fibromatosis of the breast parenchyma with a benign-like ... · fibromatosis exhibits infiltrative,...

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Licensee OA Publishing London 2013. Creative Commons Attribution Licence (CC-BY)

F : Salvatorelli L, Musumeci G, Vecchio GM, Parenti R, Vasquez E, Magro G. Fibromatosis of the breast parenchyma with a benign-like nodular appearance. OA Case Reports 2013 Feb 28;2(2):18.

Fibromatosis of the breast parenchyma with a benign-likenodular appearance

L Salvatorelli1, G Musumeci2*, GM Vecchio1, R Parenti3, E Vasquez1, G Magro1

ically, neoplastic cells were stained diffusely with vimentin, smooth muscle actin and β-catenin.ConclusionWe believe that a correct diagnosis of breast fibromatosis, even on froz-en sections, is primarily dependent on awareness by pathologists that this tumour can rarely arise in this unusual site.

IntroductionDeep-sited fibromatosis, also known as ‘desmoid-tumour’ or desmoid-type fibromatosis, is an infiltrative fibroblastic/myofibroblastic tumour with high risk of local recurrence, but no metastatic potential1. It originates principally from the fascia or aponeu-roses of muscles of the abdominal wall, shoulder, pelvic girdle, thoracic wall, back, thigh and head and neck region. This tumour can also arise from the mesentery, pelvis and retroperitoneum (so-called ‘intra- abdominal desmoids’)1.

Only rarely, desmoid-type fibroma-tosis may occur at unusual sites, including the breast parenchyma2. Primary fibromatosis of the breast is a rare lesion with an incidence of about 0.2% that of breast carcinoma2, which can occur sporadically or in the context of genetic syndromes such as Gardner syndrome, familial multi-centric fibromatosis and hereditary desmoid disease3–9. Although most cases are reported in females3–6, a few cases have occasionally been docu-mented in males6,10,11. Breast fibroma-tosis occurs at a wide range of ages (13 to 83 years), presenting clinically as firm, palpable mass, with occa-sional skin retraction or dimpling2–6. The lesions most commonly present as a solitary, unilateral mass but multiple and bilateral lesions can

be observed5,7. One case of primary fibromatosis of the breast has also been reported concurrently with a fibromatosis of the underlying pectoralis major muscle in the same patient12. Although most cases of breast fibromatoses seemingly arise spontaneously, in some cases, an association with previous trauma, including surgery (especially for silicone implants), has been docu-mented5,6,13–15. Notably, both mammo-graphic and sonographic features exhibited by most cases of breast fibromatosis are usually indistin-guishable from those of invasive breast carcinoma3–6,12,16–18. In fact, mammography reveals non-calcified, hyperdense masses with finger-like margins, while its sonographic appearance reveals speculated, irregular hypoechoic masses with posterior shadowing3–6,12,16–18. Only rarely, cases with mammographic and sonographic features consistent with a benign lesion are available in the English literature19.

We herein describe a rare case of fibromatosis of the breast parenchyma presenting as a benign-like nodular mass in a 29-year-old woman. Clinical, sonographic and pathological features are reported and differential diagnostic problems are discussed.

Case ReportA 29-year-old woman presented with a painless mass in the lower outer quadrant of her right breast; the mass had been present for 4 months. Clinically, the mass was not movable and firm in consistency, without overlying skin dimpling or retraction. No axillary lymphad-enopathy was noted. Her medical history was unremarkable with

* Corresponding authorEmail: [email protected] Department G.F. Ingrassia, Azienda Ospe-

daliero-Universitaria ‘Policlinico-Vittorio Emanuele’ Anatomic Pathology, University of Catania, Catania, Italy

2 Department of Bio-Medical Sciences, Human Anatomy and Histology Division, University of Catania, Italy

3 Department of Bio-medical Sciences, Section of Physiology, University of Catania, Italy

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AbstractIntroductionThis report discusses Fibromatosis of the breast parenchyma with a be-nign-like nodular appearance.Case reportWe report the clinical, sonographic and pathologic features of a rare ca-se of primary fibromatosis of the br-east parenchyma in a 29-year-old fe-male. Unlike most cases reported in the literature, this tumour presented an oval-shaped nodular mass lackin-g the typical infiltrating (finger-like) margins both at ultrasonography an-d macroscopic examination. Frozen section diagnosis revealed a spindle cell proliferation entrapping mamm-ary ducts and lobules and, thus, the provisional diagnosis of ‘fibromatos-is-like spindle cell proliferation’ was rendered, but the possibility of a spi-ndle cell metaplastic carcinoma cou-ld not be completely ruled out. The final diagnosis was achieved in for-malin-fixed tissues by a combined morphological and immunohistoch-emical study. Tumour was compose-d of long, interlacing fascicles of bla-nd-looking spindle-shaped cells em-bedded in a variably fibrous stroma. Only focally tumour margins were of infiltrative type. Immunohistochem-



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Figure 1: Sonography showing an oval-shaped, heterogeneous hypoechoic mass with focally indistinct margins.

no antecedent injury or surgical trauma. The patient showed no stigmata and had no family history suggestive of Gardner’s syndrome or multicentric familial fibromatosis. Ultrasonography showed a 2.5-cm, oval-shaped, mildly hypoechoic mass with heterogeneous internal echo pattern, focally indistinct margins and slightly posterior acoustic

enhancement (Figure 1). Micro-calcifications and bilateral edge shadowing were not seen. These imaging features were non-specific and the possibility of a phyllodes tumour was suggested. The patient underwent wide surgical exci-sion of the lesion and the surgeon required intra-operative frozen section-based diagnosis. Patholo-gist made a provisional diagnosis of ‘ fibromatosis-like spindle cell prolif-eration’ (Figure 2), suggesting that

a final diagnosis could be rendered only on a formalin-fixed sample, because the possibility of a spindle cell metaplastic carcinoma could not be completely ruled out.

The surgical specimen of the breast measured 7 × 4.5 × 4 cm and contained a central firm, whitish nodular mass measuring 2.5 cm in greatest diameter, with apparently well-circumscribed margins (Figure 3). Histologically, at low magnification, a variably cellular mesenchymal tumour with a fascic-ular growth pattern and focally infil-trative margins was seen (Figure 4). Tumour was composed of uniform, bland-looking, spindle-shaped cells arranged in long interlacing fascicles separated by a variable amount of fibrous stroma, entrapping mammary ducts, lobules and fat tissue (Figure 5). The spindle cells had a palely eosino-philic cytoplasm and elongated normochromatic nuclei (Figure 5). Cellular atypia, mitoses, necrosis and haemorrhage were not seen. Notably, the more cellular areas blended into hypocellular and more fibrotic areas. Only focally keloid-like fibroscle-rotic areas were seen. Rarely, foci of lymphocytes were found. Surgical margins were tumour-free.

Immunohistochemical studies were performed with the labelled strepta-vidin–biotin peroxidase detection system using the Ventana automated immunostainer (Ventana Medical Systems, Tucson, AZ, USA). A large panel, including the following anti-bodies, was used: vimentin, epithe-lial membrane antigen (EMA), pan-cytokeratins (MNF116; AE1/AE3), CD10, S-100 protein, HMB45,

-smooth muscle actin, desmin, myogenin, P63, CD117, oestrogen and progesterone receptors, ALK-1 protein and β-catenin. Neoplastic cells were stained with vimentin,

-smooth muscle actin (Figure 6) and β-catenin. No immunoreactivity was obtained with any of other anti-bodies. On the basis of morphological and immunohistochemical features, a diagnosis of ‘fibromatosis of the breast parenchyma’ was rendered.

Figure 2: Intra-operative frozen section showing a spindle cell proliferation with pushing margins. Uninvolved mammary ducts are seen outside the tumour. Magnifica-tion ×100.

Figure 3: Surgical specimen showing a well-circumscribed, whitish, solid, nodular mass.

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The patient is well with no evidence of local recurrence after a 6-year follow-up period.

DiscussionThe typical radiological and macro-scopic appearance of primary fibromatosis of the breast is that of a solid mass with poorly, frequently finger-like, margins, highly suspi-cious for malignancy2–6. On the basis of these observations, it is note-worthy that radiological features of primary breast fibromatosis are non-specific, being similar, if not identical, to those described in invasive breast carcinoma3–6,12,16–18. Only rarely, this soft tissue tumour may present with radiological features, suggestive of a benign lesion19.

We report a rare case of primary fibromatosis of the breast which presented as a nodular mass with apparently circumscribed margins. Sonography revealed a 2.5-cm, heter-ogeneously hypoechoic, oval-shaped mass with focally indistinct margins. A wide excisional biopsy was performed and a frozen-section diag-nosis of ‘fibromatosis-like spindle cell lesion’ was proposed. Histolog-ical examination of the formalin-fixed tissues revealed a bland-looking

spindle cell tumour arranged in long, interlacing fascicles that infiltrated mammary fat and ducts/lobules. Notably, tumour margins were only focally of the infiltrative type. This finding explained the benign-like nodular appearance detected at both sonographic and macroscopic exami-nation. Although the histological diagnosis of fibromatosis is usually straightforward for superficial- and deep-seated soft tissue lesions, it may be challenging when this tumour occurs at unusual sites, including breast parenchyma. In this regard, fibromatosis of the breast potentially poses differential diagnostic prob-lems with a wide variety of benign and malignant spindle cells lesions, including nodular fasciitis, inflamma-tory myofibroblastic pseudotumour, myofibroblastoma, leiomyosarcoma, malignant myoepithelioma and fibromatosis-like low-grade sarco-matoid/metaplastic carcinoma. However, in our opinion, desmoid-type fibromatosis of the breast needs to be distinguished, especially from myofibroblastoma, inflammatory myofibroblastic pseudotumour and low-grade sarcomatoid/metaplastic carcinoma. The former is a benign tumour arising in the mammary stroma, which can be confused with fibromatosis in that it is composed

of spindle-shaped cells arranged in short intersecting fascicles inter-rupted by keloidal-like collagen bands20,21. In myofibroblastomas that contain a significant intratu-moural fatty component (lipomatous myofibroblastoma), the spindle-shaped cells, closely intermingling with adipocytes, impart a fibroma-tosis-like infiltrative pattern to the tumour22. Unlike myofibroblastoma, fibromatosis exhibits infiltrative, at least focally, margins, entraps fat and glandular breast tissue, and the neoplastic cells lack diffuse expres-sion of desmin, CD34, oestrogen/progesterone receptors and bcl-2 protein20–23. Inflammatory myofi-broblastic pseudotumour is a fibro-inflammatory lesion which can be rarely encountered in the breast parenchyma24. It is composed of spindle-shaped cells arranged in a fascicular, and less frequently, stori-form growth pattern. Unlike fibroma-tosis, this reactive lesion contains a significant component of inflam-matory cells, including plasma cells, lymphocytes and eosinophils24. Although it shows immunoreac-tivity for -smooth muscle actin, ALK-1 protein is expressed in about 40%–50% of cases, while β-catenin, a marker which is typically found

Figure 4: Histological section from formalin-fixed tissue. The spindle cell proliferation exhibited focally infil-trative margins (lower right corner). Magnification ×80.

Figure 6: Neoplastic cells are stained with -smooth muscle actin. Myoepi-thelial cells of entrapped hyperplastic mammary ducts served as internal control. Magnification ×100.

Figure 5: Typical features of desmoid-type fibromatosis. Long fascicles of bland-looking spindle-shaped cells are embedded in a fibrous stroma. Mammary lobule is entrapped by the neoplastic proliferation. Magnifica-tion ×80.



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in most cases of fibromatosis, is not expressed. Fibromatosis-like low-grade sarcomatoid/metaplastic carcinoma is a malignant tumour composed predominantly/exclu-sively of spindle cells with a minority of epithelioid cells which tend to aggregate in small nests or, more rarely, in pseudo-glandular struc-tures25. Although there is the possi-bility that a minority of neoplastic cells of this carcinoma may express

-smooth muscle actin, they show immunoreactivity, at least focally, for epithelial markers, such as cytokeratins and EMA25.

The present case emphasizes that primary fibromatosis of the breast may rarely exhibit as a nodular mass with circumscribed margins. This suggests that breast fibromatosis may lack the typical radiological features suspicious for malignancy. The diagnosis is histologically-based and the morphological criteria are similar to those of desmoid-type fibromatosis of soft tissues. We believe that a correct diagnosis of breast fibromatosis, even on frozen sections, is primarily dependent on awareness by pathologists that this tumour can rarely arise in this unusual site. However, due to morphological overlapping between fibromatosis and fibromatosis-like low-grade spindle cell sarcomatoid carcinoma, we recommend a provi-sional diagnosis of ‘fibromatosis-like spindle cell lesion’ at frozen section biopsy, suggesting that a final diag-nosis can be rendered on a surgi-cally-excised lesion by a combined interpretation of morphological and immunohistochemical features.

ConclusionThe present case emphasizes that primary fibromatosis of the breast may rarely exhibit as a nodular mass with circumscribed margins. This suggests that breast fibromatosis may lack the typical radiological features suspicious for malignancy. The diagnosis is histologically-based, and the morphological criteria are

similar to those of desmoid-type fibromatosis of soft tissues. We believe that a correct diagnosis of breast fibromatosis, even on frozen sections, is primarily dependent on awareness by pathologists that this tumour can rarely arise in this unusual site. However, due to morphological overlapping between fibromatosis and fibromatosis-like low-grade spindle cell sarcomatoid carcinoma, we recommend a provi-sional diagnosis of ‘fibromatosis-like spindle cell lesion’ at frozen section biopsy, suggesting that a final diag-nosis can be rendered on a surgi-cally-excised lesion by a combined interpretation of morphological and immunohistochemical features.

Consent Written informed consent was obtained from the patient for publi-cation of this case report and accom-panying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.

Acknowledgement No financial assistance or support was received in any form for the review and writing this case report.

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fibromatosis of the breast parenchyma with a benign-like ... · fibromatosis exhibits infiltrative,...

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