Kidney tumor

Benign/borderline adult tumors

Epithelioid angiomyolipoma


Resident / Fellow Advisory Board: Alcino Pires Gama, M.D.
Deputy Editor-in-Chief: Maria Tretiakova, M.D., Ph.D.
Amr Soliman, M.B.B.Ch.
Anil Parwani, M.D., Ph.D., M.B.A.

Last author update: 5 December 2023
Last staff update: 5 December 2023

Copyright: 2003-2024, PathologyOutlines.com, Inc.

PubMed Search: Renal epithelioid angiomyolipoma

Amr Soliman, M.B.B.Ch.
Anil Parwani, M.D., Ph.D., M.B.A.
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Cite this page: Soliman A, Parwani A. Epithelioid angiomyolipoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/kidneytumorepitheliodaml.html. Accessed April 14th, 2024.
Definition / general
  • Epithelioid angiomyolipoma (EAML) is a distinct rare subtype of angiomyolipoma with unique histological features
  • EAML is characterized by the presence of at least 80% epithelioid cells, which is defined by round to polygonal cells with abundant pink to amphophilic to focally clear cytoplasm
Essential features
  • Rare mesenchymal tumor first reported in 1995 (Int J Surg Pathol 1995;2:539)
  • In contrast to other angiomyolipomas, EAML have malignant potential
  • Presence of at least 80% epithelial component required for EAML diagnosis
  • EAML shows positive staining with melanocytic markers, smooth muscle markers and cathepsin K, while negative for PAX8 and cytokeratins
Terminology
  • Pure epithelioid PEComa of the kidney
  • Traditionally, the term epithelioid angiomyolipoma is used for tumors in the kidney; at other sites, the term epithelioid PEComa is used
ICD coding
  • ICD-O: 8860/1 - angiomyolipoma, epithelioid
  • ICD-11
    • 2F35 & XH0QR3 - benign neoplasm of urinary organs & angiomyolipoma, epithelioid
    • 2B5F.2 & XH0QR3 - sarcoma, not elsewhere classified of other specified sites & angiomyolipoma, epithelioid
Epidemiology
  • Rare in clinical practice
  • Incidence rate among renal tumor is 1% and among renal angiomyolipoma is 4.6 - 7.7% (Mod Pathol 2013;26:1355)
  • Mean patient age is 50 years (range: 30 - 80 years) and there is no sex predilection; EAMLs represent 4.6% of all resected angiomyolipomas (Mod Pathol 2013;26:1355)
Sites
  • Kidney
Etiology
Diagrams / tables

Images hosted on other servers:
Potential pathogenesis

Potential pathogenesis

Clinical features
  • Patients with small EAML may be asymptomatic but larger tumors tend to be symptomatic, often found during physical examination
  • Depending on the size and location, it may present with fatigue, fever, low back pain, abdominal pain, hematuria, bleeding, dysuria and renal dysfunction; renal rupture may rarely occur (Urol Case Rep 2021;38:101645)
  • It is known to cause paraneoplastic syndromes like high erythrocyte sedimentation rate (ESR), high platelet count and disruption of the immune system (J Int Med Res 2021;49:3000605211032493, Kaohsiung J Med Sci 2022;38:925)
Diagnosis
Radiology description
  • Ultrasound: lack of specific findings (Abdom Radiol (NY) 2018;43:880)
  • Computed tomography (CT) scan
    • Shows irregular mixed density mass shadows (usually > 45 HU) with heterogeneous enhancement, "fast in and fast out" type on contrast enhanced CT scan (Abdom Imaging 2014;39:588, World J Surg Oncol 2015;13:280)
    • Features suggestive of malignancy: large tumor size > 9 cm, necrosis, metastases, extrarenal extension, formation of tumor thrombus in a vein (Sci Rep 2015;5:10030)
  • Magnetic resonance imaging (MRI): T2 hypointense reticular enhancement and "fast in and fast out" attributes (Kaohsiung J Med Sci 2022;38:925)
  • Unlike conventional angiomyolipomas, EAML may have a reduced amount of fat within the tumor tissue; this can make it more challenging to differentiate from other kidney tumors using imaging techniques like CT scans and MRIs
Radiology images

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CT, MRI

CT, MRI

Case with TSC

Case with TSC

Large renal mass

Large renal mass

Heterogeneous mass

Heterogeneous mass

Prognostic factors
  • EAML has the potential to be malignant, recur and metastasize; however, the observed variation in its aggressive behavior, ranging from 5 - 66%, should be considered (Am J Surg Pathol 2010;34:715, Am J Surg Pathol 2011;35:161, Clin Neprol Case Stud 2018;6:11, Urol Case Rep 2018;18:52)
  • The following factors have been correlated with poor prognosis: epithelial nuclear atypia ≥ 70%, mitotic count ≥ 2 per 10 high power fields, atypical mitoses, necrosis, epithelial cells > 70% or atypical epithelial cells > 60% (Am J Surg Pathol 2010;34:715, Sci Rep 2015;5:10030)
  • Risk stratification model, based on prognostic parameters (presence of tuberous sclerosis complex, tumor necrosis, extrarenal extension or renal vein invasion, carcinoma-like histology and tumor size > 7.0 cm), classifies tumors into 3 distinct categories (Am J Surg Pathol 2011;35:161)
    • Low risk (0 - 1 parameter)
    • Intermediate risk (2 - 3 parameters)
    • High risk (≥ 4 parameters)
  • For patients possessing at least 3 adverse parameters, a substantial 80% experienced disease progression (Am J Surg Pathol 2011;35:161)
    • Recent risk model has been suggested using different parameters (pT3 - pT4 stage, presence of necrosis, severe nuclear atypia, presence of atypical mitoses, mitotic count ≥ 2, Ki67 ≥ 10% and negative SMA expression) (BMC Urol 2022;22:148)
  • Mutant p53 expression may be an adverse prognostic indicator for renal EAML (Diagn Pathol 2023;18:14)
Case reports
Treatment
Gross description
  • Large nodular or irregularly infiltrative in gross view, soft in texture, heterogeneous, partially cystic appearance with a grayish tan to grayish brown cut surface
  • Hemorrhage and necrosis may be seen
  • Potential extension into the renal vein or IVC may also occur
  • EAML could involve lymph nodes; however, in some cases, it does not represent metastatic disease (Am J Surg Pathol 2010;34:715, Am J Surg Pathol 2011;35:161, Transl Androl Urol 2021;10:1506)
Gross images

Contributed by Judy Sarungbam, M.D.
Circumscribed, pink-tan mass

Circumscribed, pink-tan mass



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Circumscribed, lobulated cut surface

Circumscribed, lobulated cut surface

Frozen section description
Frozen section images

Contributed by Judy Sarungbam, M.D.

Abundant pink, granular cytoplasm

Microscopic (histologic) description
  • According to WHO, more than 80% epithelial cells is required to diagnose EAML
  • Malignant features on core needle biopsy: epithelial nuclear atypia ≥ 70%, mitotic count ≥ 2 per 10 high power fields, atypical mitoses, necrosis, epithelial cells > 70% or atypical epithelial cells > 60% (Kaohsiung J Med Sci 2022;38:925, Am J Surg Pathol 2010;34:715, Sci Rep 2015;5:10030)
  • 2 distinct histologic patterns were described as follows
    • Carcinoma-like growth pattern
      • This pattern is characterized by the presence of large, polygonal cells with densely eosinophilic cytoplasm, diffusely atypical nuclei and prominent nucleoli
      • These cells are arranged in cohesive nests, broad alveoli and compartmentalized sheets that are separated by thin vascular septa
      • In some cases, intranuclear inclusions, nuclear degeneration and multinucleation are observed
      • Mitotic activity is variable, with some cases showing > 2 mitotic figures per high power field (HPF), while the majority do not exhibit mitosis; atypical mitosis is not observed
      • Hemorrhage and necrosis may be present to varying degrees
      • Combination of prominent nucleoli, intranuclear inclusions and large, discohesive cells with eosinophilic cytoplasm gives the tumor cells a ganglion cell-like appearance
    • Epithelioid and plump spindled cells in diffuse growth
      • This pattern consists of epithelioid and plump spindled cells that are densely packed in diffuse sheets with homogenous growth without separation by vascular septa unlike the carcinoma-like pattern
      • Cells are relatively uniform with epithelioid features, clear to granular, feathery eosinophilic cytoplasm and may lack atypia throughout; nuclei exhibit vesicular chromatin, prominent nucleoli, with intranuclear inclusion being less commonly observed
      • Multinucleated giant cells may be present, either singly or in groups, areas of hemorrhage are often absent in this pattern (Am J Surg Pathol 2011;35:161)
  • *Besides those 2 patterns, morphology of a papillary component has been described; the papillae are by epithelioid cells containing abundant eosinophilic cytoplasm and round nuclei with conspicuous eosinophilic macronucleoli and perinucleolar halos (Int J Surg Pathol 2023 May 9 [Epub ahead of print])
Microscopic (histologic) images

Contributed by Anil Parwani, M.D., Ph.D., M.B.A.

Diffuse growth

Cytologic and nuclear features

Cytologic and nuclear features

Cytologic features

Cytologic features

Carcinoma-like growth pattern

Carcinoma-like growth pattern

Cytologic features

Cytologic features


MelanA

MelanA

HMB45

HMB45

Cytology description
Positive stains
Negative stains
Electron microscopy description
  • Presence of glycogen, mitochondria and prominent electron dense, membrane bound granules (60 - 250 nm)
  • Absence of melanosomes or premelanosomes (Am J Surg Pathol 1998;22:663)
Electron microscopy images

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Tumor cells with premelanosomes

Tumor cells with premelanosomes

Molecular / cytogenetics description
Molecular / cytogenetics images

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Molecular analysis of TFE3 gene

Molecular analysis of TFE3 gene

TSC2 mutation

TSC2 mutation

Sample pathology report
  • Kidney, left, radical nephrectomy:
    • Epithelioid angiomyolipoma, 6.5 cm, involving renal parenchyma and extending into sinus fat (see comment)
    • Surgical margins, negative for tumor
    • Comment: Focal necrosis (5%) is present. Immunohistochemical stains show the tumor to be positive for cathepsin K, MelanA and HMB45, supporting the diagnosis.
Differential diagnosis
Board review style question #1
Which of the following is true in epithelioid angiomyolipoma?

  1. Positive for cathepsin K, HMB45, MelanA and MITF
  2. Positive for PAX8
  3. Positive for S100, SOX10, HMB45 and MelanA
  4. Positivity for TFE3 immunohistochemical stain usually correlates with TFE3 gene rearrangement
Board review style answer #1
A. Positive for cathepsin K, HMB45, MelanA and MITF. Angiomyolipomas are positive for melanoma markers including cathepsin K, HMB45, MelanA and MITF; however, they are negative for S100 and SOX10. Answer D is incorrect because TFE3 gene rearrangement is extremely uncommon in epithelioid angiomyolipoma. Positivity of TFE3 immunohistochemical stain does not correlate with TFE3 gene rearrangement. Answer C is incorrect because malignant melanoma is positive for S100, SOX10, HMB45 and MelanA. Answer B is incorrect because angiomyolipomas are negative for PAX8 and cytokeratins.

Comment Here

Reference: Epithelioid angiomyolipoma
Board review style question #2

A radiological image of 40 year old man complaining of painless gross hematuria and left flank pain showed left renal mass with a central stellate scar measuring 16 x 14 x 11 cm. Left nephrectomy revealed a tumor with morphology depicted in the image above. Necrosis was present in ~30% of tumor cells. Immunohistochemistry showed diffuse strong staining for HMB45, MelanA and focal moderate staining for SMA. The tumor cells showed negative staining for EMA, AE1 / AE3, CK7, S100 and desmin. Which of the following genetic syndromes can be associated with this entity?

  1. Birt-Hogg-Dubé syndrome
  2. Succinate dehydrogenase deficiency
  3. Tuberous sclerosis complex
  4. Von Hippel-Lindau syndrome
Board review style answer #2
C. Tuberous sclerosis complex. Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder resulting from inactivating losses of TSC1 (9q34) or TSC2 (16p13.3) genes. This is characterized by mental retardation, seizures and the development of neoplasms such as angiomyolipoma, subependymal giant cell tumors, cutaneous angiofibromas, cardiac rhabdomyomas, lymphangioleiomyomatosis and pulmonary multifocal micronodular hyperplasia. Answers A, B and D are incorrect because they are not associated with renal epithelioid angiomyolipoma (EAML).

Comment Here

Reference: Epithelioid angiomyolipoma
Board review style question #3
Which is a true feature of epithelioid angiomyolipoma (EAML)?

  1. Diagnosis requires at least 20% epithelioid cells
  2. They are a common (> 10%) variant of angiomyolipoma
  3. Tumors are almost always associated with tuberous sclerosis
  4. Tumors may have malignant behavior
Board review style answer #3
D. Tumors may have malignant behavior. EAML has the potential to be malignant and recur and metastasize. Answer B is incorrect because it is a distinct rare subtype of angiomyolipoma with unique histological features. Answer A is incorrect because EAML is characterized by the presence of at least 80% epithelioid cells. Answer C is incorrect because more than half of tuberous sclerosis (TSC) patients have renal angiomyolipoma but this does not imply it is always associated with TSC.

Comment Here

Reference: Epithelioid angiomyolipoma
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