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Background
These are rare benign soft tissue tumors, usually found in the breasts of men in their 5-7th decades. Rarely, extra-mammary cases have been reported.
OUTLINE
EPIDEMIOLOGY CHARACTERIZATION SYNONYMS INCIDENCE/PREVALENCE AGE SEX GEOGRAPHY EPIDEMIOLOGIC ASSOCIATIONS
DISEASE ASSOCIATIONS CHARACTERIZATION GYNECOMASTIA
Myofibroblastoma associated with bilateral gynecomastia: a case report and literature review.
Yoo CC, Pui JC, Torosian MH.
Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA.
Oncol Rep. 1998 May-Jun;5(3):731-3 Abstract quote.
Myofibroblastoma of the breast is a recently recognized benign mesenchymal mammary tumor that typically occurs as a unilateral, solitary lesion. Myofibroblastomas are well-circumscribed, unencapsulated tumors characterized by spindle cells in fascicles which exhibit varying degrees of myogenic and fibroblastic differentiation.Our case reports a mammary myofibroblastoma occurring in an 82-year-old male with gynecomastia and reviews the reported incidence of this benign spindle cell tumor in the world literature.
PATHOGENESIS CHARACTERIZATION ANDROGENS
Myofibroblastoma of the breast revisited: an etiologic association with androgens?
Morgan MB, Pitha JV.
Department of Pathology, University of South Florida, Veteran's Administration Hospital, Tampa, USA.
Hum Pathol. 1998 Apr;29(4):347-51 Abstract quote.
Myofibroblastoma of the breast is an uncommon benign stromal tumor encountered predominantly among elderly men.Histologically, myofibroblastoma is a well-circumscribed tumor comprised of bipolar spindle cells arranged in short fascicles traversed by collagen bundles. Based on previous histological, immunohistochemical, and ultrastructural observations, this tumor is thought to be derived from myofibroblasts. The pathogenesis of myofibroblastoma is unknown. Given the demographics of this lesion, the established trophic effect of steroid hormones, and the potential diagnostic utility of hormone receptor analysis in differentiating spindle cell tumors, we immunohistochemically tested for estrogen and androgen receptors in a host of spindle cell lesions including myofibroblastoma of the breast.
Five cases reported herein of histological confirmed myofibroblastoma obtained from male and female breasts each showed strong nuclear antibody staining for the androgen receptor, not seen in four cases of leiomyosarcoma, three cases of fibromatosis, three cases of dermatofibrosarcoma protuberans, and two cases of monophasic synovial sarcoma.
We postulate that the androgen receptor or its ligands may be pathologically related to the development of myofibroblastoma of the breast and diagnostically useful in differentiating it from other spindle cell lesions.
CHROMOSOMAL ALTERATIONS
Myofibroblastoma of the breast: genetic link with spindle cell lipoma.
Pauwels P, Sciot R, Croiset F, Rutten H, Van den Berghe H, Dal Cin P.
Stichting PAMM, Catharinaziekenhuis, Eindhoven, The Netherlands.
J Pathol. 2000 Jul;191(3):282-5 Abstract quote.
Mammary myofibroblastoma is a rare tumour, mainly occurring in male patients. This paper describes two cases of mammary myofibroblastoma, with typical histological features, including the presence of fat cells and mast cells.Immunohistochemically, the spindle cells stained positively for desmin and CD34. Cytogenetically, both tumours showed partial monosomy 13q and in case 1, there was, in addition, partial monosomy 16q. Rearrangements affecting 13q and 16q occur typically in spindle cell lipomas.
In addition to histological similarities, the hitherto unreported chromosomal changes in mammary myofibroblastoma, which are similar to the chromosomal aberrations in spindle cell lipoma, strongly suggest a link between these two tumours and are not in favour of myofibroblastoma being a primary solitary fibrous tumour of the breast.
LABORATORY/
RADIOLOGIC/
OTHER TESTSCHARACTERIZATION RADIOLOGIC Male breast myofibroblastoma and MR findings.
Vourtsi A, Kehagias D, Antoniou A, Moulopoulos LA, Deligeorgi-Politi H, Vlahos L.
Department of Radiology, Aretaion Hospital, University of Athens Medical School, Greece.
J Comput Assist Tomogr. 1999 May-Jun;23(3):414-6. Abstract quote
Myofibroblastoma of the breast is a rare benign tumor seen predominantly in men in the sixth to seventh decades of life.We present a case of breast myofibroblastoma in a man and describe the mammographic, sonographic, and MR findings.
GROSS APPEARANCE/
CLINICAL VARIANTSCHARACTERIZATION GENERAL BREAST
Myofibroblastoma of the breast.
Formby MR, Hehir M.
Nowra Community Hospital, New South Wales, Australia.
Pathology. 1997 Nov;29(4):431-3 Abstract quote.
Myofibroblastoma of the breast is an uncommon stromal tumor most often found in older men. It usually presents as a solitary well-circumscribed breast lesion consisting of slender bipolar spindle cells and broad bands of hyalinised collagen.This is the first documented case of myofibroblastoma of the breast in Australia. Found in a 71-year-old man, this case demonstrates many of the typical features of this entity. A history of previous trauma to the chest wall was present in this case, a finding only rarely associated with this lesion.
INTRACRANIAL
Myofibroblastoma in the suprasellar region. Case report.
Shinojima N, Ohta K, Yano S, Nakamura H, Kochi M, Ishimaru Y, Nakazato Y, Ushio Y.
Department of Neurosurgery, Kumamoto University School of Medicine, Kumamoto, Japan.
J Neurosurg. 2002 Nov;97(5):1203-7. Abstract quote
Myofibroblastoma is a rare type of benign mesenchymal tumor; only two cases of intracranial myofibroblastoma have been reported in the literature.The authors report on the case of a 34-year-old woman with a myofibroblastoma in the suprasellar region who presented with the complaint of sudden onset of headache followed within 2 weeks by progressively worsening visual disturbance. Computerized tomography scanning demonstrated a mixed low- and high-density mass in the suprasellar region and contrast-enhanced magnetic resonance imaging revealed the mass to be of mixed intensity with heterogeneous enhancement. The tumor was subtotally removed via a right frontobasal translamina-terminalis approach and her vision improved immediately.
Histologically, the tumor was characterized by alternating areas of spindle-shaped and round cells that were separated by collagen fibers. The diagnosis of myofibroblastoma was based on the tumor's intense immunoreactivity for alpha-smooth-muscle actin and the ultrastructural identification of myofibroblasts. The tumor was thought to have originated from the meninges in the suprasellar region.
INTRANODAL
Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555-0743, USA.
Intranodal palisaded myofibroblastoma (IPM) usually presents as a painless, slow-growing inguinal mass. Our review of 42 cases from 13 publications indicates that two thirds of IPMs occur between the ages of 45 and 55 years, the male-female ratio is 2:1, and there is a lack of ethnic predilection. Grossly, the IPM cut surface shows areas of hemorrhage.
Five microscopic features are seen: (a) compressed remnants of lymphoid tissue at the periphery; (b) spindle cells with nuclear palisading; (c) intraparenchymal hemorrhage and erythrocyte extravasation; (d) so-called amianthoid fibers; and (e) intracellular and extracellular fuchsinophilic bodies that stain positive for smooth muscle actin.
Immunohistochemically, IPM is positive for smooth muscle actin and cyclin D1 and negative for S100, glial fibrillary acidic protein, CD34, and desmin, and it shows a low proliferative index of Ki-67. Electron microscopy demonstrates features of myofibroblasts and smooth muscle cells.
Excellent prognosis is seen after surgical treatment, with an approximately 6% recurrence rate and no malignant transformation.Intranodal palisaded myofibroblastoma: report of three new cases.
Rossi A, Bulgarini A, Rondanelli E, Incensati R.
Unita Operativa Anatomia Patologica, Ospedale Misericordia, USL 9, Grosseto, Italy.
Tumori. 1995 Nov-Dec;81(6):464-8. Abstract quote
Intranodal palisaded myofibroblastoma is a well-defined entity in the group of spindle-cell neoplasms of lymph nodes. The authors report 3 new cases of this unusual tumor. The nature of the proliferating cells is discussed.SOFT TISSUE
Amianthoid myofibroblastoma of the soft tissues.
Corsi A, Camassei FD, Bosman C.
Dipartimento di Medicina Sperimentale e Patologia, Universita La Sapienza, Roma, Italy.
Tumori. 1997 Sep-Oct;83(5):862-7 Abstract quote.
Myofibroblastoma (MF) is an uncommon, usually benign, mesenchymal tumor infrequently described in soft tissues.We report here on the clinicopathologic findings of a soft tissue MF (STMF) presenting in the neck of a 90-year-old man as a slowly growing and non-painful nodule, 4 cm in greatest diameter. Histology revealed a circumscribed lesion constituted of monomorphous bipolar spindle cells arranged in swirling fascicles with intervening broad bands of hyalinized collagen and well formed "amianthoid" fibers.
Immunohistochemistry showed the spindle cells to be immunoreactive for vimentin, smooth muscle actin and muscle specific actin and, focally, for desmin; immunostaining for cytokeratin, epithelial membrane antigen, S-100 protein, factor VIII-related antigen, and CD34 was negative. Based on the present case and on those previously reported in the literature, STMF is characterized by: 1) exclusive incidence in the male sex; 2) variable immunoreactivity of the neoplastic cells for desmin, probably reflecting an origin from a peculiar subset of myofibroblasts, or, alternatively, a further myoid differentiation; 3) variable abundance of (hyalinized) collagen; 4) presence of amianthoid fibers.
The combination of desmin immunoreactivity, frequently observed in MF of the breast, and amianthoid fibers, the main feature of MF of the lymph nodes, has never been observed in soft tissue MF. It is important to recognize STMF as a specific clinicopathologic entity to avoid confusion with other types of spindle cell proliferation and to differentiate it from other types of myofibromatosis.
TOUNGE
Myofibroblastoma of the tongue. An immunohistochemical, ultrastructural, and flow cytometric study.
Sahin AA, Ro JY, Ordonez NG, Luna MA, el-Naggar AK, Goepfert H, Ayala AG.
Department of Pathology, University of Texas, M. D. Anderson Cancer Center, Houston 77030.
Am J Clin Pathol. 1990 Dec;94(6):773-7. Abstract quote
A case of myofibroblastoma arising in the tongue of a 77-year-old man is described. The patient presented with a submucosal tongue mass without other associated symptoms. The tumor was 2 cm in diameter, well circumscribed, and composed of uniform spindle cells arranged in fascicles.Electron microscopic examination and immunohistochemistry demonstrated a myofibroblastic origin for the tumor cells. DNA flow cytometric analysis showed a diploid DNA content of this tumor.
To the authors' knowledge, this is the first report of myofibroblastoma occurring in the tongue.
HISTOLOGICAL TYPES CHARACTERIZATION GENERAL BREAST
Giant myofibroblastoma of the male breast.
Ali S, Teichberg S, DeRisi DC, Urmacher C.
Department of Laboratories, North Shore University Hospital-Cornell University Medical College, Manhasset, NY 11030.
Am J Surg Pathol. 1994 Nov;18(11):1170-6. Abstract quote Myofibroblastoma of the breast is a rare, benign neoplasm, seen predominantly in men. The gross appearance is that of a well-circumscribed nodule, characteristically small, seldom exceeding 3 cm.
We report a case of giant myofibroblastoma measuring 10 cm and weighing 169 g in the breast of an 83-year-old man. Light microscopic, immunohistochemistry, and electron microscopic features are described.
Histologically, these neoplasms may exhibit a varied cellularity that can be misinterpreted as sarcoma. However, they lack marked cellular pleomorphism, tumor necrosis, and mitosis and are characteristically composed of plump and long bipolar, spindly cells arranged in swirling fascicles with intervening broad collagen bands. As we report, immunostaining is strongly positive for vimentin, desmin, and muscle common antigen and negative for cytokeratins and S-100-associated protein.
Electron microscopy shows predominantly cells suggestive of myofibroblastic differentiation. The patient has remained free of disease 2 years after mastectomy.
Uncommon presentation of mammary myofibroblastoma.
Hamele-Bena D, Cranor ML, Sciotto C, Erlandson R, Rosen PP.
Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York 10021, USA.
Mod Pathol. 1996 Jul;9(7):786-90. Abstract quote
Myofibroblastoma, a rare benign mesenchymal mammary neoplasm, has been diagnosed largely in men as a unilateral, solitary lesion.We studied nine examples occurring in the breasts of eight patients, all but one of whom were women. In the man, the lesions were bilateral. Patients ranged in age from 44 to 67 years (mean and median, 55 yr). The tumors were well circumscribed and measured 0.9 to 3.0 cm (mean, 1.5 cm). They were composed of cells with a spectrum of appearances including small, compact cells, spindle cells, large histiocytoid cells, and epithelioid cells. All had broad bands of dense collagen, and adipose tissue was present in seven tumors. Foci of pseudoangiomatous hyperplasia were present in two cases.
Strong vimentin positivity was present in seven tumors, which were cytokeratin negative. Weak S100 positivity was demonstrated in one lesion, and actin was positive in two lesions. Desmin was positive in six tumors and negative in one tumor. Treatment for all of the patients was excisional biopsy. Follow-up, available in five cases, was from 10 months to 6 years, 11 months (mean, 37 mo; median, 63 mo). All patients are alive and without evidence of disease.
The clinical and pathologic characteristics of myofibroblastoma in women are similar to published data on the tumor in men. The tumors exhibit heterogeneous immunoreactivity for markers associated with myofibroblasts. Excisional biopsy is adequate therapy.
Myofibroblastoma of the breast. Sixteen cases of a distinctive benign mesenchymal tumor.
Wargotz ES, Weiss SW, Norris HJ.
Am J Surg Pathol. 1987 Jul;11(7):493-502. Abstract quote
The clinical and pathologic findings of 16 examples of a distinctive stromal tumor of the breast designated as "myofibroblastoma" are reported. Eleven of the 16 patients were men, and the average age at presentation was 63 years.Fourteen were treated by local excision and two by simple mastectomy. None of the lesions recurred or metastasized. The tumors were grossly nodular and well-demarcated from the surrounding mammary tissue. Ducts and lobules were not engulfed by the neoplasm. Microscopically, the lesions were formed by uniform, slender, bipolar spindle cells haphazardly arranged in fascicular clusters separated by broad bands of hyalinized collagen.
Ultrastructural examination of four lesions identified a predominance of myofibroblasts. Immunoreactivity for S-100 protein and cytokeratin was absent in the 10 tumors examined, but desmin immunoreactivity was focally present in three lesions. The differential diagnosis of myofibroblastoma includes reactive processes and benign neoplasms such as nodular and proliferative fascititis, fibromatosis, spindle-cell lipoma, neurofibroma, neurilemmoma, and leiomyoma.
Malignant neoplasms such as stromal sarcoma, malignant fibrous histiocytoma, and spindle-cell or metaplastic carcinoma should not be confused with a myofibroblastoma. The clinical significance of this entity lies primarily in its recognition as a distinctive benign neoplasm.
VARIANTS LEIOMYOMATOUS DIFFERENTIATION
Mammary myofibroblastoma with leiomyomatous differentiation.
Thomas TM, Myint A, Mak CK, Chan JK.
Department of Pathology, Kwong Wah Hospital, Hong Kong.
Am J Clin Pathol. 1997 Jan;107(1):52-5. Abstract quote
An unusual example of mammary myofibroblastoma in a 36-year-old woman was reported. The central portion resembled mammary myofibroblastoma or solitary fibrous tumor of other sites and showed reactivity for CD34 and muscle-specific actin, with few cells staining for desmin.The peripheral portion resembled leiomyoma and showed strong reactivity for actin and desmin but only focal staining for CD34. We interpret this tumor as mammary myofibroblastoma showing frank peripheral leiomyomatous differentiation. Although closely related to solitary fibrous tumor, mammary myofibroblastoma appears slightly different because of its consistent slant toward myoid differentiation in the form of actin and variable desmin reactivity as opposed to the rare and sparse immunohistochemical expression of myoid features by solitary fibrous tumors of other sites.
This case demonstrates this phenomenon carried to an extreme, a feature not previously documented in mammary myofibroblastoma. It is of interest to note the modulation of the antigenic profile with the differentiation process, that is, loss of CD34 and gain of desmin accompanying the myoid differentiation.
LIPOMATOUS
Lipomatous myofibroblastoma: a potential diagnostic pitfall in the spectrum of the spindle cell lesions of the breast.
Magro G, Michal M, Vasquez E, Bisceglia M.
Istituto di Anatomia Patologica, Universita di Catania, Via Biblioteca 4, 95124 Catania, Italy.
Virchows Arch. 2000 Nov;437(5):540-4 Abstract quote.
We report on two cases of myofibroblastoma (MFB) of the breast comprised predominantly of a mature fatty component, representing approximately three quarters of the entire tumour area.Both tumours consisted of a well-circumscribed lipomatous tumour mass containing dispersed nodular or irregularly shaped spindled cellular areas. The fatty component was represented exclusively by mature adipocytes, uniform in size and shape, lacking nuclear pleomorphism. The cellular areas contained spindly to oval cells with morphological and immunophenotypical features typical of MFB. The two components were so intimately admixed that a finger-like infiltrating growth pattern was apparent.
The cases reported here as "lipomatous MFB" aim to clarify further the morphological spectrum of MFB of the breast. Lipomatous MFB may potentially mimic other benign or aggressive tumour-like lesions or even bland-looking malignant spindle cell tumours such as fibromatosis, nodular fasciitis, spindle cell lipoma, spindle cell liposarcoma, spindle cell variant of metaplastic carcinoma, spindle cell malignant myoepithelioma, and low-grade fibrosarcoma/malignant fibrous histiocytoma.
The histogenesis of the present bimorphic mesenchymal tumours could be explained as the result of a dual, myofibroblastic and lipomatous, differentiation from a common pluripotential mesenchymal precursor cell, probably represented by the vimentin+/CD34+ fibroblast of the mammary stroma.
SPECIAL STAINS/
IMMUNOPEROXIDASE/
OTHERCHARACTERIZATION SPECIAL STAINS IMMUNOPEROXIDASE
Solitary fibrous tumour (myofibroblastoma) of the breast.
Damiani S, Miettinen M, Peterse JL, Eusebi V.
Institute of Anatomic Pathology, University of Bologna, Italy.
Virchows Arch. 1994;425(1):89-92 Abstract quote.
Three new cases of the spindle cell tumour of the breast, usually termed myofibroblastoma, are reported. The histology and the immunological profile (expression of vimentin, CD34 antigen and of muscular markers) appear similar to those of solitary fibrous tumours recently described in various sites.It is proposed to include these mammary lesions into the group of solitary fibrous tumours and to regard breast as an additional site of origin.
CALDESMON
H-caldesmon expression in myofibroblastoma of the breast: evidence supporting the distinction from leiomyoma.
Magro G, Gurrera A, Bisceglia M.
Dipartimento F. Ingrassia, Anatomia Patologica, Catania, Italy.
Histopathology. 2003 Mar;42(3):233-8 Abstract quote.
AIMS: The ultrastructural detection of leiomyomatous rather than myofibroblastic features in some cases of myofibroblastoma of the breast led some electron microscopically orientated pathologists to doubt the commonly accepted myofibroblastic nature of such a tumour, so the alternative terms 'myogenic stromal tumour' or 'variant of leiomyoma' have been proposed. The aim of this study was to analyse the immunohistochemical expression of h-caldesmon, a reliable marker in distinguishing smooth muscle versus myofibroblastic cellular differentiation, in a large series of myofibroblastomas of the breast to clarify whether these tumours are basically leiomyomatous. Moreover, cases from primary myofibroblastic lesions of the breast, such as fibromatosis and inflammatory myofibroblastic tumour, were analysed to assess whether h-caldesmon expression parallels that observed in their soft tissue counterparts.METHODS AND RESULTS: Paraffin-embedded sections from 12 cases of myofibroblastoma, seven cases of fibromatosis, and one case of inflammatory myofibroblastic tumour were evaluated immunocytochemically for the expression of h-caldesmon. As expected, all myofibroblastic lesions failed to express h-caldesmon. Conversely, focal staining, ranging from 2% to 10% of neoplastic cells, was detected in myofibroblastomas, even though it was restricted to 50% of analysed cases.
CONCLUSIONS: Our results, indicating that smooth muscle differentiation occurs in a minority of the myofibroblastoma cells exclusively in half of the analysed cases, support the separation of myofibroblastoma from leiomyoma. The detection of smooth muscle cells in breast myofibroblastoma is easily explained if we postulate its histogenesis from the CD34+ fibroblasts of mammary stroma capable of multidirectional mesenchymal differentiation, including smooth muscle. We recommend retention of the term myofibroblastoma for all the desmin-positive and/or alpha-smooth muscle actin-positive spindle cell tumours of the breast consistent with the previously well-established morphological criteria for such neoplasms, unless one is dealing with a typical leiomyoma easily recognizable at light microscopy.
ELECTRON MICROSCOPY
Myofibroblastoma of breast: evidence favoring smooth-muscle rather than myofibroblastic differentiation.
Eyden BP, Shanks JH, Ioachim E, Ali HH, Christensen L, Howat AJ.
Department of Histopathology, Christie Hospital National Health Service Trust, Manchester, UK.
Ultrastruct Pathol. 1999 Jul-Aug;23(4):249-57. Abstract quote
A histopathological study of two cases of the tumor known in the literature as myofibroblastoma of the breast is presented. The tumors occurred in Caucasian males aged 57 and 62 years.Histologically, these were moderately cellular, lobulated spindle-cell lesions, each with a reasonably well-delineated edge with surrounding fatty connective tissue. No breast ducts or lobules were present. Tumor cell nuclei were bland, with small nucleoli and some nuclear grooving. Nuclear atypia and mitoses were absent.
Immunostaining revealed positivity for a-smooth-muscle actin, desmin, and CD34. Tumor cells contained rough endoplasmic reticulum, bundles of myofilaments with focal densities, intermediate filaments, attachment plaques alternating with plasmalemmal caveolae, and focal lamina. Ultrastructural findings pointed to true smooth-muscle differentiation, and the cell-surface in particular lacked surface features of myofibroblasts (fibronectin fibrils [microtendons] and fibronexus junctions).
These and published data suggest that at least some of the lesions referred to in the literature as myofibroblastoma may not be myofibroblastic and may be better designated as myogenic stromal tumors or as variants of leiomyoma.
Myofibroblastoma of the axilla.
Mackay B, Ordonez NG, Salter JE Jr, Pollock RE.
Department of Pathology, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Ultrastruct Pathol. 1995 Jul-Aug;19(4):265-8. Abstract quote
A mass in the axilla of a 47-year-old woman was biopsied and resected. The mass was composed of a loosely distributed population of spindle cells that were immunoreactive for smooth-muscle actin.Ultrastructurally, the cells possessed abundant endoplasmic reticulum, and some contained peripheral smooth muscle myofilaments, establishing that they were myofibroblasts. Mitotic activity was sparse, there was no cytologic atypia, and by flow cytometry the tumor was diploid with a low S phase.
A diagnosis of myofibroblastoma was favored, although the possibility of a low-grade sarcoma could not be excluded. There has not been any indication of recurrence over a 4-month period of follow-up.
DIFFERENTIAL DIAGNOSIS KEY DIFFERENTIATING FEATURES SOLITARY FIBROUS TUMOR
PROGNOSIS CHARACTERIZATION GENERAL Benign
TREATMENT CHARACTERIZATION GENERAL SURGICAL Complete removal Macpherson and Pincus. Clinical Diagnosis and Management by Laboratory Methods. Twentyfirst Edition. WB Saunders. 2006.
Rosai J. Ackerman's Surgical Pathology. Ninth Edition. Mosby 2004.
Sternberg S. Diagnostic Surgical Pathology. Fourth Edition. Lipincott Williams and Wilkins 2004.
Robbins Pathologic Basis of Disease. Seventh Edition. WB Saunders 2005.
DeMay RM. The Art and Science of Cytopathology. Volume 1 and 2. ASCP Press. 1996.
Weedon D. Weedon's Skin Pathology Second Edition. Churchill Livingstone. 2002
Fitzpatrick's Dermatology in General Medicine. 6th Edition. McGraw-Hill. 2003.
Weiss SW and Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors. Fourth Edition. Mosby 2001.
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