Granulocytic sarcomas have been reported in nearly every part of the body, including the gastrointestinal (GI) and genitourinary (GU) tracts, central nervous system (CNS), and respiratory, lymphatic, and skeletal systems. A few case series have been reported through the years. The majority of extramedullary myeloid cell tumors are seen in the skin, GU tract, and CNS. They are considered a sign of progression of previously diagnosed bone marrow disorders or, in the absence of bone marrow abnormalities, a representation of acute leukemia. There is no standard therapy for this diagnosis, although both chemotherapeutic and radiation therapy options have been used.
An Unusual Presentation
The article by Dr. Shah and colleagues reviews an unusual presentation of a gastric granulocytic sarcoma (GS) and probable extramedullary disease in the spleen and lymph nodes in an elderly woman with a history of high-grade myelodysplastic syndrome (MDS). Most reported data reveal that prognosis is worse in patients with extramedullary disease as a manifestation of hematologic malignancies than in those without extramedullary involvement, and therefore this patient was offered intensive treatment. Because she refused this option, she was treated with lower-intensity, standard MDS treatment, as is being utilized more often in elderly patients with AML, with limited success.
The patient had an impressive 9-month response, after which she was treated with local therapy, again with response, but her disease quickly progressed. At that point, she agreed to intensive chemotherapy and subsequently died of complications. The question of whether she would have had a comparable response if treated with intensive chemotherapy upfront is unknown. The fact that this patient was able to live for several months with some quality of life is very important, however, and does make this low-intensity choice a good option for many in her situation.
Individual Case Variables
Of course, this case involves a rare situation in which randomized trials are unlikely to ever be performed, and thus we must rely on retrospective case series for guidance. Success has been reported in children (as well as in adults) treated with chemotherapy with or without the addition of radiotherapy. Therefore, to group all patients with MDS-associated GS is probably not wise.
In this case, the patient was elderly. Her comorbidities were not mentioned but should be considered. To state that elderly patients treated with aggressive chemotherapy have a high rate of mortality may be accurate to some degree, if one reviews outcomes for elderly patients with secondary AML in general. As in all individual cases, however, patients should be given the opportunity to choose their own treatment course while being made aware of the risks and our lack of experience.
One concern in this particular case would have been the possibility of perforation if aggressive chemotherapy was given, theoretically making a lower-intensity option safer while allowing some healing of the gastric wall. This just shows how important it is to consider individual case differences. That said, the question of aggressive treatment upfrontâ€”prior to the possible development of chemorefractory disease—remains.
As more patients are diagnosed earlier with MDS, such cases may increase in number in comparison to those who present initially with a GS. An important area of research is to understand the biology of granulocytic sarcomas and other extramedullary tumors. The role of neural cell adhesion molecules was investigated in 1996 by Byrd et al, as mentioned by Shah and coauthors.
More recently, Tsimberidou et al discussed patients with nonleukemic granulocytic sarcomas in the absence of AML or high-grade MDS. Almost one-third of cases reviewed had chromosome 8 abnormalities. Patients were treated with chemotherapy and/or radiotherapy. Although not statistically significant, probably due to the small number of patients, the investigators found a trend for worse survival in those with chromosome 8 abnormalities compared to others. Overall, a high number of patients did achieve a complete remission with treatment, but failure-free survival was short. Tsimberidou and colleagues concluded that those with chromosome abnormalities may require more aggressive treatment.
As more is learned about granulocytic sarcoma and exramedullary disease, the specific differences among cases may lead to better and more targeted treatments and might aid in prediciting disease progression. This would be ideal for all patients, regardless of age.
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