# Epithelioid Sarcoma of the Forearm Arising from Perineural Sheath of Median Nerve Mimicking Carpal Tunnel Syndrome

Authors: Hiromasa Fujii; Kanya Honoki; Hiroshi Yajima; Akira Kido; Yasunori Kobata; Daisuke Kaji; Yoshinori Takakura
Journal: Sarcoma
 (2009)

---

## Abstract

We report here a case of epithelioid sarcoma in the forearm of a 33-year-old male presenting with symptoms and signs of carpal tunnel syndrome originating from the direct involvement of the median nerve. Due to the slow growing of the tumor, the patient noticed the presence of tumor mass in his forearm after several months from the initial onset of the symptoms. Magnetic resonance imaging showed an8×4 cm mass involving the median nerve in the middle part of the forearm, and histological analysis of the biopsy specimen revealed the diagnosis of epithelioid sarcoma. Radical surgical resection was performed in conjunction with adjuvant chemotherapy. The function of the flexors were restored by the multiple tendon transfers (EIP→FDS; ECRL→FDP; BrR→FPL; EDM→opponens) with superficial cutaneous branch of radial nerve transfer to the resected median nerve. The function of the affected hand showed excellent with the DASH disability/symptom score of 22.5, and both the grasp power and sensory of the median nerve area has recovered up to 50% of the normal side. The patient returned to his original vocation and alive with continuous disease free at 3.5-year follow-up since initial treatment.


---

## Body

## 1. Introduction

Epithelioid sarcoma (ES) is a rare distinctive
soft tissue neoplasm with a predilection for the distal part of extremities,
more often in upper than lower extremities, involving the subcutaneous tissue,
tendon and fascia, and more often occurring in young adults and in the male
than female
[1–3]. It mostly
presents as superficial nodules or ulcers; however deep-seated lesions can
occur rarely. Although the clinical presentations are varying with a variety of
physical-radiological features [4], it is extremely uncommon that ES involves
the deep nerves [5, 6]. The initial treatment should be considered in a way of
an aggressive wide resection with radical margins, sometimes in association
with chemo- and radiotherapy [7]. It often recurs locally and also metastasizes
usually in a few years time span preferably to the lung and sometimes to the
lymph node. The reported long-term survival rates are around 50–60% [7].We report a case of ES in the forearm
presenting median nerve palsy as carpal tunnel syndrome clinically, and being
treated by initial surgery in a form of radical resection of the bulk of tumor
with finger flexors and median nerve as well. We describe the results of
successful restoration of the finger flexors and median nerve function with
multiple tendon transfers and nerve transfer from radial superficial cutaneous
nerve branch after the radical resection of
the tumor located in the forearm.


## 2. Case Report

A 33-year-old male presented with complaints
of progressive sensory disturbance in median nerve area on his right hand since
the Spring of 2005, and consulted a doctor in a district hospital then. Initial
clinical assessment was the carpal tunnel syndrome, and he was conservatively
treated with medication for a while with a wrist brace. However, median nerve
palsy gradually progressed with weakening ofopponens pollicis and abductor
pollicis brevis muscles.In October 2005, the patient himself
eventually noticed the presence of tumor mass in the middle part of his
forearm. Magnetic resonance imaging evaluation has been performed at that time,
showing a tumor measured approximately 8 × 4 × 3 cm, encircled by theflexor carpi radialis (FCR), flexor digitorum superficialis (FDS), flexor digitorum profundus (FDP), and flexor pollicis longus (FPL)
(see Figure 1).
Open biopsy was subsequently performed, and histological appearance showed that
tumor was consisted with malignant spindle cells with epithelioid features (see
Figure 2), then he was referred to our institution afterward. The physical
examination revealed an elastic hard tumor palpable in middle portion of his
right forearm with remarkable Tinel’s sign to the median nerve area. Positron
emission topography showed very high uptake only at the middle part of right
forearm, and no other abnormal uptake was detected. The computed tomography of
the chest and laboratory data showed no other abnormalities.
Immunohistochemical (IHC) analysis of the biopsy specimen was performed in our Pathology
Department’s laboratory, demonstrating the positive immunoreactivity to
cytokeratin, CAM5.2, AE1/AE3, EMA, CD34, and smooth muscle action, in contrast
negative immunoreactivity to desmin, S-100, Myc-2, MyoD, myogenin, myoglobin,
and c-kit. These results of IHC with epithelial features from hematoxylin-eosin
staining suggested the possible diagnosis of epithelioid sarcoma.(a) Coronal T1-weighted, (b) T2-weighted, and (c)
Gd enhanced magnetic resonance imaging shows a tumor
measured approximately 8 × 4 × 3 cm. (d) Tumor encircles by theflexor
carpi radialis (FCR), flexor digitorum
superficialis (FDS), flexor digitorum
profundus (FDP), and flexor pollicis
longus (FPL), and pushes aside median
nerve (arrow).
(a)(b)(c)(d)Histological appearance of open biopsy showing
that tumor is consisted with malignant (a) spindle and (b) rounded cells with
epithelioid features.
(a)(b)Chemotherapy consisted of two courses of
ifosfamide (IFO; 12 g/m2/5 d) and adriamycin
(ADM; 80 mg/m2/3 d)
was administered; however tumor showed no regression of the size, therefore the
surgery was performed in January 2006. Resection with curative wide surgical
margin was achieved by en-block tumor mass resection in conjunction with
surrounding tissues including median nerve and a part of ulnar artery, FDS,
FCR, FDP, FPL, and palmaris longus (PL). After the resection, reconstruction of
finger flexor was performed in a way of tendon transfers with extensor indicus proprius (EIP) to flexor digitorum superficialis (FDS); extensor carpi radialis longus (ECRL) to flexor digitorum profundus (FDP);
brachioradialis (BrR) to flexor pollicis
longus (FPL), and extensor digiti
minimi (EDM) for opponens reconstruction. The superficial cutaneous branch of radial nerve was transferred
to the distal end of the resected median nerve in order to recover the sensory
deficit of median nerve under the sacrifice of sensory on dorsal side.The macroscopic appearance of the resected
tumor showed that the median nerve was directly involved in the tumor.
Microscopically, no tumor cell was infiltrated into the nerve, but the
pseudocapsule of the tumor was transitioning to the perineural sheath of the
median nerve (see Figure3), suggesting that epithelioid sarcoma could arise
from nerve sheath as well as deep fascia or tendon sheath. The effect of
preoperative chemotherapy showed Grade II of
Huvos grading system [8]. Postoperative
alternative chemotherapy consisted of a course of cisplatin (CDDP;
120 mg/m2/d)
and adriamycin (ADM; 20 mg/m2/2 d) was administered, then rehabilitation
has started. The fusion gene of SYT-SSX was not detected by reverse
transcriptase-polymerase chain reaction in the specimen from definitive
surgery. Thus, the final diagnosis was confirmed as epithelioid sarcoma. He has
gained finger mobility and gotten back to his vocation within 3 months after
the therapy.  After 3 years of operation, the patient is alive with continuous disease free. The function of the affected hand showed DASH score of disability/symptom
score of 22.5 and optional component score (sports/music or work optional
module) of 50
(see Figure 4) [9]. Grasp power of the affected hand has
gained up to 50%, and the sensory of the median nerve area has also been
recovered up to 50% of the unaffected side.(a) Histological appearance of postoperative
section showing that no tumor cell is infiltrated into the nerve, but (b) the
pseudocapsule of the tumor is transitioning to the perineural sheath of the
median nerve.
(a)(b)Photograph of right
forearm on 2 years after operation. Grasp power of the affected hand has gained
up to 50%, and the sensory of the median nerve area has also been recovered up
to 50% of the unaffected side.
(a)(b)


## 3. Discussion

Epithelioid sarcoma (ES) is a rare malignant
soft tissue neoplasm, usually slow and indolent growing, but very aggressive in
occasion. Thus, the clinical behavior and outcome is unpredictable [10, 11]. In
the series of Mayo clinic, 38% of the patients had at least one recurrence and
47% had metastatic lesions, then 27% of the
patients died out of
disease [11].
Although ES is one of the most common soft tissue sarcomas in the forearm,
wrist and hand, soft tissue sarcomas themselves are very rare in these body
parts [12]. In addition, ES is often difficult to diagnose because it may
behave like a benign tumor both clinically and on imaging [4]. ES around the
hand often mimics ganglion cyst [1] or other type of benign tumors like
peripheral nerve sheath tumor, both possibly presenting the clinical symptoms
compatible with carpal tunnel syndrome [6]. However, involvement and growth
around a major peripheral nerve and presentation as a peripheral nerve sheath
tumor are extremely rare [5]. In our case, due to the slow growing of the
tumor, the patient noticed the mass presentation in his forearm after several
months from the occurrence of symptoms mimicking with carpal tunnel syndrome,
and MRI eventually revealed the tumor involvement of the median nerve.Histologically, ES is often mistaken for
benign entities as well as other type of malignancies including synovial
sarcoma. The metaplastic conversion of mesenchymal cells to epithelia in a fashion that is not
dissimilar to synovial sarcoma is a possible cause [1, 13]. The neoplastic
cells generally coexpress keratin and vimentin, and often positive for CD34. In
the series of Miettinen et al., the IHC profiles of 112 cases of ES including
88 typical and 24 variant (8 angiomatoid, 9 large cell/rhabdoid, and 7
fibroma-like) demonstrated that both typical and variant cases were found
frequent expression of CD34, consistent expression of EMA and keratin [13]. Our
case showed positive immunoreactivity to cytokeratin, CAM5.2, AE1/AE3, EMA,
CD34. and smooth muscle actin, which are compatible to the diagnosis of ES.Aggressive radical excision seems to be most
effective in preventing local recurrence as well as the occurrence of distant
metastasis. Halling et al. reported that no recurrence was observed in the patients
treated with wide or radical resection with adjuvant therapy of either
chemotherapy or radiotherapy [11]. However, it is very difficult to accomplish
the radical or even wide resection with minimizing the functional loss for the
lesion of forearm, wrist and hand. Thus, reconstruction of flexion function of
the forearm remains a challenge to the reconstructive surgeon. With development
of microsurgical techniques, the functional microsurgical muscle flap has been
proved as a reliable technique in reconstructive surgery. Several reports
depicted the usefulness of various muscle flaps for reconstruction of the upper
extremity function
[14–18]. However, the
free-muscle flaps with microsurgical techniques are rather troublesome and may encounter
the postsurgical complications including the vascular embolization. There have
been several reports suggesting the usefulness of tendon transfers to
reconstruct the flexion function after massive loss of function by tumor
resection in the forearm [17, 18]. In general, reconstruction should be accomplished
by the simplest means possibly; therefore tendon transfers should be considered
as an option for reconstruction of hand function. In our case, the multiple
tendon transfers were performed to restore the flexion function despite of
sacrificing some extensor mechanisms, and resulted in good functional outcome
with patient’s satisfaction. An argue will arise on the transfer of the
superficial cutaneous branch of the radial nerve, because the sensory of the
dorsal side of the hand is sacrificed. Usually, the nerve graft from sural
nerve for instance would be performed such a case. However, the recovery of the
grafted nerve function will take a longer period for the massive defect. The
advantage in our case was that it took only 6
months to recover the sensory of the hand which is feasible for the daily use.The administration of chemotherapy and
radiotherapy for epithelioid sarcomas is still controversial. We cannot
determine the advantage of the chemotherapy consisted of IFO, ADM, and CDDP
from our case, because of the inefficiency as a neoadjuvant and the very short
followup duration. Several authors described that the use of chemotherapy and
radiotherapy had no significant effect on the long-term survival [10, 11, 19].
However, further studies will be required to determine the benefit of
chemotherapy as adjuvant, especially for a
patient with advanced disease.



---

*Source: 595391-2009-04-14.xml*