Epithelioid angiomyolipoma of the liver with striking giant cell component: Fine‐needle aspiration biopsy findings of a rare neoplasm

Angiomyolipoma (AML) is a uncommon benign neoplasm of the liver with cyto‐ and histologic features similar to the more commonly encountered renal AML. Tumors composed predominantly of epithelioid cells have been referred to as epithelioid AML. Because most liver lesions are first evaluated by fine‐needle aspiration biopsy (FNAB), it is important to distinguish this variant of AML from more common hepatic neoplasms such as hepatocellular carcinoma (HCC) or metastatic tumors. Rare reports of epithelioid AML of the liver diagnosed by FNAB are in the literature. Here, we describe the cytologic findings of a unique case of epithelioid AML with numerous giant cells. Diagn. Cytopathol. 2009. © 2009 Wiley‐Liss, Inc.     

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.     

Multiple angiomyolipomata of the liver: a case report.

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

Malignant angiomyolipoma of the liver: a hitherto unreported variant

AIMS: After their original recognition in the kidney, angiomyolipomas (AMLs) have been reported in the liver for more than 20 years. In the kidney, five cases of malignant AML have been reported. We report the first case of malignant hepatic AML. METHODS AND RESULTS: A 70-year-old female patient presented with abdominal discomfort. Clinical examination revealed a palpable liver. CT scan showed a polymorphous hypervascular lesion in the right liver lobe. A biopsy was taken and resulted initially in a differential diagnosis between a hepatocellular carcinoma, a metastatic tumour (possibly of renal origin) and angiomyolipoma (AML). After immunohistochemistry, a hepatic AML was suggested, given the immunoreactivity for HMB45/NKIC-3. The mass was resected 5 years later because of relapsing abscess formation. Gross examination of the resection specimen showed a focally encapsulated brown mass with focal necrosis. Microscopic examination showed a tumour growing in sheets, separated by sinusoidal-like vessels. Most of the tumour cells had a large, polygonal, clear cytoplasm, often with eosinophilic condensation around the nucleus. There was prominent vascular invasion. Immunohistochemistry (reactivity for HMB-45, NKIC-3, S100 and alpha smooth muscle actin, negativity for cytokeratin and vimentin) and electron microscopy confirmed the diagnosis of monomorphic epithelioid AML with prominent vascular invasion. Seven months after tumour resection, the patient died of recurrent disease. CONCLUSIONS: This case highlights the importance of immunohistochemistry and electron microscopy in diagnosing this type of tumour. Possibly, in the past, malignant AML of the liver has been misdiagnosed as HCC.     

Is preoperative cytologic diagnosis of epithelioid sarcoma possible?

Epithelioid sarcoma (ES) is a rare malignant neoplasm of the soft tissues with a predilection for distal extremities of young adults. A "proximal" variant was recently described. The preoperative fine-needle aspiration cytology (FNAC) differential diagnosis with necrotizing granuloma, carcinoma, melanoma, and other neoplasms with epithelioid morphology can be difficult and few cases have been described in the literature. The authors present the preoperative FNAC findings of 10 aspirates of ES, corresponding to seven patients (four men and three women, ages 13-72 years). The cytologic features were compared with histologic features as well as with the FNA patterns of other neoplasms with epithelioid morphology that may be included in the differential diagnosis. Cytologic smears showed tumor cells with an epithelioid to spindle cell morphology, dispersed and in loose clusters in close relation with a fibrillar hyaline material. The cells showed moderate anisocariosis, a vast well-defined, often dense cytoplasm with immunoexpression of vimentin, cytokeratin, and CD 34. When the FNA cytologic features described above are accompanied by the adequate clinical setting and are supported by immunocytochemistry, an accurate preoperative cytologic diagnosis of ES is possible.     

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.     

Characterization of smooth muscle components in renal angiomyolipomas: Histological and immunohistochemical comparison with renal capsular leiomyomas

The smooth muscle components of angiomyolipoma (AML) of the kidney have a wide histological and immunohistochemical spectrum. In the present study, 50 cases of AML and seven cases of renal capsular leiomyoma (RCL) were reviewed histologically and immunohistochemically, and the results compared with those of leiomyomas of soft parts. The AML cases were subclassified into 34 cases of common, 12 of leiomyomatous and four of lipomatous type. Even the common-type AML tissues showed a variety of histologic features, including lymphangiomyoma. The cytoplasm of leiomyomatous cells in AML was usually plump and eosinophilic, but sometimes clear with abundant glycogen, and an ovoid or irregular cleaved nucleus. AML cells, irrespective of whether they were epithelioid or leiomyomatous, stained positively for HMB45, S100 protein, and α-smooth muscle actin. RCL cells had histologic features identical to those of the leiomyomatous cells in AML. Moreover, the immunohistochemical profiles of the RCL cells were also identical to those of AML. These morphologic and immunohistochemical findings are different from those of smooth muscle tumors in soft parts and confirm that AML and RCL are closely related proliferative entities.     

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.     

Hepatic angiomyolipoma and hepatic stellate cells share a similar gene expression profile

BACKGROUND AND AIMS: Angiomyolipomas (AMLs) of the liver are rare neoplasms composed of large epithelioid cells with intermixed fat and blood vessels. Hepatic AMLs have no clear normal-cell counterpart in the liver. However, AMLs and stellate cells both are positive for neural crest-derived markers including HMB-45 antigen. METHODS: To further explore the similarities between hepatic AMLs and stellate cells, gene expression of a hepatic AML was studied by cDNA microarray. Real-time polymerase chain reaction was used to confirm gene expression. Hepatic stellate cells can be quiescent, activated, or have a myofibroblastic phenotype depending on their state of activation. Expression of known markers of activated stellate cells was compared between the AML, activated primary mouse stellate cells, and stellate cell lines with activated and myofibroblastic phenotypes. Next, 5 novel genes from the AML were selected because they were not previously known to be markers of stellate cells and mRNA expression measured in the activated mouse stellate cells and in myofibroblastic stellate cell lines. Finally, expression levels of 10 novel genes were determined in 5 cirrhotic and 5 noncirrhotic human livers. RESULTS: Overexpression of known markers of activated stellate cells including transforming growth factor beta (TGF- beta ), smooth muscle actin, and collagen was found in the hepatic AML. Three of 5 novel markers that were identified in the AML, RRAD (Ras-related associated with diabetes), CTSK (cathepsin K), and NIBAN were also found to be overexpressed in activated stellate cells compared with quiescent or myofibroblastic stellate cells. In addition, 9 of 10 novel genes overexpressed in AML were also overexpressed in cirrhotic human livers versus noncirrhotic livers. CONCLUSIONS: Hepatic AMLs share a similar gene expression profile and may differentiate toward activated stellate cells.     

Angiomyolipoma of the liver: a reappraisal of morphological features and delineation of new characteristic histological features from the clinicopathological findings of 55 tumours in 47 patients

Nonomura A, Enomoto Y, Takeda M, Takano M, Morita K & Kasai T
(2012) Histopathology  61, 863–880 Angiomyolipoma of the liver: a reappraisal of morphological features and delineation of new characteristic histological features from the clinicopathological findings of 55 tumours in 47 patients Aims: The aim of this study was to characterize and delineate the broad histological spectrum of hepatic angiomyolipoma (AML) and to obtain a better understanding of its clinicopathological diagnosis by reviewing a large series of AMLs. Methods and results: According to the proportions of three histological components, AML could be classified into 10 types; 36 of 55 tumours (65%) were classified as myomatous, eight as myoangiomatous, six as mixed (conventional), two as lipomatous, two as myolipomatous, and one as lipomyomatous. The morphology of smooth muscle cells (SMCs) in AML was quite variable, giving a wide variety of growth patterns. Fourteen (25%) of 55 tumours showed severe cellular atypia, and invasive growth of tumour cells was found in 69% of the tumours. However, except for two autopsy cases, all of the patients were in good health at follow‐up, without metastases. Immunostaining for HMB‐45 was positive in all cases. We found frequent lymphocyte infiltration, and the occasional presence of abnormally large blood vessels around the tumour at the tumour–background liver interface, features which have not been reported previously. Conclusions: The majority of hepatic AMLs were myomatous in type, showing variable cellular morphology and growth patterns. Cellular atypia and invasive growth were frequent, indicating that hepatic AMLs often show malignancy‐like histological features. Although the majority of cases behave as benign tumours, AML should be considered to have uncertain malignant potential, and careful follow‐up of patients is recommended. Immunostaining for HMB‐45 is specific for AML, and establishes the diagnosis. The occasional presence of abnormally large blood vessels around the tumour may give new insights into the evaluation of findings from imaging.     

A case report of brown tumor in a patient with chronic renal failure and renal cell carcinoma

We report a case of a 72 year old male with hyperparathyroidism secondary to end stage diabetic renal disease and coexisting bilateral chromophobe renal cell carcinomas. The patient presented with back and groin pain, right pelvic hemorrhage, and multiple lytic bone lesions concerning for metastatic renal cell carcinoma. Fine needle aspiration cytology demonstrated benign appearing osteoclasts and spindled cells. A concurrent core biopsy showed foci of spindled cell proliferation populated by osteoclast‐like giant cells with stromal hemorrhage without evidence of metastatic carcinoma. The cytologic and histologic findings, in correlation with the clinical history, radiographic features, markedly increased parathyroid hormone levels and other serologic studies, were diagnostic of the reactive lesion seen in brown tumor of hyperparathyroidism secondary to chronic renal failure.     

Invasive growth of hepatic angiomyolipoma; a hitherto unreported ominous histological feature

AIMS: Although histological features of hepatic angiomyolipoma (AML) are highly variable, true malignant change is extremely rare. The aim was to review the histological features of invasive growth and clinical outcomes in 39 cases of hepatic AML. METHODS AND RESULTS: An invasive growth pattern into surrounding hepatic parenchyma, portal triads and/or around hepatic veins was found in 24 of 39 tumours (62%). One variant showed tumour cells replacing hepatocytes within the liver cell cords. The other consisted of portal or perivascular invasive growth along blood vessels. In the former pattern, small isolated tumour cell clusters were occasionally found in the vicinity of the main mass, showing a sprouting pattern. Although these histological features suggest malignancy, distant metastases were not found in any of the cases within a mean follow-up period of 6.8 years. CONCLUSIONS: A previously unrecognized histological feature of an invasive growth pattern, which suggests malignancy and might promote an erroneous diagnosis, was frequently found in hepatic AMLs. However, among about 180 reported hepatic AMLs, including the present cases, only one hepatic AML with distant metastasis has been reported to date and nearly all hepatic AMLs behave in a benign fashion. Therefore, pathologists should not overdiagnose malignancy based solely on the histological invasive growth patterns described in this paper.     

Fine-needle aspiration of renal angiosarcoma

Angiosarcoma of the kidney is an unusual neoplasm, and primary renal angiosarcoma is exceedingly rare, with fewer than 11 well-documented cases reported to date. To our knowledge, no publication to date has correlated the fine-needle aspiration cytologic findings in renal angiosarcoma with the gross, histologic, and immunohistochemical findings. A 50-year-old man presented with a left kidney mass and multiple liver and pulmonary nodules. Computed tomography-guided fine-needle aspiration biopsies of the renal mass and a hepatic nodule were performed and demonstrated malignant spindle cells consistent with angiosarcoma. The diagnosis was confirmed at autopsy through histologic examination and associated ancillary studies. This case presents the fine-needle aspiration cytologic findings in renal angiosarcoma and correlates these findings with the gross pathologic, histologic, and immunohistochemical findings.     

Angiomyolipoma: Immunohistochemical and Ultrastructural Study of 14 Cases

Angiomyolipoma (AML) is a mesenchymal neoplasm of unclear histogenesis. In addition to varying amounts of smooth muscle, adipose tissue, and blood vessels, it contains a population of clear or pale eosinophilic epithelioid cells often arranged around blood vessels. Various phenotypes of AML have been described: leiomyoma-like, lipoma-like, epithelioid, and atypical. AMLs show consistent immunopositivity for HMB-45. This has been associated with the ultrastructural observation of melanosome-like structures in rare instances. In the present study, 14 AMLs from 13 patients were analyzed by electron microscopy and immunohistochemistry to determine the appearance and nature of cells composing AMLs. Overlap between cell types (spindle smooth muscle cells, epithelioid cells, and adipocytes) was found by both electron microscopy and immunohistochemistry. Melanosomes were found in 7 tumors. The cell of origin remains mysterious. Nevertheless, the study demonstrates that the AML is likely derived from a single cell that shares homology with the pericyte.     

Angiomyolipoma: immunohistochemical and ultrastructural study of 14 cases

Angiomyolipoma (AML) is a mesenchymal neoplasm of unclear histogenesis. In addition to varying amounts of smooth muscle, adipose tissue, and blood vessels, it contains a population of clear or pale eosinophilic epithelioid cells often arranged around blood vessels. Various phenotypes of AML have been described: leiomyoma-like, lipoma-like, epithelioid, and atypical. AMLs show consistent immunopositivity for HMB-45. This has been associated with the ultrastructural observation of melanosome-like structures in rare instances. In the present study, 14 AMLs from 13 patients were analyzed by electron microscopy and immunohistochemistry to determine the appearance and nature of cells composing AMLs. Overlap between cell types (spindle smooth muscle cells, epithelioid cells, and adipocytes) was found by both electron microscopy and immunohistochemistry. Melanosomes were found in 7 tumors. The cell of origin remains mysterious. Nevertheless, the study demonstrates that the AML is likely derived from a single cell that shares homology with the pericyte.     

Sensitivity of fine-needle aspiration biopsy in the detection of mycobacterial infections

A series of 290 fine needle aspiration biopsies (FNABs) processed for mycobacterial cultures are reviewed. The clinicopathologic features in 162 cases were suggestive of tuberculous infection and 86 (53%) of the samples in these cases were culture positive. A comparative histologic and cytologic correlation was carried out in 23 cases. Aspiration smears from caseating granulomas were composed of necrotic debris containing large numbers of polymorphonuclear cells and scattered histiocytes, epithelioid cells, and multinucleated giant cells. In cases of noncaseating granulomas, the smears revealed well-defined aggregates of epithelioid cells without necrotic debris or significant numbers of other inflammatory cells. There was a close correlation between the histologic and cytologic diagnosis of caseating and/or noncaseating granulomatous inflammation.     

Fine-needle aspiration cytology of papillary renal cell carcinoma: the association with concomitant secondary malignancies

Papillary renal cell carcinoma is a rare type of renal malignancy. Cytogenetic findings characteristic for this tumor have been described as well as mutations of the proto-oncogene c-met. Secondary malignancies occurring together with papillary renal cell carcinomas are rare, and are often of genitourinary tract origin. We describe two cases of papillary renal cell carcinoma occurring in association with two other visceral malignancies, gastrointestinal stromal tumor and colon adenocarcinoma.Two cases of papillary renal cell carcinoma diagnosed by fine-needle aspiration (FNA), occurring in association with gastrointestinal malignancies were reviewed.Both aspirates showed cytologic features characteristic for papillary renal cell carcinoma, namely papillary structures, foamy histiocytes, intracytoplasmic hemosiderin, and nuclear grooves. Subsequent histology and immunohistochemical stains supported the cytologic diagnosis. The histologic diagnosis of gastrointestinal stromal tumor and colon adenocarcinoma were confirmed.Papillary renal cell carcinoma is a type of renal carcinoma that can be often accurately diagnosed by FNA. The occurrence of associated visceral malignancies has never been reported. The possible role of the protooncogene c-met in the development of these tumors was explored.     

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.     

Epithelioid angiomyolipoma of the liver: a clinicopathologic study of 5 cases

This study aimed to study the clinicopathologic characteristics of epithelioid angiomyolipoma, a variant of angiomyolipoma (AML) in the liver; and to discuss the diagnostic challenges. Five cases of primary liver epithelioid AML were retrieved from our archives from January 2003 to October 2012. The clinicopathologic features of each case were retrospectively reviewed. All 5 patients were female, with age ranging from 36 to 70 years (median, 41 years). The size of the tumor ranged from 1.2 to 25 cm. Histologically, the tumor comprised polygonal cells with granular eosinophilic cytoplasm and accompanied by immunohistochemical expression of HMB-45 ± Melan-A. Variations in growth pattern and cytology were observed. Estrogen receptor was negative in all 5 cases. None showed cytologic atypia, coagulative necrosis, increased mitotic count, or vascular invasion. Epithelioid AML is an uncommon primary liver tumor with a female predominance. The size of the tumor can be variable. This tumor might impose diagnostic difficulty both clinically and histologically. Immunohistochemical staining with melanocytic markers is a promising means to confirm the pathologic diagnosis. A careful assessment of aggressive histologic features is recommended to stratify the risk of aggressive behavior of this tumor.     

Hepatocellular carcinoma: Needle biopsy findings in 74 cases

Needle aspiration specimens from 74 cases of hepatocellular carcinoma (HCC) diagnosed between January 1986 and December 1992 were reviewed and compared with 57 other lesions. The most specific cytologic findings for HCC included capillaries separating tumor cells (34%), bile associated with malignant cells (19%), and endothelial cells lining clusters of neoplastic cells (18%). Less specific findings included polygonal cells with central nuclei resembling normal hepatocytes and intranuclear inclusions. Tissue core fragments available in 53 cases of HCC disclosed that a weak keratin (AE1/AE3) stain (75% of HCC), a canalicular pattern of polyclonal carcinoembryonic antigen (54%), and a positive alpha-fetoprotein stain (58%) are diagnostic of HCC. All HCCs were negative for monoclonal carcinoembryonic antigen. In situ hybridization for albumin mRNA was positive in 27 of 33 cases of HCC. The diagnosis of HCC by needle biopsy should include cytologic findings and the appropriate immunohistochemical profile, along with detection of albumin mRNA by in situ hybridization. Diagn. Cytopathol. 16:8–13, 1997. © 1997 Wiley-Liss, Inc.