Relative size of fungiform papillae in patients with neurofibromatosis Type 1.

OBJECTIVE: To explore possible manifestations of neurofibromatosis on the tongue, especially, enlarged papillae fungiformes. According to the literature, enlarged fungiform papillae of the tongue are a very common oral finding in patients with Neurofibromatosis Type 1 (NF1). MATERIALS AND METHODS: Firstly, photos of 18 NF1 patients' tongues, taken at different times were compared to rule of possible fluctuating papillae size. Secondly, 60 photos of 60 patients with NF1 were age/sex matched, blinded and compared to 60 photos of 60 healthy patients. Three independent medical doctors rated the photos in regard of the fungiform papillae as smaller/same/larger at two different times. The inter- and intraindividual results were compared. Thirdly, fungiform papillae of 11 NF1 patients were quantitatively measured using the Denver protocol. RESULTS: The fungiform papillae showed a stable size. The comparison of the healthy individuals to the NF1 patients suggests that the larger papillae are significantly more frequent in NF1 patients than in age- and gender-matched non-NF1 individuals. The agreement between two ratings of each of the 3 raters at different time points was two moderate and one substantial, the agreement among raters was only fair, since the Fleiss' Kappa value of all 6 ratings was 0.38. CONCLUSION: Although this study confirms that the evaluation of the size of the fungiform papillae by visual inspection only is very subjective, the fungiform papillae in NF1 patients do seem to be enlarged at a statistically significant level. Nonetheless the statistical difference is not distinctive enough to establish this as a diagnostic tool in diagnosing NF1. CLINICAL RELEVANCE: Facilitating the diagnosis of NF1 is an important factor in finding the correct treatment for these patients. A clinical inspection of the tongue is a simple and non-invasive procedure. This paper addresses the question if an inspection of the tongue, especially the fungiform papillae is a reliable indicator for the diagnosis of NF1.

Overexpression of TACE and TIMP3 mRNA in head and neck cancer: association with tumour development and progression.

BACKGROUND: TACE/ADAM17 is a transmembranous protease that cleaves membrane-bound growth factors like EGFR ligands. TACE-dependent proteolysis is regulated by its inhibitor, tissue inhibitor of metalloproteinases 3 (TIMP3). This study analyses the role of TACE and TIMP3 mRNA expression in squamous cell carcinomas of the head and neck (HNSCCs). METHODS: We analysed TACE and TIMP3 mRNA expression in HNSCCs from 106 patients by RNA in situ hybridisation. RESULTS: TACE mRNA was upregulated in HNSCCs compared with dysplastic (P<0.05) and normal epithelia (P<0.001), with strong hybridisation signals in 21.9% of invasive tumour tissues and 4.5% of dysplasia. Elevated mRNA levels were accompanied by increased amounts of TACE protein in HNSCCs. TIMP3 mRNA expression in HNSCC-associated stroma was significantly higher than in the stroma adjacent to dysplastic or normal epithelia. Expression of TACE mRNA in HNSCCs was associated with tumour stage (P=0.019) and regional lymph node metastasis (P=0.009). Furthermore, levels of TACE mRNA in HNSCCs correlated with the expression of TIMP3 mRNA in HNSCC-associated stroma. Concomitantly, patients expressing high levels of TACE and TIMP3 mRNA showed significantly reduced overall survival compared with those with low mRNA levels. CONCLUSION: Our results indicate an important role of TACE and TIMP3 during development and progression of HNSCCs.

Hypercementosis and odontogenic epithelial hyperplasia associated with a tooth root remnant mimicking a neoplasm. A case report.

Hypercementosis presents as painless, single or multiple non-neoplastic cementum formation beyond the physiological limits of the tooth. It often occurs in the apical area of the involved tooth following infection, chemical or mechanical trauma. We report on radiographic and histopathological findings in a single case of late intraosseous hypercementosis and odontogenic epithelial hyperplasia associated with a minute apical tooth root remnant years after its extraction, mimicking a tumour.

Expression and distribution of tenascin in rat submandibular glands following irradiation.

UNLABELLED: The aim of this study was to investigate the late changes in the expression of tenascin-C (TN-C) in salivary glands (SG) following irradiation (IRR). MATERIALS AND METHODS: In 124 submandibular SG from 62 Wistar rats, the effect of IRR dose (fractionated IRR, 2 Gy per day, total dose of 20, 40, or 60 Gy), time since IRR (6 months vs. 12 months), and animal age (1 year vs. 1.5 years) on TN-C expression profile and its distribution pattern was investigated. RESULTS: Expression of TN-C showed slight to moderate alterations in the irradiated specimens. The expression differed in frequency and degree among various tissue structures. The most striking finding was pronounced dose-dependent heterogeneity, with increases, decreases and fluctuations in staining. CONCLUSION: The staining of TN-C predominantly showed notable dose-dependent heterogeneity, persisting for up to 1 year after completion of IRR. Thus, these findings can be attributed to late radiation effects. The altered expression of tenascin-C may play at least a partial role in late radiogenic dysfunction of the submandibular SG.

Clinical characterisation of 29 neurofibromatosis type-1 patients with molecularly ascertained 1.4 Mb type-1 NF1 deletions.

BACKGROUND: Large deletions of the NF1 gene region occur in approximately 5% of patients with neurofibromatosis type-1 (NF1) and are associated with particularly severe manifestations of the disease. However, until now, the genotype-phenotype relationship has not been comprehensively studied in patients harbouring large NF1 gene deletions of comparable extent (giving rise to haploinsufficiency of the same genes). METHOD: We have performed the most comprehensive clinical/neuropsychological characterisation so far undertaken in NF1 deletion patients, involving 29 patients with precisely determined type-1 NF1 (1.4 Mb) deletions. RESULTS: Novel clinical features found to be associated with type-1 NF1 deletions included pes cavus (17% of patients), bone cysts (50%), attention deficit (73%), muscular hypotonia (45%) and speech difficulties (48%). Type-1 NF1 deletions were found to be disproportionately associated with facial dysmorphic features (90% of patients), tall stature (46%), large hands and feet (46%), scoliosis (43%), joint hyperflexibility (72%), delayed cognitive development and/or learning disabilities (93%) and mental retardation (IQ<70; 38%), as compared with the general NF1 patient population. Significantly increased frequencies (relative to the general NF1 population) of plexiform neurofibromas (76%), subcutaneous neurofibromas (76%), spinal neurofibromas (64%) and MPNSTs (21%) were also noted in the type-1 deletion patients. Further, 50% of the adult patients exhibited a very high burden of cutaneous neurofibromas (N>or=1000). CONCLUSION: These findings emphasise the importance of deletion analysis in NF1 since frequent monitoring of tumour presence and growth could potentiate early surgical intervention thereby improving patient survival.

High bone turnover and accumulation of osteoid in patients with neurofibromatosis 1.

UNLABELLED: Although it is known that neurofibromatosis 1 (NF1) patients suffer from vitamin D deficiency and display decreased bone mineral density (BMD), a systematic clinical and histomorphometrical analysis is absent. Our data demonstrate that NF1 patients display high bone turnover and accumulation of osteoid and that supplementation of vitamin D has a beneficial effect on their BMD. INTRODUCTION: Neurofibromatosis 1 results in a wide range of clinical manifestations, including decreased BMD. Although it has been reported that NF1 patients have decreased vitamin D serum levels, the manifestation of the disease at the bone tissue level has rarely been analyzed. METHODS: Thus, we performed a clinical evaluation of 14 NF1 patients in comparison to age- and sex-matched control individuals. The analysis included dual X-ray absorptiometry osteodensitometry, laboratory parameters, histomorphometric and quantitative backscattered electron imaging (qBEI) analyses of undecalcified bone biopsies. RESULTS: NF1 patients display significantly lower 25-(OH)-cholecalciferol serum levels and decreased BMD compared to control individuals. Histomorphometric analysis did not only reveal a reduced trabecular bone volume in biopsies from NF1 patients, but also a significantly increased osteoid volume and increased numbers of osteoblasts and osteoclasts. Moreover, qBEI analysis revealed a significant decrease of the calcium content in biopsies from NF1 patients. To address the question whether a normalization of calcium homeostasis improves BMD in NF1 patients, we treated four patients with cholecalciferol for 1 year, which resulted in a significant increase of BMD. CONCLUSION: Taken together, our data provide the first complete histomorphometric analysis from NF1 patients. Moreover, they suggest that low vitamin D levels significantly contribute to the skeletal defects associated with the disease.

Bone health and fracture rate in individuals with neurofibromatosis 1 (NF1).

BACKGROUND: Patients with neurofibromatosis 1 (NF1) are shorter than expected and often have low bone mineral density (BMD), but the pathogenesis of these bony problems is poorly understood. METHODS: We performed an exploratory study of BMD, 18 laboratory measures of bone metabolism, and fracture history in 72 adult NF1 patients. RESULTS: Eight of the 18 clinical biochemical measures of bone health had at least 10% of NF1 patients outside the standard reference range. Serum 25-hydroxy-vitamin D concentrations were low in 56% of the NF1 patients, serum parathyroid hormone (PTH) concentrations were high in 34%, and urine deoxypyridinoline cross-link concentrations were high in 50%. Mean serum 25-hydroxy-vitamin D concentrations were significantly lower in people with NF1 than in season matched controls in both summer (p = 0.008) and winter (p<0.001). 36 (50%) of the 72 people with NF1 studied had BMD consistent with osteopenia, and 14 (19%) had BMD consistent with osteoporosis. High serum PTH concentration, high serum bone tartrate resistant acid phosphatase concentration, and high serum calcium concentration were associated with lower BMD among the NF1 patients. Males were more likely than females to have low BMD. The reported frequency of fractures in individuals with NF1 was much higher than in their unaffected siblings and spouses (p<0.001), and pathological fractures were reported only in NF1 patients. CONCLUSION: People with NF1 often have a generalised abnormality of bone metabolism. Further studies are needed to determine the biochemical and molecular basis of this abnormality.

Longitudinal study of neurofibromatosis 1 associated plexiform neurofibromas.

BACKGROUND: Plexiform neurofibromas are benign tumours that occur in more than half of people with neurofibromatosis 1 (NF1). These tumours can cause serious complications and can also progress to malignant peripheral nerve sheath tumours (MPNSTs), one of the leading causes of death among NF1 patients. Plexiform neurofibromas are clinically heterogeneous, and knowledge of their natural history is limited. In order to characterise the growth of plexiform neurofibromas better, we performed serial magnetic resonance imaging (MRI) in NF1 patients with such tumours. METHODS: MRI was done on 44 plexiform neurofibromas in 34 NF1 patients (median age 10 years; range 1-47 years). Each tumour was measured in two dimensions from the MRI scan, and the area and growth rate were calculated. The median length of follow-up was 6 years, with an average interval of 3 years between scans. RESULTS: 36 tumours remained stable in size throughout the period of follow-up. 8 tumours increased in size; all occurred in patients who were under 21 years of age when first studied. The single exception was a man who developed rapid tumour growth and pain in a plexiform neurofibroma that had been followed for 10 years. Biopsy showed the presence of an MPNST. CONCLUSION: Longitudinal MRI is a valuable means of monitoring the growth of plexiform neurofibromas in individuals with NF1.

Navigation-assisted resection of a primary extraocular melanoma of the orbit.

UNLABELLED: A 22-year-old male presented with proptosis of the right eye and diplopia. On magnetic resonance images (MRI), a well-delineated orbital tumor medio-distal to the eye was detected, respecting the eye-ball and the orbital walls. The aim of navigation-assisted surgery was to excise the progressive tumor while maintaining vision. A modified latero-cranial orbitotomy was used to approach the tumor. Microscopic analysis of the resection specimen revealed a melanoma. The patient's postoperative course was uneventful. The diplopia improved rapidly. Two further eye-saving second-look revisions of the tumor site excluded further melanoma infiltrates and revealed melanophages in scar tissue. Intraoperative navigation was used during all procedures. The tumor showed some interesting features concerning its histopathological appearance and magnetic resonance imaging. Detailed histopathological investigations supported the decision for organ-saving surgery. Follow-up MRI and positron emission tomograms up to 14 months later showed neither local tumor recurrence nor distant spread. CONCLUSION: In the presented case with the incidental finding of orbital melanoma without invasion of the globe or orbital walls, navigation-assisted surgery supported the eye-saving operating procedures.

Clinical relevance of positron emission tomography and magnetic resonance imaging in the progression of internal plexiform neurofibroma in NF1.

Neurofibromatosis type 1 (NF1) is a frequent and inherited disease with a predisposition for malignant peripheral nerve sheath tumor (MPNST) development. MPNST are soft tissue sarcomas that arise from peripheral nerves, being one of the most aggressive malignancies in humans with extremely poor prognosis. MPNST frequently arise from a previously undetected plexiform neurofibroma (PNF). The malignant transformation of an internal PNF to an MPNST is difficult to assess and requires advanced imaging techniques like magnetic resonance imaging or positron emission tomography. Despite the high quality of current diagnostics, the changing tumor biology inside a plexiform neurofibroma cannot currently be visualized accurately. We report 4 cases of NF1 patients with PNF who showed imaging findings suspicious for malignant degeneration, but proved to have MPNST in only one case. Three tumors might represent an intermediate type between PNF and MPNST. Ablative surgery and complete histological work-up of specimens is the only way to clarify tumor status, thereby enabling provision of adequate local treatment.

Malignant peripheral nerve sheath tumors (MPNST) in NF1-affected children.

BACKGROUND: Malignant peripheral nerve sheath tumors (MPNST) constitute a heterogeneous group of malignant tumors that probably arise from cells of the peripheral nerve sheath. Association of MPNST with neurofibromatosis type 1 (NF1) is frequently reported. MPNST contribute significantly to the reduced life-span of NF1-patients. At present there are only sparse data on MPNST in NF1-children. The aim of this study was to determine the outcome of children affected with NF1 who developed an MPNST. MATERIALS AND METHODS: Over the period of 1985 to 2005, we followed 52 NF1 patients with MPNST at our outpatient department. All patients were diagnosed and re-evaluated according to the updated NIH diagnostic criteria for NF1. RESULTS: Out of this cohort, 8 patients with MPNST were aged 1 to 17 years at the time of MPNST diagnosis (mean age: 12 years; 5 girls and 3 boys). We noticed the following characteristics: MPNST arose from plexiform neurofibromas (PNF) with invasive or displacing growth pattern on MRI. Many patients reported pain and neurological deficits at the time of presentation. Diagnosis of MPNST in this age group took longer compared to adults. This cohort did not show longer survival periods than adults with MPNST. Adjunctive treatment with chemotherapy or radiation had no lasting effect. The overall survival time of this small cohort was 30.5 months. Those children who died showed a median survival time after diagnosis of 20 months. The longest survival of 112 months was achieved for a girl who presented with MPNST of the distal upper arm and underwent amputation. The NF1 mutation analysis in the MPNST pediatric age group revealed the same mutational spectrum as the adult group. CONCLUSION: Our data reveal MPNST in children with NF1. Children cannot verbalize physical alterations adequately; therefore the correct diagnosis might be hampered in these patients. Unresolved complaints of children with NF1 should be investigated thoroughly due to the risk for malignancy in NF1.

Expression and distribution of cytokeratins and vimentin in rat larynx and trachea following irradiation.

BACKGROUND: External irradiation (IRR) of advanced head and neck tumors often includes tissues of the larynx and trachea unaffected by cancer. In these normal tissues, both single-cell damage (necrosis, apoptosis, functional cell death) and interstitial damage (edema, fibrosis, vascular alterations, cellular infiltrations) resulting in tissue remodeling can occur, depending on various IRR parameters. However, reports on radiogenic intermediate filament protein alterations in laryngeal-tracheal tissues are very rare. In this study, we investigated the phenotypic characterization of the normal integrity-supporting cytokeratins (CK) and vimentin following a clinically relevant IRR protocol in laryngeal-tracheal tissues. MATERIALS AND METHODS: In 61 laryngo-tracheal specimens from Wistar rats the expression profile and distribution pattern of CK (CK13, CK17/19, CK18) and vimentin were investigated according to IRR dose (fractionated IRR, 2 Gy per day, total dose of 20, 40 or 60 Gy), time from IRR (6 months vs. 12 months) and animal age (1 year vs. 1.5 years) using immunohistochemical methods, semiquantitative assessment and multivariate analysis. RESULTS: In irradiated specimens, expression of both CK and vimentin showed slight to moderate dose-dependent alterations. The expression differed in frequency and level among the various tissue structures and showed remarkable heterogeneity, with increases, decreases and fluctuations in staining. In the glottic mucosal layer (non-keratinizing squamous epithelium), CK13 expression decreased with increasing dose. The CK17/19 expression of supra- and subglottic respiratory epithelia following 20 and 60 Gy exposure was significantly lower than in controls. The respiratory epithelia and, in part, the cuboidal epithelia of the indifferent type at the inner side of the aryepiglottic fold revealed increasing CK17/19 immunoreactions up to 40 Gy IRR, but a distinct decrease in expression at 60 Gy. In subglottic gland structures, CK18 was detected at significantly higher levels than in controls. There was increasing expression with increasing dose. CK18 reactions of supra- and subglottic respiratory mucosal layer, supraglottic gland structures and thyrocytes tended towards increasing expression with increasing dose and in older animals. Tracheal mucosal epithelia, tracheal glands, and respiratory epithelia of the inner side of the aryepiglottic fold tended towards decreasing expression of CK18 with increasing dose and in older animals. In part, these tissues showed dose-dependent fluctuations. Furthermore, the vimentin reactions showed dose-dependent, heterogeneous patterns, with increases, decreases, and fluctuations in staining. Moreover, there were differences in frequency and intensity of expression among the various tissue structures. Age and time from IRR had no significant effect on immunoreaction. CONCLUSION: The staining of CK and vimentin predominantly showed a notable dose-dependent heterogeneity, with increases, decreases and fluctuations in expression. The expression pattern persisted for up to 1 year after the completion of irradiation. Thus, these findings must reflect late radiation effects. The altered expression of CK and vimentin may play at least a partial role in structural (e.g. edema) and functional (e.g. voice disorders) changes associated with irradiation of the head and neck.

Expression of insulin-like growth-factor-1 receptor (IGF-1R) in peripheral nerve sheath tumors in neurofibromatosis type 1.

BACKGROUND: Neurofibromatosis type 1 (NF1) is an autosomal-dominant inherited disease, characterised by the development of nerve sheath tumors. NF1 is the most frequently inherited disease associated with a predisposition for cancer (in particular malignant peripheral nerve sheath tumors: MPNST). NF1 is a progressive disease with phase-like growth spurts of dermal or plexiform neurofibroma (PNF). These tumors can cause severe disfigurement of patients. Growth control of these tumors is poorly understood. The aim of this study was to identify the expression of insulin-like growth factor 1-receptor (IGF-1R) in peripheral nerve sheath tumors. Factor and receptor are involved in the growth control of numerous physiological and pathological processes, including Schwann cell development. MATERIALS AND METHODS: The investigation included tumors of NF1-patients only (neurofibroma, MPNST). Sections of the specimens were immunohistochemically typed for several antigens (target antigens: IGF-1R, S-100, EMA, CD34, MIB-1), using both single and double-staining methods. Double-staining allowed the sub-typing of the IGF-1R-expressing cells in the mixed nerve sheath tumors. The expression was also investigated in Schwann cell cultures and co-cultures with fibroblasts. RESULTS: Staining of S-100 and IGF-1R, PNF were more intensely marked than MPNST (r = -0.439, p < 0.002, N = 49). The proliferation index was tumor-type dependent: MPNST > neurofibroma. The IGF-1R-expression correlated positively with the MIB-1 index in neurofibroma (r = 0.372, p = 0.021, N = 38). The receptor expression was higher in PNF than in dermal neurofibroma (r = 0.335, p = 0.040, N = 38). IGF-1R was detected in Schwann cells (S-100 positive) and in perineurial cells (EMA-positive) of all nerve sheath tumors. However, the receptor was also identified in CD34-marked endothelia of neurofibromas but not in endothelia of MPNST. In Schwann cell cultures, a strong receptor-expression became evident. This expression was independent of co-cultivation of tumor cells with fibroblasts. The statistical calculations excluded the impact of gender on the receptor expression. CONCLUSION: This investigation provides evidence for the expression of IGF-1R in nerve sheath tumors in NF1. The expression pattern varied between the tumor types, the cell types, and between tumors of the same type. IGF and IGF-1R are a prerequisite to maintain Schwann cell stability in the postnatal period and to prevent Schwann cell apoptosis. The first evidence for IGF-1R expression in mutated Schwann cells may indicate a tumor-type associated receptor expression in NF1.

Mutagenicity testing of mouthwash brands.

Several mouthwash brands were investigated for the evaluation of mutagenicity and cell-transforming activity in short-term mutagenicity test systems. The tests were: the Salmonella typhimurium mutagenicity assay (Ames tests), the unscheduled DNA-repair induction assay in primary rat hepatocytes (UDS-test), and the V79-HGPRT mutagenicity assay. Mouthwash, with and without an external metabolic activation system (S9), consistently showed no mutagenic or cytotoxic activity in the Ames test, UDS assay or the V79-HGPRT-assay. These results indicate that the tested mouthwash brands are unlikely to present a mutagenic or carcinogenic hazard. However, these findings derived from an in vitro study cannot imitate the situation in situ, where a plethora of pharmacologically or bio-chemically active agents pass the oral cavity, thereby reacting with each other and the oral mucosa, in particular when the use of such rinses occurs regularly over a long-term period.

Vitamin D deficiency associated with number of neurofibromas in neurofibromatosis 1.

Neurofibromatosis 1 (NF1) is a tumour suppressor gene syndrome characterized by multiple cutaneous and plexiform neurofibromas. Focal osseous abnormalities, short stature, and decreased bone mineral density are also frequent in people with NF1. We measured serum 25-hydroxyvitamin D concentrations in 55 patients with NF1 and 58 healthy controls, and correlated the findings in the patients with NF1 with their estimated number of dermal neurofibromas. Geometric mean (SD) serum 25-hydroxyvitamin D concentration was 14.0 (1.6) ng/mL among the patients with NF1 compared with 31.4 (1.7) ng/mL among healthy controls (p<<0.0001). The serum vitamin D concentration and number of dermal neurofibromas reported by patients with NF1 were inversely correlated (Spearman's rho = -0.572, p<0.00001). The occurrence of low serum vitamin D concentrations in people with NF1, especially those with many dermal neurofibromas, may provide new pathogenic insights and have important therapeutic implications.

MRI growth patterns of plexiform neurofibromas in patients with neurofibromatosis type 1.

Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder with an incidence of 1:3000. Approximately 30% of NF1 patients develop plexiform neurofibromas (PNF) which often cause severe clinical deficits. We studied the growth patterns of 256 plexiform neurofibromas (PNF) by magnetic resonance imaging (MRI) and associated disfigurement and functional deficits to determine whether there are definable growth types of these tumors. Retrospectively, we evaluated MRI scans obtained during 1997 to 2003 of 256 plexiform neurofibromas from 202 patients with NF1. Clinical investigation was carried out at the same time as the MRI scans. We identified three growth patterns: superficial in 59, displacing in 76, and invasive growth in 121 tumors. The majority (52%) of invasive PNF were found in the face, head and neck area. While superficial PNF primarily caused aesthetic problems, displacing PNF led in most cases to aesthetic problems and pain, while invasive PNF led mainly to functional deficits and disfigurement. Our study demonstrates that PNF have different growth patterns that are associated with specific clinical features. Classification of PNF may open new opportunities in clinical management, especially regarding decisions and options associated with surgical intervention.

Diagnosis, treatment and follow-up control in 124 patients with basal cell carcinoma of the maxillofacial region treated from 1992 to 1997.

AIM: The aim of this study was to analyze diagnostic and therapeutic procedures and the outcome of patients treated for the most common malignant tumor of the facial skin, basal cell carcinoma. PATIENTS AND METHODS: The files of patients with basal cell carcinoma (BCC) treated over a period of 6 years were evaluated. Emphasis was placed on the frequency of second interventions, local recurrences and histological subtyping of tumors. RESULTS: One-hundred and twenty-four patients were treated for 216 basal cell carcinomas (solitary: 67%, multiple: 33%). The tumors were predominantly located in the skin covering the middle third of the face. The tumors were 30 mm or less in diameter in 86%. Treatment was exclusively surgical. Histopathological subtyping revealed solid (83%), sclerodermiform (10%), metatypical (4%) and multicentric (3%) tumors. Resection of adjacent bone was mandatory in 12 patients and orbital exenteration in 2. Further local resections were necessary after thorough histological investigation in 71% of patients. Local recurrences occurred in 14 patients, predominantly within the first year after ablative surgery. Relative to the small number of sclerodermiform BCC, this subtype was the most frequent tumor that developed local recurrences. CONCLUSION: Basal cell carcinoma is a malignant tumor, slowly growing and often showing wide extension to macroscopically non-affected sites. Resection of tumors is delicate in the maxillofacial region due to the predilection for sites of origin adjacent to structures of eminent importance for facial appearance. The sclerodermiform subtype is prone to local recurrence and these patients should be followed up carefully.

Hyperfractionated externally irradiated primary oral squamous cell carcinomas: vital tumor cells in resection specimens.

UNLABELLED: Oral squamous cell carcinoma (OSCC) is among the most frequent malignancies worldwide. Ablative surgery for OSCC is the therapy of choice, however, severe disfigurement and loss of function is a consequence of therapy. On the other hand, R0-resection margins following ablative surgery do not guarantee disease-free survival, in particular due to the widespread, interconnecting lymphatic vessels. Therefore, irradiation of the primary and efferent lymphatics is a valuable therapeutic alternative to surgery. The combination of both irradiation and surgery might even improve overall survival. It has been argued that curatively planned irradiation (isodose of the primary: 60-70 Gy) might not routinely be followed by ablative surgery. Indeed, the sequelae of surgery in an irradiated field are well known. The aim of this study was to determine vital tumor cells in the resection specimens of irradiated advanced stage OSCC in order to estimate the effect of radiotherapy. MATERIALS AND METHODS: One hundred patients (male 78, female: 22, mean age 60.2 years) with primary OSCC (T2: n=41, T3: n=26; T4: n=33) and suspected regional lymph node metastases were externally irradiated up to a total dosage of 70 Gy (single dose 1.4 Gy, twice daily, minimum daily interval 6 hours; 5 days a week). Ablative surgery followed radiotherapy about 3 months later. RESULTS: In 51% of the primaries, specimens showed vital tumor cells after completion of radiotherapy. The evidence of vital tumor cells increased with T-stage and with N-stage, but showed no correlation to grading. CONCLUSION: Irradiation of the head and neck region following a hyperfractionation scheme for the treatment of advanced stage OSCC offers a 50% chance of deletion of malignant cells. Despite high total dosages and sophisticated irradiation protocols, the number of patients with vital tumor cells is high. Short-term follow-up controls are mandatory in patients who were subjected to a primary radiotherapy. Ablative surgery following irradiation is a salvage option for pre-irradiated OSCC patients.