Soft Tissue





Nodular Fasciitis


Clinical Features





  • Primarily affects young adults aged 20 to 40 years; occasionally seen in children



  • Presents as a rapidly growing solitary mass; may be painful



  • Inconsistently associated with recognized previous trauma (10% to 15%)



  • Can involve any site; flexor aspect of forearm, chest, and back are common sites



  • Spontaneous regression is expected



Gross Pathology





  • Located in the deep dermis or subcutis; occasionally occurs intramuscularly



  • Round to oval, nodular, well-circumscribed mass; usually smaller than 3 cm



  • Cut surface may be fibrous, myxoid, or cystic



Histopathology





  • Usually well circumscribed but occasionally infiltrative



  • “Tissue culture” appearance with long fascicles of spindled cells with a whorled growth pattern; extravasated red blood cells are a helpful feature ( Figure 17.1 )




    Figure 17.1


    Nodular fasciitis.

    Bland plump spindle cells with a “tissue culture” appearance are present in a myxoid to collagenous stroma with admixed inflammatory cells and extravasated RBCs.



  • Newer lesions have a loose, feathery collagenous stroma with myxoid or microcystic appearance, whereas older lesions are less cellular and more densely collagenized



  • Zonal pattern with cellular periphery and loose, feathery center that may be cystic



  • Scattered inflammatory cells, typically lymphocytes and macrophages



  • Occasional mitotic figures; no abnormal mitotic figures



  • Variants




    • Intravascular fasciitis




      • Primarily affects children and adolescents



      • Involves arteries and veins




    • Cranial fasciitis




      • Affects infants younger than 1 year



      • Involves the scalp and skull




    • Ossifying fasciitis




      • Often shows osseous metaplasia



      • Periosteal location



      • Similar to myositis ossificans but lacks triphasic zonal pattern





Special Stains and Immunohistochemistry





  • Vimentin and smooth muscle actin (SMA) positive



  • Immunohistochemistry does not help to exclude other myofibroblastic or smooth muscle proliferations



Other Techniques For Diagnosis





  • Translocation t(17;22)(p13;q13.1), producing a MYH9-USP6 fusion demonstrable by molecular or in situ hybridization studies, typically cryptic by karyotype




    • Only seen in nodular fasciitis, not its variants




Differential Diagnosis


Kaposi Sarcoma





  • Ill-defined margins



  • Prominent vasculature, extravasated red blood cells



  • Found in immunocompromised individuals; typically patients with acquired immunodeficiency syndrome (AIDS)



  • Immunoreactive for human herpesvirus type 8 (HHV-8) latent nuclear antigen 1 (LANA-1), and endothelial markers



Myxoma





  • Characterized by a paucity of cells, myxoid matrix, and sparse vascularity



Fibrous Histiocytoma (Dermatofibroma)





  • Spindle cell proliferation admixed with epithelioid and foamy histiocytes



  • Typically arranged in a storiform pattern



  • Lacks prominent vasculature and extravasated red blood cells



Fibromatosis (Desmoid Tumor)





  • Dense collagenous stroma usually lacking inflammatory component



  • Lacks thin-walled vessels



  • Nuclear immunoreactivity for β-catenin in most cases



Pearls





  • Nodular fasciitis is commonly misdiagnosed as a sarcoma



  • Confirmed as a neoplastic condition



  • Benign lesion with an excellent prognosis



  • May progress through myxoid, cellular, and fibrous phases



  • Conservative surgical resection is the treatment of choice, but close follow-up is also acceptable





Selected References




  • Amary M.F., Ye H., Berisha F., Tirabosco R., et. al.: Detection of USP6 gene rearrangement in nodular fasciitis: an important diagnostic tool. Virchows Arch 2013; 463: pp. 97-98.



  • Erickson-Johnson M.R., Chou M.M., Evers B.R., et. al.: Nodular fasciitis: a novel model of transient neoplasia induced by MYH9-USP6 gene fusion. Lab Invest 2011; 91: pp. 1427-1433.



  • Montgomery E.A., Meis J.M.: Nodular fasciitis: its morphologic spectrum and immunohistochemical profile. Am J Surg Pathol 1991; 15: pp. 942-948.



  • Price E.B., Sillaphant W.M., Shuman R.: Nodular fasciitis: a clinicopathologic analysis of 65 cases. Am J Clin Pathol 1961; 35: pp. 122-136.



  • Sarangarajan R., Dehner L.P.: Cranial and extracranial fasciitis of childhood: a clinicopathologic and immunohistochemical study. Hum Pathol 1999; 30: pp. 87-92.


Proliferative Fasciitis and Myositis


Clinical Features





  • Typically occurs in adults (usually about 50 years of age)



  • Firm, palpable, rapidly growing subcutaneous or intramuscular nodule; may be painful




    • Proliferative fasciitis




      • Most common site is forearm, followed by leg and trunk



      • Often associated with a history of trauma




    • Proliferative myositis




      • Commonly located in the flat muscles of the trunk and shoulder girdle





Gross Pathology





  • Poorly circumscribed, gray-white soft tissue mass



  • Typically measures 1 to 3 cm in diameter



  • Proliferative myositis is commonly a pale, gray, scarlike induration involving muscle and overlying fascia



Histopathology





  • Ill-defined lesions characterized by large myofibroblasts that have large vesicular nuclei, prominent nucleoli, and abundant eosinophilic cytoplasm (ganglion-like cells) admixed with immature spindle cells in a matrix composed of varying proportions of mucoid material and collagen



  • Often numerous mitotic figures in spindled and ganglion-like cells; they are not atypical ( Figure 17.2 )




    • Proliferative fasciitis




      • Typically grows along fibrous septa between fat lobules




    • Proliferative myositis




      • Endomysial and epimysial growth separates bundles of atrophic skeletal muscle, creating a checkerboard pattern





    Figure 17.2


    Proliferative fasciitis.

    Numerous ganglion-like cells are seen in a collagenous stroma.



Special Stains and Immunohistochemistry





  • Ganglion-like cells are often nonreactive toward muscle markers and react with vimentin only



Other Techniques for Diagnosis





  • Noncontributory



Differential Diagnosis


Rhabdomyosarcoma





  • Tumor of children, rarely seen in adults



  • Presence of rhabdomyoblasts rarely with cytoplasmic cross-striations



  • Immunoreactivity for desmin, muscle-specific actin (MSA), myogenin, and MyoD1



Ganglioneuroblastoma





  • Intermixed neuroblasts and ganglion cells in a background of Schwannian spindle cell stroma



  • S100 protein is present in the Schwannian stroma



  • Tumor of young children; extremities an unusual location



Pearls





  • Pathogenesis of proliferative fasciitis and myositis remains unexplained; fascial or muscular injury is thought to be a likely contributor



  • Benign, self-limited, reactive process treated with conservative surgical excision



  • Proliferative fasciitis and proliferative myositis are similar reactive proliferations that are best distinguished by their locations





Selected References




  • Chung E.B., Enzinger F.M.: Proliferative fasciitis. Cancer 1975; 36: pp. 1450-1458.



  • El-Jabbour J.N., Bennett M.H., Burke M.M., et. al.: Proliferative myositis: an immunohistochemical and ultrastructural study. Am J Surg Pathol 1991; 15: pp. 654-659.



  • Enzinger F.M., Dulcey F.: Proliferative myositis: report of thirty-three cases. Cancer 1967; 20: pp. 2213-2223.



  • Meis J.M., Enzinger F.M.: Proliferative fasciitis and myositis of childhood. Am J Surg Pathol 1992; 16: pp. 364-372.



  • Wong N.L.: Fine needle aspiration cytology of pseudosarcomatous reactive proliferative lesions of soft tissue. Acta Cytol 2002; 46: pp. 1049-1055.


Myositis Ossificans


Clinical Features





  • Commonly affects young, athletic adults; usually involves the extremities



  • Uncommon in children



  • Presents as a solitary, tender mass; often associated with a history of trauma (>50% of cases)



  • Radiographic findings show characteristic zonal ossification, with rapid mineralization evident on sequential studies



Gross Pathology





  • Well-circumscribed, gray-yellow lesions with gritty areas



  • Some cases have central blood-filled spaces and are regarded as a variant of aneurysmal bone cyst occurring outside of bone ( Figure 17.3 )




    Figure 17.3


    Myositis ossificans/aneurysmal bone cyst of soft tissue.

    In this variant of myositis ossificans, a rim of bone is present around a central hemorrhagic cyst.



Histopathology





  • Typically shows a triphasic pattern with distinct zonation




    • Central cellular region




      • Resembles nodular fasciitis



      • Cells have bland nuclear features and a variable mitotic rate



      • Occasional multinucleated giant cells




    • Intermediate region is composed of immature osteoid



    • Peripheral zone is composed of mature, “purposeful” lamellar bone




      • Cartilage may be present





Special Stains and Immunohistochemistry





  • Noncontributory



Other Techniques for Diagnosis





  • USP6 translocation is detectible by fluorescence in situ hybridization (FISH) in some cases



Differential Diagnosis


Extraskeletal Osteosarcoma





  • Characterized by disordered growth of hyperchromatic, pleomorphic cells with delicate lacelike osteoid formation, often with faint bluish calcification



  • Absence of zonation



Ossifying Fibromyxoid Tumor





  • Chords and aggregates of plump spindle cells in a fibromyxoid matrix, with osteoblastic differentiation and bone formation generally around the outer rim of the tumor



  • Lacks inflammatory cells and granulation tissue appearance



Pearls





  • Myositis ossificans is a benign, self-limited process with an excellent prognosis



  • Spontaneous regression can occur



  • A subset, likely those with USP6 translocation, have features of aneurysmal bone cyst





Selected References




  • Ackerman L.V.: Extra-osseous localized non-neoplastic bone and cartilage formation (so-called myositis ossificans): clinical and pathological confusion with malignant neoplasms. J Bone Joint Surg Am 1958; 40: pp. 279-298.



  • Clapton W.K., James C.L., Morris L.L., et. al.: Myositis ossificans in childhood. Pathology 1992; 24: pp. 311-314.



  • Nuovo M.A., Norman A., Chumas J., et. al.: Myositis ossificans with atypical clinical, radiographic, or pathologic findings: a review of 23 cases. Skeletal Radiol 1992; 21: pp. 87-101.



  • Wilson J.D., Montague C.J., Salcuni P., et. al.: Heterotopic mesenteric ossification (“intraabdominal myositis ossificans”): report of five cases. Am J Surg Pathol 1999; 23: pp. 1464-1470.



  • Zhang L., Hwang S., Benayed R., et. al.: Myositis ossificans-like soft tissue aneurysmal bone cyst: a clinical, radiological, and pathological study of seven cases with COL1A1-USP6 fusion and a novel ANGPTL2-USP6 fusion. Mod Pathol 2020; 33: pp. 1492-1504.


Ischemic Fasciitis


Clinical Features





  • Also referred to as atypical decubital fibroplasia



  • Occurs over bony prominences or other pressure points in debilitated patients



  • Almost exclusively seen in late adulthood and rarely in younger patients



  • More commonly found in females



Gross Pathology





  • Poorly circumscribed, multinodular mass up to 10 cm in diameter



  • May have overlying ulceration



Histopathology





  • Typical zonation pattern




    • Central necrotic region




      • Liquefactive or coagulative necrosis with fibrin deposition ( Figure 17.4 )




        Figure 17.4


        Ischemic fasciitis.

        A transition is seen between fibrin-rich necrosis and stellate myofibroblastic cells.




    • Peripheral fibroblastic and vascular proliferation




      • Granulation tissue-like with plump endothelial cells



      • Atypical fibroblasts with abundant eosinophilic cytoplasm and ganglion-like features



      • Vascular thrombosis and fibrinoid necrosis





Special Stains and Immunohistochemistry





  • Noncontributory



Other Techniques for Diagnosis





  • Noncontributory



Differential Diagnosis


Atypical Lipomatous Tumor





  • Typical cases show scattered atypical cells present in adipose tissue with fibrous septa, which may resemble the reactive myofibroblasts in ischemic fasciitis



  • Myxoid change may be extensive, making adipocytic component difficult to find, especially in small samples



  • Fat necrosis is common, but not coagulative necrosis with fibrin



Bursitis





  • May produce a mass with a central cavity, adjacent to a joint



  • Cavity lining is generally denuded with fibrin exudate, and surrounded by inflammatory cells



Pearls





  • Ischemic fasciitis is a benign, reactive process likely related to intermittent ischemia



  • Surgical excision is the treatment of choice; can recur owing to the persistence of the underlying cause





Selected References




  • Ilaslan H., Joyce M., Bauer T., Sundaram M.: Decubital ischemic fasciitis: clinical, pathologic, and MRI features of pseudosarcoma. Am J Roentgenol 2006; 187: pp. 1338-1341.



  • Liegl B., Fletcher C.D.: Ischemic fasciitis: analysis of 44 cases indicating an inconsistent association with immobility or debilitation. Am J Surg Pathol 2008; 32: pp. 1546-1552.



  • Perosio P.M., Weiss S.W.: Ischemic fasciitis: a juxta-skeletal fibroblastic proliferation with a predilection for elderly patients. Mod Pathol 1993; 6: pp. 69-72.


Elastofibroma


Clinical Features





  • Usually presents as a deeply seated mass located in the lower subscapular area



  • Almost exclusively seen in late adulthood and rarely in younger patients



  • More commonly found in females



Gross Pathology





  • Firm, rubbery soft tissue mass with ill-defined margins



  • Cut surface is gray-white and glistening with entrapped foci of fat



  • Focal cystic degeneration often seen



Histopathology





  • Poorly defined lesion composed of thickened, coarse slightly basophilic elastic fibers and scant fibroblastic cells embedded in a heavily collagenized stroma ( Figure 17.5A )




    Figure 17.5


    Elastofibroma.

    A, Gross photo of cut section (with the surface inked black) showing a poorly marginated gray-white mass. B, The tumor is paucicellular with bland fibroblasts and prominent elastic fibers in longitudinal and transverse cross section, evident on H&E (arrows) , highlighted by elastic stain (inset) .



  • Entrapped mature adipose tissue is typically seen



Special Stains and Immunohistochemistry





  • Verhoeff–van Gieson elastic stain: highlights elastic fibers ( Figure 17.5B )



Other Techniques for Diagnosis





  • Noncontributory



Differential Diagnosis


Fibrolipoma





  • Characterized by predominance of mature adipocytes with intervening fibrous connective tissue



  • Lacks elastic fibers



Spindle Cell Lipoma





  • Subcutaneous mass in neck and shoulder region



  • Ropy collagen present, but not prominent elastic fibers. May show extensive myxoid change and contain few to no adipocytes



Pearls





  • Histology of elastofibroma is described as “spaghetti and meatballs” owing to long and globular elastic fibers



  • Increased incidence in manual laborers; related to repetitive motion injury



  • Can usually be diagnosed by radiology or fine-needle aspiration





Selected References




  • Lococo F., Cesario A., Mattei F., et. al.: Elastofibroma dorsi: clinicopathological analysis of 71 cases. Thorac Cardiovasc Surg 2013; 61: pp. 215-222.



  • Vincent J., Maleki Z. Elastofibroma.: cytomorphologic, histologic, and radiologic findings in five cases. Diagn Cytopathol 2012; 40: pp. E99-E103.



  • Yamazaki K.: An ultrastructural and immunohistochemical study of elastofibroma: CD 34, MEF-2, prominin 2 (CD133), and factor XIIIa-positive proliferating fibroblastic stromal cells connected by Cx43-type gap junctions. Ultrastruct Pathol 2007; 31: pp. 209-219.


Superficial Fibromatoses


Clinical Features





  • Presents as a small, slow-growing, subcutaneous nodule or thickening




    • Palmar fibromatosis (Dupuytren contracture)




      • Palmar surface of the hand; may result in contractures



      • Almost exclusively in adults, males affected more than females



      • Often bilateral, especially in alcoholics




    • Plantar fibromatosis (Ledderhose disease)




      • Plantar, non-weight-bearing area of the foot



      • Occurs in both children and adults



      • Often multinodular




    • Penile fibromatosis (Peyronie disease)




      • Dorsal aspect of the shaft of the penis



      • Exclusively seen in adults





Gross Pathology





  • Single or multiple, gray-white, firm nodules or scarlike tissue in the subcutis



Histopathology





  • Proliferative and involutional phases



  • Proliferative phase shows variably cellular fascicles of bland, spindled cells often arranged in a nodular pattern ( Figure 17.6 )




    Figure 17.6


    Superficial fibromatosis.

    Dupuytren contracture. Area of transition between cellular and collagenous zones.



  • Occasionally prominent giant cells in plantar lesions



  • Mitotic figures may be seen



  • Involutional or residual phase shows paucicellular, densely collagenized tissue



Special Stains and Immunohistochemistry





  • Noncontributory



Other Techniques for Diagnosis





  • Noncontributory



Differential Diagnosis


Desmoid Type of Fibromatosis





  • Rare in hands and feet



  • Nuclear expression of beta-catenin is not helpful to distinguish between these entities



Fibroma of Tendon Sheath





  • Well-circumscribed, sometimes multinodular mass firmly attached to tendon sheath



  • Hypocellular with bland spindle cells widely separated by hyalinized collagenous stroma



Fibrosarcoma (Infantile and Adult Types)





  • Infantile fibrosarcoma usually affects children younger than 1 year



  • Adult fibrosarcoma is only rarely found in distal extremities



  • Highly cellular, infiltrative tumor composed of uniform fibroblasts with hyperchromatic nuclei and scant cytoplasm, arranged in a distinctive herringbone pattern



  • High mitotic rate is common; atypical mitotic figures may be seen



  • Areas of necrosis or hemorrhage may be seen



Pearls





  • Superficial fibromatosis may be multifocal



  • Plantar or palmar fibromatosis may be highly cellular and mistaken for sarcoma



  • Associated conditions may include diabetes, cirrhosis, and epilepsy; some fibromatoses may have a hereditary component



  • Surgical excision is the treatment of choice





Selected References




  • Allen P.W.: The fibromatoses: a clinicopathologic classification based on 140 cases. Am J Surg Pathol 1977; 1: pp. 255-270.



  • Evans H.L.: Multinucleated giant cells in plantar fibromatosis. Am J Surg Pathol 2002; 26: pp. 244-248.



  • Montgomery E., Lee J.H., Abraham S.C., et. al.: Superficial fibromatoses are genetically distinct from deep fibromatoses. Mod Pathol 2001; 14: pp. 695-701.


Fibrous Hamartoma of Infancy


Clinical Features





  • Rapidly growing, painless subcutaneous mass in young children, sometimes congenital



  • Common sites include trunk, shoulder, axilla, and groin



  • Most cases occur within the first 2 years of life



Gross Pathology





  • Poorly defined deep dermal or subcutaneous mass



  • Gray, firm cut surface with yellow flecks



  • Usually 2 to 5 cm but may be larger



Histopathology





  • Triphasic appearance comprising an admixture of fibrous tissue, adipose tissue, and bundles of immature mesenchymal cells ( Figure 17.7 )




    Figure 17.7


    Fibrous hamartoma of infancy.

    The triphasic population of collagen fascicles, primitive myoid bundles, and fat forms a stellate lesion.



  • Often has a stellate configuration and infiltrates surrounding fat



Special Stains and Immunohistochemistry





  • Noncontributory



Other Techniques for Diagnosis





  • Noncontributory



Differential Diagnosis


Lipofibromatosis





  • Lacks a primitive mesenchymal component



Lipoblastoma





  • Lobulated mass with fat lobules separated by fibrous bands



  • Lacks a primitive mesenchymal component



  • Myxoid stroma and lipoblasts are present



Embryonal Rhabdomyosarcoma





  • Lacks fibrous and adipose tissue



  • Positive for desmin, myogenin, and MyoD1



Pearls





  • Fibrous hamartoma of infancy is a benign lesion usually cured with local excision





Selected References




  • Coffin C.M., Dehner L.P.: Fibroblastic-myofibroblastic tumors in children and adolescents: a clinicopathologic study of 108 examples in 103 patients. Pediatr Pathol 1991; 11: pp. 569-588.



  • Dickey G.E., Sotelo-Avila C.: Fibrous hamartoma of infancy: current review. Pediatr Dev Pathol 1999; 2: pp. 236-243.



  • Groisman G., Lichtig C.: Fibrous hamartoma of infancy: an immunohistochemical and ultrastructural study. Hum Pathol 1991; 22: pp. 914-918.


Lipofibromatosis


Clinical Features





  • Previously referred to as infantile fibromatosis, nondesmoid type



  • Occurs in childhood, between birth and second decade; males affected more than females



  • Slowly growing, painless mass most commonly presenting in an extremity or on the trunk; rare cases in the head and neck



  • May cause isolated macrodactyly



Gross Pathology





  • Poorly defined subcutaneous mass with admixed adipose tissue



  • Usually 1 to 3 cm



Histopathology





  • Bands of bland spindled cells and collagen traversing through mature adipose tissue ( Figure 17.8 )




    Figure 17.8


    Lipofibromatosis.

    Fascicles of bland spindle cells and collagen are admixed with mature adipose tissue.



  • Infiltrative borders



Special Stains and Immunohistochemistry





  • Noncontributory



Other Techniques for Diagnosis





  • Noncontributory



Differential Diagnosis


Fibrous Hamartoma of Infancy





  • Contains a primitive mesenchymal component



Lipoblastoma





  • Lobulated mass with fat lobules separated by fibrous bands



  • Myxoid stroma and presence of lipoblasts



Desmoid-Type Fibromatosis





  • Contains moderately cellular areas of fibrous growth, which infiltrate into fat (or skeletal muscle); adipose tissue is not a primary component



Pearls





  • Lipofibromatosis has a high rate of local recurrence but no metastatic potential



  • Wide local excision is the standard treatment





Selected References




  • Deepti A.N., Madhuri V., Walter N.M., et. al.: Lipofibromatosis: report of a rare paediatric soft tissue tumour. Skeletal Radiol 2008; 37: pp. 555-558.



  • Fetsch J.F., Miettinen M., Laskin W.B., et. al.: A clinicopathologic study of 45 pediatric soft tissue tumors with an admixture of adipose tissue and fibroblastic elements, and a proposal for classification as lipofibromatosis. Am J Surg Pathol 2000; 24: pp. 1491-1500.



  • Kenney B., Richkind K.E., Friedlaender G., et. al.: Chromosomal rearrangements in lipofibromatosis. Cancer Genet Cytogenet 2007; 179: pp. 136-139.


Calcifying Aponeurotic Fibroma


Clinical Features





  • Also known as juvenile aponeurotic fibroma or Keasbey tumor



  • Most commonly affects children but may also occur in adults



  • Presents as a slow-growing, painless mass, usually on the palmar or plantar surfaces of the hands or feet, rarely in other locations



Gross Pathology





  • Poorly circumscribed, firm, gray-white, rubbery nodule usually smaller than 3 cm



  • Gritty cut surface



Histopathology





  • Bland oval plump fibroblasts in a heavily collagenized stroma



  • Foci of stippled to confluent amorphous calcifications surrounded by rounded chondrocyte-like cells ( Figure 17.9 )




    Figure 17.9


    Calcifying aponeurotic fibroma.

    Nodular calcifications are surrounded by chondrocyte-like cells with intervening spindle cells in a hyalinized stroma.



  • Infiltrative margins with extension into adipose tissue



  • Osteoclast-like giant cells may be associated with calcification



Special Stains and Immunohistochemistry





  • Noncontributory



Other Techniques for Diagnosis





  • Noncontributory



Differential Diagnosis


Fibromatosis (Palmar, Plantar)





  • Characterized by fascicles of spindled uniform-appearing fibroblasts with varying amount of collagen



  • Growth along fascial planes and tendons



  • Absence of calcification or chondroid differentiation



  • Usually found in adults, but plantar fibromatosis occasionally seen in children



Chondroma of Soft Tissue





  • Typically occurs in hands of adults



  • Characteristically a lobulated lesion composed of mature hyaline cartilage



  • “Chondroblastoma-like” variant undergoes calcification in a diffuse pericellular rather than in a focal manner



Pearls





  • Calcifying aponeurotic fibroma is a locally aggressive lesion characterized by local recurrence (> 50% recur)



  • Younger lesions are less heavily calcified, and older lesions show more extensive calcification and chondroid differentiation



  • Surgical excision is the preferred treatment





Selected References




  • Allen P.W., Enzinger F.M.: Juvenile aponeurotic fibroma. Cancer 1970; 26: pp. 857-867.



  • Coffin C.M., Dehner L.P.: Fibroblastic-myofibroblastic tumors in children and adolescents: a clinicopathologic study of 108 examples in 103 patients. Pediatr Pathol 1991; 11: pp. 569-588.



  • Fetsch J.F., Miettinen M.: Calcifying aponeurotic fibroma: a clinicopathologic study of 22 cases arising in uncommon sites. Hum Pathol 1998; 29: pp. 1504-1510.


Fibroma of Tendon Sheath


Clinical Features





  • Most commonly affects the hands of young to middle-aged adults; slight male predominance



  • Presents as a slow-growing, painless mass, usually on the preaxial digits or wrist but may affect foot or knee joint



Gross Pathology





  • Circumscribed, firm, gray-white, lobulated nodule attached to the tendon, usually smaller than 3 cm



  • Fibrous, often multinodular cut surface separated by clefts



Histopathology





  • Spindled to stellate cells embedded in a collagenous stroma, sometimes myxoid



  • Clefted, pseudovascular spaces separate the nodules ( Figure 17.10 )




    Figure 17.10


    Fibroma of tendon sheath.

    Slitlike pseudovascular spaces are present between hypocellular, collagenous nodules.



  • Degenerative cytologic atypia may be present; giant cells are rare



Special Stains and Immunohistochemistry





  • Noncontributory



Other Techniques for Diagnosis





  • Noncontributory



Differential Diagnosis


Giant Cell Tumor of Tendon Sheath





  • Numerous giant cells, plump mononuclear cells, and variable amounts of xanthoma cells



Superficial Fibromatosis (Palmar, Plantar)





  • Growth along fascial planes and tendons with infiltrative borders



Pearls





  • Fibroma of tendon sheath is benign and typically cured by surgical excision; recurrence is rare





Selected References




  • Maluf H.M., DeYoung B.R., Swanson P.E., et. al.: Fibroma and giant cell tumor of tendon sheath: a comparative histological and immunohistological study. Mod Pathol 1995; 8: pp. 155-159.



  • Pulitzer D.R., Martin P.C., Reed R.J.: Fibroma of tendon sheath: a clinicopathologic study of 32 cases. Am J Surg Pathol 1989; 13: pp. 472-479.



  • Sciot R., Samson I., van den Berghe H., et. al.: Collagenous fibroma (desmoplastic fibroblastoma): genetic link with fibroma of tendon sheath?. Mod Pathol 1999; 12: pp. 565-568.


Collagenous Fibroma


Clinical Features





  • Also known as desmoplastic fibroblastoma



  • Most commonly presents as slow growing painless mass in subcutaneous or deep tissues of upper extremities



  • The majority occur in late adulthood but can occur in childhood



Gross Pathology





  • Well-circumscribed mass, usually less than 5 cm ( Figure 17.11A )




    Figure 17.11


    Collagenous fibroma.

    A, Gross photos showing lobulated, smooth surface with a thin fibrous pseudocapsule (left) , and cut surface showing a white, fibrous, to edematous/myxoid areas. B, Bland to mildly activated fibroblasts with elongated or stellate morphology are sparsely distributed in stroma with a predominantly lightly collagenized appearance.



  • Cut surface gray-white with a lobulated or whorled appearance



Histopathology





  • Hypocellular spindle to stellate cell mass embedded in a loose collagenous stroma ( Figure 17.11B )



  • Mitotic figures are typically not seen



Special Stains and Immunohistochemistry





  • Noncontributory



Other Techniques for Diagnosis





  • Noncontributory



Differential Diagnosis


Desmoid Fibromatosis





  • Typically seen in younger patients



  • Fascicular growth pattern with infiltrative borders that entrap connective tissues



  • Nuclear immunoreactivity for beta-catenin usually seen



Pearls





  • Surgical resection is the standard treatment, typically does not recur



  • May have a genetic link to fibroma of tendon sheath





Selected References




  • Evans H.L.: Desmoplastic fibroblastoma: a report of seven cases. Am J Surg Pathol 1995; 19: pp. 1077-1081.



  • Macchia G., Trombetta D., Moller E., et. al.: FOSL1 as a candidate target gene for 11q12 rearrangements in desmoplastic fibroblastoma. Lab Invest 2012; 92: pp. 735-743.



  • Miettinen M., Fetsch J.F.: Collagenous fibroma (desmoplastic fibroblastoma): a clinicopathologic analysis of 63 cases of a distinctive soft tissue lesion with stellate-shaped fibroblasts. Hum Pathol 1998; 29: pp. 676-682.



  • Nishio J., Akiho S., Iwasaki H., et. al.: Translocation t(2;11) is characteristic of collagenous fibroma (desmoplastic fibroblastoma). Cancer Genet 2011; 204: pp. 569-571.


Myofibroma/Myopericytoma and Myofibromatosis


Clinical Features





  • Also known as infantile congenital myofibromatosis or congenital myofibromatosis in children



  • Most common fibrous tumor of infancy



  • About 90% occur within the first 2 years of life; however, adults may be affected



  • Myofibroma refers to a solitary lesion (common), whereas myofibromatosis denotes multiple skin and soft tissue lesions with variable visceral involvement




    • Solitary subcutaneous nodules typically involve the head and neck but can occur anywhere



    • Multicentric form may involve the lungs, heart, bones, and gastrointestinal (GI) tract




Gross Pathology





  • Cut surface is rubbery gray-white with a lobulated or whorled appearance



  • May have central necrosis or cyst formation



  • Margins may be well defined or focally infiltrative



  • Size from 0.5 cm up to 8 cm



Histopathology





  • Typically shows a biphasic pattern or zonal phenomenon




    • Peripheral areas show fascicular or whorled growth of plump, spindled cells with eosinophilic cytoplasm (myofibroblasts)



    • Central areas of the lesion are more cellular with oval cells and a staghorn-appearing, hemangiopericytoma-like vasculature ( Figure 17.12 )




      Figure 17.12


      Myofibroma.

      Plump, bland ovoid cells are arranged around curved, slitlike vascular channels in the central zone of this tumor.




  • Variable mitotic activity but no atypical division figures



  • Scattered lymphoplasmacytic infiltrate typically present



  • Polypoid protrusion into vascular spaces is typical at the edge of the lesion



  • Focal areas of hemorrhage, calcification, and necrosis may be seen centrally



  • May be well circumscribed or infiltrative



Special Stains and Immunohistochemistry





  • SMA and MSA positive



  • Desmin variable



  • Immunohistochemistry does not help to exclude other myofibroblastic or smooth muscle proliferations



Other Techniques for Diagnosis





  • Noncontributory aside from ruling out other selected lesions such as infantile fibrosarcoma



Differential Diagnosis


Angioleiomyoma





  • Occurs in skin and subcutis of adults



  • Less cellular with more complete smooth muscle differentiation



Pearls





  • Patients with solitary and multiple lesions of myofibroma or myofibromatosis confined to soft tissues have an excellent prognosis; visceral involvement imparts a worse prognosis depending on the particular locations and extent of growth



  • Bilateral symmetric bone lesions are a radiographic clue to diagnosis in infants



  • Lesions may spontaneously regress



  • Surgical resection is the standard treatment





Selected References




  • Chung E.B., Enzinger F.M.: Infantile myofibromatosis. Cancer 1981; 48: pp. 1807-1818.



  • Coffin C.M., Dehner L.P.: Fibroblastic-myofibroblastic tumors in children and adolescents: a clinicopathologic study of 108 examples in 103 patients. Pediatr Pathol 1991; 11: pp. 569-588.



  • Daimaru Y., Hashimoto H., Enjoji M.: Myofibromatosis in adults (adult counterpart of infantile myofibromatosis). Am J Surg Pathol 1989; 13: pp. 859-865.



  • Zand D.J., Huff D., Everman D., et. al.: Autosomal dominant inheritance of infantile myofibromatosis. Am J Med Genet 2004; 126: pp. 261-266.


Gardner Fibroma


Clinical Features





  • Benign lesion of childhood and early adulthood that has a strong association with desmoid-type fibromatosis and familial adenomatous polyposis (Gardner syndrome)



  • Poorly defined, plaquelike soft tissue mass in superficial and deep tissues of back and paraspinal region, head and neck, extremities, and chest



Gross Pathology





  • Ill-defined firm mass with a white-gray, rubbery cut surface



  • Ranges in size from 1 to 12 cm



Histopathology





  • Sheets of densely hyalinized bundles of collagen containing scant, small spindle cells ( Figure 17.13 )




    Figure 17.13


    Gardner fibroma.

    This tumor of low cellularity has small, bland fibroblasts and heavy collagenization with cracks between collagen bundles. Entrapped adipocytes are present.



  • Collagen fibers are separated by cracks or clefts



  • Infiltrative borders are seen with entrapped connective tissue



Special Stains and Immunohistochemistry





  • CD34 positive



  • β-Catenin: most are positive with nuclear labeling



Other Techniques for Diagnosis





  • Noncontributory



Differential Diagnosis


Desmoid-Type Fibromatosis





  • More cellular spindle cell proliferation with fascicular growth pattern



Nuchal Fibroma





  • Bundles of hyalinized collagen with entrapped adnexal structures and connective tissues



  • Frequently has proliferation of small nerves similar to traumatic neuroma



  • Distinct clinical presentation, occurs in the posterior neck of middle-aged adults (males affected more than females); associated with diabetes mellitus in about half of cases



  • CD34 and β-catenin stains typically negative



Elastofibroma





  • Densely eosinophilic elastic fibers intermixed with collagen as highlighted with the Verhoeff–van Gieson elastic stain



  • Occurs in older patients, frequently in subscapular location



  • Not associated with familial adenomatous polyposis



Pearls





  • Gardner fibroma may be the first presentation of familial adenomatous polyposis (Gardner syndrome)



  • About half of patients will develop desmoid-type fibromatosis



  • Surgical resection is the standard treatment





Selected References




  • Allen P.W.: Nuchal-type fibroma appearance in a desmoid fibromatosis. Am J Surg Pathol 2001; 25: pp. 828-829.



  • Coffin C.M., Hornick J.L., Zhou H., et. al.: Gardner fibroma: a clinicopathologic and immunohistochemical analysis of 45 patients with 57 fibromas. Am J Surg Pathol 2007; 31: pp. 410-416.



  • Wehrli B.M., Weiss S.W., Yandow S., et. al.: Gardner-associated fibromas (GAF) in young patients: a distinct fibrous lesion that identifies unsuspected Gardner syndrome and risk for fibromatosis. Am J Surg Pathol 2001; 25: pp. 645-651.


Desmoid-Type Fibromatosis


Clinical Features





  • Also referred to as aggressive or deep fibromatosis



  • Relatively common neoplasm that typically occurs in adolescents and young adults, but age range is wide



  • Comprises a group of proliferative tumors that present as deep-seated masses



  • Shoulder region, chest wall, thigh, and mesentery are favored sites




    • Musculoaponeurotic fibromatosis



    • Abdominal fibromatosis



    • Mesenteric fibromatosis




      • Lesions are associated intimately with muscular aponeuroses



      • Rectus muscle is the favored location



      • Occurs almost exclusively in women who are pregnant or postpartum



      • Found in mesentery of the bowel or retroperitoneum



      • Often associated with previous history of abdominal surgery



      • May be associated with Gardner syndrome (familial adenomatous polyposis, mesenteric fibromatosis, osteomas, and multiple epidermal inclusion cysts)





Gross Pathology





  • May appear well defined but actually has infiltrative margins



  • Often grows along fascial planes



  • Firm tumor that often has a gritty cut surface



  • Sectioning reveals a glistening, white, trabeculated surface



Histopathology





  • Composed of uniform-appearing, spindle-shaped fibroblasts and abundant collagen ( Figure 17.14 )




    Figure 17.14


    Desmoid-type fibromatosis.

    This area shows intermediate cellularity with bland fibroblasts and myofibroblasts in a collagenous to edematous stroma. Immunostain for β-catenin (inset) shows nuclear and cytoplasmic reactivity in many of the cells.



  • Infiltrative margins



  • Occasional mitotic figures are present in more cellular areas



  • Inconspicuous vasculature



  • Myxoid matrix may be seen, primarily in abdominal fibromatosis



Special Stains and Immunohistochemistry





  • β-Catenin: positive nuclear immunoreactivity



  • SMA positive



Other Techniques for Diagnosis





  • Recurrent chromosomal abnormalities include trisomies 8 and 20 and loss of 5q, not usually needed for diagnosis; CTNNB1 gene sequencing may identify mutations with prognostic relevance.



Differential Diagnosis


Low-Grade Fibromyxoid Sarcoma





  • Alternating collagenized and myxoid zones with prominent curvilinear vessels



  • May contain hyaline collagen rosettes



  • Negative for nuclear β-catenin; positive for MUC4



  • Presence of t(7;16)(q33;p11), producing an FUS-CREB3L2 fusion in molecular or cytogenetic analysis



Fibrosarcoma (Infantile and Adult Types)





  • Most commonly affects children younger than 1 year; occasionally seen in adults



  • Highly cellular, infiltrative tumor composed of fibroblasts with hyperchromatic nuclei and scant cytoplasm arranged in a herringbone pattern



  • Mitoses are obvious, and atypical mitotic figures may be seen



  • Areas of necrosis or hemorrhage may be present



  • Infantile fibrosarcoma harbors t(12;15)(p13;q26), producing an ETV6-NTRK fusion demonstrable by molecular or cytogenetic studies



Pearls





  • Desmoid-type fibromatosis has a high recurrence rate and may be locally aggressive but has no metastatic potential



  • Surgical removal is controversial for most cases due to high recurrence rate



  • Recurrence rate ranges between 25% and 80%





Selected References




  • Bhattacharya B., Dilworth H.P., Iacobuzio-Donahue C., et. al.: Nuclear beta-catenin expression distinguishes deep fibromatosis from other benign and malignant fibroblastic and myofibroblastic lesions. Am J Surg Pathol 2005; 29: pp. 653-659.



  • Carlson J.W., Fletcher C.D.: Immunohistochemistry for beta-catenin in the differential diagnosis of spindle cell lesions: analysis of a series and review of the literature. Histopathology 2007; 51: pp. 509-514.



  • De Wever I., Dal Cin P., Fletcher C.D., et. al.: Cytogenetic, clinical, and morphologic correlations in 78 cases of fibromatosis: a report from the CHAMP Study Group. CHromosomes And Morphology. Mod Pathol 2000; 13: pp. 1080-1085.


Calcifying Fibrous Tumor


Clinical Features





  • Benign fibrous tumor that occurs predominantly in adolescents and young adults



  • Most common in subcutaneous and deep soft tissues of extremities, trunk, groin, and neck but has been described in many locations, including viscera



Gross Pathology





  • Typically a circumscribed solid mass, 3 to 5 cm, but may be larger



  • Cut surface is solid, firm, and gray-white



Histopathology





  • Hypocellular, sclerotic tissue with a sparse lymphoplasmacytic infiltrate and discrete calcifications ( Figure 17.15 )




    Figure 17.15


    Calcifying fibrous tumor.

    Paucicellular, sclerotic lesion contains lymphoplasmacytic infiltrate and psammomatous calcifications.



  • Calcification may be psammomatous or dystrophic



  • Germinal center formation may be seen at lesion periphery



Special Stains and Immunohistochemistry





  • Noncontributory



Other Techniques for Diagnosis





  • Noncontributory



Differential Diagnosis


Desmoid-Type Fibromatosis





  • Characterized by fascicles of spindle-shaped fibroblasts with varying amounts of collagen and infiltrative borders



  • More cellular than calcifying fibrous tumor. Lacks significant calcification



  • Positive for β-catenin nuclear reactivity in most cases



Calcifying Aponeurotic Fibroma





  • Typically seen on hands and feet of young children



  • Stippled calcification with surrounding chondroid differentiation



  • Infiltrative margins



  • Inflammation not typical



Pearls





  • Calcifying fibrous tumor is a benign lesion with rare reports of recurrence



  • Treatment is complete surgical resection





Selected References




  • Hill K.A., Gonzalez-Crussi F., Chou P.M.: Calcifying fibrous pseudotumor versus inflammatory myofibroblastic tumor: a histological and immunohistochemical comparison. Mod Pathol 2001; 14: pp. 784-790.



  • Kirby P.A., Sato Y., Tannous R., et. al.: Calcifying fibrous pseudotumor of the myocardium. Pediatr Dev Pathol 2006; 9: pp. 384-387.



  • Lau S.K., Weiss L.M.: Calcifying fibrous tumor of the adrenal gland. Hum Pathol 2007; 38: pp. 656-659.



  • Nascimento A.F., Ruiz R., Hornick J.L., et. al.: Calcifying fibrous “pseudotumor”: clinicopathologic study of 15 cases and analysis of its relationship to inflammatory myofibroblastic tumor. Int J Surg Pathol 2002; 10: pp. 189-196.


Inflammatory Myofibroblastic Tumor


Clinical Features





  • Previously known as inflammatory pseudotumor and plasma cell granuloma



  • Most often occurs in children and young adults but has a wide age range



  • Commonly seen in the lung; the most frequent extrapulmonary sites are mesentery and omentum, but it can involve any location



  • Systemic symptoms and signs may be present, including fever, weight loss, anemia, increased erythrocyte sedimentation rate, and elevated C-reactive protein levels



Gross Pathology





  • Typically circumscribed, but nonencapsulated; often multinodular



  • Cut surface is solid, firm, and gray-white



Histopathology





  • Variably cellular tumor comprised of spindle cells and mixed inflammatory cells in a myxoid or collagenized background ( Figure 17.16 )




    Figure 17.16


    Inflammatory myofibroblastic tumor.

    Loose fascicles of plump myofibroblasts with admixed inflammatory cells are present. Immunostain for ALK1 (inset) shows membranous and cytoplasmic reactivity in this case.



  • Some lesions contain large histiocytoid ganglion-like cells



  • May be hypocellular and resemble scars



  • Mitotic figures may be numerous



Special Stains and Immunohistochemistry





  • Variably positive for smooth muscle markers



  • ALK-1 protein present in about 40% of cases, more frequently in childhood tumors



Other Techniques for Diagnosis





  • Rearrangement of ALK locus at 2p23 by molecular or cytogenetic analysis



Differential Diagnosis


Leiomyosarcoma





  • Characterized by fascicles of cytologically atypical spindle cells with hyperchromatic nuclei and variable but present mitotic activity



  • May have inflammatory infiltrate, usually patchy



  • Typically, middle-aged and elderly adults are affected



Desmoid-Type Fibromatosis





  • Fascicles of spindle-shaped fibroblasts with variable amounts of collagen and infiltrative borders



  • Positive for β-catenin with nuclear labeling in most cases



  • Lacks inflammatory infiltrate



Embryonal Rhabdomyosarcoma





  • Primitive spindle cells, usually in a myxoid background; focal strap cells may be present



  • Usually lacks inflammation



  • Positive for desmin, myogenin, and MyoD1



Inflammatory Pleomorphic Undifferentiated Sarcoma





  • Usually occurs in older adults; retroperitoneum is the most common location



  • Cases with associated liposarcoma or MDM2 amplification are best classified as dedifferentiated liposarcoma



  • Atypical hyperchromatic cells with prominent mixed inflammation rich in xanthomatous cells



  • Negative for SMA and ALK-1



Metastatic Sarcomatoid Carcinoma





  • Usually supported by clinical history or imaging, with similar histology as primary



  • May have areas of squamous differentiation



  • At least focally positive for keratin, EMA, MOC31, or p63



Spindle Cell Melanoma





  • Variably cellular spindle cell lesion with variable cellular pleomorphism, prominent nucleoli, and nuclear pseudoinclusions



  • May show perineural invasion extending beyond the tumoral component



  • Positive for S100 protein, Sox10; rarely for tyrosinase, Melan-A, or HMB-45



Pearls





  • Inflammatory myofibroblastic tumor is a neoplastic process



  • Treatment is based on surgical resection



  • May recur after excision





Selected References




  • Coffin C.M., Dehner L.P., Meis-Kindblom J.M.: Inflammatory myofibroblastic tumor, inflammatory fibrosarcoma, and related lesions: an historical review with differential diagnostic considerations. Semin Diagn Pathol 1998; 15: pp. 102-110.



  • Coffin C.M., Hornick J.L., Fletcher C.D.: Inflammatory myofibroblastic tumor: comparison of clinicopathologic, histologic, and immunohistochemical features including ALK expression in atypical and aggressive cases. Am J Surg Pathol 2007; 31: pp. 509-520.



  • Cook J.R., Dehner L.P., Collins M.H., et. al.: Anaplastic lymphoma kinase (ALK) expression in the inflammatory myofibroblastic tumor: a comparative immunohistochemical study. Am J Surg Pathol 2001; 25: pp. 1364-1371.


Solitary Fibrous Tumor


Clinical Features





  • Typically occurs in middle-aged adults but has a wide age range



  • Includes cases previously called hemangiopericytoma (except nasal type)



  • Presents as a localized, slow-growing, painless mass



  • Most commonly involves the pleura; extrapleural sites include subcutaneous and deep soft tissues, orbit, retroperitoneum, mediastinum, pericardium, and other locations



Gross Pathology





  • Ranges in size from 1 to 27 cm



  • Typically well circumscribed with a firm, tan-white cut surface; sometimes multinodular



  • Focal necrosis, hemorrhage, and cystic degeneration may be seen



Histopathology





  • Characterized by uniform spindle cells haphazardly arranged in a collagenized background ( Figure 17.17 ); collagen focally surrounds individual cells




    Figure 17.17


    Solitary fibrous tumor.

    Monotonous ovoid and spindle tumor cells arranged around a hyalinized vasculature.



  • Hypercellular and hypocellular, collagenous areas (so called “patternless pattern”)



  • “Hemangiopericytoma-like” open, staghorn-shaped, and hyalinized blood vessels



  • Epithelioid areas may be present



  • Low mitotic activity (<4 mitotic figures/10 high-power fields)



  • Criteria for malignancy include dense cellularity, numerous mitotic figures, obvious cytologic atypia, necrosis, and infiltrative growth; “dedifferentiation” (transformation to high-grade sarcoma) has been reported



Special Stains and Immunohistochemistry





  • CD34 positive in about 85% of cases, CD99 and bcl-2 positive in about 75% of cases



  • Nuclear immunoreactivity for STAT6 in 98% of cases




    • STAT6 staining may be lost with transformation to high grade




Other Techniques for Diagnosis





  • Genomic inversion at 12q13 leading to fusion NAB2-STAT6 in majority of cases



Differential Diagnosis


Spindle Cell-Rich (Cellular Fibrous) Zone of Atypical Lipomatous Tumor





  • Lipomatous area may not be appreciated if incompletely sampled



  • Shows MDM2 and CDK4 amplification/expression. Lacks STAT6 translocation, but may show STAT6 expression



Synovial Sarcoma





  • Monophasic spindle cell or biphasic spindle cell and epithelioid tumors with high nuclear-to-cytoplasmic ratios



  • Herringbone growth pattern is common, but areas may resemble solitary fibrous tumor (SFT)



  • Mitotic activity is usually easily seen



  • Intratumoral calcifications and metaplastic bone are sometimes present



  • Immunoreactive for keratin or TLE1, EMA, CD99, and bcl-2; CD34 negative



Pearls





  • Solitary fibrous tumor can occur at any location



  • Has “patternless pattern” of spindle cells with hemangiopericytoma-like vasculature



  • Usually behaves in an indolent manner but may recur or metastasize even if histologically banal; borderline tumor



  • Surgical resection is the preferred treatment





Selected References




  • Dagrada G.P., Spagnuolo R.D., Mauro V.: Solitary fibrous tumors: loss of chimeric protein expression and genomic instability mark dedifferentiation. Mod Pathol 2015; 28: pp. 1074-1083.



  • Doyle L.A., Vivero M., Fletcher C.D., et. al.: Nuclear expression of STAT6 distinguishes solitary fibrous tumor from histologic mimics. Mod Pathol 2014; 27: pp. 390-395.



  • Mohajeri A., Tayebwa J., Collin A., et. al.: Comprehensive genetic analysis identifies a pathognomonic NAB2/STAT6 fusion gene, nonrandom secondary genomic imbalances, and a characteristic gene expression profile in solitary fibrous tumor. Genes Chromosomes Cancer 2013; 52: pp. 873-886.



  • Mosquera J.M., Fletcher C.D.: Expanding the spectrum of malignant progression in solitary fibrous tumors: a study of 8 cases with a discrete anaplastic component: is this dedifferentiated SFT?. Am J Surg Pathol 2009; 33: pp. 1314-1321.


Hemosiderotic Fibrolipomatous Tumor and Myxoinflammatory Fibroblastic Sarcoma


Clinical Features





  • Hemosiderotic fibrolipomatous tumor (HFLT; also known as hemosiderotic fibrohistiocytic lipomatous lesion ) and myxoinflammatory fibroblastic sarcoma (MIFS) are discussed together due to their clinicopathologic and molecular similarities; hybrid tumors have been reported



  • Presents as a localized, slow-growing, infiltrative mass of the distal extremities




    • HFLT is most common in the subcutis of the dorsum of the foot and ankle



    • MIFS is usually on the hands and is locally infiltrative into synovium and tendons




  • Adults are affected more often than children, and HFLT is more common in women



Gross Pathology





  • Ranges in size from 1 to 20 cm and has infiltrative borders



  • Tan to yellow cut section but may be gelatinous or fatty; hemorrhage may be present



Histopathology





  • HFLT is characterized by spindle cells admixed with mature adipose tissue




    • Abundant hemosiderin-laden macrophages and scattered inflammatory cells are present in the spindle cell component ( Figure 17.18A )




      Figure 17.18


      Hemosiderotic fibrolipomatous tumor/myxoinflammatory fibroblastic sarcoma; a case with mixed histology from the ankle of an adult woman.

      A, A fibrohistiocytic and adipocytic proliferation with abundant hemosiderin deposition is present. B, Other areas show a myxoid matrix with lipoblast-like tumor cells.




  • MIFS is heterogenous with a myxoid component containing pseudolipoblasts, neutrophils and lymphocytes, and a bland spindle cell proliferation ( Figure 17.18B )




    • Large ganglion celllike or Reed-Sternberg–like cells with prominent nucleoli are present in MIFS



    • Low mitotic activity (<3 mitotic figures/10 high-power fields)




Special Stains and Immunohistochemistry





  • CD34 immunoreactivity in the spindle cell component in both HFLT and MIFS



  • SMA, desmin, and S100 are negative



Other Techniques for Diagnosis





  • Presence of t(1;10) (p22;q24) producing a TGFBR3-MGEA5 fusion has been reported in both HFLT and MIFS (as well as pleomorphic hyalinizing angiectatic tumor)



Differential Diagnosis


Atypical Lipomatous Tumor/Well-Differentiated Liposarcoma





  • Presents in the retroperitoneum and deep soft tissues of proximal extremities



  • Typically lacks prominent spindle cell component; variation in size of adipocytes and lipoblasts may be present



  • Morphology of dedifferentiated, inflammatory areas resemble MIFS



  • The large hyperchromatic nuclei in scattered cells of typical atypical lipomatous tumor (ALT) lack prominent nucleoli



  • Lacks prominent hemosiderin deposition



  • MDM2 and CDK4 amplification and expression



Inflammatory Pleomorphic Undifferentiated Sarcoma





  • Usually occurs in older adults; retroperitoneum is the most common location



  • Some cases best classified as dedifferentiated liposarcoma if associated liposarcoma or MDM2 amplification is found



  • Atypical hyperchromatic cells with prominent mixed inflammation rich in xanthomatous cells



Plexiform Fibrohistiocytic Tumor





  • Dermal/subcutaneous mass in the extremities of young adults



  • Distinct nodules composed of mononuclear histiocytoid cells, osteoclast-like giant cells, and fibroblasts in whorls or fascicles



  • Hemorrhage may be present



Myxofibrosarcoma





  • Usually more proximal extremity



  • Lacks granulation tissue-like areas with dense inflammatory cell infiltrate



Pearls





  • HFLT and MIFS are genetically linked tumors



  • Considered benign but locally aggressive, with up to a 50% recurrence rate



  • Metastasis is rare and more common in those with MIFS histology, and dedifferentiation of HFLT has been reported





Selected References




  • Antonescu C.R., Zhang L., Nielsen G.P., et. al.: Consistent t(1;10) with rearrangements of TGFBR3 and MGEA5 in both myxoinflammatory fibroblastic sarcoma and hemosiderotic fibrolipomatous tumor. Genes Chromosomes Cancer 2011; 50: pp. 757-764.



  • Elco C.P., Marino-Enriquez A., Abraham J.A., et. al.: Hybrid myxoinflammatory fibroblastic sarcoma/hemosiderotic fibrolipomatous tumor: report of a case providing further evidence for a pathogenetic link. Am J Surg Pathol 2010; 34: pp. 1723-1727.



  • Laskin W.B., Fetsch J.F., Miettinen M.: Myxoinflammatory fibroblastic sarcoma: a clinicopathologic analysis of 104 cases, with emphasis on predictors of outcome. Am J Surg Pathol 2014; 38: pp. 1-12.



  • Solomon D.A., Antonescu C.R., Link T.M., et. al.: Hemosiderotic fibrolipomatous tumor, not an entirely benign entity. Am J Surg Pathol 2013; 37: pp. 1627-1630.



  • Weiss V.L., Antonescu C.R., Alaggio R., et. al.: Myxoinflammatory fibroblastic sarcoma in children and adolescents: clinicopathologic aspects of a rare neoplasm. Pediatr Dev Pathol 2013; 16: pp. 425-431.



  • Wettach G.R., Boyd L.J., Lawce H.J., et. al.: Cytogenetic analysis of a hemosiderotic fibrolipomatous tumor. Cancer Genet Cytogenet 2008; 182: pp. 140-143.


Low-Grade Fibromyxoid Sarcoma


Clinical Features





  • Also known as Evans tumor. One variant originally termed “hyalinizing spindle cell tumor with giant rosettes”



  • Typically seen in young adults but can occur in children and elderly



  • Deep soft tissue mass most often in proximal extremities or trunk



  • May be present for several years before diagnosis



Gross Pathology





  • Usually a large and nonencapsulated but well-circumscribed mass



  • Cut surface is firm, white, or tan, sometimes with a myxoid appearance



Histopathology





  • Bland fusiform cells with variably collagenous to myxoid stroma ( Figure 17.19 )




    Figure 17.19


    Low-grade fibromyxoid sarcoma.

    This bland spindle cell tumor with low cellularity shows variably myxoid to collagenous stroma.



  • Collagenized areas are arranged in short haphazard fascicles



  • A whorling growth pattern, myxoid nodules, and a prominent arcade of hyalinized vessels may be present



  • Rosettes may be present, characterized by hyalinized nodules cuffed by tumor cells



  • Mitotic figures are absent or sparse



  • May be seen as a hybrid with sclerosing epithelioid fibrosarcoma or less commonly with an undifferentiated round cell component



Special Stains and Immunohistochemistry





  • Immunoreactive toward MUC4



  • Variably positive for EMA, SMA, desmin, and CD34



Other Techniques for Diagnosis





  • Presence of t(7;16)(q34;p11), producing an FUS-CREBL2 fusion, can be demonstrated by cytogenetic or molecular analysis in most cases



Differential Diagnosis


Desmoid-Type Fibromatosis





  • May be indistinguishable on routine morphology, especially in small samples



  • Usually shows nuclear beta-catenin



  • Lacks MUC4 expression and FUS-CREBL2 fusion



Spindle Cell-Rich (Cellular Fibrous) Zone of Atypical Lipomatous Tumor





  • Lipomatous area may not be appreciated if incompletely sampled



  • Shows MDM2 amplification



Myxoma (“Cellular Variant”)





  • Less cellular overall than low-grade fibromyxoid sarcoma (LGFMS)



  • Less collagenous, even in most fibrous areas



  • GNAS mutations present, as in typical myxoma



Low-Grade Myxofibrosarcoma





  • Almost exclusively myxoid with prominent thin-walled vessels



  • Mild cytologic atypia and pseudolipoblasts



  • Older patients



Myxoid Neurofibroma





  • Lacks zonation



  • Slender, wavy nuclei with tapered ends



  • Positive for S100 protein, CD56, and CD57



Pearls





  • Recurrence is common if incompletely excised



  • Metastatic rate varies widely in case series reports, with average interval of 5 years, and up to 45





Selected References




  • Billings S.D., Giblen G., Fanburg-Smith J.C.: Superficial low-grade fibromyxoid sarcoma (Evans tumor): a clinicopathologic analysis of 19 cases with a unique observation in the pediatric population. Am J Surg Pathol 2005; 29: pp. 204-210.



  • Doyle L.A., Moller E., Dal Cin P., et. al.: MUC4 is a highly sensitive and specific marker for low-grade fibromyxoid sarcoma. Am J Surg Pathol 2011; 35: pp. 733-741.



  • Evans H.L.: Low-grade fibromyxoid sarcoma: a clinicopathologic study of 33 cases with long-term follow-up. Am J Surg Pathol 2011; 35: pp. 1450-1462.



  • Evans H.L.: Low-grade fibromyxoid sarcoma: a report of 12 cases. Am J Surg Pathol 1993; 17: pp. 595-600.



  • Guillou L., Benhattar J., Gengler C., et. al.: Translocation-positive low-grade fibromyxoid sarcoma: clinicopathologic and molecular analysis of a series expanding the morphologic spectrum and suggesting potential relationship to sclerosing epithelioid fibrosarcoma: a study from the French Sarcoma Group. Am J Surg Pathol 2007; 31: pp. 1387-1402.



  • Rekhi B., Deshmukh M., Jambhekar N.A.: Low-grade fibromyxoid sarcoma: a clinicopathologic study of 18 cases, including histopathologic relationship with sclerosing epithelioid fibrosarcoma in a subset of cases. Ann Diagn Pathol 2011; 15: pp. 303-311.


Low-Grade Myofibroblastic Sarcoma


Clinical Features





  • Also known as myofibrosarcoma



  • Distinctive low-grade tumor with myofibroblastic differentiation



  • Tumor of middle-aged adults, rarely reported in children



  • Most commonly involves head and neck



Gross Pathology





  • Firm mass with white cut surface and poorly defined margins



Histopathology





  • Moderately cellular spindle cell lesion arranged in fascicles and whorls ( Figure 17.20 )




    Figure 17.20


    Low-grade myofibroblastic sarcoma.

    Fascicles of fibroblasts with low to moderate cellularity are present. Mild cytologic atypia is evident on higher magnification (inset) . Scattered inflammatory cells are present in this example.



  • Modest nuclear hyperchromasia and mild cellular pleomorphism



  • Infiltrates adjacent tissues



  • Mitotic figures are variable in number



Special Stains and Immunohistochemistry





  • Desmin, MSA, SMA: at least one is positive



Other Techniques for Diagnosis





  • Noncontributory



Differential Diagnosis


Desmoid-Type Fibromatosis





  • Lacks cellular pleomorphism



  • Positive for β-catenin with nuclear labeling in most cases



Low-Grade Fibromyxoid Sarcoma





  • Hypocellular myxoid areas and collagenized foci



  • Possible presence of hyalinizing rosettes



  • Presence of t(7;16)(q34;p11), producing an FUS-CREBL2 fusion, is characteristic



Pearls





  • Wide surgical resection is necessary for low-grade myofibroblastic sarcoma



  • Local recurrence is common; metastases are rare but may be seen after many years





Selected References




  • Cai C., Dehner L.P., El-Mofty S.K.: In myofibroblastic sarcomas of the head and neck, mitotic activity and necrosis define grade: a case study and literature review. Virchows Arch 2013; 463: pp. 827-836.



  • Fisher C.: Myofibrosarcoma. Virchows Arch. 2004; 445: pp. 215-223.



  • Gonzalez-Campora R., Escudero A.G., Rios Martin J.J., et. al.: Myofibrosarcoma (low-grade myofibroblastic sarcoma) with intracytoplasmic hyaline (fibroma-like) inclusion bodies. Ultrastruct Pathol 2003; 27: pp. 7-11.



  • Mentzel T., Dry S., Katenkamp D., et. al.: Low-grade myofibroblastic sarcoma: analysis of 18 cases in the spectrum of myofibroblastic tumors. Am J Surg Pathol 1998; 22: pp. 1228-1238.


Infantile Fibrosarcoma


Clinical Features





  • Occurs primarily in children younger than 2 years; about 25% are congenital



  • Most common on extremities, followed by trunk and head and neck



  • May mimic a vascular lesion both clinically and radiographically; large “hemangiomas” in young children should undergo biopsy if they enlarge



Gross Pathology





  • Infiltrative borders



  • Firm, fleshy, lobulated mass, often large



  • Cut surface is gray-white to tan-yellow



Histopathology





  • Cellular tumor is characterized by apposed, spindle-shaped fibroblasts arranged in interlacing fascicles or a herringbone pattern ( Figure 17.21 )




    Figure 17.21


    Infantile fibrosarcoma.

    Cellular fascicles of spindle cells are arranged in herringbone growth pattern.



  • Frequent mitotic activity is seen, sometimes with atypical forms



  • Necrosis and hemorrhage are common



  • Myxoid or collagenous stroma may be seen



  • May have focal hemangiopericytoma-like vasculature



  • Scattered chronic inflammatory cells and focal extramedullary hematopoiesis are seen



Special Stains and Immunohistochemistry





  • Negative for epithelial, muscle, and neural markers as well as CD34, bcl-2, and CD99



Other Techniques for Diagnosis





  • Up to 90% of cases have t(12;15)(p13;q26) that creates a fusion gene, ETV6-NTRK3 ( TEL-TRCKC ): this may be cryptic on conventional karyotyping and requires reverse transcription polymerase chain reaction or fluorescent in situ hybridization studies



Differential Diagnosis


Myofibroma and Myofibromatosis





  • Infantile fibrosarcoma may contain foci indistinguishable from those of myofibroma; shows more cellular and atypical areas as well



  • Biphasic areas of cellular density



  • Possible intravascular polypoid projections



Spindle Cell Rhabdomyosarcoma





  • Usually paratesticular when seen in children



  • Possible presence of strap cells



  • Positive for desmin, myogenin, and MyoD1



Pearls





  • Wide surgical excision is the preferred treatment for infantile fibrosarcoma



  • Chemotherapy is reserved for unresectable tumors



  • About 15% to 30% of cases recur, but metastases are rare



  • Presence of t(12;15) is also seen in cellular mesoblastic nephroma of the kidney and secretory carcinoma





Selected References




  • Bourgeois J.M., Knezevich S.R., Mathers J.A., et. al.: Molecular detection of the ETV6-NTRK3 gene fusion differentiates congenital fibrosarcoma from other childhood spindle cell tumors. Am J Surg Pathol 2000; 24: pp. 937-946.



  • Coffin C.M., Jaszcz W., O’Shea P.A., et. al.: So-called congenital-infantile fibrosarcoma: does it exist and what is it?. Pediatr Pathol 1994; 14: pp. 133-150.



  • Sandberg A.A., Bridge J.A.: Updates on the cytogenetics and molecular genetics of bone and soft tissue tumors: congenital (infantile) fibrosarcoma and mesoblastic nephroma. Cancer Genet Cytogenet 2002; 132: pp. 1-13.


Adult Fibrosarcoma


Clinical Features





  • Rare tumor of middle-aged to elderly adults



  • Located in deep tissue of extremities, trunk, or head and neck; rarely other locations



  • A similar histologic pattern is seen in transformation of dermatofibrosarcoma protuberans



  • May be seen as a post-irradiation neoplasm



Gross Pathology





  • Firm, lobulated mass usually 3 to 10 cm in diameter



  • Small tumors may be well circumscribed



  • Cut surface is gray-white to tan-yellow with hemorrhage or necrosis



Histopathology





  • Variably hyperchromatic spindle cells with eosinophilic or amphophilic cytoplasm, may show a herringbone growth pattern



  • Variable mitotic activity



  • Lacks significant pleomorphism



Special Stains and Immunohistochemistry





  • Negative for epithelial, muscle, and neural markers as well as CD34, CD99, bcl-2, STAT6, and nuclear β-catenin. Preserved expression of H3K27me2



Other Techniques for Diagnosis





  • Noncontributory except to rule out other tumors, especially monophasic synovial sarcoma t(X;18)



Differential Diagnosis


Desmoid-Type Fibromatosis





  • Lacks dense cellularity, nuclear hyperchromasia, and herringbone growth



  • No hemorrhage or necrosis



  • Positive for nuclear β-catenin in most cases



Synovial Sarcoma (Monophasic)





  • May have herringbone or hemangiopericytoma-like growth patterns



  • Commonly shows areas of hypercellularity and hypocellularity



  • Immunoreactivity for cytokeratin, EMA, TLE1, CD99, bcl-2, and CD57



  • Presence of t(X;18); SYT translocation by FISH



Malignant Peripheral Nerve Sheath Tumor





  • Composed of elongated cells with variably pleomorphic, wavy nuclei



  • Cells arranged in fascicles or whorls; possible formation of neural tactoids



  • Nuclear palisading sometimes seen



  • May be positive for S100 protein, glial fibrillary acidic protein (GFAP), and CD56, or may show loss of H3K27me3 and H3K27me2



Dedifferentiated and Spindle Cell Liposarcoma





  • May be seen de novo through the clonal evolution of well-differentiated liposarcoma



  • Dedifferentiated areas may mimic fibrosarcoma, but extensive sampling usually reveals low-grade adipocytic component



  • Most commonly occurs in the retroperitoneum



  • MDM2 and CDK4 amplification and expression detected



Low-Grade Fibromyxoid Sarcoma





  • Alternating hypocellular myxoid areas and collagenized spindle cell foci



  • Lacks herringbone grown pattern



  • Presence of t(7;16) or FUS rearrangement by FISH



Pearls





  • Wide resection, with or without adjuvant radiotherapy, for adult fibrosarcoma is standard therapy; chemotherapy may be indicated for high-grade tumors



  • Fibrosarcoma is a pathologic diagnosis of exclusion and likely makes up less than 1% of sarcomas





Selected References




  • Bahrami A., Folpe A.L.: Adult-type fibrosarcoma: a reevaluation of 163 putative cases diagnosed at a single institution over a 48-year period. Am J Surg Pathol 2010; 34: pp. 1504-1513.



  • Hansen T., Katenkamp K., Brodhun M., et. al.: Low-grade fibrosarcoma: report on 39 not otherwise specified cases and comparison with defined low-grade fibrosarcoma types. Histopathology 2006; 49: pp. 152-160.



  • Pritchard D.J., Soule E.H., Taylor W.F., et. al.: Fibrosarcoma: a clinicopathologic and statistical study of 199 tumors of the soft tissues of the extremities and trunk. Cancer 1974; 33: pp. 888-897.


Sclerosing Epithelioid Fibrosarcoma


Clinical Features





  • Distinctive variant of fibrosarcoma



  • Tumor of middle-aged adults, but has been reported in children



  • Common locations include deep soft tissue of extremities, trunk, chest wall, or head and neck; may be painful



Gross Pathology





  • Firm, oval, or lobulated soft tissue mass ranging in size from 2 to 20 cm



  • Cut surface is gray-white; may have myxoid or cystic areas



Histopathology





  • Nests or cords of uniform, round to oval tumor cells with eosinophilic to clear cytoplasm embedded in a densely hyalinized stroma ( Figure 17.22 )




    Figure 17.22


    Sclerosing epithelioid fibrosarcoma.

    Small epithelioid cells with nuclear atypia are set in a sclerotic matrix.



  • May have fascicular, myxoid, or cystic areas and hemangiopericytoma-like vasculature



  • Mitotic figures are infrequent



  • Some cases have an associated low-grade fibromyxoid sarcoma



Special Stains and Immunohistochemistry





  • Most cases are positive for MUC4, variably for EMA. Typically negative for cytokeratins



Other Techniques for Diagnosis





  • Rearrangements in FUS have been reported in tumor with LGFMS component



Differential Diagnosis


Metastatic Carcinoma





  • Histology may suggest lobular breast carcinoma or signet ring cell adenocarcinoma



  • Positive for keratin, p63, MOC31, or CA72.4



Sclerosing Lymphoma





  • Positive for leukocyte common antigen (CD45) and B-cell markers (CD20, CD79a, and PAX5)



Deep Fibromatosis





  • Cells tend to be more fusiform, and margins are infiltrative



  • Positive for nuclear β-catenin in most cases



Spindle Cell/Sclerosing Rhabdomyosarcoma





  • Eosinophilic, hyperchromatic, and spindled to ovoid cells



  • Positive for desmin, myogenin, and MyoD1



Sclerosing, Well-Differentiated Liposarcoma





  • Usually retroperitoneal



  • Usually contains lipomatous areas if well sampled



  • Nuclear pleomorphism and lipoblasts are present



Pearls





  • Wide surgical resection is mainstay of therapy for sclerosing epithelioid fibrosarcoma



  • Local recurrence in about 50% of cases; distant metastases are common



  • Genetic and histologic overlap with low-grade fibromyxoid sarcoma in some cases





Selected References




  • Antonescu C.R., Rosenblum M.K., Pereira P., et. al.: Sclerosing epithelioid fibrosarcoma: a study of 16 cases and confirmation of a clinicopathologically distinct tumor. Am J Surg Pathol 2001; 25: pp. 699-709.



  • Doyle L.A., Wang W.L., Dal Cin P., et. al.: MUC4 is a sensitive and extremely useful marker for sclerosing epithelioid fibrosarcoma: association with FUS gene rearrangement. Am J Surg Pathol 2012; 36: pp. 1444-1451.



  • Guillou L., Benhattar J., Gengler C., et. al.: Translocation-positive low-grade fibromyxoid sarcoma: clinicopathologic and molecular analysis of a series expanding the morphologic spectrum and suggesting potential relationship to sclerosing epithelioid fibrosarcoma: a study from the French Sarcoma Group. Am J Surg Pathol 2007; 31: pp. 1387-1402.



  • Ogose A., Kawashima H., Umezu H., et. al.: Sclerosing epithelioid fibrosarcoma with der(10)t(10;17)(p11;q11). Cancer Genet Cytogenet 2004; 152: pp. 136-140.


Myxofibrosarcoma


Clinical Features





  • Previously known as myxoid malignant fibrous histiocytoma



  • Almost exclusively occurs in older adults and elderly



  • Usually presents as a slow-growing, painless mass in subcutaneous or deep tissues of the proximal extremities, rarely on trunk or head and neck



Gross Pathology





  • Multilobulated or single ill-defined mass with gelatinous, myxoid cut surface ( Figure 17.23A )




    Figure 17.23


    Myxofibrosarcoma, low grade.

    A, The tumor is grossly well circumscribed with a shiny yellow-tan, soft appearance, but infiltrated to the margins microscopically, necessitating re-excision. B, On microscopic examination, tumor cells with mild to moderate atypia are present singly in abundant myxoid stroma, or apparently clinging (arrows) to the delicate thin-walled vasculature. Tumor cells with intracytoplasmic mucoid material known as “pseudo-lipoblasts” (inset) are present.



Histopathology





  • Multilobulated lesion demarcated with incomplete fibrous septa containing a myxoid stroma and pleomorphic cells




    • Low-grade myxofibrosarcoma




      • Abundant myxoid matrix with scattered spindled or stellate hyperchromatic tumor cells with irregular borders and eosinophilic cytoplasm ( Figure 17.23B )



      • Pseudolipoblasts show eccentric, pleomorphic nuclei and abundant vacuolated cytoplasm



      • Curvilinear blood vessels with perivascular condensation of tumor cells




    • High-grade myxofibrosarcoma




      • Cellular tumor composed of fascicles or sheets of highly pleomorphic fusiform or stellate cells, many of which are multinucleated



      • Lower grade areas may be present



      • Myxoid stroma that is less apparent but variable throughout the lesion



      • Numerous mitotic figures and atypical mitoses



      • Hemorrhage and necrosis common



      • Rarely, has an epithelioid phenotype





Special Stains and Immunohistochemistry





  • Noncontributory



Other Techniques for Diagnosis





  • Noncontributory



Differential Diagnosis


Atypical Lipomatous Tumor/Well-Differentiated Liposarcoma with myxoid stroma





  • Fatty component is usually evident if well sampled



  • MDM2/CDK4 expression and amplification



Low-Grade Fibromyxoid Sarcoma





  • Much more fibroblastic, collagenous tumor, despite similarity of name



Myxoid Liposarcoma





  • Deeply seated tumor that most commonly occurs in the thighs of adults



  • Bland spindled or fusiform cells with presence of true lipoblasts



  • Tumor cells are less pleomorphic



  • Vasculature is delicate and arborizing and lacks condensed perivascular tumor cells



  • Presence of t(12;16)(q13;p11), producing an FUS-DDIT3 fusion



Myxoma





  • Paucicellular lesion with small, bland nuclei that lack pleomorphism



  • Usually intramuscular



Pearls





  • Wide surgical resection with radiation, chemotherapy, or both for high-grade lesions is the standard therapy for myxofibrosarcoma



  • Low-grade tumors show local recurrence in up to 50% of cases but rarely metastasize



  • High-grade tumors have a high rate of local recurrence and metastasize in about one third of cases





Selected References


Mar 11, 2021 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Soft Tissue
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