and Aysegul A. Sahin2
Division of Pathology, Singapore General Hospital, Singapore, Singapore
The University of Texas, M. D. Anderson Cancer Center, Houston, TX, USA
KeywordsNodular fasciitisFibrous scarringFibromatosisMetaplastic carcinomaPhyllodes tumourSarcoma
A spindle cell is a fusiform cell that is tapered at both ends. Although both luminal epithelial and myoepithelial cells may assume spindle shapes, spindle cell lesions of the breast usually refer to conditions that are composed of mesenchymal or mesenchymal-like cells that harbour elongated and stretched cytoplasm. A variety of different lesions may comprise mesenchymal spindle cells, including nodular fasciitis, fibrous scarring, pseudoangiomatous stromal hyperplasia, myofibroblastoma, fibromatosis, stromal overgrowth in phyllodes tumour, and sarcoma. Mesenchymal-like malignant epithelial cells are encountered in fibromatosis-like and spindle cell metaplastic carcinomas.
Nodular fasciitis is a self-limited clonal proliferation of fibroblasts and myofibroblasts.
Clinical and Epidemiological Features
Nodular fasciitis is rare in the breast parenchyma. It may occur in the subcutis and deeper in the chest wall, clinically masquerading as a breast mass. Rapid onset with pain and tenderness is typical, with spontaneous involution over a couple of months.
Nodular fasciitis is a mimic of breast malignancy on imaging, usually presenting as ill-defined, spiculated nodular masses, although well-circumscribed, benign-appearing masses have also been described. It is commonly seen superficially in the subcutaneous fascia but can also be found deep to the muscle or intramuscularly. It is usually hypoechoic on sonography because of its fibrous content [1, 2].
Nodular fasciitis has a greyish-white, myxoid appearance.
Histologically, plump, spindled fibroblasts and myofibroblasts are arranged in a fascicular pattern with oedema, microhaemorrhages with red cell extravasation, and scattered inflammatory cells, giving a “feathery” tissue culture-like appearance (Figs. 11.1 and 11.2). Reactive nuclear changes with vesicularity and rare mitoses may be observed (Fig. 11.3). Immunohistochemically, there is reactivity for smooth muscle actin, but desmin is usually negative (Fig. 11.4). No staining is seen for keratins, CD34, or S100. Proliferative myositis is a microscopically similar lesion, differing from nodular fasciitis by the presence of plump, ganglion-like cells (Figs. 11.5, 11.6, and 11.7).
Nodular fasciitis. Low-magnification view shows a spindle cell lesion with ill-defined boundaries. A few skeletal muscle fibres are seen in the vicinity (left upper field)
Nodular fasciitis. A feathery tissue culture-like oedematous appearance is seen at medium magnification. Several dark nuclei of scattered lymphocytes are present
Nodular fasciitis. High magnification shows elongated and ovoid vesicular nuclei with inconspicuous nucleoli. Cytoplasm is tapered, with ill-defined outlines. Rare mitoses may be seen. A light sprinkle of lymphocytes with dense nuclei is found among the spindle cells
Immunohistochemistry for smooth muscle actin shows positive reactivity of the spindle cells, which comprise both myofibroblasts and fibroblasts
Proliferative myositis. The patient presented clinically with a breast lump. Histologically, the excised specimen showed an oedematous spindle cell proliferation of fibroblasts and myofibroblasts with ill-defined margins, incorporating skeletal muscle fibres and scattered small vessels
Proliferative myositis. Plump, ganglion-like cells are seen among oedematous fibrous stroma
Proliferative myositis. Ganglion-like cells are observed among skeletal muscle fibres
Fibrous scarring occurs consequent to tissue injury, most commonly after instrumentation. In the immediate postoperative or post-biopsy period, granulation tissue may resemble nodular fasciitis. An exuberant tissue response can lead to a nodular spindle lesion referred to as a spindle cell nodule .
In fibromatosis, there are long, intersecting fascicles of spindle cells in a collagenous background. The spindle cells show elongated, wavy nuclei. Oedema and inflammation seen in nodular fasciitis are usually absent.
Fibromatosis-Like Metaplastic Carcinoma
Fibromatosis-like metaplastic carcinoma shows bland spindle cells arranged in interlacing fascicles. There is usually no tissue culture-like appearance. Transitioning to plumper epithelioid cells and occasional squamous foci are seen. Immunohistochemical positivity for keratins confirms its epithelial nature, with p63 often being expressed as well.
Inflammatory Myofibroblastic Tumour
This extremely rare condition in the breast is composed of myofibroblasts with minimal atypia accompanied by prominent inflammatory infiltrates. Ganglion-like cells may be observed. Immunohistochemistry shows positive reactivity for smooth muscle actin, and some lesions also demonstrate desmin and keratin staining. Anaplastic lymphoma kinase (ALK) rearrangements are seen in 50 % of cases, manifesting as positive immunohistochemical staining for the ALK protein (Figs. 11.8, 11.9, 11.10, and 11.11).
Inflammatory myofibroblastic tumour. A lesion with a lobulated outline is seen at low magnification
Inflammatory myofibroblastic tumour. Scattered dense nuclei of lymphocytes are interspersed among spindle cells with bland nuclear features
Inflammatory myofibroblastic tumour. (a) Immunohistochemistry shows smooth muscle actin (SMA) positivity of the spindle cells, supporting a myofibroblastic origin. (b) Anaplastic lymphoma kinase (ALK) shows patchy cytoplasmic reactivity
Inflammatory myofibroblastic tumour. Interphase nuclei show rearrangement of the ALK break-apart probe using fluorescence in situ hybridisation. The signal pattern consists of one yellow fusion signal (yellow arrow), one red signal (3′ ALK gene, red arrow), and one green signal (5′ ALK gene, green arrow), indicating disruption of the ALK gene at 2p23 (Courtesy of Cytogenetics Laboratory, SGH Pathology)
Apart from angiosarcoma of the breast occurring as a primary tumour or secondary to radiation treatment of breast cancer, primary breast sarcoma is exceedingly rare. There have been anecdotal reports of sarcomas of myofibroblastic origin (Figs. 11.12, 11.13, 11.14, 11.15, and 11.16) [4, 5]. The possibility that the sarcoma originates from an underlying malignant phyllodes tumour must be ruled out.
Myofibroblastic sarcoma. Chest wall lesion occurring after mastectomy for recurrent ductal carcinoma in situ with prior wide excision and radiation treatment for invasive ductal carcinoma
Myofibroblastic sarcoma. Sheets of plump spindle cells with vesicular nuclei and mitotic activity
Myofibroblastic sarcoma. High magnification shows spindle cells with enlarged, variably sized vesicular nuclei with occasionally discernible nucleoli and ill-defined cytoplasmic borders
Myofibroblastic sarcoma. SMA immunohistochemistry shows diffuse cytoplasmic reactivity of the spindle cells. Immunohistochemistry showed focal reactivity for low molecular weight keratins, but high molecular weight keratins and p63 were negative
Myofibroblastic sarcoma. MIB1 (Ki67) immunohistochemistry shows positively stained nuclei of spindle cells
Prognosis and Therapy Considerations
Nodular fasciitis is a spontaneously resolving lesion.
Fibromatosis is a locally aggressive but non-metastasising lesion composed of fibroblasts and myofibroblasts.
Clinical and Epidemiological Features
Fibromatosis presents as a breast mass or may arise in the interpectoral region with extension into the breast parenchyma. Skin retraction may be observed. There can be an association with trauma or breast implants.
Fibromatosis can mimic breast malignancy, presenting as an ill-defined mass with spiculations, typically adjacent to or arising from the pectoralis muscle.
A fibrous, whorled appearance with ill-defined borders may be observed on cut sections (Fig. 11.17). Size can range from a few millimetres detected radiologically to clinical presentation as a mass.
Fibromatosis. Gross specimen shows a whitish whorled lesion with both circumscribed and ill-defined margins within the breast parenchyma and involving the chest wall muscle
Fibromatosis consists of long, intersecting fascicles of spindle cells with flattened wavy nuclei without atypia (Figs. 11.18, 11.19, and 11.20). Mitoses are usually absent; if present, they are few. Extension around benign breast lobules and a few chronic inflammatory infiltrates may be observed at the periphery. Immunohistochemically, there is reactivity for nuclear beta-catenin (Fig. 11.21), but this is not specific, as beta-catenin staining has been found in metaplastic spindle cell carcinoma, phyllodes tumours, and fibrosarcoma. SMA and desmin may be expressed. No staining is seen for keratins, CD34, or S100 (Fig. 11.22). The diagnosis of fibromatosis is particularly challenging on core biopsy (Figs. 11.23, 11.24, 11.25, 11.26, 11.27, and 11.28).
Fibromatosis of breast. Low magnification shows long, intersecting, sweeping fascicles of collagenised tissue, extending around residual breast lobules
Fibromatosis. Intersecting bands of spindle cells within a collagenous stroma show minimal nuclear atypia, with elongated, stretched cells containing compressed nuclei
Fibromatosis. High magnification shows the spindle cell nuclei to have slender shapes with narrow, tapered ends, with some nuclei displaying slight waviness. The nuclei are separate from each other, without significant overlapping. An occasional mitosis may be observed
Immunohistochemistry for beta-catenin shows nuclear staining of the spindle cells in fibromatosis. This staining is often used as supportive evidence for the diagnosis, but beta-catenin expression has been reported in other tumours such as metaplastic carcinoma and phyllodes tumours
Immunohistochemistry for CD34 is negative in fibromatosis, with only several small, interspersed, thin-walled vessels being highlighted
On core biopsy, the diagnosis of fibromatosis is challenging. Radiologically, fibromatosis often forms a stellate mass with spiculations mimicking cancer. Careful assessment of the cores is needed in order to identify the spindle cell proliferation (arrows). An immunohistochemical workup may narrow the differential diagnostic spectrum and suggest the diagnosis, but complete excision is usually required for confirmation
Fibromatosis on core biopsy. The spindle cell process has low cellularity, with a few chronic inflammatory cell infiltrates
Fibromatosis on core biopsy. A dense, fibrocollagenous process is seen partially encircling a breast lobule
Fibromatosis on core biopsy. High magnification shows slender, elongated, and slightly wavy nuclei with tapered ends. Cytoplasmic outlines are indistinct
Excision biopsy shows the stellate outlines of the lesion at low magnification. With the history of a prior core biopsy, a differential that needs to be excluded is fibrous scarring, but this excision was performed within a week after the core biopsy, and histologically the reparative process would comprise relatively fresh granulation rather than a fibrous-like lesion. Inset shows a higher magnification of the spindle cell lesion, which resembles the observations on the core biopsies. Correlation with the core biopsy findings is important in finalising the diagnosis
Excision specimen of fibromatosis, with the previous biopsy site identified as an area of haemorrhage and granulation (arrows). Inset shows fibrin and blood, with granulation representing tissue reaction to the previous biopsy
Reparative granulation in the immediate postoperative or post-biopsy period may resemble nodular fasciitis, but more remote instrumentation can lead to fibrous organisation that can mimic fibromatosis (Figs. 11.29 and 11.30). A clinical history and histological evidence of prior instrumentation (such as foreign-body-type giant cells and haemosiderin deposits) are useful in reaching the correct diagnosis.
Fibrous scar resembling fibromatosis. At low magnification, there is a somewhat stellate fibrous lesion with focal haemorrhage. Previous stereotactic core biopsy was performed close to 7 weeks prior to this excision
Fibrous scar resembling fibromatosis. A few foreign-body-type, multinucleated giant cells are seen amid the fibrosis. A history of previous biopsy is useful in reaching the correct diagnosis. Correlation with the radiological appearance is also important, as fibromatosis presents as a stellate lesion or as an architectural distortion on imaging, whereas a fibrous scar is consequent to instrumentation, which may have been performed for other reasons such as calcifications or a mass. The organised fibrosis reflects tissue injury that was more remote, which can be temporally compared with when the biopsy was performed
Myoid hamartoma is regarded as a variant of breast hamartoma, comprising spindle cells in short fascicles that extend around lobules. The spindle cells are histologically bland and show smooth muscle differentiation, which may be verified with desmin and smooth muscle markers on immunohistochemistry (Figs. 11.31, 11.32, and 11.33) .
Myoid hamartoma. Low magnification shows a spindle cell lesion incorporating breast lobules, especially towards its periphery
Myoid hamartoma. Spindle cells in short fascicles and vague storiforming, extending around breast lobules. Inset shows high magnification of the spindle cells with ovoid-to-elongated, banal nuclei. No mitoses are found
Myoid hamartoma. Immunohistochemistry shows positive reactivity of the spindle cells for desmin (a) and SMA (b), corroborating a smooth muscle origin. Epithelial markers including high molecular weight keratins are negative
Fibromatosis-Like Metaplastic Carcinoma
On light microscopy, fibromatosis-like metaplastic carcinoma closely resembles fibromatosis. The presence of histological transitioning to more epithelioid and squamous foci and the coexistence with ductal carcinoma in situ are clues to metaplastic carcinoma, which also can be corroborated with positive keratin immunostaining.
Fibrosarcoma is a more cellular tumour than fibromatosis, with a greater degree of cytological atypia and mitotic activity. Fibrosarcoma is very rare in the breast; when observed, it may be part of a dermatofibrosarcoma with secondary involvement of the breast, or it may be associated with a borderline or malignant phyllodes tumour.
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The intermingling of adipocytes with spindle cells in lipomatous myofibroblastoma can mimic fibromatosis extending among adipose tissue . The general circumscription of myofibroblastoma and its CD34 positivity differentiate it from fibromatosis (Figs. 11.34, 11.35, 11.36, 11.37, 11.38, 11.39, 11.40, 11.41, 11.42, 11.43, and 11.44). Monosomy of chromosome 13q14 and 16q helps corroborate the diagnosis of myofibroblastoma.
Myofibroblastoma. Gross appearance shows a well-circumscribed border with a cut surface that is yellowish white. Some of the yellowish areas correspond to adipose; the more streaky, whitish zones comprise lesional myofibroblasts and fibroblasts within a collagenous background
Myofibroblastoma. A lobulated appearance resembling a fibroadenoma can be seen. Cut section shows a whitish appearance with slightly rubbery consistency and a few linear indentations
Myofibroblastoma. Low-magnification view shows a well-circumscribed border. Scattered adipocytes are seen among pink, collagenous stroma that contains bland spindle cells. Variable cellularity and oedema are seen
Myofibroblastoma. Spindle cells with ovoid-to-elongated nuclei are seen with pink collagen. Several adipocytes are noted
Myofibroblastoma. Ropy, pink collagen fibres are seen among the spindle cells with ovoid nuclei. Some of the spindle cells appear relatively plump and are aligned in a vaguely linear fashion, which can mimic an invasive lobular carcinoma of classic type, especially when nuclear reactivity for oestrogen receptor is seen (which can be encountered in myofibroblastoma). Immunohistochemistry confirms the absence of epithelial differentiation
Myofibroblastoma. Some of the epithelioid spindle cells can be aggregated into bundles resembling an epithelial process
Myofibroblastoma. Occasional individually dispersed epithelioid cells are present (arrows)