Intraocular lymphoma
Encyclopedia
Intraocular lymphoma is a rare malignant form of eye cancer. Intraocular lymphoma may affect the eye secondarily from a metastasis from a non-ocular tumor or may arise within the eye primarily (primary intraocular lymphoma, PIOL). PIOL is a subset of primary central nervous system lymphoma
(PCNSL). PCNSL (and PIOL) are most commonly a diffuse large B-cell immunohistologic subtype of non-Hodgkin's lymphoma according to the World Health Organization
(WHO) classification of lymphomas. The most common symptoms of PIOL include blurred or decreased vision due to tumor cells in the vitreous. Interestingly, most cases of PIOL eventuate to central nervous system involvement (PCNSL) while only 20% of PCNSL lead to intraocular (PIOL) involvement. PIOL and PCNSL remain enigmas because both structures are immunologically privileged sites (the brain sits behind the blood-brain barrier
and the retina sits behind the blood-retinal barrier
) and so do not normally have immune cells trafficking through these structures. What is more, while the vast majority of PCNSL in patients with acquired immune deficiency syndrome (AIDS) is related to the Epstein-Barr virus (EBV), the development of PCNSL and PIOL in immunocompetent patients is unknown and shows no general relation to infectious DNAs.
In immunocompetent patients, PIOL most commonly affects patients in their fifties and sixties. AIDS
patients typically develop the disease earlier in their lives.
PIOL affects the sub-retinal pigment epithelium (RPE), can invade into the retina, the vitreous, and the optic nerve. Ophthalmoscopy
frequently reveals creamy yellow-to-orange colored subretinal infiltrates. Fluorescein angiography
may reveal "leopard spot" patterns due to sub-RPE infiltrates that stain early and progressively or mottling of the RPE due to hyper- and hypofluorescent window defects
PIOL is known as a masquerade syndrome because it frequently simulates the signs and symptoms of uveitis. As such, PIOL is frequently treated with corticosteroids. Occasionally, PIOL has mimicked a retinitis and has been treated with antiviral medication. It is not until the supposed uveitis fails to respond to treatment, becomes recalcitrant to treatment, or shows worsening with discontinuation of corticosteroid treatment that another cause is sought out. If PIOL is suspected, it is important to first obtain a magnetic resonance image (MRI) of the brain to rule out cerebral involvement (PCNSL). If MRI is negative, lumbar puncture with cerebrospinal fluid
(CSF) cytology should be performed to further rule out CNS disease. Histopathologic identification of atypical lymphocytes is considered the gold standard for diagnosing PCNSL/PIOL. If CSF cytology is negative or inconclusive and PIOL is suspected, a vitrectomy is often performed with cytologic analysis. Furthermore, adjunctive testing including polymerase chain reaction (PCR) amplification to identify monoclonal rearrangements of the immunoglobulin heavy chain (IgH) gene (for B-cell lymphomas) or T-cell receptor (TCR, for the very rare T-cell lymphomas) can be performed.
Previously, radiation therapy
was the mainstay treatment for PCNSL/PIOL, but methotrexate
has now become first-line.
Primary central nervous system lymphoma
A primary central nervous system lymphoma , also known as microglioma and primary brain lymphoma, is a primary intracranial tumor appearing mostly in patients with severe immunosuppression . PCNSLs represent around 20% of all cases of lymphomas in HIV infections...
(PCNSL). PCNSL (and PIOL) are most commonly a diffuse large B-cell immunohistologic subtype of non-Hodgkin's lymphoma according to the World Health Organization
World Health Organization
The World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health. Established on 7 April 1948, with headquarters in Geneva, Switzerland, the agency inherited the mandate and resources of its predecessor, the Health...
(WHO) classification of lymphomas. The most common symptoms of PIOL include blurred or decreased vision due to tumor cells in the vitreous. Interestingly, most cases of PIOL eventuate to central nervous system involvement (PCNSL) while only 20% of PCNSL lead to intraocular (PIOL) involvement. PIOL and PCNSL remain enigmas because both structures are immunologically privileged sites (the brain sits behind the blood-brain barrier
Blood-brain barrier
The blood–brain barrier is a separation of circulating blood and the brain extracellular fluid in the central nervous system . It occurs along all capillaries and consists of tight junctions around the capillaries that do not exist in normal circulation. Endothelial cells restrict the diffusion...
and the retina sits behind the blood-retinal barrier
Blood-retinal barrier
The blood–retinal barrier, or the BRB, is part of the blood–ocular barrier that consists of cells that are joined tightly together to prevent certain substances from entering the tissue of the retina...
) and so do not normally have immune cells trafficking through these structures. What is more, while the vast majority of PCNSL in patients with acquired immune deficiency syndrome (AIDS) is related to the Epstein-Barr virus (EBV), the development of PCNSL and PIOL in immunocompetent patients is unknown and shows no general relation to infectious DNAs.
In immunocompetent patients, PIOL most commonly affects patients in their fifties and sixties. AIDS
AIDS
Acquired immune deficiency syndrome or acquired immunodeficiency syndrome is a disease of the human immune system caused by the human immunodeficiency virus...
patients typically develop the disease earlier in their lives.
PIOL affects the sub-retinal pigment epithelium (RPE), can invade into the retina, the vitreous, and the optic nerve. Ophthalmoscopy
Ophthalmoscopy
Ophthalmoscopy is a test that allows a health professional to see inside the fundus of the eye and other structures using an ophthalmoscope . It is done as part of an eye examination and may be done as part of a routine physical examination...
frequently reveals creamy yellow-to-orange colored subretinal infiltrates. Fluorescein angiography
Fluorescein angiography
Intravenous Fluorescein angiography or fluorescent angiography is a technique for examining the circulation of the retina using the dye tracing method...
may reveal "leopard spot" patterns due to sub-RPE infiltrates that stain early and progressively or mottling of the RPE due to hyper- and hypofluorescent window defects
PIOL is known as a masquerade syndrome because it frequently simulates the signs and symptoms of uveitis. As such, PIOL is frequently treated with corticosteroids. Occasionally, PIOL has mimicked a retinitis and has been treated with antiviral medication. It is not until the supposed uveitis fails to respond to treatment, becomes recalcitrant to treatment, or shows worsening with discontinuation of corticosteroid treatment that another cause is sought out. If PIOL is suspected, it is important to first obtain a magnetic resonance image (MRI) of the brain to rule out cerebral involvement (PCNSL). If MRI is negative, lumbar puncture with cerebrospinal fluid
Cerebrospinal fluid
Cerebrospinal fluid , Liquor cerebrospinalis, is a clear, colorless, bodily fluid, that occupies the subarachnoid space and the ventricular system around and inside the brain and spinal cord...
(CSF) cytology should be performed to further rule out CNS disease. Histopathologic identification of atypical lymphocytes is considered the gold standard for diagnosing PCNSL/PIOL. If CSF cytology is negative or inconclusive and PIOL is suspected, a vitrectomy is often performed with cytologic analysis. Furthermore, adjunctive testing including polymerase chain reaction (PCR) amplification to identify monoclonal rearrangements of the immunoglobulin heavy chain (IgH) gene (for B-cell lymphomas) or T-cell receptor (TCR, for the very rare T-cell lymphomas) can be performed.
Previously, radiation therapy
Radiation therapy
Radiation therapy , radiation oncology, or radiotherapy , sometimes abbreviated to XRT or DXT, is the medical use of ionizing radiation, generally as part of cancer treatment to control malignant cells.Radiation therapy is commonly applied to the cancerous tumor because of its ability to control...
was the mainstay treatment for PCNSL/PIOL, but methotrexate
Methotrexate
Methotrexate , abbreviated MTX and formerly known as amethopterin, is an antimetabolite and antifolate drug. It is used in treatment of cancer, autoimmune diseases, ectopic pregnancy, and for the induction of medical abortions. It acts by inhibiting the metabolism of folic acid. Methotrexate...
has now become first-line.