Benign and Intermediate Fibrosing Lesions



Benign and Intermediate Fibrosing Lesions





INTRODUCTION

A group of benign fibrosing spindle cell lesions is composed of various proportions of myofibroblasts, fibroblasts (see Chapter 3, Table 3.1 for comparison), collagenous or elastic tissue, and inflammatory cells of all types. They occur in all locations, and in some, the component elements change over time. This chapter includes those in which fibrosis is a prominent feature. Immunohistochemistry is of limited value, and diagnosis depends on attention to subtle morphologic features, but some entities cannot be identified by microscopy alone and careful clinicopathologic correlation is required. Cellular fibroblastic-myofibroblastic lesions are considered in Chapter 3, and tumors composed predominantly of myofibroblasts in Chapter 7. The differential diagnosis is summarized in Table 2.1.


ELASTOFIBROMA


Clinical Features

Elastofibroma is typically located in subcutis and muscles of the back near or beneath the inferior border of the scapula (elastofibroma dorsi) in adults over 50, with a female predominance, and sometimes with a history of physical labor or other repetitive activity. The lesion is probably an exaggerated reaction to trauma or friction since lesser but similar changes are found in some elderly persons at autopsy. There is an increased incidence in parts of Japan, and a familial predisposition to elastofibroma has been reported. Some cases are bilateral, and examples have been described in other locations including oral cavity, rectum, and omentum. It is usually a painless infiltrative mass in which lesional tissue can extend deeply into subcutis, between muscles, and adhere to periosteum of middle ribs.


Pathologic Features

Elastofibroma forms an ill-defined firm tumor up to 10 cm in diameter with fibrous and fatty areas. Infiltration of skeletal muscle imparts a variegated red, white, and yellow appearance. Microscopically, the appearances are




characteristic, with numerous randomly orientated thick focally branching elastic fibers, in places fragmented into small bead-like spheroids or “globules,” within collagen containing a few bland fibroblasts or myofibroblasts, admixed with mature adipocytes (Fig. 2.1, e-Figs. 2.1 to 2.3).








TABLE 2.1 Differential Diagnosis of Fibrosing Lesions

Typical Clinical Features

Microscopic Features

Ancillary Investigations


Elastofibroma

F > M, lower scapular area, beneath bone, infiltrative in subcutis and muscle

Poorly defined, infiltrative


Thick, focally beaded elastic fibers randomly dispersed in collagen

Elastic stain positive


Amyloidoma (tumoral amyloidosis)

Older adults, extremities, especially lower, in skin or subcutis


Idiopathic, or associated with myeloma, plasmacytoid lymphoma, long-term dialysis, chronic inflammation

Islands of amorphous eosinophilic material, plasma cells, multinucleated giant cells, calcification, metaplastic bone


Vessel walls involved

PASD+, apple green birefringence with Congo Red that persists after pretreatment with permanganate in AL amyloid


Nuchal type and Gardner fibroma

M > F, neck, shoulder, back


Associated with diabetes and Gardner syndrome


Can later develop desmoid fibromatosis

Poorly defined infiltrative lesion, dense collagen, very sparse cells, increased entrapped nerves

CD34+, CD99+


beta-catenin+


Nuchal fibrocartilaginous pseudotumor

Back of neck. History of trauma to neck. At junction of nuchal ligament and deep fascia

Dense fibrous tissue containing nodules of metaplastic mature cartilage

S100 protein+ in chondrocytes


Fibroma of tendon sheath

M > F, hands, feet, circumscribed


Slowly growing

Circumscribed, multinodular tumor, comprising hyalinized nodules, spindle cells, slits, or fasciitis-like more cellular areas

SMA+, CD34-, t(2;11) (q31-32;q12)


Calcifying fibrous tumor

Children, young adults, M = F


Subcutaneous, subfascial, or intracavitary

Circumscribed, unencapsulated lesion


Hypocellular collagen, aggregates of lymphocytes, rounded calcifications, scanty fibroblasts

Occasionally CD34+, or SMA+


Calcifying aponeurotic fibroma

Childhood, extremities, digits, palm

Cords and files of spindle or rounded cells in fibrous stroma with focal calcification and chondroid metaplasia


Less commonly, osteoclast-like giant cells and ossification

S100 protein+ in chondrocytes


Fibromatosis-superficial

Palm, sole, penis; infiltrative plaque

Variable cellular nodules in dense collagen


Cells are parallel aligned, lack atypia


Mast cells

SMA+, nuclear beta-catenin±, CD34-


Fibromatosis-desmoid type

Deep in limbs, head and neck, body cavities

Parallel myofibroblasts evenly dispersed in collagen, slit-like and thick-walled small-caliber vessels, perivascular and interstitial mast cells


Normal mitoses allowed but no atypia or necrosis

SMA+, nuclear beta-catenin+, CD34-


Low-grade fibromyxoid sarcoma

Skin, deep soft tissue, limbs/girdles

Fibromatosis-like areas, swirling fibromyxoid transitions, cellular myxoid areas without pleomorphism


Some nuclei lozenge shaped, inconspicuous nucleoli


Giant collagenous rosettes

Occasionally SMA+, EMA+, claudin-1 in some


Nuclear beta-catenin usually negative t(7;16)(q34;p11), FUS-CREB3L2 or FUSCREB3L1 fusion, rarely EWSR1-CREB3L1


Perineurioma

Skin, subcutis, most locations. Subset in colon


Sclerosing variant: M > F, affects fingers, thumb, palm

Long thin nuclei, very long slender terminal cytoplasmic processes


Fascicles or perivascular whorls


Fibrous or myxoid stroma


Sclerosing variant has cords and whorls of rounded or epithelioid cells in dense stroma

EMA+, claudin-1+, CD34+ in some, GLUT-1+, beta-catenin-


Sclerosing epithelioid fibrosarcoma

Deep soft tissue, limbs/girdles, head and neck


Can involve or arise in bone

Multinodular, focally calcified


Cellular islands in dense fibrosis, nests of ovoid cells, clear cytoplasm, or single files simulating carcinoma


Fibrosarcoma-like spindle cell areas in many cases

Occasional and variable expression of bcl-2, EMA, CK, S100 protein


No specific immunophenotype


EWSR1-CREB3L1 fusions


Infantile digital (inclusion body) fibromatosis

Congenital or up to about 2 years, rarely older, F > M

Digits except first


Rarely other sites


Can be multiple


50% of digital lesions recur

Infiltrative, moderately cellular, bland cells


Rounded eosinophilic paranuclear inclusions

SMA+, occasionally nuclear beta-catenin+ or CD34+


Fibromatosis colli

Infants in first months, M > F


Mass lower third of sternomastoid or trapezius


Associated with torticollis


Eventual regression

Infiltrative, at first cellular, later fibrous, between muscle bundles that show focal atrophy or swelling

Nil specific


Juvenile hyaline fibromatosis

Childhood


Skin of head and neck, limbs, bones

Dense homogeneous eosinophilic stroma with small islands of ovoid cells with clear cytoplasm

Stroma is positive with PASD and Alcian blue


Desmoplastic fibroblastoma (collagenous fibroma)

M > F, mostly subcutaneous, limbs and limb girdles

Mostly circumscribed, unencapsulated, sparse stellate or spindle cells in dense collagenous stroma, occasional myxoid change, hyalinized vessels

Focal SMA+, rare nuclear beta-catenin+, t(2;11) (q31;q12)







FIGURE 2.1 Elastofibroma. Wavy or fragmented eosinophilic elastic fibers are dispersed in sparsely cellular and focally hyalinized collagen.


Ancillary Investigations

Histochemical stains such as Weigert’s elastic and immunohistochemistry with antielastin highlight the elastic fibers, which also fluoresce with ultraviolet illumination (Fig. 2.2, e-Fig. 2.4). This can be differentiated from amyloid deposits (e-Fig. 2.5), which shows apple-green birefringence after staining with Congo Red. Electron microscopy of elastofibroma shows irregular rounded mass of electron-dense preelastin surrounding less dense elastin, which is produced within rough endoplasmic reticulum of adjacent fibroblasts. Abnormalities in chromosome 1p and Xq1 have been identified.1


NUCHAL FIBROMA AND NUCHAL-TYPE FIBROMA


Clinical Features

Nuchal fibroma was originally described as predominantly occurring in the skin and subcutis of the back of the neck. Subsequently, it has been reported in other locations, including upper and lower back, buttock, shoulder, and face, indicating the term nuchal-type fibroma.2 Over 80% arise in males, with a mean age of 40 years, and nearly half are associated with diabetes mellitus. Histologically identical lesions are associated with
Gardner syndrome (see below), and diabetic scleredema has the same appearance. These are benign conditions which can, however, recur if incompletely excised.






FIGURE 2.2 Elastofibroma. Elastic van Gieson stain highlights numerous globules of elastic fibers scattered throughout the lesion.


Pathologic Features

This is a poorly circumscribed firm mass usually <8 cm in maximum dimension, with similar histologic appearances in all locations. The lesion infiltrates dermis (around adnexa), fat, and, sometimes, skeletal muscle and comprises very sparse fibroblasts dispersed in thick irregularly orientated collagen bundles with scattered fine elastic fibers and, at most, a scanty lymphocytic infiltrate (Fig. 2.3, e-Figs. 2.6 to 2.8). Nerve bundles entrapped within the fibrous tissue (e-Fig. 2.9) can appear increased in number.


Ancillary Investigations

Immunohistochemistry is positive in the spindle cells for CD34 and CD99.


GARDNER (GARDNER-ASSOCIATED) FIBROMA


Clinical Features

Gardner syndrome is an autosomal dominant condition with variable penetrance associated with mutations in the adenomatous polyposis coli (APC) gene at 5q21.3 The syndrome includes colonic and rectal polyps and multiple osteomas as well as fibromatosis (in about 10% of patients) of mesentery or abdominal wall,4 fibromas, leiomyomas, lipomas, and skin manifestations such as dermoid cysts, many of which have pilomatricoma-like features.
Gardner-associated fibroma arises mostly in children and can be an antecedent marker for familial adenomatous polyposis (FAP)5 or for Gardner syndrome, in which the osteomas appear later followed by the polyps. Some examples of Gardner fibroma eventuate in fibromatosis, especially after surgery to the lesion. Clinically, there is an infiltrative, subcutaneous plaque-like lesion in back, paraspinal region, chest wall, head and neck, and extremities. A similar desmoid-precursor lesion has been described in the mesentery.6






FIGURE 2.3 Nuchal fibroma. Subcutaneous fat is irregularly infiltrated by confluent short bands of dense collagen with sparse fibroblastic spindle cells


Pathologic Features

The microscopic features in Gardner fibroma are identical to those of nuchal-type fibroma with sparse fibroblastic spindle cells, randomly arranged thick collagen bundles showing focal cracking artifact, and occasional mast cells. Rarely, there is mild atypia or multinucleation.


Ancillary Investigations

The spindle cells are immunoreactive for CD34 and CD99, and some cases show nuclear immunoreactivity for beta-catenin. However, the cellularity is usually less and the collagen more coarse than in fibromatosis.


NUCHAL FIBROCARTILAGINOUS PSEUDOTUMOR


Clinical Features

This rare lesion, which is associated with prior soft tissue injury, is situated within the nuchal ligament in young adults, of either sex, and presents as a tender nodule up to 3 cm in diameter at the lower part of the back of the
neck, where the nuchal ligament meets deep fascia.7 It probably represents fibrocartilaginous metaplasia of the lower portion of the nuchal ligament, as a result of trauma.


Pathologic Features

This is a poorly circumscribed lesion composed of dense fibrous tissue with ill-defined foci of chondroid metaplasia containing mature chondrocytes (e-Figs. 2.10 and 2.11). Atypia, mitoses, inflammation, and calcification are absent.


Ancillary Investigations

The cartilage cells are immunoreactive for S100 protein. Ultrastructural examination shows fibroblastic and chondroid differentiation without features of myofibroblastic differentiation.


FIBROMA OF TENDON SHEATH


Clinical Features

Most commonly seen in males between 20 and 50 years, this is a small (<2 cm diameter) slowly growing lesion which forms a circumscribed lobulated firm mass attached to tendons in hands or, less commonly, feet. The thumb, first finger, dorsum and palm of hand, and wrist are the most frequently affected sites. Fibromas occasionally arise in other locations including the knee region and ankle, and within a joint. Some cases have antecedent trauma. The lesions are benign but up to a quarter recur, usually within weeks.


Pathologic Features

Fibroma of tendon sheath is circumscribed but nonencapsulated. Histologically, the lobular architecture is emphasized by cleft-like spaces, at least some of which represent thin-walled blood vessels (Fig. 2.4, e-Figs. 2.12 and 2.13). The lesions are mostly of low cellularity; scattered bland fibroblastlike spindle or stellate cells are dispersed in a densely collagenized stroma, with rare foci of myxoid change or occasionally osteochondroid metaplasia, and slit-like blood vessels. Some cases, however, display increased cellularity with nodular fasciitis-like areas (e-Fig. 2.14). These are presumed to represent an early stage of the lesion since transition to hyalinized areas is seen, and it has been suggested that fibroma of tendon sheath represents the tenosynovial counterpart of nodular fasciitis. The genetic rearrangements, however, differ in the two tumors8 (see also Chapter 3). Multinucleated cells can be seen, but the range of appearances seen in giant cell tumor of tendon sheath is lacking, and these are probably two separate entities. Some examples have diffuse nuclear atypia with occasional (but no abnormal) mitoses; such lesions, termed pleomorphic fibroma of tendon sheath, behave in the same way as the usual fibroma of tendon sheath.







FIGURE 2.4 Fibroma of tendon sheath. Note circumscribed margin, sparse cellularity, hyalinized collagen, and thin-walled blood vessels.


Ancillary Investigations

Some cells show positivity for SMA, indicating focal myofibroblastic differentiation. Electron microscopy shows fibroblasts and myofibroblasts, with the latter being more prominent in the fasciitis-like areas. A chromosomal rearrangement t(2;11)(q31-32;q12) has been described in one case,8 suggesting a possible relationship with desmoplastic fibroblastoma (collagenous fibroma) in which similar genetic findings have been reported.


CALCIFYING FIBROUS TUMOR


Clinical Features

This entity was described in 1988 as childhood fibrous tumor with psammoma bodies9 and then in 1993 as calcifying fibrous pseudotumor.10

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Jun 18, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Benign and Intermediate Fibrosing Lesions

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