The depth of perineural invasion is an independent prognostic factor for stage II colorectal cancer.

BACKGROUND: Perineural invasion (PNI) is the invasion of nerves by cancer cells and is associated with poor survival in stage II colorectal cancer. However, PNI can be further subdivided according to the depth of invasion, and the depth of PNI has not been clearly linked to prognosis. METHOD: This study aimed to assess the prognostic value of different depths of PNI in stage II colorectal cancer. We defined PNI in the submucosal plexus and myenteric plexus as superficial perineural invasion (sup-PNI) and PNI in the subserous plexus as deep perineural invasion (deep-PNI). Patients were divided into three groups based on the depth of PNI: sup-PNI, deep-PNI and non-PNI. Then, univariate and multivariate Cox regression analyses were conducted to evaluate the role of PNI in the prognosis of stage II colorectal cancer. RESULTS: This study enrolled 3508 patients with stage II colorectal cancer who underwent resection for primary colorectal lesions between January 2013 and September 2019. Clinicopathological features, including elevated carcinoembryonic antigen (CEA) levels, T4 stage, poor differentiation, deficient DNA mismatch repair (dMMR), and vascular invasion, were correlated with deep-PNI. Multivariate analyses revealed that deep-PNI was associated with worse overall survival (OS; hazard ratio [HR], 3.546; 95% confidence interval [CI], 2.307-5.449; P < 0.001) and disease-free survival (DFS; HR, 2.921; 95% CI, 2.032-4.198; P < 0.001), compared with non-PNI. Conversely, no significant difference in OS or DFS was observed between the sup-PNI and non-PNI groups in multivariate analyses. CONCLUSIONS: The study demonstrated that the depth of PNI was an independent prognostic factor for patients with stage II colorectal cancer, and patients with deep PNI had a worse prognosis. Thus, patients with PNI require further subdivision according to the depth of invasion.

Autoreactive T cells target peripheral nerves in Guillain-Barré syndrome.

Guillain-Barré syndrome (GBS) is a rare heterogenous disorder of the peripheral nervous system, which is usually triggered by a preceding infection, and causes a potentially life-threatening progressive muscle weakness1. Although GBS is considered an autoimmune disease, the mechanisms that underlie its distinct clinical subtypes remain largely unknown. Here, by combining in vitro T cell screening, single-cell RNA sequencing and T cell receptor (TCR) sequencing, we identify autoreactive memory CD4+ cells, that show a cytotoxic T helper 1 (TH1)-like phenotype, and rare CD8+ T cells that target myelin antigens of the peripheral nerves in patients with the demyelinating disease variant. We characterized more than 1,000 autoreactive single T cell clones, which revealed a polyclonal TCR repertoire, short CDR3ß lengths, preferential HLA-DR restrictions and recognition of immunodominant epitopes. We found that autoreactive TCRß clonotypes were expanded in the blood of the same patient at distinct disease stages and, notably, that they were shared in the blood and the cerebrospinal fluid across different patients with GBS, but not in control individuals. Finally, we identified myelin-reactive T cells in the nerve biopsy from one patient, which indicates that these cells contribute directly to disease pathophysiology. Collectively, our data provide clear evidence of autoreactive T cell immunity in a subset of patients with GBS, and open new perspectives in the field of inflammatory peripheral neuropathies, with potential impact for biomedical applications.

When biopsy goes wrong: a case series of misdiagnoses and complications from biopsies of masses of unknown origin potentially originating from a peripheral nerve.

OBJECTIVE: Biopsies of peripheral nerve tumors (PNTs) are often used to plan an efficient treatment strategy. However, performing a biopsy is controversial when the mass is likely to be a benign PNT (BPNT). The aim of this study was to evaluate the side effects of biopsies in patients with potential PNTs. METHODS: A retrospective and cross-sectional study was conducted on 24 patients who underwent biopsy of a mass of unknown origin potentially originating from a peripheral nerve (MUOPON), performed in nonspecialty services, and who were later referred to the authors' service for resection of their lesion between January 2005 and December 2022. The patients were evaluated for pain score, presence of a motor or sensory deficit, biopsy diagnosis, and definitive histopathological postsurgical diagnosis. RESULTS: The location of the tumor was supraclavicular in 7 (29.2%) patients, in the axillary region in 3 (12.5%), in the upper limb in 7 (29.2%), and in the lower limb in 7 (29.2%). Twenty-one (87.5%) patients were evaluated by MRI before biopsy, and 3 (12.5%) underwent ultrasound. One patient did not have an examination before the procedure. Based on the biopsy findings, 12 (50%) analyses had an inconclusive histopathological result. The preexisting pain worsened, as measured 1 week after biopsy, in all patients and had remained unchanged at the first evaluation by the authors (median 3 months, range 2-4 months). In 1 case, the open biopsy had to be interrupted because the patient experienced excruciating pain. Four (16.7%) patients developed motor deficits. Subsequent surgery was hampered by scar formation and intratumoral hemorrhage in 5 (20.8%) patients. The initial diagnosis obtained by biopsy differed from the final histopathological diagnosis in all patients, of whom 21 (87.5%) had BPNTs, 2 (8.3%) malignant peripheral nerve sheath tumors, and 1 (4.2%) an ancient schwannoma. CONCLUSIONS: Biopsies of PNTs are controversial and may result in misdiagnosis, neuropathic pain, or neurological deficit due to axonal damage, and they may also hinder microsurgical resection when if performed when not indicated. Indications for biopsy of an MUOPON must be carefully considered, especially if BPNT is a possible diagnosis.

Granuloma, vasculitis, and demyelination in sarcoid neuropathy.

BACKGROUND: Despite the suggestion that direct compression by granuloma and ischemia resulting from vasculitis can cause nerve fiber damage, the mechanisms underlying sarcoid neuropathy have not yet been fully clarified. METHODS: We examined the clinicopathological features of sarcoid neuropathy by focusing on electrophysiological and histopathological findings of sural nerve biopsy specimens. We included 18 patients with sarcoid neuropathy who had non-caseating epithelioid cell granuloma in their sural nerve biopsy specimens. RESULTS: Although electrophysiological findings suggestive of axonal neuropathy were observed, particularly in the lower limbs, all but three patients showed ≥1 abnormalities in nerve conduction velocity or distal motor latency. Additionally, a conduction block was observed in 11 of the 16 patients for whom waveforms were assessed; five of them fulfilled motor nerve conduction criteria strongly supportive of demyelination as defined in the European Academy of Neurology/Peripheral Nerve Society (EAN/PNS) guideline for chronic inflammatory demyelinating polyneuropathy (CIDP). In most patients, sural nerve biopsy specimens revealed a mild to moderate degree of myelinated fiber loss. Fibrinoid necrosis was observed in one patient, and electron microscopy analysis revealed demyelinated axons close to granulomas in six patients. CONCLUSIONS: Patients with sarcoid neuropathy may meet the EAN/PNS electrophysiological criteria for CIDP due to the frequent presence of conduction blocks. Based on our results, in addition to the ischemic damage resulting from granulomatous inflammation, demyelination may play an important role in the mechanism underlying sarcoid neuropathy.

M2 macrophage-derived cathepsin S promotes peripheral nerve regeneration via fibroblast-Schwann cell-signaling relay.

BACKGROUND: Although peripheral nerves have an intrinsic self-repair capacity following damage, functional recovery is limited in patients. It is a well-established fact that macrophages accumulate at the site of injury. Numerous studies indicate that the phenotypic shift from M1 macrophage to M2 macrophage plays a crucial role in the process of axon regeneration. This polarity change is observed exclusively in peripheral macrophages but not in microglia and CNS macrophages. However, the molecular basis of axonal regeneration by M2 macrophage is not yet fully understood. Herein, we aimed to identify the M2 macrophage-derived axon regeneration factor. METHODS: We established a peripheral nerve injury model by transection of the inferior alveolar nerve (IANX) in Sprague-Dawley rats. Transcriptome analysis was performed on the injured nerve. Recovery from sensory deficits in the mandibular region and histological reconnection of IAN after IANX were assessed in rats with macrophage depletion by clodronate. We investigated the effects of adoptive transfer of M2 macrophages or M2-derived cathepsin S (CTSS) on the sensory deficit. CTSS initiating signaling was explored by western blot analysis in IANX rats and immunohistochemistry in co-culture of primary fibroblasts and Schwann cells (SCs). RESULTS: Transcriptome analysis revealed that CTSS, a macrophage-selective lysosomal protease, was upregulated in the IAN after its injury. Spontaneous but partial recovery from a sensory deficit in the mandibular region after IANX was abrogated by macrophage ablation at the injured site. In addition, a robust induction of c-Jun, a marker of the repair-supportive phenotype of SCs, after IANX was abolished by macrophage ablation. As in transcriptome analysis, CTSS was upregulated at the injured IAN than in the intact IAN. Endogenous recovery from hypoesthesia was facilitated by supplementation of CTSS but delayed by pharmacological inhibition or genetic silencing of CTSS at the injured site. Adoptive transfer of M2-polarized macrophages at this site facilitated sensory recovery dependent on CTSS in macrophages. Post-IANX, CTSS caused the cleavage of Ephrin-B2 in fibroblasts, which, in turn, bound EphB2 in SCs. CTSS-induced Ephrin-B2 cleavage was also observed in human sensory nerves. Inhibition of CTSS-induced Ephrin-B2 signaling suppressed c-Jun induction in SCs and sensory recovery. CONCLUSIONS: These results suggest that M2 macrophage-derived CTSS contributes to axon regeneration by activating SCs via Ephrin-B2 shedding from fibroblasts.

Indolent Multinodular Synovial Sarcoma of Peripheral Nerves Mimicking Schwannoma: A Case Report and Literature Review.

BACKGROUND/AIM: Most cases of synovial sarcoma (SS) are aggressive and large-sized; only few show indolent behavior, having a small size. Nerves are rare sites of SS occurrence. An atypical case of SS can lead to its misdiagnosis as a benign tumor and delay its treatment. CASE REPORT: Here, we report a case of primary SS of indolent multinodular synovial sarcoma of peripheral nerves. Considering the clinical and imaging findings at the first visit, we suspected a benign tumor and continued careful follow-up. Three years later, marginal resection was performed and SS was suspected. We then performed an additional wide resection using a free flap. Histopathologically, the proximal tumor showed a diffuse proliferation of spindle cells without pleomorphism, whereas the distal tumor showed a similar histology with more hypercellularity. Additional wide-resection specimens showed remnant tumors derived from the peripheral nerve. Immunohistochemistry (IHC) showed positive staining for SS18:SSX and SSX in both tumors and fluorescence in situ hybridization showed positive staining for the SS18 split in both tumors. Finally, SS of the peripheral nerve was diagnosed. Owing to FNCLCC grade 2 tumor and tumor size, adjuvant chemotherapy was not performed. CONCLUSION: In cases of SS or other sarcomas with atypical clinical courses, with imaging findings mimicking benign tumors, we recommend marginal resection along with pathological examination for correct diagnosis.

Unraveling the Mysteries of Perineural Invasion in Benign and Malignant Conditions.

Perineural invasion (PNI) is defined as the dissemination of neoplastic cells within the perineural space. PNI can be a strong indicator of malignancy and is linked to poor prognosis and adverse outcomes in various malignant neoplasms; nevertheless, it can also be seen in benign pathologic conditions. In this review article, we discuss various signaling pathways and neurotrophic factors implicated in the development and progression of PNI. We also describe the methodology, benefits, and limitations of different in vitro, ex vivo, and in vivo models of PNI. The spectrum of presentation for PNI can range from diffuse spread within large nerves ("named" nerves) all the way through localized spread into unnamed microscopic nerves. Therefore, the clinical significance of PNI is related to its extent rather than its mere presence or absence. In this article, we discuss the guidelines for the identification and quantification of PNI in different malignant neoplasms based on the College of American Pathologists (CAP) and World Health Organization (WHO) recommendations. We also describe benign pathologic conditions and neoplasms demonstrating PNI and potential mimics of PNI. Finally, we explore avenues for the future development of targeted therapy options via modulation of signaling pathways involved in PNI.

Localization and Diagnostic Evaluation of Peripheral Nerve Disorders.

OBJECTIVE: This article provides a framework for the initial evaluation of patients with suspected peripheral nerve disease. The key clinical elements of peripheral nerve diseases can help the practicing neurologist differentiate among peripheral neuropathies with similar presentations. LATEST DEVELOPMENTS: The wide range of peripheral nerve diseases with similar clinical presentations can pose a diagnostic challenge. The large array of available testing modalities (including imaging and electrodiagnostic, autonomic, laboratory, biopsy, and genetic testing) further complicates clinical decision making. Recent developments (eg, discovery of new autoantibodies, genetic variations, and histopathologic techniques) across the peripheral neuropathy spectrum have resulted in an increased need to evaluate patients logically and with a tailored diagnostic approach. ESSENTIAL POINTS: A careful approach that focuses on key clinical elements combined with an understanding of purposeful diagnostic testing can lead to a successful diagnosis of peripheral nerve diseases.

A malignant peripheral nerve-sheath tumor: A CARE case report.

INTRODUCTION: Malignant peripheral nerve-sheath tumor (MPNST) is an extremely rare sarcoma of the nasal cavity and paranasal sinuses. Non-specific clinical and radiological presentation and challenging histological diagnosis make it little known by physicians. We describe a case of maxillary sinus MPNST, following CARE guidelines. CASE REPORT: A 62-year-old woman consulted for swelling of the right cheek and hard palate with several months' progression. CT and MRI revealed a tissue mass in the right maxillary sinus with osteolysis of the orbital and maxillary floors, hard palate and lateral and medial walls of the maxillary sinus. Biopsy confirmed diagnosis of low-grade MPNST. After total resection and 60Gy adjuvant radiotherapy, 2-year follow-up showed no signs of recurrence. CONCLUSION: MPNST in the nasal cavity and paranasal sinuses is very rare. Because of a high risk of recurrence, wide resection should be implemented, possibly completed by radiotherapy if resection cannot be complete because of proximity to at-risk structures.

Small vessel platelet thrombosis in the peripheral nerves in POEMS syndrome.

INTRODUCTION/AIMS: Vascular thrombosis is prevalent among patients with polyneuropathy, organomegaly, endocrinopathy M-protein, and skin changes (POEMS) syndrome. The endothelial cells in the endoneurium are often hypertrophied and the lumen is frequently occluded. Consequent local hypoxia may increase vascular endothelial growth factor (VEGF), which induces hypercoagulation and vascular permeability. METHODS: This study presents two patients in the fifth decade of life, who had rare nerve biopsy findings of vascular occlusion mainly by platelets. Before the cases presented here, we encountered nine confirmed POEMS patients whose nerve biopsies did not show similar findings. RESULTS: A small artery and a vein were occluded, but no atherosclerotic changes were observed. The endothelial cells that adhered to the packed platelets lost their junctions. DISCUSSION: Platelet aggregation, degranulation, and ischemia may cause a loose endothelial barrier and leak proinflammatory cytokines, such as interleukin-12. This may increase production of VEGF and may cause nerve demyelination. Small vessel platelet thrombosis may contribute to the pathogenesis of this disorder.

Structural changes in Schwann cells and nerve fibres in type 1 diabetes: relationship with diabetic polyneuropathy.

AIMS/HYPOTHESIS: Our aim was to investigate structural changes of cutaneous Schwann cells (SCs), including nociceptive Schwann cells (nSCs) and axons, in individuals with diabetic polyneuropathy. We also aimed to investigate the relationship between these changes and peripheral neuropathic symptoms in type 1 diabetes. METHODS: Skin biopsies (3 mm) taken from carefully phenotyped participants with type 1 diabetes without polyneuropathy (T1D, n=25), type 1 diabetes with painless diabetic polyneuropathy (T1DPN, n=30) and type 1 diabetes with painful diabetic polyneuropathy (P-T1DPN, n=27), and from healthy control individuals (n=25) were immunostained with relevant antibodies to visualise SCs and nerve fibres. Stereological methods were used to quantify the expression of cutaneous SCs and nerve fibres. RESULTS: There was a difference in the number density of nSCs not abutting to nerve fibres between the groups (p=0.004) but not in the number density of nSCs abutting to nerve fibres, nor in solitary or total subepidermal SC soma number density. The overall dermal SC expression (measured by dermal SC area fraction and subepidermal SC process density) and peripheral nerve fibre expression (measured by intraepidermal nerve fibre density, dermal nerve fibre area fraction and subepidermal nerve fibre density) differed between the groups (all p<0.05): significant differences were seen in participants with T1DPN and P-T1DPN compared with those without diabetic polyneuropathy (healthy control and T1D groups) (all p<0.05). No difference was found between participants in the T1DPN and P-T1DPN group, nor between participants in the T1D and healthy control group (all p>0.05). Correlational analysis showed that cutaneous SC processes and nerve fibres were highly associated, and they were weakly negatively correlated with different neuropathy measures. CONCLUSIONS/INTERPRETATION: Cutaneous SC processes and nerves, but not SC soma, are degenerated and interdependent in individuals with diabetic polyneuropathy. However, an increase in structurally damaged nSCs was seen in individuals with diabetic polyneuropathy. Furthermore, dermal SC processes and nerve fibres correlate weakly with clinical measures of neuropathy and may play a partial role in the pathophysiology of diabetic polyneuropathy in type 1 diabetes.

Avoiding scar tissue formation of peripheral nerves with the help of an acellular collagen matrix.

INTRODUCTION: Extensive scar tissue formation after peripheral nerve injury or surgery is a common problem. To avoid perineural scarring, implanting a mechanical barrier protecting the nerve from inflammation processes in the perineural environment has shown promising results for functional recovery. This study investigates the potential of an acellular collagen-elastin matrix wrapped around a peripheral nerve after induction of scar tissue formation. MATERIALS AND METHODS: In the present study, 30 Lewis rats were separated into three groups and sciatic nerve scarring was induced with 2.5% glutaraldehyde (GA-CM) or 2.5% glutaraldehyde with a supplemental FDA-approved acellular collagen-elastin matrix application (GA+CM). Additionally, a sham group was included for control. Nerve regeneration was assessed by functional analysis using the Visual Statisc Sciatic Index (SSI) and MR neurography during the 12-week regeneration period. Histological and histomorphometry analysis were performed to evaluate the degree of postoperative scar tissue formation. RESULTS: Histological analysis showed an extensive scar tissue formation for GA-CM. Connective tissue ratio was significantly (p < 0.009) reduced for GA+CM (1.347 ± 0.017) compared to GA-CM (1.518 ± 0.057). Similarly, compared to GA+CM, MR-Neurography revealed extensive scar tissue formation for GA-CM with a direct connection between nerve and paraneural environment. Distal to the injury site, quantitative analysis presented significantly higher axon density (p = 0.0145), thicker axon diameter (p = 0.0002) and thicker myelinated fiber thickness (p = 0.0008) for GA+CM compared to GA-CM. Evaluation of functional recovery revealed a significantly faster regeneration for GA+CM. CONCLUSION: The supplemental application of an acellular collagen-elastin matrix showed beneficial effects in histological, radiological, and functional analysis. Therefore, applying a collagen-elastin matrix around the nerve after peripheral nerve injury or surgery may have beneficial effects on preventing scar tissue formation in the long run. This represents a feasible approach to avoid scar tissue formation in peripheral nerve surgery.

Magnetic Resonance Neurography of the Foot and Ankle.

Peripheral neuropathies of the foot and ankle can be challenging to diagnose clinically due to concomitant traumatic and nontraumatic or degenerative orthopedic conditions. Although clinical history, physical examination, and electrodiagnostic testing comprised of nerve conduction velocities and electromyography are used primarily for the identification and classification of peripheral nerve disorders, MR neurography (MRN) can be used to visualize the peripheral nerves as well as the skeletal muscles of the foot and ankle for primary neurogenic pathology and skeletal muscle denervation effect. Proper knowledge of the anatomy and pathophysiology of peripheral nerves is important for an MRN interpretation.

Avian riboflavin deficiency causes reliably reproducible peripheral nerve demyelination and, with vitamin supplementation, rapid remyelination.

Riboflavin deficiency produces severe peripheral neve demyelination in young, rapidly growing chickens. While this naturally-occurring vitamin B2 deficiency can cause a debilitating peripheral neuropathy, and mortality, in poultry flocks, it can also be a useful experimental animal model to study the pathogenesis of reliably reproducible peripheral nerve demyelination. Moreover, restitution of normal riboflavin levels in deficient birds results in brisk remyelination. It is the only acquired, primary, demyelinating tomaculous neuropathy described to date in animals. The only other substance that causes peripheral nerve demyelination similar to avian riboflavin deficiency is tellurium and the pathologic features of the peripheral neuropathy produced by this developmental neurotoxin in weanling rats are also described.

Peripheral Neuropathy in Diabetes: What Can MRI Do?

Diabetes peripheral neuropathy (DPN) is commonly asymptomatic in the early stage. However, once symptoms and obvious defects appear, recovery is not possible. Diagnosis of neuropathy is based on physical examinations, questionnaires, nerve conduction studies, skin biopsies, and so on. However, the diagnosis of DPN is still challenging, and early diagnosis and immediate intervention are very important for prevention of the development and progression of diabetic neuropathy. The advantages of MRI in the diagnosis of DPN are obvious: the peripheral nerve imaging is clear, the lesions can be found intuitively, and the quantitative evaluation of the lesions is the basis for the diagnosis, classification, and follow-up of DPN. With the development of magnetic resonance technology, more and more studies have been conducted on detection of DPN. This article reviews the research field of MRI in DPN.

Autoimmune nodo-paranodopathies 10 years later: Clinical features, pathophysiology and treatment.

BACKGROUND AND AIMS: Autoimmune neuropathies are classified, on the basis of pathophysiology, as demyelinating or axonal. The term nodo-paranodopathy, introduced in 2013 to better categorize the neuropathies with antiganglioside antibodies and later expanded to include neuropathies with antibodies to nodal and paranodal axoglial complexes, characterizes disorders in which the nodal region is critical in the pathogenesis. These neuropathies, although presenting electrophysiologic demyelinating features do not show pathologic evidence of segmental demyelination, or, although being classified as axonal, can show reversible nerve conduction failure and rapid recovery contrary with the communal concept of an axonal neuropathy. METHODS: In this personal view is reported, with a splitting approach, an update on autoimmune nodo-paranodopathies, classified according to the domains of peripheral nerve fiber, the target antigens and the antibody class and subclass involved. The clinical features, the electrophysiologic findings, the results of the immunopathological and ultrastructural studies, the pathophysiology and treatment are also described. RESULTS AND INTERPRETATION: The nodo-paranodopathy category integrates the clinical classification of autoimmune neuropathies and expands the traditional dichotomous demyelinating and axonal classification. It helps to a better systematization pointing to the domain and target antigens of the autoimmune process, it resolves conflicting pathologic and electrophysiologic findings, reconciles the contradiction that axonal neuropathies may be rapidly reversible, avoids taxonomical confusion and possible misdiagnoses. Finally this categorization, through the identification of the specific antibody and its prevalent class and subclass, clarifies the pathophysiological mechanisms and addresses to a more targeted therapeutic approach.

Pretreatment pain predicts perineural invasion in patients with head and neck squamous cell carcinoma.

OBJECTIVES: Perineural invasion (PNI) in head and neck cancer (HNC) is a distinct pathological feature used to indicate aggressive tumor behavior and drive treatment strategies. Our study examined the prevalence and predictors of PNI in HNC patients stratified by tumor site. STUDY DESIGN AND METHODS: A retrospective analysis of head and neck squamous cell carcinoma (HNSCC) patients who underwent surgical resection at the University of Pittsburgh Medical Center between 2015 and 2018 was performed. Pretreatment pain was assessed at least 1 week before surgery using the Functional Assessment of Cancer Therapy-Head and Neck (FACT-H&N). Demographics, clinical characteristics, and concomitant medications were obtained from medical records. Patients with cancers at the oropharynx and non-oropharynx (i.e., cancer at oral cavity, mandible, larynx) sites were separately analyzed. Tumor blocks were obtained from 10 patients for histological evaluation of intertumoral nerve presence. RESULTS: A total of 292 patients (202 males, median age = 60.94 ± 11.06) were assessed. Pain and PNI were significantly associated with higher T stage (p < 0.001) and tumor site (p < 0.001); patients with non-oropharynx tumors reported more pain and had a higher incidence of PNI compared to oropharynx tumors. However, multivariable analysis identified pain as a significant variable uniquely associated with PNI for both tumor sites. Evaluation of nerve presence in tumor tissue showed 5-fold higher nerve density in T2 oral cavity tumors compared to oropharyngeal tumors. CONCLUSIONS: Our study finds that PNI is associated with pretreatment pain and tumor stage. These data support the need for additional research into the impact of tumor location when investigating targeted therapies of tumor regression.

Quantitative Measurement of Perineural Invasion for Prognosis Analysis of Oral Cavity Cancer Treated by Radical Surgery With or Without Adjuvant Therapy.

Objectives: Perineural invasion (PNI) was quantitatively analyzed in oral squamous cell carcinoma (OSCC) specimens obtained by radical surgery to correlate with survival outcomes. Methods: This is a retrospective study that reviewed the Cancer registry data between 2009 and 2015. Inclusion criteria were oral cavity cancer, treatment by radical surgery, presence of PNI, and available pathologic samples for S100 staining. Patients with M1 disease and those with synchronous or metachronous cancer during staging work-up were excluded. All pathologic samples were reviewed to confirm PNI status and processed by immunohistochemical staining for S100 to quantify PNI. Pathologic information and staging results were also reviewed, and clinical outcomes were analyzed. Results: The retrospective study included 92 patients; 63 had intratumoral PNI (IPNI) and 29 had extratumoral PNI (EPNI). The average number of PNI foci (APNI) was higher in the EPNI group than in the IPNI group (6.7 vs 3.8, t-test 2-tail significance = 0.021). The 3-year overall survival (OS) and time-to-recurrence (TTR) rates of all patients were 82.5% and 81.2%, respectively. Univariate analysis showed that pathological T4 or N2-3 stage correlated with poor OS, whereas APNI ≥4 correlated with poor TTR. In multivariate analysis, only the pathological N2-3 stage was significantly correlated with poor OS, whereas only APNI ≥ 4 was an independent factor of poor TTR. The 3-year TTR rates were 92.4% and 65.6% for diseases with APNI < 4 and ≥ 4, respectively (P = .008). Conclusions: In patients with OSCC with PNI, a greater amount of PNI identified by S100 staining indicated a poorer TTR regardless of stage and other prognostic factors. Quantification of PNI by S100 immunohistochemistry is a potential method for prognosis prediction.

Schwannoma intraóseo en fémur, una presentación inusual. Reporte de caso / Intraosseous Schwannoma in femur, an unusual presentation. Case report

El Schwannoma o Neurilemoma es un tumor benigno de derivación neuroectodérmica que se origina en las células de Schwann, que constituyen la envoltura de los nervios. Es el tumor benigno más común de los nervios periféricos, tiene predisposición a originarse a partir de nervios periféricos sensoriales y puede presentarse como tumores en tejidos blandos. La presentación intraósea del Schwannoma es rara y corresponde al 0,2% de los tumores óseos primarios. Se presenta caso clínico de paciente masculino de 36 años de edad con tumor en cóndilo femoral medial de rodilla derecha de 4 años de evolución, cursando con dolor intermitente moderado a quien se le practicó el protocolo oncológico, imagenológico e histológico, de la Unidad de Oncología Ortopédica del estado Monagas. Se diagnosticó Schwannoma intraóseo, se procedió a realizar resección marginal y reconstrucción con alloinjerto y fijación con placa y tornillos con excelente evolución postoperatoria. El Schwannoma intraóseo es extraordinariamente raro y su ubicación en el fémur lo es aún más. El objetivo del presente trabajo es reportar un caso de Schwannoma Intraóseo, mostrar las estrategias para su diagnóstico y los tratamientos aplicados, así como la revisión de los datos al respecto existentes en la literatura(AU)

Schwannoma or Neurilemoma is a benign tumor of neuroectodermal derivation that originates in Schwann cells, which constitute the nerve sheath. It is the most common benign tumor of the peripheral nerves, has a predisposition to originate from peripheral sensory nerves, and can present as soft tissue tumors. The intraosseous presentation of Schwannoma is rare and corresponds to 0,2% of primary bone tumors. A clinical case of a 36-yearold male patient with a tumor in the medial femoral condyle of the right knee of 4 years of evolution is presented, presenting with moderate intermittent pain who underwent the oncological, imaging and histological protocol of the Oncology Unit. Monagas State Orthopedic. Intraosseous Schwannoma was diagnosed, marginal resection and allograft reconstruction and plate and screw fixation were performed with excellent postoperative evolution. Intraosseous Schwannoma is extraordinarily rare and its location in the femur is even more so. The objective of this paper is to report a case of Intraosseous Schwannoma, show the strategies for its diagnosis and the treatments applied, as well as the review of the existing data in the literature(AU)