THE SIGNIFICANCE OF MUCUS IN CARCINOMA OF THE

THE SIGNIFICANCE OF MUCUS IN CARCINOMA OF
T H E PROSTATE GLAND
FREDERICK PILCHER, JR.*
Fellow in Urology, The Mayo Foundation, Rochester, Minnesota
Although occasional cases of gelatinous carcinoma of the prostate gland have been observed, the frequent occurrence of mucus
in smaller quantities in cases of prostatic carcinoma has not been
recognized. In routine examinations of sections of carcinoma of
the prostate gland at the clinic occasional areas were noted which
had the appearance of mucus. It was therefore decided to stain
sections from a considerable number of glands in which carcinomas were growing with stains specific for mucus and from
them determine the frequency of mucus and its significance in
this type of neoplasm.
In the literature and standard textbooks there is little information on this subject. Generally in the textbooks on histology
there is no note concerning mucus in the epithelium of the prostate
gland or in its secretions. Occasionally its occurrence is denied.
Stieve, however, made the statement that the prostatic secretion
stains weakly with mucicarmine. Apparently the only careful
study of the prostate in regard to the presence of mucous glands
and the formation of mucus is that of Schlachta who reported
mucus-producing cells of two types, those which occurred occasionally in some of the prostatic acini, and those which occurred
in true mucous glands, both types being more common along the
ducts. Mucus-producing cells occur principally near the apex
of the prostate gland distal to the utricle and in that portion of
the gland anterior to the urethra. These regions of the gland
are less often examined in routine histologic studies. Mucusproducing cells are most common in the fetus; they rapidly be* Now residing in Calgary, Alberta, Canada.
September 25, 1937.
366
Submitted for publication
CARCINOMA OF PROSTATE
367
come less numerous after birth until, in adults, they are very few
in number and difficult to find. Concerning prostatic carcinoma,
Simmonds said that colloid degeneration could occur. Oberndorfer thought that colloid carcinoma of this organ belonged
among the most extreme rarities. Apparently Boyd reported
the first case of colloid or mucoid carcinoma of the prostate gland.
His diagnosis was made on gross examination without the aid of
any special staining technic. More recently, Klissurow made a
careful detailed study in another case of colloid carcinoma.
METHODS
In this study sections were made from tissue removed during transurethral
resection in seventy-one cases of adenocarcinoma, in four cases of squamous-cell
carcinoma, and in thirteen cases of ordinary benign hyperplasia of the prostate
gland. Generally, three to five pieces of tissue were examined in each case.
Sections were also made from normal glands obtained at necropsy in ten cases,
the subjects having varied in age from being stillborn to eighty-three years.
These glands weighed less than 15 gm. and microscopically were within the
limits of normal. All the specimens had been fixed in 10 per cent formalin for
periods of from two months to three years. Sections from each case were
stained with hematoxylin and eosin by a standard technic, and with mucicarmine according to the following technic: (1) The formalin-fixed tissue was embedded in paraffin, (2) sections were cut at 8 microns, (3) sections were then
deparaffinized, (4) sections were placed for twenty minutes in picric acid solution, which was made by adding 5 cc. of glacial acetic acid to 75 cc. of a saturated
aqueous solution of picric acid, (5) sections were then washed fifteen minutes
or longer in running tap water, and (6) stained in alum hematoxylin for five
minutes, (7) they were again washed well in tap water, (8) immersed in a saturated aqueous solution of lithium carbonate for one minute, (9) washed in tap
water, (10) stained in mucicarmine for twenty minutes, (11) washed in water,
(12) dehydrated in 95 per cent alcohol, acetone, carbol xylol, and (13) mounted
in balsam. The mucicarmine stain was made fresh each time by mixing 4 grams
of carmine (Alum Lake), 1 gram of aluminum chloride, and 8 cc. of water.
This was heated slowly for several minutes and then made up to 400 cc. with
50 per cent alcohol. Mucicarmine stains mucus and tissue containing mucus
a bright red, in contrast to the surrounding tissue which is stained pale blue.
Each carcinoma was graded microscopically according to Broders' method
for determining the degree of malignancy. A method was then devised for
grading the amount of mucus in the sections, although this was difficult because
of its irregular distribution. If any mucus at all was present in any portion
of any section, the case was classed as being of grade 1 for mucus. If a fourth
368
FBEDEBICK PILCHEB
to a half of the acini or cell groups of any given microscopic field in any portion
of the tissue contained mucus, then it was classed as grade 2 for mucus. When
more than half the cell groups contained mucus it was classed as grade 3, and
those cases were considered as being of grade 4 for mucus when any microscopic
field was found to contain mucus in more than three-fourths of its area.
Not all of the microscopic fields showed the same amount of mucus. Occasionally in a section classed as containing mucus of grade 4 there would be
microscopic fields containing none at all. Generally the number of areas containing mucus was proportional to the mucous content of the area showing the
maximal amount of mucus. In a section classed as grade 4 because of a very
large amount of mucus in one particular microscopic field there would generally
be mucus in nearly every microscopic field and, usually, much mucus in every
field. On the other hand, a section classed as grade 1 because of the relatively
small amount of mucus in a given area would reveal only a few areas containing
mucus while most of the fields contained none at all.
RESULTS
In the sections of ten normal prostate glands mucus was found
in four. There was only the slightest trace of mucus in each of
these four cases and, in two of them, the mucus was definitely in
a short gland adjacent to the urethra and not in the deeper acini
of the prostate gland itself. Table 1 and figure 1 illustrate the
distribution of mucus in the other cases: There were thirteen
cases of hyperplasia of the gland. Some mucus was present in
every case, nine of them having mucus of grade 1, two mucus of
grade 2, and two mucus of grade 3. There were eight cases of
grade 1 adenocarcinoma of the prostate; one with mucus of
grade 1, three with mucus of grade 2, two with mucus of grade 3,
and two with mucus of grade 4. Of twenty cases of grade 2
adenocarcinoma of the prostate gland, two showed an absence of
mucus, twelve mucus of grade 1, two mucus of grade 2, three
mucus of grade 3, and one mucus of grade 4. Out of twenty-six
grade 3 adenocarcinomas of the prostate, ten revealed no mucus,
nine mucus of grade 1, four mucus of grade 2, two mucus of grade
3, and one mucus of grade 4. In the seventeen grade 4 adenocarcinomas of the prostate, there was no mucus in eleven, four
contained mucus of grade 1, one mucus of grade 2, and one mucus
of grade 3. There was no mucus in any of the four cases of
squamous-cell carcinoma of the prostate gland.
369
CABCINOMA OP PBOSTATE
TABLE 1
AMOUNT OF MUCUS PRESENT IN PROSTATE GLAND
10
13
8
20
26
17
4
8
n
0
2
10
n
4
0
?
2
3
2
1
0
80 2
0 9
0 1
10 12
39 9
65 4
100 0
20
70
12.5
60
34
23
0
$
o
0
9
3
2
4
1
0
a
8
0
15
25
15
8
6
0
Cases
!?
00
Grade 4
••3
o
O
H
O
a
8
Cases
09
<
Grade 3
Per cent
0
15
37.5
10
15
6
0
•*3
u
Normal
Hyperplasia
Adenocarcinoma, grade 1..
Adenocarcinoma, grade 2..
Adenocarcinoma, grade 3 . .
Adenocarcinoma, grade 4 . .
Squamous cell carcinoma..
Cases
18
Grade 2
Per cent
w
Grade 1
Per cent
AMOUNT OP MUCUS
00
n
0
2
1
1
0
0
0
25
5
4
0
0
100%
T5
50
2.5
0
100%
75
50
£5
0
100%
75
50
2.5
0
100%
75
50
Hyperplasia
Grade I
<B
1
G r a d e II
8
0 G r a d e III
ZS
0
G r a d e IV
Squamous celi
carcinoma
O
I
Amount
II
of
III
IV
mucus
100%
75
50
&5
0
100%
75
50
25
0
FIG. 1. SHOWING THE AMOUNT OF MUCUS PRESENT IN VARIOUS LESIONS OF
PROSTATE GLAND
AMERICAN JOURNAL OF CLINICAL PATHOLOGY, VOL. 8 , N O . 3
370
FREDERICK
PILCHER
COMMENT
It is at once apparent that the amount of mucus present in
prostatic carcinomas is definitely related to the degree of malignancy. Its amount is inversely proportional to the degree of
malignancy, the lower the degree of malignancy the greater being
the production of mucus. On the other hand, when the degree of
malignancy was high, the production of mucus was small. Even
the high-grade carcinomas contained mucus only in their somewhat slower-growing areas, the extremely rapidly growing areas
containing no mucus whatever.
Embryologically the prostate gland is derived from the urethra.
It is the most highly specialized gland derived from this source
and has a specific function. Ordinarily the adult gland contains
very few mucous cells and produces little mucus. Other glands
derived from the urethra, which are less highly specialized, have
as their principal function the production of mucus. Schlachta
observed considerable mucus in the young developing prostate of
the fetus. The occurrence of mucus in carcinoma of the prostate
gland may be due to the less differentiated and less specialized
carcinoma cell reverting to a more primitive function of mucus
formation which is rarely exhibited in the fully differentiated
adult cell of the prostate. In the more rapidly growing high-grade
carcinomas, the cells are too undifferentiated to function as producers of mucus.
REFERENCES
(1) BOYD, STANLEY: A case of colloid scirrhus of the prostate. Tr. Path. Soc.
London. 33: 200-203. (April 4) 1882.
(2) KLISSUROW, A.: Ein Fall von Carcinoma gelatinosum prostatae. Virchow's Arch. f. path. Anat. u. Physiol. 268: 515-523. (July) 1928.
(3) OBERNDORFER, S.: In: H E N K E , F. UND LUBARSCH, 0 . : Handbuch
speziellen pathologischen Anatomie und Histologic.
Springer, Part 3, 5, p. 496. 1931.
der
Berlin, Julius
(4) SCHLACHTA, JULIUS: Beitrage zur mikroskopischen Anatomie der Prostata
und Mamma der Neugeborenen.
1904.
Arch. mikr. Anat. 64: 405-483.
(5) SIMMONDS, M . : I n : ASCHOFF, LUDWIG: Pathologische Anatomie.
Jena,
Gustav Fischer, 2, p. 610. 1919.
(6) STIEVE, H . : In: v. MOLLENDORFF, WILHELM: Handbuch der mikroskop-
ischen Anatomie des Menschen.
7, p. 267. 1930.
Berlin, Julius Springer, Part 2