Cancer ~esearch Clinical @neology

J Cancer Res Clin Oncol (1988) 114:541-545

9 Springer-Verlag 1988

Meeting report Malignant tumours of the nasal cavity and paranasal sinuses 19 th National Cancer Congress of the German Cancer Society* 28 February to 5 March 1988, Frankfurt/Main, FRG W. Schwab and B. Clasen Hals-Nasen-Ohren-Klinik, Klinikum rechts der Isar der TU M/inchen, Ismaninger Strage 22, D-8000 Miinchen 80, Federal Republic of Germany

The topic has been chosen to reflect the growing interest in malignant turnouts of the nasal cavity and the paranal sinuses as an occupational disease. Furthermore, the 4th revision of the general rules for classification of malignant tumours issued by the UICC (1987) has become a target of criticism as it considers only the maxillary sinuses (and not the whole organ nasal cavity and paranasal sinuses). Classification of malignant tumours of the nasal cavity and the paranasal sinuses

Since 1987 new classification rules (UICC's TNM Classification of Malignant Tumours, 4th edition) have been valid for head and neck tumours. New rules have been established for the salivary glands and the maxillary sinus. The inclusion of the salivary glands has at least closed one of the gaps in classification of malignant disease in the head and neck region. The nasal cavity and the paranasal sinuses might be considered to be the last remaining gap. Regarding its evolution and functions this anatomical region appears as one organ and should be considered as such. The decision taken by the UICC (4th issue 1987) to consider only the maxillary sinuses is both inadequate and inconsistent. It is regarded as inadequate because the remaining sites and subsites (of the organ nasal cavity and paranasal sinuses) are neglected. Thus, the primary tumours that occur in these sites in more than 40% of the cases cannot be classified. Data from different publications are presented, including our own retrospective study on 1296 cases by the Clinical Oncology Cooperative Group (Arbeitsgemeinschaft Klinische Onkologie = AO/HNO; chairman W. Schwab, Munich) of the German Society of Otolaryngology, Head * The highlights of important symposia and seminars of the 19th German Cancer Congress are reported by the respective chairmen or moderators in the present and forthcoming issues. Offprint requests to: W. Schwab

and Neck surgery, showing the functional entity of the organ. The decision is regarded as inconsistent since the UICC, in its classification rules for the nasopharynx, has noted: "The margin of the choanal orifices including the posterior margin of the nasal septum is included with the nasal fossa." Hence, the localization next to the nasopharynx is addressed as the "nasal cavity", but then excluded in the new classification rules, which apply only to the maxillary sinus. The AO/HNO will therefore stick to its own classification rules, which have been valid since 1974, following a proposal of Schwab in the light of the abovementioned UICC note, which includes the choanal orifices in the "nasal cavity" site. The practicability of these classification rules has undoubtedly risen since the introduction of organ-specific questionnaires in 1985. It is no accident that one of these forms contains references to both the organs nasopharynx and nasal cavity and paranasal sinuses. A steadily rising number of follow-up forms will make therapy studies feasible in the near future. The usefulness of the AO/HNO classification rules has been proven in 1363 cases between the years 1972 and 1987. Therefore there is no need to adjust them (including those relating to the nasal cavity and the paranasal sinuses) to match those issued by the UICC which, for the reasons mentioned above, are by no means convincing. H. J. Peseh (Erlangen) Malignant tumors of the nasal cavity and paranasal sinuses - pathological considerations

Malignant tumours are now defined according to the criteria of typing, grading and staging. The histological typing of the tumours of the nasal cavity and the paranasal sinuses is based on the 1978 classification published by the World Health Organization and is internationally binding. The malignant epithelial tu-

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W. Schwab and B. Clasen: Meeting-report: Malignant turnouts of the nasal cavity and paranasal sinuses

mours include various forms of squamous cell carcinoma and of adenocarcinoma, but also transitional, adenoid cystic and mucoepidermoid carcinomas. These tumours are rare; even rarer are malignant lymphomas and sarcomas. Histopathological grading is based on the updated TNM grading (UICC 1987). Here, four differentiation grades, ranging from well differentiated to undifferentiated (G1-4); are distinguished. Staging, the clinical and histopathological classification of stages, is also carried out in accordance with the TNM or pTNM system (UICC 1987). As a result, the malignant tumours with respect to their size, lymph nodes and distant metastases, are not only correctly defined as to stage, but are also internationally comparable. This means that large-scale therapeutic studies are now possible. Although the aetiopathogenesis of most of the malignant tumours mentioned here ist largely unclear, in the case of adenocarcinomas an occupational exposure to oak and beech sawdust is assumed to be a carcinogenic factor. H. Glanz, O. Kleinsasser (Marburg) Surgical treatment of tumours of the nasal cavity and the paranasal sinuses Modern imaging techniques have improved diagnosis and treatment planning of tumours of the nasal cavity and sinuses. Radical removal of the tumour by surgical means is essential, as local recurrence control is often not possible. Depending on the tumours localisation there are mainly two surgical approaches: (1) maxillectomy and (2) lateral rhinotomy with resection oftumour in the nasal cavity and ethmoidectomy. Both techniques may have to be combined and enlarged. Small tumours at the floor of the maxillary sinus or of the lateral nasal wall can be removed by approaching through the oral cavity or using the techniques of Denker, thus combining the maxillary sinus and inner nose in one cavity. In most of the cases a transfacial maxillectomy is necessary using the WeberFerguson approach. The resection often has to include neighbouring structures. Surgically the most problematic are tnmour infiltrations into the retromaxillary space, because of the danger of violating the plexus pterygoideus and the maxillary artery. In these cases the subciliar incision has to be prolonged laterally towards the ear (Fisch and Obwegeser). In spite of the radical extension of these operations morbidity is low. Postoperatively occurring problems of mastication and swallowing can be managed by obturators, which have to be hollow. Skin grafts placed in the operation cavity can improve the fixing of the obturators. Fiveyear survival rates after surgical treatment are reported in from 24% to 50% of cases. Tumours of the nasal cavity and the cellulae ethmoideae, are approached by lateral rhinotomy. To avoid defects in the

facial contours the osteoplastic technique (Kleinsasser and Glanz 1983) has proven to be useful. Tumours of the ethmoid cellulae, with penetration through the skull base, require a combined transfacial and neurosurgical approach. H. J. Thiel (Erlangen) Radiotherapy of malignant tumours of the nasal cavity and paranasal sinuses Prognosis and therapy of malignant tumours of the nasal cavity and paranasal sinuses depend on the histological type, site of origin and extent of the tumour. The variety of possible treatment modalities demands an individual treatment planning. A single-modality approach is only feasible in very early tumour stages. Generally a combined modality, surgical and radiotherapeutic approach, possibly supplemented by small-volume intercavitary brachytherapy or polychemotherapy in some defined histological tumour types, has been accepted as the treatment of choice. The radiotherapeutic treatment modalities are teletherapy (external-beam megavoltage irradiation with photons and electrons) as well as brachytherapy (interstitial implantation of Ra needles, Au grains or Ir-seed ribbons and intracavitary surface therapy with 6~ pearls or 2Z6Ra tubes). Irradiation can be given preoperatively (young age, positive nitrogen balance, good general health, radiosensitive tumours) or postoperatively (age over 70 years, negative nitrogen balance, reduced performance and nutrition status, radioresistent tumours). Tumour dose is 50 Gy in 5 weeks preoperatively and 60 Gy in 6 weeks postoperatively with a boost to the tumour region to 70-80 Gy in 7-8 Weeks if necessary. In accordance with major treatment centers the following treatment strategy is recommended: Combination of surgery and irradiation for all squamous cell carcinomas (sequence of modalities depending on age, general health and nutrition of the patient, extent of tumour and infiltration of skin and bone) Radiotherapy only for malignant non-Hodgkin lymphomas Surgery only (in selected cases with small-volume irradiation postoperatively) for adenocarcinomas, malignant melanomas, bone and soft-tissue sarcomas Adjuvant chemotherapy for rhabdomyosarcomas, Ewing's sarcomas, non-Hodgkin lymphomas (depending on histological subtype and clinical stage). O. Kleinsasser (Marburg) Adenocarcinoma of the nasal cavity induced by sawdust exposure Since Hadfield first reported the coincidence of sawdust and carcinoma of the inner nose in 1965, the same

w. Schwaband B. Clasen: Meeting-report:Malignant tumours of the nasal cavityand paranasal sinuses has been observed in several small international studies. In some European countries adenocarcinoma of the nasal cavity is registered as an occupational disease, and in Germany it is about to be registered. In a retrospective study, data including histological samples of 187 registered tumours of the nasal cavity have been reviewed. Four groups could be distinguished: (1)tumours other than adenocarcinoma, (2) adenocarcinoma of the salivary gland type (mucoepidermoid carcinoma, acinus cell tumour, adenoid-cystic carcinoma), (3)terminal-tubulus carcinoma; cases 1-3 no exposure to sawdust could be demonstrated; (4) colonic-type adenocarcinoma: 90% of the patients were exposed to sawdust. Most common are tumours of the cylinder-cell type, more rare are those of the beaker-cell type, sometimes with excessive production of mucus. Both types can be graded histologically on the basis of their degree of differentiation. The exposure time ranged from 2 to 50 years (average 30.5 years), and the exposure-free interval was 8 to 65 years (average 39 years). Promoting factors could not be confirmed. Most of the tumours were incurable at the time of presentation. In the light of the clinical experience that the middle nasal concha is mostly the primary tumour site, endoscopic screening tests could become valuable. In no case could the paranasal sinuses be proved to be site of the tumour's origin. In only 4% did neck node metastases occur, and in 2% there where distant metastases. In this therapeutically heterogeneous group the cumulative survival rate after 5 years was 34.40%. Single late recurrences after 10 or more years were recorded. Poorly differentiated tumours, beaker-cell and signet-cell carcinomas showed a far worse prognosis than well-differentiated cylinder-cell types. Radiotherapy and chemotherapy did not influence the tumour growth. Only radical surgery was of any benefit.

M. Hartung, H. J. Wolf (Erlangen/Munich) Malignant Disease of the nasal cavity: epidemiology and aspects of occupational medicine Particles of 30-40 gm are deposited in the nasal cavity, nasopharynx and trachea. Cancerogenicity has been proven, besides ionising radiation, for the following substances: (1)chromium VI compounds, (2)nickel and its compounds, (3)arsenic compounds, (4)oak dust, (5) beechwood dust. Most adenocarcinomas of the colonic type occur after exposure to sawdust. The following factors are being discussed: genuine wood agents, adjuvant agents used in the industrial processing of wood, fungus metabolics, agents that arise during industrial processing (for instance polycyclic aromatic hydrocarbon compounds).

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The fact that induction times for tumour occurence were much shorter in patients who worked with laky paints might focus interest on chemical agents.

T. Deitmer (Miinster) Tumours of the nose and paranasal sinuses induced by asbestos? Tumours of the nose and the paranasal sinuses are not yet accepted as an occupational disease. Asbestos is known as a carcinogenic substance for pleural mesothelioma and bronchial carcinoma in relation to an asbestosis of the lung. Concerning the aerodynamics and the mode of deposition the nose must be looked upon as being prone to an asbestos disease, since asbestos shows a wide range of particle size. These modes of deposition and experiments on the carcinogenicity of asbestos in the respiratory epithelium are reviewed. Some trades are listed on the basis of their known exposure, such as asbestos mining, shipyard work, building crafts, and brake-repair work.

P. Held, H. Obletter, S. Braitinger (Passau) The value of MRI when applied to malignancies of the nose and of the paranasal sinuses The method employed a superconducting magnet (1 T), surface coil, Tl-weighted, balanced and T2weighted images and fast sequences (FISP, FLASH). In most cases of MRI it is not necessary to inject contrast medium. The tissue of soft parts, which cannot be distinguished clearly on computed tomography (CT) can be made out distinctly by evaluating the T land T2-weighted magnetic resonance images. Magnetic resonance imaging does not reveal any indication of compact bone. Compared with CT this is a disadvantage when paranasal sinuses are being examined. However, MRI makes it possible to distinguish clearly between more extended bone lesions. By means of MRI vessels can be identified definitely and haemorrhages can also be visualized in all modes. With regard to the diagnostics of malignant tumours, the assessment of the tumour extension especially, is of great importance. A large proportion of the tumours in this area only accept a relatively small amount of contrast medium during CT examination. In T2-weighted images the tumour's signal intensity is most markedly increased; it is, however, not so pronounced and homogeneous as in inflammatory processes. One advantage of MRI is that ist makes a multiplanar imaging of the complex structure of the viscerocranium possible and that it establishes the evidence of affected lymph nodes.

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w. Schwaband B. Clasen:Meeting-report:MMignanttumoursof the nasalcavityand paranasalsinuses

K.-F. Hamann (Munich) Ultrasound in pre-therapeutic diagnosis and post-therapeutic care of patients with malignant turnouts of the nasal cavity and the paranasal sinuses Sonographic assessment (A and B scan mode) is nowadays a routine method of diagnosis in otolaryngology. Neither scan is yet able to visualize tumours of the nasal cavity. With the paranasal sinuses, it is different: an echo of the posterior wall reveals pathological contents of the sinus. The echo pattern gives hints of the nature of the contents. An echo-free interval is seen as a homogeneously filled (liquid) cavity. Echoes in between are suspected to be of tumorous origin. The compact bone is also accessible by sonographic means, which can be used directly in the case of the maxillary, frontal and superficial ethmoidal sinuses, the deep ethmoidal sinuses are detectable by linking them to the bulbus oculi. The free choice of view angles and scans is of advantage compared with radiological imaging. The B scan mode is mainly used to detect cervical lymph nodes. The taking of sonographically controlled biopsies is becoming more and more common and compression or destruction of blood vessels can be visualized. Thus tumour control and post-therapeutic care can easily be carried out.

B. Schrader, W. Schwartz (Bremen) Malignant fibrous histiocytoma of the paranasal sinuses Malignant fibrous histocytoma (MFH) is the most common sarcoma of the soft tissue in adults. The histiogenetic development of MFH is assumed to start from omnipotent soft-tissue stem cells. Their potential to differentiate into various cell types is reflected in the histological pattern of the tumour. Immunochemistry and MET are helpful and necessary for diagnosis. The head and neck region is rarely involved. In six out of ten patients at the hospital in Bremen the primary sarcoma was located in the maxillary sinus. All patients underwent operative treatment, two patients were irradiated afterwards. Local recurrence appeared in two cases, neck node metastases have been proven histologically in only one case, but distant metastases occurred in five patients. Four patients died, the medial survival was 14 months. Three patients are now without evidence of disease 2-3 years after the first diagnosis. Tumour depth and spred, rather than histological typing, are considered to be relevant prognostic factors. Data published up to now, including our own observations, show the high malignancy of MFH in the head and neck regions. Prognosis depends largely on the rate of distant metastases. Operation is regarded to

be the therapy of choice, the value of irradiation is uncertain and an adjuvant chemotherapy does not prolong recurrence-free survival.

M. Voilrath, M. Altmannsberger (Giessen) Aesthesioneuroblastoma; histogenesis and diagnosis Aesthesioneuroepthelioma is a rare tumour of the nasal cavity appearing both extracranially and intracranially. Its histological diagnosis is difficult and impossible by means of light microscopy alone. Discussion of its histogenesis is contraversial. The authors succeeded in inducing aesthesioneuroepthelioma artificially in rats. The tumours show exactly the same cytological morphology as they do in man. By light microscopy, the tumours appear as undifferentiated cells cumulating in the form of rosettes. The socalled Flexner rosettes of the most common ependymorea type of aesthesioneuroepthelioma are often so numerous and elongated that they may be wrongly diagnosed as adenocarcinoma. Desmosomes or tight junctions, which are common in epithelioma, are missing, but in the Flexner rosettes nerve fibres are found and structures reminiscent of nerve receptors in olfactory cells. Immunochemistry showed a negative reaction with antibodies to all known intermedial filalments. This becomes clear from the tumour's histogenesis: the olfactory receptor cell and its precursor, the bright basal cell, behave the same way. So these cells are to be regarded as the stem cells for aesthesioneuroepithelioma.

J. Wustrow, H. Rudert, M. Diercke, A. Beigel (Kiel) Malignant tumours of the nasal cavity and the paranasal sinuses In the years between 1949 and 1982 a total of 275 patients with malignant tumours of the nasal cavity and the paranasal sinuses were treated. 53% of the tumours were squamous-cell carcinomas, 19% were malignant tumours of the small salivary glands and 6% were malignant melanomas. Mesenchymal and neurogenie tumours made up the remainder of the cases. The maxillary sinus is in 50% of cases the most frequent localisation of squamous-cell and adenoidcystic carcinomas. Adenocarcinomas, however, are mostly found at the nasal roof(56%). By far the most malignant melanomas were detected at the nasal septurn and on the nasal floor (88%). The most important prognostic factor for squamous-cell carcinomas was the size of the tumour. In squamous-cell carcinomas, age and degree of differentiation had no influence on the rate of survival. Therapy was mostly surgical and a combined surgical and radiological approach.

W. Schwab and B. Clasen: Meeting-report: Malignant turnouts of the nasal cavity and paranasal sinuses

W. Draf, M. Samii (Fulda) Surgery of malignant tumours of the paranasal sinuses involving the skull base In tumours of the paranasal sinuses with signs of skull-base infiltration several approaches may be considered: 1. Extracranial partial resection of the anterior skull base with partial or total removal of the paranasal sinuses and preservation of orbital contents 2. Extracranial radical resection of the maxilla, ethmoid and anterior skull base with orbital exenteration 3. Combined intra-extracranial approach. This strategy needs rhino-neurosurgical cooperation.

A. Naszaly, G. Nemeth (Miinster) Radiotherapy for paranasal sinuscancer treatment results and optimization In all, 30/patients were treated in this institute, 157 of whom were treated with combined radiotherapy and surgery, /33 underwent radiotherapy only, and /1 with local recurrence were treated many years after initial treatment. Intracavitary brachytherapy was applied in 82 patients either alone or in combination with an external beam as a postoperative treatment. Survival data are presented with particular regard to the prognostic factors and to treatment modality: 5-year survival was observed, for all stages in 34% of patients in the combined treatment group and in 15% of those receiving radiotherapy alone. The best result of 42% was found with the preoperative irradiation + operative+postoperative irradiation treatment group, the data suggest that preoperative radiotherapy+surgery + postoperative radiotherapy seems to be the optimum treatment modality and underlines the reasons for the application of intracavitary brachytherapy after no radical surgery. By the systematic changing of the irradiation parameters we attempted to develop field arrangements and brachytherapy source arrangements with optimal dose distribution and easy reproducibility. Computerized treatment planning was performed simultaneously in two or more parallel CT scans.

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R. Schwarz, K.-H. Hiibener (Hamburg) Fast neutron radiotherapy for advanced malignant tumonrs of the paranasal sinuses From 1976 to 1987 16 patients with advanced and highly differentiated malignant tumours of the paranasal sinuses were treated at the Department of Radiotherapy, University Hospital of Hamburg-Eppendorf, with fast neutrons of a 14-MeV-DT generator. Nine patients had adenoid-cystic carcinomas, two patients had adenocarcinomas of grading l, one patient had an osteosarcoma of grading 1, one patient had a fibrosarcoma of grading 1 and three patients had highly differentiated carcinomas. All patients had advanced primary tumours or recurrences. In all cases the tumour region was irradiated, the local lymph nodes were only irradiated when a metastasis was demonstrable. The dose ranged from 12.3 Gy to 16.6 Gy (DT, neutron dose) The neutron therapy was very effective in the treatment of adenoid-cystic carcinomas. In seven patients in whom a macroscopic tumour was demonstrable, a complete or partial remission occurred in six cases. Eight out of nine patients are alive with no evidence &disease. These results are in accordance with neutron therapy results in a total group of 40 patients with adenoid-cystic carcinomas in the head and neck region: 90% CR or PR and, after a follow-up of 2 years, a local tumour control rate of 73%. The patients with adenocarcinoma , fibrosarcoma and osteosarcoma of grading 1 showed a good clinical and roentgenological remission. In these cases no recurrence occurred during follow-up periods of 13 months to 66 months. The three patients with highly differentiated carcinomas did not profit from neutron therapy. The side-effects of neutron therapy were tolerable in all 16 cases. Regarding these preliminary results in a limited number of rare tumours, treatment with fast neutrons, if available, is thought to be the best choice for highly differentiated tumours, especially adenoid-cystic carcinomas of the paranasal sinuses. Received June 13,1988