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.     

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.     

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.     

Renal angiomyolipoma in a case of tuberous sclerosis, an electron microscopy study.

Electron microscopic study of bilateral renal angiomyolipoma in a case of tuberous sclerosis showed two cell types: smooth muscle cells and fibroblasts. There were no tubular or glomerular elements within the tumor mass. To our knowledge this study represents the first ultrastructural demonstration of smooth muscle cells occurring in the renal lesions of this complex.     

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.     

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.     

Uterine angiomyolipoma: case report and review of the literature

Extrarenal angiomyolipomas (AML) have been reported at various anatomical sites, but infrequently in the gynecological region. In the uterus, only a few cases have been described. We describe a uterine angiomyolipoma occurring in a 40-year-old woman without evidence of tuberous sclerosis. The tumor arose on the right wall of the uterine body and was partially cystic, and it was associated with marked degeneration. It was composed of mature adipose tissue, anomalous blood vessels and non-vascular smooth muscle cells. Immunohistochemistry revealed that non- vascular smooth muscle cells were positive for alpha-smooth muscle actin (alpha-SMA), desmin, vimentin, antihuman muscle actin (HHF35) and progesterone receptor (PR), and negative for cytokeratin, antihuman melanoma (HMB45), CD34, S-100 and estrogen receptor (ER). It is of particular interest that non-vascular smooth muscle cells were negative for HMB45, in contrast to renal and other extrarenal AML in which HMB45 immunoreactivity has been demonstrated in these cells.     

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.     

Renal angiomyolipoma resembling gastrointestinal stromal tumor with skenoid fibers

We report an unusual case of renal angiomyolipoma occurring in 68-year-old man. The tumor lacked well-developed vascular and adipose components and was composed almost exclusively of smooth muscle cells. Numerous skenoid-like periodic acid-Schiff-positive globules were interspersed between the tumor cells; the lesion therefore closely resembled a low-grade stromal tumor of the gastrointestinal tract. The HMB45-positive/CD34-negative immunophenotype was essential for the diagnosis of angiomyolipoma. Neither gastrointestinal tumor nor any signs of tuberous sclerosis were found. This lesion should be included in the list of morphologic variations of angiomyolipoma, which may cause diagnostic difficulties.     

Retroperitoneal lipomatous angiomyolipoma associated with amyloid deposition masquerading as well-differentiated liposarcoma

Reported herein is a case of retroperitoneal angiomyolipoma associated with amyloid deposition, masquerading as well-differentiated liposarcoma. A 16 x 13 cm lipomatous tumor was resected from the perirenal retroperitoneum of a 71-year-old woman. Microscopically, the tumor was exclusively composed of mature adipose tissue and abnormal thick blood vessels, but bundles of smooth muscle were lacking. In addition, amyloid was deposited between fat cells. Initially, well-differentiated liposarcoma was highly suspected. However, there were a few epithelioid cells with clear vacuolated cytoplasm within the vessel walls, which were immunoreactive for smooth muscle markers and HMB-45. Real-time polymerase chain reaction failed to demonstrate the amplification of the murine double-minute type 2 gene and cyclin-dependent kinase 4 gene in this tumor. Therefore, the tumor was diagnosed as lipomatous angiomyolipoma. After the diagnosis, it was found that the patient had multiple myeloma and cardiac amyloidosis, suggesting that the amyloid deposition within the tumor was a complication of the myeloma. Lipomatous angiomyolipoma may be a diagnostic pitfall of retroperitoneal lipomatous tumors.     

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.     

Fat-predominant mixed epithelial stromal tumor (MEST): report of a unique case mimicking angiomyolipoma

A unique case of a mixed epithelial stromal tumor (MEST) that was predominantly composed of adipose tissue is reported here. Radiographically and grossly, the lesion was thought to be an angiomyolipoma, based upon its fatty appearance. Microscopically, the lesion was predominantly composed of mature adipose tissue but also contained clusters of bland tubules surrounded by smooth muscle bundles and collagen. By immunohistochemistry, the stroma labeled diffusely for estrogen and progesterone receptors, while the muscle bundles labeled for desmin. Melanocytic markers HMB45 and Melan A, typically positive in angiomyolipoma, were nonreactive. This case expands the morphologic spectrum of MEST to include mimics of 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.     

Clear cell renal cell carcinoma with smooth muscle stroma

A recent publication described 5 unusual clear cell renal tumors with prominent smooth muscle stroma that were characterized only by immunostaining. We report 3 additional tumors composed of clear cell renal cell carcinoma intimately admixed with abundant smooth muscle stroma. Epithelial differentiation of the malignant clear cell components and smooth muscle differentiation of the benign spindle cell stroma was confirmed by the immunostaining profiles and by electron microscopy. Fluorescence in situ hybridization analysis of chromosome 3 showed loss of the entire chromosome in 2 cases and loss of 3p in the third case. We therefore interpret these tumors as unique low-grade variants of clear cell renal cell carcinoma that have induced a prolific metaplastic stromal reaction. Extensive tissue sampling and immunostaining are recommended to distinguish cases with an extensive smooth muscle component from morphologically similar but benign lesions including angiomyolipoma, leiomyoma, or mixed epithelial and stromal tumor of the kidney.     

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.     

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.     

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.     

Pleomorphic Angiomyolipoma of Digestive Tract: A Heretofore Unrecognized Entity

Two cases of pleomorphic angiomyolipoma (AML) composed of bizarre epithelioid smooth muscle cells located in the gastrointestinal tract are reported. One involved the appendix of a 6-year-old girl, and the second the cecum of a 22-year-old woman. In both instances the tumor cells were immunoreactive for HMB-45 and A103. To the best of our knowledge, this peculiar variant of an AML has not previously been recognized in this location. Int J Surg Pathol 8(1):67-72, 2000     

Leiomyomatosis-like lymphangioleiomyomatosis of the colon in a female with tuberous sclerosis.

Smooth muscle lesions of the large bowel, excluding the rectum, are generally rare, and diffuse smooth muscle lesions, termed leiomyomatosis, are even rarer. In this report, we document, for the first time, leiomyomatosis-like lymphangioleiomyomatosis (LAM) of the ascending, transverse, and descending colon in association with bilateral renal angiomyolipoma (AML) in a 30-year-old Chinese female with tuberous sclerosis complex (TSC). She presented with protracted constipation for which a colectomy was performed. Histology disclosed multiple confluent nodular CD34 and CD117 negative smooth muscle proliferation within the large bowel wall, whereas the renal biopsy revealed typical features of AML. Interestingly, the epithelioid smooth muscle cells of both the colonic and renal lesions were HMB45 positive, suggesting that leiomyomatosis-like LAM of the colon, pulmonary LAM and AML are closely related entities. The patient remained free of complications for the last five years after surgery. Leiomyomatosis-like LAM of the large bowel probably represents another manifestation of the tendency of TSC to be associated with proliferative lesions.     

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.