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Detection of an Activating Mutation of the Thyrotropin Receptor in a Case of an Autonomously Hyperfunctioning Thyroid Insular Carcinoma—Authors’ Response¹

Università di Reggio Calabria 88100 Catanzaro, Italy

G. Grasso and Osp. S. Pietro e Gravina

Caltagirone, Italy

S. Tumino and A. Belfiore

Universitá di Catania 95123 Catania, Italy

We would like to thank Drs. Baloch and Livolsi for their interest in our work (see preceding letter) and for the opportunity they give us to add some details about the hyperfunctioning insular thyroid carcinoma we described (1). The original slides have now been reviewed by two additional experienced pathologists, and both have confirmed the original diagnosis of insular carcinoma on the basis of the following characteristics. Both the primary tumor and the metastatic lymph node were almost entirely composed of nests of cells, surrounded by a rim of hyalinized collagen, and occasionally, by thick fibrous tissue and artificial clefts. The neoplastic cells were small, with scanty, pale, eosinophilic cytoplasm and with rather uniform morphology. The nuclei were regular and round, with chromatin arranged in small clumps. The nucleolus was generally inconspicuous and only rarely prominent, at variance with what we stated in our original report. Necrosis was absent. Although necrosis is a frequent feature in insular carcinoma, it is not an invariable finding, as it was absent in 21 out of 31 cases in the series reported by Papotti et al. (2). Mitoses were present but not frequent, on average 2 per 10 high power fields, a frequency well within the range reported in the literature (1:10 per 10 high power fields) (2, 3, 4). As mentioned in the original description, neither cytological (ground glass nuclei, pseudoinclusions, grooves) nor structural characteristics (papillae, psammoma bodies) suggesting a papillary carcinoma were present.

In summary, the review of the original slides indicated that the case described was indeed a typical insular carcinoma and provided no evidence for the diagnosis of a papillary carcinoma with a solid growth pattern, as hypothesized by Drs. Baloch and Livolsi. These aspects are better documented by the photomicrographs enclosed and are available upon request from the editorial office.

From the clinical point of view the aggressive behaviour of this tumor is documented by its clinical evolution. After total thyroidectomy the patient was treated with a cumulative dose of 650 mCi radioiodine in 4 yr for diffuse lung metastases and, although these metastases showed a good radioiodine uptake, to date they have not been cured.\.

View larger version (157K): [in this window] [in a new window]   Figure 1. Micrograph showing an insula of cells surrounded by a rim of hyalinized collagen. The cell nuclei were regular, round, and with chromatin arranged in small clumps. (Original magnification, x125, H.E. staining.)

View larger version (175K): [in this window] [in a new window]   Figure 2. Well-defined nests and islands of cells with uniformly oval or round shape. A typical microfollicle is also evident. (Original magnification, x60, H.E. staining.)

¹ Address correspondence to: Antonino Belfiore, Istituto di Medicina Interna e di Malattie Endocrine del Metabolismo, Università di Catania, Catania, Italy 95123.

Received August 8, 1997.

References

1. Russo D, Tumino S, Arturi F, et al. 1997 Detection of an activating mutation of the thyrotropin receptor in a case of an autonomously hyperfunctioning thyroid insular carcinoma. J Clin Endocrinol Metab. 82:735–738.[Abstract/Free Full Text]
2. Papotti M, Botto Micca F, Favero A, Palestini N, Bussolati G. 1993 Poorly differentiated thyroid carcinomas with primordial cell component. Am J SurgPathol. 17:291–301.
3. Killen RM, Barnes L, Watson CG, Marsh WL, Chase DW, Schuller DE. 1990 Poorly differentiated (insular) thyroid carcinoma. Arch Otolaryngol Head Neck Surg. 116:1082–1086.
4. Zakowski MF, Schlesinger K, Mizrachi HH. 1991 Cytologic features of poorly differentiated "insular" carcinoma of the thyroid. Acta Cytol. 36:523–526.

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