Result
Gross and microscopic examination of the radical parotidectomy specimen
(S2) showed a 4 cm high grade carcinoma (AFIP grading for MEC) invading
salivary gland, skeletal muscle and trapping hypertrophic nerves (Figure
1a&b). The tumour consisted of solid lobules, cords and trabeculae of
moderate to highly pleomorphic carcinoma cells with focal keratinization
(Figure 1c). Primitive glandular differentiation with foamy cells and
abortive lumens staining positive for mucicarmine (Figure 1d) could be
focally seen. Atypical mitoses (5/10 HPF) and necrosis were present.
Immunohistochemical studies showed tumour cells positive for cytokeratin
AE1/3, p63 and p40; negative for S100. Ki67 proliferative index varied
from 15-30%. There was marked stromal sclerosis forming fibrous strands
and bands. Heavy chronic inflammatory infiltrates including many
Langerhans cells (CD1a positive, Figure 1d) and eosinophils were present
in the background. The adjacent salivary gland showed non-sclerosing
chronic sialadenitis with intralobular lymphocytic infiltrates and
scanty lymphoepithelial lesions (Figure 1b). This high-grade carcinoma
with mucoepidermoid differentiation and the accompanying features fit
into the published criteria of SMECE. Ten regional lymph nodes dissected
showed no malignancy.
Slide review of the initial excisional specimen (S1) was performed and
showed a well-circumscribed low grade (AFIP grading) carcinoma hiding
within a fibroinflammatory background (Figure 2a) and focally touching
resection margin. Compared with S2, there was a similar SMECE picture
but much less aggressive. It consisted of lobules and cords of squamoid
cells with keratinization and minimal nuclear pleomorphism (Figure 2b).
Cystic change and ductal differentiation with well-formed lumen positive
for PAS (diastase resistant, Figure 2b&d) lined by foamy columnar
mucinous cells were focally seen. Mitosis numbered about 1-2/10 HPF.
There was no evidence of IgG4 associated disease. Immunohistochemistry
profile (Figure 2d) was the same as that in S2 (Ki67 not available).
There were distinctive sheets of Langerhans cells and eosinophilia
forming eosinophilic abscesses mimicking Langerhans cell histiocytosis
(Figure 2c). Definite tumour progression on recurrence from low (S1) to
high grade carcinoma (S2) could be demonstrated with respect to cellular
pleomorphism, necrosis, tumour differentiation and invasiveness. The
AJCC pathological staging also progressed from pT2 to pT4a.
FISH using break-apart probe for CSF1 was performed to detect possible
derangement of CSF1 gene with subsequent CSF1 over-expression. In most
tumour cells there was 1 copy of the normal gene (fused green and orange
signal giving orange-red color), and multiple green signals signifying
duplicated CSF1 3’ end with deletion of the 5’ end in the other
chromosome (Figure 3a). Illumina TruSight RNA pan-cancer assay detected
no fusion transcripts in the specimen. On the other hand, expression of
CSF1 gene in tumour cells could be demonstrated by RNA in-situ
hybridization (RNA scope) as coarse and fine granules (Figure 3b).