American Journal of Hematology 54:84–92 (1996)

LETTERS AND
CORRESPONDENCE

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Suite 3157, Tampa, FL 33612-9497 to permit rapid consideration
for publication.

Case of Schwachman’s Syndrome With Intermittent

Neutropenia and Lymphocyte Subset Disturbances

To the Editor: Schwachman’s syndrome, a familial disease transmitted as an

autosomal-recessive trait, is characterized by moderate chronic neutropenia,
marked marrow hypocellularity, occasional thrombocytopenia and anemia,
metaphyseal dysostosis of tubular bones, pancreatic fatty infiltration, and
accompanying pancreatic insufficiency with absence of pulmonary and
sweat elecrolyte pathology. Steatorrhea and growth failure are prominent.
Pancreatic enzyme replacement may compensate for pancreatic insuffi-
ciency, but no therapy has been fully effective on the hematologic abnor-
malities. Fig. 1. The case and the fatty infiltration of the pancreas.
We report on a 6-year-and-9-month-old white male with Schwachman
syndrome, admitted with complaints of stunted growth, distended abdomen,
and fatty diarrhea. He was ,3rd percentile with a McLaren scoring of 5.
His liver extended 1.5 cm below the costal margin; his right iliac–malleol encountered in the present case, as seen in the ill-defined disease of cyclic
length was 2 cm shorter than the left. Roentgenograms revealed right femur neutropenia which is characterized with fever and oral ulcers in older
neck shortness, acetabular hypoplasia, and infantile vertebrae. children [1]. In addition, an immune-deficient state was also disclosed, with
Fat globules and fatty acids were positive in stool specimens and tripsin a median T4/T8 ratio of 0.40: 12% (low) T-helper and 30% T-suppressor cell
activity, and Giardia trophozoites were absent in repeated duodenal juice counts. There was normal B-lymphocyte count, but also hypoimmunoglo-
and stool examinations. Repeated sweat test chemistry was found normal bulinemia with median serum immunoglobulin values of IgA, 11 mg/dl;
(median Na, 30 mEq/l; Cl, 10 mEq/l). History, and physical and radiologic IgM, 17 mg/dl; IgG, 107 mg/dl; and normal IgE our laboratory normal
examinations, revealed that the child was generally free of pulmonary ranges are close to Hong’s International Reference Standard Values) [3].
disease. Following informed parental consent, endoscopic examination of The patient’s glomerule filtration rate, acid-loading test, and thyroid
the small intestine disclosed only mucosal edema. An abdominal CT scan functions were normal. Other systemic and routine hematologic and bio-
[2] showed fatty infiltration of the pancreas (Fig. 1). chemical findings were remarkable. No medication was instituted during
During hospitalization, he presented with intermittent neutropenia (me- his stay in the hospital.
dian, 1.1 3 109/l) in cycles of 3 weeks, instead of the moderate chronic We did not come across such disturbances as were seen in the present
neutropenia characteristic of Schwachman syndrome, and with moderate case in other cases with Schwachman’s syndrome reported formerly, except
marrow cellularity during neutropenic periods, with normal maturity and in the case of Brueton et al. [4], presenting with cyclic neutropenia and
ratio attained before the advent of each neutropenic cycle. However, there variability in immunoglobulins.
was no intense myelopoiesis beginning with the advent of neutropenia, and The patient returned for a single follow-up examination 3 months after
the typically elevated monocytes at the nadir of the neutrophil count were discharge with pancreatic enzyme replacement. His findings suggested a
Q 1997 Wiley-Liss, Inc.

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 Letters and Correspondence 85
constitutional immunodeficiency state rather than a secondary phenomena clinical evidence of activity (oral ulcers, diffuse hair loss, and arthritis).
to malnutrition. However, blood coagulation test results remained within normal ranges.
Most patients with LA do not bleed abnormally. When this happens, an
FIGEN OKSEL abnormality other than LA must be suspected. Anticoagulants directed
BAHA TANELI against von Willebrand factor, factor VIII, factor IX, factor XI, and fibrin
polymerization have been described in patients with SLE [2]. Another
˙Department of Pediatrics, Faculty of Medicine, Ege University,
Izmir, Turkey associated condition which may predispose to hemorrhage is a specific
factor II deficiency [2,3]. Although minimal to moderate prolongation of
PT can be accounted for by LA, the finding of a substantially prolonged
REFERENCES
PT represents presumptive evidence of an associated factor II deficiency.
1. Corrigan JJ Jr: Disorders of the leukocytes. In Behrman RE, Kliegman RM, Nelson The interrelationship between LA and factor II deficiency is not clearly
WE, Vaugmann RC III (eds): “Nelson Textbook of Pediatrics,” Ed 14. Philadelphia: understood. There is evidence that several LA IgG preparations can bind
W.B. Saunders Co.: 1992, p. 1266. directly to prothrombin without neutralizing its coagulant activity. It is
2. Robberecht E, Nachtegaele F, Rattinghe R, Afschrift M, Kunnen M, Verhaaren R:
also recognized that hypoprothrombinemia is associated with a concordant
Pancreatic lipomatosis in the Schwachman-Diamond syndrome: Identification by
depletion of plasma prothrombin antigen. The deficiency is presumed to
sonography and CT-scan. Pediatr Radiol 15:348, 1985.
3. Hong’s International Reference Standard Values: Springfield, VA: NCI Immuno- be secondary to a rapid clearing of prothrombin/antiprothrombin complexes
globulin Reference Center. in the liver [4]. Finally, most cases respond to corticosteroid therapy with
4. Brueton MJ, Mauromichalis J, Goodchild MC, Anderson CM: Hepatic dysfunction or without the administration of fresh-frozen plasma [5].
in association with pancreatic insufficiency and cyclical neutropenia: Schwachman- We have described a patient with SLE who developed hemorrhagic
Diamond syndrome. Arch Dis Child 52:76, 1977. tendencies as a consequence of a factor II deficiency. The presence of LA
and hypoprothrombinemia was confirmed by several commonly-used tests.
In addition, a circulating neutralizing antibody to factor II was not detected.
Our patient improved promptly after initiation of corticoid therapy. Reevalu-
ation 1 month later showed that all “in vitro” coagulation test results had
returned to normal. After a follow-up of 5 months, SLE showed activity,
but blood coagulation test results remained normal. Thus, LA-associated
hypoprothrombinemia seems to have a high sensitivity to corticoid therapy
Prothrombin Deficiency and Hemorrhage Associated With and a weak correlation with the clinical evolution of SLE.
a Lupus Anticoagulant Our case indicates that this unusual complication of LA should be consid-
ered in the differential diagnosis of patients who have abnormal bleeding.
To the Editor: Lupus anticoagulant (LA) is a common clotting abnormality We suspect that this complication may be more common than is suggested
found in patients with systemic lupus erythematosus (SLE). Although LA by the existing literature.
is responsible for an “in vitro” hypocoagulability, it is not associated with
an “in vivo” hemorrhagic tendency. In contrast, it is now well-established ENRIC GRAU
that LA is a risk factor for thrombosis [1]. We describe a patient with SLE ESPERANZA REAL
and LA who developed hemorrhagic tendencies as a consequence of a EMILIO PASTOR
clotting factor II (prothrombin) deficiency. ´
JOSE IVORRA
A 12-year-old girl was referred because of abnormal hemorrhage follow- ESTHER QUECEDO
ing cutaneous biopsy. She had had a 2-month history of localized erythema- Departments of Hematology, Rheumatology, and Dermatology,
tous skin lesions in the malar region and bridge of the nose, frequent `
Hospital Luis Alcanyis, Xativa, Spain
epistaxis, and easy bruisability. She was not receiving any medications.
There was no family history of abnormal bleeding. Laboratory examination
REFERENCES
showed a leukocyte count of 2,900/mm3 with 1,000 lymphocytes/mm3,
hemoglobin 12.4 g/dl, and platelet count of 102,000/mm3. Prothrombin time 1. Hughes GRV: The antiphospholipid syndrome: Ten years on. Lancet 342:341–
(PT) was 23 sec (normal values (NV), 12.5–13.5 sec), activated partial 344, 1993.
thromboplastin time was 47\sec (NV, 26–35 sec), thrombin time was 20 sec 2. Feinstein DI, Francis RB: The lupus anticoagulant and anticardiolipin antibodies.
In Wallace DJ, Hahn BH (eds): “Dubois’ Lupus Erythematosus.” Wallace DJ,
(NV, 18–22 sec), and factor II clotting activity was at 30% (NV, 60–140%).
Hahn BH, eds. Philadelphia: Lea & Febiger, 1993, pp 246–253.
Clotting assay results for other coagulation factors were within normal
3. Eberhard A, Sparling C, Sudbury S, Ford P, Laxer R, Siverman E: Hypoprothrombi-
ranges. Factor II inhibitor assay was negative. Diluted Russell’s viper venom nemia in childhood systemic lupus erythematosus. Semin Arthritis Rheum 24:12–
time (DVV test, American Diagnostica,) was 73 sec (NV, 28–48 sec), and 18, 1994.
platelet neutralization procedure (DVV Confirm, American Diagnostica) 4. Permpikul P, Mohan Rao LV, Rapaport SI: Functional and binding studies of the
was positive. Anticardiolipin antibody test (ACA, Cheshire Diagnostic roles of prothrombin and B2-glycoprotein I in the expression of lupus anticoagulant
Ltd., UK) gave results of IgG 46.2 (NV, ,15) and IgM 15.9 (NV, ,13). activity. Blood 83:2878–2892, 1994.
Antinuclear antibodies (ANA) were positive (1:160 dilution), anti-native 5. Bernini JC, Buchanan GR, Ashcraft J: Hypoprothrombinemia and severe hemor-
DNA antibodies were positive (1:80 dilution), C3 was 0.35 g/l (NV, rhage associated with a lupus anticoagulant. J Pediatr 123:937–939, 1993.
0.5–1.2 g/l), and C4 was 0.01 g/l (NV, 0.2–1.2 g/l).
Skin bleeding stopped using local measures, and blood derivatives trans-
fusion was not required. She was started on deflazacort therapy (30 mg a
day given in a single oral dose for 7 days, 22.5 mg a day for 7 days, and
then maintenance treatment with 15 mg per day). One month later, physical
examination revealed a marked improvement of the skin lesions. The patient
was free of bleeding complications. Laboratory data revealed the following: Tumor Lysis Syndrome in a Case of Chronic Lymphocytic
platelet count of 103,000/mm3, normal blood coagulation with factor II Leukemia Induced by High-Dose Corticosteroids
80% and LA-negative, anticardiolipin antibodies-negative, ANA-positive
(dilution 1:80), and anti-native DNA antibody-positive (dilution 1:40). Five To the Editor: Tumor lysis syndrome (TLS) results from massive tumor-
months after diagnosis, corticoid doses were increased because SLE showed cell destruction that usually occurs hours or days after the beginning of

85678KP477 07-22-97 15:52:28

 86 Letters and Correspondence
mmol/l, uric acid of 726 micromol/l, potassium of 5.0 mmol/l, magnesium
of 1.3 mmol/l, calcium of 2.4 mmol/l, and phosphate of 3.0 mmol/l (Fig. 1).
Abdominal ultrasound showed only ascites and splenomegaly at that
time. He was then treated for legionella pneumonia with normalization of
his renal function and metabolic abnormalities. His lymphadenopathies and
splenomegaly disappeared, and his lymphocyte counts decreased signifi-
cantly after the pulses of methylprednisolone.
The occurrence of TLS in patients with CLL was previously described
with purine analogs such as fludarabine [3] and 2-chlorodeoxyadenosine
[4], as well as with aggressive combination chemotherapy regimens [5].
This case illustrates, therefore, that high doses of corticosteroids can
also produce TLS in CLL patients. Thus, before the administration of
high-dose corticosteroid regimens to patients with CLL, one may consider
instituting the usual precautions for patients at risk for TLS, such as hydra-
tion, urine alkalinization, and allopurinol administration.

ANELISA K. COUTINHO
Grupo de Estudos en Medicina, Bahia, Brazil
MARCELO DE O. SANTOS
´
HELIO PINCZOWSKI
OLAVO FEHER
Grupo de Altas Doses de Quimioterapia do Hospital,
˜ ˜
Samaritano-Sao Paulo, Sao Paulo, Brazil
AURO DEL GIGLIO
Department of Hematology, ABC Foundation School of
˜
Medicine, Sao Paulo, Brazil

REFERENCES
1. Chasty RC, Liu-Yin JA: Acute Tumor lysis syndrome. Br J Hosp Med 49:488–
492, 1993.
2. Loosveld OJL, Schouten HC, Gaillard CA, Blijham GH: Acute tumor lysis syn-
drome in a patient with acute lymphoblastic leukaemia after a single dose of
prednisone. Br J Haematol 77:122–123, 1991.
3. Frame JN, Dahut WL, Crowley S: Fludarabine and acute tumor lysis in chronic
lymphocytic leukemia. N Engl J Med 327:1396–1397, 1992.
4. Dann EJ, Gillis S, Polliak A, Rund D, Rachmilewitz E: Brief report: Tumor lysis
syndrome following treatment with 2-chlorodeoxyadenosine for refractory chronic
lymphocytic leukemia. N Engl J Med 329:1547–1548, 1993.
5. McCroskey RD, Mosher DF, Spencer CD, Prendergast E, Longo WL: Acute tumor
lysis syndrome and treatment response in patients treated for refractory chronic
Fig. 1. Biochemical and hematological parameters of the patient
lymphocytic leukemia with short-course, high-dose cytosine arabinoside, cisplatin,
described before and after administration of high-dose cortico-
and etoposide. Cancer 66:246–250, 1990.
steroids.

cytotoxic-specific therapy [1]. As a result of this major tumor cytorreduc-

tion, severe hyperuricemia, hyperkalemia, hyperphosphatemia, and hypo-
calcemia may occur [1]. This syndrome usually occurs in patients with
tumors highly sensitive to the cytotoxic chemotherapeutic agents employed,
such as high-grade lymphomas and acute leukemias. Although TLS was Detection of HTLV-I Proviral DNA by Fluorescence
reported in high-grade lymphoproliferative disorders after the use of cortico- In Situ Hybridization
steroids [2], so far we have found no reports in the literature of TLS
induced by corticosteroids used as a single agent in chronic lymphocytic To the Editor: Human T-cell lymphotropic virus type I (HTLV-I) is the
leukemia (CLL). causative agent of adult T-cell leukemia (ATL) and of HTLV-I-associated
A 44-year-old male had a diagnosis of CD5-positive B CLL made in myelopathy/tropical spastic paraparesis (HAM/TSP). The HTLV-I genome
1993. The patient refused treatment and was lost to follow-up. In May can be detected by several methods, including Southern blot hybridization
1995 he was diagnosed with legionella pneumonia, as confirmed by lung [1], polymerase chain reaction (PCR) [2], in situ hybridization (ISH) [3], and
biopsy and serology. At the time of this admission he had cervical and axillary PCR-ISH [4]. In this study, attempts were made to apply the fluorescence in
bilateral lymphadenopathy and splenomegaly. Laboratory studies showed situ hybridization (FISH) technique for the detection of integrated HTLV-
WBC of 36.8 3 109/l, with 27.2 3 109/l lymphocytes and 45 3 10a/l I proviral DNA.
platelets. His creatinine consisted of 83 mmol/l, potassium 4.1 mmol/l, Peripheral blood mononuclear cells (PBMC) from 3 patients with ATL
magnesium 0.8 mmol/l, calcium 2.0 mmol/l, glucose 6.2 mmol/l, and LDH and 3 asymptomatic HTLV-I carriers, and four HTLV-I-infected cell lines
3.6 mkat/l. Creatinine clearance was 74.7 ml/min. In an attempt to avoid (MT-I, MT-2, Ra-1, and ATL-1K), were examined. PBMC from 3 seronega-
endotracheal entubation the patient received two doses of 2 g of methylpred- tive healthy persons and one HTLV-I uninfected cell line (TALL-1) were
nisolone endovenously for 2 consecutive days. Forty-eight hr after cortico- used as negative controls. A full-length HTLV-I probe pMT-2 (kindly
therapy, he developed TLS with a creatinine of 283 micromol/l, BUN of 23.4 provided by Dr. G. Franchini, Bethesda, MD) was used after biotin-labeling.

85678KP477 07-22-97 15:52:28

 Letters and Correspondence 87

Fig. 1. FISH detection of HTLV-I in ATL-1K cell line. a: Single hybrid-

ization signal is seen at homologous sites on a nucleus (arrowhead).
b: Above, single hybridization signal is seen on a chromosome
(arrowhead). Below, G-banding demonstrates that this signal is at
chromosome region Xq21–q22 (arrow).

Hybridization signals for the probe were cytochemically detected with 3.9% of PBMC from virus carriers. Therefore, FISH appears to be highly
fluorescein isothioctanate-avidin. One thousand nuclei without overlapping sensitive for the detection of low HTLV-I proviral load, and may be useful
truncation were evaluated per sample. FISH signals were counted and for the identification of cellular localization of HTLV-I in HTLV-I-associ-
photographed with an Olympus BH-2 microscope. The percentage of posi- ated diseases such as uveitis, polymyositis, and arthropathy, as well as ATL
tive cells, which ranged from 57.5–95.5% in PBMC from ATL patients and HAM/TSP. In addition, mapping of HTLV-I integration sites may
and virus-infected cell lines, was ,3.9% in PBMC from HTLV-I carriers. provide clues to the interaction between cellular and viral sequences leading
The fresh samples from ATL patients and virus-infected cell lines showed to these HTLV-I-associated diseases.
multiple signals per cell, except for ATL-1K, which contained one signal
per cell in most cells (Fig. 1a). In addition, we detected one hybridization
YOSHIKI UEMURA
signal of ATL-1K at chromosome region Xq21–q22 by FISH combined
TETSUYA KUBOTA
with G-banding (Fig. 1b). Although similar signals were seen in ,1% of
TATSUSHI MIYAGI
cells from seronegative control persons, they were interpreted as false-
JUN IMAMURA
positive due to the background effect. The presence of multiple signals in
ICHIRO KUBONISHI
these HTLV-I-infected cell lines was consistent with Southern blot analysis
HIROKUNI TAGUCHI
that showed multiple bands after EcoRI digestion (data not shown).
ISAO MIYOSHI
Yoshida et al. [5] demonstrated a monoclonal integration of the HTLV-
Third Department of Internal Medicine, Kochi Medical School,
I provirus in primary tumor cells of 88 ATL patients, and showed that Kochi, Japan
integration of single intact HTLV-I provirus was typical. The sense ribo- KIICHI SHIMIZU
probe, complementary to viral DNA, can theoretically hybridize to one Shionogi Biomedical Laboratories, Osaka, Japan
copy, but the conventional ISH technique is not sensitive enough to detect
low copy numbers. In order to increase the sensitivity of ISH, PCR-ISH
has recently been developed, and this technique demonstrated HTLV-I tax REFERENCES
DNA in 1 of 5,000–10,000 PBMC from patients with HAM/TSP [4]. 1. Yoshida M, Miyoshi I, Hinuma Y: Isolation and characterization of retrovirus from
Detection of positive signals would be more difficult in HTLV-I carriers cell lines of human adult T-cell leukemia and its implication in the disease. Proc
than in HAM/TSP patients, because the number of infected cells is small. Natl Acad Sci USA 79:2031, 1982.
Despite this, FISH allowed us to visualize one signal per nucleus in 2.1– 2. Kwok S, Ehrlich G, Poiesz B, Kalish R, Sninsky JJ: Enzymatic amplification of

85678KP477 07-22-97 15:52:28

 88 Letters and Correspondence
HTLV-I viral sequences from peripheral blood mononuclear cells and infected survey for 301 cases of therapy-related leukemia/myelodysplastic syn-
tissues. Blood 72:1117, 1988. drome, only 3 cases of Ph-positive ALL, including our case, were reported.
3. Greaves MF, Verbi W, Tilley R, Lister TA, Habeshaw J, Guo HG, Trainor CD, A few cases of ALL have been reported in association with LCH [2,3],
Robert-Guroff M, Blattner W, Reitz M, Gallo RC: Human T-cell leukemia virus
and this is the first case of ALL with the Ph chromosome after radiotherapy
(HTLV) in the United Kingdom. Int J Cancer 33:795, 1984.
4. Levin MC, Fox FJ, Lehky T, Walter M, Fox CH, Flerlage N, Bamford R, Jacobson
and chemotherapy for LCH. Our case is suggestive of a radiotherapy-
S: PCR-in situ hybridization detection of human T-cell lymphotropic virus type I associated leukemia. Cooperative studies of LCH patients may identify
(HTLV-I) tax proviral DNA in peripheral blood lymphocytes of patients with an association between LCH and acute leukemia, as well as any risk factors
HTLV-I-associated neurologic disease. J Virol 70:924, 1996. or predisposing agents.
5. Yoshida M, Seiki M, Yamaguchi K, Takatuki K: Monoclonal integration of human
T-cell leukemia provirus in all primary tumors of adult T-cell leukemia suggests TETSUYA TATSUMI
causative role of human T-cell leukemia virus in the disease. Proc Natl Acad Sci CHIHIRO SHIMAZAKI
USA 81:2534, 1984.
SHIN-ICHI ARAKI
YOSHIKAZU SUDO
NOBORU YAMAGATA
EISHI ASHIHARA
HIDEO GOTO
TOHRU INABA
NAOHISA FUJITA
MASAO NAKAGAWA
Second Department of Medicine
SHIN-ICHI MISAWA
Third Department of Medicine
Philadelphia Chromosome-Positive Acute Lymphoblastic SHINSAKU IMASHUKU
Leukemia After Therapy for Langerhans Cell Histiocytosis Division of Pediatrics, Children’s Research Hospital, Kyoto
Prefectural University of Medicine, Kyoto, Japan
To the Editor: Langerhans cell histiocytosis (LCH) is a group of poorly
understood disorders characterized by infiltration of involved tissues by REFERENCES
Langerhans cells. LCH may present with a solitary bone lesion or a multisys- 1. Yoshihara T, Hibi S, Imashuku S, Sawada T: Primary eosinophilic granuloma of
tem, life-threatening disorder. Most patients with systemic disease usually the cervical lymph nodes in a child: Report of a rare case with invasion into the
receive chemotherapy. Recently, the association of LCH with a second soft tissue [in Japanese]. Jpn J Pediatr 91:3346, 1987.
neoplasm has been reported. We report a case of acute lymphoblastic 2. Egeler RM, Neglia JP, Puccetti DM, Brennan CA, Nesbit ME: Association of
leukemia (ALL) with the Philadelphia (Ph) chromosome which developed Langerhans cell histiocytosis with malignant neoplasms. Cancer 71:865, 1993.
after radiotherapy and chemotherapy for LCH. 3. Arico M, Comelli A, Bossi G, Raiteri E, Piombo M, Egeler RM: Langerhans cell
A 9-year-old boy had a right cervical mass partially resected in April, histiocytosis and acute leukemia: Unusual association in two cases. Med Pediatr
1986 [1]. The diagnosis of LCH was made by standard histiopathology Oncol 21:271, 1993.
4. Horibe K, Matsushita T, Numata S, Miyajima Y, Katayama I, Kitabayashi T, Yanai
and immunochemistry. Three months later, the remaining mass enlarged,
M, Sekiguchi N, Egi S: Acute promyelocytic leukemia with t(15;17) abnormality
and subtotal resection was performed. He then developed a presternal soft- after chemotherapy containing etoposide for Langerhans cell histiocytosis. Cancer
tissue mass and was treated with radiotherapy (29.62 Gy), followed by 72:3723, 1993.
chemotherapy consisting of vinblastine (VLB; 0.1–0.3 mg/kg, weekly for 5. Kapoor G, Bajpai S, Nair CN, Badrinath Y, Gladstone B, Advani SH: CALLA
five doses), 6-mercaptopurine (6-MP; 2 mg/kg, daily for 6 months), and positive acute lymphoblastic leukemia after etoposide-based therapy for Ewing’s
prednisolone (PSL; 1 mg/kg, daily for 6 months, then tapered). A complete sarcoma. Leuk Res 19:771, 1995.
remission was maintained for 7 years. He was readmitted in June, 1993
because of fever, epistaxis, pallor, and purpura on his legs. Laboratory
findings were as follows: Hb 8.8 g/dl, platelets 26 3 109/l, and WBC
340 3 109/l with 96% blasts. Bone marrow showed hypercellularity with
97.4% blasts with FAB-L1 morphology. Serum of lactate dehydrogenase
was 3,404 IU/l. Blasts were negative for peroxidase; surface marker analysis
revealed positivity for CD10, CD19, and CD34. Cytogenetic examination
revealed all cells analyzed to be 46,XY,t(9;22)(q34;q11). A rearrangement
of bcr-abl in the minor breakpoint region was shown by the reverse tran-
scriptase-polymerase chain reaction (RT-PCR) method. He was initially Hemophagocytic Syndrome Responding to High-Dose
treated with the Japan Adult Leukemia Study Group (JALSG) ALL-90 Gammaglobulin as Presenting Feature of Sarcoidosis
protocol. No remission was obtained, and central nervous system (CNS)
leukemia occurred in September, 1993. Despite whole-brain irradiation To the Editor: The sporadic form of fulminant hemophagocytic syndrome
and high-dose chemotherapy, the patient died of multiple organ failure in (FHS) is an aggressive and often fatal disorder characterized by fever,
February, 1994. jaundice, multiple organ failure, cytopenias, coagulopathy, and hypertri-
The association of LCH with a second neoplasm has been the subject glyceridaemia [1]. The most striking histopathologic feature is the prolifera-
of isolated case reports [2–4]. Egeler et al. [2] postulated that this association tion within lymph nodes and bone marrow of macrophages phagocytizing
follows two distinct processes: reactive, and therapy-related. They reported all sorts of blood cells. Sporadic FHS has been described in association
that the simultaneous association of LCH with malignant lymphoma or with viral and bacterial infections, immunodeficiency, systemic lupus, Still’s
lung carcinoma suggested a reactive process, while leukemias or other solid disease, and malignancies.
tumors developing after treatment of LCH were suggestive of a therapy- Treatment has been generally disappointing, although recently three re-
related process. Thus far, secondary acute myelogenous leukemia (AML) ports described single patients responding to high-dose gammaglobulin
developing after treatment of LCH with VP16 [2–4] has been reported. therapy [2–4].
However, VP16 was not used in our case. We recently observed a patient in whom FHS preceded a diagnosis of
On the other hand, secondary leukemias are rare in ALL [5]. In a Japanese sarcoidosis, and i.v. gammaglobulin therapy was successful.

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 Letters and Correspondence 89
effective in FHS, and shows for the first time that this syndrome may be
associated with sarcoidosis.

CARLO L. BALDUINI
PATRIZIA NORIS
Institute of Internal Medicine and Medical Oncology, Istituto di
Ricovero e Cura a Carattere Scientifico San Matteo-University
of Pavia, Pavia, Italy
CARLO LONI
CARLO AIOSA
Division of Medicine, Pietrasanta Hospital, Lucca, Italy

REFERENCES
1. Cline MJ: Histiocytes and histiocytosis. Blood 84:2840, 1994.
2. Freeman B, Rathore MH, Salman E, Joyce MJ, Vitel P: Intravenously administered
immune globulin for the treatment of infection-associated hemophogocytic syn-
Fig. 1. Temporal changes in platelets (l), reticulocytes (L), and drome. J Pediatr 123:479, 1993.
serum LDH intravenous i.v. Ig, high-dose i.v. gammaglobulin. 3. Fort DW, Buchanan GR: Treatment of infection-associated hemophagocytic syn-
drome with immune globulin. J Pediatr 124:332, 1994.
4. Gill DS, Spencer A, Cobcroft RG: High-dose gamma-globulin therapy in the
reactive haemophagocytic syndrome. Br J Haematol 88:204, 1994.
5. Watson HG, Goulden NJ, Manson ML, McDermid G, Gray JA, Parker AC: Virus-
associated haemophagocytic syndrome: Further evidence for a T-cell mediated
This patient, a 23-year-old female, was hospitalized at the beginning of
disorder. Br J Haematol 86:213, 1994.
March 1994 for an acute febrile illness. Investigation revealed anemia (Hb
hemoglobin 6.3 g/dl), leukopenia (2.4 3 109 WBC/l with normal differential
count), and mild thrombocytopenia (124 3 109 platelets/l). Based on ele-
vated values of bilirubin (55.7 mM/l) and LDH (3,427 U/l) and low haptoglo-
bin (,40 mg/dl), an acute hemolytic anemia was suspected. She received
a single dose of i.v. gammaglobulin (10 g) and was started on prednisone
therapy (100 mg/day). Three days later she was transferred to our institution.
Physical examination revealed fever (398C), splenomegaly (4 cm below
the costal arch), and jaundice. Laboratory investigations (pancytopenia,
clear signs of hemolysis, negative direct and indirect Coombs’ test, and
hypertriglyceridaemia) and bone-marrow aspirate (showing histiocytosis
and haemophagocytosis of all types of marrow and blood cells) led to a Sideroblastic Anemia Terminating in Chronic
diagnosis of FHS. The patient improved without further therapy, and all Myeloid Leukemia
clinical and laboratory parameters normalized within 1 month (Fig. 1).
The subsequent clinical course was uneventful until July, when the patient To the Editor: Acquired refractory sideroblastic anemia (ARSA) frequently
was hospitalized again because the clinical and laboratory features of FHS lasts for years without progression. However, over a 10–15-year period,
recurred. Therapy with i.v. gammaglobulin (20 g 3 4 days) was initiated, about 10% of patients with ARSA develop acute myeloid leukemia. Also,
and 2 days later laboratory data began to improve, reaching normal values a transformation of ARSA to acute lymphocytic leukemia has been de-
within 1 month. Meanwhile, chest X-ray revealed bilateral hilar adenopathy scribed [1]. Evolution of ARSA into a chronic myeloproliferative disease
and a diffuse reticulonodular lung infiltrate suggesting a diagnosis of sar- is an exceptional finding. Only two cases of ARSA terminating in idiopathic
coidosis. Lung function tests, gallium 67 chest scan, bronchoalveolar lavage, myelofibrosis, and only one case of ARSA terminating in polycythemia
serum angiotensin-converting enzyme, and biopsy of scalene nodes were vera, have been documented so far [2,3]. We describe the first case of
consistent with this diagnosis. typical ARSA terminating in Philadelphia (Ph) chromosome-negative and
The patient undertook prednisone therapy that induced remission of bcr-negative chronic myeloid leukemia (CML), with typical clinical and
sarcoidosis within 6 months. During this period she also received mainte- morphological features.
nance therapy with i.v. gammaglobulin (monthly injection of 20 g). After A 58-year-old man was admitted for evaluation of anemia on January
remission of sarcoidosis, no further gammaglobulin therapy was given, and 1991. Physical examination was unremarkable, with no hepatosplenomeg-
FHS did not reappear. aly. Laboratory examination at that time revealed: hemoglobin 5.7 g/dl,
Our observation adds further support to the hypothesis that i.v. gamma- red blood cell count of 2.48 3 1012/l, MCV 68.2 fl, reticulocytes 2%,
globulin therapy may be truly effective in FHS, in that it induced remission platelets 335 3 109/l, and a leukocyte count of 6.4 3 109/l. Serum iron
in our patient both when associated with prednisone and when used as a levels and saturation of transferrin were slightly increased. Serum ferritin
single agent. The mechanisms of action of high-dose gammaglobulin are concentration was 545 ng/ml (normal values, 27–300 ng/ml). Hemoglobin
complex and include the blockade of histiocyte Fc receptors, reduction of A1 concentration was normal, while hemoglobin A2 concentration was
activated T helpers, and increase of T-suppressor cell number. All these only slightly increased: 4.5% (normal values, 1.5–3.5%). The blood film
mechanisms of action are consistent with a possible effect of high-dose showed a population of hypochromic red cells with anisocytosis and
¨
gammaglobulin in FHS, where hypercytokinemia and abnormal activation poikilocytosis, and hypogranular neutrophils with Pelger-Huet anomaly.
of histiocytes have a pathogenetic role. A bone-marrow aspirate and biopsy showed increased cellularity as a
Although it has never been reported previously, the association between result of erythroid hyperplasia. Prussian blue staining of the marrow
FHS and sarcoidosis is not surprising, since both conditions seem to derive showed pathologic ringed sideroblasts. Granulopoiesis was not altered
from an immune regulation defect characterized mainly by T-cell abnormali- and thrombopoiesis was normal, except for slight signs of dysmegakaryo-
ties and increased lymphokine production [5]. poiesis (micromegakaryocytes). Marrow iron stores were increased, while
In conclusion, our observation confirms that i.v. gammaglobulin may be significant fibrosis was absent. A diagnosis of ARSA was made, and

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 90 Letters and Correspondence
the patient received periodic transfusions of red cells, while the administra-
tion of folic acid and danazol gave only a transient benefit. Sixteen
months after onset of the myelodysplastic syndrome (MDS), the patient
presented marked splenomegaly. Laboratory examination revealed: hemo- Residual Leukemic Blasts or Regenerating Normal
globin 7.5 g/dl, platelets 200 3 109/l, and a leukocyte count of 26 3 109/l, Precursors? The Hematologist’s Dilemma
with the following differential count: neutrophils, 70%; basophils, 2%;
lymphocytes, 6%; promyelocytes, 3%; myelocytes, 10%; metamyelocytes, To the Editor: A practical problem faced by hematologists is of differentiat-
6%; and blasts, 3%. A bone-marrow aspirate and biopsy showed a massive ing acute leukemia from regenerating marrow especially with acute myeloid
hyperplasia of granulocytes with normal maturation. Megakaryocytopoiesis leukemia (AML). At present, the diagnosis of “remission” is usually made
appeared normal, while erythropoiesis was reduced, in the absence of by morphological examination of postchemotherapy bone-marrow smears.
significant fibrosis. The neutrophil alkaline phosphatase was markedly Although this is satisfactory in most instances, it is not always possible to
increased (score of 260). Cytogenetic analysis of the bone marrow revealed distinguish with absolute confidence residual leukemic blasts from regener-
a normal karyotype. A detailed molecular study of the bcr gene, by Southern ating marrow precursors. The use of growth factors may compound the
blot analysis of the patient’s bone-marrow DNA, allowed us to exclude problem by altering the maturation kinetics of hemopoietic precursors.
the presence of breakpoints in the M-bcr region [4]. Furthermore, the A proper distinction is important, however, as it may influence clinical
absence of the p190 as well as of the p210 chimeras was documented by management decisions for the patient. A mistaken diagnosis of residual
reverse-transcriptase polymerase chain reaction assays performed on RNA leukemia/relapse may lead to unnecessary and potentially dangerous chemo-
extracted from the patient’s bone marrow and peripheral leukocytes [4]. A therapy, where a more conservative approach may be more reasonable,
diagnosis of Ph chromosome-negative and bcr-negative CML was made particularly in certain groups of patients. It is important for all clinical
and the patient received hydroxyurea, which was effective in controlling hematologists to be aware of this while treating AML patients. Morphologi-
the leukocyte count for about 1 year. In April 1993, the patient was referred cal evaluation should be supplemented by other techniques.
to us for bone pain. Peripheral blood analysis revealed: hemoglobin 9.9 g/dl, The techniques useful for the detection of leukemic clones include cytoge-
platelets 68 3 109/l, and a sudden rise in the leukocyte count, to 125 3 109/l, netics, immunophenotyping, gene rearrangement studies, and the polymer-
with the following differential count: neutrophils, 41%; basophils, 4%; ase chain reaction for detection of molecular lesions [1]. Of these, immuno-
lymphocytes, 5%; monocytes, 2%; promyelocytes, 11%; myelocytes, 10%; phenotyping is the most widely available, is applicable to cases of acute
metamyelocytes, 5%; and blasts, 22%. A bone-marrow aspirate revealed myeloid leukemia, and appears to be useful. It is particularly applicable
almost absent erythropoiesis and megakaryopoiesis, with an increase in to cases with certain combinations of antigens. Examples are cases with
myeloblasts. The patient died 5 days after admission, of cerebral hem- coexpression of CD13/CD33/CDW65 with “aberrant” antigens such as
orrhage. CD2/CD7 and/or nuclear TdT [2], and of CD34 and CD4 or CD56 [3]. A
Very few cases of refractory anemia, with or without excess of blasts, recent study has also shown that leukemic myeloid cells may co-express
and no cases of classical ARSA, have been reported so far to terminate in CD-117 and CD15 whereas normal myeloid cells very rarely do so [4].
Ph-negative CML [5]. One could consider the entities of MDS and Ph- The other feature that may be usefully studied is the light-scatter pattern
negative CML as a continuous spectrum of diseases. At one end of the on flow cyometry, which can help in the identification of different types of
spectrum are processes characterized by major dysplasia and categorized as AML blasts [5]. Two- or three-color analysis to demonstrate cell populations
MDS. At the other end, excessive proliferation with myeloid differentiation would also be very helpful.
defines cases of Ph-negative CML. Thus, our case suggests that ARSA The purpose of this letter is to draw the attention of all hematologists
may be included at one end of this spectrum, and a possible, although to the problem of distinguishing leukemic blasts from normal precursors
exceptional, evolution of ARSA into a Ph-negative CML with typical and to stress the need for detailed immunophenotypic, cytogenetic, and,
clinical and morphological features should now be considered. whenever possible, molecular analysis routinely in cases of AML at diagno-
sis and at appropriate phases during treatment. Finally, although immuno-
phenotyping is not essential for diagnosis of otherwise typical AML, it
E. BANDIERI should be performed for the above reasons, as well as to exclude bipheno-
C. DI DONATO typic/mixed-lineage leukemias [6].
F. ARTIOLI
C. CARAPEZZI
First Medical Division, Ospedale “Ramazzini,” Carpi, Italy
H.S. KESHAVA-PRASAD
University of Nevada School of Medicine,
M. LUPPI
Las Vegas, Nevada
T. ARTUSI
G. TORELLI
Section of Hematology, Department of Medical Sciences, REFERENCES
University of Modena, Modena, Italy
1. Campana D: Detection of minimal residual disease in leukemia and lymphoma.
In: Ed. Brenner, MK “Recent Advances in Haematology,” Vol 7. Edinburgh:
Churchill-Livingstone, 1993, pp. 21–31.
2. Campana D, Coustan-Smith E, Behm FG: The definition of remission in acute
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leukaemia with immunologic methods. Bone Marrow Transplant 8:429, 1991.
1. Lichtman MA, Brennan JK: Myelodysplastic disorders. In Williams WJ, Beutler 3. Coustan-Smith E, Behm FG, Hurwitz CA, Rivera GK, Campana D: N-CAM
E, Erslev AJ, Lichtman MA (eds): “Hematology.” New York: McGraw-Hill, Inc., (CD56) expression by CD31 malignant myeloblasts has implications for minimal
1995, pp 257–272. residual disease detection in acute myeloid leukemia. Leukemia 7:853, 1993.
2. Beris P, Grof J, Miescher PA: Primary acquired sideroblastic and primary acquired 4. Macedo A, Orfao A, Martinez A, Vidriales MB, Valverde B, Lopez-Berges MC,
refractory anemia. Semin Hematol 20:101–113, 1983. San Miguel JF: Immunophenotype of c-kit cells in normal human bone marrow:
3. Lokowicz DF, Myers TJ, Grasso JA, Albala MM: Sideroblastic anemia terminating Implications for the detection of minimal residual disease in AML. Br J Haematol
in myelofibrosis. Am J Hematol 13:253–257, 1982. 89:338, 1995.
4. Luppi M, Morselli M, Emilia G, Temperani P, Marasca R, Barozzi P, Selleri 5. Vidriales MB, Orfao A, Lopez-Berges MC, Gonzalez M, Lopez-Macedo A, Garcia
L, Torelli G: Spontaneous loss of Ph chromosome with maintenance of clonal MA, Galende J, San Miguel JF: Light scatter characteristics of blast cells in acute
hemopoiesis in an untreated patient with myeloproliferative disease and long sur- myeloid leukaemia: Association with morphology and immunophenotype. J Clin
vival. Genes Chromosomes Cancer 12:237–240, 1995. Pathol 48:456, 1995.
5. Oscier DG: Atypical chronic myeloid leukaemia, a distinct clinical entity related 6. Rowan RM, Bain BJ, England JM, Hyde K, Matutes E, Reilly JT, Stephens AD,
to the myelodysplastic syndrome? Br J Haematol 92:582–586, 1996. Lewis SM, Shinton NK, Murphy MF, Wood JK: General Haematology Task Force

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 Letters and Correspondence 91
of BCSH-Immunophenotyping in the diagnosis of acute leukamias. J Clin Pathol
47:777, 1994.

Recurrent Reversible Nephrotic Syndrome During Therapy

With Recombinant Interferon Alpha

To the Editor: Recombinant interferon alpha (rIFNa) is increasingly used

in the treatment of hematological malignancies, solid tumors, viral infec-
tions, and AIDS-related complications. Toxicities commonly associated
with IFN therapy include “flu-like” symptoms, gastrointestinal disorders,
and central nervous system abnormalities. Severe renal toxicity has rarely
been reported in IFN recipients. We describe a patient with renal-cell
cancer in whom recurrent nephrotic syndrome developed after treatment
with rIFNa.
A 54-year-old patient was admitted to our hospital because of back pain.
On radiographic examination, he was found to have right renal cancer with
multiple metastases of the liver, lungs, and skeleton. Following radical
nephrectomy and radiotherapy of the bone metastases, the patient was
treated with interferon-a2b (Intron A, Essex, Munich, Germany) at a daily
dose of 1 million units (MU) subcutaneously. Over the ensuing weeks, the
IFN dosage was increased to 3 and 5 MU daily (Fig. 1) Additional therapy
consisted of biweekly injections of vindesine (5 mg) and slow infusions
of pamidronate (60 mg). Except for the first days of IFN therapy, the patient
did not receive comedication with paracetamol or other analgetics. A follow-
up evaluation 7 months later revealed complete regression of all metastatic
lesions. After 8 months of IFN therapy, the patient developed fatigue,
breathlessness, and periorbital and peripheral edema. The serum albumin
concentration was 2.l g/dl, and the 24-hr urinary protein excretion was 28.9
g/day. Urinary protein electrophoresis showed nonselective proteinuria.
Microscopic examination of urinary sediment disclosed numerous hyaline
and granular casts, as well as 5–15 red cells and leukocytes per high-
power field. The serum creatinine was increased to 1.7 mg/dl. Viral and
autoimmune serology, anti-phospholipid antibodies, anti-IFN antibodies, Fig. 1. Urinary protein excretion and serum creatinine levels during
circulating immune complexes, and cryoglobulins were negative. There IFN-a therapy for renal cancer.
was no evidence of recurrent renal cancer on ultrasonography and chest
radiograph. Renal vein thrombosis was excluded by Doppler ultrasound
venography. Interferon was stopped, and the patient was treated with diuret-
ics, albumin infusions, and high-protein diet, resulting in gradual improve- REFERENCES
ment of abnormal clinical and laboratory findings. Treatment with vindesine
1. Averbuch SD, Austin HA, Sherwin SA, Antonovych T, Bunn PA, Longo DL:
and pamidronate was reinstituted without recurrence of renal abnormalities. Acute interstitial nephritis with the nephrotic syndrome following recombinant
Three months later, IFN therapy was resumed at a reduced dosage (1–3 leukocyte A interferon therapy for mycosis fungoides. N Engl J Med 310:32, 1984.
MU interferon-a2a, Roferon A, Roche, Grenzach, Germany). Within 2 2. Noel C, Vrtovsnik F, Facon T, Noel-Walter MP, Hazzan M, Jouet JP, Bauters F,
months, massive proteinuria and hypoalbuminemia occurred, but again `
Lelievre G: Acute and definitive renal failure in progressive multiple myeloma
normalized when IFN was withdrawn (Fig. 1). treated with recombinant interferon alpha-2a: Report on two patients. Am J Hematol
While mild degrees of proteinuria have been described in up to 20% of 41:298, 1992.
IFNa recipients, severe renal disorders are rare. They manifest as oliguric 3. Stratta P, Canavese C, Dogliani M, Thea A, Degani G, Mairone L, Vercellone A:
Hemolytic-uremic syndrome during recombinant a-interferon treatment for hairy
and nonoliguric acute renal failure, nephrotic syndrome, or hemolytic ure-
cell leukemia. Ren Fail 15:559, 1193.
mic syndrome [1–3]. Among these complications, nephrotic syndrome ap-
4. Aul C, Schneider W (eds): “Interferons—Biological Activities and Clinical Effi-
pears to carry the best prognosis, because proteinuria is always reversible cacy.” Heidelberg: Springer, 1996, pp. 180–192.
after withdrawal of IFN [4]. Our case report confirms this impression. In
our patient, massive proteinuria recurred after reexposure to IFN, supporting
a causal relationship between renal dysfunction and drug therapy. We con-
clude that close clinical monitoring and frequent urinalyses are required
in each patient undergoing treatment with IFNa.

CARLO AUL
HORST MINNING Aleukemic Leukemia Cutis Preceding Overt Acute Myeloid
¨
THOMAS SUDHOFF Leukemia in Myelodysplastic Syndrome
NORBERT GATTERMANN
AXEL HEYLL To the Editor: We report on the case of a patient with myelodysplastic
Department of Internal Medicine, Hematology and Oncology syndrome (MDS) who presented with aleukemic leukemia cutis preceding
¨
Division, Heinrich Heine University, Dusseldorf, Germany the developement of acute myeloid leukemia.

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 92 Letters and Correspondence
A 76-year-old man had been studied 4 years previously due to anemia from other tumoral infiltrations of the skin, including atypical cutaneous
and leukopenia. Peripheral blood showed: Hb, 11.8 g/l; WBC, 2.5 3 109/l B- or T-cell lymphoma and cutaneous metastasis [3]. Although possible
(36% neutrophils, 53% lymphocytes, 8% monocytes, 1% eosinophils, and advantages of treating MDS either before or after leukemization have not
2% basophils); Plt, 135 3 109/l. The rest of the studies performed (including been recognized, in our opinion, and due to the fact that in a short period
serum biochemistry, serum immunoglobulins, hemoglobin electrophoresis, most of these aleukemic cases terminate in leukemia with a poor prognosis
coagulation, vitamin B12, folic acid, ferritin, and serum erythropoietin) were (death occurs in 50% of cases in ,3 months after diagnosis) [4], treatment
all within normal limits. Bone-marrow aspirate was hypercellular, with gran- should be initiated immediately.
ulocytic hyperplasia and dysplastic features in the granulocytic and megakar- In conclusion, aleukemic leukemia cutis must be considered as an early
yocytic series. Karyotype was normal (46,XY). Myelodysplastic syndrome, manifestation of leukemic transformation [5] and an indicator of poor
FAB refractory anemia subtype, was diagnosed. For 4 years the patient was prognosis in MDS. Chemotherapy should be applied promptly to avoid
followed up without relevant changes in peripheral blood. After this time he this high risk of development of overt leukemia.
presented with progressive anemization and thrombocytopenia (86 3 109/l).
´
Bone-marrow aspirate showed intense dyshemopoiesis in all series and 8% J.N. RODRIGUEZ
myeloblasts (myeloperoxidase positive), and a diagnosis of refractory anemia A. FERNANDEZ-JURADO
with excess of blasts was considered. One month later, erythemato-violaceous A. NAVARRO
no pruriginous painless papules appeared in anterior and superior areas of M.L. MARTINO
the trunk. Biopsy of these lesions was performed, showing infiltration of D. PRADOS
´
the skin by myeloblasts (CD151), and leukemia cutis was diagnosed. Three Section of Hematology and Dermatology, Hospital “Juan Ramon
´
months later, due to a deterioration in peripheral blood (Hb 8.8 g/l, WBC Jimenez,” Huelva, Spain
1.6 3 109/l (2% myelocytes, 2% metamyelocytes, 11% neutrophils, 73%
lymphocytes, 8% monocytes, and 2% blasts), and Plt 72 3 109/l), a new bone- REFERENCES
marrow aspiration was performed, and 55% blasts were observed; FAB type ´ ˜ ´
1. Sanz GF, Sanz MA, Vallespı T, Canizo MC, Torrabadella M, Garcıa S, Irriguible
M2 leukemia was diagnosed. Considering the patient’s age, treatment with D, San Miguel JF: Two regression models and a scoring system for predicting
low doses of Ara-C (10 mg/m2/12 hr) was administered for 21 days without survival and planning treatment in myelodysplastic syndromes: A multivariate
response (8% blasts in peripheral blood), though cutaneous lesions improved analysis of prognostic factors in 370 patients. Blood 74:395–408, 1989.
slightly. Ara-C doses were increased to 20 mg/m2/12 hr for 12 days, but no 2. Kaiserling E, Horny HP, Geerts ML, Schmid U: Skin involvement in myelogenous
response was observed. The patient died 10 days after termination of treat- leukemia: Morphologic and immunophenotypic heterogeneity of skin infiltrates.
ment due to a stroke. Mod Pathol 7:771–779, 1994.
Transformation into acute myeloblastic leukemia occurs in 6–37% of 3. Horlick HP, Silvers DN, Knobler EH, Cole JT: Acute myelomonocytic leukemia
patients with MDS [1]. Cutaneous lesions in the course of acute leukemia presenting as a benign-appearing cutaneous eruption. Arch Dermatol 126:653–
656, 1990.
is frequent (30–50%), mainly in myeloid leukemia. However, leukemia ´
4. Aractingi S, Bachmeyer C, Miclea JM, Verola O, Rousselot P, Dubertret L, Daniel
cutis (leukemic cell infiltration of the skin) occurs in ,10% of cases, MT: Unusual specific cutaneous lesions in myelodysplastic syndromes. J Am Acad
mostly in coexistence with overt leukemia [2,3]. This type of lesion is Dermatol 33:187–191, 1995.
exceptional in MDS. No more than 40 cases of aleukemic leukemia cutis 5. Longacre TA, Smoller BR: Leukemia cutis. Analysis of 50 biopsy-proven cases
have been reported in the literature (the majority in acute granulocytic or with an emphasis on occurrence in myelodysplastic syndromes. Am J Clin Pathol
monocytic leukemias) [3]. The appearance of these lesions varies greatly 100:276–284, 1993.
[3,4], from macules to tumors, and the diagnosis must be differentiated

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