LMNA-NTRK1 rearranged mesenchymal tumor (lipofibromatosis-like neural tumor) mimicking pigmented dermatofibrosarcoma protuberans.

We present the case of a 31-year-old female with a 1.5 cm pigmented nodule on the scalp. Histopathological examination revealed a proliferation of relatively bland spindle cells and pigmented dendritic cells, with interspersed lymphoid follicles diffusely infiltrating the adipose tissue. The microscopic differential diagnosis included pigmented dermatofibrosarcoma protuberans (DFSP). The spindle cells showed S-100 and CD34 labeling but were negative for SOX-10. Immunohistochemical stain for pan-TRK was positive, while fluorescence in-situ hybridization for PDGFB gene rearrangement was negative. Targeted RNA sequencing revealed an LMNA-NTRK1 (exon2/exon10) fusion. This molecular result coupled with the histopathological findings and immunohistochemical profile supported the diagnosis of the recently characterized NTRK-rearranged spindle cell neoplasm termed "lipofibromatosis-like neural tumor (LPF-NT)." These neoplasms typically occur in superficial soft tissue and are characterized by a distinctive immunoprofile (CD34+, S-100+, SOX10-). Histopathological differential diagnosis for LPF-NT tumors includes lipofibromatosis, DFSP, low-grade malignant peripheral nerve sheath tumor, and spindle cell/desmoplastic melanoma. The pigmented dendritic cells reminiscent of pigmented DFSP and lymphoid follicles noted in our case have not been previously reported in LPF-NT, thus expanding the morphological spectrum of this entity. LMNA-NTRK1 fusion serves both as a diagnostic and therapeutic biomarker, as cases with advanced disease may be amenable to targeted therapy using tyrosine kinase inhibitors.

Neurogenic Tumors of the Mediastinum.

Neurogenic tumors represent a broad ill-defined category of neoplasms that includes tumors of Schwann cell and/or neuroblastic derivation, as well as neoplasms that typically develop in the central nervous system, but rarely present in ectopic sites including the mediastinum. Neurogenic tumors may occur at many different anatomic sites, but the mediastinum represents a uniquely challenging site given the complex anatomy. Additionally, some of these neoplasms may present with multicentric involvement in the context of genetic syndromes, including NF1, NF2 and schwanomatosis. Most of these develop in posterior structures, often in association with paraspinal structures. Fine needle biopsy/small biopsies play an important role in the diagnosis of these neoplasms, given its record of safety and the increased applicability of ancillary testing to these smaller samples at the present time. In this review we focus on the major categories of neurogenic tumors that may be encountered in the mediastinum, including schwannoma, neurofibroma, malignant peripheral nerve sheath tumors, ganglioneuroma and ganglioneuroblastoma, as well as rarer members of this category. We discuss diagnostic approaches applicable to small cytologic and tissue samples and relevant differential diagnoses.

Granular cell tumour of the tongue treated by radiofrequency ablation.

AIM: To report on a case of granular cell tumour occurring in the tongue surgically removed by surgical radiofrequency, with histological examination. MATERIAL OF STUDY: Discussion on the clinico-pathological characteristics of the granular cell tumour and the surgical treatment by surgical radiofrequency: the differential diagnosis is also discussed. RESULTS: Histological examination is mandatory for the final diagnosis. Surgical radiofrequency is an useful medical device to achieve good quality surgery with minimal post-operative course. DISCUSSION CONCLUSIONS: Although rare, granular cell tumour should be always considered in the differential diagnosis of nodular lesions of the oral mucosa above all when the tongue is involved and a yellow appearance is detectable. The surgery will be guided by the clinical diagnosis and accurately performed to prevent recurrence. A medical device promoting reduction of the intra-operative bleeding is suggestable for such surgical treatments. KEY WORDS: Granular cell tumour, surgical radiofrequency, neurogenic tumour.

Ancient Schwannoma of Radial Nerve: A Report of Two Cases.

Ancient schwannoma is a rare variant of schwannoma associated with a longstanding course. They differ from classical schwannomas in the long duration for this subtype of schwannoma to develop and also by demonstrating haemorrhagic and degenerative changes with nuclear atypia. It is because of these histologic hallmarks that they are frequently misdiagnosed as malignant tumours. They usually involve the major nerves of flexor surfaces in upper extremity such as the ulnar and median nerve but schwannomas of the radial nerve are a rare entity. We report two cases of ancient schwannoma involving the radial nerve at mid arm and dorsum of the hand. The differential diagnoses included atypical soft tissue sarcomas and tumours of neural origin. Imaging and histopathology are crucial in diagnoses of these tumours.

Intrathoracic neurogenic tumor with malignant transition-20 years operation experience in a medical center of China.

OBJECTIVE: Malignant peripheral neurogenic tumor is always found in large peripheral nerve of the extremities, however, benign peripheral neurogenic tumors of chest is an uncommon disorder, furthermore, malignant transition is even rare. So far, few cases have been reported. We studied 45 neurogenic thoracic tumors patients with malignant transition. METHODS: We retrospectively reviewed clinical data of 45 malignant neurogenic thoracic tumors from 1992 to 2012, including 11 (24.44%) cases of borderline tumors (group X), 13 cases of (28.88%) low-grade malignant tumor (group L), and 21 cases (46.66%) of malignant tumors (group M). Specifically, we reviewed the clinical characteristics, surgical approach, postoperative outcome, complications and prognosis of these patients. RESULTS: All tumors are located in the thoracic cavity, and arising from sympathetic or spinal nerve or their branches from the lung or posterior mediastinum. The patients from groups X and L had more complete resection than group M. Unfortunately, one patient was dead intra operatively in Group M. Group M had more recurrence than groups X and L. Our results indicates that, the survival rate may be correlated with tumor size, malignant degree (P=0.018), tumor recurrence and incomplete resection (P<0.05). CONCLUSION: The most effective treatment method for these tumors is early identification and resection by minimally invasive surgery during benign stage. In addition, regarding low-grade malignant tumor, non-radical surgery could also be responsible for the low survival rate.

A probabilistic assessment of the diagnosis of paraganglioma/pheochromocytoma based on clinical criteria and biochemical/imaging findings.

UNLABELLED: Paragangliomas (PGL) and pheochromocytomas (P) are rare neural-crest-derived neoplasms. Very recently guidelines on diagnosis and treatment of PGL/P have been presented by the US Endocrine Society. In the following overview we assessed the implementation of these guidelines with probabilistic reasoning (calculating with Fagan nomograms the post-test probability of PGL/P for a given pre-test probability). CONCLUSION: Biochemical evaluation of PGL/P showed excellent diagnostic characteristics with post-test probabilities that are very different from the pre-test probabilities, thus a positive biochemical test is usually indicative of disease whereas a negative one usually rules out disease. The post-test probabilities of anatomical and functional imaging modalities (i.e. in nuclear medicine) were different from the pre-test probabilities but to a lesser degree than the biochemical tests; furthermore in biochemically-proven PGL/P a negative imaging modality is not useful, while a positive one may indicate only one of multiple foci of metastatic/extra-adrenal disease. Thus, regarding imaging modalities, they should be combined in order to get the most of their characteristics for the localization of PGL/P.

Glomus-like bodies within a neurofibroma: a novel neoplasm arising in neurofibromatosis type 1 or a coincidence?

Neurofibromatosis type 1 is a relatively common genetic disorder with variable phenotypes. Tumors with features of both glomus tumors and neurofibromas are exceedingly rare in literature. Herein, we report a not yet described neoplasm with features of both a glomangioma/glomus tumor and a neurofibroma arising in a patient with segmental neurofibromatosis. Our case report supports the theory of a common lineage/ancestor cell between neurofibromas and glomus tumors and adds it to the spectrum of neoplasms that may arise in the setting of Von Recklinghausen's disease.

THE IMPORTANCE OF IMMUNOHISTOCHEMICAL STUDIES IN THE DIAGNOSIS OF CANCER OF UNKNOWN PRIMARY ORIGIN.

The purpose of the research is to give a comparative diagnostic characteristic to tumors of unknown primary origin by admission diagnosis and morphological diagnosis. 162 treated cases with tumors of unknown primary at Oncologic Dispensary for 5 years were analyzed in details. Besides clinical, instrumental, cytological, morphological methods, immunnohistochemical research of tumors was carried out by avidin-biotin-peroxydase tecnics. The cases with poorly differentiated carcinoma (33,3±4,3%) and lymphoproliferative disorders (27,2±3,5%) prevailed among the cases with tumors of unknown primary by histological research. High degree of noncoincidence of cytologic and histological diagnoses (χ2=515, р=0,00001), histological and immunohistochemical diagnoses (χ2=378, р=0,00001), cytologic and immunohistochemical diagnoses (χ2=556, р=0,00001) were revealed. Cytologic overdiagnosis of undifferentiated carcinoma by 13,6% (р<0,05) and hypodiagnosis of benign diseases by 4,4% (р<0,05) and histological overdiagnosis of poorly differentiated carcinoma by 11,1% (р<0,05) and hypodiagnostics of tumors of nerve tissue by 8,0% (р<0,05) are marked, that points to the necessity of making immunohistochemical research in the cases of given pathology. Statistically significant connection of mean degree between diagnoses of poorly differentiated tumors made by cytologic, histological and immunohistochemical investigation is revealed.

Imaging of the perivertebral space.

The perivertebral space extends from the skull base to the mediastinum and is delineated by the deep layer of the deep cervical fascia. The different tissue types, including muscles, bones, nerves, and vascular structures, give rise to the various disorders that can be seen in this space. This article defines the anatomy of the perivertebral space, guides lesion localization, discusses different disease processes arising within this space, and reviews the best imaging approaches.

Soft tissue sarcoma misdiagnosed as benign peripheral neurogenic tumor.

BACKGROUND: Because of the distinctive clinical and MR findings associated with benign peripheral neurogenic tumors (BPNTs), they are commonly diagnosed without histological confirmation. As such, they are one of the most frequently misdiagnosed entities among the soft tissue sarcomas (STSs) that undergo initial unplanned excision. In this study, we investigate the characteristics of STSs misdiagnosed as BPNTs. METHODS: We present a series of nine STS patients with an initial preoperative diagnosis of BPNT (BPNT-STS), and compare their clinical and MR findings to those of the 18 genuine BPNT patients, matched for site, depth, and size of tumors as well as related nerves. RESULTS: Among the nine BPNT-STS cases, the most common histological diagnosis was synovial sarcoma (n = 4). Six patients (67 %) had deep-seated tumors; four patients (44 %) had tumors 5 cm or greater in size. BPNT-STS patients were more likely to experience pain (78 % vs. 22 %) and shorter symptom duration (9 vs. 55 months) compared to BPNT patients. A target sign on MR imaging was observed only in BPNT patients (0 % vs. 50 %), whereas peritumoral edema was found only in BPNT-STS patients (33 % vs. 0 %). CONCLUSIONS: If a tumor suggestive of a BPNT is painful, with a relatively short symptom duration, and presents with peritumoral edema without a definite target sign on MR images, the possibility of an STS must be considered.

Defining key signaling nodes and therapeutic biomarkers in NF1-mutant cancers.

UNLABELLED: NF1 encodes a RAS GTPase-activating protein. Accordingly, aberrant RAS activation underlies the pathogenesis of NF1-mutant cancers. Nevertheless, it is unclear which RAS pathway components represent optimal therapeutic targets. Here, we identify mTORC1 as the key PI3K effector in NF1-mutant nervous system malignancies and conversely show that mTORC2 and AKT are dispensable. However, we find that tumor regression requires sustained inhibition of both mTORC1 and MEK. Transcriptional profiling studies were therefore used to establish a signature of effective mTORC1-MEK inhibition in vivo. We unexpectedly found that the glucose transporter GLUT1 was potently suppressed, but only when both pathways were inhibited. Moreover, unlike VHL- and LKB1-mutant cancers, reduction of (18)F-FDG uptake required the suppression of both mTORC1 and MEK. Together, these studies identify optimal and suboptimal therapeutic targets in NF1-mutant malignancies and define a noninvasive means of measuring combined mTORC1-MEK inhibition in vivo, which can be readily incorporated into clinical trials. SIGNIFICANCE: This work demonstrates that mTORC1 and MEK are key therapeutic targets in NF1-mutant cancers and establishes a noninvasive biomarker of effective, combined target inhibition that can be evaluated in clinical trials.

Intrathoracic neurogenic tumors.

BACKGROUND: Intrathoracic neurogenic tumors are uncommon neoplasms arising from nerve tissues. This study reports on our 24-year single-center experience with intrathoracic neurogenic tumors. PATIENTS AND METHODS: We retrospectively analyzed the postoperative pathological records of 19,378 operations performed in our clinic between January 1988 and December 2011 and included cases with diagnosis of neurogenic tumors. RESULTS: The study included 149 patients (90 females and 59 males) with an average age of 24.5 years (7 months to 77 years). The study group comprised 29 infants and children, and 120 adults. Of the patients, 72 had benign schwannomas, 10 malignant schwannomas, 17 neurofibromas, 24 ganglioneuromas, 9 ganglioneuroblastomas, 4 neuroblastomas, 9 primitive neuroectodermal tumors, and 4 paragangliomas. Concerning the location of these lesions, 131 were located in the posterior mediastinum, 8 in the lung parenchyma, 5 in the chest wall, 3 in the anterior mediastinum, and 2 in the thoracic inlet. The majority of nerve cell tumors were in infants and children (79.3%), whereas the nerve sheath tumors most commonly occurred in adults (78.3%). There were 117 benign and 32 malignant tumors across all age groups. The rate of malignancy was 41.4% in infants and children, compared with 16.7% in adults. Symptoms were seen in 65% of the adult patients and 79.3% of the infant and children patients. Seven tumors were associated with von Recklinghausen's disease. In six patients (4.0%), the tumor showed an intraspinal extension. Surgical resection of the tumor was complete in 142 of 149 patients (95.3%). CONCLUSION: The treatment of choice for malignant and benign thoracic neurogenic tumors is complete resection. The objective of resection is to avoid local invasion, facilitate differential histopathological diagnosis to determine other treatment options, and to prevent malignant degeneration.

Spectrum of superficial nerve-related tumor and tumor-like lesions: MRI features.

Superficial soft-tissue masses arising from skin appendages, metastasis, and inflammatory lesions have been widely reported. However, nerve-related superficial mass-like lesions other than peripheral nerve sheath tumors are less commonly described. High resolution magnetic resonance imaging (MRI) is an excellent non-invasive tool for the evaluation of such lesions. In this article, the authors discuss the entire spectrum of these lesions and also outline a systemic diagnostic approach.

[Benign conjunctival tumors]. / Tumeurs conjonctivales bénignes.

Benign conjunctival tumors include congenital, melanocytic, epithelial and stromal lesions. Clinical observation often fails to make the diagnosis, and complete excisional biopsy must be performed as soon as growth is suspected. Histology remains the best way to exclude malignancy or lesions with a risk of transformation, because malignant lesions carry a poor prognosis and require specific therapy and follow-up. Onco-ophthalmologists must have a perfect knowledge of benign conjunctival tumors, since during adulthood, nevi can be confused with melanomas, and epithelial or stromal lesions with carcinomas. For children and teenagers, surgery is only recommended when growth or functional problems are observed.

Preoperative symptoms and postoperative sequelae of intrathoracic neurogenic tumors: a single institution's experience.

OBJECTIVE: Most intrathoracic neurogenic tumors are resected for therapeutic diagnosis; many adult tumors are benign. However, few studies have reported the preoperative symptoms, postoperative modalities, and sequelae of these tumors. We focused on and evaluated the diversity and postoperative prognosis of these tumors. METHODS: We assessed 31 consecutive cases of intrathoracic neurogenic tumors resected at Tsuchiura Kyodo General Hospital between 1988 and 2012. Two cases involved multiple tumors; therefore, complete resection or enucleation was performed only in the remaining 29 cases. The patients' clinical records were investigated retrospectively. RESULTS: All tumors were benign. Five cases (16.1 %) presented with preoperative symptoms; 2 cases with non-neurologic symptoms (dysphagia due to tumor oppression and a massive hemothorax with neurofibromatosis type 1) improved after surgery, but 3 others with neurologic symptoms (back pain, hand motor paralysis, and Horner's syndrome) did not. Ten cases (32.3 %) presented with postoperative modalities or sequelae. Eight cases presented with neurologic sequelae (Horner's syndrome, 4 cases; grip weakness, 3 cases; hypohidrosis, 3 cases; and hand numbness, 2 cases). All the patients presenting with neurologic sequelae had tumors proximal to the first or second thoracic vertebra; no tumors proximal to or under the third thoracic vertebra caused neurologic sequelae. Severe neurologic sequelae in daily life were observed in 2 cases, but they did not radically improve. CONCLUSIONS: While the non-neurologic symptoms caused by intrathoracic neurogenic tumors can be resolved by resection, the neurologic symptoms may not improve. Tumors proximal to the first or second thoracic vertebra can cause postoperative neurologic sequelae.

Contemporary evaluation and management of parapharyngeal space neoplasms.

OBJECTIVE: This review summarises the contemporary, multidisciplinary approach to managing parapharyngeal space neoplasms. OVERVIEW: Parapharyngeal space neoplasms are uncommon head and neck tumours and are most often benign. Most tumours are of either salivary gland or neurogenic origin. Patients tend to be asymptomatic even when tumours reach large sizes. Patients may present with a mass in the pharynx or neck, although frequently the tumour is found incidentally on an imaging study. Due to the limitations of physical examination in this anatomical area, imaging studies are essential to the evaluation of parapharyngeal space neoplasms. Cytopathology may provide additional diagnostic information. Open biopsy is rarely necessary and can be hazardous. Treatment is primarily surgical, and various surgical approaches can be tailored for a given neoplasm. Recently, a trend toward observation of select patients with asymptomatic neurogenic tumours has been advocated. CONCLUSION: The evaluation and management of parapharyngeal space tumours is best done by a multidisciplinary team. Treatment should be individualised, and the risks and benefits of surgical intervention need to be carefully weighed. Complications are best avoided by careful surgical planning.

[Orbital neoplasia. Part I: Introduction, vascular and neurogenic tumors]. / Orbitale Neoplasien. Teil I: Einführung, vaskuläre und neurogene Neoplasien.

Tumors of the orbit are rare but the huge variability of clinical symptoms and findings are challenging for the ophthalmologist who is frequently contacted as the first resort. If the patient history and clinical findings are suspicious for an orbital mass the result of the initial examination should allow a rough estimation of localization (intra/extraconal), type of growth (expansive/infiltrative), dignity (vascular/solid etc.) and threat to visual functions. An adequate initial diagnostic pathway enables a precise question to the radiologist to be formulated and selection of the disciplines required for an interdisciplinary workup and therefore for early treatment.