Soft Tissues PDF

41 Soft Tissues John R. Goldblum CHAPTER...

41 Soft Tissues John R. Goldblum CHAPTER CONTENTS Normal anatomy, 1810 Tumors of adipose tissue, 1849 Infections and hematomas, 1811 Tumors and tumorlike conditions of blood and lymph Tumors, 1811 vessels, 1858 Classification, 1811 Tumors of smooth muscle and modified smooth Clinical features, 1811 muscles, 1865 Diagnosis and special techniques, 1811 Tumors of striated muscle, 1868 Grading and staging, 1812 Osseous or cartilaginous tumors, 1873 Prognosis, 1812 Tumors of extragonadal germ cells, 1874 Therapy, 1813 Tumors of neural tissue (other than peripheral Pathogenesis, 1814 nerves), 1875 Tumors and tumorlike conditions of fibroblasts and Tumors of hematopoietic tissue, 1876 myofibroblasts, 1814 Miscellaneous tumors and tumors of uncertain cell Fibrohistiocytic tumors, 1829 type1876 Tumors of synovial tissues, 1836 Metastatic tumors, 1889 Tumors and tumorlike conditions of peripheral Other tumorlike conditions, 1889 nerves, 1838 (especially perirenal region).3 Brown fat, whose main function is Normal Anatomy heat production, is much more conspicuous in infants and children. Soft tissue is loosely defined as the complex of nonepithelial White fat consists of round or oval cells having most of the cytoplasm extraskeletal structures of the body exclusive of the supportive tissue occupied by a single large lipid droplet that pushes the crescent-shaped of the various organs and the hematopoietic/lymphoid tissue. It is nucleus to the periphery. Brown fat cells are smaller, with an acidophilic composed of fibrous (connective) tissue, adipose tissue, skeletal multivacuolated cytoplasm and a centrally located nucleus showing muscle, blood and lymph vessels, and peripheral nervous system. fine indentations; mitochondria are numerous at the ultrastructural Fibrous tissue consists primarily of fibroblasts and an extracellular level. matrix that contains fibrillary structures (collagen and elastin) and Skeletal muscle is mainly derived from within myotomes through nonfibrillary extracellular matrix (“ground substance”). Fibrous tissue the formation of myoblasts and eventually of myotubes (muscle is classified according to its texture into loose (most locations) and fibers). The most distinguishing feature of these fibers is the presence dense (tendons, aponeuroses, and ligaments). Fibroblasts are respon- of myofibrils, which are composed of two types of microfilament: sible for the production of the various extracellular materials, including thin (made of actin) and thick (made of myosin). The periodic the many types of collagen. Their shape varies from spindle (especially arrangement and interdigitation of thin and thick filaments results when stretched along bundles of collagen fibers) to stellate (in myxoid in the cross-banding seen at the light microscopic level. The I areas). Immunohistochemically, they stain for actin, including smooth (isotropic) band is made only of thin filaments, the adjacent A muscle actin (SMA), but are negative for h-caldesmon and often (anisotropic) band is a zone of overlapping thin and thick filaments, desmin as well. Fibrocytes represent the quiescent stage of fibroblasts. and the H band is made up only of thick myofilaments. The I band Myofibroblasts are modified fibroblasts that show features intermediate is divided in its center by the Z line or disc, which is thought to between fibroblasts and smooth muscle cells.1,2 serve as an attachment site for the sarcomere, the repeating individual Adipose tissue is divided into two major types: white fat, mainly unit of the muscle fiber. located in the subcutaneous tissue, mediastinum, abdomen, and Vessels are divided into blood vessels and lymph vessels. Blood retroperitoneum; and brown fat, which is concentrated in the inter- vessels are further subdivided into arterial and venous compartments scapular region, neck, mediastinum, axillae, and retroperitoneum joined by a network of capillaries. Blood vessels have two major 1810  Tumors 41 Abstract Soft tissue tumors (and tumor-like lesions) are some of the most difficult diagnostic issues faced by practicing pathologists. The wide array of reactive and neoplastic soft tissue lesions can be overwhelm- ing, and this chapter provides a comprehensive discussion of these entities, including some of the more recently described soft tissue tumors and their molecular genetic alterations. A thorough discussion of useful ancillary diagnostic techniques is also provided. Keywords fat, fibroma, fibroblast, solitary fibrous tumor, fibrosarcoma, neuroma, schwannoma, perineurioma, peripheral nerve sheath, lipoma, hibernoma, liposarcoma, hemangioma, glomus, hemangioendothelioma, smooth muscle tumors, striated muscle tumors 1810.e1  Tumors 41 cell types: endothelial cells (located toward the lumen) and a closely blastomycosis, coccidioidomycosis, sporotrichosis, cryptococcosis, and related group of cells including pericytes, smooth muscle cells, and dirofilariasis. A proper search for microorganisms should be made glomus cells (located toward the outside). Ultrastructurally, endo- with appropriate special stains and cultures. thelial cells exhibit numerous pinocytotic vesicles, cytoplasmic Hematoma, if deep and encysted, can simulate a sarcoma both microfilaments, specialized cell junctions, microvilli, continuous clinically and radiographically. They occur most commonly in and basal lamina, and—most important—the Weibel–Palade body, a around the tensor fasciae latae and have been variously referred to membrane-bound organelle thought to be specific to this cell type as ancient hematoma, calcifying myonecrosis, chronic expanding and shown to contain the von Willebrand factor (factor VIII-related hematoma, and post-traumatic cyst of soft tissues.11,12 antigen).4 Immunohistochemically, endothelial cells express a number of antigens including factor VIII-related antigen (FVIII-RA), CD34, Tumors CD31, FLI-1, and ERG.5–7 CD31 is both highly sensitive and specific, although histiocytes and plasma cells are also positive. FVIII-RA is Classification also very specific (the only other positive cell type being the mega- Soft tissue tumors constitute a large and heterogeneous group of karyocyte), but the labile nature of this antigen and its tendency to neoplasms. This chapter deals primarily with tumors located in the diffuse out in the tissues limit its utility. FLI-1 (a nuclear transcription somatic soft tissues; it excludes those arising from the soft tissues factor involved in the pathogenesis of Ewing sarcoma/primitive of the mediastinum, retroperitoneum, and visceral organs and those neuroectodermal tumor [PNET]) is also a sensitive vascular marker. primarily involving the dermis, such as Kaposi sarcoma and derma- Perhaps most useful is ERG, given its strong nuclear positivity in tofibrosarcoma protuberans (DFSP). virtually all benign, intermediate, and malignant vascular tumors, Traditionally, soft tissue sarcomas have been classified according although it too is not completely specific. to a histogenetic concept (e.g., fibrosarcoma as a tumor arising from The cells of the pericyte–smooth muscle–glomus family are fibroblasts, osteosarcoma as a tumor arising from osteoblasts). characterized ultrastructurally by cytoplasmic microfilaments exhibit- However, it seems clear that most if not all sarcomas arise from ing focal condensations, numerous pinocytotic vesicles, and a thick primitive multipotential mesenchymal cells, which in the course of continuous basal lamina. Immunohistochemically, they show neoplastic transformation undergo differentiation along one or more reactivity for actin and myosin; positivity for desmin is largely lines.13 The acceptance of this alternative scheme does not require restricted to smooth muscle cells. a change in terminology: a liposarcoma remains as such but is now Lymph vessels are lined by endothelial cells exhibiting a much viewed not as a tumor arising from a lipoblast but as a tumor weaker staining for FVIII-RA than endothelial cells from blood vessels. exhibiting lipoblastic differentiation. They also stain for Lyve-1 and podoplanin (D2-40).8 Peripheral nerves are formed by axons, Schwann cells, perineurial cells, and fibroblasts. Most of the fibroblasts are located in the Clinical Features epineurium, which is the outer sheath of fully developed nerves. Each A definite relationship exists between soft tissue tumor type and the nerve fascicle is surrounded by the perineurium, a structure continuous age of presentation.14 For instance, embryonal rhabdomyosarcoma with the pia arachnoid of the central nervous system (CNS); unlike is typically a tumor of infants and children, synovial sarcoma mainly Schwann cells, perineurial cells are immunoreactive for epithelial affects adolescents and young adults, and liposarcomas and undif- membrane antigen (EMA) and GLUT-1 and negative for S-100 ferentiated pleomorphic sarcomas (UPSs) are usually seen in protein.9 Schwann cells look somewhat similar to fibroblasts at the middle-aged and elderly patients. Most soft tissue sarcomas are light microscopic level but are easily distinguished from them solitary; synchronous or metachronous multiple sarcomas are immunohistochemically because of their strong immunoreactivity exceedingly rare.15 for S-100 protein and ultrastructurally by an intimate relationship to axons (with the formation of mesoaxons) and the presence of a continuous basal lamina that coats the surface of the cell facing the Diagnosis and Special Techniques endoneurium. For any large soft tissue tumor in which the possibility of malignancy exists, the proper initial diagnostic procedure is to obtain material through excisional or incisional biopsy, core needle biopsy, or per- Infections and Hematomas cutaneous fine-needle aspiration. The latter technique is being used Soft tissue involvement by infectious processes usually is the result with increasing frequency in the United States, with rates of accuracy of direct extension from cutaneous, visceral, or osseous foci or the equivalent to those obtainable with frozen section.16 Excisional or complication of trauma or surgery. Rarely, the process has a hema- incisional biopsy has the advantage of providing more tissue for togenous source. diagnosis but, given the risk of bleeding and infection, should be The severity of the inflammatory reaction and the type of tissue performed only when a definitive diagnosis cannot be made by less response observed pathologically depend on the type, dose, and invasive techniques. Importantly, site of biopsy or aspiration should virulence of the infecting organism, the resistance of the host tissues, be excised in continuity with the tumor at the time of definitive surgery. the presence or absence of necrotic tissue, hematoma, or foreign Performance of frozen sections is useful in determining the type body, and the anatomic features of the infected area. of neoplasm, the degree of malignancy, and the adequacy of surgical Clinical types of infectious processes such as hemolytic streptococ- margins, but margins are often best assessed grossly at the time cal gangrene and necrotizing fasciitis must be diagnosed by clinical the specimen comes to surgical pathology, often done most effectively appearance and bacteriologic study. Necrotizing fasciitis is accom- when the surgeon and pathologist examine the specimen panied by severe systemic toxicity and is usually caused by group A simultaneously. streptococci.10 All of the pyogenic and necrotizing infections result Light microscopic evaluation of hematoxylin–eosin-stained in acute inflammatory tissue reactions that are indistinguishable sections remains the standard technique for the initial diagnostic microscopically. Granulomatous inflammation of soft tissue can approach to these tumors and is sufficient in the majority of the be caused by tuberculosis, atypical mycobacteriosis, actinomycosis, cases. However, a significant percentage of cases require ancillary 1811 41 Soft Tissues diagnostic techniques including immunohistochemistry, molecular genetic methods, and rarely electron microscopy. Occasionally, Table 41.1 Differentiation score in sarcomas as component of FNCLCC histochemical stains may be used (e.g., PAS for assessing for intra- cytoplasmic crystals in alveolar soft part sarcoma), but many of DIFFERENTIATION these stains have been supplanted by other techniques. HISTOLOGIC TYPE SCORE The systematic use of cytogenetics has shown the existence of nonrandom chromosomal alterations (mainly translocations) in Atypical lipomatous tumor 1 association with many types of soft tissue tumor.17 The findings have validated the morphologic approach to classification of soft tissue Well-differentiated leiomyosarcoma 1 tumors, helped to refine the boundaries of some entities (such as Myxoid liposarcoma 2 broadening morphology and location of desmoplastic small cell tumor, merging of spindle cell lipoma with pleomorphic lipoma, Conventional leiomyosarcoma 2 and merging of round cell liposarcoma with myxoid liposarcoma), Conventional MPNST 2 and offered insight into the genesis of the tumors. Furthermore, the molecular alterations (gene fusions) that result from the chromosomal Myxofibrosarcoma 2 translocations can now be readily demonstrated in routine paraffin- embedded tissues by reverse transcription-polymerase chain reaction Myxoid chondrosarcoma 2 (RT-PCR) or fluorescence in situ hybridization (FISH). Such studies Conventional angiosarcoma 2 can be extremely helpful in the diagnosis of these tumors, especially in small biopsies, tumors with unusual morphology, or tumors in Round cell liposarcoma 3 unusual sites.18 A break-apart FISH probe for EWSR1 is particularly Pleomorphic liposarcoma 3 helpful since this gene is implicated in many different soft tissue tumor types, including Ewing sarcoma/PNET, angiomatoid fibrous Dedifferentiated liposarcoma 3 histiocytoma, extraskeletal myxoid chondrosarcoma, myxoid lipo- Rhabdomyosarcoma 3 sarcoma, clear cell sarcoma, and desmoplastic small cell tumor. Similarly, a break-apart FISH probe for FUS can aid in the diagnosis Pleomorphic leiomyosarcoma 3 of low-grade fibromyxoid sarcoma (LGFMS), myxoid liposarcoma, Poorly differentiated/epithelioid 3 and angiomatoid fibrous histiocytoma. FISH may be a particularly angiosarcoma useful technique when evaluating cytologic preparations. As in other fields of oncology, gene expression profiling has significantly con- Poorly differentiated MPNST 3 tributed to our understanding of the molecular underpinnings of Synovial sarcoma 3 many types of soft tissue tumors.19–21 The specific applications of these various methods are described under the respective tumor types. Extraskeletal osteosarcoma 3 Ewing family of tumors 3 Grading and Staging Mesenchymal chondrosarcoma 3 Some degree of microscopic grading of soft tissue tumors is already built into the conventional microscopic classification of these tumors. Clear cell sarcoma 3 For example, DFSP is by definition a low-grade neoplasm, whereas Epithelioid sarcoma 3 all alveolar rhabdomyosarcomas are high-grade tumors. In addition, several attempts have been made to establish general guidelines for Alveolar soft part sarcoma 3 the grading of soft tissue sarcomas independent of their histologic Undifferentiated pleomorphic sarcoma 3 type.22–24 The number of grades has varied including two (low grade and high grade), three (I, II, and III, or low grade, intermediate MPNST, malignant peripheral nerve sheath tumor. grade, and high grade), and four (I, II, III, and IV) grade systems. Data from Amin M, Edge S, Greene F, et al., eds. AJCC Cancer Staging The criteria used to grade sarcomas have included degree of cel- Manual. Vol. 8. New York: Springer; 2017. lularity, pleomorphism, mitotic activity, and necrosis, and these features have been found to be of definite prognostic value for both adult and pediatric soft tissue tumors. However, there are some limitations Prognosis to grading, including the inherently subjective nature of the evaluation, The prognosis of soft tissue tumors depends on a variety of parameters, limited sampling in biopsy material, and the confounding effect of many of which are interrelated. preoperative therapy.25 Despite these limitations, grading (within the 1. Tumor size. There is a definite relationship between tumor size various histotypes and whenever applicable) remains one of the most and outcome. This is true for practically all tumor types in which powerful and inexpensive ways of assessing prognosis in a soft tissue this parameter has been analyzed.27,28 sarcoma. The system devised by the French Federation of Cancer 2. Depth. Superficially located tumors (dermis and subcutaneous Centers Sarcoma Groups (also known as the FNCLCC grading system) tissue) have a much better prognosis than deep-seated ones is a three-grade system that is most widely used to grade sarcomas (intermuscular or intramuscular, retroperitoneal) of similar and is based on the evaluation of three separate parameters: tumor microscopic type.29,30 The difference is largely due to the fact that differentiation, mitotic rate, and extent of tumor necrosis.22,24 superficial lesions tend to be considerably smaller at the time of The most widely used staging system is that proposed by the excision and are generally more amenable to complete excision. American Joint Committee on Cancer (AJCC), which is largely based 3. Location. Tumors of the retroperitoneum do much worse than on the TNM system, in that it uses the size of the primary tumor microscopically similar lesions located in the extremities.28,31 Among (T), the status of lymph nodes (N), the presence of distant metastasis the latter, local recurrence has been found to be more frequent with (M), and the tumor’s histologic grade (G) (Tables 41.1–41.4).26 those of the upper extremity than those of the lower extremity.30 1812  Tumors 41 Table 41.2 Details of FNCLCC grading system Table 41.3 Definitions of American Joint Committee on Cancer TNM* PARAMETER DEFINITION Definition of Primary Tumor (T) Tumor Score 1: Closely resembles normal T Category T Criteria differentiation adult mesenchymal tissue; potentially TX Primary tumor cannot be assessed difficult to distinguish from counterpart T0 No evidence of primary tumor benign tumor T1 Tumor 5 cm or less in greatest dimension Score 2: Sarcomas for which histologic type is T2 Tumor more than 5 cm and less than or equal certain (e.g., myxoid to 10 cm in greatest dimension liposarcoma) Score 3: Embryonal and T3 Tumor more than 10 cm and less than or equal undifferentiated to 15 cm in greatest dimension sarcoma, synovial T4 Tumor more than 15 cm in greatest dimension sarcoma, sarcomas of uncertain type Definition of Regional Lymph Node (N) Mitotic count Score 1: 0–9/10 HPF N Category N Criteria Score 2: 10–19/10 HPF N0 No regional lymph node metastasis or unknown Score 3: >19/10 HPF lymph node status Tumor necrosis Score 0: No necrosis N1 Regional lymph node metastasis Score 1: