Journal of Cutaneous Pathology 1977: 4: 99-104.
Granuloma Annulare with Transfollicular Perforation H. G. BARDACH Department of Dermatology II, University of Vienna, Vienna, Austria
In recent years the phenomenon of transepithelial elimination has been found to be the underlying mechanism in a variety of skin disorders. "Perforating dermatoses" may show transepidermal or transfollicular elimination or a combination of the two. A case of papular granuloma annulare is reported, where in one lesion the pilary apparatus actively participated in the elimination of necrobiotic collagen from the dermis. To our knowledge, perforating granuloma annulare with a transfollicular pathway has not previously been described. Also, a classification of perforating dermatoses is presented. (Reeeived for publieation January 27, 1977)
Ever sinee Pinkus (1954) first ealled attention to the biologic phenomenon of transepithelial elimination, this unique epithelial reaction pattern to alterations in the neighboring dermis has caught the interest of various investigators (for a review see Mehregan 1970, 1977; Bardach 1976). In fact, by recognizing this process as the common denominator in a number of heterogeneous skin diseases (Mehregan 1970, 1977), a new classification of "perforating dermatoses" was introduced, all of whieh are characterized by this "cathartic" aetion of the epithelium (Bardach 1976). Granulomatous dermal lesions with transepidermal penetration include granuloma annulare and reactive perforating collagenosis. Recently, infective granulomas have been added to the list (Wood et al. 1976). In the following report a case of papular granuloma annulare is described, where in one lesion the hair follicle actively participated in the elimination of altered connective tissue. Material and Methods
Case Report: In October 1976 a 68-year-old man was seen
who, 2 months previously, had notieed the appearance of asymptomatic red, slightly elevated papules on the neck, upper chest, and shoulders, A eutaneous biopsy revealed the typical pathology of granuloma annulare, with numerous small foci of incomplete collagen degeneration surrounded by palisading granulomas in the dermis. Both parents had suffered from diabetes mellitus and the patient had a normal fasting plasma glucose level, but a slightly abnormal glucose tolerance test indicative of latent diabetes mellitus. On closer inspection, a red, flattened papule 4 mm in diameter was seen over the right breast with the eenter oeeupied by a tiny, pin point-sized horny plug. This lesion was removed by punch biopsy and forms the basis of the subsequent report.
Preparation of the Specimen: The tissue was fixed in 10% formaldehyde and serial sections of the paraffin embedded material were stained with hematoxylin and eosin, periodic acid-Schiff (PAS), Goldner's trichrome and also with an elastic stain (Weigert).
BARDACH
100 Results
The results will be presented three-dimensionally as they were observed on serial sectioning. First, the charaeteristie pathologic picture of granuloma annulare was seen in the dermis. Then, a "channel" of necrobiotie tissue surrounded by keratinizing, partly parakeratotic .squamous epithelium became visible "floating" free in the upper dermis. The material enclosed by the epithelial sheath appeared amorphous and "lumpy". With Goldner's trichrome method it stained green like the small foci of degenerated collagen in the adjacent dermis and was separated from the surrounding epithelium by a deep red line of condensed parakera-
totic keratinocytes. Soon, the epithelium became eonnected with the overlying epidermis by a thin "stalk" of epithelial cells (Fig. 1). Whereas in the beginning the epithelial wall of the channel was only a few layers thick, it now formed irregular projections into the surrounding dermis that, in the area beneath the "channel", showed discrete islands of squamous cells (Fig. 1). The lumen of the channel was much wider now, and contained dark green and red material (Goldner's triehrome). In hematoxylin and eosin stained seetions the material appeared slightly more eosinophilie than the necrobiotic foci of collagen in the neighboring dermis (Fig. 2). The epithelial sheath becarne broadly joined to the epidermis (Fig. 3). In
\
•
' r l ' 4^ ,^ '
*-. .
V Fig. 1. Goldner's trichrome stain: The epithelial sheath joins with the epidermis by a thin "stalk" of cells. In the dermis deep to the channel a few cross-sections of pseudoepitheliomatous extensions are recognizable (X 100).
•- ..
V
Pig. 2. H & E stain: The intradermal channel is now broadly connected with the epidermis. It contains "lumpy" material slightly more eosinophilie than the necrobiotic foci in the surrounding dermis (X I 57).
Fig. 3. Goldner's trichrome stain: The entire pilary apparatus has become visible, its upper third being replaced by lepitheliomatous hyperof the follicular epithelwith the lumen of the cut tangentially in the (X 60).
BARDACH
102
Fig. 4. H & E stain: Part of the follicular opening filled with parakeratotic material is seen in the upper portion of the hyperplastic follicular epithelium (XlOO).
I
' • '
/^(f. 5. H & E stain: The epidermal invagination forming the follicular orifice extends tongue-like projections into the dermis to the lower right, engulfing a large focus of degenerated collagen. The follicular opening is plugged with parakeratotic material The dermis shows foei of necrobiotie collagen surrounded by palisading granulomas (X 60).
PERFORATING GRANULOMA ANNULARE subsequent sections, part of a hair follicle and sebaceous gland lobules were seen deep to the pseudoepitheliomatous proliferation occupying the upper third of the dermis. The pseudoepitheliomatous hyperplasia containing the perforating ehannel eventually beeame continuous with and merged into the pilary apparatus (Fig. 3). The channel was replaced by a deep epidermal invagination, presumably the site of the original foUieular opening (Figs. 4 and 5). Although a hair was present in the lower dermis, this was not apparent in the parakeratotie plug occupying the follicular "infundibulum". The neerobiotic tnaterial had largely disappeared and only remnants of it could be observed in the center of the plug (Figs. 4 and 5). In no section did the eontents of the perforating ehannel stain for elastic tissue or with the PAS technique. Tongue-like epi-
103
thelial projections extended from the epidermal invagination into the adjacent dermis engulfing necrobiotie connective tissue (Fig. 5). Discussion The most plausible interpretation of the histologie findings is that of a giant reactive transepithelial elimination process involving the upper (infundibular) portion of a hair follicle aecompanied by loss of the follicular architecture in that region, As has been pointed out earlier (Bardaeh 1976), the periepithelial and subepidermal zone of fibrovascular mesenchymal tissue closely interaets with the adjoining epithelium (Sweet 1971). Alterations in this subepithelial structure may not only induce neoplastic epithelial transformation, but
Table 1 Transepithelial routes in perforating dermatoses Perforating Dermatoses A) Epidermal lesion (dyskeratosis) as primary event: Kyrle's disease Traumatic hyperkeratosis "en b o u c h o n s " (Tapernoux & Delaeretaz 1971) Perforating foUiculitis B) Dermal lesion as primary event (1) Elastic tissue Elastosis perforans serpigino.sa Pseudoxanthoma elasticum (observed by Lund 1975) Actinic elastosis (Pinkus 1954) Actinic keratoacanthoma (Bardach 1976) (2) Granulomatous tis.sue (a) Non-infectious Granuloma annulare Necrobiosis Iipoidica (Parra 1977) Reactive perforating collagenosis (b) Infectious Blastomycosis (giant cells) Schistosomiasis (Wood et al. 1976) (3) "Foreign" Material Amyloidosis Black Heel Osteoma perforans
Transepithelial Route transepidermal transfollicular
+
+
-t—
-I+
+
+
+ ^-
— —
+
-
+ — +
-(+ —
-I+
— —
+ + +
— — —•
104
BARDACH
also initiate a unique epithelial, two-step, reparative process: First, a pseudoepitheliomatous hyperplastie proliferation engulfs the "foreign" material in the neighboring dermis. Then, a perforating channel is formed, through which the tnaterial is eliminated at the surface. That the follicle actively takes part in elimination processes is not surprising in view of the vast reparative potential inherent in the follicular wall as can easily be observed in acne lesions and other instances of follicular rupture. TransfoUicular perforation has been known to occur secondarily to dermal changes in elastosis perforans serpiginosa, where originally only a transfollicular pathway of elimination was postulated (Lutz 1953, Miescher 1955). In perforating folliculitis the transfollicular elimination of the dermal inflammatory response occurs as a sequel to primary changes within the pilary apparatus. Many cases of perforating granuloma annulare have been reported since the histologic description by Owens & Freeman (1971), although this condition had already been documented in a different context by Pinkus in 1934. The elimination of necrobiotic connective tissue together with the surrounding palisading granuloma seems to have exclusively occurred via the transepidermal route. To the best of our knowledge, this is the first observation of a transfollicular pathway in perforating granuloma annulare. In Table 1 we propose a classification of perforating dermatoses and pathways of transepithelial elimination. It appears that the location of the dermal alteration determines the route chosen by the perforating channel. In granuloma annulare, whenever the necrobiotic foci involve the subepidermal fibro-vascular component, the pathway will run via the epidermis. In the present case, the foci of connective tissue degeneration have obviously come in close juxtaposition with the follicular wall and touched off the strong reparative response inherent in the follicular epithelium. As this foUieular "rescue operation" proceeds, the structure of the upper pilary
apparatus is destroyed. In other words, the original biologic determination of the follicle is sacrificed in favor of the more urgent reparative transepithelial elimination of dermal "foreign" material. References
Bardaeh, H. (1976) Dermatosen mit Transepithelialer Perforation. Archives of Dermatologieat Research 257, 213-226. Lund, H. (1975) In Cutis 17, May 1976, eds. Arnold, H. L. & Rees, R. B. Ameriean Academy of Dermatology, 898. Lutz, W. (1953) Kerato.sis Follieularis Serpiginosa. Dermatologiea (Basel) /06, 318-320. Mehregan, A. H. (1970) Transepithelial Elimination. Current Problems in Dermatology, Vol. 3, pp. 114-147. Karger: Basel, Munieh, Paris, New York. Mehregan, A. H. (1977) Perforating Dermatoses: A Clinieopathologie Review. Internationat Journat of Dermatotogy 16, 19-27. Mieseher, G. (1955) Elastoma Intrapapillare Perforans Verruciforme. Dermatologiea (Basel)
110,254-266. Owens, D. W. & Freeman, R. G. (1971) Perforating Granuloma Annulare. Arehives of Dermatology 103, 65-67. Parra, C. A. (1977) Transepithelial elimination in neerobiosis lipoidiea. British Journat of Dermatotogy 96, 83-86. Pinkus, H. (1934) Uber atypisehe Tuberkulide, zugleieh ein Beitrag zur Atiologie des Granuloma annulare. (pp. 204-205 Tig. 2) Archiv fur Dermatotogie und Syptiitis 1 70, 194-222. Pinkus, H. (1954) Biology of Epidermal Cells. In Physiotogy and Biochemistry of the Skin, ed. Rothman, S., pp. 597-598. University of Chieago Press. Sweet, R. D. (1971) Orientations. Transactions and Annual Report of the St. John's Hospital Dermatological Society 57, 135-138. Tapernoux, B. & Delaeretaz, J. (1971) Hyperkeratose "en bouehons" d'origine meeanique. Dermatologica (Basel) 143, 201-208. Wood, M. G., Srolovitz, H. & Sehetman, D. (1976) Sehistosomiasis. Arehives of Dermatology 112 690-695. Address: H. G. Bardaeh Department of Dermatology (II) University of Vienna Alser Strasse 4 A-1090 Vienna Austria
Granuloma Annulare with Transfollicular Perforation H. G. BARDACH Department of Dermatology II, University of Vienna, Vienna, Austria
In recent years the phenomenon of transepithelial elimination has been found to be the underlying mechanism in a variety of skin disorders. "Perforating dermatoses" may show transepidermal or transfollicular elimination or a combination of the two. A case of papular granuloma annulare is reported, where in one lesion the pilary apparatus actively participated in the elimination of necrobiotic collagen from the dermis. To our knowledge, perforating granuloma annulare with a transfollicular pathway has not previously been described. Also, a classification of perforating dermatoses is presented. (Reeeived for publieation January 27, 1977)
Ever sinee Pinkus (1954) first ealled attention to the biologic phenomenon of transepithelial elimination, this unique epithelial reaction pattern to alterations in the neighboring dermis has caught the interest of various investigators (for a review see Mehregan 1970, 1977; Bardach 1976). In fact, by recognizing this process as the common denominator in a number of heterogeneous skin diseases (Mehregan 1970, 1977), a new classification of "perforating dermatoses" was introduced, all of whieh are characterized by this "cathartic" aetion of the epithelium (Bardach 1976). Granulomatous dermal lesions with transepidermal penetration include granuloma annulare and reactive perforating collagenosis. Recently, infective granulomas have been added to the list (Wood et al. 1976). In the following report a case of papular granuloma annulare is described, where in one lesion the hair follicle actively participated in the elimination of altered connective tissue. Material and Methods
Case Report: In October 1976 a 68-year-old man was seen
who, 2 months previously, had notieed the appearance of asymptomatic red, slightly elevated papules on the neck, upper chest, and shoulders, A eutaneous biopsy revealed the typical pathology of granuloma annulare, with numerous small foci of incomplete collagen degeneration surrounded by palisading granulomas in the dermis. Both parents had suffered from diabetes mellitus and the patient had a normal fasting plasma glucose level, but a slightly abnormal glucose tolerance test indicative of latent diabetes mellitus. On closer inspection, a red, flattened papule 4 mm in diameter was seen over the right breast with the eenter oeeupied by a tiny, pin point-sized horny plug. This lesion was removed by punch biopsy and forms the basis of the subsequent report.
Preparation of the Specimen: The tissue was fixed in 10% formaldehyde and serial sections of the paraffin embedded material were stained with hematoxylin and eosin, periodic acid-Schiff (PAS), Goldner's trichrome and also with an elastic stain (Weigert).
BARDACH
100 Results
The results will be presented three-dimensionally as they were observed on serial sectioning. First, the charaeteristie pathologic picture of granuloma annulare was seen in the dermis. Then, a "channel" of necrobiotie tissue surrounded by keratinizing, partly parakeratotic .squamous epithelium became visible "floating" free in the upper dermis. The material enclosed by the epithelial sheath appeared amorphous and "lumpy". With Goldner's trichrome method it stained green like the small foci of degenerated collagen in the adjacent dermis and was separated from the surrounding epithelium by a deep red line of condensed parakera-
totic keratinocytes. Soon, the epithelium became eonnected with the overlying epidermis by a thin "stalk" of epithelial cells (Fig. 1). Whereas in the beginning the epithelial wall of the channel was only a few layers thick, it now formed irregular projections into the surrounding dermis that, in the area beneath the "channel", showed discrete islands of squamous cells (Fig. 1). The lumen of the channel was much wider now, and contained dark green and red material (Goldner's triehrome). In hematoxylin and eosin stained seetions the material appeared slightly more eosinophilie than the necrobiotic foci of collagen in the neighboring dermis (Fig. 2). The epithelial sheath becarne broadly joined to the epidermis (Fig. 3). In
\
•
' r l ' 4^ ,^ '
*-. .
V Fig. 1. Goldner's trichrome stain: The epithelial sheath joins with the epidermis by a thin "stalk" of cells. In the dermis deep to the channel a few cross-sections of pseudoepitheliomatous extensions are recognizable (X 100).
•- ..
V
Pig. 2. H & E stain: The intradermal channel is now broadly connected with the epidermis. It contains "lumpy" material slightly more eosinophilie than the necrobiotic foci in the surrounding dermis (X I 57).
Fig. 3. Goldner's trichrome stain: The entire pilary apparatus has become visible, its upper third being replaced by lepitheliomatous hyperof the follicular epithelwith the lumen of the cut tangentially in the (X 60).
BARDACH
102
Fig. 4. H & E stain: Part of the follicular opening filled with parakeratotic material is seen in the upper portion of the hyperplastic follicular epithelium (XlOO).
I
' • '
/^(f. 5. H & E stain: The epidermal invagination forming the follicular orifice extends tongue-like projections into the dermis to the lower right, engulfing a large focus of degenerated collagen. The follicular opening is plugged with parakeratotic material The dermis shows foei of necrobiotie collagen surrounded by palisading granulomas (X 60).
PERFORATING GRANULOMA ANNULARE subsequent sections, part of a hair follicle and sebaceous gland lobules were seen deep to the pseudoepitheliomatous proliferation occupying the upper third of the dermis. The pseudoepitheliomatous hyperplasia containing the perforating ehannel eventually beeame continuous with and merged into the pilary apparatus (Fig. 3). The channel was replaced by a deep epidermal invagination, presumably the site of the original foUieular opening (Figs. 4 and 5). Although a hair was present in the lower dermis, this was not apparent in the parakeratotie plug occupying the follicular "infundibulum". The neerobiotic tnaterial had largely disappeared and only remnants of it could be observed in the center of the plug (Figs. 4 and 5). In no section did the eontents of the perforating ehannel stain for elastic tissue or with the PAS technique. Tongue-like epi-
103
thelial projections extended from the epidermal invagination into the adjacent dermis engulfing necrobiotie connective tissue (Fig. 5). Discussion The most plausible interpretation of the histologie findings is that of a giant reactive transepithelial elimination process involving the upper (infundibular) portion of a hair follicle aecompanied by loss of the follicular architecture in that region, As has been pointed out earlier (Bardaeh 1976), the periepithelial and subepidermal zone of fibrovascular mesenchymal tissue closely interaets with the adjoining epithelium (Sweet 1971). Alterations in this subepithelial structure may not only induce neoplastic epithelial transformation, but
Table 1 Transepithelial routes in perforating dermatoses Perforating Dermatoses A) Epidermal lesion (dyskeratosis) as primary event: Kyrle's disease Traumatic hyperkeratosis "en b o u c h o n s " (Tapernoux & Delaeretaz 1971) Perforating foUiculitis B) Dermal lesion as primary event (1) Elastic tissue Elastosis perforans serpigino.sa Pseudoxanthoma elasticum (observed by Lund 1975) Actinic elastosis (Pinkus 1954) Actinic keratoacanthoma (Bardach 1976) (2) Granulomatous tis.sue (a) Non-infectious Granuloma annulare Necrobiosis Iipoidica (Parra 1977) Reactive perforating collagenosis (b) Infectious Blastomycosis (giant cells) Schistosomiasis (Wood et al. 1976) (3) "Foreign" Material Amyloidosis Black Heel Osteoma perforans
Transepithelial Route transepidermal transfollicular
+
+
-t—
-I+
+
+
+ ^-
— —
+
-
+ — +
-(+ —
-I+
— —
+ + +
— — —•
104
BARDACH
also initiate a unique epithelial, two-step, reparative process: First, a pseudoepitheliomatous hyperplastie proliferation engulfs the "foreign" material in the neighboring dermis. Then, a perforating channel is formed, through which the tnaterial is eliminated at the surface. That the follicle actively takes part in elimination processes is not surprising in view of the vast reparative potential inherent in the follicular wall as can easily be observed in acne lesions and other instances of follicular rupture. TransfoUicular perforation has been known to occur secondarily to dermal changes in elastosis perforans serpiginosa, where originally only a transfollicular pathway of elimination was postulated (Lutz 1953, Miescher 1955). In perforating folliculitis the transfollicular elimination of the dermal inflammatory response occurs as a sequel to primary changes within the pilary apparatus. Many cases of perforating granuloma annulare have been reported since the histologic description by Owens & Freeman (1971), although this condition had already been documented in a different context by Pinkus in 1934. The elimination of necrobiotic connective tissue together with the surrounding palisading granuloma seems to have exclusively occurred via the transepidermal route. To the best of our knowledge, this is the first observation of a transfollicular pathway in perforating granuloma annulare. In Table 1 we propose a classification of perforating dermatoses and pathways of transepithelial elimination. It appears that the location of the dermal alteration determines the route chosen by the perforating channel. In granuloma annulare, whenever the necrobiotic foci involve the subepidermal fibro-vascular component, the pathway will run via the epidermis. In the present case, the foci of connective tissue degeneration have obviously come in close juxtaposition with the follicular wall and touched off the strong reparative response inherent in the follicular epithelium. As this foUieular "rescue operation" proceeds, the structure of the upper pilary
apparatus is destroyed. In other words, the original biologic determination of the follicle is sacrificed in favor of the more urgent reparative transepithelial elimination of dermal "foreign" material. References
Bardaeh, H. (1976) Dermatosen mit Transepithelialer Perforation. Archives of Dermatologieat Research 257, 213-226. Lund, H. (1975) In Cutis 17, May 1976, eds. Arnold, H. L. & Rees, R. B. Ameriean Academy of Dermatology, 898. Lutz, W. (1953) Kerato.sis Follieularis Serpiginosa. Dermatologiea (Basel) /06, 318-320. Mehregan, A. H. (1970) Transepithelial Elimination. Current Problems in Dermatology, Vol. 3, pp. 114-147. Karger: Basel, Munieh, Paris, New York. Mehregan, A. H. (1977) Perforating Dermatoses: A Clinieopathologie Review. Internationat Journat of Dermatotogy 16, 19-27. Mieseher, G. (1955) Elastoma Intrapapillare Perforans Verruciforme. Dermatologiea (Basel)
110,254-266. Owens, D. W. & Freeman, R. G. (1971) Perforating Granuloma Annulare. Arehives of Dermatology 103, 65-67. Parra, C. A. (1977) Transepithelial elimination in neerobiosis lipoidiea. British Journat of Dermatotogy 96, 83-86. Pinkus, H. (1934) Uber atypisehe Tuberkulide, zugleieh ein Beitrag zur Atiologie des Granuloma annulare. (pp. 204-205 Tig. 2) Archiv fur Dermatotogie und Syptiitis 1 70, 194-222. Pinkus, H. (1954) Biology of Epidermal Cells. In Physiotogy and Biochemistry of the Skin, ed. Rothman, S., pp. 597-598. University of Chieago Press. Sweet, R. D. (1971) Orientations. Transactions and Annual Report of the St. John's Hospital Dermatological Society 57, 135-138. Tapernoux, B. & Delaeretaz, J. (1971) Hyperkeratose "en bouehons" d'origine meeanique. Dermatologica (Basel) 143, 201-208. Wood, M. G., Srolovitz, H. & Sehetman, D. (1976) Sehistosomiasis. Arehives of Dermatology 112 690-695. Address: H. G. Bardaeh Department of Dermatology (II) University of Vienna Alser Strasse 4 A-1090 Vienna Austria
