Endometriosis, defined as the ectopic growth of endometrial tissue outside of the uterine cavity, is an inflammatory and hormone-dependent disease that causes excruciating pelvic pain, infertility, and significantly decreases quality of life in affected patients. The JUN N-terminal kinases (JNKs) are a leading class of nonhormonal therapeutic targets that have been validated in preclinical models of endometriosis and in a Phase 1/2 clinical trial. Despite their therapeutic potential, JNK inhibitors with increased potency and specificity are needed to address the inflammatory pathology of endometriosis and to prevent disease progression. Leveraging a DNA-encoded chemical library collection of ~4 billion compounds, we identified lead inhibitor CDD-2428 and optimized derivatives, CDD-2728 and CDD-3013, with excellent binding affinity to JNK1-3 (Kd = 0.12 to 3.7 nM), enhanced selectivity, metabolic stability, and cellular permeability. Crystallographic and biochemical studies confirmed that CDD-3013 exhibited superior kinase selectivity with improved efficacy compared to existing JNK inhibitors. In primary endometriosis cell models, CDD-2728 and CDD-3013 suppressed JNK-dependent inflammatory signaling, dampening pathways linked to pain, invasion, angiogenesis, and macrophage recruitment. In an endometriosis mouse model, both CDD-2728 and CDD-3013 reduced endometriotic lesion size, macrophage infiltration, and cellular proliferation, showing in vivo efficacy. When tested in a lipopolysaccharide-induced hyperalgesia model, CDD-2728 and CDD-3013 decreased markers of induced pain, as measured by changes in a dynamic weight bearing test and Grimace scores. These findings nominate CDD-2728 and CDD-3013 as potent, nonhormonal therapeutic candidates for endometriosis with broad anti-inflammatory and analgesic activity, addressing a critical unmet clinical need.

Extended pelvic lymph node dissection (ePLND) during robot-assisted radical prostatectomy (RARP) may impair lymphatic drainage, causing lower-limb and genital lymphedema with a potential negative impact on postoperative recovery and quality of life. This prospective randomized study evaluated whether an oral formulation containing diosmin, bromelain, melilotus, and hesperidin (Meliven Top®) could reduce postoperative lymphatic morbidity after RARP with ePLND. One hundred patients undergoing RARP with ePLND for prostate cancer were randomized 1:1 to standard postoperative care alone or standard care plus oral Meliven Top® for one month. Lower-limb volumes were assessed preoperatively and at 1 and 3 months postoperatively using circumferential measurements and truncated-cone volume estimation. Secondary endpoints included genital swelling, genital pain, and lymphocele formation. Multivariable ANCOVA models adjusted for baseline limb volume, body mass index, and number of lymph nodes removed were applied.Ninety-eight patients completed follow-up. No significant differences in lower-limb volumetric changes were observed between groups at 1 or 3 months. However, genital pain at 1 month was significantly lower in the treatment group (2% vs. 18%; p = 0.008), and persistent genital swelling at 3 months was absent in treated patients compared with controls (0% vs. 8%; p = 0.041). Lymphocele rates were similar between groups. In conclusion, Meliven Top® did not significantly reduce postoperative lower-limb volume changes after RARP with ePLND, but it was associated with improved genital symptom recovery. Larger studies with longer follow-up are warranted.Clinical trial registration This study was not registered in a public clinical trial registry.

An elderly postmenopausal woman with untreated vulvar lichen sclerosus and lichen planus (LP) overlap presented with abdominal pain, constipation and urinary symptoms. Severe vulvovaginal scarring caused complete vaginal obliteration, preventing conventional speculum examination and transvaginal ultrasonography. Endorectal and abdominal ultrasonography revealed a large cystic pelvic mass. Urgent laparotomy identified extensive haematocolpos and uterine distension due to complete outflow obstruction. The patient underwent a hysterectomy, bilateral salpingo-oophorectomy and subtotal colpectomy. Histopathology confirmed Stage International Federation of Gynecology and Obstetrics (FIGO) IIB endometrioid endometrial carcinoma with mismatch repair deficiency while the vaginal tissue showed benign fibrosis. Postoperatively, she received topical corticosteroids for her vulvar disease and remained recurrence-free at a 24-month follow-up. This case emphasises that advanced vulvovaginal scarring can mask gynaecological malignancies and obstruct conventional diagnostics, necessitating alternative imaging and prompt surgical intervention to optimise outcomes.

Both embryonic-type neuroectodermal tumor and nephroblastoma arising as somatic-type malignancies are rare, particularly nephroblastoma. Concurrent embryonic-type neuroectodermal tumor and nephroblastoma have only been reported once in literature, identified in metastatic pelvic lymph nodes in association with a mixed germ cell tumor. Herein, we report the first concurrent embryonic-type neuroectodermal tumor and nephroblastoma within the primary testicular tumor, arising associated with a mixed germ cell tumor. A 36-year-old man presented with a 4.5 cm right testicular mass. He underwent right orchiectomy. Gross examination revealed a well-circumscribed, solid to cystic mass confined to the testis (pT1). Histological examination demonstrated a mixed germ cell tumor composed of teratoma (40% of the tumor mass), seminoma (10%), embryonal carcinoma (2.5%), and yolk sac tumor (2.5%), with associated germ cell neoplasia in situ. Additionally, two somatic-type malignancy components were identified, including embryonic-type neuroectodermal tumor (40%) and nephroblastoma (5%). The embryonic-type neuroectodermal tumor consisted of primitive neural tubules, rosettes, and blastemal cells. The nephroblastoma was composed of tubules, blastemal cells, and stromal cells. Immunohistochemically, the embryonic-type neuroectodermal tumor showed diffuse positivity for SOX11, with focal expression of synaptophysin and CD99, while the nephroblastoma was positive for PAX8 and WT1. The patient developed metastasis to a retroperitoneal lymph node 1 month after the orchiectomy, subsequently received chemotherapy, and is alive without metastatic disease at 13 months of follow-up.

Primary ovarian epithelioid angiosarcoma (EAS) is an exceptionally rare and highly aggressive vascular malignancy with only isolated cases reported in the literature. Owing to its nonspecific clinical presentation and overlapping radiological features, preoperative diagnosis is extremely challenging and often mimics more common gynecologic malignancies. Consequently, evidence regarding optimal diagnosis and management remains limited. A 61-year-old postmenopausal woman presented with abdominal pain and a rapidly enlarging pelvic mass. Ultrasonography, computed tomography, and magnetic resonance imaging demonstrated a giant hypervascular pelvic tumor with extensive pelvic and para-aortic lymphadenopathy, initially suggesting uterine sarcoma. Serum CA125 and lactate dehydrogenase levels were elevated. Exploratory laparotomy identified a dominant right ovarian hypervascular tumor with diffuse peritoneal dissemination and bulky pelvic and para-aortic nodal metastases. Comprehensive clinical, radiological, intraoperative, gross pathological, histopathological, and immunohistochemical assessment demonstrated a primary ovarian origin, with no evidence of an extra-ovarian primary angiosarcoma. The patient underwent radical cytoreductive surgery, including total hysterectomy, bilateral salpingo-oophorectomy, omentectomy, appendectomy, resection of visible metastatic lesions, and systematic pelvic and para-aortic lymphadenectomy, achieving complete macroscopic cytoreduction. Histopathological examination demonstrated epithelioid tumor cells with vasoformative differentiation, while immunohistochemistry showed diffuse strong positivity for CD31, CD34, and FLI1, confirming primary ovarian epithelioid angiosarcoma. The patient declined adjuvant chemotherapy, developed rapid postoperative disease progression, and died approximately 2 months after surgery. This case highlights the marked diagnostic challenges and highly aggressive biological behavior of primary ovarian EAS with extensive pelvic and para-aortic lymph node metastases and diffuse intra-abdominal dissemination. Accurate diagnosis required a comprehensive clinicopathological correlation supported by histopathological and immunohistochemical evaluation. Although complete macroscopic cytoreduction and systematic lymphadenectomy were technically feasible, their therapeutic benefit cannot be inferred from a single case. This report expands the limited literature and emphasizes the need for improved diagnostic strategies, collaborative data collection, and more effective systemic therapies for this rare malignancy.

Endometriosis may rarely present with atypical manifestations that closely mimic intra-abdominal malignancy or severe pelvic sepsis, resulting in significant diagnostic uncertainty. We present two contrasting cases of presumed severe endometriosis with uncommon clinical and radiological presentations. In the first case, a woman in her 30s presented with acute abdominal pain, progressive abdominal distension, and respiratory compromise associated with massive haemorrhagic ascites and markedly elevated cancer antigen 125 levels. Cross-sectional imaging demonstrated extensive deep infiltrative endometriosis with haemoperitoneum and multiple extra-pelvic endometriotic deposits. In the second case, a woman in her 30s presented with a complex adnexal mass, para-aortic lymphadenopathy and inflammatory features initially concerning for tubo-ovarian abscess or underlying malignancy. Following prolonged antibiotic therapy, complete radiological resolution of the adnexal lesion was observed, with subsequent imaging findings considered highly suggestive of an infected endometrioma. These cases emphasise the diverse spectrum of endometriosis presentations, the limitations of non-histological diagnosis and the importance of multidisciplinary assessment, radiological expertise and longitudinal follow-up in complex presentations.

Intestinal involvement by urothelial malignancy is uncommon and can obscure the primary diagnosis. We report a woman in her 70s who presented with shock, profound anemia, acute kidney injury, and bilateral hydronephrosis caused by a necrotic pelvic mass suspected to arise from the bladder. Despite resuscitation and urinary decompression, she developed abdominal distention, rising lactate levels, and respiratory decline. Exploratory laparotomy revealed combined small- and large-bowel obstruction with ischemic bowel caused by an invasive pelvic mass. Pathology from the resected small bowel showed poorly differentiated urothelial carcinoma with basal/squamous features. This case highlights an unusual presentation of advanced urothelial malignancy.

Uterine leiomyosarcoma (uLMS) is a rare and aggressive mesenchymal malignancy associated with a high risk of recurrence and metastatic spread. Although recurrent disease commonly presents with infiltrative or bulky pelvic masses, atypical patterns of dissemination may create diagnostic challenges. We present the case of a 49-year-old woman with a history of FIGO stage IB uterine leiomyosarcoma who underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy in 2023 and subsequently received treatment for recurrent metastatic disease. She presented with acute lower abdominal pain, persistent vomiting, and progressive obstipation. Computed tomography demonstrated a large heterogeneous pelvic mass measuring approximately 14 cm, together with features of a closed-loop small bowel obstruction and mesenteric vessel twisting suggestive of volvulus. Following clinical deterioration despite conservative management, emergency exploratory laparotomy was performed, revealing a 360-degree small bowel volvulus around the superior mesenteric artery pedicle, which was successfully reduced. A large fixed pelvic mass involving adjacent bowel and mesentery was identified, along with numerous smooth, firm, pedunculated nodules distributed throughout the mesentery, bowel serosa, and parietal peritoneum. These nodules had a gross appearance resembling benign parasitic leiomyomas or disseminated peritoneal leiomyomatosis rather than metastatic sarcoma. Segmental small bowel resection with double-barrelled ileostomy was undertaken due to bowel compromise and extensive serosal injury. Histopathological examination of the resected nodules demonstrated atypical spindle cells arranged in intersecting fascicles with moderate nuclear atypia and a mitotic rate of 5-10 mitoses per 10 high-power fields. Immunohistochemical analysis showed diffuse positivity for smooth muscle actin, desmin, and h-caldesmon, with abnormal mutant-pattern p53 expression, confirming multifocal metastatic uterine leiomyosarcoma. This case demonstrates an unusual pattern of metastatic uLMS presenting with a benign-appearing peritoneal distribution and complicated by acute small bowel volvulus and obstruction. The findings highlight the importance of histopathological and immunohistochemical assessment in distinguishing metastatic smooth muscle malignancy from benign-appearing lesions and emphasise the need for multidisciplinary management in complex recurrent disease.