Leukaemia cutis and leukaemic vasculitis - Wiley Online Library

British Journal of Dermatology 2000; 143: 773±779.

Leukaemia cutis and leukaemic vasculitis S.PAYDAS AND S.ZORLUDEMIR* Departments of Oncology and *Pathology, CËukurova University Faculty of Medicine, 01330 BalcalAdana, Turkey Accepted for publication 4 May 2000

Summary

Background Leukaemia cutis (LC) and leukaemic vasculitis (LV) are uncommon but important features of haematological malignancy. Objectives We aimed to evaluate clinicopathological features of a series of such cases. Methods Thirty-four patients with LC were studied. Nineteen had acute myeloblastic leukaemia, six had acute lymphoblastic leukaemia, three had myelodysplastic syndrome±refractory anaemia with excess blast in transformation, three had non-Hodgkin's lymphoma in leukaemic phase, two had chronic lymphocytic leukaemia and one had multiple myeloma. Results Cutaneous lesions were widely dispersed in 15 patients, but were restricted to the extremities in eight patients. In other patients lesions were localized on the face, hands and feet. Cutaneous lesions were generally erythematous, maculopapular, squamous, nodular, haemorrhagic or necrotic. Two localizations were very interesting: in one case, lesions were confined to the site of previous varicella zoster virus infection; in the other case, leukaemic infiltration occurred within a lesion of cutaneous leishmaniasis. All of the patients had high white blood cell count and/or other findings of high tumour burden. Vasculitis with leukaemic cell infiltration (LV) was detected in 24 patients, and was high-grade LV in 16 patients. Patients with high-grade LV tended to have a higher white blood cell count and other findings associated with an aggressive clinical course compared with patients not having LV. Thirteen patients with LV died within 1 month but five patients lived more than 1 year. Conclusions LC, and especially LV, is generally an indicator of poor prognosis. Its pathogenesis must be evaluated further with additional studies, including adhesion molecules, angiogenic factors and other biological parameters. Key words: fibrinoid necrosis, haematopoietic neoplasia, leukaemia cutis, leukaemic vasculitis, prognosis

Cutaneous manifestations in haematopoietic neoplasia, especially in leukaemia, are not rare but may be very variable. They can be divided into two groups: nonspecific lesions (leukaemids) and specific leukaemic infiltrations (leukaemia cutis, LC). Leukaemids include haemorrhagic lesions, generalized pruritus, exfoliative erythroderma, pyoderma gangrenosum, urticaria, erythema multiforme, erythema nodosum, acute febrile neutrophilic dermatosis, panniculitis, hyperpigmentation, morbilliform eruptions and leucocytoclastic vasculitis. Leucocytoclastic vasculitis usually presents as palpable purpura, but can also appear as erythematous papules and nodules, ulcers or urticarial plaques. These non-specific skin lesions are found in approximately one-third of patients with leukaemia.1,2 LC is less

common than non-specific lesions. The incidence of LC varies with the type of leukaemia, ranging from 1% to 50%. The highest incidence is in myeloid leukaemias with monocytic differentiation. The clinical picture of LC is also variable and includes macules, papules, nodules, plaques, ecchymoses, palpable purpura, ulcers, erythroderma and bullae.3±5 Histologically, there are typically dense dermal collections of neoplastic and benign inflammatory cells infiltrating collagen bundles, and these cells surround the adnexal structures.6 Epidermal involvement is unusual and there is usually a Grenz zone. Vasculitis composed of leukaemic cells may accompany the leukaemic skin infiltrates, and a new histopathological entity named leukaemic vasculitis (LV) was reported in 1997.7±9

Correspondence: Semra PaydasË. E-mail: [email protected] q 2000 British Association of Dermatologists

773

774 S.PAYDASË AND S.ZORLUDEMIR

Materials and methods Skin biopsy samples taken from patients with haematopoietic neoplasia during the last 9 years in our department were re-evaluated and 34 cases of LC identified. Clinical and laboratory findings and biopsy samples were re-examined by an expert pathologist (S.Z.). Skin biopsy samples were stained with haematoxylin and eosin. Monoclonal antibodies for T and B cells, and lysozyme, were used to differentiate the types of leukaemic cell. Antifactor VIII-related antigen was used to identify the vessels surrounded by the leukaemic cells. Criteria for LV described by Jones et al. were applied.7 Low-grade lesions were characterized by small vessel injury with endothelial swelling, red cell extravasation, and at least focal fibrin deposition. Highgrade lesions were defined by significant necrotizing vasculitis with luminal obliteration and extensive fibrin deposition, and also leucocytoclasia.7

Results

(CLL). There was only one patient with multiple myeloma (MM) and skin infiltration. Sex, age, initial haematological findings, lactate dehydrogenase (LDH) levels, predominant surface antigen, organomegaly, skin findings, grade of LV and overall survival of the patients are shown in Table 2. The male/female ratio was 24 : 10 and mean ^ SD age was 42´4 ^ 18´3 years (range 17±77). Initial white blood cell (WBC) count was between 0´9 and 530 109 L21 (mean 88´55 ^ 101´06 109). LDH levels were between 252 and 12,666 IU L21 (mean 1808 ^ 2424). Overall survival of the patients (from skin infiltration to death) was between 2 days and 5 years. Skin lesions were widely distributed in six patients with de novo AML. These lesions were erythematous, maculopapular, palpable, purpuric, violaceous or black lesions. In eight patients with AML, lesions were confined to the extremities. Figure 1 shows leukaemic infiltration limited to the legs and mimicking haemorrhagic purpura (patient 8). In one patient, a necrotic skin lesion on the neck occurred on a lesion of cutaneous

There were 34 patients with LC. In the same period there were 85 skin biopsy samples taken from patients with haematopoietic neoplasia. LC was the most common skin lesion. Leucocytoclastic vasculitis was detected in 32 samples. Sweet's syndrome was found in seven cases and other lesions were found in 12 cases (Table 1). More than half of the patients with LC had acute myeloblastic leukaemia (AML): 15 had de novo and four had relapsed disease. There were six patients with acute lymphoblastic leukaemia (ALL) and skin infiltration. In three patients LC was found in myelodysplastic syndrome (MDS) ±refractory anaemia with excess blast in transformation (RAEB/t). There were three patients with non-Hodgkin's lymphoma (NHL) and two with chronic lymphocytic leukaemia Table 1. Histopathological diagnoses of 85 skin biopsy samples from patients with haematopoietic neoplasia Histological diagnosis

No. of cases

Leukaemia cutis Vasculitis Sweet's syndrome Fungal infection (Mucor, actinomycosis) Bullous dermatosis Psoriasis vulgaris Drug eruption Ephelide Subcorneal pustular dermatosis

34 32 7 4 3 1 2 1 1

Total

85

Figure 1. Leukaemic infiltration limited to the legs and mimicking haemorrhagic purpura (patient 8).

q 2000 British Association of Dermatologists, British Journal of Dermatology, 143, 773±779

LEUKAEMIA CUTIS AND LEUKAEMIC VASCULITIS 775

Table 2. Patient characteristics Patient Sex/age no. (years) 1

M/25

2

F/30

3

F/40

Diagnosis De novo AML De novo AML De novo AML De novo AML De novo AML

4

M/70

5

M/52

6

M/29

De novo AML De novo AML De novo

7

M/30

8

M/34

9

M/66

10

M/25

11

M/77

12

M/59

13

M/49

14

F/43

15

F/18

16

F/53

17

F/42

18

M/28

19

M/40

20

M/37

21

F/43

22

M/20

23

M/20

24

M/17

25

M/17

WBC count Platelets Hb Vasculitis (g dL21) 109 L21 109 L21 ± HG ±

48

13

110

31

13, 33, 34,

±

976

1

±

±

±

±

±

1

55

62

34

±

±

±

100

7

13

1505

1

1

1

±

5´4

32

13

560

±

±

±

6´4

LG

5

4´2

31

13

1251

±

±

±

HG

7´6

1´8

56

NA

688

±

±

±

De novo AML De novo AML De novo AML De novo AML De novo AML De novo AML De novo AML Relapsed AML Relapsed AML Relapsed AML Relapsed AML De novo ALL De novo ALL

HG

6´2

100

30

NA

1212

±

±

±

HG

5´7

102

7

13, 14, 19

1330

±

±

±

530

137

NA

4968

±

±

1

627

±

±

±

±

12

±

8

4´2

23 430

2, 7, 34, HLA-DR 34, 2, 3

LG

6´6

84´1

LG

4´5

78

24

HG

4´7

98

100

HG

8

90

70

NA

HG

7´4

116

81

?

7´2

63

985

1

±

±

NA

1459

±

1

1

7, 8, 13, 34

1501

1

±

1

549

±

±

±

13, 19, 5, 3

986

1

±

1

27

13, 33, 34

508

±

1

1

HG

6

100

56

NA

NA

±

±

±

HG

8´9

169´5

28

2, 3, 5, 7

2800

±

±

±

HG

7´4

250

34

2, 5, 7

6148

±

1

±

Relapsed ALL Relapsed ALL

HG

6´3

91

19, 13

±

7

100

15

4, 7

Relapsed ALL Relapsed ALL

HG

15

44

18

19, 2, 13

2000

30´5

63

2, 4, 5, 7, HLA-DR

1070

HG

NHL

LG LG

28

M/19

NHL

29 30

F/55 F/66

MDS-RAEB/t MDS-RAEB/t MDS-RAEB/t

34

267

9

±

3´8

NHL

33

6´5

NA

5´3

F/21

M/60

NA

±

M/55

M/68

100

LG

26

31

95

LDH (IU L21) LAP HM SM

5580 HLA-DR 602

27

32

6

Surface antigen

± LG LG

8´3 5´2 10´1 7´2 9 8

0´9

780

±

±

±

2100

1

1

1

± 1

1 1

1 1

1

50

NA

12,666

±

1

1

9

210

NA

655

1

1

1

1´5

54

NA

265

1

1

1

34´8 55

53 123

NA NA

463 652

± ±

± 1

1 ±

NA

HG

6

150

34

1423

±

1

1

CLL

HG

11´2

132

124

5, 19, 20

252

±

±

1

M/64

CLL

HG

14

20

166

5, 19, 20

465

±

±

1

M/70

MM

?

8

15

NA

912

±

±

±

7´5

Skin findings Disseminated erythematous, squamous, maculopapular lesions Disseminated erythematous, papular, pruritic lesions Palpable purpuric, pruritic lesions on the lower extremities Disseminated purpuric, pruritic lesions; 2-month history Palpable, 1±3-cm diameter, violaceous skin lesions on the extremities Necrotic skin lesion on the left side of the neck on a lesion of leishmaniasis 4-cm necrotic skin lesion on the face

OS 12 months; LFU 9´5 months 8 days 1 month 4 weeks 5 months 1 LFU 3 weeks

Haemorrhagic skin lesions on the legs Disseminated 0´2±2-cm indurated skin lesions Maculopapular lesions on the lower extremities Disseminated 0´2±1-cm indurated lesions, some haemorrhagic Violaceous plaques on the lower extremities Papular lesions on the extremities

13 months; LFU 1 month

Erythematous, squamous skin lesions predominantly on the forearms Disseminated pruritic maculopapular lesions and accompanying pregnancy 5 6 cm black, necrotic lesion on the inguinal region 1±3-cm maculopapular lesions with pain on the lower extremities Black, necrotic skin lesions on the hands and scalp Hyperpigmented skin lesions on the abdominal wall Disseminated nodular lesions

LFU

Disseminated 0´5±3-cm indurated skin lesion, severe hypoxia, Coombs positivity Disseminated erythematous, macular 1±2-mm plaques 1±5-mm papular lesions on the face, and nasal and buccal masses: infiltration confirmed by biopsy Disseminated 0´5±3-cm indurated lesions Disseminated 8±10-mm diameter bullous brownish lesions

2 days

Skin lesions confined to the previous zoster infection Disseminated erythematous, papular, pruritic lesions Necrotic skin lesion on the left side of the neck Disseminated hyperaemic skin lesions Disseminated pruritic, squamous lesions, 2-year history Hyperaemic indurated lesions on the hands and feet 2±10-mm indurated lesions on the lower extremities, repeat biopsy 2 years later showed infiltration Macular, indurated lesion on the right inguinal region Disseminated maculopapular lesions, 1-year history

4 years 3 days

10 months 1

10 days 12 days 3 months 1 month 13 weeks 6 months

2 years 1 LFU 6 months 1 LFU 1 month 10 days 6 months 1 1 year LFU 2 months 6 weeks

4 years 5 years 1 month

Hb, haemoglobin; WBC, white blood cell; LDH, lactate dehydrogenase; LAP, lymphadenopathy; HM, hepatomegaly; SM, splenomegaly; OS, overall survival, from development of skin lesion until death; AML, acute myeloblastic leukaemia; NA, not assessed; LFU, lost to follow-up; HG, high grade; LG, low grade; ALL, acute lymphoblastic leukaemia; NHL, nonHodgkin's lymphoma; MDS-RAEB/t, myelodysplastic syndrome±refractory anaemia with excess blast in transformation; CLL, chronic lymphocytic leukaemia; MM, multiple myeloma.

leismaniasis, and Leishmania parasites and leukaemic cells were detected together. There was a large necrotic skin lesion on the face in one patient and in the inguinal region in another. Vasculitis was detected in 12 patients, in eight of whom it was severe, and typical of high-grade LV. Figure 2 shows a black induration affecting the hand in a patient with relapsed AML

(patient 18). In one patient, skin lesions were clinically similar to pemphigus vulgaris and were reported histopathologically at the first evaluation as pemphigus vulgaris, but subsequently as leukaemic infiltration. In one of six patients with ALL, skin lesions were limited to the face; lesions were widespread in the other five patients. Figure 3 shows skin infiltration limited to



Figure 2. Black induration of the hand in a patient with relapsed acute myeloblastic leukaemia (patient 18).

the face in a patient with relapsed ALL (patient 23). Two patients had de novo and four had relapsed disease. Four patients had T-cell and two had B-cell phenotype. One of these patients had Ph(1) ALL with T-cell phenotype. Figure 4 shows widely distributed lesions in a patient with relapsed ALL (patient 24). All three patients with MDS-RAEB/t had myeloid type leukaemic transformation confirmed by cytochemistry. Lesions were widespread in two patients and affected hands and feet in one patient. Figure 5 shows leukaemic infiltration of the hands in a patient with RAEB/t (patient 30). Skin lesions preceded the haematological manifestations in this patient. All three patients with NHL had bone marrow infiltration. One patient had lesions on the neck, one had disseminated lesions and in the third patient lesions were confined to previous varicella zoster scarring.10 Skin infiltration was long-lasting in the two patients with CLL, who lived for 4 and 5 years after skin lesions developed. Repeated skin biopsies showed leukaemic infiltration, but the peripheral blood and

Figure 3. Cutaneous infiltration limited to the face in a patient with relapsed acute lymphoblastic leukaemia (patient 23).

bone marrow findings improved with specific antileukaemic therapy. The patient with MM had had skin lesions and pruritus for 1 year when he was diagnosed as having MM stage III-B. Fine-needle aspiration cytology taken from an area of skin induration suggested plasma cell neoplasia, which was confirmed by skin biopsy. He died within 1 month without healing of his skin lesions. Laboratory findings showed an elevated WBC count in 25 patients, especially in those with severe vasculitis; however, the WBC count was , 10 109 L21 in nine patients. The WBC count was . 50 109 L21 in 21 patients. LDH level was high in all but two patients and apparently related to high tumour burden. In patients with acute leukaemia who survived initial chemotherapy the cutaneous lesions completely disappeared with specific antileukaemic therapy. Histopathologically, lesions were typical for LC. There was leukaemic cell infiltration in the vessels and perivascular area. Vasculitis due to neoplastic cells



Figure 6. Photomicrograph showing fibrinoid necrosis and leukaemic cells at the dermal capillary walls (haematoxylin and eosin; original magnification 100).

Figure 4. Disseminated cutaneous nodules in a patient with relapsed acute lymphoblastic leukaemia (patient 24).

Figure 7. Photomicrograph showing focal fibrinoid necrosis of the capillary walls, endothelial swelling and leukaemic infiltration at the lumen (haematoxylin and eosin; original magnification 400).

Figure 5. Cutaneous infiltration of the hands in a patient with myelodysplastic syndrome±refractory anaemia with excess blast in transformation (patient 30).

Figure 8. Photomicrograph showing mixed cell infiltration consisting of eosinophils and lymphocytes, and erythrocyte extravasation (haematoxylin and eosin; original magnification 400).



Figure 9. Photomicrograph showing leukaemic cell infiltration at and around the vessel and lumen (haematoxylin and eosin; original magnification 400).

accompanied LC in 24 patients. According to the criteria described by Jones et al. vasculitis was graded as high grade in 16 patients.7 There was focal or disseminated fibrinoid necrosis in the capillary vessels of the upper dermis, endothelial swelling, proliferation and erythrocyte extravasation. A lymphocyte-rich mixed inflammatory cell infiltrate containing eosinophil and neutrophil leucocytes was present in and around the vessels, with nuclear dust. Vasculitis was detected in 12 of 19 AML patients, two of three NHL patients, five of six ALL patients and in all patients with CLL and MDSRAEB/t. High-grade vasculitic lesions generally tended to be more ulcerative and destructive, with evidence of high tumour burden. Figures 6±9 show the histopathology of leukaemic skin infiltration and LV.

Discussion LC is characterized by extravascular collections of blasts in the dermis and in adnexal structures of the skin. The incidence of LC changes with the type of leukaemia and is reported in 1±50% of patients with leukaemia.5,9,11 LC was documented by biopsy in 18 of 677 patients with AML (2%) at Roswell Park Memorial Institute.12 On the other hand, 30±50% of infants with congenital leukaemia have skin involvement.13 Although we know the number of patients with each type of leukaemia followed by us during the study period, we have not used this to calculate the incidence of LC, because skin infiltration may be confused with other non-specific skin lesions, and because not all skin lesions seen in these patients were biopsied. There are many reports that LC may simulate purpuric, haemorrhagic, inflammatory or infective lesions,

including vasculitis, exfoliative erythroderma, bullous pyoderma gangrenosum, erythema multiforme or urticaria, and may even respond to antimicrobial and/or blood product support. It is therefore difficult to know the real incidence of leukaemic infiltration in haematopoietic neoplasia.6,14±17 There were some cases of LC simulating haemorrhagic skin lesions among our patients. The frequency of LC as a proportion of the cutaneous lesions seen in patients with leukaemia is not known. Desch and Smoller examined 123 skin biopsy samples taken from patients with leukaemia, and LC was found in 30% of these lesions.18 In our study, LC was found in 34 of 85 (37%) of skin biopsies. Clinically, LC can present in a number of forms such as papules, nodules, plaques, ecchymoses, bullous lesions, erythroderma or vasculitic lesions.3±5 These lesions may be single or multiple, large or small. Legs are involved most commonly, followed by arms, back, chest, scalp and face.4,5,12 The type and localization of the skin lesions in our patients were similar to other reports. In two patients, the involved sites were interesting. In one patient, infiltration was at the site of previous varicella zoster virus infection.10 Fifteen similar cases have been reported in the English language literature.19±22 In the other patient, cutaneous leishmaniasis and leukaemic infiltration were detected simultaneously in a biopsy taken from a skin ulcer; this situation can be explained by the hypothesis that infiltration can occur at a site of inflammation. Skin lesions may be detected at the same time as or before the diagnosis of leukaemia.4,12 Cutaneous infiltration by leukaemic cells is seen most commonly in patients with AML, especially M4 and M5 subtypes, at initial presentation or at relapse.11 However, LC is unusual in ALL and the frequency may be as low as 1%.23 We had six patients with ALL and LC. In chronic leukaemias, skin involvement has been associated with transformation into the blastic phase and may suggest disease progression.24 Our three patients with MDS and LC had leukaemic transformation, which suggests the development of more aggressive clones and leukaemic dissemination. In contrast, our CLL patients were in the stable phase and did not show an aggressive clinical course associated with the presence of LC. This may suggest a different biology of skin infiltration in acute and chronic leukaemias. The most interesting finding in our patients with LC was the presence of accompanying LV. For many years leucocytoclastic vasculitis has been reported in leukaemias, especially in myelomonocytic types, but no



association between LC and LV was reported until 1997 when Jones et al. presented six patients with vasculitis due to leukaemic cells of monocytic differentiation and proposed the term LV.7 Minimal criteria for LV are infiltration of vessels by malignant cells and fibrin deposition within vessel walls or focal endothelial cell necrosis. When we used these criteria, two-thirds of the patients had evidence of LV. Sixteen of them had highgrade and eight had low-grade LV. We believe that if all skin infiltration associated with leukaemias were reevaluated, more cases would be found in other series. This entity shows that leukaemic cells may cause severe vascular injury and may be responsible for necrotic and other severe skin infiltration seen in leukaemic patients. For this reason, LV should be considered in the differential diagnosis of necrotic and vasculitic lesions. LC seems to be dissemination of systemic leukaemia to the skin. Like other forms of extramedullary disease, LC usually suggests a very poor prognosis in leukaemic patients. In most reported series, the great majority of patients (85%) died within 4 months after appearance of skin infiltration.3,25±27 The probability of extramedullary involvement in patients with LC is high. In other words, LC may accompany other extramedullary involvement and/or high tumour burden.7 More than half of our patients had a high WBC count (. 50 109 L21) and organomegaly, which are suggestive of high tumour burden. Thirteen such patients died within 1 month. This point suggests that skin infiltration is an indicator of very poor prognosis in haematopoietic neoplasia. On the other hand, some of our patients lived as long as 5 years after the detection of skin involvement; therefore, the clinical course of patients with leukaemic skin infiltration is variable.

References 1 Arrowsmith ER, Greer JP, Macon WR. Complications of hematopoietic neoplasms. In: Wintrobe's Clinical Hematology, 10th edn, Vol. 2, 1999: 2033±75. 2 Cohen PR, Kurzrock R. Mucocutaneous paraneoplastic syndromes. Semin Oncol 1997; 24: 334±59. 3 Su WPD, Buechner SA, Li CY. Clinicopathologic correlations in leukemia cutis. J Am Acad Dermatol 1984; 11: 121±8. 4 Longacre TA, Smoller BR. Leukemia cutis. Analysis of 50 biopsyproven cases with an emphasis on occurrence in myelodysplastic syndromes. Am J Clin Pathol 1993; 100: 276±84. 5 Sepp N, Radaszkiewicz T, Meijer CJLM et al. Specific skin manifestations in acute leukemia with monocytic differentiation. Cancer 1993; 71: 124±32.

6 Buechner SA, Li CY, Su WP. Leukemia cutis: a histopathologic study of 42 cases. Am J Dermatopathol 1985; 7: 109±19. 7 Jones D, Dorfman DM, Barnhill RB, Granter SR. Leukemic vasculitis. A feature of leukemia cutis in some patients. Am J Clin Pathol 1997; 107: 637±42. 8 Smoller BR. Leukemic vasculitis: a newly described pattern of cutaneous involvement. Am J Clin Pathol 1997; 107: 627±9. 9 Serra A, Estrach MT, Marti R et al. Cutaneous involvement as the first manifestation in a case of T-cell prolymphocytic leukaemia. Acta Derm Venereol (Stockh) 1998; 78: 198±200. 10 PaydasË S, Sahin B, Yavuz S et al. Lymphomatous skin infiltration at the site of previous zoster virus infection in a patient with T cell lymphoma. Leukemia Lymphoma 2000; in press. 11 Braverman IM. Skin Signs of Systemic Disease, 2nd edn. Philadelphia: W.B.Saunders, 1981; 179. 12 Baer MR, Barcos M, Farrell H et al. Acute myelogenous leukemia with leukemia cutis. Cancer 1989; 63: 2192±200. 13 Resnik KS, Brad RB. Leukemia cutis in congenital leukemia. Arch Dermatol 1993; 129: 1301±6. 14 Stawiski MA. Skin manifestations of leukemias and lymphomas. Cutis 1978; 21: 814±18. 15 Horlick HP, Silvers DN, Knobler EH, Cole JT. Acute myelomonocytic leukemia presenting as a benign appearing cutaneous eruption. Arch Dermatol 1990; 126: 653±8. 16 Berger BJ, Gross PR, Daniels RB, Lankton BB. Leukemia cutis masquerading as guttate psoriasis. Arch Dermatol 1973; 108: 416±18. 17 Baden TJ, Gammon WR. Leukemia cutis in acute myelomonocytic leukemia. Arch Dermatol 1987; 123: 88±90. 18 Desch JK, Smoller BR. The spectrum of cutaneous disease in leukemias. J Cutan Pathol 1993; 20: 407±10. 19 Cerroni L, Zenahlik P, Kerl H. Specific cutaneous infiltrates of B-cell chronic lymphocytic leukemia arising at the site of herpes zoster and herpes simplex scars. Cancer 1995; 76: 26±31. 20 Mikesell JF, Bailin PL, Bergfeld WF. Leukemia cutis presenting as a chronic herpes zoster ulceration. Cleve Clin Q 1984; 5: 667±9. 21 Bahadaron P, Lacour JP, Del Guidice P et al. Cutaneous localizations of chronic lymphoid leukemia in a zona area. Ann Dermatol Venereol 1996; 123: 471±3. 22 Gibney MD, Nahass GT, Leonardi CL. Cutaneous reactions following herpes zoster infections: report of three cases and review of the literature. Br J Dermatol 1996; 134: 504±9. 23 Forjaz de Lacerda J, Alves de Carmo J, Luerdes Guerra M et al. Leukemia cutis in acute lymphoblastic leukemia. J Am Acad Dermatol 1994; 30: 1041±3. 24 Ratnam KV, Khor CJL, Su WPD. Leukemia cutis. Clin Dermatol 1994; 12: 419±31. 25 Shaikh BS, Frantz E, Lookingbill DP. Histopathologically proven leukemia cutis carries a poor prognosis in acute nonlymphoblastic leukemia. Cutis 1987; 39: 57±60. 26 Ratnam KV, Su WP, Ziesmer SC. Value of immunohistochemistry in the diagnosis of leukemia cutis: study of 54 cases using paraffin-section markers. J Cutan Pathol 1992; 19: 193±200. 27 Byrd JC, Wels RB, Arthur DC. Extramedullary leukemia adversely affects hematologic complete remission rate and overall survival in patients with t(8:21;)(q22;q22): results from Cancer and Leukemia Group B 8461. J Clin Oncol 1997; 15: 466±75.
