Pleural metastasis from parotid secretory carcinoma: First report of morphology on effusion cytology, and role of pan‐TRK immunohistochemistry

Abstract

Distant metastasis from salivary gland secretory carcinoma (SC) is rare, with lung and pleura being the most frequent site. While cytological features of SC on fine needle aspirates are well documented, its morphology in serous effusions has not been described. We describe the cytomorphological features on effusion cytology of two patients with ETV6::NTRK3 fusion-positive SC, who subsequently developed pleural metastases. Cytospin preparations of pleural fluid showed tightly cohesive, irregularly shaped and ball-like clusters of large tumor cells with scant to abundant uni-and multi-vacuolated cytoplasm. Nuclei were eccentrically placed, round to oval, vesicular, with finely granular chromatin, irregular nuclear membranes and conspicuous to prominent nucleoli. With these features, the tumors resembled an adenocarcinoma, indistinguishable from a lung primary. Cell blocks from both cases showed tumor fragments, some of which had the hollow appearance of transversely sectioned cell spheres as seen in lung and breast adenocarcinomas. Immunohistochemistry on cell blocks revealed nuclear pan-TRK positivity in both cases. Case 1 also showed focal mammaglobin staining, and TTF1 negativity. Pleural metastases from SC may mimic other adenocarcinomas. As targeted therapy, that is, selective TRK inhibitors are available for treatment of metastatic disease, NTRK3 fusion status is not only diagnostic, but also required to plan treatment. Pan-TRK immunohistochemistry serves as a viable cost-effective, easy to apply surrogate marker for NTRK3 fusion, particularly in diagnostic laboratories lacking easy access to molecular testing on cytological material.

Fluorescence in situ hybridization for ETV6 gene rearrangements on destained cytological smears: Role in diagnosis of secretory carcinoma of salivary gland

“…Thus ETV6::NTRK3 fusion FISH can be performed to confirm NTRK3 as the fusion partner and can identify the patients who would benefit from these drugs. Interestingly, one of the patients included in our study developed pleural metastasis, and we used the fusion probe on a pleural fluid CB to confirm the diagnosis because the cytological features were nonspecific and akin to the features of any metastatic adenocarcinoma 20 …”

“…ETV6::NTRK3 fusion is seen in approximately 90% of SCs, whereas a minor subset have non‐ NTRK3 fusions, such as ETV6::RET , ETV6::MET , and VIM::RET 10–15 . SC is a low‐grade malignancy that generally has an indolent course; however, regional lymph node metastases occur in 5%–25% of patients, 16–19 and distant metastases have been described 17,20 . Radical surgical excision is the treatment of choice, with local radiation being used for large tumors, positive margins, and perineural invasion 21–23 ; systemic chemotherapy is considered in patients with distant metastasis 24,25 .…”

“…[10][11][12][13][14][15] SC is a low-grade malignancy that generally has an indolent course; however, regional lymph node metastases occur in 5%-25% of patients, [16][17][18][19] and distant metastases have been described. 17,20 Radical surgical excision is the treatment of choice, with local radiation being used for large tumors, positive margins, and perineural invasion [21][22][23] ; systemic chemotherapy is considered in patients with distant metastasis. 24,25 More recently, targeted therapy in the form of NTRK inhibitors, such as larotrectinib and entrectinib, has become available and is recommended by the National Comprehensive Cancer Network guidelines for the treatment of recurrent and metastatic, NTRK fusion-positive tumors; it has also been tried as neoadjuvant therapy with favorable results.…”

“…Thus ETV6::NTRK3 fusion FISH can be performed to confirm NTRK3 as the fusion partner and can identify the patients who would benefit from these drugs. Interestingly, one of the patients included in our study developed pleural metastasis, and we used the fusion probe on a pleural fluid CB to confirm the diagnosis because the cytological features were nonspecific and akin to the features of any metastatic adenocarcinoma 20. Therefore, ETV6 FISH testing on cytological smears in cases of suspected SC improves the diagnostic accuracy of salivary gland Comparative features of (A-E) secretory carcinoma (SC) and (F-J) acinic cell carcinoma (ACC):both show pseudopapillary fragments along with dispersed cells (Pap staining in A and F).…”