Undifferentiated pleomorphic sarcoma of the chest wall: a rare diagnosis

Abstract

A 31-year-old man with no predisposing factors and no history of chronic disease presented with a small painless lump over his anterior chest wall. On evaluation, it was found to be undifferentiated pleomorphic sarcoma. He underwent wide local excision of the tumour with clear margins, followed by adjuvant radiotherapy. At 6-month follow-up, the patient is clinically and radiologically disease free.

Background

Soft tissue sarcoma (STS) constitutes 0.7% (12 400) of all new malignancies in adults diagnosed in a year, and among these, about 10% or less have been reported to appear in the trunk and 40%–50% occur in the extremities.^{1 2} Most STSs are sporadic in nature and do not have a definite cause. There are a number of histologic subtypes of STSs, the most common being liposarcoma, leiomyosarcoma and undifferentiated pleomorphic sarcoma (UPS). Usually, the chest wall sarcomas present at a later stage with locally advanced disease, necessitating a highly morbid surgery.

In view of rarity of this malignancy in the chest wall, unusual age of presentation, early stage and no identifiable aetiology, we feel the urge to report our case.

Case presentation

A 31-year-old normotensive, non-diabetic and euthyroid man with no history of trauma, lymphedema or any prior radiotherapy, presented with report of a painless lump, initially of the size of a peanut, which was gradually increasing in size over the upper anterior aspect of the right chest wall. On examination, the lump was around 4–5 cm in size, non-tender and firm to hard in consistency. Skin and the underlying structures were free. There was no history of any discharge, bleeding, any weakness, numbness or any altered sensation over the right upper limb, chest wall and neck.

Investigations

The patient was initially treated in a primary healthcare facility, where he underwent excision of the lesion. Preoperative imaging was not done, considering it to be a benign lesion. Histopathological examination of the excised lesion (5 cm grey white firm to hard tissue) was suggestive of tumour comprising of sheets and fascicles of spindle cells with admixed tumour giant cells. Cells showed marked degree of pleomorphism and anaplasia. Mitosis of 12/10 hpf with large areas of necrosis were seen. Resected margin was positive for tumour tissue. No angioinvasion or perineural invasion was seen. The overall picture was that of pleomorphic sarcoma. In view of malignancy, he was referred to a tertiary care centre where his slides were reviewed and immunohistochemistry was performed.

Slide and bloc review was suggestive of tumour with large area areas of ischaemic necrosis and hyalinisation. It was composed of sheets and fascicles of spindle to oval cells (figure 1) with moderate nuclear atypia and increased mitosis (>10/10) (figure 2). Many capillary-sized blood vessels were seen in the background. Immunohistochemistry was positive for vimentin (figure 3) and smooth muscle actin (SMA), negative for calretinin, S100, PanCK Desmin, myogenin, stat 6, CD31 and CD34. Ki67 was 25% (figure 4), which was suggestive of UPS. Contrast-enhanced (CE) CT of the chest (figure 5) was suggestive of ill-defined lesion involving the infraclavicular right upper anterior chest wall with nodularity along the cutaneous aspect of the lesion and ill-defined fluid attenuating and soft tissue component in the subcutaneous fat. It was measured approximately 5.1 cm (TR) × 2.4 cm (AP) × 4.2 cm (CC) in the maximum extent. The stranding extending to the underlying pectoralis major muscle, however does not appear to be direct extension into the underlying muscle. The lungs and mediastinum were normal. Neck and axillary ultrasonography (USG) did not reveal any significant lymphadenopathy. Hence, it was ycT2N0M0 disease (American Joint committee on cancer (AJCC) 8th edition). He underwent wide local excision 11 days after the first surgery. Histopathological examination after wide local excision was suggestive of UPS, ypT2NxMx (AJCC 8th edition), mitotic rate >10/10 hpf in focal areas, tumour necrosis was not identified, FNLCC grade 2, all margins were free from tumour, lymph vascular invasion was not identified.

Figure 1.

Histopathology showing spindle cell covered with skin (H&E ×20).

Figure 2.

Sheets and fasciles of tumour cells showing moderate nuclear atypia. Increased mitosis is seen (arrow) (H&E ×40).

Figure 3.

Tumour is highly positive of vimentin.

Figure 4.

Ki67 shows high proliferative activity.

Figure 5.

Coronal, axial and sagittal planes of the preoperative contrast-enhanced CT of the chest with the pointer showing the nodular lesion over the right infraclavicular region.

Differential diagnosis

The most common differentials of such a small and superficial tumour of the chest wall being lipoma, myositis ossificans among many other benign lesions. The patient often has a history of trauma with calcification in imaging in myositis ossificans. However, the diagnosis can be established by biopsy, preferably true cut or incisional followed by immunohistochemistry.

Treatment

In view of positive margins after excisional biopsy, he underwent revised wide local excision followed by closure by rotation advancement flap done under general anaesthesia. In view of the aggressive nature of the disease, the patient was treated with adjuvant radiotherapy to the postoperative bed to a dose of 50 Gy in 25 fractions followed by boost to a dose of 10 Gy in five fractions, one fraction per day, five fractions per week over a period of 6 weeks. He was treated with helical tomotherapy (HT)-based Intensity Modulated radiotherapy (IMRT) on tomotherapy using MD precision treatment planning system (Accuray Radixact X9 Tomotherapy, Sunnyvale, California, USA). Treatment planning was based on thin slice kV CT simulation images of the chest acquired in the treatment position using a thermoplastic mask for immobilisation. Target delineation (figures 6 and 7) consisted of identification of the primary lesion with the surgical clips placed during the surgery and using the preoperative CECT of the chest. He received 60 Gy in 30 fractions, 1 fraction per day, 5 fractions per week over a period of 6 weeks. An IMRT plan was designed to optimise dose distribution, delivering maximum dose to the target volume and doses to the organs at risk were within acceptable limits. We designed a plan to deliver the prescription dose to 95% of the PTV volume and attained a coverage of 99.9% (V95=99.9%) (figures 6 and 7). The dose constraints of the organs at risk were respected attaining a D_mean of 2 Gy to the heart, V5Gy=2.6%, D_max of 6.1 Gy to the ipsilateral lung, D_max of 2.5 Gy to the contralateral lung and a D_max of 16.6 Gy to the spinal cord. Treatment was delivered under daily image guidance. During treatment, the patient experienced Radiation Therapy Oncology Group grade 1 skin reaction of the right upper chest wall including the infraclavicular region, which was managed symptomatically.

Figure 6.

Helical tomotherapy technique planning images. Dose colour wash in axial, sagittal and coronal planes with the lower dose limit set to 95% of 50 Gy, demonstrating conformal dose deposition around the planning target volume (shown in red contour) in the first phase. The inner red contour shows the preoperative gross tumour volume.

Figure 7.

Helical tomotherapy technique planning images. Dose colour wash in axial, sagittal and coronal planes with the lower dose limit set to 95% of 10 Gy, demonstrating conformal dose deposition around the planning target volume (shown in red contour) in the second or the boost phase. The inner red contour shows the preoperative gross tumour volume.

Outcome and follow-up

At 6-month follow-up, the skin reactions healed. Clinical examination and CECT of the chest showed postradiotherapy changes with no evidence of any disease recurrence or lung metastasis (figure 8).

Figure 8.

Coronal, axial and sagittal planes of the contrast-enhanced CT of the chest showing complete response 6 months post radiotherapy.

Discussion

UPS was previously known as malignant fibrous histiocytoma (MFH). MFH was removed from the 2013 WHO classification of tumours of soft tissue and bone. It was after careful immunohistochemical and histopathological analysis, which showed many sarcomas previously classified as pleomorphic MFH had a specific line of differentiation. These could be classified as myxofibrosarcoma, myogenic sarcoma, myofibroblastic sarcoma, liposarcoma, soft tissue osteosarcoma or malignant peripheral nerve sheath tumour, whereas only 16% of them had no specific line of differentiation, which are now known as UPS.³

UPS has a peak incidence in the later adult life, that is, 60–70 years. It usually occurs in lower extremity followed by upper extremity with a subset of patients with a history of prior radiotherapy. It has an aggressive biological behaviour and a poor prognosis, with 5-year disease-specific survival being 65%.³ Factors that increased the local recurrence were positive margins, age, recurrent disease at presentation. Factors that increased the disease specific death were tumour size, depth, grade, recurrent presentation and positive margins. Distant recurrence was associated with tumour size, depth, grade and recurrent presentation. The most common site for distant metastasis is lung. Patients with superficial trunk and extremity lesions do better than patients with visceral and retroperitoneal sarcomas.

Surgical resection is the principal therapeutic procedure, but it is often prohibited due to tumour location^{4 5} along with the fact that patient usually presents at later stages with large mass. Since STS are so rare in comparison to the benign lesions, the initial procedure for early-stage lesions are usually unplanned excision (shell out) with resulting positive margins, and hence it is very important to perform a re-excision to get clear margins. Wide en bloc resection with a 1–2 cm of clear margin is the surgery of choice. Adjuvant radiotherapy should be added to enhance local control. Two landmark studies have showed the advantage in local control with postoperative adjuvant radiotherapy.^{6 7} In spite of the perks of preoperative radiotherapy, some being intact blood supply, well-defined treatment volume, postoperative radiotherapy remains the first and the most widely practiced approach because it allows timely surgery, sterilisation of microscopic nests of residual disease and accurate histopathological examination. The postoperative external beam radiotherapy can be given by various techniques, some being 3 dimensional conformal radiotherapy (3DCRT), IMRT, Image Guided Radiotherapy (IGRT). HT tomotherapy emerged to have an advantage over linac-based IMRT, 3DCRT and direct tomotherapy in view of target coverage (D90% and D98%).^{8 9} The treatment volumes comprised of clinical target volume (CTV) being tumour bed +4 cm margin longitudinally and 1.5–2 cm margins radially. An additional margin of 3–5 mm is given to the CTV to form PTV. A total dose of 50 Gy in daily fractions of 1.8–2 Gy/fractions, five fractions per week is given in the first phase followed by boost to the tumour bed. Surgery and radiotherapy remain the mainstay of treatment, with a limited role of chemotherapy. There is an established role of chemotherapy in Ewings sarcoma and rhabdomyosarcoma.^{10 11} For other histologies, the role of chemotherapy has not been established yet.

Patient’s perspective.

Soft tissue sarcomas diagnosed at an early stage are curable. In view of the above case, it is advisable to get a proper biopsy (true cut/incisional) even in small lesions irrespective of the presence or absence of risk factors such as genetic predisposition, prior radiotherapy, lymphedema or history of trauma. Proper diagnosis at an early stage can reduce mortality and morbidity to a large extent.

Learning points.

• Sarcoma diagnosed at an early stage is curable.

• Clear surgical margins has a major role in prognosis.

• Adjuvant radiotherapy has a significant role in local control.

• Helical tomotherapy emerged to have an upper hand in view of target coverage of the chest wall tumors as compared with linac-based IMRT, 3DCRT and direct tomotherapy.

Ethics statements

Patient consent for publication

Consent obtained directly from patient(s)