View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector PATHOLOGIC PATTERNS OF THE SEBACEOUS GLAND* JOHN S. STRAUSS, M.D.t AND ALBERT M. KLIGMAN, M.D. By studying the way in which a structurecells which subsequently rupture in the fundus reacts to an imposed experimental stress, oneof the gland. Fragments of the thin eosinophilie can often better understand the changes ex-cell wall, which morphologically resemble kera- hibited in spontaneous dlsease. Much has beentin, persist in the sebum; occasionally the entire learned about the potentialities of the eccrinecell walls survive as ghosts. Furthermore, the in- and apocrine sweat units in this fashion (1—12).dividual oil droplets are separated by keratin- Previous study of the response to injury in thelike trabeculae. A dual potentiality is exhibited sebaceous gland has been restricted mainly to theby sebaceous cells in their capacity to produce changes that occur in the sebaceous duct per sefat predominantly and keratin to a minor de- (13). In this study we have followed the reac-gree. Epidermal cells have this bipotentiality tion of the sebaceous gland itself to a variety ofwith keratin as the major product. cutaneous insults and have correlated the findings with those which occur in disease states. MA.TERIALS AND METRODS The scalp and cheek of post-puberal individuals MOBPOLOGY AND FUNCTION OF were selected for study because the glands here TRN SEACEOUS GLAND are among the largest and most numerous. Biopsy 1.Morphology: The glands of the glabrous skinspecimens were obtained before the experimental are not free but are associated with hair follicles,stresses as well as at varying intervals afterwards. a combination recognized as the pilosebaceousAll specimens were serially sectioned and stained unit. In terminal hair follicles which bear coarsewith hematoxylin and eosin. hairs, as on the scalp and beard, the gland is the The experimental stresses were as follows: minor component of the unit, actually an ap- 1. Contact dermatitis: (a) A moderate primary pendage of the follicle. By contrast, the sebaceousirritant dermatitis was produced by painting the glands of vellus hair follicles are proportionallycheek daily with benzene for one month. larger. Indeed, the vellus hair follicles of the (b) Severe allergic contact dermatitis of the glabrous skin of the face are truly sebaceouscheek was produced by applying 0.25 ml. of 0.1% follicles in which the hair has been reduced to anacetone solutions of dinitrochlorobenzene and inconspicuous appendage of an extraordinarilypentadecyl catechol to sensitive skins. large sebaceous gland. These differences must be 2. Occlusion with adhesive tape: A inch pointed out because this study has focusedsquare area of the cheek was kept constantly primarily upon the sebaceous follicles of the face.covered with plastic adhesive tape for six to 2. Function: (14) The sebaceous gland is aeight weeks. holocrine organ. Sebum is excreted through the 3. Plucking: All of the scalp hairs within a steady casting off of cells, a process of continuoushalf inch area were epilated manually with a growth. The division of relatively undifferenti-forceps; only those individuals in whom complete ated basal cells is followed by progressive trans-extraction was possible were used. formation into mature fat-ladened sebaceous 4. Puncture: In the scalp and on the cheek, multiple punctures through the follicular wall, * Fromthe Department of Dermatology (Don- ald M. Pillsbury, M.D., Director), University ofand probably through the gland itself, were made Pennsylvania School of Medicine, Philadelphia 4,by introducing a fine needle into the long axis Pennsylvania,and The Department of Dermatol-of the follicle and plunging it up and down in ogy (Herbert Mescon M.D., Professor), Boston University School of Medicine, 80 East Concordvarious directions. Street, Boston 18, Massachusetts. 5. Dermabrasion: After freezing with ethyl This work was supported by a grant from The National Institutes of Health, PHS E-1589. chloride, the cheek was abraded to a depth of t Formerly Public Health Service Researchapproximately 1 to 2 mm. with a revolving Fellow of the National Institutes of Health. wire brush. Presented at the Eighteenth Annual Meeting of The Society for Investigative Dermatology, 6. Derinal inflammation: Nodular inflamma- Inc., New York, N. Y. June 1, 1957. tory reactions of varying degrees of severity were 51 52 THE JOURNAL OF INVESTIGATIVE DERMATOLOGY produced by intradermal injections of the fol-fail to undergo the normal sebaceous transforma- lowing substances: (a) sebum (ether extractedtion. In its complete form the entire lobule may from hair), concentrated, and in dilutions upbe occupied by these undifferentiated epithelial to 1 :100; (b) comedones (ground up and sus-cells. The replacement of the gland by undiffer- pended in saline); (c) fatty acids of varying chainentiated epithelial cells may be incomplete with lengths suspended in olive oil; (d) cholesterolvarying percentages of cells showing the presence suspended in olive oil; (e) squalene suspended inof varying amounts of fat. Those cells which are olive oil; (f) turpentine suspended in olive oil;in varying stages of sebaceous transformation at (g) croton oil suspended in olive oil; and (h)the time of injury may fail to mature in the nor- olive oil alone. mal way and instead show apparent excessive 7. Galvanic injury: The ostia of sebaceouskeratinization of the cell walls and retention of follicles on the face were lightly coagulated withthick eosinophilic, keratin-like cytoplasmic tra- a fine needle activated by a low amperage gal-beculae. These excessively keratinized cells are vanic current. This superficial injury did nothardier, do not rupture, and persist as ghosts directly involve the sebaceous gland. clogging up the fundus of the gland. 8. Thallium: 0.25cc of a 0.1% thallium acetate 4. Proliferation: Tongues and cords of indiffer- solution in saline was injected intradermallyent epitheial cells may grow out of the undiffer- into the scalp. entiated lobules into the dermis. 9. Cotchicine: 0.25 cc of a 0.1% coichicine 5. Keratinous metaplasia: The periphery of the solution was injected intradermally into the scalp.gland may be transformed into a stratified 10. Methylcholanthrene: A 0.6% solution ofsquamous epithelium similar to the epidermis. 20-methyicholanthrene in benzene was paintedKeratinized squamae fill the cavity formerly on the cheek daily for one month. The oppositeoccupied solidly by sebaceous cells. control cheek was painted with benzene (see number la). B. Detailed Observations 11. Acne: Biopsy specimens of experimental The experimental stresses divide themselves chloracne as well as acne vulgaris have beeninto four groups: examined. 1) Superficial surface injuries (contact derma- titis, adhesive tape). RESULTS 2) Localized damage to the pilosebaceous A. General Patterns of Response unit (galvanic injury, plucking, puncture, derma- brasion, and dermal inflammation). Several patterns of response were discernible. 3) Cellular inhibitors (colehicine, thallium 1. Destruction: Severe stress destroys the gland totally. The terminal hair follicle is far moreacetate). resistant to destruction. 4) Carcinogens (methyicholanthrene). 2. Atrophy: Following certain stresses, not1. Superficial surface injuries quite severe enough to destroy the gland, involu- tion of varying degrees may occur. There were no important changes in the 3. Failure of 8ebcweous maturation: This change sebaceous glands in four biopsy specimens will be emphasized because it is so characteristic.taken at varying intervals (1—4 weeks) after the The sebaceous cells may become replaced toproduction of allergic or primary irritant type varying degrees by undifferentiated epithelialcontact dermatitis. Similarly, there were no cells. The mature sebaceous cells are cast off andchanges in the sebaceous glands in three speci- are replaced from the basal layer by cells whichmens taken 6 to 9 weeks after the continuous application of adhesive tape. The deep location The use of the word "sebum" throughout thisof the glands protects them from superficial article is not technically correct, for in reality the ether extracted material was "surface lipid" con-injury. Minor changes in the fofficular ostia were sisting of sebum from the sebaceous glands plusnot reflected in the morphology of the gland. the ether soluble products of keratinization. Nev- ertheless, because the collections were made from the scalp where relatively great amounts of sebum2. Localized damage to the pilosebaceous unit are rapidly produced from large sebaceous glands, it is probable that the material was mostly se- a. Plucking: (Figure 1A, 1B) Fourteen biopsy baceous in origin. specimens removed immediately and one to four Fin. 2. Check, one week after repeated punc- ture of the pilosebaceous apparatus. (A) (X50). Ona smaller scale the changes are like those FIG. 1. Scalp—18 clays after plucking. (A) which follow plucking: follicular hvperkeratosis, (X66). The upper portion of the follicle is dilated some glandular atrophy and partial replacement and filled with keratin. Below this the sebaceous of the sehaceous gland with undifferentiated cells. glands are atrophic and have been replaced al- (B) Sehaceous acinus from the same follicle as most completely by cells of the undifferentiated shown in 2A (deeper cut) (X102). The periphery type. The changes mimic comcdo formation. (B) of the gland is mostly undifferentiated