Multifaceted TGF-ß signaling, a master regulator: From bench-to-bedside, intricacies, and complexities.

Physiological embryogenesis and adult tissue homeostasis are regulated by transforming growth factor-ß (TGF-ß), an evolutionarily conserved family of secreted polypeptide factors, acting in an autocrine and paracrine manner. The role of TGF-ß in inflammation, fibrosis, and cancer is complex and sometimes even contradictory, exhibiting either inhibitory or promoting effects depending on the stage of the disease. Under pathological conditions, especially fibrosis and cancer, overexpressed TGF-ß causes extracellular matrix deposition, epithelial-mesenchymal transition, cancer-associated fibroblast formation, and/or angiogenesis. In this review article, we have tried to dive deep into the mechanism of action of TGF-ß in inflammation, fibrosis, and carcinogenesis. As TGF-ß and its downstream signaling mechanism are implicated in fibrosis and carcinogenesis blocking this signaling mechanism appears to be a promising avenue. However, targeting TGF-ß carries substantial risk as this pathway is implicated in multiple homeostatic processes and is also known to have tumor-suppressor functions. There is a need for careful dosing of TGF-ß drugs for therapeutic use and patient selection.

Tumor-associated macrophages: A sentinel of innate immune system in tumor microenvironment gone haywire.

The tumor microenvironment (TME) is a critical determinant in the initiation, progression, and treatment outcomes of various cancers. Comprising of cancer-associated fibroblasts (CAF), immune cells, blood vessels, and signaling molecules, the TME is often likened to the soil supporting the seed (tumor). Among its constituents, tumor-associated macrophages (TAMs) play a pivotal role, exhibiting a dual nature as both promoters and inhibitors of tumor growth. This review explores the intricate relationship between TAMs and the TME, emphasizing their diverse functions, from phagocytosis and tissue repair to modulating immune responses. The plasticity of TAMs is highlighted, showcasing their ability to adopt either protumorigenic or anti-tumorigenic phenotypes based on environmental cues. In the context of cancer, TAMs' pro-tumorigenic activities include promoting angiogenesis, inhibiting immune responses, and fostering metastasis. The manuscript delves into therapeutic strategies targeting TAMs, emphasizing the challenges faced in depleting or inhibiting TAMs due to their multifaceted roles. The focus shifts towards reprogramming TAMs to an anti-tumorigenic M1-like phenotype, exploring interventions such as interferons, immune checkpoint inhibitors, and small molecule modulators. Noteworthy advancements include the use of CSF1R inhibitors, CD40 agonists, and CD47 blockade, demonstrating promising results in preclinical and clinical settings. A significant section is dedicated to Chimeric Antigen Receptor (CAR) technology in macrophages (CAR-M cells). While CAR-T cells have shown success in hematological malignancies, their efficacy in solid tumors has been limited. CAR-M cells, engineered to infiltrate solid tumors, are presented as a potential breakthrough, with a focus on their development, challenges, and promising outcomes. The manuscript concludes with the exploration of third-generation CAR-M technology, offering insight into in-vivo reprogramming and nonviral vector approaches. In conclusion, understanding the complex and dynamic role of TAMs in cancer is crucial for developing effective therapeutic strategies. While early-stage TAM-targeted therapies show promise, further extensive research and larger clinical trials are warranted to optimize their targeting and improve overall cancer treatment outcomes.

Comparison of the modified Masood's scoring index versus international academy of cytology Yokohama system in the categorization of breast fine needle aspirates.

CONTEXT: The Modified Masood Scoring Index (MMSI) categorizes breast fine needle aspirates into four categories non-proliferative breast diseases (PBD), PBD without atypia, PBD with atypia and carcinoma in situ/carcinoma. The International Academy of Cytology Yokohama System classifies the aspirates into five categories - inadequate, benign, atypical, suspicious, and malignant. Very few studies have been conducted so far to compare the diagnostic accuracy of this system. AIMS: The objectives of the study were to classify breast fine needle aspirates according to the MMSI and IAC Yokohama and assess their risk of malignancy (ROM) and performance parameters. MATERIALS AND METHODS: All breast FNAs received from June 2020 to May 2023 were classified according to the MMSI and IAC Yokohama. Using histopathological diagnosis as the gold standard, ROM and performance parameters were calculated. RESULTS: Out of the 559 breast fine needle aspirates, the histopathological correlation was available for 337 cases. The ROM for non-PBD, PBD without atypia, PBD with atypia and carcinoma in situ/carcinoma categories were 0%, 1.2%, 9.1% and 93%, respectively. The ROM for each of the categories of Yokohama system was 16.6%, 1.1%, 4.3%, 86.2% and 97.6%, respectively. The values for the sensitivity, specificity, PPV, NPV and diagnostic accuracy were slightly higher for IAC Yokohama (97.3%, 97.2%, 94.7%, 98.6% and 97.2%, respectively) than the MMSI (96.4%, 96.2%, 93%, 98.1% and 96.3%, respectively). Furthermore, another shortfall of MMSI is the inability to compare the Inadequate category of the Yokohama system. CONCLUSION: Overall Yokohama system proved to be a better system for categorizing breast lesions on FNAB as the scoring system provides more objective categorization and minimizes false positive and false negative cases.

Follicular Becker's nevi: A case series and review of literature.

The follicular variant of Becker's nevus is an under-reported entity. We present the rare occurrence of follicular Becker's nevus in 7 patients, confirmed through dermoscopy and histopathological examination. Dermoscopy shows perifollicular hypopigmentation surrounded by a well-defined net-like pigmentation corresponding clinically to the presence of folliculocentric macules. Histology shows prominent basal and suprabasal melanization surrounding the follicle, corresponding to well-defined net-like pigmentation seen on dermoscopy. However, the melanization does not extend along the entire length of the follicular epithelium leading to perifollicular hypopigmentation on dermoscopy. Though biopsy is confirmatory, it is not usually necessary.

A rare case of primary neuroendocrine carcinoma of the central nervous system.

Primary neuroendocrine carcinoma (NEC) of the brain is an extremely rare presentation, with only a few previous case reports. We describe a primary NEC arising from the left parieto-occipital lobe. The 55-year-old patient presented with complaints of headache and dizziness for the preceding 7 months. Magnetic resonance imaging revealed a large ill-defined mass in the left parieto-occipital lobe, with possible differential diagnosis of meningioma. A craniotomy was performed, and a firm vascular tumor was removed. Histopathological examination revealed a large cell NEC. Immunohistochemistry was performed to exclude the possibility of an extracranial primary. Based on the immunohistochemical expression and absence of any extracranial tumor on positron emission tomography, the diagnosis of primary NEC of the brain was made. It is important to differentiate between primary and metastatic neuroendocrine tumors because they show a significant difference in prognosis and treatment.

Pituitary tuberculoma with panhypopituitarism masquerading as a pituitary adenoma.

Tuberculosis of the hypothalamo-pituitary axis is extremely uncommon. The presentation of panhypopituitarism in a case of sellar tuberculosis is an even rarer occurrence. We present a case of a 44-year-old man who presented with complaints of headache and right-sided diminution of vision for six months. A hormone profile showed abnormal anterior pituitary assay suggestive of panhypopituitarism. Magnetic Resonance imaging of the brain showed a sellar mass measuring 1.8 × 1.5 × 1.3 cm with suprasellar extension suggestive of a pituitary adenoma. Histopathological examination showed multiple epithelioid cell granulomas along with Langhans giant cells and mixed inflammatory infiltrates against a necrotic background. Zeihl Neelson stain demonstrated the presence of acid-fast bacilli. Thus, a final diagnosis of pituitary tuberculoma was made, and the patient started on antitubercular therapy. It is extremely important to correctly diagnose sellar tuberculosis as the treatment is entirely different, and the patient usually responds well to therapy.

Cytomorphological spectrum of pilomatricoma - A series of 28 cases.

BACKGROUND: Pilomatricoma is a benign tumour that originates in the outer sheath of the hair follicle root. The clinical diagnosis of this rare entity is often missed, possibly due to a lack of awareness. Its characteristic cytomorphological features are sheets of ghost cells, basaloid cells, calcification and foreign body giant cell reaction. However, the above features may not all be present in all cases, rendering cytological diagnosis difficult. MATERIALS AND METHODS: This retrospective study included all cases of pilomatricoma diagnosed on fine needle aspiration over a period of 4 years. The histopathological diagnosis was retrieved for the cases wherever possible. A detailed histopathological and cytological evaluation was performed for the various components-basaloid cells, ghost cells, calcified debris, foreign body giant cells, bare nuclei, neutrophils, and macrophages-and they were graded on a scale of 0 to 3+. RESULTS: The 28 cases included 8 female and 20 male patients with a mean age of 34.6 years. Most cases (22 cases; 78.6%) were located in the head and neck, with the scalp being the most common site. Twenty-five cases were cytologically diagnosed as pilomatricoma based on a variable admixture of the various components-nests of basaloid cells, ghost cells, foreign body giant cell reaction, calcified debris and viable squamous cells. However, in two cases which showed an absence of basaloid cells, a differential diagnosis of epidermal inclusion cyst was also included. Another case showed a predominance of basaloid cells with a paucity of ghost cells, so a differential diagnosis of adnexal tumour was also included. Among all the cytological parameters, sheets of ghost cells followed by nests of basaloid cells and foreign body giant cell reaction had the highest sensitivity in the cytological diagnosis of pilomatricoma. CONCLUSION: The presence of sheets of ghost cells is the most sensitive parameter for the cytological diagnosis of pilomatricoma. It is important that pilomatricoma should be considered in the differential diagnosis of subcutaneous masses, particularly in the head and neck region.

Cryptococcal lymphadenitis-First presentation in an HIV-positive patient.

Cryptococcal infection is a life-threatening, opportunistic infection in human immunodeficiency virus-infected individuals. The infection most commonly begins in the respiratory tract, with secondary involvement of the brain, skin, and lymph nodes. We report a rare case of isolated cervical cryptococcal lymphadenitis diagnosed on fine needle aspiration cytology, which was the initial presentation of secondary immunodeficiency in the patient. Periodic acid-Schiff stain, India ink preparation, and culture were done to confirm the diagnosis. He was diagnosed as HIV-positive on further investigation.

Synchronous ipsilateral adrenal cortical adenoma and ganglioneuroma: A case report.

Synchronous tumors comprising of cortical as well as medullary differentiation are rare in the adrenal gland. Collision tumors comprise of two independent neoplasms arising from the cortex and the medulla without any histological admixture. Adrenal cortico-medullary mixed tumors are rare tumors comprising of adrenal cortical and chromaffin cells intermixed with each other. Ganglioneuroma is a rare benign tumor originating from the paravertebral sympathetic ganglia and is rarely seen in the adrenal medulla. The presence of a synchronous ganglioneuroma with an adrenal cortical adenoma in the ipsilateral adrenal gland is exceedingly rare. We report a collision tumor comprising of an adrenal cortical adenoma and a ganglioneuroma detected as an incidental finding in a pediatric patient who presented with hypertension and palpitations.

Evaluation of accuracy of salivary gland fine needle aspirates using the Milan System for Reporting Salivary Gland Cytopathology.

CONTEXT: The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) is a standardised six-tier reporting format aimed at ensuring better communication and improved patient management. AIMS: The main objectives of our study were to classify salivary gland fine needle aspirates into six categories of the MSRSGC and assess risk of malignancy (ROM), specificity, sensitivity, positive predictive value, and negative predictive value. SETTINGS AND DESIGN: This retrospective study covered a period of three years from January 2017 to December 2020. MATERIALS AND METHODS: All salivary gland FNAs performed in the above period were retrieved and classified into six categories based on the Milan system. Histopathological diagnosis was also retrieved wherever available. STATISTICAL ANALYSIS: Using histopathological diagnosis as the gold standard, ROM was calculated. Specificity, sensitivity, positive and negative predictive values, and diagnostic accuracy were also assessed. RESULTS: Out of the 202 salivary gland FNAs, histopathological diagnosis was available in 102 cases. ROM for the Non-Diagnostic, Non-Neoplastic, Atypia of Undetermined Significance (AUS), Benign, Salivary Gland Neoplasm of Uncertain Malignant Potential (SUMP), Suspicious for Malignancy (SM), and Malignant categories was 30%, 8.3%, 25%, 3.9%, 33.3%, 71.4%, and 93.3% respectively. Highest specificity and diagnostic accuracy were achieved when only Malignant and SM were considered as positive results. Maximum sensitivity was observed when AUS, SUMP, SM, and Malignant were included in positive test results. CONCLUSION: The MSRSGC is an excellent system for accurately classifying salivary gland FNAs with better reproducibility of reports and enhanced communication between pathologist and surgeon.

Categorisation of lymph node aspirates using the proposed Sydney system with assessment of risk of malignancy and diagnostic accuracy.

BACKGROUND: The Sydney system has been proposed as a uniform format for reporting lymph node cytopathology under five standardised categories: Non-Diagnostic (ND), Benign (B), Atypical (Cells) of Undetermined Significance/Atypical Lymphoid (Cells) of Uncertain Significance (AUS/ALUS), Suspicious for Malignancy (SFM), and Malignant (M). Very few studies have been conducted so far to confirm the risk of malignancy (ROM) of the different categories. The main objectives of our study were to classify lymph node aspirates according to the proposed Sydney system and assess the ROM and other performance parameters. MATERIALS AND METHODS: All lymph node aspirates done at our centre from January 2018 to December 2020 were reclassified according to the Sydney system. Using histopathological diagnosis as gold standard, ROM and performance parameters were calculated. RESULTS: A total of 1205 lymph node aspirates were reclassified: 53 (4.4%) ND, 488 (40.5%) B, 10 (0.8%) AUS/ALUS, 275 (22.8%) SFM, and 379 (31.5%) M. The ROM for each category was 9.1%, 1.5%, 37.5%, 96.9%, and 98.2%, respectively. The highest sensitivity was achieved when AUS/ALUS, SFM, and M were considered positive for malignancy, whereas maximum diagnostic accuracy was observed when only SFM and M were considered positive. CONCLUSION: The Sydney system is an excellent system for accurately categorising lymph node aspirates with greater reproducibility of reports and better patient management through improved communication between cytopathologist and clinician.

Categorisation of serous effusions using the International System for Reporting Serous Fluid Cytopathology and assessment of risk of malignancy with diagnostic accuracy.

CONTEXT: The International System for Reporting Serous Fluid Cytopathology (ISRSFC) standardises the reporting of serous effusion cytology under five categories: Non-Diagnostic (ND), Negative for Malignancy (NFM), Atypia of Undetermined Significance (AUS), Suspicious for Malignancy (SFM), and Malignant (M). Very few studies have been conducted so far to confirm the risk of malignancy of the different categories. AIMS: The main objectives of our study were to classify serous effusions according to the ISRSFC categories and assess their risk of malignancy (ROM) and performance parameters. MATERIALS AND METHODS: All serous effusion samples received from January 2019 to December 2020 were reclassified according to the ISRSFC. Using histopathological diagnosis as the gold standard, ROM and performance parameters were calculated. RESULTS: A total of 831 pleural effusion samples were reclassified as follows: ND, 3 (0.4%); NFM, 635 (76.4%); AUS, 65 (7.8%); SFM, 60 (7.2%); and M, 68 (8.2%). For 457 peritoneal effusion samples, the reclassifications were ND, 5 (1.1%); NFM, 368 (80.5%); AUS, 19 (4.2%); SFM, 17 (3.7%); and M, 48 (10.5%). All 12 (100%) pericardial effusions belonged to the NFM category. The ROM for the ND, NFM, AUS, SRM, and M categories was 0%, 2.1%, 33.3%, 94.1%, 100%, respectively, in pleural effusions, and 50%, 4.8%, 22.2%, 83.3%, 100%, respectively, in peritoneal effusions. The ROM was 0% for NFM in pericardial effusions. CONCLUSION: The ISRSFC is an excellent system for accurately classifying serous effusions with greater reproducibility of reports and better communication between pathologist and clinician.

Flow cytometry in reactive lymph node aspirates: Evaluation of distribution of populations with immunophenotypic outliers.

BACKGROUND: Diagnostic accuracy of fine needle aspiration cytology for lymphomas has markedly improved when used in conjunction with flow cytometry (FCM), especially to differentiate reactive lymph node aspirates from low-grade lymphomas, a challenge for cytopathologists. Lymphoma diagnosis by FCM depends on detection of immunophenotypic B- and T-cell outliers, also present in benign lymph nodes albeit in subsets of cells. These can mimic heterogenous populations obtained from lymphomas partially involving lymph nodes. METHODS: In the present study, FCM of fine needle aspiration/scrape material from 30 cases of benign lymph nodes was evaluated for the distribution of lymphoid populations and the presence and percentages of immunophenotypic outliers. RESULTS: The majority of the samples were cervical nodes with all cases showing T-cell predominance. CD5/CD19 co-expression was seen in 23.94 ± 9.51% (20 cases) and CD10/CD19 co-expression in 3.2%-20.2% (8 cases) of B-cell events. None of these cases showed light chain restriction. Loss of CD7 (2%-28.4%) and CD5 (12.7%) expression was seen in 17 cases and 1 case, respectively, of T-cell events. CONCLUSION: Immunophenotypic outliers suggestive of lymphomas could be seen in non-lymphomatous lymph node aspirates in a subset of the cell population. However, they could be defined as benign due to absence of light chain restriction and normal CD4:CD8 ratios in all but one case, which was confirmed to be benign after clinical correlation and excisional biopsy. Thus, multiparameter FCM along with clinicoradiological correlation can prevent overdiagnosis of lymphomas.

Uterine Serous Cystadenoma or Endosalpingiosis?: A Case Report with a Review of Literature.

Endosalpingiosis is a nonneoplastic lesion defined by the presence of tubal epithelium at ectopic sites such as the peritoneum, bladder, appendix, and even uterus. They may be asymptomatic and detected incidentally on ultrasonography. However, cystic endosalpingiosis is also known to be a mimicker of ovarian neoplasms. It is crucial for both the clinician and the pathologist to be aware of this benign lesion so that overdiagnosis and overtreatment can be avoided. We report a case of endosalpingiosis of the uterine serosa in a 45-year-old woman which was misdiagnosed as an adnexal cyst on radiological investigations.

Squamous Cell Carcinoma of the Middle Ear-A Common Tumor at an Uncommon Site.

Squamous cell carcinoma of the middle ear is a very rare tumor. Early detection is uncommon as the tumor usually manifests as persistent ear discharge and otalgia, often misdiagnosed as chronic suppurative otitis media. We present a rare case of squamous cell carcinoma of the middle ear which clinically presented as chronic suppurative otitis media. Therefore, clinicians should have a high index of suspicion for clinically refractive cases of otorrhea, otalgia, excess bleeding, and non-responsiveness to treatment. All polyps and granulation tissue in EAC and middle ear should be submitted for histopathological examination especially in cases refractory to treatment.

Evaluation of Histomorphological Changes in Breast Cancer Post-Neoadjuvant Chemotherapy.

Breast cancer, a leading cause of global female mortality, demands comprehensive diagnostic and therapeutic strategies. This study delves into the nuanced realm of post-neoadjuvant chemotherapy breast cancer specimens, emphasizing the imperative need for pathologists to discern stromal and nuclear alterations adeptly. The investigation, encompassing 100 female patients with a mean age of 47.5 years, elucidates the demographic and clinicopathological parameters. Predominantly presenting as palpable lumps (85%), invasive ductal carcinoma emerged as the predominant histological type (98%). The primary focus of the study revolves around the morphological changes post-neoadjuvant chemotherapy, with a meticulous qualitative analysis encompassing stromal elements (fibrosis, elastosis, calcification) and nuclear features (pyknosis, hyperchromasia). Notably, the response to chemotherapy, classified by the International Union against Cancer criteria, delineates a substantial pathological complete response (55%), partial response (35%), and limited non-response (10%). The therapeutic landscape includes a majority of cases undergoing extensive chemotherapy cycles, primarily featuring the cyclophosphamide, doxorubicin, and paclitaxel regimen. Remarkably, this investigation unveils fibrosis (63%) and elastosis/collagenization (51%) as prevalent stromal changes, while pyknosis (58%) and hyperchromasia (48%) dominate nuclear alterations. In conclusion, this retrospective study provides a comprehensive overview of post-neoadjuvant chemotherapy breast cancer specimens, shedding light on the intricate interplay of clinical parameters, treatment responses, and histopathological changes. The findings underscore the pivotal role of pathologists in accurately diagnosing and grading tumors in the evolving landscape of breast cancer management.

Unraveling the intricacies of cancer-associated fibroblasts: a comprehensive review on metabolic reprogramming and tumor microenvironment crosstalk.

Cancer-associated fibroblasts (CAFs) are crucial component of tumor microenvironment (TME) which undergo significant phenotypic changes and metabolic reprogramming, profoundly impacting tumor growth. This review delves into CAF plasticity, diverse origins, and the molecular mechanisms driving their continuous activation. Emphasis is placed on the intricate bidirectional crosstalk between CAFs and tumor cells, promoting cancer cell survival, proliferation, invasion, and immune evasion. Metabolic reprogramming, a cancer hallmark, extends beyond cancer cells to CAFs, contributing to the complex metabolic interplay within the TME. The 'reverse Warburg effect' in CAFs mirrors the Warburg effect, involving the export of high-energy substrates to fuel cancer cells, supporting their rapid proliferation. Molecular regulations by key players like p53, Myc, and K-RAS orchestrate this metabolic adaptation. Understanding the metabolic symbiosis between CAFs and tumor cells opens avenues for targeted therapeutic strategies to disrupt this dynamic crosstalk. Unraveling CAF-mediated metabolic reprogramming provides valuable insights for developing novel anticancer therapies. This comprehensive review consolidates current knowledge, shedding light on CAFs' multifaceted roles in the TME and offering potential targets for future therapies.

The evolving landscape of immunohistochemistry in cervical and uterine carcinoma in gynecologic oncology: current status and future directions.

Immunohistochemistry (IHC) has become an indispensable tool in routine gynecological pathology, particularly with the advancements in molecular understanding and histological classification of gynecological cancers. This evolution has led to new immunostainings for diagnostic and classification purposes. This review describes the diagnostic utility of IHC in gynecological neoplasms, drawing insights from literature reviews, personal experiences, and research findings. It delves into the application of IHC in resolving morphologically equivocal cases, emphasizing its role in achieving an accurate diagnosis. The selection of appropriate immunomarkers for common scenarios encountered in gynecological pathology aids pathologists in navigating complex cases. Specifically, we focus on cervical and endometrial malignancies, elucidating the molecular rationale behind the use of specific immunohistochemical markers. An updated overview of essential immunohistochemical markers provides knowledge for precise diagnosis and classification of gynecological cancers. This review serves as a valuable resource for clinicians and researchers involved in the management and study of gynecological malignancies, facilitating improved patient care and outcomes.

Spermatocytic tumor with extensive lymphovascular invasion in a young male.

Spermatocytic tumors are rare testicular cancers, accounting for less than 1 % of all testicular neoplasms, usually affecting older men. This report details a 35-year-old male with a spermatocytic tumor featuring extensive lymphovascular invasion. The patient had a painless, slow-growing right testicular mass, with normal serum tumor markers. Ultrasound and CT scans suggested malignancy. Post-orchiectomy, histopathology confirmed a spermatocytic tumor with polymorphic cells and lymphovascular invasion. Immunohistochemical staining was positive for SALL4 and CD117, negative for OCT4, AFP, and CD30. The patient underwent chemotherapy and remained recurrence-free for a year, highlighting the need for accurate diagnosis and long-term monitoring.

Association of tumor budding and tumor infiltrating lymphocytes with clinicopathological parameters in gallbladder carcinoma.

PURPOSE: Gallbladder carcinoma (GBC) poses significant challenges in oncology due to its aggressive nature and limited treatment options. The lack of effective biomarkers for early detection and prognosis exacerbates the prognosis for GBC patients. Tumor budding (TB) and tumor infiltrating lymphocytes (TILs) have emerged as potential prognostic indicators in various cancers, reflecting tumor-host immune interactions and tumor aggressiveness. The study of TB and TILs in GBC is particularly important due to the limited literature available. METHODS: This retrospective observational study aimed to evaluate the association of TB and TILs with clinicopathological parameters in GBC patients. Clinicopathological data were collected from patients with histologically confirmed GBC who underwent surgical resection. The sections were evaluated for TB and TILs using standardized methods. Statistical analysis was performed to assess associations between these parameters and clinicopathological variables. RESULTS: Tumor stage and grade showed significant associations with TB and TILs, indicating their potential as prognostic markers. High TB correlated with advanced tumor stage and higher grade, while high TIL infiltration was associated with early tumor stage and lower grade. Additionally, TILs exhibited a significant association with lymphovascular invasion. Interestingly, an inverse association was observed between TB and TILs, highlighting the dynamic interplay between tumor aggressiveness and host immune response. CONCLUSION: TB and TILs hold prognostic significance in GBC, offering insights into its pathogenesis and potential therapeutic targets. Future research exploring the mechanistic underpinnings of tumor-host immune interactions in GBC is crucial for translating these findings into clinical applications and improving outcomes for patients.