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.

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.

[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.

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.

Delayed lymph node metastases after elective neck dissection in patients with oral and oropharyngeal cancer and pN0 neck.

PURPOSE: Patients with surgically treated head and neck cancer and clinical N0 neck with high risk of occult lymph node metastasis undergo elective neck dissection (ND). Late lymph node metastasis may appear in those patients with pN0 neck. The aim of the present study was to analyze the incidence and clinical relevance of late lymph node metastasis in patients with head and neck cancer. MATERIALS AND METHODS: The clinical data of 61 patients with head and neck cancer who had undergone elective ND with pN0 neck were retrospectively analyzed. Only patients without local failure, second primary, or radiochemotherapy were included in the study. RESULTS: Late lymph node metastasis could be observed in 4 (6.5%) cases at the margin or outside the initially dissected lymph node levels. In those patients, the primary tumor was localized in the oral cavity (n = 3) or oropharynx (n = 1) and was classified in all cases as T1 or T2. Lymph node metastasis could be found in levels I (n = 2), II (n = 1), and IV (n = 1), respectively. CONCLUSION: Even in the case of pN0 neck after an elective ND, the appearance of late lymph node metastases must be expected. The low proportion of patients with late lymph node metastases after a selective ND in clinical and histologic N0 does not justify an extended form of neck surgery.

Metastatic squamous cell carcinoma of the oropharynx in a child with a mutation in the Connexin 26 gene.

Pediatric oral squamous cell carcinoma is an extremely rare occurence. In our report, we describe a 6-year-old White female with sensorineural hearing loss found to have a Connexin 26 gene mutation who developed a well-differentiated squamous cell carcinoma of the hard palate with metastatic disease to submandibular lymph nodes and the lungs. This association emphasizes the need to consider Connexin 26 gene mutations in children who develop oral squamous cell carcinoma and to monitor for oral squamous cell carcinoma in children with Connexin 26 gene mutations.

[Metastatic melanoma to the oropharynx]. / Métastase oropharyngée d'un mélanome cutané.

INTRODUCTION: Metastatic mucosal melanoma to the oropharyngeal area is extremely rare. Only 0.6% to 3% of patients with cutaneous malignant melanoma will have metastases to the mucosa of the upper aerodigestive tract. CASE REPORT: A 60-year-old woman presented with a past history of dorsal melanoma and metastatic inguinal node was referred to our department for odynophagia. Physical examination revealed a mass of the right tonsil. A cervico-facial computed tomography, a magnetic resonance imagery and PET-scanner were performed and showed the tumefaction located at the right tonsil. Biopsy was performed under general anesthesia. The histological examination revealed a metastatic melanoma. After discussion a palliative treatment with chemotherapy was begun. The patient died of disseminated disease 2 months after the beginning of the chemotherapy, only 4 months after the initial diagnosis. DISCUSSION/CONCLUSION: The case presentation indicates that careful examination of the head and neck should be part of the routine follow-up examination in all melanoma patients. The discovery of mucosal metastasis in head and neck indicated widespread dissemination and a poor prognosis.

Lysyl oxidase expression is an independent marker of prognosis and a predictor of lymph node metastasis in oral and oropharyngeal squamous cell carcinoma (OSCC).

Proteins of the lysyl oxidase (LOX) family are important modulators of the extracellular matrix. However, they have an important role in the tumour development as well as in tumour progression. To evaluate the diagnostic and prognostic value of the LOX protein in oral and oropharyngeal squamous cell carcinoma (OSCC) we performed QRT-PCR and immunohistochemical analysis on two tissue microarrays (622 tissue samples in total). Significantly higher LOX expression was detected in high grade dysplastic oral mucosa as well as in OSCC when compared to normal oral mucosa (P < 0.001). High LOX expression was correlated with clinical TNM stage (P = 0.020), lymph node metastases for the entire cohort (P < 0.001), as well as in the subgroup of small primary tumours (T1/T2, P < 0.001). Moreover, high LOX expression was correlated with poor overall survival (P = 0.004) and disease specific survival (P = 0.037). In a multivariate analysis, high LOX expression was an independent prognostic factor, predicting unfavourable overall survival. In summary, LOX expression is an independent prognostic biomarker and a predictor of lymph node metastasis in OSCC. Moreover, LOX overexpression may be an early phenomenon in the pathogenesis of OSCC and thus an attractive novel target for chemopreventive and therapeutic strategies.

Sarcomatoid renal cell carcinoma presenting in the oropharynx.

Metastasis stemming from a distant malignancy is far less common than an oropharyngeal primary and represents only 1% of all oral neoplasms. The difficulty in diagnosing a metastasis in the oropharynx may be compounded if the lesion is poorly differentiated and bears little resemblance to the primary tumor. We present the case of synchronous metastatic renal cell carcinoma of the mandibular gingiva in a woman with sarcomatoid clear cell renal cell carcinoma. The metastatic lesion was poorly differentiated and lacked expression of the renal cell carcinoma (RCC) antigen. In contrast, PAX-8 staining was strongly positive. This case serves to highlight the diagnostic difficulty posed by poorly differentiated lesions in the oropharynx and reinforces the sensitivity of the cell lineage-specific transcription factor PAX-8 in poorly differentiated RCC.

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.

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.

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.

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.

[A case of renal clear cell carcinoma metastasis to the oropharynx]. / Przerzut raka jasnokomórkowego nerki do czesci ustnej gardla.

A rare case of 61-yrs-old male was reported, in whom distant metastasis from renal clear-cell carcinoma to the oropharynx had been diagnosed. It was presented as pedunculated tumor at the level of palatine tonsil, 11 months after nephrectomy, and treated by surgical excision. Other metastatic sites--pulmonary and skeletal had also developed and a patient died 16 months after the time of primary diagnosis.

[Toluidine blue in monitoring of recurrences and second primary tumors in patients treated for oral cavity and pharynx cancer]. / Zastosowanie blqkitu toluidyny do monitorowania wznów i drugich pierwotnych ognisk nowotworowych w jamie ustnej i gardle u chorych leczonych z powodu raka jezyka i migdalka podniebiennego.

UNLABELLED: Assesment of recurrences in the oral cavity and pharynx is a serious diagnostic challenge particularly in patient after surgery and irradiation. Observed visible local lesions like oedema, formation of postoperative scars and pain made the diagnostic procedure difficult. Sometimes it's impossible to distinguish recurrences and inflammatory reaction. The aim of this research was to evaluate the usefulness of toluidyne blue in monitoring of recurrences and second primary tumors in the patients with oral and pharyngeal cancer. It was perform by comparison of the three methods: physical examination, endoscopic ultrasound probe and toluidine blue staining in detection of early malignancy. A group of 80 patients with oral and pharyngeal squamous cell cancer was treated in the years between 2000-2003 in the Department of Otolaryngology in Poznan. In 7 positive tested cases toluidine blue staining was confirmed in histological examination. 3 cases were false-positive staining (patients after reconstructive with infrahyoid and pectoral major flap). CONCLUSIONS: (1) toluidine blue staining is cheap effective diagnostic procedure in monitoring recurrences in patients after surgery and irradiation; (2) procedure is limited in patients after reconstructive flap surgery; (3) ultrasound endoscopy is of value in assesment of advanced tumors of oral cavity and pharynx, but it's limited in flat and superficial mucosal infiltrations.

[Influence of clinical features of oral cancer on incidence of regional metastasis].

The regional metastasis has a high frequency in oral cancer and significantly influences the prognosis of this disease. It is known that some clinical features determine the incidence of regional metastasis. Accordingly, the study of these features represents an important issue in the improving the results of the treatment. The aim of our study was the evaluation of different clinical features in relation to the regional metastasis. The study group was composed by 478 patients. It was revealed that the patient's sex, age, period of tumor existence, tumor ulceration and the pre-cancer diseases doesn't influence the incidence of regional involvement. It was found that the primary tumor sizes, the pattern of growth, invasion in surrounding tissues, number of involved anatomical regions and the pain symptom are significant clinical features of regional metastasis. The statistical evaluation of received results, along with the consideration of pathology criteria will allow (in the framework of future study) to work out of individual prognosing method for development of regional metastasis in oral cancer.

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.

Branchiogenic carcinoma--conceptual or true clinico-pathological entity?

The existence of branchiogenic carcinoma remains controversial. According to some authors, this malignancy is more conceptual than a true clinicopathologic entity. The originally proposed diagnostic criteria of branchiogenic carcinoma have been subsequently challenged. Many reports regarding primary branchiogenic carcinoma have failed to provide sufficient evidence to distinguish this entity from nodal metastases arising from unrecognized primary tumours. There is growing evidence that the majority of branchiogenic carcinomas are in fact cystic metastases from oropharyngeal carcinoma, most commonly originating in the tonsils, and not true carcinomas arising in a branchial cleft cyst. The missing link between branchial cyst and branchiogenic squamous cell carcinoma could be fulfilled by the occurrence of in situ branchial cyst carcinomas, yet such cases are extremely rare. Isolated cystic neck lesions, necessitate a thorough search for a primary tumour, similarly to other occult primaries presenting with cervical metastases. The treatment of cervical cyst with dysplasia or carcinoma in situ includes complete surgical excision. The true branchiogenic carcinomas should be approached with postoperative irradiation to the half neck. A cervical metastatic cystic squamous carcinoma of unknown origin should be treated as for other cases of occult primaries, i.e. with surgery and radiotherapy. The data on the prognosis of branchiogenic carcinoma are scarce, though long-term survival has been reported. Further histopathologic and clinical studies are warranted in order to better understand the biology and natural history of cervical cystic lesions. The existence of true branchiogenic carcinoma remains to be verified with new clinical and molecular criteria.