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 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.

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.

Necrotizing sialometaplasia: a practical approach to the diagnosis.

CONTEXT: Necrotizing sialometaplasia is a benign, self-limited lesion of both major and minor salivary glands, although more commonly the latter. It can represent a diagnostic dilemma and may be mistaken for a malignant neoplasm, such as mucoepidermoid carcinoma, as well as invasive squamous cell carcinoma. A major causal relationship has been ascribed to ischemia. Bulimia, an eating disorder with increasing prevalence in our society, may also be an underlying underreported cause. OBJECTIVE: To discuss the potential pathogenesis, diagnostic pitfalls, and the application of immunohistochemistry as an aid in the diagnosis of necrotizing sialometaplasia. DATA SOURCES: This report uses a previously published case history for illustrative purposes and a review of the current literature. CONCLUSIONS: The diagnosis of necrotizing sialometaplasia may be difficult and is reliant upon a well-oriented biopsy section and a complete clinical history. Diagnosis may be further supplemented via immunohistochemistry, demonstrating focal to absent immunoreactivity for p53, low immunoreactivity for MIB1 (Ki-67), and the presence of 4A4/p63- and calponin-positive myoepithelial cells. Interpreted in context collectively, these findings may be helpful adjuncts in the diagnosis of necrotizing sialometaplasia; nonetheless, to date, hematoxylin-eosin staining remains the gold standard.

Necrotizing sialometaplasia versus invasive carcinoma of the head and neck: the use of myoepithelial markers and keratin subtypes as an adjunct to diagnosis.

AIMS: To investigate the use of immunohistochemistry in distinguishing necrotizing sialometaplasia (NSM) from squamous cell (SCC) and mucoepidermoid carcinoma (MEC) by (i) the identification of myoepithelial cells and (ii) cytokeratin (CK) expression. METHODS AND RESULTS: Thirteen cases with the histological changes of NSM, eight SCCs and eight MECs were examined with the following immunohistochemical markers: calponin, S100, smooth muscle actin (SMA), p63, CK7, CK5, CK6 and CAM5.2. The distribution and intensity of staining were recorded. Residual myoepithelial cells (best demonstrated by calponin and SMA) were identified at the periphery of the epithelial islands in all cases of NSM (although not in all islands), in contrast to MEC and SCC. S100 showed a similar pattern, although staining fewer cells. Moderate rather than extensive expression of CK7 may help to distinguish NSM from MEC. CONCLUSION: Identification of myoepithelial cells and CK7 expression may help to distinguish NSM from its mimics.