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Objective: Facial nerve paralysis due to parotid carcinoma is sometimes misdiagnosed as Bell's palsy. This study aimed to compare patients with parotid carcinoma with and without accompanying facial nerve paralysis and to capture the features of patients misdiagnosed with Bell's palsy. Methods: Among 209 patients, 42 (20%) had facial nerve paralysis. Of these 42 patients, 14 had received treatment for facial nerve paralysis without being diagnosed with parotid carcinoma (pretreatment group); the remaining 28 patients had not received any pretreatment and were diagnosed with parotid carcinoma at the initial visit to our hospital (no pretreatment group). This study compared patients with and without facial nerve paralysis and the pretreatment and no pretreatment groups. Results: The 42 patients with facial nerve paralysis had a significantly higher frequency of pain/tenderness and adhesion with surrounding tissues, significantly higher proportions of deep lobe tumors, and a significantly higher proportion of high-grade malignancy. In addition, the disease-specific and disease-free 5 year survival rates were significantly poorer in patients with than in those without facial nerve paralysis. The comparison between the pretreatment and no pretreatment groups revealed no significant differences in any factors nor survival rate. Five patients in the pretreatment group complained of palpable masses or pain/tenderness at the time of their initial treatment for paralysis. Conclusion: Patients with parotid carcinoma who present with facial nerve paralysis at the initial visit have a significantly poorer prognosis. The number of cases in the pretreatment group can be reduced by performing a detailed examination, which can potentially improve the prognosis.
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Parotid salivary duct carcinoma (SDC) is a rare and aggressive parotid gland carcinoma (PGC). SDC has two origins: de novo and ex pleomorphic adenoma (SDC ex PA); however, because of its rarity, the clinical and molecular features of the two types of SDC are not sufficiently understood. Here, we studied the differences in their clinicopathological and molecular features using clinical specimens while comparing them to those of adenoid cystic carcinoma (AdCC), an intermediate-grade PGC. Clinicopathological analysis of tissues from patients with PGC revealed significant associations between histological types and malignant phenotypes, including nodal metastasis, recurrence, vascular invasion, and neural invasion, and revealed more malignant phenotypes of de novo SDC than of SDC ex PA. The de novo SDC showed a significantly higher frequency of intra-neural invasion (intra-NI) and vascular invasion than AdCC and SDC ex PA. PGCs with high intra-NI were significantly correlated with malignant phenotypes and survival rates. Recently, we observed the overexpression of tropomyosin receptor kinase B (TRKB), a receptor tyrosine kinase, in PGC cells. Here, immunohistochemical and clinicopathological analyses showed that TRKB was highly expressed in SDC cells, particularly de novo SDC cells, and was significantly associated with poor survival and highly malignant phenotypes, including intra-NI and vascular invasion. Collectively, these data show that TRKB expression is significantly elevated in PGC, particularly in de novo SDC, and can be one of the biomarkers of their aggressiveness.
Subject(s)
Adenoma, Pleomorphic , Carcinoma, Adenoid Cystic , Carcinoma, Ductal , Parotid Neoplasms , Salivary Gland Neoplasms , Humans , Parotid Gland/pathology , Tropomyosin , Salivary Ducts/pathology , Salivary Gland Neoplasms/pathology , Adenoma, Pleomorphic/pathology , Parotid Neoplasms/pathology , Carcinoma, Adenoid Cystic/pathology , Carcinoma, Ductal/pathology , Receptor Protein-Tyrosine Kinases , Biomarkers, Tumor/geneticsABSTRACT
OBJECTIVE: Facial nerve paralysis is the most problematic complication of surgery for parotid tumors. This study aimed to examine the progress of recovery from postoperative transient facial nerve paralysis (POFNP). METHODS: Participants were 203 patients who developed POFNP after benign parotid surgery. A Kaplan-Meier showed the progress of recovery from paralysis. Factors involved in recovery were examined. For factors for which a significant difference was found, recovery from paralysis was examined over time. RESULTS: Rates of recovery from paralysis were as follows: 28.6% of patients at 1 month, 58.3% at 3 months, 85.9% at 6 months, and 95.1% at 12 months after surgery. Deep lobe tumors were shown to be significantly associated with delayed recovery from paralysis. The relationship between tumor location and the time of recovery from was that deep lobe tumors had a significantly worse recovery from paralysis at 4 and 5 months after surgery. CONCLUSION: Patients who develop POFNP must be informed about the progress of recovery and factors involved in recovery from paralysis. We believe that the results of the present study are a useful reference to that end.
Subject(s)
Bell Palsy , Facial Paralysis , Parotid Neoplasms , Humans , Facial Nerve/pathology , Postoperative Complications/etiology , Facial Paralysis/etiology , Parotid Gland/surgery , Parotid Gland/pathology , Parotid Neoplasms/pathology , Bell Palsy/complications , Retrospective StudiesABSTRACT
OBJECTIVES: Controversy exists on how to handle central lymph nodes in papillary thyroid carcinoma, particularly regarding indications for prophylactic central neck dissection (CND). Central node metastases are more difficult to diagnose preoperatively than lateral node metastases. METHODS: We enrolled 493 patients with papillary thyroid carcinoma treated at our department in the past 22 years. Metastatic lymph nodes were diagnosed preoperatively mainly by ultrasonography. In principle, CND was performed for all cases; ipsilateral CND was performed for hemithyroidectomy, and bilateral CND was performed for total thyroidectomy. Lateral neck dissection (levels II to V; LND) was performed for metastases to lateral neck lymph nodes (clinical node (cN) 1b). RESULTS: The cN stage was cN0 in 365 patients, cN1a in 10, and cN1b in 118. Of the 357 patients with stage cN0 who underwent CND, 42.9 % had pathologically positive nodes (pN+) in level VI, and of the 118 with stage cN1b who underwent CND, 78.0 % had pN+ in level VI. Cases with advanced T stage were significantly more common with pN+ in level VI. Level VI metastases were significantly associated with pN+ in level IV. As the total number of pN+ at each level of the lateral neck increased, the rate of patients with pN+ in level VI increased, and in patients with 3 or more pN+, about 85 % had level VI metastases. CONCLUSION: Because about half of the patients with cN0 patients had pN+ in level VI, and the rate of pN+ in level VI in each clinical T stage was 46 to 65 %, prophylactic CND should be performed, considering the various clinical benefits. Central nodes will have metastases in about 80 % of cases with lateral node metastases, requiring more accurate dissection. In lateral node metastases, there is a significant association between metastases in levels IV and VI.
Subject(s)
Carcinoma, Papillary , Carcinoma , Thyroid Neoplasms , Humans , Thyroid Cancer, Papillary/surgery , Thyroid Cancer, Papillary/pathology , Thyroid Neoplasms/diagnostic imaging , Thyroid Neoplasms/surgery , Carcinoma/diagnostic imaging , Carcinoma/surgery , Carcinoma, Papillary/diagnostic imaging , Carcinoma, Papillary/surgery , Lymphatic Metastasis/pathology , Lymph Nodes/pathology , Neck Dissection/adverse effects , Thyroidectomy , Retrospective StudiesABSTRACT
OBJECTIVE: High-grade parotid carcinoma generally has a poor prognosis, and the histological type is mucoepidermoid carcinoma (MEC), salivary duct carcinoma (SDC), carcinoma ex pleomorphic adenoma (CEPA), or adenoid cystic carcinoma (AdCC) in the majority of cases. METHODS: During the 23-year period from September 1999 to December 2022, 250 patients with parotid carcinoma underwent initial treatment and had the histopathological type of their carcinoma. Retrospective study evaluated 111 MEC, SDC, CEPA, or AdCC cases among 134 patients with high-grade parotid carcinoma. We examined pathological and clinical features and prognosis, evaluated factors associated with recurrence, and performed immunohistological examinations. RESULTS: Pathological and clinical features and factors associated with recurrence were different for each histological type. The 10-year disease-free survival rates were as follows: MEC, 34.9%; SDC, 22.6%; CEPA, 47.1%; and AdCC, 56.3%. Human epidermal growth factor receptor type-2 and androgen receptor were positive in 48% and 56% of patients with SDC, respectively, 38% and 25% of those with CEPA. CONCLUSION: Each histological type has its own pathological and clinical features, recurrence types, and tumor activities, suggesting that differentiating between high-grade parotid carcinomas according to histological type will improve diagnosis, and thus prognosis.
Subject(s)
Adenocarcinoma , Adenoma, Pleomorphic , Carcinoma, Adenoid Cystic , Carcinoma, Ductal , Carcinoma , Parotid Neoplasms , Salivary Gland Neoplasms , Humans , Retrospective Studies , Parotid Neoplasms/pathology , Salivary Gland Neoplasms/pathology , Adenoma, Pleomorphic/pathology , Carcinoma, Adenoid Cystic/pathology , Carcinoma, Ductal/pathologyABSTRACT
BACKGROUND: Prognostic factors and survival rate are difficult to determine for adenoid cystic carcinoma(AdCC) of salivary glands. AIMS/OBJECTIVES: To clarify the clinical characteristics of AdCC and examine factors associated with recurrence and prognosis by histopathological grade classification. MATERIALS AND METHODS: Twenty-five patients with AdCC of the parotid gland and 10 patients with AdCC of the submandibular gland were included. We classified AdCC histopathologically by the proportion of solid components. Clinical features, fine-needle aspiration cytology (FNAC), and patient outcomes were examined according to grade. Factors associated with local recurrence and distant metastases were examined. RESULTS: Age was significantly higher in the grade III group than in the grade I group. The grade III group had significantly higher proportions of patients with cN+, pN+, and perineural invasion. In FNAC, lower-grade groups showed higher rates of correct histopathological type. Five-year disease-specific survival and disease-free survival rates were significantly lower in the grade III than in the grade I. Distant metastases were more common among patients with high-stage and perineural invasion. CONCLUSIONS: Five-year survival is significantly worse in patients with grade III.
Subject(s)
Carcinoma, Adenoid Cystic , Salivary Gland Neoplasms , Humans , Carcinoma, Adenoid Cystic/therapy , Salivary Gland Neoplasms/therapy , Salivary Gland Neoplasms/pathology , Salivary Glands/pathology , Prognosis , Disease-Free Survival , Retrospective Studies , Neoplasm Recurrence, LocalABSTRACT
It has long been known that high-grade mucoepidermoid carcinoma (MEC) has a poor prognosis, but the detailed molecular and biological mechanisms underlying this are not fully understood. In the present study, the pattern of chymase-positive mast cells, as well as chymase gene expression, in high-grade MEC was compared to that of low-grade and intermediate-grade MEC by using 44 resected tumor samples of MEC of the parotid gland. Chymase expression, as well as chymase-positive mast cells, was found to be markedly increased in high-grade MEC. Significant increases in PCNA-positive cells and VEGF gene expression, as well as lymphangiogenesis, were also confirmed in high-grade MEC. Chymase substrates, such as the latent transforming growth factor-beta (TGF-ß) 1 and pro-matrix metalloproteinase (MMP)-9, were also detected immunohistologically in high-grade MEC. These findings suggested that the increased chymase activity may increase proliferative activity, as well as metastasis in the malignant condition, and the inhibition of chymase may be a strategy to improve the poor prognosis of high-grade MEC of the parotid gland.
Subject(s)
Carcinoma, Mucoepidermoid , Salivary Gland Neoplasms , Humans , Parotid Gland/metabolism , Chymases/genetics , Carcinoma, Mucoepidermoid/pathology , Mast Cells/metabolism , Serine Proteases , Salivary Gland Neoplasms/pathologyABSTRACT
OBJECTIVES: To investigate a method for predicting postoperative facial nerve paralysis (POFNP) during parotid surgery using intraoperative nerve monitoring (IONM). METHODS: We assessed prediction for POFNP by using IONM, comparing between stimulation in the facial nerve trunk and each branch by using facial nerve monitoring. The amplitude response ratio (ARR) was calculated for the trunk/periphery. In addition, we then examined the correlation between ARR and time to recovery of paralyzed branches. RESULTS: 372 branches of 93 patients did not develop POFNP and were classified as group A. Among 20 patients who developed POFNP, 51 branches without POFNP were classified as group B, and 29 branches with POFNP were classified as group C. The ARR was approximately 1 in group A and B. but less than 0.5 in all branches in Group C. When the cut off value of ARR was set at 0.55, the sensitivity, specificity, and accuracy of POFNP diagnosis by ARR were 96.5%, 93.1%, and 96.8%, respectively. CONCLUSION: Using IONM during parotid surgery enables easy prediction of POFNP.
Subject(s)
Bell Palsy , Facial Nerve Injuries , Facial Paralysis , Parotid Neoplasms , Humans , Facial Nerve , Parotid Neoplasms/surgery , Monitoring, Intraoperative/methods , Facial Paralysis/diagnosis , Facial Paralysis/etiology , Facial Paralysis/surgery , Parotid Gland/surgery , Parotid Gland/innervation , Facial Nerve Injuries/diagnosis , Facial Nerve Injuries/etiology , Facial Nerve Injuries/prevention & control , Postoperative Complications/diagnosis , Postoperative Complications/etiology , Postoperative Complications/surgeryABSTRACT
OBJECTIVE: Postoperative facial nerve paralysis is the most problematic complication after surgical treatment of parotid tumors. Localization of tumors is highly relevant for the surgical approach, but existing classification systems do not focus on the association between localization and surgical technique. Therefore, we created a new localization-based classification system for benign parotid tumors and investigated the characteristics of tumors in each localization and the frequency of postoperative facial nerve paralysis by retrospectively applying the classification to previous cases. METHODS: First, we defined 6 portions of the parotid gland (upper, U; lower, L; posterior, P; anterior, A; superficial, S; deep, D) by dividing the transverse plane into an upper and lower portion at the mandibular marginal branch, the longitudinal plane into a posterior and anterior portion at the midline of the parotid anteroposterior diameter, and the sagittal plane into a superficial and deep portion along the course of the facial nerve. Then, we defined 8 locations by combining the 6 portions in all possible ways (i.e., U-P-S, U-P-D, U-A-S, U-A-D, L-P-S, L-P-D, L-A-S, L-A-D). We used this classification to define the tumor localization in 948 patients who had undergone partial superficial parotidectomy for benign parotid tumors and then investigated the incidence, histopathological type, signs/symptoms, diagnosis, surgery, and complications in each area. RESULTS: Pleomorphic adenomas comprised approximately 70% of tumors in the upper portion but only approximately 35% in the lower portion. The rate of postoperative facial nerve paralysis was significantly higher for tumors in deep locations than in superficial locations (33.9% vs 14.9%, respectively), and the odds ratios for postoperative facial nerve paralysis in the U-P-D and U-A-D locations were 7.6 and 4.8 compared to the L-P-S location. When maximum diameter, operation time, bleeding volume, sex (reference: female), and age were added as control variables, the odds ratios were 4.2 and 3.0. CONCLUSION: Determining tumor localization preoperatively with the new localization-based classification of parotid tumors is helpful not only for predicting the histopathological type but also for predicting surgical complications, particularly postoperative facial nerve paralysis.
Subject(s)
Bell Palsy , Facial Paralysis , Parotid Neoplasms , Humans , Female , Parotid Neoplasms/pathology , Retrospective Studies , Postoperative Complications/epidemiology , Parotid Gland/surgery , Parotid Gland/pathology , Facial Paralysis/epidemiology , Facial Paralysis/etiology , Facial Paralysis/pathology , Bell Palsy/complicationsABSTRACT
The Practical Guideline for the Management of Allergic Rhinitis, the fist guideline for allergic rhinitis in Japan, was prepared after a symposium held by the Japanese Society of Allergology in 1993. The current 9th edition was published in 2020 and is widely used today. The most recent collection of evidence from the literature was supplemented to the revised guideline to incorporate evidence-based medicine. The revised guideline includes updated epidemiology of allergic rhinitis in Japan, a figure representing the mechanisms of allergic rhinitis in both the onset and sensitization phases with the introduction of regulatory T cells and type 2 innate lymphoid cells, practical assessment for diagnosis, new pharmacotherapy agents such as anti-IgE mAb and a new drug delivery system for antihistamines, sublingual immunotherapy for children, dual sublingual immunotherapy for house dust mites and Japanese cedar pollen extract, new classification for surgery for allergic rhinitis, and treatment and prescriptions for older adults. An evidence-based step-by-step strategy for treatment is also described.
Subject(s)
Immunity, Innate , Rhinitis, Allergic , Child , Animals , Humans , Aged , Lymphocytes , Rhinitis, Allergic/diagnosis , Rhinitis, Allergic/epidemiology , Rhinitis, Allergic/therapy , Allergens , PyroglyphidaeABSTRACT
The parotid gland contains intra-glandular lymph nodes, the distribution of which is crucial for understanding the pathogenesis of intra-parotid lymph node metastases of parotid carcinoma and other head and neck carcinomas. Positive intra-parotid lymph node metastasis predicts the risk of positive cervical nodal metastasis. It is important to establish whether prophylactic neck dissection, including intra-parotid lymph nodes, contributes to treatment outcomes. The presence or absence of intra-parotid lymph nodes or metastasis-positive lymph nodes warrants further study. A preoperative diagnosis by imaging and fine-needle aspiration cytology of intra-parotid lymph nodes is difficult. Although intraoperative frozen section biopsy is performed during surgery, it is challenging to identify intra-parotid lymph nodes. The number of lymph nodes was the largest (47%) in the lower half of the superficial lobe, with 35% of nodes being concentrated in the inferior part of the cervicofacial branch, i.e., the lower pole of the parotid gland. Therefore, superficial parotidectomy and lower pole lobectomy need to be performed in cases in which a malignant tumor localizes to the superficial lobe or a lower pole. When intra-parotid lymph node metastases are detected during surgery, selective neck dissection (at least levels II and III) needs to be simultaneously performed.
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Fine-needle aspiration (FNA) cytology is widely used in clinical practice as a simple and minimally invasive test for parotid tumors that allows for preoperative estimation of benignancy and malignancy, histological type, and malignancy grade and can be performed on an outpatient basis. In recent years, cell blocks prepared with core needle biopsy (CNB) and liquid-based cytology (LBC) have increased the reliability of immunostaining and molecular biological testing, leading to improved diagnostic accuracy. In 2018, the Milan System for Reporting Salivary Gland Cytology was introduced, but it does not include malignancy grade or histological type, so we proposed the Osaka Medical College classification as a more clinically based cell classification that includes both types of information, and we have reported on its usefulness. This review gives an overview of the history and use of FNA and describes CNB and LBC and the two classification systems.
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Parotid gland cancer (PGC) is a rare malignancy and its molecular characteristics remain poorly understood, which has precluded the development of effective drug therapies. Given the poor prognosis of many human cancers in which tropomyosin receptor kinase B (TRKB) is highly expressed, we investigated the involvement of brain-derived neurotrophic factor (BDNF)/TRKB pathway in PGC cells using clinical specimens and observed upregulation of TRKB and BDNF. In primary culture systems of patient-derived PGC cells and cancer-associated fibroblasts (CAFs), PGC cells co-cultured with CAFs exhibited significant upregulation of BDNF and epithelial-mesenchymal transition (EMT). Similar results were observed in PGC cells treated with conditioned medium from co-cultures of PGC cells with CAFs. Administration of TRK inhibitors suppressed BDNF-induced cell migration in PGC cells. Immunohistochemical and clinicopathological analyses of tumors from patients with PGC revealed that BDNF and TRKB were highly expressed in both tumor cells and stromal cells such as CAFs, and TRKB expression levels in PGC cells were significantly correlated with aggressive features, including vascular invasion, nodal metastasis, and poor prognosis. Collectively, these data suggest that the BDNF/TRKB pathway regulates PGC cell aggressiveness via crosstalk with CAFs and is a potential therapeutic target for PGC harboring invasive and metastatic features.
Subject(s)
Brain-Derived Neurotrophic Factor , Cancer-Associated Fibroblasts , Receptor, trkB , Salivary Gland Neoplasms , Humans , Brain-Derived Neurotrophic Factor/metabolism , Cancer-Associated Fibroblasts/metabolism , Cell Line, Tumor , Culture Media, Conditioned , Epithelial-Mesenchymal Transition , Parotid Gland/metabolism , Receptor, trkB/metabolism , Salivary Gland Neoplasms/metabolism , Salivary Gland Neoplasms/pathologyABSTRACT
Allergen-specific immunotherapy (AIT) is the only causative treatment for allergic diseases by modification of the immune response to allergens. A key feature of AIT is to induce immunotolerance to allergens by generating antigen-specific regulatory T (Treg) cells in allergic patients. Type 1 regulatory T (Tr1) cells and forkhead box protein 3 (Foxp3)-expressing Treg cells are well known among Treg cell subsets. Foxp3 was identified as a master transcription factor of Treg cells, and its expression is necessary for their suppressive activity. In contrast to Foxp3+ Treg cells, the master transcription factor of Tr1 cells has not been elucidated. Nevertheless, Tr1 cells are generally considered as a distinct subset of Treg cells induced in the periphery during antigen exposure in tolerogenic conditions and can produce large amounts of anti-inflammatory cytokines such as interleukin-10 and transforming growth factor-ß, followed by down-regulation of the function of effector immune cells independently of Foxp3 expression. Since the discovery of Tr1 cells more than 20 years ago, research on Tr1 cells has expanded our understanding of the mechanism of AIT. Although the direct precursors and true identity of these cells continues to be disputed, we and others have demonstrated that Tr1 cells are induced in the periphery by AIT, and the induced cells are re-activated by antigens, followed by suppression of allergic symptoms. In this review, we discuss the immune mechanisms for the induction of Tr1 cells by AIT and the immune-suppressive roles of Tr1 cells in AIT.
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Objective: Mucoepidermoid carcinoma (MEC) is the most common malignancy of the parotid gland, but the outcome depends on the histological grade. Therefore, the aim of this study was to evaluate MEC on the basis of histological grade. Study Design: Retrospective analysis. Methods: We performed a retrospective analysis of data from patients whose initial treatment for MEC of the parotid gland was performed at our department between 1999 and 2021. We examined the association between the Armed Forces Institute of Pathology (AFIP) grade and outcome. Results: The AFIP grades were as follows: low, 26 cases; intermediate, 9 cases; and high, 31 cases. About 50% of cases were correctly diagnosed as malignant, and both grade and histology were accurately determined by fine-needle aspiration cytology in 20% of cases. The 5-year disease-free survival rate was 95.5% and 53.8% in the low-/intermediate- and high-grade cases, respectively. In the high-grade group, cases with recurrence were found to have a higher rate of lymph nodes metastasis than cases without recurrence. Furthermore, in this high-grade group, total sacrifice of the facial nerve did not reduce local recurrence. However, radical resection in the cases without tumor invasion to the nerve has decreased the local recurrence rate. The CRTC1-MAML2 fusion gene was expressed in 42.3% of low-/intermediate- and 14.3% of high-grade cases. Conclusions: The survival rate in MEC was quite different between the low-/intermediate- and high-grade cases. However, the rate of correct assessment of the grade by fine-needle aspiration cytology was poor. In high-grade cases, total sacrifice of the facial nerve may improve the rate of local recurrence in cases without invasion of the main trunk of the nerve. Expression of the CRTC1-MAML2 fusion gene could be helpful in not only the assessment of grade but the prediction of recurrence. Level of Evidence: 4.
ABSTRACT
PURPOSE: This study investigated the characteristics, diagnosis, and treatment of Warthin tumors (WTs) to explore the possibility of managing patients by observation. METHODS: We reviewed the records of 1167 patients with benign parotid tumors who were seen in our department between September 1999 and April 2021. Among them, 387 cases were WT and 668 cases were pleomorphic adenoma. We evaluated preoperative diagnoses of WT by symptoms/signs, fine-needle aspiration cytology (FNAC), imaging, such as ultrasonography and magnetic resonance imaging, and technetium-99m pertechnetate (Tc-99m) scintigraphy. Fisher's exact test and the Mann-Whitney U test were used in statistical analyses. RESULTS: Warthin tumors were treated by surgery in 238 cases and follow-up in 149 cases. The 238 patients were diagnosed as WT at the final pathology after surgery. Among them, 172 patients (72.3%) were determined as benign histological type by preoperative FNAC; in these 172 patients, 170 (71.4%) were correctly diagnosed as WT in the final pathology. Preoperative Tc-99m scintigraphy was performed in 69 patients diagnosed with WT by final pathology or FNAC, and the positive rate of Tc-99m scintigraphy in WT was 75.4%. CONCLUSIONS: Combining FNAC and Tc-99m scintigraphy, as well as considering clinical findings, enables the diagnosis of WT in most cases. In particular, WT is more common in the elderly, grows more slowly, and is less likely to be malignant. Therefore, if WT can be diagnosed preoperatively with a high rate of correct diagnosis, it could be an accurate and effective means of managing patients through follow-up without surgery.
ABSTRACT
Some patients with chronic rhinitis have a positive nasal allergen provocation test (NAPT) without systemic IgE sensitization by skin prick tests or serum allergen-specific IgE (sIgE). This novel concept is called local allergic rhinitis (LAR) and affects children and adults worldwide, but is underdiagnosed. LAR is not just the initial state of allergic rhinitis (AR), it is a unique form of chronic rhinitis that is neither classical AR nor non-AR. Many of the features of AR and LAR are similar, such as a positive NAPT, positive type 2 inflammatory markers, including the nasal discharge of sIgE, and a high incidence of asthma. A differential diagnosis of LAR needs to be considered in patients with symptoms suggestive of AR in the absence of systemic atopy, regardless of age. The diagnostic method for LAR relies on positive responses to single or multiple allergens in NAPT, the sensitivity, specificity, and reproducibility of which are high. The basophil activation test and measurement of IgE in nasal secretions also contribute to the diagnosis of LAR. Treatment for LAR is similar to that for AR and is supported by the efficacy and safety of allergen exposure avoidance, drug therapy, and allergen immunotherapy. This review discusses current knowledge on LAR.
ABSTRACT
Incomplete excision of pleomorphic adenoma (PA) may result in recurrent pleomorphic adenoma (RPA). Furthermore, long-term neglected PA may become carcinoma ex pleomorphic adenoma (CXPA). In the present study, the relationships between mast cell-derived chymase and these tumors were examined. The tumor tissues of PA consisted of either or both glandular and fibrotic structures. Histological features of RPA were almost similar to those of PA, except that they showed multinodular structures. CXPA is composed of a mixture of PA and carcinoma. The main stromal cells in PA were myofibroblasts, whereas fibroblasts constituted the main cellular portion in the stromal tissue of RPA. Cancer-associated fibroblasts (CAFs) were present abundantly in CXPA. With increased VEGF expression, neovascularization tended to increase in RPA or CXPA. Compared with PA, chymase-positive mast cells, as well as chymase gene expression, were increased in the tumor tissues from patients with RPA or CXPA. SCF, TGFß1, and PCNA-positive staining was widely observed in these tumor tissues. The above results suggest that mast cell-derived chymase through its direct or cooperative effects with other mediators may participate in the pathophysiology of RPA and CXPA.
Subject(s)
Adenoma, Pleomorphic/metabolism , Chymases/metabolism , Mast Cells/metabolism , Parotid Neoplasms/metabolism , Up-Regulation , Adenoma, Pleomorphic/pathology , Adult , Aged , Aged, 80 and over , Cancer-Associated Fibroblasts/metabolism , Cancer-Associated Fibroblasts/pathology , Chymases/genetics , Female , Gene Expression Regulation, Neoplastic , Humans , Male , Mast Cells/pathology , Middle Aged , Neoplasm Recurrence, Local , Parotid Neoplasms/pathologyABSTRACT
BACKGROUND: Parotid cancer is relatively rare, and malignancy varies; therefore, novel markers are needed to predict prognosis. Recent advances in matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS), useful for visualization of lipid molecules, have revealed the relationship between cancer and lipid metabolism, indicating the potential of lipids as biomarkers. However, the distribution and importance of phospholipids in parotid cancer remain unclear. OBJECTIVE: This study aimed to use MALDI-IMS to comprehensively investigate the spatial distribution of phospholipids characteristically expressed in human parotid cancer tissues. METHODS: Tissue samples were surgically collected from two patients with parotid cancer (acinic cell carcinoma and mucoepidermoid carcinoma). Frozen sections of the samples were assessed using MALDI-IMS in both positive and negative ion modes, with an m/z range of 600-1000. The mass spectra obtained in the tumor and non-tumor regions were compared and analyzed. Ion images corresponding to the peak characteristics of the tumor regions were visualized. RESULTS: Several candidate phospholipids with significantly different expression levels were detected between the tumor and non-tumor regions. The number of unique lipid peaks with significantly different intensities between the tumor and non-tumor regions was 95 and 85 for Cases 1 and 2, respectively, in positive ion mode, and 99 and 97 for Cases 1 and 2, respectively, in negative ion mode. Imaging differentiated the characteristics that phospholipids were heterogeneously distributed in the tumor regions. CONCLUSION: Phospholipid candidates that are characteristically expressed in human parotid cancer tissues were found, demonstrating the localization of their expression. These findings are notable for further investigation of alterations in lipid metabolism of parotid cancer and may have potential for the development of phospholipids as biomarkers.