Histological diagnosis

Histological diagnosis should be made according to the latest (2013) WHO classification.13Except in a few situations (e.g. pre-operative chemotherapy, rarely metastasising tumours or newer entities not categorized in the current grading system), grading of the sarcoma should be provided following the Federation Nationale des Centres de Lutte Contre le Cancer (FNCLCC) grading system (see Table 1), which is based on tumour differentiation, mitotic count, and necrosis. Histological assessment of these tumours involves careful morphological examination complemented by ancillary investigations. Morphological examination involves a systematic pattern-based approach analysing parameters that generally include: a) architecture, b) cyto-morphological features, and c) stromal characteristics. Identifying specific types of cells (e.g. lipoblasts, rhabdomyoblasts) can be extremely helpful in subtyping the tumour. For pleomorphic sarcomas it is critically important to subtype these tumours accurately wherever possible because each sarcoma is biologically and prognostically distinct. For example, a pleomorphic liposarcoma has a considerablye worse diagnosis prognosis than a dedifferentiated liposarcoma. Furthermore, what is seen to be UPS under the microscope may actually be one aspect of a well-differentiated/dedifferentiated liposarcoma.

Ancillary Investigations

A panel of immunohistochemical stains is routinely ordered primarily to determine the tumour lineage. Some of the common stains used in approaching retroperitoneal sarcomas would include: a) MDM2 and CDK4 for well-differentiated or dedifferentiated liposarcoma; b) H-caldesmon and desmin for smooth muscle differentiation, c) membranous CD99 expression for PNET, d) S-100 for neural differentiation, which (in some cases of dedifferentiated liposarcoma can be positive), and d) broad spectrum cytokeratin to exclude sarcomatoid carcinomas or mesotheliomas or more rarely other cytokeratin positive sarcoma (e.g. synovial sarcoma).

Molecular tests play a critical role in the diagnostic algorithm of problematic cases. These tests are often regarded as the gold standard in confirming diagnosis, especially in sarcomas with recurrent chromosomal translocations. In the context of retroperitoneal sarcoma, molecular tests could be used to detectHDM2andCDK4amplification for well-differentiated and dedifferentiated liposarcoma, translocation t(12;16)(q13;p11) for myxoid liposarcoma andEWSgene rearrangement for Ewings/ primitive neuroectodermal tumour and desmoplastic small round cell tumour. As with other ancillary investigations, molecular tests are complementary but not a substitute for histological diagnosis.

In summary, due to its complexity, diagnosing retroperitoneal sarcoma requires meticulous pathological examination with careful clinical and radiological correlation. With the availability of new ancillary diagnostic tools, every effort should be made to accurately subtype a high-grade sarcoma before signing it out as a high-grade undifferentiated pleomorphic sarcoma

Table 1: Federation Nationale des Centres de Lutte Contre le Cancer (FNCLCC) Histological Grading Criteria

The individual score for each parameter (i.e. tumour differentiation, necrosis, and mitotic count) is in parenthesis. The sum of the scores of the three parameters determines the grade of malignancy.

Grade 1: total score 2,3; Grade 2: 4,5; Grade 3: 68.

Tumour differentiation


Mitotic count*

(1) Well

(0) No necrosis

(1) 09

(2) Moderate

(1) < 50% tumour necrosis

(2) 1019

(3) Poor

(2) 50% tumour necrosis

(3) > 19

*Established on the basis of per 10 HPF; 1 HPF measures 0.1734 mm2.