Discussion
The present case highlighted the difficult diagnoses in anatomical pathology of a sclerosing salivary gland lesion accompanied by lympho-histiocytic infiltrates and eosinophilia. Differential diagnoses included Langerhans cell histiocytosis, fibroinflammatory conditions such as IgG4 associated disease, benign lymphoepithelial lesion and necrotizing sialometaplasia. Malignant tumours obscured by the fibroinflammatory background should also be considered. An accurate and early diagnosis with appropriate treatment would certainly improve prognosis and mitigate patient morbidity.
SMECE of the salivary gland is extremely rare, numbering about 12 in literature reviews2,4,8. It is not a well-defined entity and was not listed in the 2022 WHO Classification of Head and Neck Tumours. According to most reports, tumours falling into this category showed mucoepidermoid differentiation with low grade cytology and a sclerotic background with heavy eosinophilic infiltrates, without mention of Langerhans cells. No molecular markers have been found associated with this tumour, except for the negative MAML2 rearrangement. A host of molecular defects have been demonstrated in ‘MAML2 translocation-negative mucoepidermoid carcinoma’ in one study9, but there was no mention of this SMECE subtype. Thus, the true nature and nomenclature of this group of tumours awaits further clarification.
The present case with the abundant Langerhans cells masquerading as Langerhans cell histiocytosis triggered the search for an underlying mechanism. Our studies were inspired by the findings of CSF1 rearrangement and its overexpression in tenosynovial giant cell tumours (TSGCT), attracting dendritic cells including Langerhans cells (CSF1 receptor+) to migrate into the mesenchymal tumour and proliferate10,11. Instead of CSF1 gene rearrangement, we detected increased CSF1 (3’end) copy number with deletion of the 5’ end, coupled with increased expression of CSF1 in tumour cells on RNA scope. Over-expression of CSF1 without documented translocation has also been found in a proportion of TSGCT12. CSF1 over-expression is the most likely cause of the marked Langerhans cell reaction, leading to subsequent eosinophilia and sclerosis. Whether this molecular defect with subsequent ‘landscape effect’ was an isolated event, or a significant tumour marker merits further studies on this group of tumours.