Soft Tissue Tumors — An Ultrastructural Perspective
Bruce Mackay, University of Texas M.D. Anderson Cancer Center

An electron microscopist studying a soft tissue tumor for diagnostic purposes will almost certainly review its light microscopic appearance, at least in semi-thin sections and ideally also in the routine paraffin sections. Correlation between the ultrastructural and conventional preparations should be a part of every case in which the electron microscope (EM) is used. This bridging of the two levels of microscopy allows the pathologist to comprehend and interpret the fine structure within the context of the broader view of tissue architecture, and inclusion of immunohistochemical data further illuminates the morphologic findings. The pathologist who examines many soft tissue neoplasms with the electron microscope in time develops a unique perspective of this broad and complex group of tumors. In part, this stems from the small tissue sample —commonly a single section less than one millimeter across cut from a single EM tissue block, but even more it builds from constantly scrutinizing and evaluating the interior of the neoplastic cells. The patterns that the cells are forming may not be obvious or even evident with the electron microscope, and the composition of the intercellular stroma is not as a rule of particular significance. While the degree of apposition of neighboring cells and the presence of specializations of the cell surface are clearly seen and the shapes of the cells and nuclei can be appreciated, albeit within the single plane of an ultrathin section, it is the contents of the cytoplasm of soft tissue tumor cells that dominate the perception of the electron microscopist and, after many of these tumors have been studied, come to the mind’s eye as being characteristic of particular tumor types.

 Glomus Tumor

 Leiomyosarcoma

There is nothing very specific about the fine structure of a mesenchymal cell other than the absence of obvious epithelial features like mature desmosomes or uniform arrays of microvilli. Ultrastructural features may not serve to distinguish between a poorly differentiated sarcoma and carcinoma, and the cells of even a benign soft tissue tumor are often unremarkable. A differentiated fibroblast is sufficiently distinctive to be recognizable with the electron microscope, largely because of the abundant, well-developed rough endoplasmic reticulum. Collagen fibrils can be present inside the cell, or the cisternae may contain amorphous electron dense material, but these are occasional findings. To the electron microscopist, the spectrum of neoplasms of flbroblast-like cells is extensive, and within it there is considerable variability in the structure of the component cells, reflecting the structural pliability and relative lack of specificity of the fibroblast. The changes may reflect loss of differentiation, in which the distinctive characteristics of the mature fibroblast are progressively lost, and a comparable appearance is seen in certain dedifferentiated sarcomas. The changes can also be a manifestation of the overlap in fine structure that occurs between the fibroblast and other soft tissue cells, as in the development of smooth muscle myofilaments in the peripheral cytoplasm of myofibroblasts, or an accumulation of cytoplasmic lipid droplets, or even an affinity for erythrocytes which, like intracytoplasmic collagen fibrils, demonstrates the phagocytic ability of neoplastic fibroblasts. Ultrastructural observations on malignant fibrous histiocytomas offer support for their falling within the spectrum of fibroblastic neoplasms.

Cytoplasmic filaments are a frequent constituent of soft tissue tumor cells and they are frequently non-specific in appearance and arrangement. Myofilaments are less common and more specific though they are encountered in a number of different tumors. Keratin filaments are seen less often than immunohistochemical results might indicate.

A hallmark of neural differentiation in soft tissue tumors is the presence of cell processes. They are seen to good advantage in benign schwann cell and perineurial cell neoplasms but are only seen in the better differentiated neurosarcomas. They are also found in some spindle cell melanomas, and in a few examples of Ewing’s tumor that merge with peripheral neuroectodermal tumors.

The cellular morphology of a number of soft tissue tumors of disputed histogenesis has been clarified by ultrastructural study even when it has failed to elucidate the type of the proliferating cell. As examples, the nature of the small cell desmoplastic peritoneal tumor remains uncertain. Synovial sarcomas do not display a close resemblance to true synovial tissue. The presence of many compartments in a granular cell tumor is at best only suggestive of schwannian derivation. Distinctive crystals in alveolar soft part sarcoma cells do not reveal the cell of origin.

Much of the information on the ultrastructure of soft tissue tumor cells can be of diagnostic value. The findings are to varying degrees useful in identifying the cell type in benign neoplasms and sarcomas when it is uncertain from light microscopy, and electron microscopy can determine when sarcomas truly lack differentiating structural features and are made up of structurally primitive cells.

References: