Thyroid gland papillary carcinomas with “micropapillary pattern,” a recently recognized poor prognostic finding: clinicopathologic and survival analysis of 7 cases

Summary

Micropapillary carcinoma is a histologic pattern, rather than an independent entity, that has an aggressive clinical behavior regardless of location. Histologically, it is characterized by papillary cell groups in clear spaces. The micropapillary pattern in the thyroid gland has not been studied until recently but under other names such as hobnail features or oncocytic and, therefore, is poorly understood, and reported cases are few. We report the clinicopathologic features of 7 cases obtained from a cohort of 496 papillary thyroid carcinomas, which corresponds to a prevalence of 1.4%. The proportion of the micropapillary component accounted for between 5% and 20% of the tumors, was slightly more prevalent in men, correlated with the presence of lymphovascular permeation, and, in the survival analysis, showed lower survival (even at a short follow-up, 8.5 years) than conventional carcinoma without this component (P = .001); this is consistent with poor overall survival in the short term (2-5 years) reported for carcinomas with micropapillary pattern of other locations. We believe that owing to this difference in survival (>95% of patients with conventional papillary carcinoma are alive at 8.5 years versus 42% of those having at least 5% of micropapillary pattern), the micropapillary pattern should be correctly identified and stated in the pathology report when comprising at least 5% of the tumor.

Introduction

The incidence of thyroid carcinoma has been increasing over recent decades; its prevalence in the United States is 1 case per 100 000 people annually [1], and the most common subtype is papillary carcinoma (papillary thyroid carcinoma, or PTC). Overall, survival at 10 years for PTC is greater than 90%. In our country, Mexico, PTC is reported to affect 1500 people each year, mostly young women, at a ratio of 8:1 compared with men [2]. It is an entity whose prognosis is not based solely on surgical or histologic parameters but on clinical variables such as sex, age, and hormonal status [3]. However, there are few variants associated with poor prognosis, such as the presence of columnar cells, tall cells, or solid, diffuse, sclerosing [4]; these variants are rarely found as pure forms and, in most cases, represent at least 10% of the tumor.

Micropapillary carcinoma (MPC) is accepted as a phenotype or histologic pattern found in adenocarcinomas and is associated with poor prognosis regardless of location. Small papillary clusters surrounded by lacunar spaces characterize it histologically. It was first described in the breast and ovary and, subsequently, in other organs such as the urinary bladder (perhaps the most studied), lung, pancreas, and salivary glands [5], [6]. Other studies in several organs have shown its association with lymphovascular invasion, lymph node metastasis, and the consequent reduction in survival in follow-up periods as short as 2 to 5 years [5], [6], [7], [8], [9], [10], [11], [12], [13]. One of the hallmarks of this micropapillary pattern is that of “reverse polarity,” which is best demonstrated by immunohistochemical and ultrastructural studies [14], [15] and is probably associated with the high invasive potential.

To date, as far as we know, there is only 1 large series and few reported cases of this phenotype in the thyroid gland [16], [17], although there are some reports where micropapillary neoplasms similar to those described in other organs have been called oncocytic papillary carcinoma with hobnail features. The purpose of this study was to explore the frequency, clinical and pathologic characteristics of thyroid MPC, and their impact on survival.