PD-1, PD-L1, NY-ESO-1, and MAGE-A4 expression in cutaneous angiosarcoma: A case report

Rationale: The genomic alteration of cutaneous angiosarcoma (cAS) is complex. Treatment efficacy of immunotherapy for cAS remains controversial and prognosis remains poor. Herein, we report a case of cAS with programmed cell death 1, programmed cell death ligand-1, New York esophageal squamous cell carcinoma-1, and melanoma-associated antigen 4. Patient concerns: A 69-year-old man presented with a chief complaint of left thumb pain, with a soft tissue mass in the palmar side of the thumb. He had no past medical history. Three months prior, the man experienced the pain while scuba diving. He visited a nearby clinic, and magnetic resonance imaging revealed a soft tissue tumor on the palmar side of the thumb. He was referred to our hospital and a marginal excisional biopsy was performed. Diagnosis: Pathological findings revealed an angiosarcoma with high-flow serpentine vessels. Interventions: An excision was performed from the base of the thumb to achieve a wide margin. Outcomes: One year after the treatment, the patient has not experienced recurrence, metastasis, or complications. Lessons: Histopathology of the excised specimen was positive for programmed cell death 1, programmed cell death ligand-1, New York esophageal squamous cell carcinoma-1, and melanoma-associated antigen 4; their expression may be a therapeutic target for cAS. Combining immunotherapy with surgical treatment may be effective for cAS.


Introduction
Angiosarcoma, a malignant vascular neoplasm that variably recapitulates the morphological and immunohistochemical features of endothelial cells, [1] accounts for approximately 3% of soft tissue sarcomas.Angiosarcomas are predominantly found in men, with peak incidence in the seventh decade of life and a wide age range, although they are very rare in children. [1]ore than 50% of angiosarcomas occur in cutaneous sites (cutaneous angiosarcoma [cAS]), with the remaining 50% occurring within deep soft tissues, the breast, bone, or viscera. [1]] Recently, it was reported that programmed cell death 1 (PD-1), programmed cell death ligand-1 (PD-L1) immune checkpoint mechanism, and cancer-testis antigens, New York esophageal squamous cell carcinoma-1 (NY-ESO-1) and melanoma-associated antigen 4 (MAGE-A4), are involved in the pathogenesis of soft tissue sarcomas (STS). [4,5]e present a case of cAS, which was positive for PD-1, PD-L1, NY-ESO, and MAGE-A4.

Discussion
Approximately 50% of cASs occur in the head and neck, especially on the skull of the elderly, and are aggressive malignant tumors with poor prognosis. [1,6]Recently, several molecules, such as FOXM1, HSP90, KCa3.1, miR-497-5p, miR210, and survivin, were identified as potential markers and therapeutic targets for angiosarcoma. [7]In the current report, we presented a case of cAS of the thumb that expressed PD-1, PD-L1, NY-ESO, and MAGE-A4.
Risk factors for angiosarcoma include radiation, exposure to polyvinyl chloride, use of contrast agent, and chronic lymphedema.Notably, 2 previous reports suggested that angiosarcoma arises from pseudoaneurysms. [8,9]Some studies reported that scuba diving causes vascular abnormalities, such as internal carotid artery dissection, stroke, and vascular dissociation. [10,11]In the current case, the patient's hobby was scuba diving, and this may have contributed to the development of the angiosarcoma.
Angiosarcoma typically presents as a hemorrhagic, diffuse, or multinodular mass of variable size (mean, 5 cm; range, 1-15 cm). [1]In general, the larger the size of the soft tissue sarcoma, the more likely it is to be malignant. [12]In the current study, although the tumor size was relatively small, the angiosarcoma was malignant.Therefore, oncologists should consider malignancy, even for small tumors.
Early diagnosis of soft tissue sarcoma is extremely important for successful treatment and favorable outcomes; [13,14] however, delayed diagnoses of STS and angiosarcomas are common. [15,17]Although MRI findings are relatively nonspecific, they often indicate malignancy and should prompt biopsy for confirmation of diagnosis. [1,8,9]A recent report showed that PD-1/PD-L1, induced by IL-1 and IFN-ɤ, was involved in the pathogenesis of STSs. [16,17]Further, PD-1, PD-L1, NY-ESO, and MAGE-A4 are reportedly useful as diagnostic markers of STS. [18,19]These findings suggest that PD-1, PD-L1, NY-ESO, and MAGE-A4 expression may be useful diagnostic markers for cAS.
[22] In the current case, we had planned to perform marginal resection as an open biopsy because the tumor was too small for needle biopsy.Subsequently, we performed wide-margin resection.
Angiosarcoma has a poor prognosis, with a reported 5-year overall survival rate of approximately 30%. [22,28,29]The local recurrence rate is approximately 20%, and distant metastases occur in approximately 50% of recurrent cases. [1]The most frequent site of distant metastasis is the lung, followed by the lymph nodes, soft tissues, bone, liver, and other sites. [1,22]Although no lung metastasis was observed in the current case, careful follow-up is necessary.
The present case study had the following limitations: positron emission tomography-CT imaging was not performed; meanwhile, positron emission tomography-CT is useful for tumor staging and response assessment. [30]In addition, 2 genes, protein tyrosine phosphatase receptor type B gene and phospholipase C gamma 1 gene, which were recently identified, have not been investigated. [31,32]Moreover, we could not determine the presence of fusion genes, such as NUP160-SLC43A3, to confirm the diagnosis. [33]Despite these limitations, we confirmed the diagnosis using histological assessment and successfully treated the patient via wide-margin resection.
In conclusion, we reported a case of a tiny cAS of the thumb.We believe that the combined expression of PD-1/PD-L1 and NY-ESO-1/MAGE-A4 may be a useful diagnostic marker and therapeutic target for cAS.

Figure 1 .
Figure 1.(A) Appearance of the left thumb at the first visit.There is no obvious swelling or abnormal pigmentation.(B) Sagittal T 1 -weighted MRI of the left thumb.A low-intensity mass is observed on the subcutaneous palmar side of the distal thumb (red arrowheads).(C) Coronal T2-weighted MRI of the left thumb.The iso-low-intensity mass is on the subcutaneous palmar side of the distal thumb (red arrowheads).MRI = magnetic resonance imaging.

Figure 3 .
Figure 3. (A) Radiograph of the thumb after surgical treatment.(B) Excised specimen of the thumb.(C) Cut surface of the resected specimen of the thumb.