Upload
hima-bindu
View
51
Download
3
Tags:
Embed Size (px)
Citation preview
OCULAR LYMPHOMA
Lymphoid tumors represent ~10% of biopsy-
proven orbital disorders
Lymphatic tissues do not exist in orbit.
Point of dispute
Orbit contains scattered lymphocytes.
04/15/23
04/15/23
04/15/23
Ocular lymphoma
Orbit is an extranodal site
Depending on the site of involvement,
Orbital
Adnexal
Intraocular
Distribution of common lymphoproliferative lesions of the orbit.
04/15/23
Ocular manifestationsFrequently masquerade as other more benign intraocular
conditions
Proptosis
Visible conjunctival mass
Allergic or infectious conjunctivitis
Uveitis
Multiple evanescent white dot syndrome
Acute retinal necrosis
Herpetic retinitis.
Orbital & Adnexal lymphoma
04/15/23
04/15/23
Orbital and ocular adnexal lymphoma
Insidious onset
Progress over a year before producing symptoms.
Symptoms :20 to pressure effects on surrounding structures.
Clinical features
Painless proptosis with or without motility disturbances
Double vision
Ptosis
Decreased vision.
04/15/23
Orbital and ocular adnexal lymphoma
Unilateral or bilateral.
More common in the anterior superior orbit.
Preseptal portion of the eyelid can be involved.
Usually rubbery to firm on palpation
No palpable bony destruction.
The lacrimal gland, lacrimal sac, EOM can be
similarly involved.
04/15/23
Systemic disease to be suspected
Cervical lymphadenopathy,
Preauricular lymphadenopathy
Parotid gland swelling
Abdominal mass
Thorough physical evaluation
Of primary orbital lymphoid lesions,
50% reactive or atypical hyperplasia
50% malignant lymphoma.
Recent evidence, show systemic disease occurring in
15% to 25% of reactive hyperplasias,
40% of atypical hyperplasias,
20% of well-differentiated lymphomas, and
60% of poorly differentiated lymphomas.
Reactive lymphoid hyperplasia of the bulbar conjunctiva and upper fornix.Appearance is similar to that of malignant lymphoma.
Lymphoid tumor (malignant lymphoma) of bulbar
conjunctiva.
Tumor involves inferior bulbar and forniceal
conjunctiva
(a)Anterior epibulbar extension of a deeper orbital
lymphoma.
(b)The computed tomography (CT) scan reveals a
large molding soft tissue mass tracking along the
medial orbit and extending onto the epibulbar
surface of the LE.
(a)Bilateral lymphoid lesions of the preseptal
portion of the eyelid. On palpation, the lesions had
a doughy consistency.
(b) CT scan demonstrates masses involving the
eyelids and anterior orbit. The clinical examination
is therefore important in the correct interpretation
of these findings.
04/15/23
Differential diagnosis of orbital lymphoma
Idiopathic inflammatory pseudotumor
Orbital lymphoid hyperplasia
Orbital sarcoidosis
Wegener granulomatosis
Chronic dacryoadenitis.
Lymphoma of the lacrimal gland Painless mass
Characteristic salmon-colored mass seen in the
superolateral cul-de-sac,
Often fixed to the orbital rim and is rubbery
Radiographic appearance of the bone is usually normal
CT scan a homogeneous consistency with indistinct
borders
Tendency to mold into the contour of the lacrimal fossa
and the surrounding bony contour.
Bilateral painless enlargement of the lacrimal glands leading to mechanical ptosis.
Intraoperative photo shows the enlarged lacrimal gland.
After chemotherapy for systemic lymphoma.`
Fish flesh appearance
lymphoma
Conjunctiva Lacrimal glandTend to be more
benign ,better long-term prognosis
Those that extend into the orbit tend to be more malignant.
Remain localized in 90% of cases
Appear as a diffuse vertical expansion of the gland,
Mold to both the globe and orbital bone
No bony fossa erosion.
Conjunctival lymphoid ‘salmon-patch’ lesion. This
lymphoid tissue is located within the substantia propria
of the conjunctiva and is freely mobile over the
underlying tunics.
NON HODGKINS B CELL LYMPHOMAS
04/15/23
Subtypes of B-cell nonHodgkin's malignant lymphoma—1. Extranodal B-cell marginal zone
lymphoma, 2. Follicle center cell lymphoma,3. Small lymphocytic lymphoma, 4. Lymphoplasmacytoid lymphoma, 5. Large cell lymphoma, 6. Mantle cell lymphoma,7. Burkitt's lymphoma
1. EXTRANODAL B-CELL MARGINAL ZONE LYMPHOMA
Most common type
Both conjunctival and lacrimal
gland MALT contribute
lysozyme to the tear film.
Chlamydia psittaci is
associated with ocular adnexal
mucosa-associated lymphoid
tissue (MALT) lymphoma
FOLLICULAR LYMPHOMA
04/15/23
• Is relatively rare
• Middle-aged to elderly
• Females
• Relapses are frequent
• Long-term survival: favorable
JAMA Ophthalmol. doi:10.1001/jamaophthalmol.2014.376Published online April 24, 2014.
, A uniform population ofsmall cells (centrocytes) with irregular nuclei (arrows) consistentwith a grade 1 follicular lymphoma
follicles express CD10,
B CELL-CHRONIC LYMPHOCYTIC LEUKEMIASMALL LYMPHOCYTIC LYMPHOMA
Predominantly a disease of the elderly
Present with leukemia involving the orbit
Relatively indolent disease, but it is virtually
incurable with current therapy
May progress to a higher grade large cell
lymphoma (richter transformation).
LYMPHOPLASMACYTOID LYMPHOMA Occurs in elderly
Paraproteinemia is common
Hyperviscosity state
The optic nerve can be
invaded
Papilloedema from CNS
invasion
Resembles lymphoma in its
diffuse infiltration into
lymphoid tissues.
Bone marrow Biopsy:
characteristic mixture of
small lymphoid cells with
various degrees of plasma
cell differentiation.
PLASMA CELL TUMORS Tumors of mature B cells Secrete monoclonal immunoglobulin detected
as the M-spike on serum electrophoresis, associated with high urine and blood content of immunoglobulin.
Light chain fragments excreted in the urine are known as Bence Jones protein.
Multiple myeloma Prototypic systemic plasma cell tumor
Occurs in the elderly, more commonly men
Multiple masses of plasma cells disseminated throughout
the skeletal system and soft tissue.
Extraskeletal metastases in 70% of cases, either by
hematogenous spread or by direct extension.
Metastasize to the kidney, adrenal gland, heart, and liver
Punched-out lesions of the skull and vertebral fractures.
LARGE CELL LYMPHOMA
04/15/23
• Worst prognosis for survival.
• Death occurs within 2 years of
diagnosis JAMA Ophthalmol. doi:10.1001/jamaophthalmol.2014.4644Published online November 13, 2014.
High Ki-67proliferative index exceeding 90%(yellow arrowhead) (originalmagnification ×400).
Burkitt’s lymphoma
A rare tumor
Originally described
in africa.
Most common in
children
Comprising 90% of
pediatric lymphomas
in endemic regions
and one third of
nonendemic pediatric
lymphomas..
•In the orbit, it
typically originates
from the maxillary
marrow space.
•Rapid tumor growth
in the face, with a
doubling time of 3
days
•Tumor of monstrous
proportion in 2 to 4
weeks
"starry sky“ appearance.
B, At high power, -monotonous appearance
Management of Burkitts lymphomaChemotherapy regimens based on cyclophosphamide,
doxorubicin, vincristine, and methotrexate.
Prognosis depends on the volume of disease at
presentation,
If the disease is localized, it can be surgically debulked.
Fifty percent of tumors recur, commonly in the
meninges.
Aggressive disease with meningeal invasion -
chemotherapy with bone marrow transplant.
Mantle cell lymphoma
04/15/23
A, At low power, neoplastic lymphoid cells surround a
small, atrophic germinal center, exhibiting mantle zone
pattern of growth.
B, High-power view shows a homogeneous population of
small lymphoid cells with somewhat irregular nuclear
outlines, condensed chromatin, and scant cytoplasm.
04/15/23
HODGKINS LYMPHOMA
HODGKIN'S LYMPHOMA
30% of all systemic
lymphomas,
Is rare in the orbital soft
tissues and lacrimal
gland, generally
Occurs late in the
patients with
widespread systemic
disease.
Eyelid involvement and tissue necrosis.
mixed cellularity type. diagnostic, binucleate Reed-Sternberg cell
04/15/23
T CELL LYMPHOMAS
T-CELL LYMPHOMA
Rare
Usually occurs during the
late stage of systemic
disease ,or
As a manifestation of
mycosis fungoides.
Only one case of primary t-
cell lymphoma in the orbit
has been described.
(a)T-cell lymphoma limited to the eyelid with
ulceration.
(b)The histopathologic features include the
Pautrier-like microabscess
(a and b) Courtesy of Seymour Brownstein,
MD.
Intra ocular lymphoma
04/15/23
Subtypes of Intra ocular involvement
Primary Central Nervous System
Lymphoma (PCNSL)
Primary Uveal Lymphoma
Metastatic Uveal Lymphoma
Secondary Uveal Lymphoma
Hodgkin’s Lymphoma.
PRIMARY INTRAOCULAR LYMPHOMA
Primary vitreoretinal lymphoma
Vitreous cells and
Geographical subretinal pigment epithelial infiltrative
masses.
Independent nonmetastatic foci of pcnsl
Primary uveal lymphoma
Diffuse or multifocal creamy yellow choroidal
infiltrates in one or both eyes.
Associated with independent foci of visceral NHL
04/15/23
Primary CNS Lymphoma (PCNSL) A subset of diffuse large B-cell NHL
Increasing incidence and high mortality
Usually affects elderly and is unilateral or bilateral
Infiltrates the retina, vitreous, or optic nerve head
60-80% cases develop CNS disease
Often masquerades as a chronic uveitis
Typical clinical findings: vitritis and sub-RPE
yellow–creamy infiltrates
Tumor cells in the anterior chamber ~75% of patients.
Cells simulate iridocyclitis and form a pseudohypopyon.
20anterior segment changes :
Neovascularization of the iris
Neovascularization of the iridocorneal angle
Possible glaucoma.
In rare circumstances, PCNSLO can form a mass in the
iris or angle.
04/15/23
Primary vitreoretinal lymphoma.
Typical geographical subretinal pigment epithelial lesion with relatively few vitreous cells.
Posterior segment : vitreous cells are a typical finding
Fundus :low-lying, yellow-to-white mass deep to the
sensory retina.
Single or multiple, confluent or discrete.
May appear as multiple punctate lesions.
Infiltrative and involve all layers of the retina.
PCNSLO : increased frequency in immunosuppressed
04/15/23
Classical pathological findings: atypical
lymphoid cells between the RPE and Bruch's
membrane, with monoclonality demonstrating
IgH (for B-cell) or TCR (for T-cell) gene
rearrangement
Cytokines: elevation of IL-10 levels in the
vitreous (for B-cell PIOL
04/15/23
Gross photograph of enucleated globe with PCNSL, revealing retinal thickening, hemorrhage, and RPE involvement
large neoplastic cells with necrosis
Vitreous cytology showing large neoplastic cells
Retinal hemorrhage is rarely seen.
Deep infiltrates can give rise to exudative
retinal detachment.
If chorioretinal lesions regress, scarring and
atrophy of the retinal pigment epithelium may
be the only remaining fundus findings.
Optic neuropathy may also be a feature
04/15/23
PCNSL involving vitreous and subretinal space
Fluorescein angiogram of left eye during laminar flow phase, revealing early hypofluorescence of lesions noted in A.
Fluorescein angiogram of same eye after 6 minutes, revealing intense staining of infiltrates.
Primary uveal lymphoma.
Diffuse, creamy uveal infiltration with focal nodular accentuation inferotemporal to macula.
DIFFERENTIAL DIAGNOSISPRIMARY VITREORETINAL LYMPHOMA PRIMARY UVEAL
LYMPHOMA Chronic Idiopathic Vitritis Vitiliginous Choroiditis Vitreous Amyloidosis Metastatic Carcinoma Cytomegalovirus
Retinitis. Pars Planitis
(Intermediate Uveitis) Leukemic Intraocular Infiltration
Metastatic carcinoma Pneumocystis carinii
choroiditis Benign reactive lymphoid Hyperplasia Posterior scleritis , Harada’s disease Bilateral diffuse uveal
melanocytic proliferation associated with systemic carcinoma
Metastatic systemic lymphoma
Confined to the uvea (esp: the choroid).
Compared with PCNSLO, metastatic systemic
lymphomas are
much less prevalent
have a better prognosis
less likely to create a diagnostic dilemma.
04/15/23
04/15/23
Diagnosis High index of suspicion Radiologic imaging Histologic analysis
Vitreous biopsy Flow cytometrySubretinal aspiration Retinal biopsy
04/15/23
Laboratory studies Complete blood count (CBC) with
differential
Serum immunoprotein
electrophoresis
Rapid plasma reagin (RPR)
screening
Erythrocyte sedimentation rate
(ESR)
Fluorescent treponemal antibody
absorption (fta-abs) test
Toxoplasma titers
.
Antinuclear antibodies (ANA) test
Rheumatoid factor
Angiotensin-converting enzyme
(ACE)
Cytomegalovirus (CMV) titers
A tuberculosis skin test is
advisable.
The serum lactate dehydrogenase
(LDH)
Enzyme-linked immunosorbent
assay (ELISA) for HIV is also
recommended
04/15/23
B-scan ultrasonography
intraocular mass.
retinal detachment.
CT and MRI:
low sensitivity for intraocular lymphoma
do not facilitate differentiating the diagnosis against uveitis
or ocular melanoma
Imaging of the CNS with contrast to look for lesions
elsewhere.
04/15/23
Lumbar puncture : if CNS lymphoma is suspected.
Bone marrow aspiration for staging systemic
lymphomas.
CT scans of the chest and abdomen to rule out
retroperitoneal lymphoma.
Bone scans may also be done
Vitreous biopsy
Retinal biopsy
Orbital biopsy
04/15/23
Because of the fragility of neoplastic lymphocytes, a specimen
may contain numerous abnormal-appearing but uninterruptable
cells.
Molecular analysis : adjuncts to cytology for establishing the
diagnosis of PCNSLO.
immunoglobulin gene rearrangements and
ocular cytokine levels
elevated interleukin (IL)–10
IL-10–to–IL-6 ratio greater than 1.0, are helpful
CDR3 polymorphism analysis to confirm clonality.
DIAGNOSIS OF LYMPHOMA
CT helps in localizing orbital involvement
Biopsy can provide the definitive diagnosis.
Histopathology - cornerstone of the diagnostic
process.
Molecular pathology -to detect monoclonal gene
Cytogenetic abnormalities such as chromosomal
translocations or karyotypic abnormalities
04/15/23
TreatmentRadiotherapy
RT + chemotherapy in the presence of central
nervous system involvement.
For non-Hodgkin's lymphoma, chemotherapy
involves the use of
iv Cyclophosphamide 750mg/m2 on days 1 and 8,
iv Adriamycin 45mg/m2 on days 1 and 8,
iv Vincristine 1.5mg/m2 on days 1 and 8 and
oral Prednisolone 20mg 8 hourly for 10days.
04/15/23
For Hodgkin's lymphoma, chemotherapy involves the
use of ABVD regimen
iv Adriamycin 25mg/m2 on days 1and15;
iv Bleomycin 10U/m2 on days 1and15;
iv Vinblastine 6mg/m2 on days 1and15 and
iv Dacarbazine 375mg/m2 on days 1and15).
High dose methotrexate and Leucovorin rescue may also
be used for ocular lymphoma.
Multimodality therapy
Boosted radiation dose (5000-10,000 cGy) to
the spinal cord and
Intrathecal methotrexate,
Vision can be improved and life can be
prolonged, with some patients alive at 9
years after treatment.
04/15/23
Multiagent primary chemotherapyDesigned to reduce radiation-associated
cognitive defects
Can occur in up to 40% of patients older
than 50 years.
Methotrexate and procarbazine, vincristine,
thiotepa, or both vincristine and cytarabine.
Complete remission for long as 30 months
04/15/23
Lymphoid tumors of the conjunctiva Traditionally treated with local radiation
therapy.
Cryotherapy suggested Fewer ocular and systemic complications and
lower cost
04/15/23
Primary orbital lymphomaRadiotherapy alone is highly effective Bilateral orbital disease with no systemic disease,
is not an indication for chemotherapy.
High-grade tumors may require up to 4000 cGy.shielding of the globe (lens-sparing technique) is to
minimize ocular complications
04/15/23
,
In some cases, combining such systemic therapy with local radiation treatment is beneficial.
After radiotherapy, local control was achieved in 97-100% of patients.
04/15/23
Monoclonal antibody (mAb)Lymphomas respond well to mAb therapy,
Rituximab,
Ibritumomab
Epratuzumab
IV rituximab –for low-grade lymphoma showed
good results.
Antiangiogenic drugs – use of thalidomide is in
study04/15/23
ReferencesAlbert & Jakobiec's principles & practice of
ophthalmologyYanoff & Duker: ophthalmology, 3rd ed.2008,ch 8.4Robbins and Cotran Pathologic Basis of Disease 7th
ed 2005, pg 667 - 690JAMA ophthalmol.
Doi:10.1001/jamaophthalmol.2014.4644 published online november 13, 2014.
JAMA ophthalmol. Doi:10.1001/jamaophthalmol.2014.376 published online april 24, 2014
AAO Textbook of Ophthalmic Pathology & Intraocular tumors.2011-2012, pg 323-326
04/15/23
THANK YOU