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.