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.     

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.     

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.     

Epithelioid angiomyolipoma of kidney with atypical nuclear features and intranuclear inclusions on cytology

Described herein are the cytological findings of epithelioid angiomyolipoma (EAML) of the kidney with atypical nuclear features mistaken for renal cell carcinoma (RCC) in a 61‐year‐old male patient. Aspirates from this large renal mass were cellular and showed epithelioid cell clusters with focally crowded nuclei showing moderate anisonucleosis, small nucleoli, and prominent eosinophilic intranuclear inclusions. Failure to recognize the scanty adipose tissue component and preponderance of epithelioid cells with nuclear pleomorphism lead to a diagnosis of RCC on cytology. On histology, the tumor was essentially composed of epithelioid and spindle cells that showed the typical immunoprofile of an angiomyolipoma and only occasional foci of typical AML were seen. The hilar lymph node was involved in contiguity. However, in view of lack of obvious features of malignancy, the tumor was labeled as EAML with atypical features. Immunocytochemistry on the destained cytology aspirates revealed strong smooth muscle actin staining of all cells. To conclude, EAML can mimic a RCC. In such instances, lack of arborizing vasculature, absence of cytoplasmic fatty vacoulation, crowded nuclei with intranuclear inclusions, and lack of prominent nucleoli along with typical immunophenotype of EAML may assist in the cytology diagnosis. Diagn. Cytopathol. 2011;39:278–282. © 2010 Wiley‐Liss, Inc.     

Monotypic epithelioid angiomyolipoma of the adrenal gland: an unusual site for a rare extrarenal tumor

Epithelioid angiomyolipoma (AML) is an uncommon renal mesenchymal tumor with malignant potential and is frequently associated with tuberous sclerosis. Extrarenal AMLs are rare, and to the best of our knowledge, this is the first reported case of a primary monotypic epithelioid AML of adrenal gland in a patient without evidence of tuberous sclerosis. The patient is a 42-year old man who presented with retroperitoneal hemorrhage resulting from spontaneous rupture of adrenal mass. Histologically, the tumor showed a prominent component of epithelioid smooth muscle cells with slightly pleomorphic nuclei, sometimes with prominent nucleoli and eosinophilic cytoplasm resembling oncocytic tumors. Epithelioid cells were positive for melanoma (HMB45 and positive MelanA) and smooth muscle markers (α-smooth muscle–specific actin), but not for epithelial markers (cytokeratin, EMA). Differential diagnosis from renal cell carcinoma, adrenal gland carcinoma, and metastatic carcinoma is often challenging because of its epithelioid morphology. Because primary and secondary malignant tumors are much more common and aggressive neoplasms, establishing the correct diagnosis has important therapeutic and prognostic implications.     

Coexistence of renal epithelioid angiomyolipoma and clear cell carcinoma in patients without tuberous sclerosis

Renal epithelioid angiomyolipoma (EAML) is a rare but distinct variant of angiomyolipoma, closely simulating renal cell carcinoma or sarcoma both clinically and histopathologically. This report presents an unusual case of unilateral simultaneous renal EAML and renal clear cell carcinoma. A 52-year-old man without any sign of tuberous sclerosis had a complaint of 6-month history of pain in left renal area and had macroscopic hematuria twice within the recent 1 month. Computed tomography showed the presence of 2 masses in the upper and lower portion of the left kidney. The patient underwent left radical nephrectomy. Histological examination revealed the upper mass was composed of medium to large epithelioid cells with clear or eosinophilic cytoplasm and numerous giant multinucleated cells. Adult-appearing adipose tissue and coagulative necrosis could also be observed focally in the mass. Immunohistochemically, the tumor cells in the upper mass showed positive reactions to actin, HMB-45, Melan-A, and CD68 but negative reactions to pan-cytokeratin (pan-CK), epithelial membrane antigen, and CD10. However, the lower mass was composed of diffusely monomorphic clear cells with strongly immunoreactive for pan-CK, vimentin, and CD10, whereas without expression for HMB-45 and actin. The patient showed no evidence of recurrence or metastasis during 1-year postoperative following-up period. To the authors' knowledge, this is the first report of coincidental renal EAML and clear cell carcinoma in the same kidney. Unlike classic triphasic angiomyolipoma, adjuvant therapy after resection should be considered for renal EAML because of its malignant potential, more aggressive behavior and poor prognosis.     

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.     

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.     

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

BackgroundEpithelioid 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.MethodsConsecutively 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.ResultsA 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.ConclusionsStrong 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.     

Renal epithelioid angiomyolipoma: a case report and literature review

BACKGROUND: Renal epithelioid angiomyolipoma is a recently recognized variant of angiomyolipoma, closely simulating renal cell carcinoma both clinically and histologically. Only a relatively small number of cases of epithelioid angiomyolipoma of the kidney have been reported. AIM: To highlight clinicopathological features of this rare tumour. OBSERVATION: We report herein a new case of renal epithelioid angiomyolipoma in a 38-year-old male with no stigmata of tuberous sclerosis. The tumour was composed of diffuse sheets of epithelioid cells, small numbers of adipocytes and occasional blood vessels. Immunohistochemically, neoplastic cells were immunoreactive for HMB-45, but negative for cytokeratin. The patient showed no evidence of recurrence or metastatic disease one year after radical nephrectomy. CONCLUSIONS: Epithelioid angiomyolipoma may be locally aggressive and can metastasise; therefore, long-term post-operative follow-up is mandatory.     

肾脏上皮样型血管平滑肌脂肪瘤临床病理分析

目的 探讨肾脏上皮样型血管平滑肌脂肪瘤(EAML)的临床病理特点及诊断与鉴别诊断.方法 通过对3例EAML临床病理学观察与免疫组化标记及复习有关文献,讨论其组织学特征及临床生物学行为.结果 3例年龄分别为28、40和32岁,均有腰痛病史,其中1例伴有肉眼血尿,均无结节硬化症.眼观:肿瘤位于肾脏,直径大小分别为6 cm、8 cm和3 cm.3例境界清楚,例2伴囊性变.肿瘤无包膜,2例出血、坏死明显,质脆或韧.镜检:瘤细胞体积大或巨大,呈多边形,胞质丰富,嗜酸性或空泡状,核仁明显,可见核内包涵体,多核巨细胞散在其中.瘤细胞弥漫性或巢团状排列.2例瘤组织出血、坏死明显,呈浸润性边缘.3例未见典型AML图像.免疫组化染色显示瘤细胞HMB-45阳性,SMA和vimentin散在性阳性,CK、EMA和CD10均阴性.结论 EAML是一种单一方向分化的,含有大上皮样细胞的肿瘤,瘤细胞较为特异的表达HMB-45.辅以免疫组化可以与其它肾脏肿瘤相鉴别.     

Epithelioid angiomyolipoma: appearance on fine-needle aspiration report of a case

Epithelioid angiomyolipoma is a recently recognized clinicopathologic entity first described by Martignoni et al. in 1995. Since then, several articles have further clarified its histogenesis and histologic features. Due to the presence of polygonal cells with voluminous cytoplasms, this neoplasm is often mistaken for renal-cell carcinoma. In this case presentation, we describe the cytologic features of an epithelioid angiomyolipoma obtained by fine-needle aspiration. The histogenesis and how it relates to diagnosis is briefly discussed. The importance of ancillary techniques in the differential diagnosis of epithelioid cells obtained in a renal aspirate is reviewed.     

A hepatic tumor associated with bilateral renal angiomyolipomas: A variant of angiomyolipoma?

Angiomyolipoma is usually derived from the kidney and composed of well developed vessels, smooth muscle and fat tissue. The liver is the only extra-renal site of angiomyolipoma. A peculiar type of hepatic tumor accompanied by bilateral renal angiomyolipomas is reported here. The tumor was mostly composed of large epithelioid cells and a small part of hyalinized large vessels and foam cell infiltration. Mature adipose tissue was absolutely absent. Epithelioid tumor cells arranged in an alveolar pattern had abundant glycogen and some diastase-resistant periodic acid-Schiff granules without obvious crystals. Immunohistochemical studies revealed that the epithelioid cells were positive for melanoma specific antibody (HMB-45), S-100 protein, aromatic L-amino acid decarboxylase and focally a-smooth muscle actin. Many melanosome- or premelanosome-like, electron-dense granules were observed in these cells. Thus, these cells were characterized by differentiation to both immature melanocytes and smooth muscle ceils. These epithelioid cells were similar to some cells in the renal angiomyolipomas of the same patient. The hepatic tumor was considered to be a result of monotonous proliferation of the epithelioid cells seen in renal angiomyolipoma. Differential diagnosis of this tumor was discussed.     

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。     

肾脏上皮样色素性透明细胞肿瘤病理形态观察

目的 探讨上皮样色素性透明细胞肾脏肿瘤形态学特点,加强对该肿瘤的认识,减少误诊.方法 回顾性分析2000余例肾脏肿瘤,符合上皮样色素性透明细胞肿瘤3例,通过HE、免疫组织化学EnVision法观察3例肿瘤形态学特点,对其中1例行超微结构观察,同时复习相关文献.结果 女性2例,男性1例,2例形态学表现为透明细胞癌样,1例见透明细胞和嗜酸性细胞构成乳头结构.免疫组织化学上皮标记及S-100蛋白均为阴性,HMB45均为阳性,2例Melan A阳性.电镜末见黑色素小体结构.结论 色素性透明细胞上皮样肿瘤是非常罕见的肾脏肿瘤,病理学特征兼有肾细胞癌、上皮样血管平滑肌脂肪瘤与黑色素瘤等肿瘤特征,免疫组织化学有利于鉴别诊断.其可能是上皮样血管平滑肌脂肪瘤的一种亚型.     

肾脏上皮样血管平滑肌脂肪瘤的病理观察

目的对肾脏上皮样血管平滑肌脂肪瘤（epithelioid agiomyolipoma,EAML）的病理诊断、鉴别诊断和预后进行分析。方法2例肾脏EAML（其中1例为复发病例）,复习其临床资料,病理学检查包括常规病理学、免疫组织化学和超微结构,并进行随访。结果光镜下肿瘤均主要由具有多形性和不典型性的上皮样细胞组成,部分区域有明显的血管周上皮样排列;可见出血和坏死;并可见静脉内瘤栓;淋巴结内可见上皮样肿瘤细胞累及。免疫组织化学肿瘤细胞（包括淋巴结内肿瘤）HMB45、平滑肌肌动蛋白（SMA）、神经元特异性烯醇化酶（NSE）和波形蛋白弥漫阳性;S-100、melanpan和CD68散在阳性;而上皮细胞膜抗原（EMA）、AE1／AE3、CK7、CD117、肌肉特异性肌动蛋白（MSA）、结蛋白、白细胞共同抗原（LCA）、CD20、CIM5RO、CD30、CD15、嗜铬素（CgA）、突触素（Syn）、bcl-2、雌孕激素受体（ER、PR）和p53均为阴性。电镜检查可见一些肿瘤细胞内有黑色素小体样的致密颗粒、肌丝、密体,肿瘤细胞外可见不连续的基膜。2例患者手术后10个月状态良好,无肿瘤局部复发和转移征象。结论血管周上皮样排列、寻找经典血管平滑肌脂肪瘤的结构和肿瘤细胞表达HMIM5和SMA对于诊断和鉴别诊断至关重要。而细胞的不典型性、出血坏死和核分裂象可能只表明肿瘤的恶性潜能：淋巴结受累、肾静脉瘤栓不是恶性的诊断依据：只有远处转移才是恶性的证据。     

Klarzelltumor der Lunge

Clear cell tumors of the lung are rare tumors composed of epithelioid HMB45 positive tumor cells. It has been proposed that clear cell tumors generate from perivascular epithelioid cells which are also found in renal angiomyolipoma. Due to its morphologic epithelioid features with clear cytoplasm the distinction from either primary or metastatic clear cell carcinoma is difficult. Usually clinical investigations do not lead to the final diagnosis so that only subsequent histological examination and immunophenotyping can establish the correct tumor classification. We describe the case of a 52 year old woman who underwent exploratory thoracotomy because of a lung mass in the right lower lobe. In frozen sections a solid trabecular tumor was diagnosed, paraffin histology and immunohistochemistry revealed a clear cell tumor of the lung. The difficulty of the correct diagnosis of the clear cell tumor of the lung in frozen sections is discussed as well as the differential diagnosis.     

Renal angiomyolipoma with a clear cell component

Case report of a 52-year-old woman with angiomyolipoma of the left kidney. The tumor had appearance of a typical angiomyolipoma predominantly composed of spindle cells, some epithelioid cells and few large hyalinized vessels. Adipose tissue was concentrated into small foci. Unusual presence of large cells with a clear fine granular cytoplasm closely resembled cells of the "sugar tumor" of the lung. Epithelioid cells and occasionally spindle cells were HMB45 positive. A minority of cells also coexpressed S100 protein. Clear cells were usually strongly positive for HMB45 too. Our findings supported consideration of a close relation between clear cell ("sugar") tumor of the lung and angiomyolipoma.     

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.