No abstract

Objective Patients with head and neck squamous cell carcinoma (SCC) often present with cervical lymph node metastasis. Occasionally the primary tumor site remains unknown even after thorough investigation. Management of such cases is problematic and may result in over-treatment and consequent increased morbidity. High risk HPV has been advocated recently as an important etiologic factor for a subset of head and neck SCC. These are believed to have a special predilection for the oropharyngeal tonsils and are characterized by nonkeratinizing basaloid morphology, and a strong reactivity to p16 immunostain. Identifying HPV-related SCC in the lymph nodes may thus provide a means for localizing the primary tumor site. Design Ninety-three cases of SCC metastatic to the neck from known primary tumors were classified morphologically into conventional keratinizing SCC (KSCC) and non-keratinizing SCC (NKCa). In situ hybridization (ISH) for high risk HPV as well as immunostaining for p16 were performed on all metastsatic and primary tumors. Results Of the 93 cases of metastatic carcinomas 32 were oropharyngeal, 35 oral, and 26 arose in the laryx/hypopharynx. Twenty-three cases were found to be HPV+ by ISH, of which 22/23 had oropharyngeal origin (P \ 0.0001), with 95.7% sensitivity and 85.7% specificity. Twenty-one of these HPV+ oropharyngeal tumors were NKCa (P \ 0.0001). The remaining case showed overlapping NKCa/KSCC hybrid morphology. All NKCa were HPV+ and stained diffusely and strongly with p16 antibodies. Conclusion We have demonstrated that HPV status of the lymph node metastasis can be assessed not only by ISH and p16 immunoreactivity but also histomorphologically. In addition, a positive microscopic identification of HPVrelated carcinoma is a reliable predictor of oropharyngeal origin.

Many uveal melanoma patients die of metastasis despite ocular treatment. Transcriptomic profiling of enucleated tumors can identify patients at high metastatic risk. Because most uveal melanomas do not require enucleation, a biopsy would be required for this analysis. Here, we establish the feasibility of transcriptomic analysis of uveal melanomas from fine needle aspirates. Transcriptomic profiles were analyzed from postenucleation "mock" needle biopsies and matching tumors from eight enucleated eyes and from fine needle aspirates in 17 uveal melanomas before radiotherapy. Predictive accuracy was assessed using a weighted voting classifier optimized for probe set selection using a minimal redundancy/maximum relevance algorithm. Transcriptomic profiles from mock biopsies were highly similar to those from their matching tumor samples (P < 0.0001). Transcriptomic profiles from fine needle aspirates clustered into two classes with discriminating probe sets that overlapped significantly with those for our published classification (P < 0.00001). No loss of predictive accuracy was identified among eight needle aspirates obtained from a distant location. Thus, it is feasible to obtain RNA of adequate quality and quantity to perform transcriptomic analysis on uveal melanoma samples obtained by fine needle biopsy. This method can be applied to specimens obtained from distant geographic locations and can stratify uveal melanoma patients based on metastatic risk.

Background In all, 20% of fine‐needle aspiration (FNA) biopsies of thyroid nodules have an indeterminate diagnosis; of these, 80% are found to be benign after thyroidectomy. Some previous reports indicate that positron emission tomography (PET) with 18F‐fluorodeoxyglucose (FDG) imaging may predict malignancy status. We now report results on the first 51 patients in the largest prospective study of FDG‐PET in patients with an indeterminate thyroid nodule FNA. Methods Eligible patients had a dominant thyroid nodule that was palpable or ≥1 cm in greatest dimension as seen by ultrasonography, and indeterminate histology of the FNA biopsy specimen. Participants underwent preoperative neck FDG‐PET alone or FDG‐PET with computed tomography (FDG‐PET/CT). Images were evaluated qualitatively and semiquantitatively using the maximum standardized uptake value (SUVmax). Final diagnosis was determined by histopathologic analysis after thyroidectomy. Descriptive statistical analysis was performed. Results A total of 51 patients underwent preoperative FDG‐PET or FDG‐PET/CT. Studies without focally increased uptake localized to the lesion were considered negative. For all lesions (10 malignant, 41 benign), the sensitivity, specificity, positive‐predictive value (PPV), and negative‐predictive value (NPV) were 80%, 61%, 33%, and 93%, respectively. Postoperatively, two malignant and six benign lesions were found to be <1 cm by pathology examination; one lesion was not measured. When these lesions were excluded, the sensitivity, specificity, PPV, and NPV were 100%, 59%, 36%, and 100%, respectively. Conclusions Based on these preliminary data, FDG‐PET may have a role in excluding malignancy in thyroid nodules with an indeterminate FNA biopsy. This finding justifies ongoing accrual to our target population of 125 participants.

II-3.