Primary Lymphomas of the Female Genital Tract: Recognizing the Rare Mimicker of Gynecologic Malignancy

Primary lymphomas of the female genital tract (PLFGT) are extremely rare neoplasms, representing a minor fraction of both extranodal lymphomas and gynecologic malignancies. Due to their nonspecific clinical presentation and overlapping imaging features with more common gynecologic tumors, diagnosis is often delayed or missed. This narrative review aims to synthesize current evidence on the clinical characteristics, histologic subtypes, diagnostic approaches, treatment strategies, and prognostic factors of PLFGT, emphasizing recent developments that may influence clinical practice. A comprehensive literature review was conducted, incorporating data from institutional case series, population-based studies, and recent genomic investigations focusing on PLFGT across various anatomical sites: ovary, uterus, cervix, and vagina. PLFGT typically affects women aged 44-68 years, with the ovary being the most frequently involved organ. The most common subtype is diffuse large B-cell lymphoma (DLBCL), followed by Burkitt lymphoma and marginal zone lymphoma. Patients usually present with pelvic pain, mass, or abnormal bleeding, while B symptoms are infrequent. Image-guided core needle biopsy has emerged as a valuable diagnostic approach that may reduce unnecessary surgery. Characteristic sonographic findings, such as hypoechoic, well-defined lesions and homogeneous uterine echo reduction, should raise clinical suspicion, though primary and metastatic disease cannot be distinguished solely by imaging. Rituximab-containing regimens (R-CHOP) are the mainstay of treatment and have improved outcomes. Despite treatment, central nervous system (CNS) recurrence remains a concern, particularly in ovarian involvement. Additionally, mutations in MYD88 and CD79B, although not prognostic, offer potential for personalized therapy. Timely diagnosis and appropriate systemic therapy are critical for improving survival in PLFGT. Advances in imaging, biopsy techniques, and molecular profiling are reshaping the diagnostic and therapeutic landscape of this rare but clinically significant disease.