Pleural Malignant Solitary Fibrous Tumor Mimicking a Nerve Sheath Tumor in a Patient with Neurofibromatosis Type 1
William Green*, Michael Sherman, Huijian Sun, Ranjana Nawgiri, Nahal Boroumand and Luba Frank
University of Texas Medical Branch, USA
Submission: October 15, 2016; Published: October 19, 2016
*Corresponding author: William Green, University of Texas Medical Branch, 301 University Blvd, Galveston, TX 77555, USA.
How to cite this article: Green W, Sherman M, Sun H, Nawgiri R, Boroumand N, Frank L. Pleural Malignant Solitary Fibrous Tumor Mimicking a Nerve Sheath Tumor in a Patient with Neurofibromatosis . Canc Therapy & Oncol Int J. 2016; 2(1): 555581. DOI:10.19080/CTOIJ.2016.02.555581
Neurofibromatosis type 1 (NF1), formerly known as von Recklinghausen’s disease is a nervous system tumor disorder of variable expressivity. Malignant solitary fibrous tumors (SFT) are rare spindle cell soft tissue tumors. We report a case of a 35-year-old male who presented clinically with NF1 and a mass that mimicked a nerve sheath tumor radiologically, but pathologically was, in fact, a malignant solitary fibrous tumor. Based on a literature review, the association between NF1 and malignant SFT has never been published.
Keywords: Neurofibromatosis type 1; Malignant solitary fibrous tumor
Abbreviations: SFT: Solitary Fibrous Tumors; NF1: Neurofibromatosis type 1
Neurofibromatosis type 1 (NF1) is a multisystem disease characterized by cutaneous findings, as well as benign and malignant tumors of the nervous system. NF1 occurs in about 1 in 3,000 individuals, and about half of the affected individuals are first cases in their family .
A solitary fibrous tumor (SFT) is a rare spindle cell tumor that most commonly arises in the pleura. These tumors comprise only 1-2% of all soft tissue tumors, and of those, between 12 to 22% are malignant [2-3].
No link has ever been made between NF1 and a malignant SFT Conzo et al. [4-5] first described SFT in an NF1 patient, and Yamamoto, et al later reported another case, but neither case dealt with malignant SFT.
Here, we describe a patient with clinical NF1, who presented with a mass that mimicked a nerve sheath tumor, but biopsy and immunohistochemical assays showed that the correct diagnosis was of a malignant solitary fibrous tumor.
In August 2015, a 35-year-old man presented from an outside hospital with chest pain, recurrent left lower lobe pneumonia and a pleural mass seen on chest radiograph. Physical exam revealed multiple café-au-lait spots on his face, back, chest, abdomen, and legs that ranged from 5mm to 15mm, as well as nodules present on the patient’s right flank, as seen in (Figure 1), and lateral to his left eyebrow. Ophthalmologic exam revealed bilateral Lisch nodules. Due to the array of clinical findings, a biopsy of the right flank nodule was performed and revealed a neurofibroma with plexiform features (Figure 2).
The chest x-ray from the outside hospital was not available
at the time of writing, but, as a surrogate, scout images from the initial CT scan performed in our institution may be seen in
(Figure 3), displaying the thoracic mass initially appreciated at
the outside hospital. A CT scan of the thorax with contrast was
performed in our institution, which showed a left posterior
intrathoracic soft tissue mass with areas of enhancement, neural
foraminal widening and rib splaying (Figures 4a & 5a). An MRI
of the same area was performed (Figure 4b & 5b) to better show
the mass in question, and a biopsy was recommended as the
mass was more suggestive of a nerve sheath tumor, or, less likely,
a pleural fibroma.
Ultrasound-guided fine needle aspiration and
biopsy of the left pleural mass showed bland spindle
cells without defined architectural pattern within a
collagenous background without necrosis or mitotic activity.
Immunohistochemical staining was positive for CD34,
supporting a diagnosis of solitary fibrous tumor (Figure 6).
Subsequently, the pleural mass was resected and histologic
evaluation showed a spindle cell lesion with biphasic
morphology. The majority of the tumor showed classic solitary
fibrous tumor with benign features (Figures 7a & b) with a
portion of the tumor showing markedly increased cellularity,
cytologic atypia and increased mitotic activity (>4/10 high
power fields) diagnostic of malignant transformation (Figures
7c & d). Immunohistochemical stain for CD34 (Figure 7e) was
positive, confirming the findings.
Neurofibromatosis type 1 (NF1), also known as von
Recklinghausen’s disease, is caused by an alteration of the NF1
gene, which is a tumor suppressor gene located on the long
arm of chromosome 17 (17q11.2). While genetic testing is not
required, it is helpful in confirming the diagnosis. The NF1 gene
encodes a protein called neurofibromin, which is a member of
the GTPase activating protein family. A loss of function mutation
to the NF1 gene results in increased cellular proliferation that
manifests as multisystemic tumorous growth. Neurofibromatosis
can be diagnosed clinically if at least 2 of the 7 following criteria
are fulfilled: 6 or more hyperpigmented macules, axillary or
inguinal freckles, two or more neurofibromas or one plexiform
neurofibroma, optic nerve glioma, two or more iris hamartomas,
body dysplasia, or a first degree relative with NF1 .
On the other hand, SFT classically presents as a pleural
mass. Klemperer and Rabin first described the tumor in the
pleura in 1931 . Most of the tumors are benign neoplasms
that are diagnosed in adults with an age range between 50-70
years-old and a male/female ratio of approximately 1 [8-10]. Of
the pleural-based SFTs, most arise from visceral pleura (80%)
with the remainder arising from parietal pleura . Gross
examination of an SFT typically shows a smooth glistening
capsule surface . Histologically, most tumors are composed of
collagen-forming spindle-cells, arranged in interlacing fascicles
with a classic “patternless” pattern . The morphologic findings
are typical, though not always demonstrable in small biopsy
sections; therefore the characteristic immunohistochemical
positivity for CD34 is significantly helpful in separating SFT
from other spindle cell neoplasms . Criteria for malignancy
include the presence of necrosis, increased mitotic activity,
greater cellularity, and cellular polymorphism . Malignant
SFT is diagnosed with presence of at least one of these criteria
. Approximately 15-35% of SFT are malignant at the time of
diagnosis with clinical characteristics of higher recurrences and
lower overall survival . Nonetheless, regardless of benign.
Or malignant presentation of SFT, the hallmark of treatment
is large en-bloc resection of the primary tumor with close
clinical surveillance for recurrences. Mediastinal lymph node
dissection and adjuvant treatments such as radiotherapy and
chemotherapy are not usually employed for treatment purposes,
but rather as palliative options for cases of distant metastasis
and locally advanced recurrence that are not amenable to surgery .
Historically, NF1 has been associated with various tumors,
most notable of which are malignant peripheral nerve sheath
tumor, rhabdomyosarcoma, and gastrointestinal stromal tumor
(GIST), with an overall occurrence rate that reaches up to 5-13%,
0.5%, and 6% respectively [12-14]. However, there are no
systematic reviews that link NF1 with development of SFT. Only
two case reports have been published with anecdotal evidences
where SFT were found concurrently in NF1 patients. Of these
two reports, both patients had pathologic diagnoses of benign
SFTs. Specifically, Conzo et all described a patient who had an
encapsulated tumor arising from the upper pole of the right
kidney that mimicked an adrenal gland or renal tumor, but later
proved to be a SFT . Yamamoto et al described a patient who
underwent Tc-99m MIBI parathyroid scinitigraphy, which showed
uptake highly suggestive of an ectopic parathyroid adenoma, but
also later proved to be a SFT . Our case appears to be the first
documented case of malignant pleural SFT in an NF1 patient,
which also showed signs of mimicry, as seen in the first two
cases. Initial radiologic evaluation of the pleural mass suggested
nerve sheath tumor, especially in the setting of other clinical
findings of neurofibromatosis such as plexiform neurofibroma,
as well as presence of a para-orbital mass. Nonetheless, other
neoplastic causes such as pleural lipoma, pleural fibrosarcoma,
mesothelioma, and metastatic pleural disease could not be ruled
out by imaging alone without a definitive biopsy of the mass.
Therefore, fine needle aspiration of the mass was performed
and showed diagnostic features of SFT and subsequent excision
showed areas of malignant transformation.
While NF1 patients have an increased risk of developing
various tumors and malignancies, there is no definitive link
between NF1 and SFT due to lack of published data . Hence,
it is difficult to comment on the exact relationship between these
two disease processes. Whether or not NF1 is associated with
the development of SFT and the relationship between such, as
well as possible malignant transformation of SFT would need to
be investigated further.