CLINICOPATHOLOGICAL AND IMMUNOHISTOCHEMICAL STUDIES OF PAPILLARY THYROID MICROCARCINOMA PRESENTING WITH CERVICAL LYMPHADENOPATHY

Although most papillary thyroid microcarcinomas (PMCs) are of little c linical significance, patients with PMCs occasionally have an unfavora ble outcome, especially when they present with bulky nodal metastasis or distant metastasis. We have attempted to identify ''high-risk'' PMC s by evaluating clinical, pathologic, and immunohistochemical prognost ic factors. Among 190 patients with a PMC, 156 without clinically appa rent nodal metastasis had a benign course. The remaining 34 patients, who presented with cervical lymphadenopathy of at least 1 cm, were stu died, Three of the four patients who developed distant metastasis died of the disease, and the other died of local recurrence. All patients who developed distant metastasis or died of the disease had both nodal metastasis of at least 3 cm and a nonencapsulated type of primary les ion. All patients who developed distant metastasis showed both extraca psular extension of the metastatic lesions in lymph nodes and positive staining for transforming growth factor-beta 3 (TGF beta 3) (a potent growth inhibitor) in the primary lesion, The Ki-67 (an indicator of c ell proliferation) labeling indices in the primary and metastatic noda l lesions of patients who died of cancer were significantly higher tha n those of the others,with nonfatal disease. None of the patients show ed P53 (nuclear tumor-suppressor phosphoprotein) overexpression. In co nclusion, patients with PMC who have both 3 cm or larger lymphadenopat hy and a nonencapsulated type of primary lesion may be regarded as hig h-risk patients. Immunohistologic positivity for Ki-67 and TGF beta 3 in cancel cells is a potential indicator of aggressively malignant PMC .