Tomoyuki Kamijo

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

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.

Hyaluronan synthase expression in pleural malignant mesotheliomas

Hyaluronan (HA) is thought to play several important roles in tumor growth, tumorigenicity, and tumor dissemination and metastasis. Recently, three isoforms of hyaluronan synthase (HAS) have been cloned. Our objective was to determine which of the HAS isoforms were expressed in pleural malignant mesotheliomas, the most representative lesion of HA-producing tumors. We studied 10 cases of pleural malignant mesothelioma using novel antibodies of HAS. We compared HAS expression patterns of mesothelioma and pulmonary adenocarcinoma. Immunohistochemically, 9 of 10 (90%) cases of mesothelioma had extensive reaction to anti-HAS1 and anti-HAS2 antibodies, while HAS3 overexpression was present in 4 of 10 cases (40%). Of 20 cases of pulmonary adenocarcinoma, 5 overexpressed HAS1 (25%), 16 of 20 HAS2 (80%), and 4 of 20 HAS3 (20%). The expression level of HAS1 was significantly higher in mesotheliomas than in pulmonary adenocarcinoma (P=0.0036). Our data suggests that HAS1 might be a useful positive marker of malignant mesothelioma. However, a definitive conclusion should be based on further large-scale studies.

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

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.

Topographical distribution of allelic loss in individual lung adenocarcinomas with lymph node metastases

Adenocarcinomas of the lung are characterized by morphological heterogeneity, and since carcinogenesis has been suggested to be a multistep process involving sequential accumulation of multiple genetic alterations, the morphological heterogeneity may represent a cross-sectional view of genetic alterations within individual tumors. Therefore, to elucidate whether, and which, genetic alterations accumulated in relation to morphological cancer progression, we examined 56 microdissected sites for topographical distribution of loss of heterozygosity (LOH) in 12 adenocarcinomas of the lung with bronchioloalveolar (BA) and invasive components in their primary tumors and metastases to lymph nodes. The morphological changes from noninvasive BA lesions to invasive and metastatic components were characterized by a significant rise in the prevalence of allelic losses (P<0.05). Individually, eight cases (67%) showed accumulation of genetic alterations from BA lesions to metastases. LOHs in multiple foci in one case were compared to determine whether they were shared at all tumor sites as an early event or localized in metastases as an additional event. LOHs at 5q and 17p may be crucial steps in the early phase of development to metastasis, while 18q loss may be an additional step. These findings suggested that the cancer cells in some pulmonary adenocarcinomas evolved from the BA lesions to the invasive and metastatic lesions.

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

Salivary duct carcinoma with rhabdoid features is extremely rare.

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

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.

Simultaneous squamous cell carcinoma with leiomyosarcoma of the larynx

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 patients 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.

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

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.

Risk factors for complications after pharyngolaryngectomy with total esophagectomy

BackgroundPharyngolaryngectomy 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.MethodsFrom 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.ResultsOf 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.ConclusionOne-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.

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

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.