Bullous lesion with central umbilication in leukemia

Abstract

A 51-year-old woman presented with a history of low-grade fever, easy fatigability, and intermittent diarrhea for eight months. A week before presentation, she developed multiple painful bullous lesions on the chest and limbs. On examination, there was pallor and multiple tender bullous lesions on the face, chest, and abdomen (Fig. 1). The bullae were variably sized (maximum diameter approximately 5 cm) with irregular erythematous and edematous margins and depressed, necrosed centers imparting a varicelliform appearance. Investigations revealed hemoglobin 6.9 g/dl, platelets 153 × 109/l, and white blood count 11 × 109/l with 30% blasts on the peripheral smear. In view of the presence of blasts in the peripheral smear, leukemia was considered as a diagnosis. Bone marrow examination revealed 100% cellularity with diffuse replacement by blasts, most of which were myeloperoxidase positive (Fig. 2: left panel and right panel) compatible with the diagnosis of acute myeloid leukemia. A punch biopsy from the margin of a bullous lesion showed infiltration of the superficial dermis and perivascular region by mononuclear cells (Fig. 3a,b) with high nuclear–cytoplasmic ratios, vesicular chromatin, and prominent nucleoli. These were positive on immunohistochemistry for CD34 (Fig. 4a) and myeloperoxidase (Fig. 4b) but negative for CD20, CD3, CD30, and cytokeratin. leukemia cutis – the infiltration of the dermis by atypical cells with myeloperoxidase and CD34 positivity confirms myeloid lineage blasts. Leukemia cutis is a generic term referring to cutaneous lesions caused by leukemic infiltration. Lesions can be found anywhere in the body and are usually multiple. They usually occur several months after the diagnosis of leukemia; however, concomitant involvement occurs in one-third and can even precede recognition of leukemia.1, 2 Leukemiacutis commonly manifests as violaceous, red–brown, or hemorrhagic papules, nodules, and plaques.1 Bullous lesions (as in this case) are uncommon, and the targetoid (depressed necrotic center) has not been described. Indeed, bullous lesions were found in only two of 42 cases in the Mayo Clinic series (both in chronic lymphocytic leukemia) and none in another series of 26 patients with myeloid leukemia.2, 3 The mechanism of bullae formation has been speculated to be extensive upper dermal edema, lymphatic obstruction, vascular occlusion, or minor injury at the dermoepidermal junction.4 Flow cytometry of the bone marrow aspirate in our patient revealed that the blasts were positive for CD13, CD14, CD33, CD34, CD64, CD117, and HLA-DR, suggesting myelomonocytic differentiation. Reverse transcriptase polymerase chain reaction was negative for the bcr-abl1, t(8;21) and inv(16) molecular abnormalities. The final diagnosis was acute myeloid leukemia (compatible with the FAB subtype AML-M4, acute myelomonocytic leukemia). Leukemia cutis is most commonly associated with acute myeloid leukemia (10–15%), in particular the myelomonocytic and monocytic subtypes (up to 50%). It can also be found in chronic myeloid leukemia (often signifying blast crisis). In acute lymphocytic leukemia, it is uncommon in the precursor B- or T-cell lymphocytic leukemia; however, it is found in 20–70% of the mature T-cell leukemias. In addition, it occurs in 30% of congenital leukemias.1 Leukemia cutis portends a poor prognosis, with one study finding that the average survival in acute myelomonocytic leukemia was 7.6 months.5 Treatment is directed at the systemic disease with intensive chemotherapy and hematopoietic stem cell transplantation. Radiotherapy has a role in the control of cutaneous lesions if they persist after chemotherapy or for palliation.6 Our patient declined treatment and shifted to alternative forms of therapy. An important differential is leukemids, i.e., skin manifestations in leukemia not due to leukemic infiltration. These are more common than leukemia cutis and include opportunistic infections such as herpes simplex or zoster (especially vesicular or bullous lesions), ecchymoses, cutaneous drug reactions, and neutrophilic dermatoses such as Sweet's syndrome. Histopathology and immunohistochemistry are essential for differentiating the two.1