Institute of Pathology, Ansbach, Germany.
Pathobiology. 2010;77(4):169-80. doi: 10.1159/000305552. Epub 2010 Jul 7.
Diagnosis of systemic mastocytosis (SM) is mainly based on the morphological demonstration of compact mast cell infiltrates in various tissue sites. In almost all patients such infiltrates are detected in the bone marrow. Reliable immunohistochemical markers for the diagnosis and grading of SM have been established, but various differential diagnoses including myeloproliferative neoplasms, basophilic and eosinophilic leukemias may be very difficult to delineate. Even more challenging is the recognition of hematological neoplasms with signs of mast cell differentiation but not fulfilling diagnostic criteria for SM, especially the rare myelomastocytic leukemia. It is also important to separate the reactive state of mast cell hyperplasia from indolent variants of SM, especially those with a very low degree of bone marrow infiltration and absence of compact mast cell infiltrates. When the lymphocytic component of the SM infiltrate is very prominent, SM may be confused with an indolent lymphoma, especially lymphoplasmacytic lymphoma which almost always shows a marked reactive increase in mast cells. In aggressive and leukemic variants of SM, mast cells may be very atypical and devoid of metachromatic granules. This hypogranulation can be regarded as cellular atypia and may lead to the misdiagnosis aspect of monocytic leukemia or histiocytic neoplasm. Regarding immunohistochemical anomalies, mast cells in aggressive and leukemic SM have been found to express CD30 (Ki1-antigen). Thus, anaplastic large cell lymphoma or Hodgkin's disease may first be considered rather than SM. There is increasing evidence that most patients with long-standing adult-type urticaria pigmentosa-like skin lesions have in fact indolent SM. Therefore, such skin lesions are an important clue to the correct diagnosis in these patients. However, in aggressive or leukemic SM skin lesions are usually absent and then the correct diagnosis relies on an appropriate investigation of bone marrow biopsy specimens using both SM-related immunohistochemical markers (tryptase, KIT, CD25, CD30) but also markers excluding potential differential diagnoses. Investigation for presence of the activating KIT point mutation D816V is very helpful to establish a correct diagnosis of SM in all the difficult cases exhibiting a low degree of bone marrow infiltration or puzzling morphological findings.
系统性肥大细胞增多症 (SM) 的诊断主要基于在各种组织部位中致密肥大细胞浸润的形态学表现。几乎所有患者的骨髓中均检测到这种浸润。已经建立了可靠的用于诊断和分级 SM 的免疫组织化学标志物，但各种鉴别诊断，包括骨髓增生性肿瘤、嗜碱性和嗜酸性白血病，可能非常难以界定。更具挑战性的是识别具有肥大细胞分化迹象但不符合 SM 诊断标准的血液系统肿瘤，尤其是罕见的骨髓肥大细胞白血病。区分肥大细胞增生的反应性状态与惰性 SM 变体也很重要，尤其是那些骨髓浸润程度非常低且无致密肥大细胞浸润的变体。当 SM 浸润的淋巴细胞成分非常突出时，SM 可能与惰性淋巴瘤混淆，尤其是淋巴浆细胞淋巴瘤，其几乎总是显示出明显的肥大细胞反应性增加。在侵袭性和白血病性 SM 变体中，肥大细胞可能非常非典型且缺乏异染颗粒。这种低颗粒形成可被视为细胞异型性，可能导致误诊为单核细胞白血病或组织细胞肿瘤。关于免疫组织化学异常，侵袭性和白血病性 SM 中的肥大细胞已被发现表达 CD30（Ki1 抗原）。因此，首先考虑的可能是间变性大细胞淋巴瘤或霍奇金病，而不是 SM。越来越多的证据表明，大多数具有长期成人型荨麻疹性色素沉着症样皮肤病变的患者实际上患有惰性 SM。因此，这些皮肤病变是这些患者正确诊断的重要线索。然而，在侵袭性或白血病性 SM 中，皮肤病变通常不存在，然后正确的诊断依赖于对骨髓活检标本进行适当的检查，同时使用与 SM 相关的免疫组织化学标志物（类胰蛋白酶、KIT、CD25、CD30）以及排除潜在鉴别诊断的标志物。检测激活的 KIT 点突变 D816V 非常有助于在所有表现出低度骨髓浸润或令人困惑的形态学发现的困难病例中建立 SM 的正确诊断。
