Case Report
Epitheloid Variant of Angiomyolipoma in a Patient with Tuberous Sclerosis.
Authors
Vasu Reddy Challa, Resident of Surgical Oncology,
Krishnamurthy Swamyvelu, Professor of Surgical Oncolgy,
Usha Amirtham, Associate Professor of Pathology,
Poornima Rangappa, Resident,
Basavanna Goud YG, Resident,
Kidwai Memorial institute of Oncology, Bengaluru, Karnataka, India.
Address for Correspondence
Dr. Vasu Reddy Challa,
Resident in Surgical Oncology,
Kidwai Memorial Institute of Oncology,
Bengaluru, Karnataka, India.
E-mail:
vasureddyc@gmail.com
Citation
Challa VR, Swamyvelu K, Amirtham U, Rangappa P, Goud BYG. Epitheloid Variant of Angiomyolipoma in a Patient with Tuberous Sclerosis. Online J Health Allied Scs.
2012;11(4):18. Available at URL:
http://www.ojhas.org/issue44/2012-4-18.html
Open Access Archives
http://cogprints.org/view/subjects/OJHAS.html
http://openmed.nic.in/view/subjects/ojhas.html
Submitted: Oct 10,
2012; Accepted: Jan 2, 2013; Published: Jan 25, 2013 |
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Introduction
Epitheloid angiomyolipoma(AML) of kidney is a type of PEComas included in the new WHO classification of renal tumours. Perivascular endothelial cell is the cell of origin for a group of tumours like clear-cell “sugar” tumor (CCST) of the lung and extrapulmonary sites, lymphangioleiomyomatosis, clear-cell myomelanocytic tumor of the falciform ligament/ligamentum teres and rare clear-cell tumors of other anatomical sites including Angiomyolipomas.[1] Epitheloid AMLS were associated with tuberous sclerosis in more than 50% of cases. These tumours are related to loss of tuberous sclerosis complex genes TSC1 (9q34) or TSC2 (16p13.3) which seem to have a role in the regulation of Rheb/mTOR/p70S6K pathway.[1] Tuberous sclerosis complex is an autosomal dominant disorder characterised by features described in Table 1.[2]
| Table 1: Diagnostic criteria for tuberous sclerosis[2] |
Major features |
Minor features |
Facial angiofibromas |
“Confetti” skin lesions |
Hypomelanotic macules |
Gingival fibromas |
Shagreen patches |
Pits in dental enamel |
Cortical tubers |
Cerebral white matter radial migration lines |
Subependymal nodules |
Retinal achromatic patches |
Subependymal gaint cell tumors |
Bone cysts |
Retinal hamartomas |
Hamartmatous rectal polyps |
Cardiac Rhadomyomas |
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Renal Angiomyolipoma |
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Pulmonary Lymphangioleiomyomatosis |
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Definitive diagnosis: 2 major features or one major and one minor feature
Probable diagnosis: One major and one minor feature
Possible diagnosis: One major or two or more minor features
Note: Cortical tubers together with cerebral white matter radial migration lines are counted as one feature. In patients with LAM or renal AML, other features are required for diagnosis. |
Nearly only 120 cases of epitheloid angiomyolipoma were reported in literature.[1]
Case Report:
A 22 years old female presented with dull aching pain over right side of abdomen with no other assosciated symptoms. On general examination, patient was normal. On abdominal examination, there was mass abdomen located in right hypochondrium extending to lumbar region of size 10 cms below the costal margin and was bimanually palpable. A contrast enhanced computer tomography showed a 12.8 x14.2x17.2 cms heterogeneously enhancing lesion arising from upper pole of kidney, with large packets of fatty density[-35 to -20 HU] and an aneurysm [Fig.1 a & b]. The lesion was abutting liver with no obvious infiltration. Renal Vein and Inferior vena cava were normal without any significant lymphadenopathy. Liver showed multiple hypodense non enhancing areas involving both lobes of liver and these lesions were hyperechoic in ultrasonography.[Fig.1c] Lung showed multiple cysts characteristic of lymphangioleiomyomatosis [Fig.1e & f]. A MRI scan was performed to rule out any central nervous system lesions and was found to be normal.
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Fig. 1: (a,b,c,e,f) CT image showing Angiomyolipoma of kidney with characteristic fat content, aneurysm formation, multiple Angiomyolipomas of Liver and multiple cavitory lesions in Lung- Lymphangioleiomyomatosis; (d)Intraoperative image showing Angiomyolipoma of Liver |
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Fig.2: Triphasic and epithelioid AML photomicrographs (a) Hematoxylin-eosin staining (x40) of an epithelioid AML with epithelioid cells (arrows) adjacent to a typical AML demonstrating fat (arrowheads). (b) HMB-45 immunostaining (x40) of the epithelioid cells (arrows) with the HMB-45 stain. |
With a diagnosis of angiomyolipoma of right kidney, a right nephrectomy had been performed. Liver had multiple angiomyoipomas[ Fig. 1d]. Grossly there was 12.5x9x7 cms sized tumor involving upper pole with areas of necrosis and hemorrhage. Microscopically the tumor showed fat cells, mixed with spindle shaped epitheloid cells with nuclear atypia, pleomorphism, and hyperchromatism. Epitheloid component was less than 10% of tumor. Four perihilar lymph nodes were resected which were free of tumor. Immunohistochemistry revealed HMB45 positivity, focally c-kit positive and negative for cytokeratin. Hence a diagnosis of angiomyolipoma with an epitheloid component.
Post operative recovery was uneventful and patient was discharged on postoperative day six. Patient was in followup for 6 months and there was no features of recurrence.
Discussion:
Renal AMLs are present in 50-75% of cases with tuberous sclerosis and 20% of patients with AML have TS.[3] Bonetti et al in 1992 [4] described a special type of cells called perivascular endothelial cell and later in 1996 Zamboni et al [5] described “PEComas” which constitutes group of related mesenchymal tumors with cell of origin as PEC. These tumors are similar in morphology and immunohistochemistry and are positive for HMB 45.
Angiomyolipomas can be classified as classical AML and epitheloid AML. Epitheloid AML can be further classified as Atypical AML or Malignant Epitheloid AML(MEAML). Classical AML is a triphasic tumor with abnormal blood vessels, fat and smooth muscles. Atypical AML have little fat content and have less probability of having abnormal tortuous vessels which are characteristically seen in classical AML. Malignant epitheloid AML was first reported by Pea et al in 1998, following only few cases had been reported in literature. The distinguishing features of MEAML are its size, relatively less or absent fat and blood vessels, high mitotic index, and the only confirmatory sign is presence of metastases. Epitheloid AML can occur in a pure form or along with classical AML as in our case. The aggressiveness of the epitheloid variant depends on the percentage of epitheloid component in the tumor. A new classification had been described taking this into account for AMLs a) Classical/ typical AML b) Pure/Predominant Epitheloid histology with >95% of epitheloid component c) Angiomyolipoma with component of epitheloid histology < 95%- need to specify the amount of epitheloid component. Of 120 cases of epitheloid AML reported in literature 47% had progressive disease.[1]
Pulmonary lymphangioleiomyomatosis is a progressive disorder affecting lungs occurs in 1-3% of patients with tuberculosis and estrogen hormone was thought to play a role in LAM as they are rare in men , unusual before menarche and after menopause in women . They can manifest acute onset of breathlessness, chest pain, cough, pneumothorax, chylous effusions, etc., and later progressively leading to respiratory failure. These lesions need to be identified before surgery for kidney as they may develop spontaneous pneumothorax in 60-70% of patients.
Hepatic AMLs are rare with nearly 120 cases reported in literature and most of them are sporadic. Only 5.8% cases have been found to be associated with tuberous sclerosis. When both hepatic and renal AMLs are present, tuberous sclerosis may be a possible diagnosis.
Conclusion:
Epitheloid variant of AML can occur in pure form or in cases with AML. These patients require close follwup as they have aggressive behaviour. Renal AMLs can be associated with Hepatic AML and Pulmonary LAM which needs evaluation to rule out TS complex.
References:
- Nese N, Martignoni G, Fletcher CD, Gupta R, Pan CC, 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 Feb;35(2):161-176.
- Roach ES, Gomez MR, Northrup H. Tuberous sclerosis complex consensus conference: Revised clinical diagnostic criteria. J Child Neurol. 1998;13:624-628.
- Logue LG, Acker RE, Sienko AE. Best cases from the AFIP: Angiomyolipomas in tuberous sclerosis. Radiographics. 2003;23:241-246.
- Bonetti F, Pea M, Martignoni G,Zamboni G. PEC and sugar. Am J Surg Pathol 1992;16:307-308.
- Zamboni G, Pea M, Martignoni G et al. Clear cell ‘sugar’ tumour of the pancreas. A novel member of the family of lesions characterised by the presence of perivascular epitheloid cells. Am J Surg Pathol 1996;20:722-730.
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