An Electron Microscopic Study of Hepatic Angiomyolipoma

Three cases of hepatic angiomyolipoma, each composed of an intimate mixture of numerous abnormal blood vessels and various-sized fat, spindle and/or epithelioid cells, are presented along with the findings of an electron microscopic study. The spindle cells were confirmed to be smooth muscle by immunohistochemical staining for des-min and by their ultrastructural characteristics. The mature fat cells, smooth muscle cells, immature short spindle cells apparently intermediate or transitional between the former two cell types, and the epithelioid cells were observed adjacent to the endothelial cells. Ultra-structurally, the epithelioid cells were characterized by unusual cytoplasmic organelles such as myofilaments having focal densities and dense attachments, numerous large electron-dense bodies, and a large number of glycogen particles and lipid droplets. Therefore, it is considered that the immature short spindle and epithelioid cells in hepatic angiomyolipoma might be primitive mesenchymal cells having an ability to differentiate toward both smooth muscle and fat cells. Acta Pathol Jpn 39 : 743-749, 1989.     

An electron microscopic study of hepatic angiomyolipoma

Three cases of hepatic angiomyolipoma, each composed of an intimate mixture of numerous abnormal blood vessels and various-sized fat, spindle and/or epithelioid cells, are presented along with the findings of an electron microscopic study. The spindle cells were confirmed to be smooth muscle by immunohistochemical staining for desmin and by their ultrastructural characteristics. The mature fat cells, smooth muscle cells, immature short spindle cells apparently intermediate or transitional between the former two cell types, and the epithelioid cells were observed adjacent to the endothelial cells. Ultrastructurally, the epithelioid cells were characterized by unusual cytoplasmic organelles such as myofilaments having focal densities and dense attachments, numerous large electron-dense bodies, and a large number of glycogen particles and lipid droplets. Therefore, it is considered that the immature short spindle and epithelioid cells in hepatic angiomyolipoma might be primitive mesenchymal cells having an ability to differentiate toward both smooth muscle and fat cells.     

Lymphangiomyomatosis and angiomyolipoma: closely related entities characterized by hamartomatous proliferation of HMB-45-positive smooth muscle

Angiomyolipoma is a hamartomatous condition which can occur as a component of the tuberous sclerosis complex. Lymphangiomyomatosis, another hamartomatous lesion occurring predominantly in the lungs, has long been suspected to be related to angiomyolipoma and tuberous sclerosis because of occasional clinical associations. We undertook this study to provide further support for the close relationship between these two entities. Five cases of lymphangiomyomatosis and 20 case of angiomyolipoma were retrieved for histological review and immunohistochemical studies. The antibodies used were anti-muscle specific actin (HHF-35), anti-desmin (D33) and antimelanoma (HMB-45). Lesions featuring smooth muscle proliferation were used as controls. The proliferated smooth muscle cells in both lymphangiomyomatosis and angiomyolipoma were much plumper and paler or even clear, when compared with the deeply eosinophilic cytoplasm of the normal spindly smooth muscle cells and those of leiomyomas. Their nuclei were round to oval and pale rather than elongated and dark. Cells with bizarre nuclei were commoner in angiomyolipoma (18/20 cases) than lymphangiomyomatosis (1/5). In 12 cases of angiomyolipoma there were foci indistinguishable from lymphangiomyomatosis, i.e. plump spindle cells arranged in short fascicles around ramifying endothelium-lined spaces. All five cases of lymphangiomyomatosis stained for muscle-specific actin, desmin and HMB-45. For angiomyolipomas, the positivity rates for these markers were: 20/20, 17/20 and 18/20, respectively, including one case that was negative for both desmin and HMB-45. The various smooth muscle proliferations and tumours selected as controls were uniformly HMB-45 negative. The distinctive cytological features, morphological overlap and immunophenotypic profile all support a close relationship between lymphangiomyomatosis and angiomyolipoma, which probably represent different morphological manifestations of hamartomatous proliferation of a peculiar form of HMB-45-positive smooth muscle.     

Angiomyolipoma of the bladder

Angiomyolipoma of the bladder is an extremely rare neoplasm. We report a case of a 55-year-old woman with an angiomyolipoma of the bladder visualized on pelvic sonogram as a 5 mm polyp in the floor of the bladder. The lesional tissue consisted of spindle cells, epithelioid cells, and adipocytes, with occasional thick-walled blood vessels. Immunohistochemical studies showed the spindle and epithelioid cells to be focally positive for HMB-45 and diffusely positive for actin and muscle cell antigen (HHF-35), which confirmed the diagnosis of angiomyolipoma. A review of the recent literature on the pathogenesis of angiomyolipoma follows.     

High‐grade endometrial stromal sarcoma with smooth muscle and skeletal muscle differentiation: Report of a case with cytomorphologic and immunocytologic analysis

We report a case of high‐grade endometrial stromal sarcoma with cytological and immunocytochemical findings. Cytologically, major tumor cells showed round‐to‐short spindle shapes with round‐ to oval‐shaped nuclei and moderately abundant delicate cytoplasm. Tumor cells with tapered shapes and eccentric nuclei were also observed. A few spindle cells having enlarged cigar‐shaped nuclei with conspicuous nucleoli and delicate wispy cytoplasm, which resembled leiomyosarcoma, were intermingled. One rhabdomyoblast cell with both α‐sarcomeric muscle actin and myoglobin was also observed. Most of the tumor cells, including the leiomyosarcomatous spindle cells, were positive for CD10, and negative for desmin and h‐caldesmon. Accordingly, when relatively monotonous round‐to‐short spindle tumor cells and taper‐shaped tumor cells are observed in the female genital tract, high‐grade endometrial stromal sarcoma should be considered in the differential diagnosis. Immunocytochemistry contributed to the correct diagnosis. This case was high‐grade endometrial stromal sarcoma with smooth muscle and skeletal muscle differentiation. Diagn. Cytopathol. 2010. © 2010 Wiley‐Liss, Inc.     

Hepatic angiomyolipoma

Hepatic angiomyolipoma is a rare, benign, hepatic mesenchymal neoplasm found in both males and females, and most commonly in adult females. Angiomyolipoma occurs most commonly in the kidneys. The liver represents the second most frequent site of involvement. Hepatic angiomyolipomas are composed of varying amounts of smooth muscle cells, adipose tissue, and vessels. The smooth muscle cell component is the most specific to the diagnosis. The smooth muscle cells can have varying morphologies and are positive for homatropine methylbromide-45 but are negative for hepatocyte paraffin 1 and S100 protein. The definitive diagnostic study remains the histologic examination of the surgically resected lesion coupled with immunohistochemical stains. The differential diagnosis includes hepatocellular carcinoma, hepatic adenoma, leiomyoma, hepatoblastoma, melanoma, and gastrointestinal stromal tumor. The immunohistochemical staining pattern differentiates this lesion from other malignant and benign liver lesions. If the diagnosis of hepatic angiomyolipoma has been made, it can be followed conservatively or surgically resected.     

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.     

Hepatic angiomyolipoma. A case report with review of the literature

Hepatic angiomyolipoma in a 59-year-old woman is reported. The tumor was located at the lower edge of the left lobe of the liver, measured 3 x 2 x 2 cm, and appeared solid. Histologically, it consisted of abundant blood vessels of varying caliber, mature fat cells, and round, spindle-shaped or epithelioid interstitial cells. The latter were considered to be of smooth muscle origin, because myofilamentous structures were demonstrated ultrastructurally in the cytoplasm and because they were positive for desmin by the PAP method. Based on these findings, the diagnosis of angiomyolipoma was confirmed. A review of the literature revealed only 15 cases of hepatic angiomyolipoma. From a clinicopathological viewpoint, a comparison was made between hepatic angiomyolipoma and its more frequent renal counterpart. The hepatic tumor is considered to be a kind of hamartoma.     

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.     

HEPATIC ANGIOMYOLIPOMA

Hepatic angiomyolipoma in a 59-year-old woman Is reported. The tumor was located at the lower edge of the left lobe of the liver, measured 3 × 2 × 2 cm, and appeared solid. Histologically, It consisted of abundant blood vessels of varying caliber, mature fat cells, and round, spindle-shaped or epithelioid interstitial cells. The latter were considered to be of smooth muscle origin, because myofilamentous structures were demonstrated ultrastructurally in the cytoplasm and because they were positive for desmin by the PAP method. Based on these findings, the diagnosis of angiomyolipoma was confirmed. A review of the literature revealed only 15 cases of hepatic angiomyolipoma. From a clinlcopathological viewpoint, a comparison was made between hepatic angiomyolipoma and its more frequent renal counterpart. The hepatic tumor is considered to be a kind of hamartoma.     

肝血管平滑肌脂肪瘤的形态学变异和免疫组织化学特征

目的探讨肝血管平滑肌脂肪瘤(AML)的临床病理学和免疫组织化学特征、诊断和鉴别诊断要点。方法对44例手术切除肝AML的临床病理学特征进行详细分析,并对10种免疫组织化学标志物的表达状况进行检测。结果肿瘤由平滑肌细胞、厚壁血管及脂肪3种成分混合组成,根据瘤组织成分的比例可分为经典型(13例)、肌细胞为主型(25例)、脂肪细胞为主型(4例)、血管瘤型(2例);肌细胞可呈多种形态变异,主要有上皮样细胞型、中间细胞型、梭形细胞型、嗜酸细胞型和多形细胞型5种;8例可见髓外造血。免疫组织化学染色显示,瘤细胞呈HMB45(44／44,100％)、SMA(38／38,100％)和CD117(30／38,78．9％)阳性。结论肝AML形态学变异较大,容易造成误诊,HMB45阳性瘤细胞具有重要的诊断意义,CD117可作为诊断AML的一个有用的辅助标记物。     

Periorbital angioleiomyosarcoma in dog, case report

A 3-year-old, male, German shepherd dog was presented with a unilateral, progressively enlarging subcutaneous mass around the left eye. A series of diagnostic tests were performed based on the suspicion of neoplasia. Ultrasonography revealed a large hyperechoic structure with a soft tissue density behind the affected eye. No fluid or polymorphonuclear cells were detected on fine needle aspiration, however, lymphocytes and unidentifiable cells that were potentially neoplastic were observed. Exenteration surgery was done, and several samples were obtained for histopathologic examination. Histopathologically, the tumor mass consisted of high cellular interlacing bundle of pleomorphic, plump spindle to round cell that blended into muscular layer of vessels included arteries, veins, capillaries, and thin cleft-like vascular spaces. Tumor cells nuclei were cigar-shaped in well-differentiated areas and pleomorphic oval to round in poorly differentiated areas. Mitotic figures were frequently observed (38 mitoses per 10 high power fields). Immunohistochemical staining revealed strongly positive staining of cytoplasm of tumoral cells for vimentin and alpha smooth muscle actin, and negative for desmin, S100, and myogenin. On the basis histopathological and immunohistochemical finding, diagnosis of periorbital angioleiomyosarcoma was made. Angioleiomyosarcoma has not been reported previously in periorbital tissue in dogs.     

Paratesticular liposarcoma with smooth muscle differentiation mimicking angiomyolipoma

AIMS: To discuss the differential diagnosis of a case of well-differentiated liposarcoma which had areas resembling angiomyolipoma-a feature which, to our knowledge, has not been reported previously. METHODS AND RESULTS: A tumour in the paratesticular region had apparently been present for 40 years, but had grown recently. A fat component containing lipoblasts was admixed with areas resembling angiomyolipoma, i.e. desmin positive, but HMB45-negative smooth muscle proliferation with atypia and thick-walled blood vessels devoid of elastin. CONCLUSION: The diagnosis of liposarcoma, rather than angiomyolipoma with adipose atypia, in this case is based on the fact that smooth muscle differentiation is documented in liposarcoma, lack of HMB45 staining and recent clonality studies which suggest that the fat in angiomyolipoma is not neoplastic.     

Massive retroperitoneal angiomyolipoma. A lesion that may be confused with well-differentiated liposarcoma

A benign massive retroperitoneal lipomatous tumor is described. The tumor, from a 72-year-old woman with increasing abdominal girth, consisted of a mixture of mature lipocytes, smooth muscle cells, and thick-walled medium-size blood vessels. Although the tumor focally involved the uterine serosa, suggesting the possible diagnosis of uterine leiomyoma with fatty change, the authors think that, because the bulk of the tumor was located in the retroperitoneum and because the tumor contained characteristic thick-walled blood vessels from which smooth muscle cells radiated, this tumor would be best classified as a retroperitoneal angiomyolipoma. Although both angiomyolipomas and leiomyomas with fatty change presenting as large retroperitoneal tumors are rare, and therefore are not well-recognized by surgical pathologists, they are benign and must be distinguished from liposarcomas.     

Usefulness of ultrasonography-guided fine needle aspiration cytology in a case of jejunal leiomyosarcoma

The patient was a 45-year-old man with the symptoms of abdominal pain and constipation. Laboratory data showed no remarkable changes. Ultrasonic and CT-scan examinations revealed a mass deeply situated in the abdominal cavity. Ultrasonography guided needle aspiration cytology was performed. Obtained specimen showed a large cluster accompanied by numerous smaller clusters, and dispersed single cells. Most of cells were spindle in shape with abundant cytoplasm, and uniform in size. These cells have moderately hyperchromatic nuclei with finely granular pattern, which were round or oval, and have tiny nucleoli. Some cells were binucleated. The nuclear membrane was sharp and well preserved. Giant cells or mitotic figures were not observed. As a result, cytological diagnosis was "suspicious of leiomyosarcoma". The tumor was resected. The specimen consisted of a segment of the jejunum with an irregularly-shaped, and reddish soft first-sized mass continued to jejunum muscle layer. The cut surface of the mass showed central cavitation and necrosis in part. Histological diagnosis was well differentiated leiomyosarcoma originated from the jejunum. The tumor was composed of smooth muscle like cells arranged in bundles with some bizarre multinucleated cells and rare mitotic figures.     

Nuclear pseudoinclusions in fine-needle aspiration cytology of hepatic angiomyolipoma: case report

A nodular lesion was found in the fourth segment of the liver in a 51-yr-old Caucasian woman and subjected to aspiration cytology. Smears exhibited solid sheets or small aggregates of epithelioid cells with numerous nuclear pseudoinclusions, scanty mature adipocytes, and red blood cells. With a presumptive diagnosis of angiomyolipoma, the patient underwent laparotomy with resection of the nodule; histologic and immunohistochemical findings confirmed the diagnosis, identifying the trabecular variant. Although the presence of nuclear pseudoinclusions has been previously reported in renal angiomyolipomas, this cytologic feature has not received adequate attention in liver localization, where only cell block samples have been reported. Therefore, when the typical different cellular components of angiomyolipomas are absent in cytologic smears, nuclear pseudoinclusions should not be regarded as a criterion of malignancy, but they may be considered as an additional nonspecific cytological feature in hepatic angiomyolipoma.     

Hepatic angiomyolipoma resembling an inflammatory pseudotumor of the liver. A case report

Hepatic angiomyolipoma (AML) may demonstrate a marked histologic diversity and is frequently misdiagnosed. HMB45 is a promising marker for this tumor and is expected to facilitate the recognition of some AMLs with unusual morphology. We report on a case of hepatic AML exhibiting histologic features that were similar to inflammatory pseudotumor (IPT) or to IPT-like follicular dendritic cell (FDC) tumor of the liver. The patient was a 21-year-old Japanese woman with a mass in the left lobe of the liver (70 x 73 mm). There were no clinical features of tuberous sclerosis. Histologically, numerous inflammatory cells, including small lymphocytes, plasma cells, and histiocytes, showed diffuse infiltration throughout the lesion. However, the present case also shared some of the morphologic findings of hepatic AML, including clusters of smooth muscle cells with clear cytoplasm, a few scattered adipose cells, and thick-walled blood vessels. Moreover, the smooth muscle cells consisted of spindle-shaped cells or larger, more rounded cells with either clear cytoplasm or eosinophilic epithelioid cell features positive for vimentin, muscle-specific actin, and smooth muscle actin. HMB45 immunostaining confirmed the diagnosis of AML. The present case indicates that IPT or IPT-like FDC tumor should be added to the list of differential diagnoses for AML of the liver.     

Cutaneous lipomatous neoplasms.

Benign and malignant lipomatous tumors are the most common neoplasms of subcutaneous and deep soft tissues in adults. In contrast, purely cutaneous lipogenic neoplasms are exceptionally rare, and some entities and variants of adipocytic neoplasms have not yet been described in the skin. In addition, some dermal lipogenic neoplasms are characterized by different specific clinicopathologic features in comparison with more deeply located tumors. Cutaneous angiolipoleiomyoma ("angiomyolipoma") is seen most often in male patients and in an acral location. It is characterized histologically by mature adipocytes, thick-walled blood vessels, and smooth muscle cells arranged in well-defined fascicles and around blood vessels. Smooth muscle cells in cutaneous angiolipoleiomyoma stain negatively for HMB-45, in contrast to renal and extrarenal angiomyolipoma. Adenolipoma of the skin is a superficially located form of lipoma composed of large lobules of mature adipocytic tissue admixed with eccrine ducts and glands. Cutaneous spindle cell/pleomorphic lipomas, in contrast to subcutaneous forms, are more common in female patients and have a wide anatomic distribution. Histologically, cutaneous spindle cell/pleomorphic lipomas are characterized by an infiltrative growth pattern mimicking more aggressive lesions. Rarely, liposarcoma may occur as a purely cutaneous lesion with a favorable clinical prognosis despite high-grade morphologic features in many cases.     

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.     

肝脏血管平滑肌脂肪瘤9例临床病理分析

目的探讨肝脏血管平滑肌脂肪瘤(hepatic angiomyolipoma,HAML)的临床病理特点、诊断及鉴别诊断。方法对9例HAML进行临床病理学观察与免疫组化标记及复习有关文献。结果 9例HAML年龄28～56岁,平均44.2岁,均无结节硬化症。术前影像诊断多数为肝癌。眼观:肿瘤直径1.2～14 cm。肝左叶4例、肝尾状叶3例和肝右叶2例。肿瘤境界清楚,无包膜,质地脆、易碎,可见出血、坏死。镜检:瘤组织由上皮样细胞、平滑肌样细胞、脂肪组织和厚壁血管组成。上皮样细胞体积大或巨大,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,偶见多核巨细胞。平滑肌样细胞呈梭形,9例中有4例几乎缺如脂肪组织。瘤细胞弥漫性或巢团状排列。瘤组织出血、坏死明显,呈浸润性边缘。免疫组化标记:瘤细胞HMB-45及Melan-A阳性,SMA和vimentin散在阳性,CK、EMA、AFP均阴性。结论 HAML是一种罕见的间叶组织源性肿瘤,多见于女性,组织学上以单一方向分化的大上皮样细胞为主,瘤细胞较为特异的表达HMB-45及Melan-A。免疫组化标记可与其它肝脏肿瘤鉴别。