From diagnosis to treatment: Navigating a rare case of angiosarcoma of the scalp

INTRODUCTION

Angiosarcoma is an uncommon malignant vascular tumor originating from the endothelial cells lining blood vessels and lymphatic channels.¹ The preferred approach involves resecting with negative margins, followed by comprehensive postoperative radiotherapy. Only eight cases of angiosarcoma of the scalp have been reported in India over the past 2 decades. Due to their infrequent manifestation and tendency to mimic benign conditions, lesions are often diagnosed at a late stage. Our case adds to the understanding of this rare tumor and underscores the importance of early diagnosis and comprehensive management in improving outcomes for affected individuals. Here, we discuss a rare case of angiosarcoma of the scalp.

CASE REPORT

A 66-year-old male presented with a grayish, soft, growth on the scalp located over the right temporoparietal aspect of the scalp for 6 months. Initial lesion over the right temporoparietal aspect was 1 × 1 cm and increased to size 4 × 4 cm, [Figure 1] hyperpigmented, hypertrophic plaque with a fragile epidermis which bleeds on manipulation and revealed atrophic scarring on one side. There was mild induration on the peripheral margin of the plaque. The rest of the scalp appeared normal. Differentials included pyogenic granuloma or pigmented bcc, melanoma, Kaposi sarcoma, and contusion.

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Figure 1:

Hyperpigmented hypertrophic plaque with fragile epidermis, bleeds on manipulation with atrophic scarring on one side.

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A diagnostic biopsy suggestive of epithelioid angiosarcoma [Figure 2]. On immunohistochemistry: Positive CD34, CD31, and nuclear staining ETS-related gene (ERG) [Figure 3 a-d]. Routine investigations including X-ray chest, abdominal ultrasound sonography (USG), and multislice multiplanar computed tomography brain with and without non-ionic IV contrast scan to rule out distant metastasis were done. On magnetic resonance imaging, features were consistent with neoplastic lesion with mild ischemic changes [Figure 4]. A positron emission tomography scan was not done due to resource-poor setting and the nonaffordability of the patient.

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Figure 2:

(a) Typical angiomatous proliferation with infiltration mild to moderate degree of atypia is noticed with atrophic superficial epidermis. Dermal proliferation of epithelioid cells (hematoxylin and eosin [H&E], ×4). (b) Irregular anastomosing, vascular channels, lined by a single layer of enlarged endothelial cells seen between collagen bundles (H&E, ×10). (c) Endothelial cells are large epithelioid with intracytoplasmic vacuoles that contain red blood cells as depicted by black arrow (H&E, ×40). (d) Endothelial cells have focal multilayered appearance; and focal free floating intraluminal endothelial cells (H&E, ×40) is shown by red circle.

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Figure 3:

The tumor cells were positive. (a) Anti-D34 antibody shows that angiosarcomatous cells formed irregular vessels (CD34 ×10). (b) For nuclear staining ERG ×40 c: 40×; d: 20×. (c and d) Immunohistochemical marker CD31, confirming angiosarcoma (CD31 ×40).

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Figure 4:

Multislice multiplanar computed tomography (CT) brain was performed on multidetector computed tomography scanner. (a) CT without non-ionic IV contrast-focal thickening infiltrates the scalp musculature and abuts the outer table of the skull (green arrow), no calvarial involvement or intracranial extension. (b) CT with IV contrast. Post-contrast study exhibits exaggerated heterogeneous enhancement.

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Treatment

After routine investigations and ruling out the presence of distant metastasis by an X-ray chest and abdominal ultrasonography, the patient underwent wide excision with 2 cm gross margins taken for complete clearance under general anesthesia [Figures 5 and 6]. The lesion was excised with complete depth down to the periosteum in order to achieve en bloc 3D excision, ensuring clear margins on all sides [Figure 5b]. The defect was closed by performing a scalp advanced flap. Prior to closure with Ethilon and Vicryl, a negative suction drain was inserted below the flap. Procedure was uneventful, but there was flap necrosis at the tumor site. The second surgery was performed after 4 weeks to close the defect, where rotation flap surgery was done with skin graft to cover the defect [Figure 5c-d]. Sutures were removed on the 9^th postoperative day and the wound healed well [Figure 5d, 6d]. Histopathology of the excised specimen showed the margins to be clear. Once the healing was complete, radiotherapy was given for 6 weeks at a dose of 60 Gy in 30 treatment fractions taking a margin of 3 cm on all sides of postoperative bed to prevent recurrence. He was followed up every 6 months and has had no recurrence with malignancy-free periods till date which is approximately 6 months. Step by step surgical reconstruction is given in the Flowchart 1.

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Figure 5:

(a) Defect 4 × 4 cm over the right temporoparietal aspect of the scalp (orange). (b) A 2 cm gross margin was ensured for complete clearance. En bloc excision of the scalp was performed, resulting in a 8 × 8 cm (blue) Pre-flap closure-Extensive defect following wide resection surgery (orange + blue). (c) Scalp rotation flap. (d) Closed the defect with sutures.

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Figure 6:

(a) Pre flap closure; (b) advanced flap; (c) rotational flap; (d) wound healed well.

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Flowchart 1:

Step by step surgical reconstruction.

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DISCUSSION

Scalp angiosarcoma, a rare but aggressive tumor with poor prognosis and lower median survival rates, especially in older individuals Therefore, recognizing the risk of local recurrence is crucial.

Due to its highly aggressive and multifocal characteristics, angiosarcoma carries a grim prognosis with a 5-year survival rate of < 35% and 75% of individuals experience local recurrence within 24 months of undergoing local treatment.² In a clinical context, angiosarcomas of scalp commonly manifest as macules resembling bruises to plaques and nodular lesions as in our patient. This benign clinical presentation frequently results in delayed presentation and diagnosis.³

Our case of a 66-year-old male, exhibiting features of angiosarcoma upon histopathological examination and immunohistochemistry. Despite wide excision and flap closure, flap necrosis occurred, necessitating further surgery and subsequent radiotherapy to prevent recurrence. This case highlights the aggressive nature and challenges in managing scalp angiosarcoma, reinforcing the importance of early diagnosis and comprehensive treatment strategies. In our patient, there was no identifiable predisposing risk factor.

Histopathological identification of angiosarcoma can be challenging due to its resemblance to other vascular tumors. In its early stages, it may mimic hemangioma, while the aggressive form can share features with anaplastic melanoma and epithelial carcinomas.

CD31, platelet endothelial cell adhesion molecule-1, is a transmembrane glycoprotein that is expressed by endothelial cells and a variety of hematolymphoid cells. In formalin-fixed, paraffin-embedded tissue, the JC70 monoclonal antibody has been shown to be a highly sensitive and specific marker of endothelial cells and their neoplasms and it is widely held that CD31 is the single best and proves highly reliable marker of endothelial differentiation in routinely fixed tissues. In contrast to less specific markers like CD34, CD31 proves highly reliable in diagnosing endothelial differentiation. ERG (ETS-related gene), part of the ETS family, is a sensitive vascular differentiation indicator, its presence indicates vascular differentiation, with strong diffuse nuclear expression observed.⁴

The standard treatment is often radical surgery followed by postoperative radiotherapy. As patients are elderly, the preferred reconstructive algorithm used is skin grafts, local flaps and free flap except when the excision includes the pericranium or when there is history of previous radiotherapy.

In our case we have treated the patient with wide excision with 2cm gross margins of the lesion to achieve a histologically tumor-free margin, as this has a direct impact on prognosis. As the tumor is extensive microscopically, primary closure of the wound is often not possible after wide excision. A reconstruction was performed after confirming histopathologically tumor-free margins. There are various reconstructive options for initial temporary coverage and definitive reconstruction. In our case, the defect was initially closed using an advancement flap, followed by a rotation flap, with postoperative radiotherapy employed to minimize the risk of recurrence.

Other innovative treatments such as paclitaxel, liposomal docetaxel, pembrolizumab, an inhibitor targeting the programmed death 1 checkpoint, have gained approval.⁵ Alternative checkpoint inhibitors, including agents targeting programmed death-ligand 1 or cytotoxic T- lymphocyte associated protein 4 (CTLA-4), have also demonstrated diverse responses.

CONCLUSION

Angiosarcoma exhibits intricate biology and aggressive behavior. The benign clinical presentation frequently results in delayed presentation and diagnosis. It is noteworthy to emphasize that, in diagnosing angiosarcoma, the integration of markers, alongside clinical and histopathological findings are essential. Treatment involves wide-margin resection and a staged multimodal approach for even those cases without evident metastasis. This staged strategy enables precise margin assessment during the initial resection, allowing for re-excision and reconstruction if necessary.