Oligometastatic renal cell carcinoma in the palatine tonsil: successful resection using trans-oral robotic surgery.

A man in his mid 70s was referred to head and neck outpatients with bulky tissue in the left tonsillar fossa. He had previously been treated for oligometastatic renal clear cell carcinoma (diagnosed over 15 years prior to disease recurrence) by tonsillectomy and adjuvant radiotherapy (years from primary treatment), followed by trans-oral laser surgery to his oropharyngeal recurrence 3 years later. Examination under anaesthetic and biopsy confirmed further recurrence of disease in the left tonsillar fossa, with parapharyngeal extension, which has not been previously reported in the literature. After discussion in the head and neck and urology multi-disciplinary teams meeting, the patient was offered trans-oral robotic-assisted surgery (TORS) for local control and prevention of progression of a fungating oropharyngeal mass. TORS partial pharyngectomy and left buccal artery myomucosal flap reconstruction were successfully carried out, with preservation of some swallow function.

Prognostic value of nodal involvement in patients with oropharyngeal carcinoma according to the HPV status. / Valoración de la capacidad pronóstica de la afectación ganglionar de los pacientes con carcinoma de orofaringe en función del estatus HPV.

BACKGROUND AND OBJECTIVE: Different studies performed in populations with a high incidence of HPV infection have found no prognostic capacity of clinical nodal involvement (cN+) in patients with HPV-positive oropharyngeal carcinomas. The objective of this study was to assess the prognostic ability of nodal involvement in patients with oropharyngeal carcinomas according to HPV status in a cancer population with a low incidence of HPV infection. MATERIAL AND METHODS: Retrospective study of a cohort of 420 patients with oropharyngeal carcinomas treated during the period 1990-2016 for whom information on HPV status was available. RESULTS: 14.8% of the patients included in the study had HPV-positive tumours. In relation to patients without nodal involvement (cN0), nodal involvement at diagnosis (cN+) significantly decreased the specific survival of patients with HPV-negative oropharyngeal carcinomas. Conversely, no differences in survival were found for patients with HPV-positive tumours according to the presence of nodal involvement. A history of toxic consumption did not change the absence of prognostic significance of nodal involvement for patients with HPV-positive tumours. CONCLUSIONS: Regional involvement at the time of diagnosis is not a prognostic variable for patients with HPV-positive oropharyngeal carcinomas.

Solitary cystic metastatic lymph node of occult human papillomavirus-related oropharyngeal cancer mimicking second branchial cleft cyst: A case report.

RATIONALE: Human papillomavirus (HPV)-related oropharyngeal cancer is becoming more common, the primary cancer AQ4 usually occult and appearing only as cystic cervical lymph node (LN) metastasis. Distinguishing between a benign cystic lesion and cystic LN metastasis is challenging given their similar radiologic and histologic appearances. PATIENT CONCERNS: A 54-year-old man presented with a bulging cystic mass measuring 6.4cm on the right side of neck. DIAGNOSES: Postexcision diagnosis was second branchial cleft cyst. After 2 years, the cystic mass recurred, and HPV-related tonsillar squamous cell carcinoma with cystic metastatic LNs was confirmed after wide tonsillectomy and neck dissection. The previous cystic lesion proved to be a cystic metastatic LN from the same malignancy with additional p16 immunostain. INTERVENTIONS: The patient was treated with adjuvant concurrent chemoradiation therapy. OUTCOMES: The patient was followed up in the outpatient department with no evidence of recurrence after 1 year. LESSONS: When an adult has a cystic mass in the upper neck, we must rigorously exclude it as a cystic metastatic LN of occult HPV-related oropharyngeal cancer. Additional p16 staining might be helpful.

Human papillomavirus (HPV) is absent in branchial cleft cysts of the neck distinguishing them from HPV positive cystic metastasis.

BACKGROUND: Distinguishing branchial cleft cysts (BCCs) from cystic metastases of a human papillomavirus (HPV) positive oropharyngeal squamous cell carcinoma (OPSCC) is challenging. Fine needle aspirates (FNAs) from cystic metastasis may be non-representative, while reactive squamous cells from BCC can be atypic. Based on cytology and with the support of HPV DNA positivity many centers treat cystic metastasis oncological and thus patients are spared neck dissection. To do so safely, one must investigate whether HPV DNA and p16INK4a overexpression is found exclusively in cystic metastases and not in BCC. PATIENTS AND METHODS: DNA was extracted from formalin fixed paraffin embedded (FFPE) surgically resected BCCs from 112 patients diagnosed 2007-2015 at Karolinska University Hospital and amplified by PCR. A multiplex bead-based assay used to detect 27 HPV-types and p16INK4a expression was analyzed by immunohistochemistry (IHC). RESULTS: All 112 BCCs were HPV DNA negative, and of 105 BCCs possible to evaluate for p16INK4a, none overexpressed p16INK4a. CONCLUSIONS: HPV DNA and p16INK4a overexpression were absent in BCCs. Lack of HPV DNA and p16 protein overexpression in BCCs is helpful to discriminate benign BCCs from HPV+ OPSCC metastasis. HPV testing definitely has a role in the diagnostics of cystic masses of the neck.

Extensive Regional Metastasis of High-Grade Mucoepidermoid Carcinoma of an Unknown Primary Tumor.

PURPOSE: Mucoepidermoid carcinoma (MEC) is the most common salivary carcinoma. It arises most frequently in the major salivary glands, but can also arise in minor glands or intraosseous sites. MEC of an unknown primary occurs very rarely. The present report documents only the third case reported in medical studies. METHODS: A 66-year-old man with previous carcinoma in situ (CIS) of the left posterior oral tongue that had been excised in 2004 and again in 2010 presented with a hard lymph node, 3 × 2 cm at level II of the right neck in July 2015. Positron emission tomography-computed tomography (PET-CT) revealed multiple, bilateral cervical lymphadenopathy, with no primary site identified. Fine needle aspiration biopsy and cytologic examination from the right neck was positive for malignancy, suggestive of metastatic squamous cell carcinoma. Panendoscopy and biopsy revealed CIS at the tongue bases and tonsils bilaterally (p16-negative). The patient's case was presented to a tumor board, and definitive concurrent cispl.atin-based chemoradiation was recommended for TisN2cM0, stage IVA oropharyngeal CIS, which was completed in November 2015. PET-CT in January 2015 showed complex interval changes, with some areas demonstrating improvement (ie, no uptake in the left neck) and worsening in others (ie, increased metabolic activity in the right neck), suggestive of residual disease. Repeat PET-CT in March 2016 showed increased nodal involvement and increasing standardized uptake value. Bilateral modified radical neck dissection was undertaken, and histologic examination showed high-grade MEC in 51 of 61 lymph nodes with extracapsular spread and soft tissue involvement. RESULTS: The patient died in May 2016 at 2 months after surgery. CONCLUSIONS: Metastatic MEC of an unknown primary is a diagnostic challenge. PET-CT might not be the most reliable diagnostic investigation to identify the primary or metastatic foci, such as was demonstrated in the present case.

Transoral Robotic Surgery-Assisted Endoscopy With Primary Site Detection and Treatment in Occult Mucosal Primaries.

Importance: Management of cervical lymph node metastasis without a known primary tumor is a diagnostic and treatment challenge for head and neck oncologists. Identification of the occult mucosal primary tumor minimizes the morbidity of treatment. Objective: To analyze the role of transoral robotic surgery (TORS) in facilitating the identification of a primary tumor site for patients presenting with squamous cell carcinoma of unknown primary (CUP). In addition, we assessed treatment deintensification by determining the number of patients who did not undergo definitive radiation therapy and chemotherapy. Design, Setting, and Participants: In this retrospective case series from January 2011 to September 2015, 60 consecutive patients with squamous cell CUP who underwent TORS-assisted endoscopy and ipsilateral neck dissection were included from an academic medical center and studied to study the rate success rate of TORS identifying occult mucosal malignancy. Main Outcomes and Measures: Success rate of identifying occult mucosal malignancy; usage of radiation therapy and chemotherapy. Results: Overall, 60 patients (mean [SD] age, 55.5 [8.9] years) were identified; 48 of the 60 patients (80.0%) had a mucosal primary identified during their TORS-assisted endoscopic procedure. The mean (SD) size of the identified mucosal primary lesions was 1.3 (0.1) cm. All mucosal primaries, when found, originated in the oropharynx including the base of tongue in 28 patients (58%), palatine tonsil in 18 patients (38%), and glossotonsillar sulcus in 2 patients (4%). Among patients in this study, 40 (67%) did not receive chemotherapy, and 15 (25%) did not receive radiation therapy. Conclusions and Relevance: Advances in transoral surgical techniques have helped identify occult oropharyngeal malignancies that traditionally have been treated with comprehensive radiation to the entire pharyngeal axis. We demonstrate the efficacy of a TORS-assisted approach to identify and surgically treat the primary tumor in patients presenting with CUP. In addition, patients managed with the TORS-assisted endoscopic approach benefit from surgical and pathological triage, which in turn results in deintensification of treatment by eliminating the need for chemotherapy in the majority of patients, as well as avoiding radiation therapy in select patients.

Current Role of Surgery in the Management of Oropharyngeal Cancer.

The 1990s saw an increased use of chemoradiotherapy protocols, commonly referred to as organ-sparing therapy, for the treatment of oropharyngeal cancer after the Groupe d'Oncologie Radiothérapie Tête et Cou trial. Since that time, human papillomavirus-associated oropharyngeal squamous cell carcinoma has been identified as a unique disease, with improved survival regardless of treatment modality. The improved outcomes of this population has led to re-evaluation of treatment paradigms in the past decade, with a desire to spare young, human papillomavirus-positive patients the treatment-related toxicities of chemoradiotherapy and to use new minimally invasive surgical techniques to improve outcomes. Numerous retrospective and prospective studies have investigated the role of surgery in treatment of oropharyngeal carcinoma and have demonstrated equivalent oncologic outcomes and improved functional outcomes compared with chemoradiotherapy protocols. Ongoing and future clinical trials may help delineate the role of surgery in the future.

Sevoflurane-Based General Anesthesia Induction via Nasopharyngeal Endotracheal Tube Prior to Definitive Airway Control in Pediatric Oral Tumors.

Airway-related tumors in pediatrics are always challenging for anesthesiologists. We present 2 cases of friable, bleeding large tumors in the oral cavity where conventional methods of securing the airway were not possible. Induction of general anesthesia could potentially lead to complete airway collapse and catastrophic obstruction in such cases. Awake fibrotic intubation is limited in pediatric patients. We describe the innovative use of an endotracheal tube inserted blindly as a nasopharyngeal airway guided by end-tidal carbon dioxide trace. This allowed us to bypass the anatomical obstruction and induce anesthesia using sevoflurane in high-flow oxygen. By the described technique, we were able to maintain and assist the spontaneous breathing of the child as well. We also highlight limitations of the use of a conventional nasopharyngeal airway in such situations.

Conjonctival melanoma metastatic to the breast: a case report.

BACKGROUND: Breast metastasis is fairly uncommon and prognosis is dismal. Breast metastasis might be the first symptom or may occur during the course of other malignancies dominantly arising from the contralateral breast. Leukemia, lung cancer and conjunctival melanoma may spread to the breast. CASE PRESENTATION: A 43-year-old female patient was operated on for conjunctival melanoma. After two years the disease progressed quickly and cutaneous nodes appeared on the back and paraumbilical region. Physical and radiological examination showed a breast mass. No palpable lymph's nodes were noted. She underwent an open biopsy. Histopathologic examination and immunohistochemistry confirmed breast metastases from melanoma. During post-operative staging multiple nasopharyngeal and oropharyngeal lesions were also objective. The patient was given palliative dacarbazine (250 mg/m2 per day for 4 days) for 4 cycles. She died 4 months after the diagnosis of breast metastases. CONCLUSION: Histopathological evaluation should be mandatory in patients with medical history of malignancies in order to differentiate new primary tumors, metastases, and benign tumors.

High-risk human papillomavirus and lymph node size in patients with single node metastasis of oral and oropharyngeal cancer.

CONCLUSION: High-risk human papillomavirus (HPV) infection was significantly related to lymph node size in patients with single node metastasis of oral and oropharyngeal cancer. OBJECTIVE: The purpose of this study was to examine the relationship between high-risk HPV infection and lymph node size in patients with single node metastasis of oral and oropharyngeal carcinoma. METHODS: This study included 48 patients with oral and oropharyngeal carcinoma. Pathologic lymph node stages comprised 36 N1 and 12 N2a. RESULTS: High-risk HPV in situ hybridization was positive in 29% of patients (14/48). Of those patients with high-risk HPV, there was a significant difference (p = 0.008) between oral (9.5%) and oropharyngeal (44.4%) cancers. Average lymph node diameter was 20.7 ± 12.6 mm (range 5-54 mm). We found a positive correlation between high-risk HPV status and lymph node size (p = 0.018). Mean lymph node diameter in high-risk HPV-positive cases was 27.3 ± 13.1 mm and 18.0 ± 11.5 mm in high-risk HPV-negative cases. Extracapsular spread (p = 0.030) and cystic nodal metastases (p = 0.019) were also significantly related to lymph node size. High-risk HPV negative status (p = 0.043), advanced tumor stage (p = 0.009), and extracapsular spread (p = 0.038) all had significant adverse effects on 5-year disease-specific survival.

[HPV-associated oropharyngeal carcinoma. Status quo and relationship with cancer of unknown primary]. / HPV-assoziierte oropharyngeale Karzinome. Aktueller Stand und Verhältnis zum Karzinom unbekannter Herkunft.

Carcinomas of the oropharynx with association to high-risk types of human papillomavirus (HPV) have been identified as a new tumour entity with favourable prognosis, distinct from classical nicotine- and alcohol-associated carcinoma. They develop through oncogenic transformation of the basal cells of reticulated cryptal epithelium of the palatinal tonsils and the base of the tongue. Positivity for HPV strongly correlates with an atypical, non-keratinizing histological differentiation and cystic transformation of lymph node metastases. Strong immunohistological positivity for p16 reliably detects transcriptionally active infection with high-risk HPV. Hence, p16 staining has been regarded as an effectual diagnostic tool in the appropriate setting. Frequent nodal metastasation as well as considerable size of (cystic) metastases, and frequent small size as well as submucosal location of primary tumours all contribute to frequent initial manifestation of cervical cancer of unknown primary (CUP). In a situation of CUP diagnostic testing for HPV (in negative cases in addition to EBV) is recommended in lymph node metastases, due to the high predictive value for the localization of occult primary carcinomas. Intense clinicopathological cooperation is mandatory for improved detection of small, occult primary carcinomas. The relevance of this new carcinoma entity will increase, as the incidence continues to increase worldwide.

Relationship between extracapsular spread and FDG PET/CT in oropharyngeal squamous cell carcinoma.

CONCLUSION: Median maximum standardized uptake (SUVmax) cut-off values of FDG PET/CT higher than 3.85 were found to be associated with a greater risk cervical lymph node metastasis with extracapsular spread (ECS) in patients with oropharyngeal squamous cell carcinoma (OPSCC). OBJECTIVES: The purpose of this study was to evaluate the use of FDG PET/CT for the identification of ECS and to establish its histologic correlates in OPSCC. METHODS: The medical records of 78 patients who underwent FDG PET/CT for OPSCC before surgery were reviewed. RESULTS: ECS was present in 42% (42/69) of dissected necks and in 51% (54/106) of dissected cervical levels. The SUVmax values of cervical lymph nodes with and without ECS were found to be significantly different (6.73 ± 3.78 vs 3.02 ± 2.24, p < 0.001). The SUVmax cut-off value for differentiating necks with ECS from those without ECS was 3.85. The presence of ECS (p = 0.036) and median SUVmax (using 3.85 as a cut-off) (p = 0.037) were found to have a significant adverse effect on 5-year disease-specific survival by univariate analysis. The multivariate analysis showed a significant association of 5-year disease-specific survival with ECS (hazard ratio (HR) = 32.3 in cervical metastasis with ECS, p = 0.012; and HR = 19.6 in cervical metastasis without ECS, p = 0.024).

Transoral robotic retropharyngeal lymph node dissection with or without lateral oropharyngectomy.

Retropharyngeal lymph node (RPLN) metastases can occur from advanced head and neck malignancies. Surgical access to RPLNs can be challenging. Considering the more aggressive conventional approach methods, there is an increasing need for minimally invasive techniques. Applying transoral robotic surgery (TORS) to access the RPLN has never been reported in the literature. The purpose of this study was to describe our experience with transoral robotic RPLN dissection for oropharyngeal and hypopharyngeal squamous cell carcinomas. We conducted a retrospective review of TORS cases performed at Severance Hospital, a tertiary care medical center from December 2011 to July 2012. Demographic, clinicopathologic, and treatment characteristics were abstracted from the medical record as well as complications and were analyzed descriptively. A total of 5 TORS procedures with transoral robotic RPLN dissection have been performed at Severance Hospital. Of these, 4 patients were treated for oropharyngeal squamous cell carcinoma and 1 for hypopharyngeal squamous cell carcinoma. The mean operation time for TORS including the robotic RPLN dissection was 84 ± 18.5 minutes. The operation time included time for docking of the robotic arms (4.8 ± 1.3 minutes), console working time for primary tumor removal (50 ± 8.9 minutes), and console working time for RPLN dissection (29.2 ± 9.4 minutes). No patients experienced complications related to the transoral robotic RPLN dissection. Transoral robotic RPLN dissection is a feasible approach for accessing retropharyngeal lymph nodes. This particular operative technique can serve as a minimal invasive surgery in removing pathologic RPLNs.

Highly aggressive human papillomavirus-related oropharyngeal cancer: clinical, radiologic, and pathologic characteristics.

OBJECTIVE: Although the majority of human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinomas have a favorable prognosis, we search for markers of poor prognosis by carefully examining a subset of highly aggressive cases. STUDY DESIGN: Seven patients with HPV-positive oropharyngeal cancer who presented with non-pulmonary distant metastasis or developed distant metastasis posttreatment were identified. Eight control cases were chosen which responded well to treatment. Pathologic and radiologic studies were reviewed and compared. RESULTS: Two cases displayed a small cell carcinoma (SmCC) component upon pathologic review. Biomarker analysis revealed lower expression of NOTCH1 in the aggressive cohort in comparison to controls (P = .04). Cases showed a predominance of clustering of lymph nodes, extracapsular spread, and central tumor necrosis. CONCLUSION: Although most HPV-related oropharyngeal cancers display a positive prognosis, it is evident that there is a subset, which behaves more aggressively. This early investigation identifies pathologic and radiologic features that may help to predict this behavior.

p16 expression in carcinoma of unknown primary: diagnostic indicator and prognostic marker.

BACKGROUND: Carcinoma of unknown primary (CUP) of the neck are heterogeneous tumors in their clinical and biological characteristics, and a preoperative prognostic marker is desirable to optimize staging and therapy and to improve outcome and survival. For CUP syndrome, no optimized diagnostic and treatment strategy or biomarker have yet been determined. METHODS: Forty-seven patients presenting with CUP syndrome were analyzed after thorough standard diagnostic staging procedures. All patients were surgically treated with tonsillectomy, neck dissection of the diseased neck, as well as adjuvant chemoradiation. The tissue of lymph node metastases (and, if found, of the primary tumor) was analyzed regarding expression of p16, epidermal growth factor receptor (EGFR), and presence of human papillomavirus (HPV) DNA. RESULTS: In 39% of all cases (20 of 47), the primary cancer was found during diagnostic workup. If HPV DNA was detected in the neck lymph node metastasis, the primary cancer was significantly more frequently found in the oropharynx (p = .002). Patients with a p16-positive tumor had a significantly higher 5-year overall survival (OS; 33% vs 69%; p = .045, disease-free survival [DSF] 77% vs 89%; p = not significant [NS]). Patients with p16-positive neck metastasis and no detectable primary cancer had a better prognosis. Expression of EGFR in this series did not have a significant effect on prognosis. CONCLUSION: In patients presenting with CUP syndrome, p16 immunohistochemistry can serve to locate the primary cancer in the oropharynx. It is a positive prognostic indicator in patients with those heterogeneous cancers.

p16 expression in cutaneous squamous carcinomas with neck metastases: a potential pitfall in identifying unknown primaries of the head and neck.

BACKGROUND: Human papillomavirus (HPV) positivity (+) has been used to identify oropharyngeal squamous carcinomas (SCCs) presenting as unknown primaries in the neck. p16 overexpression correlates with HPV+ in the oropharynx; however, the use of p16 alone as a surrogate marker of oropharyngeal HPV+ tumors has not been validated. METHODS: We immunohistochemically analyzed p16 expression in surgically resected aggressive cutaneous head and neck SCC primaries and their nodal metastases from 24 patients to determine the potential overlap of p16 expression outside of the oropharynx. RESULTS: Five of 24 primary tumors (20.8%) and 3 lymph node metastases (12.5%) in levels II, III, and V, and the periparotid region diffusely expressed p16. HPV (high-risk types by in situ hybridization) was negative. CONCLUSIONS: p16 expression is relatively common in lymph node-positive cutaneous head and neck SCCs; thus, p16 expression as an independent biomarker and mechanism to determine the oropharyngeal source of an unknown primary is not advised.