Lymphoma

Lymphomas of the orbit and adnexa (OAL)

• Most ocular lymphomas are non-Hodgkins type therefore are B cell lymphomas (Typically low-grade)

• Incidence of systemic disease

• Conjunctiva: 20%

  • “Salmon-patch” appearance of conjunctiva
  • Multiple small cells with pleomorphism seen on histology

• Orbit: 35%

  • Lacrimal gland: 40%
  • Eyelid: 67%

• Benign lymphoid hyperplasia

  • 20-25% will become lymphoma within 5 years. 6-monthly follow-ups are therefore recommended
  • Often involves lacrimal gland: non-axial proptosis, ptosis, palpable mass
  • Mature T cells

• Atypical lymphoid hyperplasia: middle-ground between benign and malignant lymphoma

  • Borderline cellular maturity, larger nuclei

• Malignant lymphoma

  • Immature malignant B cells

  • Extranodal marginal zone lymphoma (EMZL): most common ocular lymphoma. Low grade B-cell lymphoma derived from MALT

    • Typically arises from lacrimal gland: responds well to radiotherapy and R-CHOP

  • Follicular lymphoma

  • Diffuse large B-cell lymphoma: aggressive

• CT-scan: lesions will mold to orbital structures rather than erode them

  • Otherwise they all look the same on CT, so biopsy required

• Biopsy: fresh tissue and formalin fixed for H&E staining

• Radiotherapy is the mainstay of treatment (cp. PIL)

Primary intraocular lymphoma (PIL)

• Most common type of lymphoma affecting the eye

• May mimic conditions like uveitis (masquerade)

• The immunohistochemical stain CD20 can be used to detect lymphocytes and suggest lymphoma

• Risk factors: immunosuppression

• Categories

  • Vitreoretinal: commonest type of intraocular lymphoma

    • 90% bilateral, 85% coexistent intracranial disease
    • Associated with CD4 counts <30 in HIV patients and with EBV infections
    • Presents as uveitis masquerade syndrome: ‘vitritis’, yellow sub-RPE plaques (‘leopard spotting’)
      • Steroids may be helpful at first but course is then refractory
    • CNS features: SOL features, meningeal, dementia, stroke-like episodes
    • Requires diagnostic vitrectomy as well as MRI, LP etc.
    • Main treatment is radiotherapy and chemotherapy

  • Uveal: choroidal, ciliary, iridal

    • Uveal lymphoma is much more likely to be secondary than primary
    • Commonest types spreading to the eye are
      • Diffuse large B-cell lymphoma
      • Multiple myeloma
      • Waldenstrom's macroglobulinaemia
    • Diffuse yellowish, choroidal thickening, may mimic melanoma, scleritis, multifocal choroiditis

• Hodgkin’s: characterised by the Reed-Sternberg cell (abnormal B cell). 20% of lymphomas

• Non-Hodgkin’s: all other lymphomas

  • Mostly B-cell type which include follicular, Burkitt’s, MALToma, mantle cell and Waldenstrom’s macroglobulinemia
  • T cell type: includes cutaneous lymphoma and others

• Typically high-grade (cp. OAL)

• Cytological assessment of lymphoma cells via vitreous, retinal or sub-retinal biopsy is gold standard for diagnosis

  • Usually via diagnostic vitrectomy
  • Cytokine analysis: B-cell malignancies secrete high levels of IL-10. Therefore high IL-10:IL-6 ratios (>1.0) are suggestive of primary intraocular lymphoma
  • Monoclonal IgH gene rearrangement on PCR is suggestive
  • High frequency of myeloid differentiation primary response gene 88 mutations (can be detected via PCR)
  • Kappa:lambda light-chain ratio of >3 or <0.6 suggests monoclonality

• Chemotherapy is the mainstay of treatment (cp. OAL)