TGF-ß3 from fibroblasts promotes necrotising sialometaplasia by suppressing salivary gland cell proliferation and inducing squamous metaplasia.

Necrotising sialometaplasia (NSM) is a non-neoplastic lesion mainly arising in the minor salivary glands of the oral cavity. In the clinical features, NSM shows swelling with or without ulceration, and can mimic a malignant disease such as squamous cell carcinoma. Histopathologically, NSM usually shows the lobular architecture that is observed in the salivary glands. Additionally, acinar infarction and squamous metaplasia of salivary ducts and acini are observable. The aetiology of this lesion remains unknown, although it has a characteristic feature that sometimes requires clinical and histopathological differentiation from malignancy. In this study, we investigated upregulated genes in NSM compared with normal salivary glands, and focused on the TGF-ß3 (TGFB3) gene. The results of the histopathological studies clarified that fibroblasts surrounding the lesion express TGF-ß3. Moreover, in vitro studies using mouse salivary gland organoids revealed that TGF-ß3 suppressed salivary gland cell proliferation and induced squamous metaplasia. We demonstrated a possible aetiology of NSM by concluding that increased TGF-ß3 expression during wound healing or tissue regeneration played a critical role in cell proliferation and metaplasia. © 2024 The Pathological Society of Great Britain and Ireland.

Necrotizing sialometaplasia: a malignant masquerade but questionable precancerous lesion, report of four cases.

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.

Necrotizing sialometaplasia: a case report of a non-ulcerated histopathological presentation.

A 27-year-old woman presented with the chief complaint of severe pain in the palate region, which had been present for two months. Upon examination, she was found to have a firm, non-ulcerated nodule measuring about 2.5cm at the palatal junction. Incisional biopsy was recommended because the clinical differential diagnosis was mucoepidermoid carcinoma or squamous cell carcinoma. Anatomopathological examination revealed squamous metaplasia of the salivary gland ducts with preservation of the lobular architecture. Immunohistochemistry showed metaplastic ducts with low reactivity for p53 and Ki67, as well as positivity for CK AE1/AE3, CK7, p63, S-100, and SMA. The final diagnosis was necrotizing sialometaplasia. No treatment is required for this disease. Thirty-nine days after biopsy, total remission was observed with no signs of relapse after two years.

Necrotizing Sialometaplasia and Bulimia: A Case Report.

Bulimia is an eating disorder with a great prevalence in young women. Due to its multifactor ethiology, bulimia has systemic consequences. In the literature, necrotising sialometaplasia is seldom associated with bulimia. Its etiopathogenesis is discussed by several authors; nevertheless, the consensus does not consider the relevance of local trauma associated with induced vomiting. A case of necrotising sialomethaplasia, presented with a single hard palatal ulcer in a bulimic woman is described in the present report. The patient did not present significant systemic laboratorial values, nor physical weight variations, which highlights the relevance of performing a complete medical clinical history when diagnosing this rare pathology.

[Immunohistochemical diagnosis of necrotizing sialometaplasia]. / Immunogistokhimicheskaya diagnostika nekroticheskoi sialometaplazii.

The article presents a clinical case of an immunohistochemical study of a rare disease: necrotizing sialometaplasia in the hard palate. Due to the complexity of the differential diagnosis between necrotizing sialometaplasia and squamous cell carcinoma, an immunohistochemical method was used with antibodies to proteins Ki-67, P53, P63 and cytokeratins-7 and Immunohistochemical study established low proliferative activity of glandular cells in excretory ducts and metaplastic squamous epithelium for Ki-67 protein, significant expression of protein P63 was detected both in the ductal epithelium nuclei and in metaplastic areas and expression of the mutant protein P53 was approximately absent. Marked expression of cytokeratin-7 in the ducts cells and weak expression in necrotic acini of the glands and metaplastic epithelium was noted. It was shown that cytokeratin-15 homogeneously stains the peripheral zone of metaplastic epithelium, which is characteristic of a benign lesion. Thus, the panel of antibodies to proteins Ki-67, P53 and cytokeratins-7 and 15 allows to verify necrotizing sialometaplasia.

Necrotizing sialometaplasia can hide the presence of salivary gland tumors: A case series.

OBJECTIVE: Necrotizing sialometaplasia (NS) is an uncommon benign process which affects minor and, more rarely, major salivary glands. While self-limiting, the condition might be clinically and histologically mistaken for malignancy. Furthermore, NS may accompany neoplasms. The aim of this paper was to report a series of Italian patients affected by NS associated with an unusual high presence of neoplasms of minor and major salivary glands. STUDY DESIGN: Clinical and histological features of twelve patients with NS were retrospectively evaluated. RESULTS: Eight patients presented NS of the minor salivary glands of the palate, and two of them had associated neoplasms (pleomorphic adenoma and adenoid cystic carcinoma) at the same site. Four patients had NS of the parotid gland associated with a history of fine-needle aspiration biopsy performed to diagnose parotid neoplasms. These were epithelial-myoepithelial carcinoma, adenoid cystic carcinoma, Warthin's tumor, and oncocytoma, respectively. CONCLUSION: Tumors of minor and major salivary glands might be associated with NS more frequently than previously reported. While NS of the parotid is generally the result of invasive diagnostic procedure and is detected after the excision of the tumor, NS of the minor salivary glands may obscure an underlying neoplasm, resulting in delays in referral or treatment.

Necrotising sialometaplasia: a diagnostic perplexity? An innocent entity to malignant masquerade.

OBJECTIVE: Necrotising Sialometaplasia is a benign self limiting reactive condition of major and minor salivary glands, which can arouse suspicion for malignancy, clinically and histopathologically. Here, we report a case of 38-year-old female with a painful ulcer on the palate. The case enlightens the importance of clinicopathologic correlation and diligent follow up in diagnosis and management of the case.

Necrotizing sialometaplasia of the lacrimal sac mimicking squamous cell carcinoma: Necrotizing dacyocystometaplasia.

INTRODUCTION: Necrotizing sialometaplasia is thought to represent an inflammatory reaction directed against an ischemic insult or local trauma within a glandular tissue and is most commonly observed in the minor salivary glands of the oral mucosa. The importance of this condition arises from the fact that its clinical and histological aspects may raise issues of differential diagnosis with malignant neoplasms. The authors present a case of necrotizing sialometaplasia involving the lacrimal sac simulating a well-differentiated squamous cell carcinoma. CASE: A 52-year-old man presented with epiphora in the left eye after having sustained an orbital blowout fracture during a motor vehicle accident. During subsequent external dacryocystorhinostomy, an abnormal lacrimal sac mucosa was observed and analyzed histologically revealing a well-differentiated squamous cell carcinoma. However, the subsequent biopsies of the lacrimal sac were negative for malignancy; in view of these findings, two pathologists reviewed the first specimen and immunohistochemical staining was performed allowing us to arrive at a diagnosis of necrotizing sialometaplasia. We suggest the term necrotizing dacryocystometaplasia for the involvement at this site. CONCLUSION: Although exceedingly unusual, necrotizing dacryocystomeplasia should be considered in patients presenting with epiphora in the appropriate clinical context. Notably, this condition can be mistaken for a malignant disease, presenting a diagnostic challenge both clinically and histopathologically.

HIF-1α, VEGF, and EGFR: contributing factors in the pathogenesis of necrotizing sialometaplasia.

OBJECTIVES: Necrotizing sialometaplasia (NS) is an uncommon reactive lesion involving the minor salivary glands. This study aimed to investigate the expression of hypoxia-inducible factor alpha (HIF-1α), vascular endothelial growth factor (VEGF), and epithelial growth factor receptor (EGFR) in the pathogenesis of NS. METHODS: Paraffin-embedded tissue sections from 10 cases of NS were immunohistochemically stained for HIF-1α, VEGF, and EGFR. A semiquantitative morphometric analysis was performed and compared with normal palatal salivary glands and traumatic ulcerations. RESULTS: Hypoxia-inducible factor alpha staining was observed in most elements of the affected area, the acini and ducts of the involved salivary glands as well as in the inflammatory infiltrate, the endothelial cells, and stromal cells. HIF-1α was almost absent in the control glands (P < 0.0001). VEGF staining was positive in the stromal capillaries and in the inflammatory infiltrate. The expression was higher in cases of NS compared with the normal salivary glands (P < 0.001). EGFR was expressed in the surface epithelium, the pseudo-epitheliomatous hyperplasia, and the islands of squamous metaplasia. VEGF expression in traumatic ulcerations was lower than that in cases of NS. CONCLUSION: This study provides molecular evidence to the role of hypoxia in NS; HIF-1α, the main regulator of hypoxia, was expressed in the infarcted salivary glands, EGFR in the metaplastic epithelium and VEGF in the stromal capillaries, all three components are the key factors induced by hypoxia.

Necrotizing sialometaplasia of the palatal mucosa in patient with history of anorexia: review and case report.

Necrotizing sialometaplasia is a self-limiting disorder affecting minor salivary glands resembling a malignant process both clinically and histopathologically. The etiology of this rare inflammatory` disorder is related to an ischemic event. Identified risk factors include alcohol abuse, smoking, drugs, denture wearing, injury and systemic diseases. Also reported are cases of necrotizing sialometaplasia associated with bulimia. This paper identifies the whole body incitement among additional risk factors by presenting a case of necrotizing sialometaplasia in an 18 year old patient with the history of anorexia nervosa. Furthermore it describes the effects of extreme cooling of palatal mucosa with ice chips resulting in constriction of blood vessels as the direct cause, reinforcing ischemic etiology of necrotizing sialometaplasia.

Two rare entities in the same palate lesion: hyalinizing-type clear cell carcinoma and necrotizing sialometaplasia.

Hyalinizing clear cell carcinoma is a low-grade malignant epithelial neoplasm of the salivary glands. The tumor has epithelial cells and lacks myoepithelial cells. Necrotizing sialometaplasia is a benign, self-limiting lesion of the salivary glands. The clinical and histologic features mimic those of mucoepidermoid carcinoma or squamous cell carcinoma. The importance of these entities are the rarity of both of them and their potential to be misdiagnosed as other lesions. Pathologists and clinicians should be aware of these entities to prevent misdiagnosis. This is the first clinical report of 2 rare and consecutive different entities of the same location on the hard palate to our knowledge.

[Necrotizing sialometaplasia--diagnostic difficulties--literature review]. / Necrotizing sialometaplasia--trudnosci diagnostyczne--przeglad pismiennictwa.

Necrotizing sialometaplasia is a benign, self-limiting inflammatory process, which concerns small salivary glands. This kind of lesion is very rare, with difficulties in clinical and histopathological diagnosis. Ulceration is the dominating symptom, which may suggest that it is a malignancy. Lesions usually heal spontaneously.

[Necrotizing sialometaplasia]. / Nekrotisoiva sialometaplasia--suun tuumori ei ollutkaan syöpä.

Necrotizing sialometaplasia is a rare inflammatory condition clinically and histologically resembling a malignant tumor. The lesion is usually present on the palatal mucosa, and heals up without treatment during a couple of months. Differential diagnosis is essential in order to avoid excessive therapy. We describe a case where an oral tumor was not a cancer after all.

Necrotizing sialometaplasia in a patient with an eating disorder: palatal ulcer accompanied by dental erosion due to binge-purging.

This report describes a case of necrotizing sialometaplasia (NS) accompanied by significant dental erosion of the maxillary teeth of the palatal surfaces owing to chronic self-induced vomiting. This observation contributed to the determination of an immediate and appropriate provisional diagnosis of NS in a patient with an eating disorder, which subsequently was confirmed histopathologically as NS. The diagnostic challenges presented by NS associated with eating disorders and its management are discussed.

A case of necrotizing sialometaplasia involving bilateral parotid glands.

Necrotizing sialometaplasia of the parotid gland is infrequent and can be mistaken as a malignant disease. Its etiology is thought to be an insufficient blood supply. Bilateral involvement of this disease in parotid glands has been rarely reported in the English literature. We report a case of necrotizing sialometaplasia diagnosed after superficial parotidectomy due to bilateral parotid masses in a 69-year old heavy smoking female.

Necrotizing sialometaplasia in an HIV positive cocaine user: a case report.

The aim of this paper was to present a case report of a male patient attending a Semiology and Stomatology Clinic with an erythematous ulcerated lesion on his palate. The patient reported that he was HIV positive as well as being addicted to cocaine. After a biopsy and a histopathological exam, he was diagnosed as having necrotizing sialometaplasia. The lesion diminished spontaneously in thirty days after the exam. Correct diagnosis as well as physical and complementary exams are paramount to avoid any incorrect therapy. As drug addiction and HIV infection have both been associated to necrotizing sialometaplasia, as in the present case, it is difficult to establish if the aetiological factor was drug usage or the HIV infection or even, the combination of these two factors. Although considering the influence of HIV infection on the oral health, we may assume that, at least, it favored the onset of this oral lesion.

Diagnostic dilemma: our experience with necrotising sialometaplasia.

A man in his 40s presented to our outpatient department with a painful ulcer in the oral cavity for 1 week. After intraoral examination, a single hard palate ulcer, which was non-tender on palpation, was noted. Baseline blood investigations such as haemogram and serological evaluation were within normal limits. Under local anaesthesia, an excisional biopsy was performed. The histopathological examination revealed a reactive necrotising inflammatory process involving minor salivary glands with no cytological atypia. Weekly follow-up was performed and at the end of 4 weeks, complete healing of the lesion had occurred without any further intervention.

Simultaneous presentation of dual pathologies within the oral cavity: an unusual and diagnostically challenging presentation.

Necrotising sialometaplasia (NS) is a rare condition, with a limited scientific evidence base regarding its aetiology and pathophysiology. Diagnosing NS demands extensive investigatory tests. Their accuracy is vital in order to exclude oral malignancy and prevent unwarranted, invasive management.Within Birmingham Dental Hospital, a 22-year-old, South Asian woman presented with generalised pain from the lower right third molar extending to involve the palate, to which the patient's general medical practitioner previously attributed to a viral upper respiratory infection. Clinical examination revealed bilateral erythematous: non-ulcerated, palatal swellings (10 mm x 5 mm) at the greater palatine foramina. Following extensive investigations, the challenging definitive diagnoses of two distinct pathologies were made: non-ulcerative NS and pericoronitis.This case report describes the successful diagnosis and management of non-ulcerating NS, an 'atypical' presentation of a rare condition, that was confounded by a simultaneous episode of pericoronitis - a presentation not previously documented within scientific literature.

Significance of Ki-67 and p53 immunoexpression in the differential diagnosis of oral necrotizing sialometaplasia and squamous cell carcinoma.

Necrotizing sialometaplasia (NS) is a benign condition that usually involves the hard palate and can be mistaken for invasive squamous cell carcinoma (SCC). In this study, we have demonstrated that p53 and Ki-67 staining may assist in the differential diagnosis of NS from SCC. Thirteen cases of NS and 20 cases of oral cavity SCC were randomly selected from our surgical pathology archive from 1992 to 2009. Each case was additionally stained with Ki-67, p53, BCL-2, p16, and epidermal growth factor receptor (EGFR) antibodies. All 13 cases of NS were negatively stained for BCL-2, EGFR, and Ki-67. Three cases (23%) showed weak and focal positive nuclear staining for p53. Two cases (15%) showed positive staining for p16. In 16 well-differentiated SCC cases, p53 was positive in 12 cases (75%); BCL-2, p16, EGFR were positive in 3 cases (18%); and Ki-67 was positive in all cases (100%). In 4 moderately differentiated SCC cases, p53 expression was positive in all cases. Two tumors (50%) had a positive expression of BCL-2. Three cases (75%) had a positive p16 staining, and 1 (25%) had a positive EGFR staining. All cases were positive with high nuclear staining greater than 35% of cells for Ki-67. Ki-67 and p53 showed more intense staining and increased in moderately differentiated SCC comparing with well-differentiated SCC and NS. BCL-2, EGFR, and p16 had the same pattern of staining with the same extent in NS and SCCs. The diagnosis of NS may be difficult and may be supplemented via immunohistochemistry by demonstrating focal or absent p53, low to absent Ki-67 (<10% of cells). Although Ki-67 and p53 staining are generally more intense and are increased in malignancy, these findings may be helpful adjuncts in the differential diagnosis of NS from SCC in appropriate clinical setting.