Case 1 -
Multilocular Cystic Renal Cell Carcinoma
Wayne State University School of Medicine
Click on each slide thumbnail image for an enlarged view
A 74 year old woman is found to have a 3 cm complex cystic mass involving the right kidney. A partial
nephrectomy is performed. Grossly the lesion measures 2.8 x 1.8 x 1.8 cm and bulges from the cortical
surface. It is multicystic with thin septae and no solid areas. The cysts contain translucent pale
Case 1 - Figure 1 - Low power photomicrograph illustrating multiloculated cystic mass with thin fibrous septae and adjacent renal parenchyma.
Case 1 - Figure 2 - Additional low power photomicrograph illustrating multiloculated cystic mass with thin fibrous septae and adjacent renal parenchyma.
Case 1 - Figure 3 - Center of mass illustrating the thin nature of the septae.
Case 1 - Figure 4 - Tumor edge illustrating a fibrous capsule and the hypocellular, fibrotic appearance of the septae.
Case 1 - Figure 5 - The thin fibrous septae are covered by a predominantly single layer of cuboidal cells with clear cytoplasm. Note the absence of cells within the septae.
Case 1 - Figure 6 - High power photomicrograph illustrating the clear cells. Note the small, uniform hyperchromatic nuclei.
Case 1 - Figure 7 - Photomicrograph highlighting the fibrous septae and clear cells.
Case 1 - Figure 8 - In this septae there are nests of clear cells within the fibrous stroma some of which are forming tubules. Note again the low grade nuclei.
Case 1 - Figure 9 - High power photomicrograph highlighting the clear cells with low grade nuclei in the stroma.
Cystic degeneration is not uncommon in renal cell carcinoma. In a review of the AFIP experience,
Hartman et al found that 15% of all renal cell carcinomas in their files were cystic . They
acknowledged that this likely represented an overestimation due to the nature of their practice. Hartman
et al subclassified cystic renal cell carcinomas into 4 subtypes, (i) those resulting from an intrinsic
multilocular pattern of growth, (ii) those resulting from an intrinsic unilocular pattern of growth;
(iii) those resulting from cystic degeneration of a previously solid tumor; and (iv) those originating in
a benign cyst.
For the most part "cystic RCC" does not represent a specific entity but rather reflects a degenerative
or unusual growth pattern in a tumor belonging to one of the recognized subtypes of RCC . One
specific cystic tumor, multiclocular cystic RCC has been included in current
classifications as a subtype of clear cell RCC
Additionally, RCC frequently arises in the context
of kidneys with cysts such as von Hippel Lindau disease, tuberous sclerosis and acquired cystic kidney
Multilocular cystic RCC is most frequent and
is characterized by variably sized, noncommunicating cysts, separated by irregular, thick fibrous
septae. The septae usually show marked hyalinization and may contain calcifications or even foci of
ossification. Nests of tumor cells can be found which most often are of the clear cell type. The cysts
are lined by tumor cells but in some areas may be markedly attenuated or even absent. This group of
tumors is usually of low nuclear grade, confined to the kidney and associated with an excellent prognosis
In those cases meeting the criteria listed in the table below, no examples of metastases have
This has led to uncertainty as to the actual nature of these
tumors . We have
found high expression of G250, a tumor associated protein expressed highly in clear cell RCC in these
tumors supporting the current classification  and recently have identified mutations of the VHL gene
in tumor cells microdissected from these lesions adding greater strength to the current approach .
Diagnostic Criteria For Multilocular Cystic Renal Cell Carcinoma
The unilocular variant has a thick irregular wall and a lining of tumor cells that is also usually
clear. Papillary excrescenses are seen with the papillae covered by clear cells. In cases resulting
from cystic necrosis of a previously solid tumor the cyst contains old and recent hemorrhage as well as
necrotic tissue. The cyst wall is thickened and irregular. Papillary renal cell carcinoma frequently
has this appearance. These cases may be the most problematic as an epithelial lining is often absent.
Any cystic mass in the kidney containing hemorrhagic or necrotic material should be suspected as
malignant and extensive sampling performed for evidence of tumor. In these cases viable tumor may be
only focally present and the identification of any clear or papillary cell areas indicates a malignant
diagnosis. Finally carcinomas may arise in benign cysts in the kidney.
- Tumor growth as an expansile mass surrounded by a fibrous pseudocapsule
- Tumor interior composes of cysts and septae without grossly visible expansile nodules
- Septae containg aggregates of clear cells
Brinker et al  described a pathologic classification for RCC with extensive cystic change. In 2
types the cystic change was related to near compete tumor necrosis or to partial necrosis. The third
pattern corresponds to the multilocular cystic pattern (Hartmann type 1). In their series none of the 6
multilocular cystic tumors developed progression in keeping with previous series.
The differential diagnosis of multilocular cystic kidney tumors is with cystic nephroma (multilocular
cyst) and a recently defined tumor of presumed collecting duct origin that also has a complex multicystic
gross appearance (tubulocystic carcinoma). In the 3rd series AFIP fascicle,
illustrated an unusual tumor with a multicystic gross appearance and striking mixture of tubules and
micro/macro cysts histologically. Similar cases were subsequently included in the low-grade collecting
duct carcinoma paper of MacLennan et al .We have seen a large number of cases now that are remarkable
for the uniformity on gross and microscopic characteristics . The tubules and cysts are lined by
cuboidal to columnar cells with eosinophilic cytoplasm. Nuclei are uniform and contain nucleoli. In our
experience approximately 10% metastasize. Whether these truly derive from the collecting system is
uncertain. This tumor is not recognized as a distinct entity in the current classification systems but
likely will be in the next few years. Clinically it occurs predominantly in men and in the limited cases
reported has demonstrated a low rate of metastases .
Cystic nephroma may occur at any age but shows a distinctive bimodal age distribution with about 50%
of cases occurring before 2 years of age and 40% of cases between 40 and 69 years . In the latter age
group there is a striking predominance of females; 7:1 in one series . The tumors are unilateral,
solitary, and surrounded by a thick fibrous capsule. The cysts do not communicate and have a smooth,
glistening lining. The cysts are lined by a single layered epithelium that typically is made up of cells
with eosinophilic cytoplasm and a "hob nail" morphology. In larger cysts the epithelium may be more
cuboidal or attenuated; clear cells restricted to the lining epithelium are acceptable but nests of clear
cells in the septae indicate a diagnosis of renal cell carcinoma. Stromal cellularity is quite variable
and in most is hypocellular and fibrotic – similar to multilocular cystic RCC. In many cases the stroma
is at least focally more cellular and often has an ovarian-like appearance. The latter is a useful
differential diagnostic feature. There is currently debate concerning the relationship between this
tumor and mixed epithelial stromal tumor with some considering these to represent the same lesions while
others believe they are 2 distinct entities.
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