gms | German Medical Science

ESBS 2005: Skull Base Surgery: An Interdisciplinary Challenge
7. Kongress der Europäischen Schädelbasisgesellschaft & 13. Jahrestagung der Deutschen Gesellschaft für Schädelbasischirurgie

18. - 21.05.2005, Fulda

Cytogenetic analysis of anterior skull base carcinomas

Meeting Contribution

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  • Ziv Gil - The Department of Otolaryngology Head and Neck Surgery, The Genetic Institute, Tel-Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
  • Avi Orr-Urterger - The Department of Otolaryngology Head and Neck Surgery, The Genetic Institute, Tel-Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
  • Dan M. Fliss - The Department of Otolaryngology Head and Neck Surgery, The Genetic Institute, Tel-Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel

ESBS 2005: Skull Base Surgery: An Interdisciplinary Challenge. 7th Congress of the European Skull Base Society held in association with the 13th Congress of the German Society of Skull Base Surgery. Fulda, 18.-21.05.2005. Düsseldorf: German Medical Science GMS Publishing House; 2009. Doc05esbs70

doi: 10.3205/05esbs70, urn:nbn:de:0183-05esbs701

Veröffentlicht: 27. Januar 2009

© 2009 Gil et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen ( Er darf vervielfältigt, verbreitet und öffentlich zugänglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.




The classification and different diagnosis of sinonasal carcinomas may be difficult. Due to their low frequency, the cytogenetic data on these tumors is limited, and the only previous study, which included 2 cases of adenocarcinoma and 3 of SCC reported various complex chromosomal abnormalities, with no specific karyotipic patterns.

We have cytogenetically characterized the short-term cultures of NK SCC, and SNUC originating in the nasal cavity and paranasal sinuses. Most of these patients were operated via the subcranial approach.

Materials and methods

We have performed cytogenetics analysis to 100 tumors involving the anterior skull base; of them 18 were squamous cell and undifferentiated carcinomas. G banding (Figure 1A [Fig. 1]) and spectral karyotyping were used in order to find specific chromosomal aberrations.

Our study involves 18 patients who were operated in our institution between 2001–2004 for extirpation of sinonasal carcinomas. Of the 18 tumors 15 pathologically confirmed samples have successfully analyzed using conventional cytogenetic methods. Nine tumors originated in the maxillary sinus and 5 in the ethmoidal sinuses. One patient had undergone several excisions of SCC of the scalp. In his current operation the tumor invaded his ethmoid and sphenoid sinuses. All patients had received postoperative radiation therapy except patient 4 who had tumor recurrence and received 7700 cGy 2 years previous to her current operation. The oncological outcome of the patients is based on 10–42 months of clinical and radiological follow-up. Tumor staging was performed using the American Joint Committee on Cancer-Union Internationale Contre le Cancer (AJCC-UICC) 2002.


Fresh tumor samples were excised during surgery and submitted for pathological and cytogenetic analysis. Ten to 30 metaphase cells from primary cultures were studied in each specimen using G-banding technique (230 metaphase overall). Seven of the 14 sinonasal carcinomas had an abnormal karyotype (50%). Four of the 9 NK SCC's (cases 2, 4, 9 and 18) had chromosomal abnormalities. One tumor displayed 2 cytogenetically related clones and one subclone with 45–47 chromosomes. The principal chromosomal abnormality found in all cells of this case was inv(2)(p11;q13), which is frequently found in the Jewish population in Israel. Another tumor had a near diploid complex karyotype with multiple structural abnormalities involving chromosomes: 1–3, 5–12, 14, 16–17, 19–22 and X. A third case showed a near diploid karyotype with loss of chromosome Y in 12 of the examined cells and a normal karyotype in 3 cells. The forth tumor, which had suffered from NK-SCC originating in the maxillary sinus also had a complex karyotype involving 1p, 2p, 3q, 4p, 5p, 6q, 7p, 7q, 10p, 15q and 17p. Among the cases with complex karyotype (01, 04 , 13, 15 and 18), recurrent chromosomal abnormalities (ten tumor breakpoints per arm or more) were found in 1p, 1q, 2q, 6q, 7p, 8q, 12q and q13 (Figure 1B [Fig. 1]).

Of the 5 patients with SNUC, 3 had an abnormal karyotype (cases 01, 08 and15). One of the 5 SNUC had a complex karyotype, with 2 translocations involving chromosomes 1, 6, 12 and 17 in three cells. Another patient had a karyotype showing t(5;18)(q13;q23) in 1/20 cells. The third patient with SNUC originating in the maxillary sinus had a complex karyotype with 60–69 chromosomes.

All patients were followed on regular bases using both clinical and radiological examinations. Four of the patients enrolled in this study have died of disease and all displayed a complex karyotype. In the other hand, 2 of the 9 patients who are alive had a complex karyotype. Statistical analysis of the data suggested that abnormal karyotype may be associated with poor prognosis of patients with paranasal SCC (P=0.01 Fisher Exact test).

Clinical Relevance

In our study, we have found that 7 of the 14 analyzed sinonasal carcinoma specimens displayed an abnormal karyotype. Most of the chromosomal abnormalities involved few clones with complex karyotypes. This report is also the first to describe two abnormal karyotypes of sinonasal carcinoma: one with two novel translocations t(1;6)(p22;p23) and t(12;17)(q13;p13) and a second with loss of chromosome Y. SCC of the upper aerodigestive tracts frequently harbors a highly complex karyotype as found in our study. Chromosomal aberrations involving similar breakpoints were previously described in SCC of the oral cavity, larynx, hypopharynx and nasopharynx. In addition to the cytogenetic data, we described the association between karyotype and prognosis. We have found that 4 of the 4 patients, who died of disease, displayed a complex karyotype, whereas only 2 of the 9 patients who are free of tumor had a complex karyotype. These differences were statistically significant (p<0.01).

Taking together, this finding suggests that abnormal karyotype may be associated with poor prognosis in patients with sinonasal SCC or SNUC.

Previous studies have demonstrated the prognostic value of cytogenetic data in head and neck SCC. To date, the extent of the cytogenetic data on sinonasal carcinomas is too limited to furnish precise association between karyotype and prognosis. Additional studies are required in order to determine whether cytogenetic data may serve as an adjunct to conventional pathology for the diagnosis and prognosis assessment of these rare and highly aggressive tumors.