Encapsulated follicular thyroid tumor with equivocal nuclear changes, so-called well-differentiated tumor of uncertain malignant potential: a morphological, immunohistochemical, and molecular appraisal.
There is a continuous debate regarding the classification of thyroid follicular lesions and the term "well-differentiated tumor of uncertain malignant potential (WDT-UMP)" was recently introduced to cover this problematic spectrum of tumors. The objective of this study was to reappraise WDT-UMP using morphological, immunochemical, and molecular analysis and to shed more light on encapsulated thyroid follicular-patterned tumors. A total of 30 cases of WDT-UMP with equivocal papillary thyroid carcinoma-type nuclear changes (PTC-N) or focal unequivocal PTC-N were examined. As a control, follicular adenoma (n = 29), follicular carcinoma (n = 8), hyalinizing trabecular adenoma (n = 5), and PTC (n = 48) were included. HBME-1, cytokeratin 19, and galectin-3 were positive in 12 (40.0%), 10 (33.3%) and 11 (36.7%) cases of WDT-UMP, respectively. According to the positivity of those markers, significant differences were obtained between WDT-UMP and PTC encapsulated common type (P = 0.028, 0.010, and 0.004, respectively), infiltrative follicular variant (P = 0.020, 0.026, and 0.008, respectively), and infiltrative common type (P = 0.004, 0.001, and 0.005, respectively), but not between WDT-UMP and follicular adenoma or follicular carcinoma. BRAF(V600E) mutation was absent but RET/PTC1 rearrangement was found in only two (6.7%) cases of WDT-UMP. None of the 20 patients with WDT-UMP developed recurrence, with an average follow-up of 80 months. These findings indicate that WDT-UMP has a favorable outcome and is distinct from PTC in morphological, immunohistochemical, and molecular characteristics. We propose that WDT-UMP should be classified as "well-differentiated tumor with uncertain behavior".
Department of Human Pathology, Wakayama Medical University, Wakayama City, Japan.
Zhiyan
Z
Liu
Gengyin
G
Zhou
Misa
M
Nakamura
Eisuke
E
Koike
Yaqiong
Y
Li
Takashi
T
Ozaki
Ichiro
I
Mori
Emiko
E
Taniguchi
Kennichi
K
Kakudo
D018263:Adenocarcinoma, Follicular / Q000737:chemistry / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000473:pathology*; D005260:Female; D037502:Galectin 3 / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D053539:Keratin-19 / Q000032:analysis; D008297:Male; D008875:Middle Aged; D013964:Thyroid Neoplasms / Q000737:chemistry / Q000473:pathology*; D000951:Antigens, Neoplasm
D014408:Biomarkers, Tumor; D037502:Galectin 3; D053539:Keratin-19; C432845:HBME-1 antigen; D000951:Antigens, Neoplasm