STK11 (LKB1) immunohistochemistry is a sensitive and specific marker for STK11 adnexal tumours

Abstract

Aims: STK11 adnexal tumour is a rare, recently described malignant neoplasm that is associated with Peutz-Jeghers syndrome. [Correction added on 3 October 2024, after first online publication: 'ST11' in preceding sentence has been corrected to 'STK11' in this version.] It predominantly originates from the para-adnexal soft tissues and often shows secondary involvement of the fallopian tube and ovary. STK11 adnexal tumours have a broad differential diagnosis due to their variable morphology and non-specific immunoprofile, and diagnostic confirmation currently requires sequencing to identify an STK11 mutation. We investigate the diagnostic utility of STK11 (LKB1) immunohistochemistry (IHC) in a cohort of STK11 adnexal tumours and morphological mimics.

Methods and results: IHC for STK11 was performed on 122 tumours, including 17 STK11 adnexal tumours and 105 morphological mimics (10 female adnexal tumours of Wolffian origin, 22 adult granulosa cell tumours, 10 juvenile granulosa cell tumours, four Sertoli-Leydig cell tumours, two Leydig cell tumours, one Sertoli cell tumour, one steroid cell tumour, four extra-ovarian sex cord-stromal tumours, 16 ovarian endometrioid carcinomas, eight tubo-ovarian high-grade serous carcinomas, five ovarian mesonephric-like adenocarcinomas, 14 ovarian carcinosarcomas, five peritoneal malignant mesotheliomas, two pelvic plexiform leiomyomata and one ovarian solid pseudopapillary tumour). All STK11 adnexal tumours showed complete loss of cytoplasmic staining for STK11. All other tumour types showed retained cytoplasmic staining, except for one endometrioid carcinoma with mucinous differentiation which showed complete loss of STK11 expression and a high-grade serous carcinoma with subclonal loss.

Conclusions: STK11 is a highly sensitive and specific immunohistochemical marker for distinguishing STK11 adnexal tumour from its histological mimics, and can obviate the need for confirmatory molecular studies in the appropriate morphological context.

Keywords: LKB1; STK11; STK11 adnexal tumour; fallopian tube; female adnexal tumour of Wolffian origin; ovary.

Figure 1.

Architectural features of STK11 adnexal tumors: (A) nodules composed of cords and trabeculae separated by fibrous septa, (B) small nests in myxoid matrix, (C) reticular, (D) cystic with eosinophilic secretions, (E) microcystic, (F) nodular, (G) large nests with basophilic secretions, (H) solid sheets, and (I) cribriform gland-like structures.

Figure 2.

Cytologic variablility of STK11 adnexal tumors: (A) cuboidal cells with moderate eosinophilic cytoplasm, (B) prominent nucleoli, (C) ovoid to spindled cells, and (D) vacuolated, signet ring-like cells.

Figure 3.

Loss of STK11 expression in sequencing-confirmed STK11 adnexal tumors with positive staining of endothelial cells as an internal positive control: (A) case 4, and (B) case 11. Loss of expression was also seen in (C) tumors in which sequencing was not possible (case 12), and (D) a tumor for which sequencing did not detect a point mutation and was not validated to report copy number changes (case 5).

Figure 4.

Retained STK11 expression in potential morphologic mimics of STK11 adnexal tumor, including (A) female adnexal tumor of Wolffian origin (FATWO), (B) Sertoli cell tumor, (C) peritoneal mesothelioma, (D) ovarian mesonephric-like adenocarcinoma, and (E) adult granulosa cell tumor. (F) One tumor, a high grade-serous carcinoma, showed subclonal loss of STK11 expression (lost on left side, retained on right side).