ARTICLE
In 1982, Schwab et al. first described the production of a monoclonal
antibody, named Ki-1, directed against Reed-Sternberg cells in Hodgkin's
disease but which could stain a small population of cells in normal and
reactive lymph nodes as well [1]. This antibody was later shown to recognize
a surface antigen of lymphocytes called CD30, considered as a marker of
activation of lymphoid cells; however, its physiological function remains
elusive to date even if it may play a role in lymphocyte apoptosis. In
1985, Stein et al. identified a distinct clinicopathological entity
among non Hodgkin's lymphomas, characterized by large, anaplastic, cohesive
neoplastic cells which uniformly expressed CD30 (more than 75%) [2-4].
These lymphomas, called "CD30 (Ki-1) positive anaplastic large cell lymphomas"
(CD30+ ALCL) [5], mostly arise in lymph nodes but may appear
in other parts of the body, especially in the skin even if true primary
cutaneous CD30+ ALCLs remain infrequent [5-10]. They are ranked
as high-grade malignant lymphomas in the Updated Kiel Classification [11]
when they involve lymph nodes but, despite its alarming histological appearance,
the primary cutaneous subset has been associated by Beljaards and coworkers
[12] with a usually indolent clinical course. Primary cutaneous CD30+
ALCLs are mainly of T cell lineage [3, 13, 14], often display self-healing
tumoral lesions at the beginning of their evolution, are usually highly
responsive to therapy and have a more favorable outcome than extra-cutaneous
CD30+ ALCLs with a 4-year survival rate of 90% [4, 12]. Extra-cutaneous
spreading of the disease has been reported but remains rare.
The pathogenesis of CD30+ ALCL is still unclear. Epstein-Barr
virus (EBV) gene products have been found in tissues obtained from patients
with various lymphoproliferative diseases including Hodgkin's disease
[15-18] which is considered to be phenotypically close to CD30+
ALCL [8-10, 19, 20]. Some authors have reported a relationship between
CD30+ ALCL and EBV infection as well [21-25]. More precisely,
the observation of monoclonal integration of the EBV genome in certain
CD30+ ALCL lesions suggests that EBV may play an aetiopathogenic
role in this type of lymphoma [21].
In an attempt to clarify the relation of EBV infection with cutaneous
primary CD30+ ALCL, we present the first study combining three
different methods to detect the presence of EBV in skin lesions. This
work was conducted in 8 patients with primary cutaneous CD30+
ALCL, investigated for the presence of EBV DNA by the polymerase chain
reaction (PCR) technique, for the presence and localization of EBV-encoded
small nuclear RNAs (EBERs) by in situ hybridization (ISH) and for
the expression of EBV-encoded latent membrane protein 1 (LMP-1) by immunohistochemistry
(IHC).
Material and methods
Tissues
Formalin-fixed paraffin-embedded skin biopsies from 8 primary cutaneous
CD30+ ALCL occurring in patients without immunodeficiency (5
men, 3 women, 26-68 years-old) were selected from the files of the Departments
of Dermatology of two referral university hospitals (Montpellier and Nimes,
France) for ISH and IHC analysis. PCR analysis was performed on frozen
specimens of neoplastic and non-neoplastic skin from 6 of these patients
and on neoplastic skin only for the two last patients. Diagnosis was based
in all cases on the usual clinical (in particular, absence of extra-cutaneous
involvement at the time of diagnosis), histomorphological and immunological
data (Table I). All of
these cases but one displayed a T cell phenotype whereas the last one
expressed no T nor B membrane marker and was accordingly classified as
a non-T non-B lymphoma. No serological data as to previous or current
EBV infection were available.
Polymerase chain reaction
DNA was extracted from frozen tissue samples using the QIamp tissue
Kit (Quiagen Inc, Santa-Clara, CA USA). DNA extracted from an EBV-infected
cell line was used as a positive control. Samples containing all PCR reagents
with the exception of the target DNA were used as negative control. To
amplify EBV DNA we used a nested PCR assay with two external primers for
standard PCR and two internal primers for nested PCR, with resulting amplified
fragments of 479 and 285 bp respectively. Sequences and nucleotide positions
of primers are shown in Table
II. For the first round of amplification, 1 mug of DNA template
was mixed with 40 muL of a solution containing 8 mM deoxynucleotide triphosphate,
2 units of Taq polymerase, 10 mM Tris HCl, 50 mM KCl, 1.5 mM MgCl2,
0.1% Triton x 100, 0.2 mg/ml BSA, 20 pmol of the respective primers and
32.75 muL of sterile distilled water. For the internal amplification,
aliquots of 5 muL of the primary products were incubated in 45 muL of
the same solution except for the presence of the second set of primers.
Both primary and secondary PCR consisted in denaturation at 94° C
for 5 min followed by 28 cycles of denaturation at 94° C for 1 min,
annealing at 46° C for 1 min, extension at 72° C for 1 min and
final elongation at 72° C for 5 min. PCR products were analysed on
a 2% ethidium bromide-stained agarose gel and fragments sizes were determined
by comparison with control DNA ladder.
In situ hybridization
To detect EBV nuclear RNA transcripts, ISH was performed with fluorescein-conjugated
peptide nucleic acid (PNA) probes specific for the EBV-encoded nuclear
RNAs EBER (DAKO PNA ISH Detection Kit, DAKO, Glostrup, Denmark) according
to the manufacturer's instructions. Briefly, deparaffinized sections were
rehydrated in xylene and ethanol. After pretreatment with proteinase K
(10 mug/mL), 25 muL of hybridization mixture containing the fluorescein-conjugated
PNA probe was applied to each tissue section. Hybridization was carried
out at 55° C for 90 min followed by incubation in a washing solution
for 25 min at 55° C. The specimens were then incubated with alkaline
phosphatase-labeled anti-fluorescein isothiocyanate antibody for 30 min,
washed and a colorimetric reaction was finally performed by incubation
at room temperature for 30 min with a substrate solution containing 5-bromo-4-chloro-3-indoxyl
phosphate, nitroblue tetrazolium chloride combined with levamisole, an
inhibitor of endogenous alkaline phosphatase. Positive and negative controls
provided with the kit were performed in parallel.
Immunohistochemistry
To detect LMP-1, deparaffinized biopsy specimens were immersed in citrate
buffer (pH 6) and submitted to an antigen-retrieval procedure with high
pressure cooking for 5 min. The sections were then incubated with a mixture
of mouse monoclonal antibodies (CS1-4) directed against LMP-1 (DAKO Glostrup,
Denmark) at 1/100 dilution. A streptavidin-peroxydase staining was finally
performed with the Peroxydase/DAB kit (DAKO) using the TechMate DAKO 500
automate.
Results
The first round of PCR displayed the presence of a 479 bp fragment in
only one of the neoplastic tissue specimens (patient n° 7), and the
specificity of this result was confirmed by the second round of the nested
PCR with amplification of the expected 285 bp fragment (Fig.
1). By contrast, EBV-DNA was not identified in any non-neoplastic
skin sample. Positive and negative controls gave the expected results.
ISH was performed in all 8 cases and showed EBERs-specific signal in
tumor cells only in the case displaying the presence of EBV DNA by nested
PCR, whereas non-neoplastic cells did not express EBERs (Fig.
2). One patient with less than 1% EBER-positive cells in the infiltrate
was considered to be negative. No EBER-specific signal was present in
the other studied patients. Positive and negative controls showed the
expected results.
Immunostaining for LMP-1 was negative in all malignant samples including
the patient with positive PCR and ISH for EBV.
Discussion
EBV has been implicated in the oncogenetic pathomechanisms of a wide
variety of lymphoproliferative disorders including endemic Burkitt's lymphomas,
Hodgkin's disease and non Hodgkin's lymphomas arising in immunosuppressed
individuals [15-18, 26-28]. More recently, EBV has been associated with
a variable proportion (4.5 to 47%) of nodal CD30+ ALCL occurring
in non-immunosuppressed patients, since EBV DNA and proteins have been
found in neoplastic lesions by various authors [21, 22, 24, 25]. Moreover,
the observation of a monoclonal EBV genome integration in some nodal CD30+
ALCL cases might be a clue that the EBV infection precedes clonal expansion
and thus suggests an aetiological role for the virus in the pathogenesis
of this type of lymphoma [21, 23] rather than being an innocent bystander.
However, the presence of EBV in tumoral cells seems to be a rare finding
in primary cutaneous (CD30+ ALCL), a subset that affects primarily
the skin and which is usually characterized by an indolent course [12],
and this regardless of the methods used (PCR, ISH or IHC) [22, 24, 25,
29-32]. More precisely, EBV DNA and RNA have been identified in one case
of primary cutaneous CD30+ ALCL by Borish et al. using
PCR and ISH methods [33] and, more recently, in one out of three cases
by Su et al. using ISH and Southern Blot analysis [34]. Therefore,
the role of EBV in the pathogenesis of primary cutaneous CD30+
ALCL, subtype, remains questionable and we present here the first study
of the relationship between EBV and this peculiar subset of cutaneous
lymphoma using a combined search by PCR, ISH and IHC.
Using a nested PCR assay to amplify DNA extracted from 8 primary cutaneous
CD30+ ALCL, we detected EBV genomes in only one of them. PCR
was negative for non-neoplastic skin lesions as well, including the patient
with positive PCR on neoplastic samples. The PCR method can achieve different
levels of sensitivity depending on the amplification conditions and the
methods of product detection [35]. However, the use of nested amplification
primers enhances the sensitivity and the specificity of the PCR technique
[36]. Moreover, PCR data were correlated with ISH employing EBERs-specific
probes, another highly sensitive method for detecting the presence of
EBV at the single cell level due to the huge numbers of target EBER RNAs
in latently infected cells (up to 107 copies per cell) [23,
29]. These data provide evidence that neoplastic cells of this patient
were really infected by EBV. The sensitivity of ISH may be questioned
but it must be pointed out that EBERs are stable RNAs, allowing the analysis
of paraffin-embedded tissue specimens, as in our study [23]. The biological
relevance of this result is unclear since the presence of EBV infection
does not necessarily mean that the virus plays a relevant aetiological
role in neoplastic transformation. Instead, it might be a coincidental
event as EBV is a ubiquitous agent with a high incidence of latent viral
infection in the adult population [23], and, in this hypothesis, EBV would
only be an innocent bystander in lesions triggered by different aetiological
factors. This possibility is indeed supported by the detection of this
virus in a variety of reactive and neoplastic lymphoid lesions [35]. However,
EBV RNAs were found only in neoplastic (and not in non-neoplastic) tissue
of our patient, which suggests its possible involvement in lymphomagenesis.
Unfortunately, no additional tissue was available to perform Southern
Blot analysis, which is the only method to assess the monoclonal integration
of the virus in the infected cells. Indeed, a monoclonal integration of
the virus is a strong, although not definite, clue for responsability
of the virus in the oncogenetic pathomechanisms even if additional factors
are probably involved. Finally, it is of interest to point out that this
PCR and ISH positive patient followed an indolent course like most of
the patients with primary cutaneous CD30+ ALCL.
The absence of immunoreactivity for the EBV-associated LMP-1 in the
EBER- and PCR-positive case can be compared to the low rates of LMP-1
positivity already reported in EBV-positive CD30+ ALCL (15-18%)
[37]. The explanation of this discrepancy is still unknown but it might
be speculated that it could reflect a phenomena allowing neoplastic cells
to escape from the immune surveillance system, since LMP can be a target
for the cytotoxic T cell-mediated control of EBV infection in vivo
[32]. Alternatively, these results might simply reflect the limited sensitivity
of the method due to technical problems such as in vitro degradation
of the antigen by storage, fixation or embedding [38]. Finally, the absence
of protein expression is possible in latent EBV infection, as in some
cases of Burkitt's lymphoma.
Apart from this positive case, the significance of which remains questionable
as discussed above, our results do not support the hypothesis that EBV
plays any role in the pathogenesis of primary cutaneous CD30+
ALCL. Because of the sensitivity of the PCR and ISH methods we used, it
is not likely that our negative results are technique-dependent. These
data are consistent with previous negative reports [22, 24, 25, 29, 30,
32] but it must be pointed out that the present study is the only one
to combine PCR, ISH and IHC methods. Lymphomatoid papulosis (LyP), another
cutaneous CD30+ lymphoproliferative disorder closely related
to primarily cutaneous CD30+ ALCL, does not seem to have any
consistent relationship with EBV infection either [39-41]. Therefore,
identification of other relevant endogenous or exogenous oncogenic factors
remains mandatory in future research. The detection by Anagnostopoulos
et al. of human T cell lymphotropic virus (HTLV-1) proviral sequences
in some cutaneous CD 30+ in a study [42] indeed supports the
idea that other specific viral infections, involving perhaps yet unidentified
retrovirus, could be implicated in the pathogenesis of this subset of
lymphoma. Genetic factors might be in cause as well by analogy with the
non-random chromosomal translocation t(2;5)(p23;q35) identified in a high
but variable proportion (15 to 65%) of lymph node ALCL [43-48]. This t(2;5)
translocation results in transcription of a novel tyrosine kinase, the
anaplastic lymphoma kinase (ALK), the kinase domain of which, located
on 2p23, is driven off the nucleophosmin (NPM) gene promoter located on
5q35 [49]. This rearrangement leads to the expression of a fusion protein
called p80 probably playing a pathogenic role in the CD30+
ALCL cases that express it [36, 44, 47, 49]. Other translocations involving
the breakpoint at 2p23 have been identified as well [47], suggesting that
genes other than NPM could be implicated in the expression of the ALK
catalytic domain, a hypothesis that seems to be supported by recent experimental
data, especially the description of the fusion of ALK with the gene TFK-fused
gene (TFG) in a patient with nodal ALCL [50, 51]. However, the identification
of the t(2;5) translocation and the expression of the p80 protein in the
primary cutaneous subset of CD30+ ALCL has been only rarely
reported and remains a matter of debate [36, 52]. Finally, another interesting
hypothesis is based on the possibilitity that the signalling pathway of
TGFbeta, a molecule that inhibits lymphocyte proliferation, might be impaired
by inactivating mutations of the type I TGFbeta-receptor as demonstrated
in a recent report [53].
CONCLUSION
In conclusion, our results do not support the hypothesis that EBV plays
a significant role in the oncogenesis of primary cutaneous CD30+
ALCL. Future investigations are therefore required to clarify these mechanisms,
and will probably focus on genetic alterations by analogy with the (2;5)
translocation identified in the nodal CD30+ ALCL and/or on
other virus responsability.
Article accepted on 26/02/01
REFERENCES
1. Schwab U, Stein H, Gerdes J, Lemke H, Kirchner H, Schaadt M,
Diehl V. Production of a monoclonal antibody specific for Hodgkin and
Sternberg-Reed cells of Hodgkin's disease and a subset of normal lymphoid
cells. Nature 1982; 299: 65-7.
2. Stein H, Mason DY, Gerdes J, O'Connor N, Wainscoat J, Pallesen
G, Gatter K, Falini B, Delsol G, Lemke H, Schwarting R, Lennert K. The
expression of the Hodgkin's disease associated antigen Ki-1 in reactive
and neoplastic lymphoid tissue: evidence that Reed-Sternberg cells and
histiocytic malignancies are derived from activated lymphoid cells. Blood
1985; 66: 848-58.
3. Suchi T, Lennert K, Tu LY, Kikuchi M, Sato E, Stansfeld AG,
Feller AC. Histopathology and immunochemistry of peripheral T cell lymphomas:
a proposal for their classification. J Clin Pathol 1987; 40: 995-1015.
4. Willemze R, Beljaards RC. Spectrum of primary cutaneous CD30
(Ki-1)-positive lymphoproliferative disorders: a proposal for classification
and guideliness for management and treatment. J Am Acad Dermatol
1993; 28: 973-80.
5. Falini B, Pileri S, Pizzolo G, Dürkop H, Flenghi L, Stirpe
F, Martelli MF, Stein H. CD30 (Ki-1) molecule: a new cytokine receptor
of the tumor necrosis factor receptor superfamily as a tool for diagnosis
and immunotherapy. Blood 1995; 85: 1-14.
6. Banerjee SS, Heald J, Harris M. Twelve cases of Ki-1 positive
anaplastic lymphoma of skin. J Clin Pathol 1991; 44: 119-25.
7. Kadin ME, Sako D, Berliner N, Franklin W, Woda B, Borowitz
M, Ireland K, Schwed A, Herzog P, Lange B, Dorfman R. Childhood Ki-1 lymphoma
presenting with skin lesions and peripheral lymphadenopathy. Blood
1986; 5: 1042-9.
8. Kadin ME. The spectrum of Ki-1+ cutaneous lymphomas.
Curr Probl Dermatol 1990; 19: 132-43.
9. Kaudewitz P, Stein H, Dallenbach F, Eckert F, Bieger K, Burg
G, Braun-Falco O. Primary and secondary cutaneous Ki-1+ (CD30)
anaplastic large cell lymphomas. Am J Pathol 1989; 135: 359-67.
10. Kaudewitz P, Burg G, Stein H. Ki-1 (CD30) positive cutaneous
anaplastic large cell lymphomas. Curr Probl Dermatol 1990; 19:
150-6.
11. Stansfeld AG, Diebold J, Kapanci Y, Kelenyi G, Lennert K,
Mioduszewska O, Noel H, Rilke F, Sundstrom C, van Unnik J, Wricht D. Updated
Kiel classification for lymphomas. Lancet 1988; 1: 292-3.
12. Beljaards RC, Kaudewitz P, Berti E, Gianotti R, Neumann C,
Rosso R, Paulli M, Meijer CJLM, Willemze R. Primary cutaneous CD30-positive
large-cell lymphoma: definition of a new type of cutaneous lymphoma with
a favorable prognosis: a European multicenter study of 47 patients. Cancer
1993; 71: 2097-104.
13. Harris NL, Jaffe ES, Stein H, Banks PM, Chan JKC, Cleary
ML, Delsol G, De Woolf-Peters C, Falini B, Gatter KC, Grogan TM, Isaacson
PG, Knowles DM, Mason DY, Muller-Hermelink HK, Pileri SA, Piris MA, Ralfkiaer
E, Warnke R. A revised European-American classification of lymphoid neoplasms:
a proposal from the international lymphoma study group. Blood 1994;
84: 1361-92.
14. Willemze R, Kerl H, Sterry W, Berti E, Cerroni L, Chimenti
S, Diaz-Peréz JL, Geerts ML, Goos M, Knobler R, Ralfkiaer E, Santucci
M, Smith N, Wechsler J, van Vloten WA, Meijer CJLM. EORTC classification
for primary cutaneous lymphomas: a proposal from the cutaneous lymphoma
group of the European organization for research and treatment of cancer.
Blood 1997; 90: 354-71.
15. Slater D. Epstein-Barr virus: an aetiological factor in lymphoproliferative
disorders. J Pathol 1991; 165: 1-4.
16. Weiss LM, Movahed LA, Warnke RA, Sklar J. Detection of Epstein-Barr
viral genomes in Reed-Sternberg cells of Hodgkin's disease. N Engl
J Med 1989; 320: 502-6.
17. Weiss LM, Chen YY, Liu XF, Shibata D. Epstein-Barr virus
and Hodgkin's disease: a correlative in situ hybridization and
polymerase chain reaction study. Am J Pathol 1991; 139: 1259-65.
18. Wright CF, Reid AH, Tsai MM, Ventre KM, Murari PJ, Frizzera
G, O'Leary TJ. Detection of Epstein-Barr virus sequences in Hodgkin's
disease by the polymerase chain reaction. Am J Pathol 1991; 139:
393-8.
19. Kaudewitz P, Burg G. Lymphomatoid papulosis and Ki-1 (CD30)-
positive cutaneous large cell lymphomas. Semin Diag Pathol 1991;
8: 117-24.
20. Volkenandt M, Bertino JR, Shenoy BV, Kloch OM, Kadin ME.
Molecular evidence for a clonal relationship between lymphomatoid papulosis
and Ki-1-positive large cell anaplastic lymphoma. J Dermatol Sci
1993; 6: 121-6.
21. Anagnostopoulos I, Herbst H, Niedobitek G, Stein H. Demonstration
of monoclonal EBV genomes in Hodgkin's disease and Ki-1-positive anaplastic
large cell lymphoma by combined southern blot and in situ hybridization.
Blood 1989; 74: 810-6.
22. Herbst H, Dallenbach F, Hummel M, Niedobitek G, Finn T, Young
LS, Rowe M, Müller-Lantzsch N, Stein H. Epstein-Barr virus DNA latent
gene products in Ki-1 (CD30)-positive anaplastic large cell lymphomas.
Blood 1991; 78: 2666-73.
23. Herbst H, Stein H, Niedobitek G. Epstein-Barr virus and CD30+
malignant lymphomas. Crit Rev Oncongen 1993; 4: 191-239.
24. Kanavaros P, Jiwa NM, De Bruin PC, van der Valk P, Noorduyn
LA, Van Heerde P, Gordijn R, Horstman A, Mullink R, Willemze R, Walboomers
JMM, Meijer CJLM. High incidence of EBV genome in CD30 positive non-Hodgkin's
lymphomas. J Pathol 1992; 168: 307-15.
25. Peris K, Niedermeyer H, Chimenti S, Radaskiewicz T, Kerl
H, Hoefler H. Detection of Epstein-Barr virus in cutaneous and lymph nodal
anaplastic large cell lymphomas (Ki-1+). Br J Dermatol
1995; 133: 542-6.
26. Borish B, Gatter KC, Tobler A, Theilkäs L, Bunch C,
Wainscoat JS, Fey MF. Epstein-Barr virus-associated anaplastic large cell
lymphoma in renal transplant patients. Am J Clin Pathol 1992; 98:
312-8.
27. Carbone A, Gloghini A, Zanette I, Canal B, Volpe R. Demonstration
of Epstein-Barr viral genomes by in situ hybridization in acquired
immune deficiency syndrome-related high grade and anaplastic large cell
CD30+ lymphomas. Am J Clin Pathol 1993; 99: 289-97.
28. Van Gorp J, Doornewaard H, Verdonck LF, Klöpping C,
Vos PF, van den Tweel JG. Posttransplant T cell lymphoma. Report of three
cases and a review of the literature. Cancer 1994; 73: 3064-72.
29. Anagnostopoulos I, Hummel M, Kaudewitz P, Korbjuhn P, Leoncini
L, Stein H. Low incidence of Epstein-Barr virus presence in cutaneous
T cell lymphoproliferations. Br J Dermatol 1996; 134: 276-81.
30. De Bruin PC, Jiwa M, Joost JO, Van der Volk P, Sabourin JC,
Csanaky G, Gaulard P, Noorduyn AL, Willemze R, Meijer CJLM. Presence of
Epstein-Barr virus in extranodal T cell lymphomas: differences in relation
to site. Blood 1994; 83: 1612-8.
31. Pabst H, Sander C, Tronnier M, Katzner H, Hugel H, Kandewitz
P. Absence of anaplastic lymphoma kinase (ALK) and Epstein-Barr virus
gene products in primary cutaneous anaplastic large cell lymphoma and
lymphomatoid papulosis. Br J Dermatol 1997; 137: 680-6.
32. Iwatsuki K, Ohtsuka M, Harada H, Han G, Kaneko F. Clinicopathologic
manifestations of Epstein-Barr virus-associated cutaneous lymphoproliferative
disorders. Arch Dermatol 1997; 1081-6.
33. Borish B, Böni J, Bürki K, Laissue JA. Recurrent
cutaneous anaplastic large cell (CD30+) lymphoma associated
with Epstein-Barr virus. Am J Surg Pathol 1992; 16: 796-801.
34. Su Ih-Jen, Tsai TF, Cheng AL, Chen CC. Cutaneous manifestations
of Epstein-Barr virus associated T cell lymphoma. J Am Acad Dermatol
1993; 29: 685-92.
35. Ross CW, Schlegelmilch JA, Grogan TM, Weiss LM, Schnitzer
B, Hanson CA. Detection of Epstein-Barr virus genome in Ki-1 (CD30)-positive,
large-cell anaplastic lymphomas using the polymerase chain reaction. Am
J Pathol 1992; 141: 457-65.
36. Beylot-Barry M, Lamant L, Vergier B, de Muret A, Fraitag
S, Delord B, Dubus P, Vaillant L, Delaunay M, Mac Grogan G, Beylot C,
de Mascarel A, Delsol G, Merlio JP. Detection of t(2;5)(p23;q35) translocation
by reverse transcriptase polymerase chain reaction and in situ
hybridization in CD30-positive primary cutaneous lymphoma and lymphomatoid
papulosis. Am J Pathol 1996; 149: 483-92.
37. Lopategui JR, Gaffey MJ, Chan JKC, Frierson HF, Sun LH, Bellafiore
FJ, Chang KL, Weiss LM. Infrequent association of Epstein-Barr virus with
CD30-positive anaplastic large cell lymphomas from American and Asian
patients. Am J Surg Pathol 1995; 19: 42-9.
38. Park CK, Ko YH. Detection of EBER nuclear RNA in T cell lymphomas
involving the skin: an in situ hybridization study. Br J Dermatol
1996; 134: 488-93.
39. Kadin ME. Lymphomatoid papulosis and associated lymphomas.
Arch Dermatol 1993; 129: 351-3.
40. Kadin ME, Vonderheid EC, Weiss LM. Absence of Epstein-Barr
viral RNA in lymphomatoid papulosis. J Pathol 1993; 170: 145-8.
41. Sangueza OP, Galloway J, Eagan PA, Braziel RM, Gulley ML.
Absence of Epstein-Barr virus in lymphomatoid papulosis: an immunohistochemical
and in situ hybridization study. Arch Dermatol 1996; 132:
279-82.
42. Anagnostopoulos I, Hummel M, Kaudewitz P, Herbst H, Braun-Falco
O, Stein H. Detection of HTLV-1 proviral sequences in CD30 positive large
cell cutaneous T cell lymphomas. Am J Pathol 1990; 137: 1317-22.
43. Bitter MA, Franklin WA, Larson RA, McKeithan TW, Rubin CM,
Le Beau M, Stephens JK, Vardiman JW. Morphology in Ki-1 (CD30)-positive
non-Hodgkin's lymphoma is correlated with clinical features and the presence
of unique chromosomal abnormality, t(2;5)(p23;q35). Am J Surg Pathol
1990; 14: 305-16.
44. Downing JR, Shurtleff SA, Zielenska M, Curcio-Brint AM, Behm
FG, Head DR, Sandlund JT, Weisenburger DD, Kossakowska AE, Thorner P,
Lorenzana A, Ladanyi M, Morris SW. Molecular detection of the t(2;5) translocation
of non-Hodgkin's lymphoma by reverse transcriptase-polymerase chain reaction.
Blood 1995; 12: 3416-22.
45. Kaneko Y, Frizzera G, Edamura S, Maseki N, Sakurai M, Komada
Y, Sakurai M, Tanaka H, Sasaki M, Suchi T, Kikuta A, Wakasa H, Hojo H,
Mizutani S. A novel translocation t(2;5)(p23;q35), in childhood phagocytic
large T cell lymphoma mimicking malignant histiocytosis. Blood
1989; 3: 806-13.
46. Mason DY, Bastard C, Rimokh R, Dastugue N, Huret JL, Kristoffersson
U, Magaud JP, Nezelof C, Vannier JP, Hemet J, Warnke R. CD30-positive
large cell lymphomas (Ki-1 lymphoma) are associated with a chromosomal
translocation involving 5q35. Br J Haematol 1990; 74: 161-8.
47. Lamant L, Meggetto F, Al Saati T, Brugières L, Bressac
de Paillerets B, Dastugue N, Bernheim A, Rubie H, Terrier-Lacombe MJ,
Robert A, Brousset P, Rigal F, Schlaifer D, Shiota M, Mori S, Delsol G.
High incidence of the t(2;5)(p23;q35) translocation in anaplastic large
cell lymphoma and its lack of detection in Hodgkin's disease. Comparison
of cytogenetic analysis, reverse transcriptase-polymerase chain reaction,
and p80 immunostaining. Blood 1996; 87: 284-91.
48. Lopategui JR, Sun LH, Chan JKC, Gaffey J, Frierson HF, Glackin
C, Weiss LM. Low frequency association of the t(2;5)(p23;q35) chromosomal
translocation with CD30+ lymphomas from American and Asian
patients. Am J Pathol 1995; 146: 323-8.
49. Morris SW, Kirstein MN, Valentine MB, Dittmer KG, Shapiro
DN, Saltman DL, Look AT. Fusion of a kinase gene, ALK, to a nucleolar
protein gene, NPM, in non-Hodgkin's lymphoma. Science 1994; 263:
1281-4.
50. Falini F, Pulford K, Pucciari A, Carbone A, De Wolf-Peeters
C, Cordell J, Fizzotti M, Santucci A, Pelicci PG, Pileri S, Campo E, Ott
G, Delsol G, Mason DY. Lymphoma expressing ALK fusion protein(s) other
than NPM- ALK. Blood 1999; 94: 3509-15.
51. Hernandez L, Pinyol M, Hernandez S, Dea S, Pilford K, Rosenwald
A, Lamant L, Falini F, Ott G, Mason DY, Delsol G, Campo E. TRK-fused gene
(TFG) is a new partner of ALK in anaplastic large cell lymphomas producing
two structurally different TGF-ALK translocations. Blood 1999;
94: 3265-8.
52. DeCoteau JF, Butmarc JR, Kinney MC, Kadin ME. The t(2;5)
chromosomal translocation is not a common feature of primary cutaneous
CD30+ lymphoproliferative disorders: comparison with anaplastic
large-cell lymphoma of nodal origin. Blood 1996; 87: 3437-41.
53. Schiemann WP, Pfeifer WM, Levi E, Kadin ME, Lodish HF. A
deletion in the gene for transforming growth factor beta type I receptor
abolishes growth regulation by transforming growth factor beta in a cutaneous
T cell lymphoma. Blood 1999; 94: 2854-61.
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