Retinoblastoma (Rb) mutation in thyroid neoplasia has been identified in a
few molecular studies; however, the utility of Rb immunohistochemistry in d
istinguishing benign and malignant thyroid lesions has not been documented
in formalin-fixed, paraffin-embedded tissues. The present study investigate
d Rb immunohistochemistry in a series of 111 formalin-fixed, paraffin-embed
ded benign and malignant thyroid lesions. All of the major histologic subty
pes were included to detect any heterogeneity in Rb-l expression that might
influence the diagnostic utility of this technique or further elucidate th
e pathogenesis of thyroid neoplasia among the categories. Altogether, 34 fo
llicular adenomas, 9 follicular carcinomas, 7 Hurthle cell adenomas, 5 Hurt
hle cell carcinomas, 23 papillary carcinomas (8 of which were follicular va
riants), 4 insular carcinomas, 4 anaplastic carcinomas, 6 medullary carcino
mas, and 19 nodular goiters were analyzed. Avidin-biotin immunohistochemist
ry was performed using the Dako Rb-l clone. Pronase digestion was introduce
d into the epitope retrieval protocol to eliminate false-positive cytoplasm
ic staining. Nuclear immunoreactivity was assessed as positive if 10% or mo
re of thyroid epithelial nuclei stained positively, and conversely as negat
ive. The majority of benign non-Hurthle thyroid lesions, whether hyperplast
ic or neoplastic, retained Rb nuclear immunopositivity in most cells (51 of
53 cases [96%]). Conversely, malignant thyroid neoplasms lacked Rib immuno
reactivity in the majority (42 of 51 cases [82%]), including all papillary
carcinomas (23 of 23) and almost all follicular carcinomas (8 of 9 [89%]).
Virtually all Hurthle cell neoplasms were negative (11 of Ii [92%]), whethe
r benign or malignant. In conclusion, Rb imnunohistochemistry can aid in th
e distinction between benign and malignant thyroid lesions in conjunction w
ith morphology. This seems to be most applicable to the often problematic d
ifferentiation between follicular adenoma and the follicular Variant of pap
illary carcinoma (P <.0001; sensitivity and specificity, 100%) or minimally
invasive follicular carcinoma (P = .0007; sensitivity, 89%; specificity, 1
00%).