Adrenal PEComa Treated by Surgical Resection and Postoperative Radiotherapy: A Case Report

Introduction

According to the definition of the World Health Organization, PEComa, defined as a mesenchymal tumor containing distinctive perivascular epithelioid cells, is evaluated in the same tumor family as tumors such as angiomyolipoma, sugar cell tumor of the lung, lymphangioleiomyomatosis, and clear cell myomelanocytic tumor of the false ligament. Immunohistochemically, it can express melanocytic and myogenic markers, such as HMB45, HMSA1, MelanA/Mart1, and actin. PEComa can occur in association with tuberous sclerosis complex, an autosomal dominant disease that occurs due to the loss of TSC1 or TSC2 genes [1–4]. PEComa, which especially affects young adult women, can be seen in almost every organ, including the bladder, colon, gallbladder, heart, and adrenal gland, and especially the uterus and retroperitoneum [5–9]. It constitutes a very rare group of adrenal gland malignancies and is difficult to diagnose. Immunohistochemistry is critical for the diagnosis of the disease. The primary treatment approach for the treatment of localized disease is surgical resection; adjuvant systemic therapy can be applied in high-risk patients [10–13]. Studies in the literature on the results of postoperative radiation therapy in PEComa cases are far from making a clear recommendation on this issue [11–14]. We present a case of PEComa of adrenal gland origin in which we applied postoperative radiation therapy.

Case Report

Informed consent was obtained from the patient. A 24-year-old female patient with a history of no chronic illness, smoking, or alcohol use, visited the doctor in April 2022 due to abdominal pain that had been increasing steadily for the previous few months. After a contrast-enhanced abdominopelvic computed tomography (CT) scan showed a solid mass of 10 cm on the right adrenal gland (Figure 1), the patient was referred to the General Surgery Department. The patient was found suitable for surgery, and right adrenal gland mass excision surgery was performed in May 2022. PEComa was diagnosed after surgery, and it was appropriate to evaluate the tumor as malignant PEComa due to its necrosis, size (10 cm), Ki-67 activity, pleomorphism, and mitotic activity (2/10BBA) (Figures 2, 3). Surgical boundaries were reported as uncertain. Postoperative thoracic and abdominopelvic CT scans were reported as normal in September 2022. In hemogram and biochemical examinations, no abnormalities were detected. The patient was admitted for postoperative radiotherapy because the diagnosis was malignant PEComa, and there was uncertainty about the surgical boundaries. Systemic treatment was not required for the patient, per an interview by our Oncology Council. A fraction dose of 4680 cGy/26 was applied by 8-field IMRT to the tumor bed area, taking into account liver and kidney normal organ doses (Figure 4). Between November 2022 and December 2022, the patient’s radiotherapy was completed. No acute adverse effects from the radiotherapy were observed. The patient’s follow-up after treatment continued, without disease (Figure 5) and long-term adverse effects (latest follow-up, April 2024).

Discussion

In the literature, the nomenclature of the disease, which is a rare mesenchymal tumor, is relatively new [2]. Pathologically, it is typical for neoplastic cells to contain mild eosinophilic granular stoplasm. The disease, which is most often reported to be caused by the uterus, can be caused by almost any organ. Due to its extremely rarity, it is quite difficult to diagnose PEComa, and the possibility of confusion with the more common pathologies of the organ is emphasized in adrenal gland-related diseases [7,8]. Adrenal gland PEComa can be confused with adrenocortical tumors, melanoma, clear cell sarcoma, and metastatic carcinoma from an extraadrenal site. To make a diagnosis, the immunohistochemical characteristics of the disease should be considered. The disease contains melanocytic differentiation, such as HMB45 and MelanA/Mart1, and myogenic markers, such as actin, while the epithelial membrane does not express markers, such as epithelial membrane antigen, keratin, and S-100. It is stated that some types can express progesterone receptors. Adrenocorical tumors are negative for HMB-45 and myogenic markers. Inhibin or calretinin expression by immunohistochemistry would confirm a diagnosis of an adrenocortical neoplasm. Metastatic carcinomas exhibit positive immunoreactivity for keratin and/or epithelial membrane antigen and negative immunoreactivity for melanocytic or muscle-associated antigens. Melanomas are negative for muscle antigens. Clear cell sarcomas are also negative for myoid markers [7,8].

Most PEComas are benign. Although the criteria for malignant disease have not been definitively established, tumors containing histologically widespread necrosis and showing an infiltrative growth pattern, vascular invasion, pleomorphism, and a high mitosis rate can be considered malignant. In addition to these histological features, the fact that the tumor has a large size also suggests that the disease can have a more aggressive clinical course [14,15]. Malignant PEComa can follow an aggressive course that can cause recurrence and metastasis. The most common places where the disease metastasizes are lymph nodes, lungs, and bones, although the location can vary depending on the primary location of the tumor [14].

Surgical resection is the primary treatment approach in the treatment of localized disease. Neoadjuvant treatment has been used in a small number of cases, and its only goal is conversion of unresectable disease to resectable. The role of adjuvant therapy for PEComa is also unclear. It is stated that adjuvant anthracycline-based or ifosfamide-based chemotherapy regimens can be applied in high-risk patients, according to pathological risk factors that determine the risk of recurrence after surgery. The most important risk factors are tumor size >5 cm and a high mitosis rate [10,11]. Regardless of the postoperative therapy, long-term surveillance is very important because the disease can relapse even after many years. Due to the fact that the disease can occur in association with tuberous sclerosis complex, an autosomal dominant disease that occurs due to the loss of TSC1 or TSC2 genes, it is thought that mTOR inhibition-based treatment can be useful in some cases [12,13]. In the literature, it is observed that postoperative radiotherapy is applied in many cases, especially uterine PEComa; however, the indication of radiotherapy for the disease remains unclear. Given the available data in the literature, it is clear that many different treatments have been tried for the disease; however, there is no definitive treatment strategy.

Conclusions

Surgical resection is the primary treatment approach in the treatment of localized disease. Although the literature is far from making a clear recommendation on adjuvant therapy, pathologic risk factors should be considered when deciding on its use.