Beta-HCG Producing Anaplastic Thyroid Carcinoma – A Variant with Improved Prognosis?
Nils Becker, Rebecca D Chernock, Brian Nussenbaum, James S Lewis. Washington University School of Medicine, St. Louis, MO
Background: Anaplastic thyroid carcinoma (ATC) is a rare malignancy which is clinically very aggressive. The median survival is 5 months after diagnosis. No treatment is associated with a significant improvement in survival. Recently, we identified what we believe is the first case of a beta-hCG secreting ATC. It responded dramatically to chemotherapy and radiation and was subsequently surgically resected. The patient's serum beta-hCG was 53 IU/L at diagnosis and dropped to 6 IU/L two weeks after surgery. After 14 months, the patient has no evidence of disease or detectable serum beta-hCG. Although beta-hCG secretion has been reported in many neoplasms, it has not yet been described in ATC.
Design: After characterization of the sentinel beta-hCG secreting case, which was strongly positive in almost all tumor cells for beta-hCG and negative for PAX8, an additional 29 cases of anaplastic thyroid carcinoma were retrieved from our files and immunostained for beta-hCG and PAX8. Staining was graded for intensity (weak, moderate, strong) and distribution (quartiles) by 3 study pathologists. Clinical follow up information was obtained by chart review.
Results: Beta-hCG staining was present in five of 30 cases (17%), but only the sentinel case showed strong, diffuse staining. The remaining positive cases showed either strong beta-hCG staining in <25% of cells, or moderate staining in up to 75% of the cells. PAX8 staining was present in 18 of 30 (60%) cases, including two of the five (40%) beta-hCG positive cases. Follow up of the beta-hCG positive patients showed that only the index case was treated with chemoradiation and surgery. The remaining beta-hCG positive patients either went to hospice or received palliative treatment only. Twenty-seven of 29 patients died of disease at a median of 3.3 months, including all four additional beta-hCG positive patients at a median of 2.7 months. PAX8 positive cases had improved overall survival (median survival 4.9 months versus 2.0 months; p=0.0164).
Conclusions: Our study demonstrates the first beta-hCG secreting ATC. It was treatment responsive and has had a provisionally favorable outcome. Four additional cases showed beta-hCG expression but none was treated with curative intent. Although only a single case, our findings suggest that strongly beta-hCG positive ATC may be a unique entity within the larger group. In addition, our results suggest that PAX8 expression by ATC may correlate with a better prognosis.
Monday, March 19, 2012 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 93, Monday Morning