Epithelioid angiomyolipoma: a morphologically distinct variant that mimics a variety of intra-abdominal neoplasms

This review examines the histopathologic, immunohistochemical, ultrastructural, and molecular biologic features of epithelioid angiomyolipoma (EAML), with an emphasis on the differential diagnosis of intra-abdominal EAML. Epithelioid angiomyolipoma is an uncommon mesenchymal tumor with malignant potential, frequently associated with tuberous sclerosis complex. Histologically, EAML is characterized by sheets or nests of large polygonal epithelioid cells with abundant eosinophilic or occasionally clear cytoplasm, often with prominent nucleoli, and EAML may include multinucleated and markedly pleomorphic forms. As these tumors share a distinctive perivascular epithelioid cell phenotype, they belong to the PEComa tumor family. Nearly all EAMLs show immunoreactivity for both melanocytic and myoid markers. Ultrastructurally, EAMLs show evidence of melanogenesis by the presence of premelanosomes. Epithelioid angiomyolipoma can pose significant diagnostic challenges as it mimics morphologically a variety of neoplasms including renal cell carcinoma, renal oncocytoma, adrenal cortical neoplasm, epithelioid smooth muscle tumor, epithelioid peripheral nerve sheath tumor, epithelioid gastrointestinal stromal tumor, epithelioid melanoma, hepatoblastoma, and hepatocellular carcinoma. The variation in immunophenotype in these tumors requires a prudent use of immunohistochemistry, which may occasionally need complementation by electron microscopy to establish the correct diagnosis.     

Clinicopathologic features of renal epithelioid angiomyolipoma: report of one case and review of literatures

Epithelioid angiomyolipoma (EAML) is a rare renal mesenchymal tumor with malignant potential and is frequently associated with tuberous sclerosis complex (TSC). As metastasis of the tumor cells occur early, EAML is considered a potentially malignant tumor type and intrigues further research on it. Under the microscope, we could find the tumor was composed of atypical polygonal cells sheet mixed with classic angiomyolipoma (AML) components such as blood vessels with notable thick vascular walls, smooth muscle-like cells and adipocytes. Immunohistochemical studies showed that epithelioid cells were focally positive for vimentin, melanocytic markers (HMB-45), myoid markers (α-smooth muscle actin), CD34 and CD68; negative for cytokeratin, epithelial membrane antigen, CD10, and S-100. And the Ki67 index showed approximately 3%. Here, we report the morphological and immunohistochemical features of clinically or histologically malignant renal EAML and discuss its diagnosis, differential diagnosis and the prognosis.     

Multiple giant angiomyolipomas with a polygonal epithelioid cell component in tuberous sclerosis: An autopsy case report

A recent case of angiomyolipoma (AML) with a prominent Component of polygonal epithelioid cells is described. A 27-yearoid Japanese male with tuberous sclerosis presented with massive abdominal tumors increasing progressively in size. The patient died of respiratory disturbance and the autopsy revealed massive tumors in the bilateral kidneys, liver and lymph nodes, subependymal giant cell glioma of the brain and lymphangiomyomatosis of the lungs. The giant tumors were an unusual type of AML with a component of polygonal epithelioid cells, which showed a hepatocel-lular carcinoma-like pattern in some areas. Smooth muscle components comprising spindle cells, short or plump spindle cells and polygonal epithelioid cells frequently exhibited positive staining for HMB-45 but negative staining for epithelial cell markers. The unusual AML presented in this case was thought to be of low-grade malignancy and slow growing. it has been suggested that angiomyollpomas with diffuse areas of epithelioid cell component are potentially malignant. Immunostalnings positive for HMB-45 but negative for epithelial cell markers are considered to be useful in differentiating AML with polygonal epithelioid cell component from other tumors, especially from renal cell carcinoma and hepatocellular carcinoma.     

Hepatic epithelioid angiomyolipoma with trabecular growth pattern: a mimic of hepatocellular carcinoma on fine needle aspiration cytology

Epithelioid angiomyolipomas (AMLs) of the liver are rare tumors with imaging and cytologic features overlapping with those of hepatocellular carcinomas. We report the fine needle aspiration and core biopsy findings of an epithelioid AML in the right hepatic lobe of a 32-year-old female with tuberous sclerosis. She had undergone renal transplantation 8 years previously after bilateral nephrectomy for renal AMLs and a 3-cm chromophobe renal cell carcinoma. Hepatocellular carcinoma was suspected during the initial cytologic and histologic examination based on the presence of numerous large polygonal cells with ample finely vacuolated or granular cytoplasm, low nucleocytoplasmic ratio, and mild nuclear pleomorphism in the smears, as well as a distinctive trabecular histologic pattern in the core biopsies. Immunoperoxidase stains showed that the neoplastic cells were negative for cytokeratins and positive for HMB45, Melan-A, and smooth muscle actin, establishing the diagnosis of epithelioid AML. To determine the distinguishing cytomorphologic features between epithelioid AML and HCC, we have compared the cytologic features of 15 cases of hepatic AML reported in the literature, including the present case, to the FNA cytologic findings of 38 consecutive cases of HCC diagnosed at out institution.     

Renal epithelioid angiomyolipoma: Histopathologic review,immunohistochemical evaluation and prognostic significance

Epithelioid angiomyolipoma (EAML) is considered to be a potentially malignant tumor and requires a differential diagnosis from renal cell carcinoma. In this study, we assessed the clinicopathologic features of renal EAML and evaluated the prognostic significance. Among 78 angiomyolipoma (AML) patients, a total of 5 EAMLs were identified, accounting for 6.4% of the total AML cases. The mean age was 41.4 years, and the average tumor size was 12.7 cm in diameter. Association of tuberous sclerosis complex was identified in two cases. One EAML case showed malignant behavior with local recurrence and distant metastasis. The malignant EAML had a larger tumor size, a higher percentage of epithelioid component and atypical epithelioid cells, ≥2 mitoses per 10 high power fields with atypical mitosis, necrosis, extrarenal extension, and carcinoma‐like growth pattern. Furthermore, the malignant case revealed p53 immunoreactivity and decreased membranous E‐cadherin expression. Pathologic evaluation of adverse prognostic factors will be helpful for risk stratification and prognosis estimation of EAML patients.     

Sclerosing variant of epithelioid angiomyolipoma

Presented herein are two unusual epithelioid angiomyolipomas (AML) displaying prominent stromal sclerosis. Both patients were middle-aged women without a clinical history of tuberous sclerosis. One patient (case 1) had a 2 cm lesion arising in the renal cortex, and another (case 2) had a pararenal retroperitoneal tumor measuring 13 cm. Both tumors were composed of sheets or nests of polygonal epithelioid or short spindle cells having uniform round to oval nuclei and eosinophilic cytoplasm with cords of hyalinized sclerotic stroma between them. The tumor in case 2 had small areas of mature-looking fat cells. Immunohistochemically, epithelioid tumor cells were diffusely positive for actins and desmin in both cases, and melanoma antigen recognized by T cells (MART)-1 was positive in patient 2. Scattered HMB-45-immunoreactive cells were identified in the sclerotic cords of both tumors, but epithelioid tumor cells were essentially negative for HMB-45. The characteristic clinicopathological and immunohistochemical features of the present cases are analogous to a subset of epithelioid AML or sclerosing perivascular epithelioid cell tumors previously reported.     

Atypical angiomyolipoma of kidney in a patient with tuberous sclerosis: a case report with p53 gene mutation analysis

Angiomyolipoma (AML) is the most common benign mesenchymal tumor of the kidney. It belongs to the family of perivascular epithelioid cell tumors and is typically composed of blood vessels, adipose tissue, and smooth muscle- like cells, which are characteristically positive for HMB-45. Results of recent studies suggest that p53 mutation may play an important role in AML progression. Here, we describe a locally destructive renal AML in a patient with tuberous sclerosis. The tumor consisted of mostly epithelioid cells with marked nuclear pleomorphism and frequent mitoses and was positive for HMB-45. The diagnosis of atypical epithelioid AML was made. Codon alteration in the p53 gene was not detected, despite focal p53 immunoreactivity and single nucleotide polymorphism at exon 6. Our finding indicates no definite link between p53 abnormalities and the atypical appearance of AML. To the best of our knowledge, this is the second renal AML case investigated for p53 mutations.     

Angiomyolipoma of the kidney--an immunohistochemical study

The study included 25 patients with angiomyolipoma of the kidney. None of them had any signs of tuberous sclerosis. Serious clinical complications such as massive hemorrhage (2/25) and hydronephrosis (2/25) were documented in four patients. Concomitant adenoma of the adrenal gland and renal cell carcinoma were found in one patient each. All tumors consisted of a differing mixture of mature adipose tissue, smooth muscle cells and blood vessels, with thickened walls devoid of elastic lamina. Immunohistochemically, the smooth muscle cells stained strongly with antibodies against vimentin, desmin and actin, as well as HMB-45 and NKI/C3. Immunohistochemical staining for NKI/C3 was stronger and more diffusely distributed. These two markers proved to be very useful in the diagnosis of angiomyolipoma, when only needle biopsy specimens are available.     

Mucocutaneous angiomyolipoma. A report of 2 cases arising in the nasal cavity.

OBJECTIVE: Angiomyolipoma (AML) is a distinctive tumor that usually occurs in the kidney and rarely in the liver. Angiomyolipoma of other sites is extremely rare, and, to our knowledge, only 2 cases have been described in the nasal cavity. We present 2 additional cases of AML of the nasal cavity and discuss the difference between them and renal AML. CASE REPORTS AND PATHOLOGIC FINDINGS: Two tumors in a 66-year-old man and an 88-year-old woman without tuberous sclerosis are described. They showed 20-mm, well-circumscribed, polypoid shapes. Histologically, they were composed of mature smooth muscle cells, fat cells, and various-sized blood vessels. In addition, aggregated small lymphocytes were noted. Neither epithelioid smooth muscle cells nor HMB45 immunoreactivity was seen in either case. CONCLUSIONS: The clinicopathologic features of AML of the nasal cavity are distinct from renal and hepatic AML and are common to those of AML arising in the skin and oral and pharyngeal mucosa. The term mucocutaneous angiomyolipoma is thought to be appropriate to express these characteristic tumors.     

Renal epithelioid angiomyolipoma with malignant features: Histological evaluation and novel immunohistochemical findings

Renal epithelioid angiomyolipoma (EAML) is a potentially malignant tumor type whose characteristics and biomarkers predictive of malignant behavior have not been elucidated. Here, we report three cases of renal EAML with malignant features but without histories of tuberous sclerosis complex. Case 1 involved a 29‐year‐old man with a 12‐cm solid mass in the right kidney who underwent radical right nephrectomy. Case 2 involved a 22‐year‐old woman with a retroperitoneal mass who underwent radical right nephrectomy and retroperitoneal tumorectomy. Local recurrence was detected 7 years post‐surgery. Case 3 involved a 23‐year‐old man with a 14‐cm solid mass in the left kidney who underwent radical left nephrectomy. Microscopically, the tumors in all cases demonstrated proliferation of epithelioid cells with atypia, mitotic activity, necrosis, hemorrhage, and vascular invasion. Epithelioid cells in all cases were immunohistochemically positive for melanocytic and myoid markers and weakly positive for E‐cadherin and β‐catenin. Immunohistochemistry revealed activation of the mammalian target of rapamycin pathway. Here, we report the morphological and immunohistochemical features of clinically or histologically malignant renal EAML.     

Angiomyolipoma of the liver and lung: a case explained by the presence of perivascular epithelioid cells

We report a case of synchronous hepatic and pulmonary angiomyolipoma not associated with tuberous sclerosis or renal angiomyolipoma. The liver tumor contained tortuous vessels, smooth muscle tissue, and fat. It was partially necrotic and made up of pleomorphic epithelioid smooth muscle cells. Positivity for HMB-45 confirmed the diagnosis of angiomyolipoma. Lung biopsy showed multiple abnormal proliferation of smooth muscle cells exhibiting spindle-shaped or epithelioid morphology. The tumor grew around the vessels, and the cells were positive for HMB-45. The occurrence of this case could be explained by a simultaneous proliferation of perivascular epithelioid cells. To the best of our knowledge, this is the first case of hepatic angiomyolipoma associated with multiple pulmonary angiomyolipomas, mimicking hepatic tumor lung metastases on X-ray examination.     

Abdominopelvic sarcoma of perivascular epithelioid cells. Report of four cases in young women, one with tuberous sclerosis.

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. We report four examples of a new member of this family of perivascular epithelioid cell neoplasms that occur in abdominopelvic location and show metastatic properties. The patients, all women, were aged 19 to 41 years (mean, 32), and presented with a tumor mass involving the serosa of the ileum, uterus or pelvic cavity. Morphologically, the tumors were composed of sheets of large polygonal cells with glycogen-rich clear or eosinophilic cytoplasm and moderately pleomorphic nuclei, traversed by a delicate vasculature, mimicking clear cell carcinoma. There were areas of coagulative necrosis and occasional mitotic figures. Intracytoplasmic brown pigment was present in two cases. Spindly cells, smooth muscle and fat were absent. Lymphovascular invasion was present in all, lymph node metastasis was documented in two and metastasis to the ovary was present in one case. Two patients developed widespread metastatic disease after 10 and 28 months from diagnosis. One patient showed the clinical signs of tuberous sclerosis. In spite of the epithelial-like appearance, the tumor cells were negative for epithelial markers but were strongly positive with the melanogenesis-related marker HMB45. Another melanogenesis marker (MART-1) was positive in two cases. Other markers including S-100 protein, vimentin, muscle-specific actin, desmin and chromogranin A were negative. Thus, these tumors are not readily classifiable in the existing schema of known entities, and show overlapping morpho-phenotypic features of clear cell "sugar" tumor of the lung and epithelioid angiomyolipoma. We consider them as sarcomas composed of a pure population of uncommitted perivascular epithelioid cell, that lack modulation toward smooth muscle or adipose cells.     

C-Kit-positive metastatic malignant pigmented clear-cell epithelioid tumor arising from the kidney in a child without tuberous sclerosis

We report the first pediatric case of malignant pigmented epithelioid clear-cell tumor arising from kidney; the lesion occurred in a 12-year-old girl without tuberous sclerosis. The tumor was widely metastatic to the retroperitoneum and chest, and the patient died of the disease 9 months after diagnosis, despite active chemotherapy. Pigmented epithelioid clear-cell tumor of the kidney is a rare variant of epithelioid angiomyolipoma and a member of the family of perivascular epithelioid cell tumors (PEComas). The tumor demonstrated overlapping features between clear-cell sugar tumor and epithelioid variant of angiomyolipoma. Tumor cells were positive for HMB-45 expression, negative for any evidence of muscular differentiation, and contained melanin pigment and premelanosomes in the cytoplasm. Diffuse C-Kit (CD117) positivity was identified throughout the tumor. This is the first report of C-Kit–positive malignant PEComas.     

Perivascular epithelioid cell tumor of the uterus: a case report

A case of a perivascular epithelioid cell tumor (PEComa) arising in the uterus of a 35-year-old woman is presented. Imaging studies revealed a 5 cm well circumscribed mass in the uterine fundus. The tumor was composed of clear to faintly eosinophilic, epithelioid and spindled cells. Immunohistochemically, most tumour cells were strongly positive for HMB-45, smooth muscle actin and desmine, but negative for epithelial markers, S-100 Protein and neuroendocrine markers. Reevaluation of the patient for signs of tuberous sclerosis complex after the diagnosis gave negative results. At the most recent follow-up 4 months later there was no evidence of recurrence.     

肾上皮样血管平滑肌脂肪瘤肺转移1例报告并文献复习

目的：探讨肾上皮样血管平滑肌脂肪瘤病理特点及生物学行为。方法：对1例低热患者行肺肿块穿刺活检,然后行HE染色和免疫组织化学染色。复习肾肿瘤病理切片并进行文献复习。结果：穿刺活检病理分析：密集分布的上皮样细胞,细胞体积大,呈圆形、多边形;异型明显;无血管平滑肌脂肪瘤结构;免疫组织化学：人黑色素瘤蛋白阳性,平滑肌肌动蛋白阳性,上皮膜抗原阴性。病理诊断：左肺上皮样血管平滑肌脂肪瘤;考虑来源于肾。结论：上皮样血管平滑肌脂肪瘤是一种有恶性潜能的间叶性肿瘤,可以发生远处转移。     

Renal epithelioid angiomyolipoma--a close mimic of renal cell carcinoma. Report of a case and review of the literature

The epithelioid variant of angiomyolipoma (EAML) is a rare tumor of unpredictable behavior that is composed of epithelioid, spindle, and giant cells and contains no or only a minimal amount of lipomatous tissue. The picture can lead to an erroneous diagnosis of renal cell carcinoma or sarcoma. We report on a case of EAML in the kidney of a 47-year-old female without any signs of tuberous sclerosis and review the literature. Grossly, a well-demarcated, spheroid, largely hemorrhagic tumor measuring 4.2 cm in diameter occupied the central third of the kidney. Histologically, it was solid, highly cellular, with occasional microcysts, composed of medium to large epithelioid cells with clear or oxyphilic cytoplasm, short spindle cells, and numerous giant multinucleated cells. After extensive sampling, adult-appearing fat tissue was found to present as rare foci of microscopic dimensions. Immunohistochemically, the tumor cells showed positive reactions with antibodies against HMB-45, melan A, CD-68, muscle-specific actin, and, rarely, smooth muscle actin. Cytokeratins and epithelial membrane antigen were negative. The EAML is a variant growing in a carcinoma-like pattern that can lead to an erroneous diagnosis of renal cell carcinoma. An extensive sampling and HMB-45 and CD-68 positivity combined with cytokeratin negativity are of paramount importance for the correct diagnosis. As a sporadic renal tumor it followed a benign course in most of the reported cases.     

Primary adrenal gland epithelioid sarcoma: A case report and literature review

Epithelioid sarcoma is a malignant mesenchymal neoplasm with morphologic and immunophenotypic epithelioid differentiation, which rarely arises in solid organs. We report a case of primary epithelioid sarcoma in the adrenal gland of a 31‐year‐old female. The patient initially presented with nausea and rectal bleeding, and subsequent imaging studies revealed a 4.4 cm left adrenal gland mass and left retroperitoneal lymphadenopathy. Clinical and radiological studies did not reveal tumor elsewhere in the patient. Histologic features were those of epithelioid sarcoma, proximal type with cohesive clusters of epithelioid tumor cells harboring frequent mitoses, and areas of necrosis. Immunohistochemical stains showed strong, diffuse expression of epithelial markers (pancytokeratin), and CD34 and Fli‐1. Partial and focal positive staining of CK7 was also noted. Nuclear expression of SMARCB1 (INI‐1) protein was lost. ERG was negative in this case. We believe that this is the second‐case report of a primary adrenal gland epithelioid sarcoma. Fli‐1 positivity was seen in our case, and ERG was negative as shown in some recent publications regarding epithelioid sarcomas.     

Multiple angiomyolipomata of the liver: a case report.

Angiomyolipoma (AML) is a rare benign tumor that occurs most commonly in the kidney. Occasionally it may be found in the liver. Lesions in the liver are usually solitary. Multiple AMLs are extremely rare and are typically seen in patients with tuberous sclerosis. We now report an unusual case of a 46-year-old woman with multiple hepatic AMLs. There were more than 15 lesions distributed predominantly in the right hepatic lobe. The tumors ranged from 0.2 to 6 cm in size and consisted of a variable admixture of proliferating blood vessels, adipose tissue, and smooth muscle. There was no clinical evidence of tuberous sclerosis in this patient. Polymerase chain reaction amplification of the highly polymorphic human androgen receptor gene (HUMARA) was performed and the pattern of X chromosome inactivation was analyzed. Three of the five representative AML nodules showed a preferential loss of one of the two HUMARA alleles indicating a clonal proliferation with involvement of different alleles. Histologic examination of the corresponding lesions showed clonal lesions to be predominantly composed of epithelioid myoid cells while the polyclonal lesions were predominantly composed of adipose tissue. While the histologic diagnosis of AML in a surgical resection specimen is often straightforward, the radiographic, cytologic and intra-operative interpretation of a case with multiple lesions presents a considerable challenge.     

Epithelioid angiomyolipoma of the kidney: case report

Renal angiomyolipoma is a benign tumour histologically characterized by a mixture of adipose tissue, smooth muscle cells and thick walled blood vessels. Long-believed to be a benign hamartoma, angiomyolipoma is now considered to arise from perivascular epithelioid cells. Epithelioid angiomyolipoma is a rare type of angiomyolipoma, composed partially or completely of epithelioid cells, with a potentially aggressive behaviour. Histologically it can mimic renal cell carcinoma. Positivity for HMB45, Melan A, CD68 and CD117 are useful for diagnosis. Herein, we report the clinicopathologic and immunohistochemical features of a renal tumour composed of large epithelioid mononucleated or multinucleated cells with abundant acidophilic cytoplasm and prominent nucleoli. Despite the morphologic resemblance of this tumour to renal cell carcinoma, its phenotype (HMB45, Melan A and CD68 positivity and keratin negativity) parallels the phenotypic profile of angiomyolipoma. Therefore, immunohistochemistry should be considered when diagnosing this variant of angiomyolipoma.