Biphenotypic acute leukemia (BAL)1 is a new member of hematologic diseases, which shows a mixed phenotype of myeloid and lymphoid leukemias ...
Pyoderma gangrenosum associated with biphenotypic acute leukemia Mutsuyo Asai, MD,a Yoshinori Aragane, MD, PhD,a Akira Kawada, MD, PhD,a Takahiro Shimada, MD, PhD,b Akihisa Kanamaru, MD, PhD,b Hidekazu Yamada, MD, PhD,c and Tadashi Tezukam, MD, PhDa Osaka and Nara, Japan Pyoderma gangrenosum is a neutrophilic dermatosis that may be associated with myeloid malignancies. Less information is available about the association of pyoderma gangrenosum with lymphoid malignancies. We present, to our knowledge, the first case of pyoderma gangrenosum associated with biphenotypic acute leukemia wherein the malignant cells show a phenotype specific for myelogenic and lymphocytic leukemia. Histopathologic examination revealed rather nonspecific features without involvement of leukemic cells in the skin lesions. Treatment with systemic steroids was followed by characteristically rapid healing of the skin lesion. (J Am Acad Dermatol 2001;44:530-1.)
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iphenotypic acute leukemia (BAL)1 is a new member of hematologic diseases, which shows a mixed phenotype of myeloid and lymphoid leukemias, respectively. Malignant cells of BAL express both myeloid antigens (CD13, CD33) and lymphocytic markers specific either for T cells (CD3, CD5) or for B cells (CD10, CD19, CD22, or CD24). BAL is a rare disease that comprises 5% to 10% of acute leukemias.2 Earlier studies have suggested that BAL may arise by malignant transformation of pluripotent stem cells or cells whose developmental step is close to hematopoietic progenitor cells.3 Its prognosis is rather poor in terms of achievement of complete remission with therapy and overall survival rates.4 There is little knowledge about cutaneous manifestations associated with BAL. In contrast to myeloid leukemias, BAL has not until now been reported in association with pyoderma gangrenosum.
CASE REPORT A 62-year-old woman presented in February 1999 with a 2- × 2-cm erythematous macule with occasional itching on her abdomen. It rapidly enlarged From the Department of Dermatology,a and the Third Department of Internal Medicine,b Kinki University School of Medicine, Osaka, and the Department of Dermatology, Kinki University School of Medicine, Nara Hospital.c Reprint requests: Mutsuyo Asai, MD, Department of Dermatology, Kinki University School of Medicine, 377-2 Ohnohigashi, Osakasayama-shi, 589-8511 Osaka, Japan. Copyright © 2001 by the American Academy of Dermatology, Inc. 0190-9622/2001/$35.00 + 0 16/91/112377 doi:10.1067/mjd.2001.112377
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with intense pain while scratching. She visited a private practice and was treated with antibiotics, which were not effective. Soon thereafter, the lesion was ulcerated, had an undermined bluish-gray margin, and covered the entire whole lower abdomen (Fig 1). On her visit to our clinic, further tests were conducted, revealing complete blood cell count, hemoglobin 9.0 g/dL, white blood cell count 3000/µL (neutrophils 72.2%, lymphocytes 25.0%, monocytes 1.1%, eosinophils 1.5%, basophils 0.1%, atypical lymphocytes 0%), platelet count 26.3 × 103/µL, erythrocyte sedimentation rate 123 mm/h, and C-reactive protein 28.6 mg/dL. Chest and abdominal roentgenograms showed no detectable abnormalities. Swab culture from the ulcer base grew no pathogens. The histopathologic findings of the biopsy specimen taken from an erythematous border of the ulcer were consistent with pyoderma gangrenosum, showing moderate perivascular infiltrates consisting mainly of neutrophils and lymphocytes. T cells, but not B cells or myeloid cells, appeared to be a predominant lymphocytic population in the skin lesion as determined by immunostaining with antibodies to various hematologic markers (results not shown). To search for underlying diseases, bone marrow aspiration was conducted, demonstrating 57.9% malignant cells that had irregularly shaped nuclei and basophilic cytoplasm (Fig 2). Although the nature of vacuoles seen in cytoplasm in malignant cells (Fig 2) is not known, it is frequently observed in leukemia cells bearing lymphocytic phenotypes. An individual malignant cell was positive for a B-cell specific marker (CD19) and myeloid cell markers (CD13, CD33), respectively, as determined by flow cytometry.
J AM ACAD DERMATOL VOLUME 44, NUMBER 3
Fig 1. Macromorphology of lesion occupying entire lower abdomen.
Southern blot analysis revealed a rearrangement pattern of the heavy chain gene of immunoglobulin. On the basis of these laboratory data, a diagnosis of BAL associated with pyoderma gangrenosum was made. Treatment with systemic prednisolone (60 mg/day) was followed by a characteristically rapid response. The ulcer healed and was covered by epithelium within 10 days. There was no recurrence of the lesion even after the dose of prednisolone was reduced progressively to 15 mg/day. No chemotherapy was performed for BAL because during the treatment of pyoderma gangrenosum the percentage of malignant cells in the marrow significantly decreased. She stayed in reasonably well condition until sudden death from an acute severe episode of BAL in October 1999.
DISCUSSION Pyoderma gangrenosum is an uncommon ulcerative cutaneous condition with distinctive characteristics.5-7 Although the etiology of pyoderma gangrenosum is not yet clear, many reports have described associated internal disorders, including inflammatory bowel diseases (Crohn’s disease, ulcerative colitis), arthritis, preleukemic states (myeloid metaplasia, refractory anemia, or polycythemia rubra vera) and myeloid leukemia.5
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Fig 2. Giemsa-stained microscopic morphology of biphenotypic acute leukemia cells. Note irregularly shaped nuclei that contain large nucleoli and basophilic cytoplasm with vacuoles. (Original magnification ×1000.)
To our knowledge this is the first case of pyoderma gangrenosum associated with BAL; therefore the question arises whether this association is specific. This remains to be seen. REFERENCES 1. Kantarjian HM, Hirsch-Ginsberg C, Yee G, Huh Y, Freireich EJ, Stass S. Mixed-lineage leukemia revisited: acute lymphocytic leukemia with myeloperoxidase-positive blasts by electron microscopy. Blood 1990;76:808-13. 2. Carbonell F, Swansbury J, Min T, Matutes E, Farahat N, Buccheri V, et al. Cytogenic findings in acute biphenotypic leukemia. Leukemia 1996;10:1283-7. 3. Hanson CA, Abaza M, Sheldon S, Ross CW, Schnitzer B, Stoolman LM. Acute biphenotypic leukemia: immunological phenotypic and cytogenic analysis. Br J Haematol 1993;85:49-60. 4. Legrand O, Perrot JY, Simonin G, Baudard M, Cadiou M, Blanc C, et al. Adult biphenotypic acute leukemia: an entity with poor prognosis which is related to unfavourable cytogenetics and Pglycoprotein over-expression. Br J Haematol 1998;100:147-55. 5. Powell FC, Su WP, Perry HO. Pyoderma gangrenosum: classification and management. J Am Acad Dermatol 1996;34:395-409. 6. Hay CR, Messenger AG, Cotton DW, Bleehen SS, Winfield DA. Atypical bullous pyoderma gangrenosum associated with myeloid malignancies. J Clin Pathol 1987;40:3387-92. 7. Wahba A, Cohen HA. Herpes simplex virus isolation from pyoderma gangrenosum lesions in a patient with chronic lymphatic leukemia. Dermatologica 1979;158:373-8.
