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Introduction: Stem cells from various sources including major salivary glands have been used to establish pancreatic differentiation in an attempt to provide new treatment options for patients with diabetes mellitus. In contrast, the potential of using the more easily accessible intraoral minor salivary glands has not been evaluated so far. Materials and Methods: Salivary stem cells were isolated from normal labial minor salivary glands that were removed during the excision of a mucocele and were attempted to differentiate into pancreatic cell lines using a culture medium enriched with activin A, retinoic acid and GLP-1.Real time RT-PCR was used to evaluate the expression of the genes of pancreatic transcription factors MafA, Ptf1a, Hb9 and Arx. Complementary, 22 labial minor salivary gland paraffin-embedded specimens were examined using immunohistochemistry for the presence of the relevant gene products of the pancreatic transcription factors Arx, MafA, Ptf1a and Pdx1. Results: The differentiated salivary stem cells(cells of passage 3) expressed the genes of the pancreatic transcription factors MafA, Ptf1a, Hb9 and Arx even on the first day of the experiment while immunohistochemistry also confirmed the presence of the protein products of Arx, MafA, Ptf1a as well as Pdx1[> 50% of the specimens for Arx(5/8) and MafA(7/8), < 50% for Ptf1a(5/11) and Pdx1(5/11)] in ducts, mesenchymal connective tissue and acinar cells. Conclusions: Labial minor salivary glands may share gene and protein characteristics with pancreas suggesting a possible usefulness for pancreatic regeneration or substitution in cases of deficiency. [ABSTRACT FROM AUTHOR]

Salivary gland tumors are a rare and heterogeneous group of neoplasms of the head and neck region. The mixed category of these tumors include the following entities: pleomorphic adenoma (PA), carcinoma ex pleomorphic adenoma (CEPA), salivary carcinosarcoma (CS), and metastasizing PA (MPA). The most common benign tumor of the salivary glands is PA. Metastasis and malignant degeneration have been reported in cases of PA of a salivary gland origin. Judging by their behavior, MPA, CEPA, and CS can be considered aggressive tumors. Invasive CEPA has been identified in the parotid gland more frequently. MPA and CS cases reported in the current literature are rare. In this paper, we present, narratively, the clinico-morphological features of this group of mixed tumors. [ABSTRACT FROM AUTHOR]

Raised lesions on the tongue can drastically affect a patient's ability to eat and speak, and their overall quality of life, thus, warranting prompt diagnosis and management. The present report describes the case of an exophytic lesion on the tongue of a 6-year-old boy that was excised using a diode laser. The lesion was diagnosed with papillary cystadenoma (PCA) following meticulous clinical and histopathological analysis in conjunction with immunohistochemistry. PCA is a rare minor salivary gland neoplasm. While the majority of intraoral cases occur in the parotid gland followed by lips and buccal mucosa, the tongue is rarely involved. Because of a significant overlap between the clinical and histopathological features of PCA with a multitude of other lesions, it is a diagnostic challenge, particularly when it occurs on unusual sites as observed in the present case. PCA This case report adds to the scant number of reported cases of PCA occurring on an unusual site such as the anterior two-thirds of the dorsal surface of the tongue. It would serve to guide clinicians and pathologists in planning the diagnostic approach for such uncommon lesions. [ABSTRACT FROM AUTHOR]

To determine the indications for neck dissection in the management of parotid, submandibular or minor salivary gland cancers depending on the clinical situation: i.e., clinical lymph node involvement (cN+) or not (cN0); low or high risk of occult nodal metastasis; diagnosis of malignancy before, during or after surgery. The French Network of Rare Head and Neck Tumors (REFCOR) formed a steering group which drafted a narrative review of the literature published on Medline and proposed recommendations. The level of adherence to the recommendations was then assessed by a rating group according to the formal consensus method. In cN+ salivary gland cancer, ipsilateral neck dissection is recommended. In cN0 salivary gland cancer, ipsilateral neck dissection is recommended, except for tumors at low risk of occult nodal metastasis. If definitive pathology reveals a high risk of occult nodal involvement, additional neck treatment is recommended: ipsilateral neck dissection or elective nodal irradiation. The rate of occult lymph node involvement, and therefore the indication for elective neck dissection, depends primarily on the pathologic grade of the salivary gland cancer. [ABSTRACT FROM AUTHOR]

In the case of any pathologies arising in the hard palate, it is always important to exclude their possible odontogenic origins. Cone-beam computed tomography is mandatory. In cases where a possible non-teeth-related pathology is confirmed, each clinician should remember possible differential diagnostics. Many small salivary glands between the mucosa and bone are present in this palatal area. Both benign and malignant tumors arising from the small glands, and mucosa of the hard palate, might occur. The case presented here mimics a solid tumor because of the nodule consistency. Because of a healthy palatal mucosa without any erosions or irritations with firm attachment to the submucosal nodule, a possible malignant tumor of small salivary gland origins was suspected in this case. When the tumor diameter is small, an excisional biopsy is required to collect good and representative material for further histopathological evaluation. In most cases, bulky nodules present on the palate are hard on palpation, non-movable, and covered with healthy mucosa. Possible bone infiltrations with mucous membrane ulcerations could manifest a more expansive character of the lesion. In the presented case, an unusual occurrence of a traumatic neuroma without any past traumatic etiology of the palate was first differentiated from the occurrence of adenoid-cystic carcinoma (ACC), pleomorphic adenoma, other benign/malignant small gland tumors, or atypical, fibroma/schwannoma of the palate. This paper presents treatment options for this rare oral neural tumor occurrence in the palate and differential diagnosis between hard palate tumors in a 42-year-old male patient, furthermore highlighting the role of an excisional biopsy as a good source for a tissue sample. [ABSTRACT FROM AUTHOR]

Salivary gland tumors make up a relatively small proportion, ranging from 1% to 4%, of all neoplasms in the human body. Among these, pleomorphic adenoma stands out as a distinct benign tumor of the salivary glands, characterized by a combination of epithelial and mesenchymal elements. Only 0.3% to 1.5%, of biopsies in oral and Maxillofacial pathology laboratories are associated with tumors originating from minor salivary glands. Keratinizing pleomorphic adenoma, a rare variant accounting for 5-10% of all pleomorphic adenomas, differs from the typical form due to the presence of keratin within the tumor cells, serving as a distinguishing histological feature. The incidence of keratinizing pleomorphic adenoma is not well-established but is believed to be less than 1 case per 100,000 people per year. Here we present an atypical histopathological variation of pleomorphic adenoma, featuring extensive keratinization and manifesting in a less typical anatomical location in a 57-year-old male patient. [ABSTRACT FROM AUTHOR]

Introduction Mucocele is a commonly encountered lesion in the oral mucosa, resulting from alterations in minor salivary glands. There are two histological types - extravasation and retention, with distinct causative factors such as trauma leading to duct severance and mucin spillage into adjacent connective tissue, and obstruction, respectively. Clinically, mucoceles manifest as soft, bluish, and transparent cystic swellings, often resolving spontaneously. Painless yet troublesome, mucoceles can disrupt eating or speaking and, when untreated, may lead to a persistent bump on the inner lip. Treatment options include surgical removal, micro marsupialization, cryosurgery, steroid injections, and CO2 laser. Material and Methods In this case study, we present the case of a 10-year-old female patient with a painless, gradually progressing swelling in the anterior mandibular labial gingiva. Conclusion Treatment involved conservative surgical intervention, confirming the suspected clinical diagnosis of mucocele through radiographic assessments, substantiated by histological examination. [ABSTRACT FROM AUTHOR]

Pleomorphic adenoma is a non-cancerous neoplasm that develops in the salivary glands. Originating from minor salivary glands, it is extremely uncommon and primarily affects females. The peak incidence is observed between 40 and 60 years of age. It usually presents as a slowly growing, painless, solid tumor that does not cause ulcers on the overlying mucosa. Here, a 47-year-old woman experienced repeated swelling on the buccal mucosa following surgical extraction of a pleomorphic adenoma three years ago. The swelling was solid with clearly defined boundaries. An excisional biopsy was conducted under general anesthesia, resulting in total mass removal. The histological evaluation revealed the existence of a recurring pleomorphic adenoma. This instance emphasizes the significance of addressing this entity as a potential etiology for persistent painless and intraoral swellings. [ABSTRACT FROM AUTHOR]

Abstract Background Cystadenoma of the salivary glands is a rare benign clinical condition affecting both major and minor salivary glands equally. It constitutes approximately 2% of total neoplasms and 4.2–4.7% of benign formations in minor salivary glands. Typically presenting as a slow-growing, painless neoplasm, it can be distinguished from Cystadenolymphoma (Whartin’s Tumor) by the absence of lymphoid elements in histological examination. While mostly located in the oral cavity and oropharynx, it can also be found in sinonasal mucosa, and rare cases have been identified in the larynx. Case presentation A 75-year-old Caucasian woman presented to the ear, nose, and throat department with complaints of dysphonia and headaches persisting for several months. Dysphonia had developed months after an unspecified vocal cord surgery elsewhere. Flexible laryngoscopy identified a left-sided cystic swelling affecting the supraglottic space, leading to respiratory obstruction and dysphonia. Head and neck computed tomography confirmed a 1.9 × 1.7 cm bilobed cystic mass originating from the left Morgagni ventricle. Microlaryngoscopy with CO2 laser excision and biopsy revealed a histopathological diagnosis of oncocytic papillary cystadenoma. Post-surgery, the patient fully recovered from dysphonia, with no significant complications noted. Long-term clinical surveillance was advised to detect potential recurrences promptly. Conclusion Ectopic minor salivary gland tumors, both benign and malignant, should be taken into consideration as potential differential diagnosis for any swelling arising within the upper digestive tract mucosa. Ears, nose, and throat clinical examination completed by videolaryngoscopy can easily point out the location of the mass. Imaging is mandatory for differential diagnosis and for surgical planning. Surgical excision can provide both diagnosis and definitive cure.

Background: Intraoral adenoid cystic carcinoma (ACC) arising from minor salivary glands (MSG) is a rare malignancy associated with delayed diagnosis and unfavorable outcomes. This study aimed to comprehensively review ACC of MSGs, focusing on clinical characteristics, imaging modalities, treatment approaches, and long-term outcomes. Methods: A systematic search was conducted in PubMed, Web of Science, and MEDLINE databases to identify relevant articles reporting cases of ACC of MSGs between January 1997 and March 2023. The study was registered in PROSPERO (ID: CRD42023449478). A total of 10 studies that met the inclusion criteria were selected for critical review. In total, 902 patients were diagnosed with ACC of MSGs with an age range of 44.3 to 63 years, and an average age of 56.6 years. The female to male ratio ranges from 1:1 to 2.4:1. Regarding the primary site of ACC, the palate was the most common location, accounting for 30.5% to 83.3%, followed by the buccal mucosa, floor of the mouth, and lip and the retromolar area. For histology, the solid mass pattern was the most prevalent, seen in 95.2% of patients, followed by the cribriform pattern. Regarding treatment modalities, surgery was the most common approach, applied in 76.3% of cases, with a combination of surgery and radiotherapy used in 29.0% of cases. A smaller fraction, 3.2%, received a combination of surgery, chemotherapy, and radiotherapy, and 8.3% underwent radiotherapy alone. Local recurrence rates varied between 1% and 28.5%, and distant metastasis occurred in 18.2% to 33.3% of cases, predominantly to lymph nodes (14.5%). An analysis of overall survival across various stages and patient numbers indicated a 5-year survival rate of 68.0%. The findings of this study provide valuable insights for physicians in making treatment decisions and emphasize the need for ongoing research and collaborative clinical efforts to improve the management and outcomes of this challenging disease. Conclusion: ACC of MSGs is a multifaceted condition typically manifesting as asymptomatic enlargement and ulceration. This disease is marked by distinct histopathological patterns and perineural invasion (PNI). Recognizing these distinctive aspects is key in shaping the treatment plan, which can range from surgical procedures to radiation therapy, chemotherapy, and evolving targeted treatments. Continuous research and collaborative clinical efforts remain critical for ongoing progress in the treatment and management of this challenging condition. [ABSTRACT FROM AUTHOR]

Simple Summary: Polymorphous adenocarcinoma (PAC), the second most prevalent malignant tumour of the minor salivary glands, primarily affects the palate but can also involve the buccal mucosa. This systematic review investigates PAC's clinical characteristics, emphasizing its presence in less-explored anatomical sites. Following PRISMA guidelines, we conducted a thorough search across PubMed, Scopus, and Web of Science, identifying and analysing 29 relevant studies. Among the 143 PAC patients included in the systematic review (62 males, 75 females, and 6 undefined, with a mean age of 57.4 ± 14.5 years), the palate was the predominant site affected by PAC (69.2%), followed by the buccal mucosa (8.4%). Additionally, we report two cases of PAC affecting the buccal mucosa, describing the mean features of an uncommon malignant neoplasm of the salivary glands. These findings underscore the significance of recognizing the buccal mucosa as a potential PAC site, urging careful examination during oral assessments due to the polymorphism and lack of pathognomonic signs. Background: Polymorphous adenocarcinoma (PAC) is the second-most common malignant tumour of the minor salivary glands. Although PAC predominantly affects the palate, it can also involve the buccal mucosa. This systematic review aims to investigate the literature data about PAC. Furthermore, we report two cases of patients affected by PAC in an infrequently considered anatomical site. Methods: According to PRISMA guidelines, a systematic review search was conducted on PubMed, Scopus, and Web of Science. Observational studies conducted on patients with a histological diagnosis of PAC were selected and analysed. Furthermore, two cases of patients with PAC affecting the buccal mucosa were reported. Results: Twenty-nine studies were included, and 143 patients affected by PAC were analysed (62 males, 75 females, and 6 undefined, with a mean age of 57.4 ± 14.5 years). The palate was the most affected site (99/143, 69.2%), followed by the buccal mucosa (12/143, 8.4%). Moreover, we report two cases of patients with PAC affecting the buccal mucosa (one male and one female, with a mean age of 70.5 ± 2.5 years). Conclusions: The present study underscores the importance of considering the buccal mucosa as a possible location of minor salivary gland tumours; although it is a less-considered affliction, it is not uncommon. [ABSTRACT FROM AUTHOR]

Salivary gland tumors are a rare and heterogeneous group of neoplasms of the head and neck region. The mixed category of these tumors include the following entities: pleomorphic adenoma (PA), carcinoma ex pleomorphic adenoma (CEPA), salivary carcinosarcoma (CS), and metastasizing PA (MPA). The most common benign tumor of the salivary glands is PA. Metastasis and malignant degeneration have been reported in cases of PA of a salivary gland origin. Judging by their behavior, MPA, CEPA, and CS can be considered aggressive tumors. Invasive CEPA has been identified in the parotid gland more frequently. MPA and CS cases reported in the current literature are rare. In this paper, we present, narratively, the clinico-morphological features of this group of mixed tumors.

In the case of any pathologies arising in the hard palate, it is always important to exclude their possible odontogenic origins. Cone-beam computed tomography is mandatory. In cases where a possible non-teeth-related pathology is confirmed, each clinician should remember possible differential diagnostics. Many small salivary glands between the mucosa and bone are present in this palatal area. Both benign and malignant tumors arising from the small glands, and mucosa of the hard palate, might occur. The case presented here mimics a solid tumor because of the nodule consistency. Because of a healthy palatal mucosa without any erosions or irritations with firm attachment to the submucosal nodule, a possible malignant tumor of small salivary gland origins was suspected in this case. When the tumor diameter is small, an excisional biopsy is required to collect good and representative material for further histopathological evaluation. In most cases, bulky nodules present on the palate are hard on palpation, non-movable, and covered with healthy mucosa. Possible bone infiltrations with mucous membrane ulcerations could manifest a more expansive character of the lesion. In the presented case, an unusual occurrence of a traumatic neuroma without any past traumatic etiology of the palate was first differentiated from the occurrence of adenoid-cystic carcinoma (ACC), pleomorphic adenoma, other benign/malignant small gland tumors, or atypical, fibroma/schwannoma of the palate. This paper presents treatment options for this rare oral neural tumor occurrence in the palate and differential diagnosis between hard palate tumors in a 42-year-old male patient, furthermore highlighting the role of an excisional biopsy as a good source for a tissue sample.

Objective: To compare the efficacy of micro-marsupialization with surgical excision for the treatment of mucoceles originating from the minor salivary glands of the lower lip. Our primary endpoints were the mean procedural time and the duration of post-operative healing. Study Design: Randomized Controlled Trial (RCT). Setting: Department of Oral and Maxillofacial Surgery, Faisalabad Medical University, Faisalabad. Period: 1st July 2022 to 31th Dec 2022. Material & Methods: We enrolled a total of 60 patients, with 30 in each group (Group X: micro-marsupialization, Group Y: surgical excision). Random allocation was performed using a lottery method. Procedural time (in minutes) and post-operative healing duration (in days) were recorded for both groups, with follow-up assessments conducted over a 3-month period. Results: The study comprised 60 patients (40 males and 20 females) with a mean age of 34.60±10.15 years in Group X and 36.03±9.25 years in Group Y. In Group X, the mean surgical time was 6.23±0.935 minutes, while in Group Y, it was 34.70±2.493 minutes. A statistically significant difference in surgical time was observed between the two groups (p 0.0001). Regarding postoperative healing, Group X had a mean duration of 4.67±0.844 days, while Group Y had a mean duration of 6.57±0.504 days. A statistically significant difference was also noted in post-operative healing duration between the two groups (p 0.008). Conclusion: This study underscores the superiority of micro-marsupialization over surgical excision as a treatment option for mucoceles originating from the minor salivary glands of the lower lip. Micro-marsupialization offers several advantages, including significantly shorter procedural times and faster post-operative healing periods. [ABSTRACT FROM AUTHOR]

Pleomorphic adenoma is a benign tumor of the salivary glands. It commonly occurs in the parotid gland, palate, upper lip and cheek. The authors present a rare case of a pleomorphic adenoma of the lower lip in a 30 years old female admitted on 20th of July, 2022 at Akbar Niazi Teaching Hospital, Islamabad with a complaint of painless, slightly itchy swelling on the lower lip for the last four months. Careful history and examination revealed a swelling of the lower lip which had gradually increased in size but was static for the last three months. As the patient complained of cosmetic and social inconvenience, it was surgically managed. Any post-operative complications were ruled out and the patient was sent home in a good condition. Much research is warranted to know the exact etiopathogenesis and appropriate management of pleomorphic adenoma of the lower lip. [ABSTRACT FROM AUTHOR]

Introduction Based on ACR/EULAR classification criteria, minor salivary glands biopsy (MSGB) is a useful diagnostic tool for the diagnosis of primary Sjögren’s syndrome (SS). The main objective of our study was to evaluate the diagnostic role of MSGB, as well as to highlight correlations between histological findings and autoimmune profiles. Material and methods We retrospectively evaluated histological and autoimmunity data from patients who underwent MSGB in our department in cases of suspected SS, from March 2011 to December 2018. Salivary gland samples were evaluated using Chisholm and Mason (CM) grading and the focus score (FS). Results A total of 1,264 patients (108 males, 1,156 females) were included. The median age was 55.22 ±13.51 years (range: 15–87). In univariate binary logistic regression, CM ≥ 3 and FS ≥ 1 were significantly predicted by antinuclear antibodies (ANA), anti-extractable nuclear antigens (ENA) and anti-Ro/SSA titer as well as anti-La/SSB, anti-Ro/SSA, rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA) positivity. In multivariate analysis, CM ≥ 3 and MSGB positivity were significantly associated with ANA titer; FS ≥ 1 was not associated with laboratory findings. A positive biopsy was associated with laboratory findings, as ANA and ENA titers, anti-Ro/SSA, anti-La/SSB, RF and ACPA positivity may discriminate patients with SS-related histological findings. Conclusions Minor salivary glands biopsy is a useful tool to diagnose SS in cases of highly suggestive clinical symptoms but in the absence of a specific autoimmunity.

There are major and minor salivary glands that aid in the digestive process. Major glands are discrete and exist in predictable locations; minor salivary glands are more widespread and usually found dispersed in the mucosa of the mouth. Glands have their own contractile abilities, which allow them to secrete products without the assistance of vasculature or skeletal, or smooth muscle. This study will describe a cadaveric histological specimen in which an ectopic buccal gland was embedded within bucinator muscle fibers. Potential causes and explanations for this finding will be discussed, as well. [ABSTRACT FROM AUTHOR]

Sjögren's Disease (SjD) is a chronic autoimmune disorder that affects the salivary and lacrimal glands, leading to xerostomia and xerophthalmia. Ultrasonography of Major Salivary Glands (SGUS) is a well-established tool for the identification of the salivary glands' abnormalities in SjD. Recently, a growing interest has arisen in the assessment of the other exocrine glands with ultrasonography: lacrimal glands (LGUS) and labial salivary glands (LSGUS). The objective of this study is to explore the practical applications of ultra-high frequency ultrasound (UHFUS) in the assessment of lacrimal glands and labial salivary glands. Indeed, UHFUS, with its improved spatial resolution compared to conventional ultrasonography, allows for the evaluation of microscopic structures and has been successfully applied in various medical fields. In lacrimal glands, conventional high-frequency ultrasound (HFUS) can detect characteristic inflammatory changes, atrophic alterations, blood flow patterns, and neoplastic lesions associated with SjD. However, sometimes it is challenging to identify lacrimal glands characteristics, thus making UHFUS a promising tool. Regarding labial salivary glands, limited research is available with conventional HFUS, but UHFUS proves to be a good tool to evaluate glandular inhomogeneity and to guide labial salivary glands biopsy. The comprehensive understanding of organ involvement facilitated by UHFUS may significantly improve the management of SjD patients. [ABSTRACT FROM AUTHOR]

Adenocarcinoma, not otherwise specified (NOS) exhibits ductal differentiation without the diagnostic histomorphological features of other defined salivary carcinomas. Adenocarcinoma, NOS rarely occurs in the lip, and when adenocarcinomas occurs in more than one organ, it is often difficult to identify the primary site. We report a case of adenocarcinoma of the left-upper lip occurring in a 67-year-old woman, which need to clearly identify the type of tumor required collaboration with Department of Respiratory Surgery to identify the primary origin site. The woman was referred to our department because of a painless mass in the upper lip. The clinical diagnosis was a benign tumor or mucous cyst and we performed a biopsy. The histopathological diagnosis was adenocarcinoma, NOS. Chest computed tomography demonstrated a mass in the lower-right-lung lobe. We suspected lung metastases and histopathologically attempted to identify the primary lesion. Immunohistochemical analysis showed positive staining for cytokeratin 7 and negative staining for thyroid transcription factor 1 and napsin A. The analysis identified the primary lesion as a salivary adenocarcinoma, NOS. We performed a full-thickness resection of the left-upper lip and reconstructive surgery of the upper lip. Postoperative computed tomography at the 3-month follow-up showed no mass in the lower-right-lung lobe. Follow-up examinations have shown no evidence of recurrence for 4 years after the surgery. [ABSTRACT FROM AUTHOR]

Objectives: Cheilitis Glandularis (CG) is an uncommon entity of obscure etiology. A cases series is presented with emphasis on etiopathogenesis. Materials and Methods: Fourteen CG cases were analyzed according to their demographic and clinicopathologic characteristics. Results: The mean age of the patients with CG was 68.1 years, while a male‐to‐female ratio of 1.8:1 was observed. One or more potential causative factors were identified for each patient, including long‐term smoking (9 cases), xerostomia (4 cases), cosmetic filler injections (2 cases), and actinic cheilitis (1 case). The lesions were located on the lips, buccal mucosa, or both in 7, 2, and 5 cases, respectively. Multiple submucosal nodules with dilated ductal orifices and mucous or purulent discharge were observed in all cases. Histopathologically, ductal ectasia with metaplasia, intraductal mucin, and chronic or mixed inflammation were noted, as well as pools of hyaluronic acid in 2 cases with a history of cosmetic filler injections. Conclusions: CG etiopathogenesis is probably multifactorial. Reduced salivary flow rate and increased viscosity of saliva, potentially caused by long‐term smoking, diabetes mellitus, and drug‐induced xerostomia, may participate in the initial pathogenesis, while local irritants, for example, poor oral hygiene and local trauma, may further contribute to the development and aggravation of the condition. [ABSTRACT FROM AUTHOR]

Introduction: Aim of this study was to explore the incidence, pathology, clinical behaviour and evaluate factors predictive on survival and treatment outcomes in a cohort of patients with minor salivary gland (MiSG) malignancies treated at a single center over a period of 25 years. Materials and methods: Patients who had received primary treatment for MiSG malignancy during 25 years observation period were identified. Outcomes that were evaluated were overall survival (OS), disease specific survival (DSS), recurrence free survival (RFS), locoregional recurrence free survival (LRFS) and distant metastasis free survival (DFS). Results: A total of 88 patients with MSG malignancies were included in the study. The most common location for MiSG malignancies was the oral cavity (65 tumors; 77%). Cumulative OS for 5 and 10 year follow up period was 82% and 62% respectively. Cumulative DSS for 5 and 10 year follow up period was 85% and 73% respectively. Twenty one (23%) patients developed distant metastases during follow-up. High-grade pathology and tumor stage were significant variables on multivariate analysis for all survival and treatment outcomes. Conclusions: Minor salivary gland malignancies are minor only by name. Tumor histological grade, AJCC tumor stage and pT stage were the strongest predictive factors for survival and treatment outcomes. The elective neck dissection could be considered therapeutic approach for selected cases of high grade MiSG malignancies. Distant metastases were the main cause of death and treatment failure. [ABSTRACT FROM AUTHOR]

Cystadenocarcinoma is an extremely rare lesion with a low incidence rate of 0.18% of all salivary gland tumors in the oral and maxillofacial region. Here, we report two cases of cystadenocarcinoma in the lip. Case 1 was of a 79-year-old woman who presented with discomfort in the right upper lip. On examination, a 16 × 10 mm mass was observed on her right upper lip. The superficial mucosa was smooth but with an irregular margin. The mass was clinically suspected to be a malignant tumor, and tumor resection was performed. Case 2 was of a 51-year-old man who presented with a 20 × 20 mm mass on the left lower lip. The mass was hard, and adhesion to the skin was suspected. On T2-enhanced magnetic resonance imaging, high signal intensity and internal non-uniform features were noted. Before the operation, fine-needle aspiration cytology was performed, and atypical cells were observed; therefore, resection was performed assuming a malignant tumor. The surgeries were performed 3 years ago, and no recurrence or lymph node metastasis has been observed in either case to date. [ABSTRACT FROM AUTHOR]

Background: Oral squamous cell carcinoma (OSCC) is one of the most established oral cancers in India, with high morbidity and mortality. The most common etiological agent associated with it is tobacco (in any form), which releases chemical carcinogens that affect not only the oral epithelial lining but also deep stromal structures such as minor salivary glands. They may cause changes in ductal or acinar part of gland depending on tumor grade, thus providing a fertile soil for tumor growth and recurrence. Aims and Objective: To observe the frequency of minor salivary gland changes associated with tobacco as well as to measure the length and depth of ductal involvement in routine tissue sections of OED and OSCC. Materials and Methods: A total of 94 hematoxylin and eosinstained archival slides which included cases of well, moderate, and poorly differentiated OSCC and oral epithelial dysplasia were histopathologically evaluated to observe changes in different components of minor salivary gland. Ductal hyperplasia, ductal metaplasia, mucous pooling within duct, acinar degeneration, pattern of malignant cell invasion (single/clusters), inflammatory infiltrate, eosinophilic cuffing around the gland, and glandular/vascular involvement were evaluated in each slide and correlated with different grades of OSCC. Results: Ductal hyperplasia, inflammatory cell infiltrate, mucous pooling, and pattern of malignant cell infiltration came out to be statistically significant with the highest percentage of changes being observed in poorly differentiated squamous cell carcinoma > moderately differentiated squamous cell carcinoma> well differentiated squamous cell carcinoma>oral epithelial dysplasia. Further, the results of this study suggest that extension of dysplasia or squamous cell carcinoma from overlying oral epithelium along salivary gland ducts is an uncommon finding. Conclusion: Hence, histopathological interpretation for OED and OSCC should also include changes related to associated minor salivary gland tissue as detection and eradication of the putative precursors are the best way of decreasing the overall morbidity caused by tumors. [ABSTRACT FROM AUTHOR]

Introduction: Based on ACR/EULAR classification criteria, minor salivary glands biopsy (MSGB) is a useful diagnostic tool for the diagnosis of primary Sjögren's syndrome (SS). The main objective of our study was to evaluate the diagnostic role of MSGB, as well as to highlight correlations between histological findings and autoimmune profiles. Material and methods: We retrospectively evaluated histological and autoimmunity data from patients who underwent MSGB in our department in cases of suspected SS, from March 2011 to December 2018. Salivary gland samples were evaluated using Chisholm and Mason (CM) grading and the focus score (FS). Results: A total of 1,264 patients (108 males, 1,156 females) were included. The median age was 55.22 ±13.51 years (range: 15-87). In univariate binary logistic regression, CM = 3 and FS = 1 were significantly predicted by antinuclear antibodies (ANA), anti-extractable nuclear antigens (ENA) and anti-Ro/SSA titer as well as anti-La/SSB, anti-Ro/SSA, rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA) positivity. In multivariate analysis, CM = 3 and MSGB positivity were significantly associated with ANA titer; FS = 1 was not associated with laboratory findings. A positive biopsy was associated with laboratory findings, as ANA and ENA titers, anti-Ro/SSA, anti-La/SSB, RF and ACPA positivity may discriminate patients with SS-related histological findings. Conclusions: Minor salivary glands biopsy is a useful tool to diagnose SS in cases of highly suggestive clinical symptoms but in the absence of a specific autoimmunity. [ABSTRACT FROM AUTHOR]

Secretory carcinoma (SC) is an uncommon salivary gland tumor that has been recently conceptualized. The present report describes a case of SC that was diagnosed as a mucocele on preoperative examination. A 46-year-old man presented to the Department of Oral and Maxillofacial Surgery at Saiseikai Senri Hospital (Suita-shi, Japan) with a main complaint of swelling of the right buccal mucosa. A mobile, elastic, hard mass was found beneath the right normal-appearing buccal mucosa. T2-weighted magnetic resonance imaging revealed a well-defined, internally homogeneous high-signal area with a maximum diameter of 18 mm. Based on the clinical diagnosis of mucocele, the buccal lesion was excised. Histopathological, immunohistochemical and fluorescence in situ hybridization analyses revealed the cystic lesion to be a macrocystic SC of a minor salivary gland. SC may have a mucocele-like appearance on magnetic resonance imaging. Even if a non-neoplastic lesion is suspected, the possibility of a malignant lesion such as SC must be considered for salivary gland disease. [ABSTRACT FROM AUTHOR]

We report a case of mucocele of the lower lip in a 17-year-old female patient. She complained of a painless swelling on her lower lip for the last one month. The patient also gave a history of lip-biting. Upon clinical inspection, a soft, round, dome-shaped bluish lesion with a pearly appearance was identified on the right lower labial mucosa. On palpation, the lesion was mobile and non-adherent to the underlying tissues. An excisional biopsy was performed under local anesthesia, and the excised sample was sent for histopathological evaluation. Histopathology revealed mucus pooling, surrounded by compressed connective tissue stroma and areas of chronic inflammation indicative of a mucocele. The post-excisional review was done after 10 days, and the patient's healing was satisfactory. The patient had no signs of recurrence after two years of follow-up., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Kannan et al.)

Sjögren’s Disease (SjD) is a chronic autoimmune disorder that affects the salivary and lacrimal glands, leading to xerostomia and xerophthalmia. Ultrasonography of Major Salivary Glands (SGUS) is a well-established tool for the identification of the salivary glands’ abnormalities in SjD. Recently, a growing interest has arisen in the assessment of the other exocrine glands with ultrasonography: lacrimal glands (LGUS) and labial salivary glands (LSGUS). The objective of this study is to explore the practical applications of ultra-high frequency ultrasound (UHFUS) in the assessment of lacrimal glands and labial salivary glands. Indeed, UHFUS, with its improved spatial resolution compared to conventional ultrasonography, allows for the evaluation of microscopic structures and has been successfully applied in various medical fields. In lacrimal glands, conventional high-frequency ultrasound (HFUS) can detect characteristic inflammatory changes, atrophic alterations, blood flow patterns, and neoplastic lesions associated with SjD. However, sometimes it is challenging to identify lacrimal glands characteristics, thus making UHFUS a promising tool. Regarding labial salivary glands, limited research is available with conventional HFUS, but UHFUS proves to be a good tool to evaluate glandular inhomogeneity and to guide labial salivary glands biopsy. The comprehensive understanding of organ involvement facilitated by UHFUS may significantly improve the management of SjD patients.

Lymphoepithelial carcinoma (LEC) of the oral mucosa is a rare histopathologic subtype of squamous cell carcinoma (SCC), which shares morphologic similarities with nasopharyngeal carcinoma (NPC), non-keratinizing undifferentiated subtype. The admixture of neoplastic epithelial tumor cells and a dense lymphoplasmacytic infiltrate makes microscopic diagnosis challenging. LEC etiopathogenesis has been variably associated with Epstein–Barr virus (EBV) infection, depending on the specific anatomic location and racial predilection, with a higher incidence in endemic populations. Although described in several subsites of the head and neck region, including the major salivary glands, the oral mucosa is considered an infrequent location for LEC development, deriving either from minor salivary glands (MSGs) or the surface epithelium. Herein, we report a rare case of an EBV-negative LEC arising from the oral surface epithelium, presenting as gingival swelling, and review the pertinent English-language literature, which revealed only 26 previously reported oral LECs. Our case is only the fourth oral LEC originating from the surface epithelium and the first one to affect the gingiva. [ABSTRACT FROM AUTHOR]

Purpose: This review study presents literature review and discusses the clinical significance of Adenomatoid Hyperplasia; a commonly misdiagnosed lesion. This rare entity has been seldom presented and is not well enough described in the literature. Methods: Only 15 reports with 95 cases could be attained during the online literature search using the keywords: Adenomatoid, Tumor, Hyperplasia, Minor salivary Glands. Results: Data revealed a tendency towards the male gender. Age distribution of patients did not reveal a tendency towards a specific age group but presented a peak incidence in the 4th and 5th decades. Location data revealed a tendency towards the palate, especially the hard palate. Most of the presented cases were asymptomatic and the most common initial diagnosis made was salivary gland tumor. Conclusion: Adenomatoid hyperplasia of the oral cavity may resemble a wide range of pathologies. In order to differentiate and to achieve a correct diagnosis, histological evaluation is fundamental.

Introduction: Cribriform adenocarcinoma of the tongue and minor salivary glands (CATMSG) is a rare neoplasm, accounting for less than 1% of salivary gland tumors. In the past it has been considered a possible variant of polymorphous low-grade adenocarcinoma (PLGA), while nowadays it is accepted as a provisional entity in the WHO classification. The aim of this paper is to systematically review the existing literature about CATMSG with a particular attention to differential diagnosis and prognostic factors. Methods: This study was performed in accordance with the PRISMA checklist. A comprehensive search in PubMed, Cochrane, and Google Scholar databases was carried out in June 2021, in partnership with a medical librarian, without time restriction. Search items include the following keywords: "cribriform adenocarcinoma of the tongue" OR "cribriform adenocarcinoma of the tongue and minor salivary glands." Results: A total of 56 patients were evaluated. Patient age across the studies ranged from 13 to 85 years (mean 59.6 year). The most common site of involvement was the tongue (58.9%), followed by palate (19.6%), tonsil (7.1%), buccal (3.6%) and reticular mucosa (3.6%), lip (3.6%), retromolar pad (1.7%), and floor of the mouth (1.7%). Lymph node involvement at the diagnosis was very common (58.9%), while there was no evidence of patients diagnosed with metastatic disease. The most common surgical approach was surgical excision (17, 30.3%); neck dissection was performed in 16 patients (28%). Radiotherapy was the most common adjuvant treatment reported (46.4%); only one patient underwent adjuvant chemotherapy (1.7%). Five patients experienced a recurrence (8.8%). Conclusion: To our knowledge, only 56 five cases of CATMSG have been previously described. The results of this review seem to confirm the low frequency of relapses and distant metastases, but we observed that almost 60% of cases presented with cervical lymph node involvement. In our opinion, CATMSG should be considered as a distinct tumor entity from PLGA. [ABSTRACT FROM AUTHOR]

Denture-induced fibrous hyperplasia or epulis fissuratum refers to reactive tissue alteration occurring in response to trauma and chronic irritation due to the badly fitted prosthesis. Pathologic changes observed in the oral mucosa may vary depending on the severity of trauma to the mucosa. Trauma to minor salivary glands caused by the impingement of denture flanges can result in chronic sialadenitis. In this article, we discuss a case of denture-induced fibrous hyperplasia with prominent minor salivary gland changes in a Male patient of age 63 years.

Peritonsillitis (PT) is defined as cellulitis in peritonsillar tissue without pus. The pathogenesis of peritonsillar infections is controversial. To explore whether minor salivary glands are involved in the development of PT and to identify clinical findings that predict the evolution of PT to peritonsillar abscess (PTA). We included 146 adult patients treated for acute tonsillitis (AT; n = 54), PT (n = 34), or PTA (n = 58) at the Helsinki University Hospital. The treating physician recorded tonsillar, oropharyngeal, and dental findings. We analysed serum C-reactive protein (S-CRP) and amylase (S-Amyl). For PTA, pus samples were analysed; for AT and PT, throat cultures were collected. Patients with PT or PTA (PT/PTA; n = 92) were classified into groups with or without tonsillar exudate or hyperaemia (tonsillar findings). The PT group without tonsillar findings had lower S-CRP than the PT group with tonsillar findings (p=.0275). The PT/PTA group without tonsillar findings had higher S-Amyl than the PT/PTA group with tonsillar findings (p=.0278). Three out of 34 (8.8%) patients with PT returned to the emergency department; 1 (2.9%) developed PTA. Elevated S-Amyl in the PT/PTA group without tonsillar findings suggests that minor salivary glands are sometimes involved in the development of peritonsillar infections. [ABSTRACT FROM AUTHOR]

Mucoceles are cavities filled with mucus and are one of the most common benign soft tissue masses that occur in the oral cavity. They are traumatic in origin and are formed when the main duct of a minor salivary gland is traumatized with subsequent extravasation of the mucus into the fibrous connective tissue forming a cyst like cavity. Mucoceles can appear by an extravasation or a retention mechanism. They appear as discrete, small, translucent, soft, painless swelling of the mucosa ranging from normal pink to deep blue in color and are most commonly found on the lower lip, lateral to the midline and may occur at any age, but they are more frequently seen in the second and third decade of life. The lesion has no sex predilection and occurs more frequently in children, adolescents. Generally managed by conservative surgical excision. [ABSTRACT FROM AUTHOR]

Abstract Background Necrotizing sialometaplasia (NSM) is an extremely rare benign lesion with an uncertain pathogenesis. The differential diagnosis of this lesion is challenging due to little familiarity with this entity and histologic similarity with carcinomas, especially mucoepidermoid carcinoma (MEC). The purpose of this study is to raise awareness about NSM, which is often overlooked or misdiagnosed as malignancy in a small biopsy. Methods We reviewed all biopsy materials taken from the oral cavity in a single institution in Korea from 2012 to 2018 and found 4 cases of NSM out of 726. Clinicopathologic characteristics and comparison with other lesions were discussed. Results Unlike previous reports, patients in our series were relatively young, and NSM was not related to smoking and not associated with malignancies, although one patient was misdiagnosed with MEC on the basis of the initial biopsy. High-grade squamous dysplasia was observed in one patient; however, all four patients showed excellent prognoses without further management. Conclusions A conservative approach is recommendable for necrotizing lesions of the palate in young adults to avoid unnecessary treatment. However, careful monitoring is also required due to uncertainty of premalignant potential.

The Pleomorphic Adenoma is the most frequent benign tumor of the salivary glands. The cheeks, lips and gingiva are rare sites of appearance. The objective of this study is to report a case of a Pleomorphic Adenoma arising from the buccal mucosa. A 57-year-old female patient who presented with an increase in volume in the right facial region with one year of evolution, asymptomatic and without treatment. Physical examination revealed a nodular lesion of approximately 3 cm in diameter, located in the right cheek. MRI revealed a hyperintense image in STIR sequence. Excisional biopsy of the lesion was made under balanced general anesthesia, where extracapsular dissection of the tumor was performed, using a transoral approach. The histopathological study resulted in pleomorphic adenoma. Despite the low rate of recurrence of this neoplasm, short, medium and long term follow-ups are recommended.

Epithelial-myoepithelial carcinoma is a biphasic low-grade malignant tumor, which represents approximately 1% of all salivary gland tumors. This tumor occurs mostly in the parotid gland, followed by submandibular gland and minor salivary glands. Women, mostly fifth to the eighth decade of life, are commonly affected. Histopathologically, epithelial-myoepithelial carcinoma is composed of an inner single layer of eosinophilic cuboidal ductal cells and outer single or multiple layers of clear myoepithelial cells. We present a case of a 69 years old man who had a scar on lower the lip for 10 years and voice annoyance for three months. The biopsy for lower lip was reported 'infiltrative clear cell epithelioid neoplasm' and vocal cord biopsy result was 'verrucous carcinoma'. After cordectomy and wedge resection of the lower lip, histopathology revealed Epithelial-Myoepithelial Carcinoma for the lower lip and microinvasive verrucous carcinoma for the left vocal cord. Our case has a very uncommon location and presentation for EMC. The tumor location was minor salivary glands of the lower lip and the clinical presentation was quite different. Coexistence with microinvasive verrucous carcinoma of the vocal cord is the other unique part of our case.

Abstract Background Secretory carcinoma is a more recently described subtype of salivary gland carcinoma that may pose diagnostic challenges and frequently harbors NTRK fusions that may successfully be targeted by TRK inhibitors in advanced disease. Case We present the case of a female patient with secretory carcinoma arising in the base of tongue with persistent disease after debulking surgery and definitive chemoradiation. As an alternative to salvage surgery, which would have resulted in significant impairment of swallowing and speech function, a targeted therapy with the TRK‐inhibitor larotrectinib against an identified ETV6‐NTRK3 fusion product was initiated. Larotrectinib treatment has been well tolerated, resulted in durable complete response and the patient maintains good swallowing and speech function. Conclusion The presented case underscores the importance of the accurate diagnosis of secretory carcinoma. It further highlights the impact of molecular testing as targeted therapies may play an important role in the management of advanced salivary gland cancers.

Polymorphous adnenocarcinoma (PAC) is a less aggressive malignant tumour, mainly occurs in the minor salivary glands. It is less frequently seen in the upper lip. As there aren't any specific features to differentiate PAC from other benign tumours of the minor salivary glands of the upper lip, PAC must be considered in the differential diagnosis of the minor salivary gland tumours of the upper lip.

Pleomorphic adenoma (PA) is the most prevalent benign salivary gland tumor. Although rare, among the minor salivary glands, palatal PA exhibits the highest incidence. Unlike other benign tumors, PA infiltrates the surrounding tissues, posing challenges for complete removal through conservative measures. Surgeons often resort to aggressive surgical procedures involving resection of adjacent tissue to ensure clear margins and prevent recurrence. This study aims to analyze diverse histological characteristics of palatal PA, seeking statistical correlations for early prediction of tumor aggressiveness. The goal is to facilitate the preservation of the periosteum during surgical resection and attain conservative surgical margins. A retrospective histopathological investigation encompassed 18 patients diagnosed with palatal PA who underwent surgical treatment at Hadassah Medical Centre, Jerusalem, Israel. Evaluated parameters included tumor size, pseudocapsule thickness, tumor-periosteum distance, and the presence of pseudopodia and satellite nodules indicating tumor penetration. Statistical significance was set at P < 0.05. Tumors of varying sizes, whether large or small, lack consistent features. Neither tumor size, pseudocapsule thickness, nor tumor-periosteum distance displayed correlations with tumor penetration features. Palatal PA exhibits varied histological attributes impacting surgical technique. The absence of correlations among these attributes impedes early prediction of tumor aggressiveness, casting doubt on periosteum preservation. The periosteum is sufficiently robust to contain the tumor and should be excised. There is no data to support either ostectomy or a through-and-through surgical resection as part of the treatment., Competing Interests: Declaration of competing interest None., (Copyright © 2024 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Aims: There is a widespread perception among clinicians and pathologists that the histomorphological assessment of minor salivary gland (MinSG) tumours is more difficult and hampered by more misdiagnoses than that of major salivary gland tumours. This is based on a vague, subjective clinical impression, lacking scientific proof. The aim of the present study was to identify and statistically verify potential reasons that could explain this difference. Methods and results: We identified 14 putative clinical, pathological and combined clinicopathological reasons that, altogether, could explain the phenomenon of the perceived greater diagnostic difficulty associated with MinSG tumours. We performed a comprehensive literature search and a statistical comparison of data from a large personal consultation series (biased for difficult cases) with cumulated data from straightforward, unselected (non‐consultation) series from the literature. By performing this comparison, we identified, with statistical significance, a comprehensive series of reasons, as well as of consequences, of the greater difficulty in diagnosing MinSG tumours. Conclusions: Among the 14 criteria, high frequencies of initial incisional biopsies and of a low‐grade category in malignant tumours emerged as the two most important reasons for enhanced diagnostic difficulty. Very rare entities, unusual locations, shortcomings in clinicopathological communication, and pecularities of the special anatomical location of the hard palate, such as tumour necrosis, mucosal ulceration, pseudoinvasion, and the peculiar phenomenon of 'tumoral–mucosal fusion', contribute to further diagnostic difficulties. The awareness of these shortcomings and pitfalls enables us to provide a series of recommendations for clinicians and pathologists that might aid in assessment and reduce the rate of misdiagnosis of MinSG tumours. [ABSTRACT FROM AUTHOR]

Cribriform adenocarcinoma is a rare tumor that arise in tongue and minor salivary glands. Previously, only 56 case have been described. In this paper, we report a case of a 83‐year‐old man and we focus about the differential diagnosis with polymorphous adenocarcinoma. [ABSTRACT FROM AUTHOR]

The objective of this study was to investigate the accuracy of fine needle aspiration cytology (FNAC) and biopsy for the clinical diagnosis of minor salivary gland tumours (MSGTs). This retrospective study of 32 MSGT cases was conducted over a 5-year period. Clinical features including age, sex, and location of the tumour were obtained from the patient clinical records. All cases were also assessed histologically according to the 2017 World Health Organization Classification of Head and Neck Tumours. The results of FNAC and biopsy were correlated with those of histopathology, and their sensitivity, specificity, and diagnostic efficacy were calculated using histopathology as the gold standard. Eighteen malignant MSGTs (56.3%) and 14 benign MSGTs (43.8%) were diagnosed by pathological diagnosis. The most common malignant tumour was mucoepidermoid carcinoma (seven cases, 38.9%). Most benign cases were pleomorphic adenomas (13 cases, 92.9%). FNAC was performed for 23 cases and biopsy for 13 cases. The sensitivity and specificity of FNAC were 66.7% and 91.0%, respectively, while those of biopsy were 90.0% and 100.0%, respectively. Although FNAC is a minimally invasive and cost-effective procedure, it is less accurate than biopsy in the assessment of MSGTs. Repeated FNAC or biopsy should be considered in negative and unsatisfactory FNAC cases. [ABSTRACT FROM AUTHOR]

Abstract Cribriform adenocarcinoma is a rare tumor that arise in tongue and minor salivary glands. Previously, only 56 case have been described. In this paper, we report a case of a 83‐year‐old man and we focus about the differential diagnosis with polymorphous adenocarcinoma.

Presence of minor salivary glands in the oral mucosa and its potential use as an autograft for treating dry eye disease has been widely reported in humans. But there is a paucity of literature regarding the histological evidence for the presence of minor salivary glands in the oral mucosa of dogs. The present pilot study histologically identified and topographically described the minor salivary glands in the oral mucosa of two dogs, as a potential autograft for keratoconjunctivitis sicca. The samples were collected from different sites of the upper and lower lips and the commissures. Samples were processed for routine paraffin embedding; 5 μm sections were taken and were stained using Hematoxyline and Eosin staining. Histological examination revealed exocrine, compound, tubulo-acinar glands and the secretion was mixed type

There is a critical need to deconvolute the heterogeneity displayed by the minor salivary glands of primary Sjögren’s syndrome (pSS) patients. This is challenging primarily because the disease etiology remains unknown. The hypothesis includes that initial events in the disease pathogenesis target the salivary glands, thereby triggering the development of focal infiltrates (≥50 mononuclear cells) and finally germinal center-like structures. However, the proportion of key mononuclear immune cells residing at these sites, in combination with the overall ratio of morphometric tissue atrophy and adipose infiltration within the minor salivary glands (MSG) parenchyma at distinct phases of inflammatory disease establishment and progression have not been quantified in detail. In this cross-sectional study, we intended to address this problem by stratifying 85 patients into mild (S1), moderate (S2), and severe (S3) stages using the Inflammatory severity index. We found that mild (