|Year : 2022 | Volume
| Issue : 2 | Page : 136-138
Congenital leukemia cutis in an infant
Carol Lobo, JP Prathibha
Department of Dermatology, St Johns Medical College Hospital, Bengaluru, Karnataka, India
|Date of Submission||14-Mar-2021|
|Date of Decision||19-Nov-2021|
|Date of Acceptance||19-Nov-2021|
|Date of Web Publication||30-Mar-2022|
Dr. J P Prathibha
Department of Dermatology, St Johns Medical College Hospital, Kormangala 5th Block, Sarjapura Road, Bengaluru - 560 034, Karnataka
Source of Support: None, Conflict of Interest: None
Background: The infiltration of neoplastic leukocytes or their progenitors into the epidermis, dermis, or subcutis, resulting in clinically evident cutaneous lesions, is known as leukemia cutis. Leukemia cutis may arise after, before, or concurrently with a diagnosis of systemic leukemia. Case Report: We present a case of congenital leukemia cutis that was later diagnosed as acute myeloid leukemia. Discussion: Congenital leukemia is defined as leukemia that is present at birth or develops within the first 6 weeks of life. Leukemia cutis has been identified in 25%–30% of patients with congenital leukemia. Typical clinical features often include papules, macules, and nodules.
Keywords: Acute, congenital, cutis, leukemia, myeloid
|How to cite this article:|
Lobo C, Prathibha J P. Congenital leukemia cutis in an infant. Indian J Paediatr Dermatol 2022;23:136-8
| Introduction|| |
Congenital leukemia is an extremely rare lethal condition that occurs at birth or develops within the first 6 weeks of life. Leukemia cutis is characterized by the infiltration of neoplastic leukocytes into the skin, which leads to clinically evident skin lesions such as patches, papules, and nodules which may appear prior to or concurrently with the diagnosis of systemic leukemia. Leukemia cutis has been identified in 25%–30% of patients with congenital leukemia. Diagnosis of leukemia cutis usually indicates a poor prognosis and is significantly associated with extramedullary involvement. The incidence of acute myeloid leukemia (AML) presenting as leukemia cutis has been reported between 2.9% and 3.7%. We describe a case of congenital leukemia cutis in an infant who was subsequently diagnosed with AML.
| Case Report|| |
A 2½-month-old male infant born of third-degree consanguineous marriage through full-term vaginal delivery to a healthy primigravida with a birth weight of 2400 g and a height of 48.5 cm was admitted to the pediatric intensive care unit with recurrent fever, abdominal distension, vomiting, and breathlessness for 3 days and four reddish-blue nodules on the left thigh, buttock, abdomen, and neck since 1 month of age, for which dermatologists' opinion was sought. Antenatal history was unremarkable. There was no documented history of maternal drug use or exposure to a known teratogen. The family history was nonspecific. The baby was being exclusively breastfed and had received age-appropriate vaccinations.
On day 20 of life, the infant was admitted to another hospital with fever, rash and neutropenia (absolute neutrophil count was 300 cells/ul) and was diagnosed with sepsis and given systemic antibiotics (details not known), after which fever subsided and the hematological parameters improved. He had received topicals for the skin nodules (details of which are not known). which lesions remained persistent. The admission was prior to COVID pandemic.
On admission, the baby weighed 2800 g and was underweight and malnourished. On physical examination, the infant was febrile and had pallor, with moderate tachypnea of 54 breaths/min and tachycardia of 110 beats/min. Abdominal distension, hepatosplenomegaly, and bilateral crepitations were noted. Cutaneous examination revealed four firm, tender dusky red nodules and plaques (1 cm × 1 cm to ∼3 cm × 3 cm in diameter) on the left thigh, buttock, neck, and abdomen [Figure 1] and [Figure 2]. No lymphadenopathy was noted. Mucosa, hair, and nails were normal. Investigations showed hemoglobin of 9 g/dl. Total leukocyte counts on day 1 of admission were 5750 cells/ul and on day 6: 3230 cells/ul. Neutropenia progressed from 8% (460 cells/ul) on day 1 to 2% (64.6 cells/ul) on day 6 after admission. Other hematological parameters were normal. Lactate dehydrogenase was 4881 U/L (N 170–283). Peripheral smear showed normocytic normochromic anemia with leukemic blasts. In the context of the haematological abnormalities, we considered the unusual differential diagnosis of blueberry muffin lesions, extramedullary hematopoiesis, leukaemia cutis, and subcutaneous fat necrosis as possible diagnostic possibilities. Skin biopsy was done with a 3-mm punch from the thigh nodule [Figure 3]. Hematoxylin and eosin staining of thigh nodule showed unremarkable epidermis and a dense infiltrate of rounded atypical cells with high nuclear–cytoplasmic ratio, hyperchromasia, and nuclear pleomorphism with irregular nuclear contours in the dermis and subcutis. Few cells exhibited prominent mitotic figures, suggestive of malignant small round cell tumor. Bone marrow aspiration revealed blasts comprising 85% of the marrow. Myeloid series showed mainly blast cells with nucleus showing fine chromatin.
|Figure 3: Biopsy from the nodule on left thigh showing malignant small round cell tumor (H and E x 40)|
Click here to view
Flow cytometry was positive for CD34, CD13, CD33, CD117, HLA-DR, CD64, and CD7 and direct immunofluorescence was positive for myeloperoxidase, suggestive of acute myeloblastic leukemia with aberrant CD7 expression.
Serology for TORCH, HIV, and hepatitis B antigen was nonreactive. Abdominal ultrasound showed hepatosplenomegaly with moderate ascites.
A final diagnosis of congenital leukemia cutis with AML was made. The parents were counseled regarding the poor prognosis and need for further management at a hemato-oncology center, however, they got discharged against medical advice.
| Discussion|| |
Congenital leukemia accounts for <1% of all childhood leukemia, with an incidence of 1 in every 5 million births and a higher predilection for males., Pallor, anemia, leukocytosis, hepatosplenomegaly, and cutaneous and central nervous system involvement are typical clinical features.
Leukemia cutis affects 30% of newborns with congenital leukemia. Most cases of leukemia cutis occur in patients with concurrent systemic leukemia; the most common is acute myelocytic leukemia, with myelomonocytic (M4) or monocytic (M5) FAB subtypes being common and lymphoblastic variations being rare. Clinical signs include multiple red-violaceous papules, macules, nodules, purpura, petechiae, and ecchymoses. Oral and ocular mucosal involvement is uncommon. Chromosomal instability is the hallmark of congenital leukemia. The MLL-AF4 fusion gene involving chromosome 11 is involved in majority of the cases.
Diagnostic criteria for leukemia cutis are as follows:,
- Immature cell proliferation in myelomonocytic, lymphoid, or erythroid series
- Infiltration into extrahematopoietic tissue
- Absence of leukemoid reactions mimicking congenital leukemia such as TORCH syndrome, hemolytic disease of the newborn (ABO or Rh incompatibility), hereditary spherocytosis, twin-twin transfusion, and other neoplastic infiltrates (metastatic neuroblastoma, rhabdomyosarcoma, and Langerhans cell histiocytosis)
- Absence of Down syndrome/chromosome 21 abnormalities with a transient abnormal myeloproliferative disorder.
Infants with acute myeloblastic leukemia tend to present with a more aggressive systemic and cutaneous involvement and a worse prognosis compared to older children., The survival rate is 20% at 2 years of age. Leukemia cutis does not alter the course in congenital leukemia as compared to adult-onset leukemia.
Histopathology of the skin lesion reveals a subepidermal grenz zone with patterns of infiltration varying from dense diffuse dermal infiltrate of pleomorphic leukemic cells arranged in an Indian file pattern between collagen bundles in the reticular dermis to compact nodular infiltrates. Immunohistochemistry and cytogenetics help in determining the subtype of the infiltrate.
Spontaneous remission in congenital leukemia cutis with a normal karyotype has been observed. In contrast, congenital leukemia cutis with AML-M5 and MLL gene rearrangement has an aggressive disease course that necessitates multiagent chemotherapy.
The limitations were the inability to conduct cytogenetic studies and loss to follow-up as the patient got discharged against medical advice. We present this case of clinical significance, emphasizing the importance of early disease detection and treatment initiation to reduce overall mortality. If a dermatologist notices nodules in an infant, the differential diagnosis of leukemia cutis should be considered.
Declaration of consent
The authors certify that they have obtained all appropriate consent forms, duly signed by the parent(s) of the patient. In the form the parent(s) has/have given his/her/their consent for the images and other clinical information of their child to be reported in the journal. The parents understand that the names and initials of their child will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Bayhan T, Çiki K, Tavil B, Gümrük F, Çetin M, Ünal Ş. An infant with congenital leukemia cutis and AML-M5 with MLL gene rearrangement. J Pediatr Hematol Oncol 2015;37:566-7.
Choi JH, Lee HB, Park CW, Lee CH. A case of congenital leukemia cutis. Ann Dermatol 2009;21:66-70.
Rao AG, Danturty I. Leukemia cutis. Indian J Dermatol 2012;57:504.
] [Full text]
Resnik KS, Brod BB. Leukemia cutis in congenital leukemia. Analysis and review of the world literature with report of an additional case. Arch Dermatol 1993;129:1301-6.
Pui CH. Childhood leukemias. N Engl J Med 1995;332:1618-30.
Yonal I, Hindilerden F, Coskun R, Dogan OI, Nalcaci M. Aleukemic leukemia cutis manifesting with disseminated nodular eruptions and a plaque preceding acute monocytic leukemia: A case report. Case Rep Oncol 2011;4:547-54.
Winters AC, Bernt KM. MLL-rearranged leukemias – An update on science and clinical approaches. Front Pediatr 2017;5:4.
Creutzig U, Ritter J, Zimmermann M, Reinhardt D, Hermann J, Berthold F, et al
. Improved treatment results in high-risk pediatric acute myeloid leukemia patients after intensification with high-dose cytarabine and mitoxantrone: Results of study Acute Myeloid Leukemia-Berlin-Frankfurt-Münster 93. J Clin Oncol 2001;19:2705-13.
Hilden JM, Dinndorf PA, Meerbaum SO, Sather H, Villaluna D, Heerema NA, et al
. Analysis of prognostic factors of acute lymphoblastic leukemia in infants: Report on CCG 1953 from the Children's Oncology Group. Blood 2006;108:441-51.
Longacre TA, Smoller BR. Leukemia cutis. Analysis of 50 biopsy-proven cases with an emphasis on occurrence in myelodysplastic syndromes. Am J Clin Pathol 1993;100:276-84.
Rossoff J, Akpan I, Platanias LC. Spontaneous remission in congenital leukemia. Leuk Lymphoma 2018;59:2271-2.
[Figure 1], [Figure 2], [Figure 3]