“A 13 Year-old Girl with a Recurrent Mass in the Thumb”
California Tumor Tissue Registry’s
Case of the Month
www.cttr.org
CTTR COTM, Vol 7(5), February, 2005
A 13-year-old girl with a previous diagnosis of a giant cell tumor of the right thumb presented
with a mildly tender, slow growing, recurrent mass at the same site. An x-ray (Fig. 1) and MRI
of the hand revealed erosion of the cortex of metacarpal bones. At surgery the tumor extensively
involved the dermis and was found to completely encircle the extensor pollicis brevis tendon and
dorsal radial digital nerve, with erosion into the neck of the right thumb metacarpal. She
underwent radical excision which included a skin graft from the forarm to cover the defect.
The tumor was resected piecemeal, and was described as being firm, and pink-tan.
Microscopically, it was shown to be multi-nodular, mostly located within the deep dermis and
extending into the subcutaneous tissue (Fig. 2). The nodules were of varying sizes but generally
well circumscribed, and composed of swirling mononuclear histiocytic cells and scattered
multinucleated giant cells (Fig. 3). The surrounding stroma was composed of fibroblastic cells
some arranged in fascicles and associated with dense collagen. They highlighted tumoral
elements in a plexiform pattern (Fig. 4). Focal areas of hemorrhage were focally seen (Fig. 5).
Mitotic figures were rare, and significant pleomorphism was not seen. Vascular invasion,
however, was common (Fig. 6).
Diagnosis: “Plexiform Fibrohistiocytic Tumor”
Sajjad Syed, MD, Wilson Chick, MD, Donald Chase, MD.
Loma Linda University School of Medicine
Loma Linda University Medical Center, Loma Linda, California
Plexiform fibrous tumor (PFT, aka plexiform fibrous histiocytoma (PFH)) is a biphasic low-grade
malignant mesenchymal neoplasm of children, adolescents, and young adults, first described by
Enzinger and Zhang in 1988. It is centered in the superficial subcutis and is characterized by
fibrohistiocytic cytomorphology, and a multinodular growth pattern.
PFH has a mean age of presentation of approximately 14.5 years (1,2), but has also been reported
in children of only a few months of age, and in adults in up to their eighth decade. There is a
slight predilection for females. PFH usually presents as a small, poorly demarcated, painless
dermal or subcutaneous mass that slowly enlarges for months to years. The majority of cases
occur on the upper extremities (65%), particularly the hands and wrists (45%). About 25% are
seen in the lower extremities (1,2). The head and neck region is rarely involved.
The tumor is usually described as being gray-white and firm, and usually is less than 3 cm in
greatest diameter, however cases of up to 6.0 cm have been described.
Microscopically, the ray-like extensions of fibrous tissue into the surrounding fat apparent on
low-power is quite distinctive of PFH. There is almost always a rim of normal dermis above the
lesions and the overlying epidermis is unremarkable. The nodular component is composed of
CTTR’s Case of the Month
February, 2005
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small nodules or elongated cellular clusters that are interconnected in a characteristic plexiform
arrangement. Three distinct cell types are observed in variable amounts:



mononuclear histiocyte-like cells (MNHC) with abundant, pale-staining, granular
cytoplasm and central nuclei;
spindle fibroblast-like cells which may be partially arranged in fascicles and set in dense
collagen; and
multinucleate giant cells (MNGC).
The tumors vary considerably in the proportion of these three elements, and form a spectrum. On
one side are tumors formed predominantly of histiocyte-like cells and giant cells arranged in
nodules (36%). The nodules are present in center of the tumor as well as within arms of fibrous
tissue radiating out. At the other end of the spectrum are tumors mostly composed of fibrocytes
(32%). These thin bland spindled cells form a central fibrous mass, with long radiating arms of
fibrous tissue extending into the surrounding subcutaneous tissue. In between, are tumors with an
almost equal mix of fibrocytes and histiocyte-like cells (32%) (2). In all three types, necrosis is
absent, and cellular atypia/pleomorphism is minimal. Hemorrhage, however, is commonplace,
and is a helpful diagnostic feature. Mitotic figures are infrequent, especially in primary tumors
(<3 mitoses/10hpf), but may be increased in recurrences or metastases. Curiously, vascular
invasion/intravascular growth has been observed in 10%-20% of cases. Hyalinization may be
prominent and rare cases may show osseous metaplasia. One exhibiting myxoid changes has
been described in an adult (58-year old male), and may reflect an adult variant of the tumor (3).
As expected, fine needle aspiration cytologic findings shows a spectrum of plump fibroblastic
spindle cells, histiocyte-like cells and osteoclast-like giant cells, within a finely granular myxoid
backgroud (4).
The immunohistochemical staining pattern reported in PFH is as follows (5,6,7):
Vimentin
CD68 (KP1)
Smooth Muscle Actin
Alpha-1-antitrypsin
Alpha-1-antichymotrpsin
S100
CD45
HLA-DR
HFVII
Desmin
Lysozyme
Positive
Positive (mainly seen in MNGCs and MNHCs)
Positive
Positive
Positive
Negative
Negative
Negative
Negative
Negative
Negative
Ultrastructural studies show PFH to have features of undifferentiated cells, myofibroblasts, and
fibroblasts. Despite the MNHCs and MNGCs show strong CD68 positivity, there appears to be
no ultrastructural evidence to link PFH to bone marrow-derived macrophages. Chromosomal
studies have reported abnormalities in two PFHs, however no shared abnormalities have been
(8,9).
The major differential diagnosis includes a large number of mesenchymal entities:
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
Fibrous histiocytomas may contain foam cells, however these tumors usually arise in
older individuals. They also do not show the characteristic long plexiform extensions of
fibrous tissue nor the nodules of MNHCs or MNGCs, characteristic of PFH.

The young age of the patients, along with absence of pleomorphism and significant
numbers of mitotic figures help in the exclusion of atypical fibroxanthoma, pleomorphic
MFH, and giant cell sarcoma of soft parts.

Presentation early in life and the rays of fibrous tissue may raise the possibility of fibrous
hamartoma of infancy (FHI), however the myxoid stroma, immature cells, and strands of
mature fibrous tissue would be unusual in fibrous hamartoma, and the characteristic
“organoid” structures of FHI are not encountered.

Architectural similarity may be observed in plexiform neurofibroma, however it should
be S-100 positive, and usually associated with neurofibromatosis.

PFH may histologically resemble desmoid fibromatosis in some areas, however the
plexiform architecture, superficial location, small size, and nodules of MNGCs and
MNHCs are not seen in desmoid fibromatosis.

Angiomatoid fibrous histiocytoma (AFH) is marked by a distinctive chronic lymphocytic
inflammatory infiltrate, which makes the tumor appear like a lymph node. This
lymphotrophism is lacking in PFH. Radiating strands of fibrous tissue would also be
unusual in AFH.
Following complete surgical resection, PFH reportedly has a local recurrence rate of between
12.5% - 37.5% (23). Although the number of reported cases continues to be few, it appears to
have approximately a 5% metastatic rate, generally to regional lymph nodes or to lung (10).
Figures
Fig. 1 X-ray of thumb showing focal areas of erosion on the cortex.
Fig. 2 Low power view demonstrates the nodular growth pattern and ray-like extensions of
fibrous tissue. Note the rim of normal superficial dermis.
Fig. 3 Internodular fibrous tissue set in a dense collagenous stroma. The fibrocytes are arranged
in fascicles, This photomicrograph clearly depicts the biphasic histology of this low malignant
potential neoplasm.
Fig. 4 The nodules are composed of mononuclear histiocytic cells and scattered multinucleated
giant cells.
Fig. 5 A high power view highlights the benign vesicular nuclei and the pale eosinophilic
cytoplasm of the histiocytic cells. A rare mitotic figure is noted. The giant cells resemble
osteoclast-like giant cells.
Fig. 6 The histiocytic nodules are seen with in the fibrous extensions.
Fig. 7 Focal areas of hemorrhage are occasionally seen within some nodules. Vascular invasion is
seen in 20% of cases.
Suggested Reading:
1. Enzinger FM, Zhang R. Plexiform fibrohistiocytic tumor presenting in children and
young adults. Analysis of 65 cases. Am J Surg pathol;12:818-826, 1988.
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2. Remstein ED, Arndt CA, Nascimento AG. Plexiform fibrohistiocytic tumor:
clinicopathologic analysis of 22 cases. Am J Surg Pathol;23:662-670, 1999.
3. Cho S, Chang SE, Choi JH, et al. Myxoid plexiform fibrohistiocytic tumor. J Eur Acad
Dermatol Venereol,16(5):519-521, 2002.
4. Redlich G, Bocklage T, Joste N. Fine needle aspiration cytology of plexiform
fibrohistiocytic tumor. A case report. Acta Cyto;43(5):867-872, 1999.
5. Wilkin MM, Lane JW. Plexiform fibrohistiocytic tumor of the foot. J Foot Ankle
Surg;38(2):135-138, 1999.
6. Giard F, Bonneau R, Raymond GP. Plexiform fibrohistiocytic tumor. Dermatologica,
183:290-293, 1991.
7. Hollowood K, Holley MP, Fletcher CD. Plexiform fibrohistiocytic tumor:
clinicopathological, immunohistochemical and ultrastructural analysis in favor of a
myofibroblastic lesion. Histopathology, 19:503-513, 1991.
8. Smith S, Fletcher CD, Smith MA, Gusterson BA. Cytogenetic analysis of a plexiform
fibrohistiocytic tumor. Cancer Cytogenet;48:31-34, 1990.
9. Redlich GC, Montgomery KD, Allgood GA, Joste NE. Plexiform fibrohistiocytic tumor
with a clonal cytogenetic anomaly. Cancer Genet Cytogenet, 108:141-143, 1999.
10. Salomao DR, Nascimento AG. Plexiform fibrohistiocytic tumor with systemic
metastases: a case report. Am J Surg Pathol. 21(4):469-476, 1997.
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