CONGENITAL
CYSTIC
PAMILY
KIDNEY
AND
LIVER
WITH
TENDENCY.
BY C. H. B U N T I N G ,
Associate in Pathology, Johns Hopkins University.
(From the Pathological Laboratory of the Johns Hopkins University and Hospital).
So much has already been written concerning congenital
cystic kidney t h a t an additional communication upon the subject
m a y seem to demand an apology. The author's excuse is a
recent opportunity to study two cases in which the lesion was so
early that they seem to offer some indication as to the pathogenesis of the condition. The cases were both new-born infants
delivered in the obstetrical service of Dr. J. Whitridge Williams
in the Johns Hopkins Hospital. some interest attaches to the
fact t h a t they w e r e b o t h children of the same mother, being the
first and second children of Mary P., an apparently healthy negro
who was sixteen years of age at the time of the delivery of her
first child in April, x9o 4. Her first confinement occurred on April
14, 19o4, when a perfectly normal labor resulted in the b i r t h
of a male child 44 centimeters in length and weighing 2o26 grams.
The labor was clinically estimated to have occurred early in the
ninth month of pregnancy. The child was placed in the incubator
and seemingly did well, gaining in weight after the initial loss,
but it died suddenly on the eleventh day.
The second child, a girl, was born on March 21, 19o5, eleven
and a half months after the birth of the first child. The child
was also born prematurely, apparently toward the end of the
eighth month of pregnancy. Labor was normal. The child was
42.5 centimeters in length and weighed 2o05 grams at birth.
It did not do well after birth but lost gradually in weight up to
the time of its death when it weighed 138o grams.
The abbreviated post-mortem protocols of both children will
be found appended to this article. For the sake of convenience
in descriPtion the children will be designated child " A " and
child " B . "
27I
272
Congenital @tie I(idne9 and Liver
This family tendency has been previously noted a number of
times, not however, in the negro race, and I emphasize it here
not only to indicate the part inheritance plays in the condition
b u t also to show that the cases here reported are related in this
feature to a considerable group of cases of cystic kidney. Dunger
in his admirable review of the subject of congenital cystic
kidney has collected eleven cases and added one of his own observation, in which the lesion has occurred in two or more
members in the same generation or in two generations of a
single family. To these I am able to add several others from
literature in addition to the present case.
S c h u p m a n n 2 is often credited with having r e p o r t e d the first case showing
family tendency, b u t a reference to his article shows, as Dunger suggests, t h a t
he r e p o r t s not t h e occurrence of congenital cystic kidney in t h r e e children b u t
in the t h i r d child of a m o t h e r who had given b i r t h to two m a l f o r m e d children
previously. This child showed in addition to the kidney lesion h y d r o c e p h a l u s
w i t h encephalocoele a n d a bicornuate uterus and double vagina. Luzzatto~
includes Adamkiewicz* a m o n g those who r e p o r t cases of family tendency, b u t
I have been unable to gain access to his thesis. Virchows in i855 published
the notes of a family in which the m o t h e r gave b i r t h successively to t h r e e prem a t u r e children. A p o s t - m o r t e m e x a m i n a t i o n on the t h i r d showed bilateral
cystic kidneys as the cause of the abdominal swelling. A s u b s e q u e n t child
showed a similar condition at the autopsy, and t h e r e is little d o u b t t h a t the
same condition existed in the o t h e r two children which were not examined.
The m o t h e r gave b i r t h to four o t h e r children, who lived, although one died a t
the age of ten m o n t h s as the result of acute hydrocephalus.
In z867 Wolff
r e p o r t e d a case of bilateral cystic kidney associated with h y d r o c e p h a l u s in the
male child of a w o m a n who had given b i r t h to a female child, previously recorded, with similar lesion of the kidneys eleven m o n t h s before. The w o m a n
h a d previously borne h e a l t h y children.
In I869 Brflckner 7 reported two
children of t h e same m o t h e r , the t h i r d a n d s e v e n t h child, w i t h cystic kidneys
a n d o t h e r malformations. The first of these two children showed six fingers
on t h e right h a n d a n d seven on the left. The head was set far b a c k w a r d almost
on the b u t t o c k s and there was also h y d r o c e p h a l u s with hernia of the brain.
The second child showed six digits on b o t h h a n d s and b o t h feet and also had
1Ziegler's Beilrdge, i9o4, x x x v , 445.
2 Organ f. d. ges. Heilkunde, i842, ii, z35.
L a degenerazione cistica dei reni, Venice, i9oo.
* Inaugural Dissertation, Berlin, I843.
s Verh. d. Phys. Med. Gesellsch., Wflrzburg i85.~, v, 447.
~Berlin klln. Woch., z867, iv, 480
7 Virchow's Archiv, i869, xlvi, 5o3
C. H. Bunth~g
273
h y d r o c e p h a l u s w i t h encephaloco~le a n d atresia of the h y m e n . I n 1894
Singer 8 described a family in w h i c h t h e first (male), f o u r t h (male), s e v e n t h
(female), t e n t h (female), a n d t h i r t e e n t h (male) children showed t h e lesion of
congenital cystic kidneys, t h e t u m o r masses causing g r e a t difficulty in delivery,
resulting in t h e d e a t h of t h e children a t birth. Only t h r e e of these cases were
e x a m i n e d p o s t - m o r t e m , b u t a g a i n t h e presence of t u m o r masses in t h e region
of t h e k i d n e y leaves n o d o u b t as to t h e existence of t h e lesion in t h e two u n e x a m i n e d cases. Carbonnel 9 h a s f o u n d t h e lesion in t h e kidneys of twins.
H 6 h n e ,0 in 1896 r e p o r t e d t h e r e m o v a l a t o p e r a t i o n of a cystic r i g h t k i d n e y from
a girl of 2o years whose m o t h e r , dying a t t h e age of 49 years, h a d s h o w n bilateral
cystic kidneys, cystic liver, a n d cysts in t h e ovaries. A n o t h e r child of t h e
same w o m a n h a d died a t t h e age of 9 weeks of some k i d n e y disease, t h e
a u t h o r suggests possibly also cystic disease.
S t e i n e r t ' in 1899 recorded two
i n t e r e s t i n g families. I n t h e first a m a n aged 53 died showing bilateral cystic
k i d n e y s a n d cystic liver. His sister also showed t h e condition of cystic kidneys,
a n d his son of io years showed a t a u t o p s y a cystic r i g h t kidney, while several
smaller children were also suspected to h a v e t h e disease because of a l b u m i n u r i a
a n d palpable n o d u l a r kidneys. I n t h e second family t h e diagnosis of t h e condition of cystic k i d n e y h a d b e e n e s t a b l i s h e d in a m a n aged 46, a n d in a sister
aged 38, while it h a d been d e m o n s t r a t e d p o s t - m o r t e m in a n o t h e r sister dying a t
42 years of age. I n t h e t e n - y e a r - o l d son of t h e m a n a cystic r i g h t k i d n e y h a d
also been diagnosed. D a v i d a n d J a c o b s o h n '2 in 19oo f o u n d bilateral cystic
k i d n e y s a t t h e a u t o p s y on a w o m a n 50 years of age whose sister h a d s h o w n
p o s t - m o r t e m a similar lesion. T h e m o t h e r of these two w o m e n who h a d died
previously .presented s y m p t o m s suggesting t h a t she h a d this disease, t h o u g h
it was n o t a c t u a l l y d e t e r m i n e d b y p o s t - m o r t e m e x a m i n a t i o n . These a u t h o r s
q u o t e L a u e n s t e i n ' s o b s e r v a t i o n of cystic k i d n e y in m o t h e r a n d d a u g h t e r , as t h e
first to d e n o t e a [family t e n d e n c y , b u t I h a v e been u n a b l e to find t h e o r i g i n a l
publication. I n 19o1 Beck 1~ r e p o r t e d a n o p e r a t i o n on a w o m a n of 55 y e a r s
a t which a cystic left k i d n e y was removed. A f t e r d e a t h i1 days l a t e r t h e
o t h e r k i d n e y was f o u n d e x t e n s i v e l y diseased. Two sisters of t h e p a t i e n t h a d
clied previously from t h e same disease, one a t 4o years after a n operation,
a n d t h e o t h e r a t 54 years. Carrez ,* records t h e e s t a b l i s h m e n t of t h e clinical
diagnosis of bilateral cystic k i d n e y in a w o m a n of 48 , as a result of
finding a t operation a large cystic left k i d n e y in her d a u g h t e r of 37 .
Morris '~ records the following two cases. Two children of one m o t h e r died
of congenital cystic kidney, one a t 6.5 m o n t h s , t h e o t h e r a t 3.5 m o n t h s . Of
four o t h e r children in t h e family 3 showed o t h e r congenital defects a n d one was
b o r n dead.
The f a t h e r of these children was t h e only s u r v i v o r of 13 children,
8 I n a u g u r a l Dissertation. Greifswald. 1894.
9 Q u o t e d b y Couvelaire, Annales de gyn. et obst., 1899 , lii, 453.
,o Deutsch. reed. Woeh. i896, xxii, 757.
,, Deutsch rned. Woch., i899, xxv, 667.
l~Charit6-Annalen, igoo, xxv, i6.
'3Ar~nals of Surgery, i 9 o i , xxxiii, 147.
'*Thesis, Lyon, i 9 o i .
"S Surgical Diseases of the K i d n e y and Ureter, 19Ol, i, 656.
274
Co~g(',~it~l C#.~tic I~Tid~ey r ~ d Licer
eleven of whom had died at birth and the other at five months. Morris quotes
also the report of Bar of three successive children of the same mother, who had
died of the disease. Osler~6 in ~9o2 reported the establishment of the diagnosis of bilateral cystic kidney in a man aged 39, whose mother had shown a
similar condition at autopsy. Meyer ~ reported in i9c 3 the autopsies on two
brothers, one 8 months old, the other two years, who had died of diphtheria.
In one of these there was present an atrophic cystic kidney on the right side,
and in the other a similar lesion on the left. Dunger ~s reports observing a
mother aged 64 years and daughter aged 26 years in both of whom bilateral
cystic kidney and cystic liver occurred. Both died of cerebral hsemorrhage.
I n this list it m a y b e n o t e d t h a t a n u m b e r of t h e cases s h o w e d ,
in a d d i t i o n to the c y s t i c k i d n e y s , o t h e r lesions in t h e n a t u r e of
c o n g e n i t a l m a l f o r m a t i o n s , a n d s u c h is t h e f r e q u e n c y of t h i s
a s s o c i a t i o n t h a t it m a y b e c o n s i d e r e d a l m o s t t h e rule. T h e list
of a s s o c i a t e d m a l f o r m a t i o n s is l o n g a n d v a r i e d . I t is h e a d e d
a p p a r e n t l y b y h y d r o c e p h a l u s , a l t h o u g h p o l y d a c t y l i s m is of
frequent occurrence.
I t includes v a r i e d lesions to b e a t t r i b u t e d
t o i m p e r f e c t i o n s in d e v e l o p m e n t in t h e c o m p l i c a t e d e m b r y o n i c
folds of t h e face a n d p e r i n e u m , s u c h as hairlip, h y p o s p a d i a s ,
a t r e s i a of t h e v a g i n a , v e s i c o - r e c t a l fistula, r u d i m e n t a r y c o n d i t i o n
o f t h e e x t e r n a l g e n i t a l i a . M a l f o r m a t i o n s of t h e i n t e r n a l g e n i t a l i a
:are also n o t e d .
I n a f e w cases t h e r e h a v e b e e n d e f e c t s in t h e
c a r d i o - v a s c u l a r s y s t e m , a m o n g t h e m a b s e n c e of t h e d u c t u s
Botalli, d e f e c t s in t h e i n t e r v e n t r i c u l a r s e p t u m a n d of t h e a o r t i c
valves.
I n one case t h e r e w a s situs t r a n s v e r s u s of t h e
t h o r a c i c v i s c e r a ; in a n o t h e r a b s e n c e of t h e spleen.
T h e t w o cases h e r e r e p o r t e d , h o w e v e r , s h o w e d n o s u c h g r o s s
d e f e c t s or m a l f o r m a t i o n s .
Both children though small and
prematurely delivered were well-formed externally and their
o r g a n s w e r e a p p a r e n t l y n o r m a l , grossly. O n m i c r o s c o p i c a l
e x a m i n a t i o n , h o w e v e r , t h e r e w a s f o u n d in a d d i t i o n t o t h e c y s t i c
c o n d i t i o n of t h e k i d n e y , t h e e a r l y s t a g e of a s i m i l a r c y s t i c c o n d i t i o n in t h e liver, a n d in one case also in t h e p a n c r e a s . T h i s
b r i n g s t h e cases i n t o a f a i r l y l a r g e g r o u p of c y s t i c k i d n e y s .
Lejars~9
collected
from
literature
6o cases
of
cystic
k i d n e y a n d of t h e s e 28. 3 p e r cent. s h o w e d also t h e c y s t i c
,6 American Medicine, i9o2 , iii, 95 i.
t7 Virchow's Archly, i9o 3, clxxiii, 209.
~Loc. cit.
~ Thesis, Paris, ~888.
C. H . B u n t i n g
lesion
in
the
liver.
cases found 43 cases
in the two organs.
ing the
Turning
the
pathogenesis
to the
second
of the
lesion
Luzzatto
than
x9oo in
o r ~ 9. ~ ~ p e r c e n t .
This association
of the
kidneys
child,
~° i n
275
disease
themselves
child
" B"
was
shown
as
by
a larger
series
with the associated
seems important
and
in consider-
will be discussed
I shall first describe
they
those
showed
an
of child
of
lesion
later.
those
earlier
of
stage
"A."
T h e k i d n e y s were n o r m a l l y placed in t h e b o d y c a v i t y a n d a p p r o x i m a t e l y
of n o r m a l size, p e r h a p s slightly enlarged. T h e ureters, bladder, u r e t h r a , a n d
genitalia were n o r m a l . T h e ureters allowed t h e passage of a small p r o b e w i t h
ease. T h e k i d n e y s showed n o t h i n g a b n o r m a l u n t i l t h e y were incised, w h e n a
considerable a m o u n t of urinous fluid poured o u t a n d it was f o u n d t h a t a n u m b e r
of small cysts h a d b e e n incised. The larger of these were a b o u t 2 or 3 ram.
in d i a m e t e r while t h e r e were m a n y o t h e r s scarcely visible. The cysts a p p e a r e d
to t h e n a k e d eye to b e confined a l m o s t exclusively to t h e m e d u l l a of t h e kidney,
w i t h here a n d t h e r e a visible cyst in the cortex. T h e different m e d u l l a r y
p y r a m i d s did n o t a p p e a r equally affected, some of t h e m b e i n g a l m o s t free from
visible cavities. The two k i d n e y s were affected a n d a p p a r e n t l y a l m o s t equally
SO.
T h e tissues were fixed in Z e n k e r ' s fluid a n d six sets of serial sections cut in
paraffin from various p a r t s of t h e organs, i n c l u d i n g a series from t h e p a r t m o s t
affected as well as one from t h e area a p p a r e n t l y freest from lesions. T h e sect i o n s showed t h a t t h e k i d n e y s in general were well formed. T h e cortical stria t i o n was well m a r k e d , w i t h a n o r m a l relation b e t w e e n m e d u l l a r y rays a n d
l a b y r i n t h , a n d t h e cortex was of n o r m a l width, m e a s u r e d b y t h e n u m b e r of
rows of glomeruli b e t w e e n t h e capsule a n d t h e m e d u l l a w h i c h t h e s t u d y of
n u m e r o u s infantile k i d n e y s has s h o w n to be as a general average ten. T h e
glomeruli were well f o r m e d a n d a p p e a r e d n o r m a l w i t h v e r y s c a t t e r e d exceptions. I n a few sections were f o u n d one or two glomeruli w i t h a dilated capsular space. T h e t u b u l e s of t h e secreting t y p e were also n o r m a l in a p p e a r a n c e
h a v i n g a high g r a n u l a r e p i t h e l i u m a n d a small u n d i l a t e d lumen. I n t h e m e d u l l a r y rays t h e loops of Henle a p p e a r e d s h o r t e r t h a n n o r m a l a n d in m a n y places
did n o t r e a c h to t h e b o u n d a r y zone. T h e r e were few cysts in t h e cortex u n t i l
one came to a p o r t i o n of t h e l a b y r i n t h b o u n d i n g on t h e medulla. Here t h e r e
were m a n y e l o n g a t e d a n d oval cystic cavities lined b y a fairly high cubical
epithelium. B y following o u t series of sections these could easily be f o u n d to
be c o n t i n u o u s a t one end w i t h t u b u l e s w h i c h e n t e r e d t h e m e d u l l a r y rays a n d
followed a course t o w a r d t h e medulla. T h e y often joined o t h e r t u b u l e s of t h e
collecting type. These t u b u l e s were u n c o n n e c t e d w i t h t h e loops of Henle, a n d
were q u i t e e v i d e n t l y collecting tubules, a n d t h e cysts t h u s corresponded to t h e
portions of t h e t u b u l a r s y s t e m k n o w n as t h e j u n c t i o n a l tubules. T h e conn e c t i o n s a t t h e distal e n d of t h e cysts were more difficult to trace, b u t in several
places t h e y were f o u n d to pass over into t u b u l e s w i t h t h e secreting t y p e of
epithelium.
2o Loc. cir.
Congenital Cystic ]~idney and Live~,•
276
In the medulla the cystic formation reached its maximum. In many places
there was scarcely a tubule found with a normal lumen. All were dilated. The
cysts were larger than those of the cortex and were variously shaped, tending
to be circular and were lined by high cubical epithelium. On the cortical side
the cysts opened into several finger-like tubular projections which tapered
rather abruptly so that in the boundary zone they were of the width of normal
ducts and from here were continued as collecting tubules into the medullary
rays.
Toward the papilla the cysts became somewhat contracted and in
favorable sections could be seen opening freely at the apex of the papilla, into
the pelvis. There was no obstruction to the lumen of the ducts at the papilla.
In very many places mitotic figures could be found in the lining epithelial cells
of the cysts, indicating an active proliferation rather than any compression.
There was, however, no evidence of numerical increase in the ducts. Intracystic papillary growths were not made out.
In the kidneys of child " B " the interstitial tissue of the medulla was not
increased in amount. The walls of the adjacent cysts lay almost against each
other, separated by only a few cells and strands of a rather embryonic connective tissue. The same condition held true for the cortex. In only one or
two places was there a slight patchy increase in connective tissue and it was
in relation to these patches that the few dilated glomeruli were found.
The sections from the part of the kidney which grossly appeared almost unaffected showed a condition similar to, but of less degree than, that in the other
parts. There were almost as many cysts in both cortex and medulla, but they
were smaller, resembling more a simple dilatation of the affected tubules.
T h e r e is c l i n i c a l e v i d e n c e t h a t t h e k i d n e y f u n c t i o n a t e d , if n o t
normally
at least approximately
so.
and apparently passed a normal amount
Death
The
child lived
was t h e r e s u l t of a c u t e g a s t r o - i n t e s t i n a l
sections showed also that
19 d a y s
of u r i n e i n t o i t s n a p k i n s .
infection.
The
the kidney was active and that
there
was no o b s t r u c t i o n to t h e p a s s a g e of u r i n e t h r o u g h
the tubules.
I n s o m e of t h e c y s t s a n d t u b u l e s t h e r e w e r e u r i c - a c i d d e p o s i t s
but
not in such amount
as t o c a u s e a n y a p p a r e n t
obstruction.
I n s o m e of t h e t u b u l e s o f t h e c o r t e x t h e r e w e r e h y a l i n e c a s t s a n d
in one or t w o places s u c h n a r r o w
into the
cortical cysts,
casts were found
demonstrating
the
c y s t s w i t h t h e t u b u l e s of t h e s e c r e t i n g t y p e .
continuity
projecting
of t h e s e
There was precipi-
t a t e d a l b u m i n i n s o m e of t h e g l o m e r u l a r s p a c e s a n d i n t h e t u b u l e s ,
b u t n o r e d b l o o d c e ll s w e r e d e m o n s t r a t e d .
The kidneys of child " A " were in general like those of child " B . " They
were about normal in size though the left kidney seemed slightly enlarged.
This enlargement was found to be due especially to one foetal lobule which
projected above the others as a rounded pale mass. On section this was found
to be much more cystic than the rest of the kidney. The cysts were large,
C. H. Bunting
277
m e a s u r i n g in places 5 ram. in diameter. T h e tissue b e t w e e n t h e m was pale a n d
fibrous in a p p e a r a n c e . I n several places in t h e m e d u l l a t h e r e were small
hmmorrhages, a n d uric-acid deposits were m a d e o u t in t h e form of b r i g h t yellow
dots a n d streaks. T h e microscopical sections showed also a m a r k e d similarity
to those a l r e a d y described. T h e r e was, however, one i m p o r t a n t difference,
a n d t h a t was a new g r o w t h of c o n n e c t i v e tissue, m o s t m a r k e d in t h e m e d u l l a
b u t e x t e n d i n g also into t h e p o r t i o n s of t h e cortex implicated. This c o n n e c t i v e
tissue was quite richly cellular, b u t a Mallory connective-tissue s t a i n s h o w e d t h e
presence of a b u n d a n t fibers w h i c h h a d a t e n d e n c y to t a k e a concentric a r r a n g e m e n t a b o u t t h e cystic tubules. I n this k i d n e y t h e greater p a r t of t h e cystic
d e v e l o p m e n t was in t h e medulla, t h o u g h t h e cortex was also implicated, a n d
t h e cortical cysts occupied a position similar to t h o s e in t h e o t h e r case, in t h e
p o r t i o n of t h e l a b y r i n t h n e a r e s t t h e b o u n d a r y zone. T h e r e were, in this kidn e y also, h~emorrhages i n t o t h e i n t e r s t i t i a l tissue of t h e medulla.
Before treating of the pathogenesis of the renal lesion, I shall
describe briefly the lesions of the other organs in so far as they
have a bearing on the subject. The liver merits most attention
and in the lesions of this organ again child "B" showed an
earlier stage than child "A."
Grossly t h e liver of child " B " a p p e a r e d slightly smaller t h a n n o r m a l for a n
i n f a n t of t h a t age. Superficially it was n o r m a l in a p p e a r a n c e , t h e surface being s m o o t h t h r o u g h o u t , a n d t h e l o b u l a t i o n distinct. T h e gall b l a d d e r a n d
bile d u c t s were n o r m a l . T h e cut surface, however, h a d a s t r i k i n g a p p e a r a n c e
a n d one t h a t is a p p a r e n t l y c h a r a c t e r i s t i c of t h i s condition i/a its early stages.
T h e p a r e n c h y m a was quite n o r m a l in a p p e a r a n c e , h u t e v e r y w h e r e t h r o u g h o u t
t h e o r g a n t h e p o r t a l systems were sharply o u t l i n e d as grayish t r a n s l u c e n t somew h a t b r a n c h e d areas, resembling r a t h e r closely a n o a k leaf in shape. T h e s e
spaces were e v i d e n t l y m u c h wider t h a n normal. T h e r e was a similar increase
of c o n n e c t i v e tissue a b o u t t h e e n t e r i n g p o r t a l vessels a t t h e h i l u m of t h e organ.
T h e microscopical sections showed t h a t t h e cause for t h e increase in t h e size of
t h e p o r t a l spaces was a m a r k e d increase in t h e size a n d n u m b e r of t h e d u c t s
in t h e m , w i t h a slight increase in t h e c o n n e c t i v e tissue. This change was unif o r m t h r o u g h o u t t h e organ. T h e ducts were lined b y a high c o l u m n a r e p i t h e lium, a n d were free from c o n t e n t o t h e r t h a n a finely g r a n u l a r eosin-staining
precipitate. These ducts were t o r t u o u s , were m u c h b r a n c h e d , a n d were irregularly dilated into cyst-like spaces.
I n m a n y places t h e y could be t r a c e d
to t h e o u t e r limits of t h e lobules, where t h e y e n d e d in columns of liver cells of
t h e secreting type. I n o t h e r places t h e y e n t e r e d t h e lobules a c c o m p a n i e d b y
a connective-tissue sheath, a n d in m a n y places cross-sections of a d u c t were
found, w i t h a similar h i g h e p i t h e l i u m w i t h clear p r o t o p l a s m , well inside t h e
lobule a n d e v e n close beside t h e c e n t r a l vein. T h e d u c t s w i t h t h e i r cyst-like
d i l a t a t i o n s in t h e p o r t a l spaces were s u r r o u n d e d b y a n increased a m o u n t of
c o n n e c t i v e tissue w h i c h was richly cellular a n d c o n t a i n e d m a n y cells of t h e
l y m p h o i d a n d plasma-cell type, as well as m a n y eosinophiles. As stated, t h e
c o n d i t i o n prevailed t h r o u g h o u t t h e liver, as s h o w n b y sections from various
278
Congenital Cqstic ~:idney and Liver
parts of the organ. The picture offered by the liver is identical with that
drawn to illustrate a case of Borst. 21
T h e l i v e r of c h i l d " A " w a s a l m o s t i d e n t i c a l i n g r o s s a n d m i c r o s c o p i c a l a p p e a r a n c e s w i t h t h a t of c h i l d B, t h e o n l y d i f f e r e n c e
being a more marked increase in the connective tissue, a difference already noted as existing between the kidneys of the two.
T h e c o n n e c t i v e t i s s u e i n t h i s c h i l d ' s l i v e r w a s a l s o less c e l l u l a r
and more fibrous and showed a tendency to encapsulate the ducts
with concentric layers of fibers.
In the pancreas of child "B" there was found a similar hypertrophic condition
of the duct epithelium. The larger ducts showed a much-folded involuted
epithelium, and there were more numerous branching ducts in the spaces about
the major ducts. Mitotic figures were found in the duct epithelium. The
cells of the parenchyma were not so high nor so granular as those of a normal
pancreas, and resembled more t h e duct epithelium. There was some increase
in the connective tissue of the organ especially near the larger ducts. I t was
richly cellular and resembled the tissue about the ducts in the liver. This
condition was less marked in the pancreas of child "A."
Section of the duodenum of child "B" showed a definite tendency to hyperplasia of the epithelium, though one hesitates to assign to it any important connection with the lesions of the organs described. The crypts of Lieberk;ihn
were very deep and wide with a high coarse-appearing epithelium of an indifferent type. Some of the crypts were indeed cystic.
In the lungs of both children the terminal bronchi were extremely dilated,
but there was no sacculation and the lesion was not apparently of the nature
of a congenital bronchiectasis, but of a compensatory nature following incomplete aeration of the lungs.
The other organs showed no lesions which could in any way be interpreted
as having a bearing on the disease of the liver and kidneys.
To summarize then, briefly, in two small children of the same
p a r e n t a g e t h e r e w a s f o u n d a c o n d i t i o n of h y p e r p l a s i a o f d u c t
epithelium with a tendency to cyst formation especially marked
in the kidneys and the liver, where there was also an increase
i n t h e n u m b e r o f d u c t s , b u t o c c u r r i n g a l s o t o a less d e g r e e i n t h e
pancreas and possibly in the intestine.
T h e a t t e m p t s t o e x p l a i n t h e p a t h o g e n e s i s of t h e c o n g e n i t a l
c y s t i c k i d n e y h a v e b e e n s o n u m e r o u s a n d so v a r i e d t h a t o n e
is i n c l i n e d t o q u e s t i o n w h e t h e r p a t h o l o g i s t s h a v e b e e n d e a l ing throughout
with a single pathological process. Though
different processes may be operative in the condition it seems
2~ Festschr#t der Phys.-Me& Gesellsch., WO,rzburg, I899.
C. H. Bunting
279
safe to assume that but a single one accounts for the group in
which both kidney and liver are affected, and it is to this group
that the present case belongs. Any light that m a y be gained
from a study of it m a y accordingly, it would seem, be applied
to the whole group.
If one omits the view that the cysts are formed in the interstitial tissue of the kidney which was early abandoned, and
confines himself to those theories which recognize their formation
either in the tubules or in the glomeruli, the attempted explanations of the pathogenesis of the condition fall naturally
• into three or possibly four groups:
(i) that the cysts are the result of obstruction and of retention
of secretion ;
(2) that they are of the nature of a neoplasm;
(3) that they are the result of malformation; and
(4) that the condition lies between the last two, partaking
somewhat of the nature of each.
The literature of the subject has been extensively reviewed
in m a n y papers, notably those of Luzzatto, 22 Dunger, 2a von
Kahlden, 24 and Busse,2S and I shall make but brief reference to the more important opinions under the several
headings of the above classification, acknowledging m y indebtedness to these authors, where specific references are not given.
The great exponent of the retention theory was Virchow, and
it has probably been the weight of his opinion that has gathered
and held so m a n y adherents to this view. There have been m a n y
variations in the theory, the contention being as to the nature
of the obstruction. The general group of views may, however,
be well summarized in the words of Henry Morris 26: " R e g a r d ing as I do the congenital cystic kidney of the foetus and the
new born and the large polycystic kidney of the adult as essentially the same disease, both being due to dilatation, the result of
obstruction, one must yet recognize different causes of obstruction
22 L o c . eit.
2a L o c . cir.
2*Ziegler's Beitrage, 1893 , iii, 291.
25 Virchow's Archiv, 19o4, c l x x v , 4a2.
26 L o c .
cit.
280
Congenital Cystic Ki&~ey and Lb'er
in different cases some congenital, some inflammatory, some malformation, some traumatic, some in the kidney, some in the ureter,
and some in the urethra. The affection m a y commence in utero
or during the first months of extrauterine life, or in early childhood, or not until middle age, or advanced, or quite old age."
Virehow 27 first a d v o c a t e d the view that uric-acid.deposits were
the cause of the obstruction b u t in a later paper 28 advanced the
theory t h a t the lesion was the result of a foetal papillitis or pyelonephritis which caused an increase in the interstitial tissue of the
papilla. This in its contraction resulted in the atresia of the
papilla and thus in the formation of retention cysts in the tubules.
To this view he still adhered in x892} 9 Frerichs attributed the
cysts to retention following obstruction b y casts; Bouillard and
L e h m a n n to obstruction b y uric acid and calcium salts; Klein,
Rosenstein, and for a time Brigidi and Severi, to haemorrhage
from the glomerular tufts with obstruction of the outlet and
dilatation of the capsule. Sabourin, Cornil, and Brault a t t r i b u t e d
the lesion to an inflammatory condition in the kidney resulting,
through an interstitial new growth of tissue or cirrhosis, in a
constriction of tubules and retention. The retention theory has
had m a n y other supporters who see in the cysts of the kidneys of chronic nephritis a lesion analogous to t h a t of the
congenital cystic kidney.
In ~87 S Sturm a0 expressed the view t h a t the origin of the cysts
lay in the epithelium of the convoluted tubules, which at first
as the result of a dilatation underwent a simple h y p e r t r o p h y b u t
later led to the putting out of bud-like processes of an adenomatous nature. B y the early f a t t y degeneration of these
constantly growing tumor-like processes, the cysts were formed.
In x876 Mihalkowicz al expressed the view that the condition
in the kidney was analogous to the cystic disease of ovary, testicle, and breast. Chotinsky a2 could find no evidence t h a t the
a7 Verh. der Gesellsch. ~. Geburtshiil~e, Berlin, 1847, ii, 17o ,
28Verh. der, Phys.-Mcd. Gesellsch., Wtirzburg, i855, v, 447.
29Berlin. klin. Woch., i892 , xxix, lO 5.
aoArch, der Heilkunde, i875, xvi, i93.
al Thesis, Paris, 1876.
a2Thesis, Bern, 1882.
C. H. Bunting
281
glomeruli took part in the cystic formation, but found signs,
instead, of an active growth of the tubules in outgrowths from
the tubules, solid cellular processes, and probably new formation
of tubules. He concluded the primary factor was a hyperplasia of the tubules and of the stroma. Lejars 33 described the
condition as a persistent congenital lesion, in the great majority
of cases of the type of an " Epithelioma Muco'ide." In i893
Nauwerk and Hufschmid 34 recognized buds from the tubules,
intracystic papillary growths, and solid nests of epithelial cells
and placed the lesion definitely in the group of adeno-cystomata.
Von Kahlden 35 supported this idea, but emphasized farther the
co6rdinate growth of the stroma analogous to that in the adenofibromata. He considered the lesion of cystic liver of the same
nature. There are numerous other supporters of the theory
of active growth of the epithelium of the tubules, among them
Hommey, Hausmann, Albert, and Schmitz.
The frequent association of the congenital cystic kidney with
malformation of various parts and organs has led to the idea t h a t
it too is to be regarded as a malformation or the result of an error
in development. This view gains some support from the extreme
complexity of the process of development of the genito-urinary
system as a whole. Koster 36 was the first to describe the lesion as
an error in development, but he based his theory on a faulty
embryology. With the assumption that the tubules of the kidney
grew from a separate " anlage" from that of the pelvis and joined
it secondarily, he postulated a failure of union between the two
parts and a consequent hyperplasia of the epithelium of the
tubules with the cystic result. Hildebrand 37 has made use of
quite a similar explanation on the basis of the modern dualistic
theory of the formation of the kidney, i.e., that glomeruli and convoluted tubules arise from one anlage and secondarily join the
collecting tubules which are an outgrowth from the pelvis.
Hildebrand postulated a failure of union between these two
3~ Thesis, Paris, ~888.
34 Ziegler's Beitr~ge, z893, xii, i.
35 Ziegler's Beitrage, x893, xiii, 291.
36 Quoted by Dunger.
37Archly far klin. Chirurgie, i894, xlviii, 343-
282
Congenital Cystic Kidney and Liver
systems of tubules, with a retention of secretion and cystformation in the convoluted portion. Ribbert 3s has made use
of the same facts of development to explain the pathology of
the condition, b u t has emphasized, instead of retention of secretion
as the causal formation, a wild excessive proliferation of the cells
of the tubules which fail to join, particularly of the ampulla of
the collecting tubules and the portion of the other section, corresponding to the junctional tubule. He calls attention also to
the point t h a t in this active hyperplasia of the epithelium the
condition bears some resemblance to a new growth. Meyer 39
and Busse 40 express a similar opinion. Shattock 41 attributed
the lesion to the development of retention cysts from portions of
the Wolffian b o d y included within the kidney. Bard and
Lemoine 42 expressed the opinion t h a t the lesion was due not to
a primary epithelial hyperplasia, b u t to a defective resistance of
the walls of the tubules, in particular of the basement m e m brane, which allowed dilatation under the normal pressure of the
secreted fluid t h e y contained.
Quite a group of recent writers have t a k e n what m a y be t e r m e d
a middle position between the neoplastic and malformation
theories. Thus Couvelaire 43 objects to the consideration of the
lesion as a t u m o r of the eystoma or adenocystoma type, and
concludes t h a t the process which leads to the cystic transformation consists essentially in an exuberant b u t general proliferation of the epithelial cells of the excretory ducts, with a correlated reactive growth of the connective tissue.
The specific
character of the cells is lost. This hyperplasia and perversion
in the evolution of the cellular elements take place while the
organ is developing and is to be considered as a malformation in
t h a t sense. Borst, 44 though retaining the lesion among the cystic
adenofibromata, considers the process as an error of development,
38 Verh. der deutsch, path. Gesellsch., 1899 , 2te T a g u n g , ~87.
39 Virchow's Archly, i903, clxxiii, 209.
40 Loe. cir.
41 Trans. of the Path. Soc., L o n d o n , ~886, x x v i i , 287.
*2Arch. de rag&, i 8 9 o , ii, i 5 I .
4~ A n n a l e s de gyn~c, et d'obstet., i899 , lii, 453.
44 Loc. cit. a n d Die L e h r e y o n d e r G e s c h w f l l s t e n , i9o2, p. 596.
C. tI. Bunting
283
not in the sense of Ribbert, but in a disturbance of equilibrium
between the growth of epithelium and connective tissue, the s i n e
qua n o n for the normal development of an organ. In the cystic
liver and kidney, he postulates a failure of the epithelium to
develop in a normal way, as the result of a pathological agent,
and to possess an increased power of growth. As a result, the
connective tissue is invaded. Luzzatto 4s concludes t h a t the
pathogenesis of the cystic kidney is not uniform: t h a t in a
small number of cases--the shrunken cystic kidneys--the lesion
is a result of an interstitial nephritis of foetal origin; t h a t in
the more common type it is to be regarded as either a malformation or a tumor of congenital origin, between which he is
unable to draw a sharp line. Still he is inclined to include four
congenital cases of his study under the fibrocystadenomata, and
a fifth under malformations, due to an excessive development
of connective tissue in the organ.
Dunger 46 recognizes an inflammatory type, but also places the
more common in the unsettled province between congenital
neoplasms and mMformations. He considers the primary factor,
however, an error in development, with a secondary proliferation of the epithelial and connective tissues.
In considering these theories from the standpoint of the cases
here presented, one notices first that the kidneys offer no evidence
whatever in support of the obstruction and retention theory.
The urinary path was open throughout from pelvis to urethral
orifice. The children lived eleven and nineteen days respectively and passed urine freely. In the kidney the microscopical
sections showed the orifices of the ducts of Bellini free and if
anything wider t h a n normal. In the kidneys of child "B " there
was practically no increase in the interstitial tissue to cause
constriction of the tubules. The tubules were in great part free
from other than fluid content, and uric-acid deposits and casts,
though present, were for the greater part in the least dilated
tubules.
While studying these cases, the author has had opportunity
~s L o c . c i t .
~Loc. cit.
284
Uor~genital @stic Kidney and Live~"
to compare the picture afforded by the congenital cystic kidney
with that of a congenital hydronephrosis following a stricture of
the ureter (Autopsy 25o4) , in a child which lived but a fewdays
after delivery. The sections of the two lesions were entirely
different. In the hydronephrosis there was but moderate dilatation of the ducts of the pyramids, with beginning flattening
of the papilla and a beginning proliferation of the interstitial
tissue near the mouths of the ducts. There was no indication
of active growth of the epithelium. Further, the dilatation of
the tubules consequent on the damming back of the urine was
noticed not only in the medulla, but also in the cortex, in the
convoluted tubules where the lumen was wide and the epithelium
somewhat flattened, and even in the glomeruli where the capsules
were considerably dilated. In the congenital cystic kidneys, on
the other hand, the tubules of the secreting type in the cortex
and the glomeruli, with very few exceptions, were entirely unaffected.
These cases then give absolutely no support to the theories
which refer the lesion to obstruction and retention. There is as
little evidence afforded to support the idea of any malformation
or error in development of the kidneys in the sense of Hildebrand
and R i b b e r t - - t h a t is, of a failure of the two sets of tubules to join
with each other. The glomeruli and cortical tubules were well
formed and apparently normal in number. The loops of Henle
were possibly somewhat shorter and less well developed than in
kidneys of an equal age, but this was the only possible deviation
from the normal. If there were a failure of union, one would
expect a dilatation of the convoluted tubules or glomeruli due
to retained secretion. But in these kidneys no such dilatation
was found, and, though the cystic formation was diffuse throughout the kidney, there was anatomical and physiological evidence
that the urinary path from glomerulus to pelvis was free.
The sole malformation, if it m a y be called such, was an active
proliferation of the epithelium of the collecting ducts of the
medulla and of the junctional tubules in the cortex, chiefly in
the inner part. Of such active proliferation, there was positive
evidence in the numerous mitotic figures found in the epithelial
C. H. Btmting
285
lining of the cysts in child " B . " The absence of an increase of connective-tissue growth in the kidney of this child and its presence
in t h a t of the other seems evidence also t h a t such sclerosis is a secondary phenomenon. In the kidney I was unable to satisfy myself
t h a t there was an excessive formation of tubules. In the liver, on
the other hand, where t h a t point is more easily determined from
the architecture of the organ, the ducts were not only larger t h a n
normal b u t much more numerous, and in m a n y cases p e n e t r a t e d
the lobules almost to the central vein. There seems no question
t h a t one m u s t consider the processes in the two organs as essentially the same, and this suggests the possibility t h a t some of the
cystic tubules in the labyrinth of the kidney cortex, which clearly
showed a connection with the ducts of the medullary rays, b u t
which much less rarely could be found to continue into tubules
of the secreting type, were new-formed tubules, analogous to
those ducts of the liver which penetrated the lobule. The condition in some particulars thus resembles a neoplasm, y e t it is
as readily eonsidered a malformation in the sense of an abnormal
power of growth of the d u c t epithelium. If one accepts the
Cohnheim t h e o r y for the origin of certain tumors in the congenital
misplacement of tissues, an error in development, there is no
sharp line b e t w e e n the t w o conditions. However, it seems to
the author scarcely appropriate to t e r m the congenital cystic
kidney an adenocystoma. Instead of a localized growth more
or less sharply outlined from normal tissue, one finds here a
diffuse and widespread influence affecting the conducting tubules
generally in the kidney, liver, and pancreas, and even possibly
in the intestine. The occurrence of multiple tumors in the b o d y is
not unusual, b u t it is to be regarded more or less as a coincidence,
and in no group of tumors do we have as constant bilateral
occurrence as in congenital cystic kidneys, or as frequent an association as is found b e t w e e n t h a t lesion and the cystic liver.
Further, in the several organs the abnormal tubules were directly
connected with normal parenchyma, and in the kidney there
seems physiological and anatomical evidence t h a t in the cases
here reported the cystic tubules carried on their normal function
of carrying a w a y the secretion from the p a r e n c h y m a of the
286
Congenital @,stic IfSid~ey and Liver
organ. T h a t this functional activity persists for a n y great length
of time I do not maintain. It is readily seen t h a t the increase
in the size of the cysts, their encroachment on each other, and
the co6rdinate growth of connective tissue might soon lead to
obstruction of a great n u m b e r of tubules and ducts. This, however, would be a secondary effect.
Primarily, then, one finds evidence of an epithelial hyperplasia
in ducts which otherwise appear normal. This leads at first to a
general cylindrical increase in the size of the ducts, b u t gradually
there is a greater dilatation at points in the ducts less fixed b y
the architecture of the organ, and cystic tubules are t h e result.
The expansile force m u s t at first be the normal pressure of the
secreted urine, a force which secondarily becomes much greater
owing to the m u t u a l pressure of the dilated tubules and consequent
obstruction of some of them at various points. It m a y be objected t h a t a primary weakness of interstitial supporting tissue
has not been excluded as the stimulus to the epithelial hyperplasia. To explain w h y one finds the cystic formation instead of
intratubular epithelial growths in case of a primary epithelial
hyperplasia, one m u s t assume t h a t the normal urinary pressure
is greater than the resistance offered b y the supporting kidney
tissue.
However, t h a t there is a n y abnormal weakness of this
tissue does not necessarily follow, and in fact the specimens offer
no evidence of a n y deficiency in the supporting m e m b r a n e of the
tubules. The tortuosity of certain dilated ducts in the b o u n d a r y
zone, where there appears to be the greatest resistance to expansion, seems an added point in the favor of a p r i m a r y epithelial
process. The position of the lesion in pathological classification
would seem to depend on a definition of terms. If it be a
neoplasm, it differs from the conditions usually included under
t h a t term. If it be a malformation, it is one only in the sense of
Couvelaire and B o r s t - - a disproportionate activity in the g r o w t h
of the epithelium.
The frequent occurrence of associated
malformations of other parts and organs would appear to indicate that the condition bears a closer relation to malformations
than to new growths in the commonly accepted i n t e r p r e t a t i o n
of the latter term.
C. H. Bunting
287
F r o m the m a r k e d hereditary and family tendency shown in
the disease, one is led to search for the etiological factor in the
parents. Where the condition has appeared in two generations
it has generally been transmitted from father to son and from
m o t h e r to daughter. Where it appears in several members of one
generation, several successive children of either sex m a y be
affected or healthy children m a y intervene. In one case, Singer's,
there was a definite regularity in the appearance of the disease,
e v e r y third child of thirteen having shown cystic kidneys. The
condition then in the parent which determines the lesion in the
child is not always operative.
W h a t this factor is m u s t for
the present be left undetermined.
The a b b r e v i a t e d a u t o p s y protocols of the two cases are as
follows :
AuToPsY No. 229L April 28, 19o4. P o s t - m o r t e m e x a m i n a t i o n on B a b y F.
(child " A " ) , aged i i days.
The b o d y is t h a t of a small b u t well-formed colored male infant, 44 cm. in
length. There is some d e s q u a m a t i o n of the epidermis from the arms and hands,
a n d there are signs of nasal discharge. The a b d o m i n a l cavity shows a slight
excess of clear fluid w i t h m a r k e d cedema of t h e r e t r o p e r i t o n e a l tissues. The
pleural a n d pericardial cavities are normal.
The h e a r t is of a b o u t n o r m a l size, and, e x c e p t for m a r k e d distension of the
coronary veins, is n o r m a l t h r o u g h o u t .
The lungs are of pinkish color, deepening to a red in t h e posterior portion,
a n d crepitate t h r o u g h o u t . On section t h e y show m a r k e d congestion of the
vessels, a n d t h e cut surface is moist.
The spleen m e a s u r e s 4 x 2. 5 x 15. cm. a n d is d a r k red in color. On section
t h e pulp is increased in a m o u n t , obscuring the architecture of the organ; Malpighian corpuscles visible.
The liver is a b o u t n o r m a l in size w i t h s m o o t h regular surface. On section it
has a dark purplish color, m o t t l e d w i t h areas of light grayish t r a n s l u c e n t appearance, w h i c h are leaf-like in shape. These areas seem firmer t h a n the liver
p a r e n c h y m a . There are s c a t t e r e d t h r o u g h o u t the organ also, small light colored areas which are j u s t visible. The limits of the lobules c a n n o t easily be
m a d e out. There is an increase in t h e connective tissue a b o u t t h e larger vessels. The gall b l a d d e r a n d ducts a p p e a r normal.
The pancreas, stomach, a n d intestine show no definite lesions.
The kidneys are described on page 276.
Adrenals, testicles, and epididymes show no lesions.
The lines of ossification in the f e m u r a n d tibia are sharp, clean cut, a n d regular
A o r t a a n d b r a n c h e s are normal.
Microscopical examination. W i t h the exception of the organs
described no lesions of importance were found.
288
Congc~zital @stic I~idne!/ and Live~'
Liver.
See page 278.
Pancreas. The secreting p a r e n c h y m a is well formed. Many of the cells
contain clear spaces and vacuoles. The ducts are p r o m i n e n t in t h e section, are
dilated, are more branched, a n d seem c o m p a r a t i v e l y more n u m e r o u s t h a n in
o t h e r pancreases of this age.
Kidney. See page 277.
Anatomical diagnosis. Congenital cystic kidneys and liver;
catarrhal enteritis. Acute splenic tumor.
AuToPsY 25i 5. April Io, I9o 5. B a b y F. (child " B " ) , aged 19 days.
The b o d y is t h a t of an emaciated colored female child, 42. 5 cm. in length.
There are no external lesions.
The serous cavities show no lesions.
The h e a r t is of a b o u t normal size, a n d the cavities are filled w i t h r a t h e r t h i c k
u n e l o t t e d blood. The valves, endocardium, a n d m y o c a r d i u m are normal.
The left lung is of light pinkish color, is dry on section, and crepitates t h r o u g h out. The right lung resembles the left.
The spleen is enlarged a n d measures g X 3 x L 5 cm.
On section the p u l p ,
which is of d a r k brownish red color, seems increased in a m o u n t . The Malpighian corpuscles are enlarged.
The liver is small m e a s u r i n g ro x 5"5 x 3 cm. The surface is s m o o t h a n d
glistening a n d the organ seems n o r m a l l y formed. The color is a deep brown. On
section the brownish surface shows everywhere leaf-like grayish t r a n s l u c e n t
areas, a p p a r e n t l y r e p r e s e n t i n g enlarged portal spaces. Otherwise the architecture of the organ c a n n o t be m a d e out. The gall bladder contains a small a m o u n t
of thick greenish bile. The ducts a p p e a r normal.
The pancreas appears normal in size a n d t e x t u r e , w i t h no increase in its
stroma.
The s t o m a c h is distended. Its mucosa is swollen, injected, and covered w i t h
thick mucus.
The intestine shows a greenish fluid f~ecal content, a n d considerable m u c u s o n
its epithelial surface. The mucosa is injected a t intervals t h r o u g h o u t its length,
a n d is swollen and velvety.
Mesenteric l y m p h glands are enlarged, opaque whitish in color, a n d soft a n d
moist to the touch.
The left kidney is slightly enlarged, a n d measures g x 2.7 x 2. 5 cm.; the right
measures 4.5 x 2.8 x 2.4 era.
}'or description see page 275.
The adrenals show no lesion. The bladder a n d genitalia are normal t h r o u g h o u t .
The lines of ossification at the lower end of the f e m u r and u p p e r end of the
tibia are sharp a n d clean cut, n o t thickened or irregular.
MICROSCOPICAL EXAMINATION--Liver. See page 277.
Pancreas. See page 278.
Duodenum. See page 278 .
Kidney. See page 275.
The lesions in t h e o t h e r organs are n o t of interest.
Anatomical diagnosis. Congenital cystic kidney, liver, and
pancreas ; acute catarrhal gastro-enteritis ; acute splenic tumor ;
acute mesenteric lymphadenitis.