Unique Considerations in Rare Gynecologic Tumors: Gestational Trophoblastic Neoplasia, Germ Cell Tumors, and Clear Cell Ovarian Cancers.

A 10-year-old, overweight girl presents to the clinic with 3 weeks of fever. She was in her usual state of health until 21 days before presentation, when she developed a fever in the setting of cough, congestion, abdominal pain, and myalgias. Her symptoms subsided within 5 days of onset, but she continued to have waxing and waning fevers, ranging between 102°F and 104°F (38.9°C–40.0°C), lasting for several days at a time, with occasional defervescence for up to 48 hours. She was seen in the pediatric clinic on day 7, where she was afebrile with normal examination findings. Respiratory viral polymerase chain reaction panel revealed a positive reaction to rhinovirus/enterovirus. She was diagnosed as having a viral illness and sent home with supportive care instructions regarding pyrexia management, optimizing hydration status, expected clinical course, and primary care follow-up as needed. For the next 2 weeks she had daily fevers and was seen in the emergency department several times, with documented examination findings suggesting no focal abnormalities and serial laboratory evaluations showing increasing values of inflammatory markers (white blood cell count, from 10,200/µL [10.2 × 109/L] to 15,300/µL [15.3 × 109/L]; C-reactive protein level, from 14 mg/dL [140 mg/L] to 21 mg/dL [210 mg/L]; and erythrocyte sedimentation rate, from 35 mm/hr to 51 mm/hr), with negative serial blood and urine cultures. She was seen again in the clinic during week 3 of illness with review of systems at that time noting 3 days of nausea as well as mild, intermittent abdominal bloating and discomfort. Vital signs at this visit show tachycardia (heart rate, 127 beats/min) and tachypnea (respiratory rate, 36 breaths/min), with normal pulse oximetry (99%) and blood pressure (105/68 mm Hg). Weight and height are both greater than the 99th percentile (Fig 1). Examination reveals an ill- and anxious-appearing young lady. She demonstrates rapid but nonlabored breathing and has a slightly distended, nontender abdomen without peritoneal signs, palpable mass, or hepatosplenomegaly. Her abdominal examination was functionally challenging due to baseline developmental delays, resulting in difficulty achieving a relaxed complete examination. A genitourinary examination was declined by the family.Her medical history is significant for idiopathic tall stature; chronic, presumed functional constipation; and a diagnosis of level 1 autism made at age 3 years with normal genetic testing. She is verbal with friends and family with an age-appropriate IQ but primarily communicates to providers through her parents. Historically, compliance with examinations has been limited due to communication delays. Nine months earlier her developmental pediatrician commented that she “appears much older than her stated age” and referred her to women’s health due to recent onset of menarche, which occurred shortly after her 10th birthday. Her periods at that time were listed as infrequent and irregular, lasting for 3 to 4 days on average and occurring every 4 to 8 weeks, with an estimated 2 and 3 pads per day needed to control flow on her heaviest days. Her parents reported that thelarche occurred between 6 and 7 years of age, with adrenarche concurrently appearing around this same time. A diagnostic evaluation for precocious puberty, including bone age, had not yet been pursued.The differential diagnosis at the time of her current evaluation in the clinic included infectious, connective tissue, and malignant pathologies. Specifically, there were concerns for secondary bacteremia after initial viral insult, an occult localized bacterial infection (urinary tract infection, intra-abdominal or pelvic abscess, pneumonia), a less typical bacterial process (mycobacterial, salmonellosis, toxoplasmosis) although no overt suggestive exposures were identified, or a protracted viral illness (cytomegalovirus, Epstein-Barr virus, adenovirus, enteroviruses). Primary vasculitis (immunoglobulin A vasculitis, polyarteritis nodosa), early manifestations of systemic lupus erythematosus, and inflammatory bowel disease were also considered. The presence of presumed precocious puberty and abdominal swelling increased concern for a hormonally active neoplastic process such as a gonadal tumor, adrenocortical carcinoma, or hepatoblastoma.Repeated inflammatory markers at this time were significantly elevated (white blood cell count, 23,800/µL [23.8 × 109/L]; C-reactive protein level, 302.1 mg/dL [3,021 mg/L]; erythrocyte sedimentation rate, 54 mm/hr). Radiographs of her chest and abdomen revealed a gasless abdomen and lingular atelectasis with a left-sided pleural effusion. A computed tomographic (CT) scan of the abdomen and pelvis showed ascites and a large, left-sided, complex pelvic mass that appeared adnexal in origin. Her serum α-fetoprotein (AFP) level was markedly elevated at 4,710 ng/mL (4,710 µg/L) (reference range, <8 ng/mL [<8 µg/L]), and her cancer antigen 125 (CA-125) level was high at 951 U/mL (951 kU/L) (reference range, <35 U/mL [<35 kU/L]). Based on these elevated tumor markers, presence of systemic symptoms, and abnormal chest radiographs, a CT scan of the chest was obtained and showed masses in the mediastinum with large, bilateral pleural effusions. She was diagnosed as having suspected metastatic primary ovarian malignancy. Surgical resection of her ovarian mass revealed a 30-cm, 4.59-kg mixed germ cell tumor consisting of 90% immature teratoma and 10% yolk sac tumor (Fig 2).Ovarian and other adnexal tumors are rare in the pediatric population, with an estimated incidence of 2.6 cases per 100,000 girls per year. (1) Most of these masses are benign, with approximately 10% demonstrating malignant potential. (2) In contrast to the adult population, the age-adjusted incidence of ovarian malignancy is 0.1 per 100,000 per year in girls and adolescent females compared with 11.4 per 100,000 per year in women older than 20 years. (3) Despite their infrequency, ovarian tumors are among the most common neoplasms of the genital tract in childhood and account for approximately 1% of all malignancies in females younger than 17 years. (4) These tumors thus represent an important component of pediatric oncology and often present a diagnostic dilemma for the general pediatrician because their clinical manifestations are nonspecific and often subtle.The most common presenting symptom of ovarian cancer is abdominal pain (57%), followed by a palpable abdominal or pelvic mass (46%). A small case series showed fever present in only 12% of patients, with nausea, vomiting, poor appetite, weight loss, constipation, precocious puberty, and urinary symptoms also occasionally noted on presentation. (5) Approximately 18% of cases are asymptomatic, with tumor being detected incidentally on routine physical examination or during diagnostic imaging for another purpose. There is tremendous overlap regarding the clinical manifestations of the various ovarian tumors, and distinguishing between tumor types often requires histopathologic determination. However, there are a few key features that can help distinguish benign from malignant neoplasms and may help direct the diagnostic evaluation and surgical approach. Children with a palpable mass or precocious puberty have a reportedly higher likelihood of malignancy. (6) Systemic inflammatory response syndrome, and pyrexia in particular (as described in this case), is an uncommon feature of ovarian tumors and, if present, suggests malignancy with metastatic spread. Ovarian torsion, although more commonly associated with no underlying pathologic lesion, seems to be a more frequent symptom of benign rather than malignant tumors. (7) Although not specific to ovarian malignancy, delays and errors in cancer diagnosis have been linked to cancers for which there is an atypical or nonspecific presentation, for which there is a very low prevalence of disease burden in the general population, and in children with comorbidities that may mask, alter, or add to the complexity of the presentation and examination. (8)Primary pediatric ovarian tumors generally fall into 1 of 3 categories based on their cell origins: germ cell tumors, epithelial-stromal tumors, and sex cord–stromal tumors (Table 1).Unlike in the adult population, where epithelial-stromal tumors predominate, germ cell tumors are by far the most common ovarian neoplasm discovered in children, accounting for 60% to 80% of cases. Although germ cell tumors are predominantly benign in adults, up to one-third of ovarian germ cell tumors are malignant in children. (9) In the category of germ cell tumors, 3 histologic subtypes predominate: teratomas, dysgerminomas, and yolk sac tumors. Teratomas include both immature (malignant) and mature (benign, predominantly cystic) forms. Dysgerminomas occur almost exclusively in patients with gonadal dysgenesis and thus have a proclivity for chromosomal conditions where this is a feature (eg, Turner syndrome). Yolk sac tumors, also known as endodermal sinus tumors, are rare and tend to be the most aggressive, malignant, and rapidly growing of the germ cell tumors. These tumors often present with extensive abdominopelvic cavity spread. Sex cord–stromal tumors arise from granulosa, theca, Leydig, or Sertoli cells and are unique in their proclivity to be hormonally active. Specifically, tumors with granulosa or theca cells typically produce estrogen, resulting in isosexual precocity. Sertoli-Leydig cell tumors have a tendency to produce androgen analogues, resulting in phenotypic androgen excess. Epithelial-stromal tumors are extremely uncommon before menarche because hormonal stimulation is typically required to activate their growth. (13)The stages of diagnostic evaluation depend on the clinical features evident at the onset of evaluation. Well-appearing females with a palpable abdominal mass suspected to be adnexal in origin should undergo imaging to determine whether the finding is more likely physiologic (eg, simple ovarian cyst) or neoplastic. Transabdominal ultrasonography is the imaging modality of choice in this case. If features concerning for malignancy are present, CT or magnetic resonance imaging should be pursued to elucidate the nature and extent of the tumor. Although it is difficult to distinguish between benign and malignant ovarian tumors purely from imaging, findings that suggest malignancy can be found in Table 2. (11)Once an ovarian tumor is discovered, assay of targeted tumor markers is the recommended next step to help facilitate diagnosis, dictate preoperative planning, and follow postoperatively for response to therapy. The most commonly cited serologic markers are serum AFP, β-human chorionic gonadotropin (β-hCG), CA-125, and inhibin. Serum AFP levels are primarily elevated in patients with malignant germ cell tumors, including yolk sac tumors, immature teratomas, and embryonal carcinomas. Although it is uncommon, AFP level can also be elevated in sex cord–stromal tumors. β-hCG levels are primarily linked to embryonal carcinomas and mixed germ cell tumors. CA-125 levels are commonly more elevated in patients with epithelial ovarian tumors than with germ cell tumors. This tumor marker, however, has low sensitivity and specificity for detection of ovarian malignancy in the pediatric population and can be elevated for a variety of benign reasons in postpubertal patients (endometriosis, ovarian torsion, menses). It thus has limited clinical utility in evaluation of pediatric ovarian tumors. Lactate dehydrogenase level is commonly elevated in dysgerminomas, and inhibin is a sensitive marker of tumor activity in sex cord–stromal tumors. Although tumor markers can be helpful, it is important to note that up to 46% of malignant tumors have no detectable elevations in tumor markers. (13) The ultimate nature of the tumor, malignant or benign, cannot be confirmed until histologic analysis is performed. Absence of metastases also does not exclude malignant histology.Contemporary management of ovarian germ cell tumors is evolving as collaboration among pediatric, genitourinary, and gynecologic oncologists continues to better characterize effective risk classifications, adjuvant therapy candidates, and surveillance strategies. (14) Surgical resection is the primary therapeutic modality for ovarian germ cell tumors, with oophorectomy or salpingo-oophorectomy serving as the definitive treatment for most cases. Adjuvant chemotherapy is considered for patients based on tumor stage, histologic findings, and risk stratification at the time of diagnosis but is typically reserved for children with metastasis beyond the ovary, residual disease, or failure of serum markers to normalize after resection (Table 3). (14) Candidates for postoperative chemotherapy are recommended to receive a platinum-based regimen, traditionally consisting of bleomycin, etoposide, and cisplatin. (14) A fertility-sparing surgical approach is considered the standard of care in pediatric patients with ovarian germ cell tumors, although surgical planning must take into account the unique clinical manifestations, presence of serum tumor markers, distinctive imaging features, and population-based tumor characteristics to generate an optimal approach. (12) Although cryopreservation of the nonaffected ovary may be considered, patients undergoing fertility-sparing unilateral salpingo-oophorectomy, even those requiring postoperative chemotherapy, have favorable fertility outcomes. Case series have shown that regular menstrual cycles return in 87% to 97% of women who had complete response to treatment (consisting of fertility-sparing surgery and platinum-based chemotherapy). (17)(18) Of those attempting conception after treatment, 75% were able to successfully achieve pregnancy. (18) Prognosis, including event-free and overall survival rates, depend primarily on age (<11 years old is considered a positive prognostic indicator), histopathologic tumor type, as well as the tumor stage at diagnosis but are generally favorable (Table 4). (19)(20) Of note, in children with hormonally active tumors resulting in precocious puberty, pediatric endocrinology plays a critical role in the initial evaluation and postoperative surveillance. Treatment of the primary malignancy with fertility-sparing techniques resolves or diminishes pubertal findings in almost all surviving patients with an intact hypothalamic-pituitary-gonadal axis. (21)The patient was diagnosed as having a rapidly growing mixed germ cell tumor with metastatic spread to the omentum and spread beyond the abdomen to the mediastinal lymph nodes (Children's Oncology Group stage IV). After salpingo-oophorectomy and greater oomenectomy she was started on chemotherapy with bleomycin, etoposide, and cisplatin. Her pleural effusions resolved shortly after tumor resection, and cytologic analysis showed transudative fluid with absent tumor burden. At the time of this writing, the patient tolerated her first round of chemotherapy well, with excellent response to interventions. Her most recent AFP levels were within normal limits.

Ovarian germ cell tumors (OGCTs) and sex cord stromal tumors (SCSTs) are rare gynecologic tumors that are derived from germ and stromal cells, respectively. Unlike their epithelial counterparts, molecular pathogenesis of these tumor types is still poorly understood. Here, we characterized microRNA (miRNA) expression profiles of 9 OGCTs (2 malignant and 7 benign) and 3 SCSTs using small RNA sequencing. We observed significant miRNA expression variations among the three tumor groups. To further demonstrate the biological relevance of our findings, we selected 12 miRNAs for validation in an extended cohort of 16 OGCTs (9 benign and 7 malignant) and 7 SCSTs by reverse transcription-quantitative polymerase chain reaction. Higher expression of miR-373-3p, miR-372-3p and miR-302c-3p and lower expression of miR-199a-5p, miR-214-5p and miR-202-3p were reproducibly observed in malignant OGCTs as compared to benign OGCTs or SCSTs. Comparing with benign OGCTs, miR-202c-3p and miR-513c-5p were more abundant in SCSTs. Additionally, we examined Beclin 1 (BECN1), a target of miR-199a-5p, in the clinical samples using western blot analysis. Our results show that BECN1 expression was higher in malignant OGCTs than benign OGCTs, which is concordant with their lower miR-199a-5p expression. This study suggests that these miRNAs may have potential value as tumor markers and implications for further understanding the molecular basis of these tumor types.

Both ovarian and testicular germ cell tumors (GCTs) arise from the primordial germ cell and share many similarities. Both malignancies affect mainly young patients, show remarkable responsiveness to cisplatin-based therapy, and have an excellent prognosis, which also highlights the importance of minimizing long-term side effects. However, certain differences can be noted: The spreading of the disease differs, and the staging system and treatment recommendations are dissimilar. Moreover, the prognosis for ovarian GCTs is significantly inferior to that for testicular cancer, as exemplified in this review comparing the survival in Swedish patients diagnosed with testicular (1995-2022) and ovarian (1990-2018) GCTs. The 5-year overall survival in ovarian GCTs was 85.2%, versus 98.2% for testicular GCTs. How can this be explained? One reason may be the difference in knowledge, experience, and evidence because the incidence rate of testicular cancer is more than 15 times that of ovarian GCTs. Given the rarity of the disease in women and the lack of established guidelines, a comprehensive understanding of the disease and treatment decisions is challenging. The main objective of this review is to derive insights from testicular GCTs (seminoma and non-seminoma) by reviewing etiological, tumor biological, and clinical knowledge, and to thereafter suggest actions for ovarian GCTs based on this. We hypothesize that by adopting specific treatment strategies from testicular GCTs-including de-escalating adjuvant chemotherapy for low-risk patients and implementing more standardized and intensive treatment protocols in cases of relapse-we can improve the prognosis and minimize long-term side effects in ovarian GCT patients.

Introduction: Germ cell tumours comprise approximately 15-20% of all ovarian tumours. Two third of ovarian tumours in first two decades of life are germ cell tumours. Majority of ovarian germ cell tumours are benign teratomas. The malignant germ cell tumours are usually solid and arise from totipotent germ cells. Over the past 3 decades the clinical outcome of women with ovarian germ cell tumours (OGCT) have significantly improved mainly due to development of more effective chemotherapy regimens. Objective: To study the clinic pathological features, treatment and survival of women with ovarian germ cell tumours. Methods: This is a retrospective descriptive study taken from the case files of patients with histo-pathologically proven ovarian germ cell tumours who were treated in JIPMER over 8 years from 2007 to 2014. Results: There were totally 63 patients with ovarian germ cell tumours over 8 years who were treated in JIPMER. The age at presentation varies from 12 years to 65 years with a median age of 26.5 years. Three were pre pubertal and 1 was post-menopausal. Twenty two women (34%) were unmarried and 5 were pregnant at the time of presentation. Forty eight (76%) of them did not have any menstrual abnormalities. Pain abdomen (55%) was the most common presentation. Ten of them presented with acute abdomen of which 8 were torsion, 1 was ruptured dermoid and 1 was infected dermoid. Another 6 patients had torsion which was diagnosed only during surgery. Majority (68%) were benign tumours (dermoid) and among malignant tumours, there were 6 dysgerminomas, 5 immature teratomas, 5 mixed germ cell tumours and 4 yolk sac tumours. Almost half (22 out of 43) of women with benign tumours were &lt;25 years whereas 3/4th (14 out of 20) of women with malignant germ cell tumours were &lt;25 years. The most common tumour marker which was elevated was alpha feto protein (8) followed by LDH (5). Fertility sparing surgery (salpingo-ovariotomy) was commonly performed which was 95% (41/43) in benign tumours and 60% (8/20) in malignant tumours. Contra lateral ovary was biopsied in only 5 patients with suspected involvement (negative on final HPR). Out of 20 women with malignant ovarian tumours 7 were in advanced stage (Stage III). Majority of them recovered well from surgery, only 12% had post-operative febrile morbidity and one patient had subclavian vein thrombosis on post op D9 which required anticoagulants. 7 of 20 women received chemotherapy (BEP) for 4 cycles. No serious side effects of chemotherapy were noted in these women. 3 out of 20 women with malignant germ cell tumour were lost to follow up. No recurrences have been found in rest of the women and there are no deaths till last follow up. Conclusion: Advances in the field of medicine like effective chemotherapy regimens, improved imaging, precise surgical staging and fertility sparing surgical procedures enable women not only to preserve the reproductive function but also to improve their quality of life.

Prompted by the observation of retroviral particle formation in teratocarcinoma cell lines and the consistent finding of antibodies against Gag and Env proteins encoded by human endogenous retrovirus (HERV)-K genomes in the sera of patients with classical seminoma, we studied ovarian and testicular germ cell tumours, their precursor lesions, dysgenetic gonads, and trophoblast lesions for expression of HERV-K sequences by in situ hybridization using radioactive and non-radioactive probes. HERV-K transcripts were detected in all testicular and ovarian germ cell tumours with the exception of teratomas and spermatocytic seminomas. HERV-K expression was also common to testicular carcinoma in situ as well as gonocytes of dysgenetic gonads. Among gestational trophoblastic lesions, HERV-K expression was regularly found in choriocarcinomas, but not in molar lesions. The patterns of HERV-K expression suggest a common molecular pathogenesis of most germ cell tumour entities and malignant gestational trophoblastic disease. They furthermore support the concept of carcinoma in situ as a precursor lesion common to most testicular germ cell neoplasms. The detection of HERV-K gene products in body fluids and tissues may aid diagnosis and monitoring of germ cell tumours and related lesions.

Ovarian germ cell tumors (OGCTs) account for approximately 30% of all primary ovarian neoplasia, secondary only to epithelial ovarian tumors. OGCTs occur mostly in younger women and account for approximately 60% of all ovarian tumors in women under 21 years of age. Most OGCTs are pure, and about 10% of OGCTs contain more than one component. For these mixed tumors, the behavior and prognosis are largely determined by the most malignant component; therefore, thorough examination and extensive specimen sampling are critical for identifying and quantifying all components of the tumor. Germ cell tumors generally mimic various stages of normal embryogenesis and have the potential to develop into any normal tissue type; however, the haphazard distributions and composition of various tissue types can be diagnostically challenging. Achieving the correct diagnosis depends on familiarity with this potentially haphazard pattern of various tissue types, correct identification of all tissue components, and recognition of foci of possible malignant transformation. This chapter focuses on the clinicopathologic features of OGCTs and also briefly covers mixed germ cell and sex cord-stromal tumors.

The embryonic stem cell transcription factors SOX2, NANOG, and OCT3/4 are involved in the regulation of germ cell tumor growth and differentiation. They, and D2-40 (podoplanin), an antigen expressed in seminomas, are emerging as useful diagnostic markers in testicular germ cell tumors. This study evaluates the use of these markers in ovarian tumors. Ovarian germ cell tumors (n=31) have distinct immunostaining profiles, depending on the type of differentiation as follows: dysgerminoma (SOX2-, NANOG+, OCT3/4+, D2-40+), embryonal carcinoma (SOX2+, NANOG+, OCT3/4+, D2-40-), immature teratomas (SOX2+, NANOG-, OCT3/4-, D2-40-), yolk sac tumors, and choriocarcinoma (SOX2-, NANOG-, OCT3/4-, D2-40-). In immature teratomas, SOX2 positivity was limited to neural and epithelial tissues, and OCT3/4 was positive only in scattered epithelial cells (<10% of cells). Nongerm cell tumors (n=57, including surface-epithelial stromal tumors and sex-cord stromal tumors) were negative for NANOG and D2-40. OCT3/4 was positive in 4 of 9 adult granulosa cell tumors (15% to 85% of cells). In a small number of surface-epithelial stromal tumors, SOX2 and/or OCT3/4 were variably positive (20% to 90% of cells). Of the markers, SOX2 and D2-40 discriminated between dysgerminoma and embryonal carcinoma. NANOG distinguished between either of these 2 tumors and nongerm cell tumors. The inclusion of these markers should therefore be considered in cases of pure or mixed ovarian germ cell tumors that are difficult to classify, and to exclude nongerm cell tumor mimics.

Overview of non-epithelial ovarian tumours: Incidence and survival in the Netherlands, 1989–2015

Introduction/BackgroundAbout 5% of ovarian tumours have a non-epithelial histology, including germ cell tumours (GCTs), sex cord-stromal tumours (SCSTs), and sarcomas. Since the rarity of these non-epithelial ovarian tumours and the...

Gynecologic Oncology. Fundamental Principles and Clinical Practice

Introduction/BackgroundMany gynecologic cancers fulfill the criteria of a rare tumor with an annual incidence of <6 per 100,000 women. As these tumor entities are difficult to treat, specialized knowledge and...

BackgroundOvarian germ cell tumours comprise 28% of all diagnosed ovarian cancers and malignant germ cell tumours specifically account for around 13% in Saudi Arabia. Although most of germ cell tumour...

9 - The Diagnosis and Treatment of Early (Preclinical) Invasive Cervical Cancer

Malignant ovarian germ cell tumors (MOGCT) and ovarian sex cord stromal tumors (SCST) are rare ovarian tumors. Since 2013, all German federal states are obliged to record data on diagnosis, pathology, therapy, and clinical course of tumor diseases. We gathered data on MOGCT and SCST from thirteen federal cancer registries and the German Childhood Cancer Registry. Each of the participating registries provided aggregated data on MOGCT and SCST with date of diagnosis between 01.01.2016 and 31.12.2021. 629 MOGCT and 872 SCST were included, age peaks at diagnosis for MOGCT and SCST were between 20 and 24 years and between 55 and 59 years, respectively. Of all MOGCT, 23%, 22%, 13% and 12% were malignant teratoma, dysgerminoma, neuroendocrine tumors and yolk sac tumors, respectively. The large majority (94%) of SCST represented malignant granulosa cell tumors. Most tumors were diagnosed in FIGO stage I (66% of MOGCT and 85% of SCST). Surgery was reported in 58% of patients with MOGCT and in 73% of patients with SCST. Chemotherapy was administered to 26% of MOGCT patients and 8% of SCST patients. This study highlights the great potential of cancer registries as high numbers of patients are recorded, however, data are highly dependent on the reporting institutions.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-025-32998-5.

The tumour microenvironment of rare ovarian germ cell tumours (OGCT) and sex-cord stromal tumours (SCST) remains unexplored. To better understand their immune and stromal landscape, we constructed a blueprint using single-cell RNA sequencing (scRNA-seq). We performed scRNA-seq of 66, 919 cells from twelve fresh tumour samples: seven adult granulosa cell tumour (aGSCT), one juvenile GSCT (jGSCT), one Sertoli-Leydig (SL) tumour, two immature teratoma (IT) and one dysgerminoma (DG). We characterised immune cell subtypes and fibroblasts based on their specific marker genes. Validation included combined positive score (CPS) of 46 OGCTs and 66 SCSTs, and bulk RNA sequencing (n = 32). Cell clustering and annotation revealed a immune-activated microenvironment in DG, driven by PD-1- exhausted T cells, reflected in high CPS (≥10) and upregulated immune pathways. IT samples displayed no immunoreactive profile, consistent with a negative CPS. aGSCTs exhibited a fibroblast-enriched, immune-desert phenotype, with low T cell infiltration and increased immunosuppressive LYVE1 and CX3CR1+ macrophages, corresponding to negative CPS. We constructed a detailed blueprint of the OGCT and SCSTs microenvironment of, elucidating potential modulators that shape their immune landscape. The immune-suppressive environment in aGSCTs likely limits immunotherapy response, as immunosuppressive macrophages inhibit T cell expansion along with EMT activation and fibroblast predominance.