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
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