A cytogenetic approach to the differential diagnosis of metastatic clear cell renal carcinoma

Aims: To determine by cytogenetic analysis the origins of two clear cell tumours in a 70-year-old Caucasian woman, one in the thyroid gland, and the other in the skin, 16 and 20 years, respectively, after tumour nephrectomy. We sought a conclusive distinction between primary clear cell thyroid carcinoma and its cutaneous metastasis, and between thyroid and cutaneous metastases of clear cell renal carcinoma (RCC), Methods and results: Paraffin sections of the previously formalin-fixed thyroid tumour, and the fresh cutaneous tumour were stained with haematoxylin and eosin (H&E) and periodic acid-Schiff (PAS), Additionally, samples of both tumours were examined electron microscopically. Immunohistochemistry was performed with antibodies against thyroglobulin, pancytokeratin, keratin 7, 8, 18 and 19, chromogranin, calcitonin, CEA, vimentin and EMA. Five to six micrometre sections of both tumours were analysed with ci-satellite probes of chromosomes 3, 7 and 17 using chromosomal in-situ hybridization (CISH), The cutaneous tumour was also cultured and analysed cytogenetically. The thyroid tumour displayed some follicle-like structures that stained positive with both PAS and antithyroglobulin, giving evidence of possibly entrapped thyroid follicles in metastatic RCC, The cutaneous tumour was negative for both stains. The tumours were ultrastructurally completely devoid of neurosecretory granules. Classical cytogenetical analysis of the cultured cutaneous tumour cells revealed monosomies 3 and 14, well-known specific primary and secondary aberrations, respectively, in clear cell RCC, and hitherto not reported in thyroid carcinomas. CISH of both tumours revealed monosomy 3, indicating a cytogenetical correlation between them. There was no evidence of typical chromosomal aberrations for thyroid carcinomas like structural changes on 10q, structural rearrangements or translocations of chromosome 7, Conclusion: Although neither histological sections, nor paraffin blocks of the original nephrectomy specimen were available for review, the original tumour was on record as clear cell RCC. Therefore the two tumours' renal origin was confirmed.