Faculty Bibliography

PURPOSE: Squamous cell carcinoma of unknown primary (SCCHNUP) is commonly treated with comprehensive radiation to the laryngopharynx and bilateral necks. In 1998, we established a departmental policy to treat SCCHNUP with radiation directed to the oropharynx and bilateral neck. METHODS: From 1998-2011, 60 patients were treated - N1: 18%, N2: 75% and N3: 7%. 82% underwent neck dissection. 55% received IMRT and 62% underwent concurrent chemoradiotherapy. RESULTS: At median follow-up of 54months, 5 patients failed regionally and 4 emerged with a primary (tongue base, hypopharynx and thoracic esophagus). Five-year rates of regional control, primary emergence, distant metastasis, disease-free survival and overall survival were 90%, 10%, 20%, 72% and 79%, respectively. The 5year rate of primary emergence in a non-oropharynx site was 3%. CONCLUSION: This is the first demonstration that an oropharynx-directed approach yields low rates of primary emergence in SCCHNUP with excellent oncologic outcomes.

BACKGROUND: Encapsulated non-invasive follicular variant papillary thyroid cancer (ENIFVPTC) has recently been re-termed noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). This designation specifically omits the word "cancer" to encourage conservative management since patients with NIFTP tumors have been shown to derive no benefit from completion thyroidectomy or adjuvant radioactive iodine (RAI) therapy. METHODS: IRB approved retrospective study of consecutive cases of tumors from 2007 to 2015 that met pathologic criteria for NIFTP. The Conservative Management (CM) group included patients managed with lobectomy alone or appropriately indicated total thyroidectomy. Those included in the Aggressive Management (AM) group received either completion thyroidectomy or radioactive iodine or both. RESULTS: From 100 consecutive cases of ENIFVPTC reviewed, 40 NIFTP were included for the final analysis. Of these, 10 (27%) patients treated with initial lobectomy received completion thyroidectomy and 6 of 37 (16%) also received post-surgical adjuvant RAI. The mean per-patient cost of care in the AM group was $17629+/-2865 nearly twice the $8637+/- 309 costs in the CM group, and was largely driven by the cost of completion thyroidectomy and RAI. CONCLUSIONS: The term NIFTP has been recently promulgated to identify a type of thyroid neoplasm, formerly identified as a low-grade cancer, for which initial surgery represents adequate treatment. We believe that since the new NIFTP nomenclature intentionally omits the word "cancer" the clinical indolence of these tumors will be better appreciated, and cost savings will result from a more conservative and appropriate clinical management.

BACKGROUND: Commonly occurring in the head and neck, paragangliomas are typically benign, highly vascular neoplasms embryologically originating from the extra-adrenal paraganglia of the neural crest. Frequently, these tumors are associated with the vagus or tympanic plexus nerve or the carotid artery, or jugular bulb. Their clinical presentation can vary across a wide spectrum of signs and symptoms. METHODS: We reviewed and compared standard treatment approaches for paragangliomas of the head and neck. RESULTS: In general, surgery is the first-line choice of therapy for carotid body tumors, whereas radiotherapy is the first-line option for jugular and vagal paragangliomas. CONCLUSIONS: Because of the complexity of clinical scenarios and treatment options for paragangliomas, a multidisciplinary algorithmic approach should be used for treating paragangliomas. The approach should emphasize single-modality treatment that yields excellent rates of tumor control, low rates of severe, iatrogenic morbidity, and the preservation of long-term function in this patient population.

Carotid paragangliomas, commonly known as carotid body tumors, are the most commonly reported head and neck paragangliomas. They are slow growing and always associated with the carotid arteries and adjacent nerves. They are rarely malignant. The estimates for familial transmission of this tumor range from 30%-50%. When multiple paragangliomas are present, the most common combination is 2 carotid paragangliomas. There are no absolute indications for surgical resection, but tumors expressing biochemical activity, a growth rate >1-2 mm per year or demonstrating airway or alimentary tract compression should be resected. Patients younger than 50 years should have small-to-medium sized paragangliomas resected. Patients with significant comorbidities or a contralateral cranial nerve dysfunction should not have surgery. Large carotid paragangliomas involving the skull base would likely result in multiple lower cranial nerve dysfunction after resection requiring multispecialty care afterwards. When dealing with bilateral carotid paragangliomas, resection of the smaller tumor first is recommended. Simultaneous carotid paraganglioma excision is discouraged because of acute baroreceptor failure. The second carotid paraganglioma may be observed for growth or it may be radiated depending on symptoms, size, or growth. The role and indications for angiography and embolization are covered elsewhere in this issue. If a carotid paraganglioma is biochemically active, alpha-adrenergic blockade followed by beta blockade is recommended and should be commenced 10 days before surgery. The complications associated with carotid paraganglioma excision are lower cranial nerve palsies and cerebrovascular accidents, although these are quite uncommon for small-to-medium sized tumors. Meticulous surgery and control of the carotid arteries can decrease these morbidities dramatically. Recently, a "top down" or craniocaudal approach to these tumors has gained acceptance among many surgeons. This approach controls the cephalad internal carotid artery and external carotid artery and removes the tumor down to the bifurcation. This technique has decreased the incidence of cranial neuropathy and blood loss in these patients. Following treatment, the uncomplicated patient requires yearly follow-up consisting of physical examination and magnetic resonance imaging. The familial patient should be genetically tested for succinate dehydrogenase mutations. Depending on the type of mutation yearly imaging and evaluation of siblings, parents and children is strongly advised. As metachronous lesions are possible, this follow-up is a lifetime undertaking

BACKGROUND: Several recent analyses of indeterminate thyroid nodules classified as Bethesda III (follicular lesion of undetermined significance) have reported considerably greater rates of malignancy than those initially reported by the Bethesda System for Reporting Cytopathology (BSRTC). These values, however, may be overestimates owing to several sources of bias, such as referral, selection, and publication biases. Our aim was to analyze the prevalence of malignancy in Bethesda III and IV thyroid nodules in a comprehensive health system less prone to institutional referral bias, excluding incidental carcinomas, and we examine the literature for publication bias. METHODS: We performed a retrospective analysis with pathologic re-review of 119 patients with Bethesda III/IV cytology undergoing surgery in a comprehensive health system by examining patient and nodule characteristics. A review of the literature was performed and analyzed for publication bias. RESULTS: The malignancy rate in resected thyroid nodules was 13% (6/48) for Bethesda III and 28% (20/71) for Bethesda IV. There were 9 of 119 patients (8%) with incidental microcarcinomas. Age <30 years was associated with an increased risk of malignancy (odds ratio, 25.8; P = .005). Sex, nodule size, and ultrasonographic features were not associated with risk of malignancy. Analysis of the literature was indicative of publication bias for Bethesda III cohorts, with reported rates positively skewed (P = .039). CONCLUSION: In a comprehensive health system, the rate of malignancy in Bethesda III nodules was similar to the range reported by the BSRTC. Recent reports of greater rates of malignancy may be attributable to institutional referral patterns, operative selection, inclusion of incidental microcarcinomas, and publication bias.

Objectives: To study the MRI and PET/CT imaging of osteoradionecrosis of the sub-axial cervical spine, a serious long-term complication of radiation therapy for head and neck cancers that can lead to pain, vertebral instability, myelopathy, and cord compression. Methods and Materials: This is a single-institution retrospective review of patients diagnosed and treated for osteoradionecrosis of the sub-axial cervical spine following surgery and radiation for head and neck cancer. Results: We report PET/CT and MRI imaging for four patients, each with extensive treatment for recurrent head and neck cancer. Osteomyelitis and discitis are the end stage manifestations of osteoradionecrosis of sub-axial spine. Conclusions: Osteoradionecrosis of the sub-axial spine has variable imaging appearance and needs to be differentiated from recurrent or metastatic disease. Surgical violation of the posterior pharyngeal wall on top of compromised vasculature in patients treated heavily with radiation therapy may predispose the sub-axial cervical vertebrae to osteoradionecrosis, with possible resultant osteomyelitis and discitis. MRI and PET/CT imaging are complimentary in this setting. PET/CT images may be misinterpreted in view of history of head and neck cancer. MRI should be utilized for definitive diagnosis of osteomyelitis and discitis in view of its imaging specificity. Advances in Knowledge: We identify the end-stage manifestation of osteoradionecrosis in the sub-axial spine on PET/CT and MRI to facilitate its correct diagnosis.