Pecoma—A Rare Liver Tumor

Journal of Clinical Medicine

Article PEComa—A Rare Liver Tumor

Marek Krawczyk 1, Bogna Ziarkiewicz-Wróblewska 2, Tadeusz Wróblewski 1, Joanna Podgórska 3, Jakub Grzybowski 2, Beata Gierej 2, Piotr Krawczyk 1, Paweł Nyckowski 4, Oskar Kornasiewicz 1, Waldemar Patkowski 1, Piotr Remiszewski 1, Krzysztof Zaj ˛ac 1 and Michał Gr ˛at 1,*

1 Department of General, Transplant and Liver Surgery, Medical University Warsaw, 02-097 Warsaw, Poland; [email protected] (M.K.); [email protected] (T.W.); [email protected] (P.K.); [email protected] (O.K.); [email protected] (W.P.); [email protected] (P.R.); [email protected] (K.Z.) 2 Department of Pathology, Medical University of Warsaw, 02-097 Warsaw, Poland; [email protected] (B.Z.-W.); [email protected] (J.G.); [email protected] (B.G.) 3 2nd Department of Clinical Radiology, Medical University of Warsaw, 02-097 Warsaw, Poland; [email protected] 4 Department of General, Gastroenterological and Oncological Surgery, Medical University Warsaw, 02-097 Warsaw, Poland; [email protected] * Correspondence: [email protected]; Tel.: +48-22-599-2545

Abstract: PEComa (perivascular epithelioid cell tumor) is a rare liver tumor. Decisions regarding patient management are currently based on a few small case series. The aim of this study was to report the clinicopathological features of PEComa in order to provide guidance for management, complemented by our own experience. This retrospective observational study included all patients with PEComa who underwent surgical treatment in two departments between 2002 and 2020. A total Citation: Krawczyk, M.; of 20 patients were diagnosed with PEComa following histopathological examination. The age of the Ziarkiewicz-Wróblewska, B.; patients ranged from 21 to 73 years. The majority of patients were women (85%). In most patients, Wróblewski, T.; Podgórska, J.; the tumors were incidental. In diagnostic studies, PEComas with high arterial vascularization Grzybowski, J.; Gierej, B.; Krawczyk, P.; Nyckowski, P.; Kornasiewicz, O.; have been described. Liver resection was the treatment of choice. There was only one postoperative Patkowski, W.; et al. PEComa—A complication. During histopathological evaluation, tumors were composed mostly of epithelioid cells, Rare Liver Tumor. J. Clin. Med. 2021, rarely with spindle cell components, thick-walled vessels, and adipocytes in different proportions. 10, 1756. https://doi.org/10.3390/ Melanocytic markers (HMB45, MelanA) and at least one smooth muscle marker were expressed in jcm10081756 all tumors. Features suggestive of malignancy were found in three cases. In conclusion, PEComa is a rare liver tumor that is usually diagnosed incidentally. In radiological studies, tumors with high Academic Editor: Kenya Kamimura arterial vascularization are observed. Liver resection is the treatment of choice.

Received: 16 March 2021 Keywords: PEComa; rare liver tumor; management; liver resection; perivascular epithelioid cell Accepted: 14 April 2021 tumor; surgery; histopathology; mesenchymal tumor; angiomyolipoma Published: 18 April 2021

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in 1. Introduction published maps and institutional affil- iations. In 1992, Bonetti et al. described a mesenchymal liver tumor derived from perivascular cells for the first time [1]. The name PEComa (perivascular epithelioid cell tumor) was introduced four years later by Zamboni [2]. PEComas are mesenchymal tumors composed of characteristic perivascular cells that show focal association with blood vessel walls and usually express melanocytic and smooth muscle markers [3]. Until recently, PEComa Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. tumors included angiomyolipoma (AML) (PEComa subtype that also contains adipose This article is an open access article tissue and thick-walled blood vessels), clear cell/sugar tumor of the lung, lymphangi- distributed under the terms and oleiomyomatosis, and other histologically and immunohistochemically similar tumors conditions of the Creative Commons (e.g., clear cell myomelanocytic tumor) that develop in different locations in the soft tissues Attribution (CC BY) license (https:// and visceral sites [3]. According to the newest edition (the 5th edition) of the WHO 2020 creativecommons.org/licenses/by/ classification, the terms clear cell myomelanocytic tumor and sugar tumor of the lung are 4.0/). not recommended, and epithelioid AML is a synonym for PEComa [4].

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PEComa most often occurs in the uterus. It also develops in a wide variety of organs, such as the kidneys, bladder, prostate, lungs, pancreas, and liver [5]. Compared to other liver tumors, these lesions are rare and difficult to recognize. Clinical presentation is non-specific; therefore, these tumors are most often detected accidentally [6–8]. Laboratory tests in patients with PEComa did not show any specific abnormalities [9]. Symptoms such as abdominal pain, increased tension of the abdominal wall, constipation, or signs of ileus usually occur in cases involving very large PEComa lesions [10]. PEComa is more common in young women, with a 6:1 female to male ratio [6,11]. Usually, these are single lesions; however, multifocality was also reported more frequently in cases involving malignant lesions [12]. Differential diagnoses include other liver tumors, such as hepatocellular carcinoma (HCC), hemangiomas, focal nodular hyperplasia, and liver adenomas [8,13]. In liver ultrasound examination, computed tomography (CT), and magnetic resonance imaging (MRI), the tumors are often misdiagnosed as HCC. Diagnosis of PEComa should be considered when the tumor looks similar to HCC, the alpha-fetoprotein (AFP) concentration is within normal limits, and there is no history of viral hepatitis or cirrhosis [6,14]. Until now, PEComa tumors reported in the literature were mostly benign; however, malignant tumors have also been reported in a small number of patients. In cases involving malignant lesions, recurrences or metastases were observed in patients with tumors exceeding 5–7 cm in size, with marked nuclear atypia, pleomorphism, high mitotic index, presence of necrosis, and infiltrative margins [4,5]. Malignant PEComa originating from the liver can affect many abdominal organs simultaneously, including the omentum, resulting in massive bleeding into the peritoneal cavity [15]. PEComas are tumors with profuse arterial vascularization both inside the tumor and on the periphery, which is why imaging studies using intravenous contrast are more accurate for the evaluation of this type of lesion. It is emphasized that in ultrasound studies, the echogenicity of the tumor can be mixed; however, these tumors are most often hyperechogenic [6,15,16]. In power Doppler imaging, strong vascularization of the lesion can be observed, while in ultrasonography involving intravenous contrast administration, the lesion is strongly and heterogeneously enhanced, followed by rapid contrast drainage into the venous vessels. Similarly, both in CT and MRI, the main features of these tumors are the strong enhancement in the arterial phase and contrast wash-out in the veno-portal and delayed phases, as a consequence of rich vascularization from the branches of the hepatic artery (Figures1–4). The presence of adipose tissue, which is easier to detect on MRI, is typical only for some PEComas, such as AMLs [12]. In addition, the tumor does not show MR-specific features; it is usually hyperintense in T2-weighted images and hypointense in T1-weighted images and may show restriction of water diffusion [6,10,15]. Because the entire radiological image, including possible fat content, is similar to that of HCC or hepatic adenoma, clinical and laboratory information is crucial for differential diagnosis. In the literature, PEComas which did not show contrast “wash-out” have also been noted, which overlap with features of benign, well vascularized tumors such as focal nodular hyperplasias (FNH) and hemangiomas [6]. These, however, should not be mistaken, as FNHs show very homogenous enhancement and in turn, hemangiomas have a typical blood pooling appearance, which both differ significantly from heterogenous enhancement of PEComas. Some overlapping may also be noted with another rare entity: hepatic epithelioid hemangioendothelioma (HEHE), however these, unlike PEComas, are frequently multiple and subcapsular, with capsular retraction and vessels terminating at the edge of the lesions (the lollypop sign). The final diagnosis is mostly made after histological and immunohistochemical analysis of the resected tumor using the following markers: human melanoma Black-45 (HMB- 45), melan-A, MITF, smooth muscle antigen, desmin, and caldesmon [4,17]. Preoperative diagnosis, even in core needle biopsy, is difficult [16]. J. Clin. Med. 2021, 10, x FOR PEER REVIEW 3 of 11

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Figure 1. Computed tomography shows tumor with perivascular epithelioid cell tumor with strong contrast enhancement in the arterial phase.

FigureFigure 1. 1. ComputedComputed tomography tomography shows shows tumor tumor with with perivascular perivascular epithelioid epithelioid cell cell tumor tumor with with strong Figure 1. Computed tomography shows tumor with perivascular epithelioid cell tumor with contraststrong contrast enhancement enhancement in the arterial in the arterial phase. phase. strong contrast enhancement in the arterial phase.

Figure 2. Computed tomography of the patient from Figure 1—“washing out” the contrast—the FigurelesionFigureFigure appears 2. 2. ComputedComputed2. Computed in the tomographydelayedtomography tomography phase of less the attenuatedpatient patient of the from from comparedpatient Figure Figure 1—“washing1 —“washingfromto the liverFigure parenchyma.out” out” 1—“washing the the contrast—the contrast—the out” the contrast—the lesion appears in the delayed phase less attenuated compared to the liver parenchyma. lesionlesion appears appears in the in delayed the delayed phase less phase attenuated less compared attenuated to the compared liver parenchyma. to the liver parenchyma.

Figure 3. Magnetic resonance, T2 fat saturated images—hyperintensive and heterogeneous lesion. Figure 3. Magnetic resonance, T2 fat saturated images—hyperintensive and heterogeneous lesion.

FigureFigure 3. Magnetic 3. Magnetic resonance, resonance, T2 fat saturated T2 fat images—hyperintensive saturated images—hyperintensive and heterogeneous lesion. and heterogeneous lesion.

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FigureFigure 4. Magnetic4. Magnetic resonance, resonance, arterial phase arterial images phase after contrast images administration—strong after contrast administration—strong heteroge- hetero‐ neousgeneous contrast contrast enhancement. enhancement.

The basic treatment for patients with PEComa is surgery (excision of the lesion), which in the caseThe of final benign diagnosis tumors (and is PEComa,mostly made which occursafter histological in the majority and of the immunohistochemical patients) anal‐ isysis sufficient. of the In resected malignant tumor lesions, using apart fromthe following surgical treatment, markers: there human is no established melanoma Black‐45 (HMB‐ post-operative45), melan‐ therapy,A, MITF, chemotherapy, smooth muscle or radiotherapy antigen, [12 ,17desmin,]. and caldesmon [4,17]. Preoperative 2.diagnosis, Materials and even Methods in core needle biopsy, is difficult [16]. ThisThe was basic a retrospective treatment observational for patients study performedwith PEComa in two surgical is surgery departments (excision of the lesion), atwhich the Medical in the University case of of benign Warsaw: tumors the Department (and ofPEComa, General, Transplant, which occurs and Liver in the majority of the Surgery and the Department of General, Gastroenterological, and Oncological Surgery. Consecutivepatients) is patients sufficient. with histologically In malignant confirmed lesions, PEComa apart who from underwent surgical surgical treatment, there is no es‐ treatmenttablished between post‐operative 2002 and 2020 therapy, were included. chemotherapy, As this was or a retrospective radiotherapy analysis, [12,17]. neither informed patient consent nor ethical committee approval was required according to2. the Materials national legislation. and Methods Patient baseline characteristics, results of imaging studies, and data on operative managementThis was and postoperativea retrospective courses observational were obtained study from patient performed medical documen-in two surgical departments tationat the and Medical internal electronicUniversity databases. of Warsaw: Survival the data Department were obtained of from General, a national Transplant, and Liver database. Postoperative complications were defined as primary outcome measures. Patient survivalSurgery was and the secondarythe Department outcome measure. of General, It was defined Gastroenterological, as the time between and opera- Oncological Surgery. tiveConsecutive management patients and patient with death. histologically Observations confirmed were censored PEComa at the time who of the underwent last surgical treat‐ follow-upment between visit. 2002 and 2020 were included. As this was a retrospective analysis, neither Histopathological specimens were re-evaluated for the purposes of this study. Data oninformed immunohistochemical patient consent analysis nor results ethical were committee captured. approval was required according to the na‐ tionalSurvival legislation. outcomes were assessed using the Kaplan–Meier estimator. Patient baseline characteristics, results of imaging studies, and data on operative man‐ 3. Results agementA total ofand 20 patientspostoperative were diagnosed courses with were PEComa obtained following from histopathological patient medical exam- documentation and inationinternal in the electronic Department databases. of General, Transplant,Survival anddata Liver were Surgery obtained and the from Department a national of database. Postop‐ General,erative Gastroenterological, complications were and Oncological defined as Surgery primary at the outcome Independent measures. Public Central Patient survival was the Clinicalsecondary Hospital outcome of the Medical measure. University It was of Warsaw defined between as the 2002 time and 2020. between The age operative of management the patients ranged from 21 to 73 years. The vast majority were women (n = 17, 85%). In mostand patients, patient the death. tumor Observations was detected accidentally were censored during ultrasound at the time tests of performed the last for follow‐up visit. other reasons.Histopathological One patient with specimens an 8 cm diameter were lesion re‐evaluated complained of for distressing the purposes pain in of this study. Data theon right immunohistochemical costal arch. analysis results were captured. None of the patients had a history of parenchymal liver disease. Laboratory test resultsSurvival were normal. outcomes Serum AFP, were carcinoembryonic assessed using antigen, the and Kaplan–Meier Ca 19-9 concentrations estimator. were also within the normal limits. Liver resection was the treatment of choice. The scope of3. resection Results included anatomical and non-anatomical excisions, and the extent depended on the size and location of the lesions in the liver (Figure5). A total of 20 patients were diagnosed with PEComa following histopathological ex‐ amination in the Department of General, Transplant, and Liver Surgery and the Depart‐ ment of General, Gastroenterological, and Oncological Surgery at the Independent Public Central Clinical Hospital of the Medical University of Warsaw between 2002 and 2020. The age of the patients ranged from 21 to 73 years. The vast majority were women (n = 17, 85%). In most patients, the tumor was detected accidentally during ultrasound tests per‐ formed for other reasons. One patient with an 8 cm diameter lesion complained of dis‐ tressing pain in the right costal arch. None of the patients had a history of parenchymal liver disease. Laboratory test re‐ sults were normal. Serum AFP, carcinoembryonic antigen, and Ca 19‐9 concentrations were also within the normal limits. Liver resection was the treatment of choice. The scope

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J. Clin. Med. 2021, 10, 1756 5 of 11 of resection included anatomical and non‐anatomical excisions, and the extent depended of resection included anatomical and non‐anatomical excisions, and the extent depended on the size and location of the lesions in the liver (Figure 5). onof resectionthe size and included location anatomical of the lesions and nonin the‐anatomical liver (Figure excisions, 5). and the extent depended on the size and location of the lesions in the liver (Figure 5).

Figure 5. Segments 6 and 7 together with PEComa. FigureFigure 5. 5.Segments Segments 6 6 and and 7 7 together together with with PEComa. PEComa. Figure 5. Segments 6 and 7 together with PEComa. InIn one one patient patient with with an an extensive extensive size size change change of of 8 cm 8 cm (Figure (Figure6), partial 6), partial hepatic hepatic ischemia ische‐ In one patient with an extensive size change of 8 cm (Figure 6), partial hepatic ische‐ wasmia performedwas performed with with resection resection of segments of segments 4b, 5, 4b, and 5, 6 and (Figures 6 (Figures7 and 87). and 8). mia wasIn one performed patient with with an resection extensive of segmentssize change 4b, of 5, 8 and cm (Figure6 (Figures 6), 7partial and 8). hepatic ische‐ mia was performed with resection of segments 4b, 5, and 6 (Figures 7 and 8).

Figure 6. CT of a patient with PEComa. The arterial phase is associated with a strong, heterogene‐ FigureFigure 6. 6.CT CT of of a a patient patient with with PEComa. PEComa. The The arterial arterial phase phase is is associated associated with with a strong,a strong, heterogeneous heterogene‐ ousFigure enhancement 6. CT of a patient of contrast with changes. PEComa. The arterial phase is associated with a strong, heterogene‐ enhancementous enhancement of contrast of contrast changes. changes. ous enhancement of contrast changes.

Figure 7. Intraoperative image of PEComa. Tumor segments 5, 6, and 4b reached the round liga‐ Figure 7. Intraoperative image of PEComa. Tumor segments 5, 6, and 4b reached the round liga‐ ment (the same patient as in Figure 6). FigurementFigure (the 7. 7.Intraoperative Intraoperativesame patient imageas image in Figure of of PEComa. PEComa. 6). Tumor Tumor segments segments 5, 5, 6, 6, and and 4b 4b reached reached the the round round ligament liga‐ ment (the same patient as in Figure 6). (the same patient as in Figure6).

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Figure 8. Specimen after resection—the same patient from Figures 6 and 7. FigureFigure 8. 8.Specimen Specimen after after resection—the resection—the same same patient patient from from Figures Figures6 6and and7. 7. Postoperative complications occurred in one patient who had an external biliary fis‐ PostoperativePostoperative complicationscomplications occurred in in one one patient patient who who had had an an external external biliary biliary fis‐ tula. The patient was treated conservatively. ﬁstula.tula. The The patient patient was was treated treated conservatively. conservatively. InIn microscopic Inmicroscopic microscopic studies,studies, studies, 1313 tumors tumors 13 tumors (65%) (65%) had(65%) had features features had features consistent consistent consistent with with typical typical with AML AML typical AML (Figure(Figure(Figure9 ).9). 9). TheyThey They were were composed composed of of mature mature of mature adipose adipose adipose tissue, tissue, tissue,thick thick-walled‐walled thick ‐bloodwalled blood vessels, blood vessels, and vessels, and andepithelioidepithelioid epithelioid cells cells cells with with with abundant abundant abundant clear clear or eosinophilic or eosinophiliceosinophilic cytoplasm cytoplasm cytoplasm forming forming forming nests and nests nests trabec and and‐ trabec‐ trabeculae.ulae.ulae. The The proportions The proportions proportions of components of of components components varied varied significantly. signiﬁcantly.significantly. In two In cases,In two two cases, the cases, adipose the the adipose tissue adipose tissue tissuewaswas very was very scarce. very scarce. scarce. The The remaining The remaining remaining seven seven seventumors tumors tumors did not diddid contain not not contain contain adipose adipose adiposetissue. tissue. The tissue. size The ofThe size of sizethethe tumors of tumors the tumors was was similar was similar similarin both in both groups in both groups (AML/PEComa groups (AML/PEComa (AML/PEComa lacking lacking adipocytes). lacking adipocytes). adipocytes). No differences No No differences differenceswerewere found found were in mitoticin found mitotic activity, in activity, mitotic cytological activity, cytological atypia, cytological atypia, and necrosis atypia, and necrosis and between necrosis between the two between groups. the two the groups. two groups.

(a) (b)

Figure 9. Two( aimages) (a,b) of angiomyolipoma. Hematoxylin & eosin. Objective( bmagnification) 20×.

Figure 9. Two images (a,b) of angiomyolipoma. Hematoxylin & eosin. Objective magniﬁcation 20×. Figure 9. Two imagesExtramedullary (a,b) of angiomyolipoma. hematopoiesis Hematoxylin was observed & eosin. in 7/20 Objective tumors. magnification The spindle 20×.cell com‐ ponent was found in four cases; however, it was never dominant and was not related to the otherExtramedullary morphological featureshematopoiesis of the tumors. was observed in 7/20 tumors. The spindle cell com‐ ponent was found in four cases; however, it was never dominant and was not related to the other morphological features of the tumors.

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ExtramedullaryImmunohistochemical hematopoiesis features was observed were typical. in 7/20 tumors.Melanocytic The spindle markers cell compo-(HMB45, MelanA) nentand wasat least found one in foursmooth cases; muscle however, marker it was neverwere dominantexpressed and (Figure was not 10). related to the other morphologicalImmunohistochemical features of the features tumors. were typical. Melanocytic markers (HMB45, MelanA) andImmunohistochemical at least one smooth features muscle were marker typical. were Melanocytic expressed markers (Figure (HMB45, 10). MelanA) and at least one smooth muscle marker were expressed (Figure 10).

(a) (b) (a) (b) Figure 10. Two examples (a,b) of positive immunohistochemical stain with smooth muscle antigen and Melan A. Objective Figure 10. Two examples (a,b) of positive immunohistochemical stain with smooth muscle antigen and Melan A. Objective magnificationFigure 10. Two 10×. examples (a,b) of positive immunohistochemical stain with smooth muscle antigen and Melan A. Objective magnification 10×. magnification 10×. InIn three three cases, cases, at least at threeleast of three the following of the following features potentially features suggesting potentially malignancy suggesting malig‐ werenancy found: Inwere three size found: cases,≥ 5 cm, size at high-grade least ≥ 5 cm,three high atypia, of the‐grade mitoses following atypia, > 1/50 features mitoses high-power potentially > 1/50 fields, high necrosis,suggesting‐power fields, malig ne‐ ‐ infiltrativecrosis,nancy infiltrative were growth, found: and growth, lymphovascularsize ≥ 5and cm, lymphovascular high invasion‐grade (Figure atypia, invasion 11 mitoses)[18]. (Figure > 1/50 11)high [18].‐power fields, ne‐ crosis, infiltrative growth, and lymphovascular invasion (Figure 11) [18].

FigureFigureFigure 11. 11. 11.PEComa—inﬁltrative PEComa—infiltrative PEComa—infiltrative growth growth of the tumor.of thethe Objectivetumor.tumor. Objective Objective magniﬁcation magnification magnification 10×. 10×. 10×.

Two patients died during the follow-up period, with one-, three-, ﬁve-, and ten-year TwoTwo patients patients died died duringduring the follow‐‐upup period,period, with with one one‐,‐ three, three‐, ‐five, five‐, ‐and, and ten ten‐year‐year survival estimates of 100%, 90.9%, 80.8%, and 80.8%, respectively. The survival curve is survival estimates of 100%, 90.9%, 80.8%, and 80.8%, respectively. The survival curve is shownsurvival in Figure estimates 12. of 100%, 90.9%, 80.8%, and 80.8%, respectively. The survival curve is shownshown in in Figure Figure 12. 12.

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Figure 12. Overall survival of patients with PEComa undergoing surgical treatment. Figure 12. Overall survival of patients with PEComa undergoing surgical treatment. 4. Discussion 4. DiscussionIn the literature, PEComa tumors of the liver have been reported for 28 years. Most reportsIn the are literature, based on individual PEComa tumors cases [2 of,7 ,the8,11 liver,15,17 have,19]. Onlybeen reported two publications for 28 years. presented Most reportsa larger are series: based seven on individual cases in thecases first [2,7,8,11,15,17,19]. publication [5] andOnly 13 two cases publications in the second presented pub- alication larger series: [14]. Our seven study cases included in the first 20 publication patients who [5] and underwent 13 cases in surgery the second in two publication surgical [14].departments Our study of included the Medical 20 patients University who of underwent Warsaw, making surgery it in one two of surgical the studies departments with the oflargest the Medical sample University size from one of Warsaw, institution. making it one of the studies with the largest sample size fromSome one of theinstitution. issues that were reported in the published studies were confirmed in our study.Some of Patients the issues admitted that were to both reported departments in the published had no established studies were diagnosis. confirmed In in most our study.cases, thePatients lesions admitted resembled to both HCC departments on CT and MRI had [no8,13 established]. All patients diagnosis. treated In in most our center cases, thedeveloped lesions resembled hepatic lesions HCC even on CT though and MRI they [8,13]. had healthy All patients livers, treated did not in haveour center a history devel of‐ opedhepatitis, hepatic and lesions did not even have though any factors they thathad damagehealthy thelivers, parenchyma. did not have These a history characteristics of hepa‐ weretitis, and also did observed not have by any other factors authors that [6 damage,14]. Similar the parenchyma. to other published These studies,characteristics the patients were alsoin our observed study were by other mostly authors female [6,14]. patients, Similar constituting to other 85% published of the group.studies, the patients in our studyCT of were the arterial mostly phasefemale showed patients, intensive constituting saturation 85% of of the the group. vessels in the periphery of theCT tumor, of the with arterial a marked phase decreaseshowed intensive in the amount saturation of contrast of the in vessels the portal in the and periphery delayed ofphases. the tumor, In MR with studies a marked in the decrease T1 phase, in the a significant amount of intensity contrast wasin the visible, portal while and delayed the T2 phases.intensity In decreased. MR studies Similar in the observations T1 phase, a have significant been reported intensity in was the literaturevisible, while [6,10 ,the15]. T2 intensityPatients decreased. were qualified Similar forobservations surgical treatment have been based reported on the in results the literature of their radiological[6,10,15]. examination,Patients were which, qualified although for did surgical not provide treatment a clear based diagnosis, on the results indicated of their the radiologi need for‐ calsurgical examination, treatment. which, The extentalthough of liver did not resection provide was a clear dependent diagnosis, on the indicated location the and need size for of surgicalthe tumor. treatment. In our opinion, The extent there of is liver no need resection for extensive was dependent liver resection on the or location hemihepatectomy. and size of theMost tumor. patients In our underwent opinion, non-anatomical there is no need resection. for extensive However, liver we resection have always or hemihepatec strived for‐ tomy.oncological Most completeness.patients underwent The oncological non‐anatomical margin resection. in the patient However, with thewe largesthave always tumor (8strived cm) was for oncological only 1 mm. completeness. This resection, The with oncological such a small margin margin, in the was patient performed with the due larg to‐ estthe tumor size of (8 the cm) tumor, was only and 1 the mm. non-expanded This resection, segments with such of a the small tumor margin, that didwas not performed contain duecancerous to the cells,size of which the tumor, remained and after the thenon resection‐expanded should segments be sufficiently of the tumor large that in relationdid not to patient’s body weight. contain cancerous cells, which remained after the resection should be sufficiently large in None of the patients in the reported series underwent preoperative biopsy. The relation to patient’s body weight. decision on surgery was based on the results of the imaging studies. We assumed that the None of the patients in the reported series underwent preoperative biopsy. The de‐ patients had indications for resection and a biopsy would not change our decision. In other cision on surgery was based on the results of the imaging studies. We assumed that the series, a biopsy was however performed. For example, out of seven treated patients, the patients had indications for resection and a biopsy would not change our decision. In authors [9] performed a fine-needle biopsy in two, finding cells suggestive of PEComa, other series, a biopsy was however performed. For example, out of seven treated patients,

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but the result did not change their decision and they performed a liver resection. While non-anatomical resection is sufficient for patients with PEComa, anatomical resection may be superior over non-anatomical resection in the case of HCC diagnosis [20–23]. Nevertheless, patients with PEComa typically have no underlying liver disease, which makes this population more similar to patients with HCC occurring in a healthy liver. In the latter, achieving an R0 resection status seems to be of the most importance [24]. Histopathological diagnosis of PEComa is based on morphological and immunohistochemical features that allow differentiation of the tumor from other focal lesions in the liver, including HCC. Pecoma, as a neoplasm with myomelanocytic differentiation, typically expresses both melanocytic (HMB-45, MelanA, Mitf) and myogenic markers (actin, myosin, calponin) with variable intensity and distribution of staining [4]. TFE3 is a new marker that is strongly expressed in 15% of PEComas, indicating the presence of TFE gene rearrangement. Pecomas containing TFE3 gene rearrangements stain strong with HMB45 and TFE 3, but the expression of MelanA and smooth muscle markers tend to be focal or negative [18]. Patients with this abnormality are younger. Microscopically, the tumors have an alveolar pattern, consist of epithelioid cells, and often do not express smooth muscle markers [4]. Molecular genetic data on PEComas are limited, but nowadays, two distinct molecular groups have been described: PEComas with TSC2 mutations and tumors with TFE3 fusions (TFE3-translocation associated PEComas). Furthermore, TP53 mutations have been identified in 63% of the TSC2 mutated Pecomas. The patients of the first group (if diagnosed with malignant tumors) may benefit from targeted therapy with mTOR inhibitors [4,25]. RAD51B fusions and HTR4-ST3GAL1 fusion are other rearrangements found in PEComas [18,26]. One study described a lesion that was different from primary lesions in the liver. The aforementioned study involved a young man who underwent surgery for a rectal tumor, which turned out to be a PEComa following histopathological analysis. The patient was treated surgically, and anterior low rectal resection was performed. Four years later, a small metastatic lesion was diagnosed in the liver. The patient agreed to the surgery four years later, after the number of lesions had increased to three and the size had increased. Non-anatomic liver resection with confirmed PEComa metastasis was performed, followed by a satisfactory postoperative course [19]. Surgical treatment of patients with primary liver PEComa is the treatment of choice and is effective. The number of postoperative complications was relatively small. Nev- ertheless, these patients require constant oncological supervision similar to patients with cancerous tumors in the liver. In the case of disseminated malignant PEComas, chemotherapy becomes the treatment of choice, considering the potential effectiveness of mTOR inhibitors [27,28]. There are very few reports on non-surgical treatment of patients with liver PEComas. In rare situations, transarterial chemoembolization and ablation have been applied [9,29]. Those non-surgical methods should be considered in case of contraindications for surgery.

5. Conclusions PEComa is a rare liver tumor that is usually diagnosed incidentally. In radiological studies, as a tumor with high arterial vascularization, it is necessary to differentiate it primarily from HCC. The treatment of choice is surgery, that is liver resection. The ﬁnal diagnosis is conﬁrmed only after histopathological examination of the resected specimen and requires a number of immunohistochemical tests.

Author Contributions: Conceptualization, M.K., B.Z.-W., T.W., P.N., W.P.; methodology, M.K., B.Z.-W., J.P., J.G., B.G., M.G.; formal analysis, M.K., B.Z.-W., J.P., J.G., B.G.; investigation, M.K., B.Z.-W., T.W., J.P., J.G., B.G., P.K., P.N., O.K., W.P., P.R., M.G.; data curation, M.K., T.W., P.K., P.N., O.K., W.P., P.R., K.Z., M.G.; writing—original draft preparation, M.K.; writing—review and editing, B.Z.-W., T.W., J.P., J.G., B.G., P.K., P.N., O.K., W.P., P.R., M.K., K.Z., M.G.; visualization, B.Z.-W., J.P., J.G., B.G.; supervision, M.K. All authors have read and agreed to the published version of the manuscript. J. Clin. Med. 2021, 10, 1756 10 of 11

Funding: Michał Gr ˛atreceived a stipend for outstanding young scientists from the Ministry of Science and Higher Education of the Republic of Poland (571/STYP/14/2019). Institutional Review Board Statement: According to national legislation, the study was neither subject to institutional board approval nor the necessity to obtain informed consent due to its retrospective nature. Informed Consent Statement: According to national legislation, the study was neither subject to institutional board approval nor the necessity to obtain informed consent due to its retrospective nature. Data Availability Statement: The data is available from the Authors upon reasonable request. Conﬂicts of Interest: The authors declare no conﬂict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript or in the decision to publish the results.

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