Chemoradiotherapy and Lymph Node Metastasis Affect Dendritic Cell Infiltration and Maturation in Regional Lymph Nodes of Laryngeal Cancer.

Dendritic cells (DCs) are the most specialized antigen-presenting cells, and lymph nodes (LNs) play an important role in the DC-mediated T-cell response. We evaluated the infiltration of CD1a-positive DCs (CD1a-DCs), i.e., immature DCs, and S100-positive dendritic cells (S100-DCs), a mixture of immature and mature DCs, in 73 cases of laryngeal cancer and its regional LNs. Among them, 31 patients underwent radiotherapy (RT) or chemoradiotherapy (CRT) prior to surgery. No significant difference was found for CD1a-DC infiltration in the primary tumors, metastatic LNs and non-metastatic LNs, while S100-DCs were significantly fewer in number in the primary tumors and metastatic LNs compared to non-metastatic LNs. The cases which showed a high infiltration of S100-DCs in the metastatic LNs appeared to show a favorable prognosis, although statistical significance was not reached. In the RT/CRT group, the infiltration of the CD1a-DCs and S100-DCs was less in the primary tumors and metastatic LNs compared to the treatment-naive group. Conversely, the RT/CRT group showed higher CD1a-DC and S100-DC numbers in the non-metastatic LNs compared to the treatment-naïve group. Thus, DC maturation in metastatic LNs plays an important role in tumor immunity in laryngeal cancer, and the infiltration of DCs into the primary tumor and metastatic LNs is impaired by RT/CRT.

Collision tumor of a papillary and follicular thyroid carcinoma: a case report.

BACKGROUND: Papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC) are common differentiated thyroid cancers, but the detection of a collision tumor is an extremely rare event. CASE PRESENTATION: The patient was a 69-year-old Japanese female with multiple cervical lymph node swellings and a thyroid tumor. Preoperative fine needle aspiration cytology of the enlarged lymph node revealed a cytological diagnosis of papillary thyroid carcinoma (PTC). A total thyroidectomy, right cervical dissection and paratracheal dissection were performed. Histopathological and immunohistochemical analyses of resected specimens revealed a collision tumor of PTC and FTC. Multiple metastases of papillary carcinoma were found in the dissected lymph nodes. In the PTC lesion, IHC for BRAF (V600E) was positive but negative for the FTC lesion. Genetic analyses further revealed a TERT promoter C228T mutation in PTC and a NRAS codon 61 mutation in FTC. The patient died of recurrent cancer 8 months after surgery. CONCLUSIONS: A case of a collision tumor of PTC and FTC is very rare, and even fewer cases have been subjected to genetic scrutiny. The present case was successfully diagnosed by pathological examination using immunohistochemical and genetic analyses. The TERT promoter mutation in the PTC lesion was consistent with the aggressive behavior of the cancer.

Cetuximab Plus Concurrent Radiotherapy in Patients With Nasopharyngeal Carcinoma.

BACKGROUND/AIM: Several reports have evaluated the efficacy and safety of concurrent radiotherapy with cetuximab (BRT) in patients with nasopharyngeal carcinoma (NPC). Combination therapy with cetuximab can be a treatment option for NPC. Although clinical data regarding the efficacy and safety of BRT without induction chemotherapy (ICT) or adjuvant chemotherapy is essential for the development of new therapeutic strategies, such data are rarely reported. PATIENTS AND METHODS: We retrospectively investigated a series of patients with NPC treated in our institution to evaluate the efficacy and safety of BRT. Eleven patients with newly diagnosed NPC were identified from an inpatient database from July 2015 to April 2018. Seven patients who received BRT were reviewed. RESULTS: All patients completed BRT without cessation of treatment. Six (85.7%) patients achieved a complete response and one (14.3%) achieved stable disease. The response rate was 85.7%. All patients with ≤T3 disease achieved a complete response. Both patients with T3 disease developed local recurrence, and one of the four patients with T1-2 disease developed distant metastases. The 1- and 3-year overall survival rates were 85.7% and 47.6%, respectively. The most common adverse events (AEs) were pharyngeal mucositis (100%), radiation dermatitis (100%), anorexia (28.6%), weight loss (28.6%), acneiform rash (28.6%), and dry mouth (28.6%). Grade 3 AEs were pharyngeal mucositis (42.9%), radiation dermatitis (28.6%), and anorexia (14.3%). No grade 4/5 AEs were observed. CONCLUSION: BRT for NPC was tolerable, but our findings suggest that BRT without induction chemotherapy or adjuvant chemotherapy is insufficient at least for ≥T3 disease.

WPOI-4/5 Correlates With Lymph Node Recurrence and Poor Prognosis in Early-stage Tongue Squamous Cell Carcinoma.

BACKGROUND/AIM: Neck management in patients with early-stage tongue cancer remains controversial. The worst pattern of invasion (WPOI) of the primary tumor has been associated with the incidence of regional metastasis. We investigated the prognostic role of WPOI, especially in relation to regional lymph node recurrence and disease-specific survival (DSS). PATIENTS AND METHODS: We retrospectively reviewed medical records and evaluated tumor specimens of 38 patients with early-stage tongue cancer who underwent primary tumor resection without elective neck dissection. RESULTS: Regional lymph node recurrence rates were significantly higher in patients with WPOI-4/5 compared with WPOI-1 to -3. The 5-year DSS rates were significantly higher for WPOI-1 to -3 than for WPOI-4/5. Notably, patients with WPOI-1 to -3 achieved a 100% 5-year DSS rate with salvage neck dissection and postoperative treatment, even those with cervical lymph node recurrence, whereas patients with WPOI-4/5 had a poorer prognosis. CONCLUSION: Patients with WPOI-1 to -3 tumors can be followed up without neck dissection until regional lymph node recurrence is detected, with a good course after salvage treatment. In contrast, patients with WPOI-4/5 tumors who are followed up until the appearance of regional lymph node recurrence have a poor prognosis, even with adequate treatment for recurrent disease.

Induction Chemotherapy With 5-Fluorouracil, Cisplatin, and Cetuximab in Advanced Head and Neck Squamous Cell Carcinoma.

BACKGROUND/AIM: Chemoradiotherapy (CRT) with high-dose cisplatin has become the standard of care for larynx preservation in patients with locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN). However, the long-term results are unsatisfactory. Induction chemotherapy (ICT) with docetaxel/cisplatin/5-fluorouracil (TPF) is associated with hematologic toxicity, and a safer therapy with comparable efficacy is desired. We conducted a pilot study to investigate the efficacy and safety of 5-fluorouracil/cisplatin/cetuximab (FPE) therapy as a candidate regimen for ICT in comparison with TPF. PATIENTS AND METHODS: Patients with stage cN2/3 LA-SCCHN of the larynx/oropharynx/hypopharynx were treated with FPE or TPF followed by radiotherapy. We reviewed patients' medical records and evaluated treatment efficacy and safety retrospectively. RESULTS: The response rates for ICT and ICT-radiotherapy were 71% and 93%, respectively, in the FPE group and 90% and 89%, respectively, in the TPF group. The 1-year progression-free and overall survival rates were 57% and 100%, respectively, in the FPE group and 70% and 90%, respectively, in the TPF group. TPF was linked to significantly higher rates of Grade 3/4 hematologic toxicity during ICT. The rates of Grade 3 or higher toxicity did not differ between the two groups during radiotherapy. CONCLUSION: The efficacy of ICT was comparable between the FPE and TPF groups, whereas FPE was associated with less toxicity. It is suggested that FPE therapy is an alternative ICT regimen to TPF therapy, but further long-term follow-up is needed.

Infiltration of CD1a-positive dendritic cells in advanced laryngeal cancer correlates with unfavorable outcomes post-laryngectomy.

BACKGROUND: The prognosis of advanced laryngeal cancer is unfavorable despite advances in multidisciplinary therapy. Dendritic cells (DCs) play a central role in antitumor immunity. Tumor-infiltrating CD1a+ DCs have been reported to be associated with clinical outcomes in carcinomas of various organs, but the clinical impact of CD1a+ DCs in laryngeal cancer remains to be unequivocally established. METHODS: We retrospectively analyzed the cases of 57 patients with Stage III or IV laryngeal cancer who underwent a total laryngectomy. Immunohistochemistry detection of CD1a, S100 and CD8 was performed on representative resected specimens. CD1a+ DCs, S100+ DCs and CD8+ cytotoxic T-lymphocytes (CTLs) were evaluated, and the cases divided into high and low groups according to the cut-off of the median values for each of these 3 parameters. RESULTS: Compared to the CD1a-low group, the CD1a-high group had more advanced cases and showed significantly worse disease-specific survival (DSS) (P = 0.008) and overall survival (OS) (P = 0.032). The analyses of S100 DCs and CD8+ CTLs revealed no significant impact on clinical outcomes. However, multivariate analysis revealed that infiltration of CD1a+ DCs was an independent unfavorable prognostic factor for both DSS (P = 0.009) and OS (P = 0.013). CONCLUSIONS: Our results demonstrated that the infiltration of CD1a+ DCs was associated with unfavorable clinical outcomes in patients with advanced laryngeal cancer who underwent a total laryngectomy as the initial treatment.

Formalin fixation on HER-2 and PD-L1 expression in gastric cancer: A pilot analysis using the same surgical specimens with different fixation times.

BACKGROUND: The needs for human epidermal growth factor receptor 2 (HER-2) and/or programmed death-ligand 1 (PD-L1) evaluations in gastric cancer are dramatically increasing. Although the importance of standardization of sample fixation has been widely recognized, most of the evidence regarding the fixation duration or type of fixing solution are based on breast cancer. AIM: To investigate the real effects of fixation conditions on HER-2 testing or PD-L1 testing for gastric cancer using gastrectomy specimens. METHODS: Thirty-two patients who underwent gastrectomy for gastric cancer were enrolled. Their resected specimens were each divided into four pieces and fixed in four strictly controlled different durations (6 h, 24 h, and 48 h, and 1 wk) by 10% formalin (n = 22) or 10% neutral buffered formalin (NBF) (n = 10). Immunohistochemistry (IHC) of HER-2 and PD-1 was performed, and a pathology examination was conducted. In the HER-2-immunoreactive cases, all four specimens were subjected to dual-color in situ hybridization (DISH). Five cases were assessed as HER-2-positive by IHC and DISH. We used the cut-off values of 1%, 10%, and 50% to assess the IHC findings of PD-L1. RESULTS: No significant difference was observed in comparisons between the shorter fixation period groups (6 h, 24 h, and 48 h) and the prolonged fixation period (1 wk) group in the HER-2 and PD-L1 analyses. Although no significant difference was observed between 10% formalin and 10% NBF within 1 wk of fixation, the superiority of 10% NBF was confirmed in a long-term (> 3 mo) fixation in both the HER-2 and PD-L1 analyses. CONCLUSION: In this small-numbered pilot study, prolonged fixation within 1 wk showed no inferiority in HER-2 or PD-L1 testing. However, a large-numbered prospective study is needed to obtain conclusive results.

Dental and oropharyngeal lesions in rats with chronic acid reflux esophagitis.

OBJECTIVE: In this study, we evaluated pathological changes in the tooth and pharynx of GERD rats to elucidate the association between gastric acid reflux and oral and pharyngeal diseases. METHODS: An experimental rat model of chronic acid reflux esophagitis was surgically created. The oral cavities were observed histologically every 2 weeks until 20 weeks after surgery. RESULTS: At 10 weeks after surgery, molar crown heights in GERD rats were shorter than that in control rats, and inflammatory cell infiltration by gastric acid reflux was found in the periodontal mucosa of GERD rats. Furthermore, dental erosion progressed in GERD rats at 20 weeks after surgery, and enamel erosion and dentin exposure were observed. During the same period, inflammatory cell infiltration was observed in the mucosa of the posterior part of the tongue. These findings suggest that gastric acid reflux may be one of the exacerbating factors of dental erosion, periodontitis and glossitis. CONCLUSION: We investigated oral changes in an experimental rat model of GERD and observed development of dental erosion, periodontitis and glossitis. Our findings suggested chronic gastric acid reflux may be involved in the pathogenesis of oral disease.

Difficulty in the Cytodiagnosis of Mammary Analogue Secretory Carcinoma: Survey of 109 Cytologists with a Case Originating from a Minor Salivary Gland.

BACKGROUND: Mammary analogue secretory carcinoma (MASC) of the salivary gland shows morphologic similarities and shares an immunophenotype and characteristic ETV6-NTRK3 translocation with secretory carcinoma of the breast. We present a buccal case of MASC along with a survey-based debate about its cytologic diagnosis by fine-needle aspiration (FNA). CASE: FNA of the buccal nodule of a 58-year-old Japanese man was initially performed by 3 cytologists who gave different assessments of the Papanicolaou classification (i.e., class II, III, and V). To investigate the potential for discrepant diagnosis of MASC on a larger scale, we distributed a survey with questions about the cytological diagnosis of the present case to cytologists at other institutions. A total of 109 cytologists completed the survey, providing varying assessments of the Papanicolaou classification: class I/II (14%), class III (53%), and class IV/V (33%). Most of the respondents (72%) could not identify a particular tumor or disease. Even the respondents who identified a particular tumor suggested widely differing diagnoses, from a benign lesion to various malignant tumors. Only 2 respondents correctly identified MASC. CONCLUSION: Our experience and the results of the survey suggest difficulty in the cytodiagnosis of MASC.