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.