Sporadic facial angiofibroma and sporadic angiomyolipoma mimicking tuberous sclerosis complex.

Tuberous sclerosis complex (TSC) is a genetic syndrome due to mutations in either TSC1 or TSC2, leading to the development of hamartomatous tumours at multiple body sites, including facial skin (facial angiofibroma (FAF)), brain (cortical tubers) and kidney (angiomyolipoma (AML)). In this report, we describe an individual with minimal TSC clinical features, who had 'no mutation identified' (NMI) by prior genetic testing in a clinical laboratory. Our massively parallel sequencing (MPS) analysis of multiple samples from different body sites and tumours (including blood, saliva, normal skin, AML and FAF) revealed an extraordinary situation in which FAF and AML had completely independent inactivating biallelic variants in TSC2, not present in other matched samples. This suggests that the two different lesions (AML and FAF) are not due to the same underlying germline or mosaic mutation, rather both are likely sporadic events. This case demonstrates the relevance of thorough clinical examination, high-coverage MPS of multiple tumours and matched normal tissues, and appropriate genetic counselling for individuals with marginal TSC features and possible TSC1 or TSC2 mosaicism.

Malignant Pigmented Epithelioid Angiomyolipoma of the Kidney in a Child with Tuberous Sclerosis Complex.

INTRODUCTION: Pigmented epithelioid angiomyolipoma is a variant of epithelioid angiomyolipoma (EAML) that has not previously been described in children with tuberous sclerosis. CASE PRESENTATION: A 15-year-old boy with tuberous sclerosis had a rapidly enlarging renal mass associated with a left lung nodule. Microscopically it was a pigmented EAML, confirmed by immunohistochemistry. DISCUSSION/CONCLUSION: The pigmented variant of EAML can arise and metastasize from the kidney of a teenager with tuberous sclerosis.

[Expression of GPNMB in renal eosinophilic tumors and its value in differential diagnosis].

Objective: To investigate the expression of glycoprotein non metastatic melanoma protein B (GPNMB) in renal eosinophilic tumors and to compare the value of GPNMB with CK20, CK7 and CD117 in the differential diagnosis of renal eosinophilic tumors. Methods: Traditional renal tumor eosinophil subtypes, including 22 cases of renal clear cell carcinoma eosinophil subtype (e-ccRCC), 19 cases of renal papillary cell carcinoma eosinophil subtype (e-papRCC), 17 cases of renal chromophobe cell carcinoma eosinophil subtype (e-chRCC), 12 cases of renal oncocytoma (RO) and emerging renal tumor types with eosinophil characteristics [3 cases of eosinophilic solid cystic renal cell carcinoma (ESC RCC), 3 cases of renal low-grade eosinophil tumor (LOT), 4 cases of fumarate hydratase-deficient renal cell carcinoma (FH-dRCC) and 5 cases of renal epithelioid angiomyolipoma (E-AML)], were collected at the Affiliated Drum Tower Hospital of Nanjing University Medical School from January 2017 to March 2022. The expression of GPNMB, CK20, CK7 and CD117 was detected by immunohistochemistry and statistically analyzed. Results: GPNMB was expressed in all emerging renal tumor types with eosinophil characteristics (ESC RCC, LOT, FH-dRCC) and E-AML, while the expression rates in traditional renal eosinophil subtypes e-papRCC, e-chRCC, e-ccRCC and RO were very low or zero (1/19, 1/17, 0/22 and 0/12, respectively); the expression rate of CK7 in LOT (3/3), e-chRCC (15/17), e-ccRCC (4/22), e-papRCC (2/19), ESC RCC (0/3), RO (4/12), E-AML(1/5), and FH-dRCC (2/4) variedly; the expression of CK20 was different in ESC RCC (3/3), LOT(3/3), e-chRCC(1/17), RO(9/12), e-papRCC(4/19), FH-dRCC(1/4), e-ccRCC(0/22) and E-AML(0/5), and so did that of CD117 in e-ccRCC(2/22), e-papRCC(1/19), e-chRCC(16/17), RO(10/12), ESC RCC(0/3), LOT(1/3), E-AML(2/5) and FH-dRCC(1/4). GPNMB had 100% sensitivity and 97.1% specificity in distinguishing E-AML and emerging renal tumor types (such as ESC RCC, LOT, FH-dRCC) from traditional renal tumor types (such as e-ccRCC, e-papRCC, e-chRCC, RO),respectively. Compared with CK7, CK20 and CD117 antibodies, GPNMB was more effective in the differential diagnosis (P<0.05). Conclusion: As a new renal tumor marker, GPNMB can effectively distinguish E-AML and emerging renal tumor types with eosinophil characteristics such as ESC RCC, LOT, FH-dRCC from traditional renal tumor eosinophil subtypes such as e-ccRCC, e-papRCC, e-chRCC and RO, which is helpful for the differential diagnosis of renal eosinophilic tumors.

First Case Report of a Uterine Angiolipoleiomyoma With KRAS and KIT Mutations.

Angiolipoleiomyoma is a very rare lesion of the uterus. To the best of our knowledge, only 20 cases have been described in the literature. It is an insufficiently defined entity, which is not included in the WHO classification. This lesion may be therefore underdiagnosed and underestimated. We describe here a case of a 58-yr-old woman who underwent routine gynecological examination. Ultrasonography revealed a heterogeneous myometrial mass, while magnetic resonance imaging showed a voluminous corporeal and fundic myometrial mass protruding into the uterine cavity. A total hysterectomy was performed. The macroscopic examination revealed an intramural solitary round mass with a heterogeneous cut-surface. Microscopically, the lesion consisted of an admixture of smooth muscle, adipose tissue, and blood vessels. Desmin was positive, while HMB45 was negative in the tumor. Molecular tests were performed and revealed, for the first time to our knowledge, a case of an angiolipoleiomyoma harboring KRAS and KIT mutations.

Fine needle aspiration of hepatic angiomyolipoma with extramedullary hematopoiesis: A case report.

Angiomyolipoma, a perivascular epithelioid cell tumour, is easily identifiable as a benign tumour in the kidneys. However, when occurring in extrarenal sites it can mimic malignancy (Cancer Cytopathol. 2017;125:257). Pathologists must be aware of the classical morphological features of this lesion, its pitfalls in extrarenal sites, and the need for immunohistochemistry in order to establish the correct diagnosis (World J Gastroenterol. 2000;6:608). We report a case of angiomyolipoma with extramedullary hematopoiesis presenting as a large hepatic mass, diagnosed by cytology through endoscopic ultrasound guided fine needle aspiration. Our case exemplifies the classic cytological findings that are important in the differentiation between hepatic angiomyolipoma (HAML) and differentials in this organ such as hepatocellular carcinoma (HCC) and focal nodular hyperplasia. A brief literature review and comparison of significant features between HAML and HCC are presented.

Epithelioid angiomyolipoma of the liver: an incidental diagnosis.

We present the exceptional case of a 76-year-old woman with an incidental finding of a liver tumor compatible with an epithelioid angiomyolipoma, a rare neoformation about which there is still controversy regarding its management, due to its presumed potential for malignancy.

Primary Epithelioid Angiomyolipoma of Adrenal Gland: Case Report and Literature Review.

Angiomyolipomas (AMLs) are mesenchymal tumours derived from perivascular epithelioid cells. Although AMLs are generally known as benign and extremely rare epithelioid variants of AML, they may be potentially aggressive. Here we present an adrenal epithelioid AML and the literature review. A 64-year-old female patient was diagnosed with a left adrenal mass detected incidentally on ultrasonography. Preoperative abdominal CT (computed tomography) showed a 95×68 mm heterogeneous contrast enhancement mass lesion in the left adrenal gland. The lesion was hormone inactive in the endocrinological evaluation, and left laparoscopic adrenalectomy was performed. The patient was discharged on the 2nd postoperative day. Pathology was reported as epithelioid subtype AML. The patient has no local recurrence or metastasis in the 18-month follow-up period and imaging. Adrenal epithelioid AML is an extremely rare and potentially aggressive variant. According to the literature, open or laparoscopic adrenalectomy seems to be suitable option for disease management.

Tuberous sclerosis complex with skin lesions as the initial presentation: A case report and multidisciplinary discussion. / 1例以皮肤损害为首发症状的结节性硬化症并多学科讨论.

We reported a case of tuberous sclerosis complex with facial angiofibroma as the initial presentation and conducted a multidisciplinary discussion. The patient, a young female, was admitted to the Department of Dermatology for cosmetic purpose. After the examination, she was found to have multiple system involvement, including a large renal angiomyolipoma pressing on the liver. She never had any subjective symptom. After consultation by the multidisciplinary team of tuberous sclerosis complex, the patient was treated with everolimus orally and followed up regularly. It is suggested that dermatologists should pay attention to the systemic involvement of patients with tuberous sclerosis complex. Early intervention can prolong the life of patients and improve their life quality. Multidisciplinary collaboration for lifelong disease management is the key to enhance the diagnosis and treatment for tuberous sclerosis complex and enhance the prognosis of patients.

Renal tumors in tuberous sclerosis complex.

Tuberous sclerosis complex (TSC) is a multisystem hereditary disorder characterized by the growth of benign tumors (hamartomas) in multiple organs, including the kidneys. Renal angiomyolipomas (AML) are a major diagnostic feature of TSC and are present in the majority of patients by adulthood. However, AML are usually asymptomatic during childhood when neurological and developmental manifestations are the main source of morbidity. Kidney manifestations of TSC have historically been the main cause of morbidity and mortality of adults with TSC. The recognition that the complications of TSC are caused by dysregulation of the mammalian target of rapamycin (mTOR) pathway has led to an enormous progress in the management of patients with TSC in the last two decades, the establishment of diagnostic guidelines, and trials which have shown the therapeutic benefit of mTOR inhibitors. Kidney surveillance of children with TSC now provides the opportunity for timely interventions to reduce the impact of TSC in adulthood. In this review, we discuss the current management of kidney tumors associated with TSC, including the diagnosis, surveillance, and treatment options for these lesions. We also present outcome data from international registries demonstrating the effectiveness of the current management strategies. With clear management guidelines and efficient treatment of kidney tumors, we envisage that the long-term outcomes of patients with TSC will further improve in the future.

Epithelioid angiomyolipoma: a pathological entity discovered in Verona with the endorsement of Doctor Rosai.

In this manuscript, we summarize the main features of angiomyolipoma highlighting the recognition of epithelioid angiomyolipoma and the discovery of immunohistochemical expression of HMB45 in a group of tumors that now are referred to as as PEComas. In this scenario, Dr. Rosai believed in our intuition, demonstrating his intellectual honesty and motivated us with his experience ("when a tumor seems malignant it is malignant") and enthusiasm for the new entities ("in Verona, you use HMB45 instead of H&E"). He really pushed the improvement of the knowledge in this field.

Epithelioid angiomyolipoma mimicking metastatic melanoma in a liver tumor.

It is well known to pathologists that melanoma is "the great mimicker," looking like almost any other tumor, and able to metastasize anywhere in the body. We report a case of a 48-year-old female with a history of metastatic melanoma 4 years before, who presented with a hepatic mass. Microscopic examination of the liver mass revealed sheets of pleomorphic, epithelioid cells, which expressed a pan-melanocytic cocktail (MART1, HMB45, and tyrosinase). These findings were initially interpreted as metastatic melanoma and the case was transferred for dermatopathology consultation. We compared the morphology of this tumor to the primary melanoma and noticed that the primary melanoma showed nevoid cytology, morphologically distinct from the liver lesion. Consequently, we performed additional immunohistochemical studies, which determined that the liver mass was negative for S100 and SOX10, and established a final diagnosis of epithelioid angiomyolipoma. The key for reaching the correct diagnosis was the morphologic comparison with the original lesion and the evaluation of a wider immunohistochemical profile. For appropriate management in patients with new lesions, even in the context of a patient with known metastatic disease, it is essential to consider other neoplasms in the differential diagnosis.

Imaging hepatic angiomyolipomas: key features and avoiding errors.

Hepatic angiomyolipomas (HAMLs) are rare mesenchymal neoplasms, which have highly variable imaging appearances, often leading to misdiagnosis. They belong to the family of perivascular epithelioid cell neoplasms (PEComas). HAMLs have a wide spectrum of imaging appearances due to variable amounts of smooth muscle cells, adipose tissue, and blood vessels in their makeup. Although typically sporadic, they are also associated with tuberous sclerosis. Sporadic lesions tend to be solitary whilst patients with tuberous sclerosis often have multiple HAMLs invariably accompanied by renal AMLs. Having been originally considered benign hamartomas, increasing reports of complications, including malignant behaviour, has also resulted in uncertainty in regard to their optimal management. Typically described imaging characteristics are of a hypervascular fat-containing lesion with prominent intratumoural vessels and an early draining vein; however HAMLs commonly demonstrate a paucity of fat or wash-out on contrast-enhanced imaging, and not all HAML lesions are hypervascular. HAMLs can therefore easily be misdiagnosed as other hepatic lesions, in particular hepatocellular carcinoma. This review describes the imaging characteristics of HAMLs, illustrating the wide variety of potential appearances across ultrasound, contrast-enhanced ultrasound, computed tomography, and magnetic resonance imaging, and highlights the challenges and potential errors that can be made. This review will aid radiologists in avoiding potentially major pitfalls when faced with this rare but important liver pathology.

Renal angiomyolipoma: Clinico-pathologic study of 17 cases with emphasis on the epithelioid histology and p53 gene abnormalities.

BACKGROUND: Epithelioid angiomyolipoma (EAML) is a rare potentially malignant variant of renal angiomyolipoma (RAML). This study aims to determine whether RAML clinico-pathologic and molecular features (i.e. p53 gene abnormalities) differ significantly with regards to its histologic variant or to the presence of an epithelioid component within it. METHODS: Consecutively resected RAML were reviewed, tumours comprising at least 80% of epithelioid cells were considered as EAML according to the 2016 World Health Organization classification of tumours of the kidney. P53 gene abnormalities were investigated using both immunohistochemical and molecular analysis. RESULTS: A total of 3 EAML among 17 RAML were identified, accounting for 3.9% of the total AML cases. Fatty aspect on imaging was more observed within tumours devoid of an epithelioid component. EAML showed a higher mitotic rate and a stronger p53 staining, no renal poles involvement and was not treated by nephron sparing surgeries. RAML comprising an epithelioid component demonstrated severer nuclear atypia as well as stronger p53 staining. P53 gene sequencing revealed a missense mutation (c.747G > C) in one classic AML harbouring a strong labelling with p53. CONCLUSIONS: Strong p53 staining in a RAML, even in the absence of gene mutation, may suggest the presence of an epithelioid component or of a truly EAML. To the best of our knowledge, c.747G > C p53 gene mutation is being reported for the first time in a RAML, although its role in AML pathogenesis is still unknown.

[Angiomyolipoma of the liver-a case report and review of the literature]. / Angiomyolipom der Leber ­ Ein Fallbericht in Zusammenschau mit der Literatur.

We report the case of a 70-year-old female patient with an unclear liver mass after clinical and radiological evaluation. In histopathological evaluation, we diagnosed a hepatic angiomyolipoma, which is a rare entity and belongs to the perivascular epithelioid group of tumours (PEComa). In this report, we illustrate the typical histomorphology, immunohistochemical profile and molecular changes based on the case presentation and discuss and review the current literature on hepatic angiomyolipomas. In addition, typical differential diagnostic problems are highlighted.

[Hereditary kidney cancers: The pathologist's view in 2020]. / Les cancers du rein héréditaires vus par le pathologiste en 2020.

Hereditary predispositions to adult kidney tumors involve around 5% of tumors and include a dozen of autosomal dominant syndromes. The most frequent tumors encountered in these setting are clear cell renal cell carcinomas, papillary renal cell carcinomas, chromophobe renal cell carcinomas and angiomyolipomas. Their detection is essential in order to adapt individual care and perform genetic screening of at-risk relatives, especially in the national french network PREDIR, labeled by the National Cancer Institute and dedicated to hereditary predispositions to kidney tumors. Targeted genetic analysis, which was guided in particular by the renal tumor subtype, has recently evolved into genetic analysis using panels of genes. Pathologist contribution's remains however central in the diagnosis of hereditary forms since we currently have immunohistochemical biomarkers that allow us to diagnose two specifically hereditary entities: hereditary leiomyomatosis and renal cell carcinoma associated-renal cell carcinoma, associated with a loss of fumarate hydratase and succinate dehydrogenase-deficient renal cell carcinoma associated with a loss of succinate deshydrogenase B expression. These diagnoses must however be confirmed by the identification of pathogenic germline variation in the corresponding genes. Improvement of kidney tumors characterization has also lead to identify new subtypes, expanding the algorithm of renal tumors associated with hereditary setting. Here we aim to review all subtypes of adult renal tumors encountered in predisposition syndromes.

Hepatic angiomyolipoma: an international multicenter analysis on diagnosis, management and outcome.

BACKGROUND: Hepatic angiomyolipoma (HAML) may easily be misdiagnosed as a malignancy. The study aim was to assess diagnostic dilemmas, clinical management and outcome of this rare tumor. METHODS: This retrospective international multicenter study included all patients with pathologically proven HAML diagnosed between 1997 and 2017. Data on patient characteristics, diagnostic work-up, management and follow-up were analyzed. RESULTS: Thirty-eight patients were included, 32 female. Median age was 56yrs (i.q.r. 43-64) and median HAML-diameter was 57.5 mm (i.q.r. 38.5-95.3). Thirty patients had undergone CT and 27/38 MRI of the liver, diagnostic biopsy was performed in 19/38. Initial diagnosis was incorrect in 15/38 patients, of which 13 were thought to have malignancy. In 84% biopsy resulted in a correct preoperative diagnosis. Twenty-nine patients were managed with surgical resection, 4/38 with surveillance and 3/38 with liver transplantation. Recurrence after resection occurred in two cases. No HAML related deaths or progression to malignancy were documented. CONCLUSION: HAML diagnosis proved problematic even in hepatobiliary expertise centers. Biopsy is indicated and may provide valuable additional information when HAML diagnosis is considered on cross-sectional imaging, especially when surgical resection imposes a risk of complications. Conservative management with regular imaging follow-up might be justified when biopsy confirms (classic type) HAML.

[Abdominal pain and unclear focal liver lesion in 46-year-old female patient]. / Rechtsseitiger Oberbauchschmerz und unklare Leberraumforderung bei einer 46-jährigen Patientin.

A 46-year-old woman presented with recurrent right upper quadrant pain. Abdominal ultrasound revealed an inhomogeneous liver lesion (4â€¯× 7 cm) with complex echotexture. Since further contrast-enhanced imaging tests were inconclusive and lesion integrity remained unclear, a left hemihepatectomy was performed. Histological examination revealed a hepatic epithelioid angiomyolipoma. Hepatic epithelioid angiomyolipoma is a rare, mostly benign, mesenchymal hepatic tumor, composed of smooth muscle cells, adipose tissue, and blood vessels of varying proportions, and its correct diagnosis remains a clinical challenge.

Benign liver angiomyolipoma: a case study.

INTRODUCTION: Hepatic angiomyolipoma is a rare mesenchymal tumor. It consists of vessels, fatty tissue and muscle tissue. These can appear in various ratios. While the kidney is the most common localization of angiomyolipoma, only about 300 cases have been described in the liver so far. It is a tumor of uncertain behavior. Most of the patients suffering from the lesion is asymptomatic. It is often preoperatively misdiagnosed using various imaging methods given its similarity to other hepatic tumors. CASE REPORT: Our 64 years old female patient was being examined for dull abdominal pains with no other symptoms. Her close relatives suffered from no malignancies. Imaging exams showed a liver lesion highly suspicious for hepatocellular carcinoma. However, the patient showed no elevation of typical oncomarkers. We performed left lateral sectionectomy. A grey solid focal lesion was found in the resected tissue. Histological and immunohistochemical evaluation determined the diagnosis of angiomyolipoma. The postoperative period was uncomplicated. The patient has been followed at an office for hepato-pancreato-biliary diseases, with no signs of recurrence until the present. CONCLUSION: Hepatic angiomyolipoma is a rare disease. The diagnostic process can be challenging as illustrated by the presented case. Even though the working diagnosis proved false, the chosen treatment was appropriate and delivered good results. Long-term postoperative follow-up is required.

Renal angiomyolipoma in patients with tuberous sclerosis complex: findings from the TuberOus SClerosis registry to increase disease Awareness.

BACKGROUND: Renal angiomyolipoma occurs at a high frequency in patients with tuberous sclerosis complex (TSC) and is associated with potentially life-threatening complications. Despite this frequency and severity, there are no large population-based cohort studies. Here we present baseline and follow-up data of the international TuberOus SClerosis registry to increase disease Awareness (TOSCA) with an aim to provide detailed clinical characteristics of renal angiomyolipoma among patients with TSC. METHODS: Patients of any age with a documented clinic visit for TSC within 12 months or who were newly diagnosed with TSC before participation in the registry were eligible. Data specific to renal angiomyolipoma included physical tumour characteristics (multiple, bilateral, lesion size and growing lesions), clinical signs and symptoms, and management. The effects of age, gender and genotype on the prevalence of renal angiomyolipoma were also evaluated. RESULTS: Renal angiomyolipoma was reported in 51.8% of patients at baseline, with higher frequency in female patients (57.8% versus 42.2%). The median age at diagnosis was 12 years. Prevalence of angiomyolipoma was higher in patients with TSC2 compared with TSC1 mutations (59.2% versus 33.3%, P < 0.01). Of the 1031 patients with angiomyolipoma at baseline, multiple lesions were reported in 88.4% and bilateral in 83.9% of patients, while the size of angiomyolipoma was >3 cm in 34.3% of patients. Most patients were asymptomatic (82%). Frequently reported angiomyolipoma-related symptoms included bleeding, pain, elevated blood pressure and impaired renal function. Embolization and mammalian target of rapamycin inhibitors were the two most common treatment modalities. CONCLUSIONS: The TOSCA registry highlights the burden of renal angiomyolipoma in patients with TSC and shows that renal manifestations are initially asymptomatic and are influenced by gender and genotype. Furthermore, the occurrence of significant problems from angiomyolipoma in a minority of younger patients suggests that surveillance should begin in infancy or at initial diagnosis.

Can we predict the existence of extrarenal feeders to renal angiomyolipomas?

OBJECTIVES: To identify factors predicting the presence of extrarenal feeders to renal angiomyolipomas (AMLs) METHODS: This is a retrospective study of 44 patients with 58 renal AMLs embolized in our department. Arteriography obtained during embolization and CT angiography obtained before and after embolization were reviewed to characterize AMLs with and without extrarenal feeders. Tumor characteristics were compared between the two groups. Simple logistic regression and ROC curve analysis were performed. P < 0.05 was considered to be statistically significant. RESULTS: Of the 58 AMLs reviewed, 29% had extrarenal arteries and 71% did not. AMLs with extrarenal feeders were significantly larger than those without, in terms of volume (median, 368 mL versus 109 mL, p < 0.0002) and the largest diameter (mean, 12.0 cm versus 7.7 cm, p < 0.0001). Patient age, presence of tuberous sclerosis complex or sporadic lymphangioleiomyomatosis, and tumor location did not differ between the groups. The largest diameter and volume had similar predictive values for the presence of extrarenal feeders (AUC, 0.83 versus 0.82, p = 0.673). Extrarenal feeders were present in 0%, 21%, and 79% of the AMLs ≤ 6.5 cm, AMLs 6.6-10.5 cm, and AMLs > 10.5 cm, respectively. CONCLUSIONS: AML size correlates with the presence of extrarenal feeders, with the largest diameter and volume being significant predictors. AMLs > 10.5 cm had a high chance of extrarenal feeders, making it mandatory to search for feeders to them in order to avoid incomplete embolization; AMLs ≤ 6.5 cm did not have extrarenal feeders, making a search for them unnecessary in these cases. KEY POINTS: • The presence of extrarenal feeders to renal angiomyolipoma is associated with tumor size, but not with patient age, concomitant disease, or tumor location. • The largest diameter and volume predict the presence of extrarenal feeders to AML, with similar predictive values. • AMLs > 10.5 cm have a high chance (79%) of extrarenal feeders, making it mandatory to search for feeders to them in order to avoid incomplete embolization; AMLs ≤ 6.5 cm do not have extrarenal feeders, making a search for them unnecessary in these cases.