Clinicopathological Correlation Research Articles

Automated analysis of computerized morphological features of cell clusters associated with malignancy on bile duct brushing whole slide images.

Bile duct brush specimens are difficult to interpret as they often present inflammatory and reactive backgrounds due to the local effects of stricture, atypical reactive changes, or previously installed stents, and often have low to intermediate cellularity. As a result, diagnosis of biliary adenocarcinomas is challenging and often results in large interobserver variability and low sensitivity OBJECTIVE: In this work, we used computational image analysis to evaluate the role of nuclear morphological and texture features of epithelial cell clusters to predict the presence of pancreatic and biliary tract adenocarcinoma on digitized brush cytology specimens. Whole slide images from 124 patients, either diagnosed as benign or malignant based on clinicopathological correlation, were collected and randomly split into training (ST , N= 58) and testing (Sv , N= 66) sets, with the exception of cases diagnosed as atypical on cytology were included in Sv . Nuclear boundaries on cell clusters extracted from each image were segmented via a watershed algorithm. A total of 536 quantitative morphometric features pertaining to nuclear shape, size, and aggregate cluster texture were extracted from within the cell clusters. The most predictive features from patients in ST were selected via rank-sum, t-test, and minimum redundancy maximum relevance (mRMR) schemes. The selected features were then used to train three machine-learning classifiers. Malignant clusters tended to exhibit lower textural homogeneity within the nucleus, greater textural entropy around the nuclear membrane, and longer minor axis lengths. The sensitivity of cytology alone was 74% (without atypicals) and 46% (with atypicals). With machine diagnosis, the sensitivity improved to 68% from 46% when atypicals were included and treated as nonmalignant false negatives. The specificity of our model was 100% within the atypical category. We achieved an area under the receiver operating characteristic curve (AUC) of 0.79 on Sv , which included atypical cytological diagnosis.

The ultrasonographic appearance of renal medullary striations and their association with renal disease and renal histopathology in domestic cats.

Medullary striations (MS) have been anecdotally observed on ultrasound of feline kidneys; however, their significance is unknown. Aims of this retrospective, case control, pilot study were to describe the appearance, prevalence, and clinicopathological correlates of MS in a referral feline population. Still images from 1247 feline abdominal ultrasound studies performed between 2011 and 2021 were reviewed. Cats with MS were identified and compared with age-matched controls. Serum urea, creatinine, calcium, phosphate, and calcium-phosphate-product, plus urine specific gravity, urine protein: creatinine ratio (UPC), prevalence of active sediment (defined as>5red (RBC) or white blood cells (WBC) per high-power field) and prevalence of positive urine culture were compared between MS and control groups using the Mann-Whitney U test or Fisher's Exact test. Data are presented as median [range]. 27 cats were identified as having MS, giving a prevalence of 2.2% with a significantly higher proportion being seen in males (P =0.018). Medullary striation cats had significantly higher UPC values than controls (0.46 [0.16-7.57] vs. 0.16 [0.07-2.27]; P=0.006). Cats with MS were more likely to have active urinary sediments (39%vs 8%, P=0.023), but no difference in prevalence of positive urinary cultures was observed between groups. There was no significant difference in other parameters between MS and control cats. Renal histopathology performed in three MS cats revealed focal regions of linear medullary fibrosis. Medullary striations are associated with proteinuria and urinary tract inflammation in cats, which may reflect renal tubular dysfunction and/or inflammation. Hence identification might allow for earlier detection of renal pathology.

Cytomorphology, immunoprofile, and clinicopathologic correlation of metastatic prostatic carcinoma

It may be challenging to diagnose metastatic prostatic carcinoma (PC). This study focused on clinicopathologic correlation, and pitfalls of cytomorphology and immunostains of metastatic PCs. A total of 146 metastatic PCs including 134 (92%) PC without neuroendocrine differentiation-prostatic adenocarcinoma (PAC) and 12 (8%) with neuroendocrine differentiation (PC-NED) were retrieved. Triplicate tissue microarrays (TMA)of 54 surgically excised PCs were constructed for immunostains. Most cases showed Gleason 4 or 5 patterns. Nine percent of cases did not have a prior history of PC and 7% had 2 or more primary malignancies. PAC metastasized more commonly to lymph nodes (49%), and PC-NED metastasized more commonly to liver (58%). Cytologically, metastatic PCs show acini, cribriform, nest, and solid clusters. Most PACs showed conspicuous or prominent nucleoli. PC-NEDs showed typical cytologic features of low-grade or high-grade neuroendocrine neoplasm, or small cell carcinoma features. PACs could be immunoreactive to CDX2 (25%), CK20 (11%), NKX3.1 (99%), PSA (88%), PSAP (78%), and PSMA (92%). PC-NEDs were immunoreactive to neuroendocrine immunomarkers (CD56 [100%], chromogranin [67%], and synaptophysin [100%]) and p63 (25%), and lost expression of prostate-specific markers (NKX3.1, PSA, PSAP, and PSMA). Both PACs and PC-NEDs might be immunoreactive to CK7 (18% versus 33%), GATA3 (4% versus 0%), PAX8 (2% versus 50%, P<.05), and TTF1 (3% versus 57%, P<.05). It is critical to recognize these cytologic features and abbreviation of immunomarkers of metastatic PCs to avoid misinterpretation as metastatic carcinoma from nonprostate organs and inappropriate treatment. In addition, NED may be seen after hormone and chemoradiation treatment.

Blockade of growth hormone receptor signaling by using pegvisomant: A functional therapeutic strategy in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is an aggressive neoplasm with poor clinical outcome because most patients present at an advanced stage, at which point curative surgical options, such as tumor excision or liver transplantation, are not feasible. Therefore, the majority of HCC patients require systemic therapy. Nonetheless, the currently approved systemic therapies have limited effects, particularly in patients with advanced and resistant disease. Hence, there is a critical need to identify new molecular targets and effective systemic therapies to improve HCC outcome. The liver is a major target of the growth hormone receptor (GHR) signaling, and accumulating evidence suggests that GHR signaling plays an important role in HCC pathogenesis. We tested the hypothesis that GHR could represent a potential therapeutic target in this aggressive neoplasm. We measured GH levels in 767 HCC patients and 200 healthy controls, and then carried out clinicopathological correlation analyses. Moreover, specific inhibition of GHR was performed in vitro using siRNA and pegvisomant (a small peptide that blocks GHR signaling and is currently approved by the FDA to treat acromegaly) and in vivo, also using pegvisomant. GH was significantly elevated in 49.5% of HCC patients, and these patients had a more aggressive disease and poorer clinical outcome (P<0.0001). Blockade of GHR signaling with siRNA or pegvisomant induced substantial inhibitory cellular effects in vitro. In addition, pegvisomant potentiated the effects of sorafenib (P<0.01) and overcame sorafenib resistance (P<0.0001) in vivo. Mechanistically, pegvisomant decreased the phosphorylation of GHR downstream survival proteins including JAK2, STAT3, STAT5, IRS-1, AKT, ERK, and IGF-IR. In two patients with advanced-stage HCC and high GH who developed sorafenib resistance, pegvisomant caused tumor stability. Our data show that GHR signaling represents a novel “druggable” target, and pegvisomant may function as an effective systemic therapy in HCC. Our findings could also lead to testing GHR inhibition in other aggressive cancers.

PSG7 indicates that age at diagnosis is associated with papillary thyroid carcinoma: A study based on the cancer genome atlas data.

The age of the patients at diagnosis (age at diagnosis) is a self-contained element of danger for the prognosis of patients with papillary thyroid carcinoma (PTC), which has been well recognized and continuously adopted by the international cancer staging system. However, few studies have investigated its intrinsic mechanisms. In this study, we aim to comprehensively reveal the age-related pathogenesis of PTC and identify potential prognostic biomarkers. We divided the samples into two groups, young and elderly, to filter differentially expressed genes in The Cancer Genome Atlas (TCGA), with an age of 55 years serving as a cutoff. Moreover, we combined univariate, LASSO, and multivariate Cox regression analyses to construct age-related signatures for predicting progression-free survival. Additionally, functional enrichment analysis, immune infiltration analysis, differential expression analysis, clinicopathological correlation analysis, and drug sensitivity analysis were performed in different risk subgroups and expression subgroups. We screened 88 upregulated genes and 58 downregulated genes. Both the LASSO regression model that is validated in TCGA and the model of six age-related prognostic genes (IGF2BP1, GPRC6A, IL37, CRCT1, SEMG1, and PSG7) can be used to evaluate the progression-free survival of PTC patients. The GO, KEGG, and GSEA analyses revealed that each key gene was closely associated with PTC development. Furthermore, CD8+ T cells decreased significantly, while regulatory T cells increased dramatically in the high-risk and PSG7 high expression groups. PSG7 was remarkably correlated with clinicopathological parameters (pathologic stage, T stage, and N stage) of PTC patients, and PSG7 expression was elevated in tumor samples from both TCGA and the Gene Expression Omnibus and was strongly associated with progressive stage and poor prognosis. Our results provide an innovative understanding of the age-related molecular mechanisms of PTC development. PSG7 was identified to exert a critical role in PTC progression and may serve as a promising strategy for predicting the prognosis of PTC.

Radiological evaluation of ovarian mass by contrast-enhanced computed tomography abdomen with clinicopathological correlation in Eastern Indian population

Background: Adenexal masses present diagnostic challenges. After identification of the ovarian mass, the most critical step is to determine the degree of suspicion for malignancy. It is mainly based on imaging modalities and clinicopathological correlation. Aims and Objectives: This radiological study was designed to differentiate benign and malignant ovarian masses by contrast enhanced-computed tomography (CECT) of abdomen and correlation of the radiological findings with histopathological report. Materials and Methods: This was a hospital-based prospective study conducted in Department of Radiodiagnosis, Nilratan Sircar Medical College and Hospital, Kolkata during January 2019–June 2020. The study was done on clinically suspected 50 patients of 15–50 years with ovarian mass having CECT diagnosed solid/complex solid cystic mass. Results: Among 50 cases under study, 37(74.0%) were benign which was significantly higher than that of malignant cases (26.0%). Malignancy was significantly associated with wall irregularity, solid-cystic composition, presence of thick septations, septal enhancement, presence of both septal, and solid enhancement pattern in CECT. Conclusion: Based on the results of the present study, multi-detector contrast-enhanced CT could be a rapid non-invasive and cost-effective step in the evaluation of ovarian masses.

Imaging review in case of cervical spine tuberculosis

Tuberculosis of the cervical spine differs from other vertebral localizations by its extreme rarity, the clinical images are very diversified, the radiological measurements allow a good diagnostic orientation and specifically the MRI which allows a multi-planar study of the various lesions. Only bacteriological evidence can confirm the diagnosis. The treatment is based on a 12-month antituberculosis multidrug therapy and much debate upon the surgical indication. History: In this case, the patient presented with pain in cervical region with restricted movements of the neck and pain on examination at the mobilization of the cervical spine. Biopsy of the cervical lymph node had already been done which was positive for Koch’s etiology. Discussion: Cervical CT scan and a cervical MRI were performed, showing changes of spondylitis involving C1-C3 vertebrae with adjacent large loculated abscess in prevertebral and bilateral paravertebral regions and cord compression at the level of C2 vertebrae. Findings favoring an infective etiology. Conclusion: Cervical spine tuberculosis is considered a catastrophic disease due to the associated probability of spinal cord compression and quadriplegia. This emphasizes the importance of early diagnosis in the management of cervical tuberculosis with radiological and clinicopathological correlation.

ALL-473 Dilemma of Diagnosing and Treating BPDCN; Case Report With Clinicopathological Correlation

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive hematological malignancy with a rare incidence with poor outcome. Usually, it presents by skin infiltration then dissemination and only 10% may present first by bone marrow (BM) infiltration. It has overlapping features with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) clinically and pathologically, and there are many diseases to be differentially diagnosed from them. There is no consensus for treating BPDCN, but there are some novel therapies that have emerged in the field for treating this group of patients. A case report of 47-year-old diabetic male, presented to the hematology unit of Oncology Center of Mansoura University with a large, elevated scalp mass on the anterior part near the forehead with overlying pressure necrosis of the skin and face edema and with similar lesions on the back. There were enlarged cervical and inguinal lymph nodes. Skin biopsy revealed infiltration by monomorphous medium-sized blastoid cells, with fine chromatin and scanty cytoplasm, pannicular extension, and no detected epidermotropism. Immunohistochemistry revealed diffuse membranous immunoreactivity for CD4, CD56, and BCL2. Ki-67 proliferation index was about 90%. CD117, MPO, CD34, CD20, CD5, CD3, ALK, CD79a, and CD30 showed negative immunoreactivity in the tumor cells. BM examination showed infiltration by 80% large blastoid cells with basophilic cytoplasm and fine chromatin. Multi-color-flowcytometry (MCF) revealed low CD45 expression (located in the blast pocket) and positive CD123, a spectrum of CD56 (moderate to negative), dim CD4, CD43, partial dim CD33, CD38, CD81, and partial CD36 (predominantly negative), and was negative for the rest of the panel. The patient received Hyper-CVAD protocol (cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride, and dexamethasone) and skin lesions showed marvelous response after 1st cycle of chemotherapy. BM and FDG -PET/CT evaluation was free from abnormal cell infiltration. Now he is completing his chemotherapy and planned for allogenic stem cell transplantation (SCT). The diagnosis and management of such cases are challenging at all levels from the beginning of the disease, through the steps of diagnosis and finally in choosing the appropriate treatment protocol. We recommend ALL-based chemotherapy protocols especially Hyper-CVAD then allogenic SCT for better response and overall survival.

Unilocular thymic cyst with features of intra-thymic bronchogenic cyst: A clinicopathological correlation of 4 cases.

Four cases of primary unilocular thymic with features of bronchogenic cyst are presented. The patients are three men and a woman between the ages of 43 and 57 years. All the patients presented with symptoms of cough, chest pain, and dyspnea. Diagnostic imaging revealed the presence of an anterior mediastinal cystic lesion. Initial mediastinoscopic biopsies were non-diagnostic. Surgical resection of the anterior mediastinal cystic lesion was performed in all patients. Macroscopically, all the lesions were described as large cystic lesions measuring from 2 to 4cm in largest diameter and containing yellowish fluid. The surface of the cysts was described as corrugated and of brownish color. The walls of the cysts were not thickened and no other elements were described. Histologically, the cystic lesions were characterized by single cystic structures lined by ciliated epithelium. No atypia or mitotic activity was present in any of the cases. Immunohistochemical stains show positive staining of the respiratory epithelium with keratin and negative staining for GATA3, PAX-8, TTF-1, and Napsin. All the patients have recovered well after surgical resection.

Hidradenoma with an atypical localization mimicking lipoma

Sir, Nodular hidradenoma is a rare, benign adnexal tumor usually located in the head, neck, and extremities [1]. The difficulty of the diagnosis is due to the non-specificity of the clinical and histological presentation, often requiring a clinicopathological correlation [2]. Herein, we report a case of atypical abdominal hidradenoma mimicking lipoma. Our patient was a 51-year-old Moroccan female operated for bowel obstruction and fibroma presenting with a slowly growing, painless, subcutaneous abdominal nodule persistent for the last two years. The nodule had gradually increased in size in a context of apyrexia and general state preservation. A clinical examination was remarkable for a subcutaneous nodule (2.5 cm long axis) at the left iliac fossa, painless, indurated, and not fixed to the deep tissues, with slightly purplish skin (Fig. 1). The rest of the examination was featureless. In addition, dermoscopy was non-specific.

Focal cortical dysplasia pathology: diagnostic difficulty, classification, and utility for pathogenesis.

In the histopathological examination of treatment-resistant epilepsy, focal cortical dysplasia (FCD) is the most common diagnosis in the pediatric group. FCD is classified histopathologically according to the International League Against Epilepsy (ILAE) classification. In the last decade since the ILAE classification has been released, molecular genetic studies have revealed mTOR pathway-related mutations as a major etiology. The objective of this study was to determine the incidence of FCD in treatment-resistant epilepsy patients, explore histomorphological and immunohistochemical features, examine clinicopathological correlation, demonstrate mTOR pathway activation using a pS6 antibody immunohistochemically, and try to introduce a candidate for possible targeted therapies. Paraffin blocks and slides of tissue from patients with treatment-resistant epilepsy were reexamined retrospectively. Histopathological subtypes of FCD were determined according to the ILAE classification. NeuN and neurofilament H (NF-H) staining were performed, and additionally a pS6 antibody was used to demonstrate mTOR pathway activation. In 32 cases diagnosed with FCD, or 17.5% of 183 surgical epilepsy materials, there were no significant differences in the statistical analysis of clinical variables between the ILAE FCD subtypes. Recommended antibody NeuN revealed microcolumnar alignment in the FCD type Ia and IIIa groups and the loss of lamination in the type Ib group. Another recommended antibody, NF-H, was not found to be useful in discriminating between normal and dysmorphic neurons. pS6 expression, showing mTOR pathway activation, was observed in dysmorphic neurons and balloon cells in all FCD type II cases. Significant pS6 expression in FCD type II represents the genomic nature of the disease noted in the literature. Nevertheless, the known MTOR gene and mTOR pathway-related mutations remain behind proportionally to explain the mTOR pathway activation in all FCD type II cases. Clinicopathologically and genetically integrated classification and usage of mTOR pathway inhibitors in treatment are expected as a recent evolution.

Histopathological study of scalp tumors and tumor like lesions

Introduction: A variety of inflammatory and neoplastic scalp lesions is encountered in clinical practice, which can be attributed to trauma, infection, abscess, allergic reaction, or tumor. Though a majority of scalp involvement is by benign processes, still it can be a site of malignant neoplasm.Aims and objectives 1.To study the morphological, histopathological types and clinico-pathological correlation of various scalp tumors.2.To know the proportion of benign and malignant lesions in the scalp lesions.3.To compare the data and other investigations with similar studies from other regions.Materials and methods: The present retrospective study is conducted in the department of pathology, B.J. Medical college and civil hospital, Ahmedabad over a duration of 5 years. A total of 105 cases of scalp lesions were evaluated. Scalp biopsies with clinical suspicion of a tumor which presented with a swelling, with or without pain or with non-healing ulcer were included in the study. The spectrum of lesions that appeared in the scalp were tabulated. Results: In our study, total 105 cases were observed during period of five years. Out of the total of 105 cases majority of them were benign accounting for 92.38% of all cases and malignant cases accounting for 7.62% of all cases. The sex distribution of scalp lesions in the present study was slightly greater in male accounting for 60% cases. Out of 105 cases majority are non-tumorous keratinous cysts accounting for 53.3% of all cases with trichilemmal cyst being most common. Conclusion: Benign tumors and tumor like lesions are more common than malignant tumors. Although mostly benign diagnosis and treatment of these lesions pose significant challenge due to distinct histopathological features. A high index of clinical suspicion is essential to ensure early detection of malignancies and initiate treatment.

TCL-306 Application of the Proposed Immunohistochemistry Algorithm for the Prognostication of GATA3 and TBX21 Subtypes of Peripheral T-Cell Lymphoma, Not Otherwise Specified.

Recent molecular studies have indicated the varied oncogenic pathways resulting in the subtypes of peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS), which affect prognosis and may have predictive value. To evaluate the immunohistochemistry (IHC) algorithm (Amador et al.) for the subtyping of PTCL, NOS and ascertain their relevance with correlation to the clinicopathological profile. This 7-year (2015-2021) ambispective study included 43 patients with diagnoses of PTCL, NOS from the archives of the Department of Pathology (AIIMS, New Delhi). IHC for transcription factors GATA3 (>50% immunopositivity considered positive) and TBX21 (>20%) and their target proteins CCR4 (>50%) and CXCR3 (>20%) was performed followed by subtyping by two pathologists. Detailed clinicopathological correlation was done. The association between the subtypes and clinical factors (demographics, performance status, organomegaly, IPI/PIT score, stage, marrow involvement), histologic features (monomorphous/polymorphous population), and survival (overall and progression-free survival) was analyzed. With the application of the algorithm by Amador et al., the cases were categorized into the subtypes GATA3 (18), TBX21 (13), and unclassifiable (7). There was no significant association observed with the clinical parameters of the subtypes. Though an increased proportion of TBX21-subgroup cases showed a polymorphous population compared to the GATA3 subgroup with monomorphous population, no significant P-value was found. Two of the Lennert lymphomas were categorized in the GATA3 subgroup. On multivariate analysis, no significant difference was present for overall survival (P-value=0.149) and progression-free survival (P-value=0.066) amongst the IHC-defined subtypes; the trends suggest that the GATA3 subgroup has worse overall and progression-free survival. The IHC-derived subtypes of GATA3 and TBX21 may have a role in prognostication and may guide further therapeutics aiding in better patient management of this aggressive group of lymphomas. The algorithm is reproducible, however some of the cases may be left unclassifiable and require further work up and gene expression profiling. The results trend toward the GATA3 subgroup having a monomorphous population with a worse overall prognosis, requiring a larger sample size for validation. The application of this algorithm in routine practice can help in risk stratification of the patients. Thanks to Science-Engineering-Research-Board and AIIMS-Research section (SERB-EEQ/2016/402, AIIMS-A-653).

Epilepsy-associated death in the Southwestern Ontario: A clinicopathological correlation study.

Patients with epilepsy are at elevated risk for premature mortality, of which sudden unexpected death in epilepsy (SUDEP) is one of the leading causes. SUDEP incidence varies significantly depending on the population and the methods used to document the cause of death. We performed retrospective case review at the London Health Sciences Centre for the period of 2000 to 2018. Clinical information, scene investigations, general pathology findings, toxicology, and neuropathology findings were obtained, examined, and confirmed by two neuropathologists and one epileptologist. The characteristics were compared and summarized. We also evaluated the impact of 2010 revision of Ontario Coroner Act Regulation, which significantly limited whole brain examination. Among the 12,206 cases reviewed, we identified 152 cases with a known history of epilepsy. Ninety-seven cases (64%) were classified as SUDEP. There were significantly more SUDEP decedents found dead unwitnessed at night in prone position, than non-SUDEP. Generalized seizures were strongly associated with SUDEP. A male predominance was observed in SUDEP group between 15 and 35 years old. Near half of the brains examined were "unremarkable." There was no difference in neuropathology findings between SUDEP and non-SUDEP groups. After implementation of the 2010 revision of Ontario Coroner Act Regulation, fixed whole brain examination was reduced from 88% to 7% of the epilepsy-related death investigation. Except a lower diagnosis rate of "inflammatory/infectious changes," there were no significant differences in neuropathology findings. This is the first detailed clinical-pathological study on epilepsy-related death based on a Canadian cohort. This study reinforces the previously reported findings in SUDEP and highlights the importance of clinicopathological correlation for accurate classification of epilepsy-related death.

Clinicoepidemiological Profile of Childhood Leprosy in a Tertiary Care Hospital of North Karnataka

Abstract Background: Childhood leprosy is an indicator of ongoing transmission of the disease. The prevalence rate of pediatric leprosy is considered an important epidemiological index for determining the level of transmission of the disease. Our aim was to estimate the proportion of leprosy cases among children aged 0–14 years in our tertiary care hospital. Methods: A retrospective study was carried out for a period of 4 years from January 2017 to December 2020. Secondary data were collected from leprosy records pertaining to childhood leprosy (aged between 0 and 14 years). Only new cases presented during the period were included. Details of the patients such as age, sex, family history, number and site of lesions, nerve involvement, reactions, and deformities were noted. Slit-skin smear and biopsy findings were tabulated and descriptive analysis was done. Results: Fifty-five cases (9.54%) of childhood leprosy were diagnosed. Majority of the cases were in the age group of 10–14 years. The most common leprosy type was borderline tuberculoid found in 42 patients (76.36%). Forty-nine patients (89.09%) had paucibacillary (PB) and 6 (10.91%) had a multibacillary type. The most common presenting symptom was patch (61.8%). Eleven patients had a family history. Clinicopathological correlation was observed in 50 (90%) patients. Lepra reactions were seen in six (10.9%) patients and two deformities in three patients. Conclusion: The proportion of pediatric leprosy cases was 11.61% in 2017 and decreased to 6.45% in 2020. PB type is the most common type. To achieve zero childhood leprosy cases, thorough follow-up and contact tracing of adult leprosy patients, early diagnosis of childhood leprosy to prevent disabilities is the need of the hour.

Clinicopathological Correlations in Enucleated Globes of Late-Stage Coats Disease with a Review of the Literature

BackgroundCoats disease may cause diagnostic dilemma because of its variable clinical presentation that can be suspicious of retinoblastoma. Late sequelae of the disease are blinding with possible enucleation. We demonstrate the main histopathological findings of Coats enucleated eyes with literature review.MethodsThis was a retrospective study of all enucleated globes diagnosed as Coats disease over 30 years and were reviewed by two pathologists. The corresponding demographic data, clinical presentation, pre-operative clinical impression, and indication for enucleation were collected. Descriptive analysis of our own series data was performed. Our findings were then correlated to published data that were collected from 1983 to 2021 from the PUBMED database in English-written language. Shields classification was used as an inclusion criterion for the published reports to be analyzed.ResultsWe had seven enucleated globes with Coats disease. Mean age at presentation was 3.2 years (range 3 months to 9 years). Male predominance was observed in 6 and all cases were unilateral. Strabismus was the most common initial presentation (57%, n = 4), followed by leukocoria (43%, n = 3). Indication for enucleation was mostly suspected retinoblastoma (57%, n = 4). Four eyes were classified as stage 4, and 2 had advanced stage 5 changes. Histopathologically, subretinal fluid with lipid-laden macrophages was seen in all cases, the anterior chamber was shallow in 5/7 with angle neovascularization in 2/7. Telangiectatic vessels were clearly observed in 4/7. ConclusionCoats disease is a potentially visually disabling disease that is mostly unilateral in 95%, has male predominance of 81%, and wide age range with a mean of 17 years. In Saudi Arabia, the disease seems to present at younger age, tends to be more advanced, and may be indistinguishable from retinoblastoma at the time of diagnosis. Shields staging of Coats is highly recommended to be followed clinically to unify the pathways for treatment and to correlate the concluded outcomes.

Lymphocytic Mastopathy - Entity with Diagnostic Dilemma: A Case Report

Lymphocytic mastopathy is a condition that affects the breasts of people who have had diabetes for a long time. It frequently manifests as huge hard lumps, raising cancer risk and necessitating unnecessary surgery. Histopathologically, it is characterized by sclerosing lymphocytic mastitis. A nulliparous woman appeared with a firm, palpable breast lump. Malignancy was the clinical impression. They conducted imaging tests, which confirmed a malignancy suspicion. Histopathology revealed sclerosing fibrosis with keloid-like characteristics and abundant per lobular and intralobular lymphocytic infiltrates. Most of these instances will be resolved by clinicopathological correlation, which will help to avoid invasive surgical operations. However, imaging studies may not be appropriate in many situations. Understanding this pathology's proclivity is crucial because it shares many clinical and radiological features with breast cancer. Here we report a unique case study of Lymphocytic mastopathy in a 44-year-old female patient with complaints of pain in the right breast for 15 days. Ultrasonograms and histopathological studies have been conducted, which evidenced lymphocytic mastopathy.

Clinicopathologic Correlation of CD44 + /CD24 - Expression in Breast Cancer: a Report from Tertiary Care Medical University in India.

CD44 + /CD24 - phenotype has been associated with stem cell-like characteristics with enhanced invasive properties, radiation resistance, and with distinct genetic profiles suggesting a correlation to adverse prognosis in western literature. The aim of this study was to study CD44 + /CD24 - phenotype as an adverse prognostic marker in Indian breast cancer patients. N = 61 breast cancer patients included in a tertiary care facility in India were evaluated for receptor studies (estrogen receptor ER, progesterone receptor PR, Herceptin antibody Her2 neu receptor, CD44 & CD24 stem cell markers). CD44 + /CD24 - phenotype was statistically related to adverse factors like estrogen and progesterone receptors non-expression, her 2 neu expression, and triple-negative breast cancer. Of the 39 patients with ER-ve status, 33 (84.6%) were found to have CD44 + /CD24 - phenotype and 82.5% of all the CD 44 + /CD24 - patients were ER negative (p = 0.001). Thirty-four (75.5%) of the PR-ve patients showed the CD44 + /CD24 - phenotype, and of all the CD 44 + /CD24 - patients, 85% of were PR negative (p = 0.006). Thirty-six (75%) of Her-2-Neu + ve were CD44 + /CD24 - . Approximately 90% of the Her 2 Neu patients expressed CD44 + /CD24 - and 76.9% of all the triple-negative patients were found to be CD44 + /CD24 - expression (p = 0.001). CD44 + /CD24 - had a significant association with adverse prognostic factors like stage of disease, hormonal receptor status, and molecular subtypes in Indian breast cancer patients like the Western data.

Clinico-pathological correlation of incidental focal colorectal uptake on 18F-Labelled 2-fluoro-2-Deoxyglucose PET/CT: A prospective single centre experience

ObjectivesTo assess the clinical and pathological implications of incidental focal uptakes during the 18F-FDG-PET/CT colorectal examination and the role of colonoscopy in the diagnostic algorithm of these uptakes. MethodsWe performed a single-center prospective that recruited patients with incidental uptakes during18F-FDG-PET/CT colorectal examination over five years. Patients underwent colonoscopy and biopsies to assess the usefulness of 18F-FDG-PET/CT in patients with incidental uptakes. ResultsA total of 2231 scans were performed, and 71 (3.18%) localized colorectal uptakes were identified. The colon was normal in 45.07% of these uptakes, while the remaining cases had malignant colorectal tumors (29.57%) and neoplastic lesions (25.35%). The false-positive rate was significantly higher in the proximal colon than in the distal colorectal (53.7% vs. 39.8%, P = 0.004). The bivariate analysis showed that increased SUVmax independently increases the risk of neoplastic lesions, while proximal colon uptakes independently decrease the risk of neoplastic lesions. ConclusionsOur results highlight a valuable role of incidental focal uptakes during 18F-FDG-PET/CT colorectal examination in identifying patients with increased risk of neoplastic lesions. The study supports the need for a colonoscopy in such settings, particularly with increased SUVmax.

Construction of a cancer-associated fibroblasts-related long non-coding RNA signature to predict prognosis and immune landscape in pancreatic adenocarcinoma.

Background: Cancer-associated fibroblasts (CAFs) are an essential cell population in the pancreatic cancer tumor microenvironment and are extensively involved in drug resistance and immune evasion mechanisms. Long non-coding RNAs (lncRNAs) are involved in pancreatic cancer evolution and regulate the biological behavior mediated by CAFs. However, there is a lack of understanding of the prognostic signatures of CAFs-associated lncRNAs in pancreatic cancer patients. Methods: Transcriptomic and clinical data for pancreatic adenocarcinoma (PAAD) and the corresponding mutation data were obtained from The Cancer Genome Atlas database. lncRNAs associated with CAFs were obtained using co-expression analysis. lncRNAs were screened by Cox regression analysis using least absolute shrinkage and selection operator (LASSO) algorithm for constructing predictive signature. According to the prognostic model, PAAD patients were divided into high-risk and low-risk groups. Kaplan-Meier analysis was used for survival validation of the model in the training and validation groups. Clinicopathological parameter correlation analysis, univariate and multivariate Cox regression, time-dependent receiver operating characteristic (ROC) curves, and nomogram were performed to evaluate the model. The gene set variation analysis (GSVA) and gene ontology (GO) analyses were used to explore differences in the biological behavior of the risk groups. Furthermore, single-sample gene set enrichment analysis (ssGSEA), tumor mutation burden (TMB), ESTIMATE algorithm, and a series of immune correlation analyses were performed to investigate the relationship between predictive signature and the tumor immune microenvironment and screen for potential responders to immune checkpoint inhibitors. Finally, drug sensitivity analyses were used to explore potentially effective drugs in high- and low-risk groups. Results: The signature was constructed with seven CAFs-related lncRNAs (AP005233.2, AC090114.2, DCST1-AS1, AC092171.5, AC002401.4, AC025048.4, and CASC8) that independently predicted the prognosis of PAAD patients. Additionally, the high-risk group of the model had higher TMB levels than the low-risk group. Immune correlation analysis showed that most immune cells, including CD8+ T cells, were negatively correlated with the model risk scores. ssGSEA and ESTIMATE analyses further indicated that the low-risk group had a higher status of immune cell infiltration. Meanwhile, the mRNA of most immune checkpoint genes, including PD1 and CTLA4, were highly expressed in the low-risk group, suggesting that this population may be “hot immune tumors” and have a higher sensitivity to immune checkpoint inhibitors (ICIs). Finally, the predicted half-maximal inhibitory concentrations of some chemical and targeted drugs differ between high- and low-risk groups, providing a basis for treatment selection. Conclusion: Our findings provide promising insights into lncRNAs associated with CAFs in PAAD and provide a personalized tool for predicting patient prognosis and immune microenvironmental landscape.