Malignant perivascular epithelioid cell tumor of the colorectum:Clinicopathological characterization,diagnosis and treatment process of 7 cases

BACKGROUND Perivascular epithelioid cell tumor(PEComa)of the colorectum is exceedingly rare,with only a few published reports.It presents with a wide spectrum of biological behavior,ranging from benign to malignant.The prognosis for malignant PEComa is poor and there is little consensus on its treatment.AIM To fully characterize PEComa and standardize its diagnosis and treatment.METHODS Patients with colorectal malignant PEComa were identified from the First Affiliated Hospital,Zhejiang University School of Medicine and People's Hospital of Anji.Cases with controversial pathology and cases lost to follow-up were excluded,leaving seven remaining cases that formed the basis of the study.We collected relevant clinicopathological,therapeutic and followup details.Disease stage and progression were assessed by contrast-enhanced computed tomography at baseline and at 3-month intervals.RESULTS The mean age was 43 years,with a range of 5 years to 73 years.The average body mass index was 21.8±3.0 kg/m2,and 71.4%of cases occurred in the colon.The main symptoms of colorectal PEComas were abdominal mass and hematochezia.The most common microscopic finding of malignant behavior was infiltrative growth.Immunohistochemical analysis found that 6/7 cases were positive for HMB45,5/7 were positive for melan-A,and 3/5 were positive for MiTF.The watch-and-wait approach to treatment was a risky option.Radical resection was preferable to systemic treatment.The median progression-free survival exceeded 38 months,longer than previously reported.CONCLUSION Radical or extended resection is the key to prolonged survival of malignant PEComa.More meaningful studies are urgently needed to establish the standardized diagnosis and treatment.

Hepatic perivascular epithelioid cell tumors:The importance of preoperative diagnosis

Accurate preoperative diagnosis is highly important for the treatment of perivascular epithelioid cell tumors(PEComas)because PEComas are mainly benign tumors and may not require surgical intervention.By analyzing the causes,properties and clinical manifestations of PEComas,we summarize the challenges and solutions in the diagnosis of PEComas.

Massive simultaneous hepatic and renal perivascular epithelioid cell tumor benefitted from surgery and everolimus treatment:A case report

BACKGROUND Perivascular epithelioid cell tumor(PEComa)is a rare mesenchymal neoplasm that predominantly affects the kidney and uterus.The occurrence of this tumor in the liver,particularly with simultaneous involvement of the liver and kidney,is exceedingly uncommon.Pathological diagnosis is the gold standard.PEComas usually show positive immunohistochemical staining for melanocytic(HMB-45,Melan-A)and myoid(SMA,muscle-specific actin)markers.CASE SUMMARY We presented a noteworthy case of malignant PEComa affecting both the liver and kidney in a 53-year-old man with tuberous sclerosis complex(TSC).FAT2 and TP73 mutations in the kidney were identified and positive expression of diagnostic markers including HMB-45,Melan A,and TFE3 were detected.In addition,we demonstrated that hepatic artery perfusion chemotherapy was ineffective for hepatic PEComa,while surgery remained the most effective approach.Everolimus showed an excellent efficacy in the postoperative treatment of the tumor.CONCLUSION Surgical treatment is preferred for malignant PEComa affecting liver and kidney,especially with TSC;everolimus is effective postoperatively.

Hsp70 confines tumor progression of rat histiocytoma and impedes the cytotoxicity induced by natural killer cells and peritoneal macrophages

Objective:To study the role of inducible form of heat shock protein 70(Hsp70) in the host tumor regression of rat tumor model.Methods:We examined the role of Hsp70 in host tumorigenicity and in vitro cellular cytotoxicity using a rat histocytoma.The differential tumor growth and regression kinetics were studied and correlated with the expression of Hsp70,activation of macrophages and natural killer(NK) cells,and circulating or tumor infiltrating immune molecules in the host system.Results:The sub cuteaneous(s.c.) tumor regression was correlated with increased serum cytokines such as IL-12,TNF P,IFNγand Hsp70.Despite of similar increase of Hsp70 in intraperitoneal(i.p.) tumor implanted animals,animals succumb to tumor growth,further,evidently,no immune molecule activation was observed.The viral promoter driven Hsp70 over expression in these tumor cells restrained solid tumor growth,however,failed to inhibit ascites growth.The NK cells from s.c.immunized animals induces cytotoxicity in the presence of anti-tumor antibody,which necessitated CD40-L expression,conversely,NK cells from i.p.immunized animals failed to induce cytotoxicity.The NK cells from s.c.or i.p.implanted animals with Hsp70 positive tumor cells failed to induce such cytotoxicity.The peritoneal macrophages isolated from s.c.tumor implanted animals when co-cultured with parental BC-8 cells lyses tumor cells,nevertheless entail macrophage specific TNFαexpression.On the contrary,Hsp70 expressing BC-8 tumor cells were resistant to peritoneal macrophage induced cytolysis.Conclusions:This study brings out that Hsp70 possibly involved in regulating the host tumor response and cellular cytotoxicity.

Hepatic perivascular epithelioid cell tumor in three patients

Perivascular epithelioid cell tumor （PEComa） is a rare, soft tissue tumor that can occur in various locations. The present report included three patients （one male and two females; age range, 25-51 years） with hepatic PEComas. The collected data included the clinical manifestations, diagnosis, management, treatment, and prognosis. Since it is difficult to diagnose hepatic PEComas by imaging, the patients were diagnosed by tumor tissue examination such as immunohistochemistry, which was positive for HMB-45, Melan-A, and SMA on all slides. The tumor was composed of diverse tissues including smooth muscle, adipose tissue, and thick-walled blood vessels. During the follow-up period, one of the tumors was malignant （double-positive for CD34 and Ki-67） and recurred 3 months after surgery. In addition, malignant hepatic PECo- mas were reviewed in the literature, indicating that the majority of hepatic PEComas are benign, but few hepatic PEComas exhibit malignant behaviors in older female patients （〉50 years of age） with abdominal discomfort and pain, larger tumor size （〉10 cm）, or positive staining for CD34 and Ki-67. In conclusion, there is no effective method to diagnose PEComas. Currently, the diagnosis of PEComas depends on immunohistochemical staining. Tumor resection and close follow-up are the principal methods for the management of PEComas.

A perivascular epithelioid cell tumor of the stomach:An unsuspected diagnosis

Perivascular epithelioid cell tumor(PEComa) is a rare mesenchymal neoplasia and currently well recognized as a distinct entity with characteristic morphological,immunohistochemical and molecular findings.We report a case of PEComa arising in the antrum of a 71-year-old female with melena.The tumor,located predominantly in the submucosa as a well delimited nodule,measured 3.0 cm in diameter and was completely resected,with no evidence of the disease elsewhere.Histologically,it was composed predominantly of eosinophilic epithelioid cells arranged in small nests commonly related to variably sized vessels,with abundant extracellular material,moderate nuclear variation and discrete mitotic activity.No necrosis,angiolymphatic invasion or perineural infil-tration was seen.Tumor cells were uniformly positive for vimentin,smooth muscle actin,desmin and melan A.Although unusual,PEComa should be considered in the differential diagnosis of gastric neoplasia with characteristic epithelioid and oncocytic features and prominent vasculature.

Hepatic perivascular epithelioid cell tumor:Clinicopathological analysis of 26 cases with emphasis on disease management and prognosis

BACKGROUND Perivascular epithelioid cell tumor(PEComa)is an uncommon tumor of mesenchymal origin.Cases of PEComa in the liver are extremely rare.AIM To analyze the clinicopathological features and treatment of hepatic PEComa and to evaluate the prognosis after different treatments.METHODS Clinical and pathological data of 26 patients with hepatic PEComa were collected.All cases were analyzed by immunohistochemistry and clinical follow-up.RESULTS This study included 17 females and 9 males,with a median age of 50 years.Lesions were located in the left hepatic lobe in 13 cases,in the right lobe in 11,and in the caudate lobe in 2.The median tumor diameter was 6.5 cm.Light microscopy revealed that the tumor cells were mainly composed of epithelioid cells.The cytoplasm contained heterogeneous eosinophilic granules.There were thick-walled blood vessels,around which tumor cells were radially arranged.Immunohistochemical analysis of pigment-derived and myogenic markers in PEComas revealed that 25 cases were HMB45(+),23 were Melan-A(+),and 22 SMA(+).TFE3 and Desmin were negative in all cases.All the fluorescence in situ hybridization samples were negative for TFE3 gene break-apart probe.Tumor tissues were collected by extended hepatic lobe resection or simple hepatic tumor resection as the main treatments.Median follow-up was 62.5 mo.None of the patients had metastasis or recurrence,and there were no deaths due to the disease.CONCLUSION Hepatic PEComa highly expresses melanin and smooth muscle markers,and generally exhibits an inert biological behavior.The prognosis after extended hepatic lobe resection and simple hepatic tumor resection is semblable.

Hepatic perivascular epithelioid cell tumor:A case report

BACKGROUND Perivascular epithelioid cell tumor(PEComa)is a mesenchymal tumor with histologic and immunophenotypic characteristics of perivascular epithelioid cells,has a low incidence,and can involve multiple organs.PEComa originating in the liver is extremely rare,with most cases being benign,and only a few cases are malignant.Good outcomes are achieved with radical surgical resection,but there is no effective treatment for some large tumors and specific locations that are contraindicated for surgery.CASE SUMMARY A 32-year-old woman was admitted to our hospital with a palpable abdominal mass and progressive deterioration since the previous month.An ultrasoundguided percutaneous liver aspiration biopsy was performed.Postoperative pathological immunohistochemical staining was HMB45,Melan-A,and smooth muscle actin positive.Perivascular epithelioid tumor was diagnosed.The tumor was large and could not be completely resected by surgery.Further digital subtraction angiography revealed a rich tumor blood supply,and interventional embolization followed by surgery was recommended.Finally,the patient underwent transarterial embolization(TAE)combined with sorafenib for four cycles.Angiography reexamination indicated no clear vascular staining of the tumor,and the tumor had shrunk.The patient was followed up for a short period of time,achieved a stable condition,and surgery was recommended.CONCLUSION Adjuvant combination treatment with TAE and sorafenib is safe and feasible as it shrinks the tumor preoperatively and facilitates surgery.

Perivascular epithelioid cell tumors of the liver misdiagnosed as hepatocellular carcinoma:Three case reports

BACKGROUND Hepatic perivascular epithelioid cell neoplasms(PEComas)are rare.Diagnostic and treatment experience with hepatic PEComa remains insufficient.CASE SUMMARY Three hepatic PEComa cases are reported in this paper:One case of primary malignant hepatic PEComa,one case of benign hepatic PEComa,and one case of hepatic PEComa with an ovarian mature cystic teratoma.During preoperative imaging and pathological assessment of intraoperative frozen samples,patients were diagnosed with hepatocellular carcinoma(HCC),while postoperative pathology and immunohistochemistry subsequently revealed hepatic PEComa.Patients with hepatic PEComa which is misdiagnosed as HCC often require a wider surgical resection.It is easy to mistake them for distant metastases of hepatic PEComa and misdiagnosed as HCC,especially when it’s combined with tumors in other organs.Three patients eventually underwent partial hepatectomy.After 1-4 years of follow-up,none of the patients experienced recurrence or metastases.CONCLUSION A clear preoperative diagnosis of hepatic PEComa can reduce the scope of resection and prevent unnecessary injuries during surgery.

Perivascular epithelioid cell tumor of male pelvic cavity:a case report and literature review

Perivascular epithelioid cell tumors （PEComas） are a family of rare mesenchymal neoplasms. The PEComas, composed of epithelioid and spindle cells, have the same cellular and immtmohistocherrtical features but are found in different visceral and soft tissue sites. Here, we report the histological and immunohistochemical features of one case of PEComa restricted in the pelvic visceral peritoneum of a male patient. The patient was treated with radical surgery, and was well and on follow-up visits without tumor recurrence.

Perivascular epithelioid cell tumour of the liver

Perivascular epithelioid cell tumour is not uncommon in the liver but seldom malignant.

TFE3-expressing malignant perivascular epithelioid cell tumor of the mesentery:A case report and review of literature

BACKGROUND Perivascular epithelioid cell tumor(PEComa)is a rare mesenchymal tumor that exhibits an epithelioid and spindle cell morphology.The tumor is characterized by immunoreactivity for melanocytic and myogenic markers but can be misdiagnosed as more common tumors with similar characteristics,including gastrointestinal stroma tumors or leiomyosarcomas.Recently,a subset of PEComas has been reported to harbor a transcription factor binding to TFE3 fusion.Herein,we report a rare case of TFE3-expressing malignant PEComa arising from the mesentery.CASE SUMMARY A 50-year-old woman presented with abdominal discomfort for 3 months.Results of laboratory tests were all within the normal ranges,and the patient had no notable medical history.Magnetic resonance imaging revealed a large tumor on the right side of the pelvic floor,which was originally suspected to be a primary ovarian tumor.However,during surgery,the tumor was revealed to have originated from the mesentery.Histologically,the tumor was composed of bundles of spindle cells and sheets of epithelioid cells.Extensive coagulative necrosis and numerous mitotic figures were observed.Immunohistochemistry revealed that the tumor cells were positive for smooth muscle actin,HMB-45,and TFE3 expression.Tumor involvement of the rectal serosa was identified,leading to a final diagnosis of malignant PEComa of the mesentery.Surgical resection was followed by adjuvant chemotherapy.No recurrence or metastasis was observed over a 6-month follow-up period.CONCLUSION Malignant PEComa of the mesentery is extremely rare and should be distinguished from morphological mimics through differential diagnosis and immunohistochemistry.

Pediatric case of colonic perivascular epithelioid cell tumor complicated with intussusception and anal incarceration:A case report

BACKGROUND Perivascular epithelioid cell tumor(PEComa)represents a group of rare mesenchymal tumors.PEComa can occur in many organs but is rare in the colorectum,especially in children.Furthermore,PEComa is a rare cause of intussusception,the telescoping of a segment of the gastrointestinal tract into an adjacent one.We describe a rare case of pediatric PEComa complicated with intussusception and anal incarceration,and conduct a review of the current literature.CASE SUMMARY A 12-year-old girl presented with abdominal pain and abdominal ultrasound suggested intussusception.Endoscopic direct-vision intussusception treatment and colonoscopy was performed.A spherical tumor was discovered in the transverse colon and removed by surgery.Postoperative pathologic analyses revealed that the tumor volume was 5.0 cm×4.5 cm×3.0 cm and the tumor tissue was located in the submucosa of the colon,arranged in an alveolar pattern.The cell morphology was regular,no neoplastic necrosis was observed,and nuclear fission was rare.The immunohistochemical staining results were as follows:Human melanoma black 45(HMB 45)(+),cluster of differentiation 31(CD31)(+),cytokeratin(-),melanoma-associated antigen recognized by T cells(-),smooth muscle actin(-),molleya(-),desmin(-),S-100(-),CD117(-),and Ki67(positive rate in hot spot<5%).Combined with the results of pathology and immunohistochemistry,we diagnosed the tumor as PEComa.Postoperative recovery was good at the 4 mo follow-up.CONCLUSION The diagnosis of PEComa mainly depends on pathology and immunohistochemistry.Radical resection is the preferred treatment method.

Retroperitoneal neoplasm with perivascular epithelioid cell differentiation: A case report and review of literature

The retroperitoneal neoplasm with perivascular epithelioid cell differentiation (PEComa) is an extremely rare pathological entity. In this article, we reported one case of a 45-year-old woman who was admitted to our hospital (The Second People's Hospital of Hefei, China) for retroperitoneal neoplasm with perivascular epithelioid cell differentiation. The B ultrasonic examination showed echopoor in the region of cavitas pelvis. The histologic characteristics and immunohistochemical phenotype both revealed the neoplasm with perivascular epithelioid cell differentiation.

CONDITIONED MEDIUM OF HUMAN NASOPHARYNGEAL CARCINOMA EPITHELIOID CELL LINE CNE_(1) CONTAINED THE ACTIVITIES OF TRANSFORMED GROWTH-INHIBITING FACTORS

The hormone defined serum free conditioned medium (SFCM) of human nasopharyngeal carcinoma epithelioid cell line (CNE1) was assayed by both the 3H-thymidine incorporation test and the soft agar test. It was found that the SFCM stimulated the growth of long-term serum-free cultured CNE4 cells in ac-cordence with the fact that the growth rate of long-term serum-free cultured CNE1 cells was directly proportional to the plating density. Alternatively 5% SFCM inhibited the growth of short-term serum-free cultured CNE4 cells by 51% in which the indicator cell remained the responsiveness state of growing in the serum-supplemented medium to the effector of interest. Furthermore, SFCM resulted in the inhibition of anchorage-independent growth of CNE4 cells and A431 cells. Also in soft agar test. SFCM reduced the colony formation of NRK(?),9F cells in the presence of EGF or EGF plus TGF-β. These finding suggested that CNE4 secreted autocrine growth stimulating factor(s) and growth inhibiting factor(s) in the serum-free medium, the latter strongly reverse malignant phenotypes of CNE4 and A431 cells in serum-supplemented surrounding.

AB045. Prognostic significance and characterization of small epithelioid cell population in uveal melanoma

Background:Uveal melanoma(UM)is a malignant neoplasia that is composed of two main types of cells:spindle and epithelioid.There is a subset of neoplastic small epithelioid cells located predominantly in the infiltrative tumor margins or surrounding blood vessels.The aim of this study is to characterize and evaluate the correlation between the presence of these small epithelioid cells and clinical outcome.Methods:The clinical-pathological features of 70 UM patients were evaluated.The presence of small epithelioid cells was quantified based on percentage of tumor volume,and they were characterized using melanocytic markers(HMB-45,Melan A and SOX-10),stem cell markers(CD133,CD24 and CD38),and T cell lymphocytes(CD3).Univariate and multivariate analyses were conducted.Clinical follow up was available for all patients.Results:The ratio of small epithelioid cell components of all 70 tumors ranged from 0%to 30%(median,1%).Thirty-nine tumors(55.7%)had areas with small epithelioid cells.Univariate analysis showed that mixed versus spindle cell,higher lymphocytic infiltration,macrophage infiltration,ciliary body involvement,and>5%of small epithelioid cell component had a significant negative impact on metastasis-free survival.Small epithelioid cell component>5%was present in 24 cases(34.3%).Of these,three were classified as spindle and 21 were mixed.Multivariate analysis revealed that a>5%small cell component was the most significant morphological adverse prognostic factor.Moreover,the small epithelioid cells were negative for HMB45,stem cell markers and CD3,and focally and weakly positive for MELAN A and SOX10.Conclusions:A high small epithelioid cell component is a strong negative prognostic indicator in patients with UM.

Improving recognition of hepatic perivascular epithelioid cell tumor:Case report and literature review

A 58-year-old man presented with the chief complaint of abdominal bloating and was incidentally found to have a liver tumor.As diagnostic imaging studies could not rule out malignancy,the patient underwent partial resection of segment 3 of the liver.The lesion pathologically showed eosinophilic proliferation,in addition to immunohistochemical positivity for human melanoma black 45 and Melan-A,thereby leading to the diagnosis of a hepatic perivascular epithelioid cell tumor(PEComa).A PEComa arising from the liver is relatively rare.Moreover,the name ‘PEComa' has not yet been widely recognized,and the same disease entity has been called epithelioid angiomyolipoma(EAML),further diminishing the recognition of PEComa.In addition,PEComa imaging findings mimic those of malignant liver tumors,and clinically,this tumor tends to enlarge.Therefore,a PEComa is difficult to diagnose.We conducted a systematic review of PEComa and EAML cases and discuss the results,including findings useful for differentiating perivascular epithelioid cell tumors from malignant liver tumors.

Retroperitoneal perivascular epithelioid cell tumours: A case report and review of literature

BACKGROUND The perivascular epithelioid cell tumour(PEComa)family of tumours mainly includes renal and hepatic angiomyolipomas,pulmonary lymphangioleiomyomatosis and clear cell“sugar”tumour of the lung.Several uncommon tumours with similar morphological and immunophenotypical characteristics arising at a variety of sites(abdominal cavity,digestive tract,retroperitoneum,skin,soft tissue and bones)are also included in the PEComa family and are referred to as PEComas not otherwise specified.CASE SUMMARY We present a 37-year-old female patient who underwent resection of an 8.5 cm×8 cm×4 cm retroperitoneal tumour,which eventually was diagnosed as PEComa of uncertain biological behaviour.Three years after the operation,the patient remains without any evidence of recurrence.A search was performed in the Medline and EMBASE databases for articles published between 1996 and 2018,and we identified 31 articles related to retroperitoneal and perinephric PEComas.We focused on sex,age,maximum dimension,histological and immunohistochemical characteristics of the tumour,follow-up and long-term outcome.Thirty-four retroperitoneal(including the present one)and ten perinephric PEComas were identified,carrying a malignant potential rate of 44%and 60%,respectively.Nearly half of the potentially malignant PEComas presented with or developed metastases during the course of the disease.CONCLUSION Retroperitoneal PEComas are not as indolent as they are supposed to be.Radical surgical resection constitutes the treatment of choice for localized disease,while mammalian target of the rapamycin(mTOR)inhibitors constitute the most promising therapy for disseminated disease.The role of mTOR inhibitors as adjuvant or neoadjuvant therapies needs to be evaluated in the future.

Coincidence between malignant perivascular epithelioid cell tumor arising in the gastric serosa and lung adenocarcinoma

A 4-mo history of both epigastralgia and back pain was presented in a 39-year-old male. Computed tomography showed right lung nodule and abdominal mass attached to the gastric wall, measuring approximately 30 mm and 70 mm in diameter. Since biopsy samples from the lung and abdomen revealed poorly differentiated adenocarcinoma and malignant tumor, clinicians first interpreted the abdominal mass as metastatic carcinoma, and a right lower lobectomy with following resection of the mass was performed. Gross examination of both lesions displayed gray-whitish to yellow-whitish cut surfaces with hemorrhagic and necrotic foci, and the mass attached to the serosa of the lesser curvature on the gastric body. On microscopic examination, the lung tumor was composed of a proliferation of highly atypical epithelial cells having abundant eosinophilic cytoplasm, predominantly arranged in an acinar or solid growth pattern with vessel permeation, while the abdominal tumor consisted of sheets or nests with markedly atypical epithelioid cells having pleomorphic nuclei and abundant eosinophilic to clear cytoplasm focally in a radial perivascular or infiltrative growth pattern. Immunohistochemically, the latter cells were positive for HMB45 or α-smooth muscle actin, but the former ones not. Therefore, we finally made a diagnosis of malignant perivascular epithelioid cell tumor(PEComa) arising in the gastric serosa, combined with primary lung adenocarcinoma. Furthermore, small papillary car-cinoma of the thyroid gland was identified. The current case describes the coincidence of malignant PEComa with other carcinomas, posing a challenge in distinction from metastatic tumor disease.

Pancreatic perivascular epithelioid cell tumor: A case report with clinicopathological features and a literature review

Perivascular epithelioid cell tumor(PEComa) of the pancreas is an unusual tumor deriving from mesenchyma. This paper described a case of pancreatic PEComa, which was initially suspected as neuroendocrine carcinoma by biopsy, and therefore surgical treatment was recommended due to undetermined diagnosis. Examination of the surgical specimen under a microscope showed that the tumor cell's morphology was epithelioid or spindle-shaped, and ranged in a nested pattern. Additionally, these cells had a large extent of acidophilic cytoplasm, no mitotic figures, and expressed HMB-45, melan-p, and smooth muscle actin immunohistochemically. Pathological examination indicated that PEComa originated from the pancreas, but symptoms related to tuberous sclerosis were absent. Since PEComa is extremely rare in the pancreas, it is likely to be ignored in differential diagnosis. In conclusion, our article highlighted the clinicopathological features of PEComa, and we conducted a literature review focusing on PEComa so as to deepen the understanding of this tumor type.