Objective:We describe an interesting case of primary thyroid epithelioid angiosarcoma associated with both Graves disease and multinodular goiter, presenting as thyrotoxicosis and enlarging neck mass.Methods: Chart review for this single case was approved by the Institutional Review Board and patient consent was obtained.Results: A 61-year-old female with longstanding history of multinodular goiter presented with rapidly enlarging neck girth and symptoms of thyrotoxicosis. Thyroid function testing revealed suppressed thyroid-stimulating hormone (TSH) of <0.005 µIU/mL, an elevated free thyroxine of 3.0 ng/dL (normal range, 0.7 to 1.8 ng/ dL), and free triiodothyronine of 5.9 pg/mL (normal range, 1.8 to 4.6 pg/mL). TSH receptor antibodies were significantly elevated. Iodine-123 uptake and scan demonstrated elevated 4-and 24-hour uptake with heterogeneous bilateral distribution, exhibiting background diffuse uptake with a left inferior lobe hypofunctioning nodule, and signal attenuation in the right thyroid lobe due to a right-sided mass visualized subsequently on computed tomography. She required high-dose beta-blockade and methimazole 20 mg 3 times daily with subsequent normalization of thyroid hormones. She underwent thyroidectomy 3 months later. Pathology revealed bilateral multinodular thyroid follicular hyperplasia with an 8-cm epithelioid angiosarcoma in the right lobe with a focal contralateral intrathyroidal intralymphatic metastasis. A separate microscopic focus of papillary thyroid carcinoma (1 mm) in the left lobe was also noted. The patient underwent radiation therapy followed by adjuvant chemotherapy per oncology consultation.Conclusion: Epithelioid angiosarcoma is a rare primary thyroid neoplasm that may present with thyrotoxic state, which was attributed to concomitant diagnosis of Graves disease in our patient. (AACE Clinical Case Rep. 2017;3:e374-e378) Abbreviations: CT = computed tomography; FNA = fine needle aspiration; I-123 = iodine-123; TSH = thyroid-stimulating hormone
e18085 Background: The ALK 2p23 translocation, ALK(+), is an important druggable target in 5-7% of non-small cell lung cancer (NSCLC). However, the break-part FISH assay is labor-intensive. Better understanding of the target population’s clinical features and alternative screening tests are desirable to enable cost-effective patient selection for molecular therapy. Methods: NSCLC patients (N=120) seen at the Cleveland Clinic (CC) who had clinical screening ALK 2p23 FISH (Abbott Molecular) were included in this retrospective analysis. Biopsy specimens were also tested using immunohistochemistry (IHC) for ALK overexpression via clone D5F3 (Cell Signaling Tech.) with OptiView ultrasensitive detection (Ventana Medical Sys.). Clinical data were extracted from electronic medical records. Comparison was performed using Fisher’s exact test, Wilcoxon rank sum test or log-rank test. Results: Of the 120 tumors tested, 34 (28.3%) were ALK(+) by FISH, predominantly adenocarcinomas (33/34). 97% of the samples were also tested by ALK-IHC, with a concordance rate of 99%. Comparing to ALK (-) group, ALK(+) patients were younger (median 53 vs 65, p<0.01) and mostly never/light smokers (91% vs 43%, p<0.01). ALK(+) tumors tended to have higher number of metastatic sites at diagnosis, especially for liver metastasis (26.5% vs 10.5%, p=0.04). Interestingly, venous thrombosis (DVT/PE) was also significantly more common in ALK(+) patients (35.3% vs 16.3%, p=0.03). 17 (50%) patients were treated with crizotinib in the ALK(+) group. Two cases with positive screening ALK-IHC helped to identify FISH(+) tumor areas. Of those tumors with EGFR status available (n=103), 6 were EGFR mutation-positive, all being ALK(-). No significant OS difference was seen in ALK(+)/EGFR(-) patients (n=28) compared to ALK(-)/EGFR(-) patients (n=69). Conclusions: ALK 2p23 (+) NSCLC at CC was more commonly seen in younger patients and never/light smokers. They tended to have greater number of metastases, especially in the liver, and significantly higher risk of venous thrombosis. ALK-ultrasensitive IHC using the D5F4 clone helped to identify FISH(+) tumor areas and may be considered a cost-effective screening test demonstrating high concordance with ALK FISH.
8113 Background: EGFR mutation (Mut) testing is recommended for all patients (pts) with advanced NSCLC to identify pts who may benefit from front-line EGFR tyrosine kinase inhibitor (TKI) therapy. In July 2010 the Cleveland Clinic initiated reflex EGFR testing of all new diagnoses of nonsquamous NSCLC, prior to which testing was done only by physician request. A retrospective study was designed to review how this change affected clinical practice in a large academic health center. Methods: All pts with NSCLC that had EGFR Mut testing performed at the Cleveland Clinic from 07/2009 to 02/2012 were included (n=287). Pt characteristics, tumor histology and stage, Mut status, treatments, and pt outcomes were collected from electronic medical records. Special attention was given to pts with EGFR Mut+ who received erlotinib (E). Data were analyzed using Fisher’s exact, chi-square and the Wilcoxon rank-sum tests. Results: See Table. Conclusions: Automatic EGFR mutation testing, recommended in an ASCO provisional clinical opinion in April 2011, was feasible in a large academic center and significantly shortened the time between diagnosis and EGFR status becoming available to guide treatment decisions. Although not statistically significant due to the small sample size, there were positive trends towards increased first line usage of E in pts with EGFR Mut+, better performance status, lower rates of E discontinuation due to toxicity, and higher response rate to E in the automatic testing group. There was no difference in overall survival between the two groups. [Table: see text]
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