Specific skin infiltration as first sign of chronic myelomonocytic leukemia with an unusual phenotype Donatella Braga, ]VID, a Ausilia M. Manganoni, 1V[D, a Valeria Boccaletti, MD, a Claudio Pancera, MD, a Daniela Marocolo, MD, b Fabio Facchetti, MD, b Giuseppe De Panfllis, MD a Brescia, Italy A patient who had a plaque on his forehead as the first sign of chronic myelomonocytic leu- kemia (CMML) is described. Histologic studies, which formerly led to the misdiagnosis of non-Hodgkin's lymphoma, revealed CMML with an unusual phenotype. This represents a rare type of CMML for the following reasons: (1) specific cutaneous involvement is rarely the first sign of CMML; (2) the unique phenotype was detected by immunohistology on le- sional skin, specifically, the leukemic infiltrate was CD4-positive and notably negative for CD15, the pan myeloid/monocytic marker. (J Am Acad Dermatol 1996;35:804-7.) Chronic myelomonocytic leukemia (CMML) is a polymorphous malignant hematologic stem cell dis- order, belonging to the myelodysplastic syndromes (MDS), characterized by abnormal bone marrow hyperplasia of mature or immature cells of both the monocytic and granulocytic series with predominant immature myeloblasts (up to 20% of bone marrow cells). Its course is characterized by refractory ane- mia caused by dyserythropoiesis with peripheral blood monocytosis which is usually accompanied by a neutrophil leukocytosis with evidence of dysgran- ulopoiesis and thrombocytopenia. The serum lysozyme level is characteristically elevated, and the erythrocyte sedimentation rate is markedly raised. 1 In both the peripheral blood and bone marrow are cells with features intermediate between myelocytes and monocytes. These have been termed "paramy- eloid cells."2 CMML occurs predominantly in eld- erly patients and usually runs a prolonged course, requiring only general supportive care. Skin infiltra- tion by leukemic cells is a frequent feature of acute monoblastic leukemia. Skin manifestations may be ORTHO This article is made possible through an educational grant from the Dermatological Division, Ortho Pharmaceutical Corporation. From the Department of Dermatologya Spedali Civili, Brescia, and Department of Pathology,b Brescia University Hospital. Reprint requests: Donatella Braga, Deparmaent of Dermatology, P.le Spedali Civili, 1, 1-25125 Brescia, Italy. Copyright © 1996 by the American Academy of Dermatology, Inc. 0190-9622/96 $5.00 + 0 16/4/74570 804 detected at presentation, and the skin is also a com- mon extramedullary site of relapse. Specific skin in- volvement in CMML appears to be exceptional. 3 We describe the eleventh case in the medical literature of such lesions 2' 4-6 and only the fourth in which these lesions were the first sign of hemopathy. 4 CASE REPORT A 56-year-old man had a purple plaque on his forehead for 5 months. The complete blood count was within nor- mal limits, except for a slight monocytosis (15%). A bi- opsy specimen revealed a widespread, nonepidermotro- pic dermal infiltrate composed of medium-sized cells with eosinophilic cytoplasm (Fig. 1) and an uneven, notched, or indented nucleus, which was sometimes in mitosis, with a distinct nuclear membrane, subtle chro- matin, and occasional small nucleofi (Fig. 2). lmmuno- histochemistry on frozen sections (Table I) showed that cells of the dermal infiltrate were positive only to CD4 (membrane and cytoplasm), CD68, and the transferrin receptor, OKT9, whereas about 30% of the infiltrate cells were positive for the proliferation marker Ki-67 (Table I). A bone marrow biopsy specimen revealed marked cellu- lar hyperplasia with excess and abnormal localization of immature progenitor cells, among them monocytoid cells, dysmegakaryopoiesis, and reticular fibrosis. Two months later the patient complained of bilateral swelling of the parotid glands and spread of the cutane- ous involvement with erythematous infiltrated plaques (Fig. 3). A bone marrow biopsy specimen again showed MDS monocytic infiltrate. A skin biopsy specimen from the back revealed an infiltrate highly positive for CD4 (cytoplasm), CD68, and OKT9, and negative to CD1,