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Objectives/hypothesis: The tumor immune microenvironment in temporal bone squamous cell carcinoma (TBSCC), including the programmed death-ligand 1 (PD-L1) expression and tumor-infiltrating lymphocytes (TILs), has not been established., Study Design: Retrospective cohort study., Methods: We performed immunohistochemistry analyses to retrospectively analyze 123 TBSCC cases for PD-L1 expression and TILs and their prognostic significance. We also evaluated the prognostic correlations between these immunomarkers and the therapeutic responses to chemoradiotherapy (CRT)., Results: PD-L1 expression (≥1%) was detected in 62 (50.4%) TBSCC cases and was significantly associated with worse prognosis: progression-free survival (PFS), P < .0001; overall survival (OS), P = .0009. A high density of CD8 + TILs was significantly associated with better prognosis (PFS, P = .0012; OS, P = .0120). In contrast, a high density of Foxp3 + TILs tended to be associated with an unfavorable prognosis (PFS, P = .0148; OS, P = .0850). With regard to the tumor microenvironment subtypes defined by CD8 + TILs and PD-L1 expression, the CD8 low /PD-L1 + group showed significantly worse prognosis. Among the 36 neoadjuvant CRT-treated cases, PD-L1 expression was significantly associated with worse OS (P = .0132). Among the 32 CRT-treated cases without surgery, a high density of CD8 + TILs tended to be more highly associated with complete response to CRT compared to a low density of CD8 + TILs (P = .0702)., Conclusions: These results indicate that the evaluation of the tumor immune microenvironment may contribute to the prediction of prognoses and the selection of an individualized therapeutic strategy for patients with TBSCC., Level of Evidence: 4 Laryngoscope, 131:2674-2683, 2021., (© 2021 The American Laryngological, Rhinological and Otological Society, Inc.)

Objective/hypothesis: Squamous cell carcinoma (SCC) of the temporal bone is an extremely rare condition. This rarity has led to a delay in the establishment of a standard treatment protocol and adequate staging system. Identification of prognostic markers of this disease from a variety of fields is desirable in the establishment of treatment guidelines for temporal bone SCC. The aim of this study is to assess the prognostic role of inflammation-based prognostic scores in cases of temporal bone SCC., Study Design: Case reries with chart review., Methods: A total of 71 cases of primary malignancy eligible for curative treatment at a single tertiary medical institute were retrospectively analyzed. Univariate and multivariate regression analyzes were used to investigate the association between the inflammation-based scores and 5-year overall survival., Results: Univariate Cox regression analyzes showed that a high neutrophil-to-lymphocyte ratio, high platelet-to-lymphocyte ratio, low lymphocyte-to-monocyte ratio, a Glasgow prognostic score of 2, and the systemic inflammation score of 2 were significantly associated with a poor prognosis, as well as a classification of T4 stage, presence of cervical lymph node metastasis, high white blood cell counts, and high C-reactive protein levels. The multivariate analysis showed that a clinical stage of T4 and a systemic inflammation score of 2 were independent prognostic markers., Conclusions: Inflammation-based prognostic markers are associated with the survival of patients with temporal bone SCC, as well as other head and neck SCCs., Level of Evidence: 4 Laryngoscope, 131:1782-1789, 2021., (© 2021 The American Laryngological, Rhinological and Otological Society, Inc.)

Primary temporal bone squamous cell carcinoma is sporadic. According to previous studies, margin-negative resection provides the best prognosis (Nakagawa et al., 2006; Moody et al., 2000; Yin et al., 2006; Komune et al., 2021 [1-4]). When tumors extend behind the tympanic membrane, lateral temporal bone resection, which is a well-established procedure, is insufficient to achieve a tumor-free margin. For these cases, subtotal temporal bone resection (STBR) can achieve a complete en bloc resection with a tumor-free margin. Furthermore, STBR en bloc with surrounding structures, including the temporomandibular joint and parotid gland, complicates surgical techniques. We previously reported this surgical procedure in a stepwise manner using cadaveric dissection (Komune et al., 2014 [5]). The STBR en bloc with the parotid gland and temporomandibular joint is composed of three approaches according to our previous report: high cervical exposure (neck dissection), a subtemporal-infratemporal fossa approach, and a retromastoid-paracondylar approach. However, we currently lack demonstrative surgical videos. According to our previous report, this video first demonstrates STBR en bloc with the parotid gland and temporomandibular joint (Komune et al., 2014 [5]). The histopathological diagnosis of a 57-year-old woman suffering from a large tumor protruding from her auricle indicated squamous cell carcinoma; after the diagnosis she was referred to our hospital. Computed tomography revealed the full extent of the tumor, which was about 8 cm in diameter and had damaged the middle cranial base, mastoid bone, and middle ear cavity. Magnetic resonance imaging indicated invasion of the glenoid fossa and parotid gland, equivalent to a Pittsburg stage cT4 tumor. The patient underwent STBR en bloc with the parotid gland and temporomandibular joint. Lower cranial nerves (CN IX-XII) were preserved, and the patient achieved normal oral intake without additional procedures after surgery. At six months post-operation, no recurrence was noted. In this video, we first demonstrate the surgical procedure of the STBR en bloc with the parotid gland and temporomandibular joint for far-advanced temporal bone squamous cell carcinoma, and it can be one of the surgical options to achieve the complete resection without exposure of the tumor. Informed consent was obtained from the patient. The video was reproduced with the written informed consent of the patient. Primary temporal bone squamous cell carcinoma is sporadic. According to previous studies, margin-negative resection provides the best prognosis (Nakagawa et al., 2006; Moody et al., 2000; Yin et al., 2006; Komune et al., 2021 [1-4]). When tumors extend behind the tympanic membrane, lateral temporal bone resection, which is a well-established procedure, is insufficient to achieve a tumor-free margin. For these cases, subtotal temporal bone resection (STBR) can achieve a complete en bloc resection with a tumor-free margin. Furthermore, STBR en bloc with surrounding structures, including the temporomandibular joint and parotid gland, complicates surgical techniques. We previously reported this surgical procedure in a stepwise manner using cadaveric dissection (Komune et al., 2014 [5]). The STBR en bloc with the parotid gland and temporomandibular joint is composed of three approaches according to our previous report: high cervical exposure (neck dissection), a subtemporal-infratemporal fossa approach, and a retromastoid-paracondylar approach. However, we currently lack demonstrative surgical videos. According to our previous report, this video first demonstrates STBR en bloc with the parotid gland and temporomandibular joint (Komune et al., 2014 [5]). The histopathological diagnosis of a 57-year-old woman suffering from a large tumor protruding from her auricle indicated squamous cell carcinoma; after the diagnosis she was referred to our hospital. Computed tomography revealed the full extent of the tumor, which was about 8 cm in diameter and had damaged the middle cranial base, mastoid bone, and middle ear cavity. Magnetic resonance imaging indicated invasion of the glenoid fossa and parotid gland, equivalent to a Pittsburg stage cT4 tumor. The patient underwent STBR en bloc with the parotid gland and temporomandibular joint. Lower cranial nerves (CN IX-XII) were preserved, and the patient achieved normal oral intake without additional procedures after surgery. At six months post-operation, no recurrence was noted. In this video, we first demonstrate the surgical procedure of the STBR en bloc with the parotid gland and temporomandibular joint for far-advanced temporal bone squamous cell carcinoma, and it can be one of the surgical options to achieve the complete resection without exposure of the tumor. Informed consent was obtained from the patient. The video was reproduced with the written informed consent of the patient., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives/hypothesis: The extreme rarity of temporal bone squamous cell carcinoma (TB-SCC) has delayed the accumulation of high-quality clinical evidence. For the purposes of retrospective meta-analysis in the future, a large dataset with information from various institutions would be ideal. Our objective here was to retrospectively review cases of TB-SCC encountered at a single tertiary referral center and explore survival outcomes and prognostic factors., Study Design: Retrospective chart review., Methods: The medical records of all TB-SCC cases were retrospectively reviewed. The resulting dataset contained 71 cases of primary cancer eligible for initial definitive (curative) treatment., Results: T4 status was associated with lower disease-specific 5-year survival than T1 to T3 staging (T1: 100%, T2: 92%, T3: 86%, T4: 51%). Survival was significantly higher in operable than in inoperable cases, even when restricted to advanced (T3/T4) cancers. The tumor extension to the middle ear cavity was observed in 13/17 of T3 cases, but it was not associated with poor survival. In addition, among operable cases, negative surgical margins were associated with significantly higher survival than positive margins., Conclusions: Definitive treatments can offer disease-specific 5-year survival of over 85% in T1 to T3 cases of TB-SCC. The tumor extension to the middle ear cavity is not associated with poor survival. T4 status, inoperability, nodal invasion, and positive surgical margin are identified as a predictor of poor prognosis. Still, the matter of how to deal with unresectable tumors remains an outstanding issue in the treatment of TB-SCC., Level of Evidence: 4 Laryngoscope, 131:E583-E589, 2021., (© 2020 The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: The immune checkpoint inhibitor Nivolumab was approved for the treatment of platinum-refractory head and neck squamous cell carcinoma (SCC), expanding the treatment options for recurrent or advanced head and neck SCC. However, since temporal bone squamous cell carcinoma (TB-SCC) is very rare cancer, the effectiveness of Nivolumab remains unclear. We investigated the effects of Nivolumab for TB-SCC., Method: Chart information was collected for all patients who underwent the first administration of Nivolumab for recurrent or residual TB-SCC in our hospital between September 2017 and December 2019. Tumor staging followed the modified Pittsburgh classification. Changes in the tumor burden and survival outcome were examined., Results: We examined 9 patients with recurrent or residual TB-SCC who started administration of Nivolumab. In these cases, recurrent or residual SCC was observed after chemotherapy and/or chemoradiotherapy including platinum. The duration of Nivolumab was 2-54 weeks (median 20.0 weeks). The evaluation of the therapeutic effect according to the RECIST method showed partial response in 1 case, stable disease in 2 cases, progressive disease in 4 cases, and size unevaluated in 2 case. Although the number of cases was small, comparing with 5 cases without Nivolumab, these cases showed longer overall survival (1-year OS 33.3% vs 20.0%)., Conclusion: We used Nivolumab as palliative chemotherapy in 9 patients with recurrent/residual TB-SCC, and we were able to obtain a certain therapeutic effect on TB-SCC as well as other head and neck SCC., Competing Interests: Declaration of Competing Interest There is no conflict of interest., (Copyright © 2020. Published by Elsevier B.V.)

We report an indirect temporal bone fracture with ossicular chain injury occurring only on the side opposite a facial bone fracture caused by a direct blow. A 45-year-old female was referred to our clinic complaining of right hearing loss. She had suffered a left facial bone fracture in a traffic accident 6 months earlier. Her right hearing impairment was conductive. Exploration of her right middle ear revealed a temporal bone fracture, with ossicular chain separation and a dislocated stapes with a perilymphatic fistula. These injuries were considered to be caused by an indirect force following a blow to the face on the opposite side. Well-developed mastoid cells are composed of sparse, light bone in contrast to the compact bone of the bony canal, ossicles, and otic capsule, and therefore their mechanical compliance may differ.

Simple Summary: Squamous cell carcinoma of the external auditory canal (EAC-SCC) is sporadic. Its rarity has impeded the collection of evidence from both clinical and basic research, which has delayed the establishment of a standard treatment guideline. It has been considered that negative-margin resection offers the best prognosis. On the other hand, positive-margin resection is still a major cause of recurrence. However, to date, no research has focused on cases with positive-margin resection or specifically assessed the clinical impact of positive-margin resection of EAC-SCC. Our study emphasizes the importance of achieving a negative-margin resection, and we would provide impetus for elucidating the mechanisms of treatment resistance in cases of positive-margin resection. Background: Positive-margin resection of external auditory canal squamous cell carcinoma (EAC-SCC) is still a major cause of recurrence. The aim of this study is to examine the clinical impact of positive-margin resection of EAC-SCCs. Methods: We retrospectively reviewed 40 surgical cases with en bloc temporal bone resection of EAC-SCC at a tertiary referral center from October 2016 to March 2022. Results: Two-year disease-specific, overall, and disease-free survival rates for all 40 cases reviewed were 85.2%, 88.85%, and 76.96%, respectively. En bloc resection with a negative margin significantly improved patient prognosis (p < 0.001). Positive-margin resection was observed in 9/40 cases (22.5%). Insufficient assessment of preoperative images was the cause in two of these cases. Postoperative lymph node metastasis and distant metastasis were observed in cases in which vascular, lymphatic duct or perineural invasion was found on postoperative pathological examination. In addition, three cases in which no vascular, lymphatic duct, or perineural invasion was found exhibited local recurrence during the follow-up period. Of the nine positive-margin resection cases, only two showed no postoperative recurrence. Conclusions: Once positive-margin resections are confirmed, cases might have a high risk of tumor recurrence, even with the addition of postoperative adjuvant chemoradiotherapy. [ABSTRACT FROM AUTHOR]

Objective  En bloc and margin-negative surgical resection seems to offer the best prognosis for patients with temporal bone squamous cell carcinoma (TB-SCC). In this study, we summarize the outcomes of surgical cases of advanced TB-SCC (T3–T4) that were managed in two institutions, with an accompanying description of the surgical procedure that was utilized: modified subtotal temporal bone resection (STBR), which involves the en bloc removal of the temporal bone including or transecting the otic capsule. Design  This is a case series study with chart review. Setting  The study was conducted at two academic tertiary care medical centers. Participants  Chart information was collected for all patients who underwent surgical resection of advanced TB-SCC between July 1998 and February 2019. The resulting dataset contained 43 patients with advanced TB-SCC who underwent en bloc resection during the review period. Tumor staging followed the modified Pittsburgh classification. Disease-specific survival (DSS) rates were calculated according to the Kaplan–Meier method. Main Outcome Measure  This study shows disease-specific 5-year DSS rate. Results  The 5-year DSS rate of the cases who underwent en bloc resection was 79.7%. En bloc lateral temporal bone resection was employed in a total of 25 cases (DSS: 79.0%). En bloc modified STBR was utilized in 18 cases (DSS: 81.7%). Conclusion  En bloc margin-negative resection is a reliable treatment strategy for advanced TB-SCC. Modified STBR can be a treatment option for TB-SCC without marked posterior extension. [ABSTRACT FROM AUTHOR]

There are no human cancer cell lines of external auditory canal origin available for research use. This report describes the establishment of a culture condition for external auditory canal squamous cell carcinoma, derived from human tumor tissue. Successive squamous cell carcinoma colonies were dissociated by trypsin, subcultured, and maintained on a feeder layer (MMC‐TIG‐1‐20), yielding a clonally proliferating cell culture. Two morphological types of colony were observed: (a) densely packed colonies and (b) colonies with indistinct boundaries characterized by cell–cell complexes with fibroblast feeder cells. The SCC‐like characteristics of these cells were evidenced by positivity for p53, SCCA1/2, cytokeratin, and vimentin, and cancer stem cell properties were indicated by positivity for CD44, CD133, Oct3/4, and alkaline phosphatase (ALP). One of the unique properties of cell cultures is their tendency to form steric colonies in vitro on feeder layer cells. In addition, in the presence of fresh macrophages, the cells very slowly transform to break away from colonies as free cells, a process that resembles the epidermal–mesenchymal transition, whereby cell–cell interactions are weakened and migration activity is enhanced. These factors are purported to play a key role in cancer cell metastasis. [ABSTRACT FROM AUTHOR]

Objective: The extreme rarity of temporal bone squamous cell carcinoma (TB-SCC) has delayed the accumulation of high-quality clinical evidence. Our objective here was to explore anatomical factors associated with the prognosis of T4 TB-SCC cases. Study Design: Case series with chart review. Setting: Two academic tertiary care medical centers. Subjects and Methods: The medical records of all TB-SCC cases were retrospectively reviewed in two institutions. The resulting data set contained 30 cases of primary T4 cancer eligible for initial definitive (curative) treatment. Disease-specific survival was calculated according to the Kaplan–Meier method. Cox proportional hazards model was used to identify anatomical prognosis factors. Results: The disease-specific 5-years survival rate of 30 cases of T4 TB-SCC was 53.9%. The tumor invasion to the pterygoid muscle, posterior fossa dura, and sigmoid sinus and destruction of the ossicles were associated with poor prognosis in univariate analysis. The multivariate analysis reveals that the invasion of the ossicles, posterior fossa dura, and sigmoid sinus is an independent prognostic factor [hazard ratio (HR): 4.528 (95% CI: 1.161–17.658), p = 0.030; HR: 5.135 (95% CI: 1.616–16.315), p = 0.006; HR: 4.292 (95% CI: 1.385–13.303), p = 0.012]. The invasion of the carotid canal, petrous apex, middle fossa dura, otic capsule, pterygoid muscle, and middle ear had a high HR (HR > 2). The more invaded anatomical factors present in patients resulted in a poorer patient disease-specific prognosis, with a statistically significant difference. Conclusions: Assessing which anatomical structures are susceptible to invasion by tumors may be important for predicting TB-SCC patient prognosis and selecting appropriate treatment planning, especially surgical intervention. In addition to previously reported factors, the destruction of the ossicles in the middle ear cavity can be an anatomical prognosis factor. [ABSTRACT FROM AUTHOR]