Benign Fibroblastic and Myofibroblastic Lesions

  • Cyril Fisher
Chapter
Part of the Atlas of Anatomic Pathology book series (AAP)

Abstract

A large group of relatively common soft tissue tumors are composed of a mixture of fibroblasts and myofibroblasts. Fibroblasts are slender cells with elongated tapered or serpiginous nuclei and little cytoplasm. Myofibroblasts tend to be plumper and have oval nuclei, each with a small distinct nucleolus, and variable amounts of amphophilic cytoplasm according to the functional state of the cells. Both have contractile and (stromal) secretory properties and can modulate into fibroblasts. Cell margins are poorly defined and tend to blend into adjacent collagen. Nuclear pleomorphism sometimes is a feature in both reactive and neoplastic conditions.

A large group of relatively common soft tissue tumors are composed of a mixture of fibroblasts and myofibroblasts. Fibroblasts are slender cells with elongated tapered or serpiginous nuclei and little cytoplasm. Myofibroblasts tend to be plumper and have oval nuclei, each with a small distinct nucleolus, and variable amounts of amphophilic cytoplasm according to the functional state of the cells. Both have contractile and (stromal) secretory properties and can modulate into fibroblasts. Cell margins are poorly defined and tend to blend into adjacent collagen. Nuclear pleomorphism sometimes is a feature in both reactive and neoplastic conditions. Proliferations of fibroblasts and myofibroblasts may be sparsely or highly cellular, with variable proportions of collagenous or elastic tissue and inflammatory cells of all types. They occur in all locations, and in some, the component elements—and therefore the microscopic appearances—change as the lesion ages. Cellular fibroblastic and myofibroblastic lesions with mitotic activity and sometimes nuclear pleomorphism may be mistaken for sarcomas, but large nucleoli, atypical mitoses, and tumor necrosis usually are absent. Immunohistochemical analysis is of limited value, and diagnosis depends on attention to subtle morphologic features; however, some entities cannot be identified by microscopy alone, and careful clinicopathologic correlation is required. For example, reactive conditions may appear and grow very quickly but tend to stop after reaching a relatively small size, which usually does not exceed 5 cm in diameter. Benign fibroblastic–myofibroblastic lesions are considered in this chapter, and neoplasms defined in the World Health Organization consensus classification as intermediate or malignant are presented in Chap. 4.

Sclerosing fibroinflammatory (idiopathic fibrosclerotic) lesions are a group of disorders that may arise in several anatomic locations, and the group is characterized by myofibroblastic spindle cells, acute and chronic inflammation, and fibrosis, the relative proportions of which vary with the duration of the disease. Many of the disorders have an increased number and ratio of IgG4-secreting plasma cells and are associated with hyper-IgG4 disease, which includes raised serum IgG4 levels. The group includes autoimmune pancreatitis, retroperitoneal fibrosis, orbital pseudotumor, chronic sclerosing sialadenitis, sclerosing cholangitis, Riedel thyroiditis, and some examples of sclerosing mesenteritis. Many of the lesions are infiltrative into adjacent normal tissues.
Fig. 3.1

Keloid scar. The dermis contains a variable cellular lesion with numerous randomly dispersed collagen fibers. Such lesions arise at sites of dermal injury in predisposed individuals. Unlike in nonkeloidal cellular scars, the lesion extends laterally beyond the original wound

Fig. 3.2

Keloid scar. Thick eosinophilic collagen fibers are a characteristic feature

Fig. 3.3

Calcifying (juvenile) aponeurotic fibroma. Irregular foci of amorphous calcification are seen within the fibrous tissue. Focal chondroid formation or ossification may occur. There also are cords of spindled or rounded cells and multinucleated giant cells. The tumor infiltrates fat and skeletal muscle and usually is found in the hands or feet

Fig. 3.4

Calcifying fibrous tumor. Discrete calcifications are scattered within hypocellular fibrous stroma. Lymphoid aggregates sometimes are present. This is a circumscribed lesion that arises in subcutaneous or deep soft tissue and also in the thorax or abdomen, where it may reach a large size

Fig. 3.5

Desmoplastic fibroblastoma. Although first described under this name, this lesion also has been termed collagenous fibroma. It is a circumscribed, very sparsely cellular tumor predominantly composed of collagen bundles. Typically, it occurs in adult males in the subcutis or deep soft tissue, mainly of the upper limbs or trunk

Fig. 3.6

Desmoplastic fibroblastoma. The lesional cells are spindled or stellate myofibroblasts without atypical features. They are immunoreactive for smooth muscle actin but not for CD34. Various translocations have been described, including t(2;11)(q31;q12), which also is found in fibroma of tendon sheath

Fig. 3.7

Elastofibroma. Typically arising beneath the tip of the scapula, this is an ill-defined, infiltrative subcutaneous lesion characterized by numerous thickened and fragmented eosinophilic elastic fibers in a fibrous stroma with sparse spindle cells

Fig. 3.8

Elastofibroma. An elastic van Gieson stain highlights the fibers and clearly demonstrates the bead-like fragments

Fig. 3.9

Fibroma of the tendon sheath. This is a circumscribed lesion mainly involving digits that may be multinodular. Peripheral slit-like blood vessels are present, and a hypocellular area is seen adjacent to a more cellular focus

Fig. 3.10

Fibroma of the tendon sheath. Stellate and spindle cells are sparsely distributed in a collagenous stroma

Fig. 3.11

Fibroma of the tendon sheath. The more cellular area resembles nodular fasciitis and is seen more typically in earlier stages. A t(2;11)(q31-32;q12) rearrangement has been described similar to that seen in desmoplastic fibroblastoma

Fig. 3.12

Fibromatosis colli. Cellular fibrous tissue infiltrates fibers of the sternomastoid muscle. This image shows a late stage of the ­disease with hypocellular fibrosis. The tumor occurs in newborns, sometimes follows trauma, is self-limiting, and often regresses. Immunohistochemistry for β-catenin is negative in nuclei

Fig. 3.13

Gingival fibromatosis. Sparsely cellular fibrosis tissue with mild inflammation is present beneath irregularly hyperplastic epithelium. Small foci of calcification may be seen. This forms a mass that grows over teeth and gums. It may be sporadic but also familial, most often with autosomal dominant inheritance. The appearance resembles that in gingival hyperplasia arising in pregnancy or in phenytoin users

Fig. 3.14

Infantile digital fibromatosis. This is a poorly circumscribed dermal and subcutaneous fibrosing lesion composed of bundles of bland myofibroblast-like cells. It arises mostly on the lateral or extensor aspects of the digits (fingers more often than toes) in infants up to 2 years old and may be multiple. The lesions may recur but usually regress, sometimes with scarring

Fig. 3.15

Infantile digital fibromatosis. Rounded, markedly eosinophilic cytoplasmic inclusions adjacent to nuclei in occasional cells are the hallmark of this disease. The inclusions are thought to represent aggregates of actin filaments and are best demonstrated by a Masson trichrome stain. The term inclusion body fibromatosis has been used. Similar inclusions may be seen in other lesions, such as fibroadenoma and fibromatosis in the breast

Fig. 3.16

Juvenile hyaline fibromatosis. Groups of uniform ovoid cells are dispersed evenly in characteristically heavily eosinophilic, homogeneous stroma. This is an autosomal recessive disease that may display cutaneous, soft tissue, and bony lesions. The findings overlap those of infantile systemic hyalinosis

Fig. 3.17

Nuchal and nuchal-type fibroma. Randomly oriented thick collagen bundles with scanty CD34-positive fibroblasts infiltrate the dermis and subcutaneous tissue, often entrapping nerves and adnexa. There is a cracking artifact within the collagen bundles. About half the cases arise in patients with diabetes mellitus. The lesions of Gardner and Gardner-associated fibroma are histologically identical to those of nuchal fibroma and nuchal-type fibroma (which occur in nonnuchal locations)

Fig. 3.18

Reactive nodular fibrous pseudotumor. Spindled or stellate fibroblasts are scattered in a densely collagenous stroma. This lesion arises in the mesentery or on the intestinal surface as solitary or multiple nodules; it occurs mainly in males and may follow abdominal surgery. Immunohistochemical analysis is negative for β-catenin, unlike in many intra-abdominal fibromatoses; negative for CD34, helping to exclude solitary fibrous tumor; and negative for CD117, aiding in its distinction from gastrointestinal stromal tumor

Fig. 3.19

Retroperitoneal fibrosis. In the early stages, cellular fibrous tissue may be seen containing lymphoid aggregates (mixed B and T lymphocytes), clusters of plasma cells, and sometimes eosinophils. The spindle cells are immunoreactive for smooth muscle actin, and nuclei are negative for β-catenin

Fig. 3.20

Retroperitoneal fibrosis. The inflammatory component includes neutrophil and eosinophil polymorphs and a predominance of plasma cells

Fig. 3.21

Retroperitoneal fibrosis. Later stages show paucicellular sclerosis with a sprinkling of inflammatory cells, including eosinophils

Fig. 3.22

Retroperitoneal fibrosis. Increased numbers of IgG4-secreting plasma cells may be a feature, as demonstrated by immunohistochemical technique for IgG4

Fig. 3.23

Sclerosing mesenteritis. A firm, tumor-like fibrosing mass infiltrates the root of the small bowel mesentery. There are bright yellow areas of fat necrosis

Fig. 3.24

Sclerosing mesenteritis. Variably cellular fibrous tissue infiltrates fat, which shows features of fat necrosis, including coalescence of adipocytes resulting in large irregular lipid spaces. Calcification sometimes is seen

Fig. 3.25

Circumscribed storiform collagenoma (sclerotic fibroma). Associated with Cowden syndrome, this is a dermal lesion that displays thickened collagenous laminae with occasional CD34-positive fibroblasts

Fig. 3.26

Circumscribed storiform collagenoma (sclerotic fibroma). The collagen is focally hyalinized. Stromal mucinous material is seen between the fibrous layers

Fig. 3.27

Nasopharyngeal angiofibroma. This occurs in adolescent males in nasal and paranasal areas. Lesional cells are dispersed in fibrous stroma that contain variably sized thin-walled blood vessels with an incomplete smooth muscle layer

Fig. 3.28

Nasopharyngeal angiofibroma. Plump stellate and spindle cells show mild nuclear atypia

Fig. 3.29

Nasopharyngeal angiofibroma. The lesion cells display nuclear immunoreactivity for β-catenin. Some examples are associated with familial adenomatous polyposis

Fig. 3.30

Dermatomyofibroma. This is a benign plaque-like lesion arising in the skin of the upper part of the body—head and neck, shoulder, axilla, or trunk. It forms a band in the reticular dermis and occasionally extends more deeply

Fig. 3.31

Dermatomyofibroma. Cellular fascicles of uniform myofibroblastic cells are arranged mostly parallel to the epidermal surface. The lesional cells are immunoreactive for smooth muscle actin and lack desmin and h-caldesmon

Fig. 3.32

Nodular fasciitis. This lesion is subcutaneous and abuts the deep fasciae. Sometimes it arises from the deep aspect of the fasciae and is intramuscular. There typically is a very short clinical history of a rapidly growing lesion at some time at the site of minor trauma, which reaches a diameter of up to 5 cm and then stops growing. The image shows how it is typically circumscribed. Recently, a chromosomal rearrangement t(17;22)(p13;q13.1) with formation of fusion gene USP6-MYH9 was identified in examples of nodular fasciitis

Fig. 3.33

Nodular fasciitis. Uniform myofibroblasts are arranged in a loose storiform pattern, with stromal microcysts that contain lymphocytes and extravasated red blood cells

Fig. 3.34

Nodular fasciitis. Older lesions have focal fibrosis and contain occasional giant cells. The different histologic stages may coexist in the same lesion, imparting a zoning phenomenon that is a diagnostic clue

Fig. 3.35

Nodular fasciitis. The cells have a myofibroblastic immunophenotype, with smooth muscle actin positivity in a linear subplasmalemmal distribution. Calponin and occasionally desmin also test positive, whereas h-caldesmon, CD34, and S-100 protein test negative

Fig. 3.36

Cranial fasciitis of childhood. Loosely arranged fibroblasts without atypia are dispersed in a fibromyxoid stroma

Fig. 3.37

Ossifying fasciitis. Metaplastic bone formation is an unusual feature in some examples of nodular fasciitis. The typical fasciitis-like stroma and absence of nuclear atypia help exclude the diagnosis of extraosseous osteosarcoma

Fig. 3.38

Intravascular fasciitis. Nodular fasciitis may occur within veins or, less commonly, within arteries, which become distended. The lesional tissue may infiltrate through the vessel wall and involve adjacent soft tissue, or it may grow within the vessels and form a plexiform lesion. This type of fasciitis may recur if not completely excised

Fig. 3.39

Proliferative fasciitis. This is similar to nodular fasciitis, with the addition of variable numbers of ganglion-like cells with occasionally prominent nucleoli arranged in clusters. It may occur in adults or children

Fig. 3.40

Proliferative myositis. A fasciitis-like fibroblastic proliferation in edematous inflamed stroma extends between and separates skeletal muscle fibers in a checkerboard pattern. This is seen in the body of large skeletal muscles as a rapidly appearing but benign self-limiting mass that sometimes follows trauma. It arises mostly in adults but also may occur in childhood

Fig. 3.41

Proliferative myositis. This lesion is characterized by large polygonal ganglion-like cells that have basophilic cytoplasm and prominent nucleoli; they also are similar to those found in proliferative fasciitis. Although some have, mitoses are not a feature (although they may be seen in the fasciitis-like stroma). The cells lack lineage-specific immunohistochemical markers and are considered modified fibroblasts

Fig. 3.42

Ischemic fasciitis. This lesion (also termed atypical decubital fibroplasia) appears at pressure areas in immobilized patients but also in otherwise healthy individuals. There is infarction of fat with adjacent capillary proliferation and scattered spindle or stellate cells with enlarged hyperchromatic nuclei. The overlying skin is intact, unlike in the decubitus ulcer

Fig. 3.43

Fibrous hamartoma of infancy. The three components of this lesion, found in variable proportions, are differentiated adipose tissue, moderately cellular fibrous bands, and more cellular aggregates of short spindle or ovoid cells with scanty cytoplasm. This is an infiltrative lesion that occurs predominantly in childhood

Fig. 3.44

Myofibroma. Primarily found in infants, this lesion is composed of myofibroblasts that are actin positive but lack desmin and h-caldesmon. A central focus of smaller cells with a hemangiopericytic pattern merges into focally myxoid nodules of loose myofibroblasts. Myofibromas may be solitary or multiple (myofibromatosis). Solitary lesions occur in skin, subcutis, or bone and may undergo regression; multiple lesions may involve viscera and may progress

Fig. 3.45

Myofibroma. The lesional cells are tapered with uniform ovoid nuclei. The cellular areas have a whorled pattern. In the myxoid areas, the appearance resembles nodular fasciitis

Fig. 3.46

Myofibroma. Some lesions contain multinucleated giant cells

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Authors and Affiliations

  • Cyril Fisher
    • 1
  1. 1.Department of HistopathologyThe Royal Marsden HospitalLondonUK

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