Inflammatory Rhabdomyoblastic Tumor: Clinicopathologic and Molecular Analysis of 13 Cases.

Inflammatory rhabdomyoblastic tumors (IRMTs) are newly recognized skeletal muscle tumors with uncertain malignant potential. We investigated 13 IRMTs using clinicopathologic, genetic, and epigenetic methods. The cohort included 7 men and 6 women, aged 23 to 80 years (median, 50 years), of whom 2 had neurofibromatosis type 1. Most tumors occurred in the deep soft tissues of the lower limbs, head/neck, trunk wall, and retroperitoneum/pelvis. Two tumors involved the hypopharyngeal submucosa as polypoid masses. Eight tumors showed conventional histology of predominantly spindled cells with nuclear atypia, low mitotic activity, and massive inflammatory infiltrates. Three tumors showed atypical histology, including uniform epithelioid or plump cells and mitotically active histiocytes. The remaining 2 tumors demonstrated malignant progression to rhabdomyosarcoma; one had additional IRMT histology and the other was a pure sarcoma. All 11 IRMTs without malignant progression exhibited indolent behavior at a median follow-up of 43 months. One of the 2 patients with IRMTs with malignant progression died of lung metastases. All IRMTs were positive for desmin and PAX7, whereas myogenin and MyoD1 were expressed in a subset of cases. Targeted next-generation sequencing identified pathogenic mutations in NF1 (5/8) and TP53 (4/8). All TP53 mutations co-occurred with NF1 mutations. TP53 variant allele frequency was much lower than that of NF1 in 2 cases. These tumors showed geographic (subclonal) strong p53 immunoreactivity, suggesting the secondary emergence of a TP53-mutant clone. DNA methylation-based copy number analysis conducted in 11 tumors revealed characteristic flat patterns with relative gains, including chromosomes 5, 18, 20, 21, and/or 22 in most cases. Widespread loss of heterozygosity with retained biparental copies of these chromosomes was confirmed in 4 tumors analyzed via allele-specific profiling. Based on unsupervised DNA methylation analysis, none of the 11 tumors tested clustered with existing reference entities but formed a coherent group, although its specificity warrants further study.

Efficacy of second and subsequent lines of chemotherapy for recurrent and metastatic head and neck cancer.

OBJECTIVE: The increase in treatment options resulted in successful treatment with multiple lines of chemotherapy for recurrent and metastatic (RM) head and neck cancer (HNC). The present study aimed to elucidate the beneficial effect of successive treatment for RM-HNC. METHODS: We included 78 patients with RM-HNC who received one or multiple lines of chemotherapy from January 2008 to December 2019. We divided the patients into three groups according to treatment period: January 2008 to November 2012 included those who underwent cancer chemotherapy only with cytotoxic agents (Tox group), December 2012 to March 2017 included those who received cytotoxic agents and cetuximab (Cet group), and March 2017 to December 2019 included those who received cytotoxic agents, cetuximab and immune checkpoint inhibitor nivolumab (Nivo group). Moreover, we compared the overall survival of the three groups. RESULTS: In total, 18, 33, and 27 patients were included in the Tox, Cet, and Nivo groups, respectively. The median overall survival were 8.5 months in the Tox group, 16 months in the Cet group, and 19 months in the Nivo group, and the difference in the result was significant. CONCLUSIONS: Successive treatment with second and subsequent lines of chemotherapy in patients with RM-HNC improves prognosis.

Ultrasonography findings in immunoglobulin G4-related lymphadenopathy: a report of two cases.

Lymphadenopathy is frequently observed in immunoglobulin G4 (IgG4)-related disease in some cases, and such cases are known as IgG4-related lymphadenopathy. The ultrasonography findings associated with IgG4-related lymphadenopathy have not been described in previous reports. Herein, we describe ultrasonography findings in two cases of IgG4-related lymphadenopathy in conjunction with histopathological findings. Combined ultrasound scanning with Doppler examination accurately represented the specific histopathological features of IgG4-related lymphadenopathy.

Preoperative predictors of difficult hypopharyngeal exposure by retractor for transoral robotic surgery.

INTRODUCTION: Transoral endoscopic surgeries provide excellent oncologic outcomes while preserving speech and swallowing ability. However, feasibility has been a major concern about transoral surgery. Therefore, ensuring visualization of the surgical field and sufficient working space is required. The aim of this study was to evaluate the parameters in the preoperative assessment that affect hypopharyngeal exposure. METHODS: Before transoral surgery, parameters regarding the patient's neck and face such as modified Mallampati index, thyroid-mental distance (TMD), and ability to fully open the mouth were evaluated. Cephalometry and cervical spine radiography were performed preoperatively to evaluate the size of the mandible bone, mouth opening, and cervical spine extension. Mandibular bone parameters such as intergonion distance, mental-gonion distance, articulare-gonion distance, and aperture angle were measured. According to hypopharyngeal exposure using FKWO retractor, patients were divided into difficult hypopharyngeal exposure group (DHE) and non-difficult hypopharyngeal exposure group (non-DHE). Parameters were enrolled to evaluate the relationship between these parameters and DHE status. RESULTS: This study included 51 patients, 37 in the non-DHE group and 14 in the DHE group. On radiographic evaluation, there was a significant difference in the degree of cervical lordosis between non-DHE and DHE patients. A significantly higher proportion of DHE patients had a history of radiotherapy compared with non-DHE patients. CONCLUSION: Patients with limited cervical extension and a history of previous radiotherapy might have difficult hypopharyngeal exposure during transoral surgery. This is the first report to suggest a classification system for hypopharyngeal exposure during transoral surgery.

Clinical efficacy of novel elastography using acoustic radiation force impulse (ARFI) for diagnosis of malignant thyroid nodules.

OBJECTIVE: Acoustic radiation force impulse (ARFI) imaging is a recent ultrasound elastography technique; consequently, its efficacy is not fully known. In this study, we compared ARFI imaging with conventional strain elastography (SE) and shear wave velocities (SWVs) to evaluate the utility of ARFI imaging for diagnosing thyroid nodules. SUBJECTS AND METHODS: In this study we examined 233 thyroid nodules (183 benign nodules and 50 malignant nodules) isolated from human patients. The nodules were evaluated with SE and ARFI imaging, and SWVs of the nodules were simultaneously measured. ARFI images were classified using a four-point score based on grayscale intensity of the images. The sensitivity, specificity, and diagnostic accuracy were compared between SE and ARFI imaging. Finally, SWVs for each score of SE and ARFI imaging were compared. RESULTS: The new scoring system for ARFI imaging can be divided into four virtual touch imaging (VTI) scores. Nodules with a VTI score of 3 or 4 as determined by ARFI imaging were determined to be malignant. The sensitivity, specificity, and diagnostic accuracy, respectively, were 63.2%, 66.3%, and 65.6% for SE, compared with 80.0%, 86.3%, and 85.0% for ARFI imaging. The median SWVs of the nodules were 1.57 m/s, 1.73 m/s, 1.88 m/s, and 2.09 m/s for VTI scores of 1, 2, 3, and 4, respectively. The SWVs of VTI scores 3 and 4 were significantly higher than those of VTI scores 1 and 2. CONCLUSIONS: The diagnostic accuracy of ARFI imaging for differentiating malignant thyroid nodules was higher than that of SE. The VTI scores of the nodules accurately reflected their SWVs. LEVEL OF EVIDENCE: 4.

Immunohistochemical Features of Primary Pure Squamous Cell Carcinoma in the Thyroid: An Autopsy Case.

Primary squamous cell carcinoma (SCC) in the thyroid is extremely rare and has been reported in < 1% of all thyroid cancer cases. Primary SCC in the thyroid was thought to be a transitional form derived from adenocarcinomas; therefore, the majority of reported cases have focused on the conjunction with other histological adenocarcinomas. A 73-year-old male presented to our hospital with bilateral vocal fold palsy and an anterior neck mass. Ultrasound sonography revealed a bulky tumor in the thyroid and bilateral cervical lymphadenopathy. We performed fine-needle aspiration cytology from the thyroid tumor, which revealed SCC. Positron emission tomography/computed tomography showed distant metastases in the lungs, mediastinal lymph nodes, and vertebra. We diagnosed the patient as having stage IVC SCC in the thyroid and administered weekly paclitaxel. Four and a half months after treatment initiation, the tumor progression resulted in aspiration pneumonia, which proved fatal. We performed an autopsy in accordance with the patient's wishes. Pathological findings revealed that all carcinomas in the thyroid, cervical lymph nodes, and lungs were pure SCCs. Immunohistochemical examinations for PAX8, thyroglobulin, and TTF-1 were all negative. Differentiated thyroid carcinomas have 3 major positive markers - PAX8, thyroglobulin, and TTF-1 -, and PAX8 is also sometimes positive for SCC in the thyroid. PAX8 positivity of SCC in the thyroid might, however, be associated with conjunction with other histological adenocarcinomas such as papillary or follicular thyroid carcinoma; therefore, pure SCC in the thyroid might be negative for PAX8.

Lenvatinib for Anaplastic Thyroid Cancer and Lenvatinib-Induced Thyroid Dysfunction.

BACKGROUND: Lenvatinib is an oral multitargeted tyrosine kinase inhibitor that has an anticancer action in patients with differentiated thyroid cancer that is refractory to radioiodine. Knowledge of the efficacy and safety of lenvatinib in patients with anaplastic thyroid cancer (ATC) is limited. Tyrosine kinase inhibitors frequently cause hypothyroidism, but the incidence of hypothyroidism with lenvatinib is unclear. OBJECTIVES: We conducted a retrospective study to investigate the efficacy and safety of lenvatinib in ATC. METHODS: Five patients with unresectable ATC were enrolled. Lenvatinib 24 mg once daily was administered until disease progression, unmanageable toxicity, withdrawal, or death occurred. We retrospectively analyzed the objective response rate (ORR), time to progression (TTP), overall survival, and safety. RESULTS: Three of the 5 patients (60%) had a partial response, and 5 (40%) had stable disease. The ORR was 60%. Median TTP was 88 days, and overall survival was 165 days. Hypothyroidism was a common treatment-related adverse effect; 4 patients (80%) had hypothyroidism of any grade. These 4 patients had not undergone total thyroidectomy prior to lenvatinib administration, and the other patient had undergone total thyroidectomy. Treatment-related adverse effects of any grade were hypertension in 80% of patients, diarrhea in 40%, fatigue in 80%, and decreased appetite in 80%. CONCLUSIONS: Lenvatinib is an effective treatment and may improve the prognosis of unresectable ATC. Four of the 5 patients had hypothyroidism, which may have been associated with treatment-induced injury of the thyroid gland. There were many treatment-related adverse effects, most of which were manageable by dose modification and medical therapy.

Significant Amelioration of Tracheal Stenosis following Lenvatinib in a Patient Who Has Anaplastic Thyroid Carcinoma with Bronchomediastinal Infiltration: A Case Report.

BACKGROUND: Anaplastic thyroid carcinoma has an extremely poor prognosis, and no known drugs have exhibited acceptable efficacy. In recent years, novel anticancer tyrosine kinase inhibitors have been developed. We encountered a case of tracheal stenosis due to mediastinal and tracheal infiltration of anaplastic carcinoma for which lenvatinib exhibited remarkable effects; owing to this, airway management could be performed, even though the patient's condition was considered critical. CASE REPORT: A 55-year-old man presented with locally advanced anaplastic thyroid carcinoma that was observed to have mediastinal infiltration. Tracheal stenosis due to infiltration of the trachea occurred, and the condition of the patient rapidly deteriorated. Radiation and chemotherapy consisting of cetuximab, cisplatin, and fluorouracil were ineffective, but his tracheal stenosis was relieved 2 weeks after initiation of lenvatinib, after which the patient could be discharged. However, the lenvatinib was ineffective for his liver, bone, and brain metastatic lesions, and the patient remained in a critical condition. CONCLUSION: We encountered a case in which lenvatinib was effective for locally advanced anaplastic thyroid carcinoma, leading to an improvement in quality of life and a prolonged life. The drug was effective for the primary lesion, but mixed efficacy was noted for distant metastatic lesions.

Modifications to the Fenestration Approach for Arytenoid Adduction Under Local Anesthesia.

OBJECTIVE: We modified the fenestration approach for arytenoid adduction to make it easier to perform the surgery. The aim of this study was to evaluate the usefulness of our modifications, which included (1) use of an Alexis wound retractor (Applied Medical) to secure the surgical field through a small incision, and (2) use of a 12-mm, 1/2 R, insert-molded taper needle with 3-0 nylon suture to prevent damage to the arytenoid cartilage. STUDY DESIGN: This is a retrospective non-randomized observational cross-sectional study. METHODS: We compared the operative time and skin incision length between the conventional fenestration approach and our modified procedure, and verified the improvement of patients' voice by our procedure. RESULTS: Seven patients underwent the conventional fenestration approach for arytenoid adduction with type I thyroplasty, whereas nine patients underwent our modified fenestration approach for arytenoid adduction with type I thyroplasty. The skin incision length with our modifications (median, 3.0 cm; interquartile range [IQR], 3.0-4.0) was significantly shorter than with the conventional procedure (median, 5.0 cm; IQR, 4.3-5.8) (P = 0.001). The operative time with our modifications (median, 95 minutes; IQR, 90-100) was significantly shorter than without our modifications (median, 115; IQR, 100-130) (P = 0.035). All patients who underwent our modified fenestration approach for arytenoid adduction had maximum phonation time greater than 11 seconds after surgery. CONCLUSIONS: Our two distinctive modifications reduced the operative time and skin incision length for the fenestration approach, which improved the procedure by making it less invasive.

Post-laryngectomy voice rehabilitation with a voice prosthesis in a young girl with advanced thyroid cancer.

The aim of this report is to evaluate the effects of voice rehabilitation with a voice prosthesis in a young patient with thyroid cancer. A 17-year-old girl underwent voice restoration with a voice prosthesis after laryngectomy to treat thyroid cancer. She completed voice-related questionnaires (the Voice Handicap Index-10 and Voice-Related Quality Of Life Survey) at ages 17 and 21 and underwent phonetic functional evaluation. The sound spectrograms of her phonation using the voice prosthesis showed low frequency sounds without an obvious basic frequency. She was ashamed of her hoarse voice and did not use her voice prosthesis during high school. However, after beginning to work at age 20, she used her voice to communicate in the workplace. At age 21, her questionnaire scores, especially those related to the physical and functional domains, improved compared with those at age 17. Voice restoration with a voice prosthesis is recommended for young patients who undergo laryngectomy for advanced thyroid cancer. The advantages of voice restoration with a voice prosthesis may increase when the patient reaches working age, and it may improve post-laryngectomy quality of life considerably.

Subglottic laryngeal closure: a unique modified method of laryngotracheal separation to prevent aspiration.

OBJECTIVES: Laryngotracheal separation (LTS) is an ideal surgical method for intractable aspiration; however, the oral side of the tracheal stump can easily disintegrate. Therefore, we developed a modified LTS method. We performed subglottic laryngeal closure (SGLC) as a new surgical method and evaluated the outcomes. METHODS: We retrospectively analyzed the medical records of 36 patients (28 male and 8 female; 15 to 91 years of age) who underwent SGLC between 2007 and 2011 at Tottori University Hospital, Japan. Operative data (operative time, intraoperative bleeding, and time to drain removal), outcomes (aspiration and changes in nutritional status), and complications with regard to the surgical method were examined. The occurrence of a subcutaneous proximal laryngeal stump fistula was evaluated by videofluoroscopy. RESULTS: The SGLC was performed safely in all patients. Fistulization was observed in only 1 of the patients (2.8%), and major bleeding after surgery was observed in 1 patient (2.8%). The procedure relieved aspiration pneumonia in all patients. CONCLUSIONS: We conclude that SGLC is effective for treating and preventing pulmonary aspiration. The incidence of postoperative complications, particularly that of subcutaneous fistulas, was very low. Therefore, this method may be useful for patients in poor condition.

Pathological consideration of tracheo-innominate artery fistula with a case report.

OBJECTIVES: Tracheo-innominate artery fistula (TIF) is a rare but life-threatening complication of tracheostomy. There are many reports about TIF but the mechanism of TIF formation remains poorly documented. Our objective is to investigate the TIF pathologically and suggest the possible mechanism of TIF formation. PATIENT AND METHODS: The patient was an 11-year old boy with a history of severe childhood epilepsy, cerebral palsy, and psychomotor retardation who died from TIF. We investigated the TIF histopathologically through his autopsy and reviewed bibliographical considerations. RESULTS: Autopsy revealed massive blood aspiration from a large TIF and histopathological findings showed the following: (1) fibroepithelial polyps around the fistula; (2) squamous metaplasia of tracheal mucosa; (3) disappearance of tracheal cartilages and tracheal glands; and (4) arteritis (infiltration of neutrophils into the mesarterium and endarterium). Probably, (1) and (2) indicate chronic and repetitive irritations caused by cannula. (3) and (4) indicate intense inflammation caused by local infection. In this case, it is suggested that the chronic damage by cannula and the local infection resulted in the fistula formation and rupture of innominate artery. CONCLUSION: The present case suggests a pathogenesis in which chronic damage to the anterior tracheal wall by the cannula and consequent infection led to fistulation and rupture of the innominate artery.

New method for in-office secondary voice prosthesis insertion under local anesthesia by reverse puncture from esophageal lumen.

OBJECTIVES: We clarify and demonstrate the utility of our new method of voice prosthesis insertion using puncture from the esophageal lumen. METHODS: Our new reverse puncture method using a flexible endoscope can be performed in an outpatient clinic under local anesthesia. We conducted a clinical trial with patients with head and neck cancer between April 2010 and February 2012. Our study focused on the following three points: 1) the percentage of patients for whom the procedure was successful; 2) the duration of the operation; and 3) any adverse effects. RESULTS: The puncture was performed successfully for 21 of 22 patients (95%). The mean duration of the operation, excluding the time for local anesthesia, was only 11.6 minutes. All patients began voice rehabilitation and attained peroral intake immediately after the operation. None of the patients suffered complications from the procedures. CONCLUSIONS: Most patients were treated with our new method with ease and at low risk. The high success rate and the absence of complications demonstrate the benefits of our method. We conclude that our method can be recommended for secondary reverse tracheoesophageal puncture.

Fetal anatomy of the lower cervical and upper thoracic fasciae with special reference to the prevertebral fascial structures including the suprapleural membrane.

The aim of this study was to find basic rules governing the fetal anatomy of the deep cervical fasciae and their connections to the mediastinal fasciae. We examined the histology of paraffin-embedded preparations of 18 mid-term fetuses (5 between 9 and 12 weeks of gestation, 3 between 15 and 18 weeks, and 10 between 20 and 25 weeks). The prevertebral lamina of the deep cervical fasciae (PLDCF) developed as an intermediate aponeurosis for the bilateral bellies of the longus colli muscles. In contrast, the alar fascia developed as a connecting band between the bilateral adventitiae of the common carotid artery. The retropharyngeal fascia became evident much later than the latter two fasciae. The fascia covering the thymus was thicker than the fascia for the strap muscles (the pretracheal lamina of the cervical fascia). The primitive suprapleural membrane, or Sibson's fascia, contained veins and fatty tissues, and was composed of the alar fascia rather than the PLDCF, tranversalis fascia, or endothoracic fascia. The prevertebral two-laminar configuration was rather evident in the early stages of development because, in the later stages, the fasciae together provided a multilaminar structure, especially in the lateral area in front of the longus colli, which suspended the cupula pleurae. To consider a continuation from the base of the neck to the upper mediastinum, the alar fascia seems to be a key structure for connecting the vascular sheath to the parietal pleura.

Fetal anatomy of the human carotid sheath and structures in and around it.

The aim of this study was to find basic rules governing the morphological development of the typical neurovascular sheath. We carried out histological examination of 15 paraffin-embedded mid-term fetuses at 9-25 weeks of gestation (three fetuses each at 9, 12, 15, 20, and 25 weeks). As the result, the vagus nerve showed a high propensity to change its topographical relationship with the common carotid artery (CCA) during 9-20 weeks of gestation: that is, from a primitive ventral course to a final dorsal course. The adventitia of the great arteries, which was distinct from other fascial structures, became evident by 15 weeks. The carotid sheath appeared at and after 20 weeks: it was clearly separated from the prevertebral lamina of the deep cervical fasciae, but fused with the pretracheal lamina covering the strap muscles. Thus the carotid sheath, as well as the topographical relationships of structures within it, seems to become established much later than the prevertebral and pretracheal laminae of the deep cervical fasciae. However, the adventitia of the cervical great arteries consistently becomes evident much earlier than the sheath, and it seems to be regarded as one of the basic components of the fetal deep cervical fasciae.