“A Four Day Old Infant Boy
With a Forehead Lesion”
California Tumor Tissue Registry’s
Case of the Month
CTTR COTM Vol. 15:12
September, 2013
www.cttr.org
A four day old infant boy underwent a biopsy of a firm 2.5 x 1.0 cm purplish macule on
his forehead. Microscopically the lesion showed a nodular growth pattern and biphasic
zonality with an abrupt interface between the central hypercellular component and
peripheral paucicellular component (Figs. 1, 2). Higher power views of the central region
showed a hemangiopericytoma-like pattern with abnormal staghorn vessels (Figs. 3, 4).
The hypocellular region around the perimeter showed spindled eosinophilic cells with a
fascicular growth pattern, resembling smooth muscle cells or myofibroblasts (Figs. 5, 6).
A small area of necrosis and calcification was present (Fig. 7).
Diagnosis: Myofibroma (Myopericytoma)
Summer Blount MD, Donald R. Chase MD
Department of Pathology and Human Anatomy, Loma Linda University
Medical Center, Loma Linda, California
California Tumor Tissue Registry, Loma Linda, California
Although myofibromatosis was initially described in 1951 by Williams and Schrum as a
type of congenital fibrosarcoma, the entity was quickly reclassified by Stout as congenital
generalized fibromatosis when it was shown that this tumor lacked malignant potential.
Chung and Enzinger later noted that the cellular makeup was primarily of myofibroblasts
and renamed the lesion “infantile myofibromatosis”, and adopted the term “myofibroma”
when the lesion was solitary. Later, the term “infantile” was dropped in recognition that
these tumors may occur later in life.
The 1998 WHO classification of this tumor separated it into two entities as part of a
morphologic spectrum. One was termed myopericytoma (MPC) and the other as a
myofibroma (MF). Then the 2013 WHO classification combined a group of similar
tumors under the rubric “myopericytoma” (MPC). This class of tumors is characterized
by concentric vascular proliferation of spindled cells showing differentiation towards
perivascular myoid cells. These entities include solitary myofibroma, myofibromatosis,
infantile hemangiopericytoma, angioleiomyoma and glomus tumor. It is still unclear if
these are distinct entities, or a spectrum of the same tumor.
The presented tumor is generally termed a “myofibroma.” It is the most common fibrous
tumor of childhood, accounting for 20% to 25%. These lesions usually present between
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birth and five years of age, with a slight male preponderance. However, recent studies
have shown that myofibromas may be found in any age group including children and
adults. When solitary, they are usually seen on the head and neck, commonly the
forehead, parotid region or scalp, and usually range from only a few millimeters in
diameter up to several centimeters in diameter. They are confined to the dermis and
subcutaneous tissue and have a rubbery to firm touch and a white-gray to pink-purple cut
surface. Clinically, they present as painless purple macules which may be mistaken for a
hemangioma.
Outcome is determined by disease extent at diagnosis. Individuals with fewer lesions and
no visceral involvement have an excellent prognosis. These tumors may spontaneously
regress in younger children, particularly those less than 2 years of age. Most cases are
sporadic; however, both autosomal recessive and dominant patterns of inheritance have
been described. Treatment is generally limited to complete or partial excision with a
local recurrence rate of less than 10%. In cases where surgery might cause significant
morbidity, chemotherapy has been used to reduce the tumor size and alleviate associated
symptoms.
Microscopically, myofibromas have a characteristic nodular appearance that is biphasic
with areas of hyper and hypocellularity, resulting in dark and light staining. The darkly
stained, hypercellular areas are centrally located and consist of whorling round to oval
cells with slightly pleomorphic, hyperchromatic nuclei. There is a predominant pattern of
HPC-like thin walled vessels surrounded by small spindled cells with vesicular nuclei,
eosinophilic cytoplasm and indistinct cell boarders. Commonly, coagulative type
necrosis, calcification and hemorrhage are present. Some tumors with extensive central
necrosis mimic necrotic granulomas.
The lighter staining paucicellular peripheral areas consist of plump myoid spindled cells
with elongated nuclei and moderately abundant eosinophilic cytoplasm. These spindle
cells are arranged in short fascicles often within hyaline-myxoid stroma. Of note, the
identification of peripheral myoid-appearing cells can be useful when differentiating
myofibroma from other entities.
In the majority of cases the histology of myofibroma is characteristic and additional
studies do not need to be utilized. Immunohistochemistry can be used to distinguish it
from other considerations or entities when necessary. Myofibromas stain positively for
smooth muscle actin and vimentin, and to a lesser extent muscle-specific actin. In the
central portion, smooth muscle actin highlights the myofibromatous pattern without
reactivity in the contiguous HPC-like foci.
Differential diagnosis:

Infantile fibromatosis is considered in patients with multiple lesions. The
individual nodules have similar features as myofibromas, except that they occur
not only in the dermis, subcutis, and soft tissue, but also in muscle, bone, and
internal organs. Myofibromatosis is subdivided into multifocal and generalized
forms in which visceral involvement is diagnostic for generalized
myofibromatosis.
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If only the central portion of the lesion is biopsied, various sarcomas may enter
the differential diagnosis. Extensive vascular proliferation and necrosis would
raise concern for entities such as congenital infantile fibrosarcoma, solitary
fibrous tumor, dermatofibrosarcoma protuberans, peripheral primitive
neuroectodermal tumor, or other sarcomas. In general, immunostains that will be
helpful include S-100, CD99 and cytokeratins.

Congenital infantile fibrosarcoma (CIFS) usually occurs during the first year of
life, with some diagnosed antenatally. Clinically, infantile fibrosarcoma presents
as a solitary rapidly enlarging mass, sometimes grotesque in proportion to the
child's size. The superficial and deep soft tissues of the distal extremities are the
primary site in nearly two-thirds of cases, with the remainder found on the trunk,
head and neck. Microscopically CIFS is highly cellular and may have a storiform
or herringbone pattern. The cells are predominately spindled, but have a high
nuclear to cytoplasmic ratio with hyperchromasia, tumor necrosis, and frequent
mitoses. CIFS lacks the biphasic zonal pattern and peripheral myofibroblasts seen
in myofibroma. Genetic analysis can be critical for differentiation between CIFS
and myofibroma. There is a known characteristic translocation t(12;15) identified
in CIFS, with 40-80% being congenital. Treatment is usually complete surgical
excision. However, with appropriate treatment there is a relatively good
prognosis when compared to other sarcomas. This tumor has a mortality rate of
less than 5%.

Infantile hemangiopericytoma usually occurs within the first year of life as a
solitary lesion located in the subcutis or oral cavity. Older children may have
tumors within muscle or mediastinum.
Microscopically, infantile
hemangiopericytoma closely resembles adult HPC/SFT, but differs in that the
superficial lesions are multilobulated, often with distinct intravascular and
perivascular satellite nodules outside the main tumor mass. Features such as
increased mitotic activity and focal necrosis generally do not indicate a poor
prognosis in infantile HPC as it does with the adult form. Treatment is similar to
that of myofibroma, with possible spontaneous regression or local excision.

Fibrous histiocytoma shows a pronounced proliferation of polymorphous cells
arranged in a storiform pattern often with a histiocytic component, multinucleated
cells and iron pigment. These cells may be smooth muscle actin (SMA) positive
like myofibroma, but may also express factor XIIIa and CD68.

Inflammatory myofibroblastic tumor (IMT) is composed of spindled
myofibroblasts within a variable background of collagen and inflammatory cells.
IMT often shows rearrangements of the 2p23 chromosomal region, involving the
ALK gene, and thus often stains for ALK-1, and lacks an HPC-like pattern.
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Suggested Reading:
1. Weiss SW, Goldblum JR. Enzinger & Weiss’s Soft Tissue Tumors. 5th ed. Philadelphia:
Mosby-Elsevier, 2008:264-269.
2. Stocker JT, Dehner LP. Pediatric Pathology. 3rd ed. Philadelphia: Lippincott WilliamsWilkins 2011:1052-1056, 1072.
3. Solitary, multifocal and generalized myofibromas: clinicopathological and immunohistochemical features of 114 cases. Oudijk, Lindsey; den Bakker, Michael A; Hop, Wim C J;
Cohen, Marta; Charles, Adrian K; Alaggio, Rita; Coffin, Cheryl M; de Krijger, Ronald R.
Histopathology. May2012, Vol. 60 Issue 6B, pE1-E11.
4. Myofibroma of the cheek: A case report. Kassenoff, Tali L.; Tabaee, Abtin; Kacker,
Ashutosh. ENT: Ear, Nose & Throat J. Jun2004, Vol. 83 Issue 6, p404-407.
5. Myopericytoma: a unifying term for a spectrum of tumours that show overlapping features
with myofibroma. A review of 14 cases. Dray, M. S.; McCarthy, S. W.; Palmer, A. A.; Bonar,
S. F.; Stalley, P. D.; Marjoniemi, V.; Millar, E.; Scolyer, R. A J Clin Pathol. Jan2006, Vol. 59
Issue 1, p67-73.
6. The Spectrum of Pediatric Fibroblastic and Myofibroblastic Tumors. Hicks, John; Mierau,
Gary. Ultrastructural Pathol. Sep-Dec2004, Vol. 28 Issue 5/6, p265-281.
7.
Malignant myopericytoma: expanding the spectrum of tumours with myopericytic
differentiation. McMenamin, M E; Fletcher, C D M. Histopathology. Nov 2002, Vol. 41 Issue
5, p450-460.
8. Myopericytoma: A Pleural-Based Spindle Cell Neoplasm Off the Beaten Path. Edgecombe,
Allison; Peterson, Rebecca A.; Shamji, Farid M.; Commons, Susan; Sekhon, Harman; Gomes,
Marcio M. Int J Surg Pathol. 04/01/2011, Vol. 19 Issue 2, p247-251.
9. Solitary fibrous tumour and haemangiopericytoma: evolution of a concept.
Guillou, L. Histopathology. Jan2006, Vol. 48 Issue 1, p63-74.
Gengler, C.;
10. Fletcher CDM, Unni KK, Mertens F, eds. Myofibroma and Myopericytoma. In: WHO
Classification of Tumors of Soft Tissues and Bone. Lyon: IARC Press 2013:89-90, 118-120.
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