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Sebaceous glands within the thymus: Report of three cases
Sebaceous Glands Within the Thymus: Report of Three Cases MARIANNE WOLFF, MD,* JUAN ROSAI, MD/ AND DENNIS H. WRIGHT, MD~ Sebaceous glands in the thymus were discovered in three pat i e n t s ~ t w o with myasthenia gravis and the other, who was operated on because of aortic valvular disease---with an unsuspected thymoma. Sebaceous glands not associated with hair follicles occur in diverse sites, the majority of which are in the head and neck or anogenital regions. Although most of these sites arise from the ectoderm, sebaceous glands have been reported in a thyroglossal duct, the larynx, and the esophagus, which are entodermal structures. Thus, precedents for ectodermally derived sebaceous glands in endodermal sites exist, but sebaceous glands have not previously been reported in th~ thymus. The authors speculate that their occurrence in the thymus may be related to the reported ectodermal contribution to the developing thymus by the epibranchlal placode or cervical sinus. HUM PATHOL
15:341--343, 1984.
W e r e c e n t l y o b s e r v e d microscopic s e b a c e o u s gland lobules associated with thymic epithelium in three patients. We have been unable to discover any previously published allusions to this p h e n o m e n o n .
dant non-involuted thymic tissue with a very prominent epithelial element. In some places mucous and serous glands were seen. Tubular structures were focally formed by the thymic epithelium, and well-developed Iobules of sebaceous glands were present in the vicinity (figs. 2 and 3). No hair follicles were observed, nor were any other tissue types recognized. Tile mass was diagnosed as a benign thymoma associated with a hamartomatous process. Case 3. A 62-year-old woman with myasthenia gravis, who had previously been treated with prednisone and plasmapheresis, underwent trans-sternai extended thymectomy with anterior mediastinai exenteration. The thymus was less involuted titan would be expected for a patient of this age. It contained a 3.1 • 2.6-cm benign thymoma composed of the usual mixture of epithelial cells and lymphocytes. In a section of soft tissue from the left upper mediastinum, which was separate from the most superior extension of the upper pole of the left thymic lobe, there were several separate lobules of sebaceous glands without other epithelial elements (fig. 4). DISCUSSION
REPORT OF THREE CASES Case 1.
A 29-year-old man with myasthenia gravis underwent transcervical, trans-sternai extended thymectomy with anterior mediastinal exenteration. I He had been treated previously with plasmapheresis on three occasions, bt, t recurrence of the myasthenia necessitated thymectomy. A small fatty nodule, separate from the upper pole of tile left main thymic lobe, was removed by the surgeon in the belief that it also represented thymic tissue. It contained a parathyroid gland and an adjacent Iobule of thymic tissue. The latter revealed clusters of sebaceous cells intimately associated with thymic epithelium (fig. 1). Serial sections failed to show hair structures or other types of tissue that might justify the diagnosis of teratoma. Case 2. A 56-year-old man underwent thoracotomy for replacement of a diseased aortic valve. The patient did not have any known neuromuscular, endocrine, collagen vascular, or immunologic disorder. The thymus was slightly enlarged, and a portion was removed and sent for examtnation. The mass of thymus was 2.0 X 1.5 cm and lacked any discrete nodule. Microscopic examination showed abun-
Received March 14, 1983. Accepted for publication April 26, 1983. * Laboratory of Surgical Pathology, Columbia University College of Physicians and Surgeons, New York, New York. 1- Department of Laboratory Medicine and Patlmlogy, University of Minnesota, Minneapolis. University of Southampton, Southampton, United Kingdom. Address correspondence and reprint requests to Dr. Wolff: Department of Pathology, Morristown Memorial Hospital, Morristown, NJ 07960.
341
T h e finding o f sebaceous glands in the t h y m u s is unexpected, since sebaceous glands are ectodermaily derived and the t h y m u s is an e n t o d e r m a l organ. Tile thymus originates from tile third pharyngeal pouch on each side; in some embryos there is also a contribution from the fourth pouch, near the developing p a r a t h y r o i d gland. In some mammals there is an ectodermal contribution to the thymus o f presumed placodal origin, but this has not been confirmed in man. 2 (The epibranchial placodes are thickened particles of e c t o d e r m in the region of tile dorsal end of the fourth groove; these are closely related to developing ganglia.) O t h e r investigators believe that in pigs and o t h e r mammals the cervical sinus (third groove) contributes ectoderm to tile developing thymus~; Norris 4 d e m o n s t r a t e d the same in humans. S e b a c e o u s g l a n d s a r e seen d u r i n g tile f i f t h m o n t h of gestation as solid buds arising from the cuboidal cells of hair follicles; these buds later acquire mesenchyme and branch into an alveolar pattern. In certain sites, including skin o f the palms a n d soles, nares, tarsal glands o f the eyelids, and the perianal region, sebaceous glands develop i n d e p e n d e n t l y o f hair follicles. 5 According to Guiducci and H y m a n , 6 these hair-follicle-independent sebaceous glands (referred by them as "ectopic") constitute approximately 10 per cent o f all sebaceous glands in tile body and develop two to four m o n t h s after birth. Extracutaneous (ectopic) sebaceous glands are
HUMAN PATHOLOGY
Volume 15, No. 4 (April 1984)
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FIGURE I (top left). Case 1. Thymic Iobule. Sebaceous glands can be seen In the right lower portion. [Hematoxylin-phloxin-safran stain. X 150.) FIGURE 2 (bottom left). Case 2. Thymic tissue containing duct-like structures (arrows) and sebaceous glands. (Hematoxylinphloxin-safran stain, x230.) FIGURE :3 (top right). Case 2. Higher magnification of sebaceous glands. (Hematoxylin-phloxln-safran stain, x450.)
ception is the case reported by Leider et al.,7 in which a complex racemose system of glands branched out from a major duct-like structure in the tongue. This was interpreted by tile authors as representing a thyroglossal duct associated with sebaceous glands. T h e thyroglossal duct is an entodermal derivative. Other structures of endodermai origin in which sebaceous glands have been found are the larynx 8 and the esophagus. 9'1~ T h e explanation preferred by Zak et al. i0 for the presence of sebaceous glands in these two locations is pluripotentiality of the epithelium rather than misplacement or heterotopia during development. In our cases 1 and 2, the sebaceous glands in the thymus were associated with epithelial-lined tubules, and case 2 contained other salivary gland-like elements, which made the appearance of that lesion reminiscent o f a l y m p h a d e n o m a o f the salivary glands. In case 3, tile focus of sebaceous glands was not associated with other epithelial elements; it was so minute that it was no longer present in the recuts.
found in diverse sites, of which Fordyce's g r a n u l e s - in the lips and buccal m u c o s a - - a r e so common that they are considered variations from the norm. 5 T h e y are not present in fetuses or neonates and are rarely seen in children under 3 years of age. In clfildren older than this their incidence increases until puberty. T h e sex distribution is approximately equal. It has been proposed that Fordyce's granules contribute lipase. 5 Other sites in which ectopic sebaceous glands may be found are listed in table 1. T h e occurrence of sebaceous glands in the parotid gland is generally attributed to the embryologic origin of the gland near tile angle of the mouth, from which it migrates posteriorly. S e b a c e o u s glands found in the parotid are often associated with sebaceous glands in the buccal mucosa. Another explanation is that intercalated ducts, with which the sebaceous glands are usually associated, may possess pluripotential epithelium. 5 In ectopic locations sebaceous glands are sometimes racemose, but they occur more frequently as single lobules. A notable ex342
SEBACEOUSGLANDS WITHIN THE THYMUS: REPORTOF THREECASES (Wolff et al.)
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I FIGURE 4. Case 3. Low-power view of atrophic thymus. (Hematoxylin-phloxinsafran stain, x30.) Inset, higher power view of perfectly farmed sebaceous Iobules withln the thymus. (Hematoxylinphloxin-safran stain, x250.)
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patients, two with myasthenia gravis and one with aortic valvular disease, but simply report this unusual finding and speculate on its possible pathogenesis. T h e known or suspected contribution to the thymus by the ectodermal placode or the cervical sinus constitutes the most likely explanation for our observed findings. All three of our cases were found within a year; we suspect that additional cases will be observed now that this occurrence has been recorded.
Sites of Ectopic* Sebaceous Glands
Oral cavity Lips Buccal mucosa Tongue Salivary glands Normal parotid gland, submandibular II,l~ and sublingual glands ~3 Tumors Benign mixed tumor Oncocytoma ~ Muco-epidermoid carcinoma 6 Sebaceous lymphadenoma Orbital structures Orbit Meibomian glands Lacrimal caruncle Other locations in tire head and neck Larynx ~ Esophagus 9a~ Thyroglossal duct 7 Wall of dentigerous cystss Nares *.s Female genitalia Clitoris Hymen Cervix Nipple Labia Minora Male genitalia Penis: shaft, prepuce and glans Nipple Perlanal region ~'5 Skin of palms and soles * Not associated with hair-bearing skin9
343
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In all our cases the sebaceous glands were relatively simple and u~ailobular but were well formed into an outer germinative zone and an inner mass of finely vacuolated cells. We do not attach any functional or prognostic significance lto our finding o f ectopic sebaceous glands in the thymus of one female and two male
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REFERENCES 1. jaretzki A, Bethea M, Wolff M, et al: A rational approach to total thymectomy in the treatment of myasthenia gravis. Ann Thorac Surg 24:120, 1977 2. Williams PL, Warwick R (eds): Gray's Anatomy, 36th British edition. Philadelphia, WB Saunders Co, 1980, p 198 3. ttamilton wJ, Boyd JD, Mossman HW: Human Embryology. Bahimore, Williams & Wilkins, 1947, p 165 4. Norris EH: Tile morphogenesis and histogenesis of the thymus gland in man: in which tile origin of the Hassall's corpuscles of the human thymus is discovered. Contrib Embryol Carnegie Inst 27:193, 1938 5. Gorlln RJ, Goldman HM (eds): Thoma's Oral Pathology, sixth edition. St Louis, CV Mosby, 1970 6. Guiducci AA, ttyman AB: Ectopic sebaceous glands: a review of the literature regarding their occurrence, histology and embryonic relationship. Dermatologia 125:44, 1962 7. Leider AS, Lucas j W , Eversole LR: Sebaceous cboristoma of the thyroglossal duct. Oral Surg Oral Med Oral Pathol 44:261, 1977 8. Geipel P: Talgdrfise im Kehlkopf. Zentralbl AIIg Pathol 85:69, 1949 9. De la Pava S, Pickren JW: Ectopic sebaceous glands in tire esophagus. Arch Pathol 73:397, 1962 10. Zak FG, Lawson W: Sebaceous glands in the esoptmgus: first case observed grossly9 Arch Dernmtol 112:1153, 1976 11. Micheau C: Le glandes dites sebac~e de la parotide et de la sousmaxillaire. Ann Anat Pathol 14:119, 1969 12. Thackray AC, Lucas RP: Tumors of the Major Salivary Glands. Atlas of T u m o r Pathology, second series, Fascicle 10. Washington, DC, Armed Forces Institute of Pathology, 1974 13. Linhartova A: Sebaceous glands in salivary gland tissue. Arch Pathol 8:320, 1974
15:341--343, 1984.
W e r e c e n t l y o b s e r v e d microscopic s e b a c e o u s gland lobules associated with thymic epithelium in three patients. We have been unable to discover any previously published allusions to this p h e n o m e n o n .
dant non-involuted thymic tissue with a very prominent epithelial element. In some places mucous and serous glands were seen. Tubular structures were focally formed by the thymic epithelium, and well-developed Iobules of sebaceous glands were present in the vicinity (figs. 2 and 3). No hair follicles were observed, nor were any other tissue types recognized. Tile mass was diagnosed as a benign thymoma associated with a hamartomatous process. Case 3. A 62-year-old woman with myasthenia gravis, who had previously been treated with prednisone and plasmapheresis, underwent trans-sternai extended thymectomy with anterior mediastinai exenteration. The thymus was less involuted titan would be expected for a patient of this age. It contained a 3.1 • 2.6-cm benign thymoma composed of the usual mixture of epithelial cells and lymphocytes. In a section of soft tissue from the left upper mediastinum, which was separate from the most superior extension of the upper pole of the left thymic lobe, there were several separate lobules of sebaceous glands without other epithelial elements (fig. 4). DISCUSSION
REPORT OF THREE CASES Case 1.
A 29-year-old man with myasthenia gravis underwent transcervical, trans-sternai extended thymectomy with anterior mediastinal exenteration. I He had been treated previously with plasmapheresis on three occasions, bt, t recurrence of the myasthenia necessitated thymectomy. A small fatty nodule, separate from the upper pole of tile left main thymic lobe, was removed by the surgeon in the belief that it also represented thymic tissue. It contained a parathyroid gland and an adjacent Iobule of thymic tissue. The latter revealed clusters of sebaceous cells intimately associated with thymic epithelium (fig. 1). Serial sections failed to show hair structures or other types of tissue that might justify the diagnosis of teratoma. Case 2. A 56-year-old man underwent thoracotomy for replacement of a diseased aortic valve. The patient did not have any known neuromuscular, endocrine, collagen vascular, or immunologic disorder. The thymus was slightly enlarged, and a portion was removed and sent for examtnation. The mass of thymus was 2.0 X 1.5 cm and lacked any discrete nodule. Microscopic examination showed abun-
Received March 14, 1983. Accepted for publication April 26, 1983. * Laboratory of Surgical Pathology, Columbia University College of Physicians and Surgeons, New York, New York. 1- Department of Laboratory Medicine and Patlmlogy, University of Minnesota, Minneapolis. University of Southampton, Southampton, United Kingdom. Address correspondence and reprint requests to Dr. Wolff: Department of Pathology, Morristown Memorial Hospital, Morristown, NJ 07960.
341
T h e finding o f sebaceous glands in the t h y m u s is unexpected, since sebaceous glands are ectodermaily derived and the t h y m u s is an e n t o d e r m a l organ. Tile thymus originates from tile third pharyngeal pouch on each side; in some embryos there is also a contribution from the fourth pouch, near the developing p a r a t h y r o i d gland. In some mammals there is an ectodermal contribution to the thymus o f presumed placodal origin, but this has not been confirmed in man. 2 (The epibranchial placodes are thickened particles of e c t o d e r m in the region of tile dorsal end of the fourth groove; these are closely related to developing ganglia.) O t h e r investigators believe that in pigs and o t h e r mammals the cervical sinus (third groove) contributes ectoderm to tile developing thymus~; Norris 4 d e m o n s t r a t e d the same in humans. S e b a c e o u s g l a n d s a r e seen d u r i n g tile f i f t h m o n t h of gestation as solid buds arising from the cuboidal cells of hair follicles; these buds later acquire mesenchyme and branch into an alveolar pattern. In certain sites, including skin o f the palms a n d soles, nares, tarsal glands o f the eyelids, and the perianal region, sebaceous glands develop i n d e p e n d e n t l y o f hair follicles. 5 According to Guiducci and H y m a n , 6 these hair-follicle-independent sebaceous glands (referred by them as "ectopic") constitute approximately 10 per cent o f all sebaceous glands in tile body and develop two to four m o n t h s after birth. Extracutaneous (ectopic) sebaceous glands are
HUMAN PATHOLOGY
Volume 15, No. 4 (April 1984)
t
.j~
I-
9 JL_
"
.
:
"
FIGURE I (top left). Case 1. Thymic Iobule. Sebaceous glands can be seen In the right lower portion. [Hematoxylin-phloxin-safran stain. X 150.) FIGURE 2 (bottom left). Case 2. Thymic tissue containing duct-like structures (arrows) and sebaceous glands. (Hematoxylinphloxin-safran stain, x230.) FIGURE :3 (top right). Case 2. Higher magnification of sebaceous glands. (Hematoxylin-phloxln-safran stain, x450.)
ception is the case reported by Leider et al.,7 in which a complex racemose system of glands branched out from a major duct-like structure in the tongue. This was interpreted by tile authors as representing a thyroglossal duct associated with sebaceous glands. T h e thyroglossal duct is an entodermal derivative. Other structures of endodermai origin in which sebaceous glands have been found are the larynx 8 and the esophagus. 9'1~ T h e explanation preferred by Zak et al. i0 for the presence of sebaceous glands in these two locations is pluripotentiality of the epithelium rather than misplacement or heterotopia during development. In our cases 1 and 2, the sebaceous glands in the thymus were associated with epithelial-lined tubules, and case 2 contained other salivary gland-like elements, which made the appearance of that lesion reminiscent o f a l y m p h a d e n o m a o f the salivary glands. In case 3, tile focus of sebaceous glands was not associated with other epithelial elements; it was so minute that it was no longer present in the recuts.
found in diverse sites, of which Fordyce's g r a n u l e s - in the lips and buccal m u c o s a - - a r e so common that they are considered variations from the norm. 5 T h e y are not present in fetuses or neonates and are rarely seen in children under 3 years of age. In clfildren older than this their incidence increases until puberty. T h e sex distribution is approximately equal. It has been proposed that Fordyce's granules contribute lipase. 5 Other sites in which ectopic sebaceous glands may be found are listed in table 1. T h e occurrence of sebaceous glands in the parotid gland is generally attributed to the embryologic origin of the gland near tile angle of the mouth, from which it migrates posteriorly. S e b a c e o u s glands found in the parotid are often associated with sebaceous glands in the buccal mucosa. Another explanation is that intercalated ducts, with which the sebaceous glands are usually associated, may possess pluripotential epithelium. 5 In ectopic locations sebaceous glands are sometimes racemose, but they occur more frequently as single lobules. A notable ex342
SEBACEOUSGLANDS WITHIN THE THYMUS: REPORTOF THREECASES (Wolff et al.)
i. . . .
:
,.
"
' "
"
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~
I FIGURE 4. Case 3. Low-power view of atrophic thymus. (Hematoxylin-phloxinsafran stain, x30.) Inset, higher power view of perfectly farmed sebaceous Iobules withln the thymus. (Hematoxylinphloxin-safran stain, x250.)
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patients, two with myasthenia gravis and one with aortic valvular disease, but simply report this unusual finding and speculate on its possible pathogenesis. T h e known or suspected contribution to the thymus by the ectodermal placode or the cervical sinus constitutes the most likely explanation for our observed findings. All three of our cases were found within a year; we suspect that additional cases will be observed now that this occurrence has been recorded.
Sites of Ectopic* Sebaceous Glands
Oral cavity Lips Buccal mucosa Tongue Salivary glands Normal parotid gland, submandibular II,l~ and sublingual glands ~3 Tumors Benign mixed tumor Oncocytoma ~ Muco-epidermoid carcinoma 6 Sebaceous lymphadenoma Orbital structures Orbit Meibomian glands Lacrimal caruncle Other locations in tire head and neck Larynx ~ Esophagus 9a~ Thyroglossal duct 7 Wall of dentigerous cystss Nares *.s Female genitalia Clitoris Hymen Cervix Nipple Labia Minora Male genitalia Penis: shaft, prepuce and glans Nipple Perlanal region ~'5 Skin of palms and soles * Not associated with hair-bearing skin9
343
I
L
t
In all our cases the sebaceous glands were relatively simple and u~ailobular but were well formed into an outer germinative zone and an inner mass of finely vacuolated cells. We do not attach any functional or prognostic significance lto our finding o f ectopic sebaceous glands in the thymus of one female and two male
)
<
REFERENCES 1. jaretzki A, Bethea M, Wolff M, et al: A rational approach to total thymectomy in the treatment of myasthenia gravis. Ann Thorac Surg 24:120, 1977 2. Williams PL, Warwick R (eds): Gray's Anatomy, 36th British edition. Philadelphia, WB Saunders Co, 1980, p 198 3. ttamilton wJ, Boyd JD, Mossman HW: Human Embryology. Bahimore, Williams & Wilkins, 1947, p 165 4. Norris EH: Tile morphogenesis and histogenesis of the thymus gland in man: in which tile origin of the Hassall's corpuscles of the human thymus is discovered. Contrib Embryol Carnegie Inst 27:193, 1938 5. Gorlln RJ, Goldman HM (eds): Thoma's Oral Pathology, sixth edition. St Louis, CV Mosby, 1970 6. Guiducci AA, ttyman AB: Ectopic sebaceous glands: a review of the literature regarding their occurrence, histology and embryonic relationship. Dermatologia 125:44, 1962 7. Leider AS, Lucas j W , Eversole LR: Sebaceous cboristoma of the thyroglossal duct. Oral Surg Oral Med Oral Pathol 44:261, 1977 8. Geipel P: Talgdrfise im Kehlkopf. Zentralbl AIIg Pathol 85:69, 1949 9. De la Pava S, Pickren JW: Ectopic sebaceous glands in tire esophagus. Arch Pathol 73:397, 1962 10. Zak FG, Lawson W: Sebaceous glands in the esoptmgus: first case observed grossly9 Arch Dernmtol 112:1153, 1976 11. Micheau C: Le glandes dites sebac~e de la parotide et de la sousmaxillaire. Ann Anat Pathol 14:119, 1969 12. Thackray AC, Lucas RP: Tumors of the Major Salivary Glands. Atlas of T u m o r Pathology, second series, Fascicle 10. Washington, DC, Armed Forces Institute of Pathology, 1974 13. Linhartova A: Sebaceous glands in salivary gland tissue. Arch Pathol 8:320, 1974