The 2020 WHO Classification of Soft Tissue Tumours: news and perspectives

Abstract

Mesenchymal tumours represent one of the most challenging field of diagnostic pathology and refinement of classification schemes plays a key role in improving the quality of pathologic diagnosis and, as a consequence, of therapeutic options. The recent publication of the new WHO classification of Soft Tissue Tumours and Bone represents a major step toward improved standardization of diagnosis. Importantly, the 2020 WHO classification has been opened to expert clinicians that have further contributed to underline the key value of pathologic diagnosis as a rationale for proper treatment. Several relevant advances have been introduced. In the attempt to improve the prediction of clinical behaviour of solitary fibrous tumour, a risk assessment scheme has been implemented. NTRK-rearranged soft tissue tumours are now listed as an "emerging entity" also in consideration of the recent therapeutic developments in terms of NTRK inhibition. This decision has been source of a passionate debate regarding the definition of "tumour entity" as well as the consequences of a "pathology agnostic" approach to precision oncology. In consideration of their distinct clinicopathologic features, undifferentiated round cell sarcomas are now kept separate from Ewing sarcoma and subclassified, according to the underlying gene rearrangements, into three main subgroups (CIC, BCLR and not ETS fused sarcomas) Importantly, In order to avoid potential confusion, tumour entities such as gastrointestinal stroma tumours are addressed homogenously across the different WHO fascicles. Pathologic diagnosis represents the integration of morphologic, immunohistochemical and molecular characteristics and is a key element of clinical decision making. The WHO classification is as a key instrument to promote multidisciplinarity, stimulating pathologists, geneticists and clinicians to join efforts aimed to translate novel pathologic findings into more effective treatments.

Keywords: WHO classification; molecular genetics; morphology; new entity; soft tissue sarcoma.

Figure 1A.

Atypical spindle cell lipomatous tumor. The tumor is composed of mildly atypical, hyperchromatic, spindle cells, and adipocytic cells set in a myxocollagenous stroma. A bivacuolate lipoblast is seen.

Figure 1B.

Atypical pleomorphic lipomatous tumor. The presence of multivacuolated lipoblasts is accepted.

Figure 1C.

Myxoid pleomorphic liposarcoma. Neoplastic cells are set in a myxoid stroma with plexiform vascular pattern. Rare pleomorphic lipoblasts can be observed.

Figure 2A.

Angiofibroma of soft tissue. A prominent vascular network composed of thin walled branching vessels represents one of the main features of this entity. The neoplastic spindle cells show inconspicuous palely eosinophilic cytoplasm.

Figure 2B.

EWSR1-SMAD3 fibroblastic tumour. Alternation of hyalinised hypocellular areas and more cellular areas composed of intersecting fascicles of monomorphic spindle cells is most often observed.

Figure 2C.

Superficial CD34-positive fibroblastic tumour. Striking cytologic atypia in absence of mitotic figures and necrosis is often present.

Figure 3.

Anastomosing haemangioma. Anastomosing capillary-sized vessels are lined by hobnail endothelial cells in absence of significant nuclear atypia.

Figure 4.

Intraosseous rhabdomyosarcoma. In this example an epithelioid atypical neoplastic cell population predominates.

Figure 5A.

SDH-deficient GIST. Most cases are predominantly composed of epithelioid cell with pale eosinophilic cytoplasm.

Figure 5B.

SDH-deficient GIST. The neoplastic cells show loss of staining for SDHB. Endothelial cells and lymphocytes represent the internal positive control.

Figure 6.

Malignant melanotic nerve sheath tumour. Spindle cell set in a fibrous stroma with heavy melanin pigment deposition is seen.

Figure 7A.

Lipofibromatosis-like neural tumour. Spindle cells infiltrate adipose tissue resembling lipofibromatosis.

Figure 7B.

NTRK-positive tumor resembling peripheral nerve sheath tumour. A highly cellular spindle cell proliferation organised in fascicles is seen.

Figure 8A.

CIC-rearranged sarcoma. Highly atypical undifferentiated neoplastic cells are organised in a diffuse pattern of growth.

Figure 8B.

BCOR-rearranged sarcoma. Neoplastic cell population tends to assume a spindle morphology.

Figure 8C.

NFATC2-rearramged sarcoma. Striking epithelioid morphology characterises the majority of cases.

Figure 8D.

PATZ1-rearranged sarcoma. Neoplastic cells feature round to ovoid nuclei and are organised in a diffuse pattern of growth.