Soft-tissue leiomyosarcoma on the parietal area with angiosarcoma

Dear Editor, An 88-year-old Japanese female was referred to our hospital with a rapidly growing tumor about 4 cm in diameter on her parietal area for 3 months in 2018 [Figure 1a]. She had no history of trauma on her head. A cutaneous biopsy specimen from the mass showed fusocellular proliferation from the superficial dermis to subcutaneous tissue. T2-weighted magnetic resonance imaging showed a heterogeneous isointensity signal on the parietal bone [Figure 1b]. Computed tomography from the neck to the inguinal area revealed no abnormal findings. We excised the mass at a 10 mm margin with the periosteum that partially showed a purple color, scraped off the surface of the bone, and performed a skin graft [Figure 1c and d]. The resected specimen seemed to include two types of lesions: a central large mass (blue arrow) and surrounding small-scattered lesions (blue arrowhead) [Figure 1e]. Pathologically, the two tumors did not show any gradual transition or connection. Histopathological examination of the large mass showed prominent cellular atypia of fusocellular proliferation with abundant mitosis and coagulative necrosis in the dermis, subcutaneous, and galea aponeurotica [Figure 2a-c]. In small lesions, primitive round cells with poorly formed vascular spaces formed various nests between the dermis and galea aponeurotica [Figure 2d and e]. Immunohistochemical (IHC) staining revealed smooth muscle actin and muscle-specific actin (HHF35) were positive in the large mass and negative in small lesions [Figure 2f and g]. In contrast, CD31 was negative in the large mass and positive in small lesions [Figure 2h and i]. Immunostaining of p53 showed wild type in the large mass and loss in small lesions [Figure 2j and k]. There were no IHC findings to suggest other causative mutations. We diagnosed the large mass and small lesions with soft tissue leiomyosarcoma (LMS) and angiosarcoma, respectively. Two months after the surgery, a red nodule appeared under the skin grafting, which was diagnosed as soft tissue LMS by skin biopsy. Because she did not wish for an additional resection or chemotherapy, radiation was administered. She died 10 months after the surgery. An autopsy showed the soft tissue LMS had extended beyond the skull and dura into the subarachnoid space without invasion of the brain parenchyma. soft tissue LMS was found in the lungs, the pulmonary artery, the heart, and the right rectus femoris muscle. IHC showed loss of p53 in the lung metastasis.Figure 1: (a) Clinical presentation at first visit. The dome-formed mass about 4 cm in diameter, with a blackish-brown crust and ulcer were observed on the parietal area. (b) T2-weighted magnetic resonance images. showed a heterogeneous isointensity signal on the parietal bone. (c and d) We excised the mass at a 10 mm margin with the periosteum that partially showed a purple color, scraped off the surface of the bone, and performed a skin graft (e) The resected specimen included two types: a large mass (blue arrow) and surrounding small lesions (blue arrowhead) without a clear transition.Figure 2: (a-k) Histopathological findings. The large mass showed prominent cellular atypia of fusocellular proliferation with abundant mitosis and coagulative necrosis in the dermis, subcutaneous, and galea aponeurotica (H and E; a, blue arrow, ×1; b, ×12.5; d, ×200). In small lesions, primitive round cells with poorly formed vascular spaces formed various nests between the dermis and galea aponeurotica (H and E; a, blue arrowhead, ×1; c, ×12.5; e, ×200). Immunohistochemical staining revealed that smooth muscle actin was positive in the large mass (f, ×12.5) and negative in small lesions (g, ×12.5). CD31 was negative in large mass (h, ×12.5) and positive in small lesions (i, ×12.5). Immunostaining of p53 showed wild type in soft tissue LMS (j, ×200), and loss in angiosarcoma (k, ×200).To our knowledge, this is the second case, in which soft tissue LMS and angiosarcoma were observed at nearby sites.[1] We discuss the possibility that soft tissue LMS and angiosarcoma share the same oncogenic pathway. p53 is encoded by the TP53 gene, which is known to play significant roles in suppressing bone and soft-tissue sarcoma progression.[2] Mutations of the TP53 gene have recently occurred in 50% of angiosarcoma and 80% of leiomyosarcoma.[3,4] In this case, IHC of p53 showed wild type in the primary soft tissue LMS, while loss in the metastatic site. It is possible that tumor cells with a loss of function in the tumor suppressor gene p53 may have metastasized. IHC is not a reliable tool for TP53 mutation screening when the frequency of null mutation is high,[5] which does not apply to soft tissue LMS. One study suggested that angiosarcomas constitute a distinct subgroup among sarcomas with complex genomics.[4] Although not examined in this case, proliferation of c-myc also may cause angiosarcoma[5] and leiomyosarcoma.[6] Only p53 and c-myc genetic mutations have been reported to be common to soft tissue LMS and angiosarcoma. Because soft-tissue sarcomas have a high incidence of acquired (somatic) genetic mutations,[7] there may be unknown somatic mutations in our case. Another possibility might be the background involvement of pericyte abnormalities in the development of the two malignancies since pericytes differentiate into vascular smooth muscle cells and mature blood vessels.[8] Further, case accumulation and genetic analysis are needed. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent form. In the form the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that her name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed. Data availability statement The datasets generated during and/or analyzed during the current study are not publicly available, but are available from the corresponding author on reasonable request. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.