2020-09-12 22:16  阅读(1385)  评论(0)  分类:软组织

The 2020 WHO Classification What’s New in Soft Tissue Tumor Pathology?

The new fifth edition of the World Health Organization (WHO) Classification of Tumors of Soft Tissue and Bone was published in early 2020, 7 years following publication of the fourth edition. The revisions reflect a consensus among an international expert editorial board composed of soft tissue and bone pathologists, geneticists, a medical oncologist, surgeon, and radiologist. Updates to the classification reflect extensive new genetic data, prompting expansion and reorganization of several categories. The soft tissue tumor chapter in particular includes the addition of recently described tumor types; in some cases, increasing outcome data and comparative genetic studies argued for splitting into separate tumor types or changes in nomenclature and managerial categories. Despite the expanding contribution of genetics to our understanding of the molecular pathogenetic basis for soft tissue tumors, the new classification emphasizes the continued central diagnostic importance of morphology.


In addition to a discussion of “new” soft tissue tumor entities, this review will highlight updated prognostic information for familiar tumor types, such as dedifferentiated liposarcoma (DDLPS) and solitary fibrous tumor (SFT). Finally, we will include a focused discussion of the dizzying array of recently described genetic alterations in soft tissue tumors. The past decade has seen a plethora of novel gene fusions in rare soft tissue tumor types; a comprehensive and in depth examination of these alterations is beyond the scope of this review. Instead, we will focus on selected genetic alterations with practical diagnostic relevance. An example is the undifferentiated small round cell sarcoma chapter; detection of novel gene fusions has led to subclassification of the former wastebasket of “Ewing-like” sarcomas into new categories with distinct presentations, clinical behavior, and morphologic and immunohistochemical (IHC) features. Additional practical examples include the identification of recurrent genetic alterations in SFT and malignant peripheral nerve sheath tumor (MPNST), leading to the introduction of highly sensitive and specific IHC markers, which are now in routine use in surgical pathology.




The fifth edition of the WHO Classification features “new” soft tissue tumor types that were not found in the fourth edition (Table 1). As was the case for prior editions, tumors are organized by line of differentiation, such as adipocytic, fibroblastic/myofibroblastic, vascular, and smooth muscle neoplasms. Several emerging tumor types, including the morphologically heterogenous NTRK-rearranged spindle cell neoplasms, are contained within the section on tumors of uncertain differentiation. Epithelioid hemangioendothelioma (EHE) with YAP1-TFE3 fusion will be discussed in the novel genetic changes section below. Also discussed here are “new” tumor types within the undifferentiated small round cell sarcoma chapter.



Atypical Spindle Cell/Pleomorphic Lipomatous Tumor


Atypical spindle cell/pleomorphic lipomatous tumor is a benign adipocytic neoplasm, distinct from atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDLPS) and spindle cell/pleomorphic lipoma, although it shares some histologic features with both of these other tumor types.


The largest series of atypical spindle cell lipomatous tumors reported a male-to-female ratio of 3:2 and a median age of 54 years.


Approximately two thirds of tumors occur in the limbs and limb girdles, with a predilection for the hands and feet, and an approximately equal distribution between superficial and deep sites.


Less commonly involved are the head and neck, genitals, and trunk, with very rare retroperitoneal involvement.


By contrast, ALT/WDLPS occurs equally commonly in the retroperitoneum and limbs, less commonly in the spermatic cord, mediastinum, and head and neck.


Spindle cell/pleomorphic lipomas characteristically occur in the posterior aspect of the neck or upper back, less often the face, orbital region, and oral cavity, with few reports of deepseated lesions in a broader anatomic distribution.


Histologically, atypical spindle cell lipomatous tumor shows infiltrative margins and demonstrates a range of appearances, with varying proportions of spindle cells, adipocytes, and lipoblasts, including hyperchromatic and sometimes pleomorphic cells (atypical pleomorphic lipomatous tumor).


The histology may be viewed as a spectrum flanked by 2 morphologic extremes: a paucicellular pattern with bland spindle cells, minimal nuclear atypia, adipocytes, and abundant (often myxoid) matrix, and a hypercellular pattern at the other end of the spectrum with mild-to-moderate cytologic atypia, easily identifiable lipoblasts, and less abundant matrix (Fig. 1).


The differential diagnosis includes spindle cell/pleomorphic lipoma and ALT/WDLPS.


Spindle cell/pleomorphic lipomas have a different anatomic distribution, are well circumscribed, and contain characteristic brightly eosinophilic, coarse “ropy” collagen fibers.


ALT/WDLPS rarely involves the subcutaneous compartment but shows similar histologic appearances as atypical spindle cell lipomatous tumors, although a prominent spindle cell component is uncommon; IHC or fluorescence in situ hybridization (FISH) can be helpful to make this distinction.


By IHC, the tumor cells in atypical spindle cell lipomatous tumors show variable expression of CD34, S100 protein, and desmin, whereas MDM2 and CDK4 are generally negative (rarely, weak or focal staining for the latter markers may be seen).


Spindle cell lipomas show diffuse CD34 expression, but by contrast are usually negative for desmin and S100 protein.


Notably, loss of nuclear RB1 expression is observed in 50% to 70% of atypical spindle cell lipomatous tumors, in keeping with chromosome 13q14 deletion, including the RB1 locus, which is also a consistent finding in spindle cell/pleomorphic lipomas.


MDM2 amplification is absent in atypical spindle cell lipomatous tumor, in distinction from ALT/WDLPS.


Importantly, atypical spindle cell/pleomorphic lipomatous tumors pursue a benign clinical course with a low rate of nondestructive local recurrence (10% to 15%), lower than the risk for ALT/WDLPS; in contrast to ALT/WDLPS, atypical spindle cell lipomatous tumor has no potential to dedifferentiate.



FIGURE 1. Atypical spindle cell lipomatous tumor. A, This tumor shows a variably collagenous to myxoid stroma and is dominated by spindle cells, in areas admixed with adipocytes. B, The tumor cells are relatively uniform, whereas the adipocytes show marked variation in size, including occasional lipoblasts. C, This tumor contains abundant myxoid stroma with prominent adipocytes and scattered spindle cells with hyperchromatic nuclei. D, This example shows dense collagenous stroma, notably pleomorphic and multinucleated cells, and occasional lipoblasts.