[Rare differential diagnosis of an osteolytic lesion of the mandible in a young adult]. / Seltene Differenzialdiagnose bei osteolytischer Läsion des Unterkiefers einer jungen Erwachsenen.

We report a rarely occurring hematologic neoplasm in a young adult. Hematologic neoplasms were first described in 2008 and are now included in both accepted tumor classification systems, i.e., International Consensus Classification and World Health Organization. This hematologic neoplasm shows a characteristic ALK positivity in immunohistochemical examination and correspondingly, ALK fusion genes in the molecular analysis. Pathologists should be aware of this entity, particularly as it is challenging to differentiate from other more frequent neoplasms of the same disease group or mesenchymal neoplasm with ALK aberration.

Three-dimensional accuracy of mandibular reconstruction by patient-specific pre-bent reconstruction plates using an "in-house" 3D-printer.

PURPOSE: The purpose of this study was to compare the three-dimensional accuracy of mandibular reconstruction following mandible continuity resection in patients treated with patient-specific, pre-bent reconstruction plates, using an 'in-house' 3D printer, with that in patients treated with conventional, intraoperatively bent plates. PATIENTS AND METHODS: We retrospectively analyzed 42 alloplastic mandibular reconstructions following continuity resection. 21 patients received patient-specific, pre-bent reconstruction plates using an in-house 3D printer. The control group consisted of 21 patients provided with intraoperatively bent reconstruction plates. Distances between corresponding anatomical landmarks on the mandibular angle and condyle (A-A', BB', CC', BC'), as well as the intercondylar angle (ICA), were measured and compared on the pre- and postoperative CT scans. RESULTS: Multivariate analysis of variance (MANOVA) showed significant multivariate main effect of group (F(5, 36) = 5.58, p = 0.001; Wilks lambda 0.564; partial η2 = 0.436), indicating more accurate postoperative results for the pre-bent group. Post-hoc comparison revealed significantly larger postoperative deviation in the distances between the mandibular angle and the intercondylar angle (ICA) for the intraoperatively bent group in comparison with the pre-bent group. However, there was no significant effect on the distance between the condyles. CONCLUSIONS: Mandibular reconstructions employing patient-specific, pre-bent reconstruction plates made using an in-house 3D printer show significantly better three-dimensional accuracy compared with intraoperatively bent plates. The described method prevents rotational error of the mandibular angle and improves restoration of the physiological intercondylar angle in mandible reconstruction after continuity resection.

Evaluation of a biomarker based blood test for monitoring surgical resection of oral squamous cell carcinomas.

INTRODUCTION: The potential use of determination of biomarkers in blood for the monitoring of surgical removal of oral squamous cell carcinomas (OSCC) was evaluated using the epitope detection in monocytes (EDIM) technology. MATERIALS AND METHODS: In tumor specimen, elevated Apo10 and transketolase-like 1 (TKTL1) expression was analyzed by immunohistochemistry. Apo10 and TKTL1 biomarkers have been used prospectively for EDIM blood test in patients with primary and/or recurrent OSCC (n = 92) before surgery and after curative tumor resection (n = 45). RESULTS: There were highly significant (p < 0.0001) correlations found between EDIM blood scores and the tissue expression of both biomarkers measured by immunohistochemistry (Apo10: n = 89/92, 97%; TKTL1: n = 90/92, 98%). EDIMApo10 and EDIM-TKTL1 scores were positive in 92% (EDIM-Apo10: n = 85/92) and 93% (EDIM-TKTL1: n = 86/92), respectively, in patients with OSCC before surgery. The combined score EDIM-Apo10/EDIM-TKTL1 increased significantly the detection rate of tumors to 97% (n = 89/92). After surgery, the EDIM-TKTL1 and EDIMApo10 scores significantly decreased in 75.6 and 86.7% of the patients (p < 0.0001), respectively, in the aftercare. CONCLUSIONS: The correlation of TKTL1 and Apo10 immunohistochemistry with the blood test results indicates that the EDIM blood test could serve as a non-invasive diagnostic tool (liquid biopsy) to assess surgical removal of OSCC by determination of two biomarkers. CLINICAL RELEVANCE: This is the first study that has been demonstrated a reliable and successful monitoring of OSCC cancer patients by a blood test. The specific and significant decrease of EDIM-TKTL1 and EDIM-Apo10 scores after surgery could serve as a new tool for monitoring surgical removal of OSCC.

Immunohistochemical detection of Helicobacter pylori without association of TLR5 expression in oral squamous cell carcinoma.

BACKGROUND: Approximately 15% of human deaths from cancer are associated with chronic viral or bacterial infections. Helicobacter pylori (HP), a flagellated, Gram-negative, spiral, microaerophilic bacteria is considered to be the most common chronic bacterial infection in humans. Toll-like receptor 5 (TLR5) is involved in recognition of bacterial flagella and is thought to promote tumour growth through inflammation-dependent mechanisms in epithelial cells. METHODS: Expression of HP and TLR5 was analysed in OSCC specimen (n = 191) by immunohistochemistry. TLR5 expression specificity was conducted by Western blotting in cancer cell lines (BICR3, BICR56). TLR5-stained sections were scanned and digitally analysed using ImageJ and the immunomembrane plug-in. HP expression and TLR5 expression were associated with clinicopathological characteristics and impact on survival. RESULTS: Helicobacter pylori detection was significantly associated with recurrence of the tumour, whereas TLR5 expression was not. Multivariate analysis demonstrated HP expression as an independent prognostic factor (P = 0.0260). TLR5 specificity was confirmed by Western blot analysis. CONCLUSIONS: For the first time, this study provides evidence that immunohistochemically detected HP expression in OSCC is associated with reduced disease-free survival in a large patient cohort. Although TLR5 was not associated with any clinicopathological characteristics or impact on survival, investigation of the TLR family seems to be reasonable due to the possible existence of other pathogenic bacterial or viral compounds in oral cavity cancer.

Assessment of indications and clinical outcome for the endoscopy-assisted combined subciliary/transantral approach in treatment of complex orbital floor fractures.

BACKGROUND: The treatment of complex orbital floor fractures with extensive orbital prolapse remains a surgical challenge in craniomaxillofacial traumatology and is still controversially discussed. Reduction of orbital tissue via a transcutaneous or transconjunctival approach alone can be very difficult and lead to unsatisfying results. METHODS: Over a 3-year-period, we enrolled 13 patients who underwent endoscopy-assisted reconstruction of isolated orbital floor fractures via a combined subciliary and transantral approach. Patient data, imaging and ophthalmologic examination were reviewed prospectively. RESULTS: Ten patients underwent primary surgical treatment, 3 patients had secondary surgical treatment because of unsatisfactory results of primary surgical intervention. All patients had an uneventful postoperative course without ophthalmologic deterioration, no further surgical procedures were necessary. CONCLUSIONS: The additional use of an endoscopy-assisted transantral approach provides a reliable treatment modality in selected cases. To our knowledge, this is the only study of patients treated with a combined subciliary and transantral approach. Special emphasis was given to postoperative functional results, a short algorithm for use of an additional transantral endoscopy-assisted approach is presented.

Prognostic value of histamine H1 receptor expression in oral squamous cell carcinoma.

OBJECTIVES: Overexpression of the histamine H1 receptor (H1R) has been described in a variety of tumor models, but experience in oral squamous cell carcinomas (OSCC) is not available. Current adjuvant treatment options for OSCC can be improved by the identification of new targets of therapy. Herein, we evaluated H1R expression in a large patient cohort of OSCC. MATERIALS AND METHODS: H1R immunoexpression was evaluated in 191 cases of OSCC and two OSCC cell lines BICR56 and BICR3. Scanned images were digitally analyzed using ImageJ and the immunomembrane plug-in. The combined score of computer-assisted semiquantitative analysis was correlated with manually counted percentages of tumor cells by Kendall's tau (т) correlation coefficient. Disease-free survival times were estimated using the Kaplan-Meier method and were compared by using the log-rank test. Multivariate analyses were performed using the Cox proportional hazards model. RESULTS: H1R was rarely expressed in OSCC but significantly related with advanced tumor stages (n = 21/191, mean expression 63.5% of cancer cells in positive tumor samples, 95% confidence interval of the mean 53.5 to 73.6%, p = 0.006). Following univariate analysis, patients with H1R expression showed a significant poorer prognosis (p = 0.0004). Multivariate analysis revealed H1R expression as an independent prognostic factor (p = 0.0164). Expression of H1R in cancer cell lines was confirmed by specific staining of OSCC cell lines BICR56 and BICR3. CONCLUSION: This is the first study focusing on H1R expression showing a significant poorer DFS rate in the H1R+ patient cohort. Based on these data, H1R activation may promote carcinogenesis in OSCC. CLINICAL RELEVANCE: Investigation of H1R regulation and its antagonists shows a clear rationale for future supportive anticancer therapies in OSCCs.

Transketolase-like protein 1 expression in recurrent oral squamous cell carcinoma after curative resection: a case report.

BACKGROUND: Squamous cell carcinoma of the oral cavity (OSCC) is one of the common malignant tumors of the head and neck worldwide. Transketolase-like protein 1 (TKTL1), which has an important role in controlling the nonoxidative pentose-phosphate pathway, is significantly overexpressed in several different tumor entities. TKTL1 overexpression confers an advantage on malignant cells, allowing them to grow faster and to metastasize. However, to date, there is no link between TKTL1 expression and (metastatic) OSCC. CASE REPORT: We report the first case of simultaneous penile, lung, bone, and suprarenal gland metastases from a primary bifocal moderately differentiated keratinized OSCC in a 53-year-old man that occurred 7 months after primary diagnosis. The tumor stained positive for TKTL1, epithelial growth factor receptor, and cyclooxygenase-2 (COX-2). To the best of our knowledge, no case has been reported to date on the manifestation of synchronous distant metastases of OSCC in the penile and the suprarenal gland. CONCLUSIONS: Secondary malignancy of the penis is an uncommon clinical entity. Because of the possibility of penile metastatic spread, this case report suggests that particular attention should be paid to physical examination of patients who undergo surgical procedures from OSCC, including those seemingly without metastatic disease. For the first time, our case provides evidence that TKTL1 expression in recurrent OSCC might be associated with tumor formation and metastasis. Antibodies, small molecules, COX-2 inhibitors, or a ketogenic diet might be promising for therapy of metastatic OSCC.

ABCB5 expression and cancer stem cell hypothesis in oral squamous cell carcinoma.

INTRODUCTION: The vast majority of oral cancers are squamous cell carcinomas (OSCC). The effectiveness of adjuvant cytostatic chemotherapy for OSCC is frequently restricted due to an inducible cellular mechanism called multidrug resistance (MDR) and a putative cancer stem cell (CSC) compartment in human carcinogenesis expressing multidrug efflux pumps. The novel human ATP-binding cassette (ABC) transporter ABCB5 [subfamily B (MDR/TAP) member 5] acts as an energy-dependent drug efflux transporter and marks tumour cells of a putative CSC compartment. However, to date, there is no link between ABCB5 expression and OSCC. MATERIALS AND METHODS: Expression of ABCB5 was analysed in OSCC specimen (n=191) and cancer cell lines (BICR3, BICR56) by immunohistochemistry, real-time polymerase chain reaction (RT-PCR) analysis and western blotting. Scanned images were digitally analysed using ImageJ and the immunomembrane plug-in. ABCB5 expression on protein level was correlated with clinical characteristics and impact on survival. ABCB5 was co-labelled with CD44 in immunohistochemical and immunofluorescence double labelling experiments. Expression subgroups were identified by receiver operating characteristics (ROC) analysis. RESULTS: High ABCB5 expression was significantly associated with tumour progression and recurrence of the tumour. Multivariate analysis demonstrated high ABCB5 expression as an independent prognostic factor (p=0.0004). Immunohistochemical and immunofluorescence double labelling experiments revealed ABCB5 expression by CD44+ cancer cells. ABCB5 specificity was confirmed by western blot and RT-PCR analysis. CONCLUSIONS: For the first time, this study provides evidence that ABCB5 expression in OSCC might be associated with tumour formation, metastasis and a putative CSC compartment. One of the principal mechanisms for protecting putative cancer stem cells is through the expression of multifunctional efflux transporters from the ABC gene family, like ABCB5. This provides one mechanism in which putative cancer stem cells could survive and may lead to tumour relapse. Knowledge of expression profiles of ABC transporters and other genes involved in MDR will likely help therapeutic optimisation for cancer patients in clinic. However, this hypothesis requires further in vitro and in vivo studies.

Quality of life after unilateral acoustic neuroma surgery via middle cranial fossa approach.

CONCLUSIONS: Patients with acoustic neuroma experienced reduced quality of life (QOL) after surgery. Individual factors did not have a significant effect on QOL. In the future, QOL should be a basic factor in the outcome evaluation of different therapeutic regimens in the treatment of acoustic neuroma. OBJECTIVE: To measure the QOL of patients who underwent unilateral acoustic neuroma surgery via the middle cranial fossa approach. MATERIAL AND METHODS: The Short Form-36 (SF-36) Health Survey and a self-designed disease-specific questionnaire were used during follow-up examinations to assess health-related QOL. The pure-tone average was used to specify hearing ability. Facial nerve function was described using the House-Brackmann grading system. A total of 28 male and 14 female patients who underwent surgery between 1997 and 2001 were included in the study. RESULTS: Patients' QOL scores revealed significant reductions in QOL in comparison to normative German QOL data. Gender, age, tumor size or location and clinical symptoms such as hearing loss and restricted facial nerve function did not have an effect on QOL. The SF-36 scales physical functioning, role functioning-physical, bodily pain, general health, social functioning and role functioning-emotional demonstrated significant QOL reductions.