Prognosis of oral squamous cell carcinoma with perineural invasion: A comparative study of classification types.

OBJECTIVE: To investigate the histological location and extent of perineural invasion (PNI) as prognostic factors. DESIGN: Retrospective review of medical records and histological analysis of 116 patients with oral squamous cell carcinoma (OSCC). SETTING: Two major public tertiary hospitals treating head and neck cancer, Royal Adelaide Hospital and Flinders Medical Centre, in South Australia. PARTICIPANTS: Patients diagnosed with OSCC who underwent primary surgical treatment with curative intent at these two centres from January 1, 2005 through December 31, 2015. MAIN OUTCOME MEASURES: The primary end points were disease-free survival (DFS) and disease-specific survival (DSS). RESULTS: The presence of PNI as a binary factor alone did not significantly influence the clinical outcomes. Extratumoural (ET) PNI as measured from the tumour edge was associated with worse DFS on multivariate analyses. Multifocal PNI was associated with worse DFS and DSS. DFS in multifocal PNI was worse irrespective of whether adjuvant therapy was administered. CONCLUSIONS: The presence of multifocal and ET PNI in OSCC is associated with poor clinical outcomes. Patients with multifocal PNI were associated with worse DFS even with adjuvant therapy.

International Society Of Neuropathology--Haarlem consensus guidelines for nervous system tumor classification and grading.

Major discoveries in the biology of nervous system tumors have raised the question of how non-histological data such as molecular information can be incorporated into the next World Health Organization (WHO) classification of central nervous system tumors. To address this question, a meeting of neuropathologists with expertise in molecular diagnosis was held in Haarlem, the Netherlands, under the sponsorship of the International Society of Neuropathology (ISN). Prior to the meeting, participants solicited input from clinical colleagues in diverse neuro-oncological specialties. The present "white paper" catalogs the recommendations of the meeting, at which a consensus was reached that incorporation of molecular information into the next WHO classification should follow a set of provided "ISN-Haarlem" guidelines. Salient recommendations include that (i) diagnostic entities should be defined as narrowly as possible to optimize interobserver reproducibility, clinicopathological predictions and therapeutic planning; (ii) diagnoses should be "layered" with histologic classification, WHO grade and molecular information listed below an "integrated diagnosis"; (iii) determinations should be made for each tumor entity as to whether molecular information is required, suggested or not needed for its definition; (iv) some pediatric entities should be separated from their adult counterparts; (v) input for guiding decisions regarding tumor classification should be solicited from experts in complementary disciplines of neuro-oncology; and (iv) entity-specific molecular testing and reporting formats should be followed in diagnostic reports. It is hoped that these guidelines will facilitate the forthcoming update of the fourth edition of the WHO classification of central nervous system tumors.

Nervous system tumors in adult immigrants to Sweden by subsite and histology.

BACKGROUND: The coding of histology of nervous system (NS) tumors with various degrees of malignancies differs between cancer registries, whereby the comparison of incidence rates from one registry to another seems difficult. No study has systematically defined whether the change in the risk of NS tumors upon immigration in adulthood varies by subsite or histology. Therefore, we aimed to address this issue amongst the first-generation immigrants to Sweden based on a large uniform cancer registry data (1958-2006). METHODS: The nationwide Swedish Family-Cancer Database (2008 version; >11.8 million individuals; 1.8 million immigrants; histology code in force since 1958) was used to calculate standardized incidence ratios (SIRs). We analyzed 28,981 adult cases of NS tumors amongst Swedes and 2519 amongst immigrants (age ≥ 30). RESULTS: Significantly decreased risks for brain glioma were amongst German (SIR = 0.64), Eastern European (0.62), some Asian (0.71), Chilean (0.34), and African immigrants (0.52). We found an increased risk for brain meningioma amongst Finns (1.15) and former Yugoslavians (1.33), whilst only Norwegians (0.71) and Latin Americans (0.21) had a decreased risk. The risk for spinal ependymoma and astrocytoma was increased in Germans (3.66) and former Yugoslavians (8.89). We found no significant difference for peripheral nerve tumors between immigrants and the native Swedes. CONCLUSION: Significant differences between risk of NS tumors amongst immigrants and the native Swedes may suggest different risk factor profiles for glioma compared to meningioma indicating a higher etiological role of genetic background or childhood environmental risk factors rather than exposures after immigration.

Frequent abnormalities of the immune system in gliomas and correlation with the WHO grading system of malignancy.

AIM: To investigate the cellular and humoral immunity status of gliomas, and their association with the WHO grading system. MATERIAL AND METHODS: We have conducted a case-control study of 49 patients with gliomas and 30 healthy controls. We used ELISA assays, radial immunodiffusion, indirect immunofluorescence, latex test and flow cytometry assays to estimate preoperative in serum the immunological profile. RESULTS: Patients with glioma had significantly reduced amounts of IL2 (p=0.000), TNF-a (p=0.033), IgG (p=0.011), IgA (p=0.027),C4 (p=0.026) ,CD3+ (p=0.001), CD4+ (p=0.000), CD8+ (p=0.002), ratio CD4/CD8 (p=0.000), CD19+ (p=0.04) and elevated IL10 (p=0.05) compared with healthy controls. No statistically significant differences were observed concerning viral agents, total NK cells, IgM, IgE, IL16, granzyme-b, RF, ANA, ENA, anti-dsDNA and anti-cardiolipin antibodies. A higher WHO grade, after controlling for age and gender, was associated with decreased number of CD3+ (p=0.011), CD4+ (p=0.015), CD8+ (p=0.048) and ratio CD4/CD8 (p=0.027), as well as with decreased IL2 (p=0.018), C4 (p=0.02), and IgG (p=0.05). IL2 and CD4+ counts were significant predictors of grade. CONCLUSIONS: A shift from Th1 to Th2, a CD3+ and CD19+ lymphocytopenia, a diminished fraction CD4/CD8 and a reduced amount of immunoglobulins and complement were observed in the patients with gliomas. A higher WHO grade of the tumor was associated with greater impairments of immunity. Since defects of both humoral and cellular immunity were equally observed and significant predictors of grade were assessed, a preoperative evaluation of the immune system of patients with gliomas is being proposed.

Update on diagnostic practice: tumors of the nervous system.

CONTEXT: Changes in the practice of diagnosing brain tumors are formally reflected in the evolution of the World Health Organization classification. Beyond this classification, the practice of diagnostic pathology is also changing with the availability of new tests and the introduction of new treatment options. OBJECTIVE: Glioblastomas, oligodendrogliomas, glioneuronal tumors, and primitive pediatric tumors are discussed in an exemplary way to illustrate these changes. DATA SOURCES: Review of relevant publications through Medline database searches. CONCLUSIONS: The example of glioblastomas shows how new predictive markers may help identify subgroups of tumors that respond to certain therapy regimens. The development of new treatment strategies also leads to different questions in the assessment of brain tumors, as seen in the example of pseudoprogression or the changes in tumor growth pattern in patients taking bevacizumab. Oligodendrogliomas illustrate how the identification of 1p/19q loss as a cytogenetic aberration aids our understanding of these tumors and changes diagnostic practice but also introduces new challenges in classification. Glioneuronal tumors are an evolving group of lesions. Besides a growing list of usually low-grade entities with well-defined morphologic features, these also include more poorly defined cases in which a component of infiltrating glioma is often associated with focal neuronal elements. The latter is biologically interesting but of uncertain clinical significance. Oligodendrogliomas and glioneuronal tumors both illustrate the importance of effective communication between the pathologist and the treating oncologist in the discussion of these patients. Finally, the discussion of primitive pediatric tumors stresses the clinical importance of the distinction between different entities, like atypical teratoid rhabdoid tumor, "central" (supratentorial) primitive neuroectodermal tumor, "peripheral" primitive neuroectodermal tumor, and medulloblastoma. In medulloblastomas, the recognition of different variants is emerging as a prognostic factor that may in the future also predict therapy responsiveness.

Neurofibromatosis type 1 and associated malignancies.

Neurofibromatosis type 1 (NF1) is a common autosomal dominant neurocutaneous disorder with a predisposition to the development of benign and malignant tumors. Mutations in the NF1 gene result in loss of function of neurofibromin, a guanosine triphosphatase-activating protein that helps maintain the proto-oncogene Ras in its inactive form. Loss of neurofibromin results in increased proliferation and tumorigenesis. As a result, people with NF1 are at increased risk for the development of nervous and non-nervous system malignancies. Malignancy is a major source of morbidity and mortality in NF1. The natural history of NF1-associated malignancies is often different than that of their sporadic counterparts and, as such, management strategies need to be adjusted accordingly.

Epidemiology of nervous system tumors in children: a survey of 1,485 cases in Beijing Tiantan Hospital from 2001 to 2005.

OBJECTIVE: The purpose of the present retrospective study was to describe the epidemiology of nervous system tumors in children based on the clinical data obtained from a neurosurgical center in Beijing. PATIENTS AND METHODS: During a 5-year period, from January 2001 to December 2005, 1,485 primary brain and spinal tumors in children up to 17 years of age were diagnosed histopathologically according to the World Health Organization 2000 nervous system tumor classification. The sex predilection, tumor location, and histological grade in relation to age were investigated, and the epidemiological characteristics of the 5 most common brain tumors are discussed. RESULT: Of the 1,485 cases evaluated, brain and spinal tumors comprised 92.3% (1,371) and 7.7% (114), respectively, with a predominance of low-grade tumors (65.1 and 78.9% for brain and spinal cord, respectively). For all tumors, the overall sex ratio (male to female) was 1.6:1. 61.9% of the brain tumors were supratentorial, whereas an infratentorial location was slightly more common in the 872 brain tumors of neuroepithelial tissue (53.7%). The 5 most common brain tumors were astrocytic tumors (30.5%), craniopharyngiomas (18.4%), medulloblastomas (14.6%), germ cell tumors (GCTs, 7.9%) and ependymal tumors (5.6%). The highest preponderance of boys was observed in GCTs followed by medulloblastomas. The most common types of spinal tumors were ependymal tumors (19.3%), neurilemmomas (16.7%) and astrocytomas (14.9%). CONCLUSIONS: Based on a large hospital series of pediatric patients, the present survey revealed the histopathological diversity of childhood neurological neoplasms, and provides a reliable profile of the epidemiology of nervous system tumors in children in a developing country.

Temporal paragangliomas.

Temporal paragangliomas (PGL) are usually limited to the paraganglionar system with a sporadic or familial origin. Familial PGL have recently been shown to be associated with germline alterations in SDH group of genes, and occasionally are associated with a variety of genetic multisystemic disorders (von Hippel-Lindau disease, multiple endocrine neoplasia type 2 and neurofibromatosis type 1). Temporal bone PGL are normally located in the region of the jugular foramen and on the promontory along the Jacobson nerve. Occasionally, vagal PGL may reach the jugular foramen and behave as jugular PGL. Treatment of temporal PGL must be based on the biological behavior of the tumour, age and medical condition of the patient, location and size of the PGL, and potential for treatment induced morbidity. The main treatment modalities for PGL are surgery and radiation therapy. Patients with large temporal PGL whose resection would result in potentially disabling morbidity are often selected for radiation therapy or wait and scan policy. Small tympanic PGL where resection may be carried out with a low morbidity risk can be removed through an endomeatal tympanotomy. Jugular PGL limited to the infralabyrinthine region involving only the vertical segment of the ICA, can benefit of an extended facial recess approach, which allows a postoperative normal hearing and facial nerve function. For more extensive disease in the middle ear or around the ICA, external auditory canal preservation is not possible and some kind of facial nerve mobilization is required. Preservation of lower cranial nerves is facilitated by intrabulbar dissection, previous extradural ligation of the sigmoid sinus. Management of large intracranial involvement is controversial, although most authors advocate resection of the tumour in a single stage. Surgical control of the tumour can be expected in 70-85% of the patients and is clearly dependent on the tumour stage. Tumour size determines success in hearing and lower cranial nerves preservation.

Clinical-histopathologic concordance of tumors of the nervous system at the Manuel Velasco Suárez National Institute of Neurology and Neurosurgery in Mexico City.

CONTEXT: When making a diagnosis, the main purpose of clinicians should not be to achieve certainty, but to decrease diagnostic uncertainty in order to make optimal therapeutic decisions. Diagnostic concordance is an essential characteristic if a measurement is to be considered scientific. In the case of tumors of the nervous system (TNS), one of the most accurate diagnostic tests is magnetic resonance imaging. However, histopathologic analyses are essential, because they refine the diagnosis, benefit the patient, and improve our understanding of the disease. By determining the clinical-histopathologic correlation of TNS in one of the main neurologic centers in Mexico, we sought to project reliable morbidity and/or mortality statistics. OBJECTIVE: To assess clinical and histopathologic diagnostic agreement in cases involving TNS admitted to the Manuel Velasco Suárez National Institute of Neurology and Neurosurgery between 1990 and 1999. DESIGN: Cross-sectional diagnostic concordance study, including all clinical hospital records of patients with histopathologically diagnosed TNS, classified according to World Health Organization criteria. RESULTS: Among 2041 TNS cases, the 3 most frequent types were those affecting the neuroepithelial tissue (32.9%), tumors of the sellar region (29.2%), and tumors of the meninges (25.6%). We found that, overall, clinical-histopathologic concordance for these 3 categories was substantial and statistically significant. CONCLUSIONS: Tumors of the nervous system constitute a heterogeneous group of neoplasms. In the present study, clinical diagnoses substantially agreed with pathologic diagnoses. The a priori clinical diagnosis allowed prompt treatment even before diagnostic confirmation by histopathologic analysis, which is the best way to confirm, clarify, and correct a diagnosis.

[The new WHO classification of tumors of the nervous system 2000. Pathology and genetics]. / Die neue WHO-Klassifikation der Tumoren des Nervensystems 2000. Pathologie und Genetik.

New developments in neuro-oncology have prompted an update of the World Health Organization (WHO) classification of tumors of the nervous system. Major changes include the addition of new entities and the refinement of criteria for the diagnosis and grading of various neoplasms, in particular the meningiomas. As novel clinico-pathological entities, the chordoid glioma of the third ventricle, the atypical teratoid/rhabdoid tumor (AT/RT), the solitary fibrous tumor, and the perineurioma have been listed. The former lipomatous medulloblastoma of the cerebellum, previously incorporated in the family of embryonal tumors, is now classified as cerebellar liponeurocytoma. The term mixed pineocytoma/pineoblastoma has been replaced by pineal parenchymal tumor of intermediate differentiation. Furthermore, the large cell medulloblastoma and the tanycytic ependymoma were established as novel tumor variants. A separate chapter on the peripheral neuroblastic tumors has now been included in the classification. Substantial revisions were introduced in the meningioma chapter. For both atypical meningioma WHO grade II and anaplastic meningioma WHO grade III, histopathological criteria are now precisely defined. An important new addition to the WHO 2000 classification of nervous system tumors is the inclusion of molecular pathology findings. With this combination of pathology and genetics it has set the stage for a new format of the WHO tumor classification series.

The WHO classification of tumors of the nervous system.

The new World Health Organization (WHO) classification of nervous system tumors, published in 2000, emerged from a 1999 international consensus conference of neuropathologists. New entities include chordoid glioma of the third ventricle, cerebellar liponeurocytoma, atypical teratoid/rhabdoid tumor, and perineurioma. Several histological variants were added, including tanycytic ependymoma, large cell medulloblastoma, and rhabdoid meningioma. The WHO grading scheme was updated and, for meningiomas, extensively revised. In recognition of the emerging role of molecular diagnostic approaches to tumor classification, genetic profiles have been emphasized, as in the distinct subtypes of glioblastoma and the already clinically useful 1p and 19q markers for oligodendroglioma and 22q/INI1 for atypical teratoid/rhabdoid tumors. In accord with the new WHO Blue Book series, the actual classification is accompanied by extensive descriptions and illustrations of clinicopathological characteristics of each tumor type, including molecular genetic features, predictive factors, and separate chapters on inherited tumor syndromes. The 2000 WHO classification of nervous system tumors aims at being used and implemented by the neuro-oncology and biomedical research communities worldwide.

2000 World Health Organization classification of tumors of the nervous system.

This is a review of the 2000 World Health Organization (WHO) classification of tumors of the nervous system. It contains an overview of the most important changes and short descriptions of the new entities or variants of already existing entities included in the current classification. These are: chordoid glioma of the third ventricle, cerebellar liponeurocytoma, large cell medulloblastoma, medulloblastoma with extensive nodularity and advanced neuronal differentiation, atypical teratoid/rhabdoid tumor, perineuroma, and rhabdoid meningioma. In contrast to the former WHO tumor classification series, the present one is based on the complex criteria, which include not only the clinical course and histologic appearance of the neoplasm but its immunophenotypic features and molecular/cytogenetic profile as well. Thus, it is strongly disease-oriented and uses extensively the recent advances in the basic sciences.

[The classification of nervous system tumors]. / Klassifikatsiia opukholei nervnoi sistemy.

The paper presents the classification of tumors of the nervous system, which is based on the Second Variant of the International Histological Classification of Tumors of the Nervous System which was developed by the WHO experts in 1993 and on the section "Morphology of Neoplasms" of the International Classification of Diseases, Xth review. These classifications were critically reviewed by taking into account the experience gained by the Laboratory of Pathomorphology, Academician N. N. Burdenko Research Institute, Russian Academy of Medical Sciences. The proposed classification may unify the material of our country's neurosurgical clinics and provide more corrective statistic data.

[Epidemiological and classification aspects of nervous system tumors]. / Nekotorye aspekty épidemiologii i klassifikatsii opukholei nervnoi sistemy.

The data obtained from various surveys of the epidemiology of the CNS tumors in different countries were analyzed. It was noted, the incidence of primary CNS tumors remains within the limits of 5-12.5 cases per 100,000 people, and depends on number of factors (e.g. sex, age, place of residence, etc.). Metastases double the incidence of all CNS tumors. The estimated incidence of tumors of the nervous system in Russia and particularly Moscow are given in the paper. The analysis of the data cells for the improvement in the organization of the medical care of this group of patients. With this respect the second WHO histological classification of CNS tumors (WHO, 1993) is critically analyzed. Based on the experience at the Burdenko Neurosurgical Institute (over 10,000 brain biopsies), a modified WHO neuropathological classification is suggested. The classification may be useful in research projects, and may facilitate the diagnosis, treatment, rehabilitation, and final assessment of the outcome. Series of documents of this kind help to make the evaluation of the activities of neurosurgical departments more objective, as well as to make the statistics more reliable.

The international classification of childhood cancer.

The International Classification of Childhood Cancer (ICCC) updates the widely used Birch and Marsden classification scheme. ICCC is based on the second edition of the International Classification of Diseases for Oncology (ICD-O-2). The purpose of the new classification is to accommodate important changes in recognition of different types of neoplasms, while preserving continuity with the original classification. The grouping of neoplasms into 12 main diagnostic groups is maintained. The major changes are: (1) intracranial and intraspinal germ-cell tumours now constitute a separate subgroup within germ-cell tumours; (2) histiocytosis X (Langerhans-cell histiocytosis) is excluded from ICCC; (3) Kaposi's sarcoma is a separate subgroup within soft-tissue sarcomas; (4) skin carcinoma is a separate subgroup within epithelial neoplasms; (5) "other specified" and "unspecified" neoplasms are now usually separate sub-categories within the main diagnostic groups. Draft copies of the ICCC were distributed to some 200 professionals with interest and expertise in the field and their comments are considered in this final version. This classification will be used for presentation of data in the second volume of the IARC Scientific Publication "International Incidence of Childhood Cancer." A computer programme for automated classification of childhood tumours coded according to ICD-O-1 or ICD-O-2 is now available from IARC.