Most AML patients are asymptomatic. Here, AMLs are generally incidental findings, observed on images obtained for non-related reasons. In the case of symptomatic AML, patients may present with lower back and flank pain radiating from the affected kidney(s). Accordingly, hepatic AML may provoke upper abdominal pain, sensations of early satiety and fullness. Tumors may be palpable and sensitive to pressure. Renal AML may interfere with kidney function and affected individuals may claim hematuria.

Since about one in five AML patients suffers from TSC, symptoms related to this disease shall be briefly summarized here. Besides multiple mesenchymal tumors, mental retardation and epilepsy due to cortical dysplasia, as well as dermatological and dental anomalies, are typical of TSC. With regards to the former, numerous facial angiofibroma's distributed in a butterfly-like pattern are most characteristic of the disease, but patients may also present with ungual fibromas, retinal hamartoma, subependymal astrocytoma, rhabdomyoma, lymphangioleiomyomatosis and mesenchymal tumors of the kidneys and liver [14]. In this context, cysts are often observed in close proximity to multiple AML.

While tumor size upon the initial presentation of AML patients varies, TSC-associated AML is typically larger than those deemed sporadic. According to a retrospective study conducted in Egypt, TSC-related AML usually measure more than 15 cm in diameter at the time of diagnosis, while sporadic AML have a mean size of only 4 cm [7]. Similarly, growth rates differ largely (1.25 and 0.19 cm per year in the case of TSC-associated AML and sporadic tumor growth, respectively). As has been indicated above, sporadic cases of renal AML usually manifest in form of unilateral disease.

Vessels passing through AML are prone to aneurysm formation and rupture, and this particularly applies to larger tumors. Patients diagnosed with AML measuring more than 4 cm in diameter have a risk of more than 50% of spontaneous hemorrhages [15]. Such events may lead to anemia, but rupture of major vessels may also cause life-threatening blood loss. Affected patients may present with sudden-onset abdominal pain and hemorrhagic shock.

• Pain

  However, an angiomyolipoma can cause flank pain and hematuria, which can be misdiagnosed as a kidney stone. This neoplasm can also cause abdominal pain and, as it grows, can result in a palpable abdominal mass. [patientcareonline.com]

  Of the four patients with flank pain, in three, the pain resolved during the first year of clinical follow-up. In one patient, the pain did not resolve despite successful embolization. [hemodinamiadelsur.com.ar]

  They may be associated with tuberous sclerosis and occasionally present with flank pain, a palpable mass, and gross haematuria. [casesjournal.biomedcentral.com]

• Anemia

  Ultrasonography of the right kidney of twenty five years female patient with tuberous sclerosis presenting with right flank pain, fever and anemia showing renal angiomyolipomas. A. [oatext.com]

  Anemia- Loss of blood in urine may result in anemia. How is Angiomyolipoma Diagnosed? Ultrasound Examinations for Angiomyolipoma Ultrasound examination of kidney reveals increased size of kidney with tumor. [epainassist.com]

  The clinical presentation for EAMLs is varied — most are incidental findings however haematuria, anemia, and flank pain are possible. [karger.com]

  Signs and symptoms may not occur in many patients with benign angiomyolipomas; if they do occur, the following may be seen: Sudden pain (back pain or flank pain) Nausea Vomiting Anemia Hypertension Chronic kidney disease Shock (about 20% of patients that [medicinenet.com]

• Fever

  Ultrasonography of the right kidney of twenty five years female patient with tuberous sclerosis presenting with right flank pain, fever and anemia showing renal angiomyolipomas. A. [oatext.com]

  Abstract A case of renal angiomyolipoma presenting as fever of unknown origin unassociated with tuberous sclerosis is described. [amjmed.com]

  Patients with renal angiomyolipoma often have flank pain, a palpable tender mass, abdominal discomfort, fever, and gross hematuria. [consultant360.com]

  The destroyed kidney tissue often causes postembolisation syndrome, which manifests as nausea, vomiting, fever, and abdominal pain, and lasts a few days. [wiki.alquds.edu]

• Weight Loss

  WARNING SIGNS & SYMPTOMS OF ANOREXIA NERVOSA Emotional and behavioral Dramatic weight loss Dresses in layers to hide weight loss or stay warm Is preoccupied with weight, food, calories, fat grams, and dieting Refuses to eat certain foods, progressing [nationaleatingdisorders.org]

  Physical symptoms Physical signs and symptoms of anorexia may include: Extreme weight loss or not making expected developmental weight gains Thin appearance Abnormal blood counts Fatigue Insomnia Dizziness or fainting Bluish discoloration of the fingers [mayoclinic.org]

  Other symptoms reported in patients with Tuberous sclerosis are flank or abdominal pain,weight loss, hypertension, fever and nausea. In the present study the patient presented with an ovarian mass and there was no evidence of Tuberous sclerosis. [ispub.com]

  Case history A 59 year-old woman presented to her general practitioner in 2005 with a 2-month history of right-sided flank pain, haematuria, and weight loss. [jmedicalcasereports.com]

  […] with signal loss on MRI (17, 18). [ncbi.nlm.nih.gov]

• Rigor

  These patients need rigorous follow up, one suggested regimen being the European Association of Urology guidelines for “indeterminate risk cancers”: CT scan at 6 months, then alternating CT scan/ultrasound and chest X-ray yearly for 5 years. [karger.com]

  While Nese et al 13 have recently considered only the tumors with >95% epithelioid components as epithelioid-AML, we chose 80% cutoff so that tumors falling outside the former more rigorous definition that have been reported to behave aggressively 12 [nature.com]

  Data Availability: Novartis supports the publication of scientifically rigorous analysis that is relevant to patient care, regardless of a positive or negative outcome. [journals.plos.org]

• Abdominal Pain

  Her abdominal pain was subequently diagnosed as being secondary to constipation. The diagnosis of a likely Renal Cell Carcinoma (RCC) was explained to the patient and she was booked for a laprascopic mobilisation open partial nephrectomy. [austinpublishinggroup.com]

  Affected patients may present with sudden-onset abdominal pain and hemorrhagic shock. [symptoma.com]

  A 31-year-old male visited a local hospital due to sudden-onset severe abdominal pain. [ncbi.nlm.nih.gov]

  However, an angiomyolipoma can cause flank pain and hematuria, which can be misdiagnosed as a kidney stone. This neoplasm can also cause abdominal pain and, as it grows, can result in a palpable abdominal mass. [patientcareonline.com]

• Nausea

  Angiomyolipoma Symptoms Nausea and vomiting Nausea and vomiting are symptoms of an underlying illness and due to a not a specific disease. [medicinenet.com]

• Vomiting

  The term "dry heaves" (retching) refers to an episode of vomiting where there is no food in the stomach to vomit, and only small amounts of clear secretions are vomited. [medicinenet.com]

• Abdominal Mass

  This neoplasm can also cause abdominal pain and, as it grows, can result in a palpable abdominal mass. Fat attenuation in a renal mass is virtually diagnostic. Treatment usually consists of watchful waiting. [patientcareonline.com]

  However it may present as an abdominal mass or with haematuria. The likelihood of an angiomyolipoma being symptomatic is higher with tumours greater than 4cm in diameter (1) it occurs in more than 50% of individuals with tuberous sclerosis. [gpnotebook.com]

  Luis Zegarra, Raúl Medina, Weymar Melgarejo, César Salinas Resumen We report a fifty three years old female patient, who suffered right lumbar pain, total hematuria and palpable abdominal mass. [upch.edu.pe]

  • 40% are symptomatic; these can cause a palpable abdominal mass, hematuria, or flank pain. • The solitary sporadic tumors may cause acute abdomen and shock as a result of spontaneous hemorrhage in the tumor. 7. Angiomyolipoma I. [slideshare.net]

• Early Satiety

  Also, some patients manifest symptoms like lower back and flank pain (in case of renal AML), upper abdominal pain, early satiety and a feeling of fullness (due to hepatic AML). [symptoma.com]

• Hypotension

  A 45-year-old man presented to the emergency department with severe left flank pain, tachycardia, and hypotension of about 48 hours’ duration. He had no significant medical history. [patientcareonline.com]

  After a couple of hours she was developed an episode of fetal bradycardia, hypotension, and a hematocrit continued to decline, despite repeated blood transfusion, which combined with symptoms of intense lumbar pain and hematuria. [casesjournal.com]

  On physical examination at time of presentation, the patient looked anxious, pale with extensive dark brown skin pigmentations involving the face in butterfly distribution and trunk, patient was a febrile with tachycardia and hypotension. [casereports.in]

  Lesions larger than 3.5-4.0 cm in diameter are thought to have a signffieant risk of hemorrhage, potentially with hypotension or other associated morbidity, and are generally treated with elective resection. [aureliocaronia.wordpress.com]

  Other symptoms may include fever, vomiting, anaemia, renal failure and hypotension [ 3 ]. Some angiomyolipomata can grow rapidly, up to 4 cm per year [ 13 ]. [jmedicalcasereports.com]

• Hepatomegaly

  Radiological examination included an abdominal ultrasound scan (USS), which showed hepatomegaly with dilatation of the pancreatic and common bile ducts. [jmedicalcasereports.com]

  On physical examination, there was a hepatomegaly, and the tumoral mass was palpable in the right flank and iliac region, extending to the mesogastrium and going beyond the midline; it had a smooth surface of solid consistence, of low mobility, and clear [scielo.br]

• Low Back Pain

  A 30-year-old primigravida presented to emergency at 32 weeks of gestation with history of sudden onset of severe low back pain and pain in right flank area. [joacp.org]

  Five patients firstly presented with symptom of low back pain and other two with renal tumor identified by ultrasound during physical examination, and one of those patients accompanied with hematuria. [frontiersin.org]

• Seizure

  The classic triad of tuberous sclerosis consists of adenoma sebaceum, seizures, and mental retardation, but is only seen in one-third of patients.Major features of tuberous sclerosis include facial angiofibromas, cortical tubers, subependmal nodules, [appliedradiology.com]

  They are common in patients with tuberous sclerosis (a genetic disorder in which benign tumors grow in the kidneys, brain, eyes, heart, lungs, and skin, causing seizures, mental problems, and skin lesions). [cancer.gov]

  They are common in patients with tuberous sclerosis (a genetic disorder in which benign tumors grow in the kidneys, brain, eyes, heart, lungs, and skin, causing seizures, mental problems, and skin lesions). 0 0 Improve it Add an image Part of Speech: [en.termwiki.com]

  The presence of early-onset seizures or intractable seizures is associated with cognitive impairment and learning disabilities (3,23). [cjasn.asnjournals.org]

• Flank Pain

  However, an angiomyolipoma can cause flank pain and hematuria, which can be misdiagnosed as a kidney stone. This neoplasm can also cause abdominal pain and, as it grows, can result in a palpable abdominal mass. [patientcareonline.com]

  These tumors demonstrate a slight female predominance and can present either incidentally or with symptoms, commonly flank pain and hematuria. [ncbi.nlm.nih.gov]

  Ultrasonography of the right kidney of twenty five years female patient with tuberous sclerosis presenting with right flank pain, fever and anemia showing renal angiomyolipomas. A. [oatext.com]

  CASE SUMMARY A 63-year-old female patient with history of end-stage renal disease (ESRD) and tuberous sclerosis presented to the emergency department (ED) with right flank pain. [appliedradiology.com]

  Patients with renal angiomyolipoma often have flank pain, a palpable tender mass, abdominal discomfort, fever, and gross hematuria. [consultant360.com]

• Hematuria

  These tumors demonstrate a slight female predominance and can present either incidentally or with symptoms, commonly flank pain and hematuria. [ncbi.nlm.nih.gov]

  Frequent urinary tract infections Hematuria- Microscopic hematuria observed during early phase and frank hematuria is seen during late stage. Renal Failure- Bilateral or huge tumor mass can cause renal failure. [epainassist.com]

  However, an angiomyolipoma can cause flank pain and hematuria, which can be misdiagnosed as a kidney stone. This neoplasm can also cause abdominal pain and, as it grows, can result in a palpable abdominal mass. [patientcareonline.com]

  Microscopic hematuria. Gross hematuria. Urinary tract infection (UTI). Hemorrhage. Renal failure. [medigoo.com]

• Kidney Failure

  Angiomyolipomas rarely cause symptoms, but may bleed or grow large enough to be painful or cause kidney failure. [cancer.gov]

  These growing tumors may lead to life-threatening complications, such as internal bleeding and kidney failure. TSC symptoms and manifestations vary from person to person and may change over time. [novartis.com]

  […] angiomiolipom A benign (noncancer) tumor of fat and muscle tissue that usually is found in the kidney. Angiomyolipomas rarely cause symptoms, but may bleed or grow large enough to be painful or cause kidney failure. [en.termwiki.com]

Diagnostic imaging allows for the detection of space-occupying masses in kidneys, liver or other tissues, and such findings often prompt a tentative diagnosis of tumor disease. Echography, magnetic resonance imaging, and computed tomography scans may also be carried out to determine the dimensions of such a mass and to ascertain which tissues are involved. Here, AML may appear as heterogenous tissue with a variable content of fat. It should be noted, though, that certain subtypes of AML have low-fat contents, and that malignant neoplasms may occasionally contain adipose tissue. These facts limit sensibility and specificity of imaging techniques for AML diagnosis, but renal or hepatic masses containing fat are considered highly suspicious of this type of tumor. Angiography may reveal those masses to be highly vascularized, another feature typical of AML. Arteries usually follow tortuous, irregular courses, and veins have been described to have a whorled, sunburst-like appearance [16]. Arteriovenous shunting and aneurysms are frequently observed.

Despite their characteristic appearance, AML are frequently misdiagnosed as lipoma, liposarcoma, renal cell carcinoma or hepatocellular carcinoma, or hemangioma. Thus, only histopathological analyses of tumor specimens, possibly combined with subsequent immunohistochemistry staining, allow for a definitive diagnosis of AML. Fine needle aspiration has been proposed to this end, but due to the heterogeneity of AML, findings largely depend on the site of sampling [17] [18].

• Cortical Tubers

  The classic triad of tuberous sclerosis consists of adenoma sebaceum, seizures, and mental retardation, but is only seen in one-third of patients.Major features of tuberous sclerosis include facial angiofibromas, cortical tubers, subependmal nodules, [appliedradiology.com]

  MRI revealed multiple T2 hyperintense cortical tubers (Figure 3B). [oatext.com]

  [7] Cortical tubers (malformative, epilepsy-associated).[8] Note: The same genes (TSC1, TSC2) are implicated in PEComas. [librepathology.org]

  The patient had no history of seizures/intellectual disability but a screening brain imaging revealed bilateral subependymal nodules and cortical tubers. Funduscopy did not reveal retinal tubers and echocardiogram was normal. [casereports.bmj.com]

Treatment of AML depends on the overall condition of the patient, on whether the lesion is symptomatic or not, on the size of the tumor and angiographic findings. For small, asymptomatic AML, a conservative approach is usually recommended [17]. Cryoablation or radiofrequency ablation may be applied to this end; administration of mTOR inhibitors has also yielded promising results [19]. Either embolization of the renal artery or surgery may be indicated in case of larger, symptomatic renal AML. Embolization of the renal artery is a prophylactic measure aiming at reducing the threat imposed by spontaneous hemorrhages due to rupture of aneurysms. This minimally invasive procedure has traditionally been performed if the tumor size exceeded 4 cm, but angiographic findings should be considered when evaluating the possibility of embolization in the case of smaller tumors [20]. Similarly, larger tumors with low vascularity may not require embolization. Of note, embolization is less frequently used to treat hepatic AML. There is no general consensus as to the preference of embolization over early surgery or vice versa [21]. Removal of neoplastic tissue is usually curative, but patients diagnosed with epithelioid AML should be considered for adjuvant therapy [12]. With regards to renal AML, wedge resection or partial nephrectomy is preferred over total nephrectomy. Renal parenchyma should be preserved as much as possible.

Prognosis for AML patients is generally good. Retrospective studies have shown low rates of recurrence; malignant transformation and metastasis have only been described in occasional case reports. However, epithelioid AML may be associated with a less favorable prognosis. Literature holds contradictory information to that end: While in one study, all patients affected by epithelioid AML were found to have "died of neoplastic progression of the disease, with liver, lung and bone metastases" [12], other authors state the "the rate of aggressive behaviour among epithelioid angiomyolipomas (to be) very low" [13].

AML are tumors mainly composed of adipose tissue, smooth muscle cells, vascular structures. Most cases are deemed sporadic, but about 20% of AML are encountered in TSC patients. TSC is a hereditary disease caused by mutations in either of the two tumor suppressor genes TSC1 and TSC2. These genes encode for hamartin and tuberin, respectively, and those proteins form a complex that inhibits the mTOR pathway. The respective signaling cascade has been shown to affect adipogenesis and angiogenesis, although it is more commonly related to the metabolism of striated muscle cells than to smooth musculature [4]. The mTOR pathway, more precisely the mTOR1 and mTOR2 pathways, depend on diverse stimulators and inhibitors, namely on nutrient and energy supply, the availability of oxygen, cytokines and growth factors, and regulate cell growth, division, differentiation, and death. Since histopathologically, there are no differences between sporadic and TSC-associated AML, it is tempting to speculate that at least part of those "sporadic cases" may be ascribed to gene defects associated with alterations of the mTOR signaling cascade [5]. Such has been proven for pulmonary lymphangioleiomyomatosis [6], a disease that may be accompanied by AML. Loss of heterogeneity of TSC1 and TSC2 has also been confirmed for hepatic AML [2].

The overall incidence of AML has been estimated to be 0.3%, and this value is based on the detection of such tumors in autopsy studies. Women are affected more significantly than men [7].

About one in five cases can be related to TSC, with 80% and 30% of people diagnosed with this hereditary disorder developing renal and hepatic AML, respectively. Due to the prominent role of TSC in AML etiology, selected epidemiological data shall be presented in consideration of this disease: Most patients are middle-aged women, and the median age at diagnosis of sporadic AML is 49 years, while TSC patients developing AML have a median age of 26 years. As for sporadic AML, only 5% of patients present with bilateral tumors, but TSC is associated with bilateral AML in virtually all cases [7].

Nowadays, AMLs are generally classified as PEComas, i.e., they are assumed to originate from degenerated perivascular epithelioid cells. At first glance, it may seem unlikely for AML to have a clonal origin, yet recent findings support that hypothesis and argue against the classical theory of AML being congenital malformations or hamartomatous polyclonal neoplasms [8]. Chromosomal aberrations are common, yet very heterogeneous if tumor specimens obtained from different patients are compared [9].

AML mainly consist of adipose tissue, smooth muscle cells, and vascular fragments. Depending on the prevailing tissue and the tumor's fat content as observed histopathologically, four subtypes of AML may be distinguished: lipomatous (≥70% fat), myomatous (≤10% fat), angiomatous and mixed [10]. An evaluation of smooth muscle cell morphology allows for an even more precise classification of AML, and these cells may appear spindle-shaped, be of the intermediate form, epithelioid or pleomorphic [11].

The afore-described subtypes differ with regards to their gene expression profiles, and presumably, chromosomal anomalies correlate with tissue composition, architectural features, and growth behaviour. While information regarding the prognostic value of an exact histopathological characterization is still scarce, epithelioid AML have been proposed to be re-classified as malignant neoplasms [12].

No specific measures can be recommended to prevent AML. However, patients suffering from TSC may undergo regular screening to detect mesenchymal tumors during early stages. Then, therapy may be initiated before aneurysms develop within AML and the patient's risk of life-threatening hemorrhages due to aneurysm rupture can be diminished.

Angiomyolipoma (AML) is a benign mesenchymal tumor. It derives the name from its characteristic histopathological properties: mature adipose tissue, spindle-shaped smooth muscle cells and branched vessels prone to dilation and rupture. The most common subtype of AML is renal AML, and there are several hundred case reports concerning hepatic AML. Extrarenal, non-hepatic AML are extremely rare. While most cases are sporadic, it has been estimated that one in five cases of renal AML and one in ten cases of hepatic AML corresponds to manifest tuberous sclerosis (TSC). Moreover, renal AML are very common in TSC; hemorrhages due to rupture of aneurysms forming in AML are the leading cause of death in patients suffering from this genetic disorder [1]. Hepatic lesions, namely hepatic AML, adenoma, hemangioma and hepatic cysts are detected in about 30% of TSC patients [2]. Moreover, AML may be observed in patients diagnosed with lymphangioleiomyomatosis, neurofibromatosis type 1 and Von Hippel-Lindau disease [3].

The clinical presentation of AML patients varies largely and ranges from asymptomatic condition to abdominal pain to hemorrhagic shock. Most patients are indeed asymptomatic and here, AML is usually an accidental finding. Imaging techniques may reveal a space-occupying mass in renal, hepatic or other tissues, and may provide valuable information as to the properties of that mass. Nevertheless, only histopathological features are considered diagnostic of AML. Therapeutic strategies are adapted to the individual case and primarily depend on tumor size and the presence of aneurysms prone to rupture.

Angiomyolipoma (AML) is a benign neoplasm most commonly encountered in kidneys and liver. Its name is derived from its main components: branched vessels, smooth muscle cells and fat. Its etiology is only poorly understood, but considerable shares of AML patients suffer from tuberous sclerosis or lymphangioleiomyomatosis.

Women are affected significantly more often than men, and their median age at the time of diagnosis is 49 years. AML may be diagnosed incidentally, if images of the abdominal cavity are obtained for non-related reasons. Also, some patients manifest symptoms like lower back and flank pain (in case of renal AML), upper abdominal pain, early satiety and a feeling of fullness (due to hepatic AML). Tumors may interfere with organ function and patients may note blood in their urine. Rarely, sudden-onset abdominal pain and shock due to blood loss may prompt a suspicion of AML. The latter symptoms result from the rupture of vessels passing through the tumor.

Although life-threatening blood loss is a rare event in AML patients, it still poses a major threat. Consequently, treatment aims at eliminating this threat. This can be achieved by arterial embolization, i.e., by occlusion of the artery that supplies blood to the tumor. Another approach to AML treatment consists in the surgical removal of neoplastic tissue. Surgery is often curative, but tissue preservation may be better if a conservative approach and embolization are chosen. Preference of either therapy depends on the overall condition of the patient, on whether the lesion is symptomatic or not, on the size of the tumor and angiographic findings. Of note, current research is focused on drug therapy of AML, but to date, medication is not considered a first-line treatment option.

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