bims-netuvo Biomed News
on Nerves in tumours of visceral organs
Issue of 2023–02–12
twelve papers selected by
Maksym V. Kopanitsa, The Francis Crick Institute



  1. Brain Behav Immun. 2023 Feb 06. pii: S0889-1591(23)00029-6. [Epub ahead of print]
      Pain is one of the most severe complications affecting the quality of life of cancer patients. Although substantial progress has been made in the diagnosis and treatment of cancer, the neurobiological mechanism of cancer pain is still unclear. In the present study, we identified the critical role of CXC chemokine 2 (CXCL2), released by Schwann cells after being activated by cancer cells, in maintaining cancer-induced macrophage infiltration and the resulting mechanical hypersensitivity and persistent spontaneous nociception. In vitro, Schwann cells cocultured with breast cancer cells exhibited a significant increase in CXCL2 expression; in addition, conditioned medium from Schwann cells activated by breast cancer cells had a similar effect to recombinant CXCL2 in terms of inducing macrophage migration. Targeting CXCL2 signaling by both CXC chemokine receptor 2 (CXCR2) antagonist pharmacological blockade and anti-CXCL2 mAb immunological blockade robustly prevented conditioned medium-induced macrophage migration. In vivo, both application of recombinant CXCL2 and perineural breast cancer cell implantation resulted in mechanical hypersensitivity and persistent spontaneous nociception in mice, along with increased macrophage infiltration into the sciatic nerves. Similar to the in vitro results, inhibition of CXCL2/CXCR2 signaling or conditional knockdown of CXCL2 in sciatic nerve Schwann cells effectively attenuated breast cancer cell-induced mechanical hypersensitivity, persistent spontaneous nociception, and macrophage recruitment in the sciatic nerve. Mechanistically, we found that redox effector factor-1 (Ref-1) secreted by breast cancer cells activated hypoxia inducible factor-1α (HIF-1α) expression and inhibited reactive oxygen species (ROS) production in Schwann cells, ultimately inducing CXCL2 expression in Schwann cells. In brief, the present study expands new insights into cancer pain mechanisms from promising animal models to provide new strategies for the control of cancer pain.
    Keywords:  Breast cancer; CXCL2/CXCR2 signaling; Cancer pain; Macrophage; Schwann cell
    DOI:  https://doi.org/10.1016/j.bbi.2023.02.004
  2. Int J Mol Sci. 2023 Jan 28. pii: 2540. [Epub ahead of print]24(3):
      Glutamate is a key player in excitatory neurotransmission in the central nervous system (CNS). The N-methyl-D-aspartate receptor (NMDAR) is a glutamate-gated ion channel which presents several unique features and is involved in various physiological and pathological neuronal processes. Thanks to great efforts in neuroscience, its structure and the molecular mechanisms controlling its localization and functional regulation in neuronal cells are well known. The signaling mediated by NMDAR in neurons is very complex as it depends on its localization, composition, Ca2+ influx, and ion flow-independent conformational changes. Moreover, NMDA receptors are highly diffusive in the plasma membrane of neurons, where they form heterocomplexes with other membrane receptors and scaffold proteins which determine the receptor function and activation of downstream signaling. Interestingly, a recent paper demonstrates that NMDAR signaling is involved in epithelial cell competition, an evolutionary conserved cell fitness process influencing cancer initiation and progress. The idea that NMDAR signaling is limited to CNS has been challenged in the past two decades. A large body of evidence suggests that NMDAR is expressed in cancer cells outside the CNS and can respond to the autocrine/paracrine release of glutamate. In this review, we survey research on NMDAR signaling and regulation in neurons that can help illuminate its role in tumor biology. Finally, we will discuss existing data on the role of the glutamine/glutamate metabolism, the anticancer action of NMDAR antagonists in experimental models, NMDAR synaptic signaling in tumors, and clinical evidence in human cancer.
    Keywords:  NMDAR; cancers; glutamate; metabolism; neuron
    DOI:  https://doi.org/10.3390/ijms24032540
  3. Case Rep Dermatol Med. 2023 ;2023 6944296
      We report a very rare case of pathologically confirmed sebaceous carcinoma of the glans penis with multiple areas of lymphovascular and perineural invasion and multiple lymph node metastases. The importance of immunohistochemical staining in diagnosis is also reviewed.
    DOI:  https://doi.org/10.1155/2023/6944296
  4. BMC Neurol. 2023 Feb 10. 23(1): 65
       BACKGROUND: We present the case of a patient with a rare synovial sarcoma (SS) of the tibial nerve. So far, only 4 cases of patients with SS originating from the tibial nerve have been described in the literature, and our patient is only the second patient whose limb was saved during treatment. Synovial sarcomas are malignant mesenchymal tumors, i.e., tumors arising from connective tissue. Synovial sarcomas account for 5-10% of all soft tissue sarcomas. However, the name synovial sarcoma is misleading, because the tumor does not originate from synovial cells, but rather from primitive mesenchymal cells. The name most likely originated from the localization around the large joints on the limbs, more often on the lower ones, in the area of the knee joints. We point out the aspects of correct and quick diagnosis and subsequent treatment, which has very important effect on the patient's prognosis. Primary less radical excision without prior biopsy verification leads to a higher risk of local recurrence, even if a proper reexcision was performed immediately after biopsy verification of the sarcoma.
    CASE PRESENTATION: A woman born in 1949 began to suffer at the end of 2020 with escalating pain under the left inner ankle with a projection to the sole and fingers. Her personal, family work and social history were insignificant. After the initial neurological examination, the patient was sent for an ultrasound examination of the ankle, which showed a lobular mass measuring 50 × 22 × 16 mm and according magnetic resonance imaging, the finding appeared to be a suspicious neurinoma of the tibial nerve. The tumor was surgically excised, without prior biopsy verification: a 50 × 20 mm tumor was dissected in the distal part of the tarsal canal, which grew through the structure of the tibial nerve and in some places into the surrounding area and appeared intraoperatively as a neurofibroma. But histologically the tumor was classified as monophasic synovial sarcoma. The patient was indicated for a wide reexcision of the skin with the subcutaneous tissue of size 91 × 20 × 15 mm. Now the patient is being treated with external radiotherapy to the tumor bed and she is able to walk.
    CONCLUSION: This report draws attention to a rare type of malignant nerve tumor, which both clinically and radiologically can mimic benign peripheral nerve sheath tumors. Synovial sarcoma should be considered in very painful resistances, typically located around the joints of the lower limbs, the growth of which can be slow. Because the size of the tumor is a negative prognostic factor, it is necessary to make a timely diagnosis using MR imaging and a biopsy with histological examination and to start treatment quickly. Surgical treatment should take place only after a biopsy with histological examination of the tumor so that it is sufficiently radical and does not have to undergo an additional reoperation, as happened in the case of our patient.
    Keywords:  Case report; Rare tumor; Synovial sarcoma; Tibial nerve
    DOI:  https://doi.org/10.1186/s12883-023-03061-5
  5. Pediatr Neurosurg. 2023 Feb 06.
       BACKGROUND: Neurofibromatosis type 1 and neurofibromatosis type 2 are unrelated, distinct genetic disorders characterized by the development of central and peripheral nervous system tumors.
    SUMMARY: Neurofibromatosis type 1 is the most common inherited tumor predisposition syndrome with a lifelong increased risk of benign and malignant tumor development, such as glioma and nerve sheath tumors. Neurofibromatosis type 2 classically presents with bilateral vestibular schwannoma, yet is also associated with non-vestibular schwannoma, meningioma, and ependymoma. Historically, the number of effective therapies for neurofibromatosis-related neoplasms has been limited.
    KEY MESSAGE: In the past decade there have been significant advances in the development of precision-based therapies for NF-associated tumors with an increased emphasis on functional outcomes in addition to tumor response. Continued scientific discovery and advancement of targeted therapies for NF-associated neoplasms are necessary to continue to improve outcomes for patients with NF.
    DOI:  https://doi.org/10.1159/000529507
  6. Ann Plast Surg. 2023 Feb 04.
       INTRODUCTION: The incidence of malignant peripheral nerve sheath tumors (MPNSTs) is 0.001%. Commonly, MPNST arise in neurofibromatosis; however, they can occur sporadically, de novo or from a preexisting neurofibroma. Malignant peripheral nerve sheath tumors are aggressive tumors with high rates of local recurrence and metastasis. The prognosis is poor with 5-year survival rates of 15% to 50%. Unfortunately, given the rarity of these tumors, it is not clear how to best manage these patients. The purposes of this study were (1) to discuss our experience with MPNST and particularly our difficulties with diagnosis and management, and (2) to review the literature.
    MATERIALS AND METHODS: We report on all tumors of the brachial plexus excised between 2013 and 2019. We report 3 cases of MPNST, their treatment, and their outcomes.
    RESULTS: Thirteen patients underwent surgical excision of an intrinsic brachial plexus mass. Three of these patients (2 male, 1 female; average age, 36 years) were diagnosed with an MPNST. Two patients with an MPNST had neurofibromatosis type 1. All patients with an MPNST had a tumor >8 cm, motor and sensory deficits, and pain. All 3 patients with MPNST underwent a magnetic resonance imaging (MRI) before diagnosis. The average time from initial symptom onset to MRI was 12.3 months. Only 1 of the MRIs suggested a malignant tumor, with no MRI identifying an MPNST. One patient underwent an excisional biopsy, and 2 had incisional biopsies. Because of the lack of diagnosis preoperatively, all patients had positive margins given the limited extent of surgery. Returning for excision in an attempt to achieve negative margins in a large oncologically contaminated field was not possible because defining the boundaries of the initial surgical field was unachievable; therefore, the initial surgery was their definitive surgical management. All patients were referred to oncology and received radiation therapy.
    CONCLUSIONS: Malignant peripheral nerve sheath tumors must be suspected in enlarging masses (>5 cm) with the constellation of pain, motor, and sensory deficits. Computed tomography- or ultrasound-guided core needle biopsy under brachial plexus block or sedation is required for definitive diagnosis to allow for a comprehensive approach to the patient's tumor with a higher likelihood of disease-free survival.
    DOI:  https://doi.org/10.1097/SAP.0000000000003462
  7. J Clin Med. 2023 Feb 03. pii: 1227. [Epub ahead of print]12(3):
       BACKGROUND: Combining traditional clinical parameters with neuroendocrine markers to construct a nomogram model to predict the postoperative recurrence of neuroendocrine carcinoma of cervix (NECC).
    METHODS: A total of 257 patients were included in this study. Univariate and multivariate Cox regression analyses were used to establish a nomogram model in the training cohorts, which was further validated in the validation cohorts. The calibration curve was used to conduct the internal and external verification of the model.
    RESULTS: Overall, 41 relapse cases were observed in the training (23 cases) and validation (18 cases) cohorts. The univariate analysis preliminarily showed that FIGO stage, stromal invasion, nerve invasion, lymph vascular space invasion, lymph node involvement, cervical-uterine junction invasion and CgA were correlated with NECC recurrence. The multivariate analysis further confirmed that FIGO stage (p = 0.023), stromal invasion (p = 0.002), lymph vascular space invasion (p = 0.039) and lymph node involvement (p = 0.00) were independent risk factors for NECC recurrence, which were ultimately included in the nomogram model. In addition, superior consistency indices were demonstrated in the training (0.863, 95% CI 0.784-0.942) and validation (0.884, 95% CI 0.758-1.010) cohorts.
    CONCLUSIONS: The established nomogram model combining traditional clinical parameters with neuroendocrine markers can reliably and accurately predict the recurrence risks in NECC patients.
    Keywords:  classical parameters; neuroendocrine carcinoma of cervix; neuroendocrine markers; nomogram model; recurrence
    DOI:  https://doi.org/10.3390/jcm12031227
  8. Pan Afr Med J. 2022 ;43 139
      Schwannomas are the most common benign tumors of the peripheral nerves, but represents only 5%-8% of all soft tissue tumors. Their diagnosis is usually delayed due to their slow growth and the nervous adaptation to their increased volume. Ultrasound sonography and magnetic resonance imaging (MRI) images usually ease the diagnosis. Correct enucleation offers very good postoperative outcomes and avoids recurrences. We report an unusual case of schwannoma of the radial nerve (RN) that remained asymptomatic for one year and a half, and treated well, had good outcomes.
    Keywords:  Schwannoma; case report; delayed diagnosis; enucleation; radial nerve
    DOI:  https://doi.org/10.11604/pamj.2022.43.139.37453
  9. Dermatol Surg. 2023 Feb 10.
       BACKGROUND: Malignant peripheral nerve sheath tumors (MPNSTs) are clinically aggressive soft tissue sarcomas that can present as cutaneous or subcutaneous based tumors that are commonly associated with neurofibromatosis type 1. Historically, these tumors have poor outcomes. Previously, no study has compared survival of cutaneous versus subcutaneous MPNSTs.
    OBJECTIVE: This study aims to investigate the difference in overall survival (OS) among cutaneous MPNSTs, subcutaneous MPNSTs of the head and neck, and subcutaneous MPNSTs of the trunk and extremities.
    MATERIALS AND METHODS: Nine hundred eighteen patients were included in this retrospective study using the Surveillance, Epidemiology, and End-Results (SEER-9) database with primary cutaneous or subcutaneous MPNSTs from 1975 to 2016. OS was calculated using cox proportional hazard models for each group.
    RESULTS: No significant difference was revealed in OS between cutaneous or subcutaneous MPNSTs, regardless of location. Factors associated with decreased OS included advanced age, higher grade, and nondefinitive surgical modality.
    CONCLUSION: This study results implies that unlike other soft tissue sarcomas, cutaneous presentation does not improve OS in patients with MPNSTs compared with their subcutaneous counterparts.
    DOI:  https://doi.org/10.1097/DSS.0000000000003717
  10. Int J Surg Case Rep. 2023 Feb 06. pii: S2210-2612(23)00043-3. [Epub ahead of print]103 107915
       INTRODUCTION AND IMPORTANCE: Schwannoma is the most common benign tumor of peripheral nerves and usually occurs solitary with a very low risk of recurrence. Schwannoma of the hand, particularly involving the digital nerve, is sporadic and most commonly leads to a misdiagnosis due to its rarity. Histopathology remains the gold standard diagnostic, however, with a thorough physical examination and radiologic imaging, this benign tumor can be managed well with the preservation of nerve function.
    CASE PRESENTATION: We reported a rare case of digital nerve schwannomas on the bilateral hands of a 52-year-old white male with one recurrent mass on the right hand despite a previously complete debulking of the mass.
    CLINICAL DISCUSSION: Intraoperatively, we removed lobulated whitish-yellow masses and left the nerve origin of the tumor intact (common palmar digital nerve and ulnar-side digital nerve). The histopathology supported the diagnosis of schwannoma. At the one-year follow-up, there is no recurrence and the patient remains asymptomatic.
    CONCLUSION: Determining differential diagnosis by both clinical and preoperative imaging is essential, especially in the case of recurrence and multiple tumorous lesions. Malignancy or malignant degeneration should still be kept in mind. Complete removal is needed to prevent recurrence followed by a long-term follow-up.
    Keywords:  Benign tumor; Digital nerve tumor; Hand tumor; Neurilemmoma; Schwannoma
    DOI:  https://doi.org/10.1016/j.ijscr.2023.107915
  11. J Cardiothorac Surg. 2023 Feb 10. 18(1): 69
       BACKGROUND: Schwannoma is the most common mediastinal neurogenic tumor, while schwannoma originating from mediastinal vagus nerve is rare.
    CASE PRESENTATION: This article reported one case of schwannoma originating from vagus nerve in the right superior mediastinum. The mediastinal schwannoma was completely resected through a right-sided video-assisted thoracoscopic thoracotomy. Histologic examination clarified the diagnosis as schwannoma.
    CONCLUSION: Chest CT scan and MRI can be used to determine the location of mediastinal schwannoma and its relationship with adjacent tissue. Histologic examination showing distinctive feature of Antoni A areas and Antoni B areas can help clarify the diagnosis. Complete surgical resection is the first-line treatment option for mediastinal schwannomas.
    Keywords:  Mediastinal neurogenic tumor; Schwannoma; Vagus nerve
    DOI:  https://doi.org/10.1186/s13019-023-02177-6