As part of the European Cooperative Study Group for Paediatric Rare Tumours initiative, we developed standard clinical practice guidelines for ovarian sex cord stromal tumors, based on comprehensive national and international cohort analyses, literature review, and a final expert consensus conference. Complete tumor resection is the cornerstone of treatment, with meticulous attention to preventing tumor spillage. Risk stratification of adjuvant chemotherapy decisions incorporates tumor stage and critical parameters, including histological differentiation and mitotic rate. Optimal patient management requires treatment within cooperative networks providing centralized histopathological review and comprehensive genetic testing, multidisciplinary tumor board evaluation, and prospective registry enrollment to advance knowledge for these exceptionally rare malignancies.

DICER1 syndrome is an autosomal dominant tumor predisposition disorder caused by pathogenic variants in the microRNA-processing gene DICER1. Since its initial recognition in families with pleuropulmonary blastoma, the phenotypic spectrum has expanded to encompass a wide array of benign and malignant neoplasms-including thyroid follicular nodular disease, Sertoli-Leydig cell tumor, cystic nephroma, pituitary blastoma, and embryonal rhabdomyosarcoma of the cervix-often presenting in childhood or early adulthood. This updated review synthesizes current knowledge of DICER1 biology, the historical evolution of the syndrome, the distinctive clinicopathologic features of associated tumors, provides a practical diagnostic algorithm to guide pathologists in recognizing sentinel lesions and initiating germline testing, and recent advances in the study of this syndrome and the DICER1 gene. By integrating molecular mechanisms with evolving clinical practice, this article aims to equip diagnostic pathologists and multidisciplinary teams with diagnostic tools and correlations for the detection and management of DICER1 syndrome.

Testicular sex cord stromal tumors are rare neoplasms arising from the sex cord and stromal elements of the testis, exhibiting highly heterogeneous behavior. Although 90% of cases represent biologically benign lesions, the remainder show aggressive, therapy-resistant clinical courses that can rapidly become fatal. In addition, it is challenging to distinguish them from germ cell tumors. The authors present the clinicopathological features of the following entities: Leydig cell tumor, Sertoli cell tumor not otherwise specified, large cell calcifying Sertoli cell tumor, adult-type granulosa cell tumor, juvenile-type granulosa cell tumor, the fibroma/thecoma group, mixed sex cord-stromal tumor, signet-ring stromal tumor, myoid gonadal stromal tumor, and sex cord-stromal tumor not otherwise specified. The aim of the publication is to introduce these lesions to Hungarian medical practitioners, thereby increasing their awareness, appropriate management, and the collection of cases for various targeted tests. Orv Hetil. 2026; 167(20): 784-797.

A 58-year-old man was referred to our department for further evaluation of an incidental right intratesticular mass detected on abdominal and pelvic contrast-enhanced computed tomography performed for an unrelated condition. The mass measured approximately 13 mm and was not clearly palpable on physical examination. Scrotal magnetic resonance imaging showed a well-defined, lobulated, and multinodular mass within the right testis. As a malignant testicular tumor could not be excluded, a right high inguinal orchiectomy was performed for diagnostic and therapeutic purposes. Macroscopically, the excised specimen contained a solid yellow-white mass measuring 16×13×12 mm. Histopathological examination revealed proliferation of tumor cells with round nuclei and eosinophilic cytoplasm. Immunohistochemical staining showed that the tumor cells were positive for calretinin, focally positive for Melan-A, and negative for SALL4. Based on these findings, the diagnosis of a Leydig cell tumor of the testis was made. The patient's postoperative course was uneventful, and no evidence of local recurrence or distant metastasis was observed during 9 months of follow-up. Leydig cell tumors are rare, accounting for approximately 1-3% of all testicular tumors. To our knowledge, this case represents the 128th reported case of testicular Leydig cell tumor in Japan. We report this rare case and provide a review of the literature.

DICER1 syndrome is a complex autosomal dominant tumor predisposition disorder characterized by a distinct chronological progression of benign and malignant lesions. By mapping the transition from early-childhood pulmonary and renal manifestations to the adolescent emergence of endocrine and reproductive neoplasms, this review provides a longitudinal framework for clinical vigilance. Central to this analysis is the molecular "two-hit" mechanism, specifically investigating how somatic hotspot mutations in the RNase IIIb domain disrupt the miR-140/FGF9 signaling axis and the let-7 feedback loop. The review identifies the neomorphic "Argonaute strand switch" as a primary driver of pathogenesis, resulting in a diagnostic 3p-strand bias that fuels sarcomatous transformation. Beyond the molecular substrate, we define the critical radiographic and clinical markers of malignancy, such as rapid volumetric growth, cystic solidification, and the detection of somatic hotspots via high-sensitivity droplet digital PCR. By integrating the 2024 international surveillance standards with emerging technologies, including Vision Transformer-based radiographic analysis and circulating tumor DNA monitoring, this review offers a proactive, evidence-based roadmap for identifying the predictors of malignancy and better management of the disease. Ultimately, this synthesis aims to equip clinicians and other healthcare profesionals with the predictive tools necessary to achieve definitive cures while minimizing the cumulative clinical and psychological burden on this genetically vulnerable population.

We present a case of a postmenopausal woman with androgenic alopecia and very high testosterone levels of 16 nmol/L (normal range 0.4-1.2). CT showed an enlarged right ovary with a high-density nodule and an incidental adrenal nodule. She underwent bilateral salpingo-oophorectomy and pathology confirmed a benign Leydig cell tumour of the right ovary and Leydig cell hyperplasia of the left. Testosterone levels improved to near normal postoperatively. Adrenal investigations favoured a benign adenoma, although adrenal androgen production could not be ruled out.This case highlights the challenges in investigating hyperandrogenism in postmenopausal women; the most common causes are ovarian and adrenal in origin. Leydig cell tumours are rare androgen-secreting benign ovarian tumours. The treatment of choice is bilateral salpingo-oophorectomy and provides cure in most cases.

BACKGROUND: Patients with renal allograft failure undergoing hemodialysis may be associated with an increased risk of preeclampsia. Preeclampsia can present with systemic manifestations, including organ bleeding. In this case, a suspected placental abruption was eventually confirmed to be caused by the rupture of an ovarian Sertoli–Leydig cell tumor (SLCT). A DICER1 mutation was subsequently identified in the patient. CASE PRESENTATION: A 30-year-old primigravid woman with a history of thyroidectomy and renal allograft failure on maintenance hemodialysis presented at 29 weeks of gestation with a blood pressure of 180/110 mmHg and sudden onset of abdominal pain. She was diagnosed with preeclampsia. Due to suspected placental abruption and acute fetal distress, an emergency cesarean section was performed, resulting in the delivery of a healthy baby girl. During the operation, approximately 600 g of intraperitoneal blood clots were found, secondary to a ruptured ovarian cyst. Histopathological examination revealed a moderately to poorly differentiated ovarian SLCT. Targeted next-generation sequencing identified a new DICER1 variant (c.3175 dup: p.Tyr1059LeufsTer32 in exon 20 of chr14:95571502) in peripheral blood samples. The frameshift variant induces a premature termination classified as likely pathogenic based on ACMG criteria. Analysis of the family pedigree reveals a clustering of earlier-onset renal disease. During the 22-month follow-up period, following the decline of adjuvant chemotherapy, the patient experienced a second unintended pregnancy that required medical termination. No evidence of SLCT recurrence was observed. CONCLUSIONS: This case report presents a unique pregnant patient with a history of thyroidectomy and living-renal allograft failure requiring hemodialysis, who developed preeclampsia and a ruptured ovarian SLCT. To our knowledge, this appears to be the first combination of a DICER1-mutation-associated ovarian SLCT in a pregnant patient with transplant failure. This highlights the pivotal need for systematic preconception counseling and effective contraceptive education in this population. A well-coordinated multidisciplinary team approach was imperative to secure optimal maternal and fetal outcomes.