Some patients provide a history of a rapidly growing mass present for only 1 to 2 weeks. About half of patients report associated soreness, tenderness, or slight pain. Numbness, paresthesia, or shooting pain is rare and develops only when the rapidly growing nodule exerts pressure on a peripheral nerve. Virtually all lesions are solitary.

Although nodular fasciitis may occur in patients of any age, it is most common in adults 20 to 40 years old ( Fig. 7.1 ). Males and females are about equally affected. Most lesions grow rapidly and have a preoperative duration of 1 month or less. Although nodular fasciitis may occur virtually anywhere on the body, there is a distinct predilection for certain sites, the most common being the upper extremities, especially the volar aspect of the forearm, followed by the trunk, particularly the chest wall and back. Nodular fasciitis in the head and neck is next in frequency and is the most common site in infants and children. It is less common in the lower extremities and infrequent in the hands and feet. It has also been reported in a variety of unusual locations, including the parotid gland ( Fig. 7.2 ), external ear, oral cavity, breast, and lymph node capsule ( Fig. 7.3 ). Rare intraarticular and intraneural examples have been reported. ^,

Age distribution for 1317 cases of nodular fasciitis.

Nodular fasciitis involving the parotid gland. Note the circumscription and profuse myxoid change in the central portion of the lesion.

Rare example of nodular fasciitis involving the lymph node capsule.

The gross appearance of nodular fasciitis is highly dependent on the relative amounts of myxoid and fibrous stroma and the cellularity of the lesion. Most are relatively well demarcated but nonencapsulated lesions, although some, particularly those centered on the deep fascia, are poorly demarcated and appear to infiltrate the surrounding soft tissues ( Figs. 7.4 and 7.5 ). Most are 2 cm or less in the greatest dimension when excised. ^{, ,} Although occasionally as large as 10 cm at excision, the diagnosis of nodular fasciitis should always be made with considerable trepidation in this setting. Intramuscular lesions tend to be slightly larger than those found in the subcutaneous tissue.

Gross appearance of the subcutaneous form of nodular fasciitis. The lesion is small and circumscribed; it is superficially attached to the fascia.

Nodular fasciitis with central cyst-like spaces, with accumulation of myxoid ground substance.

The appearance of the cut surface depends on the relative amounts of myxoid and collagenous material. Those with a predominantly myxoid matrix are soft and gelatinous and grossly resemble other myxoid soft tissue lesions such as myxoma, ganglion, or benign peripheral nerve sheath tumors. Those with a pronounced collagenous stroma are firm and resemble other fibrous lesions such as fibromatosis or fibrosarcoma. Although extravasated erythrocytes are a frequent microscopic feature, these lesions are rarely grossly hemorrhagic.

Nodular fasciitis can be grouped into three major subtypes based on their relationship with the fascia. The subcutaneous type, the most common form of nodular fasciitis, is a well-circumscribed spherical nodule attached to the fascia but growing upward into the subcutis. The intramuscular type is superficially attached to the fascia; it grows as an ovoid intramuscular mass and is often larger than the subcutaneous type. The fascial type, centered along the fascia, is less well demarcated than the other forms, growing along the interlobular septa of the subcutaneous fat, resulting in a ray-like or stellate growth pattern. Rare examples of nodular fasciitis arise in the dermis, where they tend to grow in an infiltrative manner. ^,

All cases of nodular fasciitis, regardless of whether they are predominantly fibrous or myxoid, are composed of plump, immature-appearing fibroblasts and myofibroblasts that closely resemble the fibroblasts found in tissue culture or granulation tissue ( Fig. 7.6 ). In general, the cells vary little in size and shape and have oval, pale-staining nuclei with prominent nucleoli ( Fig. 7.7 ). Mitotic figures are common, but atypical mitoses are virtually never seen.

Area of myxoid degeneration in nodular fasciitis.

Nodular Fasciitis.

(A) Microhemorrhages between bundles of fibroblasts. (B) Storiform growth pattern in nodular fasciitis.

Characteristically, the cells are arranged in short, irregular bundles and fascicles and are accompanied by small amounts of mature birefringent collagen. The intervening matrix is rich in mucopolysaccharides that stain with Alcian blue preparations and are depolymerized by hyaluronidase. The abundance of ground substance is responsible for the characteristic loosely textured, feathery pattern of nodular fasciitis; there are also cellular forms with only small amounts of interstitial myxoid material. Intermixed with the spindled cells are scattered lymphocytes and extravasated erythrocytes and, in the more central portion of the lesion, a small number of lipid macrophages and multinucleated giant cells. Occasionally, there are associated areas of microhemorrhage, but siderophages are rare ( Fig. 7.8 ).

Nodular fasciitis with focal hemosiderin deposition, a feature rarely seen in this lesion.

There are minor variations in the histologic picture. In some cases, the intramuscular form of nodular fasciitis contains residual atrophic muscle fibers and muscle giant cells. However, this feature is much less pronounced in nodular fasciitis than in deep fibromatoses. The fascial type of nodular fasciitis may have cells arranged radially around a central, poorly cellular, edematous area containing a mixture of mucoid material and fibrin.

There is a close correlation between the microscopic picture and the preoperative duration of the lesion. Lesions of short duration tend to have a predominantly myxoid appearance ( Fig. 7.9A and B ). In contrast, those of longer duration are characterized by hyaline fibrosis ( Fig. 7.9C and D ), tissue shrinkage, and formation of minute fluid-filled spaces, or microcysts, a sequence closely paralleling the cicatrization of granulation tissue. In cases of long duration, the microcysts sometimes fuse and form a large, centrally located cystic space ( cystic nodular fasciitis ). Additionally, young nodular fasciitis contains a higher percentage of USP6 break-apart FISH signals than nodular fasciitis of long duration, leading to potential false negative FISH results in the latter setting.

Nodular Fasciitis.

(A) Small area of myxoid breakdown imparting a loosely textured arrangement of fibroblasts. (B) More pronounced myxoid matrix with cells widely spaced by mucoid pools. (C) Nodular fasciitis showing hyaline fibrosis between fibroblasts. (D) Nodular fasciitis showing marked hyaline fibrosis, a feature usually encountered in lesions of long duration.

On rare occasions, a nodular fasciitis-like lesion has metaplastic bone, a condition described as ossifying fasciitis or fasciitis ossificans and, when arising from the periosteum, as parosteal fasciitis ( Fig. 7.10 ). Many of these lesions have features of both nodular fasciitis and myositis ossificans , but they may be less well-demarcated than nodular fasciitis and lack the zonal maturation of myositis ossificans. Occasionally, small foci of metaplastic bone are also found in morphologically typical nodular fasciitis. Panniculitis ossificans and fibroosseous pseudotumor of the digits are closely related lesions with a more irregular pattern and are now considered variants of myositis ossificans (see Chapter 31 ). Rare cases of proliferative fasciitis, proliferative myositis, and cranial fasciitis may also contain foci of metaplastic bone.

Parosteal Fasciitis.

(A) Gross appearance of parosteal fasciitis. (B) Accompanying radiograph of parosteal fasciitis. (C) Histologic appearance of parosteal fasciitis, which is identical to that seen in nodular fasciitis.

Intravascular fasciitis is a rare variant of nodular fasciitis characterized by the involvement of small or medium-sized veins or arteries. ^, Males and females are about equally affected, and most patients are young; very few patients are 30 years or older. The typical presentation is that of a slowly growing, painless, solitary subcutaneous mass, usually 2 cm or smaller. The upper extremity is the most common site, followed closely by the head and neck. Less common sites include the trunk, lower extremities, and oral cavity. ^, Grossly, the lesions may be round or oval or elongated, multinodular, or plexiform, particularly those that grow as a predominantly intravascular mass ( Fig. 7.11 ). Small- to medium-size veins are most commonly affected, but some lesions involve arteries alone or are seen in conjunction with venous structures. In most cases, there is involvement of the intima, media, adventitia, and perivascular soft tissue, frequently with a predominantly extravascular component, although some grow as an intraluminal polypoid mass ( Fig. 7.12 ). The association with a vessel may be obscured by the proliferation, so special stains (e.g., Movat) are required to highlight the involved vessel.

Intravascular Fasciitis.

(A) Low-power view showing multinodular growth in several markedly dilated veins. (B) Movat stain of intravascular fasciitis outlining intravascular growth of the spindle cell proliferation.

Movat stain of intravascular fasciitis highlighting the intravascular growth in greatly dilated vein.

Histologically, the intravascular growth closely resembles nodular fasciitis. However, it has a less prominent mucoid matrix and a conspicuous number of osteoclast-like giant cells, resembling a benign fibrous histiocytoma or a giant cell tumor of soft parts ( Figs. 7.13 and 7.14 ). Rare examples are predominantly myxoid. Clefts are often present where the proliferation has separated from the vessel wall. Because of the vessel involvement, this lesion may be confused with an organizing thrombus, intravascular capillary hemangioma, intravascular leiomyoma, or a sarcoma; 6 of 15 of the original lesions reported were initially confused with a sarcoma. Despite the intravascular growth, there is no evidence of aggressive clinical behavior, recurrence, or metastasis.

Small satellite nodule of intravascular fasciitis.

Intravascular Fasciitis.

(A) Intravascular proliferation of spindle-shaped cells with a conspicuous number of multinucleated giant cells. (B) Intravascular fasciitis composed of cytologically bland spindle cells similar to those found in nodular fasciitis.

Cranial fasciitis is a rapidly growing myofibroblastic proliferation that occurs chiefly, but not exclusively, in infants during the first year of life and involves the soft tissues of the scalp and the underlying skull. ^, It usually erodes the outer table of the cranium and frequently also penetrates the inner table, infiltrating the dura and sometimes even the leptomeninges. Radiographically, those that involve the underlying cranium create a lytic defect, often with a sclerotic rim ( Fig. 7.15 ). Histologically, cranial fasciitis exhibits the broad morphologic spectrum of nodular fasciitis; it is composed of a proliferation of fibroblasts and myofibroblasts deposited in a variably myxoid and hyalinized matrix, occasionally with foci of osseous metaplasia. The circumscription and the prominent myxoid matrix help distinguish the lesion from infantile fibromatosis or myofibromatosis.

Cranial Fasciitis.

(A) Radiograph of large soft tissue mass attached to the inner table of the skull in an infant. (B) Histologic picture of cranial fasciitis.

Birth trauma may play a role in the development of cranial fasciitis; some affected children have been delivered by forceps. ^, Interestingly, Rakheja et al. reported a case of cranial fasciitis arising in a child with familial adenomatous polyposis (FAP); this lesion showed strong and diffuse nuclear immunoreactivity for β-catenin, suggesting dysregulation of the Wnt/β-catenin pathway in a subset of cases. Another case of cranial fasciitis was associated with a deep fibromatosis, with both lesions showing staining for β-catenin. Rare cases also arise at the site of a prior craniotomy.

There is no relation between cranial fasciitis and the head banger’s tumor , a fibrosing lesion of the forehead with pigmentation of the overlying skin. Also, there is no association with an inherited fibrosing lesion of the scalp ( cutis verticis gyrata ) that occurs in adults and is associated with clubbing of the digits, enlargement of the distal extremities, and periosteal bone formation (pachydermoperiostosis).

As one would expect in a lesion composed of myofibroblasts, most cells of nodular, ossifying, intravascular, and cranial fasciitis stain with antibodies to smooth muscle actin and muscle-specific actin ( Fig. 7.16 ). Desmin is rarely expressed by the constituent cells; of the 53 cases stained by Montgomery and Meis, none expressed this antigen. h-Caldesmon has been purported to be a useful marker in distinguishing smooth muscle from myofibroblastic proliferations, as this antigen is typically expressed in smooth muscle tumors but is absent in nodular fasciitis. ^, In small biopsy specimens, nodular fasciitis may be difficult to distinguish from fibromatosis. β-Catenin and LEF1 may be useful because these antigens are consistently expressed in an aberrant nuclear pattern in most cases of fibromatoses and are absent in the myofibroblasts of nodular fasciitis. Immunostains for keratin and S-100 protein are consistently negative.

Nodular fasciitis with diffuse smooth muscle actin immunoreactivity.

In a study from Mayo Clinic in 2011, 44 of 48 (92%) cases of nodular fasciitis were found to have rearrangements of USP6 (located at 17p13). The most common fusion partner is MYH9 (22q13.1). The term “transient neoplasia” has been given to nodular fasciitis as it was the first known example of a self-limited process characterized by a recurrent gene fusion. Many subsequent studies have confirmed the consistent involvement of the USP6 gene in this lesion, although not all have MYH9 as the fusion partner. Other fusion partners include RRBP1, CALU, CTNNB1, MIR22HG, SPARC, THBS2, COL6A2, SERPINH1, SEC31A, COL1A1, COLIA2, COL3A1, EIF5A, PAFAH1B1, SNHG3, PPP6R3, PDLIM7, MYL12A, NACA, SLFN11, LDH6, TPM4 and KIF1A . The Jak1-STAT3 signaling pathway has been implicated as an effector of this proliferation. USP6 rearrangements are seen in various other tumors, including aneurysmal bone cysts, myositis ossificans, fibro-osseous pseudotumor of the digits, and cellular fibroma of tendon sheath. The morphologic features of “cellular fibroma of tendon sheath” are quite similar to those of nodular fasciitis, and it most likely represents a site-specific variant of the same process.

Nodular fasciitis may be confused with numerous benign and malignant mesenchymal lesions, and the differential diagnosis depends on the relative amounts of myxoid and fibrous stroma and the cellularity of the lesion in question. As previously mentioned, nodular fasciitis remains the most common benign mesenchymal lesion misdiagnosed as a sarcoma. Therefore, many cases of nodular fasciitis have been treated by unnecessary and excessively radical surgery.

Although nodular fasciitis and myxoma may display a prominent myxoid matrix, myxoma is readily recognized by its paucity of cells and poor vascularization. Myxomas also lack the zonal organization and regional heterogeneity of nodular fasciitis.

Cellular nodular fasciitis may be confused with benign fibrous histiocytoma , and in a small number of cases, the distinction between these two lesions may be difficult, if not somewhat arbitrary. The typical benign fibrous histiocytoma is dermal-based, less circumscribed, and composed of a more polymorphous proliferation of spindle-shaped and round cells arranged in a more consistent storiform pattern. Secondary elements, such as chronic inflammatory cells, xanthoma cells, siderophages, and Touton giant cells, are also common. Peripherally located, dense collagen fibers are typical, but similar-appearing fibers may occur in the central portion of nodular fasciitis, particularly in lesions of longer duration. Immunohistochemistry (IHC) is of limited value in this distinction, since many examples of benign fibrous histiocytoma stain for smooth muscle actin, sometimes quite strongly. IHC for factor XIIIa staining is of very little value in this differential diagnosis. In general, the distinction between nodular fasciitis and benign fibrous histiocytoma is best made on histologic grounds rather than on minor differences in immunophenotype.

Some cases of nodular fasciitis resemble fibromatosis . Grossly, fibromatosis is a large, poorly circumscribed lesion that typically infiltrates the surrounding soft tissue, in contrast to the relative circumscription of nodular fasciitis. Histologically, fibromatosis is characterized by slender, spindle-shaped fibroblasts arranged in long, sweeping fascicles and separated by abundant collagen. Mitotic figures occur in both lesions, but they are much less frequent in musculoaponeurotic fibromatosis than in nodular fasciitis. Both lesions consistently express smooth muscle actin, but nuclear expression of β-catenin and LEF1 is commonly seen in fibromatosis and absent in nodular fasciitis, although it can sometimes be challenging to evaluate β-catenin staining due to extensive cytoplasmic staining. ^{, ,}

Distinction from adult-type fibrosarcoma is primarily a matter of growth pattern, cellularity, and cytologic atypia. The cells in adult-type fibrosarcoma are almost always densely packed and are arranged in interweaving bundles, resulting in the characteristic herringbone pattern. Moreover, the individual cells are marked by a greater variation in size and shape, hyperchromatic nuclei, and a more pronounced mitotic rate, including atypical mitotic figures. The deep location, large size, and long duration of most adult-type fibrosarcomas also aid in this distinction.

Of the malignant myxoid lesions, myxofibrosarcoma may closely resemble nodular fasciitis. This lesion occurs principally in patients older than 50 years and usually measures more than 3 cm when first excised. Microscopically, the cells show more nuclear hyperchromasia and pleomorphism, and there is typically a regular arborizing vasculature composed of coarse vessels, often invested with tumor cells. Atypical mitotic figures may be seen, as may areas of transition to a high-grade pleomorphic sarcoma. Some studies have suggested that GLUT-1 and Claudin-6 immunohistochemistry may be helpful in distinguishing myxofibrosarcoma from nodular fasciitis as the expression of these markers is higher in myxofibrosarcoma. ^,

Pseudomyogenic hemangioendothelioma may also mimic dermal nodular fasciitis, particularly when composed chiefly of spindled, myoid cells. Immunohistochemistry for keratin, endothelial markers (e.g., CD31, ERG protein) and FOSB, positive in pseudomyogenic hemangioendothelioma, are helpful in this situation.

Rare cases of morphologically malignant nodular fasciitis have been reported, all of which harbored a USP6 fusion.

Although a well-documented history of trauma is present in a minority of cases, nodular fasciitis is clearly a benign neoplasm, possibly triggered by local injury or in response to a localized inflammatory process. Regardless of the precise cause, histologic recognition of this lesion is important to avoid misdiagnosing a sarcoma and unnecessary radical surgical treatment. The benign nature and excellent prognosis of nodular fasciitis have been well documented by numerous large clinicopathologic studies ( Table 7.1 ). In the series of 895 cases reported by Allen, only 9 (1%) reappeared after an attempted complete surgical excision. Even those lesions that are incompletely excised rarely recur. Of the 18 cases of recurrent nodular fasciitis in the series by Bernstein and Lattes, a review of the histology and clinical course led to revision of the original diagnosis in all 18 cases. In fact, these authors stated that a recurrence of a lesion initially diagnosed as nodular fasciitis should lead to a reappraisal of the original pathologic findings. Although most cases are surgically excised, there are well-documented cases of regression of these lesions over time. Anecdotally, we have noted local recurrence to be a feature of periauricular nodular fasciitis.

Proliferative fasciitis is a lesion of adult life, with most patients 40 to 70 years old (mean, 54). Although well recognized, it is uncommon for patients younger than 15 years to develop proliferative fasciitis. There is no gender or race predilection, and most lesions occur in the subcutaneous tissues of the extremities, with the upper extremity (especially the forearm) affected more often than the lower extremity. The lesion also occurs with some frequency on the trunk and rarely on the head and neck.

Clinically, most patients present with a firm, palpable subcutaneous nodule that is freely movable and unattached to the overlying skin, although about two-thirds of patients also have complaints of pain or tenderness. Most lesions measure less than 5 cm in greatest diameter, with a median size of 2.5 cm. Like nodular fasciitis, these lesions are typically rapidly growing, most being excised 2 to 6 weeks after their initial discovery. A history of trauma in the vicinity of the mass is elicited in about one-third of patients.

Grossly, proliferative fasciitis is usually poorly circumscribed, forming an elongated or discoid mass that predominantly involves the subcutaneous tissue, although some involve the superficial fascia. Rare lesions also involve the superficial skeletal muscle, making it difficult to distinguish from proliferative myositis. Cases that arise during childhood tend to be better demarcated and vaguely lobular, with only an occasional extension along fascial planes. ^,

Microscopically, as with nodular fasciitis, proliferative fasciitis is composed of tissue culture–like fibroblastic and myofibroblastic spindle cells with bland cytologic features, deposited in a variably myxoid and collagenous stroma. This proliferation extends along the interlobular septa of the subcutaneous tissue, with some extension along the superficial fascia ( Fig. 7.17 ). Rarely, the lesion can extend to or even be centered in the dermis. Proliferative fasciitis is characterized by large, basophilic ganglion-like cells with one or two vesicular nuclei and prominent nucleoli. The cells have abundant basophilic, slightly granular cytoplasm but lack cross-striations typical of rhabdomyoblasts ( Figs. 7.18 to 7.20 ). Some cells have intracytoplasmic inclusions of collagen. These ganglion-like cells may be packed together or loosely arranged in aggregates. Multinucleated giant cells of the type seen in nodular fasciitis are rare in proliferative fasciitis. Curiously, pediatric lesions tend to be more cellular ( Fig. 7.21 ), have numerous mitoses, and have foci of acute inflammation and necrosis, features that are distinctly unusual in the typical adult form. Childhood cases also tend to have less collagen and a less conspicuous myxoid matrix than their adult counterparts. Some lesions, particularly those that have been present for a long duration before excision, may have abundant hyalinized collagen that surrounds the ganglion-like cells, which could cause confusion with neoplastic osteoid and a misdiagnosis of osteosarcoma.

Proliferative fasciitis involving the subcutis.

Proliferative fasciitis composed of a mixture of fibroblasts and giant cells with abundant basophilic cytoplasm bearing some resemblance to ganglion cells.

Proliferative fasciitis showing variation in cellularity.

Proliferative fasciitis, with a hypercellular proliferation of “ganglion-like” myofibroblasts (A). The presence of less cellular foci with increased stromal collagen is characteristic, and helpful in the distinction from sarcoma (B).

Proliferative fasciitis with large ganglion-like cells, some of which are multinucleated.

Cellular proliferative fasciitis as often seen in children showing back-to-back cells and neutrophilic infiltrate with scattered apoptotic bodies (A) and extreme hyalinization with regression (B).

The immunohistochemical findings of proliferative fasciitis are similar to those of nodular fasciitis. The spindle and stellate-shaped cells stain for muscle-specific and smooth muscle actin. Some cells stain for CD68 (KP1); immunostains for keratins, S-100 protein, and desmin are usually negative. The ganglion-like cells may also stain for actin, although the staining is often focal and weak and may be membranous in distribution. ^, Unlike nodular fasciitis, recurrent FOS rearrangement is present in proliferative fasciitis (and myositis), which can be detected immunohistochemically. Interestingly, FOS expression is not observed in pediatric cases, indicating a different pathogenesis for these tumors. SMARCB1 expression is retained, an important finding in highly cellular pediatric lesions where the differential diagnosis includes proximal-type epithelioid sarcoma and malignant rhabdoid tumor. Ultrastructurally, the spindle- and stellate-shaped cells have the typical features of fibroblasts and myofibroblasts. The ganglion-like cells are characterized by abundant rough endoplasmic reticulum with dilated cisternae, some of which may contain short-spacing collagen fibrils.

The symptoms are nonspecific, and the diagnosis of proliferative myositis always rests on histologic examination. In most cases, the lesion is first noted as a palpable, more or less discrete, solitary nodular mass that measures 1 to 6 cm in diameter. It rarely causes tenderness or pain, even though it may double in size within a few days. The duration between onset and excision is usually less than 3 weeks.

Patients with proliferative myositis tend to be older than those with nodular fasciitis, with a median age of 50 years, although rare cases have been described in children. There seems to be no predilection for either gender. The lesion mainly affects the flat muscles of the trunk and shoulder girdle, especially the pectoralis, latissimus dorsi, and serratus anterior muscles. Occasionally, tumors are also found in the muscles of the thigh. Involvement of the head and neck is uncommon.

Similar to proliferative fasciitis, proliferative myositis typically appears pale gray or scar-like, resulting in induration of the involved skeletal muscle ( Fig. 7.22 ). When present in small or flat muscles, it often replaces most or all of the involved musculature. When involving large muscles, there is preferential involvement of the skeletal muscle immediately underneath the fascia, with a progressive decrease in the central portion of the muscle in a wedge-like manner.

Proliferative myositis characterized by a poorly circumscribed, scar-like fibrosing process involving muscle and muscle fascia.

The cellular components of proliferative myositis are identical to those found in proliferative fasciitis. There is a poorly demarcated proliferation of fibroblast-like cells that involve the epimysium, perimysium, and endomysium. Unlike the intramuscular form of nodular fasciitis and musculoaponeurotic fibromatosis, this cellular proliferation rarely completely replaces large areas of the involved muscle and, instead, is most striking in the subfascial region and interfascicular connective tissue septa. The skeletal muscle fibers are relatively unaffected except for secondary atrophy, with neither sarcolemmal proliferation nor any evidence of skeletal muscle regeneration. This alternation of proliferating fibrous tissue with persistent atrophic skeletal muscle fibers results in a typical “checkerboard pattern” that is apparent at low magnification ( Fig. 7.23 ). The other conspicuous histologic feature of proliferative myositis is the presence of large, basophilic ganglion-like cells identical to those found in proliferative fasciitis ( Figs. 7.24 and 7.25 ). Mitotic figures are often easily identified in both the spindle and the giant cells, although atypical mitoses are not seen. Rare lesions contain foci of metaplastic bone ( Fig. 7.26 ). The immunohistochemical and ultrastructural features of proliferative myositis are identical to those of proliferative fasciitis, including the expression of FOS immunohistochemically ^, ( Fig. 7.27 ).

Proliferative myositis showing splaying of muscle fascicles (A) by expanded fibrous trabecule containing reactive myofibroblasts, some having features of ganglion cells (B).

Proliferative myositis. Ganglion-like giant cells are seen immediately adjacent to and infiltrating skeletal muscle fibers.

High-power view of ganglion-like giant cells in proliferative myositis.

Unusual case of proliferative myositis with extensive metaplastic bone formation.

Proliferative myositis stained for smooth muscle actin. Most spindle cells stain for this antigen, but the ganglion-like cells, in this case, are negative.

Proliferative fasciitis and myositis may be mistaken for malignant neoplasms, most commonly rhabdomyosarcoma or ganglioneuroblastoma . In the series of 53 cases of proliferative fasciitis by Chung and Enzinger, 16 were initially diagnosed as a sarcoma. Similarly, 14 of 33 cases of proliferative myositis reported by Enzinger and Dulcey were believed to be some type of sarcoma. Errors are most likely to occur with childhood cases in which rhabdomyosarcoma, epithelioid sarcoma, and malignant extrarenal rhabdoid tumor are strong diagnostic considerations. Histologically, the ganglion-like cells lack cross-striations and show more cytoplasmic basophilia than that seen in rhabdomyoblasts. Although the IHC profiles may overlap, stains for desmin, MyoD1, and myogenin are negative in the ganglion-like cells, in contrast to the staining found in true rhabdomyoblasts. The absence of keratin expression, retained SMARCB expression, and FOS staining are helpful in differentiating it from epithelioid sarcoma and malignant extrarenal rhabdoid tumor.

Proliferative fasciitis and myositis, like nodular fasciitis, are self-limiting, benign neoplasms resulting in a proliferation of myofibroblasts. A small number of patients report a preceding injury in the exact location of the lesion, suggesting that mechanical trauma may play a role in the development of proliferative fasciitis and myositis in rare patients. Some have reported the diagnosis of these lesions by fine-needle aspiration cytology. Both proliferative fasciitis and myositis are adequately treated by local excision, and recurrence is exceedingly rare. As with some cases of nodular fasciitis, spontaneous resolution in 1 to 16 weeks has been observed in patients with proliferative fasciitis and myositis.

Although these lesions can arise anywhere in the genitourinary tract, including the prostate, vagina, urethra, and ureter, they are most common in the urinary bladder. For example, in the Hirsch study, 21 of 27 pseudosarcomatous myofibroblastic proliferations of the genitourinary tract arose in the urinary bladder. Similarly, 42 of 46 “inflammatory myofibroblastic tumors” arose in the urinary bladder. Most frequently, patients present with hematuria, although some have dysuria, abdominal pain, or weight loss. Based on the larger clinicopathologic studies, it is still unclear whether a gender predilection exists. In the Harik et al. and Montgomery et al. studies, males outnumbered females by a 2:1 or 3:1 ratio. However, Hirsch et al. found the opposite: women were affected three times more often than men. Although the age range is broad, lesions usually arise in the fourth to fifth decade of life. Up to 20% to 25% of patients have a history of antecedent trauma or surgical instrumentation; lesions that arise secondary to surgical instrumentation usually become clinically apparent between 5 and 12 weeks after the procedure.

Grossly, most lesions present as exophytic, nodular, or polypoid intraluminal lesions that may extend deeply into the visceral organ from which they arise. They range in size from 1.5 cm to up to 12 cm, although most are between 3 and 5 cm at excision. The lesion may be firm or soft, depending on the relative amounts of fibrous and myxoid stroma.

On microscopic examination, these lesions are characterized by a proliferation of spindle- to stellate-shaped cells, often with a tissue culture–like appearance reminiscent of nodular fasciitis ( Figs. 7.28 to 7.30 ). The cells lack cytologic atypia or nuclear hyperchromasia and have bipolar or stellate-shaped cytoplasmic processes. The cells are typically widely separated and haphazardly distributed in a myxoid stroma. However, some cases are characterized by more cellular areas in which the cells are arranged in irregular fascicles with variable amounts of intercellular collagen. The cells have oval- to spindle-shaped nuclei with open chromatin, variably sized nucleoli, and eosinophilic to amphophilic cytoplasm. Mitotic figures are present, usually fewer than one or two per 10 high-power fields (hpf) and are not atypical. In the more myxoid zones, there is a prominent capillary network often associated with extravasated erythrocytes. A mixed inflammatory infiltrate composed of lymphocytes, plasma cells, eosinophils, and occasional mast cells is usually conspicuous. When present, neutrophils are associated with areas of mucosal ulceration.

Pseudosarcomatous myofibroblastic proliferation of bladder showing ulcerated mucosal surface (A) and deep extension into muscle (B).

Cellular (A) and myxoid (B) areas in pseudosarcomatous myofibroblastic proliferation.

Plump myofibroblasts with prominent nucleoli within pseudosarcomatous myofibroblastic proliferation (A). Cells express actin (B) and may occasionally express keratin (C) and ALK (D).

Some cases have histologic features that cause great concern for malignancy, including a brisk mitotic rate, with up to 20 mitotic figures per 10 hpf. Invasion into the muscularis propria of the urinary bladder is a common finding, and some even infiltrate into the perivesicular adipose tissue. Although necrosis is usually focal and confined to the surface of the lesion and associated with mucosal ulceration, some cases show necrosis of the deeper tissue.

Immunohistochemically, the spindle cells stain strongly for muscle markers, including muscle-specific actin, smooth muscle actin, and desmin. In addition, many cases show focal or even diffuse staining for keratins (see Fig. 7.30C ), which can lead to diagnostic confusion. ^, Harik et al. found that 31 of 35 cases stained for keratins, and Montgomery et al. found 25 of 34 cases (73%) to stain with the AE1/AE3 antibody, including 23 cases with strong, diffuse immunoreactivity. Many cases also stained with CAM 5.2 and for keratin 18.

A significant percentage of these lesions also stain for ALK ( Fig. 7.30D ), but there is an imperfect correlation between ALK immunoreactivity and the detection of an ALK gene rearrangement by fluorescence in situ hybridization (FISH) ( Table 7.2 ). In the Harik study, 12 of 26 (46%) cases stained for this antigen, and FISH confirmed ALK rearrangement in 4 of 6 (67%) ALK-positive tumors. In the Montgomery study, 20 of 35 cases (57%) stained for ALK, and 13 of 18 ALK-positive cases (72%) showed evidence of an ALK alteration by FISH. In contrast, of the six ALK-immunoreactive cases evaluated by Hirsch et al., none showed evidence of an ALK gene translocation by FISH. Sukov et al. found ALK rearrangements in 14 of 21 cases (67%), with ALK staining in 13 of 21 (62%). All cases immunoreactive for ALK harbored ALK rearrangements; one ALK-negative case exhibited an ALK rearrangement. All other lesions studied (leiomyosarcomas, sarcomatoid carcinomas, embryonal rhabdomyosarcomas, and reactive lesions) were negative for ALK rearrangement and ALK staining. For those cases with ALK fusions, a number of fusion partners have been identified, including HNRNPA1 and FN1 . ^, In a more recent study by Acosta et al., 70% (21/30) of pseudosarcomatous myofibroblastic tumors of the urinary bladder demonstrated cytoplasmic and membranous, or cytoplasmic staining for ALK, whereas 0/28 were negative for ROS. All but 3 ALK-positive cases tested showed ALK rearrangement by FISH (86%). Of eight tumors with ALK rearrangement by FISH, targeted RNA-sequencing detected FN1::ALK fusion in 7 (88%). The authors concluded that given the different clinicopathologic differences between inflammatory myofibroblastic tumor and pseudosarcomatous myofibroblastic proliferation, they should be considered distinct entities, and they proposed the term pseudosarcomatous myofibroblastic neoplasm for these tumors.

Although a pseudosarcomatous myofibroblastic proliferation should be suspected when one encounters a spindle cell lesion in the genitourinary tract, particularly in a patient who has undergone recent instrumentation at that site, numerous other benign and malignant spindle cell proliferations must be considered ( Table 7.3 ). Myxoid leiomyosarcoma occurs in older patients and is rare before age 20. Microscopically, the lesion is composed of spindle cells with densely eosinophilic fibrillar cytoplasm, often with perinuclear vacuoles, deposited in a myxoid stroma. These lesions can also express keratins, but they do not stain for ALK. Pseudosarcomatous myofibroblastic proliferations are characterized by a more prominent vasculature, variable cellularity, and a more conspicuous inflammatory component. Moreover, these lesions characteristically have a zonal quality consisting of superficial (submucosal) myxoid zones juxtaposed to deep cellular zones associated with a prominent arcuate vascular pattern.

Table 7.3

Differential Diagnostic Features of Genitourinary Pseudosarcomatous Myofibroblastic Proliferations

Feature	PMP	ML	B-RMS	SC
Cellularity	+	+/++	+/++	++
Growth pattern	Loose	Loose	Botryoid	Biphasic
Atypia	+	+/++	++	+++
Electron microscopy	Fibroblast/myofibroblast	Smooth muscle	Striated muscle	Epithelial
Keratin	Frequent +	Rare	–	+
Desmin	±	+	+	±
SMA	+	+	–	±
ALK	50%	–	–	–

Only gold members can continue reading. Log In or Register to continue

Share this:

• X
• Facebook

Like this:

Like Loading…

Related

Related posts:

1. Approach to the Diagnosis of Soft Tissue Tumors
2. General Considerations
3. Fibrous Tumors of Infancy and Childhood
4. Borderline and Malignant Fibroblastic/Myofibroblastic Tumors

Stay updated, free articles. Join our Telegram channel

Join