Further genetic or epigenic changes produce a new clone of bone marrow plasma cells, usually descendant from the original clone, that causes the more serious, but still asymptomatic premalignant disorder smoldering multiple myeloma. This myeloma is characterized by a rise in the number of bone marrow plasma cells or levels of the circulating myeloma protein above that seen in MGUS. Subsequent genetic and epigenetic changes lead to a new, more aggressive clone of plasma cells, which cause further rises in the level of the circulating myeloma protein, further rises in the number of bone marrow plasma cells, or the development of one or more of a specific set of "CRAB" symptoms, which are the basis for diagnosing malignant multiple myeloma and treating the disease. In a small percentage of multiple myeloma cases, further genetic and epigenetic changes lead to the development of a plasma cell clone that moves from the bone marrow into the circulatory system, invades distant tissues, and thereby causes the most malignant of all plasma cell dyscrasias, plasma cell leukemia. Thus, a fundamental genetic instability in plasma cells or their precursors leads to the progression:

Monoclonal gammopathy of undetermined significance → smoldering multiple myeloma → multiple myeloma → plasma cell leukemia

Being asymptomatic, monoclonal gammopathy of undetermined significance and smoldering multiple myeloma are typically diagnosed fortuitously by detecting a myeloma protein on serum protein electrophoresis tests done for other purposes.
Each check-up should incorporate the examination of the patients regional lymph nodes and on a case-by-case basis annual chest X-rays and liver function tests. Spiradenomas
The currently preferred treatment for sporadic SA tumors (including giant vascular eccrine SA) in almost all cases is surgical excision. Many studies recommend wide local surgical excision of these tumors with surgical margins of ≥1 cm in order to ensure that all tumor cells are removed: local lymph node resections are usually reserved for those cases suspected of having lymph node metastases. Mohs micrographic surgery has been used as an alternative to surgical excision for the complete removal of these tumors. Since SA tumors may contain unidentified areas of malignancy and therefore have high recurrence rates, may metastasize to local lymph nodes and/or distant tissues, and can result in overall poor survival times, adjuvant radiation therapy has been used to minimize these aggressive events in SA tumors with equivocal signs of malignancy. However, the effectiveness of these adjuvant therapies has not been established. Adjuvant CO2 laser treatments have been used on occasion to remove these tumors in cases with multiple tumors. Some trials have using botulinum toxin A and triamcinolone injections directly into SA tumors but these trials have had limited success. Spiradenocarcinomas
With only 117 malignant cases reported in the literature as of 2022, there are no standard guidelines for the treatment of SAC tumors. Localized (i.e.