Original article / research
Year : 2026 Month : October Volume : 15 Issue : 4 Page : PO06 - PO11 Full Version

Prognostic Value of CD8 and its Association with Stroma in Periampullary Carcinoma: A Cohort Study
Sandhya Krupal Variganji, Ramya Chitturi, Muhseenah, Sreedhar Bora
1. Assistant Professor, Department of Pathology, Guntur Medical College, Guntur, Andhra Pradesh, India. 2. Assistant Professor, Department of Pathology, Guntur Medical College, Guntur, Andhra Pradesh, India. 3. Assistant Professor, Department of Community Medicine, Guntur Medical College, Guntur, Andhra Pradesh, India. 4. Professor, Department of Pathology, Guntur Medical College, Guntur, Andhra Pradesh, India.
 
Correspondence Address :
Dr. Sandhya Krupal Variganji,
Flat No: 323, Second Floor, Third Block, Indhira Towers, Near American Hospital,
Labbipet, Vijayawada-520002, Andhra Pradesh, India.
E-mail: sandhyavariganji@gmail.com
 
ABSTRACT
: Introduction: Periampullary Carcinoma (PAC) is a rare gastrointestinal malignancy originating from within 2 cm of the Ampulla of Vater. It accounts for 0.5-2% of gastrointestinal cancers and includes Ampullary Carcinoma (AC), Pancreatic head Carcinoma (PC), Distal Common bile duct Carcinoma (DCC), and Duodenal Carcinoma (DC). PACs show heterogeneous histopathological features, characterised by intratumoural spatial complexity in cellularity, extracellular matrix, and necrosis. CD8+ Tumour-Infiltrating Lymphocytes (TILs) are cytotoxic T lymphocytes. Their activity, along with that of other immune cells in the tumour microenvironment, affects cancer progression and immune regulation.

Aim: To assess and quantify CD8+ TILs and stromal density using clinicohistopathological features and Immunohistochemistry (IHC).

Materials and Methods: This cohort study was done over a 48-month period (February 2021 to January 2025) at Guntur Medical College, Guntur, Andhra Pradesh, India. Representative Formalin-Fixed, Paraffin-Embedded (FFPE) tissue blocks from ampullary growth were selected, and sections were analysed using H&E, Masson’s trichrome special stain, and CD8 and α-SMA IHC. Clinicohistopathological data were recorded. Variables {subtype, grade, stage, Lymphovascular Invasion (LVI), lymph node status} were evaluated using Fisher’s exact test, Kaplan-Meier methods, and Cox regression.

Results: A total of 31 cases were evaluated (mean age: 57.4 years). The study comprised 15 patients (48.4%) aged <59 years and 16 (51.6%) aged ≥59 years. Significant associations were identified between high total CD8+ TILs expression and patient age, tumour grading, gemcitabine use, stromal density, Smooth Muscle Actin (SMA) activity, and histological subtype (p-value <0.05 for all). High CD8+ TIL infiltration declined as stromal density increased (loose: 11/15 vs moderate: 4/11 vs strong: 0/5; p-value=0.009). Univariable Cox regression analysis revealed a favourable prognostic trend for patients with higher CD8 expression (HR=0.78, p-value=0.595). The median Overall Survival (OS) was 33 months. In multivariable analysis, high total CD8+ TILs expression was associated with significantly improved OS (HR 0.11, p-value=0.005); however, due to sample size constraints, this adjusted estimate represents an exploratory prognostic trend in patients receiving adjuvant chemotherapy.

Conclusion: A loose stromal microenvironment facilitates robust, protective CD8+ TILs infiltration, whereas a dense stroma often limits CD8+ TILs efficacy. While these exploratory findings highlight total CD8+ TILs as a promising prognostic biomarker, larger multicentre cohort validation is required before clinical integration. Combining standard chemotherapy with targeted stromal remodelling and immune checkpoint inhibitors holds significant potential to enhance CD8+ TIL cytotoxicity and improve clinical outcomes.
Keywords : Ampulla of vater, Prognostic biomarker, Tumour-infiltrating lymphocytes
DOI and Others : DOI: 10.7860/NJLM/2026/90322.3000 Date of Submission: May 15, 2026 Date of Peer Review: May 29, 2026 Date of Acceptance: Jul 08, 2026 Date of Publishing: Oct 01, 2026 AUTHOR DECLARATION: • Financial or Other Competing Interests: None • Was Ethics Committee Approval obtained for this study? Yes • Was informed consent obtained from the subjects involved in the study? Yes • For any images presented appropriate consent has been obtained from the subjects. Yes PLAGIARISM CHECKING METHODS: • Plagiarism X-checker: May 18, 2026 • Manual Googling: Jun 30, 2026 • iThenticate Software: Jul 07, 2026 (4%) ETYMOLOGY: Author Origin EMENDATIONS: 8
 
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