Histopathological Features Research Articles

Oral Leishmaniasis in HIV-Positive and HIV-Negative Patients: A Comparative Analysis with Two New Case Reports.

This case report examines the clinical presentation, diagnosis, treatment, and outcomes of mucocutaneous leishmaniasis with primary oral involvement in HIV-positive and HIV-negative patients diagnosed in Brazil. We discuss the clinical manifestations, diagnostic methods, and therapeutic strategies, highlighting the clinical and histopathologic diagnostic features and distinct progression patterns based on HIV status. Our findings are compared with patterns observed in other countries, emphasizing the differences between the Americas and Europe, Asia, and Africa. In the Americas, particularly in Brazil, mucocutaneous leishmaniasis often presents with localized oral lesions, even in the presence of systemic immunosuppression, whereas in the Europe, Asia, and Africa, oral involvement is typically associated with visceral leishmaniasis in immunocompromised patients. These differences were due to variations in the parasite species involved. This comparison underscores the importance of regional and immunological factors in diagnosing and managing this neglected infectious disease.

The Analysis Study of Histopathologic Diagnosis of Gastroesophageal Reflux Disease: An Anatomic Pathology Comprehensive Systematic Review

Introduction : This systematic review explores the histopathologic features of GERD and its differential diagnoses, emphasizing the role of endoscopic and histologic assessments in clinical practice. Methods : A systematic review was conducted following PRISMA 2020 guidelines to evaluate the histopathologic features of GERD and its differential diagnoses. Results : From an initial pool of 6006 publications, eight studies were identified as directly relevant after a thorough screening process. The findings highlight the importance of biopsy sampling and histologic evaluation in differentiating GERD from other esophageal inflammatory conditions. Key diagnostic features included basal cell hyperplasia, elongation of lamina propria papillae, and dilatation of intercellular spaces, which were critical for distinguishing GERD from other conditions. Conclusion : This systematic review emphasizes the importance of histopathologic evaluation in the accurate diagnosis of GERD and its differential diagnoses. Understanding the distinct histopathologic features of GERD, as well as technical aspects of biopsy sampling, is essential for improving diagnostic accuracy and preventing progression to severe complications.

Plonmarlimab, a novel anti-GM-CSF blocking antibody, ameliorates disease progression in the pre-clinical model of macrophage activation syndrome.

We aimed to characterize and investigate the safety and efficacy of Plonmarlimab, a novel anti-granulocyte-macrophage colony-stimulating factor (anti-GM-CSF) neutralizing antibody, on the treatment of macrophage activation syndrome (MAS), a life-threatening systemic inflammatory disease, in pre-clinical models. The binding affinity was evaluated using Biacore. The neutralizing activity was measured through the blockade of ligand-receptor interaction, inhibition of STAT5 phosphorylation and suppression of TF-1 cell proliferation. The efficacy of Plonmarlimab was evaluated in a humanized MAS model, which was established by engrafting human umbilical cord blood (UCB) cells into NOG-EXL mice. Additionally, the safety profile of Plonmarlimab was investigated in cynomolgus monkeys. At the molecular level, Plonmarlimab showed sub-nanomolar binding affinity with human GM-CSF and effectively blocked the binding of GM-CSF to its receptor. At the cellular level, Plonmarlimab dose-dependently inhibited intracellular STAT5 phosphorylation and suppressed GM-CSF-induced TF-1 proliferation. In the UCB-engrafted NOG-EXL MAS mouse model, Plonmarlimab treatment significantly ameliorated disease progression, demonstrated by the improvements in body weight loss, anaemia and some histopathological features. Furthermore, Plonmarlimab was well tolerated up to 150 mg/kg weekly in monkeys with no reported adverse effects. Plonmarlimab is a highly potent GM-CSF blocking antibody and has demonstrated promising efficacy in a pre-clinical MAS model with a favourable safety profile, supporting its clinical development.

Supra-tentorial Ependymomas with ZFTA Fusion, YAP1 Fusion, and Astroblastomas, MN1-altered: Characteristic Imaging Features.

Supratentorial (ST) ependymoma subgroups are defined by two different fusions with different prognoses. Astroblastomas, MN1-altered, have ependymal-like histopathologic features and represent adifferential diagnosis in children. We hypothesized that ZFTA-fused ependymoma and YAP1-fused ependymoma on the one hand, and astroblastoma, MN1-altered, on the other hand, show different MRI characteristics. We retrospectively analyzed the preoperative imaging of 45patients with ST ependymoma or astroblastoma between January 2000 and September 2020, blinded to histomolecular grouping. Several characteristics, such as location, tumor volume, calcifications, solid/cystic component, and signal enhancement or diffusion were evaluated. We compared imaging characteristics according to their molecular subtype (ZFTA-fused, YAP1-fused, and astroblastoma, MN1-altered). Thirty-nine patients were classified as having an ependymoma, 35with aZFTA fusion and four with aYAP1 fusion, and six as having an astroblastoma, MN1-altered. YAP1-fused ependymomas were more likely to involve at least 3lobes than ZFTA-fused ependymomas. Astroblastomas were located in the frontal lobe in 100% of the tumors versus 49% of the ependymomas. Cerebral blood flow by arterial spin labeling was higher in astroblastomas than in ependymomas. There were no differences in the other characteristics between the molecular groups. All the tumors showed common features: intra-axial extra-ventricular tumors, very frequent contrast enhancement (39/43, 91%), acystic/necrotic component (41/45, 91%), restricted diffusion (32/36, 89%), calcifications (15/18, 83%), and peri-tumoral edema (38/44, 86%). The distinction between ST ependymoma subtypes and astroblastomas can be guided by several imaging features. These tumors share common imaging features that may help to differentiate ST ependymomas and astroblastomas from other pediatric ST tumors.

More severe parotid gland histopathology in paediatric-onset than in adult-onset Sjögren’s disease

ObjectivesThe aim of this study was to assess the histopathological features of the parotid glands in patients with paediatric-onset Sjögren’s disease (pedSjD) in comparison to patients with adult-onset Sjögren’s disease...

Palmoplantar psoriasis: A clinicopathological correlation in a tertiary care hospital.

Palmoplantar psoriasis is a clinical variant of psoriasis characterized by well-defined erythematous desquamating plaques on palms and soles, which may or may not include pustules. Hyperkeratotic lesions of palm and sole commonly include Psoriasis, Eczema and Tinea. These conditions often present with overlapping clinical and histopathological features requiring clinicohistopathological correlation for a conclusive diagnosis. The presence of munro's microabscess or spongiform pustule of kogoj differentiates psoriasis of palm and sole from other hyperkeratotic lesions of palm and sole. The objective of this study was to study the clinical and histopathological profile of palmoplantar psoriasis and correlate clinical diagnosis with histopathological diagnosis. A hospital-based, descriptive study was conducted from January 1, 2020, to December 31, 2020. Fifty-two patients were clinically diagnosed as palmoplantar psoriasis with or without involving other parts of body and routine histopathological evaluation was carried out as per standard protocols. Clinically diagnosed 52 cases of palmoplantar psoriasis showed varied histopathology with hyperkeratosis (100%), parakeratosis (100%), regular acanthosis (75%), Supra-papillary thinning (44.2%), spongiosis (65.4%), tortuous vessels in the papillary dermis (78.8%) and mixed inflammatory infiltrates (predominantly lymphocytic-100%), which were observed to be prominent findings in skin biopsies of our patients.Clinicopathological correlation was achieved in 88.5% of cases. This study shows clinically diagnosed palmoplantar psoriasis with histopathological features consistent with palmoplantar psoriasis in 88.5% cases. Thus, clinically inconclusive hyperkeratotic lesions with palmoplantar psoriasis can be diagnosed with histopathological correlation improving the therapeutic intervention.

Comprehensive Analysis of a Japanese Pedigree with Biallelic ACAGG Expansions in RFC1 Manifesting Motor Neuronopathy with Painful Muscle Cramps.

Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS) is an autosomal recessive multisystem neurologic disorder caused by biallelic intronic repeats in RFC1. Although the phenotype of CANVAS has been expanding via diagnostic case accumulation, there are scant pedigree analyses to reveal disease penetrance, intergenerational fluctuations in repeat length, or clinical phenomena (including heterozygous carriers). We identified biallelic RFC1 ACAGG expansions of 1000 ~ repeats in three affected siblings having sensorimotor neuronopathy with spinocerebellar atrophy initially presenting with painful muscle cramps and paroxysmal dry cough. They exhibit almost homogeneous clinical and histopathological features, indicating motor neuronopathy. Over 10years of follow-up, painful intractable muscle cramps ascended from legs to trunks and hands, followed by amyotrophy and subsequent leg pyramidal signs. The disease course combined with the electrophysical and imagery data suggest initial and prolonged hyperexcitability and the ensuing spinal motor neuron loss, which may progress from the lumbar to the rostral anterior horns and later expand to the corticospinal tract. Genetically, heterozygous ACAGG expansions of similar length were transmitted in unaffected family members of three successive generations, and some of them experienced muscle cramps. Leukocyte telomere length assays revealed comparatively shorter telomeres in affected individuals. This comprehensive pedigree analysis demonstrated a non-anticipating ACAGG transmission and high penetrance of manifestations with a biallelic state, especially motor neuronopathy in which muscle cramps serve as a prodromal and disease progress marker. CANVAS and RFC1 spectrum disorder should be considered when diagnosing lower dominant motor neuron disease, idiopathic muscle cramps, or neuromuscular hyperexcitability syndromes.

Accuracy of an Artificial Intelligence System for Interval Breast Cancer Detection at Screening Mammography.

Background Artificial intelligence (AI) systems can be used to identify interval breast cancers, although the localizations are not always accurate. Purpose To evaluate AI localizations of interval cancers (ICs) on screening mammograms by IC category and histopathologic characteristics. Materials and Methods A screening mammography data set (median patient age, 57 years [IQR, 52-64 years]) that had been assessed by two human readers from January 2011 to December 2018 was retrospectively analyzed using a commercial AI system. The AI outputs were lesion locations (heatmaps) and the highest per-lesion risk score (range, 0-100) assigned to each case. AI heatmaps were considered false positive (FP) if they occurred on normal screening mammograms or on IC screening mammograms (ie, in patients subsequently diagnosed with IC) but outside the cancer boundary. A panel of consultant radiology experts classified ICs as normal or benign (true negative [TN]), uncertain (minimal signs of malignancy [MS]), or suspicious (false negative [FN]). Several specificity and sensitivity thresholds were applied. Mann-Whitney U tests, Kruskal-Wallis tests, and χ2 tests were used to compare groups. Results A total of 2052 screening mammograms (514 ICs and 1548 normal mammograms) were included. The median AI risk score was 50 (IQR, 32-82) for TN ICs, 76 (IQR, 41-90) for ICs with MS, and 89 (IQR, 81-95) for FN ICs (P = .005). Higher median AI scores were observed for invasive tumors (62 [IQR, 39-88]) than for noninvasive tumors (33 [IQR, 20-55]; P < .01) and for high-grade (grade 2-3) tumors (62 [IQR, 40-87]) than for low-grade (grade 0-1) tumors (45 [IQR, 26-81]; P = .02). At the 96% specificity threshold, the AI algorithm flagged 121 of 514 (23.5%) ICs and correctly localized the IC in 93 of 121 (76.9%) cases, with 48 FP heatmaps on the mammograms for ICs (rate, 0.093 per case) and 74 FP heatmaps on normal mammograms (rate, 0.048 per case). The AI algorithm correctly localized a lower proportion of TN ICs (54 of 427; 12.6%) than ICs with MS (35 of 76; 46%) and FN ICs (four of eight; 50% [95% CI: 13, 88]; P < .001). The AI algorithm localized a higher proportion of node-positive than node-negative cancers (P = .03). However, no evidence of a difference by cancer type (P = .09), grade (P = .27), or hormone receptor status (P = .12) was found. At 89.8% specificity and 79% sensitivity thresholds, AI detection increased to 181 (35.2%) and 256 (49.8%) of the 514 ICs, respectively, with FP heatmaps on 158 (10.2%) and 307 (19.8%) of the 1548 normal mammograms. Conclusion Use of a standalone AI system improved early cancer detection by correctly identifying some cancers missed by two human readers, with no differences based on histopathologic features except for node-positive cancers. © RSNA, 2024 Supplemental material is available for this article.

Clinical and pathological characterization of Tebentafusp-associated skin toxicity – a cohort study with 33 patients.

BackgroundTebentafusp is a novel treatment for patients with metastatic uveal melanoma and often causes cutaneous side effects. ObjectivesThe aim of this study was to better characterize these heterogenous cutaneous side effects. MethodsThis prospective cohort study evaluated all patients from a tertiary hospital center who were treated with tebentafusp between January 2019 and June 2023 clinically and assessed skin biopsies histologically. ResultsIn total, 33 patients were analysed. Skin toxicity was observed in 78.8% of patients and was classified in five clinical categories: 1) symmetrical erythematous patches (83.8%), 2) hemorrhagic macules (11.8%), 3) urticarial lesions (7.4%), 4) bullous lesions (1.5%) and 5) skin (8.5%) and hair depigmentation (11.4%). Histopathologic features were focal lymphocytic interface dermatitis with epidermal infiltration of CD8-positive lymphocytes. Patients with skin reactions had a significantly longer median overall survival compared to patients without any cutaneous events (34 versus 4 months, p<0.001). LimitationMonocentric study with a limited number of patients. ConclusionTebentafusp frequently induced cutaneous reactions. Pathogenesis is likely due to binding of tebentafusp to stimulated melanocytes in the skin followed by infiltration and activation of lymphocytes. Development of treatment induced skin reactions may be associated with survival benefit.

Congenital Eruption Cyst: A Case Report with Histopathological Features

Congenital Eruption Cyst: A Case Report with Histopathological Features

Final Results of the ANDROCAN Study: Histopathological Characteristics and Biochemical Recurrence at 5 Years of Localized Prostate Cancer According to Preoperative Gonadal Status

Background and objectiveFailure rates after first-line treatment of localized prostate cancer (PCa) treatment remain high; therefore, it is essential to improve the selection and identification of at-risk patients to reduce mortality. The aim of the ANDROCAN study was to evaluate the biochemical recurrence (BCR) in patients with localized PCa treated by total prostatectomy at 5 yr after surgery, according to their presurgery gonadal status. MethodsA prospective cohort study was conducted including 1318 patients undergoing total prostatectomy for localized PCa with a 5-yr postoperative follow-up. Clinical and hormonal data (assays of total testosterone [TT], bioavailable testosterone [BT], dihydrotestosterone, estrone, and estradiol were performed by gas chromatography/mass spectrometry) as well as metabolic syndrome parameters were collected at baseline before surgery. Pathological data (predominant Gleason grade 4 and stage) were collected and cross-referenced centrally. Factors associated with BCR were assessed by a multivariate analysis, and BCR-free survival was assessed by a Kaplan-Meier analysis. Key findings and limitationsAmong the 1318 patients, 237 had BCR of PCa. Considering demographic characteristics, populations with and without BCR were similar. However, patients with BCR had cancers with a higher Gleason score (p = 0.0001) and higher prostate-specific antigen (PSA) values (p = 0.0005) at baseline. Gleason score, pT >3a, and PSA level at baseline were positively correlated with BCR (p < 0.0001, p < 0.0001, and p = 0.0048, respectively), while BT and TT levels were not associated with BCR. This study includes patients with varying clinical characteristics, such as cancer history and metabolic syndrome, introducing variability that makes it challenging to isolate the specific effects of gonadal status on BCR. Another limitation is the lack of evaluation of long-term BCR beyond 5 yr, potentially overlooking recurrences that occur between 5 and 15 yr after surgery. This could lead to an underestimation of the actual long-term recurrence rates. Conclusions and clinical implicationsOverall, PSA levels, high Gleason score, and pT >3a are associated with a greater likelihood of disease recurrence following initial treatment and could serve as important prognostic indicators for predicting the risk of BCR. In this prospective study, biochemical hypogonadism was not associated with a higher occurrence of BCR within 5 yr of prostatectomy. The biological gonadal status of preoperative patients could potentially be useful for therapeutic decisions but does not provide an indication for the oncological follow-up. Patient summaryFive-year follow up of patients after surgery showed that there is no association between hypogonadism (low levels of total testosterone and bioavailable testosterone) and cancer recurrence. However, cancer recurrence seems to be more associated with aggressiveness of cancer at the time of detection.

Outcomes of Differentiated Thyroid Cancer in Children and Adolescents at King Abdulaziz Medical City, Jeddah.

Objective Differentiated thyroid cancer (DTC) is rare in the pediatric population, with most data from the Western world. We aimed to describe the clinical presentation, treatment intervention, histopathological characteristics, complications, follow-up, and response to treatment in 17 patients with DTC at or below the age of 20 years. Interventions This was a retrospective cohort study at King Abdulaziz Medical City, Jeddah, Saudi Arabia. We included patients aged younger than 20 years with DTC. Total or near-total thyroidectomy was performed in 82% of the patients, central and/or lateral neck dissection in 35% of cases, and radioactive iodine (RAI) ablation in 76% of cases. Results The study included 17 patients (14 females), with a median age of 16 years at the time of diagnosis. Thyroid nodules were the main complaint in 88% of the patients. Thyroid ultrasonography was the main method for the initial evaluation. Papillary cancer was the most common type of tumor, and lymph node spread was found in 82% of the patients. Moreover, 40% of the patients exhibited excellent responses to therapy, with 35% showing indeterminate results. Only 23.5% of the patients developed hypocalcemia postoperatively. Conclusions Classical papillary thyroid carcinoma was the predominant histopathological type, and most patientsshowed excellent responses to therapy, followed by indeterminate in most of the cases. The most common presentation was a neck nodule, signifying the role of thorough physical neck examinations. Finally, recurrence occurred in a minority of patients. However, none of these patients died.

Development of a diagnostic support system for the fibrosis of nonalcoholic fatty liver disease using artificial intelligence and deep learning.

Liver fibrosis is a pathological condition characterized by the abnormal proliferation of liver tissue, subsequently able to progress to cirrhosis or possibly hepatocellular carcinoma. The development of artificial intelligence and deep learning have begun to play a significant role in fibrosis detection. This study aimed to develop SMART AI-PATHO, a fully automated assessment method combining quantification of histopathological architectural features, to analyze steatosis and fibrosis in nonalcoholic fatty liver disease (NAFLD) core biopsies and employ Metavir fibrosis staging as standard references and fat assessment grading measurement for comparison with the pathologist interpretations. There were 146 participants enrolled in our study. The correlation of Metavir scoring system interpretation between pathologists and SMART AI-PATHO was significantly correlated (Agreement = 68%, Kappa = 0.59, p-value <0.001), which subgroup analysis of significant fibrosis (Metavir score F2-F4) and nonsignificant fibrosis (Metavir score F0-F1) demonstrated substantial correlated results (agreement = 80%, kappa = 0.61, p-value <0.001), corresponding with the correlation of advanced fibrosis (Metavir score F3-F4) and nonadvanced fibrosis groups (Metavir score F0-F2), (agreement = 89%, kappa = 0.74, p-value <0.001). SMART AI-PATHO, the first pivotal artificially intelligent diagnostic tool for the color-based NAFLD hepatic tissue staging in Thailand, demonstrated satisfactory performance as a pathologist to provide liver fibrosis scoring and steatosis grading. In the future, developing AI algorithms and reliable testing on a larger scale may increase accuracy and contribute to telemedicine consultations for general pathologists in clinical practice.

Conjunctival keratoacanthoma: a clinical and histopathological case series

ObjectiveTo present a series of conjunctival keratoacanthomas and provide clinical, histopathological, immunohistochemical, and imaging results that characterize this rare entity. MethodsA retrospective chart review of records from 2005 to 2023 from the Florida Lions Ocular Pathology Laboratory was conducted. Nine patients with histologically proven conjunctival keratoacanthoma were identified. Data extracted includes demographics, clinical history, diagnostic testing, histopathological and immunohistochemical testing, treatment modalities, and recurrences. ResultsPatients’ mean age was 55.2 ± 21.1 years (range: 22–83). 77.8% (7/9) of patients were male. 55.6% (5/9) were Hispanic. 55.6% of lesions (5/9) were in right eyes. 55.6% of lesions (5/9) were on the temporal, bulbar conjunctiva. The lesions were rapidly growing, with mean onset time of 4.71 ± 3.30 weeks (range: 2–12). High-resolution anterior segment optical coherence tomography of three lesions revealed hyper-reflective, thickened epithelium with abrupt transition between normal and abnormal epithelium. Underlying disorganized subepithelial tissue was noted. However, the overlying abnormal epithelium caused considerable shadowing, which obscured subepithelial structures. Prominent, keratin-filled, cup-shaped lesions with faulty maturational sequencing that extend full thickness, variably pale cytoplasm, and foci of dyskeratosis and hyperkeratosis were present on all lesions’ histopathology.All lesions were surgically excised, but two demonstrated partial spontaneous resolution before surgery. Two patients were lost to follow-up; the remaining seven had no signs of recurrence at a of mean of 36.9 ± 45.4 months (range: 3 to 141 months) of follow-up. ConclusionsConjunctival keratoacanthomas are rare lesions of the ocular surface with distinct clinical, histopathologic, and diagnostic features.

Decreased expression of galectin-3 in the epidermis of psoriasis patients.

Conventional histopathological features of psoriasis and atopic dermatitis often overlap. We aimed to investigate Galectin-3 (Gal-3) expression in psoriatic skin lesions and its potential as an immunohistochemical marker for distinguishing between psoriasis and atopic dermatitis on a pathological basis. Based on immunohistochemical analysis, we assessed Gal-3 expression in formalin-fixed, paraffin-embedded tissue sections from 21 patients with psoriasis and 15 patients with atopic dermatitis. Quantitative analysis of expression intensity was performed using the average density (average optical density) method. We analysed the relationship between Gal-3 expression and clinical characteristics, as well as conventional histopathological features. Patients with psoriasis exhibited significantly decreased Gal-3 expression in the epidermis (0.11±0.05) compared to the atopic dermatitis group (0.36±0.15) and healthy controls (0.49±0.13) (p<0.0001). Reduction in Gal-3 expression in the psoriatic epidermis around areas of neutrophil aggregation was more pronounced than around areas of non-neutrophil aggregation (0.07±0.02 vs 0.16±0.05, p<0.01). In both psoriasis (r=-0.48, p<0.05) and atopic dermatitis groups (r=-0.70, p<0.01), Gal-3 expression negatively correlated with epidermal thickness. When epidermal thickness was matched between the two groups, the decrease in epidermal Gal-3 expression remained significant in the psoriasis group compared to the atopic dermatitis group (0.14±0.05 Vs 0.30±0.07, p<0.01). Patients with psoriasis show specific downregulation of epidermal Gal-3, correlating with epidermal thickness and neutrophil-related factors. Gal-3 may serve as an auxiliary discriminative marker between psoriasis and atopic dermatitis, potentially associated with keratinocyte proliferation and neutrophil function.

Identify characteristics of Vietnamese oral squamous cell carcinoma patients by machine learning on transcriptome and clinical-histopathological analysis

Background/purposeOral squamous cell carcinoma (OSCC) is notorious for its low survival rates, due to the advanced stage at which it is commonly diagnosed. To enhance early detection and improve prognostic assessments, our study harnesses the power of machine learning (ML) to dissect and interpret complex patterns within mRNA-sequencing (RNA-seq) data and clinical-histopathological features. Materials and methods206 retrospective Vietnamese OSCC formalin-fixed paraffin-embedded (FFPE) tumor samples, of which 101 were subjected to RNA-seq for classification based on gene expression. Then, learning models were built based on clinical-histopathological data to predict OSCC subtypes and propose potential biomarkers for the remaining 105 samples. Results2 distinct groups of OSCC with different clinical-histopathological characteristics and gene expression. Subgroup 1 was characterized by severe histopathologic features with immune response and apoptosis signatures while subgroup 2 was denoted by more clinical/pathological features, cell division and malignant signatures. XGBoost and SVM (Support Vector Machine) models showed the best performance in predicting subtype OSCC. The study also proposed 12 candidate genes as potential biomarkers for OSCC subtypes (6/group). ConclusionThe study identified characteristics of Vietnamese OSCC patients through a combination of mRNA sequencing and clinical-histopathological analysis. It contributes to the insight into the tumor microenvironment of OSCC and provides accurate ML models for biomarker prediction using clinical-histopathological features.

Risk factors, histopathological landscape, biomarkers, treatment patterns and survival of early-onset colorectal cancer: A narrative review.

Early-onset colorectal cancer (EOCRC) incidence has increased in most Western countries over the last decade, with Australia at the forefront. Recent literature has thus focused on characterizing EOCRC from later-onset colorectal cancer (LOCRC). Earlier exposure to modifiable risk factors resulting in gut dysbiosis has been linked with EOCRC development. EOCRCs have more aggressive histopathological features with somatic mutations resulting in pro-inflammatory tumor microenvironments. There is a tendency to treat EOCRCs with multimodal chemotherapeutic regimens and more extensive surgery than LOCRCs with conflicting postoperative outcomes and survival data. Current research is limited by a lack of Australasian studies, retrospective study designs, and heterogeneous definitions of EOCRC. Future research should address these and focus on investigating the role of immunotherapies, establishing minimally invasive diagnostic biomarkers and nomograms, and evaluating the survival and functional outcomes of EOCRC.

Clinical, Genetic, and Histopathological Characteristics of CRX-associated Retinal Dystrophies

PURPOSETo describe phenotypic, genotypic, and histopathological features of inherited retinal dystrophies associated with the CRX gene (CRX-RDs). DESIGNRetrospective multicenter cohort study including histopathology. SUBJECTSThirty-nine patients from 31 families with pathogenic variants in the CRX gene. METHODSClinical data of 152 visits were collected from medical records with a median follow-up time of 9.1 years (IQR, 3.3-15.3 years; range, 0.0-48.8 years). Histopathologic examination of the eye of a 17-year-old patient with advanced early-onset CRX-RD was performed. MAIN OUTCOME MEASURESVisual acuity, retinal imaging, electroretinography (ERG), genotype-phenotype correlation, and histopathological examination were evaluated. RESULTSThe age at onset ranged from birth to the 8th decade of life. Median visual acuity was 1.00 logMAR (IQR, 0.69-1.48 logMAR; range, 0.06-3.00 logMAR) at a mean age of 52.0 ± 19.9 years (range, 4.6-81.9 years). Sufficient imaging was available for 36 out of 39 patients (92.3%), and all showed degeneration of at least the macula. Out of these 36 patients, 22 (61.1%) had only macular dystrophy. Another 10 patients (27.8%) had additional degeneration beyond the vascular arcades, and 4 patients (11.1%) panretinal degeneration. Two patients (5.1%) had Leber congenital amaurosis (LCA). In total, 21 different disease-associated heterozygous CRX variants were identified (10 missense, 8 frameshift, 2 deletion, 1 deletion-insertion variants). Missense variants in the CRX homeodomain and two variants deleting all functional domains, thus causing haploinsufficiency, generally tended to cause milder late-onset phenotypes.Histopathologic examination of the eye of a 17-year-old patient with advanced early-onset retinal dystrophy due to a heterozygous deletion of exons 3 and 4 of the CRX gene revealed loss of laminar integrity and widespread photoreceptor degeneration especially in the central retina, with extensive loss of photoreceptor nuclei and outer segments. CONCLUSIONThis study illustrates the large clinical and genetic heterogenic spectrum of CRX-RDs, ranging from LCA to mild late-onset maculopathy resembling occult macular dystrophy. Haploinsufficiency and missense variants tended to be associated with milder phenotypes. Patients showed degeneration predominantly affecting the central retina on imaging. The histopathological findings also mirror these clinical findings and features similar to previously reported animal models of CRX-RDs.

Is it time to de-escalate axillary surgery in patients with ductal carcinoma in-situ undergoing mastectomy?

IntroductionAxillary surgery has been de-escalated in invasive breast carcinoma and may be omitted in certain age groups. Up to 10–20 % of patients with ductal carcinoma in-situ (DCIS) will have an element of invasion. Therefore, SLNB is indicated to rule out nodal metastasis. Our purpose was to identify the rate and possible risk factors for lymph node metastasis in DCIS, and to measure oncological outcome of positive SLNB in this group. MethodsA retrospective analysis was performed on 113 female patients with DCIS, who underwent mastectomy and SLNB. Their clinical and radiological features, as well as pre and post-operative histopathological characteristics were evaluated and data was reported over an average follow up period of 48 months. ResultDCIS was upgraded to invasive cancer in 11 patients out of 113 (9.7 %). Five patients had positive SLNB (4.4 %), one micro-metastasis (0.8 %) and four macro-metastasis (3.5 %) All the five underwent axillary lymph node dissection (ALND) and all additional nodes retrieved were negative. High nuclear grade, Her2 neu overexpression, and palpable mass showed higher odds of association with metastasis to sentinel nodes. However, due to the low event rate, the association did not reach statistical significance. Seven patients (6.2 %) developed lymphedema, 4 of which after SLNB only. No regional recurrence was reported among our study sample. ConclusionThis study confirms the very low rate of positive SLNB in patients with DCIS. It is time to de-escalate axillary surgery for patients with DCIS undergoing mastectomy and consider delayed SLNB for high risk group of patients.

Uncommon Histopathological Subtypes and Variants of Cervical Carcinoma Diagnosed at a Tertiary Care Centre: A Case Series.

Introduction Cervical cancer ranks among the top gynaecological cancers worldwide. It is linked to lower socioeconomic status and high human papillomavirus (HPV) prevalence. This is a series of six cervical carcinoma cases analysed from 2021 to 2023 at our tertiary care centre to identify rare subtypes of cervical carcinoma. We document rare subtypes, which includeglassy cell carcinoma, small cell neuroendocrine carcinoma, papillary squamous-transitional variant,basaloid squamous cell carcinoma and serous carcinoma of the uterine cervix. Immunohistochemistry (IHC) was helpful in confirmation of the subtypes and in diagnosing HPV-associated cases. Materials and methods This case series comprises six cases, including raresubtypes and variants of cervical carcinomahistopathologically diagnosed by the Department of Pathology, Sri Ramachandra Institute of Higher Education and Research, Chennai, India, between 2021 and 2023. The demographic profile and patient details were obtained from the hospital information system and archival case files after obtaining informed consent from the patients. The H&E and relevant IHC slides along with histopathology reports of the included cases were analysed and studied. Results This series includes six cases of rare subtypes of cervical carcinoma, comprising glassy cell carcinoma, small cell neuroendocrine carcinoma, papillary squamous-transitional variant, basaloid squamous cell carcinoma (SCC), and serous carcinoma. Each subtype displays distinct clinicopathological features, emphasizing the need for specific diagnostic and treatment approaches, which are crucial in improving patient survival. Conclusion Six rare subtypes and variants of cervical carcinoma have been discussed in this case series, after correlating with histopathology reportsand clinical and radiological findings. Understanding the histopathological characteristics of these rarer subtypes is essential for accurate diagnosis and timely intervention. This series highlights the importance of comprehensive screening strategies, early diagnosis and awareness of rarer subtypes and variants of cervical carcinoma among healthcare professionals. These factors can tailor therapeutic options and improve patient outcomes.