What is CD10 (neutral endopeptidase, CALLA) used for in diagnostic pathology?

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CD10 Marker in Diagnostic Pathology

CD10 (neutral endopeptidase, also known as CALLA - common acute lymphoblastic leukemia antigen) is primarily used to classify lymphoid malignancies, particularly to identify follicular lymphoma, Burkitt lymphoma, and certain B-cell acute lymphoblastic leukemias, and secondarily serves as a marker for hepatocellular differentiation and specific epithelial tumors. 1

Primary Applications in Hematologic Malignancies

Essential Lymphoma Immunophenotyping Panel

CD10 is included in the essential paraffin immunohistochemistry panel for lymphoma diagnosis alongside CD45, CD20, CD3, Ki-67, BCL2, BCL6, and TdT 1. For flow cytometry analysis, CD10 appears in the core panel with kappa/lambda, CD45, CD20, CD3, CD5, CD19, and TdT 1.

Specific Lymphoma Subtypes

Follicular Lymphoma: CD10 positivity is a characteristic feature of follicular lymphoma, with the typical immunophenotype being CD10+, BCL2+, CD20+, and BCL6+ 1. CD10 improves classification accuracy for follicular lymphoma and diffuse large B-cell lymphoma beyond what CLL-focused panels provide 1. Notably, rare cases of follicular lymphoma may be CD10-negative, requiring additional markers for diagnosis 1.

Burkitt Lymphoma: The typical immunophenotype includes CD10 positivity along with surface immunoglobulin, CD20, Ki-67 near 100%, BCL2 negativity, and BCL6 positivity 1. CD10 is essential in the diagnostic workup to distinguish Burkitt lymphoma from other aggressive B-cell lymphomas 1.

B-Cell Acute Lymphoblastic Leukemia: CD10 establishes B-lineage when combined with strong CD19 expression and at least one of cytoplasmic CD79a, cytoplasmic CD22, or CD10 2. CD10 is widely used to define subgroups within B-ALL and detect leukemic blasts in bloodstream 3.

Consensus Lymphoproliferative Disorder Panel

In resource-limited settings, CD10 appears in 42% of recommended lymphoproliferative disorder panels and is included in the consensus 8-marker panel: CD19, CD5, kappa, lambda, CD20, CD10, CD45, and CD23 1. While the Rawstron consensus CLL panel lists CD10 as "recommended" rather than "required," its inclusion improves diagnostic accuracy for lymphoproliferative disorders beyond chronic lymphocytic leukemia 1.

Secondary Applications in Non-Hematologic Tissues

Hepatocellular Carcinoma Diagnosis

CD10 demonstrates higher specificity and sensitivity for hepatocellular carcinoma diagnosis compared to traditional markers like HepPar-1 and glypican-3 1. CD10 is part of the hepatocellular differentiation marker panel that includes HepPar-1, Arginase-1, pCEA, glypican-3, and BSEP, with CD10 showing superior performance alongside pCEA and BSEP 1. The staining pattern is typically canalicular (cytoplasmic and membrane) in hepatocellular carcinoma 1.

Urothelial Carcinoma

CD10 shows moderate to strong immunostaining in 67% of urothelial neoplasms with predominantly cytoplasmic pattern 4. High-grade urothelial carcinomas demonstrate significantly stronger staining intensity (mean 2.5) compared to dysplasia (mean 1.7) and low-grade lesions (mean 1.3), with more diffuse distribution in high-grade tumors 4.

Differential Diagnosis Considerations

CD10 expression in stromal cells (rather than tumor cells) can indicate invasive properties in basal cell carcinoma, where CD10-positive tumor cells favor well-circumscribed margins while CD10-negative tumor cells with CD10-positive stroma correlate with infiltrating margins 5. In cutaneous squamous cell carcinoma, tumor cells are consistently CD10-negative while stromal cells show expression in 81% of cases 5.

Practical Diagnostic Algorithm

Initial Assessment: Include CD10 in the first-line immunophenotyping panel when evaluating suspected lymphoma, using either paraffin immunohistochemistry (CD45, CD20, CD3, CD10, Ki-67, BCL2, BCL6, TdT) or flow cytometry (kappa/lambda, CD45, CD20, CD3, CD5, CD19, CD10, TdT) 1.

Interpretation for Lymphoid Malignancies: CD10 positivity in a CD20+ B-cell population suggests follicular lymphoma, Burkitt lymphoma, or germinal center-type diffuse large B-cell lymphoma, requiring correlation with BCL2, BCL6, Ki-67, and cytogenetics/FISH for t(14;18), MYC, and BCL6 rearrangements 1.

Hepatocellular vs. Cholangiocellular Differentiation: When evaluating primary liver tumors, use CD10 alongside pCEA and BSEP for hepatocellular differentiation, contrasting with cytokeratin 7 and 19 for cholangiocytic differentiation 1.

Critical Caveats

Post-Rituximab Evaluation: Exercise caution when interpreting CD20 and CD10 results after rituximab therapy, as surface epitopes may be blocked for several months, potentially yielding false-negative results 1. Use CD79a as an alternative pan-B-cell marker in post-treatment samples 1.

Tissue Requirements: Fine needle aspiration or core needle biopsy alone is generally insufficient for initial lymphoma diagnosis 1. Excisional or incisional biopsy provides adequate tissue architecture and material for comprehensive immunophenotyping including CD10 assessment 1.

Non-Lineage Specificity: CD10 is not lineage-specific and appears in various normal tissues including renal tubules, glomeruli, hepatic canaliculi, and germinal centers 3. In normal skin, CD10 marks periadnexal mesenchymal cells and dermal fibroblasts 6. This broad expression pattern requires careful interpretation within appropriate clinical and morphologic context 3, 7.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Diagnostic Criteria for Hematological Malignancies

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

CD10 immunohistochemical staining in urothelial neoplasms.

American journal of clinical pathology, 2005

Research

Immunohistochemical Expression of CD10 in Cutaneous Basal and Squamous Cell Carcinomas.

Journal of the Egyptian National Cancer Institute, 2007

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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