Soft Tumors Research Articles

Patterns of expression of VEGFR2, PDGFRs and c-Kit in pediatric patients with high grade non-rhabdomyosarcoma soft tissue sarcoma

IntroductionActivated vascular endothelial growth factor receptors (VEGFRs), platelet-derived growth factor receptors (PDGFRs) and c-Kit have been shown to be involved in the growth, invasion and metastasis of non-rhabdomyosarcoma soft tissue sarcoma tumor (NRSTS) with promising results for targeted therapy. Our aim was to assess the expression of these markers among different histological types and correlate with outcomes.Material and methodsThis retrospective study included pediatric patients aged ≤ 18 years diagnosed with high-grade NRSTS who were treated at Children Cancer Hospital Egypt 57357 as per the COG NRSTS protocol (ARST0332). Expression of VEGFR2, PDGFRs (α and β) and c-Kit in tumor tissue was assessed by immunohistochemistry and correlated with clinical outcome.ResultsOf 113 patients, 96 were eligible for the analysis with a median age of 11 years. Overall, 32.3% demonstrated high expression of PDGFRα, 17.7% for PDGFRβ, 19.8% for VEGFR2 and 8.3% exhibited positive expression for c-kit on the tumor cells. Most cases of synovial sarcoma (45.8%) and 43.7% of patients with undifferentiated sarcoma exhibited high expression of PDGFRα while 41.6% of MPNST showed high expression to PDGFRβ. The 5-year overall survival (OS), event free survival and relapse free survival (RFS) for the whole cohort were 59%, 54% and 60% respectively. In univariate analyses, only PDGFRα had a negative prognostic impact on relapse free survival (RFS) (p=0.03). In multivariate analyses, VEGFR2 was found to have a negative prognostic impact for OS (p = 0.02).ConclusionOur findings indicated that tyrosine kinase receptors are upregulated in NRSTS and exhibited a distinct expression pattern within various subgroups. High expression of VEGFR2 and PDGFRα significantly correlated with reduced survival and may guide targeted therapy approaches for this poor prognosis group of patients.

Retroperitoneal Myoepithelial Carcinoma with Heterologous Bone Formation and EWSR1::ZNF444

Abstract Introduction/Objective Soft tissue myoepithelial tumors are rare tumors that affect a wide age range and diverse tissue sites. Fewer than five cases have been reported in the retroperitoneum. Most tumors are benign with the only histologic criterion for malignancy being cytologic atypia. The morphology is broad ranging from spindled to epithelioid cells of varying cellularity in sclerotic to myxoid stroma. Heterologous differentiation may be present. These tumors usually express cytokeratin, EMA, S100, and GFAP and show EWSR1 and FUS rearrangements. Here we present an unusual case of retroperitoneal myoepithelial carcinoma. Methods/Case Report A 29-year-old female presented with rash and painless jaundice. CT and MRCP revealed a relatively circumscribed 3.7 cm mass in the porta hepatis. On fine needle aspiration, a possible gastrointestinal stromal tumor was considered due to DOG1 expression. The patient underwent a Whipple procedure with negative margins showing tumor in soft tissue adjacent to the common bile duct. The tumor was multinodular and consisted predominantly of mild to moderately pleomorphic epithelioid cells in fibromyxoid stroma with interspersed woven bone. Mitoses were not appreciated, and necrosis not seen. The tumor was focally positive for CK AE1/AE3, GFAP, and DOG1 and negative for S100, SOX10, p63, and CD117. INI1 was retained. NGS identified EWSR1::ZNF44 and a diagnosis of myoepithelial carcinoma was rendered. The patient received no adjuvant therapy and has not shown any evidence of metastasis or recurrence for 17 months. Results (if a Case Study enter NA) NA Conclusion Soft tissue myoepithelial carcinomas are aggressive tumors with approximately 40% recurrence and over 50% metastasis. Standard treatment is complete surgical resection. The efficacy of radiation and chemotherapy is not clear. EWSR1 fusions with various partners including POU5F1, PBX1/3, and ZNF44 have been identified. Due to their rarity and varying histology and immunohistochemical expression, identification of gene fusions can be invaluable in diagnosing soft tissue myoepithelial tumors, especially in unusual locations.

Circumferential exposure of the cavernous sinus and parasellar region through a combined open and endoscopic endonasal transcavernous approach, a morphometric study.

Although recent trends currently favor the endoscopic endonasal transcavernous approach (EETA) over the pretemporal transcavernous approach (PTA) for certain cavernous sinus pathologies, dedicated assessment of the surgical exposure and maneuverability is wanting. Toward this aim, this morphometric study quantifies these variables within four cavernous sinus compartments by comparing the PTA, EETA, and a combined approach to achieve a circumferential dissection (EETA-PTA). In five latex-injected specimens, exposure volumes of the EETA, PTA, and circumferential EETA-PTA approaches were quantified; the latter combined the most conservative options of both the endoscopic and open approaches. Two clinical cases illustrate the combined approach. EETA-PTA provided the largest volume of exposure (65.6% vs 35% PTA vs 44.6% EETA, P = 0.01) and eliminated the need to mobilize the ICA or cross cranial nerves. Although EETA and PTA approaches afforded comparable exposure volumes along the entire cavernous sinus (34.9 vs 44.6%), the EETA better exposed medial and inferior compartments (whereas the PTA exposed larger volumes in the lateral and superior compartments. The combined EETA-PTA yielded 66% of total cavernous sinus exposure volumes and eliminated the need to mobilize the ICA or cross cranial nerves. Our methodology aligns with strategies that use a modular concept to divide the skull base into compartments for maximal safe resection. Excluding soft tumors, the EETA is preferred for medial and inferior lesions and the PTA for superior and lateral lesions. A staged combined EETA-PTA may safely yield a 360-degree access for extensive multi-compartment lesions that span neurovascular structures within the cavernous sinus.

8042 A Rare Case of Papillary Thyroid Carcinoma in a Patient with Li-Fraumeni Syndrome

Abstract Disclosure: K.M. Bakhtawar: None. G. Jaiswal: None. Li-Fraumeni syndrome (LFS) is an autosomal dominant syndrome with a high lifetime probability of cancer at an early age. The spectrum of cancers primarily includes osteosarcoma, soft tissue sarcoma, breast cancer, brain tumors, leukemia, and Adenoid cystic carcinoma. Prior studies have estimated the cumulative cancer risk to be about 50% by age 40 and as high as 90% by age 60. As screening for TP53 mutations has improved and more patients are identified, the LFS cancer spectrum has expanded to include thyroid cancer. However, the occurrence of thyroid cancer in LFS has not been extensively assessed in the literature. A recent study examined cancer patients carrying the Brazilian p.R337H TP53 mutation which demonstrated that out of 101 patients, 11 had thyroid cancer (10.9%). In our case, a 45-year-old female with a past medical history of Li-Fraumeni syndrome, Von Willebrand disease, Pulmonary embolism, HER-2 positive invasive ductal carcinoma of the left breast status post chemotherapy, and bilateral mastectomy presented for evaluation of papillary thyroid carcinoma (PTC). An enlarged thyroid was initially identified on physical exam by the PCP with a follow-up thyroid ultrasound showing bilateral nodules. The right upper pole 1.9 x 1.3 x 1.6 cm nodule was biopsied revealing PCT. Following neck ultrasound demonstrated mildly enlarged lymph nodes on the right side, level 2A 1.5 cm and level 3 1.6 cm. The patient subsequently underwent total thyroidectomy and lymph node dissection. The pathology report revealed a 1.4 cm PTC in the upper right pole, a 0.9 cm PCT in the isthmus, and a 0.8 cm PTC in the left midpole. 4/62 lymph nodes were positive with the largest deposit of 1 cm. All margins were negative for carcinoma with no angioinvasion or lymphatic invasion. She was staged as T1bN1bM0. We are awaiting post-operative Thyroglobulin level to assess the need for Radioactive iodine. BRAFV600E and P53 mutation was identified. The patient carries known heterozygous mutation p.R1755H in the TP53 gene with an estimated lifetime cancer risk of 93%. This particular mutation has not been associated with thyroid cancer in prior studies. Although thyroid cancer is an uncommon manifestation of LFS, this case begs the importance of further studies to explore this association which may then lead to early screening and treatment of thyroid cancer in individuals with founder TP53 mutations. Presentation: 6/1/2024

Liposarcoma del cordón espermático

Introduction: liposarcoma of the spermatic cord (LSC) is a rare condition and accounts for about 3 to 7% of all paratesticular sarcomas. A case is presented in an 80-year-old patient who consulted for a left inguinoscrotal painless swelling, that had been present for several years. Physical examination revealed a soft left hemiscrotal tumor that appeared not to be adherent to the testicle. Ultrasonography showed a solid, heterogeneous hyperschoic paratesticular mass with central calcifications and peripheral hypervascularity. During surgery, a diffuse lipomatous tumor was found in the spermatic cord on the superior pole of the left testicle, separated from it. Anatomopathological examination revealed a well-differentiated liposarcoma of the spermatic cord. Discussion: this neoplasm features a slow-growing palpable paratesticular mass. This site of occurrence is rare and represents 7 to 10% of all scrotal tumors. Imaging differentiation between LSC and benign lesions is sometimes challenging. Surgical treatment should include radical orchiectomy wide local excision, and spermatic cord and inguinal ring surrounding soft tissue resection. Conclusion: spermatic cord liposarcoma is a rare and unusual mesenchymal tumor and should be considered among the differential diagnoses of scrotal tumors.

Management of Soft Tissue Upper Jaw Tumor in a 51 Year Old Female Patient at Sultan Fatah Hospital, Demak Regency: Case Report

Background: Benign tumors are collections of cells, tissues or organs that grow slowly and usually enlarge with peripheral expansion, pushing on surrounding structures. Squamous odontogenic tumor (SOT) is a very rare benign epithelial intraosseous tumor, which can cause arising from the neoplastic transformation of Malassez epithelial cells on the lateral surface of the periodontal ligament. Objective : To discuss the management of odontogenic squamous tumors using conservative surgical excision. The goal of treatment for oral myxoma was surgical excision. Case management : A 51 year old female patient came to the SULTAN FATAH Hospital Polyclinic, Demak Regency on May 26 2023 with complaints of a lump on the upper left gum of the jaw. The patient felt the lump about 1 year ago. The patient does not feel pain in the lump. Clinical examination showed a lump in the upper jaw on the front of the patient's left side.Conclusion : Management of the patient undergoing surgical excision of the tumor with general anesthesia and infiltration in the case of odontogenic squamous tumor, based on subjective examination the patient complained of a lump with a tumor mass measuring 10 x 8 cm, redder than the surrounding tissue, round, not moving, attached to the gums of the upper jaw.

When advanced MRI is not about naming musculoskeletal lesions.

Nowadays, the use of advanced MRI sequences such as diffusion-weighted imaging or perfusion-weighted imaging in the field of musculoskeletal radiology remains limited compared to other anatomical regions and subspecialties. Several reasons underpin this, primarily technical challenges, and a longstanding reliance on conventional and morphological evaluations of soft tissue and bone lesions. Experienced radiologists often assert that these advanced sequences do not offer added diagnostic value, claiming that a morphological approach suffices. However, in our opinion, the role of these advanced MRI sequences extends beyond merely naming an MSK lesion. In this commentary, we elucidate how these sequences can aid radiologists in various scenarios, from determining patient prognosis and tracking treatment progress to enhancing clinical-radiological correlations or guiding less experienced radiologists in evaluating soft tissues or bone tumours.

Neurofibromatosis to neoplasia transition: a rare case report of spindle cell malignant peripheral nerve sheath tumor with literature review

Introduction and Importance: Malignant peripheral nerve sheath tumor (MPNST) is a rare and aggressive soft tissue malignant tumor. MPNST in the spinal canal are rarely seen except in cases with NF1. But a long segment extradural spinal malignant spindle cell neoplasm has not been reported in current literature. Case Presentation: We present the first reported case of spinal malignant spindle cell neoplasm extended along the spine. The detected lesion is responsible for compressing various segments of the spinal cord, causing thinning of the cord and secondary stenosis of the spinal canal, leading to a condition known as multi-segment compression myelopathy. Clinical Discussion: MPNSTS are typically detected late due to nonspecific symptoms, with a higher incidence in extremities and a notable occurrence in unusual locations. Diagnosis relies on MRI and histopathology, with S_100 positivity as a neural marker. MPNSTs can arise from neurofibromas or Schwann cells, with a significant portion resulting from TP53 mutations or secondary to radiation exposure. Conclusion: This case stands out due to its unique presentation, characterized by a predominantly spindle cell morphology with certain epithelioid features. It is imperative to recognize this condition for an accurate diagnosis, emphasizing the spindle cell-type malignant peripheral nerve sheath tumor (MPNST) and highlighting its exceptionally poor prognosis.

Dermatofibrosarcoma protuberance with a unique appearance mimicking neurofibroma arising from a conventional area.

A 21year-old Japanese man had a rapidly growing pedunculated soft tumor in the abdomen within the past year, the base of which had persisted for 17years. A skin biopsy of the soft part resembled neurofibroma. However, the excised specimen showed that the tumor base comprised spindle cells arranged in a storiform fashion and expanded around fat cells with a honeycomb infiltration. All areas of the tumor were positive for CD34 and negative for S-100. Finally, the tumor was diagnosed as a myxoid dermatofibrosarcoma protuberance arising from a conventional area. The pedunculated shape on the conventional part was unique. Myxoid dermatofibrosarcoma protuberances may pose a diagnostic challenge, particularly with a small biopsy. Thus, we should carefully consider dermatofibrosarcoma protuberances or other malignant mesenchymal tumors as a differential diagnosis in cases of low cellularity and abundant stromal tumors resembling neurofibromas.

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

Fertility preservation in male adolescents with cancer (2011-2020): A retrospective study in China.

According to the studies, more than 80% of pediatric patients with cancer can achieve a survival rate greater than 5 years; however, long-term chemotherapy and/or radiation therapy may seriously affect their reproductive ability. Fertility preservation in adolescents with cancer in China was initiated late, and related research is lacking. Analyze data to understand the current situation and implement measures to improve current practices. From 2011 to 2020, data on 275 male adolescents with cancer whose age ranged from 0 to 19 years old were collected from 16 human sperm banks for this retrospective study. Methods include comparing the basic situation of male adolescents with cancer, the distribution of cancer types, and semen quality to analyze the status of fertility preservation. The mean age was 17.39 ± 1.46 years, with 13 cases (4.7%) aged 13-14 years and 262 cases (95.3%) aged 15-19 years. Basic diagnoses included leukemia (55 patients), lymphomas (76), germ cell and gonadal tumors (65), epithelial tumors (37), soft tissue sarcomas (14), osteosarcoma (7), brain tumors (5), and other cancers (16). There are differences in tumor types in different age stages and regions. The tumor type often affects semen quality, while age affects semen volume. Significant differences were found in sperm concentration and progressive motility before and after treatment (p < 0.001). Moreover, 90.5% of patients had sperm in their semen and sperm were frozen successfully in 244 patients (88.7%). The aim of this study is to raise awareness of fertility preservation in male adolescents with cancer, to advocate for fertility preservation prior to gonadotoxic therapy or other procedures that may impair future fertility, and to improve the fertility status of future patients.

Pedunculated Giant Condyloma Acuminatum of the Scrotum

The patient was a 71-year-old male whose chief complaint was a scrotum mass. The mass had gradually increased in size without any associated symptoms. The physical examination revealed a pedunculated, radish brown, and elastic soft tumor (4. 5×3. 5×3. 0 cm) in the right scrotum. Blood chemical analysis of HbA1c and squamous carcinoma antigen were 8. 3% and 38. 4 ng/ml (≦1. 5), respectively. This tumor was successfully treated with surgical resection. Histopathological examination showed condyloma acuminatum without malignant findings. Giant condyloma acuminatum commonly affects the genital and perianal areas. An immunocompromised state generally exists in the background of the patients.

Imaging findings of children with PTEN-related hamartoma tumor syndrome: a 20-year multicentric pediatric cohort.

PTEN-related hamartoma tumor syndrome results from a mutation in the PTEN gene located at 10q23.31. This syndrome represents a spectrum of different phenotypes of variable expressions, now recognized as part of the same condition. Patients with this mutation have an increased risk of developing a wide range of findings, including malignancies. Although widely described in adults, there are no large series describing the imaging findings in patients before adulthood. Knowledge of the findings seen in children and adolescents with PTEN-related hamartoma tumor syndrome can help guide further management and improve surveillance recommendations. To describe the spectrum of imaging abnormalities in pediatric patients with PTEN-related hamartoma tumor syndrome. We performed a retrospective, cross-sectional, multicenter study conducted between January 2000 and October 2021 in three tertiary pediatric institutions evaluating the imaging findings in children and adolescents (≤ 18 years) with confirmed diagnoses of a PTEN mutation. For each patient, the imaging findings, histopathology reports, and at least a 2-year follow-up of clinical outcomes for non-operative cases were documented. The cohort included 78 children (37 girls), with a mean age at diagnosis of 7.5 years (range 0 days to 18 years). Benign brain findings included enlarged Virchow-Robin perivascular spaces, white matter changes, developmental venous anomalies, and cerebellar hamartomas. Benign thyroid findings were common, but 5/45 (11.1%) with thyroid abnormalities had a malignant nodule. Soft tissue adipocytic tumors, GI/GU polyps, other soft tissue abnormalities, along with vascular anomalies in various anatomic locations were common. Brain abnormalities, benign non-vascular soft tissue abnormalities, and vascular anomalies are commonly seen in children and adolescents with PTEN-related hamartoma tumor syndrome. However, malignancies involving the thyroid gland are not uncommon. Familiarity with the phenotype of PTEN-related hamartoma tumor syndrome in the pediatric population can improve diagnosis and prompt appropriate clinical surveillance of abnormal findings that warrant further management.

Transport-of-intensity model for single-mask x-ray differential phase contrast imaging

X-ray phase contrast imaging holds great promise for improving the visibility of light-element materials such as soft tissues and tumors. The single-mask differential phase contrast imaging method stands out as a simple and effective approach to yield differential phase contrast. In this work, we introduce a model for a single-mask phase imaging system based on the transport-of-intensity equation. Our model provides an accessible understanding of signal and contrast formation in single-mask x-ray phase imaging, offering a clear perspective on the image formation process, for example, the origin of alternate bright and dark fringes in phase contrast intensity images. Aided by our model, we present an efficient retrieval method that yields differential phase contrast imagery in a single acquisition step. Our model gives insight into the contrast generation and its dependence on the system geometry and imaging parameters in both the initial intensity image as well as retrieved images. The model validity as well as the proposed retrieval method are demonstrated via both experimental results on a system developed in house as well as Monte Carlo simulations. In conclusion, our work not only provides a model for an intuitive visualization of image formation but also offers a method to optimize differential phase imaging setups, holding tremendous promise for advancing medical diagnostics and other applications.

Facile synthesis of manganese-hafnium nanocomposites for multimodal MRI/CT imaging and in vitro photodynamic therapy of colon cancer

Precise diagnosis of complex and soft tumors is challenging, which limits appropriate treatment options to achieve desired therapeutic outcomes. However, multifunctional nano-sized contrast enhancement agents based on nanoparticles improve the diagnosis accuracy of various diseases such as cancer. Herein, a facile manganese-hafnium nanocomposites (Mn3O4-HfO2 NCs) system was designed for bimodal magnetic resonance imaging (MRI)/computed tomography (CT) contrast enhancement with a complimentary function of photodynamic therapy. The solvothermal method was used to fabricate NCs, and the average size of Mn3O4 NPs and Mn3O4-HfO2 NCs was about 7 nm and 15 nm, respectively, as estimated by TEM. Dynamic light scattering results showed good dispersion and high negative (-33 eV) zeta potential, indicating excellent stability in an aqueous medium. Mn3O4-HfO2 NCs revealed negligible toxic effects on the NCTC clone 929 (L929) and mouse colon cancer cell line (CT26), demonstrating promising biocompatibility. The synthesized Mn3O4-HfO2 NCs exhibit significant enhancement in T1-weighted magnetic resonance imaging (MRI) and X-ray computed tomography (CT), indicating the appropriateness for dual-modal MRI/CT molecular imaging probes. Moreover, ultra-small Mn3O4-HfO2 NCs show good relaxivities for MRI/CT. These nanoprobes Mn3O4-HfO2 NCs further possessed outstanding reactive oxygen species (ROS) generation ability under minute ultraviolet light (6 mW·cm−2) to ablate the colon cancer cells in vitro. Therefore, the designed multifunctional Mn3O4-HfO2 NCs were ideal candidates for cancer diagnosis and photodynamic therapy.

Giant retroperitoneal myolipoma mimicking liposarcoma: report of a resected case and review of the literature.

Myolipomas are rare tumors that are often difficult to differentiate from liposarcoma. Herein, we report a case of resected giant myolipoma preoperatively diagnosed as liposarcoma. A 63-year-old woman was suspected of having a large retroperitoneal liposarcoma on October 202X. The patient was referred to our department for tumor resection and a histological diagnosis. After consultation with the urology, obstetric and gynecology, and vascular surgery departments, tumor resection was planned, including the potential resection of other organs. Intraoperative findings revealed a large, elastic, soft tumor with a smooth surface and a capsule occupying the entire abdominal cavity. The tumor was adherent to the stomach, left colon, and uterine adnexa, and no invasion was observed. The tumor was completely resected, and organ resection was not necessary. The tumor was 40cm in diameter and 4.0kg in weight. Pathological examination and immunostaining confirmed a diagnosis of myolipoma. The patient's postoperative course was uneventful, and she was discharged on postoperative day 10 with no complications. Twelve months after surgery, the patient was doing well. To the best of our knowledge, we report a complete resection of the largest retroperitoneal myolipoma reported to date. Physicians should consider surgery, even for suspected large sarcomas that may be difficult to resect completely.

Giant Retropharyngeal Lipoma

Lipoma is a common soft tumor tissue that can develop anywhere in the body. The retropharyngeal space is a rare location for these benign tumors. Clinically it procures dysphagia, pharyngeal discomfort, snoring, or sleep apnea. Imaging (CT Scan and MRI) is necessary for diagnosis, extension, and previous surgical procedures. We report in this publication a giant lipoma of retropharyngeal space in 75 year old man diagnosed after dysphagia exploration and treated with trans cervical surgical approach.

Diffusion-weighted imaging does not seem to be a predictor of consistency in pituitary adenomas.

To prospectively evaluate the usefulness of T1-weighted imaging (T1WI) and diffusion-weighted imaging (DWI) sequences in predicting the consistency of macroadenomas. In addition, to determine their values ​​as prognostic factors of surgical outcomes. Patients with pituitary macroadenoma and surgical indication were included. All patients underwent pre-surgical magnetic resonance imaging (MRI) that included the sequences T1WI before and after contrast administration and DWI with the apparent diffusion coefficient (ADC) map. Post-surgical MRI was performed at least 3months after surgery. The consistency of the macroadenomas was evaluated at surgery, and they were grouped into soft and intermediate/hard adenomas. Mean ADC values, signal on T1WI and the ratio of tumor ADC values ​​to pons (ADCR) were compared with tumor consistency and grade of surgical resection. A total of 80 patients were included. A softened consistency was found at surgery in 53 patients and hardened in 27 patients. The median ADC in the soft consistency group was 0.532 × 10-3 mm2/sec (0.306-1.096 × 10-3 mm2/sec), and in the intermediate/hard consistency group was 0.509 × 10-3 mm2/sec (0.308-0.818 × 10-3 mm2/sec). There was no significant difference between the median values ​​of ADC, ADCR and signal on T1W between the soft and hard tumor groups, or between patients with and without tumor residue. Our results did not show usefulness of the DWI and T1WI for assessing the consistency of pituitary macroadenomas, nor as a predictor of the degree of surgical resection.

Development of a c-MET x CD137 bispecific antibody for targeted immune agonism in cancer immunotherapy

BackgroundTargeting the costimulatory receptor CD137 has shown promise as a therapeutic approach for cancer immunotherapy, resulting in anti-tumor efficacy demonstrated in clinical trials. However, the initial CD137 agonistic antibodies, urelumab and utomilumab, faced challenges in clinical trials due to the liver toxicity or lack of efficacy, respectively. Concurrently, c-MET has been identified as a highly expressed tumor-associated antigen (TAA) in various solid and soft tumors. MethodsIn this study, we aimed to develop a bispecific antibody (BsAb) that targets both c-MET and CD137, optimizing the BsAb format and CD137 binder for efficient delivery of the CD137 agonist to the tumor microenvironment (TME). We employed a monovalent c-MET motif and a trimeric CD137 Variable Heavy domain of Heavy chain (VHH) for the BsAb design. ResultsOur results demonstrate that the c-MET x CD137 BsAb provides co-stimulation to T cells through cross-linking by c-MET-expressing tumor cells. Functional immune assays confirmed the enhanced efficacy and potency of the c-MET x CD137 BsAb, as indicated by activation of CD137 signaling, target cell killing, and cytokine release in various tumor cell lines. Furthermore, the combination of c-MET x CD137 BsAb with Pembrolizumab showed a dose-dependent enhancement of target-induced T cell cytokine release. ConclusionOverall, the c-MET x CD137 BsAb exhibits a promising developability profile as a tumor-targeted immune agonist by minimizing off-target effects while effectively delivering immune agonism. It has the potential to overcome resistance to anti-PD-(L)1 therapies.

Angiomatoid fibrous histiocytoma: primary intracranial lesion with thoracic spine metastasis and a malignant course. Illustrative case.

Angiomatoid fibrous histiocytoma (AFH) is an exceptionally rare soft tissue neoplasm. This tumor primarily presents as a benign soft tissue lesion in children with an average age of 14 years. The standard treatment regimen is wide local excision with interval follow-up. However, newer reports have demonstrated malignant potential with the possibility of intracranial metastasis. A 45-year-old male with no soft tissue primary tumor presented with a primary intracranial lesion and thoracic spine metastasis refractory to chemotherapy and radiation treatment. This report illustrates the potential for a highly malignant nature of metastatic AFH. In addition, the authors demonstrate an incidence of AFH in a middle-aged male without a primary soft tissue or skin lesion. This report highlights the importance of prompt treatment and excision for AFH, as there is still little understanding of successful options for systemic therapy.