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      Clonal and non-clonal mast cell activation disorders

      Embeds 0 No embeds. No notes for slide. As a result, mastocytosis is a disorder with presence of too many mast cells extra mast cells in a person's body. Both children and adults can develop mastocytosis. Traditionally, mastocytosis is classified as being either cutaneous mastocytosis CM or systemic mastocytosis SM. In cutaneous mastocytosis, mast cell accumulation is only found in the skin.

      To diagnose CM, a biopsy of affected skin has to be performed. The pure cutaneous form of mastocytosis is usually diagnosed in early childhood. By contrast, most patients in adulthood are diagnosed to have systemic mastocytosis. Most of the adult patients have typical skin lesions commonly termed urticaria pigmentosa. Since the bone marrow is almost always involved in these patients but not in those with CM , the diagnosis of systemic mastocytosis in adults is usually established by a biopsy of the bone marrow.

      In the rare patients without skin lesions, it may take a longer time until the doctors consider a systemic mast cell disease as a diagnosis, and thus it may take a longer time until the final diagnosis SM can be established. Systemic mastocytosis SM is a disease that arises on the basis of i. In contrast to a reactive mast cell hyperplasia increase in mast cells during an inflammation, cancer, or fibrosis , mast cells in systemic mastocytosis SM are monoclonal in nature, i.

      In cutaneous pediatric mastocytosis, the nature of mast cell-accumulation has not yet been entirely clarified. In some of these patients, mast cells also appear to be monoclonal in nature. Monoclonality of mast cells in mastocytosis can be documented best by demonstrating the presence of a point mutation in the c-kit proto-oncogene.

      In the majority of all patients with systemic mastocytosis, the somatic c-kit mutation DV AspVal is detected in the bone marrow, and often also in lesional skin where mast cells reside in macules. In a smaller group of patients with systemic mastocytosis, the mutation can also be found in circulating peripheral white blood cells. By contrast, in cutaneous mastocytosis, the c-kit mutation DV is usually not detectable in any organ. The natural clinical course of mastocytosis is variable depending on age, organs involved, subtype of disease, other co-existing disorders like allergies or other clonal myeloid disorders , and the response to therapy.

      The majority of all patients have a normal life-expectancy. In pediatric mastocytosis cutaneous mastocytosis in most cases , the disease often but not in all cases resolves during, shortly before, or shortly after puberty. Is Mastocytosis a Hereditary or Contagious Disorder? Mastocytosis is a non-contagious disease of mast cells and their progenitor cells. In the vast majority of all cases, no other family members are affected or will develop mastocytosis during life.

      Familial mastocytosis is an extremely rare disorder with an estimated frequency of less than , among all patients with mastocytosis. Subtypes of Mastocytosis. There are number of different subtypes variants and subvariants of mastocytosis. Cutaneous Mastocytosis CM.

      References

      Mast Cell Sarcoma. Extracutaneous Mastocytoma. Cutaneous mastocytosis usually develops in early childhood, whereas in adulthood the mast cell disease usually turns out to be a systemic variant of mastocytosis.

      All other subvariants of mastocytosis SM-AHNMD, aggressive systemic mastocytosis, mast cell leukemia, mast cell sarcoma, extra-cutaneous mastocytoma are rarely diagnosed. Most pediatric patients with CM have a benign and often self-limited clinical course. The disease often regresses spontaneously during puberty see above. Aggressive disease variants usually do not develop in children. There are some unique aspects in skin lesions developing in childhood mastocytosis. For example, blistering of skin lesions are only seen in pediatric mastocytosis.

      The same holds true for Mastocytomas of Skin, which are solid benign mast cell tumors. In general, the prognosis of childhood mastocytosis is very good. The following subvariants of CM have been described:. At the time of diagnosis, the natural clinical course of CM in children is unpredictable. The following can be found: i. The natural clinical course of systemic mastocytosis SM is also variable. Most patients are adults at diagnosis and have ISM with a good prognosis and normal or near-normal life expectancy.

      Aggressive disease variants are rarely diagnosed. These categories include mast cell leukemia and aggressive systemic mastocytosis. In these patients, the prognosis is grave.

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      Assay of Mast Cell Mediators

      Especially in patients with mast cell leukemia, where mast cells can be found in the peripheral blood, the disease has an unfavorable outcome. In almost all of these patients, skin lesions are absent. In case of an acute myeloid leukemia, the prognosis is unfavorable. Localized non-cutaneous mast cell tumors mastocytomas, mast cell sarcoma are also rare.

      The natural clinical course and prognosis of mastocytomas is good. By contrast, mast cell sarcoma, an extremely rare tumor, often evolves into mast cell leukemia and has an unfavorable prognosis similar to mast cell leukemia. An important aspect in disease-heterogeneity of mastocytosis are mediator-related symptoms SY. These symptoms can occur in any subvariant of CM and SM, and can represent a major clinical problem.

      The respective symptoms can range from mild and tolerable to repeated life-threatening episodes of hypotension and shock see below. How is Mastocytosis Diagnosed? In each case, the doctor will first perform a careful physical examination including a thorough inspection of the skin surface. The diagnosis of mastocytosis is based on a histological examination of the affected organ as well as pre-invasive done before biopsy and post-biopsy tests. Common preinvasive tests are routine laboratory parameters and the serum tryptase level, a special screen-test for patients with mastocytosis.

      For these examinations, the doctor asks the patient to donate a few mililiters of peripheral venous blood.