Table of Contents
1
UI - 11807001
AU - Nielsen M; Nissen MH; Gerwien J; Zocca MB; Rasmussen HM; Nakajima K;
TI -
Ropke C; Geisler C; Kaltoft K; Odum N
Spontaneous interleukin-5 production in cutaneous T-cell lymphoma lines
is mediated by constitutively activated Stat3.
SO - Blood 2002 Feb 1;99(3):973-7
AD - Institute of Medical Microbiology and Immunology, Section A, University
of Copenhagen, Panum 22.5, Blegdamsvej 3, 2200 Copenhagen N, Denmark.
Mycosis fungoides is a low-grade cutaneous T-cell lymphoma (CTCL) of
unknown etiology. In advanced stages of CTCL, a shift in cytokine
profile from T(H)1 to T(H)2 is observed, which coincides with
eosinophilia, high levels of immunoglobulin E, and increased
susceptibility to bacterial infections. It is, however, unknown why
T(H)2 cytokines predominate in advanced CTCL, and the cellular source of
these cytokines also remains to be identified. In several leukemias and
lymphomas, constitutively activated signal transducer and activator of
transcription (Stat) signaling pathways have been detected. In a
previous study, constitutive activation of Stat3 was found in tumor
cells isolated from affected skin and blood from CTCL patients. Here, it
is shown that CTCL tumor cell lines, but not nonmalignant cell lines,
spontaneously produce interleukin-5 (IL-5), IL-6, and IL-13.
Transfection of tumor cells with dominant-negative Stat3 almost
completely blocks IL-5 production and strongly inhibits IL-13
production, whereas IL-6 production is unaffected. Thus, the data show
that malignant CTCL cells themselves might contribute to the change in
cytokine pattern accompanying progression of CTCL. In conclusion,
constitutively activated Stat3 is found to mediate a spontaneous IL-5
production and regulate IL-13 production in CTCL cell lines, pointing
toward a new role of Stat3 in malignant transformation.
2
UI - 11803274
AU - Murphy M; Fullen D; Carlson JA
TI -
Low CD7 expression in benign and malignant cutaneous lymphocytic
infiltrates: experience with an antibody reactive with paraffin-embedded
tissue.
SO - Am J Dermatopathol 2002 Feb;24(1):6-16
AD - Department of Dermatology, University of Connecticut Health Center,
Farmington, Connecticut, USA.
Loss of CD7 expression by neoplastic lymphocytes is considered a
distinguishing characteristic of mycosis fungoides (MF) and cutaneous
T-cell lymphoma. Reports to date examining for the CD7 immunophenotype
in MF have been performed on fresh-frozen tissue. In this study, we used
a paraffin-reactive antibody directed against CD7 to determine its range
of expression in MF and to compare these results with those in controls.
Examining 22 cases of MF and 61 controls, we found minimal CD7
expression by lymphocytes in MF and in a few cases of benign
inflammatory dermatosis (BID). The lowest mean CD7 counts (as a
percentage of total lymphocytes) were found in MF (patch stage: 5% +/-
5%, range: 0-10; plaque and tumor stages: 15% +/- 5%, range: 5-25), and
these counts were significantly lower than those for BID (35% +/- 20%,
range: 5-80; p = 0.001). By logistic regression analysis, low CD7
expression (<10% lymphocytes labeling) had sensitivity and positive
predictive values of 80% and 72%, respectively, and specificity and
negative predictive values of 93% and 96%, respectively, for the
diagnosis of patch stage MF. False-positive results were found for
spongiotic dermatitis. Moreover, spongiotic dermatitides exhibited a
progressive decrease in mean CD7 counts from acute to subacute to
chronic stages (50% versus 35% versus 30%, respectively). In conclusion,
minimal CD7 expression is a specific finding for MF. Benign inflammatory
infiltrates can also show low CD7 expression, however, which rarely
matches that of patch stage MF. Progressive loss of CD7 expression in
BID is the likely consequence of expansion of antigen-selected
CD3+CD4+CD7- T cells. These inflammatory CD4+CD7- T cells may represent
the physiologic counterpart to the neoplastic lymphocyte of MF.
3
UI - 11803287
AU - Chang SE; Choi HJ; Huh J; Choi JH; Sung KJ; Moon KC; Koh JK
TI -
A case of primary cutaneous CD56+, TdT+, CD4+, blastic NK-cell lymphoma
in a 19-year-old woman.
SO - Am J Dermatopathol 2002 Feb;24(1):72-5
AD - Department of Dermatology, Asan Medical Center, College of Medicine,
University of Ulsan, Seoul, Korea.
The classification of blastic or blastoid natural killer (NK)-cell
lymphoma is controversial. Reports of primary cutaneous blastic CD56+
NK-cell lymphoma are rare, which necessitates further clinicopathologic
definition of this type of lymphoma. Most CD56+ lymphomas display
angiocentric histologic features, especially in Asian patients, and
these are mostly associated with the presence of Epstein-Barr virus
(EBV) genome and with an aggressive clinical course. We report on a
young woman with a primary cutaneous blastic NK lymphoma which showed no
angiocentric features but showed an unusual immunophenotype; CD56+,
TdT+, CD4+, EBV-, and germline configuration of T-cell receptor gene.
This unusual lymphoblastic lymphoma seems to have an immature or
progenitor NK cell lineage.
4
UI - 11850526
AU - Navas IC; Algara P; Mateo M; Martinez P; Garcia C; Rodriguez JL;
TI -
Vanaclocha F; Barrientos N; Iglesias L; Sanchez L; Piris MA;
Ortiz-Romero P
p16(INK4a) is selectively silenced in the tumoral progression of mycosis
fungoides.
SO - Lab Invest 2002 Feb;82(2):123-32
AD - Department of Genetics, Virgen de la Salud Hospital, Toledo, Spain.
Knowledge about the molecular mechanisms involved in the pathogenesis of
tumoral progression in mycosis fungoides (MF) is still scarce. Because
the 9p21 locus seems to be a good target for a detailed study in MF,
this prompted us to compare the mechanisms of inactivation of the
p16(INK4a), p15(INK4b), and p14(ARF) genes in aggressive and stable
forms of MF, performing microsatellite analysis, methylation-specific
polymerase chain reaction, direct sequencing, and p16(INK4a) protein
expression by immunohistochemistry. Additionally, the p53 gene was also
sequenced in tumoral lesions. Thirty-nine patients with stable MF were
studied. Alterations in p16(INK4a) and p15(INK4b) genes were detected in
18% and 5% of the cases, respectively. None of the cases analyzed showed
alterations of the p14(ARF) gene. In contrast with these findings, in
the 11 patients with aggressive MF, alterations of the p16(INK4a),
p15(INK4b), or p14(ARF) genes were found in 8 (73%), 3 (27%), and 2
(18%) cases, respectively. A significant proportion (4/11) of these
alterations were already present in the p16(INK4a) gene in the initial
plaque lesions in these aggressive forms of MF. Alterations in the
p16(INK4a) gene, either methylation or loss of heterozygosity, were
clearly more frequent than those in the p15(INK4b) and p14(ARF) genes.
These p16(INK4A) alterations were confirmed using immunohistochemistry.
None of the nine tumoral lesions analyzed showed mutations in exons 1-2
of the p16(INK4a) gene or in exons 5-8 of the p53 gene. These results
seem to suggest that 9p21 alterations, and selectively p16(INK4a)
silencing, could be a characteristic phenomenon in MF progression.
5
UI - 10926739
AU - Toro JR; Beaty M; Sorbara L; Turner ML; White J; Kingma DW; Raffeld M;
TI -
Jaffe ES
gamma delta T-cell lymphoma of the skin: a clinical, microscopic, and
molecular study.
SO - Arch Dermatol 2000 Aug;136(8):1024-32
AD - Dermatology Branch, National Cancer Institute, National Institutes of
Health, Bethesda, MD 20892-1908, USA. torojo@exchange.nih.gov
BACKGROUND: Only a few cases of primary gamma delta cutaneous T-cell
lymphoma (CTCL) have been reported. We encountered 3 cases of this rare
condition. OBJECTIVES: To characterize gamma delta CTCL by clinical,
microscopic, and molecular methods and to investigate the role of
Epstein-Barr virus (EBV) infection in its pathogenesis. DESIGN: Patients
were evaluated by clinical examination, and biopsy specimens of lesional
skin were examined by light microscopy and immunohistochemistry.
Polymerase chain reaction amplification for T-cell receptor gamma gene
rearrangements and in situ hybridization for EBV were performed on 3
biopsy specimens. SETTING: National Institutes of Health, a tertiary
referral center. PATIENTS: Individuals with a clinical and histologic
diagnosis of primary gamma delta CTCL. OUTCOME MEASURES: Clinical, light
microscopic, and immunohistochemical features, and the presence of
T-cell rearrangement and EBV RNA in biopsy specimens. RESULTS: Patients
exhibited multiple plaques, tumors, and/or subcutaneous nodules
primarily distributed over the extremities. Individuals exhibited an
aggressive clinical course with resistance to multiagent chemotherapy
and radiation. Microscopic examination revealed epidermotropism in 2
cases, a dermal infiltrate in all 3 cases, and subcutaneous involvement
in 1 case. Immunohistochemical studies showed the presence of CD3(+)TCR
delta(+) in 3 patients, CD8(+)in 1, and CD4(+), CD20(+), CD56(+), and
beta F1(+) in none. All 3 cases exhibited an activated cytotoxic T-cell
phenotype positive for T-cell intracellular antigen 1, perforin, and
granzyme B. A clonal T-cell receptor gamma chain gene rearrangement was
detected in all 3 cases by polymerase chain reaction. In situ
hybridization was negative for EBV sequences in all 3 cases. CONCLUSION:
gamma delta Cutaneous T-cell lymphomas are EBV-negative lymphomas that
express a mature cytotoxic phenotype and have an aggressive clinical
behavior. Arch Dermatol. 2000;136:1024-1032
6
UI - 10989649
AU - Jhala DN; Medeiros LJ; Lopez-Terrada D; Jhala NC; Krishnan B; Shahab I
TI -
Neutrophil-rich anaplastic large cell lymphoma of T-cell lineage. A
report of two cases arising in HIV-positive patients.
SO - Am J Clin Pathol 2000 Sep;114(3):478-82
AD - Department of Pathology, Ben Taub General Hospital, Houston, TX, USA.
Neutrophil-rich anaplastic large cell lymphoma (ALCL) is an uncommon
morphologic variant of ALCL. We report 2 cases of neutrophil-rich T-cell
ALCL that presented as scalp masses in HIV-positive men. Histologically,
the neoplastic cells extensively infiltrated the dermis and subcutaneous
tissue. The neoplastic cells strongly expressed CD30 and were of T-cell
lineage, positive for CD3 and CD45RO, and negative for CD20. The
neoplastic cells were negative for anaplastic lymphoma kinase-1.
Numerous admixed neutrophils also were present, representing up to 70%
of all cells in some microscopic fields. Neither patient had peripheral
blood leukocytosis. One patient had relative neutrophilia, 79% (0.79;
reference range, 50%-70% [0.50-0.70]). The absolute CD4 counts were 160
cells/microL (160 x 10(6)/L) and 150 cells/microL (150 x 10(6)/L),
respectively (reference range, 431-1,623/microL [431-1,623 x 10(6)/L]).
Both patients were treated with multiagent chemotherapy but died of
Pneumocystis carinii pneumonia within 6 months of diagnosis. In our
review of the literature, we identified 5 similar T-cell cases,
including 1 in an HIV-positive patient. Neutrophil-rich T-cell ALCL is a
rare morphologic variant of ALCL that should be considered in the
histologic evaluation of neutrophil-rich biopsy specimens.
7
UI - 11561692
AU - Argiris A; Heald P; Kuzel T; Foss FM; DiStasio S; Cooper DL; Arbuck S;
TI -
Murren JR
Phase II trial of 9-aminocamptothecin as a 72-h infusion in cutaneous
T-cell lymphoma.
SO - Invest New Drugs 2001;19(4):321-6
AD - Northwestern University Medical School, Division of Hematology-Oncology,
and Robert H. Lurie Comprehensive Cancer Center, Chicago, IL 60611, USA.
PURPOSE: To evaluate the role of 9-aminocamptothecin (9-AC), a synthetic
camptothecin analog, in advanced cutaneous T-cell lymphoma (CTCL).
METHODS: Eligible patients had stage IIB-IV CTCL. 9-AC was infused over
72 h at a dose of 1,100 microg/m2 per day (approximately 46 microg/m2/h)
every 2 weeks, with granulocyte-colony stimulating factor (G-CSF)
support. RESULTS: Twelve patients received a total of 30 cycles of 9-AC.
Nine patients had stage IV disease, 5 patients had circulating Sezary
cells, and 2 patients had evidence of tranformation to a large cell
lymphoma. Most of the patients were heavily pretreated: 10 had received
prior chemotherapy (83%), 5 of whom had received 2 or more prior
regimens, including a patient who had received high-dose chemotherapy,
and 7 had previously received total-skin electron beam therapy. The
study was prematurely terminated due to substantial toxicity. Six
patients (50%) developed an indwelling central venous catheter-related
infection, 5 during a period of neutropenia. Three patients died due to
sepsis 4-8 weeks after their last 9-AC treatment. Two of these patients
had a previous history of bacterial sepsis. Four patients (33%)
developed grade IV thrombocytopenia. Two partial responses were observed
(response rate 17%), but the duration of response was brief, 4-8 weeks.
CONCLUSION: 9-AC at this schedule and route of administration had
activity but resulted in an unacceptable rate of complicated neutropenia
and septic deaths in heavily pretreated patients with advanced CTCL who
are susceptible to catheter-related infections.
8
UI - 11813330
AU - Gatter KM; Rader A; Braziel RM
TI -
Fine-needle aspiration biopsy of anaplastic large cell lymphoma, small
cell variant with prominent plasmacytoid features: case report.
SO - Diagn Cytopathol 2002 Feb;26(2):113-6
AD - Department of Pathology, Oregon Health and Science University, Portland,
OR 97201-3098, USA. gatterk@ohsu.edu
Anaplastic large cell lymphoma (ALCL), according to the new WHO
classification, is a diagnosis limited to T/NK cell lymphomas. We
present a case that demonstrates a new morphologic variant of ALCL with
significant possible pitfalls for the cytopathologist. A fine-needle
aspiration biopsy of a cervical lymph node showed a cellular aspiration
comprised of medium-sized plasmacytoid cells in a discohesive and
focally loosely cohesive pattern. The cytologic diagnosis confirmed the
presence of malignancy and noted the prominent plasmacytoid features. An
accompanying comment favored melanoma and included a broad differential.
No cell block was available for immunohistochemical stains.
Immunophenotyping of the subsequent excisional node biopsy showed an
anaplastic lymphoma kinase (ALK)-positive ALCL. This case illustrates a
new variant of ALCL. Although ALCL variants, such as small cell and
lymphohistiocytic, are well recognized, the plasmacytoid features are an
additional potential source for misdiagnosis. This case report shows
that a cytopathologist should include ALK-positive ALCL in the
differential diagnosis of plasmacytoid proliferations cell because of
the clinical importance of the ALK-positive ALCL.
9
UI - 11815868
AU - Kahwash SB; Qualman SJ
TI -
Cutaneous lymphoblastic lymphoma in children: report of six cases with
precursor B-cell lineage.
SO - Pediatr Dev Pathol 2002 Jan-Feb;5(1):45-53
AD - Department of Laboratory Medicine, Children's Hospital, 700 Children's
Drive, Columbus, OH 43205, USA.
Precursor B lymphoblastic lymphomas (B-LBL) are generally rare, but
appear to have a higher incidence in children than in adults. In this
report, we describe in detail six cases of B-LBL presenting with
cutaneous lesions. Three occurred in the scalp, one in the skin of the
thigh, one in the skin of the face and breast, and one in the
subcutaneous tissue of the orbit. All six patients are females ranging
in age at presentation from 5 to 15 years (mean = 9.6). None of the
cases had bone marrow involvement, while two had bone involvement
(maxilla, distal tibia, and distal humerus in one case, and distal tibia
and orbital bone in another case); only one case had lymphadenopathy
(retroperitoneal). Immunohistochemical staining showed positivity for
CD79a and CD43 in all six cases. LCA and L26 positivity were also each
seen in one case. Staining for MIC-2 (CD99) showed strong positivity in
three cases. Vimentin was positive in four cases and TdT was positive in
all five patients tested. Staining for keratin, UCHL-1, or CD30 was not
encountered. Cases in which cell marker studies by flow cytometry were
performed showed positivity for CD10, CD19 with negative CD20,
pan-T-cell, and myeloid markers. The five patients who received
multiagent chemotherapy are alive with follow-up intervals of 2 to 18
years. Two patients had local recurrences and were given radiation
therapy (one with repeating multiagent chemotherapy). One patient
(diagnosed in 1962) died of disseminated disease; she had been treated
with radiation therapy and 6MP only. Cutaneous B-LBL must be included in
the differential diagnosis of small blue cell tumors, especially in
children. In contrast to its T-cell counterpart, B-LBL occurs more
frequently in females, tends to present as skin or bone lesions, and is
associated with a potential cure, even in cases that relapse.
10
UI - 11582733
AU - Marschalko M; Kovacs J; Somlai B; Berecz M; Hidvegi B; Harsing J;
TI -
Desaknai M; Horvath A
[Interferon-alpha and PUVA therapy for mycosis fungoides]
SO - Orv Hetil 2001 Sep 16;142(37):2021-3
AD - Altalanos Orvostudomanyi Kar, Bor- es Nemikortani Klinika, Semmelweis
Egyetem, Budapest.
14 patients suffering from early stage mycosis fungoides were treated
with interferon alpha 2-a and PUVA/1 patient in stage I a, 3 patients in
stage I b, 4 patients in stage II a and 6 patients in stage II b/during
3-21 months time course. Interferon alpha 2-a was administered 3 times a
week, in escalating dose from 3 MU to 9 MU, determining the individual
maximal tolerated dose. All of the patients responded well to the
treatment. Partial remission was observed after 4-13 weeks of treatment.
Total remission developed in 8 cases, after 8 weeks- 9 months of the
treatment. Side effects occurred frequently: weight loss, pain, fever,
fatigue, leucopenia, thrombopenia, liver enzyme elevation. Because of
the side effects the dose of the interferon was reduced individually,
the dose reduction did not cause relapse.
11
UI - 11606919
AU - Kashani-Sabet M; McMillan A; Zackheim HS
TI -
A modified staging classification for cutaneous T-cell lymphoma.
SO - J Am Acad Dermatol 2001 Nov;45(5):700-6
AD - Cutaneous Oncology Division, University of California San Francisco
Cancer Center, 4th Floor, 1600 Devisadero Street, San Francisco, CA
94115, USA.
BACKGROUND: Despite refinements in the diagnosis of cutaneous T-cell
lymphoma (CTCL), since 1979 there have been no changes to the staging of
CTCL used to classify mycosis fungoides and Sezary syndrome. OBJECTIVE:
We reviewed the current staging of CTCL and examined the usefulness of a
new staging scheme for mycosis fungoides and Sezary syndrome. METHODS:
We determined overall survival of 450 patients with mycosis fungoides
and Sezary syndrome using the current and modified staging
classifications. RESULTS: There were no significant differences between
survival of patients with stage IB (patches/plaques involving greater
than 10% body surface area) and IIA (peripheral adenopathy) disease and
of patients with stage IIB (tumor) and III (erythroderma) disease. There
was a significant difference in survival between patients with extensive
patch versus extensive plaque stage disease. Modification of the current
classification by splitting T2 into patch versus plaque stage disease
and incorporating tumors and erythroderma into stage III proved superior
to the current scheme in predicting overall survival. CONCLUSION:
Modification of the current staging classification for CTCL yields
subgroups useful in the prognostic assessment of CTCL.
12
UI - 11841384
AU - Knudsen H; Gronbaek K; thor Straten P; Gisselo C; Johansen P; Timshel S;
TI -
Bergmann OJ; Hansen NE; Ralfkiaer E
A case of lymphoblastoid natural killer (NK)-cell lymphoma: association
with the NK-cell receptor complex CD94/NKG2 and TP53 intragenic
deletion.
SO - Br J Dermatol 2002 Jan;146(1):148-53
AD - Department of Pathology, Herlev University Hospital, Copenhagen,
Denmark.
The clinical, histological, phenotypic and genotypic features of a
lymphoblastoid natural killer (NK)-cell lymphoma presenting in the skin
in a young caucasian woman are described. The disease behaved
aggressively, but long-lasting remission was obtained by combination
chemotherapy followed by autologous bone marrow transplantation. The
blastoid cells were positive for terminal deoxynucleotidyl transferase,
CD34, CD56 and CD4. Furthermore, the NK-cell receptor complex CD94/NKG2
was strongly expressed, as shown by examination with reverse
transcription-polymerase chain reaction. The T-cell receptor (TCR)-gamma
genes were in germline, and with the exception of CD4 all T-cell
antigens were negative, including CD3, TCR-beta, TCR-delta, TIA-1,
granzyme B and perforin. Epstein-Barr virus was negative, and no
expression was seen of myeloid cell-associated markers. Molecular
analysis showed no abnormalities of the CDKN2A (p16), CDKN2B (p15) or
TNFRSF6 (Fas) genes. By contrast, a 34-bp deletion in exon 7 of the TP53
(p53) gene was detected. It is suggested that lymphoblastoid NK-cell
lymphoma, which is a rare but distinctive disease, originates from NK
cell precursors and may be associated with and possibly caused by
alterations in the TP53 gene. Experience is too limited to warrant
therapeutic suggestions. However, stem cell transplantation may be a
useful option in younger patients.
13
UI - 11841367
AU - Bladon J; Taylor PC
TI -
Extracorporeal photopheresis in cutaneous T-cell lymphoma and
graft-versus-host disease induces both immediate and progressive
apoptotic processes.
SO - Br J Dermatol 2002 Jan;146(1):59-68
AD - Department of Haematology, Rotherham General Hospital, Moorgate Road,
Rotherham, South Yorkshire S60 2UD, UK. john.bladon@rgh-tr.trent.nhs.uk
BACKGROUND: Extracorporeal photopheresis (ECP) therapy is used in the
treatment of many T-cell-mediated conditions including cutaneous T-cell
lymphoma and graft-versus-host disease and involves the reinfusion of a
patient's own white cells following exposure to 8-methoxypsoralen and
ultraviolet A. ECP has been demonstrated to induce significant levels of
apoptosis in treated lymphocytes. Previous work has highlighted the
importance of mitochondria and the caspase cascade in the regulation and
execution of apoptosis and, more recently, a functional role for CD10
has been proposed for apoptotic lymphoid cells in vivo. OBJECTIVES: To
determine the effect of ECP on phosphatidylserine (PS) exposure,
mitochondrial function, caspase activation and CD10 expression of
treated lymphocytes. METHODS: Lymphocytes were tested pre-ECP and at
several stages post-ECP for changes to PS, mitochondrial transmembrane
potential (DeltaPsim), activated caspases and CD10 expression. RESULTS:
Early apoptosis induced a disruption in DeltaPsim, while caspase
activation was not observed until 24 h post-ECP. CD10 expression was
very weak and "late" in the apoptotic process. CONCLUSIONS: The early
induction of apoptosis by ECP involves mitochondrial dysfunction, while
later apoptosis is associated with the activation of caspases. CD10
expression was very weak and "late", preceded by a strong PS exposure.
These apoptotic processes, in vivo, would induce the immediate and
progressive phagocytosis of the majority of ECP-treated lymphocytes
within 48 h.
14
UI - 10620126
AU - Fraser-Andrews EA; Woolford AJ; Russell-Jones R; Seed PT; Whittaker SJ
TI -
Detection of a peripheral blood T cell clone is an independent
prognostic marker in mycosis fungoides.
SO - J Invest Dermatol 2000 Jan;114(1):117-21
AD - Skin Tumour Unit, St. John's Institute of Dermatology, United Medical
and Dental School of Guy's and St. Thomas's Hospital, London, UK.
e.fraser-andrews@umds.ac.uk
T cell receptor gene analysis is a sensitive method for assessment of
peripheral blood involvement in mycosis fungoides. This study uses
polymerase chain reaction/single-strand conformational polymorphism
(PCR/SSCP) analysis of the T cell receptor gamma gene and relates the
results to skin stage and outcome in mycosis fungoides. Seventy-five
peripheral blood samples from 66 patients were obtained from 1990
onwards and subjected to PCR/SSCP. Both Southern blot analysis and
PCR/SSCP analysis were performed on 63 samples from 56 patients.
Fourteen patients had T1 disease (12 IA, two IIA), 20 T2 (14 IB, five
IIA, one IVA), 29 T3 (24 IIB, two IVA, three IVB, two patients tested at
both T2 and T3), and five T4 (all III). The percentage of positive
samples was higher with PCR/SSCP than with Southern blot analysis (29 of
63 vs eight of 63 samples, p < 0.001), and the percentage of positive
samples increased with each stage (21% at T1, 35% at T2, 58% at T3, and
71% at T4). Proportional hazards analysis corrected for age, skin, and
lymph node stage showed that the presence of a peripheral blood clone is
associated with a worse outcome (p = 0.03, CI 1.1-6.03). These results
indicate that the presence of a peripheral blood clone is an independent
prognostic variable in patients with mycosis fungoides after correcting
for age, skin, and lymph node stage, and that peripheral blood
involvement is present in a large proportion of patients with early
stage mycosis fungoides. Keywords: polymerase chain
reaction/single-strand conformational polymorphism/T cell receptor gene
rearrangement. J Invest Dermatol 114:117-121, 2000
15
UI - 10951290
AU - Muche JM; Lukowsky A; Ahnhudt C; Gellrich S; Sterry W
TI -
Peripheral blood T cell clonality in mycosis fungoides -an independent
prognostic marker?
SO - J Invest Dermatol 2000 Sep;115(3):504-5
16
UI - 11231336
AU - Andrews EF; Woolford A; Jones RR; Whittaker S
TI -
A peripheral blood T cell clone is a prognostic marker in mycosis
fungoides.
SO - J Invest Dermatol 2001 Mar;116(3):484-5
17
UI - 11834843
AU - Dippel E; Poenitz N; Klemke CD; Orfanos CE; Goerdt S
TI -
Familial lymphocytic infiltration of the skin: histochemical and
molecular analysis in three brothers.
SO - Dermatology 2002;204(1):12-6
AD - Department of Dermatology, University Medical Center Benjamin Franklin,
Free University of Berlin, Germany.
edgar.dippel@haut.ma.uni-heidelberg.de
BACKGROUND: Lymphocytic infiltration of the skin (Jessner and Kanof) is
a T cell pseudolymphoma characterized by the occurrence of recurrent
asymptomatic papules and plaques and by a coat-sleeve-like perivascular
lymphoid infiltrate. Rarely, familial cases have been reported.
OBJECTIVES: Our study was performed to address the question of a genetic
predisposition in a case of familial lymphocytic infiltration by
histochemical and molecular analysis. RESULTS: We report on 3 brothers
with typical clinical and histological features of Jessner's lymphocytic
infiltration of the skin. Immunohistochemical analysis revealed a mixed
lymphocytic infiltrate with a predominance of CD8+ T cells in all 3
patients. Molecular determination of T cell clonality by PCR-based
GeneScan analysis of the T cell receptor (TCR)-gamma-chain showed
oligoclonal, pseudomonoclonal or polyclonal TCR-gamma rearrangement
patterns in lesional skin and in peripheral blood of all 3 brothers,
while no common TCR idiotype was detected. CONCLUSION: Inherited
deviations in TCR usage seem unlikely as a special cause of familial
Jessner's lymphocytic infiltration of the skin; lack of clonality
furthermore supports the notion that this variant of the disease is as
true a pseudo-T-cell lymphoma as are the spontaneous cases. Copyright
2002 S. Karger AG, Basel
18
UI - 11841422
AU - Chen N; Agosti S; Doll D
TI -
Blastic natural killer cell leukaemia/lymphoma.
SO - Br J Haematol 2002 Feb;116(2):241
AD - Division of Hematology-Oncology and Pathology, James A. Haley Veteran's
Hospital, Tampa, Florida, USA.
19
UI - 11899124
AU - Mimouni D; David M; Feinmesser M; Coire C I; Hodak E
TI -
Vitiligo-like leucoderma during photochemotherapy for mycosis fungoides.
SO - Br J Dermatol 2001 Dec;145(6):1008-14
AD - Department of Dermatology, Rabin Medical Centre, Petah Tikva, Israel.
mimouni@post.tau.ac.il
We describe four patients with mycosis fungoides (MF) in whom
depigmentation, and also leucotrichia in one, occurred following the
resolution of the eruption during phototherapy (psoralen plus
ultraviolet A treatment in three patients, climatotherapy in one). In
all cases, the depigmentation was localized to the area of the
pre-existing MF lesions. There was no clinically obvious phototoxicity.
Biopsy study including S100 staining in all cases, and electron
microscopy in one case, demonstrated the total absence of melanocytes,
with no evidence of MF. It is suggested that the phototherapy may have
activated a cell-mediated immunity leading to destruction of the
melanocytes. We recommend that vitiligo-like leucoderma be added to the
list of untoward effects of phototherapy in MF.
20
UI - 11899134
AU - Dereure O; Portales P; Clot J; Guilhou J J
TI -
Decreased expression of fas (APO-1/CD95) on lesional CD4+ T lymphocytes
in cutaneous T cell lymphomas: correlations with blood data.
SO - Br J Dermatol 2001 Dec;145(6):1031-2
21
UI - 11899146
AU - Nevala H; Karenko L; Vakeva L; Ranki A
TI -
Proapoptotic and antiapoptotic markers in cutaneous T-cell lymphoma skin
infiltrates and lymphomatoid papulosis.
SO - Br J Dermatol 2001 Dec;145(6):928-37
AD - Department of Dermatology and Venereal Diseases, Helsinki University
Central Hospital, Finland.
BACKGROUND: In cutaneous T-cell lymphoma (CTCL) lesions, both reactive T
cells and malignant T cells intermingle. The disease progression is
mostly slow. Recent evidence suggests that even if clinical remission is
reached, malignant cells persist and a relapse follows sooner or later.
To wha extent tumour cell apoptosis occurs in the skin lesions either
due to the reactive T cells or t therapeutic efforts is not known.
OBJECTIVES: To determine the extent of tumour cell apoptosis and the
expression of proapoptotic an antiapoptotic markers in serial skin
lesion samples from patients with CTCL, and to compare th findings with
those in patients with lymphomatoid papulosis (LyP). METHODS:
Thirty-four skin samples were obtained from 12 patients with CTCL at the
time o diagnosis and at a mean of 1.6, 3 and 6 years later. The patients
received psoralen plus ultraviolet (PUVA), electron beam or cytostatic
treatments. In addition, fresh post-treatment samples fro three patients
with CTCL undergoing PUVA therapy were obtained. For comparison, skin
biopsies o five patients with LyP were studied. Immunohistochemical
demonstration of the expression of th following markers was performed on
formalin-fixed skin sections: Fas (CD95), Fas ligand (FasL) bcl-2,
granzyme B, the tumour-suppressor protein PTEN and the effector caspase,
caspase-3. Th malignant cells were identified morphologically, and
apoptotic cells were identified with th terminal deoxynucleotidyl
transferase-mediated deoxyuridine triphosphate nick end labelling method
on parallel sections. RESULTS: In untreated CTCL lesions, apoptotic
lymphocytes were extremely rare, and no increase in the number of
apoptotic cells was observed after any of the treatments used. In LyP,
apoptotic cell were more frequent, comprising on average 5% of the
infiltrate. The apoptosis-associated marker Fas, FasL, caspase-3 and
granzyme B were expressed by morphologically neoplastic cells in CTCL
and by large atypical cells in LyP, with no significant differences.
However, only a few reactive cell in CTCL infiltrates expressed granzyme
B while about 10% of the corresponding cells were positive in LyP. The
expression of antiapoptotic bcl-2 was more frequent in CTCL than in LyP,
while PTE expression was high in both instances. The number of bcl-2 +
cells tended to decrease after therapy When comparing the findings
between the first and the last samples, a decrease in the number of
bcl-2+ cells and an increase in Fas+ cells was associated with disease
progression, despite therapy, while the opposite was true for
remissions. CONCLUSIONS: Apoptosis was found to be a rare event in CTCL
lesions irrespective of precedin therapy During patient follow-up, no
significant differences in the expression of apoptotic marker was
observed while in most cases a lower level of antiapoptotic bcl-2
expression was observed after all types of therapies and in association
with disease progression when compared with high expression in the
untreated lesions. The absence of apoptosis and high expression of bcl-2
together with a low expression of apoptosis-inducing granzyme B in the
reactive lymphocytes in CTC could explain the chronic nature of the
disease and the poor response to therapy, while th more frequent
occurrence of granzyme B and apoptosis together with a lower level of
expressio of bcl-2 by the large atypical cells in LyP could contribute
to the favourable outcome of the latter.
22
UI - 11899152
AU - Hodak E; Lapidoth M; Kohn K; David D; Brautbar B; Kfir K; Narinski N;
TI -
Safirman S; Maron M; Klein K
Mycosis fungoides: HLA class II associations among Ashkenazi and
non-Ashkenazi Jewish patients.
SO - Br J Dermatol 2001 Dec;145(6):974-80
AD - Department of Dermatology, Rabin Medical Center, Sackler Faculty of
Medicine, Tel Aviv University, Petah Tiqva, Israel. ehodak@clalit.org.il
BACKGROUND: An immunogenetic mechanism has been suggested to play a role
in the pathogenesis of mycosis fungoides (MF). While results of studies
on HLA class I associations haveproved inconsistent, two previous
studies showed that certain HLA class II alleles were significantly
increased among North American caucasian patients with MF: HLA-DRB1*11
and DQB1*03. OBJECTIVES: To investigate the possible HLA class I and
class II associations with MF among Jewish patients. METHODS: The
patient group comprised 68 Jewish patients with MF: 38 Ashkenazi and 30
non-Ashkenazi. The control group comprised 252 healthy Jewish
volunteers: 132 Ashkenazi and 120 non-Ashkenazi. Tissue typing for HLA
class I (A and B) was performed using the National Institutes of Health
microlymphocytotoxicity technique. DNA-based low-medium resolution
analysis for DRB1* and DQB1* alleles was performed using polymerase
chain reaction (PCR) amplification with sequence-specific primers. For
those alleles found to have significantly increased frequency,
high-resolution analysis was done by means of PCR sequence-specific
oligotyping. RESULTS: The allele frequency of HLA-DRB1*11 was found to
be significantly increased but only among Ashkenazi patients with MF
(30% vs. 19% in the controls; P = 0.034). High-resolution analysis for
DRB1*11, not previously performed, suggested that its greater frequency
is due to the increased number of Ashkenazi MF patients with the
DRB1*1104 allele (P corrected = 0.036). Analysed together, DQB1*03
alleles (DQB1*0301-0304) had a significantly greater frequency in MF as
a group as compared with controls (47% vs. 33%, P = 0.003). DQB1*0301
was demonstrated to be the specific allele associated with MF in Jewish
patients (allele frequency of 36% vs. 23% in controls; P corrected =
0.0068), which was not the case for North American caucasian patients
with MF. No greater frequencies of any of the HLA class I A or B
antigens were found. CONCLUSIONS: Our findings further demonstrate the
'universality' of MF HLA class II susceptibility alleles, i.e.
HLA-DRB1*11 and HLA-DQB1*03, suggesting that HLA polymorphism is likely
to be important in the pathogenesis of MF in Jewish patients, as it is
in North American caucasian patients. Not previously reported is our
finding that HLA-DRB1*1104 is the specific allele more prevalent among
patients with MF. Our study also underscores some differences in HLA
profiles between non-Jewish and Jewish patients with MF and between
Ashkenazi and non-Ashkenazi Jewish patients, indicating the possibility
of diverse HLA disease associations in populations with different
genetic backgrounds. Our study provides further evidence for the lack of
association between HLA class I and MF.
23
UI - 11841558
AU - Zaki MH; Wysocka M; Everetts SE; Wang KS; French LE; Ritz J; Rook AH
TI -
Synergistic enhancement of cell-mediated immunity by interleukin-12 plus
interleukin-2: basis for therapy of cutaneous T cell lymphoma.
SO - J Invest Dermatol 2002 Feb;118(2):366-71
AD - Department of Dermatology, University of Pennsylvania, School of
Medicine, Philadelphia, Pennsylvania 19104, USA.
Cutaneous T cell lymphoma is a clonally derived, skin-invasive
malignancy of CD4+ T lymphocytes with the phenotype of mature helper T
cells. Previous work has demonstrated that the Sezary form, or typically
leukemic form of cutaneous T cell lymphoma, is characterized by
prominent immunologic defects, including depressed cell-mediated
immunity associated with marked defects in the production of
interleukin-12 and other type 1 helper T cell cytokines. Recent clinical
trials with recombinant human interleukin-12 for cutaneous T cell
lymphoma have demonstrated that it is a potent therapeutic agent, which
induces cytotoxic T cell responses. Nevertheless, a high rate of
refractoriness to recombinant human interleukin-12 occurred in these
studies that may be related to the downmodulation of interleukin-12
receptor expression by chronic interleukin-12 use. In an effort to
enhance the overall response rate and to overcome the refractoriness to
recombinant human interleukin-12 therapy, we studied the immunologic
effects in vitro of adding interleukin-2 to interleukin-12 as a model to
achieve these goals. We examined the stimulation of interferon-gamma
production, natural killer cell activity and interleukin-12 receptor
expression by T cells of cutaneous T cell lymphoma patients. The
addition of interleukin-12 to cutaneous T cell lymphoma patient
peripheral blood cells resulted in the production of interferon-gamma
(mean = 7914 pg per ml +/- 2161, n = 15) as did interleukin-2 alone
(mean = 7222 pg per ml +/- 2228, n = 15). Importantly, the addition of
interleukin-2 to the interleukin-12 synergistically enhanced the levels
of interferon-gamma produced (mean = 16 792 pg per ml +/- 2492 n = 15)
(p <0.01). Similarly, addition of interleukin-2 to interleukin-12
synergistically enhanced both the natural killer cell activity of 15
cutaneous T cell lymphoma patients as well as T cell surface
interleukin-12 receptor expression in comparison with the effects of
interleukin-12 or interleukin-2 alone. Thus, interleukin-2 plus
interleukin-12 unequivocally produces the synergistic enhancement of
multiple parameters of cell-mediated immunity as well as upmodulating
interleukin-12 receptor expression; this indicates that protocols
combining these two potent immune enhancing cytokines may have added
therapeutic benefit for cutaneous T cell lymphoma.
24
UI - 11862188
AU - Radonich MA; Lazova R; Bolognia J
TI -
Cutaneous natural killer/T-cell lymphoma.
SO - J Am Acad Dermatol 2002 Mar;46(3):451-6
AD - Department of Dermatology, Yale Dermatopathology Laboratory, Yale
University School of Medicine, 15 York Street, New Haven, CT 06520-8059,
USA.
Lymphomas are classified as either Hodgkin's or non-Hodgkin's. The 2
subtypes of non-Hodgkin's lymphoma that can present primarily in the
skin are cutaneous T-cell lymphoma and cutaneous B-cell lymphoma, both
of which tend to be low-grade malignant neoplasms. Recently another
distinct subtype of lymphoma was discovered, the natural killer
(NK)/T-cell lymphoma, which can involve the skin in a primary or
secondary fashion. The NK/T-cell subtype of lymphoma is characterized by
the expression of the NK-cell antigen CD56. These CD56(+) lymphomas are
further subdivided into nasal NK/T-cell lymphomas that commonly present
as midfacial destructive disease and non-nasal NK/T-cell lymphomas that
often arise in extranodal locations, including the skin. We report a
case of aggressive NK-cell leukemia/lymphoma with numerous secondary
cutaneous lesions and review the clinical and histopathologic spectrum
of non-nasal CD56(+) lymphomas, with an emphasis on the dermatologic
findings.
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