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Hassall corpuscle

Histology / ImmunologyImmune/LymphaticThymus

Summary

Hassall corpuscles (thymic corpuscles) are whorled clusters of concentrically arranged, keratinized epithelial reticular cells found in the thymic medulla. They are a histologic hallmark of the thymic medulla and are involved in T-cell regulation/tolerance, notably by secreting thymic stromal lymphopoietin (TSLP) to promote regulatory T-cell development.

Detail

**Definition/Histology:** Hassall corpuscles are eosinophilic, concentric, whorled structures (~20–100 µm) made of terminally differentiated, keratinized medullary thymic epithelial cells (mTECs). They are found ONLY in the thymic medulla, which distinguishes the medulla from the cortex on H&E (medulla is paler, with fewer lymphocytes). Centers may calcify or become cystic with age.

**Thymus organization (high-yield):** - Cortex: densely packed immature thymocytes (double-negative → double-positive CD4+/CD8+); site of POSITIVE selection by cortical epithelial cells (MHC I/II recognition). Dark-staining. - Medulla: mature single-positive (CD4+ or CD8+) T cells, mTECs, dendritic cells, macrophages, and Hassall corpuscles; site of NEGATIVE selection (central tolerance) via AIRE-driven expression of tissue-specific antigens. - Embryology: epithelium derived from the endoderm of the 3rd pharyngeal pouch (with inferior parathyroids); lymphocytes derive from mesoderm/bone marrow precursors.

**Function:** - Not fully defined, but Hassall corpuscles secrete thymic stromal lymphopoietin (TSLP), which activates thymic dendritic cells to promote development of CD4+CD25+ FOXP3+ regulatory T cells (Tregs) and supports central tolerance. - Also may help clear apoptotic thymocytes.

**Clinical significance:** - DiGeorge syndrome (22q11.2 deletion; failure of 3rd/4th pouch development): thymic aplasia/hypoplasia → absent Hassall corpuscles, low T cells, recurrent viral/fungal infections, hypocalcemia (parathyroid hypoplasia), conotruncal cardiac defects (tetralogy of Fallot, truncus arteriosus), facial anomalies (CATCH-22). - SCID: thymic hypoplasia with a paucity of lymphocytes and sometimes absent/poorly formed Hassall corpuscles. - Thymoma (e.g., myasthenia gravis association): neoplastic epithelial cells; may show disrupted architecture. - AIRE defect (APECED/APS-1): impaired negative selection → autoimmunity (mucocutaneous candidiasis, hypoparathyroidism, adrenal insufficiency). - Thymic involution with age: the thymus is replaced by adipose tissue after puberty; Hassall corpuscles become less prominent and may calcify.

**Buzz/Exam pearls:** "Whorled eosinophilic structures in the medulla" = Hassall corpuscles. Absent in DiGeorge. Cortex = positive selection; medulla = negative selection. Don't confuse with splenic white pulp/lymphoid follicles or Peyer patches (these lack Hassall corpuscles).

Sources

  • First Aid for the USMLE Step 1 (Immunology: Lymphoid structures; Embryology)
  • Junqueira's Basic Histology: Text and Atlas (Lymphoid Organs: Thymus)
  • Robbins & Cotran Pathologic Basis of Disease (Thymus; Immunodeficiency)
  • Abbas, Cellular and Molecular Immunology (T-cell development and tolerance)
  • Watanabe N et al. Hassall's corpuscles instruct dendritic cells to induce CD4+CD25+ regulatory T cells in human thymus. Nature 2005;436:1181-5

Reviewed by Medusa editorial — medical student review. Information here is for study reference only and is not medical advice. Spotted an error? Let us know.