Dilemma in the Treatment of a Central Giant Cell Granuloma.

Management of central giant cell granuloma (CGCG) presents a clinical challenge. While eradicating a lesion known for its high recurrence rate calls for radical surgical approaches, these cause significant esthetic and functional impairment. We present an eight-year-old boy suffering from an extraordinarily large CGCG expanding into the mandible and base of the mouth in the whole anterior region. Combined treatment with surgical intervention and corticosteroid application was successfully applied, and all six attached dental germs could be preserved. Different approaches for clinical management in pediatric cases are discussed.

Epulis: a study of 92 cases with special emphasis on histopathological diagnosis and associated clinical data.

OBJECTIVES: Aim of the present study was clinical and histopathological evaluation of a series of epulides to provide clinicians data to frequency distribution and biological behaviour of different underlying entities. MATERIALS AND METHODS: Ninety-two cases of epulides removed by CO2-laser at the Department of Oral Surgery and Radiology, Medical University of Graz from 2000 to 2014 were studied retrospectively for clinical data and histopathological diagnosis. RESULTS: In the presented study, histopathological examination revealed peripheral ossifying fibroma (32.6 %), fibroma/fibrosis (29.3 %), giant cell lesion (13.1 %) and granuloma pyogenicum (8.7 %) as the most frequent underlying entities. For the first time, hyperplastic squamous epithelium (7.6 %), granulation tissue (5.4 %) and peripheral odontogenic fibromas (3.3 %) were detected to clinically appear as epulides. Irrespective of the histological diagnosis, the mean age in our patients was 43.8 years. The majority of the lesions were found in the frontal region of both jaws. In all cases, the patients showed poor oral hygiene, local gingivitis and some of them an occlusal trauma. CONCLUSIONS: To identify different entities with different biological behaviour, to exclude malignant tumours and to identify new entities among epulides, histopathological examination is required. Poor oral hygiene and occlusal trauma seem to play an important role in the pathogenesis and could be risk factors for recurrences. CLINICAL RELEVANCE: Frequency distribution of different entities in epulides is provided to clinicians, and new histopathological entities were detected to clinically appear as epulides.

Is wide resection obsolete for desmoid tumors in children and adolescents? Evaluation of histological margins, immunohistochemical markers, and review of literature.

Desmoid fibromatosis is a benign fibroblastic neoplasm with high recurrence rates predominantly observed in pediatric and adolescent patients. The use of wide resection margins has been discussed controversially in literature. In addition, data on non-surgical treatment is limited as phase III studies are still missing. Nineteen patients under the age of 18 years were identified. Tumor location, surgical treatment for primary or recurrent tumors, resection margins, medical neo-/adjuvant treatment, time to recurrence as well as immunohistochemical markers (estrogen receptor, ER α and ß, progesterone and androgen receptors, somatostatin, Ki-67, c-kit, platelet-derived growth factor receptors, PDGFRs, α and ß, ß-catenin) were evaluated. The mean age at diagnosis was 6.6 years, with a mean follow-up of 114 months. Recurrences were detected in four out of nineteen patients. Surprisingly, the recurrence rate was not influenced by type of resection used (R0, R1/2). All samples were tested negative for ER α, somatostatin, and progesterone receptor. In contrast, a majority of tumors showed positive results for PDGFR α and ß and ß-catenin. No correlation between positive immunohistochemical markers and tumor recurrences was detectable. In conclusion, recurrence rates are not depending on resection type and immunohistochemical markers seem to behave differently in children and adolescents in contrast to adult patients.

Does insulin-like growth factor 1 receptor (IGF-1R) targeting provide new treatment options for chordomas? A retrospective clinical and immunohistochemical study.

AIMS: The overall prognosis of chordoma is poor, and current treatment options are limited. The insulin-like growth factor 1 receptor (IGF-1R) pathway is important for cell signalling, and attractive for selective inhibition. We investigated the expression of IGF-1R and its ligands, IGF-1 and IGF-2, in a series of 50 chordomas, in order to assess whether IGF-1R-signalling could be a potential target for specific inhibition in chordomas. METHODS AND RESULTS: Fifty chordomas (34 primary tumours, 16 recurrences) from 44 patients were evaluated immunohistochemically for the expression of IGF-1R, IGF-1 and IGF-2. Thirty-eight chordomas (76%) expressed IGF-1R, 46 (92%) expressed IGF-1 and 25 (50%) expressed IGF-2. Semi-quantitative analyses revealed a moderate to strong staining intensity in ≥ 50% of tumour cells for IGF-1R, IGF-1 and IGF-2 in 18 (36%), 32 (64%) and eight (16%) chordomas, respectively. Tumour volume correlated significantly with IGF-1R-staining intensity in primary chordomas (P = 0.042). CONCLUSIONS: IGF-1R and IGF-1 are expressed in the majority of chordomas. IGF-1 expression is much stronger than IGF-2 expression. Patients whose chordomas show a moderate to strong staining intensity in ≥ 50% of tumour cells for IGF-1R (36%) might benefit most from IGF-1R targeting, particularly if they suffer from large and surgically non-resectable chordomas.

Microcystic/reticular schwannoma of the pancreas: a potential diagnostic pitfall.

Schwannomas occurring in the pancreatic head are rare benign non-recurring mesenchymal neoplasms and are reported to show classic morphologic features. Herein we report a case of a 62 year old male presenting with a 5 cm mass in the pancreatic head encasing the portal vein and the truncus coeliacus. Preoperative fine needle aspiration revealed malignant tumour cells consistent with a moderately differentiated adenocarcinoma. A Whipple surgery was performed after palliative chemotherapy. Histological evaluation revealed a multinodular unencapsulated tumour with focal infiltration into pancreas parenchyma and a striking microcystic/reticular growth pattern. Anastomosing and intersecting strands of spindle cells with eosinophilic cytoplasm set in a myxoid partly collagenous stroma were observed. The tumour cell nuclei were round oval and tapered and showed inconspicuous small nucleoli. Degenerative nuclear atypia was seen. Mitotic activity was sparse (1/50 HPF). Pleomorphism or necrosis was absent. The tumour cells showed strong nuclear and cytoplasmic positivity for S-100 protein, and focal positivity for glial fibrillary acidic protein. The diagnosis of a microcystic/reticular schwannoma was made. The awareness of and, to some extent, the knowledge about this rare tumour are needed to achieve the correct diagnosis and to avoid confusion, especially with malignant pancreatic neoplasms.

Establishment and characterization of three novel cell lines - P-STS, L-STS, H-STS - derived from a human metastatic midgut carcinoid.

Carcinoids are rare tumors derived from enterochromaffin (EC) cells of the embryonic neural crest. They have malignant potential and their incidence is steadily increasing. The only curative treatment option is surgery. We have focused on cultivation of human neuroendocrine tumors (NET) as relevant models for the study of potential therapy. Only a few cell lines from human carcinoids have been established so far, among them our earlier KRJ-I cell line from a human ileal carcinoid. The reason for the poor success in establishing carcinoid cell lines is due to the small amount of tissue available and the low mitotic activity in primary cultures. We have successfully established three continuously growing cell lines from tissue obtained from a metastatic human carcinoid of the terminal ileum (midgut carcinoid): P-STS was derived from the primary tumor, L-STS from a lymph node metastasis and H-STS from a hepatic metastasis. Immunocytochemistry proved the maintenance of characteristic neuroendocrine properties. Electron microscopy confirmed the presence of neuroendocrine granules. The three cell lines were tumorigenous in SCID-mice. Cytogenetic analyses revealed clonal tetraploidy, inversion and deletion in chromosome 18q, and non-clonal numerical and structural aberrations. Array CGH did not show notable imbalances. Mutation screening of P-STS excluded a MEN1-gene-associated genetic predisposition with high probability. The novel cell lines P-STS, L-STS and H-STS may be useful in vitro and in vivo models for further studies of biological characteristics and the development of new therapeutic agents.

Low telomerase activity: possible role in the progression of human medullary thyroid carcinoma.

Maintenance of telomere length has been reported to be an absolute requirement for unlimited growth of human tumour cells and in about 85% of cases, this is achieved by reactivation of telomerase, the enzyme that elongates telomeres. Only in rare cases, like in human medullary thyroid carcinomas (MTC), telomerase activity (TA) is low or undetectable; however, this does not limit tumours to become clinically significant. Here, we report that very low TA (below 5% of HEK293) observed in MTC cell strains derived from different patients, although not sufficient for immortalising the cells, is necessary for prolonging their replicative life span. Telomere erosion led to induction of a crisis period after long-term in vitro cultivation, which was reached earlier when treating the cells with MST-312, a telomerase inhibitor at non-toxic concentrations. Crisis was bypassed either by ectopic hTERT introduction or by infrequent spontaneous immortalisation, the latter of which was always associated with telomerase reactivation and changes of the cellular phenotype. While confirming the high importance of telomerase for tumour development, these data draw attention to the relevance of low TA: although insufficient for telomere stabilisation, it allows MTC cells to reach more population doublings, increasing both cell numbers as well as the risk of accumulating mutations and thus might support the development of clinically significant MTC.

Chlamydia psittaci in MALT lymphomas of ocular adnexals: the Austrian experience.

The presence of Chlamydia (C.) psittaci, C. pneumoniae and C. trachomatis DNAs in MALT lymphomas of ocular adnexals from 13 Austrian patients were studied. Gastrointestinal MALT lymphomas and gastritis specimens served as controls. Of 13 MALT lymphomas of the ocular adnexals, seven were positive for C. psittaci DNA. In contrast, one of 17 gastrointestinal specimens tested positive. All specimens were negative for C. trachomatis and C. pneumoniae DNAs. In conclusion, C. psittaci infection was observed in the majority of MALT lymphomas of ocular adnexals in Austrian patients.

Ectomesenchymal chondromyxoid tumor: a comprehensive updated review of the literature and case report.

Prompted by a unique case of an ectomesenchymal chondromyxoid tumor (ECT) of the palate in a 54-year-old female, we reviewed the English and German literature on this entity until the end of 2016 using PubMed. The search produced 74 lingual cases with a nearly equal sex distribution and a mean age of 39.3 years, and two extra-lingual cases sharing histological and immunohistological features including nodular growth, round, fusiform or spindle-shaped cellular architecture, and chondromyxoid stroma. Immunophenotyping showed the majority of cases to be positive for glial fibrillary acidic protein (GFAP), S-100 protein, glycoprotein CD57, pancytokeratin (AE1/AE3), and smooth muscle actin (SMA); in isolated cases there was molecular-genetic rearrangement or gain of Ewing sarcoma breakpoint region 1 (EWSR1) but no rearrangement of pleomorphic adenoma gene 1 (PLAG1). At present, ectomesenchymal cells that migrate from the neural crest are considered to play a pivotal role in tumor origin. All cases had a benign course, although there were three recurrences. Because of the rarity of this tumor and the need for differential diagnostic differentiation from myoepithelioma and pleomorphic adenoma, both oral surgeons and pathologists should be aware of this entity.

Minimally Invasive Excision of Epulides with a CO2 Laser: A Retrospective Study of 90 Patients.

OBJECTIVE: It is the aim of this study to evaluate if the CO2 laser can beneficially be applied for excising epulides. BACKGROUND DATA: The standard procedure for treating epulides involves the excision of the hyperplastic tissue followed in most cases by the removal of parts of the underlying bone and the final closure of the wound by a flap. The use of the CO2 laser for the treatment of epulides has been documented only in isolated case reports and very few case series. PATIENTS AND METHODS: Ninety patients with different subtypes of epulides were treated with a CO2 laser (Lasram, model OPAL 25, 25 W, 10.600 nm, gas laser); power setting 4 W, continuous wave. The surgery was performed only after a pretreatment could remedy any gingivitis or occlusal trauma. A new surgical way of working using a special applicator that allowed tangential application of the laser beam was applied for all patients. Patients were followed up to 3 years. RESULTS: No perioperative complications or recurrences after 4 weeks could be found. Six patients were lost to further follow-up, whereas 84 patients were followed up to 36 months. In 71 cases there were no recurrences over the entire observation period. Thirteen patients developed a relapse, usually a fibroma/fibrosis according to histopathological evaluation. CONCLUSIONS: Overall CO2 laser seems to be an adequate tool for minimally invasive excision of epulides, although the respective histopathological entity could possibly influence the recurrence rate and so should be considered.

CO2 Laser Excision of a Pyogenic Granuloma Associated with Dental Implants: A Case Report and Review of the Literature.

OBJECTIVE: This article reports the CO2 laser excision of a pyogenic granuloma related to dental implants and reviews the current literature on this pathology in association with dental implants. BACKGROUND DATA: Five publications describe pyogenic granulomas related to dental implants, and a further one describes the removal of such a lesion with an Er:YAG laser; removal with a CO2 laser is not reported. PATIENTS AND METHODS: A 67-year-old male patient presented with a hyperplastic gingival lesion around two implants in the left lower jaw. The hyperplastic tissue was removed with a CO2 laser (Lasram; model OPAL 25, 25 W continuous wave, 10.600 nm, gas laser), and a vestibuloplasty was performed. The excised tissue was examined histopathologically. The patient was followed up after 4 weeks, 6 weeks, 6 months, and 1 year, and a panoramic X-ray was also made. RESULTS: There were no complications during surgery or follow-up. The panoramic X-ray taken 1 year after excision showed neither vertical bone loss nor impaired osseointegration of the implant. Histopathology reported a pyogenic granuloma. After vestibuloplasty, the height of the fixed mucosa was satisfactory. CONCLUSIONS: The CO2 laser seems to be a safe and appropriate tool for removal of a pyogenic granuloma in close proximity to dental implants. The laser parameters must, however, be chosen carefully and any additional irritants should be excluded to prevent a recurrence.

Evidence of a polyclonal nature of myositis ossificans.

Myositis ossificans is a localized, self-limiting, reparative lesion that is composed of reactive hypercellular fibrous tissue and bone. Although it is clearly a benign lesion, its clinical, radiological, and histological appearance may sometimes mimic a malignant tumor. Whether myositis ossificans represents a monoclonal or polyclonal hyperplastic proliferation is not yet known. To address this question, we therefore extracted DNA from the respective paraffin-embedded tumor tissues of nine women with a median age of 50 years at diagnosis (range: 20-84 years) and studied the X inactivation pattern by means of methylation-sensitive polymerase chain reaction and primers that target the polymorphic CGG trinucleotide repeat of the FMR1 gene. The fact that we did not detect any skewing of the X inactivation pattern in the five successfully analyzed cases corroborates the notion that myositis ossificans results from a polyclonal proliferation and confirms that it is a reactive, reparative process. Analysis of the X inactivation pattern may, thus, supplement the differential diagnostic work-up of cases with an uncertain histology, at least in the informative proportion of female patients.

MUC1 and MUC2 expression in salivary gland tumors and in non-neoplastic salivary gland tissue.

The expression of MUC1 and MUC2 was studied in salivary gland tumors and non-neoplastic salivary gland tissue. Formalin-fixed paraffin-embedded specimens from 101 patients (21 pleomorphic adenomas (PA), 22 Warthin's tumors (WT), 26 adenoid cystic carcinomas (ACC), 13 acinic cell adenocarcinomas (ACA), 9 mucoepidermoid carcinomas (MC), and 10 specimens of non-neoplastic parotid and submandibular gland tissue) were immunostained. All salivary gland tumors expressed MUC1. A strong immunoreactivity was noted in WT and MC, a moderate in ACC and ACA, and a weak in PA. Strong expression of MUC2 was noted in all WT, moderate expression in MC, and weak expression in PA and ACA. All cases of ACC except for two were negative for MUC2. In general, MUC1 expression was stronger than that of MUC2. Non-neoplastic salivary gland tissue revealed a moderate MUC1 and MUC2 expression in excretory ducts and a strong expression in striated ducts. The apical plasma membrane of some serous acini expressed MUC1. Mucous acini were negative for both antigens. No change in immunoreactivity was noted in cases of chronic sclerosing sialadenitis. In conclusion, the different expression pattern of MUC1 and MUC2 in salivary gland neoplasia may be of additional value for the classification of salivary gland tumors.

'Eosinophilic fungal rhinosinusitis': a common disorder in Europe?

OBJECTIVES/HYPOTHESIS: The traditional criteria for the diagnosis of allergic fungal sinusitis include chronic rhinosinusitis, "allergic mucin" (mucus containing clusters of eosinophils), and detection of fungi by means of histological examination or culture. In 1999, a group of Mayo Clinic researchers, with a novel method of mucus collection and fungal culturing technique, were able to find fungi in 96% of patients with chronic rhinosinusitis. Immunoglobulin E-mediated hypersensitivity to fungal allergens was not evident in the majority of their patients. Because the presence of eosinophils in the allergic mucin, not a type I hypersensitivity, is probably the common denominator in the pathophysiology of allergic fungal sinusitis, the Mayo Clinic group proposed a change in terminology from allergic fungal sinusitis to eosinophilic fungal rhinosinusitis. Using new techniques of culturing fungi from nasal secretion, as well as preservation and histological examination of mucus, we investigated the incidence of "eosinophilic fungal rhinosinusitis" in our patient population. STUDY DESIGN METHODS: In an open prospective study nasal mucus from patients with chronic rhinosinusitis as well as from healthy volunteers was cultured for fungi. In patients, who underwent functional endoscopic sinus surgery, nasal mucus was investigated histologically to detect fungi and eosinophils within the mucus. RESULTS: Fungal cultures were positive in 84 of 92 patients with chronic rhinosinusitis (91.3%). In all, 290 positive cultures grew 33 different genera, with 3.2 species per patient, on average. Fungal cultures from a control group of healthy volunteers yielded positive results in 21 of 23 (91.3%). Histologically, fungal elements were found in 28 of 37 patients (75.5%) and eosinophilic mucin in 35 of 37 patients (94.6%). Neither fungi nor eosinophils were present in 2 of 37 patients (5.4%). CONCLUSIONS: Our data show that the postulated criteria of allergic fungal sinusitis are present in the majority of patients with chronic rhinosinusitis. Either those criteria will be found to be invalid and need to be changed or, indeed, "eosinophilic fungal rhinosinusitis" exists in the majority of patients with chronic rhinosinusitis. Based on our results, fungi and eosinophilic mucin appear to be a standard component of nasal mucus in patients with chronic rhinosinusitis.

Case report of bilateral cervical chondrocutaneous branchial remnants.

Cervical chondrocutaneous branchial remnants are rare and not well known lesions. Histologically the lesion per definition presents as a Choristoma. Choristoma is the pathohistological term for a developmental tumor-like anomaly consisting of tissues foreign to the site at which it is located. Treatment is complete surgical removal as promptly as possible in order to get an exact histopathological diagnosis. A case of a 4-month-old boy with cervical chondrocutaneous branchial remnants anterior to the sternocleidomastoid muscles on both sides is presented. According to literature search this appears to be the second case published on such a bilateral lesion.

The sensitivity of biomarkers for genotoxicity and acute cytotoxicity in nasal and buccal cells of welders.

Welders are inhalatively exposed to fumes which contain genotoxic carcinogens and it was found in epidemiological studies that they have increased cancer rates which may be causally related to DNA damage. In order to assess their health risks and to find out which chemicals cause the adverse effects, bioassays can be performed which enable the detection of genetic damage. The aim of the present study was a comparative investigation with exfoliated buccal and nasal cells in regard to induction of chromosomal alterations and acute cytotoxicity in welders and unexposed controls (n=22 per group). To elucidate the factors which account for genotoxic and cytotoxic effects, additional biochemical parameters were monitored reflecting the redox status as well as concentrations of different metals and 1-hydroxypyrene (1-OHP) in body fluids. We found in the nasal cells significant induction of alterations which are indicative for DNA damage, i.e. of micronuclei (MNi) and nuclear buds, while elevated rates of nuclear anomalies reflecting cytotoxic effects (condensed chromatin, karyorrhexis, karyolylsis) were detected in cells from both organs. The levels of certain metals (Cr, Cu, Mn, Mo, Ni), but not markers of oxidative damage were significantly higher in the body fluids of the welders. Multivariate Poisson regression analyses indicate that exposure to Mo (15% MNi increase by one standard deviation increase of Mo in serum), Ni (9% increase) and Mn (14% increase) are positively associated with the induction of MNi in nasal cells while Ni was associated with cytotoxic effects in both types of cells (12 and 16% increase). Taken together, our findings indicate that epithelial cells from the respiratory tract are suitable for the detection of DNA-damaging and cytotoxic effects in welders and can be used to assess health risks associated with genomic instability.

Clusterin expression in elastofibroma dorsi.

BACKGROUND: Elastofibroma dorsi is a benign soft tissue lesion composed of abnormal elastic fibers. Degenerated elastic fibers in skin and liver are associated with clusterin, an apoprotein that shares functional properties with small heat shock proteins. We evaluated the staining pattern and possible role of clusterin in elastofibroma dorsi. MATERIAL AND METHODS: Twenty-one subcutaneous elastofibromas from the scapular region were evaluated with Elastica van Gieson and Orcein stains, immunohistochemically with antibodies to clusterin, smooth muscle actin, S-100, vimentin and CD34 and correlated with clinical data with respect to physical trauma. RESULTS: Clusterin correlated with the staining pattern of Elastica van Gieson and labelled abnormal broad coarse fibrillar and globular elastic fibers in all elastofibromas. Orcein stains additionally identified fine oxytalan fibers which were not stained by clusterin. Clusterin staining was observed only on the outside of the elastin fibers, while the cores of fibers and globules were unstained. 4/21 elastofibromas showed cellular nodules with a myxoid/collagenous stroma. The round to oval cells showed cytoplasmic staining with vimentin and clusterin; CD34 labelled mostly cell membranes. The cells lacked SMA and S-100 expression. The central areas of the nodules were devoid of elastic fibers, but the periphery contained coarse fibers and globules. 9/ 11 patients, for whom clinical data were available, reported trauma to the scapular region. CONCLUSION: Many investigated ED were associated with trauma, which supports a reactive/degenerative etiology of ED. The abnormal large elastic fibers in all ED were enveloped by clusterin. Clusterin deposition may protect elastic fibers from degradation and thus contribute indirectly to the tumor-like presentation of ED.

Histone deacetylase inhibitors as potential therapeutic approaches for chordoma: an immunohistochemical and functional analysis.

Chordomas are rare malignancies of the axial skeleton. Therapy is mainly restricted to surgery. This study investigates histone deacetylase (HDAC) inhibitors as potential therapeutics for chordomas. Immunohistochemistry (IHC) was performed using the HDAC 1-6 antibodies on 50 chordoma samples (34 primary tumors, 16 recurrences) from 44 patients (27 male, 17 female). Pan-HDAC-inhibitors Vorinostat (SAHA), Panobinostat (LBH-589), and Belinostat (PXD101) were tested for their efficacy in the chordoma cell line MUG-Chor1 via Western blot, cell cycle analysis, caspase 3/7 activity (MUG-Chor1, UCh-1), cleaved caspase-3, and PARP cleavage. p-Values below 0.05 were considered significant. IHC was negative for HDAC1, positive for HDAC2 in most (n = 36; 72%), and for HDACs 3-6 in all specimens available (n = 43; 86%). HDAC6 expression was strongest. SAHA and LBH-589, but not PXD101 caused a significant increase of G2/M phase cells and of cleaved caspase-3 (p = 0.0003, and p = 0.0014 after 72 h, respectively), and a peak of caspase 3/7 activity. PARP cleavage confirmed apoptosis. The presented chordoma series expressed HDACs 2-6 with strongest expression of HDAC6. SAHA and LBH-589 significantly increased apoptosis and changed cell cycle distribution in vitro. HDAC-inhibitors should be further evaluated as therapeutic options for chordoma.

Expression of ezrin, MMP-9, and COX-2 in 50 chordoma specimens: a clinical and immunohistochemical analysis.

STUDY DESIGN: Retrospective study. OBJECTIVE: To investigate the immunohistochemical expression profile of ezrin, matrix metalloproteinase-9 (MMP-9), and cyclooxygenase-2 (COX)-2 in chordomas. SUMMARY OF BACKGROUND DATA: Ezrin, MMP-9, and COX-2 are expressed in different solid tumors, including chordomas. This study investigates the immunohistochemical expression of the aforementioned biomarkers and the clinical outcome in regard to immunohistochemistry, tumor volume, and localization. METHODS: Fifty brachyury-verified chordoma specimens of 34 primary and 16 recurrent tumors of 44 patients were tested for ezrin, MMP-9, and COX-2 as possible therapeutical targets by immunohistochemistry. The clinical evaluation concentrated on tumor location, volume, and age-related data. RESULTS: Ezrin expression was detected in 33 of 34 primary chordomas and in 16 of 16 recurrent cases. The primary chordomas located in the sacrum and the spine demonstrated a significantly higher percentage of positively stained tumor cells (P = 0.034) than the skull-based chordomas. An expression of MMP-9 and COX-2 was observed in 33 of 34 primary chordomas and in 16 of 16 recurrences, and in 13 of 34 primary chordomas and in 11 of 16 recurrences, respectively. Patients' survival was significantly influenced by age (P = 0.01), tumor location (P = 0.029), and tumor volume (P = 0.002). A significant positive correlation between tumor volume and the anatomic distance of the chordoma from the skull was calculated (P = 0.00002). CONCLUSION: En bloc resection with tumor-free margins is seldom feasible, particularly in the sacrum. Intralesional excisions mostly end in early local recurrence; therefore, the demand for further treatment options is frequently posed. The marked trend of the investigated biomarkers of this study may build a starting point for further investigations as molecular targets for future adjuvant therapies in chordomas. Future multicenter studies on larger patients' series are necessary to elucidate these preliminary data and to test new treatment options for patients with chordomas.