pathology

Susceptibility-weighted imaging (SWI) is based on a 3D high-spatial-resolution, velocity-corrected gradient-echo MRI sequence that uses magnitude and filtered-phase information to create images. It SWI uses tissue magnetic susceptibility differences to generate signal contrast that may arise from paramagnetic (hemosiderin), diamagnetic (minerals and calcifications) and ferromagnetic (metal) molecules. Distinguishing between calcification and blood products is possible through the filtered phase images, helping to visualize osteoblastic and osteolytic bone metastases or demonstrating calcifications and osteoid production in liposarcoma and osteosarcoma. When acquired in combination with the injection of an exogenous contrast agent, contrast-enhanced SWI (CE-SWI) can simultaneously detect the T2* susceptibility effect, T2 signal difference, contrast-induced T1 shortening, and out-of-phase fat and water chemical shift effect. Bone and soft tissue lesion SWI features have been described, including giant cell tumors in bone and synovial sarcomas in soft tissues. We expand on the appearance of benign soft-tissue lesions such as hemangioma, neurofibroma, pigmented villonodular synovitis, abscess, and hematoma. Most myxoid sarcomas demonstrate absent or just low-grade intra-tumoral hemorrhage at the baseline. CE-SWI shows superior differentiation between mature fibrotic T2* dark components and active enhancing T1 shortening components in desmoid fibromatosis. SWI has gained popularity in oncologic MSK imaging because of its sensitivity for displaying hemorrhage in soft tissue lesions, thereby helping to differentiate benign versus malignant soft tissue tumors. The ability to show the viable, enhancing portions of a soft tissue sarcoma separately from hemorrhagic/necrotic components also suggests its utility as a biomarker of tumor treatment response. It is essential to understand and appreciate the differences between spontaneous hemorrhage patterns in high-grade sarcomas and those occurring in the therapy-induced necrosis process in responding tumors. Ring-like hemosiderin SWI pattern is observed in successfully treated sarcomas. CE-SWI also demonstrates early promising results in separating the T2* blooming of healthy iron-loaded bone marrow from the T1-shortened enhancement in bone marrow that is displaced by the tumor.SWI and CE-SWI in MSK oncology learning objectives: SWI and CE-SWI can be used to identify calcifications on MRI.Certain SWI and CE-SWI patterns can correlate with tumor histologic type.CE-SWI can discriminate mature from immature components of desmoid tumors.CE-SWI patterns can help to assess treatment response in soft tissue sarcomas.Understanding CE-SWI patterns in post-surgical changes can also be useful in discriminating between residual and recurrent tumors with overlapping imaging features.

Primary melanocytic neoplasms of the central nervous system are rare entities and can present in different clinical forms with mild and non-specific symptoms (such as headache and tinnitus) to severe and limiting symptoms (focal deficits and intracranial hypertension), mimicking the most diverse pathologies. In addition to the peculiar changes in imaging tests, diagnosis is always a challenge given the multitude of possible differential diagnoses, including aseptic meningitis. Given this, we bring here the case of a 59-year-old patient who attended care due to headache and vertigo followed by involvement of the cranial nerves and spinal cord, corroborated by physical examination and imaging study suggesting diffuse involvement of the meninges, which was subsequently confirmed by anatomopathological examination as a primary melanocytic neoplasm of the central nervous system but ended up dying due to complications resulting from late diagnosis. The objective of this work is to raise awareness about the possibility of this pathology as a differential diagnosis in these cases where there are often frustrating clinical manifestations but with changes in imaging tests, to enable an early diagnosis and consequently the possibility of a better therapeutic result, in addition to a brief review of the propaedeutic findings of this pathology.

Background: Endometrial morular metaplasia, a clinical conundrum from a diagnostic and management angle given its rarity and low oncogenic potential, has been linked to endometrial hyperplasia and carcinoma. Case report: A 77-year-old woman with no significant past medical history, was found to have an asymptomatic thickened endometrium on pelvic imaging, after presenting with lower abdominal pain, 3yrs ago. Diagnostic hysteroscopy identified an endometrial polyp within a pyometra. Histopathology showed focal complex endometrial hyperplasia without atypia with superimposed morular metaplasia(EMM) with a negative microbiology assay.Following conservative management with multidisciplinary team(MDT) overview, as-per patient choice with 6-monthly follow-up hysteroscopy, endometrial biopsies and a short use of the Mirena® Intrauterine system (discontinued following poor tolerance), histopathology shows resolved hyperplasia with persistent EMM. Due to persistent disease, a hysterectomy is under consideration.Discussion: Current evidence suggests that a sub-type of EMM, a likely histological manifestation of beta-catenin (CTNNB1) gene mutation: could be a precursor of endometrial hyperplasia and low-grade endometrioid-endometrial carcinoma sub-type. Though low-grade in nature, the increased recurrence risk raises significant concerns.Prognostication following gene mutation identification can help with management options which include conservative, hormonal therapy with adjunct repeat endometrial sampling: or hysterectomy. The optimal frequency of endometrial sampling when uterine-sparing, is unclear, leading to a management conundrum, whilst persistent disease may require a hysterectomy.Conclusion: Management of endometrial morular metaplasia can be difficult but must reflect the woman’s choice with a MDT-overview. Immuno-histochemical tools utilizing new molecular biological advances, can simplify the diagnostic and prognostication processes, aiding clinical management.

Background: Maternal splenic cyst during pregnancy appears to be a rare pathology whose treatment is not codified. The most feared complication is rupture during pregnancy. It occurs in 60% of cases in the third trimester of pregnancy, leading to significant maternal-fetal morbidity and mortality. Case report: We describe the successful management of a 24-year-old patient, G1P0, with a history of a recurrent splenic cyst. She presented with a giant splenic cyst measuring 28 cm in diameter at 30 weeks of amenorrhea. A cesarean section was performed at 37 weeks gestation. A splenectomy was performed on day 21 postpartum.Conclusion: The incidence of splenic cysts is extremely rare during pregnancy. The diagnosis must be made as early as possible to undertake appropriate treatment before the appearance of maternal-fetal complications.

We report a rare case of 62-year-old South Asian women who visited the Molecular Pathology and Genomics Department for hereditary germline cancer genetic testing after being diagnosed with oesophageal cancer, reported as invasive keratinizing squamous cell carcinoma metastasized to the lymph nodes. Her personal history revealed that she was diagnosed with triple-negative breast cancer five years before oesophageal cancer. Germline cancer testing showed pathogenic variants in BRCA1 gene c.68_69delAG, which proved it a hereditary breast and ovarian cancer syndrome. She was started on PARP inhibitors but developed some secondary respiratory failure and succumbed to death. Less than 10 cases have been reported in the literature of the association of germline BRCA1 and Squamous cell Carcinoma – the esophagus. The article focuses on the probable pathogenesis of BRCA1 mutation with non-classic malignancies and the response of Poly adenosine diphosphate ribose polymerase inhibitors (PARP) inhibitors in such a scenario. We report an unusual manifestation of the BRCA1 gene with second primary oesophageal squamous cell cancer occurring five years later to triple-negative breast cancer.

Purpose: This study aimed to determine the relevance of first- and high-order radiomic features derived from Diffusion-Weighted Imaging (DWI) and Apparent Diffusion Coefficient (ADC) maps for predicting treatment response in patients with Undifferentiated Pleomorphic Sarcoma (UPS).Methods: This retrospective study included 33 extremity UPS patients with pre-surgical DWI/ADC and surgical resection. Manual volumetric tumor segmentation was performed on DWI/ADC maps acquired at Baseline (BL), Post-Chemotherapy (PC), and Post-Radiation Therapy (PRT). The percentage of pathology-assessed treatment effect (PATE) in surgical specimens categorized patients into responders (R; PATE ≥ 90%; 16 patients), partial-responders (PR; 89% - 31% PATE; 10 patients), and non-responders (NR; PATE ≤ 30%; 7 patients). 107 radiomic features were extracted from BL, PC, and PRT ADC maps. Statistical analyses compared R vs. PR/NR.Results: Pseudo-progression at PC and universal stability at PRT were observed in R and PR/NR based on RECIST, WHO, and volumetric assessments. At PRT, responders displayed a 35% increase in ADC mean (p = 0.0034), a 136% decrease in skewness (p = 0.0001), and a 363% increase in the 90th percentile proportion (p = 0.0009). Comparing R vs. PR/NR at BL, statistically significant differences were observed in glrlm_highgraylevelrunemphasis (p = 0.0081), glrlm_shortrunhighgraylevelemphasis (p = 0.0138), gldm_highgraylevelemphasis (p = 0.0138), glcm_sumaverage (p = 0.0164), glcm_jointaverage (p = 0.0164), and glcm_autocorrelation (p = 0.0193). At PC, firstorder_meanabsolutedeviation (p = 0.0078), firstorder_interquartilerange (p = 0.0109), firstorder_variance (p = 0.0109),    and firstorder_robustmeanabsolutedeviation (p = 0.0151) provided statistically significant differences.Conclusion: Observing a high post-therapeutic ADC mean, low skewness, and high 90th percentile proportion with respect to baseline is predictive of successfully treated UPS patients presenting > 90% PATE. Highly significant higher-order radiomic results include glrlm-highgraylevelrunemphasis (BL) and first-order-mean absolute deviation (PC).

Treatment for HIV-associated neurocognitive disorders (HAND) remains elusive. 7,8-dihydroxyflavone (DHF), an analog of brain-derived neurotrophic factor (BDNF) and a high-affinity TrkB agonist, has been proposed as a viable therapeutic alternative to BDNF in crossing the Blood-Brain Barrier (BBB) and promoting growth, differentiation, maintenance, and survival of neurons. Here, we expand on our previous study investigating the therapeutic role of DHF on the cortical and hippocampal brain regions of the Tg26 mice, an animal model of HAND. We detected increased immunoreactivity for ion channels (SUR1, TRPM4) and the water channel aquaporin-4 (AQP4), suggesting an ionic and osmotic imbalance in the brains of Tg26 mice. Tg26 mice also exhibited loss of synaptic stability (SYN, SYP) and nicotinamide metabolism (NAMPT, SIRT1) that were associated with astrogliosis. Furthermore, Tg26 mice demonstrated increased iNOS and reduced HO-1/NRF2 expressions, implicating increased ER and oxidative stress. DHF treatment in Tg26 mice reversed these pathological changes. These data suggest crosstalk among TrkB, Akt, and related transcription factors (NF-κB, STAT3, and NRF2) as an underlying mechanism of Tg26-associated pathology in the brain. Finally, taken together with our prior study, these results further highlight a therapeutic role of DHF in promoting neuroprotection in HAND that may be applied in conjunction with current antiviral therapies.

The aim of this work is to verify the pharmaceutical form in the galenic field of oral Budesonide compounded used in Crohn’s disease: capsules delay release or oral suspension. In particular ways the kinds of excipients or bases-vehicle used in the galenic pharmacy practice. The therapeutic need for Crohn’s disease requires a release of the API in delayed-release DR. The Budesonide molecule shows low systemic impacts due to its hepatic metabolism vs. a topical effect useful in this pathology. In this work, the oral pharmaceutical forms are analyzed: modified-release capsules and oral suspension with specific advantages for each one. Some formulations provided by various pharmacies are reported in this work as well as new technology like the 3D-PRINTING systems for colonic targeting tablets.

Many studies from the early 20th century on the significance of the pores of Kohn were assessed based on the pathogenesis and pathology of pneumococci pneumonia occurring in man. The pneumococci were carried in the edema fluid directly from alveolus to alveolus through the pores of Kohn and from bronchiole to bronchiole as a result of repeated aspirations, aided by breathing, coughing, and gravity. With the emerging minimally invasive and non-invasive techniques experimentations and the current medications; tackling exacerbations and improving the pulmonary function in various lung diseases remains a dilemma for clinicians and researchers. In this article, we aim to review specifically the pores of Kohn as this is the portal for the spread of infection but also lung recruitment during breathing.

Background: The study of new neuron formation in the adult brain has sparked controversy and ignited interest among scientists in recent times, these include its occurrence and location in the adult human brain, functional significance, variation in study methods, translation from animal model to human, and ethical challenges involving neural stem cell research. Aim: To provide a comprehensive understanding of adult neurogenesis, functional significance, and challenges and explore the latest advances in the study of adult neurogenesis. Methodology: An extensive and systematic search of electronic databases (Medline, Scopus, Web of Science) was conducted using keywords related to adult neurogenesis and techniques involved in its study. Results: The mechanism of adult neurogenesis was found to occur in specific brain regions such as the subgranular zone of the dentate gyrus and subventricular zone of the lateral ventricle. Adult neurogenesis is vital neural plasticity, providing a potential mechanism for the brain to adapt and reorganize in response to environmental cues and experiences. Cutting-edge research and sophisticated imaging techniques, such as two-photon microscopy, MRI, optogenetic, and stem-cell-based therapies have provided deeper insight into the study of adult neurogenesis. Conclusion: The study of neurogenesis is important for understanding nervous system development, physiology, pathology, and exploring neuroplasticity. Its advancement is challenged by some ethical concerns regarding embryonic, pluripotent stem cells, and the need for safe, and noninvasive study methods. Although recent breakthroughs in neuroimaging, microscopic techniques, and genetic tools are aiding real-time study of adult neurogenesis.

Background: Acral Fibromyxoma (AFM) is a rare benign soft tissue tumour which is described as a fibromatous and myxoid tumour of skin and soft tissue. Case details: A 40-year-old  male presented to the Dermatology outpatient department with swelling over the wrist of one year duration. The swelling was associated with mild pain, and it gradually increased in size to reach its present size. Cutaneous examination revealed a 2x2 cm mobile, cystic to firm, non-tender swelling over the dorsum of the right wrist. Based on its location and clinical features, it was provisionally diagnosed as a ganglion cyst  and excision biopsy was done. Histology showed stellate-shaped cells in a myxoid background with round to oval nuclei having a small, inconspicuous nucleolus. Acral fibromyxoma presents a distinct histopathology including a myxoid stroma and spindle-shaped cells, which are essential for accurate diagnosis and management.