Case 3 -
The University of California
San Francisco, CA
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The significance of this case is probably not in the difficulty it poses (or does not
pose) in diagnosis, but in understanding what the diagnosis implies. There is increasing diversity in
opinion on the definition of hemangiopericytoma (HPC), and the implications of that diagnosis in soft
tissues versus the CNS. This discussion begins with a brief review of current terminology and historical
Case 3 - Slide 1
Case 3 - Figure 1 - Pre-operative axial MR images (T2-weighted, FAIR and T1-weighted post-gadolinium sequences) showing a 5 x 5 x 3 cm right parietal parasagittal mass accompanied by significant vasogenic edema and right-to-left midline shift.
Case 3 - Figure 2 - Pre-operative coronal MR images (FAIR and T1-weighted post-gadolinium sequences) showing the mass.
Case 3 - Figure 3 - Nerve sheath tumor (T7-8). The morphologic features are characteristic of hemangiopericytoma. (low-power, H&E)
Case 3 - Figure 4 - Nerve sheath tumor (T7-8). The morphologic features are characteristic of hemangiopericytoma. (high-power, H&E)
Case 3 - Figure 5 - Intracranial tumor. Hemangiopericytoma. (low-power, H&E)
Case 3 - Figure 6 - Intracranial tumor. Hemangiopericytoma. (high-power, H&E)
Case 3 - Figure 7 - Intracranial tumor. Hemangiopericytoma. The tumor is negative for S-100 protein. (S-100 immunostain)
Case 3 - Figure 8 - Intracranial tumor. Hemangiopericytoma. Tumor cells exhibit positivity for neuron-specific enolase (NSE immunostain).
Case 3 - Figure 9 - Intracranial tumor. Hemangiopericytoma. Strong positivity for CD 34 is seen in endothelium, with patchy focal reactivity in the tumor cells. (CD34 immunostain)
Case 3 - Figure 10 - Intracranial tumor. Hemangiopericytoma. Tumor cells are positive for Bcl-2. (Bcl-2 immunostain)
Case 3 - Figure 11 - Intracranial tumor. Hemangiopericytoma. Strong positivity for Collagen type IV is seen. (Collagen type IV immunostain)
The current WHO Classification of Tumours of Soft Tissue and Bone discusses the two
neoplastic entities Extrapleural Solitary Fibrous Tumor and HPC in the same chapter and gives the
following definition for HPC :
"The residual group of lesions (!), previously combined
under the term hemangiopericytoma, which closely resemble cellular areas of solitary fibrous tumor (SFT)
and which appear fibroblastic in type. It has a range of clinical behavior and is closely related to, if
not synonymous with, SFT."
Whereas, the new WHO Classification of Tumours of the Nervous System identifies HPC as a
distinct neoplasm, gives it a chapter of its own outside the mesenchymal, non-meningothelial tumor group,
and proposes the following definition for HPC:
"A highly cellular and vascularized mesenchymal tumour,
exhibiting a characteristic monotonous low-power appearance and a well-developed, variably thick-walled,
branching "staghorn" vasculature; almost always attached to the dura and having a high tendency to recur
and to metastasize outside the CNS."
In this upcoming edition of the WHO classification of tumors of the CNS, there seems to be no attempt
to provide a unifying concept for HPC and SFT as is seen in the WHO classification on soft tissues
published in 2002 .
Hemangiopericytoma (HPC), was described by Stout and Murray 1942 , in a study of
nine tumors, which they believed to originate from the "pericyte" described earlier by Zimmermann
. The pericyte, described by Zimmermann was a cell that lined the capillaries at the point
of their transition from arterioles. Zimmermann contended that the pericyte resembled smooth muscle
cells and a transition between the two could be observed . The original report by Stout
& Murray acknowledged the variations in cell size and shape, in the amount of connective tissue, etc.
Thus, most features were not defining of an entity except for the so-called "stag-horn" shaped, branching
and elaborate vascular infrastructure. In time, the presence of the so-called "HPC-like vessels has
increasingly become less typical of hemangiopericytomas, and are now recognized in an array of soft
tissue neoplasms. According to a recent review, up to 15% of all soft tissue neoplasms show HPC-like
vascular features . Over the last decade, more and more tumors within the HPC category have
been redefined as other entities
Stout published a series of 25 HPCs a few years after his initial manuscript with Murray
that also included one tumor arising in the meninges . This report has introduced the entity
to the neuropathology literature. Subsequently, tumors that were originally recognized as angioblastic
meningioma were reclassified as meningeal hemangiopericytomas, and the justification was documented in
many studies . To date, the largest published series on meningeal HPCs is that of Mena et
al. (from the soon-to-be-dissolved AFIP Neuropathology Division) . This study segregated
HPCs into "differentiated" and "anaplastic" groups. Anaplastic HPC was characterized by the presence of
necrosis and/or greater than 5 mitoses per 10
HPF (400x microscopic fields), and at least two of the following microscopic features: hemorrhage, moderate-to-high nuclear atypia, and moderate-to-high cellularity.
For those patients known to be dead, median survival time was 144 months for differentiated HPC and 62
months for anaplastic HPC. Regardless of grade, the authors reported 60.6% recurrence during the
follow-up period, and a 23.4% metastasis rate. Bone, liver, lung, and abdominal cavity were the most
common sites of extracranial metastasis. The authors also suggested that adjuvant therapy increased
patient survival time.
Many subsequent studies have utilized the grading criteria proposed by Mena et al. and
have reported similar findings. A more recent study of 38 patients by Ecker et al. used the same
histological criteria suggested by Mena et al.  The results showed a 63% rate of
progression on follow-up images. The authors did not report the length of the follow-up period, but were
able to demonstrate extraneural metastases in 29% of patients. They also concluded that high-grade
tumors recurred 6.7 years earlier than low-grade HPCs. Many studies have also emphasized the importance
of complete resection in terms of prolonging progression-free and overall survival
Some studies contend that radiotherapy is "helpful" in the management of hemangiopericytoma; however,
many studies report limited or no impact of radiation on overall survival.
of HPCs in soft tissues and in the CNS seem to be quite similar. The reports on histological and
immunohistochemical features of HPCs in the CNS focus primarily on distinguishing these neoplasms from
meningioma, and, more recently, SFT. Microscopically, most tumors resemble each other with high
cellularity and numerous blood vessels with the classical "stag-horn" or delicate, slit-like, branching
appearance. The cytoplasm is often sparse with a variable degree of nuclear hyperchromasia. The
so-called "jumbled-up" pattern implies no specific architecture but gives an impression of tumor cells
organizing in haphazard, loose clusters. Epithelioid features, whorls, and psammomatous calcifications,
which are typical of meningioma, are distinctly absent. Many tumors harbor areas of paucicellularity,
giving the tumor a vague biphasic appearance. One of the most striking features of tumors classified as
HPC is the presence of an abundant and elaborate reticulin network that usually appeares as delicate
filaments wrapping around individual or small groups of cells. This feature can be demonstrated by a
special stain for reticulin as well as by immunohistochemical staining for Collagen type IV. The
immunohistochemical profile of HPC can partly overlap that of meningioma and heavily overlap that of SFT.
Typically, tumors recognized as HPC show negative staining with antibodies against EMA, S-100 protein and
GFAP, which is useful is excluding meningioma as well as schwannoma . Even though rare
cells in HPC may show EMA positivity, this is neither strong nor diffuse. Staining is often strong and
diffuse for antibodies against vimentin, Bcl-2, CD99, and Factor XIIIa. While the latter three may be
useful in distinguishing HPC from meningioma, they cannot segregate HPC from SFT. Other stains that may
show focal positivity in some HPCs include cytokeratin cocktail, desmin and Leu-7. Staining for CD34 is
markedly variable, although most HPCs demonstrate some positive-staining tumor cells in addition to
staining of the elaborate vascular network. Other tumors, on the other hand, may demonstrate diffuse
strong staining in almost all of the tumor cells. In such cases, a diagnosis of SFT is favored by most
investigators, since the operational definition of SFT involves diffuse strong staining by this antibody.
The proliferation index as determined by MIB-1 antibody (Ki-67 antigen) has been studied for prognostic
value, but does not provide added information because of the considerable overlap between low- and
high-grade tumors . Ultrastructurally, basal lamina-like material, cytoplasmic processes,
cytoplasmic filaments, and poorly formed intercellular junctions are the most frequently noted features
of tumor cells in HPC, whether in the CNS or soft tissues 
Distinguishing HPC from SFT, and the validity of such a distinction, warrants additional
consideration. After the establishment of existence of the SFT in the CNS, the challenge of segregating
these two entities became more pronounced . While CD34 staining was the main staple for
diagnosis of SFT, the extensive reticulin network highlighted by reticulin stains became the critical
feature for HPC. Earlier series of SFTs in the CNS also presented evidence that tumors considered in
this category had a much lower tendency to recur and disseminate compared to typical HPC .
Additional studies made the same observation with the caveat that the overall experience was quite
limited with "malignancy" in SFT . This suggestion is confirmed by case reports
highlighting aggressive behavior and metastases observed in tumors that were classified as SFT
. Thus, more data is needed to document whether SFTs with malignant phenotype can be
clearly defined, reliably distinguished from HPC, and demonstrated to be as aggressive as HPC. Until
such data are available, the current consensus favors a more indolent behavior for CNS tumors that are
considered to be in the SFT category. On the other hand, the overwhelming majority of studies focusing
on HPC in the CNS consistently report a tumor that has a very high rate of recurrence, even after
decades, and possibly the highest rate of extracranial metastases among all primary intracranial
neoplasms. This biological behavior is observed in both "differentiated" and "anaplastic" examples. The
limited experience with SFTs in the CNS does not appear to indicate a similar grave outcome, at least not
up to the present time. It may be quite plausible to consider the suggestion of some soft tissue
pathology experts who consider both entities to fall along the same spectrum, with SFT representing the
benign or low-grade end, and anaplastic-type HPC representing the malignant or high-grade end
. Evidence of morphologic "transformation" of tumors with classical HPC features into tumors
with classical SFT features upon recurrence  or treatment is an additional argument for
considering these tumors within the same "family of neoplasms".
One unique feature of the case presented in this conference is the spread of a spinal cord
primary neoplasm to the supratentorial space. Most tumors with HPC morphology in the CNS tend to occur
intracranially, and may spread to the spinal cord or to extracranial sites. Extension of a primary
spinal cord neoplasm to the supratentorial space is distinctly unusual, and raises the possibility that
the spread may have occurred via CSF dissemination, although a hematogenous spread is also possible.
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