Multilocular Cyst of the Kidney (Cystic Nephroma) and Cystic,

Partially Differentiated Nephroblastorna

Terminology and Criteria for Diagnosis

VIJAY V. JOSHI, MD, FRCPATH,*AND J. BRUCE BECKWITH, MDt

The entities commonly known as multi-locular cyst of the kidney (MLC) and cystic partially differentiated
nephroblastoma (CPDN) were reviewed, based on material in the National Wilms’ Tumor Study Pathology
Center. The authors recommend several modifications of existing terminology and definitional criteria for
these lesions. Because MLC probably represents a neoplastic lesion, the designation “cystic nephroma”
(CN) is preferred. This term should be used only for predominantly cystic tumors composed entirely of
differentiated tissues, without blastema or other embryonal elements. The designation CPDN should be
applied to predominantly cystic lesions, lacking nodular solid regions, in which blastemal or other embryonal
cells are present in the septa of the cysts. Solid Wilms’ tumor with multifocal cystic change should be
distinguished from CPDN. Five cases of C N and 18 cases of CPDN were reviewed. No CN, for which
follow-up data was available, showed aggressive behavior. Only one case of CPDN underwent local re-
currence, and there were no metastases. In general, nephrectomy alone appears to be adequate therapy
for CPDN, but regular monitoring by noninvasive techniques would seem advisable.
Cancer 64:466-479, 1989.

c YSTIC VARIANTS of nephroblastoma have been the

subject of a lively controversy for many years and
have engendered a voluminous literature. Much of the
literature centers upon the terminology, classification, and
natural history of these lesions. We undertook a review
of lesions with prominent c stic change that had been
i
entered into the National Wi ms’ Tumor Study (NWTS)
or were in the consultation files of J.B.B. We wanted to
define the morphology, classification, and clinical signif-
icance of such lesions better.
We reviewed the entities usually termed multi-locular
cyst (MLC) of the kidney and cystic partially differentiated
From the *Department of Pathology and Pediatrics. Children’s Hos-
pital of New Jersey, Newark. New Jersey, and the ?Department of Pa-
thology, The Children’s Hospital. Denvcr, Colorado.
Supported in part by the Pediatric Research Fund, Children’s Hospital
of New Jersey and USPHS Grant CA 42326.
The authors thank the following pathologists for referring the cases
included in this article and for providing follow-up information on these
cases: Drs. D. Aldorani, F. Askin, G. 0. Gain, K. Cove, B. Delaleu, H.
Krous, J. Nallaman, J. Hertzler, W. M. Nickey, J. Mawad. L. R. Rohr,
D. Rogers, L. M. Saba, J. Shiner, and A. G. Weinberg. Ms. Joyce Jackson
and Ms. Carole Peny assisted with manuscript preparation. Dr. Joshi
thanks the National Wilrns‘ Tumor Study committee for giving their
approval for his participation in the study.
Address for reprints: Vijay V. Joshi, MD, Department o f Clinical Pa-
thology and Diagnostic Medicine. East Carolina University School of
Medicine, Greenville, NC 27858.
Accepted for publication February 3, 1989.
nephroblastoma (CPDN) in an attempt to clarify the ter-
minology and overlapping features of the two lesions.
Subsequent articles will discuss other cystic renal tumors
of childhood, with the eventual goal of unifying the clas-
sification based upon both morphologic and clinical con-
siderations.
The terms MLC and CPDN are not applied uniformly.
Some authors have used the term cystic nephroma (CN)
to designate both MLC and CPDN,] and others have con-
fused CPDN with MLC.’ It has been suggested that MLC
is not of developmental origin but is a neoplastic le-
~ i o n . ~ -This
’ view is based upon the following observa-
tions: (1) MLC is a well-circumscribed, discrete lesion not
associated with generalized renal maldevelopment; (2) an
expansile growth pattern is suggested by compression of
the surrounding kidney and, in some cases, by herniation
into the renal pelvis; (3) MLC resembles CPDN in gross
appearance; and (4) solid Wilms’ tumor occurs concur-
rently in rare cases, either in the same kidney as the MLC
or in the contralateral organ.’,’ The first case report of
MLC by Edmunds6 in 1892 designated the lesion as cystic
adenoma of the kidney.6 However, this entity continues
to be confused with developmental cystic disorders of the
renal parenchyma.
A CPDN has been designated by various terms (poly-
cystic nephroblastoma, cystic Wilms’ tumor, cystic ne-
phroma, and differentiated nephroblastoma although the

466
No. 2 CYSTIC NEPHROMA
A N D NEPHROBLASTOMA * Joshi and Beckwith 467

term CPDN is preferred.’,* A CPDN may have many ap-

pearances; the septa between the cystic spaces contain
admixtures of blastemal cells with variably differentiated
epithelial and stromal elements. Subdivision of CPDN
into well-differentiated and poorly differentiated subtypes
has been suggested.’ However, some workers objected to
the inclusion of the former subtype under the categpry of
CPDN.4.9Although all cases of CPDN reported to date
have been benign, the presence of poorly differentiated
tissues and blastemal cells in the septa suggest that some
degree of malignant potential may e x i ~ t . ~ , ~

Materials and Methods

Specimens in the NWTS Pathology Center which had
been diagnosed as MLC, CPDN, and cystic Wilms’ tumor
were reviewed. We excluded cystic Wilms’ tumors with
obvious solid regions (Fig. 1) and those in which cysts
were the result of hemorrhage and necrosis (Fig. 2). Other
forms of cystic Wilms’ tumors will be the subject of sub-
sequent reports, but this study reviews only those lesions
that were primarily cystic, i.e., in which the cyst walls
were the only solid element. Cases whose nature could
not be adequately evaluated from available slides and in-
formation were also excluded.
Twenty-three cases were selected for review. Of these,
five had only differentiated elements in the cyst walls, and
18 had varying amounts of blastemal and other poorly
differentiated neoplastic elements in the cyst walls. Each
case was reviewed independently by both authors. Clin-
FIG. 1. Gross photograph of solid Wilms’ tumor with foci of cystic
icopathologic features, as described in the reports from change, an entity which should be distinguished from cystic nephroma
the referring pathologist and as observed on review of the (CN) and cystic partially differentiated nephroblastoma (CPDN).
slides, were recorded. Follow-up data was requested from
referring pathologists.
Before the review, we developed some tentative pro- The tumors varied in diameter from 8 to 24 cm (me-
posals concerning terminology and classification. These dian, 8.5 cm). Specimen weights ranged from 240 to 4000
were tested during the specimen review and modified g (median, 380 g); the largest lesion was from the 15-year-
where indicated. old patient. All lesions were unicentric and unilateral.
On gross examination each lesion was totally multi-
Results cystic, as documented from the gross description in all
cases and gross photographs in two cases (Fig. 3). The
Cystic Lesions Containing Only Mature tumor was sharply circumscribed and encapsulated. One
Elements in Septa lesion was partially herniated into the pelvicalyceal system.
Five specimens were found to have only mature cell The individual cysts vaned up to 5 cm in diameter. The
types in the septa. The clinicopathologic features of these septa of the lesion were usually thin (under 5 mm), but
cases are summarized in Table 1. One patient was 15 relatively thicker, fibrous-appearingsepta, whose thickness
years of age, and the other four were 18 months of age or was not measured, were described in a few foci. The cystic
younger. There was a male preponderance. linings were smooth, and most cysts contained serous yel-
Four patients were treated by nephrectomy alone. Che- lowish fluid. In one case, small foci of hemorrhage were
motherapy, consisting of dactinomycin, cyclophospha- noted in the septa, with blood in adjacent cystic spaces.
mide, and vincristine was administered in one case. Re- The surrounding kidney was unremarkable except for
gional lymph nodes from two cases were uninvolved. Fol- compression.
low-up information is available for only two cases, who Three to 11 slides of the tumor itself were available
were alive and without evidence of disease at 18 months (median, seven). On microscopic examination the cysts
and 7 years after surgery. were lined by flattened to cuboidal or hobnail epithelium
468 CANCER
July 15 1989 Vol. 64

FIG.2. Gross photographs of d i d

Wilms’ tumor with foci of pseudo-
cystic change due to hemorrhage and
necrosis.

(Fig. 4). Most septa were thin, and all corresponded to
the outlines of adjacent cystic spaces, being molded by
the spaces rather than protruding as expanding nodules
into them. Those septa which appeared thicker seemed
to reflect a tangential plane of section rather than prolif-
erative activity. The septa were composed of mature, pre-
dominantly collagenous fibrous tissue (Fig. 5). Sometimes
a zone of spindle cells several cells thick resembled a “tu-
nica propria,” (Fig. 6) imparting a highly organized ap-
pearance to the cyst, but most septa were composed of
more homogeneous connective tissues. Myxoid and spin-
dled cells of low-to-medium cell density were character-
istic. Focal chronic inflammatory infiltrates were found
in a few foci (Figs. 4 and 7). Mature tubular structures
were scattered in the septa of most lesions (Figs. 4 and 7).
Foci of recent hemorrhage with inflammatory and fibro-
blastic reaction were seen in one specimen. The sur-
rounding kidney showed compression, but no evidence
of cysts or other dysplastic lesions. No blastemal rests or
other precursor lesions of Wilms’ tumor were encoun-
tered.
Cystic Lesions With Immature Elements in Septa
There were 18 specimens in this category. Their clini-
copathologic features are summarized in Table 2. Only
two patients were over 24 months of age at diagnosis, and
12 of the 18 were in the first year of life. The two older
patients were 30 and 36 months of age (median age, 12

TABLEI. Clinicopathologic Data in Cases of Cystic Nephroma (CN)

Case no./age/sex Wt (g)/size (cm) Side Therapy FOIIOW-UP Comments

1/18 mos/M NA NA Nephrectomy NA Older sibling had

pulmonary blastoma
2/10 mos/M 38018.5 L Nephrectomy NA Regional lymph nodes
normal
316 mos/M 24018 R Nephrectomy Alive, well without disease -
at I yrs
4/ 18 mos/M 399110.5 L Nephrectomy and Alive, well without disease
chemotherapy at 18 mos
5/15 yrsfF 4000/24 L Nephrectomy NA Regional lymph nodes
normal

NA: not available.

No. 2 AND NEPHROBLASTOMA Joshi and Beckwith
CYSTICNEPHROMA - 469

months). The father of Case 6 was said to have had a

MLC, but slides were not obtainable for review. A male
predominance was noted. No patient was known to have
a syndrome associated with increased risk for Wilms’ tu-
mor development.
Eleven of the 18 patients were treated by nephrectomy
alone. In one patient a wedge biopsy of the CPDN of the
left kidney was done since the opposite kidney contained
a solid anaplastic Wilms’ tumor. The latter tumor was
treated by right nephrectomy and chemotherapy. In five
other patients, nephrectomy was followed by chemother-
apy. One lesion was considered Stage I1 on the basis of
tumor rupture during surgery. The others were all con-
sidered to be Stage I tumors. Follow-up data was available
for ten cases. Eight of these patients were alive and well
for periods ranging from 13 months to 12 years (median,
5 years). Three of these eight patients had been treated
by nephrectomy alone, the remaining by nephrectomy
followed by chemotherapy. One patient in whom only
nephrectomy was done had two local recurrences but was
alive and free of disease 4 years after therapy for the second
recurrence. The patient with anaplastic Wilms’ tumor in
the opposite kidney died of the tumor.
The diameters of these lesions ranged from 4.5 to 21
cm (median, 10 cm), with weights of 58 to 1440 g (median,
320 g). The tumor was totally multi-cystic and well cir-
cumscribed or encapsulated as ascertained from gross de-
scriptions and from a specimen photograph of one lesion
(Fig. 8). Two tumors were partially herniated into the
pelvicalyceal system. FIG.3. Gross photographs of CN with characteristic gross appearances.
Unopened cysts are protruding into the lumens of opened cysts. Note
The cysts varied from 2 mm to 3.8 cm. Their septa thin septa between cysts.
were similar in appearance to those described for the dif-
ferentiated lesions. In two lesions the cyst fluid was blood
tinged or amber colored. In the rest it was pale yellow thelium with large hyperchromatic nuclei or mucous cells
and clear. In one case the chemical composition of the (Fig. 9). In some cases microscopic papillonodular struc-
cystic fluid was as follows: blood urea nitrogen 10 mg/dl, tures composed of poorly differentiated tissues and blas-
Na 143 mEq/l, K 3.5 mEq/l, C1 116 mEq/l, Ca 6.7 mg/ temal cells and lined by epithelium projected into cystic
dl, glucose 36 mg/dl, creatinine 0.5 mg/dl, specific gravity lumens (Fig. 10). The septa contained variable amounts
1.O 1 1, pH 7.5, and protein 1 1 17 mg/dl. The surrounding and combinations of poorly differentiated tissues such as
kidney was unremarkable except for compression. With tubules, glomeruli, mesenchyme, skeletal muscle, and
the exception of the case with contralateral anaplastic rarely, cartilage admixed with blastemal cells (Figs. 9- 12).
Wilms’ tumor, all tumors were apparently unicentric. In Variable amounts of mature tissues such as tubules, skel-
summary, the gross features of these lesions were indis- etal muscle, fibrous tissue, and fat were also present. Skel-
tinguishable from those of the more differentiated speci- etal muscle differentiation was prominent (Figs. 11 and
mens. 12). In one case focal nuclear anaplasia was present
One to 25 slides (median, seven) of tumor were avail- (Fig. 13).
able. Two cases with only one and two slides, respectively, An attempt was made to grade these lesions, based on
were included in this review because poorly differentiated the relative proportions of undifferentiated elements in
tissues and blastemal cells were demonstrated in the septa. the septa of each case. In ten cases, more than 50% of the
(If only mature elements had been seen, the cases would septa1 area was composed of well-differentiated tissues
have been excluded as being unclassifiable.) Most of the (Grade 1). It should be emphasized, however, that our
cysts were lined with flattened, cuboidal, or hobnail epi- definitions required the presence of some blastemal cells
thelium, but some cysts were lined with immature epi- in each of these cases. In eight cases over 50%of the solid
No. 2 CYSTIC NEPHROMAAND NEPHROBLASTOMA - Joshi and Beckwith 47 1

FIG.4. Photomicrograph of CN with flat and hobnail lining of cysts. Septa are composed of fibrous tissues and contain numerous differentiated
tubules, In addition, there is a lymphocytic infiltrate (H & E, original magnification XIOO)

FIG.5. A CN with septa of varying width, all of which conform to cystic contours. The septa are composed of fibrous tissue with a few blood
vessels (H & E, original magnification X40).

component consisted of poorly differentiated elements
(Grade 2). The locally recumng lesion in Case 17 had a
Grade 2 lesion. Small foci of hemorrhage and necrosis
were present in the septa in some cases (Fig. 14). Fibro-
blastic proliferation was seen around these foci.
There were no distinctive clinicopathologicfeatures in
Case 17 that correlated with relapse of this lesion. Sam-
pling of the margins of the specimen was very incomplete,
and it is possible the tumor was resected incompletely. In
Case 10 there was rupture of the capsule during surgery,
but the patient was alive and well without evidence of
disease at 7 months after surgery. In Case 18, where focal
anaplasia was present, the child remained free of relapse
42 months after nephrectomy. This was a Stage 1 lesion,
and it has been shown that Stage I anaplastic Wilms’ tu-
mors in general are not associated with an increased risk
of adverse outcome.12
The renal parenchyma showed compression atrophy,
but no dysplastic phenomena were observed; there were
no precursor lesions of Wilms’ tumor encountered in this
series.
Discussion
The term MLC invites confusion with the various forms
of cystic malformations of renal parenchyma. For this
reason the term CN has been recommended by some as
an alternative, implying the benign but neoplastic nature
of this We strongly endorse the replacement of
the term MLC with CN.

FIG. 6. Photomicrograph of CN with a cellular focus due to reactive fibroblastic proliferation near a focus of hemorrhage (H & E, original
magnification X250).
472 CANCERJuly 15 1989
FIG.7. Photomicrograph of CN with differentiated epithelial lining of cyst with tubules in septa. Scattered inflammatory cells are present (H & E,
original magnification X40).
Powell et al.” proposed criteria for the definition of
CN (MLC), which included the absence of “renal ele-
ments” in the septa ofthe cysts. While this restriction was
intended to aid in distinguishing polycystic diseases from
CN, it is potentially confusing due to the occurrence of
differentiated tubular elements in the septa of some le-
sions. In a subsequent article, Boggs and Kimmelstie13
stated that “fully developed mature nephra or portions
of such should not be present within the septa of the cystic
lesion.” This statement, like Powell’s, suggests that mature
tubular structures should be absent in the septa of CN.
For this reason, one of us (V.V.J.) suggested in a previous
article’ that cystic lesions containing well-differentiated
tubules in the septa should be classified as well-differen-
tiated CPDN. However, Coleman4 suggested that such
cystic lesions should be categorized as MLC, and it is our
experience that most pediatric pathologists so diagnose
such lesions.
Because many of the cysts of CN probably represent
dilated tubular structures and CN is probably a neoplastic
lesion, a few well-differentiated tubules should be per-
Vol. 64
missible in the septa of CN. We would therefore suggest
that lesions containing mature tubular structures be cat-
egorized also as CN. It must be emphasized that only
well-differentiatedtubular structures can be present. Blas-
temal cells and poorly differentiated stromal and/or epi-
thelial elements would exclude the diagnosis of MLC.
The term CN should be used only in the restricted sense
indicated above and not as an all-incusive term for both
MLC and CPDN. However, some lesions which we pre-
viously categorized as well-differentiated CPDN should
now be moved to the category of CN.
Our revised criteria of CN are as follows: (1) the lesion
is composed entirely of cysts and their septa; (2) it forms
a discrete mass, well demarcated from the noncystic renal
parenchyma, (3) the septa are the only solid portion of
the tumor, conforming to the outlines ofthe cysts without
solid expansile nodules; (4)the cysts are lined by flattened,
cuboidal, or hobnail epithelium; and (5) the septa are
composed of fibrous tissue in which well-differentiated
tubules may be present. Poorly differentiated tissues and
blastemal cells are absent in the septa. Although not en-
No. 2 CYSTICNEPHROMAAND NEPHROBLASTOMA - Joshi and Beckwith 473

TABLE2. Clinicopathologic Data in Cases of Cystic Partially Differentiated Nephroblastoma (CPDN)

Case no./age/sex Wt (&/size (cm) Side Grade Stage Therapy Follow-Up Other comments

1/ 12 mos/M IIO/lO R I I Nephrectomy NA -

2/30 mos/F NA L I I 5-cm wedge Death at 4 mos. due to Nephrectomy and
biopsy anaplastic Stage I11 chemotherapy for right-
Wilms’ tumor in right sided anaplastic Wilms’
kidney tumor
3/ 10 mos/M NA/6 L I I Nephrectomy NA Regional lymph nodes normal
414 mos/M NA/NA NA I I Nephrectomy Alive, well without disease -
at 4 yrs
5/12 mos/F 290110 L I I Nephrectomy Alive, well without disease Regional lymph nodes normal
at 5 yrs
6/12 mos/M 5814.5 L I I Nephrectomy NA Regional lymph nodes
normal. Father had CN
7/24 mos/M 40211 1 L I I Nephrectomy, Alive, well without disease Regional lymph nodes normal
Regimen E at 12 yrs
811 1 mos/M 2?8/13 NA I I Nephrectomy, Alive, well without disease Regional lymph nodes normal
Regimen L at 3 mos
9/16 mos/M 1440121 NA I I1 Nephrectom y, Alive, well without disease Rupture of capsule during
Regimen K at 7 mos surgery, regional lymph
nodes normal
10136 mos/M 560/10 L I I Nephrectomy, Alive, well without disease Herniation of cystic mass into
Regimen L at 9 yrs renal pelvis, regional lymph
nodes normal
11/18 mos/NA NA/ 15 R I I Nephrectom y NA -
12/12 mos/NA NA/20 NA I1 NA Nephrectomy Lost to follow-up
13/ I2 mos/M NA/NA L I1 NA Nephrectomy Alive, well without disease
at 8 yrs
1414 mos/F 420113 NA I1 I Nephrectomy Lost to follow-up -
15/10 mos/M 320112 R I1 I Nephrectomy, Lost to follow-up Regional lymph nodes normal
Regimen
EE
1615 mos/F NA/9 R I1 I Nephrectom y Alive, well without disease Regional lymph nodes normal
at 5 yrs
1714 mos/M 35019 L II I Nephrectomy Two local recurrences at 1 Regional lymph nodes
and 2 yrs after surgery normal. Recurrences were
Grade 111 and Grade 1
18112 mm/M 242/NA R I1 I Nephrectomy Chemotherapy, well without Anaplastic cells present
recurrence at 42 mos focallv

NA: not available; Regimen E dactinomycin and vincristine for 6 dactinomycin and vincristine for 15 mos; Regimen EE: slight variation
mos; Regimen L: dactinomycin and vincristine for 10 mos; Regimen K: of dosage used in Regimen E.

countered in this series, mature heterologous tissue such
as skeletal muscle would be permissible in CN. Bilaterality
or multi-focality, although rare, would not exclude this
diagnosis if all other features were consistent.
The generally accepted (although variably defined)term
CPDN seems appropriate for lesions resembling CN
grossly but which contain immature elements microscop-
ically. Our suggested definition of CPDN would require,
in addition to meeting criteria 1 to 4 above for CN, the
presence of blastemal cells in any amount, with or without
other embryonal stromal or epithelial cell types. Thus,
variably differentiated glomeruli, tubules, mesenchyme,
striated muscle, cartilage, fibrous tissue, and fat may be
admixed with blastemal cells in the septa. The immature
cells may sometimes form microscopic papillonodular
projections extending from the septa into the lumen, (Fig.
11) but these retain a close relationship with the cystic
lining and do not constitute a criterion for excluding a
diagnosis of CPDN. Figure 15 diagrammaticallypresents
the nomenclature and major defining features of CN and
CPDN.
As demonstrated in one of our cases, CPDN may co-
exist with a solid Wilms’ tumor, and it is likely that a rare
case might have coexistent CN and CPDN, as separate
lesions in one or both kidneys.
Despite the generally benign outcome associated with
CPDN, we have shown that occasional recurrences may
develop. Subclassification of CPDN based on relative
amounts of immature tissues may be of some value in
predicting the risk of aggressive behavior. We propose
two histologic subtypes of CPDN: (1) CPDN, relatively
mature subtype (Grade l), and (2) CPDN, relatively im-
mature subtype (Grade 2).
It is important to distinguish CPDN from Wilms’ tumor
with foci of cystic change (Figs. 1 and 2). It should be
noted that CN and CPDN are totally multi-cystic. A thor-
474 CANCERJuly 15 1989 Vol. 64

TABLE3. Clinicopathologic Features of Cases of CN and CPDN

CN CPDN

Age
Median 18 mos 12 mos
Range 6 mos-15 yrs 4 mos-36 mos
Tumor size
Median diameter 8.5 cm 10 cm
Median weight 380 g 320 g
Cyst diameter Up to 5 cm Up to 3.8 cm
Septa Usually under 5 Usually under 5 mm
mm
Histology Well-differentiated, Variable differentiation,
epithelial and immature and
mesenchymal blastemal cell types
Dresent in senta

CN: cystic nephroma; CPDN: cystic partially differentiated nephro-

blastoma.

distinguished from the immature mesenchyme of CPDN.

FIG. 8. Gross photograph of CPDN. Note similarity to CN in Figure
3.
ough gross examination with photographic documenta-
tion, thin serial sections of the entire specimen (bread-
loafing),and detailed gross description (encapsulation,size
of cysts, thickness of septa, and a specific negative state-
ment regarding the absence of a solid component) are
imperative for arriving at the correct diagnosis. Adequate
sampling is essential to distinguish between CN and
CPDN and for grading of CPDN. The usual guideline of
one block for each cm of the tumor or ten blocks, which-
ever is greater, should represent adequate sampling. The
margins must be sampled adequately to document the
completeness of resection. The reactive fibrous tissue in
CN, associated with focal hemorrhage, must be clearly
This should not be difficult for experienced pathologists.
This study generally confirmed the benign behavior of
CPDN. Case 17, in which two local recurrences were as-
sociated with predominantly undifferentiated histology,
and Case 18, in which there was focal anaplasia, however,
demonstrate that complacency is not justified. All cases
of CN (including those previously reported as MLC) have
shown uniformly benign behavior. However, it should be
noted that mural nodules of renal adenoma, adenocar-
cinoma, and sarcoma may occur in adults with CN.".'2
Because of the rare potential for aggressive behavior, a
regular follow-up and monitoring by noninvasive imaging
techniques should facilitate early detection of such an
eventuality. Despite the aggressive behavior shown by one
case of CPDN, it appears to us that nephrectomy alone
would be adequate as an initial mode of therapy, provided
that the surgical margins are clear. Chemotherapy or local
irradiation may be reserved for cases that recur. It is re-
assuring to note that in Case 17 the recurrences were ap-
parently managed successfully by retrieval therapy. Ex-
perience with larger number of cases of CPDN will de-
termine whether the grading system of CPDN is practical
in terms of predicting frequency of aggressive behavior.
The only feature distinguishingCPDN from CN in our
classification is the presence of poorly differentiatedtissues
and blastemal cells in septa of the former (Table 3). Be-
tween these two extremes of cystic nephroblastic tumors
there is an occasional "gray-zone'' lesion, in which there

FIG.9. A CPDN with immature, columnar. and hobnail epithelium lining the cysts. The septa contain clusters of blastemal cells and immature
mesenchyme (H & E, original magnification X 100).

FIG. 10. Microscopic papillonodular projections into lumens of CPDN. These are lined by epithelium continuous with the cystic lining and contain
blastemal cells with immature mesenchyme. Clusters of immature tubules are also present (H & E, original magnification X40).
No. 2 CYSTIC NEPHROMAAND NEPHROBLASTOMA - Jushi and Beckwith 477

FIG. 1 1. A CPDN with flattened to cuboidal cyst lining. Note blastemal cells, immaturc tubules. and skeletal muscle. Under this magnification,
the appearance is indistinguishable from conventional Wilms’ tumor (H & E, original magnification X250).

FIG. 12. A CPDN with immature mesenchyme and skeletal muscle in the septum of a cyst (H & E, original magnification X400).
4

are poorly differentiated stromal and epithelial elements
but no blastemal ~e1ls.l~ It will be difficult to categorize
these lesions according to the criteria outlined in this ar-
ticle. Such cases, if they occur, will need to be categorized
individually. To maintain the conceptual consistency that
CN is a well-differentiated expression and CPDN a poorly
differentiated expression of cystic tumors of nephroblastic
origin, we would probably place such a lesion closer to
CPDN than to CN. If such lesions have only poorly dif-
ferentiated or undifferentiated mesenchymal elements
without striated muscle, distinction from rare instances
of totally cystic congenital mesoblastic nephroma and
cystic clear cell sarcoma of the kidney15 must be consid-
ered.
Several features suggest a close pathogenetic relation-
ship between CN and CPDN. These lesions are grossly
identical and histologically similar except for the degree
of differentiation of their constituent elements. The oc-
currence of alleged CN in the father of Case 6 with CPDN
and the widely varying extent of differentiation in CPDN
supports this relationship. It may be difficult to reconcile
some of the features of CN with the concept that this is
a mature CPDN. For example, skeletal muscle has not,
to our knowledge, been reported in the septa of CN, yet
it is common in CPDN. Possibly CN may arise de now
in some cases, while in others it is the result of terminal
differentiation of CPDN. The potential for differentiation
of heterologous tissues such as muscle may not be ex-
pressed in de now CN.
The close relationship between solid Wilms’ tumor and
CN/CPDN is suggested by Case 2, with CPDN in the left
kidney and anaplastic solid Wilms’ tumor in the right.
The concept that CN, CPDN, and solid Wilms’ tumor
are histogenetically related entities is analogous to the

FIG. 13. A CPDN with focal anaplasia (arrow). Inset shows the abnormal nuclei (H & E, original magnification X40 and X400).
47 8 July 15 1989
CANCER Vol. 64

FIG. 14. A CPDN with focal hemorrhage and necrosis in a septum, with fibroblastic proliferation. Identical changes may be seen in CN (Fig. 6)
(H & E, original magnification X250).

spectrum of differentiation seen in the neuroblastoma se- the spectrum, respectively, with ganglioneuroblastoma
ries. It is widely accepted that ganglioneuroma and neu- representing the transition between these two extremes.
roblastoma represent the benign and malignant ends of The pathogenesis of cystic change in CN and CPDN is

DIAGRAMMATIC REPRESENTATION OF REVISED CLASSIFICATION OF MLC (CN) AND CPDN

Multllocular Cystic Renal Tumor

INo solid component except for c y s t i c septa)

I
I
No Blastemal Cells
1
Blastemal Cells
in Septa in Septa

A
FIG. 15. Proposed classification of
CN and CPDN.

>SO% Elements
Mature (51%

I in Septa
I
No. 2 CYSTIC AND NEPHROBLASTOMA Joshi and Beckwith
NEPHROMA
not known. It is interesting to note that obstruction due
to micropapillary epithelial hyperplasia, detected by
scanning and electron microscopy, has been implicated
in the cyst formation in various developmental cystic dis-
eases of the kidney.16 It is possible that CN and CPDN
are predominantly tubular lesions with varying degrees
of differentiation from their inception. The microscopic
papillonodular projections (Fig. 10) seen in some CPDN
may be pathogenetically related to subsequent cyst for-
mation. It is also possible that some of the cystic fonna-
tions in these lesions may represent attempts to replicate
development of portions of the renal collecting system.
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