Death from Mast Cell Leukemia: a Young Patient with Longstanding Cutaneous Mastocytosis Evolving Into Fatal Mast Cell Leukemia
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CASE REPORTS Pediatric Dermatology Vol. 29 No. 5 605–609, 2012 Death from Mast Cell Leukemia: A Young Patient with Longstanding Cutaneous Mastocytosis Evolving into Fatal Mast Cell Leukemia Rattanavalai Chantorn, M.D.,*, and Tor Shwayder, M.D. *Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand, Department of Pediatric Dermatology, Henry Ford Hospital, Detroit, Michigan Abstract: Mastocytosis is a broad term used for a group of disorders characterized by accumulation of mast cells in the skin with or without extracutaneous involvement. The clinical spectrum of the disease varies from only cutaneous lesions to highly aggressive systemic involvement such as mast cell leukemia. Mastocytosis can present from birth to adult- hood. In children, mastocytosis is usually benign, and there is a good chance of spontaneous regression at puberty, unlike adult-onset disease, which is generally systemic and more severe. Moreover, individuals with systemic mastocytosis may be at risk of developing hematologic malignancies. We describe a girl who presented to us with a solitary mastocytoma at age 5 and later developed maculopapular cutaneous mastocytosis. At age 23, after an episode of anaphylactic shock, a bone marrow examination revealed mast cell leukemia. She ultimately died despite aggressive chemotherapy and bone marrow transplantation. Mastocytosis is characterized by the abnormal common forms of CM in childhood. The excoriation growth and infiltration of mast cells (MC) in various of lesions causes hives and perilesional erythema, tissues and is classified into two broad categories: which characterizes Darier’s sign (Fig. 3). SM is cutaneous mastocytosis (CM) and systemic mastocy- characterized by multifocal MC infiltrates with or tosis (SM) (1). The course of mastocytosis is variable without skin involvement and is markedly more and is dependent on the subtype and age of onset common in adults than in children. Mast cell (2–4). Mast cell disease in children is usually only leukemia is a rare variant of SM, with few cutaneous and not associatedwithsystemicor cases reported in the literature and usually associated malignant disorders. In adults, MC disease can with grave prognosis (6–12). The purpose of this be systemic and progressive (4). Mastocytosis affects article is to report a case of longstanding childhood infants and children twice as frequently as adults (5). CM evolving to fatal MC leukemia during young Mastocytoma and urticaria pigmentosa (UP) are adulthood. Address correspondence to Tor Shwayder, M.D., Director, Pediatric Dermatology, Henry Ford Hospital, Detroit, MI 48202, or e-mail: [email protected]. DOI: 10.1111/j.1525-1470.2011.01650.x Ó 2012 Wiley Periodicals, Inc. 605 606 Pediatric Dermatology Vol. 29 No. 5 September ⁄ October 2012 CASE REPORT that were positive for Darier’s sign (Fig. 3). Otherwise, review of systems was normal. She denied any symptom A girl had been diagnosed with solitary mastocytoma of histamine release, including flushing, palpitation, since 5 years of age (Fig. 1). Her first presentation was a diarrhea, shortness of breath, headaches, and bone pain. red-brown thumb print–sized plaque in front of the left Because her underlying cutaneous disease was gradually ear that had history of bullous formation after blunt spreading, she was carefully examined. General physical trauma (Fig. 2). Skin biopsy confirmed the diagnosis of examination, blood pressure, pulse, and respiration were cutaneous MC disease at age 5 (outside punch biopsy) all normal. Complete blood count, liver function test, and age 19, when this lesion was removed completely. renal function test, and urinalysis were normal. The She was regularly followed by a pediatrician and a preauricular solitary mastocytoma was sensitive and pediatric dermatologist and had had normal develop- ‘‘annoying’’ to the patient. She was treated using ment. intralesional steroids several times and topical cortico- At the age of 10, more spots had slowly appeared on steroids as needed. Eventually, at age 19, she requested the neck, the V of the neck, the shoulders, and the back removal. Histopathology showed nodular infiltration of MC with prominent infiltrate of eosinophils extending throughout the thickness of the dermis and subcutaneous fibroadipose tissue (Figs 4 and 5). Histochemical stains for Giemsa, Leder, and Alcian blue confirmed MC (Fig. 6). At age 23, she was given acetaminophen with codeine and aspirin for neck and low back pain. This precipitated anaphylactic shock, requiring intubation and hospital- ization. Diagnosis of systemic mastocytosis was made based on results as follows: hemoglobin 8.1 g ⁄dL, white blood cell count 7,200 cell ⁄mL (neutrophils 86%, lym- phocytes 6.9%, monocytes 8.3%), platelet 267,000 ⁄mL, and a serum tryptase was >200 ng ⁄mL, and urine his- Figure 1. Preauricular mastocytoma: similar clinical picture tamine greater than two times normal limits. Bone to first presentation. Figure 2. Sister kicked her in this area, resulting in prompt Figure 3. Urticaria pigmentosa macules gradually increas- large bullae. ing in number over upper back. Note positive Darier’s sign. Chantorn and Shwayder: Death from Mast Cell Leukemia 607 Figure 6. Low-power view of preauricular biopsy Giemsa stain showing multiple mast cells. attacks per day consisting of tachycardia, flushing, mild shortness of breath, chest pressure, mild headache, and low back pain, lasting approximately 20 to 30 minutes Figure 4. Low-power view of preauricular area excision. Mast cell infiltrate throughout thickness of biopsy. each, and resolving without complications. She was admitted to the hospital for further examination and monitoring. Laboratory tests demonstrated hemoglobin of 13.3 g ⁄dL, white blood cell count 26,200 cell ⁄mL (neutrophils 58.5%, lymphocytes 9%, monocytes 2.5%, eosinophil 28.7%), absolute neutrophil count 15,327 cell ⁄mL, absolute eosinophil count 7,519 cell ⁄mL, and platelet count 122,000 ⁄mL. Repeat bone marrow aspi- rate smear showed that 79% of MC had atypical spindle- shaped morphology and confirmed the diagnosis of MC leukemia with rapid progression. Abdominal ultra- sonography revealed mild splenomegaly. Induction chemotherapy with cytarabine and ida- rubicin was started and induced some response. She subsequently underwent HLA identical sibling allo- genic peripheral blood stem cell transplantation, with fludarabine and busulfan as a conditioning regimen. Twelve days later, she started to engraft. Unfortu- Figure 5. High-power view of preauricular biopsy with dense nately, she continued to have episodes of histamine mast cell infiltrate. Note rare atypical multinucleated mast cells. release symptoms. Repeat bone marrow biopsy was done and demonstrated 70% of MC with sheets of atypical MC. Flow cytometric analysis revealed an marrow aspiration and biopsy showed that multiple atypical population of cells that expressed CD117, small aggregates of MC occupied 5% of the bone mar- CD25, CD58, CD63, and CD33, but were negative for row medullary space and stained strongly positive for CD2. Cytogenic studies were positive for a BCR-ADL tryptase.Rarespindle-shapedMCwerealsoseeninthis rearrangement. C-kit mutation analysis was not per- bone marrow study. Long bone survey was unremark- formed. These findings were consistent with persistent able. Computed tomography of the chest, abdomen, and MC leukemia. In addition, she had developed skin pelvis were normal except for an ectopic right pelvic rash, with a diagnosis of acute graft versus host disease, kidney. She was treated using systemic corticosteroids and was treated with high-dose systemic steroids and and H1 and H2 antihistamine. oral tacrolimus. During the 4 months after being diagnosed with sys- Her last admission was because of progressive temic mastocytosis, she had one or two mastocytosis and refractory edema. Upon hospitalization, she had 608 Pediatric Dermatology Vol. 29 No. 5 September ⁄ October 2012 developed fever with no evidence of any signs or symp- SM is characterized by multifocal infiltration of MC toms of infection. Cultures from blood and urine were in various organs, including bone marrow, gastrointes- examined and were negative. She received broad-spec- tinal tract, lymph nodes, liver, and spleen. The bone trum antibiotics, antiviral agents, and antifungal drugs, marrow is the most common documented site of MC but she continued to have fever and developed shock, accumulation outside of the skin (17). Mast cell leukemia requiring intubation and resuscitation, complicated by is a rare disorder, accounting for 1% of SM cases in one disseminated intravascular coagulopathy and metabolic review of 342 patients of SM from the Mayo Clinic (7). acidosis. She was unresponsive to treatment and died The clinical manifestation of SM results from 5 months after she was diagnosed with MC leukemia at MC-derived chemical mediators or infiltration of various the age of 23 years and 10 months. organs by neoplastic cells (4,18). Individuals with SM are Because of her death, we reviewed the earlier pathol- at certain risk of developing secondary hematologic ogy from her preauricular lesion. There were rare mul- malignancies, especially in myeloid leukemia (19). Indi- tinucleated MC within infiltrate (Fig. 5). Several of our viduals with MC leukemia usually have significant dermatopathologists and the National Institutes of organopathy but often present without cutaneous Health (NIH) reviewed this slide and thought that it was eruptions (9,18). consistent with cutaneous MC disease.