CASE REPORT
Malignant Renal Epithelioid Angiomyolipoma With Liver Metastasis After Resection: A Case Report With Multimodality Imaging and Review of the Literature Rafael A. Vicens, MD, Corey T. Jensen, MD, Brinda Rao Korivi, MD, MPH, and Priya R. Bhosale, MD Abstract: Renal epithelioid angiomyolipoma (EAML) is a perivascular epithelioid cell tumor. Although the overwhelming majority of renal EAMLs are benign, cases of aggressive behavior and malignancy have been reported. Here, we report the case of a 62-year-old woman with a 12.5-cm renal EAML, who underwent resection and developed a 10.5-cm hepatic EAML 15 months after the surgery. Although multicentric disease is a possibility, the temporal course is consistent with metastasis from the poorly differentiated primary tumor. This is the only report with multimodality imaging to detail new metastatic disease during surveillance after intended curative resection of an EAML. Key Words: renal epithelioid angiomyolipoma, malignant renal epithelioid angiomyolipoma, metastatic renal epithelioid angiomyolipoma, perivascular epithelioid cell tumor, EAML (J Comput Assist Tomogr 2014;38: 574–577)
CASE REPORT An otherwise healthy 62 year-old white woman with recurrent urinary tract infections presented to an outside institution complaining of low-grade fever, abdominal cramping, and unintentional weight loss. Clinical examination of the abdomen revealed a palpable right upper quadrant mass. The initial evaluation at an outside hospital included pyelography, which revealed a large mass deforming the right kidney. Subsequent multiphase computed tomographic (CT) scan demonstrated a centrally necrotic, exophytic, 12.5-cm mass originating from the lower pole of the right kidney (Fig. 1). The tumor exerted local mass effect without evidence of local invasion. No lymphadenopathy or distant metastases were detected. A 0.9-cm adjacent, right renal lesion with macroscopic fat was present, compatible with a conventional angiomyolipoma (AML). The patient underwent a right radical nephrectomy. Histopathologic analysis of the surgical specimen revealed features consistent with an epithelioid angiomyolipoma (EAML). Supplementary immunohistochemical studies revealed tumor cell positivity for melanoma antigen (melan-A), cluster of differentiation (focal), and human melanoma black 45 (HMB 45) (sparse) but were negative for anti-cytokeratin (CAM 5.2/AE1), cytokeratin 7, cytokeratin 20, epithelial membrane antigen, proximal nephrogenic renal antigen, smooth muscle actin, desmin, and S-100 proteins (S-100). The resection margin was negative for tumor cells, and the immediate postoperative period was uneventful. From the Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX. Received for publication March 19, 2014; accepted March 31, 2014. Reprints: Corey T. Jensen, MD, Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Pickens Academic Tower, 1400 Pressler St, Unit 1473, Houston, TX 77030-4009 (e‐mail: [email protected]). An expanded discussion of this “Case of the Quarter” can be found at the SCBT-MR Web site: scbtmr.dnnstaging.com The authors declare no conflict of interest. Copyright © 2014 by Lippincott Williams & Wilkins
574
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Fifteen months after the surgery, the patient began complaining of low-grade fever. Repeat multiphase CT scan depicted a new 10.5-cm right hepatic mass with similar imaging characteristics as the resected renal mass (Fig. 2). Results of a histologic analysis of tissue obtained by means of ultrasound-guided tissue sampling (Fig. 3) demonstrated a poorly differentiated epithelioid neoplasm with enlarged nuclei and granular eosinophilic cytoplasm. Results of an immunohistochemical analysis showed that the lesion was positive for melan-A, HMB-45, and smooth muscle actin as well as negative for pan-cytokeratin and S-100. DNA sequencing revealed a tuberous sclerosis complex 2 gene mutation. Staging with fluorine 18 [18F] fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT demonstrated moderate hypermetabolism (maximum standardized uptake value, 7.9) within the hepatic mass (Fig. 4) without other abnormal hypermetabolism. After the patient received 6 months of neoadjuvant therapy with everolimus, restaging CT displayed increased necrosis in the mass and decreased tumor volume compatible with treatment response; no new sites of the disease were evident. A right hepatectomy was performed through the previous nephrectomy scar (subcostal approach). The resected tumor was a lobulated, well-circumscribed, tan-brown, soft mass measuring 7.7 cm in the longest diameter, with multiple hemorrhagic and microcystic alterations. The center of the tumor had a yellow necrotic area measuring 2.3 cm in the longest diameter. The tumor was positive for HMB-45 and melan-A but negative for pan-cytokeratin and hepatocyte paraffin 1. Results of the immunohistochemical analysis showed less than 1% of nuclei stained for the proliferation marker Ki-67. At the time of this writing, the patient is under surveillance and has no evidence of disease 5 months after hepatic resection.
DISCUSSION Perivascular epithelioid cell tumors are mesenchymal in origin and have been reported to occur in various organs. The most common of these tumors is the renal AML, which is sporadic in 70% to 80% of cases, usually solitary, and has a prevalence of less than 1%; they may also occur as part of tuberous sclerosis complex, in which case the lesions are more commonly multicentric.1 Although AMLs are almost universally benign in nature, exceedingly rare presentations of malignant AMLs have been documented, with both locally aggressive and metastatic behavior.2 Angiomyolipomas with higher-than-normal percentages of epithelioid cell differentiation (EAMLs) have been linked with the highest rate of aggressive behavior.3,4 In a study of 185 AML cases reported by Aydin et al,5 approximately 8% of renal AMLs demonstrated this increased degree of epithelioid differentiation. Renal EAMLs have been reported to occur at a mean patient age of approximately 40 years and to have an even distribution between sexes, according to Nese et al.3 In contrast, sporadic, conventional renal AMLs occur more commonly in women and the mean reported patient age at incidence is approximately 10 years later than that of EAML. This difference may be partly J Comput Assist Tomogr • Volume 38, Number 4, July/August 2014
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
J Comput Assist Tomogr • Volume 38, Number 4, July/August 2014
Malignant Renal EAML With Liver Metastasis
FIGURE 1. Upon initial presentation, axial noncontrast (A), arterial (B), portal venous (C), and delayed contrast (D) phase CT images demonstrated a large predominantly isoattenuating right renal mass, which enhanced heterogeneously and displayed central necrosis. Small regions of amorphous calcification are evident along the periphery of the tumor necrosis. Minimal washout is noted on the delayed contrast phase. No macroscopic fat, local invasion, or metastasis was identified.
related to the greater incidence of EAML symptoms relative to conventional AML. In addition, prior EAML evaluations have included patients with tuberous sclerosis complex, which is known to carry an earlier incidence of AML and a near-even sex distribution.3,5,6 The rarity, aspects of diagnostic uncertainty, and lack of agreement about certain diagnostic features currently limit our
understanding of EAML. For example, a conventional AML is easily diagnosed on the basis of typical portions of dysmorphic blood vessels, adipose tissue, and smooth muscle; the diagnosis of the EAML variant relies heavily on immunohistochemical data to exclude sometimes similar-appearing tumors, such as renal cell carcinomas, because the conventional AML components of dysmorphic blood vessels and adipose tissue are
FIGURE 2. Axial, contrast-enhanced CT image from a scan performed 15 months after the renal mass resection displays a new, large, enhancing, centrally necrotic right hepatic mass with an appearance nearly identical to that of the previously resected right renal EAML.
FIGURE 3. Transverse ultrasound image obtained during hepatic biopsy shows a large hyperechoic mass in the right liver with central necrosis.
© 2014 Lippincott Williams & Wilkins
www.jcat.org
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
575
J Comput Assist Tomogr • Volume 38, Number 4, July/August 2014
Vicens et al
FIGURE 4. [18F] FDG PET-CT revealed a large hypermetabolic mass (maximum standardized uptake value = 7.9) in the right liver; the relative central photopenia is consistent with necrosis. Figure 4 can be viewed online in color at www.jcat.org.
rare to absent.5,7 Similar to conventional AMLs, EAMLs are typically positive for melanocytic markers and negative for S-100 and epithelial markers.5 However, the uncertain degree of epithelioid differentiation investigators have used to warrant a diagnosis of EAML contributes difficulty to the evaluation. For instance, Brimo et al8 allowed for as little as 5% epithelioid differentiation when classifying tumors as EAMLs, whereas other authors3 have required pure epithelioid differentiation. Imaging evaluation is helpful but limited in the evaluation of EAML, as with other lipid-poor AMLs, which account for 4.5% of conventional AMLs.9 There are no specific radiologic findings of the EAML variant to reliably separate them from other lipid-poor AMLs or certain renal cell carcinomas.2 Much like conventional AMLs, many EAMLs have slightly higher attenuation than the adjacent renal parenchyma on non–contrast CT. This feature is likely related to the underlying cellular histology and not calcification or hemorrhage, which is known to be uncommon.10 Although this case did contain thin portions of calcification that immediately bordered the central necrosis and others have also reported AMLs with calcification,10 Yang et al9 showed no calcification in 33 cases of non–epithelioid AML and Froemming et al2 reported that none of their 9 cases of EAML had calcification directly attributable to the tumor. There is a paucity of data regarding AML evaluation with [18F] FDG PET-CT. Lin et al11 reported 21 non–pathologically proven cases of renal AML that were a mean diameter of 1.76 cm with no lesion demonstrating a maximum standardized uptake value greater than 2; however, a few reports have described hypermetabolic AMLs.12–14 Given the lack of strict, pathologically proven [18F] FDG PET-CT evaluation of AML and, more specifically, EAML, hypermetabolism should be cautiously regarded as concerning. Although no pathognomonic EAML imaging features exist for any current imaging modality, certain findings should be regarded as concerning. For example, Yang et al9 showed that nearly all lipid-poor, non–epithelioid AMLs demonstrated homogeneous enhancement, whereas Froemming et al2 reported that all 9 EAMLs displayed heterogeneous enhancement. In addition to heterogeneous enhancement, other features such as tuberous sclerosis complex association, multicentric lesions, necrosis, large tumor size (>7 cm), and extrarenal extension indicated risk for aggressive disease.3,15 In our case, the initial renal tumor was large, it avidly and heterogeneously enhanced, it had central necrosis, and it exhibited only a minimal decrease in attenuation on the delayed phase of imaging (17-Hounsfield unit decrease compared with peak enhancement noted during the portal
576
www.jcat.org
venous phase). In summary, knowledge of EAML imaging characteristics is evolving and pathologic standardization will allow for better future correlation with imaging. In addition to evaluation of the primary tumor, imaging evaluation for local and distant disease is useful for clinical management, such as assessing the utility of lesion resection and detailing local involvement to aid in preoperative planning. Renal EAMLs are associated with advanced local disease in 23% to 35% of cases, and a recurrence rate of 17% and metastases occur in nearly 50% of patients during the course of disease.3 The liver and lungs are the most common locations for distant metastases. Importantly, imaging assessment for possible locoregional and distant disease can indicate the aggressiveness of underlying tumor biology and thus further guide treatment decisions. It is important to note that a few previous authors have suggested the term multicentric rather than metastatic in cases such as ours with multiple sites possibly caused by the congenital presence of cell precursors or benign metastases.16 Although such a determination is beyond the scope of our report, the temporal disease course of our case is consistent with a metastatic process related to an increasingly recognized aggressive nature of EAMLs. Because of the sources of complexity surrounding EAML diagnosis, proper treatment is evolving. When solitary, EAMLs have thus far been treated with surgical resection, with or without chemotherapy. A study by Kenerson et al17 showed uniform activation of the mammalian target of rapamycin cascade in EAMLs, and evidence indicates that patients may benefit from the use of mammalian target of rapamycin inhibitors.18 In the setting of metastases, the proper therapy is also still being determined. In conclusion, renal EAML is an uncommon tumor that can be confused with other entities during pathologic analysis and is not reliably distinguished from other lipid-poor neoplasms by imaging. Certain key radiographic features can suggest EAML as a possibility rather than conventional AML; these characteristics include lipid-poor, isoattenuation to hyperattenuation (on precontrast CT), typically non–calcified, heterogeneously enhancing, large tumor, especially in patients with tuberous sclerosis complex or multicentric AMLs. The presence of necrosis and [18F] FDG PET-CT hypermetabolism is not specific, but it often indicates aggressive tumor biology. Our case used multimodality imaging to illustrate the importance of imaging surveillance after resection of a solitary EAML because these tumors have been shown to recur and metastasize. REFERENCES 1. Nelson CP, Sanda MG. Contemporary diagnosis and management of renal angiomyolipoma. J Urol. 2002;168:1315–1325. 2. Froemming AT, Boland J, Cheville J, et al. Renal epithelioid angiomyolipoma: imaging characteristics in nine cases with radiologic-pathologic correlation and review of the literature. AJR Am J Roentgenol. 2013;200:W178–W186. 3. Nese N, Martignoni G, Fletcher CD, et al. Pure epithelioid pecomas (so-called epithelioid angiomyolipoma) of the kidney: a clinicopathologic study of 41 cases: detailed assessment of morphology and risk stratification. Am J Surg Pathol. 2011;35:161–176. 4. Faraji H, Nguyen BN, Mai KT. Renal epithelioid angiomyolipoma: a study of six cases and a meta-analytic study: development of criteria for screening the entity with prognostic significance. Histopathology. 2009;55:525–534. 5. Aydin H, Magi-Galluzzi C, Lane BR, et al. Renal angiomyolipoma: clinicopathologic study of 194 cases with emphasis on the epithelioid histology and tuberous sclerosis association. Am J Surg Pathol. 2009;33: 289–297.
© 2014 Lippincott Williams & Wilkins
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
J Comput Assist Tomogr • Volume 38, Number 4, July/August 2014
Malignant Renal EAML With Liver Metastasis
6. Katabathina VS, Vikram R, Nagar AM, et al. Mesenchymal neoplasms of the kidney in adults: imaging spectrum with radiologic-pathologic correlation. Radiographics. 2010;30:1525–1540.
13. Dong A, Wang Y, Zuo C. Synchronous pure epithelioid angiomyolipoma of the kidney and retroperitoneal schwannoma in the same patient on 18F-FDG PET/CT imaging. Clin Nucl Med. 2013;38:e98–e100.
7. Bharwani N, Christmas TJ, Jameson C, et al. Epithelioid angiomyolipoma: imaging appearances. Br J Radiol. 2009;82:e249–e252.
14. Kochhar R, Brown RK, Wong CO, et al. Role of FDG PET/CT in imaging of renal lesions. J Med Imaging Radiat Oncol. 2010; 54:347–357.
8. Brimo F, Robinson B, Guo C, et al. Renal epithelioid angiomyolipoma with atypia: a series of 40 cases with emphasis on clinicopathologic prognostic indicators of malignancy. Am J Surg Pathol. 2010;34:715–722. 9. Yang W, Li G, Wei-qiang Z. Multifocal PEComa (PEComatosis) of the female genital tract and pelvis: a case report and review of the literature. Diagn Pathol. 2012;7:23. 10. Yarmish G, DiPoce J. Aggressive angiomyolipoma with renal vein thrombosis and pulmonary fat embolus. Radiology. 2013;269:615–618. 11. Lin C, Chen H, Ding H, et al. FDG PET or PET/CT in evaluation of renal angiomyolipoma. Korean J Radiol. 2013;14:337–342. 12. Welling RD, Lungren MP, Coleman RE. Extrarenal retroperitoneal angiomyolipoma mimicking metastatic melanoma: CT and FDG PET correlation. Clin Nucl Med. 2012;37:705–706.
© 2014 Lippincott Williams & Wilkins
15. Raman SP, Hruban RH, Fishman EK. Beyond renal cell carcinoma: rare and unusual renal masses. Abdom Imaging. 2012;37:873–884. 16. Lai HY, Chen CK, Lee YH, et al. Multicentric aggressive angiomyolipomas: a rare form of PEComas. AJR Am J Roentgenol. 2006;186:837–840. 17. Kenerson H, Folpe AL, Takayama TK, et al. Activation of the mTOR pathway in sporadic angiomyolipomas and other perivascular epithelioid cell neoplasms. Hum Pathol. 2007;38:1361–1371. 18. Faria E, Turturro F, Rao P, et al. Malignant epithelioid angiomyolipoma: tumor and metabolic response to everolimus as evaluated with positron emission tomography. Clin Genitourin Cancer. 2013;11:e1–e5.
www.jcat.org
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
577
Malignant Renal Epithelioid Angiomyolipoma With Liver Metastasis After Resection: A Case Report With Multimodality Imaging and Review of the Literature Rafael A. Vicens, MD, Corey T. Jensen, MD, Brinda Rao Korivi, MD, MPH, and Priya R. Bhosale, MD Abstract: Renal epithelioid angiomyolipoma (EAML) is a perivascular epithelioid cell tumor. Although the overwhelming majority of renal EAMLs are benign, cases of aggressive behavior and malignancy have been reported. Here, we report the case of a 62-year-old woman with a 12.5-cm renal EAML, who underwent resection and developed a 10.5-cm hepatic EAML 15 months after the surgery. Although multicentric disease is a possibility, the temporal course is consistent with metastasis from the poorly differentiated primary tumor. This is the only report with multimodality imaging to detail new metastatic disease during surveillance after intended curative resection of an EAML. Key Words: renal epithelioid angiomyolipoma, malignant renal epithelioid angiomyolipoma, metastatic renal epithelioid angiomyolipoma, perivascular epithelioid cell tumor, EAML (J Comput Assist Tomogr 2014;38: 574–577)
CASE REPORT An otherwise healthy 62 year-old white woman with recurrent urinary tract infections presented to an outside institution complaining of low-grade fever, abdominal cramping, and unintentional weight loss. Clinical examination of the abdomen revealed a palpable right upper quadrant mass. The initial evaluation at an outside hospital included pyelography, which revealed a large mass deforming the right kidney. Subsequent multiphase computed tomographic (CT) scan demonstrated a centrally necrotic, exophytic, 12.5-cm mass originating from the lower pole of the right kidney (Fig. 1). The tumor exerted local mass effect without evidence of local invasion. No lymphadenopathy or distant metastases were detected. A 0.9-cm adjacent, right renal lesion with macroscopic fat was present, compatible with a conventional angiomyolipoma (AML). The patient underwent a right radical nephrectomy. Histopathologic analysis of the surgical specimen revealed features consistent with an epithelioid angiomyolipoma (EAML). Supplementary immunohistochemical studies revealed tumor cell positivity for melanoma antigen (melan-A), cluster of differentiation (focal), and human melanoma black 45 (HMB 45) (sparse) but were negative for anti-cytokeratin (CAM 5.2/AE1), cytokeratin 7, cytokeratin 20, epithelial membrane antigen, proximal nephrogenic renal antigen, smooth muscle actin, desmin, and S-100 proteins (S-100). The resection margin was negative for tumor cells, and the immediate postoperative period was uneventful. From the Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX. Received for publication March 19, 2014; accepted March 31, 2014. Reprints: Corey T. Jensen, MD, Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Pickens Academic Tower, 1400 Pressler St, Unit 1473, Houston, TX 77030-4009 (e‐mail: [email protected]). An expanded discussion of this “Case of the Quarter” can be found at the SCBT-MR Web site: scbtmr.dnnstaging.com The authors declare no conflict of interest. Copyright © 2014 by Lippincott Williams & Wilkins
574
www.jcat.org
Fifteen months after the surgery, the patient began complaining of low-grade fever. Repeat multiphase CT scan depicted a new 10.5-cm right hepatic mass with similar imaging characteristics as the resected renal mass (Fig. 2). Results of a histologic analysis of tissue obtained by means of ultrasound-guided tissue sampling (Fig. 3) demonstrated a poorly differentiated epithelioid neoplasm with enlarged nuclei and granular eosinophilic cytoplasm. Results of an immunohistochemical analysis showed that the lesion was positive for melan-A, HMB-45, and smooth muscle actin as well as negative for pan-cytokeratin and S-100. DNA sequencing revealed a tuberous sclerosis complex 2 gene mutation. Staging with fluorine 18 [18F] fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT demonstrated moderate hypermetabolism (maximum standardized uptake value, 7.9) within the hepatic mass (Fig. 4) without other abnormal hypermetabolism. After the patient received 6 months of neoadjuvant therapy with everolimus, restaging CT displayed increased necrosis in the mass and decreased tumor volume compatible with treatment response; no new sites of the disease were evident. A right hepatectomy was performed through the previous nephrectomy scar (subcostal approach). The resected tumor was a lobulated, well-circumscribed, tan-brown, soft mass measuring 7.7 cm in the longest diameter, with multiple hemorrhagic and microcystic alterations. The center of the tumor had a yellow necrotic area measuring 2.3 cm in the longest diameter. The tumor was positive for HMB-45 and melan-A but negative for pan-cytokeratin and hepatocyte paraffin 1. Results of the immunohistochemical analysis showed less than 1% of nuclei stained for the proliferation marker Ki-67. At the time of this writing, the patient is under surveillance and has no evidence of disease 5 months after hepatic resection.
DISCUSSION Perivascular epithelioid cell tumors are mesenchymal in origin and have been reported to occur in various organs. The most common of these tumors is the renal AML, which is sporadic in 70% to 80% of cases, usually solitary, and has a prevalence of less than 1%; they may also occur as part of tuberous sclerosis complex, in which case the lesions are more commonly multicentric.1 Although AMLs are almost universally benign in nature, exceedingly rare presentations of malignant AMLs have been documented, with both locally aggressive and metastatic behavior.2 Angiomyolipomas with higher-than-normal percentages of epithelioid cell differentiation (EAMLs) have been linked with the highest rate of aggressive behavior.3,4 In a study of 185 AML cases reported by Aydin et al,5 approximately 8% of renal AMLs demonstrated this increased degree of epithelioid differentiation. Renal EAMLs have been reported to occur at a mean patient age of approximately 40 years and to have an even distribution between sexes, according to Nese et al.3 In contrast, sporadic, conventional renal AMLs occur more commonly in women and the mean reported patient age at incidence is approximately 10 years later than that of EAML. This difference may be partly J Comput Assist Tomogr • Volume 38, Number 4, July/August 2014
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
J Comput Assist Tomogr • Volume 38, Number 4, July/August 2014
Malignant Renal EAML With Liver Metastasis
FIGURE 1. Upon initial presentation, axial noncontrast (A), arterial (B), portal venous (C), and delayed contrast (D) phase CT images demonstrated a large predominantly isoattenuating right renal mass, which enhanced heterogeneously and displayed central necrosis. Small regions of amorphous calcification are evident along the periphery of the tumor necrosis. Minimal washout is noted on the delayed contrast phase. No macroscopic fat, local invasion, or metastasis was identified.
related to the greater incidence of EAML symptoms relative to conventional AML. In addition, prior EAML evaluations have included patients with tuberous sclerosis complex, which is known to carry an earlier incidence of AML and a near-even sex distribution.3,5,6 The rarity, aspects of diagnostic uncertainty, and lack of agreement about certain diagnostic features currently limit our
understanding of EAML. For example, a conventional AML is easily diagnosed on the basis of typical portions of dysmorphic blood vessels, adipose tissue, and smooth muscle; the diagnosis of the EAML variant relies heavily on immunohistochemical data to exclude sometimes similar-appearing tumors, such as renal cell carcinomas, because the conventional AML components of dysmorphic blood vessels and adipose tissue are
FIGURE 2. Axial, contrast-enhanced CT image from a scan performed 15 months after the renal mass resection displays a new, large, enhancing, centrally necrotic right hepatic mass with an appearance nearly identical to that of the previously resected right renal EAML.
FIGURE 3. Transverse ultrasound image obtained during hepatic biopsy shows a large hyperechoic mass in the right liver with central necrosis.
© 2014 Lippincott Williams & Wilkins
www.jcat.org
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
575
J Comput Assist Tomogr • Volume 38, Number 4, July/August 2014
Vicens et al
FIGURE 4. [18F] FDG PET-CT revealed a large hypermetabolic mass (maximum standardized uptake value = 7.9) in the right liver; the relative central photopenia is consistent with necrosis. Figure 4 can be viewed online in color at www.jcat.org.
rare to absent.5,7 Similar to conventional AMLs, EAMLs are typically positive for melanocytic markers and negative for S-100 and epithelial markers.5 However, the uncertain degree of epithelioid differentiation investigators have used to warrant a diagnosis of EAML contributes difficulty to the evaluation. For instance, Brimo et al8 allowed for as little as 5% epithelioid differentiation when classifying tumors as EAMLs, whereas other authors3 have required pure epithelioid differentiation. Imaging evaluation is helpful but limited in the evaluation of EAML, as with other lipid-poor AMLs, which account for 4.5% of conventional AMLs.9 There are no specific radiologic findings of the EAML variant to reliably separate them from other lipid-poor AMLs or certain renal cell carcinomas.2 Much like conventional AMLs, many EAMLs have slightly higher attenuation than the adjacent renal parenchyma on non–contrast CT. This feature is likely related to the underlying cellular histology and not calcification or hemorrhage, which is known to be uncommon.10 Although this case did contain thin portions of calcification that immediately bordered the central necrosis and others have also reported AMLs with calcification,10 Yang et al9 showed no calcification in 33 cases of non–epithelioid AML and Froemming et al2 reported that none of their 9 cases of EAML had calcification directly attributable to the tumor. There is a paucity of data regarding AML evaluation with [18F] FDG PET-CT. Lin et al11 reported 21 non–pathologically proven cases of renal AML that were a mean diameter of 1.76 cm with no lesion demonstrating a maximum standardized uptake value greater than 2; however, a few reports have described hypermetabolic AMLs.12–14 Given the lack of strict, pathologically proven [18F] FDG PET-CT evaluation of AML and, more specifically, EAML, hypermetabolism should be cautiously regarded as concerning. Although no pathognomonic EAML imaging features exist for any current imaging modality, certain findings should be regarded as concerning. For example, Yang et al9 showed that nearly all lipid-poor, non–epithelioid AMLs demonstrated homogeneous enhancement, whereas Froemming et al2 reported that all 9 EAMLs displayed heterogeneous enhancement. In addition to heterogeneous enhancement, other features such as tuberous sclerosis complex association, multicentric lesions, necrosis, large tumor size (>7 cm), and extrarenal extension indicated risk for aggressive disease.3,15 In our case, the initial renal tumor was large, it avidly and heterogeneously enhanced, it had central necrosis, and it exhibited only a minimal decrease in attenuation on the delayed phase of imaging (17-Hounsfield unit decrease compared with peak enhancement noted during the portal
576
www.jcat.org
venous phase). In summary, knowledge of EAML imaging characteristics is evolving and pathologic standardization will allow for better future correlation with imaging. In addition to evaluation of the primary tumor, imaging evaluation for local and distant disease is useful for clinical management, such as assessing the utility of lesion resection and detailing local involvement to aid in preoperative planning. Renal EAMLs are associated with advanced local disease in 23% to 35% of cases, and a recurrence rate of 17% and metastases occur in nearly 50% of patients during the course of disease.3 The liver and lungs are the most common locations for distant metastases. Importantly, imaging assessment for possible locoregional and distant disease can indicate the aggressiveness of underlying tumor biology and thus further guide treatment decisions. It is important to note that a few previous authors have suggested the term multicentric rather than metastatic in cases such as ours with multiple sites possibly caused by the congenital presence of cell precursors or benign metastases.16 Although such a determination is beyond the scope of our report, the temporal disease course of our case is consistent with a metastatic process related to an increasingly recognized aggressive nature of EAMLs. Because of the sources of complexity surrounding EAML diagnosis, proper treatment is evolving. When solitary, EAMLs have thus far been treated with surgical resection, with or without chemotherapy. A study by Kenerson et al17 showed uniform activation of the mammalian target of rapamycin cascade in EAMLs, and evidence indicates that patients may benefit from the use of mammalian target of rapamycin inhibitors.18 In the setting of metastases, the proper therapy is also still being determined. In conclusion, renal EAML is an uncommon tumor that can be confused with other entities during pathologic analysis and is not reliably distinguished from other lipid-poor neoplasms by imaging. Certain key radiographic features can suggest EAML as a possibility rather than conventional AML; these characteristics include lipid-poor, isoattenuation to hyperattenuation (on precontrast CT), typically non–calcified, heterogeneously enhancing, large tumor, especially in patients with tuberous sclerosis complex or multicentric AMLs. The presence of necrosis and [18F] FDG PET-CT hypermetabolism is not specific, but it often indicates aggressive tumor biology. Our case used multimodality imaging to illustrate the importance of imaging surveillance after resection of a solitary EAML because these tumors have been shown to recur and metastasize. REFERENCES 1. Nelson CP, Sanda MG. Contemporary diagnosis and management of renal angiomyolipoma. J Urol. 2002;168:1315–1325. 2. Froemming AT, Boland J, Cheville J, et al. Renal epithelioid angiomyolipoma: imaging characteristics in nine cases with radiologic-pathologic correlation and review of the literature. AJR Am J Roentgenol. 2013;200:W178–W186. 3. Nese N, Martignoni G, Fletcher CD, et al. Pure epithelioid pecomas (so-called epithelioid angiomyolipoma) of the kidney: a clinicopathologic study of 41 cases: detailed assessment of morphology and risk stratification. Am J Surg Pathol. 2011;35:161–176. 4. Faraji H, Nguyen BN, Mai KT. Renal epithelioid angiomyolipoma: a study of six cases and a meta-analytic study: development of criteria for screening the entity with prognostic significance. Histopathology. 2009;55:525–534. 5. Aydin H, Magi-Galluzzi C, Lane BR, et al. Renal angiomyolipoma: clinicopathologic study of 194 cases with emphasis on the epithelioid histology and tuberous sclerosis association. Am J Surg Pathol. 2009;33: 289–297.
© 2014 Lippincott Williams & Wilkins
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
J Comput Assist Tomogr • Volume 38, Number 4, July/August 2014
Malignant Renal EAML With Liver Metastasis
6. Katabathina VS, Vikram R, Nagar AM, et al. Mesenchymal neoplasms of the kidney in adults: imaging spectrum with radiologic-pathologic correlation. Radiographics. 2010;30:1525–1540.
13. Dong A, Wang Y, Zuo C. Synchronous pure epithelioid angiomyolipoma of the kidney and retroperitoneal schwannoma in the same patient on 18F-FDG PET/CT imaging. Clin Nucl Med. 2013;38:e98–e100.
7. Bharwani N, Christmas TJ, Jameson C, et al. Epithelioid angiomyolipoma: imaging appearances. Br J Radiol. 2009;82:e249–e252.
14. Kochhar R, Brown RK, Wong CO, et al. Role of FDG PET/CT in imaging of renal lesions. J Med Imaging Radiat Oncol. 2010; 54:347–357.
8. Brimo F, Robinson B, Guo C, et al. Renal epithelioid angiomyolipoma with atypia: a series of 40 cases with emphasis on clinicopathologic prognostic indicators of malignancy. Am J Surg Pathol. 2010;34:715–722. 9. Yang W, Li G, Wei-qiang Z. Multifocal PEComa (PEComatosis) of the female genital tract and pelvis: a case report and review of the literature. Diagn Pathol. 2012;7:23. 10. Yarmish G, DiPoce J. Aggressive angiomyolipoma with renal vein thrombosis and pulmonary fat embolus. Radiology. 2013;269:615–618. 11. Lin C, Chen H, Ding H, et al. FDG PET or PET/CT in evaluation of renal angiomyolipoma. Korean J Radiol. 2013;14:337–342. 12. Welling RD, Lungren MP, Coleman RE. Extrarenal retroperitoneal angiomyolipoma mimicking metastatic melanoma: CT and FDG PET correlation. Clin Nucl Med. 2012;37:705–706.
© 2014 Lippincott Williams & Wilkins
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