Renal Epithelioid Angiomyolipoma With Atypia: A Series of 40 Cases With Emphasis on Clinicopathologic Prognostic Indicators of Malignancy

Department of Pathology, The Johns Hopkins Hospital, Baltimore, MD, USA.
The American journal of surgical pathology (Impact Factor: 5.15). 05/2010; 34(5):715-22. DOI: 10.1097/PAS.0b013e3181d90370
Source: PubMed


As epithelioid cellular morphology can be seen in clinically benign usual angiomyolipomas (AMLs), we divide epithelioid AMLs into those without and with atypia, the latter category associated in the literature with malignant potential. We herein report the histologic spectrum and biologic behavior of 40 consecutive cases of epithelioid AML with atypia and assess whether cases can be stratified prognostically based on clinical and pathologic features. Atypical epithelioid cells were defined as atypical polygonal cells with abundant cytoplasm, vesicular nuclei, prominent nucleoli, and nuclear size that exceeds x2 the size of adjacent nuclei. The degree of atypia was divided to moderate and severe. Cases with bland epithelioid cells with minimal variation in nuclear size were not included. Mean age was 50.5 years (range 17 to 81), and the female to male ratio was 1.6:1. Average tumor size was 7.2 cm (range 1.0 to 17.7). The percentage of epithelioid component ranged from 5%-100% (mean 68%). Of the epithelioid component, the percentage of cells exhibiting nuclear atypia ranged in individual cases from 5% to 100% (mean of 58.4% atypical cells); 26/40 (65%) cases showed severe nuclear atypia. Cells displaying severe nuclear atypia were typically of large size with abundant cytoplasm, compared with those with moderate atypia being of small to intermediate in size with scant to moderate amount of cytoplasm. Neoplastic multinucleated giant cells and necrosis was present in 22 cases (55%) and 15 cases (37.5%), respectively. Mitoses were identified in 72.5% (29/40) of cases and ranged from 1 to 6 per 10 hpf with 7 cases showing atypical mitotic figures. Lymphovascular invasion or renal vein invasion was present in 3 cases each. Hilar and perinephric fat involvement was present in 5 and 6 cases, respectively. Clinical follow-up was available in 34 out of the 40 cases. Of the 34 cases, 9 (26%) were malignant and showed local recurrence or distant metastases. Of the 9 patients with malignant tumors, 4 died of the disease at 6, 12, 15, and 34 months after the original diagnosis was rendered, and 4 were alive with disease (mean follow-up period of 52 mo, range 24 to 72 mo). Twenty-four patients showed no evidence of recurrence and/or metastases with a mean follow-up period of 34 months (range 1 to 156 mo). We compared the 21 cases of atypical epithelioid AMLs that exhibited a benign clinical course with a minimum follow-up period of 6 months postsurgery to the 9 cases with malignant behavior. All of these were more frequently observed in clinically malignant cases: older age, larger tumor size, higher percentage of epithelioid component, severe atypia, higher percentage of atypical cells, higher mitotic count, atypical mitotic figures, necrosis, lymphovascular invasion, and renal vein invasion. Using these features, we developed a predictive model of 4 atypical features that included: (1) > or =70% atypical epithelioid cells, (2) > or =2 mitotic figures per 10 hpf, (3) atypical mitotic figures, and (4) necrosis; the presence of 3 or all of the features was highly predictive of malignant behavior. This model accurately categorized 78% of clinically malignant and 100% of the clinically benign epithelioid AMLs with atypia.

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Available from: Fadi Brimo
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    • "Some scholars believe EAML tumor cell atypia, mitotic figures, hemorrhage and necrosis, aggressive growth, vascular invasion, lymph node metastasis and local recurrence were potential indicators of malignancy [10]. Brimo et al. [11] proposed renal EAML has followed three or more indicators of biological behavior that highly represented malignancy: (i) Atypical epithelioid cell ratio ≥ 70%; (ii) Mitotic count ≥ 2/10 HP; (iii) Atypical mitotic; (iv) necrosis. Nese et al [12] shown those five adverse prognostic parameters of renal EAML: concurrent tuberous sclerosis or ordinary type angiomyolipoma; necrosis; tumor size > 7 cm; aggression and/or renal vein invasion: cancer-like growth pattern. "
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    ABSTRACT: Epithelioid angiomyolipoma (EAML) is a rare renal mesenchymal tumor with malignant potential and is frequently associated with tuberous sclerosis complex (TSC). As metastasis of the tumor cells occur early, EAML is considered a potentially malignant tumor type and intrigues further research on it. Under the microscope, we could find the tumor was composed of atypical polygonal cells sheet mixed with classic angiomyolipoma (AML) components such as blood vessels with notable thick vascular walls, smooth muscle-like cells and adipocytes. Immunohistochemical studies showed that epithelioid cells were focally positive for vimentin, melanocytic markers (HMB-45), myoid markers (α-smooth muscle actin), CD34 and CD68; negative for cytokeratin, epithelial membrane antigen, CD10, and S-100. And the Ki67 index showed approximately 3%. Here, we report the morphological and immunohistochemical features of clinically or histologically malignant renal EAML and discuss its diagnosis, differential diagnosis and the prognosis.
    Full-text · Article · Mar 2015 · International journal of clinical and experimental pathology
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    • "Macroscopic fat has high signal intensity on T1 and T2 sequence and leads to high sensitivity in the detection of extrarenal angiomyolipomas [18]. According to Brimo et al. [19] angiomyolipomas can be classified, depending on the consistence, in three major categories: regular, epithelioid with atypia, and epithelioid without atypia. Renal angiomyolipomas belong to the second or third group. "
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    ABSTRACT: Extrarenal angiomyolipoma (AML) is an extremely uncommon lesion, accounting for less than 9% of all angiomyolipomas. We present a previously unreported case of a rarely located gigantic extrarenal angiomyolipoma at the posterolateral chest wall of a 35-year-old woman. Clinically, the lesion had all the characteristics of a benign tumor, being soft in palpation, painless, and growing in size in a slow rate. Histologically, the lesion consisted of convoluted thick-walled blood vessels without an elastic layer, interlacing fascicles of smooth muscle, and mature adipose tissue, features consistent with an angiomyolipoma. The mass was surgically removed, without any postoperative complications, and the patient has an uneventful postoperative course. Signs of local recurrence have not been observed. The purpose of this brief report is to point out the necessity of including angiomyolipoma in the differential diagnosis of adipose layer lesions.
    Full-text · Article · Sep 2014
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    • "Although AMLs are considered benign, malignant transformation is not a rare complication associated with renal AML [11]. In recent years, the malignant transformation of hepatic AML has also been reported in the literature [12,13]. "
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    ABSTRACT: Background Hepatic angiomyolipoma is a rare benign mesenchymal tumor. We report an unusual case of a patient with multiple hepatic angiomyolipomas exhibiting high 18 F-fluorodeoxyglucose (FDG) uptake. Case presentation A 29-year-old man with a medical history of tuberous sclerosis was admitted to our hospital for fever, vomiting, and weight loss. Abdominal dynamic computed tomography revealed faint hypervascular hepatic tumors in segments 5 (67 mm) and 6 (10 mm), with rapid washout and clear borders; however, the tumors exhibited no definite fatty density. Abdominal magnetic resonance imaging revealed that the hepatic lesions were slightly hypointense on T1-weighted imaging, slightly hyperintense on T2-weighted imaging, and hyperintense with no apparent fat component on diffusion-weighted imaging. FDG-positron emission tomography (PET) imaging revealed high maximum standardized uptake values (SUVmax) of 6.27 (Segment 5) and 3.22 (Segment 6) in the hepatic tumors. A right hepatic lobectomy was performed, and part of the middle hepatic vein was also excised. Histological examination revealed that these tumors were characterized by the background infiltration of numerous inflammatory cells, including spindle-shaped cells, and a resemblance to an inflammatory pseudotumor. Immunohistochemical evaluation revealed that the tumor stained positively for human melanoma black-45. The tumor was therefore considered an inflammatory pseudotumor-like angiomyolipoma. Although several case reports of hepatic angiomyolipoma have been described or reviewed in the literature, only 3 have exhibited high 18 F-FDG uptake on PET imaging with SUVmax ranging from 3.3–4.0. In this case, increased 18 F-FDG uptake is more likely to appear, particularly if the inflammation is predominant. Conclusion Although literature regarding the role of 18 F-FDG-PET in hepatic angiomyolipoma diagnosis is limited and the diagnostic value of 18 F-FDG-PET has not yet been clearly defined, the possibility that hepatic angiomyolipoma might exhibit high 18 F-FDG uptake should be considered.
    Full-text · Article · May 2014 · BMC Medical Imaging
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