LETTER TO THE EDITOR

Myxoid myofibroblastoma of the breast with atypical cells:

a potential diagnostic pitfall
Gaetano Magro & Paolo Amico & Alessandra Gurrera
Received: 16 December 2006 / Revised: 11 January 2007 / Accepted: 18 January 2007 / Published online: 15 February 2007
# Springer-Verlag 2007
Keywords Myofibroblastoma
.
Myxoid variant
.
Atypical cells
.
Breast
Sir,
Myofibroblastoma of the breast is an unusual benign
mesenchymal tumour that belongs to the family of the so-
called benign spindle cell tumours of the mammary
stroma [5, 6]. In its classic type, it is typically composed of
bland-looking spindle cells exhibiting a variable fibro
myofibroblastic differentiation [5, 6]. In recent years, the
morphological spectrum of this tumour has been broadened
by the recognition of several variants, including epithelioid,
lipomatous, fibromatosis-like, fibrous/collagenized, myxoid
ones [46].
Recently, we have encountered two cases of mammary
myofibroblastoma with atypical cells embedded within a
prominent myxoid stroma. To the best of our knowledge,
this unusual morphological variant has not hitherto been
reported. Two male patients (63 and 56 years) presented
with two nodular breast masses, measuring 3 and 3.5 cm in
greatest dimension, respectively, which were surgically
excised.
Histologically, both surgical samples were represented
by unencapsulated mesenchymal tumours with pushing
borders, composed of spindle to epithelioid cells, embedded
in an abundant myxoid stroma containing isolated thick
eosinophilic collagen bands (Figs. 1a and 2a). Myxoid
matrix stained positively with Alcian blue at pH 2.5 and
negative for periodic acid-Schiff. One tumour was hypo-
cellular (Fig. 1a), while the other one showed alternating
hypocellular and moderately cellular areas (Fig. 2a). Neo-
plastic cells had pale to deeply eosinophilic cytoplasm and
round to oval nuclei containing one or two visible nucleoli.
In both cases, a significant number of neoplastic cells (50
60%) exhibited a moderate to severe degree of nuclear
pleomorphism (Figs. 1a,b and 2a,b). Some cells were bi- or
multinucleated (Fig. 2b). A minor mature fatty component
was scattered throughout both tumours. Mitoses were
absent in the hypocellular tumour, while one mitosis per
ten high power fields was observed in the other neoplasm.
Necrosis was absent. No epithelial component was identi-
fied within both tumours. Immunohistochemically, the cells
of both cases had a similar profile: diffuse and strong
immunoreactivity to vimentin, -smooth muscle actin and
desmin (Fig. 1c), and a variable staining to CD34, bcl-2
protein, CD99, estrogen (ER), progesterone (PR), and
androgen (AR) receptors. No immunoreactivity was
obtained for pancytokeratin, epithelial membrane antigen,
h-caldesmon, calponin, S-100 protein, and human mela-
noma black-45 (HMB-45). This immunophenotype was
consistent with a fibro-myofibroblastic nature of the neo-
plastic cells.
We believe that the tumours herein presented fit within
the spectrum of breast myofibroblastoma [5, 6], represent-
ing an uncommon morphological variant, for which the
descriptive term myxoid myofibroblastoma with atypical
cells is proposed. The following morphological and
immunohistochemical features, typically seen in myofibro-
blastoma [5, 6], support our opinion: (1) Tumours were
pure mesenchymal lesions lacking any epithelial compo-
nent; (2) Tumours had pushing borders; (3) The myxoid
extracellular matrix contained thick eosinophilic collagen
bands; (4) Neoplastic cells resulted to have a fibro-
Virchows Arch (2007) 450:483485
DOI 10.1007/s00428-007-0373-z
G. Magro (*)
:
P. Amico
:
A. Gurrera
Dipartimento G.F. Ingrassia, Anatomia Patologica,
Universit di Catania,
Via S. Sofia 87,
95123 Catania, Italy
e-mail: g.magro@unict.it
myofibroblastic profile by means of immunohistochemistry
(diffuse immunoreactivity to vimentin, -smooth muscle
actin and desmin); and (5) Neoplastic cells variably
expressed CD34, bcl-2, CD99, ER, PR, and AR receptors.
Although the presence of myxoid areas or atypical cells
has been documented in some breast myofibroblastomas [1,
3, 5, 6], their association in the same tumour could pose
diagnostic problems with some malignant myxoid neo-
plasms. However, the absence of infiltrative margins, high
mitotic activity, atypical mitoses, and necrosis argues
against malignancy. In our opinion, cellular pleomorphism
in breast myofibroblastoma should be interpreted as a
degenerative phenomenon, similarly to what is observed
in the so-called atypical bizarre leiomyomas, ancient
schwannoma, which does not adversely affect the bio-
logical behaviour of tumour, accordingly. Differential
diagnosis mainly revolved around the myxoid type of
spindle cell lipoma and solitary fibrous tumour. Discrim-
ination between myofibroblastoma and spindle cell lipoma/
solitary fibrous tumour may be difficult, as they are closely
related neoplasms, likely arising from a common mammary
stromal stem cell capable to differentiate along several
Fig. 1 a At low magnification, a hypocellular myxoid tumour with
pushing borders can be appreciated. b Myxoid hypocellular tumour
with atypical spindle-shaped cells. Thick eosinophilic collagen bands
are seen. Severe nuclear pleomorphism is evident. c Neoplastic cells
are immunoreactive to desmin
Fig. 2 a Myxoid tumour with
moderate cellularity. b At
higher magnification, neoplastic
spindle, epithelioid cells with
severe nuclear pleomorphism
are seen. Some cells are
multinucleated
484 Virchows Arch (2007) 450:483485
mesenchymal lines, including the fibroblastic, myofibro-
blastic, and lipomatous ones [46]. This hypothesis is
supported by the fact that all these tumours share some
morphological and immunohistochemical features and by
the recognition of hybrid tumours that simultaneously
exhibit features of MFB and solitary fibrous tumour or
MFB and spindle cell/pleomorphic lipoma [3, 5, 6].
Cytogenetic analyses, revealing that spindle cell lipoma
and myofibroblastoma have similar chromosome 13 rear-
rangements associated with the loss of the 13q14 chromo-
somal region [2, 7], seem to confirm what we have
previously postulated. We admit that immunohistochemis-
try was crucial for classification of our tumours as
myofibroblastomas, in consonance with the ability of
neoplastic cells to differentiate along a myofibroblastic line,
as demonstrated by their immunophenotype (-smooth
muscle actin
+
, desmin
+
, calponin

, h-caldesmon

).
In conclusion, the present paper, describing two cases of
myxoid myofibroblastoma with atypical cells, contributes
to widen the morphological spectrum of this unusual
mammary tumour. Although this rare variant exhibits some
worrisome morphological features that could alarm a
pathologist, the correct diagnosis is confidentially achieved
if the well-established morphological and immunohisto-
chemical criteria of myofibroblastoma are applied [5].
References
1. Lazaro-Santander R, Garcia-Prats MD, Nieto S, Andres-Gozalvo C,
Cortes, Vizcaino V, Vargas-Holguin S, Vera-Roman JM (1999)
Myofibroblastoma of the breast with diverse histological features.
Virchows Arch 434:547550
2. Maggiani F, Debiec-Rychter M, Verbeeck G, Sciot R (2006)
Extramammary myofibroblastoma is genetically related to spindle
cell lipoma. Virchows Arch 449:244247
3. Magro G, Fraggetta F, Torrisi A, Emmanuele C, Lanzafame S
(1999) Myofibroblastoma of the breast with hemangiopericytoma-
like pattern and pleomorphic lipoma-like areas. Report of a case
with diagnostic and histogenetic considerations. Pathol Res Pract
195:257262
4. Magro G, Michal M, Bisceglia M (2000) Lipomatous myofi-
broblastoma: a potential diagnostic pitfall in the spectrum of
the spindle cell lesions of the breast. Virchows Arch 437:540
547
5. Magro G, Michal M, Bisceglia M (2001) Benign spindle cell
tumors of the mammary stroma: diagnostic criteria, classi-
fication and histogenesis. Review. Pathol Res Pract 197:453
466
6. Magro G, Bisceglia M, Michal M, Eusebi V (2002) Spindle cell
lipoma-like tumor, solitary fibrous tumor and myofibroblastoma
of the breast: a clinico-pathological analysis of 13 cases in
favor of a unifying histogenetic concept. Virchows Arch
440:249260
7. Pauwels P, Sciot R, Croiset F, Rutten H, Van den Berghe H, Dal
Cin P (2000) Myofibroblastoma of the breast: genetic link with
spindle cell lipoma. J Pathol 191:282285
Virchows Arch (2007) 450:483485 485