Subtitle: Normal thymus histology made simple: lobules, cortex and medulla, Hassall corpuscles, T-cell selection, immunostains, involution and the diseases that matter, with virtual slides and 10 MCQs.
Author: PathologyMCQ Editorial Board
Category: Normal Histology
Last Updated: October 2026
Read Time: 7 minutes
At-a-Glance
- The thymus is a primary lymphoid organ in the anterior mediastinum where T cells mature. Its epithelium comes from the third pharyngeal pouch.
- Each lobule has a dark cortex (immature thymocytes) and a pale medulla (mature T cells, Hassall corpuscles).
- Positive selection happens in the cortex; negative selection mainly in the medulla, driven by AIRE.
- After puberty the thymus involutes and is replaced by fat, but islands of thymic tissue persist.
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Architecture at a Glance
A fibrous capsule sends septa into the gland, dividing each of the two lobes into lobules. Every lobule has an outer cortex and an inner medulla, and the medulla is continuous between neighbouring lobules.
Thymic lobule at low powerCortex vs medulla
CortexDark, denseImmature thymocytesCD4+CD8+ double positive, TdT+, CD1a+
CortexStarry skyTingible body macrophagesClear the many thymocytes that die during selection
MedullaPale, looserMature T cellsCD4 or CD8 single positive, TdT negative
MedullaHassall corpusclesEpithelial whorlsConcentric, sometimes keratinised; unique to the medulla
Spot it: lobules of dark cortex around pale medulla with Hassall corpuscles = thymus.
The Cortex
- Thymocytes: densely packed immature T cells. Precursors from the bone marrow enter via vessels at the corticomedullary junction, travel out to the subcapsular cortex, then mature as they move inwards.
- Cortical epithelial cells: a cytokeratin-positive meshwork that presents self-MHC and drives positive selection.
- Tingible body macrophages: scattered throughout the cortex, giving a normal starry-sky pattern as they clear apoptotic thymocytes.
The Medulla
- Medullary epithelial cells: express tissue-restricted self-antigens under AIRE control.
- Hassall corpuscles: concentric whorls of epithelial cells, sometimes keratinised or calcified. They are thought to help regulatory T cells develop.
- Dendritic cells: present self-antigen and help delete self-reactive T cells.
- Scattered B cells and myoid cells are normal; myoid cells are desmin positive.
How T Cells Are Selected
Thymic selection
| Step | Where | What happens |
|---|---|---|
| Entry | Corticomedullary junction | Bone marrow precursors arrive through vessels |
| Positive selection | Cortex | Thymocytes that recognise self-MHC survive; the rest die (most of them) |
| Negative selection | Mainly medulla | Strongly self-reactive T cells are deleted (AIRE, dendritic cells) |
| Regulatory T cells | Medulla | FOXP3+ Tregs develop, helped by Hassall corpuscles |
| Exit | Corticomedullary junction | Mature naive T cells leave for the periphery |
Immunostains
Normal thymus immunoprofile
| Component | Positive | Negative / notes |
|---|---|---|
| Cortical thymocytes | TdT, CD1a, CD99, CD3, CD4 and CD8 | Mimic T-lymphoblastic lymphoma: look for epithelium |
| Medullary T cells | CD3, CD4 or CD8 | TdT and CD1a negative |
| Thymic epithelium | Cytokeratins (AE1/AE3, CK19), p63, p40 | CD5 and CD117 negative (positive in thymic carcinoma) |
| Hassall corpuscles | Cytokeratins, including high molecular weight | Highlights medullary location |
| Myoid cells | Desmin, myogenin | Rare, in the medulla |
Age Changes and Involution
- Infancy and childhood: the thymus is largest relative to body size, with a thick, dark cortex.
- After puberty: the parenchyma shrinks and is progressively replaced by adipose tissue.
- Adults: small islands of cortex and medulla with Hassall corpuscles remain within fat and still produce some T cells.
- Stress involution: acute illness or steroids can rapidly deplete the cortex in children.
Virtual Slides
Compare a young thymus with an involuted adult thymus, then look at lymphoid follicular hyperplasia. Tap an annotated region to zoom to it.
Virtual slides · real casesThymus across the lifespan
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What to look for
Drag to pan · pinch or double-tap to zoom · use the + / − buttons
Clinical Significance
Thymic conditions to know
| Condition | Key histology | Association |
|---|---|---|
| Thymic follicular hyperplasia | Lymphoid follicles with germinal centres in the medulla | Myasthenia gravis, other autoimmune disease |
| True thymic hyperplasia | Enlarged gland with normal architecture | Rebound after chemotherapy or stress |
| Thymoma | Neoplastic epithelial cells with variable lymphocytes | Myasthenia gravis and other paraneoplastic syndromes; all regarded as malignant |
| Thymic carcinoma | Overtly malignant epithelium, CD5 and CD117 positive | Aggressive; few immature T cells |
| DiGeorge syndrome | Absent or hypoplastic thymus | 22q11.2 deletion, hypocalcaemia, cardiac defects |
Video lesson
Normal thymus histology, explained
A complete video walk-through of thymic histology.
Recommended course
Approach-Based Histopathology & Cytology
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Test Yourself: 10 MCQs
Normal thymus: 10 MCQs
Histology, selection, immunostains and disease, with instant explanations.
Score: 0 / 10
More practice: the thymoma types (WHO) →
Exam Pearls
- Dark cortex, pale medulla, Hassall corpuscles: thymus.
- Cortical thymocytes are TdT+, CD1a+, CD99+; do not mistake them for lymphoblastic lymphoma.
- Positive selection in the cortex, negative selection in the medulla (AIRE).
- Myasthenia gravis: thymic follicular hyperplasia or thymoma.
- Thymic carcinoma is CD5 and CD117 positive; normal thymic epithelium is negative.
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Related reads: Types of thymoma (WHO) → · Approach-based course →
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References
- Mills SE, ed. Histology for Pathologists. 5th ed. Wolters Kluwer; 2019.
- WHO Classification of Tumours Editorial Board. Thoracic Tumours. 5th ed. IARC; 2021.
- Young B, O’Dowd G, Woodford P. Wheater’s Functional Histology. 6th ed. Elsevier; 2014.
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