Monotypic epithelioid angiomyolipoma of the liver

AIMS: Monotypic epithelioid angiomyolipoma is a recently recognized renal tumour, which is composed purely of epithelioid cells coexpressing markers of both smooth muscle differentiation and melanogenesis (HMB45). We report here the first case of monotypic epithelioid angiomyolipoma arising in the liver. CASE DETAILS: A 30-year-old woman without tuberous sclerosis complex (TSC) was incidentally found to have a hepatic mass by ultrasonography. Grossly, the resected tumour showed a nodule-in-nodule appearance, with large areas of haemorrhagic necrosis. Microscopically, the tumour was composed of pleomorphic epithelioid cells with clear, eosinophilic cytoplasm. Neither adipocytes nor abnormal vessels were recognized in the tumour. Immunohistochemically, the tumour cells were strongly positive for HMB45 and S100 protein, focally positive for desmin, vimentin and smooth muscle actin, and negative for epithelial markers (cytokeratins, EMA). Ultrastructural analysis showed numerous dense granules with some striated ones resembling melanosomes, myofilaments and pinocytic vesicles in the cytoplasm. Molecular analysis showed no allelic loss of the TSC2 region or 12 other chromosomal regions. The patient is free of disease over 1 year after the operation. CONCLUSION: We consider that this hepatic tumour is closely related to angiomyolipoma, and a counterpart of renal monotypic epithelioid angiomyolipoma.     

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.     

Primary monotypic epithelioid angiomyolipoma of bone

AIMS: Monotypic epithelioid angiomyolipoma is a distinct and definable variant of angiomyolipoma, composed of monomorphous epithelioid cells that show HMB45 immunoreactivity. Angiomyolipoma, including its morphological variants, belongs to the family of perivascular epithelioid cell tumour. METHODS AND RESULTS: The tumour was examined using immunohistochemical staining and by transmission electron microscopy. Neoplastic cells showed a cytoplasmic granular positivity for HMB45. CONCLUSIONS: Extrarenal angiomyolipomas are rare and, to the best of our knowledge, this is the first reported case of a primary monotypic epithelioid angiomyolipoma of bone in a patient without evidence of tuberous sclerosis.     

Renal angiomyolipoma: further immunophenotypic characterization of an expanding morphologic spectrum

BACKGROUND: Renal angiomyolipoma is a benign tumor histologically characterized by proliferation of spindle cells, epithelioid cells, and adipocytic cells in concert with many thick-walled blood vessels. To add further diagnostic confusion, an epithelioid cell-predominant variant of renal angiomyolipoma has recently been described. HMB-45 immunoreactivity correlates with ultrastructural striated organelles that closely resemble premelanosomes, although no evidence of melanogenesis has been documented in this tumor. OBJECTIVE: To further characterize the immunophenotypic and ultrastructural profile of renal angiomyolipoma based on phenotypic cell type (epithelioid, spindle, and adipocytic cell). DESIGN: Formalin-fixed, paraffin-embedded tissues from 27 renal angiomyolipomas and 8 renal cell carcinomas were immunostained with monoclonal antibodies to the melanoma-associated antigens HMB-45, HMB-50, NKI/C3 (CD63), and tyrosinase; the smooth muscle-related antigens calponin and muscle-specific actin (HHF-35); S100; and cytokeratin (CK). All renal angiomyolipomas were also immunostained with a polyclonal antibody to renin. Ultrastructural examination was performed on 9 selected cases. RESULTS: All renal angiomyolipomas stained positive for HMB-45, HMB-50, NKI/C3, muscle-specific actin (HHF-35), and calponin. Overall, HMB-45, HMB-50, and NKI/C3 preferentially stained the epithelioid cells. Tyrosinase staining was present in 50% of the renal angiomyolipomas with adequate tissue for staining (12 of 24 cases); positive staining and intensity paralleled HMB-45, HMB-50, and NKI/C3. Muscle-specific actin (HHF-35) and calponin preferentially stained the spindle cells. The adipocytic cells stained positive for both melanoma-associated antigens and smooth muscle antigens. Epithelioid cells, spindle cells, and adipocytic cells were CK, S100, and renin negative. Ultrastructural findings paralleled immunohistochemical staining patterns. Premelanosome-like organelles and electron dense granules were more readily detected in the epithelioid cells within the tumor, whereas ultrastructural characteristics of smooth muscle cells were more easily found in the spindle cells. All renal cell carcinomas stained positive for CK, NKI/C3 staining was variable, and all were negative for HMB-45, HMB-50, smooth muscle actin (HHF-35), and calponin. CONCLUSION: In renal angiomyolipoma, the epithelioid and spindle cells have preferential staining patterns for melanoma-associated antigens versus smooth muscle antigens, respectively. Positivity in renal angiomyolipoma for HMB-50, NKI/C3, and tyrosinase, in addition to HMB-45, provides evidence for the presence of different melanoma-associated gene products. Immunophenotypic overlap of the 3 histologically distinct renal angiomyolipoma cell populations suggests a common cell line, supporting a unitarian concept for renal angiomyolipoma. Ultrastructural characteristics of the 3 renal angiomyolipoma cell phenotypes parallel the immunophenotype, giving further support to a common cell line. Our study lends further credence to the perivascular epithelioid cell concept as proposed by Bonetti and colleagues.     

Fine-needle aspiration cytology of renal angiomyolipoma: Report of a case with immunocytochemical and electron microscopic findings

A case is presented in which the diagnosis of renal angiomyolipoma was made by computed tomography (CT)-guided, fine-needle aspiration cytology and the examination of a cell block. The tumor was characterized by epithelioid smooth muscle cells, blood vessels and fat in the cytologic material. The cytodiagnosis was further substantiated by positive staining of the epithelioid muscle cells for markers of muscle-specific actin, HMB45, and trace positivity for vimentin but not with S100 protein, desmin, or cytokeratin. Further studies for the recently described crystalloids were also performed by using the periodic-acid Schiff stain with and without diastase treatment and electron microscopy on the cytologic material. However, no such crystalloids were found. A preoperative cytologic diagnosis of renal angiomyolipoma was considered to be of value due to the difference in management between angiomyolipoma and a renal carcinoma, both of which can present as a renal mass on imaging. Diagn. Cytopathol. 1998;18:297–300. © 1998 Wiley-Liss, Inc.     

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。     

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.     

Atypical pleomorphic epithelioid angiomyolipoma localized to the pelvis: a case report and review of the literature

AIMS: Angiomyolipoma is the most common mesenchymal tumour of the kidney. It has been reported in several other sites outside the kidney, mainly in the liver. We report the first case of atypical pleomorphic angiomyolipoma in a man, arising from the pouch of Douglas and extending to the entire abdominal cavity. METHODS: A 17-year-old man underwent a complete resection of a giant abdominopelvic mass. The tissue was formalin fixed and paraffin embedded and 4 micro m thick histological sections were stained with haematoxylin-eosin. Immunohistochemical stains for HMB-45, smooth muscle actin, vimentin, calponin, S100 and desmin were performed. Sections for electron microscopy were also prepared. RESULTS: Microscopic examination revealed a neoplasm composed of pleomorphic epithelioid cells with atypical features, immunoreactive for HMB-45, MART-1, actin, vimentin and calponin, while S100 protein and desmin stains were negative. Ultrastructurally, the tumour cells showed prominent nucleoli, vacuolated cytoplasm, and some premelanosomes. A diagnosis of atypical pleomorphic epithelioid angiomyolipoma was then made. CONCLUSIONS: To date five patients with abdominal epithelioid angiomyolipoma have been described in the literature. All were women. Three of the five patients reported developed metastasis, while our patient is still free of disease at 16 months of follow-up. Clear prognostic pathological features have not been identified.     

Malignant epithelioid angiomyolipoma of the kidney in a patient with tuberous sclerosis: an autopsy case report with p53 gene mutation analysis

We report an autopsy case of malignant epithelioid angiomyolipoma in a 36-year-old male tuberous sclerosis patient. He had been diagnosed to have a bilateral renal tumor 20 years previously. The left kidney had been surgically resected at the age of 34, and the left renal tumor was pathologically diagnosed as classic angiomyolipoma and epithelioid angiomyolipoma. He suddenly died of cardiac arrest, and at autopsy the right kidney weighed 7120 g. The tumor presented with massive necrosis invading the inferior vena cava, but was not hemorrhagic. Microscopic examination revealed tumor cells varying in size with a predominantly solid proliferation pattern and marked atypical large cells with vesicular nuclei and abundant eosinophilic cytoplasm. Mitotic figures were often encountered, and atypical forms were also present. Metastatic lesions were identified in the right lung, liver, diaphragm, and mesentery. Immunohistochemical examination showed epithelioid angiomyolipoma cells that were focally reactive for HMB-45 and showed diffuse positive staining for Melan-A. No mutation was detected in the p53 gene by polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) analysis despite diffuse immunoreactivity for p53. This case was proven to be malignant because of the occurrence of distant metastases, and showed that p53 mutations are not always associated with malignant transformation in epithelioid angiomyolipoma.     

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.     

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.     

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.     

Epithelioid angiomyolipoma of the kidney: a case report

Renal angiomyolipoma is a distinctive benign neoplasm that occurs either sporadically or in patients with tuberous sclerosis complex. A 45-year-old woman was admitted with history offlank pain and vomiting. There were no signs suggestive of tuberous sclerosis either in the patient or her family. At operation, she had a left renal mass with nephrolithiasis and hydronephrosis. Histopathology revealed epithelioid angiomyolipoma of the left kidney with chronic pyelonephritis. Immunohistochemistry confirmed the diagnosis of angiomyolipoma. This case is presented to highlight the epithelioid variant of angiomyolipoma which may behave in an aggressive manner.     

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.     

Retroperitoneal PEcoma (angiomyolipoma) composed exclusively of epithelioid lipoblastic-like cells: a diagnostic conundrum on needle biopsy

Angiomyolipomas are one of several distinct entities that belong to the “PEComa” (perivascular epithelioid cell tumour) family that comprise varying degrees of fatty, smooth muscle and vascular components. Angiomyolipomas occurring in the retroperitoneum are relatively uncommon; however, when all of the three components are represented, the diagnosis can be readily made. Herein, we report the first case of a retroperitoneal angiomyolipoma composed exclusively of epithelioid and lipoblast-like cells. An extra-renal retroperitoneal mass was biopsied and revealed a relatively uniform population of epithelioid cells arranged in sheets separated by both a delicate vascular network and vessels of larger calibre. The tumour cells were small to medium in size with mild nuclear pleomorphism and cytoplasmic vacuolization ranging from multiple large vacuoles to larger vacuoles, resembling lipoblasts. Occasional nuclei were seen to have prominent clear nuclear pseudo-inclusions. Immunohistochemistry revealed the cells to be strongly positive for SMA and focally positive for HMB45, MiTF and S100. The tumour cells were negative for AE1/AE3, CAM5.2, CD45, Pax8, SF-1 and TFE3. Angiomyolipomas in the retroperitoneum share morphological similarities with a wide variety of tumours, chiefly liposarcoma. Awareness of angiomyolipomas composed purely of epithelioid and lipoblast-like cells is essential to avoid misdiagnoses.     

伴有TFE3扩增的肾脏上皮样血管平滑肌脂肪瘤

目的探讨伴有TFE3扩增的肾脏上皮样血管平滑肌脂肪瘤(epithelioid angiomyolipoma,EAML)的病理学特征、鉴别诊断及生物学行为。方法对1例伴有TFE3扩增的肾脏EAML进行组织形态学观察、免疫组化染色及荧光原位杂交(fluores-cence in situ hybridization,FISH)检测,追踪随访患者预后,并复习相关文献。结果该例EAML呈片状弥漫分布,瘤细胞呈上皮样改变,细胞形态异型性较大,核分裂象易见。肿瘤侵犯包膜。瘤细胞表达SMA、TFE3、cathepsin K,TFE3基因出现多倍体扩增,未见易位发生。患者第一次手术3个月后肿瘤复发,术后半年腹腔肿瘤广泛侵犯、肺部见转移。结论伴有TFE3扩增的EAML组织学形态及生长方式更具恶性特征,预后更差,与经典型EAML有所不同,需与其他形态学相似的肿瘤相鉴别。     

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.     

Malignant pigmented clear cell epithelioid tumor of the kidney: clear cell ("sugar") tumor versus malignant melanoma

A 73-year-old woman presented with an hemorrhagic kidney tumor initially interpreted as a renal cell carcinoma (RCC). A retroperitoneal recurrence infiltrating the duodenal wall was made up of clear cells, some of which contained Fontana-Masson positive pigment, immunopositive for HMB-45, S-100 protein, actin, and vimentin. The same immunohistochemical profile was retrospectively reproduced in the kidney tumor, where melanosomes were also found ultrastructurally. Lipomatous differentiation was not observed. There was no history of malignant melanoma (MM), or stigmata of tuberous sclerosis. The patient died of disease 5 years after the initial diagnosis. This neoplasm can be considered as a malignant, pigmented, clear-cell epithelioid variant of angiomyolipoma, or "sugar" tumor of the kidney, with the peculiarity of having a previously unreported component of pigmented cells visible on light microscopy. This finding raises the possibility that the exceptional cases of MM reported in renal parenchyma may be pigmented variants of epithelioid angiomyolipoma rather than true MM.     

An unusual renal angiomyolipoma with morphological lymphangioleiomyomatosis features and coexpression of oestrogen and progesterone receptors

Angiomyolipoma is the most common mesenchymal renal tumour, the clonal origin of which has recently been demonstrated. It is composed of varying amounts of blood vessels, smooth muscle and fat. In this report, we describe a renal angiomyolipoma, which is unusual owing to the presence of a lymphangioleiomyomatosis-like component, occurring in a 41-year-old woman suffering from sporadic lymphangioleiomyomatosis. The diagnosis was based on histopathological and immunohistochemical findings. The tumour consisted of an intimate admixture of two components: one was typical of a classical angiomyolipoma and the other was reminiscent of lymphangioleiomyomatosis. HMB45 positivity was found on 5% of the cells of the angiomyolipoma component. Ten percent of the nuclei of the lymphangioleiomyomatosis and angiomyolipoma components expressed oestrogen receptors and 5% progesterone receptors. This case illustrates a very unusual pattern of a renal angiomyolipoma containing a lymphangioleiomyomatosis-like component. The oestrogen and progesterone immunoreactivity suggests that angiomyolipoma could be hormonally dependent. Therefore, we have emphasised the morphological and immunohistochemical similarities between angiomyolipoma and lymphangioleiomyomatosis.