Complete response of glottic cancer to intra-arterial infusion chemotherapy combined with radiotherapy: A report of 4 cases.

Surgical resection is recommended for advanced-stage, resectable glottic cancer. However, total laryngectomy results in the loss of vocal function and reduces patients' quality of life. At our institution, patients with cT3N0M0 stage III resectable glottic cancer who wish to preserve their larynx are treated with super-selective cisplatin infusion with concomitant radiotherapy (RADPLAT) to improve local control over systemic chemotherapy. Herein, we present 4 patients with glottic cancer who underwent biweekly intra-arterial infusion chemotherapy combined with radiation therapy 3 times. For intra-arterial infusion chemotherapy, 100 mg cis-diaminodichloroplatinum was infused into the superior thyroid artery, including the superior laryngeal artery branch. Thereafter, intensity-modulated radiation therapy was administered at doses of 70 Gy in 35 fractions for 3 patients and 66 Gy in 33 fractions for 1 patient. These patients showed complete response after chemoradiotherapy with no recurrence or metastases during the follow-up period to date (mean follow-up period: 56 months, range: 39-76 months).

Neoadjuvant Superselective Intra-Arterial Cisplatin Chemoradiotherapy Combined With Surgery in Patients With T4 Squamous Cell Carcinoma of the Maxillary Sinus.

PURPOSE: Squamous cell carcinoma of the maxillary sinus (SCC-MS) is often diagnosed at a locally advanced stage, which is associated with poor prognosis. The purpose of the present study was to investigate clinical outcomes in patients with locally advanced T4 SCC-MS including originally inoperable T4b disease treated with neoadjuvant superselective intra-arterial chemoradiotherapy combined with surgery. METHODS: This study is a retrospective case series. We examined clinical outcomes in the patients with T4 SCC-MS between 2005 and 2017. The outcome variables were 5-year overall survival rate, 5-year disease-free survival rate, and 5-year local control rate. Covariates included age, sex, T classification, N classification, stage classification, type of surgery, number of administrations and total dose of cisplatin, and radiation dose. Descriptive statistics were computed for each study variable. RESULTS: Ten patients with T4 SCC-MS (6 T4a and 4 T4b) were treated. All patients were men, and the median age was 60.5 years (range, 45 to 77). Total maxillectomy was performed in 4 patients, and extended total maxillectomy in 6. The total number of intra-arterial chemotherapy administrations ranged between 2 and 4 for patients with T4a disease and between 3 and 4 for those with T4b disease. The median intra-arterial cisplatin dose was 360 mg (range, 250 to 400) for patients with T4a disease and 360 mg (range, 320 to 480) for those with T4b disease. The 5-year overall survival, 5-year disease-free survival, and 5-year local control rates of all patients were 100%, 70%, and 80%, respectively. The 5-year disease-free survival rate and 5-year local control rate were 83% and 83%, respectively, in the 6 T4a patients and 50% and 75%, respectively, in the 4 T4b patients. CONCLUSION: Neoadjuvant intra-arterial chemoradiotherapy in patients with T4 SCC-MS can achieve good clinical outcomes, and it may enable surgical resection of T4b lesions.

Molecular characterization and secreted production of basidiomycetous cell-bound ß-glycosidases applicable to production of galactooligosaccharides.

Cell-bound ß-glycosidases of basidiomycetous yeasts show promise as biocatalysts in galactooligosaccharide (GOS) production. Using degenerated primers designed from Hamamotoa singularis (Hs) bglA gene, we newly identified three genes that encode cell-bound ß-glycosidase from Sirobasidium magnum (Sm), Rhodotorula minuta (Rm), and Sterigmatomyces elviae (Se). These three genes, also named bglA, encoded family 1 glycosyl hydrolases with molecular masses of 67‒77 kDa. The BglA enzymes were approximately 44% identical to the Hs-BglA enzyme and possessed a unique domain at the N-terminus comprising 110 or 210 amino acids. The Sm-, Rm-, and Se-BglA enzymes as well as the Hs-BglA enzyme were successfully produced by recombinant Aspergillus oryzae, and all enzymes were entirely secreted to the supernatants. Furthermore, addition of some nonionic detergents (e.g. 0.4% [v/v] Triton-X) increased the production, especially of the Hs- or Se-BglA enzyme. Out of the BglA enzymes, the Se-BglA enzyme showed remarkable thermostability (∼70°C). Additionally, the Sm- and Se-BglA enzymes had better GOS yields, so there was less residual lactose than in others. Accordingly, the basidiomycetous BglA enzymes produced by recombinant A. oryzae would be applicable to GOS production, and the Se-BglA enzyme appeared to be the most promising enzyme for industrial uses.

Value of intraoperative pathological diagnosis in decision-making regarding resection of well-differentiated retropharyngeal liposarcoma: A case report.

INTRODUCTION AND IMPORTANCE: Preoperative diagnosis of well-differentiated liposarcoma (WDLS) in the retropharyngeal space is challenging because of the difficulty in obtaining a biopsy tissue specimen that will yield the microscopic findings necessary for a definitive pathological diagnosis. This report describes a case of retropharyngeal WDLS that was successfully diagnosed intraoperatively, which allowed radical resection. CASE PRESENTATION: The patient was a 60-year-old man suspected of having a lipomatous tumor in the retropharyngeal space. On imaging, the tumor contained linear septum-like structures that were prominent behind the larynx. Pathological examination was performed using fine-needle aspiration cytology and core needle biopsy specimens. However, no malignant features were found. Given that partial biopsy of the retropharyngeal tumor by puncture was anatomically limited, we decided to collect appropriate tissue specimens for intraoperative pathological examination. During the operation, we biopsied the tumor, including the hard portion behind the larynx, anticipating inclusion of the septum-like structures seen on imaging. A pathological diagnosis of WDLS was successfully made and the tumor was completely excised. CLINICAL DISCUSSION: The fibrous septum with induration is important for intraoperative diagnosis of WDLS. The fibrous septum within the tumor was palpable as a rubbery hard portion. CONCLUSION: WDLS in the retropharyngeal space could be successfully resected surgically by making a rapid intraoperative pathological diagnosis using appropriately selected tissue sampled from a hard portion of the tumor.

The role of frozen section biopsy for submandibular gland tumors.

BACKGROUND: Although there have been several reports of the diagnostic accuracy of frozen section biopsy (FSB) for parotid gland tumors, few studies have focused on its diagnostic accuracy for submandibular gland tumors. AIM/OBJECTIVES: This study aimed to investigate the necessity of FSB with regard to its diagnostic accuracy for submandibular gland tumors (SGTs). MATERIALS AND METHODS: About 42 SGT patients underwent both fine-needle aspiration cytology (FNAC) and FSB between 2005 and 2020. The results of FNAC and FSB were analyzed and compared with the final histological diagnoses. RESULTS: The respective sensitivity and specificity in detecting malignant tumors in 38 cases, excluding the four indeterminate FNAC cases, they were 0 and 97% for FNAC, and 100 and 97% for FSB. Considering the four indeterminate FNAC cases to be malignant, the respective sensitivity and specificity in detecting malignant tumors in the 42 cases were 50 and 92% for FNAC, and 100 and 95% for FSB. CONCLUSIONS AND SIGNIFICANCE: FSB may be useful for malignancy detection as a final histological diagnosis in cases that are diagnosed as benign or indeterminate by FNAC in SGTs.

Endoscopic removal of a fish bone foreign body in the hypopharynx with the modified Killian's method.

Observing the entire circumference of the hypopharynx is usually difficult because most of the area is anatomically closed in the resting state. The modified Killian's method, consisting of a combination of the modified Killian position, head torsion, and the Valsalva maneuver, is a recently proposed procedure to improve the endoscopic view of the hypopharynx. A fish bone, which was invisible under regular endoscopy but was identified by CT, was successfully observed and removed under the modified Killian's method in a 71-year-old female. This method can be applied to diagnose and treat benign hypopharyngeal disease such as fish bone foreign body in addition to the detection of cancer.

Metasurface sensing difference in waveforms at the same frequency with reduced power level.

We numerically demonstrate a new type of waveform-selective metasurface that senses the difference in incoming waveforms or pulse widths at the same frequency. Importantly, the proposed structure contains precise rectifier circuits that, compared to ordinary schottky diodes used within old types of structures, rectify induced electric charges at a markedly reduced input power level depending on several design parameters but mostly on the gain of operational amplifiers. As a result, a waveform-selective absorbing mechanism related to this turn-on voltage appears even with a limited signal strength that is comparable to realistic wireless signal levels. In addition, the proposed structure exhibits a noticeably wide dynamic range from [Formula: see text] 30 to 6 dBm, compared to a conventional structure that operated only around 0 dBm. Thus, our study opens up the door to apply the concept of waveform selectivity to a more practical field of wireless communications to control different small signals at the same frequency.

Indications for partial superficial parotidectomy for benign parotid gland tumors using the retrograde approach.

A recent systematic review and meta-analysis suggest that retrograde parotidectomy is a safe procedure with no significant difference in facial nerve paralysis rates when compared to anterograde parotidectomy. The aim of the current study was to establish indications for partial superficial parotidectomy using the retrograde approach. To this end, the two surgical techniques were compared in terms of postoperative facial nerve paralysis, tumor size, location of the tumor, and surgical time. For tumor diameters of 30 mm or less, mean surgical time in the retrograde parotidectomy group was significantly shorter than in the anterograde parotidectomy group (p < 0.05). Our study indicates that retrograde parotidectomy may be more effective than anterograde parotidectomy for partial superficial parotidectomy for benign parotid tumors of 30 mm or less.

Salvage Reconstructive Surgery During Nivolumab Therapy for a Patient With Hypopharyngeal Cancer.

OBJECTIVES: Nivolumab, a fully IgG4-programmed death-1 inhibitor antibody, led to improved overall survival compared with single-agent therapy in patients with platinum-refractory recurrent head and neck cancers. In general, nivolumab is used in inoperable patients. To the best of our knowledge, there have been no reports of salvage surgery during nivolumab therapy for patients with head and neck cancer. We report the case of a woman treated with salvage reconstructive surgery during nivolumab therapy. METHOD: Case report and literature review. RESULTS: The patient underwent nivolumab therapy for recurrent primary and neck disease after induction chemotherapy, followed by concurrent chemoradiation therapy. The neck disease shrunk, whereas the primary disease temporarily shrunk but later progressed again. Recurrent primary disease led to a narrowing of her airway, and she required airway management. We performed total pharyngolaryngectomy with free jejunal reconstruction, and her quality of life improved. The surgery was performed without complications and the postoperative course was uneventful. She was discharged postoperative day 18 with oral intake function and a safer airway. CONCLUSION: As far as we know, this is the first report of salvage surgery during nivolumab therapy for patients with head and neck cancer. The salvage reconstructive surgery in this case proceeded uneventfully.

Implementing a flexible endoscopic evaluation of swallowing at elderly care facilities to reveal characteristics of elderly subjects who screened positive for a swallowing disorder.

OBJECTIVES: The risk of aspiration pneumonia has been reported to increase with age, especially in elderly residents of nursing homes. However, the characteristics of those with swallowing impairments at elderly care facilities have not yet been evaluated using reliable instrumental examinations. The aims of the current study were to investigate the frequency of swallowing impairment and determine the characteristics of the elderly with swallowing disorders residing at care facilities. METHODS: To reveal the characteristics of the elderly with swallowing disorders, questionnaires for dysphagia screening and flexible endoscopic evaluation of swallowing (FEES) were used. Regarding the dysphagia screening, two types of questionnaires were sent to 451 elderly persons aged 65 years and older who were living in facilities for the elderly in Japan. FEES was performed to assess swallowing impairment at each facility for those who were found to be positive for dysphagia by the questionnaires. The frequency of swallowing impairment and the characteristics of elderly subjects with swallowing disorders were investigated. RESULTS: Among 413 subjects who completed both questionnaires, 229 were screened positive for dysphagia, 160 of whom underwent FEES. Swallowing impairment was observed in 93 subjects. The subjects with swallowing impairment had a significantly high prevalence of fever, sputum, and/or history of aspiration pneumonia. Their oral intake ability and activities of daily living were significantly low. CONCLUSION: We demonstrated the frequency of swallowing disorders and the characteristics of elderly subjects with swallowing disorders living in care facilities using FEES. Our results suggest the importance of screening all elderly care facility residents for dysphagia.

The role of elective neck dissection for cT4aN0 glottic squamous cell carcinoma.

OBJECTIVE: The indication for elective neck dissection for patients with clinically T4aN0 (cT4aN0) glottic cancer is not established. The objective of this study was to evaluate the role of elective neck dissection for patients with cT4aN0 glottic cancer. METHODS: We assessed patients with cT4aN0 laryngeal squamous cell carcinoma who underwent total laryngectomy between 1998 and 2014 and conducted a retrospective analysis. We considered occult neck metastasis positive when confirmed by histological analysis. When patients with late neck metastases did not undergo therapeutic neck dissection, the presence of occult neck metastasis was judged on the basis of computed tomography. The validity of elective neck dissection for patients with cT4aN0 glottic cancer was assessed from comparisons the rates of occult neck metastases of supraglottic and subglottic cancers, which are generally recommended for elective neck dissection. The distribution of occult neck metastases in glottic cancer is described according to nodal levels. RESULTS: The rate of occult neck metastasis of cT4aN0 laryngeal cancer was 36% (14/39). There were no significant differences among the rates of glottic 7/21 (33%), supraglottic 3/8 (38%) and subglottic 4/10 (40%) cancers. Patients with glottic cancer did not have bilateral Level IIB and ipsilateral Level IV metastasis. One patient had contralateral Level IV metastasis. The metastases rates of ipsilateral Levels IIA, III, and VI were >10%. CONCLUSIONS: We think that elective neck dissection is valid for cT4aN0 glottic cancer. Ipsilateral Levels IIA, III and VI should be dissected. The omission of neck dissection for bilateral Levels IIB and IV can be considered when there is a need to avoid complications.

A case grafted with polyglycolic acid sheets and fibrin glue for protection after temporary resection of a metastatic cervical skin tumor.

The aim of this case report was to evaluate the usefulness of a grafting with polyglycolic acid sheet and a fibrin glue spray (PGA sheet grafting) after resection of a cervical skin tumor. A 61-year-old woman presented with left cervical skin tumor resistance to chemo-radiotherapy. She had been undergoing multimodal therapy for ovarian serous papillary adenocarcinoma for the previous six years. Although she had a poor general condition and a cervical skin tumor of 9cm in diameter, which was painful and easy bleeding, had offensive smell, she hoped to return to her job. Under local anesthesia, resection was performed, and PGA sheet grafting were used to shield the skin defect. After resection, she was relieved from pain, and could stay home without daily wound treatment. One and half months after resection, the wound was almost epithelialized. The PGA sheets consist of soft, elastic, nonwoven fabric made of PGA. In recent years, PGA sheet grafting has been widely used in the reconstruction and was chosen to shield the skin defect for this case. PGA sheet grafting after resection of cervical skin tumor can be an acceptable method for palliative care to relieve pain, bleeding, offensive smell, and ugly appearance.

Spontaneous regression of chemotherapy-resistant metastases from a scalp angiosarcoma.

Angiosarcomas are rare malignant tumors derived from endothelial cells and occur most commonly in the scalp and the face. The prognosis is poor. Therefore, spontaneous regression of angiosarcoma is a rare phenomenon.We describe a case of a 73-year-old man with multiple metastatic angiosarcoma.In the present case, weekly paclitaxel therapy had an effect, but could not be continued because of interstitial pneumonia (IP). Weekly docetaxel therapy did not have an effect, but further chemotherapy was not carried out because aggravation of the IP was a concern.The primary lesion and other metastatic lesions were inconspicuous on the positron emission tomography/computed tomography scan performed in one year and two months after best supportive care.We reported an extremely rare case of spontaneous regression of therapy-resistant metastases of angiosarcoma that has remained controlled for 40 months since the initial diagnosis.

Implantation of Induced Pluripotent Stem Cell-Derived Tracheal Epithelial Cells.

OBJECTIVES: Compared with using autologous tissue, the use of artificial materials in the regeneration of tracheal defects is minimally invasive. However, this technique requires early epithelialization on the inner side of the artificial trachea. After differentiation from induced pluripotent stem cells (iPSCs), tracheal epithelial tissues may be used to produce artificial tracheas. Herein, we aimed to demonstrate that after differentiation from fluorescent protein-labeled iPSCs, tracheal epithelial tissues survived in nude rats with tracheal defects. METHODS: Red fluorescent tdTomato protein was electroporated into mouse iPSCs to produce tdTomato-labeled iPSCs. Embryoid bodies derived from these iPSCs were then cultured in differentiation medium supplemented with growth factors, followed by culture on air-liquid interfaces for further differentiation into tracheal epithelium. The cells were implanted with artificial tracheas into nude rats with tracheal defects on day 26 of cultivation. On day 7 after implantation, the tracheas were exposed and examined histologically. RESULTS: Tracheal epithelial tissue derived from tdTomato-labeled iPSCs survived in the tracheal defects. Moreover, immunochemical analyses showed that differentiated tissues had epithelial structures similar to those of proximal tracheal tissues. CONCLUSIONS: After differentiation from iPSCs, tracheal epithelial tissues survived in rat bodies, warranting the use of iPSCs for epithelial regeneration in tracheal defects.

Heparin cross-linked collagen sponge scaffolds improve functional regeneration of rat tracheal epithelium.

Tracheal epithelial cells maintain airway homeostasis by mediating mucociliary clearance. Following tracheal reconstruction, timely epithelial regeneration is required to prevent respiratory compromise and infectious diseases. To achieve rapid tracheal epithelial regeneration, a heparin cross-linked collagen sponge containing fibroblast growth factor-2 (FGF-2) was prepared as a graft for tracheal reconstruction. The heparin cross-linked sponge exhibited a high FGF-2 retaining capacity, and tracheal epithelial and mesenchymal cells cultured in this sponge containing FGF-2 showed high proliferative capacities. Subsequently, heparin-free collagen sponge scaffolds (C/F scaffold) and collagen sponge scaffolds cross-linked with 10 µg/ml heparin retained FGF-2 (C/H10/F scaffold), and were transplanted into rats with tracheal defects. Invasion of both epithelial and non-epithelial cells was greater in rats treated with the C/H10/F scaffold at 1 week post-transplantation than in rats treated with the C/F scaffold. Moreover, at 2 weeks after transplantation, improved cilia formation was observed in the C/H10/F scaffold group, with higher motility and more potent posterior-anterior flow generation than in the C/F scaffold group. These results suggest that heparin improves functional regeneration of tracheal epithelium. Copyright © 2017 John Wiley & Sons, Ltd.

Association between off-hour presentation and endotracheal-intubation-related adverse events in trauma patients with a predicted difficult airway: A historical cohort study at a community emergency department in Japan.

BACKGROUND: A reduction in medical staff such as occurs in hospitals during nights and weekends (off hours) is associated with a worse outcome in patients with several unanticipated critical conditions. Although difficult airway management (DAM) requires the simultaneous assistance of several appropriately trained medical caregivers, data are scarce regarding the association between off-hour presentation and endotracheal intubation (ETI)-related adverse events, especially in the trauma population. The aim of this study was to determine whether off-hour presentation was associated with ETI complications in injured patients with a predicted difficult airway. METHODS: This historical cohort study was conducted at a Japanese community emergency department (ED). All patients with inhalation burn, comminuted facial trauma (Abbreviated Injury Scale Score Face ≥3), and penetrating neck injury who underwent ETI from January 2007 to January 2016 in our ED were included. Primary exposure was off-hour presentation, defined as the period from 6:01 PM to 8:00 AM weekdays plus the entire weekend. The primary outcome measure was the occurrence of an ETI-related adverse event, including hypoxemia, unrecognized esophageal intubation, regurgitation, cardiac arrest, ETI failure rescued by emergency surgical airway, cuff leak, and mainstem bronchus intubation. RESULTS: Of the 123 patients, 75 (61.0 %) were intubated during off hours. Crude analysis showed that off-hour presentation was significantly associated with an increased risk of ETI-related adverse events [odds ratio (OR), 2.5; 95 % confidence interval (CI), 1.1-5.6; p = 0.033]. The increased risk remained significant after adjusting for potential confounders, including operator being an anesthesiologist, use of a paralytic agent, and injury severity score (OR, 3.0; 95 % CI, 1.1-8.4; p = 0.034). CONCLUSIONS: In this study, off-hour presentation was independently associated with ETI-related adverse events in trauma patients with a predicted difficult airway. These data imply the need for more attentive hospital care during nights and weekends.

[Assessment of Cachexia in Head and Neck Cancer Patients Based on a Modified Glasgow Prognostic Score].

We retrospectively analyzed 54 patients who died of head and neck squamous cell caricinoma regarding the process and duration of cachexia using the modified Glasgow Prognostic Score (mGPS). The patients were classified as having cachexia when the serum albumin level was less than 3.5 mg/dL and the C-reactive protein (CRP) level was more than 0.5 mg/dL. The number of patients with cachexia was eight (8%) at the first visit and 50 (93%) at the time of death. In the 50 patients, the median and average time of having cachexia was 59 and 95 days, respectively. Thirty-two of the 50 patients (64%) died within three months after the presence of cachexia was confirmed. In this study, the time of having cachexia was so short, then the policy of care should be converted from aggressive into supportive in patients classified as having cachexia. mGPS would be an accurate assessment tool for cachexia and ascertain the end stage of head and neck cancer patients.

Potential of laryngeal muscle regeneration using induced pluripotent stem cell-derived skeletal muscle cells.

Conclusion Induced pluripotent stem (iPS) cells may be a new potential cell source for laryngeal muscle regeneration in the treatment of vocal fold atrophy after recurrent laryngeal nerve paralysis. Objectives Unilateral vocal fold paralysis can lead to degeneration, atrophy, and loss of force of the thyroarytenoid muscle. At present, there are some treatments such as thyroplasty, arytenoid adduction, and vocal fold injection. However, such treatments cannot restore reduced mass of the thyroarytenoid muscle. iPS cells have been recognized as supplying a potential resource for cell transplantation. The aim of this study was to assess the effectiveness of the use of iPS cells for the regeneration of laryngeal muscle through the evaluation of both in vitro and in vivo experiments. Methods Skeletal muscle cells were generated from tdTomato-labeled iPS cells using embryoid body formation. Differentiation into skeletal muscle cells was analyzed by gene expression and immunocytochemistry. The tdTomato-labeled iPS cell-derived skeletal muscle cells were transplanted into the left atrophied thyroarytenoid muscle. To evaluate the engraftment of these cells after transplantation, immunohistochemistry was performed. Results The tdTomato-labeled iPS cells were successfully differentiated into skeletal muscle cells through an in vitro experiment. These cells survived in the atrophied thyroarytenoid muscle after transplantation.

Regeneration of tracheal epithelium using mouse induced pluripotent stem cells.

Conclusion The findings demonstrated the potential use of induced pluripotent stem cells for regeneration of tracheal epithelium. Objective Autologous tissue implantation techniques using skin or cartilage are often applied in cases of tracheal defects with laryngeal inflammatory lesions and malignant tumor invasion. However, these techniques are invasive with an unstable clinical outcome. The purpose of this study was to investigate regeneration in a tracheal defect site of nude rats after implantation of ciliated epithelium that was differentiated from induced pluripotent stem cells. Method Embryoid bodies were formed from mouse induced pluripotent stem cells. They were cultured with growth factors for 5 days, and then cultured at the air-liquid interface. The degree of differentiation achieved prior to implantation was determined by histological findings and the results of real-time polymerase chain reaction. Embryoid bodies including ciliated epithelium were embedded into collagen gel that served as an artificial scaffold, and then implanted into nude rats, creating an 'air-liquid interface model'. Histological evaluation was performed 7 days after implantation. Results The ciliated epithelial structure survived on the lumen side of regenerated tissue. It was demonstrated histologically that the structure was composed of ciliated epithelial cells.

Diagnostic potential of 1-step nucleic acid amplification assay in patients with head and neck squamous cell carcinoma based on CK19 expression in a primary lesion.

BACKGROUND: The purpose of this study was to investigate the effects of CK19 expression in the primary lesions of head and neck squamous cell carcinoma on the diagnosis of the cervical lymph node (CLN) metastasis using the 1-step nucleic acid amplification assay. METHODS: Primary lesions and 54 CLNs were resected from 21 patients with head and neck squamous cell carcinoma between 2009 and 2011. Each CLN was tested by the 1-step nucleic acid amplification assay, and the CK19 mRNA copy number obtained was compared to the corresponding histopathological results. RESULTS: In the primary lesion CK19-positive group, the sensitivity and specificity of the 1-step nucleic acid amplification assay against hematoxylin-eosin staining were 86% and 100%, respectively. The p value by Fisher's exact test was < .0001, indicating statistical significance. CONCLUSION: These results suggest that 1-step nucleic acid amplification offers similar diagnostic potential to that of histopathological diagnosis of CLN biopsy in patients with a CK19-positive primary lesion. © 2015 Wiley Periodicals, Inc. Head Neck 38: E239-E245, 2016.