Clinicopathological and molecular characterization of nine cases of columnar cell variant of papillary thyroid carcinoma

Abstract

The majority of papillary thyroid carcinoma is indolent and associated with long-term survival. The columnar cell variant, however, is a rare subtype that is variable in biological behavior; some are clinically aggressive, whereas others are more clinically indolent. Tumor size, tumor circumscription, and encapsulation may influence the behavior of columnar cell carcinomas. Other variables including genetic changes and putative biomarkers associated with malignant growth have not been thoroughly examined in these neoplasms. In this study, nine cases of columnar cell variant of papillary thyroid carcinoma from three institutions were classified as clinically indolent or aggressive based on pathological features, clinical history, and outcome. Indolent tumors were typically small, circumscribed or encapsulated, and from younger female patients, whereas aggressive tumors were large, locally aggressive, associated with regional and distant metastasis, and from older male patients. The missense mutation, V600E in the BRAF oncogene (BRAF V600E ), was detected in three of nine of cases, of which two were clinically aggressive. Immunohistochemical evaluation of neoplasiaassociated markers showed increased nuclear cyclin D1 expression, elevated Ki-67 proliferation indices, and predominantly weak nuclear p53 staining in both indolent and aggressive tumors. Expression of b-catenin was largely restricted to a membranous pattern in both tumor types. Cytoplasmic expression of bcl-2 was overall mildly reduced in indolent neoplasms. Nuclear expression of estrogen and progesterone receptors was increased in both indolent and aggressive neoplasms, but was without sex-or age-related differences; however, whereas progesterone receptor expression was diffuse and strong in clinically indolent carcinomas, its expression was diminished in aggressive neoplasms. Recognition of the clinicopathological characteristics and the molecular and immunophenotypic features of the columnar cell variant of papillary thyroid carcinoma may aid in characterizing neoplasms that behave indolently or aggressively. Keywords: BRAF (BRAF V600E ); b-catenin; columnar cell variant; cyclin D1; papillary thyroid carcinoma Papillary thyroid carcinoma is a common endocrine neoplasm that is typically indolent and associated with long-term survival. This favorable biological behavior reflects the vast majority of conventional and histological variants of well-differentiated papillary thyroid carcinoma. However, a more aggressive tumoral growth characterizes a small subset that behaves more akin to poorly differentiated and undifferentiated thyroid carcinoma. Initially included in this group of aggressive neoplasms, the columnar cell variant is a rare subtype with variable biological behavior. Early reports described tumors with fast growth rates, aggressive local invasion, high rates of recurrence, early metastasis to regional lymph nodes and distant

Single thyroid tumour showing multiple differentiated morphological patterns and intramorphological molecular genetic heterogeneity

“…Chen et al have reported on the expression of BRAF V600E mutation in columnar cell carcinomas. In that study, three of nine columnar cell carcinomas exhibited this mutation and two of the three tumours had an aggressive behaviour 11. We tested two different blocks with columnar cell carcinoma, one of which had a KRAS p.G12D mutation and the other none.…”

“…The columnar cell variant is believed by most to be a subtype of papillary carcinoma although some suggest that it is a distinct entity 1 11. Chen et al have reported on the expression of BRAF V600E mutation in columnar cell carcinomas.…”

Lack of association of B-type raf kinase V600E mutation with high-risk tumor features and adverse outcome in conventional and follicular variants of papillary thyroid carcinoma

“…[13] The prevalence of BRAF V600E mutations is less frequent with other aggressive variants as 33% in columnar cell variant, 50% in Hobnail variant, and absent in diffuse sclerosing variant. [141516]…”

Molecular Markers Involved in Tumorigenesis of Thyroid Carcinoma: Focus on Aggressive Histotypes

“…The BRAF V600E mutation is found in about 33% of these tumors [Evans, 1986;Chen et al, 2011;Haugen et al, 2016].…”