According to the World Health Organization (WHO) classification standards, the definition of DDLPS is a bone and soft tissue tumor or ALT / WDLPS that has dedifferentiated into a different degree of sarcoma at the same time or before/after the development of ALT / WDLPS[2, 8]. Dedifferentiated areas usually consist of undifferentiated pleomorphic sarcoma or spindle cell sarcoma, with high to moderate cellularity and pleomorphism. Traditionally, DDLPS are all considered high-grade sarcomas, and no further histological grading is required.
Recently published clinicopathological analyses have confirmed that DDLPS can be further divided into low-grade (equivalent to Grade 2) and high-grade DDLPS (equivalent to Grade 3) according to the French National Federation of The Centers for the Fight Against Cancer (FNCLCC) grading system.
Grade 2 DDLPS occupied about 10% of all DDLPS and had a better prognosis and overall survival rate than Grade3 DDLPS[7, 9, 10]
. In contrast to ALT / WDLPS, which has a relatively clear histological subtype, DDLPS represents a morphologically heterogeneous group. In the case described above, DDLPS was characterized by the coexistence of high- and low-grade dedifferentiated components. This manifestation is rare in clinical practice. We summarize the associated pathological features and MRI findings to deepen the awareness of this rare type of DDLPS.
DDLPS presents most commonly in middle-aged and older adults and affects both genders equally. The condition is extremely rare in children and adolescents. The retroperitoneum is the site most frequently affected, followed by the limb and spermatic cord / paratesticular area. Rarely affected sites include the chest cavity, mediastinum, and head and neck (such as the larynx or esophagus). Due to the large space for tumor growth in the posterior peritoneal area, ALT / WDLPS in this area can grow for a long time without causing symptoms. There is therefore a high risk (about 28%) that dedifferentiation will be observed at the time of diagnosis[4, 7].
The histology of DDLPS usually includes ALT / WDLPS components that have transformed into non-fatty tumor components, and the two components are usually clearly demarcated under the microscope. The most common histological type of ALT / WDLPS in DDLPS is lipomatous and sclerotic. As seen in our case report, the retroperitoneal mass was huge and contained many WDLPS components, the dedifferentiated components were characterized by the coexistence of low-grade and high-grade dedifferentiated components.
High-grade dedifferentiation can coexist with low-grade dedifferentiation , but this is rare. The pathological manifestations of this case belong to this category. In this case, the histological morphological characteristics of low-grade dedifferentiation in the specimen showed bidirectionally, some areas showed inflammatory myofibroblastic tumor-like characteristics changes, while some areas showed fibromatosis-like characteristics changes, and the coexistence of these two histomorphology reflected the variability and relative instability of the histological phenotype of low-grade dedifferentiation when they are formed. The low-grade dedifferentiation components accounted for only 10% of the dedifferentiated tumor and were located in the periphery of the high-grade dedifferentiation components, and the two dedifferentiated portions suddenly transition with a clear boundary. We speculated that low-grade dedifferentiation may be a precursor to high-grade dedifferentiation, the conversion starts from the periphery in DDLPS, this manifestation has also been reported in another case report. Besides, the dedifferentiation components can also show other histological morphological characteristics, such as concentric circle-like changes, even mixed distribution, etc.
As mentioned above, DDLPS can show a wide spectrum of histological morphology. In addition to the common histological features similar to other types of soft tissue sarcomas described above, many structural characteristics that are difficult to describe in morphology can also be seen. If DDLPS occurring outside the retroperitoneum, it can simulate the more common soft tissue tumor in this site, thus confusing the differential diagnosis, particularly for the low-grade DDLPS. For example, the low-grade DDLPS occurring in the gastrointestinal tract may simulate the more common GIST or inflammatory fibrous polyp, and the low-grade DDLPS arising in the paratestcular locations may be similar to the cellular angiofibroma, etc. This also reminds us to be vigilant and carefully understand in our daily work.
Besides, in the differential diagnosis of fatty tumors other than ALT / WDLPS, immunohistochemical staining that is positive for p16, MDM2 and CDK4 have high sensitivity and specificity for the diagnosis of DDLPS. In this case, well-differentiated liposarcoma components and dedifferentiated liposarcoma components (including high-grade dedifferentiation and low-grade dedifferentiation) all diffusely express P16, MDM2, and CDK4. However, in the differential diagnosis of DDLPS and non-fat-derived tumors, the specificity of the above three markers is insufficient. At this time, the use of FISH to detect the amplification of the MDM2 gene is highly specific and sensitive for the diagnosis of DDLPS, especially when diagnosed with small biopsy specimens. The use of FISH is even more specific and sensitive in small biopsy specimens without typical WDLPS components or low-level dedifferentiation and rare types of DDLPS[7, 15]. Amplification of the MDM2 gene is generally considered as the gold standard for the diagnosis of ALT / WDLPS and DDLPS.
The diagnosis of DDLPS requires the existence of two components in the tumor: lipogenic WDLPS and cellular nonlipogenic sarcoma. MRI can easily be used to identify fat-derived components in tumors through the use of fat-suppressed T2 images or short tau inversion recovery (STIR) imaging. These approaches allow for the identification of WDLPS components in DDLPS, which is more helpful for diagnosis; however, in some cases, the WDLPS composition may go unnoticed. Because DDLPS is the conversion of WDLPS components to non-fat-derived tumor components, DDLPS lesions may lack signs of lipid characteristics on MRI.
In summary, for the diagnosis of liposarcoma, whether based on MRI or pathology, we should pay attention to typical fat components. MRI has some limitations when used for the preoperative diagnosis of liposarcoma in samples lacking fatty components or for the diagnosis of liposarcoma. The differential diagnosis for DDLPS is wide, and there are many diagnostic traps. Extensive sampling of the mass is recommended to avoid missing any component. Sampling should be performed in both non-fatty and fatty tissues. To avoid the misdiagnosis of DDLPS, it is sometimes necessary to perform immunohistochemistry (such as MDM2 gene amplification). The transition between high- and low-grade differentiation components of DDLPS characterized in this case report is an important aspect of rare pathological manifestations of DDLPS.