Endocrine Abstracts

The most frequent problems of the morphological diagnosis of thyroid tumors with clinical relevance will be discussed under four major headings:

(a) Differential diagnosis of follicular patterned lesions: follicular adenoma (encompassing adenomatous lesions of multinodular goitre), follicular carcinoma and follicular variant of papillary carcinoma. In this setting we will discuss the role of cytology (nuclear features), immunohistochemistry (Ki67/MIB1, CK19, Galectin3, HBME-1, histo-blood group antigens) and molecular genetics (RAS mutations, PAX8-PPARg rearrangement).

(b) Identification of the subgroups of follicular carcinoma: minimally invasive, widely invasive and, most important, though frequently forgotten, angioinvasive. Additional points: Is there room for the evaluation of the degree of vascular invasiveness? And for the presence of Hürthle cells?

(c) Identification (and clinical significance) of the variants of papillary carcinoma (PTC) emphasising some issues: Is there anything one can call ‘in situ’ transformation towards PTC within a benign nodule? Microcarcinoma or microtumor? What to do with the encapsulated PTC? What about the Hürthle cell (oncocytic) variant of PTC? Does molecular genetics help in the cytological diagnosis of PTC?

(d) Diagnosis of poorly differentiated carcinoma (PDTC) following the criteria of the Turin Consensus Meeting. In this field it is crucial to distinguish PDTC from the solid variant of PTC and from anaplastic (undifferentiated) carcinoma, taking into consideration morphology (e.g. nuclear features, mitoses, necrosis, invasiveness), immunohistochemistry (thyroglobulin, p53) and molecular genetics (there are a couple of promising therapeutic targets).

In case there is free time at the end of the Session we will discuss some practical (and old) issues such as the limitations of cytopathology and the strategy for studying multinodular goitres, as well as some recent developments in the field of familial thyroid tumors (eg. mutations in GRIM19 and SDH genes).

Selected references

1. Fonseca E et al. Diagnostic criteria in well-differentiated thyroid carcinomas. Endocr Pathol 2006 17 109–117.

2. Lima J et al. Germline succinate dehydrogenase subunit D mutation segregating with familial non-RET C cell hyperplasia. J Clin Endocrinol Metab 2003 88 4932–4937.

3. Lloyd RV et al. Observer variation in the diagnosis of follicular variant of papillary thyroid carcinoma. Am J Surg Pathol 2004 28 1336–1440.

4. Máximo V et al. Somatic and germline mutation in GRIM-19, a dual function gene involved in mitochondrial metabolism and cell death, is linked to mitochondrion-rich (Hürthle cell) tumours of the thyroid. Br J Cancer 2005 92 1892–1898.

5. Rosai J et al. Renaming papillary microcarcinoma of the thyroid gland: the Porto proposal. Int J Surg Pathol 2003 11 249–251.

6. Sobrinho-Simoes M et al. Hurthle (oncocytic) cell tumors of thyroid: etiopathogenesis, diagnosis and clinical significance. Int J Surg Pathol 2005 13 29–35.

7. Sobrinho-Simoes M et al. Molecular pathology of well-differentiated thyroid carcinomas. Virchows Arch 2005 447 787–793.

8. Trovisco V et al. BRAF mutations are associated with some histological types of papillary thyroid carcinoma. J Pathol 2004 202 247–251.

9. Volante M et al. Poorly differentiated thyroid carcinoma: the Turin proposal for the use of uniform diagnostic criteria and an algorithmic diagnostic approach. Am J Surg Pathol 2007 31 1256–1264.