PURE EPITHELIOID PECOMAS (SO-CALLED EPITHELIOIDANGIOMYOLIPOMA) OF THE KIDNEY: A CLINICOPATHOLOGICSTUDY OF 41 CASES: DETAILED ASSESSMENT OF MORPHOLOGYAND RISK STRATIFICATION

Nalan Nese et al AJSP Feb 2011

INTRODUCTION PEC

Prototype cell of PEComasUnique morphological, IHC, ultrastructural, genetic

featuresUnknown normal histologic counterpart

Histogenetically linked tumoursRenal & hepatic angiomyolipomas (AML)Clear cell sugar tumour of the lungPulmonary lymphangioleiomyomatosisClear cell myomelanocytic tumour of ligamentum

teres

Phenotypically – Smooth m, epithelioid, lipid-rich

IHC - Myogenic markers (spindle ) - Melanocytic markers (epithelioid )

WHO – A mesenchymal tumour composed of histologically & IHC distinctive PECs

Strong association b/w PEComas and TSC AD genetic diseaseLosses of TSC1(9q34) & TSC2 (16p13.3)

Kidney PEComas – related to triphasic typical AML

Unknown aspectsInclusionary and definitional criteria with

variable percentage of epithelioid cells required to make the diagnosis

Clinicopathologic parameters that predict malignant outcome

AIM – To investigate the clinicopathologic

parameters of a large series of well characterized pure renal PEComas using consistent definitional study criteria to potentially assist in risk stratification or progression of patients with these tumors

MATERIALS AND METHODS 41 cases from multiple institutions

Composed of purely epithelioid cells, adipocytic component < 1 – 2%“ Pure ” – separate these cases from those which

have variable epithelioid component

IHC-ve for CK, CAM5.2, EMA+ve for 1/more melanocytic and myogenic

marker

C/FsAge, Sex+/- TSCPresence of mets at time of diagnosisFollow –up information

Local recurrenceRegional lymph node involvementDistant metsTime to mets and recurrenceSites of metsPatient status at last follow up

Pathologic featuresConcurrent small AMLsTumor sizeStatus of confinement to kidneyInvolvement of renal vein

HPEMorphologic architectural patternMitotic count/50hpfNecrosisDegree of nuclear atypiaPresence of multinucleate giant cells

RESULTSAge – 14 – 69 years, mean – 40.7Even sex distributionSize – 2 – 37cm, mean – 11.9 cmGrossly

HPEPEComa with carcinoma like growth

(Pattern A) – 20 cases

PEComa with epithelioid & plump spindled cells in diffuse growth (Pattern B) – 15 cases

PEComa with combined Ca-like & diffuse growth pattern – 5 cases

PEComa with Ca like growth (Pattern A)

PEComa with pattern B

Giant cells

PEComa with mixed pattern

9/30(30%)

13/31(41.9%)

10/31(32.2%)

5/2917.2%

48.5%

10/3033%

30%

STATISTICAL ANALYSIS & RISK STRATIFICATION

DISCUSSION Pure epithelioid PEComa of kidney is a

malignant tumour

Malignant potential with % of epithelioid component

Nomenclature systemTriphasic/typical histologically classic AMLPure epithelioid PEComa - >95% epithelioid

histologyAML with components of epithelioid PEComa

histology of < 95% - specify % of epithelioid areas

Need for accurate diagnosisMalignant behaviourTargeted therapy - Sirolimus

D/DsClear cell RCCChromophobe RCCOncocytomaRCC with sarcomatoid

transformationMets from malignant melanoma

ApproachUnusual renal epithelial -appearing

Age < 50 years

Occ focal microscopic areas of adipocytic diff

Ca-like growth, epithelioid & plump spindled cells & diffuse growth, discohesive sheets of ganglion-like cells, interstitial hemorrhage, and numerous giant cells

IHC - -ve epithelial markers, +ve myogenic & melanocytic markers

Pure epithelioid PEComas have significant overlap in morphology with more commonly occurring neoplasms in the kidney, such as clear cell RCC.

Once the appropriate diagnosis of pure epithelioid PEComa is made by appropriate IHC support, these potentially malignant tumours may be stratified into low, intermediate, and high risk for progression categories based on the documentation of clinicopathologic parameters