Over 25% of active NASA astronauts are women who will be exposed to low daily doses and dose rates of galactic cosmic rays (GCR) in space. We hypothesized that exposing mice to a preliminary simulated GCR mixed heavy ion beam composed of iron, silicon, and titanium ions induces follicle depletion and dose-dependent ovarian tumors. Female mice were exposed to 10, or 20 cGy each of Fe, Si, and Ti ions or sham-irradiation in quick succession within 15 minutes for total doses of 0, 30, or 60 cGy of the three beams. 16 months later, their ovaries were removed. Hyperplasia of the ovarian surface epithelium (OSE) was noted in 13%, 59%, and 22% of the 0, 30, and 60 cGy irradiated mice, respectively. The prevalence of mixed ovarian tumors was 0, 6, and 89%, respectively, in the 0, 30, and 60 cGy groups. Low numbers of Ki67 positive OSE and tumor cells supported a benign tumor phenotype. In a separate study, Si ion irradiation alone at 32 cGy did not induce ovarian tumors in mice; however, the mixed heavy ions at all doses and Si ion irradiation alone reduced the total number of healthy ovarian follicles. Mixed heavy ion exposure reduced lipid peroxidation, fibrosis, inflammation, and lipofuscin accumulation at 60 cGy compared to 0cGy, but elevated inflammation and lipofuscin accumulation at 30 cGy compared to 60 cGy. Preliminary simulated GCR exposure causes ovarian follicle death and tumorigenesis. This study provides insight into space-radiation induced ovarian damage and cancer risk in females.

Carcinosarcomas (CSs) are aggressive biphasic tumors characterized by epithelial and mesenchymal components, whose histogenesis and differentiation dynamics remain poorly understood. We present single‐nucleus RNA sequencing (snRNA‐seq) analysis of six CSs (five endometrial and one ovarian) and two normal endometrial samples, profiling over 96,298 cells. By integrating transcriptomic data with inferred copy number variations (CNVs), immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and in situ hybridization (ISH) validation, we resolved the complex cellular architecture of these tumors, identified lineage‐specific programs, and revealed unexpected differentiation trajectories. snRNA‐seq was used to further refine the histopathological classification of three cases by uncovering heterologous differentiation not previously recognized: one rhabdomyogenic, one osteogenic, and, notably, one exhibiting a novel tenogenic program, defined by the expression of SCX, MKX, and TNMD. All CSs displayed a prominent mesenchymal compartment comprising both undifferentiated fibroblast‐like cells and distinct lineage committed populations, including rhabdomyoblasts (Rhab), tenoblasts (Teno), osteoblasts (Osteo), and chondroblasts (Chond). In some tumors, multiple mesenchymal identities co‐existed, and in others, differentiation gradients (e.g. immature versus mature rhabdomyoblasts) were observed. These patterns underscore the cellular plasticity and multilineage potential of the sarcomatous component. Furthermore, the expression of specialized interface markers (COL22A1, NCAM1, ACAN, CHRNG, MUSK) suggests that some tumors use structured developmental programs reminiscent of the muscle–tendon junction, enthesis, or neuromuscular junction. CNV analysis revealed tumor‐specific genomic alterations with clonal and subclonal patterns linked to differentiation state, which were validated by FISH. Altogether, this study demonstrates that CSs are not static biphasic tumors but rather complex ecosystems with extensive developmental plasticity. Our findings redefine their classification and support the use of single‐nucleus approaches to uncover hidden differentiation trajectories in highly heterogeneous cancers, including the discovery of a previously unreported tenogenic lineage. Our results challenge the diagnosis of homologous CS when only morphological criteria are applied. © 2026 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Introduction Germ Cell Tumors (GCT) are the second most common malignancy in adolescence. Extracranial malignant GCT (eGCT) are much more common among adolescents, representing approximately 15% of cancer diagnoses in this age group. Treatment for these tumors involves surgery, chemotherapy, and radiotherapy. Total tumor resection is a primary prognostic factor. The most common treatment regimen consists of bleomycin, etoposide, and cisplatin. In Latin America, data are scarce. Some reports show that the most frequent age of presentation is in adolescents aged 15–19 years. Material and methods A retrospective study was conducted from January 2014 to December 2024, accepting 60 newly diagnosed patients with malignant eGCT at a tertiary care hospital in Mexico. The chemotherapy regimens used were CISCA II and BEP. We performed descriptive statistics, as well as Kaplan–Meier survival analysis. Results The mean patient age was 10.5 + 4.5 years. The adolescent group was the most significant (48.3% of the total of all patients). The most common histology was mixed tumor in 35% of patients. The most frequent primary site was the gonadal region in 95% of patients; 53.3% of patients presented in advanced stages III and IV. The overall survival rate was 94.9%, and the relapse-free survival rate was 88.5%. Three deaths were recorded in 10 years. Five patients with hypoacusis were recorded, and in one case, a decrease in the LVEF was observed, with no change in functional class. Conclusions In conclusion eGCT are highly curable diseases. In this series of cases, good long-term results were observed.

Central nervous system germ cell tumors are rare intracranial neoplasms that predominantly occur in pediatric populations and exhibit characteristics similar to those of gonadal and extragonadal germ cell tumors. Neuroblastoma (NB) represents the most common type of extracranial solid tumor in children, typically arising in tissues with sympathetic innervation. We present a case involving a 14-year-old male patient diagnosed with bilateral intracranial mixed germ cell tumors and concurrent bilateral retroperitoneal ganglioneuroblastoma. To the best of our knowledge, this is the first documented instance of the co-occurrence of these two distinct neoplastic entities. Additionally, Whole-exome sequencing (WES) of the blood sample identified a chromosomal deletion consistent with the 16p11.2 microdeletion syndrome. Furthermore, a heterozygous missense variant in the ALK gene (p. Arg1275Gln) was identified.

Cutaneous adnexal tumors are a heterogeneous group of neoplasms with diverse histopathologic features. Clear cell hidradenoma (CCH) and cutaneous mixed tumors are benign adnexal neoplasms that may share overlapping morphologic characteristics, making diagnosis challenging, particularly at uncommon acral sites. We report the case of a 60-year-old man who presented with a long-standing nodule on the hand. Histopathologic evaluation suggested a possible diagnosis of clear cell hidradenoma. There were also myxoid areas and a focal chondroid area as well, which are features seen in cutaneous mixed tumors. To further clarify the diagnosis, next-generation sequencing identified an in-frame TRPS1-PLAG1 gene fusion, confirming a diagnosis of cutaneous mixed tumor with phenotypic features of clear cell hidradenoma. This case highlights the diagnostic complexity of acral adnexal tumors with overlapping morphologic features. Molecular testing, such as next-generation sequencing, can be an essential adjunct in distinguishing between morphologically similar adnexal neoplasms, thereby guiding accurate diagnosis and management.

Genetic profiling of mammary periductal stromal tumors with histologic correlation highlights high-grade and low-grade groups and similarities to phyllodes tumors.

Combined hepatocellular carcinoma-cholangiocarcinoma (cHCC-CCA) is a rare primary hepatic neoplasm that presents simultaneous differentiation into hepatocytes and cholangiocytes, predominantly in patients with chronic liver disease. Its diagnosis continues to be a challenge due to its clinical and imaging presentation similar to other liver tumors, especially in cirrhotic patients. We present the case of a 61-year-old female patient with liver cirrhosis secondary to nonalcoholic fatty liver disease, who was diagnosed with cHCC-CCA after a hepatic bisegmentectomy. During her evolution, she presented tumor recurrence at hepatic and lymph node level, managed by salvage surgery and immunotherapy. However, he developed acute on chronic hepatic failure, which forced to suspend treatment and opt for palliative management. This entity stands out for its high recurrence rate, limited response to systemic therapies and lack of standardized guidelines. The present case emphasizes the importance of an accurate histopathologic diagnosis and individualized evaluation for therapeutic selection.

Immature teratoma (IMT) is an ovarian germ cell tumour with high malignant potential. It is occasionally combined with other ovarian germ cell malignancies, but rarely just with yolk-sac tumour, which exhibits even more aggressive behaviour. We present a case of a young patient who presented with giant, atypical, steady growing tumour comprised of IMT with YST islets. Throughout adolescence the tumour grew to gigantic measures of almost 7, 2 kg, without any symptoms, and secreting no significant quantities of alpha-fetoprotein (AFP), which is the major biomarker for YST. In spite of a huge abdominal tumour, giving her body contour characteristics of a late third trimester pregnancy, the disease was fortunately in FIGO Ia stage, enabling the patient to choose the conservative treatment of fertility sparing surgery alone. The recovery was complete, with defined frequent follow-up sessions. Given that almost all of mixed malignant ovarian germ cell tumours (MOGCTs) are highly chemo-sensitive, potential neo-adjuvant chemotherapy remains an alternative treatment if the signs of recurrence appear. Today’s golden standard in chemotherapy for MOGCTs presents a BEP (bleomycine, etoposide, and cisplatin) regimen. After thorough search of recent literature we present a review of novel insights in aetiology, diagnostics and treatment options for this rare group of cancers.

Spindle cell neoplasms represent an heterogeneous group of both benign and malignant tumors. They rarely occur in the oral cavity, accounting for less than 1% of all oral tumors. Sarcomatoid squamous cell carcinoma (SSCC) also referred to as spindle cell carcinoma or Lane’s tumor is an uncommon and distinct biphasic malignant tumor that primarily affects the upper aerodigestive tract. This variant of squamous cell carcinoma features spindled or pleomorphic tumor cells that mimic true sarcoma but are of epithelial origin. Known for its aggressive behavior, SSCC has a high tendency for recurrence and metastasis, underscoring the need for accurate diagnosis. We report a case of SSCC, supported by immunohistochemical findings.

Background: Germ cell tumors are benign or malignant tumors that originate from the human embryo’s primordial germ cells. This study aims to conduct a retrospective analysis of germ cell tumors followed up at our institution, including their epidemiological data, treatment, and prognosis. Patients and Methods: Ninety-three cases were included and retrospectively evaluated for socio-demographic features, clinical data, presenting symptoms, histopathological findings, localization, staging, treatment protocol, and survival analysis. Results: Patients were diagnosed between 10 days and 17 years 10 months (median 27.2 months); 37 (40.7%) were male, 54 (59.3%) female. The tumors were located in the sacrococcygeal region (33.3%), ovaries (26.8%), testes (25.8%), abdomen (7.5%), CNS (2.1%), liver, adrenal gland, anterior mediastinum, and spine. Thirty-nine lesions were benign, and 54 were malignant. Mature cystic teratomas (40.8%), endodermal sinus tumors (28.0%), mixed germ cell tumors (12.9%), immature teratomas (9.7%), germinoma (6.5%), gonadoblastoma (1.1%), and choriocarcinoma (1.1%) were the different types of histology. We observed metastases in 17 malignant cases, with the lungs being the most commonly affected (10.7%). Stages I, II, III, and IV included 16, 17, 11, and 10 cases, respectively. Survival rates for all cases were 95.8%, and for malignant tumors, they were 92.7%. For malignant cases, the event-free survival rate was 84.2%. Conclusions: The findings provide comprehensive epidemiological and clinical data on germ cell tumors, enhancing understanding of their distribution, treatment outcomes, and prognosis. The high survival rates observed highlight the effectiveness of current treatment protocols, as well as the importance of early diagnosis and appropriate management.

The occurrence of mixed tumors in soft tissues or myoepithelial tumors is extremely rare. Herein, we report a case of a mixed tumor suspected to be a sarcoma based on imaging findings. A 64-year-old male was admitted to our hospital with a mass that had been present for 10 years and had gradually increased in size, prompting medical attention. Magnetic resonance imaging raised the suspicion of sarcoma, leading to a pathological diagnosis of myoepithelioma. Surgery was performed, and histopathological examination confirmed the presence of both epithelial and myoepithelial structures, resulting in a final diagnosis of a mixed tumor. Three years after the surgery, no recurrence was observed. In this case, considering the size and duration of the illness, a benign subcutaneous tumor was suspected. However, the heterogeneity in imaging findings raised concerns about sarcoma, making differential diagnosis challenging. Although the imaging characteristics of mixed tumors are currently unclear, their signals and internal characteristics may be heterogeneous. Therefore, clinical findings and imaging should not mislead the diagnosis, and histopathological examination remains a shortcut for diagnosis and treatment.

Mixed Neuroendocrine-Non-Neuroendocrine Neoplasm (MiNEN) of the oesophagus is an especially rare malignancy. It is composed of an adenomatous and a neuroendocrine aspect. Each histologic subtype contributes at least 30% of the immunohistopathologic features to the complex profile of these mixed neoplasms. Given the small number of cases in the existing literature and the lack of international guidelines, diagnosis and treatment may vary among different centers; however, a combined approach based on surgical resection and systemic therapies is usually the preferred pathway. In this paper, we present the case of a 68-year-old male who was initially diagnosed with oesophageal adenocarcinoma and was treated with neoadjuvant chemotherapy and oesophagectomy. After the histopathologic examination of the specimen, the tumour was histologically characterised as MiNEN and the patient underwent adjuvant therapy. Multimodal management and tailored treatment are essential in these complex cases since preoperative staging poses challenges and limitations.

Fusion-positive myoepithelial tumors (MET) are clinicopathologically heterogeneous and variably termed mixed tumors and myoepithelial carcinomas. Since FET-rearranged MET lack ductal/epithelial differentiation, we test whether FET-rearranged MET are epigenetically distinct from adnexal PLAG1-rearranged MET, which we hypothesize to be analogues of salivary gland MET. DNA methylation profiling from a multi-institutional cohort of 52 fusion-positive skin, soft tissue and bone MET cases was performed and compared to diverse tumor types, including salivary MET. The MET subgroups harbored EWSR1::KLF15, EWSR1/FUS::KLF17, EWSR1::PBX1, EWSR1::PBX3, EWSR1/FUS::POU5F1, SS18::POU5F1, EWSR1::ZNF444 and PLAG1 rearrangements. Pooled clinicopathological and outcome analysis with new and published cases (total 185) was performed. . The MET subgroups showed significant heterogeneity in age, site, and histology. Specifically, EWSR1::KLF15 MET affected predominantly young children (<5 years old); EWSR1::PBX1PBX3 MET were enriched in skin/bone; EWSR1/FUS::POU5F1, SS18::POU5F1 and EWSR1::KLF15 MET tended to display malignant histology. Conversely, PLAG1-rearranged tumors were predominantly benign, arising in older adults and located in the skin. DNA methylation profiling revealed that FET-rearranged MET were epigenetically related to SS18::POU5F1 MET and FET::NFATC2 sarcomas, but entirely distinct from PLAG1-rearranged adnexal and salivary MET. Histologic features were correlated with the degree of genome-wide copy number variation. Median disease-specific survival was shortest in SS18::POU5F1 (31 months), EWSR1::PBX3 (38 months), and EWSR1::KLF15 (45 months) MET. On multivariate analysis, age < 25 years old was a significant predictor of worse progression-free survival. FET-rearranged MET are epigenetically unrelated to cutaneous and salivary gland MET, and their malignant counterparts are best classified as sarcomas rather than carcinomas.

BRAF p.V600E Mutation in Mixed Odontogenic Tumors and Its Clinical Correlation: A Systematic Review and Meta-Analysis

Epidemiology of testicular tumour diagnoses in Australian dogs in primary care (1992-2022): A retrospective analysis of electronic patient records.

Cancer predisposition syndromes caused by germline pathogenic variants (GPV) in adult-onset cancer predisposition genes (aoCPG) are those for which there is low risk of cancer in children, with genetic testing and screening for these conditions typically deferred until adulthood. GPV in aoCPG have been identified in pediatric oncology patients, but in these cases the potential contribution of the aoCPG to cancer development is often unknown. We investigated the role GPV in aoCPG may play in childhood cancer development. Results of paired tumor-germline sequencing from pediatric oncology patients enrolled from May 2012 to October 2023 were analyzed for frequency of GPV in aoCPG. Germline testing included analysis of up to 182 cancer predisposition genes. Tumor loss-of-heterozygosity, presence of second somatic pathogenic variant, immunohistochemical stain for protein expression, and/or tumor mutation burden were used to determine possible causation. Of the 954 participants, 42 (4.4%) had GPV in aoCPG. Six (14.3%) of these 42 participants had tumor findings indicating their GPV in an aoCPG likely contributed to cancer development: three patients with Lynch syndrome (two anaplastic astrocytomas, one giant cell glioblastoma) and one each with GPV in ATM (craniopharyngioma and diffuse high-grade glioma), BRIP1 (atypical teratoid rhabdoid tumor), and CHEK2 (mixed germ cell tumor of pineal gland). These findings contribute to the literature suggesting that, rarely, GPV in aoCPG may contribute to cancer diagnoses in children, raising the question of how tumors in these cases may present differently in children than adults. Increased knowledge about potential childhood cancer risks related to what have historically been considered aoCPG could modify predictive genetic testing recommendations for children and enhance existing cancer screening protocols.

Melanotic neuroectodermal tumor of infancy (MNTI) is a rare, typically benign but locally aggressive tumor that most commonly affects the maxilla in infants under 1 year of age. Although surgical resection is the standard treatment, cases requiring total maxillectomy and immediate reconstruction have rarely been reported. Here, we report a 6-month-old male infant who presented with a rapidly enlarging maxillary mass. Imaging revealed a 60 × 57 × 50 mm lesion with extensive bone destruction and displacement of the primary teeth. A biphasic tumor composed of small round cells and melanin-containing epithelioid cells was identified histologically and confirmed to be MNTI by immunohistochemistry. Following a multidisciplinary evaluation, a total maxillectomy was performed 6 days after the initial visit. Immediate orbital floor reconstruction was achieved using cryopreserved autologous bone harvested from the resected specimen. The patient recovered without complications and was discharged on postoperative day 15. At 12-month follow-up, there was no recurrence or infection, and the reconstructed segment showed successful integration. This case highlights the feasibility of immediate reconstruction using cryopreserved autologous bone after a total maxillectomy for MNTI. Prompt diagnosis and coordinated multidisciplinary care are essential for optimal outcomes in aggressive MNTI. Long-term follow-up is necessary to assess growth, function, and aesthetic outcomes.

Transcriptomic signatures of cytomorphological heterogeneity in canine transmissible venereal tumor.

Ceruminous adenomas are benign neoplasms that arise from ceruminous glands in the external auditory canal. While these tumors are currently regarded as a single entity, they are divided into three histologically diverse subtypes: ceruminous syringocystadenoma papilliferum, ceruminous pleomorphic adenoma, and ceruminous adenoma not otherwise specified (NOS). Given the similarities of two of these subtypes to other tumors that occur at multiple anatomic sites, it is currently unclear whether ceruminous adenomas are truly a unified group. In this study, we performed targeted molecular profiling of 11 cases of ceruminous adenoma to clarify their classification. We identified BRAF V600E mutations (via PCR and/or immunohistochemistry) in five ceruminous syringocystadenomas papilliferum. We also identified HMGA2::WIF1 fusions (via RNA sequencing) in five ceruminous adenomas NOS and one ceruminous pleomorphic adenoma. Tumors with HMGA2::WIF1 fusion did not display the canalicular adenoma-like morphology seen in salivary gland pleomorphic adenomas with this fusion. Overall, these findings suggest that the three subtypes of ceruminous adenoma represent two biologically distinct groups. Recurrent BRAF V600E mutations in ceruminous syringocystadenoma papilliferum are parallel to those in cutaneous syringocystadenoma papilliferum. Histologic and molecular concordance suggests that ceruminous syringocystadenoma papilliferum should be part of the broader syringocystadenoma papilliferum category rather than a subtype of ceruminous adenoma. Conversely, HMGA2::WIF1 fusions in ceruminous adenoma NOS and ceruminous pleomorphic adenoma suggest that a stromal component may not be an essential point of distinction between these groups. These residual true ceruminous adenomas all likely represent a specialized form of mixed tumor unique to the external ear.

PurposeTo evaluate the clinical efficacy of neuroendoscopic resection of pineal region tumors via the transfrontal-transventricular-transforaminal approach.MethodsClinical data of eight patients with pineal region tumors who underwent this surgical approach at our institution between January 2020 and July 2025 were retrospectively reviewed.ResultsThe cohort consisted of seven males and one female, aged 3–52 years. Gross total resection (GTR) was achieved in three patients, near-total resection (NTR) in two, and subtotal resection (STR) in three. Three patients underwent combined radiotherapy and chemotherapy. Histopathological diagnoses included three mixed germ cell tumor, two low-grade glioma, one high-grade glioma, and one mature teratoma. Two patients developed subjective memory decline. During a follow-up period of 3–29 months, seven patients resumed normal daily activities, except for one who discontinued treatment due to tumor recurrence.ConclusionNeuroendoscopic resection of pineal region tumors via the transfrontal-transventricular-transforaminal approach is a safe and effective technique, particularly for lesions extending into the third ventricle.