Answer: E. Angiomyolipoma of the liver, associated with inactivating somatic mutations of TSC2.  

The correct answer is option E. The lesion is an angiomyolipoma of the liver. Angiomyolipoma (AML) is most commonly encountered in the kidneys followed by the liver. AML can arise sporadically or can be linked to tuberous sclerosis complex (TSC). AML is within the family of PEComa, which in addition to AML includes clear cell “sugar” tumor (of the lung), lymphangioleiomyoma, and various uncommon visceral and soft tissue tumors. In AML, as well as the other PEComa family tumors, genetic alterations of TSC are observed. TSC is an autosomal dominant disease harboring loss of TSC1 (9q34) or TSC2 (16p13.3) genes. In addition to AML, TSC-associated conditions include cardiac rhabdomyomas, brain tubers, hypomelanotic skin macules, and optic disk and retinal hamartomas, amongst. Somatic inactivating mutations of TSC2 gene are reported a common occurrence in hAMLs.^1-4

AMLs are well-delineated, unencapsulated or only partially-capsulated, heterogeneous tumors. Histologically, they are composed of several components, including variable amounts of mature adipose tissue, vascular tissue and smooth muscle-like spindle and epithelioid cells.^1,4 The morphologic spectrum of AMLs includes fat-poor and epithelioid lesions, which can be more challenging to diagnose. Imaging features of hepatic AML (hAML) vary based on its proportion of fatty and vascular tissue, at times raising considerations of hepatocellular carcinoma (HCC), liposarcoma/ lipoma or a vascular tumor. Specifically, both HCC and hAML may appear well-defined, with CT arterial phase enhancement and “washout” in the portal and delayed phases. AML must be kept in differential diagnoses when imaging suggests HCC, in particular in setting of non-cirrhotic liver. In contrast to HCC, AML typically arises in context of non-cirrhotic liver and more likely affects women than men. Histological assessment is the gold standard for diagnosis of hAML.^1,3,4,6

The smooth muscle component of these tumors typically stain positive for HMB 45, SMA, Melan A, Cathepsin K, calponin, and is negative for Hep Par, SOX 10, Arginase, and keratins (AE1/AE3, CAM5.2, etc.). Tumoral immunoreactivity for TFE3, without relevant genetic alteration, and abundant intertumoral CD68 and CD3 positive cells are reported.^1,2,4-6 Tumor size of 5 cm or greater, increased proliferation index/ increased mitosis (mitotic rate more than 1/ 50 HPF), necrosis, vascular invasion, and increased cellular atypia/epithelioid morphology are found associated with aggressive behavior and recurrence after surgery. Treatment of hAML can be conservative or interventional. In patients with good compliance, benign and asymptomatic tumors less than 5 cm can be observed with follow-up alone. Resection, with or without preoperative embolization, is however advised for larger lesions or those increasing rapidly in size, malignant and symptomatic tumors. For patients with hAML, in absence of metastasis or malignant features, literature reports good outcome and long-term survival.^3,4,6,7

Citation:

1. Giannikou K, Klonowska K, Tsuji J, et al. TSC2 inactivation, low mutation burden and high macrophage infiltration characterise hepatic angiomyolipomas. Histopathology. 2023;83(4):569-581.

2. Martignoni G, Bonetti F, Chilosi M, et al. Cathepsin K expression in the spectrum of perivascular epithelioid cell (PEC) lesions of the kidney. Mod Pathol. 2012;25(1):100-111.

3. Calleja-Stafrace D, Vella C. Tuberous sclerosis associated with multiple hepatic lipomatous tumours. Images Paediatr Cardiol. 2016;18(4):1-4.

4. Calame P, Tyrode G, Weil Verhoeven D, et al. Clinical characteristics and outcomes of patients with hepatic angiomyolipoma: A literature review. World J Gastroenterol. 2021;27(19):2299-2311.

5. Jimbo N, Nishigami T, Noguchi M, et al. Hepatic angiomyolipomas may overexpress TFE3, but have no relevant genetic alterations. Hum Pathol. 2017;61:41-48.

6. Williams CH, Hickle K, Bakke K, Jamshed S, Bozorgzadeh A. Hepatic Epithelioid Angiomyolipoma Treated with Laparoscopic Resection: Case Report and Review of the Literature. Case Reports Hepatol. 2019;2019:2362618. Published 2019 Jul 1.

7. Bleeker JS, Quevedo JF, Folpe AL."Malignant" perivascular epithelioid cell neoplasm: risk stratification and treatment strategies. Sarcoma. 2012;2012:541626.