De novo-type De-differentiated Liposarcoma of Retroperitoneum, High Grade, with Secondary (Intra-renal) Involvement of Kidney
Mahul B. Amin
Cedars-Sinai Medical Center
Los Angeles, CA, 90048
Clinical History :
A 41 year old male presented with a two week history of left flank pain. Abdominal CT scan revealed
a solid mass lesion in the left flank measuring 12 x 10 x 8 cm. Radiographically the lesion was
interpreted as renal cell carcinoma. A radical nephrectomy was performed which showed a large mass
predominantly involving the lower pole of the left kidney and the perinephric soft tissue (Case 4, Fig.
1). Microscopically, the tumor had epithelioid and spindle cell morphology (Case 4, Figs. 2-9). The
case was received in consultation with a differential diagnosis of sarcomatoid renal cell carcinoma
versus epithelioid angiomyolipoma. Outside immunohistochemical stains showed focal positivity for HMB45
and Melan A and negativity for CK 7, CK20, and CD10. Six months later, the patient had a 6 cm in
diameter local recurrence in the left renal fossa.
The left radical nephrectomy specimen showed a large mass measuring 12 cm in diameter involving the
lower pole of the kidney and adjacent perinephric tissue. The bulk of the mass involved perinephric soft
tissues. The cut surface was nodular, homogenous, fleshy and yellow-tan in color with central areas of
necrosis. The pelvicalyceal system was not involved.
The recurrent 6 cm mass in the left renal fossa had a nodular fleshy cut surface with irregular
The tumor involving the kidney was circumscribed and composed of spindled and epithelioid cells with
a prominent vascular pattern. The individual tumor cells varied from being rounded to polygonal shaped
with abundant pale eosinophilic cytoplasm, to oval to spindled cells with moderate to scant cytoplasm.
Numerous tumor giant cells and cells with marked pleomorphism were interspersed throughout the tumor.
Nuclear hyperchromasia, anaplasia and high mitotic activity was evident. Some of the epithelioid cells
had a micro-vesiculated appearance.
The recurrence showed an overall similar histology except that there were hypo- and hypercellular
areas with meningothelial whorl-like pattern. The whorls were composed of concentric lamellae of
spindled cells around small caliber vessels.
The adjacent adipose tissue showed irregular fibrous bands with associated atypical hyperchromatic
cells with scattered lipoblasts. There were areas with loose myxoid stroma and patchy hyalinization;
lymphoid aggregates and inflammatory cells (lymphocytes and plasma cells) were dispersed in the
background. There was an abrupt transition between the atypical lipomatous component and the cellular
Renal and perinephric mass: AE1/AE3, EMA, CD10, SMA, CD34 and S100- Negative. HMB45 and Melan A
were focally positive and vimentin was diffusely positive. These stains were performed at outside
institution. Melan A was negative when it was repeated.
Recurrent mass: Melan A, Micropthalmia transcription factor were negative and rare cells were
positive for HMB45. CD34 was positive in areas of meningothelial-like whorls. Other pertinent markers
Fluorescent in Situ Hybridization:
FISH analysis performed on paraffin embedded tissue from the recurrence was positive for MDM2 gene
De novo-type De-differentiated Liposarcoma of Retroperitoneum, high grade, with secondary (intra-renal) involvement of kidney
This case presents with a range of differential diagnostic considerations and the appropriate
diagnosis has prognostic relevance. The differential diagnoses considered for the primary presentation
include sarcomatoid differentiation in renal cell carcinoma, a malignant epithelioid angiomyolipoma
(PEComa) and a primary renal sarcoma such as synovial sarcoma, malignant peripheral nerve sheath tumor,
malignant solitary fibrous tumor, leiomyosarcoma and unclassified high grade sarcoma. Based on the
absence of an obvious renal cell carcinoma component, grossly and microscopically unremarkable
pelvicalyceal mucosa (against urothelial carcinoma) and negative immunoreaction for multiple epithelial
markers, the diagnosis of sarcomatoid differentiation was ruled out. HMB45 was the only melanogenic
marker that was very focally positive (primary and recurrence). Smooth muscle actin and other
melanogenic markers were negative arguing against an epithelioid angiomyolipoma (PEComa). The diagnosis
of de novo-type de-differentiated liposarcoma of retroperitoneum, high grade, with secondary intra-renal
involvement of kidney was made on the presence of an atypical lipomatous tumor / well-differentiated
liposarcoma (ALT/WDL) in the recurrence with abrupt transition to high grade sarcoma.
At this United States and Canadian Academy of Pathology meeting, we present our unique experience of
a series of similar cases that we have collected from our consultation files and collaborating
institutions.  Ten cases presenting as a primary renal mass underwent nephrectomy in which the
presenting pathology was a renal/perinephric high grade spindled neoplasm. In all cases the pathologic
workup revealed the presence of ALT/WDL. The submitting differential diagnoses in consultation cases
included sarcomatoid differentiation in renal cell carcinoma, epithelioid angiomyolipoma and primary
sarcoma such as synovial sarcoma and malignant solitary fibrous tumor. In our series of 10 cases, the
patient's age ranged from 41 to 81 years with a male to female ratio of 9:1; flank pain was the
predominant presenting symptom (70%). One patient presented with renal mass and p ulmonary metastasis.
In seven cases, the imaging findings were consistent with a renal cell carcinoma, and in 3 cases, there
was a predominant perinephric component with uncertain renal involvement. All cases were hence treated
for a preoperative clinical diagnosis of renal cell carcinoma by radical nephrectomy.
The histology of the de-differentiated liposarcoma component in the series showed a intermediate to
high grade malignant spindled to epithelioid neoplasm with distinctive meningothelial whorl-like growth
in three cases, storiform/pleomorphic malignant fibrohistiocytic histiocytoma (MFH) pattern in three
cases, myxoid MFH in one case, fibrosarcoma in one case and high grade pleomorphic sarcoma, not otherwise
specified in two cases. One case with meningothelial whorl-like areas had intratumoral metaplastic
ossification with fibrous dysplasia-like areas. Gross and / or microscopic involvement of the renal
parenchyma was seen in three of seven cases in which renal cell carcinoma was suspected on imaging, the
other cases abutted the renal capsule but did not involve it. The histology of well-differentiated
component was often subtle and not suspected in all the five cases in the series that were received as
consultation cases. Both the adipocytic lipoma-like and sclerosing-type histology were seen with patchy
and variable inflammation.
The approach to malignant spindle cell tumor in the kidney requires attention to several important
aspects at the gross and microscopic level with appropriate use of ancillary techniques in some cases.
Sarcomatoid differentiation in renal cell carcinoma or urothelial carcinoma should be the primary
consideration and examination of multiple sections as well as close attention to gross features is
necessary to identify a renal cell carcinoma or malignant urothelial component. Epithelioid
angiomyolipoma (PEComa) of kidney may morphologically resemble a renal cell carcinoma or rarely may have
a prominent sarcomatous component. The epithelioid morphology with eosinophilic cells, arranged singly
or in sheets, is the predominant histologic pattern. We have recently finished evaluation a large series
of 49 cases of epithelioid angiomyolipoma involving the kidney and our experience is as follows. The age
ranged from 14-69 years with male: female ratio of 1:1.2. 30% of cases are associated with tuberous
sclerosis; and 47.7% were associated with multiple macro- or microscopic angiomyolipomas of the usual
triphasic type.  Co-expression of melanogenic (HMB45, Melan A, tyrosinase and microphthalmic
transcription factor) and smooth muscle-associated markers (SMA, HHF35 and desmin), along with negativity
for cytokeratin markers is confirmatory.
The most important feature for the appropriate recognition of de novo de-differentiated liposarcoma
of retroperitoneum secondarily involving the kidney is attention to perinephric fat to recognize ALT/WDL
component. The ALT/WDL component may be subtle. Careful examination of multiple sections is usually
adequate to find diagnostic areas of liposarcoma. We have recently noted that perinephric fat adjacent
to and or away from a renal mass may show atypical changes that may closely mimic an ALT/WDL.  These
pseudoliposarcomatous changes include variably sized fibrous bands with atypical hyperchromatic nuclei,
variation in adipocytic size, lochkern nuclei, myxoid areas and lymphocytic aggregates.  In difficult
cases where typical lipoblasts are lacking, the diagnosis may be confirmed by FISH studies for MDM2 gene
amplification.  In our recent experience of 10 de novo de-differentiated liposarcomas involving the
kidney/perinephric region, MDM2 gene amplification was seen in two third of the cases. MDM2 gene
amplification was not seen in pseudoliposarcomatous cases studied.
In the context of distinct meningothelial whorl-like areas and renal neoplasia, two tumors are worthy
of mention. Extranodal follicular dendritic cell tumor, which to my knowledge has not involved the
kidney. It is characterized by proliferation of spindle to ovoid cell that form fascicles, storiform
patterns and whorls, the latter remniscent of meningioma. There may be rare multinucleated tumor giant
cells. The diagnosis is confirmed by CD21, CD23 and CD35 immunomarkers.  Metanephric stromal tumor
(MST) is a unique pediatric tumor that occurs in the age range of <1 to 11 years with nearly equal sex
ratio. The cytomorphology of MST is typically bland and contrasts with the usually overt sarcomatous
nature of de-differentiated liposarcoma. The tumors are variably cellular in which spindle cells
surround entrapped renal tubules or blood vessels forming "onion skin" rings or collarettes. Striking
angiodysplasia and juxtaglomerular hyperplasia is noted. 
If the morphologic presentation of a mass in the kidney is that of a monophasic sarcoma, the
differential diagnoses also includes: synovial sarcoma, malignant peripheral nerve sheath tumor,
malignant solitary fibrous tumor and leiomyosarcoma; the latter most frequently arises in the renal vein
/or its branches. A judicious panel of immunohistochemical markers including: AE1/ AE3, SMA, desmin,
S100, CD34, CD99, and Bcl2 should help in appropriate characterization.
An approach and the differential diagnostic considerations of malignant spindle cell neoplasms
involving the kidney based on the above discussion is summarized in the table below.
Differential Diagnoses of Malignant Spindle Cell Neoplasms Involving Kidney
Spindle cell component with distinct epithelial differentiation :
Spindle cell component with epithelioid cell type :
- Renal cell carcinoma with sarcomatoid change
- Urothelial carcinoma with sarcomatoid change
- Synovial sarcoma, biphasic
Spindle cell component with pure ALT/WDL :
- Epithelioid angiomyolipoma (PEComa)
- Sarcomatoid carcinoma, not otherwise specified
- Sarcoma including malignant peripheral nerve sheath
tumor, leiomyosarcoma, pleomorphic sarcoma, not otherwise specified
Monophasic malignant spindle cell component :
- De-differentiated liposarcoma
- Synovial sarcoma
- Solitary fibrous tumor
- Malignant peripheral nerve sheath tumor
A precise histopathologic classification from the differential diagnostic considerations listed above is
critical for appropriate therapeutic stratification and prognosis. The treatment protocols for
sarcomatoid differentiation in renal cell carcinoma, malignant epithelioid angiomyolipoma (PEComa) and
sarcomas involving the kidney are often institutional dependant but usually vary between the three
categories. The prognosis of sarcomatoid differentiation in renal cell carcinoma and urothelial
carcinoma is very poor with median survival of 19 months and 30 months respectively. Long time survival
is distinctively rare.
Epithelioid angiomyolipoma of the kidney (PEComa} is considered to be a
potentially malignant tumor. In our experience of 49 cases, recurrence was noted in 20%, metastasis in
42.5% (27.5% of cases had metastasis at the time of presentation) and disease-related mortality in 32.4%.
The prognosis of sarcomas involving the kidney is dependent on several parameters including
histologic type, high tumor grade, presence of metastasis at presentation, incomplete surgical resection
and positive surgical margins.  Synovial sarcoma in my experience is the most common among sarcoma
histologic subtypes involving the kidney. Several recent reports indicate that these patient's have a
particularly poor survival (6 – 8 months).
In our recent experience with 10 de novo de-differentiated liposarcomas involving kidney, the outcome
was available in 7 cases (mean 10 months, median 6 months); half of the cases recurred and one had
pulmonary metastasis at the presentation indicating high recurrence potential in the short to
intermediate range follow up. In an analysis of 155 cases of de-differentiated liposarcomas from various
sites with median follow up of 3 years, local recurrence was seen in 41%, metastasis in 17%, and
disease-related mortality in 28%. 
In summary, in my experience, sarcomatoid renal cell carcinoma is the most common malignant spindle
cell neoplasm involving the kidney. Epithelioid angiomyolipoma (PEComa) only rarely presents as a
predominantly spindle cell tumor. A range of sarcomas of different histologies and grade may also
involve the kidney usually as a primary neoplasm, and the approach is similar to that employed for soft
tissue counterparts once the other two categories are excluded. This particular case exemplifies yet a
unique and perhaps not so esoteric diagnostic challenge posed by the most common retroperitoneal sarcoma,
ALT/WDL which may be subtle or overlooked due to the more striking de-differentiated component.
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