Follicular adenoma with a papillary architecture originating from an ectopic thyroid gland: a case report.

BACKGROUND: Follicular adenomas with papillary architecture are rare tumors of thyroid origin and are composed of completely encapsulated follicular cells with a papillary architecture lacking the nuclear characteristics of papillary carcinoma. Herein, we present a case of follicular adenoma with papillary architecture originating from an ectopic thyroid gland, diagnosed from a mass in the submandibular region. CASE PRESENTATION: A 70-year-old woman was referred to our hospital with the chief complaint of a painless left submandibular mass that had been present for one year. The patient underwent left submandibular dissection for therapy and diagnosis. Microscopically, papillary lesions with fibrovascular cores were observed in the interior, and the epithelial cells were cylindrical in shape with eosinophilic cytoplasm, round or oval nuclei, with no pathological features, leading to a diagnosis of papillary carcinoma or follicular carcinoma. The mass was diagnosed as a follicular thyroid adenoma with papillary architecture. This is the first report of a follicular adenoma with a papillary architecture originating from an ectopic thyroid gland. CONCLUSION: This experience suggests that follicular adenoma should be included in the differential diagnosis of ectopic thyroid tumors.

Prognostic role of the combination of platelet count and neutrophil-lymphocyte ratio in patients with hypopharyngeal squamous cell carcinoma.

Hypopharyngeal squamous cell carcinoma (HPSCC) is an aggressive disease with poor prognosis; but has no established biomarkers on the order of human papilloma virus and p16 in oropharyngeal carcinoma. This study investigated pre-treatment serum markers, including the combination of platelet count and neutrophil-lymphocyte ratio (COP-NLR) as a prognosis predictor in patients with HPSCC treated in our hospital. We retrospectively reviewed electronic medical records of 118 consecutive patients treated with curative intent at our hospital between 2007 and 2013. Of these 118 patients, we enrolled 100 patients for whom we had sufficient data to analyze relationships between clinico-laboratory characteristics and survival, including the prognostic significance of pre-treatment serum markers and previous reported clinical factors. Multivariate analysis of clinico-laboratory characteristics associated COP-NLR with cancer-specific survival, as were lymph node metastases. Kaplan-Meier analysis and log-rank tests showed that the COP-NLR could stratify those patients into three independent groups (P = 0.003). COP-NLR might be a useful predictor of survival in patients with HPSCC.

[Solitary Fibrous Tumors of the Nasal and Paranasal Sinuses].

Solitary fibrous tumors (SFT) are uncommon neoplasm that arises in most cases from the pleura. SFT has been rarely observed in the head and neck, but SFT of the paranasal sinuses is especially rare, with 39 previously reported cases to date including those reported in this abstract. Herein we describe three cases of SFT in the paranasal sinuses that were successfully treated endoscopically. Two of the three cases involved patients with no previous history of SFT. The lesion of one of the patients was pathologically diagnosed as SFT preoperatively, but the other was diagnosed as an angiogenic tumor without any biopsies. The tumors were completely resected after arterial embolization by a transnasal endoscopic procedure. The third case involved a 43-year old man, who had undergone medial maxillectomy through a lateral rhinotomy incision to resect SFT four years and seven months before. The tumor relapsed intracranially and, therefore, a craniotomy procedure followed by endoscopic skull base surgery was performed. Radiation therapy was performed postoperatively because the recurrent tumor was pathologically identified as malignant SFT, which had been classified benign at the time of the first resection. All three patients are presently alive with no evidence of disease.

Use of quantitative diffusion-weighted magnetic resonance imaging to predict human papilloma virus status in patients with oropharyngeal squamous cell carcinoma.

Although identification of human papilloma virus (HPV) status in oropharyngeal squamous cell carcinoma (OPSCC) is essential in predicting treatment response, no imaging modality can currently determine whether a tumor is HPV-related. In this retrospective study, 26 patients with OPSCC confined to the lateral wall or the base of tongue underwent neck magnetic resonance imaging, using T1-, T2- and diffusion-weighted imaging (DWI). Apparent diffusion coefficients (ADCs) in a region of interest covering the largest available primary tumor area of OPSCC on a single slice of the ADC map were calculated using two b values (0 and 1,000 s/mm(2)). Mean and minimum ADCs were compared with HPV status, using p16 immunohistochemistry as a surrogate marker for HPV infection. Mean and minimum ADCs for HPV(+) OPSCC were significantly lower than those for HPV(-) OPSCC. A cut-off value of mean ADC for HPV(+) OPSCC of 1.027 × 10(-3) mm(2)/s yielded sensitivity and specificity of 83.33 and 78.57%, respectively. In conclusion, the present study indicates that ADC could be used to predict HPV status in patients with OPSCC.

Utility of Intraoperative Intrinsic Near-Infrared Imaging for Primary Hyperparathyroidism in Multiple Endocrine Neoplasia Type 1.

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder caused by mutations in the tumor suppressor gene MEN1 and is characterized by parathyroid, pancreatic islet, and anterior pituitary tumors. Primary hyperparathyroidism is the most characteristic finding in MEN1, and intraoperative identification and accurate removal of the diseased parathyroid glands are vital since incomplete excision results in recurrence. This case report describes a 59-year-old woman who had pancreatic islet cell tumors and pituitary tumors and underwent selective transsphenoidal adenomectomy. Based on her medical history and examination, the diagnosis of primary hyperparathyroidism in MEN1 was made, and she underwent total parathyroidectomy with autotransplantation with SPY-Elite®ï¸ Fluorescence Imaging (Stryker Corp., Kalamazoo, MI). Intraoperative identification of the parathyroid glands using autofluorescence with real-time intrinsic near-infrared (NIR) imaging made it easier to detect all of the parathyroid hyperplasia. After the surgery, she had hypoparathyroidism and continued with her oral calcium and vitamin D supplementation to maintain normal calcium levels during follow-up. Herein, we would like to advocate that the use of parathyroid gland autofluorescence with real-time intrinsic NIR imaging may be useful for identifying parathyroid tumors in patients with primary hyperparathyroidism in MEN1.

Potential of Nutritional Markers as Predictors After Immunotherapy in Advanced Head and Neck Squamous Cell Carcinoma.

BACKGROUND/AIM: Immune checkpoint inhibitors (ICIs) are the standard treatment for advanced head and neck squamous cell carcinoma (HNSCC). Programmed death-ligand 1 (PD-L1) is clinically assessed before initiating ICIs; however, there are no established biomarkers for predicting the response to immunotherapy. In this study, inflammatory and nutritional parameters were examined to determine the therapeutic outcomes of ICIs for HNSCC. PATIENTS AND METHODS: Sixty-five patients with metastatic or recurrent HNSCC who received programmed death-1 (PD-1) blockade were enrolled. Inflammatory and nutritional indices were correlated with patient outcomes, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and prognostic nutritional index (PNI). RESULTS: Patients aged <70 years were significantly associated with a high NLR, whereas those with a performance status of 2 or 3 were closely related to a high NLR, high SII, and low PNI. Although all patients achieved an objective response rate of 24.6% and a disease control rate of 36.9%, the NLR, PLR, SII, and PNI values were not significantly different between responders and non-responders. Univariate analysis showed that the NLR, PLR, SII, and PNI were significant predictors of progression-free survival (PFS) and overall survival (OS). Multivariate analysis identified PNI as an independent predictor of PFS and OS. CONCLUSION: PNI, as a nutritional marker, was identified as a significant predictor of outcomes following PD-1 blockade administration in patients with advanced HNSCC, compared to inflammatory markers, such as NLR, PLR, and SII.

[Case of pyogenic spondylitis and epidural abscess after chemoradiotherapy for hypopharyngeal cancer].

Osteomyelitis is one of the most severe late complications of radiation therapy. The condition can arise from osteoradionecrosis and can be fatal if it occurrs in vertebrae. A 71-year-old woman, who had undergone chemoradiotherapy for hypopharyngeal cancer 6 months previously, presented with severe neck pain. An MRI examination revealed pyogenic spondylitis and an epidural abscess of the neck. Neurological disturbance in the extremities developed despite the administration of antibiotics for 5 days. Drainage and a laminectomy were performed to control the infection and to relieve spinal cord compression. The patient had no postoperative complications at 15 months after surgery. Previous case reports of osteomyelitis and epidural abscess following radiation therapy for head and neck cancer with surgical treatment tended to have a good clinical course. Severe neck pain and a limitation in the range of motion of the neck are considered to be serious clinical features of osteomyelitis. Since infection in the necrotic mucosa leads to pyogenic spondylitis, a repeated cultivation survey of the mucosa is nessesary for adequate antibiotics therapy. For osteomyelitis and epidural abscess following radiation therapy, immediate specific surgical treatment of the involved region is strongly suggested if antibiotics are not effective or spinal cord compression develops.

Identification of novel oncogenes in oral cancer among elderly nonsmokers.

OBJECTIVES: In recent years, an increase in oral cancer among elderly nonsmokers has been noted. The aim of this study was to identify novel oncogenes in oral cancer in older nonsmokers. MATERIAL AND METHODS: Whole-exome sequencing (WES) data from 324 oral cancer patients were obtained from The Cancer Genome Atlas. Single nucleotide variants (SNVs) and insertions/deletions (INDELs) were extracted from the WES data of older patients. Fisher's exact test was performed to determine the specificity of variants in these genes. Finally, SNVs and INDELs were identified by target enrichment sequencing. RESULTS: Gene ontology analysis of 112 genes with significant SNVs or INDELs in nonsmokers revealed that nonsynonymous SNVs in HECTD4 were significantly more frequent in nonsmokers than in smokers by target enrichment sequencing (p = .02). CONCLUSIONS: Further investigation of the function of HECTD4 variants as oncogenes in older nonsmokers is warranted.

A retrospective analysis of tumor infiltrating lymphocytes in head and neck squamous cell carcinoma patients treated with nivolumab.

Nivolumab, an immune checkpoint inhibitor is the first-line therapy for platinum-resistant recurrent/metastatic head and neck cancer, and highly effective for some patients. However, no factors have been identified that could predict response or prognosis after nivolumab administration. We retrospectively investigated the association between tumor infiltrating lymphocytes (TILs) of initial pathology and prognosis in patients treated with nivolumab. Twenty-eight patients with human papilloma virus and Epstein-Barr virus unrelated head and neck squamous cell carcinoma were enrolled. CD8+cells, FoxP3+cells and FoxP3-CD4+cells in the tumoral and peritumoral stromal area and PD-L1 were measured. In result, FoxP3-CD4+TIL, FoxP3+TIL, and CD8+TIL were not correlated with survival in either intratumoral and stromal area. In univariate analysis, objective response was significant prognostic factor both in progression-free survival and overall survival (p = 0.01, 0.006, respectively). PD-L1 was also significant prognostic factor both in progression-free survival and overall survival (p = 0.01, 0.01, respectively). ECOG Performance status was a significant prognostic factor in overall survival (p = 0.0009). In the combined analysis of stromal CD8+TIL and PD-L1, PD-L1 positive with high stromal CD8+TIL subgroups had a better prognosis than PD-L1 negative with low stromal CD8+TIL subgroups in progression-free survival (p = 0.006). Although these results require a further investigation, PD-L1 and ECOG Performance status and the combination of stromal CD8+TIL and PD-L1 positivity have potential as useful prognostic markers in patients of virus unrelated head and neck squamous cell carcinoma treated with nivolumab.

Predicting the radiosensitivity of HPV-negative oropharyngeal squamous cell carcinoma using miR-130b.

BACKGROUND: Human papillomavirus (HPV)-negative oropharyngeal squamous cell carcinoma shows a higher rate of radiation resistance than HPV-positive oropharyngeal squamous cell carcinoma (OPSCC). Radioresistant HPV-negative OPSCC is associated with unfavourable outcomes, but validated prognostic biomarkers remain lacking. AIMS/OBJECTIVES: This study investigated biomarkers for radioresistant HPV-negative OPSCC. MATERIAL AND METHODS: The Cancer Genome Atlas included miRNA sequence and mRNA sequence data from 528 HNSCC tumours. Of these, we used gene expression data for HPV-negative head and neck squamous cell carcinoma for which data were available on the effects of radiation, and compared miRNA sequence and mRNA sequence data between radioresistant and radiosensitive groups. We subsequently estimated downstream miRNA from the results. Finally, we validated miRNAs related to the outcomes of radiotherapy in our clinical cases. RESULTS: Investigation of miRNA sequence revealed expression of miR-130b as the greatest difference between radiosensitive and radioresistant groups. We subsequently evaluated miR-130b expression in our clinical OPSCC cases. Values of miR-130b >5.372 (low expression), determined from receiver operating characteristic curve analyses, were associated with significantly longer progression-free survival and overall survival (p = .006, p = .04, respectively). CONCLUSIONS AND SIGNIFICANCE: Our results suggest that miR-130b has potential as a biomarker for the radiosensitivity of HPV-negative OPSCC.

Nivolumab-related tracheobronchial chondritis: Extremely rare manifestation of an immune-related adverse effect.

BACKGROUND: Programmed death-1 checkpoint inhibitors, such as nivolumab, have successfully been utilized for recurrent or metastatic squamous cell carcinoma of the head and neck; however, their use may be associated with immune-related adverse effects (irAEs). METHODS: We describe a case of tracheobronchial chondritis as a rare irAE in a 72-year-old man with multiple pulmonary metastases of hypopharyngeal squamous cell carcinoma treated with nivolumab, who was seen with a 2-week history of fever, nonproductive cough, and dyspnea. RESULTS: CT revealed a thickened tracheobronchial wall and narrowed intraluminal space resulting in respiratory symptoms, despite significant clinical response of the metastases. He was clinically diagnosed with tracheobronchial chondritis and treated successfully by steroid therapy. His diagnosis was confirmed by a positive serum anti-collagen type 2 antibody test. CONCLUSIONS: In addition to interstitial lung disease, tracheobronchial chondritis should be considered as a possible irAE in patients with acute respiratory symptoms after nivolumab administration.

Importance of tumor budding grade as independent prognostic factor for early tongue squamous cell carcinoma.

BACKGROUND: Factors involved in neck lymph node metastasis (NLM) and prognosis of early tongue squamous cell carcinoma (SCC) remain unknown. METHODS: We analyzed disease-specific survival (DSS) and NLM including tumor budding grade (TBG) among 64 patients with cT1/2N0 tongue SCC. RESULTS: Univariate analysis of DSS of primary lesions uncovered significant differences in new cT, pT, new pT, pDiameter, venous infiltration, and TBG. Multivariate analysis selected only TBG3 as a predictor of NLM (odds ratio, 9.55; 95% confidence interval [CI], 1.80-50.8; P = .008), and a prognostic factor for DSS (hazard ratio, 4.41; 95% CI, 1.34-14.5; P = .02). CONCLUSION: The sole predictor of NLM and the prognosis of early tongue SCC was TBG, indicating that it might help to select overwhelming risk patients.

Prognostic role of epiregulin/amphiregulin expression in recurrent/metastatic head and neck cancer treated with cetuximab.

BACKGROUND: Cetuximab combined with chemoradiotherapy chemotherapy is the standard therapy for recurrent/metastatic head and neck squamous cell carcinoma (HNSCC). However, survival benefit is limited. The purpose of this study was to investigate the expression of epiregulin (EREG) and amphiregulin (AREG), as predictive prognostic markers for the efficacy of cetuximab combined with chemotherapy in R/M HNSCC. METHODS: We conducted a retrospective analysis of 37 patients diagnosed with R/M HNSCC. Tumor samples were analyzed for EREG and AREG mRNA gene expression, and clinical outcomes evaluated. RESULTS: Values of EREG and AREG were associated with significantly longer overall survival (OS) (P = .03 and P = .01, respectively), as well as progression-free survival (PFS) (P = .04 and P = .04, respectively). Multivariate analysis revealed that AREG expression was significantly associated with OS and PFS. CONCLUSIONS: Patients with recurrent/metastatic HNSCC with higher EREG and AREG gene expression appear to benefit more from cetuximab combined with chemoradiotherapy chemotherapy than those with lower expression.

Primary Small Cell Carcinoma of the Hypopharynx: A Report of Two Cases and Review of Nine Additional Cases.

OBJECTIVE: Two patients with primary small cell carcinoma (SmCC) of the hypopharynx, an extremely rare site for the occurrence of SmCC, are reported and nine additional well-documented cases are reviewed. METHODS: Case report and review of the literature concerning primary SmCC of the hypopharynx. RESULTS: On the final analysis, we reviewed eleven cases of primary SmCC of the hypopharynx. The tumors contained mixed elements of SmCC and squamous cell carcinoma (SCC) in six (55%) of eleven patients. Out of eleven patients, two patients had distant metastasis at the initial presentation. Even though nine patients presented with locoregional disease, development of distant metastasis after treatment was seen in five patients (56%), whereas there was no report of treatment failure on the primary site. To achieve more than two-year survival, patients should have received more than 4 cycles of chemotherapy. CONCLUSION: We report two cases of primary SmCC of the hypopharynx with a review of the literature. In more than half of the cases, combined carcinomas with SCC are seen. Because this tumor has a strong propensity for distant metastasis even in patients with clinically localized tumor, new powerful systemic agents should be explored.

PD-L1 Expression Confers Better Prognosis in Locally Advanced Oral Squamous Cell Carcinoma.

BACKGROUND/AIM: Clinical trials with therapies targeting immune checkpoint molecules have shown promising results in several tumor types. However, the predictive and prognostic values of these immunological factors for locally advanced oral squamous cell carcinomas (LAOSCC) remain unclear. Our purpose was to evaluate the expression and prognostic value of programmed cell death-ligand1 (PD-L1) and PD-L2 and to correlate their expression with the degree of infiltration by CD8+ cells in LAOSCC. PATIENTS AND METHODS: A total of 84 patients with LAOSCC were included. PD-L1, PD-L2 and CD8 expression was detected in the tumor tissue using immunohistochemistry and was tested for correlation with clinical outcome. RESULTS: PD-L1 and PD-L2 were expressed in 52.4% and 23.8% of LAOSCC cases, respectively. PD-L1 positivity was significantly associated with superior disease-free (p=0.024) and overall (p=0.008) survival of the patients and retained significance in multivariate analysis. PD-L1 positivity was correlated with CD8 density. CONCLUSION: PD-L1 expression was associated with CD8+ tumor-infiltrating lymphocytes and better outcome in patients with LAOSCC.

Laryngeal osteosarcoma: case report and literature review.

BACKGROUND: Sarcomas of the larynx are uncommon tumors, and osteosarcoma is the rarest. Only 24 cases of osteosarcoma of the larynx have been reported. The only case reported in Asia was from Thailand in 1981. METHODS: A 55-year-old male patient was referred to our hospital because of an 8-month history of odynophagia and a gradually enlarging left neck mass. A neck CT scan was performed. A literature review was also performed for this report. RESULTS: The CT scan revealed extensive calcification with enlargement of the thyroid cartilage. The patient was diagnosed with osteosarcoma and was successfully treated by surgery alone. CONCLUSION: Adequate surgical resection is required for successful treatment of laryngeal sarcomas. Adjuvant therapy is not contraindicated, but chemotherapy may improve the prognosis in patients with high-grade tumors or metastatic disease.

Infectious endocarditis caused by Rhodococcus equi.

Rhodococcus equi is an unusual cause of infection. Furthermore, this infection also tends to be typically described in immunocompromised patients. This report describes a 25-year-old previously healthy man with infectious endocarditis that was found to have been caused by R equi complicated by a subarachnoid hemorrhage, subdural hematoma, and a superior mesenteric artery aneurysm. The patient was successfully treated with antibiotic therapy, followed by a resection of the superior mesenteric artery aneurysm and a repair of the mitral valve.