Mesenchymal Research Articles

Chapter 13: What is new in fibroblastic/myofibroblastic tumors in children.

Fibroblastic and myofibroblastic neoplasms represent about 12% of pediatric soft tissue tumors. Most of these neoplasms in children are either benign or locally aggressive with rare metastasis, while malignant cases are uncommon. Diagnosing these tumors is challenging due to overlapping morphologies and the limited utility of immunohistochemistry. Advances in molecular techniques, especially RNA sequencing, have improved our understanding of the molecular drivers of these tumors, leading to better classification. Key molecular alterations, such as RTK and MAPK activation, are central in the development of tumors like infantile fibrosarcoma (IFS) and inflammatory myofibroblastic tumors (IMT). The identification of alternative fusions in IFS and IMT underscores the importance of an integrated diagnostic approach. Furthermore, new RTK-driven lesions, now included in the WHO's "NTRK-rearranged mesenchymal neoplasms", have been identified. This review provides an update on recent findings in RTK-driven myofibroblastic tumors and highlights novel entities still in need of classification.

The maximum transverse diameter: an effective indicator for predicting peroral en bloc retrieval rate of mesenchymal tumors after endoscopic resection.

Gastrointestinal mesenchymal tumors (GIMTs) are being increasingly resected under endoscopy. Large GIMTs cannot be completely retrieved through the mouth, but the cut-off diameter of peroral en bloc retrieval (PEBR) for GIMTs completely resected is still unknown. This study aimed to investigate the ability of maximum transverse diameter (MTD) to predict the PEBR rate of GIMTs after endoscopic resection (ER). We retrospectively reviewed all patients who underwent ER for upper GIMTs from January 2009 to August 2023. The MTD was measured according to the maximum transverse diameter of specimen immediately retrieved after ER. For the PEBR rate, the independent predictors and optimal cut-off value of MTD were determined by logistic regression analysis and the receiver operating characteristic (ROC) curve analysis. The potential significance of preoperative CT for the evaluation of MTD was also clarified. A total of 2032 patients were diagnosed with upper GIMTs after en bloc resection under endoscopy. The overall PEBR rate was 98.72% (2006/2032). The PEBR rate was 100% for 1943 GIMTs with MTD < 2.5cm, 85.71% (60/70) for GIMTs with 2.5cm but ≤ 3.0cm, and 15.79% (3/19) for GIMTs with MTD > 3.0cm, and these rates were significantly different (P < 0.01). In terms of the PEBR rate of GIMTs, the ROC curve revealed that the optimal cut-off MTD value was 3.0cm, and logistic regression analysis revealed that MTD > 3.0cm was an independent predictive factor (OR 71.07, 95% CI 9.14-552.43; P < 0.001). The MTD of CT was related to that of the resected specimen (r = 0.7149, P < 0.01), and CT underestimated the mean MTD of upper GIMTs by 0.17cm (95% CI 0.09-0.24, P < 0.01). MTD is an effective indicator for predicting the PEBR rate of GIMTs after ER. Resected specimens with MTD > 3.0cm could not be routinely retrieved en bloc. Preoperative CT is suitable for evaluating the MTD of GIMTs, but underestimates the mean MTD of upper GIMTs by 0.17cm.

Desmoplastic Fibroblastoma (Collagenous Fibroma) of the Knee: A Case Report and Literature Review.

Desmoplastic fibroblastoma, also known as collagenous fibroma, is a rare benign mesenchymal neoplasm that primarily arises in the subcutaneous tissue of upper extremities and limb girdles. The knee is an uncommon location for desmoplastic fibroblastoma. Recent studies have demonstrated the presence of immunoreactivity for FOS like 1 (FOSL1) and rearrangements of FOSL1. A 70-year-old woman presented with a 1-year history of a palpable mass in the medial aspect of the right knee. Physical examination revealed a 4-cm, elastic hard, mobile, nontender mass. Magnetic resonance imaging (MRI) showed a well-defined mass with prominent low signal intensity on all pulse sequences. Contrast-enhanced MRI demonstrated mild internal enhancement with rim enhancement. After an open biopsy, the lesion was successfully treated by complete excision. Histologically, the tumor was composed of bland spindle or stellate-shaped cells embedded in an abundant collagenous stroma. Immunohistochemically, the tumor cells showed diffuse nuclear positivity for FOSL1. These findings were consistent with a diagnosis of desmoplastic fibroblastoma. The patient was asymptomatic and there was no evidence of local recurrence eight months after surgery. Desmoplastic fibroblastoma is a distinctive benign soft-tissue tumor with FOSL1 immunoreactivity and should be clearly distinguished from more biologically aggressive mesenchymal neoplasms.

Cytological diagnosis of follicular dendritic cell sarcoma with a unique pattern of D2-40 immunoexpression.

Fine needle aspiration procedure is routinely used for cytological diagnosis of nodal or extra nodal lesions. Follicular dendritic cell sarcoma (FDCS) is a rare mesenchymal neoplasm arising from follicular dendritic cells of lymphoid follicles at nodal and extranodal sites. Multimodal therapies have emerged for FDCS, necessitating its accurate pathologic diagnosis with additional ancillary testing for directing clinical management. By immunohistochemical analysis, FDCS is positive for the complement receptors CD21, CD23, and CD35. In addition, D2-40 is reported to be highly sensitive for FDCS with a strong membranous pattern of expression. In this study, we present the cytological diagnosis of a case of FDCS in retroperitoneal lymph nodes with an emphasis on a unique staining pattern of D2-40 which showed a strong nuclear pattern in tumor cells comparable to the membranous pattern of D2-40 on the control tissue and other surgical cases of FDCS in our comparative study.

Primitive Myxoid Mesenchymal Tumor of Infancy: A Lost Battle

ABSTRACT Primitive myxoid mesenchymal tumor of infancy (PMMTI) is a low to intermediate-grade, poorly differentiated myofibroblastic tumor and is characterized by its tendency to recur locally. It commonly occurs in the 1st year of life and is predominantly seen in the axial skeleton and rarely in the retroperitoneum. We report one such case of PMMTI, which is the second case reported in English literature.

Lipoma of the Parotid Gland Extending from the Superficial to the Deep Lobe: Case Report

Lipoma is a benign mesenchymal tumor composed largely of fat tissue. It is one of the most common of all neoplasms, but its occurrence in the parotid gland is extremely rare.

The challenge of diagnosing neuroendocrine neoplasms: experience from a national reference center.

Correctly diagnosing neuroendocrine neoplasm (NEN) has become increasingly challenging, given that more histomorphologic and immunophenotypic NEN mimics have been identified in recent years. A systemic review was conducted on the 4795 consult cases submitted with initial diagnoses of NEN to a national reference center in China from 2013 to 2021. Among them, 443 cases were misdiagnosed as epithelial NENs after reevaluation with the help of immunohistochemical and/or molecular tests, ranging from 7.1 to 13.2%, with yearly increases. The misdiagnoses varied among age groups and tumor sites. Exocrine carcinoma was the most common (63.2%), followed by mesenchymal tumors. Other common tumors that were misdiagnosed included hepatocellular carcinoma, salivary gland tumor, and gastrointestinal stromal tumor. Aberrant expression of neuroendocrine markers was frequent (218/408, 53.4%), with diffuse positivity ranging from 8.2 to 51.7% for synaptophysin, chromogranin A, and INSM1 stains in all non-NEN cases. Selecting appropriate immunohistochemical stains based on H&E morphology is the key to avoiding diagnostic pitfalls. Medical history and molecular genomic information greatly assist in correctly diagnosing NENs and their mimics.

Novel Driver Genes and Mutations in Lung Pecoma: A Case Report

Introduction: Perivascular epithelioid cell tumors (PEComa) are rare mesenchymal neoplasms characterized by perivascular epithelioid cells. Despite their common occurrence in the uterus, gastrointestinal tract, and retroperitoneum, this study presents an exceptional case of PEComa identified in the lung, warranting unique molecular exploration. Case Report: A 50-year-old man was diagnosed with a 6 cm neoplasm in the lower lobe of the right lung without enlarged lymph nodes during a routine examination. Thoracotomy, extended lower bilobectomy, and D3 lymphadenectomy were performed. Histological and immunohistochemical analysis diagnosed a PEComa. No conventional TSC1 and TSC2 mutations specific to PEComa, which resulted in mTOR pathway activation, were detected by whole-exome sequencing. In contrast, mutations were unveiled in the MTOR, EIF4EBP1, and PRAME genes that could be an alternative mechanism governing mTOR activation. Conclusion: These findings provide novel insights into the molecular intricacies of lung PEComa, showcasing the distinctive roles of MTOR, EIF4EBP1, and PRAME mutations.

Lymphoid Aggregates in Canine Cutaneous and Subcutaneous Sarcomas: Immunohistochemical and Gene Expression Evidence for Tertiary Lymphoid Structures.

Canine cutaneous/subcutaneous soft-tissue sarcomas (STS) are diversely derived mesenchymal neoplasms with a risk of recurrence and/or metastasis depending on the extent of surgical excision and histologic grade. Lymphoid aggregates (LAs) are often described in these tumours but not characterised. In humans, LA characterised as tertiary lymphoid structures (TLSs) improve the prognosis of many tumours, including sarcomas. We sought to determine if LA meeting a size criterion (> 700 cells) in canine sarcomas met the criteria of TLS and the overall prevalence of LA of any size. RNA expression in large LAs versus aggregate-adjacent sarcoma tissue (AAS) was measured in laser capture microdissected tissue and compared to curl-derived RNA from aggregate-free sarcomas and lymph nodes. CD3, CD20, MUM-1 and PNAd expressions were measured using immunohistochemistry. CD20 and CD3 mRNA were more highly expressed in LA versus AAS (13.8 fold, p = 0.0003 and 2.3 fold, p = 0.043). This was supported by the IHC findings. The large LAs were also enriched in chemokine RNA expression characteristic of TLS (CXCR5 5.8 fold, p < 00001, CCL19 3.68 fold, p = 0.0209, CCL21 6.87 fold, p = 0.0209 and CXCL13 2.68 fold, p = 0.0924). Plasma cells and high endothelial venules were identified in LA containing tumours but not in control tissue. Large LAs were present in 12% of tumours, and LA of any size in 30%. We conclude that large LAs in canine STS are consistent with TLS.

Features of Magnetic Resonance Diagnostics of Tenosynovial Giant Cell Tumor (Pigmented Villonodular Synovitis)

Aim. Demonstrate the features of magnetic resonance diagnostics of tenosynovial giant cell tumor.Materials and Methods. Using magnetic resonance imaging, we identified patients with tenosynovial giant cell tumor of the knee joint, describing the diagnostic features and clinical course of diffuse and local forms of the tumor.Results. Specific MRI patterns of tenosynovial giant cell tumor are hemosiderin deposits, villous and nodular growths of the synovium of the knee joint, joint effusion and bone erosion.Conclusion. Тenosynovial giant cell tumor is a rare mesenchymal neoplasm arising from the synovium of joints and tendon sheaths, disabling young able-bodied people. Magnetic resonance imaging, being the “gold” standard for radiological diagnostics, helps to identify specific patterns.

A Rare Case of Tumor-Induced Osteomalacia Due to Mesenchymal Tumor at Foramen Magnum Diagnosed Preoperatively on 68Ga DOTATATE PET/CT.

A 42-year-old man, a known case of FGF23-dependent hypophosphatemia, underwent 68Ga- DOTATATE PET-CT, which showed a somatostatin receptor-expressing lesion in the left arch of foramen magnum that was correlated on MRI as a soft tissue lesion measuring 2.2 × 1.3 cm. It was excised and histopathologically confirmed as phosphaturic mesenchymal tumor. Postoperatively, patient improved clinically and recovered from hypophosphatemia completely. A distinct focal uptake in a 68Ga- DOTATATE PET-CT in a patient with tumor-induced osteomalacia needs extensive workup and high degree of suspicion to rule out mesenchymal tumor at nonconventional location as seen in the present case.

Sinonasal Phosphaturic Mesenchymal Tumors Without Any Nasal Symptoms: A Case Report and Literature Review.

We present a case of phosphaturic mesenchymal tumor (PMT) in the left ethmoid without any nasal symptoms in a 63-year-old woman. Initially diagnosed with postmenopausal osteoporosis, 2-year history of hypophosphatemia and a significantly higher uptake of Fluorine-18 (18F)-AlF-NOTA-octreotide (18F-OC) in the left ethmoid sinus, provided crucial information for accurate diagnosis. We presented a case with chart review and conducted review of the literature. The patient endured 1-year history of weakness and bone pain but without any nasal symptoms before a tissue diagnosis was eventually reached. It is a challenging diagnosis to make-patients present with non-specific clinical symptoms and the culprit neoplasm is often tiny in size and difficult to detect. It emphasizes the importance of thorough patient history-taking and the whole-body functional imaging. Sinonasal PMTs are rare, and because of this most otolaryngologists are unfamiliar with its clinical presentation. This case highlights the importance of early diagnosis to enable prompt intervention and reduce the burden of associated symptoms.

Contemporaneous Inflammatory, Angiogenic, Fibrogenic, and Angiostatic Cytokine Profiles of the Time-to-Tumor Development by Cancer Cells to Orchestrate Tumor Neovascularization, Progression, and Metastasis.

Cytokines can promote various cancer processes, such as angiogenesis, epithelial to mesenchymal transition (EMT), invasion, and tumor progression, and maintain cancer stem-cell-like (CSCs) cells. The mechanism(s) that continuously promote(s) tumors to progress in the TME still need(s) to be investigated. The data in the present study analyzed the inflammatory, angiogenic, fibrogenic, and angiostatic cytokine profiles in the host serum during tumor development in a mouse model of human pancreatic cancer. Pancreatic MiaPaCa-2-eGFP cancer cells were subcutaneously implanted in RAG2xCγ double mutant mice. Blood samples were collected before cancer cell implantation and every week until the end point of the study. The extracted serum from the blood of each mouse at different time points during tumor development was analyzed using a Bio-Plex microarray analysis and a Bio-Plex 200 system for proinflammatory (IL-1β, IL-10, IFN-γ, and TNF-α) and angiogenic and fibrogenic (IL-15, IL-18, basic FGF, LIF, M-CSF, MIG, MIP-2, PDGF-BB, and VEGF) cytokines. Here, we find that during cancer cell colonization for tumor development, host angiogenic, fibrogenic, and proinflammatory cytokine profiling in the tumor-bearing mice has been shown to significantly reduce host angiostatic and proinflammatory cytokines that restrain tumor development and increase those for tumor growth. The proinflammatory cytokines IL-15, IL-18, and IL-1β profiles reveal a significant host serum increase after day 35 when the tumor began to progress in growth. In contrast, the angiostatic cytokine profiles of TNFα, MIG, M-CSF, IL-10, and IFNγ in the host serum revealed a dramatic and significant decrease after day 5 post-implantation of cancer cells. OP treatment of tumor-bearing mice on day 35 maintained high levels of angiostatic and fibrogenic cytokines. The data suggest an entirely new regulation by cancer cells for tumor development. The findings identify for the first time how pancreatic cancer cells use host cytokine profiling to orchestrate the initiation of tumor development.

Mesenchymal tumors of the mediastinum: analysis of the clinical case

Mediastinal tumors include a wide range of benign and malignant neoplasms. The latter in the early stages are characterized by a long latent course and carry a significant threat of com pression and / or invasion of vital organs of the mediastinum. The complexity of their diagnosis is complemented by a mixed clinical picture, similar to other somatic diseases. Considering all of the above, mediastinal tumors are an urgent problem for the modem oncological community, they require improving knowledge and gaining experience in their surgical and conservative treatment. Mesenchym al tumors of the mediastinum make up a small part of tumors of the mediastinal space, and the low incidence of neoplasm s of this anatomical localization dictates the need for an interdisciplinary approach to the diagnosis and treatment of mesenchym al tumors of the mediastinal space. A clinical case of the disease is considered, an effective and radical surgical treatment method is demonstrated. The asymptomatic course of the early stages of the disease, as w ell as the relatively low effectiveness of surgical intervention in the late period of oncogenesis, dictates the need to search for new approaches in the diagnosis and treatment of mediastinal tumors.

Tumor-induced phosphopenic osteomalacia: modern approaches to diagnostics and treatment

Phosphopenic osteomalacia (PPOM) is a rare variant of paraneoplastic syndrome caused by tumor synthesis of fibroblast growth factor 23 (FGF23). FGF23 secretion leads to a decrease in phosphate reabsorption and calcitriol levels, which leads to the development of severe hypophosphataemia and hypocalcaemia. FGF23 synthesis is predominantly associated with benign mesenchymal tumors, but has also been described in malignant neoplasms. The main clinical manifestations of PPOM are generalized myalgias and myopathy, ostealgia, pathological fractures, etc. The diagnosis of the disease requires a step-by-step investigation using somatostatin receptor-based imaging techniques, as these have the highest sensitivity for the detection of neoplasms causing osteomalacia. Surgical intervention is clearly the treatment of choice. Promising non-surgical methods include treatment with burosumab and somatostatin analogues.

On Vascular Lesions of the Thyroid Gland with Emphasis on Intrathyroidal Hemangioma: Clinicopathologic Characterization of Two Cases and Review of the Literature

Mesenchymal neoplasms of the thyroid gland are exceptionally rare accounting for less than 0.5% of all intrathyroidal tumors with hemangiomas comprising merely 6% of them. The clinicopathologic characteristics of two additional examples of thyroid hemangioma together with a thorough review of the pertinent literature are presented. A 62-year-old man and an 18-year-old woman presented with asymptomatic, soft-to-palpation, mobile nodules of the right thyroid lobe classified as TI-RADS 5 and TI-RADS 4, respectively, on ultrasound imaging. Microscopically, lesions featured a circumscribed, unencapsulated, lobular proliferation of variably-sized, congested, vascular channels lined by a single layer of flattened, cytologically bland endothelial cells, together with interspersed residual follicles. Vascular endothelial cells were strongly positive for CD31, CD34 and ERG, and negative for pancytokeratin AE1/AE3, TTF1, and PAX8. A diagnosis of cavernous hemangioma was rendered in the clinical setting of Hashimoto thyroiditis and follicular adenoma, respectively. Following inclusion of the current cases, a total of 53 intrathyroidal hemangiomas were identified in the literature with a patient mean age of 48.9 years (range = 0.17-84) and a slight female predilection (F:M = 1.4:1). A proclivity for the right thyroid lobe (59.6%) was noted with the striking majority of cases exhibiting features of cavernous hemangioma (95.2%). Prognosis is favorable and surgical resection is considered curative. The occasionally alarming clinical presentation in conjunction with absence of pathognomonic imaging features and limited diagnostic accuracy of FNA cytopathology for such lesions renders surgical intervention necessary for definitive diagnosis of intrathyroidal hemangiomas and exclusion of other epithelial and non-epithelial pathologic entities.

Exosomal circRNAs: The Key Role and Potential Therapeutic Target in Gastric Cancer.

A ring-stabilized endogenous non-coding RNA is called circular RNA (circRNA). Intercellular communication is mediated by exosomes, and circRNA is enriched and stabilized in exosomes. It has recently been demonstrated that cancer cells and tissues exhibit abnormal expression of exosomal circRNAs. By controlling angiogenesis, metabolism, metastasis, epithe-lial mesenchymal transition (EMT), tumor chemoresistance, immune evasion, and cell prolifera-tion, it may also have an impact on the development of different malignancies. Furthermore, ex-osomal circRNAs have strong tissue selectivity, stability, and other qualities that make them useful for diagnostic purposes. Consequently, exosomal circRNAs offer a wide range of poten-tial applications in the therapy of cancer and can be utilized as biomarkers and anti-tumor tar-gets. The features and purposes of circRNAs and exosomes are briefly discussed in this review, which also methodically explains the function and possible mechanism of the function of exo-somal circRNA in the onset of gastric cancer (GC). Furthermore, their clinical uses as targets and biomarkers for gastric cancers are also summarized and discussed in this work.

Central nervous system solitary fibrous tumors: Case series in accordance with the WHO 2021 reclassification. Framework for patient surveillance.

Solitary fibrous tumors (SFTs) are a rare type of mesenchymal tumors. The World Health Organization reclassified SFTs in 2021. Currently, guidelines concerning treatment and follow-up are lacking. We performed a retrospective case series with reclassification of SFTs, according to the most recent WHO classification, to explore tumor-behavior. The purpose is to build a framework for long-term patient surveillance. A retrospective case study was performed according to the PROCESS guidelines. Inclusion criteria were: patients operated on between 2013 and 2023 in two neurosurgical centers with the diagnosis of 'hemangiopericytoma' or SFT on histopathological stains. Patients were excluded if the original stains of the primary tumor were unavailable. The following demographic, radiologic and therapeutic parameters were included in the review: age, sex, original and reclassified anatomopathological diagnosis, location, extent of resection, use of postoperative radiotherapy, location of and time to recurrence, location of-and time to metastasis, and survival. Histological material was re-examined by experienced neuropathologists. Ten patients were identified with a solitary fibrous tumor of the central nervous system (CNS) (three females) between 2013 and 2023. Age at diagnosis ranged from 38 up to 81. Eight patients were treated by gross total resection (GTR) and postoperative radiotherapy (RT) was applied in five cases. Initial WHO grading consisted of three grade I, two grade II, and six grade III lesions. Reclassification according to the WHO 2021 classification of CNS tumors resulted in seven reclassifications, all towards a lower grade. Four patients showed local recurrence, six to eight years after diagnosis, and five patients developed systemic metastases, nine to 13 years after diagnosis. Although rare, SFT should be included in the differential diagnosis of intracranial tumors with extra-axial growth patterns. The current histological grade according to the WHO 2021 does not seem to account for local recurrence rate or systemic metastasis. When a solitary fibrous tumor is presumed, gross total resection is the recommended treatment. Lifelong patient follow-up is necessary due to the risk of delayed recurrence and distant metastasis, even after gross-total resection. We would advocate for the use of CT thorax-abdomen or full body PET in the detection of systemic metastases at diagnosis and during follow-up, however optimal intervals remain unclear.

Endoscopic "calabash" ligation and resection for small gastric mesenchymal tumors.

Gastric mesenchymal tumors (GMT) are identified as soft tissue neoplasms that arise from mesenchymal stem cells within the gastrointestinal tract. GMT primarily encompass gastric stromal tumors (GST), gastric leiomyomas, and gastric schwannomas. Although most GMT are benign, there are still potential malignant changes, especially GST. Thus, early surgical intervention is the primary treatment for GMT. We have designed a simple endoscopic "calabash" ligation and resection (ECLR) procedure to treat GMT. Its efficacy and safety need to be compared with those of traditional endoscopic techniques, such as endoscopic submucosal excavation (ESE). To assess the safety and effectiveness of ECLR in managing small GMT (sGMT) with a maximum diameter ≤ 20 mm by comparing to ESE. This retrospective analysis involved patients who were hospitalized in our institution between November 2021 and March 2023, underwent endoscopic resection, and received a pathological diagnosis of GMT. Cases with a tumor diameter ≤ 20 mm were chosen and categorized into two cohorts: Study and control groups. The study group was composed of patients treated with ECLR, whereas the control group was composed of those treated with ESE. Data on general clinical characteristics (gender, age, tumor diameter, tumor growth direction, tumor pathological type, and risk grade), surgery-related information (complete tumor resection rate, operation duration, hospitalization duration, hospitalization cost, and surgical complications), and postoperative follow-up were collected for both groups. The aforementioned data were subsequently analyzed and compared. Five hundred and eighty-nine individuals were included, with 297 cases in the control group and 292 in the study group. After propensity score matching, the final analysis incorporated 260 subjects in each cohort. The findings indicated that the study group exhibited shorter operation duration and lowered medical expenses relative to the control group. Furthermore, the study group reported less postoperative abdominal pain and had a lower incidence of intraoperative perforation and postoperative electrocoagulation syndrome than the control group. There were no substantial variations observed in other parameters among the two cohorts. ECLR is a viable and effective approach for managing sGMT.

Atypical Gastric Glomus Tumor of Uncertain Malignant Potential in A 16-Year-Old Female; A Rare Entity with Unique Findings

Abstract Introduction/Objective Gastric glomus tumor (GGT) is a rare mesenchymal tumor that is challenging to diagnose, especially when the immunoprofile overlaps with other more common gastric mesenchymal tumors. The majority of GGT are benign, however, rarely it can be atypical or even malignant. Herein, we present a case of a young female with atypical gastric glomus tumor of uncertain malignant potential. Methods/Case Report A 16-year-old female presented to the emergency with abdominal pain, coffee ground emesis, and melena. Imaging showed a 3.2 cm well-defined gastric mass arising from the muscularis propria. Results (if a Case Study enter NA) The FNA biopsy revealed clusters of tumor cells with uniform characteristics, exhibiting distinct cell membranes and eosinophilic to clear cytoplasm, surrounding prominent vasculature. Immunohistochemical analysis showed that the tumor cells were positive for SMA, synaptophysin, vimentin, calponin, and caldesmon, with weak, patchy positivity for DOG1. CD34 highlighted the vessels separating the tumor cellular clusters into lobules. CD117 and Desmin were negative. The Ki67 proliferation index varied with hotspot foci 25-30%. Morphology and immunoprofile suggest glomus tumor, however, neuroendocrine tumor and epithelioid GIST needed to be excluded. Subsequent resection specimen showed that the tumor was located within the muscularis propria with extension into the serosal vessels, suggesting vascular invasion, along with foci of cellular spindling and nuclear irregularity are identified. No necrosis noted. Tumor cells were positive for cyclin D1 while negative for myogenin, chromogranin, and DOG1. Overall, findings were consistent with GGT of uncertain malignant potential. Conclusion Although GGT are rare, they should be considered in the differential diagnosis of gastric mesenchymal tumors. The presence of diffuse SMA staining can help distinguishing them from GIST. It is crucial to scrutinize for signs of cellular and nuclear atypia, particularly in deeply seated glomus tumors.