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Cutaneous Involvement in Children With Acute Lymphoblastic Leukemia

or Lymphoblastic Lymphoma

Fre´de´ric Millot, MD*; Alain Robert, MD‡; Yves Bertrand, MD§; Franc¸oise Mechinaud, MDi; Genevie`ve Laureys, MD¶; Alice Ferster, MD#; Pe´ne´lope Brock, MD**; Pierre Rohrlich, MD‡‡;

Franc¸oise Mazingue, MD§§; Dominique Plantaz, MDii; Emmanuel Plouvier, MD¶¶; He´le`ne Pacquement, MD##; Catherine Behar, MD***; Xavier Rialland, MD‡‡‡;

Jean-Marie Chantraine, MD§§§; Franc¸ois Guilhot, MD*; and Jacques Otten, MDiiifor the Children’s Leukemia Cooperative Group of the European Organization of Research and Treatment of Cancer (EORTC)

ABSTRACT. Objective. Skin involvement in children with acute monocytic leukemia or CD30-positive ana-plastic large-cell lymphoma is well-known. In contrast, very little is known about the malignant cutaneous infil-trates in children with acute lymphoblatic leukemia (ALL) or lymphoblastic lymphoma (LBL). This study was designed to determine the frequency of these specific lesions in childhood ALL or LBL and the characteristics of such patients.

Design. We studied the clinical and biological find-ings of children with cutaneous involvement at initial diagnosis of ALL or LBL enrolled between August 1989 and March 1995 in the multicentric trial 58881 of the Children’s Leukemia Cooperative Group of the Euro-pean Organization of Research and Treatment of Cancer (EORTC).

Results. Among the 1359 children enrolled in the multicenter trial EORTC 58881, 24 presented with skin involvement at diagnosis. ALL was diagnosed in 15 pa-tients and LBL in 9. In 15 cases, skin lesions were ob-served within a median time of 6 weeks (range, a few days to 8 months) before the diagnosis of the hemato-logic disease. Twenty-one children had at least one skin lesion located on the head. Diffuse cutaneous lesions were observed in 7 infants with high-risk ALL. Seven-teen of the 24 children remain in the first complete re-mission (median follow-up of 3 years; range 2 months to 5 years) and 3 are in the second remission with a fol-low-up of 14 to 24 months.

Conclusion. The present study demonstrates that cu-taneous involvement can be an early manifestation of ALL or LBL. Cutaneous leukemic infiltrates can be ob-served in children with standard risk as well as in

high-risk ALL. Cutaneous involvement in children with LBL is mainly associated with a B-cell precursor immunopheno-type of the lymphomatous cells. The most frequent loca-tion of skin lesions in children with ALL or LBL is on the head. Further studies are needed to evaluate the progno-sis of children with such involvement at diagnoprogno-sis.

Pediatrics 1997;100:60 – 64; lymphoblastic leukemia, lym-phoblastic lymphoma, children, skin leukemia, skin dis-ease.

ABBREVIATIONS. ALL, acute lymphoblastic leukemia; LBL, lym-phoblastic lymphoma; EORTC CLCG, Children’s Leukemia Co-operative Group of the European Organization of Research and Treatment of Cancer; FAB, French-American-British (classifica-tion); NHL, non-Hodgkin’s lymphoma.

S

kin involvement can be the initial symptom of hematologic diseases in children.1 Cutaneous

infiltrates in children with acute monocytic leu-kemia or CD30-positive anaplastic large-cell lym-phoma is well-known.2,3 Scant information is

avail-able concerning the occurrence and natural history of skin involvement observed in children with acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LBL). Among the 1359 children with ALL or LBL enrolled in the Children’s Leukemia Cooperative Group of the European Organization of Research and Treatment of Cancer (EORTC CLCG) trial, 24 presented with cutaneous involvement at diagnosis. These 24 cases provide the opportunity to examine the characteristics of such patients.

PATIENTS AND METHODS

Between August 1989 and March 1995, 1259 children under 18 years of age with ALL and 100 children with LBL from 28 different pediatric hospitals (France and Belgium) were enrolled in the multicenter trial EORTC 58881 of the CLCG.4ALL and LBL with

mature B-cell immunophenotype were excluded from this trial. When bone marrow involvement was observed, patients with less than 25% blasts in a bone marrow aspirate and none in the peripheral blood were considered to have lymphoma. Patients with LBL were staged according to the Murphy’s classification using clinical and imaging criteria.5All cases were studied for

specific lymphoblastic cell characteristics, including morphologic characteristics, immunophenotype, and cytogenetic features. Mor-phologic classification of the ALL was based on criteria of the French-American-British (FAB) classification.6 Classification of

lymphomas was performed according to the Working Formula-From the *Department of Hematology, University Hospital of Poitiers,

France; and the Departments of Pediatrics and Hematology: ‡University Hospital of Toulouse, France; §University Hospital of Lyon, France; iUni-versity Hospital of Nantes, France; ¶UniiUni-versity Hospital of Gent, Belgium; #Queen Fabiola University Hospital of Brussels, Belgium; **University Hos-pital of Leuven, Belgium; ‡‡Robert Debre´ HosHos-pital, Paris, France; §§Uni-versity Hospital of Lille, France;iiUniversity Hospital of Grenoble, France; ¶¶University Hospital of Besanc¸on, France; ##Institut Curie, Paris, France; ***University Hospital of Reims, France; ‡‡‡University Hospital of Angers, France; §§§University Hospital of Liege, Belgium; andiiiUniversity Hospi-tal of Brussels, Belgium.

Received for publication Dec 9, 1996; accepted Dec 9, 1996.

Reprint requests to (F.M.) Service d’He´matologie et Oncologie Me´dicale, CHU de Poitiers, 86000 Poitiers, France.

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tion of non-Hodgkin’s lymphomas (NHLs).7Frozen specimens or

cell suspensions were evaluated for B- and T-lineage-associated antigens using standard techniques as previously reported.8,9

Re-sults were considered positive if more than 30% of the cells ex-pressed a particuliar antigen. Cytogenetic analysis of the lympho-blastic cells were performed by R or G banding and chromosomes were classified according to the International System for Human Cytogenetic Nomenclature.10Skin biopsy specimens were

avail-able for 13 children: formalin-fixed, paraffin-embedded material was sectioned at 4m, stained and examined by conventional light microscopy. Immunophenotyping was performed in 3 cases on skin tissue sections infiltrated with malignant cells using paraffin or frozen section immunohistochemical techniques. Children with ALL were assigned to risk groups based on peripheral lympho-blast count, liver and spleen size, and cytogenetic analysis of blastic cells at the time at diagnosis.4Among the 1259 children

with ALL, 1101 belonged to the B lineage and 158 to the T lineage according to the immunologic findings. Immunologic features from only 49 children with LBL were reviewed: 39 belonged to the T lineage and 10 to the B lineage. The presence of skin lesions at initial diagnosis was noted in the registration forms transmitted to the EORTC data center.

RESULTS

Twenty-four of the 1359 children (1.8%) had skin lesions at the time of diagnosis of the hematologic malignancy. Clinical and biological features of these 24 children are summarized in Tables 1 and 2.

The median age at time of diagnosis of the patients with initial skin involvement was 2 years (range, 2 days to 11 years). This group consisted of 15 girls and 9 boys. ALL was diagnosed in 15 patients. There were 11 ALL-L1 and 3 ALL-L2 according to the FAB classification; in one case the morphologic subtype could not be assigned. Eleven ALLs belonged to the B lineage (positivity for CD 19): early-pre B (CD 102) 5 cases, common (CD 101) 4 cases and pre B (Cm) 1 case; CD 10 expression was not determined in 1 case. Two ALLs belonged to the T lineage. One patient had leukemic cells positive for CD 10 and CD 7. Mixed-lineage antigen expression (positivity for 2 myeloid antigens and B-lineage markers) was ob-served in 1 case.

LBL was diagnosed in 9 children. There were 3 stage II, 1 stage III, and 5 stage IV according to the Murphy classification. Immunophenotyping of the lymphomatous cells was not informative in 2 pa-tients because of insufficient material. The 7 cases of LBL evaluated belonged to the B lineage (positivity for CD 19): common (CD 101) 5 cases (however Cm expression was not determined in 2 cases) and pre B (Cmintracytoplasmic) 2 cases.

In 15 cases, the skin lesions were observed within a median time of 6 weeks (range, a few days to 8 months) before the diagnosis of the hematologic dis-ease was made. Biopsies of the skin lesions were performed in 13 patients because of the progressive increase in the size of one or more skin lesions. Histologic examination of the tissue biopsy speci-mens revealed an infiltration of the dermis and the underlying tissue by lymphoblastic cells with unin-volved epidermis in all cases, thus leading to hema-tologic investigations in these patients. Lymphobla-tic cells were observed by cytologic examination of skin lesion imprints in one patient. Lymph node biopsy led to the diagnosis of hematologic malig-nancy in a patient with the simultaneous occurrence of cervical adenopathy and asymptomatic cutaneous

lesions located on the scalp. Skin biopsies were not performed in 9 infants because cutaneous lesions were noted in a context of evident acute leukemia (hepatosplenomegaly and hyperleucocytosis with blastic cells in the blood). The lesions were asymp-tomatic indurated papules or nodules, brown-red to violaceous without excoriation or ulceration. The size of the lesions varied from .5 cm to 6.5 cm. The head was predominantly involved: among the 24 patients, 21 had at least one skin lesion located on the face or on the scalp. Thirteen children had a single skin lesion (8 were located on the scalp, 2 on the face, 1 on the back, 1 on the armpit and 1 on the thigh). Four children had 2 or 3 lesions (all of them had at least one lesion on the head). Seven patients had diffuse cutaneous lesions (including lesions on the head): all are under 12 months of age with hepato-splenomegaly and high leucocyte count with blastic cells in peripheral blood. In the 24 children, the le-sions disappeared within a few days after beginning the cytotoxic therapy.

Complete remission was obtained in 23 patients at completion of the induction therapy. One infant died during the induction therapy due to therapy-related complications (probable veno-occlusive disease). An allogeneic bone marrow transplant was performed in 1 infant with very high-risk ALL in first remission. Seventeen of the 24 children with initial skin involve-ment remain in first continuous complete remission with a median follow-up of 3 years (range 2 months to 5 years). Three patients presented with an isolated bone marrow relapse and 3 had an isolated ex-tramedullary relapse (meningeal, 1 case; gonads, 2 cases) 4 to 40 months after the diagnosis of hemato-logic malignancy. Only 3 of them are alive in contin-uous second remission with a follow-up of 14, 19, and 24 months after the second complete remission.

DISCUSSION

Various cutaneous lesions can be observed in pa-tients with hematologic malignancies. These include specific cutaneous lesions resulting from infiltration of the skin by the malignant cells, characteristic dis-eases such as pyoderma gangrenosum and Sweet syndrome, cutaneous signs of infection or hemor-rhage resulting from the bone marrow dysfunction induced by the malignant process or chemotherapy. Cutaneous infiltrates can be an early manifestation of leukemias and lymphomas. The present prospec-tive study revealed that among the 1359 patients with ALL or LBL registered in the EORTC protocol, 24 children (1.8%) had skins lesions before diagnosis of hematologic malignancy or simultaneously. The predominant location of the cutaneous lesions in our 24 patients was on the head (21 children had at least one or more cutaneous lesions on the face or on the scalp). To our knowledge, this preferential site of involvement has not previously been reported in such a large group of children with ALL. However, in examining the literature it became evident that scalp involvement was noted in several case reports of children with B lineage LBL.11–14

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none of 74 children with LBL had initial skin involve-ment.15 In contrast, the skin seems to be an

extran-odal site more frequently involved in CD30-positive anaplastic large cell lymphoma rather than in other childhood NHLs.16Among the 100 patients with LBL

enrolled in the EORTC protocol, 9 presented with specific skin involvement at inital diagnosis. Our study emphasizes the heterogeneity of cutaneous LBL in children in terms of patient age (6 months to 11 years), in terms of extension of the disease (4 patients presented with regional disease-skin in-volvement and lymph nodes while the other 5

pre-sented with more extensive disease) and in terms of immunophenotype of the lymphomatous cells (var-ious B-cell maturation stages). Bernard et al17

re-ported 5 cases of cutaneous involvement in a group of 116 children with NHL: initial skin involvement was observed in 1 case from 58 T cell lymphomas and in 4 cases from 7 CALLA-positive NHL. The present study emphasizes the rarity of initial cutane-ous involvement in T cell LBL (none among 39 T cell LBL). In contrast, 7 of the 10 children with precursor B-cell LBL enrolled in the EORTC trial exhibited initial specific cutaneous involvement. The

associa-TABLE 1. Clinical, Immunologic Features, and Outcome of 14 Children With Acute Lymphoblastic Leukemia and Initial Skin Involvement

Pt No.

Age/Sex Clinical Features FAB* Morphology

Blasts Count in Blood (XmL)

Immunophenotype (Blastic Cells)

Karyotype (Blastic Cells)

Site(s) at Presentation/

Interval†

Outcome/Follow-up After Diagnosis

1 18 mo/F . . . L1 3500 Common B lineage 46,XX

45,XX

Thigh/ few weeks

Ovary relapse (40 mo)/

Disease-free for 54 mo

2 5 y/M Hepatosplenomegaly Lymph nodes

L1 405 Common B lineage 46,XY Forehead/ 5 months

CCR/54 mo

3 5 y/F Hepatosplenomegaly Lymph nodes

L1 3800 Common B lineage 46,XX

57,XX,14,16,18,

110,113,115,

117,1 21,13mar

Forehead/ 6 weeks

CCR/60 mo

4 8 y/F . . . L2 16000 Pre B ND Scalp/8 months CCR/15 mo

5 5 y/F . . . L1 3700 Common B lineage 46,XX

54,XX,14,16, del(6q)?,110,

117,118,121,

121,1mar

Forehead/ 3 months

CCR/2 mo

6 7 y/M Hepatosplenomegaly L2 3300 CD101, CD71 ND Forehead/chest wall one week

Testicular relapse (30 mo)/ Disease-free for 54 mo

7 10 mo/M Hepatosplenomegaly CNS

L1 485000 CD191, CD141, CD11b1

46,XY Scalp/3 weeks CCR/18 mo

8 1 mo/M Hepatosplenomegaly L1 150000 Early-pre B 46,XY, t(4; 11) (q21;q23)

Diffuse/ 3 weeks

Dead/BM relapse (8 mo)

9 5 mo/M Hepatosplenomegaly L1 485000 T 46,XY

46,XY, t(1;19) (q23;p13) PBX1

E2A-Diffuse/ few days

CCR/42 mo

10 3 mo/F Hepatosplenomegaly Inevaluable 350000 Early-pre B 46,XX Diffuse/ few days

CCR/36 mo

11 2 d/M Hepatosplenomegaly L1 140000 Early-pre B 46,XY t(4;11) (q21;q23)

Diffuse/ few days

Dead (20 d)

12 9 mo/F . . . L1 1600 CD10

ND CD191 CD221

46,XX Scalp/3

months

CCR/5 mo

13 2 mo/F Hepatosplenomegaly L1 64000 Early-pre B 46,XX Armpit/ 2 months

Dead/ BM relapse (4 mo)

14 12 mo/M Hepatosplenomegaly L1 560000 T 46,XY

add(5)(q34) del(6)(q13;q15) 47,XY, add(5)(q34), del(6)(q13;q15),

1del(6)(q13;q15)

Diffuse/ few days

CCR/5 mo

15 3 d/F Hepatosplenomegaly L2 31000 Early-pre B 46,XX, t(4;11) (q21;q23)

Diffuse/ few days

CCR/5 mo

Abbreviations: FAB, French-American-British (classification); CNS, central nervous system involvement; BM, bone marrow; CCR, continuous complete remission; ND, not done.

* Morphology according to the FAB classification.

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tion of cutaneous involvement and precursor B-cell NHL was previously reported.17 Meyers et al18

sug-gested that lymphomas with initial cutaneous in-volvement represent a unique clinical entity charac-terized by the occurrence in children under 30 months of age and by a pre B immunophenotype. Such an hypothesis cannot be supported according to our findings: whereas one of our patients with pre B cell lymphoma was within the age range of under 30 months for cutaneous lymphoma as reported by Meyers, the second case occurred in a 9-year-old girl. Morever, immunophenotyping of the lymphoma cells in 2 of our children with initial skin involve-ment revealed a lack of cytoplasmic immunoglobulin M. Our cases confirm that initial cutaneous involve-ment can be observed in older children with LBL derived from various B-cell precursors.

The frequency of leukemic infiltrates of the skin is variable according to the type of leukemia.19

Cutane-ous involvement is a common finding in acute my-eloid leukemia with monocytic differentiation while it is a rare event in ALL.20 Dunn et al21 reported 2

patients with leukemic infiltration of the skin among 40 children with ALL. The present study emphasizes the singularity of a specific skin lesion in childhood ALL: among the 1259 children with ALL enrolled into the EORTC 58881 trial, 15 (1.2%) presented with initial cutaneous involvement. We observed skin le-sions in 9 leukemic children under 12 months of age with organomegaly, a high leucocyte count, or karyotype abnormalities of blastic cells that are

known to be unfavorable prognostic factors.22 The

skin lesions were mostly diffuse in this subgroup of patients and were observed concomitant to the diag-nosis of leukemia. The skin lesions of these patients can be regarded as a dissemination of aggressive leukemia to the skin. In a previous report of 25 cases of ALL in infants, skin infiltration was associated more closely with the patient’s age (early period of infancy) than with karyotype abnormalities (4 of the 16 infants with 11q23 rearrangements had skin in-volvement).23 In contrast, 6 of our leukemic patients

were older than 1 year without initial unfavorable prognostic factors. In these patients, the cutaneous involvement was the initial sign of the hemopathy and it is of interest that the appearance of such lesions preceded the diagnosis of ALL by a long interval (3 to 8 months) in 3 of our patients. Because none of these 3 children underwent hematologic in-vestigations when the lesions occurred, it is conceiv-able that skin lesions can arise before evidence of the presence of lymphoblastic cells in the bone marrow as described in patients with myelomonocytic or monocytic acute leukemia.2,24 Our study

demon-strates that cutaneous involvement can be an early manifestation of ALL in children and can be ob-served in standard risk as well as in high-risk ALL. It was reported that any infiltration of the skin by a leukemic process is an adverse prognostic factor.19

Little data are available concerning the outcome of children with B-cell precursor ALL or LBL with ini-tial skin involvement. Grunmayer et al11 reported 4

TABLE 2 . Clinical, Immunologic Features, and Outcome of 9 Children With Lymphoblastic Lymphoma and Initial Skin Involvement

Pt No

Age/Sex Stage* Clinical Features

Skin Site(s) at Presentation/ Interval† Immunophenotype (Tissue Immunophenotyped) Karyotype (Tissue Karyotyped) Outcome/ Follow-up After Diagnosis

1 5 y/F II Cervical

lymph nodes

Scalp/ 2 months

CD45R1(skin) ND CCR/60 mo

2 9 y/F III Pleural

effusion

Face/6 weeks Pre B (pleural blastic cells)

ND Dead/

CNS relapse (24 mo)

3 11 y/F IV . . . Chest wall/

2 months

ND ND CCR/60 mo

4 6 mo/F II Cervical

lymph nodes

Scalp/6 weeks Pre B (skin) 46,XX (skin) CCR/12 mo

5 5 y/M II Cervical

lymph nodes

Scalp/ 5 months

Common B lineage (lymph node)

46,XY

54,XXY,14,16,114,

115?,117,121,121 (lymph node)

CCR/42 mo

6 4 mo/F IV . . . Scalp/1 month Common B lineage

(Skin, BM)

47,XX, der(1), add(7)(p?), der(14),121

46,XY (BM)

CCR/36 mo

7 2 y/F IV Cervical

lymph nodes, hepatosple-nomegaly Scalp/ 3 months

Common B lineage (lymph node, BM)

46,XX (BM) CCR/36 mo

8 2 y/M IV . . . Scalp, chest

wall, scrotum/ 2 months

Common B lineage (BM)

46,XY (BM) del(6)(q?) BM relapse (29 mo)/ Disease free for 40 mo

9 7 y/F IV . . . Scalp/

2 months

Common B lineage (BM, skin)

46,XX (BM, skin)

CCR/36 mo

Abbreviations: CNS, central nervous system involvement; BM, bone marrow; CCR, continuous complete remission; ND, not done. * Stage according to the Murphy classification.

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cases of children with cutaneous B lineage LBL: 3 were in continuous complete remission 26 to 40 months after the diagnosis and 1 died from the dis-ease 19 months after the initial diagnosis. In a liter-ature review on cutaneous lymphomas, among the 8 children with LBL (5 had stage I and 3 had stage IV), only 2 were disease-free with a follow-up duration of 13 and 130 months.25 Except infants with very

high-risk ALL, 4 (26%) of our patients relapsed: 1 patient died of the disease and 3 are in the second complete remission with a follow-up duration of 30 and 40 months after the relapse. This relapse rate seems to be similar to that observed in patients with ALL or LBL without initial skin involvement.15However, the

follow-up and the number of our patients are insuf-ficient to draw conclusions about the prognostic sig-nificance of initial cutaneous involvement.

The present work demonstrates that cutaneous in-volvement can be an early manifestation of ALL or LBL in childhood. Furthermore, the most frequent location of such lesions is on the head. Cutaneous leukemic infiltrates can be observed in children with standard risk as well as in high-risk ALL. Skin in-volvement in children with LBL is mainly associated with a B-cell precursor immunophenotype of the lymphomatous cells. The prognosis value of initial cutaneous involvement in children with ALL or LBL remains to be determined.

ACKNOWLEDGMENT

The authors thank Nathalie Richetin for her help in preparing the manuscript.

REFERENCES

1. Ganick DJ. Skin changes associated with hematologic and oncologic diseases in children. N Y State J Med. 1992;92:256 –261

2. Darbyshire PJ, Smith JHF, Oakhill A, Mott MG. Monocytic leukemia in infancy. Cancer. 1985;56:1584 –1589

3. Kadin ME, Sako D, Berlinger N. Chilhood Ki-1 lymphoma presenting with skin lesions and peripheral lymphadenopathy. Blood. 1986;68: 1042–1049

4. Boilletot A, Behar C, Benoit Y, et al. Treatment of acute lymphoblastic leukemia in children with the BFM protocol. Am J Pediatr Hematol Oncol. 1987;9:317–323

5. Murphy SB. Classification, staging and end results of treatment in childhood non-Hodgkin’s lymphoma: dissimilarities from lymphomas in adults. Semin Oncol. 1980;7:332–339

6. Benett JM, Catovsky D, Daniel MT, et al. Proposals for the classification of the acute leukemias. Br J Hematol. 1976;33:451– 458

7. The Non-Hodgkin’s Lymphoma Pathologic Classification Project. Na-tional Cancer Institute sponsored study of classifications on non-Hodgkin’s lymphoma: summary and description of a working formu-lation for clinical usage. Cancer. 1982;49:2112–2135

8. Linder J, Ye Y, Harrington D, Armitage JO, Weisenburger DD. Mono-clonal antibodies marking T lymphocytes in paraffin-embedded tissue.

Am J Pathol. 1987;127:1–9

9. Linder J, Ye Y, Armitage JO, Weisenburger DD. Monoclonal antibodies marking-B cell non-Hodgkin’s lymphoma in paraffin-enbedded tissue.

Mod Pathol. 1988;1:29 –35

10. First MIC cooperative study group: morphologic, immunologic and cytogenetic (MIC) working classification of acute lymphoblastic leuke-mia. Cancer Genet Cytogenet. 1986;23:189 –197

11. Grunmayer ER, Ladenstein RL, Slavc I, et al. B-cell differentiation pattern of cutaneous lymphomas in infancy and childhood. Cancer. 1988;61:303–308

12. Link MP, Roper M, Dorfman RF, Crist WM, Cooper MD, Levy R. Cutaneous lymphoblastic lymphoma with pre-B markers. Blood. 1983; 61:838 – 841

13. Sander CA, Meideiros LJ, Abruzzo LV, Horak ID, Jaffe ES. Lympho-blastic lymphoma presenting in cutaneous sites: a clinicopathologic analysis of six cases. J Am Acad Dermatol. 1991;25:1023–1021

14. Wood GS, Burke JS, Horning S, Doggett RS, Levy R, Warnke RA. The immunologic and clinicopathologic heterogeneity of cutaneous lym-phomas other than mycosis fungoides. Blood. 1983;62:464 – 472 15. Reiter A, Schrappe M, Paewaresch R, et al. Non-Hodgkin’s lymphomas

of childhood and adolescence: results of treatment stratified for biologic subtypes and stage: a report of the BFM group. J Clin Oncol. 1995;13: 359 –372

16. Reiter A, Schrappe M, Tiemann M, et al. Successful treatment stategy for Ki-1 anaplastic large-cell lymphoma of childhood: a prospective analy-sis of 62 patients enrolled in three consecutive BFM group studies.

Blood. 1994;12:899 –908

17. Bernard A, Murphy SB, Melvin S, et al. Non-T, non-B lymphomas are rare in childhood and associated with cutaneous tumor. Blood. 1982;59: 549 –554

18. Meyers L, Hakami N. Pre-B cell cutaneous lymphoma in infancy: a unique clinical entity. Med Pediatr Oncol. 1984;12:252–254

19. Su WP, Buechner SA, Li CY. Clinicopathologic correlations in leukemia cutis. J Am Acad Dermatol. 1984;11:121–128

20. Boggs DR, Wintobe MM, Cartwright GE. The acute leukemias: analysis of 322 cases and review of the literature. Medicine. 1962;41:163–225 21. Dunn NL, McWilliams NB, Mohanakumar T. Clinical and

immunolog-ical correlates of leukemia cutis in childhood. Cancer. 1982;50:2049 –2051 22. Crist W, Pullen J, Boyett J. Clinical and biologic features predict a poor prognosis in acute lymphoid leukemias in infants: a pediatric oncology group study. Blood. 1986;67:135–140

23. Kaneko Y, Shikano T, Maseki N, et al. Clinical characteristics of infant acute leukemia with or without 11q23 translocations. Leukemia. 1988;10: 672– 676

24. Peterson L, Dehner LP, Brunning RD. Extramedullary masses as pre-senting features of acute monoblastic leukemia. Am J Clin Pathol. 1981; 75:140 –148

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DOI: 10.1542/peds.100.1.60

1997;100;60

Pediatrics

and Treatment of Cancer (EORTC)

Children's Leukemia Cooperative Group of the European Organization of Research

Rialland, Jean-Marie Chantraine, François Guilhot, Jacques Otten and for the

Dominique Plantaz, Emmanuel Plouvier, Hélène Pacquement, Catherine Behar, Xavier

Laureys, Alice Ferster, Pénélope Brock, Pierre Rohrlich, Françoise Mazingue,

Frédéric Millot, Alain Robert, Yves Bertrand, Françoise Mechinaud, Geneviève

Lymphoblastic Lymphoma

Cutaneous Involvement in Children With Acute Lymphoblastic Leukemia or

Services

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DOI: 10.1542/peds.100.1.60

1997;100;60

Pediatrics

and Treatment of Cancer (EORTC)

Children's Leukemia Cooperative Group of the European Organization of Research

Rialland, Jean-Marie Chantraine, François Guilhot, Jacques Otten and for the

Dominique Plantaz, Emmanuel Plouvier, Hélène Pacquement, Catherine Behar, Xavier

Laureys, Alice Ferster, Pénélope Brock, Pierre Rohrlich, Françoise Mazingue,

Frédéric Millot, Alain Robert, Yves Bertrand, Françoise Mechinaud, Geneviève

Lymphoblastic Lymphoma

Cutaneous Involvement in Children With Acute Lymphoblastic Leukemia or

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Figure

TABLE 1.Clinical, Immunologic Features, and Outcome of 14 Children With Acute Lymphoblastic Leukemia and Initial SkinInvolvement
TABLE 2 .Clinical, Immunologic Features, and Outcome of 9 Children With Lymphoblastic Lymphoma and Initial Skin Involvement

References

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