. Case: A 60-year-old woman with history of systemic lupus erythematosus and hypertension presented with enlargement of left thyroid gland. She was diagnosed with Graves’ disease 40 years ago, which was treated with right thyroid lobectomy one year after the initial diagnosis. Five years after the surgery, she had recurrence of her symptoms and received radioactive iodine ablation with subsequent hypothyroidism. On presentation to endocrine clinic, she had thyroid ultrasound (US), which showed surgically absent right thyroid lobe and enlarged heterogenous left thyroid lobe measuring 5.1 cm x 3.8 cm x 3.9 cm with scant blood flow without discrete nodules. In interim, patient developed dysphagia and globus sensation. Repeat thyroid US showed enlargement of left lobe to 5.6 cm x 3.7 cm x 4.7 cm. Patient underwent completion thyroidectomy. Surgical pathology showed neurofibroma (S-100+, CD34+ and MSA-) without any thyroid parenchyma. Whole-body scan revealed no other evidence of tumors. Patient was referred for genetic analysis. Discussion: Neurofibromas are benign peripheral nerve system tumors primarily consist of Schwann cells along with other components of perineurium. They can occur as a sporadic lesion which accounts for 90% of solitary neurofibroma cases or be a part of NF1 on rare occasions. NF1 is an autosomal dominant genetic disorder due to germline mutation in NF1 gene located on chromosome 17q11.2, whose manifestations include café-au-lait macules, Lisch nodules, skeletal abnormalities, neurological deficits, and other benign and malignant tumors. Neurofibromas are the hallmarks of NF1. There are only few cases in the literature reported neurofibromas adjacent to or originating from thyroid gland. To the best of our knowledge, there have been only four other cases reporting primary neurofibroma of thyroid gland, one of which developed from thyroid capsule. Our patient most likely has primary neurofibroma of thyroid gland given the lack of syndromic features, however, genetic testing is needed in order to rule out NF1. In conclusion, clinicians should consider neurofibroma in their differential in cases of enlarging thyroid gland or nodules, especially in the presence of other clinical features. Presentation: 6/1/2024

5118 When Thyroid Gland is Not Made of Thyroid Cells

Abstract Disclosure: A. Bulut: None. L. Ma: None. J.P. Noordzij: None. S.Y. Lee: None. Introduction: Neurofibroma is a type of peripheral nerve tumor that can arise sporadically or be a part of neurofibromatosis type 1 (NF1), a rare genetic disorder. Neurofibromas within the thyroid gland are extremely rare. Here, we present the fifth reported case of primary neurofibroma of thyroid gland. Case: A 60-year-old woman with history of systemic lupus erythematosus and hypertension presented with enlargement of left thyroid gland. She was diagnosed with Graves’ disease 40 years ago, which was treated with right thyroid lobectomy one year after the initial diagnosis. Five years after the surgery, she had recurrence of her symptoms and received radioactive iodine ablation with subsequent hypothyroidism. On presentation to endocrine clinic, she had thyroid ultrasound (US), which showed surgically absent right thyroid lobe and enlarged heterogenous left thyroid lobe measuring 5.1 cm x 3.8 cm x 3.9 cm with scant blood flow without discrete nodules. In interim, patient developed dysphagia and globus sensation. Repeat thyroid US showed enlargement of left lobe to 5.6 cm x 3.7 cm x 4.7 cm. Patient underwent completion thyroidectomy. Surgical pathology showed neurofibroma (S-100+, CD34+ and MSA-) without any thyroid parenchyma. Whole-body scan revealed no other evidence of tumors. Patient was referred for genetic analysis. Discussion: Neurofibromas are benign peripheral nerve system tumors primarily consist of Schwann cells along with other components of perineurium. They can occur as a sporadic lesion which accounts for 90% of solitary neurofibroma cases or be a part of NF1 on rare occasions. NF1 is an autosomal dominant genetic disorder due to germline mutation in NF1 gene located on chromosome 17q11.2, whose manifestations include café-au-lait macules, Lisch nodules, skeletal abnormalities, neurological deficits, and other benign and malignant tumors. Neurofibromas are the hallmarks of NF1. There are only few cases in the literature reported neurofibromas adjacent to or originating from thyroid gland. To the best of our knowledge, there have been only four other cases reporting primary neurofibroma of thyroid gland, one of which developed from thyroid capsule. Our patient most likely has primary neurofibroma of thyroid gland given the lack of syndromic features, however, genetic testing is needed in order to rule out NF1. In conclusion, clinicians should consider neurofibroma in their differential in cases of enlarging thyroid gland or nodules, especially in the presence of other clinical features. Presentation: 6/1/2024

Early Detection of Malignant and Premalignant Peripheral Nerve Tumors Using Cell-Free DNA Fragmentomics.

Early detection of neurofibromatosis type 1 (NF1)-associated peripheral nerve sheath tumors (PNST) informs clinical decision-making, enabling early definitive treatment and potentially averting deadly outcomes. In this study, we describe a cell-free DNA (cfDNA) fragmentomic approach that distinguishes nonmalignant, premalignant, and malignant forms of PNST in the cancer predisposition syndrome, NF1. cfDNA was isolated from plasma samples of a novel cohort of 101 patients with NF1 and 21 healthy controls and underwent whole-genome sequencing. We investigated diagnosis-specific signatures of copy-number alterations with in silico size selection as well as fragment profiles. Fragmentomics were analyzed using complementary feature types: bin-wise fragment size ratios, end motifs, and fragment non-negative matrix factorization signatures. The novel cohort of patients with NF1 validated that our previous cfDNA copy-number alteration-based approach identifies malignant PNST (MPNST) but cannot distinguish between benign and premalignant states. Fragmentomic methods were able to differentiate premalignant states including atypical neurofibromas (AN). Fragmentomics also adjudicated AN cases suspicious for MPNST, correctly diagnosing samples noninvasively, which could have informed clinical management. Novel cfDNA fragmentomic signatures distinguish AN from benign plexiform neurofibromas and MPNST, enabling more precise clinical diagnosis and management. This study pioneers the early detection of malignant and premalignant PNST in NF1 and provides a blueprint for decentralizing noninvasive cancer surveillance in hereditary cancer predisposition syndromes.