Experimental Production of Metaplasia in the Human Apocrine Sweat Gland*

WALTERB. SHELLEYANDMILTONM. CAHN

(Department of Dermatology, University of Pennsylvania School of Medicine, Philadelphia, Pa.)

Any cell in the body may undergo a variety of areas of metaplasia under the stress of chronic in changes. One of the most interesting of these is the flammation. It was decided to study this process morphologic transformation of a normal adult cell more closely by attempting to produce it experi into another related, yet histologically distinct, mentally. type. Thus, the columnar epithelium of the bron chial tree may be transformed into squamous epi MATERIALS AND METHODS thelium of a normal adult type. This process is A variety of damaging or irritating technics was known as metaplasia. It has recently attracted employed in treating the axillary skin of normal special attention because of its potential relation human male subjects: ship to the growth problem of cancer. (1) Formaldehyde, aqueous solutions, 5, 10, 25, Metaplasia has been described as occurring in 50 per cent applied topically for 5 minutes, numerous tissues and organs, e.g., the thyroid (1), once daily for 2 weeks. the peritoneum (2), the uterus (3), the mucous (2) Procaine, 4 per cent aqueous solution, in membrane (6), the prostate (7), and the breast jected once. (9). In regard to the skin, Hempelmann, Lisco, and (3) Talcum, aqueous suspension, injected once. Hoffman (4), Nodi (8), Walther and Montgomery (4) Milk, pasteurized, injected once. (11), and Weidman (12) have written concerning (5) Electrocoagulation, variable intensity. metaplasia in the eccrine sweat gland ducts and in (6) Silk thread, in incision site for 2 weeks. an eccrine sweat gland tumor. (7) Hair, in incision site for 2 weeks. The generally held view is that metaplasia is a (8) Epidermis excised. benign change in cells which are undergoing a (9) Axillary tissue, wedge buried in situ by sutur reparative process. The transformation is within ing adjacent skin over it. certain restricted limits,i.e.,adifferentiatedcolum nar epithelial cell may undergo "squamous" meta (10) Simple incision. (11) Superficial undercutting of axillary epider plasia; an epithelial cell, however, never becomes mis. a mesodermal cell, such as a histiocyte. The causes (12) Deep undercutting of axillary epidermis. of metaplasia are as numerous and as nonspecific (13) Deep excision of skin followed by scarring. as the forms in which injury may appear. Many types of trauma may incite metaplasia. For ex Biopsy specimens were taken 2 weeks after the ample, chronic inflammation is a common ante noxious stimuli or traumatic procedure. In the cedent of metaplasia. Metaplasia may be seen after case of the scar excisions, specimens were obtained vitamin A deficiency and occasionally after the at the following intervals: 1, 2, 3, 5, 7 weeks, and administration of large amounts of estrogenic hor 6 months. All of the specimens were serially sec mones. It would appear that metaplasia is possibly tioned and stained with hematoxylin and eosin. a reversion under stress to a more hardy type of cell. RESULTS Although nothing could be found in the litera The only process which led to the appearance ture regarding the occurrence of metaplasia in the of squamous metaplasia in the secretory coil of the apocrine sweat gland, our histologie studies of apocrine gland was scar formation after excision of axillary skin (10) have convinced us that the axillary skin. The technics other than deep exci secretory coil of the apocrine gland shows local sion either had no effect on the gland or, as in the case of the electrocoagulation, produced only * This study was supported by U.S. Public Health Service Grant No. G-3552. occasional metaplastic cells. In the scars of healing wound sites, diffuse in Received for publication May 18, 1955. flammatory changes were found, and certain apo- 671

crine glands showed desquamating cells which metaplastic apocrine cells should prove rewarding. were highly pigmented with yellow-brown gran Recent work (5) would suggest that mucin may be ules. In others, the lumen was partially or com present in these more elementary glandular cells. pletely filled with large, pale staining, finely granu lar, and at times vacuolar cells (Fig. 1). These cells SUMMARY had small pyknotic nuclei and in certain glands Proliferative squamous metaplasia of the secre could be seen to arise from the wall of the dam tory cells of the human apocrine sweat gland has aged apocrine gland (Fig. 2). The contrast between been experimentally induced by inciting a low- these vacuolar squamous cells and the normal grade local inflammatory change in the axillary columnar secretory cells of the apocrine gland skin. The metaplasia is interpreted as a process of (Fig. 4) is remarkable. Comparison of these meta- cellular de-differentiation occurring during the re plastic cells (Fig. 3) with those of the normal generative and reparative process. sebaceous gland (Fig. 5) shows striking similari ties. Actually, some of the metaplastic apocrine coils were identified as normal sebaceous gland on REFERENCES cursory inspection. 1. BULLOCK,W. K.; HUMMER,G. J.; and KAHLEB,J. E. These metaplastic cells showed no anaplastic Squamous Metaplasia of the Thyroid Gland. Cancer, 6:966-74, 1952. changes and their growth was strictly confined to 2. CROME,L. Squamous Metaplasia of the Peritoneum. J. the cavity of the gland. Abnormal mitotic figures Path. & Bact.,62:61-68,1950. were not seen. 3. FLUHMANN,C. F. The Histogenesis of Squamous Cell A study of biopsy specimens of scars present in Metaplasia of the Cervix and Endometrium. Surgery, the axilla for over 1 month failed to reveal meta Gyn. & Obst., 97:45-58, 1953. 4. HEMPELMANN,L. H.; Lisco, H.; and HOFFMAN,J. G. plasia of the apocrine secretory coils. The Acute Radiation Syndrome: A Study of Nine Cases and a Review of the Problem. Ann. Int. Med., 36:279- DISCUSSION 510, part 1, 1952. The epidermis and all of the epidermal append 5. LENNOX,B.; PEARSE, A. G.; and SYMMERS,W. St. C. ages appear to arise embryonically from a single The Frequency and Significance of Mucin in Sweat Gland ectodermal cell which has the potential of forming Tumors. Brit. J. Cancer, 6:363-38, 1952. 6. McCuLLOUGH,K., and DALLDORF,G. Epithelial Meta all of the highly specialized cells of the adult epi plasia. An Experimental Study. Arch. Path, 24:486- dermis and the appendages. In areas of local trau 96,1937. ma of appropriate intensity, the adult cells are 7. NANSON,E. M. Squamous Metaplasia of the Prostate destroyed, and regenerative processes are called Gland. Brit. J. Urol., 22:394-403, 1950. into play. At times metaplasia may result. In this 8. NÃ–DL,F. Epidermal Metaplasia of the Sweat Gland Excretory Ducts in Basaloma. Arch. f. Derm. u. Syph., experiment, metaplasia of the apocrine cells oc 198:343-51, 1954. curred. This process is in no way limited to the 9. SCHULTZ,A. Pathologische Anatomie der BrusterdrUse apocrine gland, and has been seen in the eccrine spacing. In: LUBARSCH,O., and HENKE, J. Handbuch gland, the sebaceous gland, and elsewhere in skin, der spez. Pathol. Anatomie und Histologie, Vol. 7, Part 2. Berlin: J. Springer, 1933. by us and by other observers. 10. SHELLEY,W. B., and LEVY,E. J. Histologie Observations The metaplastic change in the apocrine gland on the Human Apocrine Sweat Gland in Health and offers special opportunities for the study of the Disease. J. Invest. Derm, (in press). growth processes of primitive epidermal cells. No 11. WALTHER,M., and MONTGOMERY,H. Schweissdrusen- tumor mit Epithelmetaplasie. Arch. f. Derm. u. Syph., other area in the skin affords this opportunity; 163:420-26, 1931. elsewhere, metaplasia is not associated with 12. WEIDMAN,F. D. Metaplasia (Acute) of Sweat Duct hyperplasia. Epithelium, in Acute Suppurations. Arch. Derm. & Syph., Further studies on the histochemistry of these 10:275-78, 1924.

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FIG. 1.â€”Squamous metaplasia and hyperplasia occurring in an apocrine secretory coil as seen in an axillary scar 2 weeks old. X HO.

Downloaded from cancerres.aacrjournals.org on September 24, 2021. © 1955 American Association for Cancer Research. FIG. 2.â€”Originof metaplastic cells from aporrille cell wall. Note granular, squamous character of cells. X570. FIG. 3.â€”Squamous metaplasia filling lumen of apocrine gland. Xote pyknotic nuclei and complete absence of normal apocrine cells. Compare with Figures 4 and 5. X240. FIG. 4.â€”Normal apocrine cells for comparison. X240. FIG. 5.â€”Normalsebaceous gland for comparison. X240.

Downloaded from cancerres.aacrjournals.org on September 24, 2021. © 1955 American Association for Cancer Research. Downloaded from cancerres.aacrjournals.org on September 24, 2021. © 1955 American Association for Cancer Research. Experimental Production of Metaplasia in the Human Apocrine Sweat Gland

Walter B. Shelley and Milton M. Cahn

Cancer Res 1955;15:671-672.

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