Radiological and clinical patterns of myeloid sarcoma

Myeloid sarcoma (MS), also known as granulocytic sarcoma or chloroma, is a solid tumor of extramedullary localization composed of malignant primitive myeloid cells.1 A first mention of the pathology was found in 1811 by Burns and later called chloroma on account of its typical green appearance caused by the presence of the enzyme myeloperoxidase in the granules of the immature granulocytic precursors.2,3 Its occurrence is linked with leukemic diseases of the myeloid cell line, primarily in patients with acute myeloid leukemia (AML) and less commonly in those with its chronic form (CML), myelodysplastic syndrome (MDS) or other myeloproliferative disorders.4 It may develop concurrently with mentioned primary diseases or be the initial manifestation of relapse in an already treated case.4 Especially, after allogenic bone marrow transplantation an increased incidence has been described.5 Very rarely, MS can occur in the absence of a systemic disease and predate onset of an underlying hematologic malignancy by months to years.6 Treatment options, including radiation and chemotherapy are based upon an early and accurate diagnosis is crucial.7 However, particularly inapparent bulks pose a diagnostic challenge lacking indicatory laboratory findings. Moreover, MS can possibly involve any organ system.4,5,8 There are only a few systematic evaluations of radiologic findings with small patient populations, mainly limited to case reports.9,13

Therefore, the purpose of this study was to evaluate imaging characteristics of MS in a large patient sample and to establish possible correlations between imaging and clinical data, assess growth patterns and typically imaging features.

The present study provides clinical and imaging findings of MS in a large patient sample. The diagnosis of MS might be challenging, even for the pathologist, and thus, typically clinical features are of importance for the radiologist and oncologist to establish the proper diagnosis. Furthermore, the occurrence of MS is associated with an overall poor survival with 15.9 months.6,8,14

According to the literature, the prevalence of MS varied from 2.5% to 9% in AML patients.9,15,16 However, due to its rare incidence, systemic data is still lacking to date. Additionally, the incidence of MS in myelodysplastic syndrome is even lower.16 Concordantly, only 2 patients with myelodysplastic syndrome and 2 patients with myeloproliferative disorders were identified in our patient sample.

As reported previously, MS can occur in three different situations. Firstly, it can occur prior to marrow/blood leukemia. In such cases systemic leukemia generally develops within one or two years after diagnosis of extramedullary relapse.6,8,9

Secondly, MS can occur in systemic disease, either at the time of diagnosis of leukemia or subsequent to diagnosis.6,8,9 Thirdly, MS can manifest itself as a relapse after therapy or stem cell transplantation.6,8,9 Most frequently, MS occurred in up to 50% after onset of AML, in 15–35% contemporaneous with the leukemic manifestation and, less frequently, before the diagnosis of the underlying malignancy.16

In the present study, in 71.30% of cases MS occurred with a mean of 40 months after the primary diagnosis. Overall, these results are in good agreement with the literature. Interestingly, the time between occurrence of MS and the initial onset of disease was longer than in a recent study by Kaur et al., in which it was only 8.8 months.6 Clearly, the diagnosis of MS is easier in cases with known AML. However, 18.3% of our patients developed MS simultaneous and even in 5.6% before the onset of a hematological disease. In these cases, the diagnosis may be very challenging to make due to several possible differential diagnoses. It has been reported that misdiagnosis rates in cases with MS varied from 25% to 47%.15 Frequently, Hodgkin-Lymphomas, MALT lymphoma, or Ewing’s sarcoma were diagnosed instead of MS.15 Furthermore, infectious diseases like abscesses have to be considered as a diagnosis because these occur very frequently in leukemic patients with immunosuppression, either due to chemotherapy or due to the malignancy itself.9

The clinical presentation largely depends on the affected site of MS, and, thus, MS can be presented with a lot of different symptoms.15 Regarding localizations, MS affects most frequently cutis, subcutis and visceral soft tissue.6,9 In an older study investigated 50 patients, 21 patients had a lesion in the soft tissue, 15 patients had lymph nodal lesions, and skin lesions in 13 patients.17 Only one patient had a brain lesion and 4 had gastrointestinal lesions.17 However, in a recent study analyzed 23 patients, skin and subcutaneous tissue was affected the most cases (69.5%).6 Furthermore, according to Neiman et al., in most cases, MS presented with one lesion, and 16% had two and more lesions.17

In the present study, MS was isolated to one body area in up to 80% of the cases. However, 42.3% of patients had more than 3 lesions, especially found in patients with subcutaneous involvement. This finding might be beneficial to rule out possible differential diagnosis like solid tumors, which only presents with a single lesion.

Concordantly to the literature, a preference for subcutaneous involvement was also identified, followed by osseous and affection of the central nervous system. Affection of visceral organs and lymph nodes were rarer in the present patient sample than in the previous studies.

Clearly, every unknown lesion no matter the localization in a patient with known AML, should be indicative for MS.

Clinically, myeloid sarcoma was apparent in half of the cases with swelling and skin discoloration, which underlines the importance of a good physical examination in oncologic patients. Furthermore, in 29.2% neurological and organ dysfunctions were found and in 21.5% pain was the main symptom. Notably, 11.3% of the MS cases were detected incidentally by imaging studies. For example, these included one patient with a cardiac manifestation. Due to increasing performance of imaging studies in oncologic patients, we hypothesize that the amount of incidentally detected MS will increase concordantly. Therefore, the radiologist and oncologist need to be aware of the entity of MS.

Shinagare et al. described MRI features of 25 patients with 41 different MS localizations.18 The authors identified lesions with a mean size of 5.6 cm (range 1–20 cm), which is good comparable with our data. Regarding signal intensities, 75.6% were isointense and 24.4% were hypointense on T1-weighted images. Moreover, on T2-weighted images, 95.1% were hyperintense and 4.9% were isointense.18 These results are also in good agreement with the present study, however, we detected more hypointense lesions on T1-weighted images, and more isointense lesions on T2-weighted images. Furthermore, Oii et al. investigated 11 patients with MS with similar imaging characteristics.13 MS lesions were concordantly isodense in the present study on CT. Regarding contrast media enhancement, every lesion showed a moderate contrast media enhancement with more lesions with a homogenous enhancement than heterogenous.

However, it should be acknowledged that neither the behavior of the signal intensity on MRI and CT nor the contrast enhancement is specific for MS lesions. For example, inflammatory lesions, such as abscess formations or other neoplastic lesions, such as lymphomas can show similar imaging findings.9

Chaundhry et al. reported a diffusion restriction in 96% of patients with cerebral myeloid sarcoma on diffusion weighted images (DWI).12 In our study, the appa rent diffusion coefficients of the lesions ranged from 0.36 to 0.84 mm2/s. This finding might be caused by high cellularity in these lesions as it was shown in several other malignancies.19 Our results are in good agreement with those of Chaundhry et al. Therefore, DWI might be a useful diagnostic tool for myeloid sarcoma evaluation. However, other cell rich tumors and tumor-like lesions, such as lymphomas, poorly differentiated carcinomas, and abscesses can also show restricted diffusion.

According to the literature, another beneficial imaging modality is PET/CT, which has better accuracy than CT alone in diagnosing MS.20 As reported, MS lesions show elevated FDG uptake and the uptake changes under therapy, which also correlates with clinical outcome.20

Our study has several limitations. First, it is a retrospective study with potential confounding factors. Second, the patient sample is relatively small, mainly caused by the rare incidence of myeloid sarcoma. However, the present study sample is one of the largest to date. Furthermore, prospective studies are lacking to this date due to low incidence. Third, some previously identified localizations like involvement of the lung was not identified in the present study sample.

Myeloid sarcoma is a rare occurrence of several hematological malignancies, predominantly of AML, which can affect any part of the body. In most cases it occurs after the diagnosis of the underlying malignancy, and affects frequently the cutis and subcutis. This study provides typical clinical and imaging findings in a large patient sample. However, the imaging findings are not specific for myeloid sarcoma and other differential diagnoses, such as inflammatory lesions or other neoplastic lesions have to be considered.