What About Gastric Schwannoma? A Review Article.

PURPOSE: Gastric schwannomas (GSs) are rare mesenchymal neoplasms of the gastrointestinal tract. Diagnosis is often achieved postoperatively, based on pathology reports of retrieved specimens. The aim of the present study is to follow up all patients with gastric schwannoma (Gs) undergoing endoscopic, partial, or more extended surgery and to evaluate the appearance of local or distant recurrence. METHODS: A PubMed, Cochrane, and Embase systematic review of the literature has been performed. Original papers, review articles, and case reports published between 1988 and 2019 were considered eligible. All the studies who met the inclusion criteria were analyzed. Statistical analysis of data has been performed using GraphPad Prism 7 software. RESULTS: Three hundred twenty-eight articles were found, and a total of 102 were included and analyzed in depth. Fifty-three papers reported the follow-up information, ranging from 1 to 417 months across different studies. Among them, 31 patients underwent endoscopic removal of the gastric lesions; 140 patients underwent local surgery, including wedge resection or partial gastrectomy; and 148 patients underwent subtotal or total gastrectomy. The median follow-up was of 27-38-33 months, respectively. No recurrence or distant metastasis was detected in the endoscopy group. Among local surgery group, liver metastasis was reported in one case; in extended surgery group, one patient died for multiple liver metastases. CONCLUSIONS: Local or more extended surgery involved a larger cohort of patients and reported satisfactory long-term results compared with endoscopy group. Surgery in absence of a definite preoperative diagnosis is considered the gold standard treatment for resectable Gs.

Transoral Robotic Surgery in the Management of a Tongue Base Schwannoma.

Schwannomas are the most common benign tumors arising from the peripheral nerve sheath, and the intraoral location is very atypical, representing less than 1% of all cases. Surgical excision is the treatment of choice, and a variety of surgical approaches have been described. The authors report the first described case of tongue base schwannoma treated with transoral robotic surgery (TORS). A 47-years-old female patient complaining mild dysphagia and snoring, presented a submucosal swelling at the right side of the tongue base. MRI showed a large well-circumscribed solid mass, homogeneously isointense in T1WI and hyperintense on T2WI, with no lymph node metastasis. According to size, location and radiological characteristic of the mass a TORS approach was chosen. An extracapsular dissection was performed, and the lesion was completely removed with no intraoperative complications. The final diagnosis based on histopathological examination and IHC analysis (S-100 positive) was a schwannoma of the tongue base. The post-operative course was uneventful, and no recurrence was observed after 6 months of follow-up. This study demonstrates the feasibility of TORS in the treatment of a tongue base schwannoma. This is a valid alternative to the common transoral approach in order to avoid more invasive external approaches, and further studies are recommended in order to clarify if this approach could be proposed as the first line treatment in selected cases.

Malignant Peripheral Nerve Sheath Tumor Arising in Schwannomatosis with Multiple Lung Metastases.

BACKGROUND: Malignant peripheral nerve sheath tumor (MPNST) is a kind of rare neurogenic malignancy, which usually arises from nerve fibers in any tissue and organ that have nerve fiber distributions, especially the trunk and extremities, but it is extremely rare in spinal canal. CASE DESCRIPTION: We report a 30-year-old woman who had a history of excision of intraspinal occupying lesions 5 times and the pathologic diagnosis based on histomorphologic and immunohistochemistry was schwannomatosis, which existed in her family history. Unfortunately, she died because her condition deteriorated rapidly and appeared multiple lung metastases. MPNST was confirmed by needle biopsy of lung lesions. CONCLUSIONS: Many cases of MPNST usually developed from neurofibromatosis type 1. However, the incidence of MPNST arising from schwannomatosis was extremely rare. More significantly, using genetic testing on her, we found a splice site mutation (c.1118+1G>A) that occurred between exons 8 and 9 of the SMARCB1 gene, which was first found in this MPNST patient and could lay the foundation for further study of its pathogenesis.

Targeted next-generation sequencing of malignant peripheral nerve sheath tumor of the pterygopalatine fossa with intracranial metastatic recurrence.

Malignant peripheral nerve sheath tumor (MPNST) is an uncommon neoplasm that rarely involves the head and neck region. Intracranial MPNSTs unrelated to cranial nerves are highly malignant tumors with poor overall survival, probably because of infiltrating growth into surrounding brain tissue. The pathogenesis of MPNST remains unclear. There are no conclusive explanations for the mechanisms underlying the initiation, progression, and metastasis of MPNST. In this paper, we describe a case of MPNST in the pterygopalatine fossa with intracranial metastatic recurrence and review related literatures. Meanwhile, targeted next-generation sequencing (NGS) revealed the presence of both a beta-catenin (CTNNB1) missense mutation p.Ser33Phe and a mediator complex subunit 12 (MED12) frameshift mutation p.Tyr1278fs in the recurrent intracranial tumor. Therapies that target CTNNB1 mutation, MED12 mutation, CTNNB1 activation, or Wnt pathway activation are worth future studying.

Natural Orifice-Assisted Laparoscopic Meckel Diverticulectomy Incidentally Found During Para-Aortic Mass Resection.

STUDY OBJECTIVE: To show a surgical video in which an incidentally found Meckel diverticulum was resected with a natural orifice-assisted laparoscopic approach during para-aortic resection of a retroperitoneal schwannoma. DESIGN: Case report (Canadian Task Force classification III). SETTING: Tertiary referral center in New Haven, Connecticut. INTERVENTIONS: This is a step-by-step illustration for resection of a retroperitoneal para-aortic schwannoma and of an incidentally found Meckel diverticulum. The patient was a 39-year-old white woman diagnosed with stage IV choriocarcinoma with metastasis to the lungs and left para-aortic area. She received chemotherapy in the form of etoposide, methotrexate, actinomycin-D, cyclophosphamide, oncovine (EMA-CO) and had an excellent clinical response with resolution of all metastatic disease except for the para-aortic mass. Therefore, she was taken to the operating room for laparoscopic resection of the persistent left para-aortic mass. After placement of four 5-mm abdominal ports, the pelvis and abdomen were explored and revealed an incidental Meckel diverticulum as well as the 5 cm left para-aortic mass. The peritoneum overlying the para-aortic mass was incised and the retroperitoneum explored. Given the proximity to the mass, left ureterolysis was performed. The retroperitoneal attachments were resected, and the left para-aortic mass was removed without any complications. At this point attention was turned to the Meckel diverticulum. In order not to extend the abdominal incisions, a posterior colpotomy was performed in the cul-de-sac equidistant from the uterosacral ligaments. Endo-GIA (Covidien, New Haven CT) was introduced through the 10-mm port site at the posterior colpotomy. Meckel diverticulum was resected without narrowing the lumen of the distal ileum. The specimen was removed in a contained manner through posterior colpotomy. MEASUREMENTS AND MAIN RESULTS: The procedure was performed without any complications. The patient had an uneventful postoperative course and was discharged home on postoperative day 0. Pathology revealed a retroperitoneal schwannoma with negative margins and benign Meckel diverticulum without ectopic gastric or pancreatic tissue. The patient has been disease-free since the completion of surgery. CONCLUSION: Laparoscopic resection of the retroperitoneal schwannoma and Meckel diverticulum were successfully performed in this patient with history of stage IV choriocarcinoma. To our knowledge, this is the first report describing a natural orifice-assisted laparoscopic approach for resection of Meckel diverticulum. Natural orifice-assisted laparoscopy should be considered when the surgeon needs to remove a large specimen and/or to introduce >5-mm diameter instruments into the peritoneal cavity without having to extend the abdominal incisions.

Spindle cell type malignant peripheral nerve sheath tumor arising in benign schwannoma with multiple intraosseous spinal metastasis: A case report.

BACKGROUND: Malignant peripheral nerve sheath tumor (MPNST) arising in benign schwannoma with multiple intraosseous spinal metastasis is extremely rare, having a highly aggressive progression and poor prognosis. In such cases, the malignant cells of MPNST usually have an epithelioid morphology. Here, the authors present a very rare case of spindle cell type MPNST arising in benign schwannoma. CASE: A 47-year-old woman had a history of wide marginal excision of right buttock spindle cell sarcoma previously. However, metastatic lesions to C7, L1 body, and the right lung were detected during follow-up. Total spondylectomy and stabilization of the C7 and L1 tumors were performed within an interval of 5 months. However, the patient expired 6 months after the last surgery. From analysis and study of three tumor specimens (right buttock, cervical and lumbar spine), the pathological diagnosis based on histomorphologic and immunohistochemical studies was spindle cell sarcoma, high grade, most consistent with MPNST arising in schwannoma. RESULTS: It is important that pathologists and surgeons recognize that spindle cell type MPNST may arise in benign schwannoma, as this recognition aids in assessment of patients with schwannoma and contributes to the pathologist making a more precise diagnosis, and the surgeon better determining the appropriate therapeutic options and surgical methods.

Metastatic malignant peripheral nerve sheath tumour presenting as a spontaneous extradural haematoma - A case report.

Malignant peripheral nerve sheath tumours may arise from any cranial or somatic nerve. The median survival with best therapy is 49 months. The present case reports a patient with an MPNST that exhibited an unusually indolent behaviour. Besides this, the patient developed a dural metastasis from the lesion and presented with a spontaneous extra-dural haematoma. This has not been reported hitherto in literature.

Low-grade Schwann cell neoplasms with leptomeningeal dissemination: clinicopathologic and autopsy findings.

Leptomeningeal dissemination of low-grade Schwann cell neoplasms is an exceptionally rare occurrence and has not been well documented in the literature. We encountered 2 cases of leptomeningeal dissemination of low-grade Schwann cell neoplasms. Patient 1 was a 63-year-old woman with neurofibromatosis type 1 and a progressive low-grade malignant peripheral nerve sheath tumor developing from a diffuse/plexiform orbital neurofibroma that arose in childhood. The neoplasm demonstrated local and leptomeningeal dissemination intracranially leading to the patient's death. There was partial loss of H3K27 tri-methylation, p16 and collagen IV. Patient 2 was a 60-year-old man without neurofibromatosis type 1 who presented with cranial nerve symptoms and a disseminated neoplasm with a Schwann cell phenotype. The neoplasm stabilized after irradiation and chemotherapy, but the patient died of medical complications. Autopsy findings documented disseminated leptomeningeal disease in the intracranial and spinal compartment. H3K27M tri-methylation was preserved. The clinicopathologic and autopsy findings are studied and presented, and the literature is reviewed.

Characterizing the immune microenvironment of malignant peripheral nerve sheath tumor by PD-L1 expression and presence of CD8+ tumor infiltrating lymphocytes.

BACKGROUND: Malignant peripheral nerve sheath tumor (MPNST) is an aggressive sarcoma with few treatment options. Tumor immune state has not been characterized in MPNST, and is important in determining response to immune checkpoint blockade. Our aim was to evaluate the expression of programmed death-ligand 1 (PD-L1), programmed cell death protein 1 (PD-1), and presence of CD8+ tumor infiltrating lymphocytes (TILs) in MPNST, and correlate these findings with clinical behavior and outcome. RESULTS: PD-L1 staining of at least 1% was seen in 0/20 nerves, 2/68 benign lesions and 9/53 MPNST. Two of 68 benign lesions and 7/53 (13%) MPNST had at least 5% PD-L1 staining. CD8 staining of at least 5% was seen in 1/20 (5%) nerves, 45/68 (66%) benign lesions and 30/53 (57%) MPNST. PD-L1 was statistically more prevalent in MPNST than both nerves and benign lesions (p=0.049 and p=0.008, respectively). Expression of PD-1 was absent in all tissue specimens. There was no correlation of PD-L1 or CD8 expression with disease state (primary versus metastatic) or patient survival. METHODS: A comprehensive PNST tissue microarray was created from 141 surgical specimens including primary, recurrent, and metastatic MPNST (n=53), neurofibromas (n=57), schwannoma (n=11), and normal nerve (n=20). Cores were stained in triplicate for PD-L1, PD-1, and CD8, and expression compared between tumor types. These data were then examined for survival correlates in 35 patients with primary MPNST. CONCLUSIONS: MPNST is characterized by low PD-L1 and absent PD-1 expression with significant CD8+ TIL presence. MPNST immune microenvironment does not correlate with patient outcome.

[Schwannoma in the Middle Mediastinum Originating from the Vagal Nerve；Report of a Case].

A 44-year-old woman was referred to our department with a mediastinal tumor detected by computed tomography performed as a preoperative examination for cervical cancer. There was a 32 mm solid mass in the area surrounded by the descending thoracic aorta, esophagus, left atrium, left lower lobe, and mediastinal pleura. The tumor was removed thoracoscopically. The mass was regarded as a neurogenic tumor arisen from the branch of the vagus nerve. Neither symptoms of postoperative neurological disorders nor signs of recurrence have been noted to date. The histopathological diagnosis was schwannoma.

Management and prognosis of malignant peripheral nerve sheath tumors: The experience of the French Sarcoma Group (GSF-GETO).

BACKGROUND: Malignant peripheral nerve sheath tumors (MPNST) are a rare subtype of soft tissue sarcoma. They can arise in irradiated fields, in patients with type 1 neurofibromatosis (NF1), or sporadically. MPNST exhibit an aggressive behaviour, and their optimal management remains controversial. An unsolved issue is whether NF1-related and sporadic forms of MPNST have a different prognosis, and should be managed differently. MATERIAL AND METHODS: Adult and paediatric patients with histologically confirmed MPNST treated between 1990 and 2013 in French cancer centres of the GSF/GETO network, were included in this retrospective study. RESULTS: A total of 353 patients (37% with NF1 and 59% with sporadic tumours) were analysed. Median age at diagnosis was 42 years (range 1-94). The majority of tumours developed in the limbs, were deep-seated and of high grade. Two hundreds and ninety four patients underwent a curative intent surgery. Among them, 60 patients (21%) had neoadjuvant treatment (mainly chemotherapy), and 173 (59%) had adjuvant treatment (mainly radiotherapy). For operated patients, median progression free and overall survival (OS) were 26.3 months and 95.8 months, respectively. In multivariate analysis, poor-prognosis factors for OS were high grade, deep location, locally advanced stage at diagnosis, and macroscopically incomplete resection (R2). NF1 status was not negatively prognostic, except in the recurrence or metastatic setting, where NF1-related MPNST patients treated with palliative chemotherapy showed worse survival than patients with sporadic forms. CONCLUSION: To our knowledge, our series is the largest study of patients with MPNST reported to date. For operated patients, we showed a worse prognosis for NF1-related MPNST, due to different clinical features at diagnosis, more than NF1 status itself. The French sarcoma group is now conducting correlative analyses on these patients, using the latest molecular tools.

Tumor-to-tumor metastasis of breast carcinoma to cervical spinal schwannoma: Case report.

Tumor-to-tumor metastasis with schwannoma as a recipient tumor is very rare. There have been no reports on tumor to spinal schwannoma metastasis. We report a case of a 57-year-old woman who presented with neck pain and who turned out to have cervical spinal nerve schwannoma with breast carcinoma metastasis.

Sternal intraosseous schwannoma mimicking breast cancer metastasis.

The preoperative diagnosis of intraosseous schwannoma is challenging because of its rarity. We report a resected case of sternal intraosseous schwannnoma mimicking late recurrence of breast cancer.A 60-year-old Japanese woman with a history of breast cancer was diagnosed as having a sternal tumor by chest computed tomography (CT) demonstrating a round, well-defined, low-density nodule measuring 3.3 × 2.8 cm, which was located almost at the center of the sternum and associated with bone lysis and erosion. [18 F]Fluorodeoxyglucose positron emission tomography (FDG-PET)/CT demonstrated FDG accumulation in the tumor, suggesting malignancy. Therefore, late isolated recurrence of breast cancer was suspected. Surgical resection was performed for both confirmation of the diagnosis and treatment.Pathological examination revealed that the tumor was composed predominantly of spindle-shaped cells arranged in a typical palisading pattern, being compatible with schwannoma. Although the periosteum was intact, the tumor was found to have destroyed the cortex of the sternum and proceeded forward to the bone marrow. Additionally, immunohistochemical staining revealed that the lesion was diffusely and strongly positive for S-100 protein. Thus metastasis from breast cancer was ruled out on the basis of the features revealed by microscopy.

Pulmonary malignant peripheral nerve sheath tumour.

Malignant peripheral nerve sheath tumours (MPNSTs) may occur in any peripheral nerve. They are often found in the chest wall and the posterior mediastinum. On the other hand, primary pulmonary MPNST is extremely rare, and surgically treated cases have been reported. Here, we present 3 cases of primary MPNST originating from the pulmonary parenchyma who underwent surgery in our institution. We discuss the possible clinical and pathological associations in the view of the literature.

Malignant melanotic schwannian tumor: a clinicopathologic, immunohistochemical, and gene expression profiling study of 40 cases, with a proposal for the reclassification of "melanotic schwannoma".

Melanotic schwannomas (MSs), variably associated with the Carney complex, are rare tumors that usually involve spinal nerve roots but may occur in other locations. Clinicopathologic evaluation poorly predicts the behavior of MS. Fewer than 200 cases have been reported. We report a series of 40 well-characterized MSs, one of the largest series to date. The tumors were comprehensively evaluated, and clinical follow-up was obtained. Immunohistochemistry for S100 protein, Melan-A, HMB45, tyrosinase, glial fibrillary acidic protein (GFAP), EMA, SMARCB1, Ki-67 antigen, ASMTL, and the Carney complex-associated PRKAR1A gene product was performed using commercially available antibodies and the Ventana Ultraview detection system. Gene microarray study was conducted on formalin-fixed, paraffin-embedded blocks from 10 MSs and the results compared with previous data from melanoma and schwannoma. Differentially expressed genes were selected at >3-fold and P<0.001. The Fisher exact test was used for statistical analysis. The tumors occurred in 18 male and 22 female patients (mean age 41 y; range, 11 to 84 y) and involved the paravertebral nerve roots (N=31), mediastinum (N=3), sacrum, cauda equina, para-aortic region, fifth cranial nerve, buttock, and cerebellum (N=1 each). Two patients had known Carney complex, and 1 patient also had a cutaneous myxoma, suggestive of Carney complex. The tumors expressed S100 protein (21/25, 84%), Melan-A (23/25, 92%), HMB45 (25/25, 100%), tyrosinase (25/25, 100%), GFAP (0/24, 0%), EMA (0/9, 0%), SMARCB1 (retained in 25/25, 100%), and ASMTL (5/19, 26%); PRKAR1A expression was lost in 7/20 cases (35%). Ki-67-labeling index was <5% in 23/25 cases (92%) and 5% to 10% in 2/25 cases (8%). Gene expression profiling showed significant differences between MS, melanoma, and conventional schwannoma. Clinical follow-up (26/40, 65%; mean 55 mo; range, 1 to 300 mo) showed local recurrences in 9/26 (35%) and metastases in 11/26 (44%) patients. Fourteen patients were alive without disease, 5 were alive with disease, and 7 had died of disease. Only a mitotic rate >2/10 HPF correlated with metastases (P=0.008). The clinicopathologic features of tumors with and without psammoma bodies were identical. We conclude that MSs are distinctive malignant tumors, rather than benign neoplasms with occasionally unpredictable behavior, and propose their reclassification as "malignant melanotic schwannian tumors." Loss of PRKAR1A expression suggests a link to Carney complex, even when this history is absent.

Melanotic schwannoma of the cervical spine progressing with pulmonary metastasis: case report.

Melanotic schwannoma (MS) is an unusual variant of nerve sheath neoplasm. Only 10% of these tumors will undergo malignant degeneration, with exceedingly rare reported metastasis. We present a 32-year-old woman with a 6-month history of cervical pain and left arm progressive weakness. Neurological examination showed a left upper limb radicular pain, with pyramidal syndrome at C5 level. The magnetic resonance imaging (MRI) study highlighted an intradural extramedullary heterogeneous mass along the spinal cord at the C4-C5 level, slightly hyperintense with T1 and hypointense with T2-weighted sequences, invading the left neural foramen. The patient underwent C3-C5 laminectomy with total resection of a black tumor. In the postoperative period, a patent deficit of shoulder abduction ensued related to the nervous section. Microscopically, compactly fascicles of spindle-shaped cells with pleomorphic and hypercromatic nuclei, dark brown intracellular pigments, as well as some mitotic figures were seen. Immunohistochemical stains for S-100, Human Melanoma Black-45 (HMB-45), and vimentin were positive, with Ki-67 Labelling Index (LI) of 15% compatible with MS. Six months after radiotherapy she presents local recurrence and lung metastatic dissemination of the MS. She underwent left pulmonary segmentectomy, followed by chemotherapy and radiosurgery. The patient developed a febrile neutropenia and worsening of general status, and died after 3 months due to respiratory complications. MS are rare tumors with potential for local recurrence and distal metastasis. Complete surgical resection remains as the treatment of choice, once the uncommon cases with malignant progression shows low response to chemo and radiotherapy.