Setting the Stage for 2018: How the Changes in the American Joint Committee on Cancer/Union for International Cancer Control Cancer Staging Manual Eighth Edition Impact Radiologists.

The updated eighth edition of the Cancer Staging Manual of the American Joint Committee on Cancer will be implemented in January 2018. There are multiple changes to the head and neck section of the manual, which will be relevant to radiologists participating in multidisciplinary head and neck tumor boards and reading pretreatment head and neck cancer scans. Human papillomavirus-related/p16(+) oropharyngeal squamous cell carcinoma will now be staged separately; this change reflects the markedly better prognosis of these tumors compared with non-human papillomavirus/p16(-) oropharyngeal squamous cell carcinoma. Nodal staging has dramatically changed so that there are different tables for human papillomavirus/p16(+) oropharyngeal squamous cell carcinoma, Epstein-Barr virus-related nasopharyngeal carcinoma, and all other head and neck squamous cell carcinomas. Extranodal extension of tumor is a new clinical feature for this third staging group. In the oral cavity, the pathologically determined depth of tumor invasion is a new staging criterion, while extrinsic tongue muscle invasion is no longer part of staging. This review serves to educate radiologists on the eighth edition changes and their rationale.

Pathology-based staging for HPV-positive squamous carcinoma of the oropharynx.

OBJECTIVE: The rapid worldwide rise in incidence of human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) has generated studies confirming this disease as an entity distinct from traditional OPSCC. Based on pathology, surgical studies have revealed prognosticators specific to HPV-positive OPSCC. The current AJCC/UICC staging and pathologic nodal (pN)-classification do not differentiate for survival, demonstrating the need for new, HPV-specific OPSCC staging. The objective of this study was to define a pathologic staging system specific to HPV-positive OPSCC. METHODS: Data were assembled from a surgically-managed, p16-positive OPSCC cohort (any T, any N, M0) of 704 patients from five cancer centers. Analysis was performed for (a) the AJCC/UICC pathologic staging, (b) newly published clinical staging for non-surgically managed HPV-positive OPSCC, and (c) a novel, pathology-based, "HPVpath" staging system that combines features of the primary tumor and nodal metastases. RESULTS: A combination of AJCC/UICC pT-classification and pathology-confirmed metastatic node count (⩽4 versus ⩾5) yielded three groups: stages I (pT1-T2, ⩽4 nodes), II (pT1-T2, ⩾5 nodes; pT3-T4, ⩽4 nodes), and III (pT3-T4, ⩾5 nodes), with incrementally worse prognosis (Kaplan-Meier overall survival of 90%, 84% and 48% respectively). Existing AJCC/UICC pathologic staging lacked prognostic definition. Newly published HPV-specific clinical stagings from non-surgically managed patients, although prognostic, showed lower precision for this surgically managed cohort. CONCLUSIONS: Three loco-regional "HPVpath" stages are identifiable for HPV-positive OPSCC, based on a combination of AJCC/UICC primary tumor pT-classification and metastatic node count. A workable, pathologic staging system is feasible to establish prognosis and guide adjuvant therapy decisions in surgically-managed HPV-positive OPSCC.

MUC4 regulates cellular senescence in head and neck squamous cell carcinoma through p16/Rb pathway.

The limited effectiveness of therapy for patients with advanced stage head and neck squamous cell carcinoma (HNSCC) or recurrent disease is a reflection of an incomplete understanding of the molecular basis of HNSCC pathogenesis. MUC4, a high molecular weight glycoprotein, is differentially overexpressed in many human cancers and implicated in cancer progression and resistance to several chemotherapies. However, its clinical relevance and the molecular mechanisms through which it mediates HNSCC progression are not well understood. This study revealed a significant upregulation of MUC4 in 78% (68/87) of HNSCC tissues compared with 10% positivity (1/10) in benign samples (P=0.006, odds ratio (95% confidence interval)=10.74 (2.0-57.56). MUC4 knockdown (KD) in SCC1 and SCC10B HNSCC cell lines resulted in significant inhibition of growth in vitro and in vivo, increased senescence as indicated by an increase in the number of flat, enlarged and senescence-associated ß-galactosidase (SA-ß-Gal)-positive cells. Decreased cellular proliferation was associated with G0/G1 cell cycle arrest and decrease expression of cell cycle regulatory proteins like cyclin E, cyclin D1 and decrease in BrdU incorporation. Mechanistic studies revealed upregulation of p16, pRb dephosphorylation and its interaction with histone deacetylase 1/2. This resulted in decreased histone acetylation (H3K9) at cyclin E promoter leading to its downregulation. Orthotopic implantation of MUC4 KD SCC1 cells into the floor of the mouth in nude mice resulted in the formation of significantly smaller tumors (170±18.30 mg) compared to those (375±17.29 mg) formed by control cells (P=0.00007). In conclusion, our findings showed that MUC4 overexpression has a critical role by regulating proliferation and cellular senescence of HNSCC cells. Downregulation of MUC4 may be a promising therapeutic approach for treating HNSCC patients.

Conservation surgery for recurrent carcinoma of the glottic larynx.

BACKGROUND: Partial laryngectomy following previous irradiation is an oncologically sound procedure with excellent local control and survival rates. Several reports suggest an increased complication rate in previously irradiated patients. METHODS: To analyze whether previous irradiation affected complications, disease control, or survival we performed a retrospective analysis of all patients who underwent vertical partial laryngectomy (VPL) for squamous cell carcinoma of the glottic larynx between January 1984 and August 1993. RESULTS: Sixty-eight patients had adequate followup. The overall 5-year survival rates were 79% for previously treated patients and 95% for primary VPL patients (P = NS). The local control rates with surgical salvage were 93% and 98%, respectively. No increase in wound complications, time to decannulation, length of hospitalization, or ability to swallow were found. CONCLUSIONS: VPL can be performed safely in selected patients following previous radiotherapy without a significant increase in complications or cost.

Angiosarcoma of the head and neck.

BACKGROUND: Angiosarcoma (AS) is an uncommon, highly aggressive tumor with a poor prognosis. METHODS: To study the impact of various treatment modalities, namely surgery, radiation, and chemotherapy, we reviewed our experience with AS of the head and neck. RESULTS: From 1978 through 1992, we treated 13 men and 5 women with AS (median age 67 years). Sixteen tumors occurred on the scalp and face and 2 in the oropharynx. Two patients presented with cervical metastases, and a third had subsequent nodal involvement. Primary surgery was used in 9 patients, including 1 who received adjunctive systemic doxorubicin hydrochloride, and 2 who received adjunctive radiotherapy. The tumors of 9 patients were unresectable: 4 were treated with intra-arterial doxorubicin hydrochloride; and 5, with systemic doxorubicin hydrochloride. Twelve patients (67%) died of disease an average of 25 months after diagnosis. Overall 5-year survival was 33%, but only 20% of the patients were disease free. Size of the tumor was an important predictor of survival, as all patients with a lesion > 10 cm died of disease, compared with 67% with a lesion < 10 cm. Four of 6 patients treated with wide local excision for lesions < 10 cm survived 5 years. CONCLUSIONS: We recommend surgery for resectable lesions with postoperative radiation for unsatisfactory margins, large tumor size, deep extension, and multicentricity. Elective treatment of the neck does not appear warranted.

The relationship of loss of heterozygosity to tobacco exposure and early recurrence in head and neck squamous cell carcinoma.

BACKGROUND: Tobacco usage contributes to carcinomas of the lung, bladder, esophagus, uterine cervix, and head and neck, and can induce specific genetic lesions. Studies of the above tumor types have documented allelic deletions affecting 3p, 5q, 9p, 9q, 10q, 11p, 13q, 17p, and 18q. Relationships between genetic loss, tobacco exposure, and patient outcome have not been described. PATIENTS AND METHODS: To confirm and further define loss of heterozygosity in head and neck squamous cell carcinoma (HNSCC), and to examine relationships between loss of heterozygosity and both tobacco exposure and early recurrence, we undertook this study on previously untreated patients with HNSCC. We performed a Southern blot analysis using 11 probes specific for loci deleted in tobacco-associated cancers. We have investigated 42 prospectively collected, paired samples of HNSCC and peripheral blood. Demographic and follow-up data were collected on these patients. RESULTS: Significant loss of heterozygosity was observed in descending order of frequency at 11p, 9p, 17p, 3p, 10q, and 13q. All nonsmokers showed loss of heterozygosity on one or more loci compared with only 53% of smokers (P < 0.05). Furthermore, patients with multiple deletions had a significantly higher rate of early recurrence than those with fewer deletions (P < 0.05). CONCLUSION: Multiple deletions occurred more frequently in nonsmokers and predicted a higher risk of early recurrence.

Recalcitrant oral ulcers caused by calcium channel blockers: diagnosis and treatment considerations.

BACKGROUND: Oral ulcers often pose a dilemma in diagnosis and treatment. Patients seen routinely in dental practices are frequently receiving multiple medications. The authors discuss the pathogenesis, clinical appearance and treatment of drug-induced oral ulcers. CASE DESCRIPTIONS: Two patients with recalcitrant painful oral ulcers caused by calcium channel blockers are described. These ulcers failed to heal despite repeated interventions, including surgery, laser ablation, and topical and systemic steroid therapy. Results of the histopathologic examinations were nonspecific. The patients were in a great deal of pain because of the initial failure to recognize the cause of these ulcers. CLINICAL IMPLICATIONS: A careful medical history, including a detailed list of medications received, is critical in identifying drug-induced oral ulcerations, especially when the ulcer is resistant to treatment and of indeterminate cause. To date, calcium channel blockers have not been reported to cause oral ulcerations.

Extracranial approaches to the repair of cerebrospinal fluid rhinorrhea.

This paper presents a review of the extracranial evaluation and treatment of cerebrospinal fluid (CSF) rhinorrhea. Diagnosis with attention to a careful history and physical with maneuvers which exacerbate drainage and thorough physical exam along with imaging techniques are discussed. The common etiologies of CSF rhinorrhea including trauma, spontaneous leakage, tumor, and iatrogenic injury are included. Management consists of conservative measures including the avoidance of straining maneuvers which increases intracranial pressure. Periodic drainage of CSF via lumbar puncture or continuous drainage via flow-regulated systems may also be of benefit in attempts of conservative management. Failure of conservative management, constant leakage, pneumocephalus, and recurrent meningitis are indicators for surgical repairs. Ethmoid-cribiform plate region repairs are generally approached by external ethmoidectomy and the development of mucoperiosteal flaps from various donor sites which are then rotated to the leak area to seal the defect. Frontal sinus leaks are usually repaired via an osteoplastic flap technique with direct repair of the dural defect or the use of fascial graft tucked under the bony defect, then obliterated with abdominal fat. CSF rhinorrhea presents a diagnostic and surgical challenge to the otolaryngologist. After diagnosis and localization, operative repair using extracranial approaches is accepted as the initial method of intervention in these cases.

Microvascular reconstruction of the head and neck after tumor ablation.

Microvascular reconstruction of the head and neck in cancer patients after surgical ablation has significantly improved the quality of life of these patients from both a functional and cosmetic standpoint. Successful management and reconstruction of these patients requires a well-coordinated team approach. Operating room times and hospital stays have significantly decreased with coordination and experience of the team members.

Biological staging of head and neck cancer and its role in developing effective treatment strategies.

The purpose of a cancer staging system is to encompass all attributes of a tumor that define its life history. We propose a biological staging system which incorporates all of the phases of the natural history of head and neck cancer beginning with the earliest cellular changes extending through the early phase of invasion to the occurrence of metastasis and, finally, culminating in therapeutically refractory disease. This temporally structured system recognizes the importance of constitutional predisposition, and the impact of environmental factors. The intent is to augment the AJCC/UICC staging system and use this system to provide a framework which will easily incorporate current and future advances in basic science, prevention, therapy and palliation which will improve the quality and quantity of life for patients.

Cervical and mediastinal abscess as a manifestation of histoplasmosis.

Histoplasmosis is the most common endemic respiratory mycosis in the United States. Disseminated histoplasmosis generally is initially seen with systemic or respiratory complaints. Presentation of histoplasmosis as a neck mass is rare. Due to this unusual presentation and the diagnostic implications, we present a case of disseminated histoplasmosis that presented as a neck abscess. Unusual presentations of histoplasmosis may occur even in patients who are not immunocompromised. The diagnosis and management of histoplasmosis is reviewed. Histoplasmosis should be considered in the workup of a cervical abscess even in the immunocompetent host.

Use of electroneuronography in monitoring facial nerve paralysis.

FNP is a disease entity seen in a variety of clinical settings. We recommend early ENoG evaluation of every total facial nerve paralysis to assess the percentage of degeneration. ENoG is an objective, permanent record with prognostic significance especially in 16% of those patients who are predicted to have a poor outcome without further intervention. In consultation with the patient a treatment plan can thus be proposed to optimize the opportunity for recovery.

Use of free fibula flap in patients with prior failed mandibular reconstruction.

PURPOSE: The purpose of this study was to assess the efficacy of the free fibula flap in patients who had failed prior attempts at bony reconstruction. PATIENTS AND METHODS: The records of all patients who had undergone free fibula reconstruction for segmental mandibular resections between 1993 and 1995 were retrospectively reviewed. Patients were divided into group I (14 patients who had failed previous bony reconstruction attempts) and group II (50 patients who had no previous reconstruction), and the two groups were compared. RESULTS: No statistical differences were found between group I and group II for mean age, mean hospital stay, mean intensive care unit stay, mean operating room time, mean intraoperative blood loss, mean colloid usage, or mean blood units transfused. Although group I had a statistically higher proportion of both patients with osteoradionecrosis and those receiving hyperbaric oxygen therapy (HBO), the number with a history of radiation therapy was not different in the two groups. Wound complication rates were not statistically different between groups I and II for all patients, or between those group I patients who did or did not receive HBO therapy. CONCLUSION: There was no increase in wound complications in the patients who had failed prior bony reconstructive attempts who underwent free fibula flaps. The free fibula flap is suggested as the reconstructive method of choice in this patient population.

Increased intracranial pressure as a complication of unilateral radical neck dissection in a patient with congenital absence of the transverse sinus.

We report a patient with increased intracranial pressure occurring after unilateral neck dissection. Subsequent vascular studies reveal a hypoplastic contralateral transverse sinus drainage and occlusion of the ipsilateral jugular bulb. We review the literature on the etiology of this vascular malformation and conclude that vascular anomalies of the venous drainage of the head be considered whenever postoperative signs of increased intracranial pressure occur after unilateral radical neck dissection.

Synovial sarcoma of the head and neck: chromosomal translation (X;18) as a diagnostic aid.

BACKGROUND: Synovial sarcoma, a rare tumor in the head and neck, has been historically diagnosed by its characteristic biphasic histologic pattern. Monophasic variants exist which can be difficult to diagnose. METHODS: Two cases of synovial sarcoma of the head and neck are presented. Both cases, cytogenetic analysis was performed using standard protocols. RESULTS: Both tumors demonstrated a chromosomal translocation, t(X;18)(p11.2;q11.2), which either made or confirmed the diagnosis. CONCLUSIONS: Synovial sarcoma contains a characteristic chromosomal translocation which is a useful diagnostic tool, especially when histologic studies are equivocal.