Accelerated chronic lymphocytic leukemia/small lymphocytic lymphoma (A-CLL/SLL) is a histologically aggressive subtype of CLL/SLL that lies in between conventional CLL/SLL (C-CLL/SLL) and Richter transformation (RT) on the biological spectrum. Although the histologic criteria for A-CLL/SLL were defined 14 years ago, the clinical and genetic characteristics and survival outcomes of these patients have yet to be studied in the era of novel therapies. We retrospectively analyzed the clinicopathologic, genetic, and survival characteristics of 34 patients with confirmed tissue diagnosis of A-CLL/SLL and compared them with 120 patients with C-CLL/SLL. Patients with A-CLL/SLL had significantly higher frequencies of B-symptoms, anemia and thrombocytopenia, splenomegaly, higher LDH, and more advanced Rai stages. A-CLL/SLL showed a significantly higher frequency of TP53 mutations (55.0% vs. 11.5%;p < 0.0001) and deletions (38.2% vs. 8.3%;p < 0.0001), lower isolated del(13q) (5.8% vs. 27.5%;p < 0.0001), and increased incidence of RT (11.76% vs. 0.83%;p = 0.0025). The overall survival of patients with A-CLL/SLL was significantly lower than C-CLL/SLL (median survival: 6.17 years vs. not reached; 2 and 5-year survival rates: 75.5% vs. 94.7% and 53.3% vs. 93.7%, respectively; p < 0.0001); however, novel agents have improved the outcomes dramatically compared to the previously published data in the pre-BTKi era. Our results support the categorization of A-CLL/SLL as a distinct biologically aggressive subtype of CLL/SLL and highlight the need to revise the diagnostic criteria utilizing a multifaceted approach that integrates the overall pathobiological profile of the disease, in addition to the histology.

Pituitary neuroendocrine tumors (PitNET) represent the vast majority of sellar masses. Some behave aggressively, growing rapidly and invading surrounding tissues, with high rates of recurrence and resistance to therapy. Our aim was to establish patterns of genomic, transcriptomic and methylomic evolution throughout time in primary and recurrent tumors from the same patient. Therefore, we performed transcriptome- and exome-sequencing and methylome microarrays of aggressive, primary, and recurrent PitNET from the same patient. Primary and recurrent tumors showed a similar exome profile, potentially indicating a stable genome over time. In contrast, the transcriptome of primary and recurrent PitNET was dissimilar. Gonadotroph, silent corticotroph, as well as metastatic corticotroph and a somatotroph PitNET expressed genes related to fatty acid biosynthesis and metabolism, phosphatidylinositol signaling, glycerophospholipid and phospholipase D signaling, respectively. Diacylglycerol kinase gamma (DGKG), a key enzyme in glycerophospholipid metabolism and phosphatidylinositol signaling pathways, was differentially expressed between primary and recurrent PitNET. These alterations did not seem to be regulated by DNA methylation, but rather by several transcription factors. Molecular docking showed that dasatinib, a small molecule tyrosine kinase inhibitor used in the treatment of chronic lymphocytic and acute lymphoblastic leukemia, could target DGKG. Dasatinib induced apoptosis and decreased proliferation in GH3 cells. Our data indicate that pituitary tumorigenesis could be driven by transcriptomically heterogeneous clones, and we describe alternative pharmacological therapies for aggressive and recurrent PitNET.

OBJECTIVE: Although the potential association between autoimmune thyroiditis and papillary thyroid cancer (PTC) has been acknowledged, whether the clinicopathological features of PTC will be affected by thyroid autoantibodies remains unknown.
METHODS: We conducted a case-control study to investigate the association of thyroid autoantibodies with clinicopathological characteristics of PTC in 15,305 patients (including 11,465 females and 3,840 males) from 3 medical centers in the central province of China. Logistic regression and restricted cubic spline models were performed to analyze the association of thyroid autoantibodies with clinicopathological features of PTC.
RESULTS: In total, out of the 15,305 patients enrolled in this study, 10,087 (65.9%) had negative thyroid autoantibodies, while 5,218(34.1%) tested positive thyroid autoantibodies. Among these individuals, 1,530(10.0%) showed positivity for TPOAb only, 1,247(8.2%) for TGAb only and a further 2,441(15.9%) exhibited dual positivity for both TPOAb and TGAb combined. Thyroid autoantibodies level demonstrated significant correlations with certain aggressive features in PTC. Specifically, TGAb level displayed a direct correlation to an increased likelihood of multifocality, bilateral tumor, extrathyroidal extension, lymph node metastasis, as well as more than five affected lymph nodes. However, TPOAb level exhibited an inverse association with the risk associated with extrathyroidal extension, lymph node metastasis, and more than five affected lymph nodes.
CONCLUSIONS: Elevated level of TGAb were positively correlated with the risk of aggressive features in PTC, while high level of TPOAb were inversely associated with the risk of extrathyroidal extension and lymph node metastasis.

BACKGROUND: This research aimed to identify the clinical profile and risk factors of retinopathy of prematurity (ROP) among \"at-risk\" newborns treated at a sick newborn care unit (SNCU) located at high altitude in North India, with the intention of contributing to formulate regional and national ROP screening guidelines.
METHODS: In a prospective observational study from 2021 to 2022, outborn and inborn babies eligible for ROP screening were screened.
RESULTS: Total 39/122 screened neonates had laser for Type 1 ROP, and 22/39 (56.4%) had aggressive ROP (AROP). The average birth weight (BW) was 1803.87 g, and the average gestational age was 34 weeks. Respiratory distress, bronchopulmonary dysplasia, sepsis, and apnea were present in 57.3%, 13%, 52.5%, and 25.4%, respectively. Sight-threatening ROP was present in 50% below 28+6 weeks, 27% between 29 and 30+6 weeks, 52% between 31 and 33+6 weeks, and 15% with gestation >34 weeks. Two babies with Type 1 ROP weighed >2 kg and one had AROP. Upon regression analysis, BW <1500 g, gestation <32 weeks, oxygen >48 h, clinical sepsis, total SNCU stay >14 days, continuous positive airway pressure support with oxygen >50%, and >10 days to achieve full feeds were associated with severe ROP. Caffeine to treat apnea and kangaroo mother care reduced ROP. None had short-term unfavorable outcome.
CONCLUSIONS: With similar infrastructure and work force shortage in most SNCUs, these findings can be generalized. The burden of Type 1 and AROP is increasing, as seen in higher gestation and BWs. This needs revision of ROP screening criteria at local and national level. It is crucial to emphasize on the importance of pediatrician and ophthalmologist collaboration, early ROP screening, diagnosis, and treatment to stop disease progression to severe ROP.

This case report explores a rare and aggressive Malignant Peripheral Nerve Sheath Tumor (MPNST) in a 7-year-old child affecting nasal sinuses, maxilla, and orbit, an exceptionally uncommon pediatric manifestation unrelated to Neurofibromatosis 1. The child presented with alarming symptoms-nasal obstruction, snoring, epistaxis, and difficulty swallowing-underscoring the case\'s urgency. Non-contrast computed tomography revealed an extensive mass infiltrating nasopharynx, nasal cavity, maxillary sinus, ethmoid sinuses, and orbit, causing destructive consequences. Histopathology confirmed a high-grade MPNST, marked by rapid growth and early metastasis, highlighting management challenges. The rarity of pediatric MPNST in the nasal cavity is discussed, emphasizing the need for a broad differential diagnosis. Treatment involves surgical resection and adjuvant chemoradiation with a grim prognosis due to diagnostic complexities and morphological mimicry in young patients.

Metaplastic breast cancer represents a very rare and histopathologically diverse subtype of breast cancer. It shows neoplastic epithelial differentiation into squamous cells and/or mesenchymal-like components, resulting in its aggressive behavior and poor prognosis compared to other types of breast cancer. Here, we describe the case of a 43-year-old woman diagnosed with metaplastic carcinoma of the breast who presented like any other case of breast lump in the right breast for six months. The tumor had a large size with an ulcerative lesion of the breast. Ultrasound showed heterogeneous echogenicity and lymph node involvement. Surgical resection with axillary lymph node dissection was done. The microscopic examination after tissue processing showed highly pleomorphic tumor cells along with chondromyxoid stroma and osseous differentiation, suggestive of metaplastic breast cancer which was triple-negative for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 on immunohistochemistry. The axillary lymph nodes identified were negative for tumor cells. The rarity and aggressive nature of this cancer pose diagnostic challenges and highlight the importance of multidisciplinary approaches for effective management.

Some patients with autism and severe intellectual disability may experience uncontrolled aggression, causing serious injury or harm to others, and the therapeutic ineffectiveness of traditional pharmacological and behavioral treatment may aggravate symptoms. Deep brain stimulation (DBS) has been tested in patients with little evidence in children and adolescents. Therefore, we analyzed the efficacy and safety of DBS in refractory aggression in pediatric subjects with autism (ASD) and severe intelligence deficit (ID).Methods A meta-analytic review of Web of Science (WOS) and Scopus articles, following Prisma criteria. A total of 555 articles were identified, but after applying the inclusion criteria, only 18 were analyzed. The review of the registries and the extraction of information was performed by 2 independent groups, to reduce the evaluator\'s bias. For the description of the results, pediatric patients with ASD or ID present in each registry, with an application of specialized scales (Overt aggression scale, OAS, and THE modified version of the OAS, MOAS) pre and post-DBS, with a clinical follow-up of at least 12 months, were considered valid. Clinical improvement was calculated using tests of aggressiveness. In each registry with available data and then pooling the means of all patients in the OAS and MOAS, the effect size of DBS (overall and per study) was estimated. Finally, the adapted NOS scale was applied to rate the studies\' quality and level of bias.Results In the studies analyzed, 65/100 were pediatric patients, with a mean age of 16.8 years. Most of the studies were conducted in South America and Europe. In all teams, aggressive behavior was intractable, but only 9 groups (53/65) applied specialized scales to measure aggressiveness, and of these, only 51 subjects had a follow-up of at least 12 months. Thus, in 48/51 a clinical improvement of patients was estimated (94.2%), with a considerable overall effect size (OAS: d = 4.32; MOAS: d = 1.46). However, adverse effects and complications were found in 13/65 subjects undergoing DBS. The brain target with the most evidence and the fewest side effects was the posteromedial hypothalamic nuclei (pHypN). Finally, applying the adapted NOS scale, quality, and bias, only 9 studies show the best indicators.Conclusion An optimal level of efficacy was found in only half of the publications. This is mainly due to design errors and irrelevant information in the reports. We believe that DBS in intractable aggressiveness in children and adolescents with ASD and severe ID can be safe and effective if working groups apply rigorous criteria for patient selection, interdisciplinary assessments, objective scales for aggressiveness, and known surgical targets.

Grade C molar-incisor pattern periodontitis (C-MIP) is a disease that affects specific teeth with an early onset and aggressive progression. It occurs in systemically healthy patients, mostly African descendants, at an early age, with familial involvement, minimal biofilm accumulation, and minor inflammation. Severe and rapidly progressive bone loss is observed around the first molars and incisors. This clinical condition has been usually diagnosed in children and young adults with permanent dentition under 30 years of age. However, this disease can also affect the primary dentition, which is not as frequently discussed in the literature. Radiographic records have shown that most patients diagnosed in the permanent dentition already presented disease signs in the primary dentition. A hyperresponsive immunological profile is observed in local (gingival crevicular fluid-GCF) and systemic environments. Siblings have also displayed a heightened inflammatory profile even without clinical signs of disease. A. actinomycetemcomitans has been classified as a key pathogen in C-MIP in both dentitions. Scaling and root planning associated with systemic antibiotics is the current gold standard to treat C-MIP, leading to GCF biomarker reduction, some systemic inflammatory response modulation and microbiome profile changes to a healthy-site profile. Further studies should focus on other possible disease-contributing risk factors.

Osteosarcoma is a highly aggressive bone tumor primarily affecting children and adolescents. Despite advancements in treatment modalities, the prognosis for osteosarcoma patients remains poor, emphasizing the need for a deeper understanding of its underlying mechanisms. In recent years, the concept of cancer stem cells (CSCs) has emerged as a crucial factor in tumor initiation, progression, and therapy resistance. These specialized subpopulations of cells possess self-renewal capacity, tumorigenic potential, and contribute to tumor heterogeneity. Sox9, a transcription factor known for its critical role in embryonic development and tissue homeostasis, has been implicated in various malignancies, including osteosarcoma. This review aims to summarize the current knowledge regarding the role of Sox9 in CSCs in osteosarcoma and its potential implications as a prognosis and therapeutic target.

This report details a rare case of squamous cell carcinoma (SCC) in the stomach, a condition accounting for only a fraction of gastric carcinomas. A 46-year-old male patient with dysphagia, abdominal pain, and haematemesis was diagnosed with primary gastric SCC displaying aggressive metastasis, an exceptionally low-incidence condition affecting mainly males in their sixth decade of life. Primary gastric SCC, though clinically similar to adenocarcinoma, involves a bleaker prognosis, lacking standardized treatment protocols. Histopathology and imaging confirmed the diagnosis, highlighting the challenges in managing advanced cases. Palliative chemotherapy showed partial remission but led to severe neuropathy. The case underscores the urgent need for research to understand the pathogenesis, effective management, and therapeutic targets for primary gastric SCC, emphasizing its scarcity and poor prognosis in medical literature. Increased clinical awareness and ongoing research are crucial for improving outcomes in such rare presentations.