Teratoma

Autoantibodies against the extracellular domain of the N-methyl-d-aspartate receptor (NMDAR) NR1 subunit cause a severe and common form of encephalitis. To better understand their generation, we aimed to characterize and identify human germinal centres actively participating in NMDAR-specific autoimmunization by sampling patient blood, CSF, ovarian teratoma tissue and, directly from the putative site of human CNS lymphatic drainage, cervical lymph nodes. From serum, both NR1-IgA and NR1-IgM were detected more frequently in NMDAR-antibody encephalitis patients versus controls (both P < 0.0001). Within patients, ovarian teratoma status was associated with a higher frequency of NR1-IgA positivity in serum (OR = 3.1; P < 0.0001) and CSF (OR = 3.8, P = 0.047), particularly early in disease and before ovarian teratoma resection. Consistent with this immunoglobulin class bias, ovarian teratoma samples showed intratumoral production of both NR1-IgG and NR1-IgA and, by single cell RNA sequencing, contained expanded highly-mutated IgA clones with an ovarian teratoma-restricted B cell population. Multiplex histology suggested tertiary lymphoid architectures in ovarian teratomas with dense B cell foci expressing the germinal centre marker BCL6, CD21+ follicular dendritic cells, and the NR1 subunit, alongside lymphatic vessels and high endothelial vasculature. Cultured teratoma explants and dissociated intratumoral B cells secreted NR1-IgGs in culture. Hence, ovarian teratomas showed structural and functional evidence of NR1-specific germinal centres. On exploring classical secondary lymphoid organs, B cells cultured from cervical lymph nodes of patients with NMDAR-antibody encephalitis produced NR1-IgG in 3/7 cultures, from patients with the highest serum NR1-IgG levels (P < 0.05). By contrast, NR1-IgG secretion was observed neither from cervical lymph nodes in disease controls nor in patients with adequately resected ovarian teratomas. Our multimodal evaluations provide convergent anatomical and functional evidence of NMDAR-autoantibody production from active germinal centres within both intratumoral tertiary lymphoid structures and traditional secondary lymphoid organs, the cervical lymph nodes. Furthermore, we develop a cervical lymph node sampling protocol that can be used to directly explore immune activity in health and disease at this emerging neuroimmune interface.

Ovarian dermoid cysts, also called mature cystic teratomas (MCTs), account for 69% of ovarian germ cell tumors in young women. The tumors are formed by tissues derived from three germ layers, and sebaceous materials are most commonly seen. The origin of MCTs is widely considered to be the germ cell origin, which completes meiosis I. The clinical symptoms vary widely, but 20% of tumors could be asymptomatic. The diagnosis of MCTs is usually made without difficulty by ultrasound and confirmed by histopathology post-operatively. The imaging findings have a high diagnostic value. The typical characteristics present in the sonographic images, including a dermoid plug or Rokitansky nodule, are considered strong evidence for a teratoma. Although the malignant transformation of MCTs is rare, it can occur in some cases, especially in women of advanced age. The treatment of MCTs depends on the risk of malignancy, the age of the patient, and the patient's fertility reserve requirement. In this article, we review the epidemiology, clinical symptoms, diagnosis criteria, cellular origin, and treatment of mature cystic teratomas.

Nonepithelial ovarian cancers (NEOC) are a group of rare malignancies, including germ cell tumours (GCT) and sex cord-stromal tumours (SCST), along with small-cell carcinomas and sarcomas. GCTs represent 2-5% of ovarian cancers, with a yearly incidence of 4:100,000, and they usually affect young women and adolescents. Precursory germ cells of the ovary form the basis of GCT. They are histologically classified into primitive GCT, teratomas, and monodermal and somatic-type tumours associated with dermoid cysts. A primitive GCT can be either a yolk sac tumour (YST), dysgerminoma, or mixed germ cell neoplasm. Teratomas are either mature (benign) or immature (malignant). Given that malignant GCTs occur rarely compared to epithelial ovarian tumours (EOC), greater focus is required in their diagnosis and treatment. In this article, we review the epidemiology, clinical manifestations, diagnosis, and molecular biology, along with the management and therapeutic challenges.

ObjectiveTo describe the clinical and ultrasound characteristics at the time of diagnosis of primary ovarian immature teratoma with no other germ cell tumor components described on histopathology.MethodsThis was a retrospective study of women with a histological diagnosis of primary ovarian immature teratoma who had undergone a preoperative ultrasound examination between 1998 and 2024. Cases were identified from the databases of 17 contributing ultrasound centers and the International Ovarian Tumor Analysis (IOTA) database. The descriptions of the ultrasound images of the tumors made by the original ultrasound examiners using IOTA terminology were reported. In addition, grayscale and color or power Doppler ultrasound images or videoclips were retrieved for all tumors. Two independent ultrasound examiners reviewed the retrieved material and searched for specific ultrasound characteristics of immature teratomas using pattern recognition. We present their agreed description of the tumors.ResultsIn total, 64 patients with ovarian immature teratoma were included, of which 38 (59.4%) were obtained from the IOTA database (IOTA studies phase 1, 1b, 2, 3, 5 and 7). The median age of the patients at diagnosis was 24.5 (interquartile range (IQR), 18.8-31.0; range, 12-50) years. The most common presenting symptoms were abdominal or pelvic pain (38/60, 63.3%) and abdominal swelling (30/60, 50.0%). All immature teratomas were unilateral. The median largest diameter of the tumor was 149.5 (IQR, 125.0-183.8; range, 27-400) mm. Using IOTA terminology, most tumors were described as multilocular-solid (32/64, 50.0%) or solid lesions (22/64, 34.4%). When present, the solid component had a median largest diameter of 98.5 (IQR, 59.8-146.8; range 6-400) mm. Most masses showed minimal (19/63, 30.2%) or moderate (35/63, 55.6%) vascularization on color or power Doppler ultrasound examination. Using pattern recognition, the most typical ultrasound feature was heterogeneous, bizarre echogenicity of the solid components, with hyperechogenic areas, cystic spaces and acoustic shadows. This feature, which we consider pathognomonic, was present in 48/57 (84.2%) immature teratomas in which the solid components were adequately assessable.ConclusionsThe typical ultrasound appearance of an ovarian immature teratoma is a large unilateral adnexal mass with large solid components that is poorly or moderately vascularized. The pathognomonic feature is heterogeneous echogenicity of the solid components with hyperechogenic areas, cystic spaces and acoustic shadows. Preoperative suspicion of immature teratoma can guide treatment, such as offering fertility-sparing surgery. © 2025 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.