Discussion
Tumors of the salivary glands account for 3-4% of the tumors of the
head and neck. The age group with the highest incidence is the one
between 30 and 60 years with a peak in the 5th decade of life for benign
forms and in the 6th decade for malign ones. The most frequently
diagnosed malignant form is mucoepidermoid carcinoma. As mentioned
earlier, initially cytological testing of the lesion led to a diagnosis
of a mucoepidermoid carcinoma. SCs are considered to be very rare
neoplasms. The typical presentation of SC, which tends to be uniform, is
that of a slow-growing asymptomatic mass of the parotid or lateral
cervical region. Despite its relatively uniform presentation, age at
onset can vary significantly. The most common subsite for its
presentation is that of the parotid gland, followed by the minor
salivary glands and then the submandibular gland.
Just as most patients with lesions originating in the salivary glands,
those with suspected SC normally undergo FNAC; but the test is
frequently unable to lead to a correct diagnosis due to SC’s rarity and
of its relatively recent reclassification. Some studies have however
shown that SC presents some well defined cytological features. It has
generally been noted that the neoplasm has a papillary architecture and
abundant, eosiphillic cytoplasm with focal oncocytic features and fine
cytoplasmic vacuoles. Cells similar to myoepithelial ones are
occasionally observed; the nuclei are moderately pleomorphic and
charactrized by focal binucleations and irregular positioning. These
characteristics are shared with other salivary gland types, and
primarily with ACC.
Investigations endeavoring to distinguish between ACC and SC from a
histological point of view are generally carried out in these cases.
Periodic Acis-Schiff (PAS) staining, for example, is useful for guiding
the diagnostic process. Its results help to differentiate between the
two tumor types since ACC presents a more granular pigmentation. The
molecular profiles of the two neoplasms differ as far as the S100 is
concerned; it is in fact normally positive in SC and negative in ACC.
With regard to DOG1, it is negative in SC and positive in ACC. But most
importantly, the molecular analysis is decisive for identifying a SC
since the ETV6-NTRK3 traslocation is virtually pathognomonic of SC, but
it is never found in ACC. The presence of break-apart probes in
>30% of neoplastic nuclei places the lesion within the
group of NTRK3-rearranged tumors. The test result is characterized by a
split in the NTRK3 signal (Bio-Optica probe). Red and green split
fluorescent signals with a wild red/green signal at the side
characterize the molecular abnormality in the diagnostic image (Leica
Instrument). It is to be remembered that the FISH is a robust molecular
cytogenic technology widely used in anatomical pathology laboratories in
connection, for example, HER2+breast cancer, ROS1 and ALK rearranged
lung cancers, 1p/19q in brain tumors, etc.
As far as patients’ clinical status is concerned, SC seems to present a
higher grade of malignancy at the time of diagnosis with respect to ACC
and thus a worse disease free survival rate. Several case reports and
case series studies have demonstrated that SC is more frequently
chracterized by the development of lymph node involvement and distant
metastasis with respect to ACC, and it has a higher rate of local
recurrence. In view of the histotype’s recent reclassification and the
paucity of data that could lead to the formation of guidelines for its
diagnosis and treatment, further research is urgent. Surgery has
traditionally been the gold standard for the treatment of neoplasms of
the salivary glands, followed by radiotherapy whenever evidence of
aggressive histotypes, perineural and lymphovascular invasion or
involvement of the seventh cranial nerve, the deep lobe, the resection
margins or locoregional recurrence is identified. Chemotherapy is
generally recommended in cases of recurrence or of distant localization
of metastases. As far as SC is concerned, more lymph node involvement
has been noted in patients with the characteristics mentioned above
requiring the use of radiotherapy. According to some case series studies
focusing on SC, some surgeons were not immediately in favor of treating
the loco-regional lymph node recurrence. For the most part, however, in
those case the patients underwent adjuvant radiotherapy or
laterocervical emptying. The only case of recurrence described in the
literature occurred in a patient who did not undergo adjuvant
radiotherapy. In the light of that report and of the higher incidence of
lymph node positivity in SC with respect to that in ACC, the degree of
tumor aggressiveness of the former appears to be greater and more
comparable to that of a mucoepidermoid carcinoma than to that of ACC.