Secretory Carcinoma of Salivary Gland: A Single-centre Cohort Study Highlighting Histomorphologic and Immunohistochemical Characteristics

Introduction: Secretory carcinoma of the salivary gland is a distinct subtype of salivary gland carcinoma that was first described by Skalova A et al., in 2010. It is characterised by the ETV6-NTRK3 translocation. Before the recognition of this entity, most cases of secretory carcinoma were misdiagnosed as acinic cell carcinoma. The accurate diagnosis of secretory carcinoma is important as inhibiting the active Ets-leukemia Virus-Neurotrophic tropomyosin Receptor Kinase 3 (ETV6-NTRK3) is highly efficient in the treatment of this carcinoma. Aim: To evaluate the clinical, histomorphological, and Immunohistochemical (IHC) characteristics of secretory carcinoma diagnosed at a tertiary care centre. Materials and Methods: This cohort study was conducted in the Department of Pathology at the Regional Cancer Centre, Thiruvananthapuram, Kerala, India (a tertiary cancer centre), from June 2021 to December 2021, after approval from the scientific review committee. A total of 13 cases diagnosed as secretory carcinoma from January 2016 to December 2020 were reviewed. Histomorphological features analysed included growth pattern, cytoplasmic vacuolisation, presence of secretion, hobnailing, nuclear shape, presence of nucleoli, chromatin characteristics, presence of necrosis, lymphovascular invasion, and perineural invasion. Clinical characteristics such as age, gender, tumour site, size, and clinical presentation were documented. Furthermore, an IHC panel of S100, DOG-1, and mammaglobin was studied, and results were interpreted as positive or negative to support the diagnosis. Follow-up details of the patients concerning local or distal recurrences and terminal events, if any, were updated from the medical records as of December 2021. An analysis of the common histopathological characteristics and immunoprofile in these cases was conducted. Results: A total of 13 cases of secretory carcinoma were identified, with a mean age of 44 years and a male-to-female ratio of 12:1. The parotid gland was the most commonly affected site, observed in eight cases. The most frequent histopathological pattern was papillary cystic, seen in nine cases. The presence of luminal secretion was consistently observed in all thirteen cases. Intracytoplasmic vacuolation was seen in three cases, and hobnailing was present in five cases. The nuclei were round to oval with vesicular chromatin and prominent nucleoli in all 13 cases (100%). Aggressive histopathological features were present in only a few cases, with perineural invasion in one case, lymphovascular invasion in two cases, and necrosis in two cases. High-grade transformation was present in one case. All cases showed positive staining with S100 and negative reaction with the DOG-1 immunomarker. Among the seven cases where mammaglobin was tested, all showed a positive reaction. All patients underwent surgery, with seven cases also requiring radiotherapy. Conclusion: Secretory carcinoma of the salivary gland is relatively rare. Histopathological features are helpful in making a diagnosis. A limited IHC panel comprising S100, DOG-1, and mammaglobin helps in narrowing down the differentials and differentiating it from acinic cell carcinoma, which is the closest differential. The diagnosis of secretory carcinoma has therapeutic implications due to the availability of targeted therapy. Multicentric studies including a greater number of cases can help in better characterising this entity.