Publications by authors named "Tomoyuki Kamijo"

36 Publications

Transoral surgery for superficial head and neck cancer: National Multi-Center Survey in Japan.

Cancer Med 2021 Jun 15;10(12):3848-3861. Epub 2021 May 15.

Department of Gastroenterology, Kobe City Medical Center General Hospital, Kobe, Japan.

Head and neck cancers, especially in hypopharynx and oropharynx, are often detected at advanced stage with poor prognosis. Narrow band imaging enables detection of superficial cancers and transoral surgery is performed with curative intent. However, pathological evaluation and real-world safety and clinical outcomes have not been clearly understood. The aim of this nationwide multicenter study was to investigate the safety and efficacy of transoral surgery for superficial head and neck cancer. We collected the patients with superficial head and neck squamous cell carcinoma who were treated by transoral surgery from 27 hospitals in Japan. Central pathology review was undertaken on all of the resected specimens. The primary objective was effectiveness of transoral surgery, and the secondary objective was safety including incidence and severity of adverse events. Among the 568 patients, a total of 662 lesions were primarily treated by 575 sessions of transoral surgery. The median tumor diameter was 12 mm (range 1-75) endoscopically. Among the lesions, 57.4% were diagnosed as squamous cell carcinoma in situ. The median procedure time was 48 minutes (range 2-357). Adverse events occurred in 12.7%. Life-threatening complications occurred in 0.5%, but there were no treatment-related deaths. During a median follow-up period of 46.1 months (range 1-113), the 3-year overall survival rate, relapse-free survival rate, cause-specific survival rate, and larynx-preservation survival rate were 88.1%, 84.4%, 99.6%, and 87.5%, respectively. Transoral surgery for superficial head and neck cancer offers effective minimally invasive treatment. Clinical trials registry number: UMIN000008276.
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http://dx.doi.org/10.1002/cam4.3927DOI Listing
June 2021

Triplet induction chemotherapy followed by less invasive surgery without reconstruction for human papillomavirus-associated oropharyngeal cancers: Why is it successful or unsuccessful?

Int J Clin Oncol 2021 Jun 8;26(6):1039-1048. Epub 2021 Mar 8.

Division of Radiation Oncology, Shizuoka Cancer Center, Shizuoka, Japan.

Background: De-escalating treatments have been focused on for HPV-associated oropharyngeal squamous cell carcinoma (OPSCC). We assessed the efficacy of a triplet induction chemotherapy (ICT) followed by surgery with or without neck dissection (ND) for locally advanced OPSCC, aiming at less invasive surgery without free-flap reconstruction and avoiding postoperative irradiation.

Methods: This was a retrospective study of 41 patients with advanced resectable HPV-positive OPSCC who underwent ICT followed by surgery of primary resection with or without ND. Patients underwent triplet ICT, including docetaxel, cisplatin, and 5-fluorouracil, or carboplatin, paclitaxel, and cetuximab.

Results: Twenty-nine patients had tonsillar cancer, 15 patients were current smokers, and 18 and 12 patients had T2N1M0 and T1N1M0 status (UICC 8th), respectively. After ICT, a surgical procedure without free-flap reconstruction and tracheostomy was possible in 90.2%. Pathological complete response at both the primary site and lymph nodes was achieved in 73.2%. Of the patients who underwent surgery, no adjuvant radiotherapy was required in 85.0%. Two patients (4.9%) experienced recurrence at regional lymph nodes, but were cured by salvage ND followed by adjuvant radiotherapy.

Conclusions: Upfront ICT using highly responsive triplet chemotherapeutic regimens may enable us to perform less invasive surgery without free-flap reconstruction and to avoid postoperative irradiation to the locoregional field through excellent postoperative pathological features.
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http://dx.doi.org/10.1007/s10147-021-01894-zDOI Listing
June 2021

Endoscopic rendezvous and diathermic dilation for complete pharyngeal obstruction.

Dig Endosc 2020 Sep 31;32(6):e130-e131. Epub 2020 Jul 31.

Division of Head and Neck Surgery, Shizuoka Cancer Center, Shizuoka, Japan.

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http://dx.doi.org/10.1111/den.13756DOI Listing
September 2020

Molecular profile of a pleomorphic adenoma of the hard palate: A case report.

Medicine (Baltimore) 2020 Jul;99(29):e21207

Division of Head and Neck Surgery, Shizuoka Cancer Center Hospital.

Rationale: Pleomorphic adenoma (PA) is the most common benign tumor of salivary glands. PAs have the potential for regional and distant metastases that preserve their benign phenotype; they also have the potential for malignant transformation. The molecular pathogenesis of malignant neoplasms has been studied extensively in recent years, unlike that of benign tumors, such as PA.

Patient Concerns: In this case report, we identified the molecular signatures of a 57-year-old Japanese woman. Our patient presented with a swelling of the hard palate with an erosive appearance.

Diagnoses: The patient was diagnosed with a right hard palate tumor suspected to be a malignant neoplasm.

Interventions: Partial maxillary resection and reconstruction were performed.

Outcomes: There was no obstacle to swallowing or dysarthria after surgery. There was no sign of recurrent palatal tumor 4 years after the operation. Using next generation sequencing, 5 nonsynonymous mutations and CHCHD7-PLAG1 fusion genes were detected. Moreover, gene expression profiling indicated the possibility of the activation of several cancer-related signaling pathways. Although the PLAG1 gene is predicted to play a crucial role in PA tumorigenesis, its over-expression is reported to mediate multiple downstream factors. In this case, various up- and downregulated RNA signaling pathways, including MAP kinase signaling, PI3K/AKT1/MTOR signaling, JAK/STAT signaling, and PD-L1 signaling, were revealed.

Lessons: These molecular profiles of PA may elucidate the mechanism of metastasis, preserving its benign phenotype and carcinoma ex PA.
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http://dx.doi.org/10.1097/MD.0000000000021207DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7373603PMC
July 2020

Chemoradiotherapy for high-risk stage II laryngeal cancer.

Int J Clin Oncol 2020 Sep 22;25(9):1596-1603. Epub 2020 May 22.

Division of Gastrointestinal Oncology, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi, Sunto-gun, Shizuoka, 411-8777, Japan.

Background: Definitive radiotherapy (RT) for stage II laryngeal cancer is known to be less effective for locoregional control and survival (LRCS) in patients with high-risk factors (e.g., subglottic extension, impaired cord mobility, or bulky tumor size) than in low-risk patients. The purpose of this study was to evaluate the safety and efficacy of chemoradiotherapy (CRT) for stage II laryngeal cancer patients with high-risk factors METHODS: Sixty-five consecutive patients with stage II laryngeal cancer who received radiotherapy (RT) alone or CRT were retrospectively analyzed. The patients were classified into three groups: RT, low risk (RT-low, n = 26); RT, high risk (RT-high, n = 25); and CRT, high risk (CRT-high, n = 14).

Results: The glottis was the most common primary tumor site in all groups. Most patients in the CRT-high group received platinum-based CRT. The 5-year locoregional control and survival (LRCS) rates were 88.3, 44.2, and 85.7% in the RT-low, RT-high, and CRT-high groups, respectively. In multivariate analysis, high-risk disease and CRT were significantly associated with 5-year LRCS rates.

Conclusion: CRT may provide better locoregional control than RT alone in high-risk stage II laryngeal cancer.
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http://dx.doi.org/10.1007/s10147-020-01705-xDOI Listing
September 2020

Pretreatment predictive factors for feasibility of oral intake in adjuvant concurrent chemoradiotherapy for patients with locally advanced squamous cell carcinoma of the head and neck.

Int J Clin Oncol 2020 Feb 16;25(2):258-266. Epub 2019 Oct 16.

Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, Japan.

Background: Prophylactic percutaneous endoscopic gastrostomy (PEG) has been widely performed before concurrent chemoradiotherapy (CCRT) for locally advanced squamous cell carcinoma of the head and neck (LASCCHN) because severe oral mucositis and dysphagia induced by CCRT lead to difficulty with oral intake. However, it is controversial whether all patients require prophylactic PEG for adjuvant CCRT. This study evaluated predictive factors for the feasibility of oral intake in adjuvant CCRT for patients with LASCCHN.

Methods: This study retrospectively analyzed 117 LASCCHN patients who underwent surgery followed by adjuvant CCRT with cisplatin at Shizuoka Cancer Center between April 2008 and December 2018. To investigate predictive factors for the feasibility of oral intake, tumor factors, treatment factors and social factors were included in multivariate analyses.

Results: Of the 117 patients, 25 received total laryngectomy and 92 received other surgery. In multivariate analysis, total laryngectomy [HR (hazard ratio) 0.09, P = 0.001] and oral cavity of primary tumor location (HR 0.21, P = 0.031) were significantly associated with the feasibility of oral intake. Difficulty obtaining adequate nutrition via oral intake from initiation of CCRT until 1 year after its completion was significantly rarer in the total laryngectomy group than in the other surgery group (16% vs. 57%, P < 0.001).

Conclusion: Our study suggests that majority of patients who underwent total laryngectomy are able to maintain oral intake during adjuvant chemoradiotherapy.
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http://dx.doi.org/10.1007/s10147-019-01560-5DOI Listing
February 2020

Safety and efficacy of concurrent carboplatin or cetuximab plus radiotherapy for locally advanced head and neck cancer patients ineligible for treatment with cisplatin.

Int J Clin Oncol 2019 May 17;24(5):468-475. Epub 2019 Jan 17.

Department of Otolaryngology-Head and Neck Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Hokkaido, Japan.

Background: Locally advanced squamous cell carcinoma of the head and neck (LASCCHN) is usually treated with cisplatin (CDDP)-based chemoradiotherapy, except when patients are elderly or have renal, cardiac, or neurogenic dysfunction. This study compared the safety and efficacy of concurrent carboplatin (CBDCA) to cetuximab (Cmab) plus radiotherapy (RT) in patients ineligible for CDDP treatment.

Methods: We retrospectively analyzed LASCCHN patients who received CBDCA plus RT (n = 29) or Cmab plus RT (n = 18) due to ineligibility for CDDP treatment at two Japanese institutions between August 2006 and December 2015.

Results: Patients characteristics for CBDCA plus RT and Cmab plus RT were: median age, 74 and 75 years; 0-1 performance status, 90% and 100%; main primary tumor site, hypopharynx 52% (n = 15) and oropharynx 39% (n = 7); and stage IV, 90% (n = 26) and 50% (n = 9), respectively. With a median follow-up time of 60.0 months for CBDCA plus RT and 53.6 months for Cmab plus RT, 3-year locoregional control rates were 56% versus 58%, and median progression-free survival was 42.7 versus 11.6 months. CBDCA plus RT was associated with more grade 3/4 hematologic toxicities, including neutropenia and thrombocytopenia, whereas Cmab plus RT was associated with more grade 3/4 oral mucositis and radiation dermatitis.

Conclusions: CBDCA or Cmab as a concurrent systemic therapy with RT is a possible treatment option for LASCCHN patients ineligible for CDDP treatment, although attention to hematological toxicity should be paid.
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http://dx.doi.org/10.1007/s10147-018-01392-9DOI Listing
May 2019

Acantholytic Squamous Cell Carcinoma and Salivary Duct Carcinoma Ex-pleomorphic Adenoma of the Submandibular Gland: A Report of Two Extremely Rare Cases with an Immunohistochemical Analysis.

Head Neck Pathol 2020 Mar 27;14(1):230-238. Epub 2018 Nov 27.

Pathology Division, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan.

Carcinoma ex pleomorphic adenoma (CXPA) is a malignant tumor of the salivary gland that arises from pleomorphic adenoma (PA). Squamous cell carcinoma (SCC) is extremely rare in the salivary glands. We report two cases of acantholytic SCC (ASCC) ex PA. Case 1 involved a 72-year-old female, and case 2 involved a 67-year-old male. Histologically, both cases involved PA, and salivary duct carcinoma (SDC) components, which were positive for androgen receptor (AR) and gross cystic disease fluid protein (GCDFP)-15 but negative for HER2, were seen in the intracapsular regions. The invasive components consisted of ASCC, which were positive for cytokeratin 5/6 and p63 but negative for AR and GCDFP-15. The SDC and ASCC components were positive for the epidermal growth factor receptor. In both cases, the cytoplasmic localization or decreased expression of E-cadherin was observed in the ASCC. In the early phase, CXPA might emerge as SDC, and it might change into SCC as it invades beyond the capsule due to changes in microenvironment. Also, the aberrant expression of E-cadherin is related to acantholysis in SCC.
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http://dx.doi.org/10.1007/s12105-018-0987-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7021842PMC
March 2020

Depth of invasion in superficial oral tongue carcinoma quantified using intraoral ultrasonography.

Laryngoscope 2018 12 16;128(12):2778-2782. Epub 2018 Oct 16.

Division of Head and Neck Surgery.

Objective: Depth of invasion (DOI) in oral carcinoma has been integrated into the primary tumor categories in the current tumor-node-metastasis staging (8th edition). However, there is no standard modality to determine DOI preoperatively. The aims of the present study were to evaluate the accuracy of a preoperative measurement of DOI using ultrasonography (US) for superficial oral tongue carcinomas, and to correlate the values obtained with histologically determined DOI measurements.

Methods: We retrospectively analyzed the records of 56 patients with oral tongue carcinoma who underwent intraoral US preoperatively, followed by curative surgery at the Shizuoka Cancer Center Hospital in Japan. For the measurement of DOI with US, our unique technique (water balloon method) was evaluated.

Results: The histologically measured tumor size (maximum diameter) showed a distribution of 7.0 to 40.0 mm (mean, 18.6 mm). The correlation between the US-obtained and histologically obtained DOIs was significant (r = 0.867; P < 0.001). In tumors characterized histologically as superficial (DOI ≤ 5 mm), a significant correlation was observed between US-obtained and histologically obtained DOIs (r = 0.870, P  < 0.001). For the entire cohort, the sensitivity and specificity of US assessment of DOI of ≤ 5 mm or > 5 mm were 92.3% and 70.6%, respectively.

Conclusion: Intraoral US provides sufficient accuracy for the measurement of tumor DOI in oral tongue carcinoma and is complementary in assessing superficial lesions.

Level Of Evidence: 4. Laryngoscope, 128:2778-2782, 2018.
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http://dx.doi.org/10.1002/lary.27305DOI Listing
December 2018

Postoperative delirium after pharyngolaryngectomy with esophagectomy: a role for ramelteon and suvorexant.

Esophagus 2017 21;14(3):229-234. Epub 2017 Jan 21.

Department of Surgery, Keio University School of Medicine, Tokyo, Japan.

Background: Postoperative delirium is common after extensive surgery, and is known to be associated with sleeping medications. In this study, we aimed to investigate the relationships between sleeping medications and postoperative delirium after pharyngolaryngectomy with esophagectomy.

Methods: We performed a retrospective analysis of 65 patients who underwent pharyngolaryngectomy with esophagectomy at Shizuoka Cancer Center Hospital between January 2012 and March 2016. All data were assessed by two psychiatrists, and univariate and multivariate analyses were performed.

Results: Postoperative delirium developed in 9 (13.8%) patients, with most cases (77.8%) occurring between postoperative day (POD) 1 and POD 3. Of the 24 patients taking a minor tranquilizer after surgery, 8 (33.3%) became delirious, but, of the remaining 41 patients taking ramelteon with or without suvorexant, only one (2.4%) became delirious after surgery. Moreover, of the 16 patients taking both ramelteon and suvorexant, no postoperative delirium was observed. Ramelteon with or without suvorexant was significantly associated with a decreased rate of postoperative delirium compared with minor tranquilizer use ( = 0.001). Multivariate analysis confirmed that the use of ramelteon with or without suvorexant was the only significant preventive factor of postoperative delirium (odds ratio 0.060,  = 0.013).

Conclusion: The use of ramelteon with or without suvorexant was the only significant preventive factor of postoperative delirium after pharyngolaryngectomy with esophagectomy. However, using minor tranquilizers was associated with postoperative delirium. We recommend ramelteon with or without suvorexant for preventing postoperative delirium after pharyngolaryngectomy with esophagectomy.
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http://dx.doi.org/10.1007/s10388-017-0570-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5486448PMC
January 2017

Survival benefit of adding docetaxel, cisplatin, and 5-fluorouracil induction chemotherapy to concurrent chemoradiotherapy for locally advanced nasopharyngeal carcinoma with nodal Stage N2-3.

Jpn J Clin Oncol 2017 Aug;47(8):705-712

Division of Gastrointestinal Oncology, Shizuoka.

Background: Concurrent chemoradiotherapy followed by adjuvant chemotherapy (CCRT-AC) has been established as the standard of care in locally advanced nasopharyngeal carcinoma (LA-NPC). The survival benefit of induction chemotherapy (ICT) for LA-NPC remains controversial. We analyzed the efficacy and feasibility of docetaxel, cisplatin and 5-fluorouracil (TPF) ICT followed by CCRT for LA-NPC with nodal Stage N2-3.

Methods: We performed a retrospective analysis of 28 LA-NPC patients with nodal Stage N2-3 receiving induction TPF followed by CCRT (TPF group; n = 12) or CCRT-AC (CCRT group; n = 16) between October 2006 and May 2016.

Results: The median follow-up periods were 36.4 (range 6.7-55.2) and 40.1 months (range 4.3-99.0) for the TPF and CCRT groups, respectively. One- and three-year overall survival for the TPF group vs. the CCRT group were 100% and 100% vs. 94% and 75%, respectively (P = 0.21). The cumulative one- and three-year incidences of locoregional recurrence or progression for the TPF group vs. the CCRT group were 10% and 21% vs. 16% and 32% (P = 0.49), and those of distant metastasis were 0% and 0% vs. 26% and 26%, respectively (P = 0.08). The common Grade 3-4 acute toxicities were neutropenia, anorexia, febrile neutropenia, and stomatitis in the TPF group. The Grade 3-4 late toxicities did not differ significantly between the two groups.

Conclusions: This study suggests that induction TPF followed by CCRT might reduce distant metastasis, so this combination may be feasible for the treatment of LA-NPC with nodal Stage N2-3.
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http://dx.doi.org/10.1093/jjco/hyx057DOI Listing
August 2017

Comparison of curative surgery and definitive chemoradiotherapy as initial treatment for patients with cervical esophageal cancer.

Dis Esophagus 2017 02;30(2):1-5

Gastrointestinal Oncology, Shizuoka Cancer Center, 1007 Shimonagakubo Nagaizumi-cho Sunto-gun, Shizuoka, Japan.

Esophagectomy and definitive chemoradiotherapy are recognized standard initial treatment modalities for cervical esophageal cancer. The goal of this study was to compare the treatment outcomes of curative surgery with those of chemoradiotherapy in patients who had potentially resectable tumor and who were candidates for surgery. We evaluated the data from 49 consecutive patients who were diagnosed with potentially resectable cervical esophageal cancer and who were deemed candidates for surgery. Thirteen patients were included in the surgery group, and 36 patients were included in chemoradiotherapy group. Baseline characteristics were balanced between the two groups. In the chemoradiotherapy group, the complete response rate was 58.3%. There was no significant difference in 5-year overall survival when comparing the surgery group and the chemoradiotherapy group (surgery, 60.6%; chemoradiotherapy, 51.4%; P = 0.89). In the chemoradiotherapy group, of the 15 patients who failed to respond to initial treatment, 11 patients subsequently underwent salvage surgery. In conclusion, curative surgery and chemoradiotherapy as initial treatment for cervical esophageal cancer have comparable survival outcomes. Chemoradiotherapy should be selected as the initial larynx-preserving treatment for patients with cervical esophageal cancer although chemoradiotherapy non-responders require additional treatment, including salvage surgery.
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http://dx.doi.org/10.1111/dote.12502DOI Listing
February 2017

Comparison of Salvage Total Pharyngolaryngectomy and Cervical Esophagectomy Between Hypopharyngeal Cancer and Cervical Esophageal Cancer.

Ann Surg Oncol 2017 Mar 6;24(3):778-784. Epub 2016 Oct 6.

Division of Head and Neck Surgery, Shizuoka Cancer Center, Shizuoka, Japan.

Background: Total pharyngolaryngectomy and cervical esophagectomy (TPLCE) after chemoradiotherapy remains a challenge because of the high rate of complications and few available data on outcomes and safety. The purpose of this study was to evaluate the clinical significance of salvage TPLCE and to compare treatment outcomes between hypopharyngeal cancer and cervical esophageal cancer.

Methods: Data from 37 consecutive patients who were diagnosed with potentially resectable hypopharyngeal and cervical esophageal cancer after chemoradiotherapy were retrospectively analyzed. The survival and surgical outcomes were investigated between the hypopharyngeal cancer and cervical esophageal cancer groups.

Results: Twenty-six patients were included in hypopharyngeal cancer group and 11 patients were included in cervical esophageal cancer group. The baseline characteristics were balanced between the two groups. Compared to the hypopharyngeal cancer group, the cervical esophageal cancer group had significantly more frequent tracheal-related complications (p < 0.05) and stronger association of distal margin of the cervical esophagus and radiation field with tracheal ischemia after salvage surgery.

Conclusions: Salvage TPLCE can offer the exclusive chance of prolonged survival. Association of tracheal ischemia with salvage TPLCE was seen more frequently for cervical esophageal cancer. Therefore, the indication for salvage TPLCE must be carefully considered to maintain the balance between curability and safety.
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http://dx.doi.org/10.1245/s10434-016-5474-yDOI Listing
March 2017

Risk factors for complications after pharyngolaryngectomy with total esophagectomy.

Esophagus 2016 31;13(4):317-322. Epub 2016 Mar 31.

Department of Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582 Japan.

Background: Pharyngolaryngectomy with total esophagectomy (PLTE) is an effective surgical treatment for synchronous or metachronous hypopharyngeal or laryngeal cancer and thoracic esophageal cancer, although it is more invasive than esophagectomy and total pharyngolaryngectomy. The aim of this study was to identify risk factors for complications after PLTE.

Methods: From November 2002 to December 2014, a total of 8 patients underwent PLTE at the Shizuoka Cancer Center Hospital, Shizuoka, Japan. We investigated the clinicopathological characteristics, surgical procedures, and postoperative complications of these patients.

Results: Of the 8 patients, 5 underwent one-stage PLTE and 3 underwent staged PLTE. There was no mortality in this study. Two cases of tracheal necrosis, two of anastomotic leakage, and one of ileus were observed as postoperative complications. Two patients who underwent one-stage PLTE with standard mediastinal lymph node dissection developed tracheal necrosis and severe anastomotic leakage.

Conclusion: One-stage PLTE and standard mediastinal lymph node dissection were identified as the risk factors for severe postoperative complications. Staged PLTE or transhiatal esophagectomy should be considered when PLTE is performed and standard mediastinal lymph node dissection should be avoided when one-stage PLTE is performed with transthoracic esophagectomy.
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http://dx.doi.org/10.1007/s10388-016-0533-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5025499PMC
March 2016

Quality of life and functional status of terminally ill head and neck cancer patients: a nation-wide, prospective observational study at tertiary cancer centers in Japan.

Jpn J Clin Oncol 2017 Jan 27;47(1):47-53. Epub 2016 Sep 27.

Department of Palliative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo.

Background: Little is known about quality of life and functional status of patients with terminally ill head and neck cancers.

Methods: We conducted a multicenter, prospective, observational study to examine quality of life and functional status in terminally ill head and neck cancer patients.

Results: Of the 100 patients meeting inclusion criteria, 72 were observed until death. There was no significant difference in the quality of life score between baseline and Week 3. Forty patients (54.9%) could speak and 22 patients (30.5%) could have oral intake upon study entry. Fifty-three patients (74.6%) received enteral nutrition. Twenty-six patients (36.6%) required dressing changes for fungating tumors. The route of nutritional intake (nasogastric tube vs. percutaneous gastric tube) might be predictive for the duration of hospital stay (64 vs. 21 days, P = 0.0372).

Conclusion: There was no significant relationship between quality of life and functional status seen in this study. Feeding tube type could have the most impact on quality of life.
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http://dx.doi.org/10.1093/jjco/hyw138DOI Listing
January 2017

Prognostic Factors and Multidisciplinary Postoperative Chemoradiotherapy for Clinical T4a Tongue Cancer.

Oncology 2016 7;91(2):78-84. Epub 2016 Jun 7.

Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, Japan.

Objective: The prognosis of patients with locally advanced squamous cell carcinoma (SCC) of the tongue is poor. Postoperative chemoradiotherapy (CRT) improves locoregional control and survival in high-risk patients. We investigated the prognostic factors for clinical T4a tongue SCC, and elucidated whether postoperative CRT has a benefit for patients with poor prognosis in terms of survival.

Methods: We performed a retrospective analysis of 61 patients with stage T4a SCC of the tongue who underwent primary resection and neck dissection.

Results: The median follow-up was 53.8 months. Multivariate analysis revealed a 4.26× relative risk of death for patients with the involvement of ≥5 regional lymph nodes (pN ≥5) compared with those with pN 0-4 (p = 0.002). In Kaplan-Meier analysis, patients with pN ≥5 who received CRT had longer overall survival rates than those who did not (hazard ratio = 0.31; p = 0.041).

Conclusions: pN ≥5 is the most powerful prognostic factor for clinical T4a SCC of the tongue. Postoperative CRT is recommended in patients with pN ≥5.
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http://dx.doi.org/10.1159/000446439DOI Listing
January 2017

Incidence and risk factors for postoperative delirium after major head and neck cancer surgery.

J Craniomaxillofac Surg 2016 Jul 26;44(7):890-4. Epub 2016 Apr 26.

Department of Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.

Background: Postoperative delirium is a common and serious complication after extensive surgery. This study aimed to investigate the incidence and risk factors for postoperative delirium after major head and neck cancer surgery.

Methods: A retrospective analysis was performed for 293 patients who underwent major head and neck cancer surgery lasting >6 h at our institution between January 2012 and November 2015. All data were assessed by two psychiatrists. Univariate and multivariate analyses were performed.

Results: Postoperative delirium developed in 50 (17.1%) patients; most cases (84.0%) of postoperative delirium were observed between postoperative day (POD) 1 and POD 3. Multivariate analysis revealed that an age >70 years was the significant risk factor for postoperative delirium incidence after major head and neck cancer surgery; the multivariate hazard ratio was 3.935 (95% confidence interval 1.873-8.265, p < 0.001).

Conclusions: Most cases of postoperative delirium after major head and neck cancer surgery were observed between POD 1 and POD 3, and a multivariate analysis revealed that an age >70 years was a significant risk factor for postoperative delirium incidence. Clinicians should pay particular attention to the possibility of delirium incidence during the first 3 days after surgery for patients aged >70 years.
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http://dx.doi.org/10.1016/j.jcms.2016.04.032DOI Listing
July 2016

Safety and efficacy of concurrent carboplatin plus radiotherapy for locally advanced head and neck cancer patients ineligible for treatment with cisplatin.

Jpn J Clin Oncol 2015 Dec 29;45(12):1116-21. Epub 2015 Sep 29.

Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka.

Objective: Cisplatin-based chemoradiotherapy is the standard treatment for patients with locally advanced squamous cell carcinoma of the head and neck. However, patients with advanced age, renal, cardiac or neurogenic dysfunction seem ineligible for cisplatin treatment. We evaluated the safety and efficacy of concurrent carboplatin plus radiotherapy in patients ineligible for cisplatin usage.

Methods: We retrospectively analyzed the records of 25 consecutive locally advanced squamous cell carcinoma of the head and neck patients who received concurrent carboplatin plus radiotherapy at Shizuoka Cancer Center between August 2006 and March 2014. Carboplatin was administered tri-weekly or weekly.

Results: Patient characteristics were analyzed. The median age was 75 years (range, 54-82), male:female ratio, 24:1; performance status, 0-1 (23) or 2 (2); primary tumor site, oropharynx (10), hypopharynx (12), larynx (1) or oral cavity (2); Stage III (3), IVa (19) or IVb (3); induction chemotherapy, with (2) or without (23); and a median creatinine clearance of 62 ml/min (range, 37-117). The main reasons for choosing carboplatin were age (40%), renal impairment (36%) and cardiac dysfunction (20%). All patients received a planned irradiation dose of 70 Gy. Median follow-up was 30.9 months. Complete response was observed 70% patients. Median progression-free survival duration was 42.7 months. Median overall survival could not be analyzed. The 2-year progression-free and overall survival rates were 68 and 74%, respectively. The main toxicity Grade 3 or 4 was oral mucositis (56%), thrombocytopenia (34%), neutropenia (28%) and infection (24%).

Conclusions: Concurrent carboplatin plus radiotherapy is tolerated and may be an option in treating locally advanced squamous cell carcinoma of the head and neck patients ineligible for treatment with cisplatin.
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http://dx.doi.org/10.1093/jjco/hyv142DOI Listing
December 2015

Distinctive mucositis and feeding-tube dependency in cetuximab plus radiotherapy for head and neck cancer.

Jpn J Clin Oncol 2015 Feb 23;45(2):183-8. Epub 2014 Nov 23.

Division of Head and Neck Surgery, Shizuoka Cancer Center, Shizuoka.

Objective: Prophylactic percutaneous endoscopic gastrostomy may be considered before chemoradiotherapy for patients with locally advanced head and neck squamous cell carcinoma, because severe mucositis is a common complication. We evaluated the mucosal findings and necessity of prophylactic percutaneous endoscopic gastrostomy in patients with head and neck squamous cell carcinoma receiving cetuximab and radiotherapy.

Methods: Fourteen consecutive patients with locally advanced head and neck squamous cell carcinoma receiving cetuximab and radiotherapy were analyzed.

Results: Patients' backgrounds were as follows: male/female, 8/6; median age, 64.5 years (range, 35-83 years); performance status, 0/1, 9/5. Primary tumor sites included the oropharynx, hypopharynx and larynx in four, seven and three patients, respectively. Patients completed a median of eight cetuximab cycles. All patients received three-dimensional conformal radiotherapy (median dose, 70 Gy). Thirteen patients were treated with elective neck irradiation at the ipsilateral (n = 3) or bilateral (n = 10) nodes. Grade ≥ 3 mucositis/stomatitis (clinical examination) occurred in 85.7% patients (n = 12). The median irradiation dose was 33 Gy at the Grade 3 mucositis onset. Eight patients showed mucositis with distinctive features, a wide range of white-coated lesions with a clear border; hypopharyngeal atresia was observed in two patients. Prophylactic percutaneous endoscopic gastrostomy was performed in 11 patients, and 11 patients (78.6%) actually required nutritional support because of Grade ≥ 3 mucositis/stomatitis (functional/symptomatic).

Conclusions: Prophylactic percutaneous endoscopic gastrostomy is recommended because most patients receiving cetuximab and radiotherapy for locally advanced head and neck squamous cell carcinoma have Grade ≥ 3 mucositis with distinctive features.
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http://dx.doi.org/10.1093/jjco/hyu196DOI Listing
February 2015

Efficacy and feasibility of docetaxel, cisplatin, and 5-fluorouracil induction chemotherapy for locally advanced head and neck squamous cell carcinoma classified as clinical nodal stage N2c, N3, or N2b with supraclavicular lymph node metastases.

Int J Clin Oncol 2015 Jun 25;20(3):455-62. Epub 2014 Sep 25.

Division of Gastrointestinal Oncology, Shizuoka Cancer Center, 1007 Shimonagakubo Nagaizumi Sunto-gun, Shizuoka, 411-8777, Japan.

Background: We evaluated the efficacy and feasibility of docetaxel, cisplatin, and 5-fluorouracil (TPF) induction chemotherapy followed by concurrent chemoradiotherapy (CRT) for locally advanced head and neck squamous cell carcinoma (HNSCC) with a high risk of distant metastases compared with CRT alone.

Methods: We retrospectively analyzed 29 HNSCC patients with clinical nodal stage N2c, N3, or N2b disease and supraclavicular lymph node metastases receiving CRT alone (CRT group; n = 16) or TPF induction chemotherapy followed by CRT (TPF group; n = 13) between April 2008 and May 2012.

Results: The median follow-up periods were 14.5 (range 5.0-65.0) and 25.0 (range 14.0-32.0) months for CRT and TPF groups, respectively. A greater proportion of patient characteristics in the CRT group had advanced T and N stages. The overall response rate to induction TPF was 50.0%; grade 3-4 toxicities included neutropenia, febrile neutropenia, anorexia, and hyponatremia. Complete response rates after CRT completion were 55.5% in the TPF and 42.9% in the CRT group; median overall survival was not reached in the TPF group and was 14.0 months in the CRT group (p = 0.037). Multivariate analysis revealed that induction TPF and T stage were independent prognostic factors [hazard ratio (HR) = 0.196; 95% confidence interval (CI) 0.043-0.898; p = 0.036, HR = 9.966; 95% CI 2.270-43.75; p = 0.002, respectively).

Conclusion: TPF followed by CRT is tolerated and may be an option for the treatment of locally advanced stage N2c, N3, or N2b HNSCC.
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http://dx.doi.org/10.1007/s10147-014-0749-4DOI Listing
June 2015

MUC expression in adenosquamous carcinoma of the head and neck regions of Japanese patients: immunohistochemical analysis.

Pathol Int 2014 Mar;64(3):104-14

Pathology Division, Shizuoka Cancer Center, Sunto-gun, Shizuoka, Japan.

Adenosquamous carcinoma (ASC) is a rare malignant neoplasm of the head and neck regions. We elucidated the relationship between ASC and MUC molecule expression. We selected 14 cases of ASC in the head and neck, and examined them immunohistohcmically. Seven cases of tongue, 3 cases of larynx and 4 cases of hypopharynx carcinoma were selected. Nine (64.3%) of 14 cases showed lymph node metastasis at the diagnosis. Laryngeal and hypopharyngeal cases showed a higher stage. Six cases (66.7%), all of which showed lymph node metastases, died of disease. Immunohistochemical examinations showed that ASC was positive for both markers of squamous cell carcinoma and adenocarcinoma. ASC showed positivity for MUC1 (13 cases: 92.3%), MUC1core (12 cases: 85.2%) and MUC4 (12 cases: 85.7%). In rare ASC of the head and neck region, it was revealed that MUC1 and MUC4 expression might be associated with its nodal status.
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http://dx.doi.org/10.1111/pin.12144DOI Listing
March 2014

Squamous cell carcinoma with rhabdoid features of the gingiva: a case report with unusual histology.

Med Mol Morphol 2014 Dec 27;47(4):240-5. Epub 2013 Dec 27.

Pathology Division, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan,

Squamous cell carcinoma (SCC) with rhabdoid features (SCCRF) is extremely rare in the oral cavity. We report herein a case of oral SCCRF. The patient was a 69-year-old Japanese woman who had been suffering from a mass in the right lower gingiva. Right hemi-mandibulectomy was performed. The gingival tumor was composed of pleomorphic, non-cohesive ovoid tumor cells with abundant cytoplasm and eccentric nuclei, which were positive for both pan-cytokeratin and vimentin. In another portion, moderately differentiated SCC and carcinoma in situ were also seen. A transition zone existed between the components. Finally, we diagnosed SCCRF. Four months after the operation, multiple bone metastases, lung and skin metastases and marked hypercalcemia were found. SCCRF, therefore, might be more aggressive than the usual type of oral SCC.
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http://dx.doi.org/10.1007/s00795-013-0066-4DOI Listing
December 2014

Salivary duct carcinoma with rhabdoid features: report of 2 cases with immunohistochemical and ultrastructural analyses.

Head Neck 2014 Mar 17;36(3):E28-35. Epub 2013 Dec 17.

Pathology Division, Shizuoka Cancer Center, Shizuoka, Japan.

Background: Salivary duct carcinoma with rhabdoid features is extremely rare.

Methods: We report 2 cases of salivary duct carcinoma with rhabdoid features treated at our institution.

Results: Case 1 was a 44-year-old Japanese man who had swelling in the left parotid region. This tumor consisted of residual pleomorphic adenoma and widely invasive carcinoma, which showed a diffuse growth pattern by atypical rhabdoid cells. Case 2 was a 66-year-old Japanese man who had swelling of the right cervical region. This submandibular tumor was also composed of both residual pleomorphic adenoma region and invasive adenocarcinoma components, whereas some metastatic lesions were purely composed of rhabdoid cells. Such cells were strongly and diffusely positive for cytokeratins (CKs), gross cystic disease fluid protein-15 (GCDFP), and androgen receptor (AR). Case 1 was also positive for Her-2 and p53.

Conclusion: Both patients were diagnosed with carcinoma ex pleomorphic adenoma and their carcinomatous components were composed of salivary duct carcinoma with rhabdoid features, which is a highly aggressive tumor, similar to salivary duct carcinoma.
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http://dx.doi.org/10.1002/hed.23466DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4296234PMC
March 2014

Is postoperative adjuvant chemoradiotherapy necessary for high-risk oropharyngeal squamous cell carcinoma?

Int J Clin Oncol 2014 Feb 5;19(1):38-44. Epub 2013 Mar 5.

Division of Gastrointestinal Oncology, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi, Sunto-gun, Shizuoka, 411-8777, Japan,

Background: High-risk factors for recurrence of head and neck squamous cell carcinoma after surgical resection include involvement of ≥ 2 regional lymph nodes, extracapsular spread, and microscopic involvement of resected mucosal margins. Adjuvant chemoradiotherapy is thought to improve postoperative locoregional control and survival. In this paper, we evaluate the efficacy of adjuvant therapy for high-risk oropharyngeal squamous cell carcinoma (OPSCC) (i.e., with ≥ 2 lymph nodes, positive extracapsular spread, or positive margins).

Methods: This is a retrospective analysis of 45 high-risk OPSCC patients who underwent surgery without adjuvant therapy (n = 19), with radiotherapy (n = 17), or with chemoradiotherapy (n = 9).

Results: The median follow-up period was 41.0 months. Radiotherapy patients showed a trend toward longer overall survival than patients without adjuvant therapy [hazard ratio (HR) = 0.32, p = 0.176]. However, overall survival for the chemoradiotherapy group seemed to be the same as that for the no adjuvant therapy group (HR = 0.79, p = 0.779). Multivariate analysis found that the relative risk of recurrence for patients without adjuvant therapy compared with any adjuvant therapy was 3.02 (p = 0.101). The relative recurrence risk in radiotherapy patients was 0.95 compared with that in chemoradiotherapy patients (p = 0.971). However, pathological T-stage was significantly associated with disease-free survival for high-risk OPSCC.

Conclusions: Although the current study uses data from a small retrospective sample of patients, our results suggest that the addition of chemotherapy to radiotherapy may not be necessary as an adjuvant therapy for all high-risk OPSCC. A novel prognostic factor, such as pathological T-stage, should be considered for selecting those patients with high-risk OPSCC who would benefit from adjuvant therapy.
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http://dx.doi.org/10.1007/s10147-013-0532-yDOI Listing
February 2014

Mucosal large cell neuroendocrine carcinoma of the head and neck regions in Japanese patients: a distinct clinicopathological entity.

J Clin Pathol 2012 Aug 20;65(8):704-9. Epub 2012 Jun 20.

Pathology Division, Shizuoka Cancer Center Hospital and Research Institute, Shizuoka, Japan.

Backgrounds: Large cell neuroendocrine carcinoma (LCNEC) is well-known as a lung cancer subtype. This study assessed the prevalence of head and neck mucosal LCNEC (M-LCNEC).

Methods: M-LCNEC was studied clinically, histologically and immunohistochemically.

Results: Of 814 surgically resected cases of mucosal head and neck carcinoma, only eight cases (0.98%; all men, mean age 64.6 years) were rediagnosed as M-LCNEC. They occurred in the oropharynx (n=3), larynx (n=4) and hypopharynx (n=1). Seven of the cases had regional lymph node metastases and four resulted in death. Histologically, M-LCNEC had a sheet-like trabacular organoid growth pattern of relatively large basaloid cells in which central necrosis, rosette formation, peripheral palisading and high mitotic figures were evident. M-LCNEC was immunopositive for two or three neuroendocrine markers (CD56, chromogranin-A and synaptophysin). All cases showed high proliferative activity.

Conclusion: M-LCNEC in the head and neck regions is a distinct histopathological entity whose positivity for neuroendocrine markers makes its diagnosis important. As about half of the patients died of the disease, M-LCNEC has a relatively poor prognosis.
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http://dx.doi.org/10.1136/jclinpath-2012-200801DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3410299PMC
August 2012

Osteoclast-type giant cell tumor of minor salivary gland with mucin-rich salivary duct carcinoma: a case report of unusual histology with immunohistochemical analysis.

Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2010 Jun 25;109(6):870-7. Epub 2010 Mar 25.

Pathology Division, Shizuoka Cancer Center Hospital and Research Institute, Shizuoka, Japan.

Objective: Salivary giant cell tumor (GCT) is exceedingly rare. This article presents an additional rare case of salivary GCT with salivary duct carcinoma (SDC).

Study Design And Results: The patient was a 40-year-old Japanese male. The peripheral region of the tumor showed SDC and partly revealed a mucin accumulation with cancer nests, which was a mucin-rich variant of SDC. In the central region of the tumor, mononuclear ovoid tumor cells contained osteoclastic-type giant cells. SDC showed immunopositivity for gross cystic disease fluid protein-15 (GCDFP-15), androgen receptor (AR), and Her-2, whereas the giant cell lesion was negative for GCDFP-15, AR, and Her-2. Mononuclear cells in salivary GCT showed immunopositivity for epithelial membrane antigen and p53.

Conclusion: The salivary GCT was thought to be neoplastic and derived from epithelial cells. The present case is the first de novo case of intraoral salivary GCT with a mucin-rich variant of SDC.
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http://dx.doi.org/10.1016/j.tripleo.2009.12.021DOI Listing
June 2010

Simultaneous squamous cell carcinoma with leiomyosarcoma of the larynx.

Auris Nasus Larynx 2009 Apr 9;36(2):239-43. Epub 2008 Jul 9.

National Cancer Center Hospital East, Kashiwa-City, Chiba, Japan.

Objective: To present the first reported case of a simultaneous squamous cell carcinoma with a leiomyosarcoma of the larynx, our treatment of the patient, and the 9-month follow-up results.

Study Design: Case study.

Methods: Review of diagnostic studies, the operative technique, and the patient's chart for the 9-month period after treatment.

Results: A case with double laryngeal tumors with simultaneous evolution but different histological patterns is described. The squamous cell carcinoma and leiomyosarcoma involved both the vocal cords and the anterior commissure. A partial laryngectomy was performed, and the patient has been free of disease for 9 months.

Conclusions: Multiple laryngeal tumors are exceedingly rare. To our knowledge, no previous reports of a simultaneous squamous cell carcinoma and a leiomyosarcoma of the larynx have been reported. Both tumors were not invasive in this case, so conservation surgery was feasible.
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http://dx.doi.org/10.1016/j.anl.2008.05.012DOI Listing
April 2009

Dedifferentiated epithelial-myoepithelial carcinoma of the parotid gland: a rare case report of immunohistochemical analysis and review of the literature.

Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2008 Jul 16;106(1):85-91. Epub 2008 Apr 16.

Pathology Division, Shizuoka Cancer Center Hospital and Research Institute, Shizuoka, Japan.

Dedifferentiation of salivary gland neoplasms is a rare event, unlike bone and soft part sarcomas, which was first described by Stanley et al. in 1988. An additional case of dedifferentiated epithelial-myoepithelial carcinoma (EMC) is reported here. The patient was a 70-year-old Japanese man who requested examination of the rapid growth of a mass in the right parotid region, which he had first noticed 25 years previously. Clinical examination showed an ill-circumscribed, 6.8 x 4.7 x 7.0-cm lesion. Histologically, most parts of the lesion were high-grade carcinoma (HGC) with sheetlike and nestlike growth of markedly atypical cells and comedonecrosis, whereas the minor part consisted of typical EMC. The outer clear cells of EMC were positive for alpha-smooth muscle actin (ASMA), p63, cytokeratin (CK) 14, and vimentin, and the inner ductal cells of EMC were positive for CKs and epithelial membrane antigen. HGC was negative for ASMA, CK14, and vimentin, but diffusely positive for p53 protein and cyclin D1. The Ki-67 labeling index of EMC was 11.5%, whereas that of HGC was 67.1%. These findings and a review of literature indicate that HGC arose from preexisting EMC, and this phenomenon is the dedifferentiation of EMC. Dedifferentiated EMC is extremely rare.
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http://dx.doi.org/10.1016/j.tripleo.2008.01.013DOI Listing
July 2008

Alveolar soft part sarcoma of the larynx: a case report of an unusual location with immunohistochemical and ultrastructural analyses.

Head Neck 2008 Sep;30(9):1257-63

Pathology Division, Shizuoka Cancer Center Hospital and Research Institute, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka 411-8777, Japan.

Background: Alveolar soft part sarcoma (ASPS) is a rare mesenchymal neoplasm of uncertain origin. In this article, we report a case of ASPS occurring in the larynx, an extremely rare location for this rather unusual tumor.

Methods And Results: The patient was a 34-year-old Japanese woman who requested an examination for hoarseness. The tumor showed a proliferation of large polygonal cells with periodic-acid-Schiff-positive diastase-resistant intracytoplasmic granules, arranged in an alveolar growth pattern. The cytoplasm of the tumor cells was eosinophilic. Tumor cells were positive for vimentin and titin. Nuclear immunoreactivity for TFE3 was observed, and the Ki-67 labeling index was 14.7%. Ultrastructurally, electron-dense rod-shaped crystals were infrequently observed in the cytoplasm. This case was finally diagnosed as ASPS of the larynx.

Conclusion: We discuss the histogenesis and differential diagnosis of ASPS with immunohistochemical and ultrastructural findings. TFE3 immunohistochemistry was found to be a very useful marker for the diagnosis of ASPS.
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http://dx.doi.org/10.1002/hed.20766DOI Listing
September 2008