[Analysis of cases of cervical cystic lymph node metastasis with an unknown primary misdiagnosed as branchial cleft carcinoma].

Objectives: To analyze the location, discovery time and possible causes of cases of cervical cystic lymph node metastasis with an unknown primary misdiagnosed as branchial cleft carcinoma. Methods: A retrospective analysis was performed on clinical and pathological data of 15 patients misdiagnosed as branchiogenic carcinoma at Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College between January 2000 and December 2020. Results: Among the 15 patients, 6 were nasopharyngeal squamous cell carcinoma, 4 tonsil squamous cell carcinoma, 2 tongue root squamous cell carcinoma, 2 hypopharyngeal squamous cell carcinoma and 1 thyroid papillary carcinoma. The median time from the diagnosis of branchial cleft carcinoma to the discovery of primary lesions was 3.58 months (0-76 months). The causes of misdiagnosis might be the lack of experience in the diagnosis and treatment of branchial cleft carcinoma, and not enough attention to comprehensive examination and close follow-up. Conclusions: Different from oropharyngeal cancer reported internationally, the proportion of misdiagnosed cases with nasopharyngeal carcinoma as the primary site in the current article is higher. As a country with a high incidence of nasopharyngeal carcinoma, the examination of nasopharynx should not be taken lightly. Most hidden cases can be found in the comprehensive examination in a short time, while a few cases need long-term follow-up. Finding the primary sites should not rely too much on imaging examination, and we cannot ignore the importance of clinical physical examination.

Methylation analysis of DCC gene in saliva samples is an efficient method for non-invasive detection of superficial hypopharyngeal cancer.

BACKGROUND: Advances in upper gastrointestinal endoscopic technology have enabled early detection and treatment of hypopharyngeal cancer. However, in-depth pharyngeal observations require sedation and are invasive. It is important to establish a minimally invasive and simple evaluation method to identify high-risk patients. METHODS: Eighty-seven patients with superficial hypopharyngeal cancer and 51 healthy controls were recruited. We assessed the methylation status of DCC, PTGDR1, EDNRB, and ECAD, in tissue and saliva samples and verified the diagnostic accuracy by methylation analyses of their promoter regions using quantitative methylation-specific PCR. RESULTS: Significant differences between cancer and their surrounding non-cancerous tissues were observed in the methylation values of DCC (p = 0.003), EDNRB (p = 0.001), and ECAD (p = 0.043). Using receiver operating characteristic analyses of the methylation values in saliva samples, DCC showed the highest area under the curve values for the detection of superficial hypopharyngeal cancer (0.917, 95% confidence interval = 0.864-0.970), compared with those for EDNRB (0.680) and ECAD (0.639). When the cutoff for the methylation values of DCC was set at ≥0.163, the sensitivity to detect hypopharyngeal cancer was 82.8% and the specificity was 90.2%. CONCLUSIONS: DCC methylation in saliva samples could be a non-invasive and efficient tool for early detection of hypopharyngeal cancer in high-risk patients.

Initial presentation of hepatocellular carcinoma as pharyngeal mass mimicking advanced hypopharyngeal carcinoma.

Hepatocellular carcinoma (HCC) is a highly malignant tumor with frequent intrahepatic and extrahepatic metastases. Extrahepatic metastasis occurs in one-third of patients with HCC and indicates a dismal prognosis. The head and neck region is an extremely uncommon site of metastatic HCC. Extrahepatic metastasis at first presentation, although uncommon, indicates advanced disease with a poor prognosis. Herein, we present the case of a 68-year-old male patient with a neck mass. Clinical examination and initial radiology were suggestive of an advanced primary pharyngeal malignancy. Biopsy showed neoplasm with large polygonal cells with clear/granular cytoplasm. The neoplastic cells showed positivity for Hep Par1, CD10, and CEA. A diagnosis of metastatic HCC was given. Subsequently, serum alpha-fetoprotein level was found to be markedly elevated and further imaging showed multiple mass lesions in the liver. It is necessary to recognize that the pharyngeal region is a potential site of HCC metastasis. Accurate diagnosis and risk stratification can help in avoiding unnecessary costs and delay in treatment.

Clinical Value of Endoscopic Esophageal Screening in Head and Neck Squamous Cell Carcinoma Patients.

OBJECTIVE: To investigate the clinical benefit of routine esophageal screening in newly diagnosed head and neck squamous cell carcinoma (HNSCC) patients. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary medical center. METHODS: This retrospective study selected newly diagnosed HNSCC patients from the Chang Gung Research Database between January 2007 and December 2019. Patients who underwent endoscopic esophageal examinations within 2 months of the initial diagnosis of HNSCC were included in the screening group. The clinical outcomes of the screening and nonscreening groups were analyzed. RESULTS: In total, 13,627 HNSCC patients were included, comprising 1032 females and 12,640 males (mean age 55.0 years), and the esophageal screening group included 7033 (51.4%) patients. The prevalence rate of esophageal tumors was 4.5%. Hypopharyngeal cancer patients were the most likely to have (13.4%) second primary esophageal tumors. The American Joint Committee on Cancer stage of the esophageal tumor was lower in the esophageal screening group than in the nonesophageal screening group. The oral, oropharyngeal, and hypopharyngeal cancer patients in the esophageal screening group had better survival outcomes than their counterparts in the nonesophageal screening group. CONCLUSION: Endoscopic esophageal screening of newly diagnosed HNSCC patients can detect esophageal tumors at an early stage and improve overall survival. Esophageal screening could be a routine survey in HNSCC patients, particularly those with lifestyle risk factors and in countries with a high prevalence of esophageal cancer.

Hypopharyngeal Diffuse Large B-Cell Lymphoma in a 74-Year-Old Man Presenting with Dysphagia: A Case Report.

BACKGROUND Malignant lymphomas can occur at various sites. Hypopharyngeal tumors are at risk for airway obstruction and require rapid diagnosis and treatment. Most hypopharyngeal malignancies are squamous cell carcinomas; other tumors are rare. To date, only a few cases of malignant hypopharyngeal lymphoma have been reported, and its specific characteristics are unknown. Herein, we report a case of right hypopharyngeal diffuse large B-cell lymphoma (DLBCL) in a 74-year-old man with dysphagia. CASE REPORT A 74-year-old man presented to our hospital with dysphagia. He had no relevant medical history. Endoscopic examination revealed a right hypopharyngeal tumor. The surface of the tumor was smooth, with no evidence of hemorrhage. Computed tomography revealed a 40-mm mass located in the hypopharynx. We performed a tracheotomy and biopsy of the tumor. Histopathological examination revealed a diffuse proliferation of large atypical B cells with negative staining for Epstein-Barr virus by in situ hybridization. Immunohistochemical staining was positive for CD20 but negative for CD3 and CD10. The patient was administered chemotherapy. The tumor reduced in size, and the patient recovered completely. During the two-year follow up, no recurrence of cancer was observed. CONCLUSIONS Although most hypopharyngeal tumors are squamous cell carcinomas (SCCs), the possibility of other types of tumors should also be considered. Malignant lymphoma of the hypopharynx is rare, and more cases need to be studied and reported in the future.

Synchronous Second Primary Cancers of Hypopharyngeal Carcinoma in the Image-Enhanced Endoscopy Era.

OBJECTIVES: To explore the prevalence of hypopharyngeal carcinoma (HPC) with synchronous second primary malignancies (Syn-SPMs), their impact on clinical outcomes, and associated risk factors in the image-enhanced endoscopy era. MATERIALS AND METHODS: We retrospectively analyzed 673 patients newly diagnosed with HPC at our cancer center between 2009 and 2019. The patients were divided into three groups: (a) no second primary malignancies (N-SPMs, n = 533); (b) synchronous carcinoma in situ (Syn-Tis, n = 60); (c) synchronous invasive tumors (Syn-invasive, n = 80). Propensity score matching was conducted to balance the N-SPMs and Syn-invasive groups at a 3:1 ratio. RESULTS: Most (96.1%) underwent pretreatment esophagogastroduodenoscopy evaluation with image-enhanced endoscopy. The incidence rates were: Syn-SPMs, 20.8%; Syn-Tis, 8.9%; Syn-invasive, 11.9%. At a median follow-up of 66.7 months, the Syn-Tis and N-SPMs groups had a similar 5-year overall survival (OS; 45.6% vs. 44.5%; hazard ratio [HR], 0.956; 95% confidence interval [CI], 0.660-1.385; p = 0.806). Compared to the N-SPMs group, the Syn-invasive group had poorer 5-year OS (27.0% vs. 52.9%; HR, 2.059; 95% CI, 1.494-2.839; p < 0.001). Alcohol consumption was significantly associated with Syn-SPMs occurrence (odds ratio, 2.055, 2.414, and 3.807 for light, intermediate, and heavy drinkers, respectively). CONCLUSION: The prevalence of Syn-SPMs among patients with HPC was high. Syn-invasive SPMs decreased the survival of patients with HPC. Routine screening with image-enhanced endoscopy should be recommended to detect early-stage SPMs, especially for heavy alcohol drinkers. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:1906-1913, 2023.

CCS-Net: Cascade Detection Network With the Convolution Kernel Switch Block and Statistics Optimal Anchors Block in Hypopharyngeal Cancer MRI.

Magnetic resonance imaging (MRI) is a common diagnostic method for hypopharyngeal cancer (HPC). It is a challenge to automatically detect HPC tumors and swollen lymph nodes (HPC risk areas) from MRI slices because of the small size and irregular shape of HPC risk areas. Herein, we propose a cascade detection network with Convolution Kernel Switch (CKS) Block and Statistics Optimal Anchors (SOA) Block in HPC MRI (CCS-Net). CKS Block can adaptively switch standard convolution to deformable convolution in some appropriate layers to detect irregular objects more efficiently without taking up too much computing resources. SOA Block can automatically generate the optimal anchors based on the size distribution of objects. Compared with other methods, our method achieves splendid detection performance and outperforms other methods on the HPC dataset (more than 1800 T2 MRI slices), achieving the highest AP50 of 78.90%. Experiments show that the proposed network can be the basis of a computer aided diagnosis utility that helps achieve faster and more accurate diagnostic decisions for HPC.

Elevated LSD1 and SNAIL Expression Indicate Poor Prognosis in Hypopharynx Carcinoma.

Head and neck squamous cell carcinomas (HNSCC) are among the most common cancers worldwide and are associated with a poor prognosis for patients. Among HNSCC, those originating in the hypopharynx have the worst prognosis. The histone demethylase LSD1 has been shown to promote cancer initiation, progression, and relapse through various mechanisms and is upregulated in many cancer tissues. LSD1 physically interacts with SNAIL and is required for SNAIL mediated transcriptional repression. Previous studies of the prognostic value of LSD1 in HNSCC have been limited in their analysis of sub-sites, and a correlation between LSD1 and SNAIL has not been shown in HNSCC patient samples. Here we used a large, representative, and clinically well-characterized cohort of 339 HNSCC patients to investigate the co-expression of LSD1 and SNAIL and their prognostic value in all HNSCC using immunohistochemical staining. Elevated LSD1 expression correlated with advanced tumor stage and poor progression-free survival (PFS) in HNSCC originating in the hypopharynx. Overexpression of the transcription factor SNAIL independently correlated with worse overall survival (OS) and PFS in HNSCC in general and prominently in tumors of the hypopharynx. Furthermore, increased LSD1 expression significantly correlated with elevated SNAIL expression in patient samples. Therefore, the presented data implicates LSD1 and SNAIL as independent prognostic biomarkers.

Human Papillomavirus in Patients With Hypopharyngeal Squamous Cell Carcinoma.

OBJECTIVE: Assess the testing rates and prognostic significance of human papilloma virus (HPV) status in hypopharynx malignancies. STUDY DESIGN: Historical cohort study. SETTING: National Cancer Database. METHODS: Review of the National Cancer Database was conducted between 2010 and 2017 for squamous cell carcinomas (SCCs) of the hypopharynx. We investigated how often the tumors were tested for HPV and whether it was associated with survival outcomes. RESULTS: A total of 13,269 patients with hypopharynx malignancies were identified. Most cases were not tested for HPV status (n = 8702, 65.6%). Of those tested, 872 (19.1%) were positive for HPV and 3695 (80.9%) were negative. The proportion of nonoropharyngeal SCCs tested for HPV increased nearly every year during the study, with roughly one-third of cases (31.9%) being tested in 2017. In the facilities classified as high-testing centers of nonoropharyngeal SCCs of the head and neck, 18.7% of hypopharyngeal tumors were HPV positive. HPV-negative status was associated with worse survival on multivariable analysis. In propensity score-matched analysis controlling for all factors significant in multivariable regression, 2-year survival remained higher in the HPV-positive cohort (77.7% vs 63.1%, P < .001). CONCLUSIONS: HPV-positive tumors constitute a sizable minority of hypopharynx tumors and are associated with improved survival. Expansion of HPV testing to hypopharynx malignancies may be warranted.

Acetaldehyde breath test as a cancer risk marker in patients with esophageal and hypopharyngeal squamous cell carcinoma.

Patients with inactive acetaldehyde dehydrogenase 2 (ALDH2) are at high risk for esophageal squamous cell carcinoma (ESCC) and hypopharyngeal squamous cell carcinoma (HPSCC). The acetaldehyde breath test (ABT) may demonstrate ALDH2 gene polymorphisms. We evaluated the usefulness of the ABT in patients with ESCC and HPSCC. The squamous cell carcinoma (SCC) group consisted of 100 patients who were treated with endoscopic submucosal dissection (ESD) for ESCC or HPSCC, and the control group (HC) consisted of 275 healthy subjects. The SCC group comprised the "single subgroup" (n = 63), in which a single lesion was initially treated with ESD, and the "multiple subgroup" (n = 31), in which multiple lesions were initially treated with ESD. First, we compared the groups' risk factors for carcinogenesis and measured the acetaldehyde-to-ethanol (A/E) ratio. Then we tested the groups' differences in the abovementioned carcinogenic risk factors. We found that the proportion of individuals in the SCC group with inactive ALDH2 (A/E ratio ≥ 23.3) was significantly higher than that in the HC group (p = 0.035), as was the A/E ratio (p < 0.001). Also, the proportion of individuals with inactive ALDH2 in the multiple subgroup was significantly higher than that in single subgroup (p = 0.015), as was the A/E ratio (p = 0.008). In conclusion, ABT may be a potential screening tool for detecting people at risk of ESCC and HPSCC. In addition, it could be a useful tool in detecting patients at risk of multiple or double carcinomas among patients with ESCC and HPSCC. Trial registration: Trial Registration number: UMIN000040615 [https://rctportal.niph.go.jp/en/detail?trial_id=UMIN000040615], Data of Registration: 01 46 June 2020, retrospectively registered.

Hypopharyngeal spindle cell lipoma: A case report and review of literature.

RATIONALE: Spindle cell lipoma is a rare, uncommon type of benign lipomatous tumor, a distinct group of lipomas composed of mature adipocytes, uniform spindle cells, and multinucleated giant cells associated with ropey collagen. Immunohistochemically, spindle cell lipoma is characterized by the diffuse expression of CD34. PATIENT CONCERNS: We present a rare case of a 56-year-old man who complained of vomiting out of a smooth and giant mass in the oral cavity provoked by an intra-abdominal pressure increase. Oral examination revealed an elongated mass protruding from the mouth. Computed tomography of the patient showed a mass from left pyriform to oral cavity, with 2.38 × 2.78 × 16.86 cm in size. The flexible fiberscope showed that the pedicle of the elongated mass originated from the posterior wall of the hypopharynx, corresponding to the left pyriform fossa. DIAGNOSIS: Histopathologically, the tumor was mainly composed of hyperplastic adipocytes, admixed with small blood vessels, and scattered inside adipose tissue spindle cells. The immunohistochemical profile revealed positivity of spindle cells for CD34, negativity for S100, and low proliferation with Ki67, which confirmed the diagnosis of spindle cell lipoma and revealed its benign behavior. INTERVENTIONS: The patient underwent hypopharyngeal mass resection using transoral suspension laryngoscopy. OUTCOMES: No recurrence was found after 5 months of follow-up. LESSONS: Spindle cell lipoma is difficult to diagnose early because of slow growth and subtle symptomatology. This entity should be differentiated from several benign or malignant subtypes of lipomas, including liposarcomas. In this case, the spindle cell lipoma is large and originates from the hypopharynx, which is a rare entity and presents with atypical symptoms. This case gave rise to further studies on the clinical and pathologic characteristics of this tumor in the future.

APE1 facilitates PD-L1-mediated progression of laryngeal and hypopharyngeal squamous cell carcinoma.

Laryngeal squamous cell carcinoma (LSCC) and hypopharyngeal squamous cell carcinoma (HSCC) seriously affect the life quality of patients. Nowadays, immunotherapy is widely used in the treatment of cancer. Tumor-infiltrating lymphocytes (TILs), programmed cell death 1 (PD-1) and its ligand programmed cell death ligand 1 (PD-L1) play key roles in the immunotherapy of cancer. Moreover, study has reported that the upregulation of PD-L1 and apurinic/apyrimidinic endonuclase 1 (APE1) are associated with tumorigenesis and poor prognosis of gastric cancer. In the present study, the number of CD3+ T lymphocytes and the expressions of PD-1 and PD-L1 in LSCC and HSCC were detected in clinical samples. In addition, the expressions of PD-L1 and APE1 and their correlation were explored. The results showed that PD-1+ T lymphocytes were wildly infiltrated and PD-L1 was overexpressed in LSCC and HSCC tissues. PD-1 had a positive correlation with cancer progression, and glottic and subglottic LSCC tissues might have a more active immune microenvironment. Moreover, the results showed that upregulated co-expression of PD-L1 and APE1 was a biomarker of LSCC, and APE1 could regulate the expression of PD-L1 through NF-κB signaling pathway. In conclusion, the combine detection of the expressions of PD-1, PD-L1 and APE1 will provide predictive value for the treatment of LSCC and HSCC via immune checkpoint inhibitors, which will help us to identify the patient population more likely to benefit from the immune checkpoint inhibitors based on the tumor immune microenvironment.

Predictive factors for simultaneous distant metastasis in head and neck cancer patients during the diagnostic work-up.

INTRODUCTION: The incidence of distant metastasis (DM) in patients affected by head and neck squamous cell carcinoma (HNSCC) is relatively low, and multiple risk factors were described for the development of distant metastasis. MATERIALS AND METHODS: Retrospective study of patients diagnosed with a HNSCC between July 2016 and July 2020 in a tertiary university hospital. RESULTS: Five-Hundred and sixty-nine patients meet inclusion criteria. In the univariate analysis we found a statistical correlation in those patients affected by a hypopharyngeal tumour (p = < 0.0001), patients older than 60 years old (p = 0.01), advanced T stage (p = < 0.0001), a proven positive lymph node (p = 0.02), poorly differentiated tumour (p = < 0.0001), patients with 3 or more positive lymph nodes (p = 0.0001), with ECS (p = 0.0001) and a second primary tumour (p = 0.03). However, according to those results from our multivariable analysis, the factor related to an increased or higher chance to detect a DM during the diagnosis work-up were the presence of a hypopharyngeal primary tumor with a hazard ratio (HR) of 1.14, p = < 0.0001, advanced T stage (T3-T4) with a HR of 1.21, p = 0.001, poorly differentiated tumor with a HR of 1.04, p = < 0.0001, have proven positive lymph node with a HR of 1.03, p = 0.04, have more than three positive lymph node metastases with a HR of 1.25, p = 0.003, the presence of ECS with a HR of 1.40, p = 0.002, and have a second primary tumor with a HR of 1.05, p = 0.01. CONCLUSION: According to the present study, factors such as hypopharyngeal tumours, advanced T-stage, poor differentiation grade, have more than three positive lymph nodes, ECS and have a second primary tumour should be considered as high-risk indicators for screening. Based on these results, the authors recommend considered an extensive diagnostic work-up in all patients with a high risk of DM development.

Benign and Malignant Granular Cell Tumor of the Hypopharynx: Two Faces of a Rare Entity.

Granular cell tumors (GCT) are rare soft tissue tumors that involve the head and neck in 50% of patients. Two distinct variants of GCT, one benign (bGCT) and the other malignant (mGCT), involving the hypopharynx, a subsite of the larynx, are presented here. The clinical presentations, radiographic features, pathologic diagnosis in these two variants of GCT are discussed. The mGCT was diagnosed only after complete tumor excision. This report highlights the importance of complete excision of the tumor mass, as diagnosis of mGCT can be exceedingly difficult to make on a small biopsy specimen. Therefore, complete excision is recommended for definitive diagnosis and treatment of GCTs.

Transoral laser resection of hypopharyngeal liposarcoma.

Liposarcomas are rare malignant tumours of the connective tissue. Microscopically they resemble lipomas. They are usually found on the limbs or trunk. Fewer than 40 cases of hypopharyngeal liposarcoma have been reported in the literature. Surgical excision with a cervical or endoscopic approach has been the first-line treatment for these cases. We present a patient with the first documented primary excision via carbon dioxide laser using an entirely transoral approach. This case suggests a new standard of management but also highlights the difficulties with investigation and diagnosis in a rare presentation.

Percutaneous Ultrasound-Guided Fine-Needle Aspiration Cytology and Core-Needle Biopsy for Laryngeal and Hypopharyngeal Masses.

OBJECTIVE: To evaluate the feasibility and diagnostic performance of ultrasound (US)-guided fine-needle aspiration cytology and core-needle biopsy (US-FNAC/CNB) for the diagnosis of laryngo-hypopharyngeal masses. MATERIALS AND METHODS: This was a single-center prospective case series. From January 2018 to June 2019, we initially enrolled 40 patients with highly suspicious laryngo-hypopharyngeal masses on laryngoscopic examinations. Of these, 28 patients with the mass involving or abutting the pre-epiglottic, paraglottic, pyriform sinus, and/or subglottic regions were finally included. These patients underwent US examinations with/without subsequent US-FNAC/CNB under local anesthesia for evaluation of the laryngo-hypopharyngeal mass. RESULTS: Of the 28 patients who underwent US examinations, a laryngo-hypopharyngeal mass was identified in 26 patients (92.9%). US-FNAC/CNB was performed successfully in 25 of these patients (96.2%), while the procedure failed to target the mass in 1 patient (3.8%). The performance of US caused minor subclinical hematoma in 2 patients (7.7%), but no major complications occurred. US-FNAC/CNB yielded conclusive results in 24 (96.0%) out of the 25 patients with a successful procedure, including 23 patients with squamous cell carcinoma (SCC) and 1 patient with a benign mass. In one patient with atypical cells in US-FNAC, additional direct laryngoscopic biopsy (DLB) was required to confirm SCC. Among the 26 patients who received US-FNAC/CNB, the time from first visit to pathological diagnosis was 7.8 days. For 24 patients finally diagnosed with SCC, the time from first visit to the initiation of treatment was 25.2 days. The mean costs associated with US-FNAC/CNB was $272 under the Korean National Health Insurance Service System. CONCLUSION: US-FNAC/CNB for a laryngo-hypopharyngeal mass is technically feasible in selected patients, providing good diagnostic performance. This technique could be used as a first-line diagnostic modality by adopting appropriate indications to avoid general anesthesia and DLB-related complications.