Abstract
Merkel cell carcinoma was diagnosed in a 79-year-old Caucasian woman. The tumour was localised to the upper lip and was in stage T2. After successful cryosurgery and a 7-year tumour-free period, a new tumour developed in her palatine tonsil. Histologically and immunohistochemically, this resembled the tumour in the lip. The regional lymph nodes were devoid of metastasis. The paraffin-embedded material of the two tumours and the unaffected lymphatic tissue were analysed with DNA microarrays for comparative genomic hybridisation to assess the genetic relationship of the tumours. In both tumours, regions on 2p and 10p were commonly over-represented, while 41 regions on chromosomes 1–4, 6, 8–9, 11 and 14–22 were commonly under-represented. Chromosomes 1, 3, 4, 16–18 and X were most frequently involved in the DNA losses. In gene copy numbers in the two tumours, 31 chromosome locations were found to be differently affected. The partly similar and partly different molecular patterns indicated a genetic relationship between the tumours and excluded the possibility that the tonsillar tumour was a metastasis. The findings suggest that a genetically altered field was the reason for the development of the tonsillar cancer; thus, it can be regarded pathogenetically as a second field tumour.
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Antoniades K, Giannouli TH, Kaisaridou D (1988) Merkel cell carcinoma in a patient with Recklinghausen neurofibromatosis. Int J Oral Maxillofac Surg 27:213–214
Bellome J, Bays DR (1998) Merkel cell carcinoma of the ear: report of case. J Oral Maxillofac Surg 56:984–988
Benning TL, Vollmer RT, Crain BJ, Shelburne JD (1990) Neuroendocrine carcinoma of the oral cavity. Mod Pathol 3:631
Bickle K, Glass LF, Messina JL, Fenske NA, Siegrist K (2004) Merkel cell carcinoma: a clinical, histopathologic, and immunohistochemical review. Semin Cutan Med Surg 23:46–53
Braakhuis BJ, Tabor MP, Leemans CR, van der Waal I, Snow GB, Brakenhoff RH (2002) Second primary tumors and field cancerization in oral and oropharyngeal cancer: molecular techniques provide new insights and definitions. Head Neck 24:198–206
Braakhuis BJ, Tabor MP, Kummer JA, Leemans CR, Brakenhoff RH (2004) A genetic explanation of Slughter’s concept of field cancerization. Cancer Res 63:1727–1730
Califano J, van der Riet P, Westra W, Nawroz H, Clayman G, Piantadosi S, Corio R, Lee D, Greenberg B, Koch W, Sidransky D (1996) Genetic progression model for head and neck cancer: implications for field cancerization. Cancer Res 56:2488–2492
Cowell JK, Wang YD, Head K, Conroy J, McQuaid D, Nowak NJ (2004) Identification and characterisation of constitutional chromosome abnormalities using arrays of bacterial artificial chromosomes. Br J Cancer 90:860–865
Furák J, Troján I, Szőke T, Tiszlavicz L, Bodosi M, Kahán ZS, Micsik T, Puskás LG, Balogh Á (2002) Development of brain metastasis 5 years before the appearance of the primary lung cancer: messenger metachronous metastasis. Ann Thorac Surg 75:1016–1017
Ha PK, Califano JA (2003) The molecular biology of mucosal field cancerization of the head and neck. Crit Rev Oral Biol Med 14:363–369
Halata Z, Grim M, Baumann KI (2003) Friedrich Sigmund Merkel and his “Merkel cell”, morphology, development, and physiology: review and new results. Anat Rec 271:225–239
Harle M, Arens N, Moll I, Back W, Schulz T, Scherthan H (1996) Comparative genomic hybridization (CGH) discloses chromosomal and subchromosomal copy number changes in Merkel cell carcinomas. J Cutan Pathol 23:391–397
Hashimoto K (1972) Fine structure of Merkel cell in human oral mucosa. J Invest Dermatol 58:381–387
Hodgson G, Hager JH, Volik S, Hariono S, Wernick M, Moore D, Nowak N, Albertson DG, Pinkel D, Collins C, Hanahan D, Gray JW (2001) Genome scanning with array CGH delineates regional alterations in mouse islet carcinomas. Nat Genet 29:459–464
Huang Q, Schantz SP, Rao PH, Mo J, McCormick SA, Chaganti RS (2000) Improving degenerate oligonucleotide primed PCR-comparative genomic hybridization for analysis of DNA copy number changes in tumours. Genes Chromosomes Cancer 28:395–403
Koss LG, Spiro RH, Hajdu S (1972) Small cell (oat cell) carcinoma of minor salivary gland origin. Cancer 30:737
Larramendy ML, Koljonen V, Bohling T, Tukiainen E, Knuutila S (2004) Recurrent DNA copy number changes revealed by comparative genomic hybridization in primary Merkel cell carcinomas. Mod Pathol 17:561–567
Lehnerdt KH, Broicher R, Tschubel K, Walther E (2001) Der interessante Fall Nr.49. Laryngorhinootologie 80:687–689
Longo F, Califano L, Mangone GM, Errico ME (1999) Neuroendocrine (Merkel cell) carcinoma of the oral mucosa: report of case with immunohistochemical study and review of the literature. J Oral Pathol Med 28:88–91
Mir R, Sciubba JJ, Bhuiya TA, Blomquist K, Zelig D, Friedman E (1988) Merkel cell carcinoma arising in the oral mucosa. Oral Surg Oral Med Oral Pathol 65:71–75
Ónody A, Zvara Á, Hackler Jr L, Vígh L, Ferdinandy P, Puskás LG (2003) Effect of classic preconditioning on the gene expression pattern of rat hearts: a DNA microarray study. FEBS Letters 536:35–40
Park GC, Shelton JB, Ow RA, Todd DH (1999) Merkel cell carcinoma of the lower lip. Arch Otolaryngol Head Neck Surg 125:907–911
Pfaffl MW (2001) A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res 29:e45
Popp S, Waltering S, Herbst C, Moll I, Boukamp P (2002) UV-B-type mutations and chromosomal imbalances indicate common pathways for the development of Merkel and skin squamous cell carcinomas. Int J Cancer 99:352–360
Puskás LG, Hackler L Jr, Kovács G, Kupihár Z, Zvara Á, Micsik T, van Hummelen P (2002) Recovery of cyanine-dye nucleotide triphosphates. Anal Biochem 305:279–281
Puskás LG, Zvara Á, Hackler L Jr, Micsik T, van Hummelen P (2002) Production of bulk amounts of universal RNA for DNA microarrays. Biotechniques 33:898–904
Reichel OA, Mayr D, Issing WJ (2003) Oropharyngeal metastasis of a Merkel cell carcinoma of the skin. Eur Arch Otorhinolaryngol 260:258–60
Schmidt-Westhausen A, Reichert PA, Gross UM (1996) Gingival metastasis of Merkel cell carcinoma: a case report. J Oral Pathol Med 25:44–47
Slaughter DP, Southwick HW, Smejkal W (1953) “Field cancerization” in oral stratified squamous epithelium. Cancer 6:963–968
Snijders AM, Nowak N, Segraves R, Blackwood S, Brown N, Conroy J, Hamilton G, Hindle AK, Huey B, Kimura K, Law S, Myambo K, Palmer J, Ylstra B, Yue JP, Gray JW, Jain AN, Pinkel D, Albertson DG (2001) Assembly of microarrays for genome-wide measurement of DNA copy number. Nat Genet 29:263–264
Telenius H, Carter NP, Bebb CE, Nordenskjold M, Ponder BA, Tunnacliffe A (1992) Degenerate oligonucleotide-primed PCR: general amplification of target DNA by a single degenerate primer. Genomics 13:718–725
Tesei F, Farneti G, Cavicchi O, Antonelli P, Zanetti G, Leone O (1992) View from beneath: pathology in focus. A case of Merkel cell carcinoma metastatic to tonsil. J Laryngol Otol 106:1100–1102
Van Gele M, Leonard JH, Van Roy N, Cook AL, De Paepe A, Speleman F (2001) Frequent allelic loss at 10q23 but low incidence of PTEN mutations in Merkel cell carcinoma. Int J Cancer 92:409–413
Van Gele M, Leonard JH, Van Roy N, Van Limbergen H, Van Belle S, Cocquyt V, Salwen H, De Paepe A, Speleman F (2002) Combined karyotyping, CGH and M-FISH analysis allows detailed characterization of unidentified chromosomal rearrangements in Merkel cell carcinoma. Int J Cancer 101:137–145
Vigneswaren N, Müller S, Lense E, Stacey B, Hewan-Lowe K, Weathers DR (1992) Merkel cell carcinoma of the labial mucosa. Oral Surg Oral Med Oral Pathol 74:193–200
Yang YH, Dudoit S, Luu P, Lin DM, Peng V, Ngai J, Speed TP (2002) Normalization for cDNA microarray data: a robust composite method addressing single and multiple slide systematic variation. Nucleic Acids Res 30:e15
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This work was supported by a grant from the Hungarian Ministry of Health (ETT 400/2003). LGP is supported by the János Bolyai fellowship of the Hungarian Academy of Sciences.
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Nagy, J., Fehér, L.Z., Sonkodi, I. et al. A second field metachronous Merkel cell carcinoma of the lip and the palatine tonsil confirmed by microarray-based comparative genomic hybridisation. Virchows Arch 446, 278–286 (2005). https://doi.org/10.1007/s00428-004-1176-0
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DOI: https://doi.org/10.1007/s00428-004-1176-0