Robotic Treatment of Adrenal Sclerosing PEComa: A Case Report with 13 Years of Follow-Up and a Literature Review

Abstract

Background: Sclerosing perivascular epithelioid cell tumors (PEComas) are rare mesenchymal neoplasms, typically benign but occasionally exhibiting aggressive behavior. This study reports a case of sclerosing PEComa of the adrenal gland that was treated with robotic partial adrenalectomy, with 13 years of follow-up and a review of the literature. Methods: A 48-year-old woman presented with abdominal pain. Imaging revealed a 10 × 9 cm adrenal mass displacing adjacent structures. MRI and 18F-FDG PET-CT suggested angiomyolipoma. Robotic partial adrenalectomy was performed. Intraoperative frozen section analysis identified the mass as angiomyolipoma, while final histopathology confirmed it as a sclerosing PEComa. Results: This case highlights the advantages of robotic surgery in the management of large adrenal tumors, allowing complete tumor removal while preserving functional adrenal tissue. The extended 13-year follow-up is significant, given the potential for recurrence or malignant transformation reported in other cases. A literature review identified 39 reported cases of sclerosing PEComas, with few documenting long-term outcomes. Conclusions: This is a documented case of robotic partial adrenalectomy for sclerosing PEComa. The findings support robotic surgery as a safe effective approach for managing this rare tumor, with excellent functional and oncological results. Extended follow-up reinforces the tumor’s benign behavior and the importance of long-term monitoring in PEComas.

1. Introduction

Perivascular epithelioid cell tumors (PEComas) represent a heterogeneous group of rare mesenchymal neoplasms. They are uniquely characterized by the presence of perivascular epithelioid cells that exhibit co-expression of both muscle and melanocytic markers [1,2]. According to the World Health Organization Classification of Soft Tissue Tumours, the PEComa group encompasses several distinct entities, including renal angiomyolipoma (AML), pulmonary clear cell “sugar” tumor (CCST), lymphangioleiomyomatosis (LAM), and a variety of other soft tissue and visceral malignancies that predominantly occur in the abdominopelvic or retroperitoneal regions [3,4]. Although they can emerge in different anatomical locations, PEComas not classified as AML, CCST, or LAM are exceedingly uncommon [5,6]. Hornick and Fletcher identified a distinct subtype of PEComa known as “sclerosing PEComa”, which is predominantly composed of sclerotic and hyalinized connective tissue. It is typically located in the retroperitoneum, often at a pararenal site. Sclerosing PEComas predominantly affect women, with the highest incidence observed during the 5th decade of life, although reported age ranges from 15 to 97 years. Generally, their behavior is benign, even if two cases of sclerosing PEComa have been documented with an aggressive clinical course, both of which were histologically distinguished by a high-grade malignant phenotype [7,8,9]. Recent analyses of case series emphasize that diagnosis is often incidental, and lesions may be initially misinterpreted as angiomyolipomas, gastrointestinal stromal tumors (GISTs), or even carcinomas, underlining the diagnostic challenge posed by these neoplasms [10,11]. A systematic review by Thway and Fisher highlighted that the distinction between benign and malignant PEComas remains problematic, given their overlapping morphological and immunohistochemical features [4]. Moreover, it has been suggested that sclerosing PEComas may be underdiagnosed due to their rarity and resemblance to other fibrosing tumors, particularly when only limited biopsy material is available [12]. However, only a few cases of sclerosing PEComa were reported in the literature, and existing data confirm the challenges in diagnosing and follow-up for this condition [10,13]. Due to limited understanding of this uncommon condition and its biology, we reported a case of primary sclerosing PEComa of the adrenal gland treated by robotic partial adrenalectomy in a 48-year-old female patient, with a long-term follow-up of 13 years. To date, adrenal involvement by PEComas is extremely rare, with most cases in the literature confined to small series or isolated case reports. Therefore, adrenal sclerosing PEComa represents an even more exceptional clinical entity, with no standardized management protocols [14]. Our primary goal was to assess perioperative and long-term oncological outcomes, while the secondary objective was to provide a comprehensive review of the relevant literature on PEComa and its sclerosing variant.

2. Materials and Methods

Case report: A 48-year-old woman experiencing abdominal pain underwent an abdominal ultrasound scan, which revealed a well-defined 10 × 9 cm mass in the right adrenal gland. Contrast-enhanced computed tomography (CECT) and magnetic resonance imaging (MRI) further characterized the mass as having features consistent with an angiomyolipoma (

Table 1. Radiological summary.

Imaging Modality	Findings	Interpretation
Ultrasound	Well-defined 10 × 9 cm echogenic mass in the right adrenal region.	Suggested adrenal origin; prompted further imaging.
Contrast-enhanced CT	Heterogeneous adrenal mass with fat-like attenuation displacing the right kidney and renal vein; no evidence of local invasion.	Compatible with a benign adrenal neoplasm, likely angiomyolipoma.
MRI	Heterogeneous mass with mixed signal intensity consistent with a fat-containing lesion.	Imaging features consistent with angiomyolipoma.
18F-FDG PET-CT	Focally increased metabolic activity within the mass.	Raised suspicion for malignancy despite benign-appearing morphology.

). The mass was noted to displace the right kidney and renal vein, though renal function remained unimpaired (Figure 1).

Laboratory tests, including serum catecholamines, cortisol, and urinary vanillylmandelic acid (VMA), were all within the normal range. Considering the clinical and instrumental findings, surgical resection of the mass was advised. Informed consent was duly obtained from the patient. For the surgical procedure, the patient was positioned in left lateral decubitus with a 45° tilt. Six trocars were strategically placed: an optical camera along the mammary line above the umbilical transverse line, two robotic trocars along the pararectal line, and one along the anterior axillary line targeting the adrenal fossa. Additionally, 10 mm and 5 mm trocar units were placed for the assistant, above the umbilicus and along the midline to elevate the liver, respectively.

Utilizing the Da Vinci Si robotic system (Intuitive Surgical, Sunnyvale, CA, USA), an intraoperative biopsy was performed, and the frozen section analysis identified the mass as an adrenal angiomyolipoma. Consequently, a robotic partial adrenalectomy was performed (Figure 2).

The operation lasted 140 min, with an estimated blood loss of 150 mL. The patient’s hospital stay was 5 days, and the postoperative course was uneventful, with no complications. Hormonal replacement therapy was not required. Postoperative serum catecholamine, cortisol, and Coombs test results remained within normal ranges. The definitive histological examination identified the mass as a sclerosing PEComa, exhibiting specific immunohistochemical features: positive for desmin and melan-A, and negative for melanocytic markers such as S100 and HMB45. The diagnosis was validated by a review conducted by the Italian Rare Tumor Network. Postoperative course was uneventful and 156 months (13 years) after surgery, the patient is in good health with no evidence of local recurrence or distant metastasis (

Table 2. Timeline of clinical course.

Phase	Details
Symptom Onset	A 48-year-old woman presented with abdominal pain.
Initial Assessment	Abdominal ultrasound revealed a well-circumscribed 10 × 9 cm mass in the right adrenal gland.
Diagnostic Work-Up	Contrast-enhanced CT and MRI confirmed a large adrenal lesion displacing the right kidney and renal vein. PET-CT showed increased uptake. Hormonal profile (serum catecholamines, cortisol, and urinary vanillylmandelic acid) was within normal limits.
Surgical Treatment	A robotic partial adrenalectomy was performed. Intraoperative frozen section suggested an angiomyolipoma.
Definitive Diagnosis	Final pathology confirmed sclerosing PEComa with characteristic immunohistochemical features. Diagnosis was validated by the Rare Tumor Network.
Postoperative Course	Recovery was uneventful. No complications occurred, and hormonal replacement therapy was not required.
Follow-up	Over a 13-year period (156 months), no local recurrence or distant metastasis was detected during regular clinical and radiological follow-up.

).

3. Discussion

Sclerosing PEComa is an uncommon subtype of perivascular epithelioid cell tumor characterized by extensive stromal hyalinization. The term “sclerosing PEComa” was introduced by Hornick and Fletcher, who reported a series of 13 cases [7]. To date, there are 39 reported cases of sclerosing PEComa in the English literature and few of them include long-term follow-up. The disease was localized in the retroperitoneum in fifteen cases, in the kidney in nine cases, in the pararenal area in three cases, in the uterus and adnexa in seven cases, and in one case each in the pelvis, adrenal gland, abdominal wall, lung, and testis (

Table 3. Literature review.

Author	Case N.	Age	Sex	Tuberous Sclerosis	Site	Size (cm)	Treatment	Follow-Up
Hornick et al. [7]	1	43	F	No	Retroperitoneum	9	Resection	NA
	2	36	F	No	Abdominal wall	8	Resection	NA
	3	46	F	No	Retroperitoneum	4.5	Resection	64 mo, no recurrence
	4	50	F	No	Retroperitoneum	11.5	Resection	51 mo, no recurrence
	5	51	F	No	Retroperitoneum	22	Resection	22 mo, no recurrence
	6	50	F	No	Pelvis	13	Resection, RT, and CH	46 mo, metastasis (lung, liver, abdominal wall)
	7	59	F	No	Retroperitoneum	NA	Resection	39 mo, no recurrence
	8	53	F	No	Retroperitoneum	4.5	Resection	15 mo, died from unknown causes
	9	34	F	No	Uterus	10	Resection	33 mo, no recurrence
	10	73	F	No	Retroperitoneum	9	Resection	23 mo, no recurrence
	11	47	F	No	Retroperitoneum	28	Resection	10 mo, no recurrence
	12	49	F	Yes	Retroperitoneum	6.1	Resection	NA
	13	48	F	No	Retroperitoneum	19	Partial resection	NA
Matsuyama et al. [8]	14	56	F	No	Kidney	2	Resection	10 mo, no recurrence
	15	44	F	No	Retroperitoneum	13	Resection	NA
Ramaiah et al. [9]	16	63	F	NA	Adnexa	15	Resection	4 mo, died due to metastasis (lung, liver, lymph node)
Santi et al. [14]	17	66	F	No	Retroperitoneum	8.5	Resection	24 mo, no recurrence
Valiathan et al. [15]	18	50	F	NA	Pararenal	8	Resection	NA
Yamada et al. [16]	19	34	F	No	Uterus	5	Resection	12 mo, no recurrence
	20	51	F	No	Uterus	7	Resection	24 mo, no recurrence
Leão et al. [17]	21	51	F	No	Pararenal	5.9	Resection	48 mo, no recurrence
Lim et al. [18]	22	59	F	Yes	Uterus	1.2	Resection, CH	15 mo, recurrence of synchronous carcinoma/sarcoma
Rekhi et al. [19]	23	56	F	NA	Retroperitoneum	7	Resection	NA
Surico et al. [20]	24	53	F	No	Adnexa	10.6	Resection	10 mo, no recurrence
Zhao et al. [21]	25	54	F	No	Kidney	16	Resection	7 mo, no recurrence
	26	65	F	No	Pararenal	7	Resection	4 mo, no recurrence
Miyai et al. [22]	27	51	F	No	Kidney	4	Partial resection	16 mo, no recurrence
To et al. [13]	28	52	F	NA	Retroperitoneum	8.5	Excision	23 mo, no recurrence
Planelles et al. [23]	29	40	M	No	Kidney	3	Resection	NA
	30	57	F	Yes	Kidney	1	Resection	3 mo, no recurrence
	31	46	F	No	Adrenal	9	Resection	4 mo, no recurrence
	32	47	M	No	Kidney	2.3	Resection	10 mo, no recurrence
	33	51	M	No	Kidney	3.3	Resection	18 mo, no recurrence
	34	71	F	No	Kidney	2	Resection	3 mo, no recurrence
Kim et al. [24]	35	51	M	NA	Lung	1	Wedge resection	NA
Jia et al. [10]	36	52	F	No	Retroperitoneum	4	Resection	92 mo, no recurrence
Kundu et al. [12]	37	29	F	NA	Uterus	21	Resection	12 mo, no recurrence
Galea et al. [25]	38	52	M	Yes	Testis	3	Resection	NA
Matkowskyj et al. [26]	39	59	F	No	Kidney	1.8	Resection	NA

Abbreviations: RT—radiotherapy; CH—chemotherapy; NA—not available; mo—months.

).

The rarity of sclerosing PEComas presents diagnostic and therapeutic challenges due to limited clinical experience and absence of standardized guidelines. Histologically, these tumors are defined by dense hyalinized stroma and perivascular epithelioid cells that express both melanocytic and smooth muscle markers, thereby distinguishing them from other soft tissue tumors [7]. However, the histological spectrum can be broad, necessitating careful immunohistochemical analysis to avoid misdiagnosis, particularly with sarcomatoid neoplasms or metastatic melanoma [11,27].

Typically, sclerosing PEComas may not include a fatty tissue component, and melanocytic markers are often only focally expressed, which can complicate their identification [7]. Accurate diagnosis requires careful histopathological confirmation, since radiological findings alone are often inconclusive [12]. The diagnosis of PEComa is established on the basis of the co-expression of melanocytic and muscle markers in addition to the histological findings. These lesions most commonly have highly specific immunohistochemical features, such as the co-expression of melanocytic (Melan-A, HMB45, MITF) and muscle markers (desmin, smooth muscle actin, and calponin) and negativity for epithelial markers (CKs, EMA). A small percentage of cases show positivity for S-100 protein and CD117 [11,27]. In contrast with conventional PEComas, sclerosing PEComas typically show more diffuse positive staining for smooth muscle markers and more limited immunoreactivity for HMB-45 [28]. Additionally, the microphthalmia transcription factor (MITF) is a valuable marker for sclerosing PEComa, being detected in 92% of cases [7]. The tumor cells may have radial arrangement around lumens: spindle cells are often found remote from vessels, while epithelioid cells are closest to vessels. These cells have an eosinophilic or clear cytoplasm and small central oval nuclei with small nucleoli [3,29].

Histologically, sclerosing PEComas can overlap with various entities, such as desmoplastic small round cell tumors, paragangliomas, round cell/epithelioid variants of gastrointestinal stromal and smooth muscle tumors, clear cell sarcomas, metastatic carcinomas, malignant melanomas, and epithelioid hemangioendothelioma of soft tissues [7,8]. However, the unique immunohistochemical profile of PEComas, along with clinicopathological correlations, usually allows for differentiation among these neoplastic entities.

PEComas generally have a favorable prognosis, but recurrence and distant metastasis are well-known phenomena that mandate a long-term surveillance program. Moreover, in some cases these tumors have been known to behave more aggressively and simulate sarcoma [29,30,31,32]. The malignancy criteria proposed by Folpe et al. include five histologic features: size greater than 5 cm, infiltrative growth pattern, high nuclear grade, necrosis, and mitotic activity exceeding one cell per 50 high-power fields. The presence of at least two of these features suggests malignancy, while a single feature indicates uncertain malignant potential [28]. In isolated instances, these tumors may spread extensively and even directly cause the patient’s death [33]. However, some authors argue that it is not possible to predict the malignant behavior of most of these tumors using current diagnostic methods.

PEComas may occur sporadically or in association with tuberous sclerosis, an autosomal dominant neurocutaneous disorder caused by genetic alterations of the TSC1 (9q34) or TSC2 (16p13) genes [34,35]. Both syndromic and sporadic PEComas contain inactivating point mutations, small insertions or deletions, and large deletions or copy-neutral loss of heterozygosity in the TSC1 or TSC2 genes, leading to the activation of the mTOR pathway [36]. An emerging body of evidence has begun to stratify PEComas based on molecular characteristics beyond TSC1 and TSC2 mutations, such as TP53 mutations or alterations in the PI3K/AKT pathway, which may correlate with prognosis and treatment response [37].

The mTOR pathway plays a central role in tumorigenesis, and its activation has direct therapeutic implications. Several studies have emphasized that mTOR-targeted therapy could be beneficial for treating both sporadic and tuberous sclerosis-related PEComas [23]. The confirmed activation of the mTOR pathway in these tumors suggests the potential for promising therapeutic options [38,39]. According to Bergamo et al., mTOR inhibitors such as sirolimus or temsirolimus represent valid options either as neoadjuvant or adjuvant treatments [40].

The recent literature emphasizes the potential of next-generation sequencing (NGS) to refine the classification and prognostication of PEComas, particularly those with ambiguous histologic features. NGS-based approaches have identified novel genetic alterations such as RAD51B or TSC1/TSC2-independent pathways, which may contribute to tumor behavior and therapeutic response [41].

Folpe et al. were the first to identify TFE3 gene fusions in a significant number of PEComas. This genetic alteration has been validated in subsequent research using FISH and immunohistochemistry. Current knowledge indicates that TFE3-positive PEComas are not associated with tuberous sclerosis. They typically appear in young people and exhibit a unique phenotype, characterized by a predominantly alveolar arrangement, epithelioid cytology, and weak or absent smooth muscle marker immunostaining [11,29,42]. Interestingly, some cases within this specific subgroup of PEComas have followed an aggressive clinical course [33,43].

Such findings underline the biological heterogeneity of PEComas and reinforce the importance of molecular profiling in cases with atypical morphology or clinical behavior. Tailoring therapeutic decisions based on genetic features, such as TFE3 fusions or mTOR pathway mutations, may improve outcomes, particularly for unresectable or metastatic tumors. Real-world clinical data suggest that the combination of mTOR inhibitors with VEGF pathway blockade or immunotherapeutic agents may improve disease control in advanced or metastatic PEComas, although prospective trials are currently lacking [44]. Furthermore, real-world evidence suggests that patients with advanced PEComas treated with nab-sirolimus, an albumin-bound form of sirolimus, demonstrate a durable response, leading to its FDA approval for malignant PEComas in adults [45]. These advances represent significant steps toward personalized therapy in rare mesenchymal neoplasms. The current gold standard treatment for PEComas is surgical excision when the patient is symptomatic, the tumor is bulky, or there is diagnostic uncertainty. Chemotherapy and radiotherapy have shown poor efficacy [13]. Potential treatment options for PEComas that cannot be surgically removed may involve conventional chemotherapy and biological agents. With the increasing amount of data available in the literature, sirolimus (or other mTOR inhibitors) is projected to be the most effective first-line treatment for advanced and metastatic PEComa [44,46]. Sanfilippo et al. described that, in patients with advanced PEComa who are no longer responding to mTOR inhibitors, introducing antiestrogen therapy has led to significant clinical improvements, especially in situations where no other treatments are viable [47].

However, in most of the published data, sclerosing PEComa exhibits a benign course [14], which aligns with the presented case. In all reported cases, surgical resection was carried out, with laparoscopic approaches performed in only two instances [16,26].

In our case, a robotic partial adrenalectomy was performed and, due to negative surgical margins, no adjuvant therapy was necessary. To our knowledge, no case of sclerosing PEComa has been reported as being treated by robotic conservative surgery. In recent decades, adrenal surgery has undergone a significant shift from open procedures toward minimally invasive techniques, particularly laparoscopic and, more recently, robotic adrenalectomy. This transition has been driven by the aim to reduce perioperative complications, postoperative pain, and hospital stay, without compromising oncologic efficacy.

Several studies comparing the three main surgical approaches—open, laparoscopic, and robotic—have consistently demonstrated significant perioperative advantages in favor of minimally invasive techniques. Laparoscopic adrenalectomy, currently considered the gold standard for most benign adrenal conditions and selected malignant lesions, is associated with significantly reduced intraoperative blood loss, shorter hospital stays, and lower complication rates compared with open surgery. In a cohort of over 600 patients, the laparoscopic approach reduced 30-day postoperative morbidity from 17.4% to 3.6%, with no adverse impact on oncologic outcomes [48].

Robotic adrenalectomy, although typically associated with longer operative times and higher costs, has shown comparable and, in some settings, superior performance relative to conventional laparoscopy in terms of blood loss, length of hospital stay, and conversion rates. Recent meta-analyses have reported that robotic adrenalectomy is associated with lower intraoperative bleeding and shorter hospitalization, while maintaining a similar safety profile [49,50]. Moreover, comparative studies have confirmed these findings, even when including open adrenalectomy as a reference [51]. Additionally, the robotic approach appears particularly advantageous in patients with obesity, large adrenal masses, or anatomically complex cases, due to enhanced dexterity and superior three-dimensional visualization [52].

The current literature on the robotic management of PEComas is extremely limited and primarily based on isolated case reports and a small series of adrenal angiomyolipomas. Gonzalez-Manso and Vazquez-Martul reported the first single-port retroperitoneal robotic adrenalectomy specifically performed for an adrenal AML, demonstrating the feasibility and safety of this minimally invasive approach in managing such uncommon lesions [53]. Additionally, Zhou et al. described their experience with 21 large adrenal tumors removed via a retroperitoneal robotic approach, indirectly supporting the use of robotic surgery for sizable lipid-rich adrenal tumors, including AML [54]. Although these preliminary findings highlight the potential advantages of the robotic platform in achieving precise dissection and favorable perioperative outcomes, robust comparative studies and long-term follow-up data are still lacking.

In our experience, the robotic approach was useful for completely removing the sclerosing PEComa and, despite its considerable size, to preserve the healthy surrounding adrenal parenchyma. Moreover, this minimally invasive strategy allowed for a quicker and complication-free postoperative course. Robotic surgery, with its enhanced dexterity, three-dimensional visualization, and precision, offers a distinct advantage in the management of retroperitoneal masses, particularly those in challenging anatomical locations such as the adrenal gland. Although laparoscopic approaches have been reported [16,26], robotic-assisted surgery allows for a more meticulous dissection and adrenal-sparing procedure, which may contribute to reduced perioperative morbidity and faster recovery.

Another notable aspect of our case is the extended follow-up period. While PEComas generally have a favorable prognosis, cases of recurrence and distant metastasis have been reported. The longest follow-up for a patient with sclerosing PEComa documented in the literature was 64 months. In our case, a 156-month follow-up revealed no evidence of local or distant recurrence. This represents the longest documented follow-up for this tumor subtype to date and strongly supports the indolent behavior of sclerosing PEComas when managed with complete surgical excision. Long-term follow-up remains critical to monitor for rare late recurrences and to improve our understanding of this rare entity.

4. Conclusions

We report a case of the rare sclerosing variant of PEComa arising from the adrenal gland in a young woman. Despite its large size, the tumor was radically removed by a robot-assisted partial adrenalectomy and, at the 13-year follow-up, no evidence of local recurrence or distant metastasis occurred. Additional studies with long-term follow-up on PEComas, regardless of their originating locations, are essential to enhance prognostic accuracy for this biologically fascinating neoplastic entity. Nonetheless, this study has limitations. The lack of comprehensive genomic profiling precludes deeper insights into the tumor’s molecular characteristics and potential therapeutic targets. Furthermore, given the single-case nature of this report, the observations presented cannot be generalized and should be interpreted with caution. Future investigations involving larger cohorts and integrated molecular analyses will be crucial to validate and expand upon these preliminary findings.