Clinicopathological Correlation Research Articles

Extranodal Rosai-Dorfman Disease of Breast Mimicker of Breast Malignancy

AbstractRosai-Dorfman-Destombes (RDD) disease is also known as sinus histiocytosis with massive lymphadenopathy. It is an uncommon heterogeneous disease of children and young adults. Most of the patients with RDD generally present with painless lymphadenopathy, while extranodal and multisystem manifestation of the disease is unusual. The diagnosis is based on the imaging with clinicopathological correlation. Flourine-18 fluorodeoxyglucose positron emission tomography/computed tomography is useful for the initial staging of the RDD lesions, which have similar appearance and avidity like intermediate and high-grade lymphomas. Here, we present the case of a 55-year-old female presented with left breast mass that turned out to be the extranodal Rosai-Dorfman disease.

Clinicopathological Correlation of Sinonasal Masses in North-East Indian Population in a Tertiary Care Hospital

Clinicopathological Correlation of Sinonasal Masses in North-East Indian Population in a Tertiary Care Hospital

Molecular Profiling of High-Grade B-Cell Non-Hodgkin Lymphomas and Its Clinicopathologic Correlation in an Indian Tertiary Cancer Care Center

Abstract Introduction Double-expressor and double-hit lymphomas (DHL) are known to be more aggressive and have poor outcomes with standard chemotherapy regimens. Objectives To assess the incidence of DHL and triple-hit lymphomas (THL) and correlate them with clinicopathologic parameters. Materials and Methods Patients who were diagnosed with high-grade lymphomas from April 2021 to September 2022 were prospectively followed up, and details comprising clinical and pathological parameters, including the immunohistochemistry expression status and gene rearrangements of MYC, BCL2, and BCL6, were recorded. Results The incidence of DHL and THL in our study was 16.43%. The separate incidence of the DHL-BCL2, DHL-BCL6, and THL groups was 16.43, 13.69, and 2.73%, respectively. The germinal center B cell subtype of histology was predominantly seen in DHLs. MYC, BCL2, and BCL6 expressions do not correlate well with translocations of these genes. Conclusion Double protein expression cannot be used for screening to decide which patients should undergo fluorescence in situ hybridization, as this would result in missing 4.5% of DHLs.

UBA2 as a Prognostic Biomarker and Potential Therapeutic Target in Glioma.

Gliomas are characterized by aggressive behavior, leading to severe disability and high mortality. Ubiquitin-like modifier activating enzyme 2 (UBA2) is a subunit of the E1-activating enzyme involved in the SUMOylation (SUMO, small ubiquitin-related modifier) of numerous proteins. Although the abnormality of UBA2 is linked to the progression of various tumor types, the role of UBA2 in glioma is still unknown. A bioinformatic analysis using several public databases was conducted to examine the expression level, clinicopathological correlations, and prognostic significance of UBA2 in glioma. The correlation between UBA2 expression and drug sensitivity in cancers was also explored. Multiple cellular experiments were conducted to validate the role of UBA2 in glioma. Analysis of multiple databases and cellular experiments revealed that UBA2 was overexpressed in glioma tissues and cell lines, respectively. UBA2 expression in gliomas correlated with World Health Organization (WHO) grade, IDH gene status, 1p19q deletion, histological type, and immune cell infiltration in glioma. UBA2 expression in carcinomas also correlated with drug sensitivity. Kaplan-Meier analysis revealed that high expression of UBA2 predicted poorer survival in glioma patients. A nomogram model containing UBA2 expression was constructed for clinical practice. Knockdown of UBA2 was observed to suppress glioma cell progression and sensitize glioma cells to irradiation in vitro. Overall, this research showed that UBA2 might be involved not only in the development of glioma but also in the regulation of immunity, drug sensitivity, and radiosensitivity. Therefore, UBA2 may be a potential target for therapy and a candidate biomarker for glioma diagnosis and prognosis.

High expression of NOTCH2 in gastric adenocarcinoma: A novel early diagnostic target.

NOTCH2 is overexpressed in gastric cancer (GC), and its enhanced activity is significantly correlated with worse tumor characteristics. We aim to analyze the clinicopathologic correlation between NOTCH2 and the molecular typing of GC by immunohistochemistry and by transcriptional sequencing. In this immunohistochemical study, we detected NOTCH2, EBER, P53, HER2, MLH1, MSH2, PMS2, and MSH6 and evaluated the association of NOTCH2 with clinical and histopathological features in a large single-institutional series of gastric adenocarcinomas (n=488). The correlation was also investigated between immunohistochemical results and survival outcomes. High NOTCH2 expression (2+/3+) was found in 139/488 (27.5%) samples analyzed. NOTCH2 expression was correlated with early stage T1 (P<0.0001), GC in the fundus (P=0.0364), and positive P53 status (P=0.0019). We did not find an association between NOTCH2 and HER2, microsatellite instability, EBER, and overall survival. Through RNA sequencing, it was revealed that NOTCH2 plays an important biological function in the pathogenesis and development of GC. Our findings suggested that NOTCH2 may be a potential diagnostic target for GC due to the fact that its high expression is closely associated with the early stages of cancer.

Clinicopathological correlation of patients with lupus nephritis: Data from a tertiary center in Saudi Arabia.

Systemic lupus erythematosus mainly affects young women, and approximately half of systemic lupus erythematosus patients develop lupus nephritis (LN). However, data on the types and remission rates of LN in Saudi Arabia are limited. Therefore, we aimed to highlight the LN remission rates in our population. A retrospective record review was conducted between January 2007 and December 2020 in a tertiary center in the western region of Saudi Arabia to determine the remission rates among patients with biopsy-proven LN who met the EULAR\ACR 2019 classification criteria. We identified 59 patients with biopsy-proven LN, mostly in young women. The common histopathological pattern was Class IV LN in 26 patients (44%). Three induction protocols were identified, along with systemic steroids: the high-dose cyclophosphamide protocol in 21 patients (35.6%), low-dose protocol in 4 patients (6.8%), and mycophenolate mofetil (MMF) in 41 patients (69.5%). Partial response, defined as the reduction of the 24-hour proteinuria by 25% at 3 months and 50% at 6 months, was achieved in 18 patients (33.3%) at 3 months and decreased to 13 patients (24.1%) at 6 months. Complete clinical response, defined as 24-hour urinary protein between 500 and 700 mg at 12 months, was achieved in 44 patients (81.5%). Complete remission was higher among patients with Class IV LN (64.4%). The achievement of partial clinical response at 3 months was significantly lower among patients with hypertension (P = .041). This study presented the LN remission rates in a single center in Saudi Arabia. Similar to previous studies, Class IV LN were the most common histopathological finding in this study. Complete remission at 12 months was achieved in 44 (81%) patients. Delayed remission is associated with hypertension at the time of LN diagnosis.

Cutaneous Vascular Anomalies: A Cross-Sectional Study in a Tertiary Care Hospital

Background: Vascular anomalies are a group of disorders that are divided into two categories: tumors and malformations. Given the vast diversity of clinical presentations with overlapping signs and symptoms, diagnosis can be difficult. Objective: We conducted a cross-sectional study to evaluate the common cutaneous vascular anomalies encountered in our outpatient department. Materials and Methods: A total of 28 patients suspected to be having cutaneous vascular anomalies were screened and subjected to biopsy. The diagnosis was based on clinicopathological correlation. Results: In our study, pyogenic granuloma was the most common vascular anomaly seen in 25% of patients; majority of these patients gave a history of trauma and spontaneous bleeding. It was followed by angiokeratoma (17.8%), infantile hemangioma, port-wine stain, and verrucous hemangioma which was seen in 10.7% of patients. Other common vascular anomalies included are glomus tumor and tufted angioma. Conclusion: Vascular anomalies comprise a spectrum of diseases, diagnosis of which is often challenging. Accurate diagnosis is critical to generate a management plan for the patient. Our study highlights the varied clinical spectrum of vascular tumors that we come across in clinical practice and it will increase familiarity of the various clinical presentations, thereby enabling clinicians to better identify and manage these challenging entities.

Integrated bioinformatics analysis reveals upregulated extracellular matrix hub genes in pancreatic cancer: Implications for diagnosis, prognosis, immune infiltration, and therapeutic strategies.

Pancreatic cancer (PC) stands out as one of the most formidable malignancies and exhibits an exceptionally unfavorable clinical prognosis due to the absence of well-defined diagnostic indicators and its tendency to develop resistance to therapeutic interventions. The primary objective of this present study was to identify extracellular matrix (ECM)-related hub genes (HGs) and their corresponding molecular signatures, with the intent of potentially utilizing them as biomarkers for diagnostic, prognostic, and therapeutic applications. Three microarray datasets were sourced from the NCBI database to acquire upregulated differentially expressed genes (DEGs), while MatrisomeDB was employed for filtering ECM-related genes. Subsequently, a protein-protein interaction (PPI) network was established using the STRING database. The created network was visually inspected through Cytoscape, and HGs were identified using the CytoHubba plugin tool. Furthermore, enrichment analysis, expression pattern analysis, clinicopathological correlation, survival analysis, immune cell infiltration analysis, and examination of chemical compounds were carried out using Enrichr, GEPIA2, ULCAN, Kaplan Meier plotter, TIMER2.0, and CTD web platforms, respectively. The diagnostic and prognostic significance of HGs was evaluated through the ROC curve analysis. Ten genes associated with ECM functions were identified as HGs among 131 DEGs obtained from microarray datasets. Notably, the expression of these HGs exhibited significantly (p < 0.05) higher in PC, demonstrating a clear association with tumor advancement. Remarkably, higher expression levels of these HGs were inversely correlated with the likelihood of patient survival. Moreover, ROC curve analysis revealed that identified HGs are promising biomarkers for both diagnostic (AUC > 0.75) and prognostic (AUC > 0.64) purposes. Furthermore, we observed a positive correlation between immune cell infiltration and the expression of most HGs. Lastly, our study identified nine compounds with significant interaction profiles that could potentially act as effective chemical agents targeting the identified HGs. Taken together, our findings suggest that COL1A1, KRT19, MMP1, COL11A1, SDC1, ITGA2, COL1A2, POSTN, FN1, and COL5A1 hold promise as innovative biomarkers for both the diagnosis and prognosis of PC, and they present as prospective targets for therapeutic interventions aimed at impeding the progression PC.

Clinicopathological correlation of cerebrospinal fluid alpha-synuclein seed amplification assay in a behavioral neurology autopsy cohort.

Lewy body disease (LBD) is a common primary or co-pathology in neurodegenerative syndromes. An alpha-synuclein seed amplification assay (αSyn-SAA) is clinically available, but clinical performance, especially lower sensitivity in amygdala-predominant cases, is not well understood. Antemortem CSF from neuropathology-confirmed LBD cases was tested with αSyn-SAA (N=56). Diagnostic performance and clinicopathological correlations were examined. Similar to prior reports, sensitivity was 100% for diffuse and transitional LBD (9/9), and overall specificity was 96.3% (26/27). Sensitivity was lower in amygdala-predominant (6/14, 42.8%) and brainstem-predominant LBD (1/6, 16.7%), but early spread outside these regions (without meeting criteria for higher stage) was more common in αSyn-SAA-positive cases (6/7, 85.7%) than negative (2/13, 15.4%). In this behavioral neurology cohort, αSyn-SAA had excellent diagnostic performance for cortical LBD. In amygdala- and brainstem-predominant cases, sensitivity was lower, but positivity was associated with anatomical spread, suggesting αSyn-SAA detects early LBD progression in these cohorts. A cerebrospinal fluid alpha-synuclein assay detects cortical LBD with high sensitivity/specificity. Positivity in prodromal stages of LBD was associated with early cortical spread. The assay provides precision diagnosis of LBD that could support clinical trials. The assay can also identify LBD co-pathology, which may impact treatment responses.

Darier disease: Histopathology revisited.

Darier disease (DD) is a rare genodermatosis. Literature on this topic is overwhelmingly dominated by case reports with rare clinical presentations, which have mentioned the histopathologic features briefly. The aim of this study was to document the histopathology of DD. Skin biopsies diagnosed as Darier disease based on clinicopathologic correlation over 12 years were reviewed for various epidermal and dermal features. There were 16 patients included, who most commonly presented in the third decade, with slight female predilection. The most common clinical presentation was hyperpigmented, hyperkeratotic, papules and plaques (91%), with 69% affecting the trunk. In addition to the classic suprabasal acantholytic clefts, we noted some unusual features: absence of parakeratosis (19%), a cornoid lamella-like pattern (62%), follicular acantholysis (13%) and multiple foci of involvement within a single biopsy (63%). Features such as the presence of dyskeratotic cells and minimal dermal lymphocytic infiltrates were concordant with previous literature. The limitation of this study was the small sample size. To conclude, pathologists must be aware of the variations in histopathology of Darier's disease, especially when challenged with atypical clinical presentations. The Darier-like pattern is met within several acantholytic diseases, and clinicopathologic correlation has the last word in arriving at a diagnosis.

NTRK-rearranged spindle cell neoplasm: Initial observation of imaging appearance and clinicopathologic correlation

ObjectiveTo explore pre-treatment imaging findings of neurotrophic tyrosine receptor kinase (NTRK)-rearranged spindle cell neoplasm, an emerging group of molecularly defined soft tissue tumors and summarize the clinical course, including TRK inhibitor therapy response. Materials and methodsThis retrospective study included 8 women and 4 men with NTRK-rearranged spindle cell neoplasm (median age, 35.5 years, range, 0–66). Available pre-treatment MRI, CT, PET, and US imaging were reviewed. Tumor histology and the patients' clinical course were reviewed. ResultsPrimary tumors were located within the soft tissue, lungs, kidney, and breast with soft tissue being the most prevalent site (n = 6). Pre-treatment MRI (n = 4) revealed linear hypointense signal foci and contrast enhancement in all patients with hemorrhage in half of the tumors. A tail sign (n = 1) and fluid levels (n = 1) were less frequent. Ultrasound showed well-marginated hypoechoic masses with internal flow. Primary tumors were all non-calcified on CT (4/4). Metastases were FDG-avid (4/4). Among the 8 patients who developed metastasis, 7 developed pulmonary metastases. All four patients who received NTRK inhibitor therapy showed an initial decrease in tumor size or FDG uptake. ConclusionNTRK-rearranged neoplasms may occur as enhancing masses with linear hypointense signal foci on MRI and FDG avid metastases on PET. Pulmonary metastases were frequent in our study. Initial treatment response is observed in most patients.

Abstract 6982: The roles of NDRG1 in HCC progression and its clinical significance

Abstract Background: Hepatocellular carcinoma (HCC) is prevalent globally and the third leading cause of cancer-related mortality. N-myc downstream regulated 1 (NDRG1) was found to be tumor promoting in some cancers while suppressive in others. The expression of NDRG1 is induced by stress signals such as DNA damage and hypoxia. In HCC, it has been found to promote proliferation and metastasis. Contradictory results, however, were also suggested on the functions of NDRG1. Methods: Our own HCC cohort and multiple publicly available databases were examined for NDRG1 expression and clinicopathologic correlation. NDRG1 expression under hypoxic conditions was investigated. Various functional assays were performed for NDRG1-knockdown HCC cell lines Huh-7 and PLC/PRF/5. Results: With RT-qPCR analysis on our 102 pairs of patients’ HCC tumor and corresponding non-tumorous liver samples, we found NDRG1 to be upregulated in HCC tumors. Similarly, RNA-sequencing analysis comparing 41 pairs of samples confirmed NDRG1 enrichment in HCC tumors. The upregulation was significantly and positively correlated with the absence of tumor encapsulation and cellular differentiation. These were further supported by TCGA and ICGC databases, in which upregulation of NDRG1 was significantly correlated with poor HCC patient overall survival. Interestingly, in the TCGA database, only 17% of the HCC cases were inferred to have copy number amplification of NDRG1 gene while NDRG1 mutations were rarely found. As hypoxia is a major tumor microenvironmental factor in HCC, we investigated NDRG1’s expression level in HCC cells under hypoxic or normoxic conditions and found significant increase in NDRG1 expression under hypoxic environment. We further found that NDRG1 knockdown inhibited cell proliferation, self-renewal ability, and migration. RT-qPCR analysis found lower LGR5 and SOX2 expression upon NDRG1 knockdown. This is in line with the positive correlation between NDRG1 and various cancer stemness-related gene expression, including LGR5, CD24, MYC, SOX2, and NOTCH1, in TCGA database. Lastly, in the resected HCC tumors on which spatial transcriptomics using Visium 10X and single-cell RNA-sequencing using Chromium 10X were performed, we found NDRG1 enrichment in both tumors cells and cancer associated fibroblasts (CAFs). Conclusion: NDRG1 was found to be significantly upregulated in HCC cells in our in-house cohort and publicly available databases. NDRG1 consistently promotes various oncogenic features of HCC cells, including proliferation, self-renewal ability, and migration. In addition, NDRG1 was found to be enriched in both the HCC cells and CAFs. Citation Format: Jingyi Lu, Lu Tian, Yu-Man Tsui, Xia Wong, Qingyang Zhang, Daniel Wai-Hung Ho, Irene Oi-Lin Ng. The roles of NDRG1 in HCC progression and its clinical significance [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6982.

Abstract 1637: EPHB4 is a key regulator of G1/S transition in hepatocellular carcinoma

Abstract Effective therapeutic regimens against advanced hepatocellular carcinoma (HCCs) have recently improved but it remains very limited. Targeting receptor tyrosine kinases (RTKs) has proven to one of the main ways of achieving better survival outcome in HCC patients, yet the precise mechanism for this success remains to be elusive. We have systematically investigated the expression profiles of RTKs transcriptomic datasets i.e. The Cancer Genome Atlas - Liver hepatocellular carcinoma (TCGA-LIHC) (n=371) and our in-house cohort of paired i.e. HKU-QMH (n=41), and identified EPHB4 as one of the most abundantly expressed and frequently mutated RTKs in human HCCs. EPHB4 expression was found to be significantly correlated with Alpha Fetoprotein (AFP) expression, a factor commonly used in the diagnosis of HCCs. Furthermore, EphB4 has been demonstrated to play a regulatory role in VEGF/VEGFR-mediated angiogenesis, critical targets for current successful drugs. We confirmed abundant membrane EphB4 expression in HCC clinical specimens and human HCC cell line models using immunohistochemistry. Clinicopathological correlation analysis of EPHB4 mRNA expression revealed that its overexpression is associated with aggressive tumor features including presence of tumor microsatellite, liver invasion, venous invasion, and absence of tumor encapsulation. Functionally, stably knocking down EPHB4 (shEPHB4) resulted in a strong reduction of proliferation and self-renewal rates of multiple HCC cell lines in vitro. It significantly reduced tumor growth rates in subcutaneous and liver orthotopic models in vivo. Furthermore, limiting dilution assay showed EPHB4 plays a role in tumor initiation property of HCC cells. Mechanistically, we performed Gene Set Enrichment Analysis (GSEA) of transcriptome profiles for shEPHB4 with respective controls and found that knocking down EPHB4 causes HCC cells undergo drastic changes in several cell cycle checkpoints including G1/S transition. Using thymidine blockade, we further confirmed that knockdown of significantly hinders the transition of HCC cells from G1 to S phase of cell cycle. Our data suggests a strong link between EphB4 and cell cycle. Conclusion: We found EphB4 plays a functional role in regulating G1/S transition in human HCCs and understanding regulatory role of EphB4 on cell cycle progression may provide mechanistic insights into the how to effectively target HCC in the clinic. Citation Format: Abdullah Husain, Elley Y. Chiu, Hoi-Tang Ma, Daniel W. Ho, Karen M. Sze, Lo-Kong Chan, Irene O. Ng. EPHB4 is a key regulator of G1/S transition in hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1637.

Clinicopathologic correlation of dermatologic diseases in patients with darker pigmentation.

Cutaneous diseases that disproportionately affect patients with darker pigmentation and their histologic features are historically understudied and undertreated. This review article aims to highlight the key clinical features, histopathology, and diagnostic pearls of several cutaneous diseases that commonly present in patients with darker pigmentation. A literature search was conducted, and a list of cutaneous diseases that frequently affect patients with darker pigmentation was compiled. A group of experts expounded upon those that were most common or misdiagnosed according to scientific evidence and clinical practice. The diseases were divided into hypopigmented disorders, hyperpigmented disorders, scarring disorders, and alopecic disorders. Within each category, the etiology, clinical features, histopathology, and key histologic differential diagnoses are described and discussed. As many clinicians are taught that there are no effective treatment options or that these diseases are considered "cosmetic" in nature, patients often do not get a thorough medical workup or skin biopsy. This article aims to decrease the knowledge gap and serve as a resource for anyone involved in the care of patients with these cutaneous conditions.

Clinicopathological Correlation of P53 Protein Expression in different Histological Subtypes of Gastric Carcinoma

Introduction: Gastric cancer is one of the common cancers after lung cancer worldwide, especially in the developing countries. p53 immunohistochemical expression has been proposed as a potential tool to evaluate the biological behavior of gastric cancer. However, its practical implication in gastric cancer prognosis or treatment by restoration of mutated p53 function is yet to be fully exploited. Hence, this study with the aim of assessing the yield of p53 expression in gastric carcinoma and its relationship with various clinicopathological parameters was formulated. Objectives: To assess immunohistochemical expression of p53 protein in different histological subtypes of gastric carcinoma cases and to study correlation between p53 protein expression and different clinicopathological parameters like age, gender, tumour location, gross pattern, histological types, degree of tumor differentiation and pathological staging in the above said cases. Materials and Methods: This was a hospital based cross-sectional study done over a period of 18 months on 60 cases of gastrectomies with proven histological diagnosis of gastric carcinoma. Observation and Results: Strong p53 expression was frequent among elderly male patients (&gt;60 years) who had ulceroproliferative tumors, located at pyloric antrum belonging to pTNM stage IIIA. In 87% cases, it was expressed, predominantly in moderately differentiated intestinal type with serosal invasion. Also, cases even with no lymph node metastasis showed p53 expression. Conclusion: Few findings were contradictory to other similar studies e.g. lymph node negative cases showing P53 expression does not support the hypothesis of predicting lymph node status by p53 expression. No significant correlation between p53 expression and different clinicopathological parameters in gastric carcinoma cases was seen. Keywords: P53, immunohistochemical, clinicopathological, histological subtypes, metastasis

Current and future advances in practice: IgG4-related disease.

IgG4-related disease (IgG4-RD) is an increasingly recognized cause of fibroinflammatory lesions in patients of diverse racial and ethnic backgrounds and is associated with an increased risk of death. The aetiology of IgG4-RD is incompletely understood, but evidence to date suggests that B and T cells are important players in pathogenesis, both of which are key targets of ongoing drug development programmes. The diagnosis of IgG4-RD requires clinicopathological correlation because there is no highly specific or sensitive test. Glucocorticoids are highly effective, but their use is limited by toxicity, highlighting the need for studies investigating the efficacy of glucocorticoid-sparing agents. B cell-targeted therapies, particularly rituximab, have demonstrated benefit, but no randomized clinical trials have evaluated their efficacy. If untreated or under-treated, IgG4-RD can cause irreversible organ damage, hence close monitoring and consideration for long-term immunosuppression is warranted in certain cases.

Clinicodemographic profile of orbital exenteration in a tertiary eye care center - A 20-year experience.

This study aimed to determine the clinical indications for orbital exenteration, demographic profile of these patients, and clinicopathologic correlations in the current times and to compare these results with previous published data. It was a retrospective study. All exenterations performed at a tertiary eye care center over a period of 20 years (from January 2001 to June 2020) were retrospectively evaluated. Patient records were reviewed to obtain demographic data, presenting symptoms and their duration, laterality, and clinical and histopathologic diagnosis. A total of 352 cases (males:females = 222:130) who underwent exenteration were identified. Patients age ranged from 11 months to 87 years (mean: 43.86 years, median: 50 years). The most common indication for exenteration was found to be eyelid malignancy in 54.36%, followed by retinoblastoma in 18.75% and primary orbital tumors in 14.49%. Out of 156 cases of eyelid malignancies requiring exenteration, squamous cell carcinoma (SCC) was the most common histologic subtype ( n = 94, 60.26%), followed by sebaceous gland carcinoma ( n = 40, 25.64%) and basal cell carcinoma ( n = 20, 12.82%). The most common primary orbital tumors requiring exenteration were adenocystic carcinoma of the lacrimal gland in adults and rhabdomyosarcoma in the pediatric age group. Benign conditions requiring exenteration included fulminant fungal orbital infections and lymphangioma among others. The number of exenterations performed have significantly increased in terms of absolute numbers. However, the ratio of exenteration to other tumor-related surgeries, mainly excision biopsy, has reduced compared to that reported from a previous study. The most common indication in our study remains eyelid malignancy followed by intraocular malignancy. However, SCC has emerged as the most common tumor histologic subtype requiring exenterations.

Clinico-Laboratory Profile of Tuberculides: An Experience at a Tertiary Care Centre from Chandigarh, India.

Tuberculides are characterised by delayed-type of immunologic reactions to Mycobacterium tuberculosis or its products in immuno-competent individuals. We herein describe clinico-epidemiological features and response to treatment in patients with tuberculides from a tertiary care centre from North India. This was a retrospective analysis of the clinical records of all the cutaneous tuberculosis (TB) patients (year 2000-2019) enrolled in the TB clinic. The patient records fulfilling the diagnostic criteria of tuberculides were considered for analysis. A total of 225 patients attended the tuberculosis clinic; out of this, 34 were diagnosed as tuberculides. Out of these 34 cases, 21 were identified as LS, 2 erythema induratum of Bazin, 1 papulonecrotic tuberculide, and 10 erythema nodosum. History of contact to open cases of TB was present in 15/34 (44.1%) patients. History of BCG vaccination was found in 15/34 (44.1%) patients. The focus of underlying TB could be identified in 20/34 (58.8%) patients. Skin biopsy was performed in all patients. In all patients, the diagnosis was confirmed by clinico-pathological correlation, positive TST, and the underlying focus of TB. All patients received 6 months regimen of anti-tubercular therapy with first-line drugs. In this study, we demonstrated various forms of tuberculides; lichen scrofulosorum was the most common form. We also included erythema nodosum cases also, which responded well to ATT. Observation from our study showed that tuberculides are important cutaneous markers for underlying tuberculosis infection, which helps in early detection of occult tuberculosis and timely management.

A Case of a 50-Year-Old Female with Dermatomyositis Secondary to a Paraneoplasm (Infiltrating Ductal Carcinoma, Grade 2)

Introduction: Dermatomyositis is an autoimmune disorder with an incidence of 5 to 10 per 1 million per year. 10 to 20% of patients with adult-onset Dermatomyositis have an underlying malignancy. There are currently no specific cutaneous markers for Paraneoplastic Dermatomyositis. This case highlights a patient with uncommon features of paraneoplasm after breast malignancy. Case Report: A 50-year-old female with Infiltrating Ductal Carcinoma, presented with patches on the face, neck, chest, upper back, outer arms, dorsal hands, thighs, hair loss and weakness. Histopathology revealed widened basal layer vacuolization with widened spaces between collagen bundles filled with mucin deposition, and pigment incontinence in the papillary dermis. Direct immunofluorescence showed granular deposits of IgG, C3, IgM and IgA in the basement membrane zone, which are consistent with Dermatomyositis. The patient was prescribed with Clobetasol ointment mixed equally with petrolatum on the body and Mometasone cream on the face. She was subsequently started on Prednisone at 0.5 mkd with eventual tapering, Omeprazole, and Calcium + Vitamin D tablet daily. Hydroxychloroquine 200 mg/tab daily was added. Referral to Rheumatology for co-management and Surgery for management of the breast mass was also done. Conclusion: This case emphasizes the rare occurrence of a Paraneoplastic Dermatomyositis following a diagnosis of breast malignancy. A careful review upon diagnosis may detect occult malignancies especially in patients who present primarily with cutaneous Dermatomyositis. Clinicopathologic correlation and a multi-disciplinary approach, with Surgery, Oncology, Rheumatology and Dermatopathology are needed to identify the underlying cause and facilitate successful treatment of a neoplasm followed by improvement of Dermatomyositis.

Multi-omics analysis of disulfidptosis regulators and therapeutic potential reveals glycogen synthase 1 as a disulfidptosis triggering target for triple-negative breast cancer.

Disruption of disulfide homeostasis during biological processes can have fatal consequences. Excess disulfides induce cell death in a novel manner, termed as "disulfidptosis." However, the specific mechanism of disulfidptosis has not yet been elucidated. To determine the cancer types sensitive to disulfidptosis and outline the corresponding treatment strategies, we firstly investigated the crucial functions of disulfidptosis regulators pan-cancer at multi-omics levels. We found that different tumor types expressed dysregulated levels of disulfidptosis regulators, most of which had an impact on tumor prognosis. Moreover, we calculated the disulfidptosis activity score in tumors and validated it using multiple independent datasets. Additionally, we found that disulfidptosis activity was correlated with classic biological processes and pathways in various cancers. Disulfidptosis activity was also associated with tumor immune characteristics and could predict immunotherapy outcomes. Notably, the disulfidptosis regulator, glycogen synthase 1 (GYS1), was identified as a promising target for triple-negative breast cancer and validated via in vitro and in vivo experiments. In conclusion, our study elucidated the complex molecular phenotypes and clinicopathological correlations of disulfidptosis regulators in tumors, laying a solid foundation for the development of disulfidptosis-targeting strategies for cancer treatment.