Utility of an immunocytochemical analysis for pan‐Trk in the cytodiagnosis of secretory carcinoma of the salivary gland

Abstract

Secretory carcinoma (SC) of the salivary gland is a rare distinct clinicopathological entity characterized by the presence of the ETV6‐NTRK3 fusion. Although the characteristic cytological features of SC have been recognized, its cytodiagnosis, especially differentiating SC from acinic cell carcinoma, is challenging. Recent studies have revealed that immunohistochemistry for pan‐tyrosine receptor kinase (Trk) and nuclear receptor subfamily 4 group member 3 (NR4A3) are specific for SC and acinic cell carcinoma, respectively. However, the usefulness of immunocytochemical detection of these markers in the diagnosis of SC has not been addressed. Hence, the present study aimed to analyze the usefulness of immunocytochemical staining for pan‐Trk and NR4A3 in the cytodiagnosis of SC. We enrolled eight patients with a histopathological diagnosis of SC who underwent preoperative fine‐needle aspiration cytological examination. The cytological characteristics were reviewed and immunocytochemical staining for pan‐Trk and NR4A3 was performed. The characteristic cytological features noted in the patient cohort included neoplastic cell clusters with a sheet‐like and papillary cluster arrangement as well as single cells. Additionally, neoplastic cells with mild to moderately enlarged nuclei and small nucleoli, multi‐vacuolated cytoplasm, and intracytoplasmic mucin were also observed. The immunocytochemical analyses clearly demonstrated that all eight specimens showed positive nuclear staining for pan‐Trk, but were negative for NR4A3 expression. Although all cases of SC do not always show positive immunoreactivity for pan‐Trk, immunocytochemical analysis for pan‐Trk may be useful for the cytodiagnosis of SC along with assessment of the characteristic cytological features.

Diagnostic accuracy of pan‐TRK immunohistochemistry in differentiating secretory carcinoma from acinic cell carcinoma of salivary gland—A systematic review

“…In this phase, 2 case reports 23,24 were excluded and finally, 13 articles were included for quantitative synthesis (Figure 1). 7,8,[12][13][14][15][16][17][18][19][20][21][22] 3.1 | Methodological characteristics of the studies Data extracted from all 13 studies including details on the country of origin, authors, total number, and histopathological type of SGTs and pattern of pan-TRK IHC manifestation are provided in Tables S1 & 1.…”

“…The included studies were conducted between 2017 and 2022, in more than 5 different countries: 4 in the USA, 7,12-14 2 in France, 16,18 3 in Japan, 8,15,21 2 in China 19,20 1 in Taiwan, 22 and 1 was multicentric. 17 A total of 623 different SGTs including 255 SCs and 82 AciCCs were identified.…”

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

“…Bell et al, 18 in a comparative study of pan‐TRK IHC on histological specimens, demonstrated sensitivity of 90.9% and specificity of 100%, indicating that it is a reasonable screening test. Ito et al 21 showed pan‐TRK nuclear staining on direct smears in all eight SC assessed by them, highlighting its utility in cytological diagnosis on conventional smears when cell blocks are not available or have sparse tumor cells. In the present case, pan‐TRK was immunopositive in the pleural metastases in both cases.…”

“…Bell et al,18 in a comparative study of pan-TRK IHC on histological specimens, demonstrated sensitivity of 90.9% and specificity of 100%, indicating that it is a reasonable screening test. Ito et al21 showed pan-TRK nuclear staining on direct smears in all eight SC assessed by them, highlighting its utility in cytological diagnosis on conventional smears when cell blocks are not available or have sparse tumor cells.In the present case, pan-TRK was immunopositive in the pleural metastases in both cases. Thus, we report the detailed cytomorphological features of pleural metastasis from SC, showing that accurate diagnosis may not be possible on morphological characteristics alone, as they differ significantly from those on FNA, and resemble pleural metastases from anyF I G U R E 4 Pleural fluid from Case 2 shows loose clusters of tumor cells admixed with mesothelial cells and lymphocytes (A; MGG, 200Â).…”

Cytological and molecular characterization of secretory breast carcinoma

“…The expression of NTRK by immunocytochemistry has been previously described in secretory carcinoma of the salivary gland. 33 This tumour was previously named "mammary analogue secretory carcinoma" due to its resemblance to secretory breast carcinoma, including the ETV6-NTRK3 fusion. 34 SBC is associated with a favourable prognosis.…”