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Ocular involvement as the initial manifestation of T-cell chronic
lymphocytic leukemia.Am
J Ophthalmol. 2007 Aug;144(2):326-9.\
PURPOSE: To
present a case of T-cell chronic lymphocytic leukemia (T-CLL)
manifesting as an intraocular lymphoma. DESIGN: Interventional case
report. METHODS: We performed a vitreous biopsy in a 67-year-old woman
who presented with blurred vision and vitreous cellular infiltration.
Morphologic, immunohistochemical, flow cytometry, and molecular
analysis by polymerase chain reaction of vitreous fluid, peripheral
blood, bone marrow aspirate, and biopsy were performed. RESULTS:
Cytofluorographic and molecular analysis of vitreous cells
demonstrated a monoclonal T-cell population consistent with a T-cell
intraocular lymphoma. Systemic evaluation established diagnosis of
T-cell CLL. CONCLUSION: T-CLL is a rare disease with an aggressive
clinical course. We present a case of T-cell intraocular lymphoma as
the initial manifestation of an otherwise asymptomatic T-CLL.
IL-10 measurement in
aqueous humor for screening patients with suspicion of primary
intraocular lymphoma.Invest
Ophthalmol Vis Sci. 2007 Jul;48(7):3253-9.
PURPOSE: To
determine the value of IL-10 measurement in aqueous humor (AH) for
screening in primary intraocular lymphoma (PIOL). METHODS: One hundred
consecutive diagnostic or therapeutic vitrectomies were performed in
patients with uveitis. During surgery, 100 muL of both AH and pure
vitreous was taken. IL-10 levels were determined with a standard
quantitative sandwich enzyme immunoassay technique. Patients were
distributed in two groups: 51 patients with proven PIOL, 108 patients
with uveitis divided into 74 with uveitis of proven etiology and 34
with idiopathic uveitis. Groups were compared by ANOVA and the Tukey-Kramer
test or nonparametric Wilcoxon test. Distributions were compared by
using the chi(2) test. Segmentation was derived from the ROC curves by
choosing a tradeoff between sensitivity and specificity. RESULTS: In
patients with PIOL, IL-10 mean values were 2205.5 pg/mL (median: 1467
pg/mL) in the vitreous and 543.4 pg/mL (median: 424 pg/mL) in AH. In
patients with uveitis (idiopathic and diagnostic uveitis), mean values
were 26.6 pg/mL (median: 8 pg/mL) in the vitreous, and 21.9 pg/mL
(median: 8 pg/mL) in AH. IL-10 mean values were significantly
different between patients with PIOL and patients with uveitis (P <
10(-3)). The areas under the curves were 0.989 and 0.962 for vitreous
and AH, respectively. A cutoff of 50 pg/mL in the AH was associated
with a sensitivity of 0.89 and a specificity of 0.93. In the vitreous,
a cutoff value of 400 pg/mL yielded a specificity of 0.99 and a
sensitivity of 0.8. CONCLUSIONS: Diagnosis of PIOL is often made
months or years after the initial onset of ocular symptoms. Cytology
remains the gold standard for diagnosis. However, measurement of IL-10
in the AH is a good screening test to reduce diagnostic delays.
Impaired
th1/tc1 cytokine production of tumor-infiltrating lymphocytes in a
model of primary intraocular B-cell lymphoma.Invest
Ophthalmol Vis Sci. 2007
Jul;48(7):3223-9.
PURPOSE:
Primary intraocular lymphoma is a high-grade non-Hodgkin lymphoma with
a pathogenesis that is still unclear. Microenvironment is known to be
crucial in controlling tumor growth and maintenance. To study the
immune microenvironment in intraocular lymphomas and to characterize
the cytokine polarization of infiltrating T-lymphocytes, a new murine
model of intraocular B-cell lymphoma was developed. METHODS:
Immunocompetent adult mice were injected intravitreally with a
syngeneic lymphomatous B-cell line. Clinical, histologic, and flow
cytometric analyses were performed to characterize the tumoral
invasion and the immune infiltration. Cytokine production of ocular
cells was investigated by RT-PCR and fluorescent immunoassay, with or
without stimulation by anti-CD3(+) anti-CD28 antibodies. RESULTS:
Intraocular lymphoma developed in eyes injected by lymphomatous
B-cells. At day 19, the retina and the vitreous cavity were
infiltrated by tumor cells. Up to 15% of living cells were
T-lymphocytes. Cytokine profile analysis of the supernatant of ocular
cells cultured ex vivo demonstrated the presence of IL10, IL6,
IFNgamma, and TNFalpha. Stimulation of ocular cells with anti-CD3(+)
anti-CD28 antibodies increased the IFNgamma level and led to the
induction of IL2 production, completing the type 1 (Th1/Tc1-like)
pattern of cytokine expression observed. IL12p70 and IL4, potent Th1
or Th2 differentiating factors, were undetectable, even after
stimulation. CONCLUSIONS: The results suggest that T-cells from
intraocular B-lymphomas are characterized by a Th1/Tc1-like profile
that could be partially inhibited in vivo. These data raise the
possibility of a T-cell immunostimulation to reactivate the
Th1/Tc1-lymphocytes and improve intraocular antitumoral immunity.
Asymptomatic conjunctival mucosa-associated lymphoid tissue-type
lymphoma with presumed intraocular involvement.Cornea.
2007 May;26(4):484-6.
PURPOSE: To
report a case of conjunctival mucosa-associated lymphoid tissue (MALT)
lymphoma with presumed intraocular involvement. METHODS: Observational
case report. RESULTS: A 73-year-old white man presented for a routine
eye examination and was found to have a salmon-colored bulbar
conjunctival mass of the left eye. Ultrasound showed a low-reflective
mass with diffuse thickening of the ciliary body and choroid.
Immunohistochemistry and flow cytometry of an incisional biopsy
specimen suggested a polyclonal lesion. Treatment with topical
steroids yielded no clinical improvement, and excisional biopsy was
performed. A diagnosis of MALT lymphoma was made after polymerase
chain reaction (PCR) analysis of the immunoglobulin heavy chain (IgH)
locus revealed a clonal B-cell population. CONCLUSIONS: Conjunctival
MALT lymphoma can present without symptoms and can extend
intraocularly. PCR analysis of the IgH locus can identify lesion
clonality when immunohistochemistry and flow cytometry fail to do so.
Biopsy
techniques and yields in diagnosing primary intraocular lymphoma.Int
Ophthalmol. 2007 Aug;27(4):241-50.
A review of
current biopsy techniques that are used in obtaining specimens from
which to make a diagnosis of primary intraocular lymphoma (PIOL) is
presented. Methods for obtaining and subsequently testing vitrectomy
specimens are discussed. In addition, the yields of external and
internal approaches for obtaining chorioretinal tissue, and diagnostic
vitrectomies, are reviewed.
Primary
intraocular lymphoma: improving the diagnostic procedure.Ophthalmology.
2007 Jul;114(7):1372-7.
OBJECTIVE: To
analyze the clinical features of primary intraocular lymphoma (PIOL)
and to describe cytochemical and immunocytochemical findings of the
vitreous specimens as well as the reasons for delayed diagnosis of
PIOL. DESIGN: Prospective noncomparative study. PARTICIPANTS: Eleven
patients referred to the uveitis or medical retina units, Department
of Ophthalmology, University of Helsinki, were diagnosed as having
PIOL between 2000 and 2005. The median follow-up of the patients was
32 months. METHODS: Clinical features and diagnostic workup of uveitis
were described. Twelve vitrectomies were performed on 9 patients. The
first 5 biopsies were fixed in an equal volume of 50% alcohol. The
specimens of the next 7 vitrectomies were handled without alcohol, and
tissue culture medium was added to the samples. MAIN OUTCOME MEASURES:
Clinical features of PIOL, intervals from ocular symptoms and from
first ophthalmological examination to diagnosis, and the role of a
proper handling of the vitreous sample in the diagnosis of PIOL.
RESULTS: Six females (54%) and 5 males (46%) (median age, 61 years)
were included. Ten patients had ocular symptoms for 1 to 30 months
(median, 8) before the first contact with an ophthalmologist. Uveitis
was bilateral in 9 patients. Vitreitis was seen in all patients, and
it was severe in 8. Fundus lesions dominated in 3 patients. Six
patients lost useful vision in one eye before the diagnosis of PIOL.
Cytologic and immunohistochemical stainings prepared of the unfixed
vitreous specimens showed PIOL in 6 patients. The samples fixed in
alcohol were nondiagnostic in 4 patients, and in them, verification of
diagnosis was based on brain biopsy (3) or cerebrospinal fluid (1)
findings. Seven patients died due to primary nervous system lymphoma.
CONCLUSIONS: Diagnosis of PIOL is difficult but can be improved.
Severe bilateral vitreitis in an elderly patient is a characteristic
finding of PIOL. Alcohol fixation may jeopardize the identification of
PIOL cells in the vitreous sample. Optimal handling of the vitreous
specimens and examination of the slides by an experienced
cytopathologist are critical in the diagnostic workup of PIOL.
Intraocular
lymphoma metastasis from larynx.Eur
J Ophthalmol. 2007 Jan-Feb;17(1):133-5.
PURPOSE:
To present a rare case of primary larynx diffuse large B cell lymphoma
non-Hodgkin's lymphoma (NHL), disseminated to the cerebellum and the
intraocular tissue. METHODS: A 69-year-old man noticed blurred vision
in both eyes. The vitreous contained infiltrating cells bilaterally,
and floating opacities were increased. We performed vitrectomy to
recover the vision and diagnose for both eyes. RESULTS: The authors
discovered diffuse large B cell NHL with cytopathologic examination
from vitreous specimen in this case, which was identical with diffuse
large B cell NHL of the larynx and cerebellum, and therefore could
diagnose the intraocular lesion as the metastasis of NHL. Although the
vision improved, the patient had remarkable visual disturbance in both
eyes at 6 months after surgery because of the chorioretinal lesion.
The authors treated by the combined curative chemotherapy and
radiotherapy to ocular tissue, since providing sufficient evidence
that the chorioretinal lesion was to predict the metastasis of diffuse
large B cell NHL After those treatments, chorioretinal lesions have
disappeared in both eyes and the vision has recovered. CONCLUSIONS:
Increased attention to the possibility of dissemination of laryngeal
NHL to the intraocular tissue is needed.
Ocular
manifestations and treatment of central nervous system lymphomas.
Neurosurg
Focus. 2006 Nov 15;21(5):E9.
Intraocular
primary central nervous system lymphoma (PCNSL), also called primary
intraocular lymphoma (PIOL), is a subset of PCNSL in which lymphoma
cells invade the subretinal pigment epithelial space and vitreous
cavity with or without central nervous system involvement at the time
of ocular diagnosis. The frequency of this rare condition has
increased over the past years in immunosuppressed as well as
immunocompetent patients. The authors review the current status of
PIOL and elaborate on their group's experience with its diagnosis and
treatment. The incidence of PIOL is increasing. There is evidence that
chronic antigenic stimulation may result in the development of PIOL.
Recent advancements in the diagnosis of PIOL include better handling
of vitreous specimens for cytological studies, immunocytological
investigation for lymphoid cells, flow cytometry, cytokine evaluation,
and molecular analysis. Because PIOL has a nonspecific presentation,
the differential diagnosis should include infectious and noninfectious
causes presenting with vitreitis and/or subepithelial infiltration as
well as paraneoplastic syndromes including CRMP-5 optic neuropathies.
Given that therapy is long-term and has significant systemic and
ocular complications, tissue diagnosis is important. Treatment of PIOL
may include systemic chemotherapy in which high-dose methotrexate-based
regimens are used as well as intraocular injections of methotrexate
and rituximab (anti-CD20 antibody). Cranial and ocular external-beam
radiotherapy is being used less often today. Further studies are
needed to prevent the tumor formation in terms of eliminating
antigenic load and inhibiting Bcell chemokines as well as to determine
the optimal local and systemic chemotherapy and immunotherapy options
in the management of PIOL.
A clinical
study of intraocular malignant lymphoma.Nippon
Ganka Gakkai Zasshi. 2006
Aug;110(8):588-93.
PURPOSE: We
investigated whether vitreous cytology and the measurement of
intravitreous cytokine were useful for the diagnosis of intraocular
malignant lymphoma. SUBJECTS AND METHODS: 8 eyes of 5 patients with
suspected intraocular malignant lymphoma during the past 15 months. 3
vitreous samples were collected from 3 patients at the time of pars
plana vitrectomy. Polymerase chain reaction(PCR) amplification and
flowcytometric analysis(FACS) of the vitreous samples were performed.
Interleukin (IL)-10 and IL-6 concentrations were measured. RESULTS:
Vitreous cytology showed increased atypical B lymphocytes. The
vitreous IL-10/IL-6 ratio was higher than 1 in all cases. Monoclonal
rearrangement of the immunoglobulin heavy chain gene and the light
chain restriction of immunoglobulin were detected. CONCLUSION: The
detection of the monoclonality of infiltrated cells into the vitreous
by PCR amplification and FACS, and the measurements of IL-10 and IL-6
concentrations in the vitreous fluid may be useful in the diagnosis of
intraocular malignant lymphoma.
Primary
intraocular lymphoma: A review.Semin
Ophthalmol. 2006 Jul-Sep;21(3):125-33.
Primary
intraocular lymphoma (PIOL) is a type of primary central nervous
system lymphoma (PCNSL). It is the most common neoplastic masquerade
syndrome involving the eye. Its protean ocular manifestations, plus in
many cases the initial positive response to corticosteroid therapy for
presumed uveitis, delay accurate diagnosis. A high index of suspicion
is essential, followed by tissue biopsy with cytology and ancillary
studies. Current treatment is based on chemotherapy featuring
high-dose methotrexate and radiation therapy. Prognosis is poor due to
CNS involvement, but newer therapies have had some success in
prolonging survival.
Detection
of the bcl-2 t(14;18) translocation and proto-oncogene expression in
primary intraocular lymphoma.Invest
Ophthalmol Vis Sci. 2006
Jul;47(7):2750-6.
PURPOSE:
Primary intraocular lymphoma (PIOL) is a diffuse large B cell lymphoma
that initially infiltrates the retina, vitreous, or optic nerve head,
with or without central nervous system involvement. This study
examined the expression of the bcl-2 t(14;18) translocation, the
bcl-10 gene, and high expression of bcl-6 mRNA in PIOL cells. METHODS:
Microdissection and PCR analysis were used to examine vitreous
specimens in patients with PIOL for the presence of bcl-2 t(14;18)
translocations, the bcl-10 gene, and expression of bcl-6 mRNA. A
medical record review was also conducted to determine whether the
bcl-2 t(14;18) translocation correlated with prognosis. RESULTS: Forty
of 72 (55%) PIOL patients expressed the bcl-2 t(14;18) translocation
at the major breakpoint region. Fifteen of 68 (22%) patients expressed
the translocation at the minor cluster region. The bcl-10 gene was
detected in 6 of 26 (23%) patients, whereas 4 of 4 (100%) PIOL
patients expressed higher levels of bcl-6 mRNA compared with
inflammatory lymphocytes. An analysis of clinical outcome in 23 PIOL
patients revealed no significant association between bcl-2 t(14;18)
translocations and survival or relapse. However, patients with the
translocation were significantly younger. CONCLUSIONS: PIOL has unique
molecular patterns of bcl-2, bcl-10, and bcl-6 when compared with
other systemic lymphomas. This study lays the foundation for future
studies aimed at exploring the genotypic classification of PIOL based
on the quantitative molecular framework of gene expression profiling,
with the goal of providing useful adjuncts to the pathologic diagnosis
of this complex disease.
Case of
spontaneous regression of intraocular lymphoma demonstrated by
subretinal biopsy.Nippon
Ganka Gakkai Zasshi. 2006
Mar;110(3):226-31.
PURPOSE: To
report a case of intraocular lymphoma suspected of spontaneous
regression based on ocular fundus findings, subretinal biopsy, and
observation of clinical course. CASE: A 64-year-old woman presented at
our clinic with multiple yellowish-white patchy lesions in the left
fundus and focal atrophy of the retinal pigment epithelium in the
right fundus. No inflammatory infiltrates were observed in either eye.
Intraocular lymphoma was suspected based on the clinical
manifestations including fluorescein angiography and optical coherence
tomography. Vitrectomy and subretinal biopsy were subsequently
performed for diagnostic purposes. Histological examination showed
that the subretinal lesion was composed mostly of necrotic tissue
derived from the lymphoid corpuscle and that there was no cellular
component except the retinal pigment epithelium. Interleukin-10 in the
vitreous humor was low at 9 pg/ml. No serious postoperative
complications were observed after surgery and the residual retinal
lesions gradually regressed spontaneously. Laboratory data and whole
body evaluation including the central nervous system (CNS) showed no
remarkable findings for 1 year after surgery. CONCLUSIONS: It is
suggested that the present case was an intraocular lymphoma which
regressed spontaneously. However, careful follow-up including the
possible occurrence of CNS lesions is required in such cases.
Extranodal
B-cell lymphoma of the uvea: a case report.Can
J Ophthalmol. 2005 Oct;40(5):623-6.
CASE
REPORT: Ocular involvement by non-Hodgkin's lymphoma is a rare
condition that can result from a primary intraocular lymphoma of the
retina or an intraocular manifestation of systemic lymphoma. Uveal
involvement is seldom the initial manifestation of extranodal
lymphoma. We describe an 80-year-old patient with a blind and painful
left eye and a history of recurrent uveitis. After ultrasound
evaluation, the eye was enucleated and histopathologic examination
revealed a malignant B-cell lymphoma of the uveal tract. The patient
has been followed for 8 years after surgery, but she has had no
further systemic manifestations of lymphoma and has not required
subsequent treatment. COMMENTS: Primary extranodal lymphoma can be
easily mistaken for recurrent uveitis or primary intraocular lymphoma
of the retina and central nervous system; it is a differential
diagnosis to be considered in cases of recurrent uveitis-like symptoms
evolving to blind painful eye.
Intraocular lymphoma 2000-2005: results of a retrospective multicentre
trial.Graefes
Arch Clin Exp Ophthalmol. 2006 Jun;244(6):663-9.
BACKGROUND: The prognosis of intraocular lymphoma (IOL) is poor, and
the optimal treatment has yet to be defined. This study assesses the
clinical characteristics and outcome of patients with IOL diagnosed
and treated in the new millennium. METHODS: Patient data in this
retrospective multicentre study were compiled by standardised
questionnaires sent to seven university ophthalmology departments. All
cases diagnosed with primary and secondary IOL in the past 5 years not
associated with HIV infection were included. RESULTS: Twenty-two
patients, 11 men and women; median age 64 (range 38-83) years, median
Karnofsky performance status 90% (range 50-100%), were included.
Nineteen patients had primary IOL (PIOL): 13 a newly diagnosed disease
and six an ocular relapse of primary central nervous system lymphoma (PCNSL).
Three patients had secondary IOL. First-line treatment for IOL
included systemic chemotherapy in 13 cases, ocular radiation in six
and intraocular chemotherapy in three. Complete remission was achieved
in 14/20 evaluable patients, partial remission in five and stable
disease in one. All patients treated with ifosfamide (IFO) or
trofosfamide (TRO) (n=8) responded. Median progression-free survival (PFS)
and overall survival were 10 (range 1+ to 44.5+) and 22.5 (range 1+ to
49+) months, respectively. Patients with newly diagnosed PIOL and
ocular relapse of PCNSL had a median PFS of 10 (range 1+ to 44.5+) and
6 (range 2 to 6+) months, respectively. Median PFS was 12 (range 3+ to
22.5+) months after systemic and 5.5 (range 1+ to 44.5+) months after
local first-line therapy. CONCLUSIONS: The prognosis of PIOL is
similar to that of PCNSL without ocular involvement. Systemic therapy
possibly prolongs PFS as compared with local management of (P)IOL. The
high response rate to monotherapy with IFO and TRO is promising.
Molecular
analysis of immunoglobulin genes in primary intraocular lymphoma.Invest
Ophthalmol Vis Sci. 2005
Oct;46(10):3507-14.
PURPOSE: To
analyze somatic hypermutations in clonally rearranged IgH chain
variable (V) genes of primary intraocular lymphoma (PIOL), to identify
the differentiation stage of B-PIOL cells. METHODS: Sixteen cases of
PIOL were diagnosed on the basis of morphology and immunohistology. In
six patients, simultaneous cerebral lymphomatous involvement was
known; stereotactic biopsy specimens were investigated in three cases.
A polymerase chain reaction (PCR) was performed on DNA extracted from
vitrectomy specimens or from paraffin-embedded sections, to amplify
the clonally rearranged heavy-chain immunoglobulin (IgH) genes. The
isolated PCR products were sequenced and compared with published VH
germ-line segments to determine the VH usage and number of somatic
mutations in the complementarity-determining region (CDR)2 and
framework region (FR)3. RESULTS: All tumors exhibited clonal IgH
rearrangements. Of the eight sequenceable cases, four had the VH4-34
gene segment, two the VH3-23, one the VH3-7, and another the VH3-30.
The pattern of somatic mutations indicated selection of PIOL cells for
expression of a functional antibody. The mean frequency of somatic
mutations detected for the IgH gene was very high (14.5%). In three
oculocerebral lymphomas, the identical B-cell clone was demonstrated
in ocular and cerebral tissues. CONCLUSIONS: The data suggest that
PIOLs (1) are derived from mature B-cells that have undergone the
germinal center reaction and (2) are closely related to primary
cerebral nervous system lymphoma (PCNSL), due to their high mutation
frequency of VH region genes. The close relationship between PIOL and
PCNSL is underlined by demonstration of the same VH segment (VH4-34)
in three of six cases of oculocerebral lymphoma.
Primary
intraocular T-cell-rich large B-cell lymphoma.Arch
Pathol Lab Med. 2005 Aug;129(8):1050-3.
We report a
primary intraocular T-cell-rich large B-cell lymphoma in a 57-year-old
woman who underwent 3 diagnostic vitrectomies for a presumed diagnosis
of panuveitis. She developed no light perception in the left eye and
underwent enucleation. Histopathologic and immunohistochemical studies
on the enucleated globe disclosed a primary intraocular large B-cell
lymphoma involving the choroid, vitreous, and retina. A large
population of T cells was identified among the neoplastic B-cell
population. B-cell immunoglobulin gene rearrangement and T-cell
receptor gene rearrangement studies using the polymerase chain
reaction method indicated that a monoclonal immunoglobulin kappa light
chain population was present and that the T-cell population was not
monoclonal. This case highlights the importance of interpreting
cytologic features in vitreous aspirates in the context of the
clinical situation.
Primary
intraocular lymphoma of T-cell type: report of a case and review of
the literature.Graefes
Arch Clin Exp Ophthalmol. 2005
Mar;243(3):189-97.
PURPOSE:
Primary intraocular lymphoma (PIOL) is an uncommon non-Hodgkin
lymphoma and is usually of B-cell type. Intraocular T-cell or T/NK-cell
lymphomas are extremely rare and mostly represent a secondary
manifestation of either a cutaneous or a systemic lymphoma. The aim of
the current paper is to report the clinical, histopathological and
molecular biological findings of a PIOL of T-cell type. METHODS:
Conventional cytological and immunocytological examination of
vitrectomy specimens. Conventional histology, immunohistochemistry and
polymerase chain reaction (PCR) for the detection of immunoglobulin
heavy chain (IgH) and T-cell-receptor gamma (TCR-gamma) gene
rearrangement, GeneScan analysis, and DNA sequencing were performed on
the chorioretinal biopsy. RESULTS: Cytology of the right vitreous
aspirate revealed a moderate cellular infiltrate consisting of
medium-sized T-cells with pleomorphic nuclei. Similar atypical
lymphocytes were seen in the partially necrotic chorioretinal biopsy.
These lymphocytes expressed CD3, CD4, betaF1 and CD30, with a growth
fraction of 90%. TCR-gamma-PCR, GeneScan analysis and DNA sequencing
demonstrated a monoclonal amplification product within the expected
range. In contrast, IgH-PCR revealed oligoclonal amplificates. The
patient was treated with low-dose radiotherapy (total 45 Gy), and was
in complete remission at final follow-up. CONCLUSION: A rare PIOL of
T-cell type was diagnosed on the basis of vitreous aspiration and
chorioretinal biopsy. In addition to conventional cytology and
immunocytology, the utilisation of gene rearrangement studies on
vitreous or chorioretinal biopsies increases the chances of diagnosing
or excluding a PIOL of either B-cell or T-cell type. Despite its
rarity, ophthalmic pathologists should always consider the diagnosis
of T-PIOL when reviewing vitreous samples.
The elusive
nature of primary intraocular lymphoma.J
Neuroophthalmol. 2005 Mar;25(1):33-6.
A 58-year-old
woman with an initial diagnosis of multiple evanescent white dot
syndrome OU experienced deteriorating vision despite corticosteroid
treatment. Reevaluation disclosed retinal and subretinal infiltrates
and pigmentary alterations, prompting a suspicion of primary
intraocular lymphoma (PIOL). Diagnostic vitrectomy yielded
inconclusive cytology, but flow cytometry demonstrated small
monoclonal B cells less suggestive of PIOL than of small lymphocytic
lymphoma originating outside the eye or central nervous system. Brain
magnetic resonance imaging, chest/abdomen/pelvis computed tomography,
lumbar puncture, and laboratory studies failed to disclose lymphoma
elsewhere. There was insufficient evidence to recommend radiation
therapy. Vision deteriorated rapidly, prompting a diagnostic retinal
biopsy and aspiration of the subretinal infiltrate, revealing
unequivocal evidence of PIOL. After 40 Gy orbital x-irradiation,
visual function improved dramatically. This case emphasizes the
unusual ocular manifestations of PIOL and the difficulty of obtaining
a definitive diagnosis by sampling vitreous, particularly after
corticosteroid treatment. In such cases, subretinal aspiration or
retinal biopsy may be necessary. Timely diagnosis is critical because
treatment can reverse visual loss if it is not severe.
Ophthalmologic and intraocular non-Hodgkin's lymphoma: a large single
centre study of initial characteristics, natural history, and
prognostic factors.Hematol
Oncol. 2004 Dec;22(4):143-58.
The aims of
this study were to define the initial characteristics, natural
history, and prognostic factors of patients with ophthalmologic and
intraocular malignant lymphoma. All patients treated at the Institut
Curie for lymphoma with ophthalmologic (orbit and/or adnexa) or
intraocular involvement were retrospectively reviewed. A pathological
review of all cases was performed according to the WHO classification.
One hundred and forty-five patients were selected for the study.
Pathological review showed 36% MALT type lymphoma, 22%
lymphoplasmocytic lymphoma, and 15% diffuse large B-cell lymphoma.
Ophthalmologic and ocular sites were intra-orbital in 61 cases (42%)
and conjunctival in 51 cases (35%), with bilateral involvement in 10%
of cases. Stage IV was found in 32% of cases, with bone marrow
involvement in 12%. With a median follow-up of 90 months, the 5-year
DFS and OS were 64 and 79% for low-grade NHL, and 43 and 50% for
high-grade NHL. On multivariate analysis, age greater than 59 years,
elevated LDH level, stage IV, high-grade histological subgroup, and
presence of B-symptoms had a negative impact on OS for the overall
population. In conclusion, with a median follow-up of 7.5 years, our
large cohort of patients represents one of the largest published
series on primary ophthalmologic and intraocular malignant lymphoma.
Primary
intraocular lymphoma: a review of the clinical, histopathological and
molecular biological features.Graefes
Arch Clin Exp Ophthalmol. 2004
Nov;242(11):901-13.
INTRODUCTION:
Primary intraocular lymphoma (PIOL) is a rare non-Hodgkin lymphoma
which arises in the retina or the vitreous. It can occur either
together with or independently of primary cerebral nervous system
lymphoma (PCNSL); the incidence of the latter has significantly
increased over the past three decades. PIOL remains one of the most
difficult diagnoses to establish, particularly due to its ability to
mimic other diseases in the eye and to the limited material which is
often available for examination. METHODS: The article reviews the
clinical, histopathological, molecular biological and biochemical
approaches to the diagnosis of PIOL. The differential diagnoses,
including other lymphomatous manifestations in the eye, e.g. primary
uveal lymphoma, as well as non-neoplastic uveal diseases are
addressed. Furthermore, the treatment strategies for PIOL are
summarised. RESULTS: Diagnostic progress has been made in various
fields, including flow cytometry and immunocytology, cytokine
analysis, and as well as molecular biological analysis of the
immunoglobulin heavy and light chains using polymerase chain reaction
on both fixed and non-fixed material. The optimal therapy of PIOL
remains to be determined: the current trends suggest that combined
radiotherapy and chemotherapy, as well as intravitreal chemotherapy,
are of value. Novel therapies which may have a role in the future
include oral trofosfamide. CONCLUSION: Our understanding of the
pathogenesis of PIOL/PCNSL remains far from complete. Intensified
efforts must be made to determine the cell of origin of PIOL, as well
as to establish "molecular signatures", which could be used to
decrease diagnostic delay. Further studies, possibly prospective ones,
are required to establish the optimal therapy for initial and
recurrent disease.
Primary
intraocular lymphoma: clinical, cytologic, and flow cytometric
analysis.Ophthalmology.
2004 Sep;111(9):1762-7.
PURPOSE: To
compare cytologic with flow cytometric results of vitreous biopsy
specimens obtained to rule out primary intraocular lymphoma (PIOL).
STUDY DESIGN: Prospective noncomparative case series. PARTICIPANTS:
Patients suspected of having PIOL who underwent vitreous biopsy were
evaluated. METHODS: Patients underwent a standard 3-port vitrectomy
and vitreous biopsy to rule out PIOL. Each undiluted specimen was
split, and half was prepared for cytologic evaluation with the
collodion bag method; the other half was submitted for flow cytometric
immunophenotyping (FCI). The diluted specimen was processed as a cell
block for cytology. MAIN OUTCOME MEASURES: Final diagnosis based on
cytology and FCI. RESULTS: Ten of 14 patients had sufficient specimens
for both cytologic and FCI evaluation. Three patients had chronic
inflammation confirmed by both methods. Six patients had large cell
lymphoma identified by both cytology and FCI. Two of those 6 patients
initially had insufficient specimen for FCI. One patient had large
cell lymphoma diagnosed cytologically that was initially negative for
a clonal population by FCI. All lymphomas were B-cell type.
CONCLUSIONS: Cytologic evaluation is an accurate diagnostic technique
to evaluate for PIOL. FCI is useful for immunophenotyping PIOL.
Multiple biopsies may be required to achieve a diagnosis.
Cytologic
diagnosis of intraocular lymphoma in vitreous aspirates.Acta
Cytol. 2004 Jul-Aug;48(4):487-91.
OBJECTIVE: To
evaluate the cytologic findings of vitreous fluids with atypical,
suspicious for malignancy or malignant lymphoid cells to assess
cytologic parameters that may help in reaching the diagnosis of
intraoclular lymphoma. STUDY DESIGN: Vitreous aspirates with a
malignant, suspicious for malignancy or atypical lymphoid population
were identified from the files of Barnes-Jewish Hospital during the
previous 11 years. Cytologic preparations were reviewed. Pertinent
clinical information was obtained from medical records. RESULTS:
Thirteen vitreous aspirates from 12 patients were included. The chief
complaints included floaters, blurred vision and decreased visual
aculity. Bilateral ocular involvement was present in 8 (67%) patients.
Three patients had a history of an extraocular lymphoid malignancy.
All patients underwent pars plana vitrectomy and collection of the
vitreous aspirate. Cytologic diagnoses included: malignant lymphoma (9
of 13), suspicious for malignant lymphoma (3 of 13) and atypical
lymphoid population (1 of 13). Most samples had high cellularity (11
of 13) and necrosis (9 of 13). Abnormal lymphoid cells were large (2-4
times the size of a lymphocyte) and had a high nuclear/cytoplasmic
ratio, prominent nucleoli, irregular nuclear contours and a fine to
coarse chromatin pattern. All cases with malignant cytology had
abundant abnormal lymphoid cells; inconclusive cases had few.
Immunocytochemistry for CD20 and CD45RO was performed on 9 of 13
samples and was conclusive in 6 of 9. CONCLUSION: Cytologic analysis
of vitreous aspirates can be useful in diagnosing intraocular
involvement by malignant lymphoma. Sparse cellularity is the main
factor leading to inconclusive diagnoses. Immunostaining can be useful
in confirming the lymphoid nature of the malignant cells.
Molecular pathology
of primary intraocular lymphoma.Trans
Am Ophthalmol Soc. 2003;101:275-92.
PURPOSE: To
evaluate immunoglobulin heavy chain (IgH) gene rearrangements,
cytokines and chemokines, and infectious agents in primary intraocular
B-cell lymphoma (PIOL) cells, in order to better diagnose and
understand PIOL. METHODS: We studied ocular specimens from 57 patients
with PIOL at the National Eye Institute from 1991 to 2001. Specimens
were analyzed for IgH gene rearrangements using microdissection and
polymerase chain reaction (PCR). We measured vitreal interleukin
(IL)-10 and IL-6 levels by enzyme-linked immunosorbent assay. IL-10
mRNA was studied in PIOL cells using microdissection and reverse
transcribed (RT)-PCR. Chemokine and chemokine receptor expression was
examined by using immunohistochemistry. Infectious DNA of human
herpetic virus-8 (HHV-8), Epstein-Bar virus (EBV), and Toxoplasma
gondii was detected by using microdissection and PCR and was confirmed
with Southern blot hybridization. RESULTS: IgH rearrangement(s) were
demonstrated in all 50 tested cases. Cytokine levels were measured in
the vitreous of 39 patients. Thirty-one had measurable cytokine
levels: 24 of 31 had elevation of IL-10 relative to that of IL-6, and,
in contrast, only 7 of 31 had elevation of IL-6 relative to IL-10.
IL-10 mRNA was abundant in lymphoma cells of 6 examined cases.
Lymphoma cells expressed chemokine receptors of CXCR4 and CXCR5 in
three tested cases. HHV-8 DNA was found in 6 of 32 cases (18.8%), EBV
DNA in 2 of 21 (9.5%), and T gondii DNA in 2 of 16 (12.5%).
CONCLUSIONS: Molecular analyses detecting IgH rearrangements and
vitreal levels of IL-10 and IL-6 are useful adjuncts for PIOL
diagnosis. A role for specific infectious agents is hypothesized in
the pathogenesis of some cases of PIOL. B-cell chemokine is likely
involved in attracting PIOL cells into the eye.
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