Lobular endocervical glandular hyperplasia diagnosed during surveillance for Peutz–Jeghers Syndrome: A case report

Abstract

Background

Lobular endocervical glandular hyperplasia (LEGH) is a benign cervical condition that has been proposed as a precursor lesion to minimal deviation adenocarcinoma (MDA), a rare but highly aggressive subtype of well-differentiated gastric-type endocervical adenocarcinoma (GAS). MDA is more frequently observed in patients with Peutz–Jeghers syndrome (PJS) and is strongly associated with mutations in the STK11 gene. While LEGH is not inherently linked to PJS, its potential progression to MDA warrants vigilance, particularly in patients with PJS due to their heightened risk of gynecologic malignancies. Here, we report a case of LEGH diagnosed during surveillance for PJS, analyzed via whole genome sequencing. LEGH is a benign cervical condition, considered a precursor lesion to minimal deviation adenocarcinoma, often observed in patients with Peutz–Jeghers syndrome (PJS) and potentially linked to mutations in the STK11 gene.

Case

A 23-year-old woman, diagnosed with PJS at age 11, was referred to a gynecologist after a cystic lesion was detected in the cervix during a follow-up computed tomography scan. Initial examinations, including imaging and colposcopy, did not indicate LEGH or a malignant tumor. Imaging alone is insufficient to exclude premalignant or malignant conditions, as abnormal cervical lesions often require biopsy for a definitive diagnosis. However, cervical cytology showed nuclear atypia was minimal, but some clusters exhibited disordered alignment, and the cytoplasm contained yellowish mucus suggestive of LEGH. Based on these findings, cytology follow-up was planned. However, the patient did not return for further follow-up. After one year and five months, the patient presented with increased mucous vaginal discharge. Cervical cytology indicated atypical glandular cells, and magnetic resonance imaging with contrast enhancement revealed an enlarged cervical lesion, suggesting minimal deviation adenocarcinoma. We performed cervical conization, and a histopathological examination helped confirm LEGH. High-throughput next-generation sequencing of the excised cervical tissue revealed a missense mutation in the serine/threonine kinase 11 (STK11) gene on chromosome 19 (c.1062C > G) and three missense mutations in STK11 interacting protein (STK11IP) on chromosome 2 (c.2G > T, c.1687G > A, c.2255C > T). Mutations in STK11, particularly those affecting its regulatory domains, may significantly increase cancer risk in patients with PJS, and that STK11IP plays a crucial role in modulating STK11 activity. The patient, seeking to preserve fertility, has been monitored for five years post-surgery without evidence of malignant transformation. Continuous monitoring with periodic imaging and cytological assessments has shown no evidence of malignant transformation. The absence of elevated tumor markers further supports the conservative approach. While there are no tumor markers specific to cervical cancer, carcinoembryonic antigen (CEA), cancer antigen 125 (CA125), and carbohydrate antigen 19–9 (CA19-9) were measured as part of the screening process in this case.

Conclusion

We conclude that whole genome sequencing in patients with PJS and LEGH could be pivotal in predicting cervical malignancy. This case emphasizes the utility of whole genome sequencing in predicting the risk of cervical malignancy in patients with PJS and LEGH and highlighting the critical role of genetic factors in the management and surveillance of these patients. Continuous monitoring post-surgery showed no evidence of malignant transformation, supporting a conservative approach in fertility-preserving treatment scenarios.