Microscopic description:

Tumor cells are relatively uniform epithelioid cells with clear to granular eosinophilic cytoplasm.

Epithelioid cells are arranged in densely packed diffuse sheets.

The tumor extends into the vascular margin of resection.

The tumor invades into the perinephric fat.

Angiolymphatic invasion is present.

Immunohistochemistry shows diffuse strong staining for HMB45, Melan A and focal moderate staining for SMA.

Negative staining for EMA, AE1/AE3, CK7, S100, Desmin.

Discussion:

Epithelioid angiomyolipomas (EAMLs) are a rare variant of angiomyolipoma (<5% of all angiomyolipoma cases) that demonstrate predominant epithelioid histology (>80%).

Unlike classical angiomyolipomas, epithelioid angiomyolipomas are potentially malignant with the capability of recurrence and metastasis.

They occur in a wide age range, 17-80 (mean 50 years) and are more common in females with a F:M ratio reported as 11:9.

They usually present as asymptomatic masses discovered as incidental findings on imaging, although they can present with abdominal pain, hematuria or palpable masses.

Microscopy:

• Histologically, they are at least 80% epithelioid.

• Two histological patterns have been described, with some tumors demonstrating variable combination of the two.

1. Carcinoma-like growth pattern: cells are arranged as cohesive nests, broad alveoli, and compartmentalized sheets separated by thin vascular-rich septae. Cells typically appear as large and polygonal with dense, deeply eosinophilic cytoplasm. Nuclei appear atypical with nuclear pleomorphism, hyperchromatism and prominent nucleoli. Combination of prominent nucleoli with intranuclear inclusions, in large discohesive cells with eosinophilic cytoplasm imparts a ganglion cell-like appearance.

2. Epithelioid and plump spindled cells in diffuse growth: epithelioid and plump spindled cells are arranged in densely packed diffuse sheets without compartmentalization by vascular sepate. Cells are relatively uniform epithelioid cells with clear-to-granular, feathery eosinophilic cytoplasm. Nuclei are more homogeneous and lack atypia.

Immuno-
histochemistry:

Tumors are positive for cathepsin K, HMB45, Melan A, microphthalmia transcription factor (MITF), tyrosinase, CD68, TFE3.

Tumors are variably positive for SMA.

Tumors are negative for PAX8, cytokeratins (AE1/AE3, CAM5.2, EMA), S100, SOX10.

Molecular profile:

Loss of heterozygosity of chromosome 16p (TSC2) has been reported in some cases.

Like classic angiomyolipoma may or may not be associated with tuberous sclerosis complex (TSC) which is caused by inactivating losses of TSC1 (9q34) or TSC2 (16p13.3).

References:

H. Faraji, B. N. Nguyen, and K. T. Mai, “Renal epithelioid angiomyolipoma: a study of six cases and a meta-analytic study. Development of criteria for screening the entity with prognostic significance,” Histopathology, vol. 55, no. 5, pp. 525–534, 2009.

Sarungbam J. Epithelioid angiomyolipoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/kidneytumorepitheliodaml.html. Accessed July 7th, 2022.

He W, Cheville JC, Sadow PM, Gopalan A, Fine SW, Al-Ahmadie HA, Chen YB, Oliva E, Russo P, Reuter VE, Tickoo SK. Epithelioid angiomyolipoma of the kidney: pathological features and clinical outcome in a series of consecutively resected tumors. Mod Pathol. 2013 Oct;26(10):1355-64. doi: 10.1038/modpathol.2013.72. Epub 2013 Apr 19. PMID: 23599151.

Nese N, Martignoni G, Fletcher CD, Gupta R, Pan CC, Kim H, Ro JY, Hwang IS, Sato K, Bonetti F, Pea M, Amin MB, Hes O, Svec A, Kida M, Vankalakunti M, Berel D, Rogatko A, Gown AM, Amin MB. 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):161-76. doi: 10.1097/PAS.0b013e318206f2a9. PMID: 21263237.

CASE IMAGES