PEComa (Perivascular epithelioid cell tumor) | Non-cancerous soft tissue tumors that keeps coming back
Perivascular epithelioid cell tumor or PEComa appears to start in cells in the walls of blood vessels, but experts are not sure. Most PEComas are non-cancerous, but in rare cases, they are cancerous.
The term PEComa was first introduced in 1996 by Zamboni and Bonetti who suggested the name PEComa for neoplasms composed of a pure proliferation of perivascular epithelioid cells (PEC). PEComas manifest different biological behavior with approximately one-third presenting with locally aggressive behavior (malignant PEComa).
- Malignant PEComa is usually resistant to conventional chemotherapy.
- Disruption of the mTOR pathway is common and results in sensitivity to inhibitors, such as sirolimus, temsirolimus and everolimus.
- Mutations involving TFE3 appear to define a subgroup of PEComes with different pathophysiology and resistant to mTOR inhibitors.
Perivascular epithelioid cells tumors (PEComas) are a group of related mesenchymal tumors and tumor-like conditions found in many locations. The PEComa “family” classification includes and this group includes:
- angiomyolipoma (AML)
- pulmonary clear cell “sugar” tumor
- lymphangioleiomyomatosis (LAM)
- primary extrapulmonary sugar tumor (PEST)
- clear cell myomelanocytic tumor (CCMMT) of the falciform ligament / ligamentum teres
- abdominopelvic sarcoma of perivascular epithelioid cells
- and other tumors with similar features at various sites that are simply termed PEComa. Unusual clear tumors of other organspancreas:
- abdominal serosa
- uterus – considered one of the commonest sites of involvement in the female pelvis
Treatment and prognosis
PEComas usually may behave in a benign version, although local recurrence and even malignant behavior are encountered, mimicking malignant sarcomas.
Surgical excision is usually curative.
Differential diagnosis is broad and largely depends upon the location of the mass.
PEComa: a heterogeneous group of mesenchymal tumors. The term PEComa, for perivascular epithelioid cell tumor, designates a heterogeneous group of rare mesenchymal tumors, whose pathological diagnosis is based on the identification, at the periphery of the small and medium vessels, of a characteristic proliferation of epithelioid cells, the immunophenotype of which combines melanocytic and smooth muscle markers.
The cell type from which these tumors are derived remains unknown. PEComas occur on average at the age of 45, with a female predominance. Their prognosis is variable. Among the tumors which are usually benign, renal or hepatic angiomyolipomas (AML) are the most common; pulmonary and extrapulmonary clear cell tumors known as “in sugar”, as well as pulmonary lymphangioleiomyomatosis (AML) are exceptional. Benign tumors frequently complicate the course of tuberous sclerosis Bourneville (TBS), but can occur from sporadically.
PEComas are known to arise from different organs
Perivascular epithelioid cell tumors (PEComas) are rare mesenchymal tumors, expressing both myogenic and melanocytic markers and lacking a normal cellular counterpart. PEComas are known to arise from different organs such as the kidneys, lungs, liver, pancreas, prostate, and female genital tract. They are also associated with tuberous sclerosis complex. Different pathologies include angiomyolipomas, lymphangioleiomyomatosis, clear-cell “sugar” tumor, and clear-cell myomelanocytic tumor. Malignant PEComas are rare and very few cases have been reported in literature. Surgery remains the cornerstone of treatment, although treatment modalities are still controversial, especially in advanced conditions.
Malignant perivascular epitheliod cell tumor (PEComa) is a very rare entity composed of distinctive perivascular epitheliod cells with variable immunoreactivity for melanocytic and muscle markers. At present this neoplasm does not have a known normal cellular counterpart and the natural history is often unpredictable. Up to now, few cases of PEComa have been described and treatment modalities are still controversial, particularly in advanced conditions.
Perivascular epithelioid cell tumors (PEComas) are a heterogeneous group of mesenchymal tumors that can complicate tuberous sclerosis or more often occur sporadically. Apart from angiomyolipomas (AML) and pulmonary lymphangioleiomyomatosis (LAM) which are generally benign, PEComas are rare and tend to occur in the retroperitoneum, gastrointestinal tract, abdominopelvic region, and uterus. Their prognosis is uncertain, and negative factors include: primary tumor diameter > 5 cm (> 2in), a high mitotic index, high cellularity, high nuclear grade, infiltrative margins, and the presence of necrosis or vascular invasion. At the metastatic stage, malignant
PEComas are usually resistant to conventional chemotherapy. mTOR inhibitors are an effective targeted therapy, the efficacy of which reflects the high frequency of abnormalities in the mTOR pathway, particularly affecting TSC1 and TSC2.
Tumors and non-cancerous conditions of the kidney
A non-cancerous (benign) kidney tumor is a lump that does not spread to other parts of the body (not metastasize). The non-cancerous tumor is usually not life threatening. It is usually removed by surgery and usually does not come back (come back).
Non-cancerous kidney disease is a change in the cells of the kidney, but it is not cancer. The non-cancerous condition does not spread to other parts of the body and is usually not life threatening.
There are various types of kidney tumors and non-cancerous conditions.
Papillary adenoma is the most common non-cancerous tumor of the kidney. It is a small, slowly growing lump that usually doesn’t cause symptoms. It is often detected on an imaging test done for other reasons.
The oncocytoma starts in the cells of the kidney’s collecting tubes. This tumor can get quite large. Several oncocytomas can be seen in a single kidney or in both. It can be detected at the same time as a cancerous tumor.
Angiomyolipoma is a kidney tumor made up of fat, blood vessels, and smooth muscle tissue. It often occurs in people with tuberous sclerosis, a genetic disorder that causes non-cancerous tumors to form in many organs, including the eyes, skin, brain, lungs, heart, and kidneys. Even though it is non-cancerous, this tumor can spread to nearby tissue and destroy it. A tumor that is more than 4 cm (1 ½ inch) in diameter can also cause sudden bleeding (hemorrhage) from the kidney into the abdomen.
Surgery is the main treatment for non-cancerous kidney tumors. Here are other treatment options:
- active surveillance
- arterial embolization (for angiomyolipoma)
Find out more about treatments for kidney cancer.
A simple cyst is the most common non-cancerous kidney disease. The simple cyst is a round or oval sac filled with fluid. One or more cysts may appear in the kidney. Simple kidney cyst is very common in people over the age of 50.
Most simple kidney cysts are found on imaging tests for other medical reasons. When seen on imaging, simple kidney cysts have rounded, smooth, and well-defined contours. This helps doctors differentiate them from kidney tumors.
If the simple kidney cyst is not causing any symptoms, it does not need to be treated. If it starts to cause problems (pain, infection, or bleeding, for example), the doctor will drain the cyst with a long needle or have it removed by surgery.
Renal angiomyolipoma is a benign tumor, which has three different components: muscular, vascular and fatty, the distribution of which is variable. The frequency of hemorrhagic changes in this type of lesion on the one hand, and the need for a differential diagnosis with a malignant renal lesion on the other hand, require the definition of an appropriate diagnostic and therapeutic strategy, the important points of which we recall.
Angiomyolipoma (AML) is a benign tumor that accounts for 1 to 3% of solid kidney tumors. This lesion is composed, in variable proportions, of a fatty contingent often the most abundant, a contingent of smooth muscle cells and a contingent of vascular origin. It sits indifferently in the cortical or medullary of the kidney, but its development is readily exo-renal. Classically, this type of tumor is part of Tuberous Sclerosis of Bourneville (TBS), which is an autosomal dominant disease with variable penetrance. Renal involvement is then multiple and bilateral in 50 to 80% of cases. However, renal AML can be discovered apart from any phacomatosis, it is then isolated, unilateral with a strong female predominance.
On the anatomo-pathological level, AML appears macroscopically as an expansive, non-infiltrating renal mass, well circumscribed but not encapsulated. When cut, there are usually yellowish, lobular, more or less significant areas corresponding to the adipose component of the mass. The distribution of the three components of angiomyolipoma is variable, so the adipose component may not be found in 5 to 15% of cases. When the smooth muscle component predominates the tumor appears as a regular solid mass giving the section the appearance of a leiomyoma. The hemorrhagic changes observed within the AML are frequent, because the vascular structures composing this lesion are abnormal. The vascular walls within the tumor are thick with smooth muscle proliferation and the absence of an elastic component giving them a histologic appearance of arterialized veins, similar to arteriovenous malformations and shunts. These malformations predispose to the formation of aneurysms and explain the highly hemorrhagic nature of these tumors. There is usually no necrosis or calcification of the renal parenchyma within an angiomyolipoma.
The aim of this work is to recall the main elements to be taken into consideration in the diagnostic and therapeutic strategy of renal angiomyolipoma.
This lesion, probably hamartomatous in nature, is benign. Few of the published cases of proven malignant transformation. The presence of figures of mitosis, especially abnormal mitosis, in an epithelioid angiomyolipoma argues in favor of malignancy.
DIAGNOSTIC AND THERAPEUTIC STRATEGY FOR ANGIOMYOLIPOMAS
The diagnosis of angiomyolipoma is based on the abdominal tomodensitometric examination, which will allow the demonstration of a fatty component quasi-pathognomonic. A single AML, less than 4 cm in diameter, requires radiological monitoring at least every two years. On the other hand, when there is a diagnostic doubt or a suspicion of a malignant tumor, surgical exploration with an extemporaneous examination is required.
When AML is revealed by intra or peri-renal hemorrhage, arteriography, performed urgently, makes it possible to locate and control the bleeding, while respecting the functional renal parenchyma as much as possible. The selective character of the embolization avoids the nephrectomy of hemostasis in the acute phase and favors the subsequent conservative surgery, necessary if the tumor volume of the AML is important.
In its typical form, angiomyolipoma presents on ultrasound as a mass syndrome of the renal parenchyma, rounded, well limited with hyperechoic echostructure compared to the renal parenchyma, iso or even hyperechoic compared to the sinus of the kidney.
Abdominal computed tomography will in the vast majority of cases allow a positive diagnosis of AML, subject to a correct examination technique. The objective is the demonstration within the renal mass of a fatty component, characterized by negative densities.
MAGNETIC RESONANCE IMAGING
As with the tomodensitometric examination, the MRI diagnosis of an angiomyolipoma is based on the demonstration of a fatty component.
Currently, this test is no longer indicated in the diagnosis of angiomyolipoma. On the other hand, arteriography retains an important place in the emergency embolization of AML during a hemorrhagic period. Performed selectively, it helps to curb the hemorrhagic syndrome while respecting the functional renal parenchyma as much as possible, which favors subsequent conservative surgery.
RENAL BIOPSY PUNCTURE
The indications for percutaneous renal biopsy remain limited to patients at high surgical risk or when the diagnosis of intra-renal metastasis, lymphoma or pseudotumoral pyelonephritis is mentioned. It was conventional not to recommend it to clarify a diagnosis of AML, because cytological abnormalities in the muscle component could suggest a sarcomatoid or even oncocytic tumor. However, the current trend is to extend the indications for percutaneous renal biopsy to small tumors discovered by chance, especially since the expression in immunohistochemistry of the HMB 45 protein seems relatively specific for AML. . In practice, only the extemporaneous histological examination performed during surgery, carried out as a last resort if the imaging data are not contributing, will most often make it possible to confirm the diagnosis of AML.
The development and increasingly frequent use of abdominal ultrasound has significantly increased the detection of small renal tumors in recent years. When a tumor of less than 4 cm in diameter is discovered, which is radiologically compatible with an angiomyolipoma, the classic therapeutic attitude remains surveillance. A renal ultrasound every two years is considered sufficient by some authors, especially since they do not observe in their experience any modification of the AML with an average clinical follow-up of 5 years. On the other hand, other teams recommend closer monitoring, every six months with a renal ultrasound or even a tomodensitometric examination. The difference in growth rate between an isolated angiomyolipoma and multiple locations of AML (5% versus 22%) seems to justify specific treatment adapted to the clinical context. It seems reasonable to propose an annual ultrasound monitoring of such a renal lesion, and to carry out a tomodensitometric examination only if the tumor volume changes.
The course of a renal tumor labeled AML is dominated by the suspicion of an underlying malignant lesion and the risk of intratumoral and peri-renal hemorrhage. In the absence of a fatty contingent within the quasi-pathognomonic renal mass and in the fear of letting a malignant tumor develop, it is recommended to perform an exploratory lumbotomy with an extemporaneous examination, which most often allows a conservative surgical procedure. respecting the safety margins recommended during a partial nephrectomy. False negatives are still possible, however the association of an AML and a clear cell adenocarcinoma is exceptional. The comparison of the tomodensitometric data and the histological result of the extemporaneous examination seems to allow, in a retrospective study carried out on 23 patients at the Singapore General Hospital, a definite diagnosis of AML in 87% of cases. This therapeutic attitude is all the more justified, as there may also be particular forms associating AML and renal adenocarcinoma.
The surgical treatment in principle of large renal angiomyolipomas, with a high risk of bleeding, must be as conservative as possible. The exo-renal development of these lesions often allows the performance of a partial nephrectomy with wedge resection of the tumor.
The various hemorrhagic risk factors of renal angiomyolipoma are perfectly identified: the initial size of the tumor, the degree of vascular anomalies and the multifocalite. A subcapsular or peri-renal hematoma should always raise suspicion of a tumor origin. The kidney lesion, often small in size and confined to the parenchyma, is sometimes difficult to identify and distinguish within the hematoma. In the majority of cases, the hemorrhagic rearrangement of the AML therefore requires close monitoring and a follow-up computed tomography examination 4 to 6 weeks after the bleeding episode. When the circumstance of discovery of AML is massive intra or peri-renal bleeding, with hemodynamic repercussions, the size of the tumor is generally greater than that of asymptomatic patients (8 cm against 2 cm) and renal involvement is frequently bilateral.
Arteriography, performed urgently, then makes it possible to localize the bleeding and to curb the hemorrhagic syndrome, while respecting the functional renal parenchyma as much as possible. Performing a first-line arteriography avoids surgical intervention, which would most often lead to hemostasis nephrectomy. The remote tomodensitometric control (2 to 3 months) shows the regression of the hematoma but without modification of the volume of the AML. When it is greater than 5 cm in diameter, surgical treatment will be required. Improved embolization equipment and catheters allow for more selective embolization, which will favor subsequent conservative surgery. One question remains: can we offer selective arterial embolization (SEA) as an alternative to surgical treatment for small AML? No complications related to EAS were observed, apart from the risk of tumor necrosis. The interest of this therapeutic alternative is to allow an almost complete disappearance of the angio-myogenic contingent. However, sufficient clinical experience is still necessary to confirm its effectiveness.
Lymphangioleiomyomatosis is an indolent and gradual development of smooth muscle cells in the lungs, pulmonary blood vessels, lymphatics, and the pleura. It is rare and occurs exclusively in young women. Symptoms are dyspnea, cough, chest pain, and hemoptysis; spontaneous pneumothorax is common. The diagnosis is suspected based on symptoms and chest x-ray and is confirmed by high-resolution CT. The prognosis is uncertain, but the disease slowly progresses, after a number of years, to chronic respiratory failure and death. Treatment is based on lung transplantation.
Lymphangioleiomyomatosis is an exclusively female disease, most often affecting women between the ages of 20 and 40. White subjects are at higher risk. Lymphangioleiomyomatosis affects <1 person per million. It is characterized by an overgrowth of atypical smooth muscle cells in the lungs, including the pulmonary parenchyma, blood and lymphatic vessels, and the pleura, resulting in deformation of the lung architecture, cystic destruction of the lungs and deterioration. progressive respiratory function.
Key points of lymphangioleiomyomatosis
- Lymphangioleiomyomatosis can mimic interstitial lung disease, but it is actually a rare and slowly progressive growth of smooth muscle cells in various organs.
- Consider diagnosis in young woman with unexplained dyspnea with interstitial changes to normal or increased lung volumes on chest x-ray, spontaneous pneumothorax, or chylous effusion.
- Perform a high resolution CT scan and, if the results are inconclusive, a biopsy.
- Consider treatment with sirolimus in case of lymphangioleiomyomatosis with abnormality or progressive decrease in pulmonary function.
Etiology (the study of causation or origination) of lymphangioleiomyomatosis
The etiology of lymphangioleiomyomatosis is unknown. The attractive hypothesis that female sex hormones play a role in its pathophysiology is not confirmed.
The disease usually begins spontaneously, but lymphangioleiomyomatosis has many similarities to the pulmonary abnormalities seen in tuberous sclerosis; Lymphangioleiomyomatosis is seen in some patients who have tuberous sclerosis and is considered by some to be a rough form of tuberous sclerosis. Mutations in the tuberous sclerosis complex-2 (TSC-2) gene have been described in cells of patients with lymphangioleiomyomatosis and in angiomyolipomas (benign renal hamartomas made up of smooth muscles, blood vessels and fatty tissue). Angiomyolipomas form in up to 50% of patients with lymphangioleiomyomatosis. These observations suggest 1 of the 2 possibilities:
Somatic mosaicism for TSC-2 mutations in the lungs and kidneys results in additional disease foci against a background of normal cells in these tissues (although multiple distinct disease sites can be observed)
Lymphangioleiomyomatosis is a low-grade, metastasizing and destructive neoplasia, possibly of uterine origin, that spreads through the lymphatic system.
Symptomatology of lymphangioleiomyomatosis
The initial symptoms of lymphangioleiomyomatosis are dyspnea, cough, chest pain, and hemoptysis. Few signs are associated with the disease, but some women have crackles and ronchi. Many patients initially develop spontaneous pneumothorax. Manifestations of lymphatic obstruction (chylothorax, chylous ascites and chyluria) may also be observed. It is believed that symptoms may worsen during pregnancy.
Renal angiomyolipomas, although usually asymptomatic, can cause bleeding if their size increases (eg,> 4 cm), which usually presents as hematuria or pain in the hypochondrium.
Diagnosis of lymphangioleiomyomatosis
- High resolution chest x-ray and CT
- VEGF-D test
- Lung biopsy if high-resolution CT and VEGF-D test do not provide a diagnosis
The diagnosis of lymphangioleiomyomatosis is suspected in young women with dyspnea, interstitial abnormalities with normal or increased respiratory volumes on chest x-ray, spontaneous pneumothorax and / or chylous effusion. Lymphangioleiomyomatosis is often misdiagnosed as interstitial lung disease. High-resolution CT is done in patients with suspicion of the disease; the discovery of multiple small, diffusely distributed cysts is generally very suggestive of lymphangioleiomyomatosis.
Serum VEGF-D (vascular endothelial growth factor D) assay is recommended. Serum VEGF-D levels are elevated in the majority of women with lymphangioleiomyomatosis and are normal in women with other forms of cystic lung disease. An elevated level can confirm acute lymphangioleiomyomatosis, but a normal level does not exclude the diagnosis.
Biopsy (surgical) is only indicated when the results of high-resolution CT and VEGF-D test do not allow a diagnosis. The discovery of an abnormal proliferation of smooth muscle cells (LAM cells) associated with cystic formations on histological examination confirms the disease.
Respiratory function tests support the diagnosis and are particularly useful for monitoring. An obstructive or obstructive / restrictive (mixed) syndrome is characteristic. The lungs are usually distended and an increase in total lung capacity (TPC) and chest gas volume is present. Pulmonary distension (an increase in the residual volume ratio [RV] and RV / CPT) is often present. PaO2 and carbon monoxide diffusion capacity (DLCO) are frequently reduced. In most patients, there is a decrease in exercise performance.
Prognosis of lymphangioleiomyomatosis
The prognosis of lymphangioleiomyomatosis is poorly understood because the disease is very rare and because the clinical course of patients with lymphangioleiomyomatosis is variable. The disease usually progresses slowly and eventually leads to respiratory failure and death, but the time to fatal outcome varies greatly from case to case. Median survival is most likely> 8 years after diagnosis. Lung function declines 2-3 times faster than in healthy people. Women should be informed that pregnancy can accelerate the course of the disease.
Treatment of lymphangioleiomyomatosis
- Lung transplant
The standard treatment for lymphangioleiomyomatosis is lung transplantation, but the disease can recur in the transplanted lungs.
Recent data suggest that sirolimus (an mTOR inhibitor) may stabilize or slow the decline in lung function in moderate pulmonary insufficiency (forced expiratory volume in 1 s [FEV1] <70% of theoretical). Sirolimus treatment is recommended in patients with abnormal or declining lung function. Other treatments, such as hormonal regulation with progestins, tamoxifen, oophorectomy, are not effective and are not recommended.
Pneumothoraxes can be difficult to treat because they are often recurrent, bilateral, and less sensitive to standard measurements. Recurrent pneumothorax requires pleural abrasion, talcage, or chemical pleurodesis or rarely pleurectomy. Embolization should be considered in the event of angiomyolipomas> 4 cm to avoid the risk of bleeding.
Air travel is well tolerated by most patients.
The clear cell myomelanocytic tumor (CCMMT)
Melanocytic tumors are tumors developed from cells making the melanin pigment (melanin): melanocytes.
Melanocytic tumors are found mainly in the skin where they are favored by excessive sun exposure, exceptionally in the eye, the nervous system or the aerodigestive mucous membranes.
On standard sections, the melanin pigment (melanin) appears as brown or blackish masses, depending on its quantity; it can be characterized by the Fontana reaction to silver; it may be scarce or absent, as in achromic melanoma.
There are 4 types of pigmented circumscribed skin lesions:
- localized increases in physiological pigmentation without cell proliferation; pigmentation can be superficial, epidermal, in ephelids (freckles) and lentigines, or dermal.
- contingent pigmentation of benign epithelial skin tumors (seborrheic wart) or malignant (basal cell carcinoma): these lesions are sometimes difficult to distinguish clinically from actual melanoma tumors.
- benign melanoma tumors (melanocytic nevus).
- malignant melanoma tumors (melanoma).
Primary Extrapulmonary Sugar Tumor (PEST)
The cell of origin and direction of differentiation of the clear cell tumor of the lung (the so-called sugar tumor) remains enigmatic. Recognition of HMB-45 immunoreactivity and identification of melanosomes have suggested a relationship to angiomyolipoma of kidney or liver and lymphangiomyoma.
This has given rise to the concept that clear cell tumors are neoplasms of so-called perivascular epithelioid cells PEComa. Although most PEST’s are probably benign, malignant forms appear to exist. These cases further support the concept of a family of systemic HMB-45 positive tumors that include sugar tumors, angiomyolipoma of kidney or liver, lymphangiomyomas, and clear-cell myomelanocytic tumors of the falciform ligament/ligamentum teres.
Clear Cell Myomelanocytic Tumor (CCMMT) of the falciform ligament / ligamentum teres
The clear cell myomelanocytic tumor (CCMMT) is a recently reported and very rare member of the perivascular epithelioid cell family of tumors (PEComa). All CCMMTs reported to date have occurred in or immediately adjacent to the falciform ligament/ligamentum teres.
Clear-cell myomelanocytic tumor (CCMT) of falciform ligament/ligamentum teres hepatis is a very uncommon lesion described as a variant of perivascular epithelioid cell tumor (PEComa), which includes smooth muscle cells, blood vessels, and express melanocytic and smooth muscle markers. Most patients are asymptomatic or have nonspecific gastrointestinal symptoms, and the tumors are usually found incidentally. The origin and definitive diagnosis of the CCMT can be made by histopathological examination of the specimen after the surgical excision. PEComas express HMB45, HMSA-1, Melan A, Mart 1, microphtalmia transcription factor (Mitf), actin, and less desmin.
Clear-cell myomelanocytic tumor (CCMT) of falciform ligament/ligamentum teres hepatis is a very uncommon lesion defined first in 2000. It is described as a variant of perivascular epithelioid cell tumor (PEComa) that includes smooth muscle cells, blood vessels, and express melanocytic and smooth muscle markers [1-3]. PEComas consist of different
clinical forms, such as angiomyolipoma, lymphangioleiomyomatosis, clear-cell sugar tumor of the lung, CCMT of the ligamentum teres hepatis, and other rare clear tumors.
PEComas are most common in young women and found in multiple organs, including uterus, vulva, liver,
rectum, heart, urinary bladder, abdominal wall, pancreas, skin, and bone. All PEComas, except the pancreatic and uterine ones, have been shown to be associated with tuberous sclerosis complex.
They may cause pain owing to compression effect of mass, but they are often recognized incidentally. CCMT of ligamentum teres hepatis is a rare tumor, and as far as we know, only 12 cases have been reported in the literature. Because of this rarity, little is known about CCMT’s behavior. Herein, we present our first experience with a CCMT of ligamentum teres hepatis.
Abdominopelvic Sarcoma of Perivascular Epithelioid Cells
The perivascular epithelioid cell has been proposed to be the unifying proliferating cell type in a number of lesions such as angiomyolipoma, lymphangiomyomatosis, clear cell “sugar” tumor and renal capsuloma. With the exception of rare examples of angiomyolipoma, they are non-metastasizing.