Moderators: Dr. John R. Goldblum and Dr. Cyril Fisher
Extra-thoracic solitary fibrous tumour, malignant
Dr. Françoise Collin
A 32-year-old man presented with urine retention. CT-scan and MRI were performed. They revealed a
large pelvic mass with well-defined margins, located in the pre-sacral area. The rectum was displaced
laterally, and the bladder was pushed forward. Sacral bone was uninvolved. A well circumscribed and
partly encapsulated tumor measuring 14 x 10 x 6 cm was resected. On cut section, it was made of a
white-grey, fibrous-appearing focally nodular tissue, with a firm consistency. There were scattered
hemorragic changes. Three years later, the tumor recurred as a 6.5 cm mass in the retroperitoneum.
The neoplasm was limited by a fibrocollagenous capsule. It was composed of bland round to spindle
cells with variably abundant pale to eosinophilic cytoplasm. The nuclei were oval, uniform in size,
slightly hyperchromatic, with small nucleoli and occasional folds. Pleomorphism was minimal. No giant
cell was identified. The lesion was hypercellular, without any remarkable architectural features. Cells
were closely packed, there was no bundle formation or storiform arrangement. Mitotic activity was
moderate, not exceeding 3 mitoses per 10 high-power fields. The most salient histologic feature was the
presence of numerous dilated branching vessels. Large vessels usually had a thin wall, or were
unfrequently hyalinized. Smaller vessels also had very thin walls. There were no hyalinized or myxoid
areas. Collagen deposition was only present in the form of sparse dense thick fibers, and a few stellate
structures suggesting amianthoid fibers. Patchy areas of necrosis represented no more than 5 per cent of
the tumour. Immunohistochemistry showed frank but focal staining for CD34 and CD99. There was no
staining for bcl2, cytokeratins, smooth muscle actin, desmin, h-caldesmon, CD117, S-100 protein,
synaptophysin, chromogranin A, or neurofilaments. Proliferation marker Ki67 stained no more than 5 per
cent of tumour cell nuclei. Positive cells were unevenly distributed.
Additionally, as an hypothesis of a gastro-intestinal stromal tumour (GIST) had been raised, a study
of mutations of KIT (4 exons) and PDGFRA (3 exons) was performed , detecting no mutation.
Extra-thoracic solitary fibrous tumour, malignant.
Extended clinical history
Three years later, a recurrent 6.5 x 5.5 cm mass was removed in the retroperitoneum. It was well
circumscribed and partly encapsulated. Microscopic and immunohistochemical findings were very similar to
those of the primary tumour. High cellularity, monomorphism and patches of necrosis were found. Mitotic
activity did not exceed 3 for 10 high-power fields. Ki67 proliferation marker expression was found in
about 20 % of the tumour cell nuclei. A 50 gy radiation therapy course was given. Two years later,
liver metastases were found. A biopsy showed a poorly differentiated neoplasm made of round/ovoid cells
with CD34 staining. The patient was treated with a chemotherapy regimen including doxorubicin,
ifosfamide and DTIC. He died of disease 6 months later.
Solitary fibrous tumour (SFT)
was first described by Klemperer and Rabin  who were studying
primary pleural neoplasms, and divided them into diffuse and localized subtypes. Most of their localized
tumours originated in the visceral pleura. They were well-demarcated and often pedunculated. They
pursued a rather indolent course, though there were a few recurrent cases, and very rare metastasizing
tumours. Conversely, diffuse neoplasms of the pleura portended a dismal prognosis. The mesothelial or
fibroblastic nature of localized tumours remained disputed for years in many studies involving electron
microscopy and immunohistochemistry
Since 1990, peritoneal, then non-serosal tumours were
reported bearing the same clinicopathologic features, until 1996 which was according to Chan  the
"year of the solitary fibrous tumour". This diagnosis became very popular in a wide variety of tumour
sites, while malignant fibrous histiocytoma and hemangiopericytoma were waning
A large number of cases have been reported to date, comprising both thoracic and extra-thoracic
To summarize, SFT is a rare tumour which occurs in adults of
all ages (mean 50 years) with no sex predilection. Extra-thoracic tumours are located in subcutaneous
tissues in 40% of cases, and deep in other cases. Apart from thoracic sites (pleural, but also
mediastinal, pericardial, thymic) which are the more frequently reported, a wide variety of locations
have been described, either related to serosal cavities (peritoneum, omentum, retroperitoneum) or not :
soft tissues of head and neck and especially orbit, extremities, pelvis, and many organs such as kidney,
thyroid, salivary glands and meninges. Clinical symptoms are more likely to occur in patients with
extra-thoracic locations. Hypoglycemia has been reported in a few cases.
Gross examination reveals a fairly well demarcated tumour made of a white or tan tissue with a firm
consistency and a whorled cut surface. Larger tumours may show areas of myxoid or hemorrhagic
degeneration. The tumours range in size from 1 to 25 cm. Microscopic examination discloses a
proliferation of spindled or rounded cells with no particular arrangement ("patternless pattern").
Cytoplasms are scanty and nuclei usually show very mild pleomorphism and rare mitotic figures.
Multinuclear cells are occasionally found. Numerous dilated branching vessels of staghorn type are one
of the hallmarks of this lesion, unfortunately shared by a number of other entities. Typically, SFT
comprises alternating hyper- and hypocellular areas with abundant hyalinized collagen deposition.
Immunohistochemical findings include diffuse and strong positivity for CD34 in most cases, and frequent
expression of CD99 and bcl-2 protein. Focal staining for cytokeratins, muscle-specific actin,
alpha-smooth actin, desmin or S100 protein has occasionally been reported. The mean number of MIB-1
positive nuclei was low (3,9%)
in one study , in primary tumours or metastatic lesions. Electron
microscopy performed in many studies showed that these tumours mostly comprised fibroblastic cells, with
focal or prominent myofibroblastic differentiation
However others would call the same cells
pericytes . Molecular genetics yielded heterogeneous data. Up to now various techniques have failed
to demonstrate recurrent abnormalities. DNA copy number changes were reported in SFTs larger than 10 cm
. All these morphologic features have been extensively reported. Two issues currently remain
controversial : malignancy in SFT, and differential diagnosis including hemangiopericytoma.
Malignancy in SFTs
Increased recognition of SFT led to a large number of published cases with clinicopathologic reviews
or extra-thoracic diseases
or both . Thoracic and
extrathoracic SFTs basically show very similar features, as reported by Gold . In his series,
thoracic neoplasms were twice as frequent as extrathoracic (including visceral) ones. Among 75 patients
who were treated by surgical excision in the same hospital, 5 had local recurrences and 4 developed
distant metastases. Most series show a range of 10 to 20% of recurring and/or metastasizing tumours, but
many of these neoplasms will have a very protracted course, and the outcome will not necessarily be
fatal. The main sites of metastases are lungs, liver and abdominal cavity.
Location is an important factor of prognosis. Among thoracic tumors of the series of England ,
pleural and pedunculated tumours had a better outcome than infiltrating or parietal or mediastinal ones,
perhaps due to a better resectability. Other studies showed that tumours presenting with some
clinicopathologic features were more likely to develop local recurrences and/or distant metastases :
large size (10 cm and above), infiltration, high cellularity, more than 4 mitoses per 10 high-power
fields, presence of a frankly sarcomatous component (sometimes called dedifferentiation), and necrosis.
When analyzed separately , tumours exhibiting at least one of these features very often recurred or
metastasized, but not all patients had a fatal outcome. Conversely, tumours devoid of adverse prognostic
features sometimes recurred. However their recurrences could often be cured by simple excision.
In spite of a better knowledge of their clinicopathologic features, SFTs of thoracic or extra-thoracic
location remain neoplasms with an essentially unpredictable prognosis, though most of the patient will
not die of their diseases. For these reasons, they have been classified into the intermediate (rarely
metastasizing] category .They need a long-term follow-up, still more careful after resection of a
recurrent tumour .
Our patient, with a tumour showing 3 adverse prognostic factors (size, high
cellularity, necrosis), was at risk for an unfavourable outcome.
Differential diagnosis including hemangiopericytoma
To distinguish SFT from morphologically related neoplasms raises many issues. As stated by Chan ,
some diagnoses are raised more in keeping with the tumour location than on the ground of pathologic
features. For example, serosal-based SFTs have to be distinguished at first from mesothelial
proliferations, which show a cytokeratin+, calretinin+, CD34– immunoprofile. Immunohistochemistry also
allows a careful evaluation of intra-abdominal SFTs, to distinguish them from gastro-intestinal stromal
tumours, the latter expressing not only CD34, but also CD117 in most cases.
The most crucial problems in differential diagnosis deal with hemangiopericytoma (HPC), an old entity
which appears nowadays largely overlapping with SFT. However the last WHO classification  retained
two different names for these tumours. Since its description in 1942 by Stout , who first collected
9 cases, then published 25 additional cases in 1949 , HPC was characterized by poorly differentiated
cells associated with a prominent vascular component made of "staghorn" dilated branching vessels, and a
largely unpredictable outcome. Its putative origin in Zimmermann's pericytes was never confirmed by
electron microscopy or immunohistochemistry. A critical reappraisal was performed by Enzinger in 1976
, based on clinical and morphological observations. He drew pathologists' attention to the fact that
some close mimickers of HPC were true sarcomas, while others, especially in children, were benign
lesions. Since that time, the relation between HPC and SFT remained a controversial issue. Thus far,
nobody could demonstrate that any of these lesions derived from pericytes. Most cases show a prominent
component of fibroblastic cells, together with a variable proportion of myofibroblasts which may be
In recent studies
the concept of HPC was reassessed. The authors retained the more basic
fact that a hemangiopericytomatous pattern of growth could be met in three categories of tumours. The
first category comprises several types of true sarcomas which must be ruled out at once. Poorly
differentiated or spindle cell monophasic synovial sarcomas are the most frequently found. Positivity
for cytokeratins is of great help for their diagnosis, molecular genetics still more if available.
Additional sampling, immunohistochemistry and cytogenetics will help diagnose other sarcomas including
fibrosarcomas, mesenchymal chondrosarcomas, or the so-called malignant fibrous histiocytoma.
The second category of tumours is made up of SFT and its variants. They show CD34 positivity, but are
devoid of muscular markers. The lesion called lipomatous HPC  is a kind of SFT including areas of
mature adipocytes. It affects deep soft tissues, retroperitoneum and thigh being its most common
locations. Similarly, giant cell angiofibroma  is a variant of SFT which harbors multinucleated
tumour cells, some of which are lining pseudo-vascular spaces. Head and neck of adult people are mostly
affected. The two latter neoplasms usually behave in a benign fashion.
The tumours in the third category are benign neoplasms with myoid differentiation. They are related
with smooth muscle neoplasms and glomus tumours. Immunohistochemical findings include positivity for
muscle-specific actin and alpha-smooth actin, variable expression of h-caldesmon, very rare positivity
for desmin, and negative CD34. Among those neoplasms, myopericytoma  is a cutaneous or subcutaneous
nodule of the extremities in adult patients. It comprises a perivascular proliferation of myoid cells.
Infantile myofibroma and myofibromatosis  are solitary or multiple similar lesions overlapping with
infantile HPC. They may show substantial mitotic activity, vascular invasion, and necrosis. They are
often present at birth, and may become life-threatening through possible visceral locations, though the
lesion is intrinsically benign. Sinonasal hemangiopericytoma was also recognized many years ago as a
benign lesion which rarely recurs. In most cases, tumour cells show immunohistochemical and
ultrastructural features consistent with myoid differentiation, though a small subset of these tumours
are probably true SFTs.
Finally, meninges are the last site in which the controversial diagnoses, SFT or HPC, are still under
debate. Though SFTs have been identified , the WHO classification retained the HPC diagnosis for
these tumours . However, they look like cellular SFTs, but they bear an ominous prognosis with high
rates of local recurrences and extracranial metastases. Such clinicopathologic features are
unequivocally different from those of conventional or even cellular SFTs.
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