| Abstract|| |
Angiomyolipomas are rare benign tumors derived from perivascular epithelioid cells that occur frequently in kidney and rarely in the liver. We present a case of hepatic angiomyolipma, with various clinical and radiological differential diagnoses. A 34-year-old male was found to have a palpable mass on the left side of the abdomen. Imaging showed heterogeneously enhancing mass lesion 15 cm Χ 7 cm, in the left lobe and segment 4 of the liver. Various benign and malignant diagnoses were entertained. The needle biopsy did not reveal any evidence of malignancy. Patient underwent resection of the lesion in view of the large size, which was diagnosed as angiomyolipoma. Angiomyolipoma is a benign tumor and accurate diagnosis is important to prevent overtreatment. Histology and immunohistochemisry may help in clinching the diagnosis, in proper clinical setting.
Keywords: Angiomyolipoma, immunohistochemistry, liver, perivascular epitheliod cell
|How to cite this article:|
Gupta A, Ramakrishna B. Hepatic angiomyolipoma: A case report with diagnostic challenge
. Indian J Pathol Microbiol 2013;56:279-81
| Introduction|| |
Angiomyolipomas are rare neoplasms of mesenchymal origin, derived from perivascular epithelioid cells (PEComas), which occur frequently in kidney. Hepatic angiomyolipomas are rare.  Angiomyolipomas may be sporadic or rarely associated with tuberous sclerosis. ,
We present a case of angiomyolipoma of liver in a 34-year-old gentleman in whom, clinico-radiological differential diagnoses included various benign and malignant neoplasms, inflammatory and parasitic lesions. The diagnosis was possible only on resection. To the best of our knowledge, this is the first case report of a sporadic hepatic angiomyolipoma from India.
| Case Report|| |
A 34-year-old male presented with excessive belching and early satiety since 4 months. There were no other complaints or any comorbidities. On palpation, there was a firm, non-tender mass in the left upper quadrant of the abdomen. Investigations including stool occult blood, blood counts, coagulation parameters, liver function tests, viral markers and alpha-fetoprotein levels were normal except for borderline increase in bilirubin (1.1 mg%).
Computerized tomography showed a well-defined heterogeneously enhancing mass lesion involving the entire left lobe and segment 4 of liver, measuring ~15 cm × 7 cm, with multiple hypodense areas suggestive of necrosis. There was no infiltration into the adjacent structures. The differential diagnoses included gastric mass, mesenchymal mass, hydatid cyst and hepatocellular carcinoma.
Ultrasound guided needle biopsy from the mass revealed small fragments with sheets of foamy macrophages, admixed in foci with clusters of polygonal cells exhibiting moderate amounts of periodic acid Schiff (PAS) positive (diastase sensitive) granular eosinophilic cytoplasm and small nuclei with occasional binucleation and separated by few thin walled vascular channels [Figure 1]. There was no significant atypia, mitotic activity or any definite evidence of malignancy. There were patchy mild infiltrates of lymphocytes, occasional eosinophils and plasma cells. Occasional clusters of mature adipocytes, separate small fragments of skeletal muscle fibers and fibrocollagenous tissue were also present. There was no normal liver tissue. On immunohistochemistry, the cells were diffusely positive for CD68 and negative for Pancytokeratin, Hep-par1 and CD31. The biopsy was reported as probably an inflammatory lesion with xanthomatous reaction and no definite evidence of malignancy.
|Figure 1: Biopsy showing abundant foamy macrophages admixed with intervening polygonal cells with eosinophilic cytoplasm (H and E, ×100)|
Click here to view
Since the lesion was very large, the patient was offered surgery. On laparotomy, a large vascular soft tumor was seen arising from left lateral segment of liver.
Grossly, the resection specimen consisted left lateral segment of liver, measuring 14 cm × 12 cm × 5.5 cm and weighing 550 g, with a congested external surface. On sectioning, the entire segment was almost entirely replaced by a spongy, friable, tan brown to hemorrhagic lesion [Figure 2]. The adjacent scanty liver parenchyma was normal.
|Figure 2: Entire segment of the liver replaced by spongy, friable, tan brown to hemorrhagic lesion|
Click here to view
Microscopy revealed a circumscribed tumor composed of many dilated vascular channels, some of them cleft like and some containing blood or proteinaceous material, surrounded in areas by sheets of spindle shaped to polygonal cells with moderate to abundant eosinophilic cytoplasm, round to oval slightly enlarged vesicular nuclei with prominent nucleoli and exhibiting occasional bi and multinucleation, without cytological atypia or significant mitotic activity [Figure 3] and interspersed lobules of mature adipocytes. There were interspersed aggregates of large foamy macrophages, aggregates of lymphocytes, few eosinophils and hemosiderophages. The adjacent liver parenchyma showed no specific lesion. Immunohistochemically, the perivascular spindle shaped and polygonal cells showed diffuse positivity for HMB45 [Figure 4] and patchy positivity for smooth muscle actin (SMA) and S100 and were negative for desmin and pan cytokeratin. A diagnosis of angiomyolipoma was made. The post-operative period was uneventful and patient was discharged. Retrospectively, the needle biopsy slides were reviewed and immunohistochemistry revealed polygonal cells displaying cytoplasmic staining for HMB-45, admixed with foamy macrophages.
|Figure 3: Vascular spaces surrounded by sheets of spindle to polygonal cells and clusters of entrapped mature adipocytes (H and E, ×100)|
Click here to view
|Figure 4: Tumor cells around vascular spaces stain positi ve with HMB45 (immunohistochemistry, ×100)|
Click here to view
| Discussion|| |
Angiomyolipomas are benign mesenchymal tumors that occur rarely in liver. They can mimic various other tumors on imaging and therefore definite histological confirmation is necessary.  Histologically, they are composed of clusters and sheets of mature adipocytes, tortuous thick walled blood vessels mixed with thin walled vessels and perivascular muscle proliferation, in variable proportions. The perivascular cells may show a spindle cell, epithelioid or intermediate morphology. Hematopoetic cells including megakaryocytes, erythroid and myeloid precursors may be present in hepatic angiomyolipomas, though not seen in their renal counterparts. Perivascular epithelioid cell proliferation is the key to diagnosis. ,, These cells are round to polygonal with large round nuclei, prominent nucleoli, oncocytic cytoplasm condensed around nucleus with clear surrounding zone giving it a spider web appearance. Foam cells containing fine droplets of fat may be seen. Rarely, inflammatory cells may be present, similar to inflammatory pseudotumor.  Various morphological appearances have been described including trabecular, pelioid, inflammatory, oncocytic and pleomorphic based upon architectural patterns and cell types. , Epithelioid cells stain positive for fat, glycogen, occasionally contain PAS-diastase positive hyaline globules, hemosiderin and rarely melanin pigment. 
In our patient, the histological features in the needle biopsy were mistaken for an inflammatory lesion, due to the presence of abundant foamy macrophages, inflammatory cells and the absence of staining for markers including Hep-par 1 and CD31 to exclude a hepatocellular neoplasm and vascular lesion respectively. Also, there were varied clinical differential diagnoses; the exact site of this lesion could not be determined as there was no normal liver tissue in the biopsy. The diagnosis of angiomyolipoma was possible only on the resection specimen.
Morphologically, angiomyolipoma can mimic a number of tumors including hepatocellular carcinoma, hepatic adenoma, metastatic carcinomas, epithelioid hemangioendothelioma, inflammatory pseudo tumor and a variety of sarcomas. Immunohistochemistry is helpful in making the diagnosis. HMB45 is consistently positive with a granular cytoplasmic staining, particularly in epithelioid smooth muscle like cells. Other markers include S-100, SMA, myosin, desmin and vimentin. Angiomyolipomas are negative for cytokeratins, allowing distinction from epithelial derived tumors including hepatic adenomas and hepatocellular, biliary and metatstatic carcinomas. , Furthermore tumor markers such as Carcinoembryonic antigen and Alpha-fetoprotein are not elevated. ,
Angiomyolipoma is a benign neoplasm, the management modalities include radiofrequency ablation for smaller tumors and excision for tumors larger than 5 cm.  Exceptionally, angiomyolipoma may show malignant behavior and present with metastases, exhibit cytological atypia and tumor necrosis.  Correct diagnosis of angiomyolipoma is therefore imperative, in order to prevent overtreatment. Histology and immunohistochemical markers may be helpful in reaching accurate diagnosis, in proper clinical setting.
| References|| |
|1.||Ferrel LD. Benign and malignant tumours of the liver. In: Odze RD, Goldblum JR, editors. Surgical Pathology of the GI Tract, Liver, Biliary Tract and Pancreas. 2 nd ed. Philadelphia: Saunders Elsevier; 2009. p. 1314-5. |
|2.||Tsui WM, Colombari R, Portmann BC, Bonetti F, Thung SN, Ferrell LD, et al. Hepatic angiomyolipoma: A clinicopathologic study of 30 cases and delineation of unusual morphologic variants. Am J Surg Pathol 1999;23:34-48. |
|3.||Mongha R, Bansal P, Dutta A, Das RK, Kundu AK. Wunderlich's syndrome with hepatic angiomyolipoma in tuberous sclerosis. Indian J Cancer 2008;45:64-6. |
|4.||Goodman ZD, Terracciano LM. Tumours and tumour-like lesions of the liver. In: Burt AD, Portmann BC, Ferrel LD, editors. Macsween's Pathology of the Liver. 5 th ed. Edinburgh: Churchill Livingstone; 2007. p. 761-814. |
|5.||Zeng JP, Dong JH, Zhang WZ, Wang J, Pang XP. Hepatic angiomyolipoma: A clinical experience in diagnosis and treatment. Dig Dis Sci 2010;55:3235-40. |
|6.||Chang Z, Zhang JM, Ying JQ, Ge YP. Characteristics and treatment strategy of hepatic angiomyolipoma: A series of 94 patients collected from four institutions. J Gastrointestin Liver Dis 2011;20:65-9. |
|7.||Nguyen TT, Gorman B, Shields D, Goodman Z. Malignant hepatic angiomyolipoma: Report of a case and review of literature. Am J Surg Pathol 2008;32:793-8. |
Department of Pathology, Christian Medical College, Vellore - 632 004, Tamil Nadu
Source of Support: None, Conflict of Interest: None
[Figure 1], [Figure 2], [Figure 3], [Figure 4]