Pediatric Case Report Epithelioid Angiomyolipoma in a Child—A Diagnostic Dilemma Rakesh Kumar Gupta, Mehar Chand Sharma, Sanjeev Chitragar, Kalpana Sinha, Sandeep Agarwala, and Raju Sharma Epithelioid angiomyolipoma (EAML) is a rare variant of angiomyolipoma found to have malignant potential and poorer prognosis. It is characterized by the predominance of epithelioid cells and frequent association with tuberous sclerosis. Its usual age of presentation is between the fourth and fifth decades of life, and only a single case has been reported in the pediatric age group. In this study, we report a case of epithelioid angiomyolipoma in a 4-year-old child with features of tuberous sclerosis, which is the youngest age of presentation. UROLOGY -: -e-, 2014. 2014 Elsevier Inc.
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pithelioid angiomyolipoma (EAML) is a rare variant of angiomyolipoma (AML) of the kidney. The 2004 World Health Organization classification of renal neoplasms defines it as “a potentially malignant mesenchymal neoplasm characterized by proliferation of predominantly epithelioid cells” and is closely related to classic AML.1 EAML shows a significant association (>50% cases) with tuberous sclerosis (TS), and one-third of these patients show distant metastases into liver, lung, lymph nodes, and so forth.1 A 2%-3% lifetime risk of renal cell carcinoma (RCC) is also noted in association with TS. The mean age at diagnosis reported is 38 years, whereas a single case report described the occurrence of EAML in a 12-year-old child in association with TS.2 A total of 18 cases of renal AMLs have been diagnosed in the Department of Pathology of this hospital in the last 5 years, of which 2 cases were reported as EAMLs, and only 1 case was in the pediatric age. In this study, we describe a case of EAML in a 4-yearold female child with stigmata of TS, which is the youngest age of tumor presentation reported so far, to the best of our knowledge.
CASE REPORT This 4-year-old female child was brought to the outpatient department of Pediatric Surgery with the chief complaint of right abdominal mass since 4 months. The patient also had a history of generalized tonic-clonic seizures since the age of 2 years, for which she was taking sodium valproate. The patient was found to have a All authors contributed equally. Financial Disclosure: The authors declare that they have no relevant financial interests. From the Department of Pathology, All India Institute of Medical Sciences (AIIMS), New Delhi, India; the Department of Pediatric Surgery, All India Institute of Medical Sciences (AIIMS), New Delhi, India; and the Department of Radiology, All India Institute of Medical Sciences (AIIMS), New Delhi, India Reprint requests: Mehar Chand Sharma, M.D., Department of Pathology, All India Institute of Medical Sciences, New Delhi 110029, India. E-mail: sharmamehar@ yahoo.co.in Submitted: October 23, 2013, accepted (with revisions): December 26, 2013
ª 2014 Elsevier Inc. All Rights Reserved
diffuse solid vague tender lump in the right lumbar region measuring approximately 10 5 5 cm. She was also having stigmata of TS in the form of Shagreen patches in the sacral region and axillary freckling. Family history was noncontributory. Her intelligence quotient level was normal. The clinical differential diagnoses of Wilms tumor (WT) and neuroblastoma were entertained. Abdominal computed tomographic scan showed a large contrast enhancing mass in the right kidney replacing normal parenchyma. No fat component was seen (Fig. 1). The other kidney revealed no abnormality. Computed tomographic scan brain revealed few subependymal nodules. No other TS-associated abnormalities were noted. Fine needle aspiration cytology (FNAC) was done to exclude the possibilities of WT and neuroblastoma. FNAC showed a tumor comprising of predominantly epithelial cells with moderate pleomorphism and minor stromal cell component. Because no definitive diagnosis could be made, cystohistologic correlation was advised. HMB-45 immunostaining was not done, as diagnosis of AML was not suspected. After FNAC, right nephroureterectomy with lymph nodes dissection was done. Intraoperatively, ureter, inferior vena cava, and surrounding structures were free. Pathologic Examination Right nephrectomy specimen measured 15 9 7 cm in dimensions and weighed 520 g. Whole of the kidney was replaced by a tumor, which was well encapsulated. The cut surface was solid, greyish white, lobulated with focal areas of necrosis and myxoid degeneration (Fig. 2). Immunohistochemistry was performed using antibodies against HMB-45 (Novocastra, dilution, 1:100), smooth muscle actin (SMA) (Thermo-scientific, dilution, 1:400), Hamartin (Acris, dilution, 1:400), Tuberin (Novocastra, dilution, 1:25), pancytokeratin (CK) (Neomarker, dilution 1:200), epithelial membrane antigen (EMA) (Dako, dilution, 1: 100), Desmin (Thermo-scientific, dilution, 1:100), Myogenin (Thermo-scientific, dilution, 1:50), 0090-4295/14/$36.00 http://dx.doi.org/10.1016/j.urology.2013.12.044
1
Figure 1. Contrast enhanced computed tomography abdomen showing homogenously enhancing mass (arrow) in the right kidney replacing normal parenchyma. (Color version available online.)
CD117 (Spring, dilution, 1:200), WT1 (Bio SB, dilution, 1:250), INI 1(Cell Morque, dilution, 1:100), and MIB-1 (Dako, dilution, 1:200). Labeled streptavidin biotin kit (Universal) was used as a detection system (Dako, Denmark). Appropriate positive and negative controls were put for each antibody.
Figure 2. Right nephrectomy specimen showing a solid, gray white, lobulated tumor replacing the entire renal parenchyma. Foci of necrosis and myxoid degeneration are noted. (Color version available online.)
controlled completely, and she developed new facial angiofibroma.
COMMENT Histopathologic Examination Microscopic examination showed a tumor comprising predominantly of moderately pleomorphic polygonal epithelioid cells with distinct cellular outlines and abundant amount of granular eosinophilic cytoplasm (Fig. 3). The epithelioid cell component was comprising >95% of the tumor. Nuclei were vesicular with prominent nucleoli. At places, focal spindling of tumor cells was seen. Amidst the tumor cells, interspersed dysmorphic thick-walled blood vessels were present. A few entrapped renal tubules were noted. Areas of geographic necrosis were present, but mitoses were not evident. Giant cells, ganglion-like cells, and adipose tissue were absent. Vascular invasion and perinephric fat infiltration were not noted. Total 8 lymph nodes isolated were free of tumor. Tumor cells were immunopositive for HMB-45 and SMA but were negative for CK, EMA, desmin, myogenin, CD117, and WT1. MIB-1 labeling index was
E
pithelioid angiomyolipoma (EAML) is a rare variant of angiomyolipoma (AML) of the kidney. The 2004 World Health Organization classification of renal neoplasms defines it as “a potentially malignant mesenchymal neoplasm characterized by proliferation of predominantly epithelioid cells” and is closely related to classic AML.1 EAML shows a significant association (>50% cases) with tuberous sclerosis (TS), and one-third of these patients show distant metastases into liver, lung, lymph nodes, and so forth.1 A 2%-3% lifetime risk of renal cell carcinoma (RCC) is also noted in association with TS. The mean age at diagnosis reported is 38 years, whereas a single case report described the occurrence of EAML in a 12-year-old child in association with TS.2 A total of 18 cases of renal AMLs have been diagnosed in the Department of Pathology of this hospital in the last 5 years, of which 2 cases were reported as EAMLs, and only 1 case was in the pediatric age. In this study, we describe a case of EAML in a 4-yearold female child with stigmata of TS, which is the youngest age of tumor presentation reported so far, to the best of our knowledge.
CASE REPORT This 4-year-old female child was brought to the outpatient department of Pediatric Surgery with the chief complaint of right abdominal mass since 4 months. The patient also had a history of generalized tonic-clonic seizures since the age of 2 years, for which she was taking sodium valproate. The patient was found to have a All authors contributed equally. Financial Disclosure: The authors declare that they have no relevant financial interests. From the Department of Pathology, All India Institute of Medical Sciences (AIIMS), New Delhi, India; the Department of Pediatric Surgery, All India Institute of Medical Sciences (AIIMS), New Delhi, India; and the Department of Radiology, All India Institute of Medical Sciences (AIIMS), New Delhi, India Reprint requests: Mehar Chand Sharma, M.D., Department of Pathology, All India Institute of Medical Sciences, New Delhi 110029, India. E-mail: sharmamehar@ yahoo.co.in Submitted: October 23, 2013, accepted (with revisions): December 26, 2013
ª 2014 Elsevier Inc. All Rights Reserved
diffuse solid vague tender lump in the right lumbar region measuring approximately 10 5 5 cm. She was also having stigmata of TS in the form of Shagreen patches in the sacral region and axillary freckling. Family history was noncontributory. Her intelligence quotient level was normal. The clinical differential diagnoses of Wilms tumor (WT) and neuroblastoma were entertained. Abdominal computed tomographic scan showed a large contrast enhancing mass in the right kidney replacing normal parenchyma. No fat component was seen (Fig. 1). The other kidney revealed no abnormality. Computed tomographic scan brain revealed few subependymal nodules. No other TS-associated abnormalities were noted. Fine needle aspiration cytology (FNAC) was done to exclude the possibilities of WT and neuroblastoma. FNAC showed a tumor comprising of predominantly epithelial cells with moderate pleomorphism and minor stromal cell component. Because no definitive diagnosis could be made, cystohistologic correlation was advised. HMB-45 immunostaining was not done, as diagnosis of AML was not suspected. After FNAC, right nephroureterectomy with lymph nodes dissection was done. Intraoperatively, ureter, inferior vena cava, and surrounding structures were free. Pathologic Examination Right nephrectomy specimen measured 15 9 7 cm in dimensions and weighed 520 g. Whole of the kidney was replaced by a tumor, which was well encapsulated. The cut surface was solid, greyish white, lobulated with focal areas of necrosis and myxoid degeneration (Fig. 2). Immunohistochemistry was performed using antibodies against HMB-45 (Novocastra, dilution, 1:100), smooth muscle actin (SMA) (Thermo-scientific, dilution, 1:400), Hamartin (Acris, dilution, 1:400), Tuberin (Novocastra, dilution, 1:25), pancytokeratin (CK) (Neomarker, dilution 1:200), epithelial membrane antigen (EMA) (Dako, dilution, 1: 100), Desmin (Thermo-scientific, dilution, 1:100), Myogenin (Thermo-scientific, dilution, 1:50), 0090-4295/14/$36.00 http://dx.doi.org/10.1016/j.urology.2013.12.044
1
Figure 1. Contrast enhanced computed tomography abdomen showing homogenously enhancing mass (arrow) in the right kidney replacing normal parenchyma. (Color version available online.)
CD117 (Spring, dilution, 1:200), WT1 (Bio SB, dilution, 1:250), INI 1(Cell Morque, dilution, 1:100), and MIB-1 (Dako, dilution, 1:200). Labeled streptavidin biotin kit (Universal) was used as a detection system (Dako, Denmark). Appropriate positive and negative controls were put for each antibody.
Figure 2. Right nephrectomy specimen showing a solid, gray white, lobulated tumor replacing the entire renal parenchyma. Foci of necrosis and myxoid degeneration are noted. (Color version available online.)
controlled completely, and she developed new facial angiofibroma.
COMMENT Histopathologic Examination Microscopic examination showed a tumor comprising predominantly of moderately pleomorphic polygonal epithelioid cells with distinct cellular outlines and abundant amount of granular eosinophilic cytoplasm (Fig. 3). The epithelioid cell component was comprising >95% of the tumor. Nuclei were vesicular with prominent nucleoli. At places, focal spindling of tumor cells was seen. Amidst the tumor cells, interspersed dysmorphic thick-walled blood vessels were present. A few entrapped renal tubules were noted. Areas of geographic necrosis were present, but mitoses were not evident. Giant cells, ganglion-like cells, and adipose tissue were absent. Vascular invasion and perinephric fat infiltration were not noted. Total 8 lymph nodes isolated were free of tumor. Tumor cells were immunopositive for HMB-45 and SMA but were negative for CK, EMA, desmin, myogenin, CD117, and WT1. MIB-1 labeling index was
