A 21-year-old woman presented with a complaint of dif fuse, flat, brown, macular lesions that first appeared 8 years ago. The lesions began on her abdomen and quickly spread over most of her body; sparing her palms, feet, and most of her face. She also reported a single episode of hypotension several years prior to presentation. Her past medical history was remarkable for congenital esophageal stricture and several skin biopsies, which were suggestive of an early chronic and slightly lichenified dermatitis. An evaluation of the skeletal survey revealed diffuse increased density involving multiple skeletal structures (Figure 1). Nuclear bane scan also revealed increased activity in the axial and appendicular skeleton. Subsequently, a bone marrow biopsy was performed:
Microscopic examination of the bane marrow specimen showed approximately 90% cellularity. Around the bony trabeculae, sheets of spindle cells with oval and elongated nuclei and a moderate amount of eosinophilic cytoplasm were noted (Figure 2): Toluidine blue staining showed metachromatic granules in several of the spindle cells (Figure 3); this finding was supported by electron microscopy (Figure 4).
What is your diagnosis?
Systemic mastocytosis is defined by mast cell hyperplasia that in most instances is indolent and nonneoplastic. It is a relatively rare disorder characterized by mast cell proliferation in several organs.1-4 Mastocytosis occurs at any age and has a slight preponderance in males. The prevalence of systemic mastocytosis is not known, and a familial occurrence has not been established.5
The clinical manifestation of mastocytosis is due to tissue occupancy by the mast cell mass, the tissue response to that mass, and the release of bioactive substances acting at both local and distant sites. The clinical symptoms are varied anti include diarrhea, weakness, fractures, weight toss, arthralgia, flushing episodes, bronchospasm, palpitations and vascular collapse, gastric distress, cramping pain in the lower abdomen, and recurrent headache. Splenomegaly may be present. Osteoblastic; osteolytic, or concurrent osteoblastic-osteolytic lesions may be found on radiologic examinations; generalized osteoporosis may also occur.
The bone marrow is the most frequent site of noncutaneous involvement in systematic mastocytosis; lesions may be found as a result of a specific search or may be detected in a biopsy performed for some purpose unrelated to suspected mastocytosis.
Horny et all described 3 histopathologic patterns of mastocytosis in the bone marrow: type I, focal lesions with normal-appearing, noninvolved marrow; type IT, focal lesions with marked granulocytic hyperplasia in noninvolved marrow; and type III, diffuse mastocytosis infiltration. Type I disease in the reported series was always associated with urticaria pigmentosa, which is a skin manifestation of the disease, and a low incidence of associated organomegaly. Type II and type III lesions were not associated with cutaneous involvement. Survival studies showed a correlation with histopathology. Type I was characterized by a prolonged course in the majority of the patients, and types II and III were generally associated with a more aggressive clinical course. The increased incidence of myeloid and monocytic leukemia in systemic mastocytosis also has been observed in other studies.2,3
The molecular biology of this disease is interesting. In type II systemic mastocytosis, there is a point mutation of the c-kit tyrosine kinase in the leukocytes or in mast cells. In types I and III, there is excessive production of the clot ligand in the microenvironment of the mast cells, and this may be autocrine in type III.
Highly specific antibody to human mast cell tryptase, which may be used on B5-fixed, decalcified, and paraffinembedded specimens, is very accurate for identification of mast cell lesions4 Antibodies that react with mast cells include antibodies to cx-antitrypsin, cq-antichymotrypsin, and CD68.6 Even when the tissue has been fixed in formalin; most of these cells are found by electron microscopy to contain cytoplasmic granules typical of mast cells. These granules are membrane-bound and contain scrolllike and latticelike material (Figure 4).
The differential diagnosis of mast cell lesions in the bone marrow includes angioimmunoblastic lymphadenopathy with dysproteinemia, Hodgkin disease, peripheral T cell lymphoma, and chronic idiopathic myelofibrosis. The primary distinguishing feature of mastocytosis is based on the immunohistochemical demonstration of mast cells with antibody to mast cell tryptase.
References
1. Horny HP, Parwarerh hlR, Lennert K. Bone marrow findings in systemic mastocytosis. Hum Pathol. 1985;16:808-814.
2. Horny HP, Rick M, Wehrmann M, Kaiserling E. Blood findings in generalized mastocytosis: evidence of frequent simultaneous occurrence of myeloproliterative disorders. Br J Haematol. 1990;76:186-193.
3. Travis W, Li GY, Bergstralh E, Yam LT, Swee RG. Systemic mast cell disease: analysis of 58 cases and literature review. Medicine (Baltimore). 1988;67:345368.
4. Wally AF, Jones 178, Williams JH, Church MK, Holgate ST. Immunohistochemical identification of mast cells in formalin-fixed tissue using monoclonal antibodies specific for tryptase. j C;lin Pathol. 1989;42:414-427.
5. Fausi AS, Branwald E, Isselbacher Kl, et al. Harrison's Principles of Internal Medicine. 14th ed. 1866-117. New York, NY`: McGraw-Hill; 1998,
6. Horny tip, Reiman O, Keiserling E. Immunoreactivity of normal and neoplastic tissue mast cells. Am f Clin P3thol. 1988;89:335-340.
Shahidul Islam, MD, PhD; Aiman Zaher, MD
Accepted for publication July 8, 1999.
From the Department of Pathology, Medical College of Ohio, School of Medicine, Toledo, Ohio.
Reprints riot available from the author:
Copyright College of American Pathologists Apr 2000
Provided by ProQuest Information and Learning Company. All rights Reserved
Contact
Home
A
Ulcerative colitis