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The aberrant cervical thymus
The Aberrant Cervical Thymus Embryology, Pathology, and Clinical Implications
Ferit Tovi, MD, Beer-Sheva, Israel Abraham J. Mares, MD, Beer-Sheva, Israel
The thymus is the central organ of the lymphoid system in infancy. It originates high in the neck in early fetal life and reaches its definitive location in the mediastinum after a process of descent, generally leaving no trace behind. Occasionally, during this descent, remnants of thymic tissue can be implanted along the cervical pathway, later appearing as a cervical mass representing the so-called ectopic or aberrant cervical thymus. On the other hand, hyperplasia of the thymus secondary to infection, or rarely displacement of the incompletely descended thymus toward the neck (due to increased intrathoracic pressure), may also give the appearance of a mass in the lower neck region. These two conditions, congenital and acquired, take part in the pathogenesis of the persistent cervical thymus. Fewer than seventy clinical cases of cervical thymus have been reported in the English literature, mostly isolated case reports. Thirty cases were ectopic solid thymic masses, whereas thirty-eight were of cystic nature. We have lately encountered six such cases and believe the lesion to be far more common than previously suggested. Our cumulated experience in the diagnosis and treatment of this entity is reported herein. Basic knowledge of the embryologic de\relopment of the cervical region is absolutely essential in understanding the pathogenesis of this entity and in evaluating the young patient with a cervical mass and its associated symptoms. Case Reports Case I. A three year old male infant was admitted because of a soft tissue mass in the upper anterior triangle of the right neck. According to t,he mother, the lump had been
Frorr the Departments of Ear, Nose, and Throat and Pediatric Surgery, Soroka Medical Center, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer-Sheva, Israel. Reprint requests should be addressed to Abraham J. Mares, MD. Department of Pediatric Surgery, Soroka Medical Center, Ben Gurion University, Faculty of Health Sciences, PO Box 151, Beer-Sheva. Israel
Volume 136, November 1976
present on and off since birth. However, the diagnosis was somewhat elusive. On one outpatient clinic examination, deep palpation of the neck suggested a lymph node consistency, whereas on another occasion the possibility of a branchial cleft cyst or cystic hygroma had been raised. The rest of the physical examination and routine laboratory tests were within normal limits. At surgery, a solid mass, 4 by 3 by 2 cm, was excised deep to the sternocleidomastoid muscle and anterior to it, in the vicinity of the carotid bifurcation along the deep jugular lymph nodes. It was surrounded by hyperplastic lymph nodes. Recovery was uneventful. Histologic diagnosis confirmed the presence of ectopic thymus presenting scattered cystic degeneration of Hassall’s bodies. Case II. A ten year old female was admitted because of dyspnea of one day’s duration without associated fever. The child was also quadriplegic due to trauma to the neck one year prior to the present admission. On chest x-ray films, an enlargement of the upper mediastinum was noted, extending towards the right side of the neck. Exploration of the base of the neck revealed a soft tissue mass in continuity with the mediastinal mass. It proved to be thymic tissue. Her postoperative course was complicated by atelectasis and pneumonia which responded well to chest physiotherapy and antibiotic administration. Histologic examination of the partially resected mass revealed necrosis and acute inflammation of Hassall’s bodies, areas of demarcation between the medulla and cortex of the thymic gland, and scattered germinal centers in the medulla of the thymic glands. Case III. A twenty-six year old man was hospitalized for surgery upon diagnosis of a cold nodule in the left lobe of the thyroid. Surgical exploration revealed a thyroid nodule as well as a 1 by 1 by 0.5 cm mass in the lower jugular vein. Hemithyroidectomy and excision of the mass were performed. Histopathologic analysis revealed a benign colloid nodular goiter, while the mass near the thyroid lohe was thymic tissue. Recovery was uneventful. Case IV. A four month old male infant was admitted with a lump appearing in the central portion 01’ the lower neck, evident mostly when crying. Episodes of dysphagia
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limits. The neck exploration revealed an 18 by 5 by 5 cm cystic mass that extended from the mediastinum to the basis cranii along the jugular vein and was in continuity with the mediastinal thymic structure. The mass was excised. Pathologic examination showed it to be multilocular, cystic, and containing brown gelatinous fluid. (Figure 2.) Microscopically, the walls of the cysts were fibrous, intermittently lined with simple squamous, cuboid, and in some areas pseudostratified cuboid epithelium. Some areas were devoid of epithelium altogether. (Figure 3A.) In addition, rich lymphoid infiltration, scattered Hassall’s bodies, and fibrosis were present in the subepithelial layer. (Figure 3B.) Some areas included cholesterol granulomas and secondary cystic formations. In one area cords of parathyroid cells and thyroid tissue were found in the cystic wall. (Figure 4.) Her postoperative course was unremarkable. Embryology, Pathogenesis, and Anatomic Presentation For better orientation and understanding of the pathogenesis and clinical significance of the thymic tissue in the neck, the embryologic development and anatomic borderlines of this structure should be considered. Embryology of the Normal Thymus
Figure 1. Case IV. lntraoperative findings of mass adherent to the incompletely descended thymus.
and dyspnea preceded his admission for one month. A superficial hemangioma of the overlying skin was observed. Chest x-ray films revealed a large mass at the thoracic inlet, thought to be a deep component of the hemangioma. However, on exploration, a solid mass adherent to the incompletely descended thymus was found on the right side of the lower neck. (Figure 1.) There was compression of the trachea by the mass. Immediately after resection the dyspnea and dysphagia disappeared. The histologic findings were consistent with aberrant thymic tissue. Case V. A nine month old female infant was hospitalized because of a lump that appeared on the right lower side of the neck while crying. The general physical examination, routine laboratory data, and chest x-ray results revealed no abnormalities. Neck exploration revealed a 3 by 1.5 by 1 cm mass adherent to the right thymic lingula. This mass was excised, and histopathologic analysis showed aberrant thymic tissue. The postoperative course was uneventful.
Case VI. An eleven year old girl was admitted because of a large lump in the right neck which appeared only the day before admission, On physical examination a large lump was found on the right side of the neck sensitive to palpation. Chest x-ray films showed enlargement of the mediastinum. Routine laboratory tests were within normal
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The third and fourth pharyngeal pouches in the embryo are characterized at their distal extremity by so-called dorsal and ventral wings. The thymus develops mainly from the ventral wing (sacculation) of the third pharyngeal pouch on each side. (Figure 5.) The dorsal wings of the same pouch give rise to the inferior parathyroid glands. The thymic primordia that develop from the fourth pharyngeal pouch, even at the time of its formation, are likely to be quite small and rudimentary. They may give rise only to vestigial tissue masses. The superior parathyroid glands develop from the dorsal wings (sacculations) of the same pouches. The primordial thymus appears in the beginning of the sixth week of fetal life. By the end of this week the connections of the primordia with the pharyngeal pouches are severed. Each primordium ‘elongates caudally and medially as a tubular structure (thymopharyngeal tract) which soon begins a process of obliteration by epithelial proliferation. By the eighth week, the bilateral thymic primordia fuse in the midline and start to slide down under the sternum in the superior mediastinum, where they lie in contact with the parietal pericardium. The fusion of the right and left thymic primordia is never really complete, so that the organ never loses entirely its paired character (this makes surgical extirpation of one lobe easier, if deemed necessary). At the end of the descent, the upper end of the thymus becomes drawn
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Figure 2. Case VI. Transection of the fresh operative specimen. Multilocular cystic thymus on righi side of the neck.
in and generally vanishes. The final location of the thymus is usually entirely in the anterior mediastinum, between the sternum, parietal pericardium, and thoracic inlet. .4t birth the thymus is large relative to total body weight (average weight, 13 gm). That is why in the early years of life a distinctive radiographic shadow of the thymus normally appears in the upper anterior mediastinum. Its absolute weight increases in the two years after birth and at approximately eleven years reaches a maximum weight of 30 to 40 gm. After this age its weight begins to decrease to an adult weight of approximately 15 gm or less. Pathogenesis of the Cervical Thymus
Until 1962, only thirty-two cases of cervical thymic masses had been described [I]. Most of them were diagnosed at necropsy; only eleven clinical cases were reported. Wenglowsky, cited by Bieger and McAdams [Z], using serial sections of the neck, demonstrated thymic rests in two of ten adults and twenty-one of sixty-five children at autopsy. Small cervical thymic cysts were verified during routine postmortem examinations [2,3]. Barrick and O’Kell [4], in their review of the literature, described thirty cases of cervical thymus, the majority of which were cysts found mostly in children. Considering that the thymus reaches its greatest absolute size at puberty and its greatest relative size between the second and fourth years of life, they found it unsurprising that the diagnosis was made mostly in children. The recognition of this entity has increased lately, as evidenced by a relative abundance of isolated case reports [1-191. Thymic tissue becomes implanted in the neck by a process of sequestration from the main gland during its normal fetal descent. In this case the tissues form a solitary mass which in essence is a true ectopic
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(aberrant) thymus in the neck (cases I and III are examples of this anomaly). Other possibilities occur, however, in the pathogenesis of cervical thymic tissue. Sometimes after descent, the upper ends of the gland, instead of involuting, form separate accessory lobes or persistent cords (cases II and V). Rarely, the thymus fails to descend [20] or descends incompletely. Naturally, it then remains wholly or partially in the cervical region (cases IV and VI). Failure of the complete descent of the thymus may locate the structure at the thoracic inlet [15]. Increased intrathoracic pressure, such as an infant’s crying, may force the gland upwards into the neck, presenting the appearance of a lower cervical mass. This was actually the presenting symptom in cases IV and V. It is usually prominent in infancy due to the small size and proportions of the infant’s chest and thoracic inlet. Other similar examples have been cited [15,21,22]. Another presentation of cervical thymus is hyperplasia of the normally situated thymus gland (case II). Hyperplasia of the thymus gland may occur secondary to infections or vaccinations. It is not merely a matter of volume. The histologic findings demonstrate increased cellularity of the cortex and medulla of the thymus, delineating a clear demarcation between these two zones 1201. The presence of germinal centers or lymphoid folliculi in the medulla is one of the most reliable criteria of this entity [23,24]. Mitchelson and Sender [25] reported a case in which hyperplasia of the cervical thymus appeared during an upper respiratory tract infect,ion and involuted immediately after antibiotic therapy, somewhat similar to the situation in case II. The pathogenesis of cyst formation within the thymus tissue is still a matter of controversy. Speer [26] in 1938 suggested that cysts may originate from: (1) embryologic remnants in the neck; (2) seques-
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Figure 3. Case VI. A, wall of the thymic cyst lined with simple squamous and pseudostratified cuboid epithelium. A large cholesterol granuloma is seen on the left side. (Magnification X 32; reduced 12 per cent). 6, normal and calcified Hassall’s bodies surrounded by lymphoid infiitrafion. (Magnification X 125; reduced 33 per cent).
tration products in pathologic involution of the thymus; (3) neoplastic processes; (4) degeneration of Hassall’s bodies; or (5) mesenchymal elements. Ellis [3] in 1967 suggested that most cysts of the thymus arise as a result of cystic degeneration of Hassall’s bodies, but he pointed out that the cause is obscure. He based his argument on the concept that progres-
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sive cystic change in Hassall’s bodies and the epithelial reticulum is an acquired and not a developmental defect. On the other hand, he accepted the fact that occasionally congenital cervical thymic remnants can undergo cystic changes. About the same time, Bieger and McAdams [2] concluded that these cysts arise from persistent thymopharyngeal ducts. Fahmy [19] in 1974 suggested that the thymic cysts arising from the vestigial remnants of the thymopharyngeal ducts should be considered a variant of branchial cleft cysts, affecting generally the youngest age group. The similarity of the epithelial lining of the branchial cyst to that of the thymic cyst [27], the presence of subepithelial lymphatic infiltration in both types of cyst, and their similar localization support the concept that they are both derived from the same vestigial structure. It may be of interest to mention at this point that in case VI we found histologic evidence of both thyroid and parathyroid tissue within the wall of the large thymic cystic mass. (Figure 5.) Gilmour [28,29] and Behring and Bergman [ll] also described the occurrence of parathyroid tissue in thymic remnants. The parathyroid glands and the anlage of the thymus are adjacent structures in the third pharyngeal pouch. The anlage of the thymus may produce parathyroid tissue under certain circumstances according to the multipotentiality of certain cells in a given region at a certain early stage of embryologic formation. Willis [30], along Van Dyke’s theory of the formation of accessory thyroid tissue in the thymus, suggested the possibility of metaplastic interconversion of the thymus and thyroid because of their similar developmental origins. This theory may explain the thyroid tissue in the wall of cystic cervical thymus. However, we think that it is more likely that due to their proximity, clusters of thyroid cells were “imprisoned” in the thymopharyngeal remnant. Hence, in the process of cystic degeneration and formation of cystic cervical thymus, we find them as well. The size and extent of the cystic mass in case VI make it likely that the mass originated from a congenital branchial remnant, as suggested by Fahmy ]191. Clinical Presentation and Implications of Cervical Thymus
Generally, most of these ectopic and aberrantly located thymic masses remain dormant. They may be found incidentally during thyroid surgery (as in case III) or after surgery on histologic examination of the resected specimen and during explorations of the neck for other causes, such as parathyroid ade-
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Figure 48. Case VI. Subepithelial layer showing parathyroid cords. ( Magnification X 725).
Figure 4A. Case VI. 7’hyroidand parathyroid tissue in thymic cyst wall. (Magnification X 60).
nomas [31]. However, occasionally, the symptomless cervical tissue tends to grow during childhood just like the main thymus gland. Thus, any time during ch:ldhood and prepubertal age it may reach proportions that will make it easily recognizable by mere inspection, palpation, or both. X-ray films may also be of help in identifying the mass or suggesting the diagnosis. The cervical thymus is mostly localized along a line extending from the angle of the mandible to the manubrium sterni [18] or around the thyroid gland [32]. Some authors suggest predominance of the left side [I]. This was not corroborated in our patients, in whom most of the masses were on the right side. Extraordinary cases with intratracheal or hypopharyngeal locations were cited by Lewis [I] in his review of the literature. Thymic cysts can occur both in the neck and in the mediastinum [33]. Diagnosis of these anomalies in the neck are obviously predominant due to the relative ease in examining the cervical region [4]. Sometimes the cervical cysts may extend into the mediastinum. Although it is claimed [34] that the thymic gland,
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no matter how large, does not compress or displace normal structures, cases of ectopic thymus causing compression, displacement, or deviation of neighboring structures have been described [ 15,21,25,35]. Some of these phenomena were quite obvious in case IV as well. Location of the gland in the thoracic inlet has the potential to compress the trachea [35], and it may also compress the esophagus. This may give rise to the appropriate symptoms, namely dyspnea, stridor, and dysphagia. The diagnosis of cervical thymus has never been made preoperatively and always came somewhat as a surprise, either during the operative procedure or after sectioning the surgical specimen and the histopathologic examination. This is due to the fact that cervical thymus is far from being a well known entity; therefore, it is not readily considered in the differential diagnosis of neck cysts and masses, particularly in infants and children. Since the neck is a common site for the occurrence of congenital anomalies, one has to consider and differentiate the thymic cysts and other ectopic or aberrant thymic tissue from more familiar anomalies, such as thyroglossal or branchial cleft, dermoid and hygroma coli cysts, as well as thyroid [9,14], parathyroid, and other cervical lymph node lesions. Solid and cystic thymic lesions may mimic benign tumors, such as hemangiomas and lymphangiomas, as well as malignant neoplasms, such as lymphoproliferative disease and other metastatic neoplasms in cervical lymph nodes. During workup of a patient with a neck mass (suspected of being of thymic origin), the familiar routine should be followed: (1) thorough physical examination with particular emphasis on the anterior triangles of the neck and oropharyngeal regions; (2) complete blood analysis; (3) x-ray films of the chest
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PHARVNGEAL
POUCHES
i-
i
Jthymlc
I
-\L---thVmlc
primordia
prlmordia
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5
Figure 5. Embryologic development of the branch/al system.
and soft tissues of the neck (both in the posteroanterior and lateral projections); (4) thyroid scanning to rule out possible thyroid involvement (unfortunately, to date we do not have a good isotope scan available for the thymus); and (5) esophagography if deemed necessary. Hurley [7] recently advised direct contrast radiographic demonstration of cystic lesions. We do not believe that this should be a routine approach to this problem. The primary therapeutic approach to cervical thymus should be identical to the approach to any other neck mass, namely surgical. Frozen section analysis during surgery will sometimes facilitate the decision as to how much of the thymus to remove. At times it may save total thymic excision, particularly in those patients in whom complete failure of descent has occurred. This is especially true in infants and young children, in whom the thymus still plays a very important role in the development of immune mechanisms. Therefore, it should not be totally removed unless it is causing severe symptoms by interfering with neighboring structures. In all cases of cervical thymus that are in continuity with the mediastinally placed portion, partial excision of the cervical and thoracic inlet portion of the thymus usually suffices in eliminating the local pressure and related symptoms. Malignant thymic neoplasms in cervical thymus are extremely rare. Neoplastic degeneration of a solid cervical thymic mass was described by Pirkey [35] in 1954 and was mentioned by Lewis [I] in 1962. Thy-
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mic cysts, on the other hand, have never been found to behave in that manner. Consequently, a solid solitary aberrant thymus should be totally removed, particularly when the presence of a normally placed mediastinal thymus can be reaffirmed by chest x-ray films or at the time of surgery. Sease [36] in 1965 described a patient with myasthenia gravis and a low cervical mass diagnosed histologically as a benign thymoma. The patient recovered completely -after removal of this neoplasm. Here also, no cysts were present histologically. The prognosis after removal of a cervical thymus (partially or totally, as mentioned) is excellent. If the lesion was symptomless, the fear of an unfavorable lesion (thymic or otherwise) is eliminated by its removal. On the other hand, if the lesion was symptomatic, certainly the indication for its removal was anywhere from moderate to urgent, and the results are just as good upon removal: all symptoms disappear immediately. In only one type of cervical thymus-hyperplasia-can there be an argument as to the necessity of surgical intervention in the face of a recent intercurrent infection. The enlarged hyperplastic thymus with a cervical projection may shrink after appropriate therapy to control the infection. Decision in favor of exploration may be momentarily deferred based on individual consideration of each such case. The general approach to this and all other thymic cervical lesions must basically remain, like that to all other neck masses, in the hands of the surgeon.
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Summary Cervical thymic anomalies are not as rare as previously suggested. Six cases were encountered over a relatively short period of time, prompting us to report them and emphasize the importance of this entity. Five of the six patients were children, two of them infants less than one year old. The occurrence oft hymic remnants in the neck of young children is not surprising, considering the nature and behavior of the thymus at different stages of life. After a brief embryologic survey, the various types of cervical thymus (solitary ectopic, cystic, or partially arrested descent) and their pathogenesis are discussed. The rare occurrence of thyroid and parathyroid tissue within the mass of a large cervical thymic cyst is reported and evaluated. Cervical thymic lesions can either be symptomless or cause severe dyspnea and dysphagia, especially in the young infant. Accurate diagnosis and an intelligent surgical approach in the child with a cervical mass can avoid the obvious parental apprehension and lead to the correct treatment. Symptoms due to pressure on neighboring structures are promptly elirninated after excision, and prognosis is excellent. References 1. Lewis MR: Persistence of the thymus in the cervical area. J fediatr Surg61: 887, 1962. 2. Bieger RC, McAdams AJ: Thymic cysts. Arch Pathol82: 535, 1966. 3. Ellis HA: Cervical thymic cysts. Br J Surg 54: 17, 1967. 4. Barrick B. O’Kell RT: Thymic cysts and remnant cervical thymus. J Pediatr Surg 4: 355, 1969. 5. Johnsen NJ, Bretlau P: Cervical thymic cysts. Acta Oto/aryngo/ Scand82: 143, 1976. 6. Thorrens SJ, Panzer JG, Bennett JE: Cervical thymus gland. Plast Reconstr Surg 44: 86, 1969. 7. Hurley F: Cervico mediastinal thymic cyst. Cyst puncture and contrast radiologic demonstration. Br J Radio/ 50: 676, 1977. 8. Gaeckle DY, Gerber ML: Thymic cyst in the neck. Am J Surg 103: 755, 1962. 9. Movitz D, Lum CL: Thymic cyst of the neck simulating goiter surgery. Surgery51: 456, 1962. 10. Ozlo C, Allen JD: Unilateral thymic cyst of the neck. J Ky Med Assoc 60: 743, 1962.
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11. Behrino CH. Beraman F: Thvmic cvst of the neck, reoort of a case: Acia Patho/ Micro&o/ S&d 59: 45, 1962. 12. Fielding JF, Farmer AW, Lindsay WK, Conen PE: Cystic degeneration in persistent cervical thymus: a report of four cases in children. Can J Surg 6: 178, 1963. 13. Simons JN, Robinson DW, Masters FW: Cervical thymic cyst. Am J Surg 108: 578, 1964. 14. Stanley M: Cervical thymic cyst. Case report and review of the literature. Arch Surg 109: 558, 1974. 15. Shalkelford GD, McAllister WNM: The aberrently positional thymus. A cause of mediastinal or neck area masses. Am J Roentgenol Rad Ther Nucl Med 120: 291, 1974. 16. Strome M, Eraklis A: Thymic cysts in the neck. Laryngoscope 87: 1645, 1977. 17. Hinds EA, Linkner LM, Cloud DT, Trump DS: Ectopic thymic tissue of the neck. J Pediatr Surg 5: 460, 1970. 18. Ratnesar P: Unilateral cervical thymic cysts. J Laryngol Otol 85: 293, 1971. 19. Fahmy S: Cervical thymic cysts. Their pathogenesis and relationship to branchial cysts. J Laryngol Otol88: 47, 1974. 20. Castleman B: Atlas of tumor pathology, sect V fast 19, p 15, 16. Tumors of the Thymus Gland. Washington DC, Armed Forces Institute of Pathology, 1955. 21. Arnheim EE, Gemson BL: Persistent cervical thymus gland: thymectomy. Surgery 27: 603, 1950. 22. Mosely JC, Som M: Cervical thymus gland. J Mt Sinai Hasp 21: 289, 1954. 23. Anderson WAB: Pathology, vol 2. St. Louis, C. V. Mosby, 1971, p 1397. 24. Robbins SL: Pathologic Basis of Diseases: Philadelphia, WB Saunders, 1974, p 1367. 25. Michelson H, Sender B: Cervical thymus. Arch Surg 72: 265, 1956. 26. Speer FD: Thymic cysts. NY Med Co// and flower Hasp Bull 1: 142, 1938. 27. Rickles NH, Little JW: The histogenesis of the branchial cyst. A study of the lining epithelium. Am J fatho/ 50: 765, 1967. 28. Gilmour JR: The embryology of parathyroid glands: the thymus and certain associated rudiments. J Pathol Bacterial 45: 507, 1937. 29. Gilmour JR: Some developmental anomalies of the thymus and parathyroids. J Pathol Bacterial 52: 2 13, 1941. 30. Willis RA: The Borderline of Embryology and Pathology, 2nd edition. London, Butterworth, 1958, p 313. 31. lndeglia RA, Shea MA, Grage TB: Congenital cysts of the thymus gland. Arch Surg 94: 149, 1967. 32. Batsakis JG: Tumors of the head and neck: clinical and pathological considerations. Baltimore, Williams & Wilkins, 1974, p 162. 33. Ackerman LV, Rosai J: Surgical Pathology, 5th edition. St. Louis, CV Mosby, 1974, p 255. 34. Dunbar S: Upper respiratory tract obstructions in infants and children. Am Roentgenol Rad Ther Nucl Med 109: 227, 1970. 35. Pirkey WP: Epithelioma of undescended thymus in a child. Arch Otolaryngol59: 237, 1954. 36. Sease Cl: Cervical thymoma. Va Med 83: 345, 1956.
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Ferit Tovi, MD, Beer-Sheva, Israel Abraham J. Mares, MD, Beer-Sheva, Israel
The thymus is the central organ of the lymphoid system in infancy. It originates high in the neck in early fetal life and reaches its definitive location in the mediastinum after a process of descent, generally leaving no trace behind. Occasionally, during this descent, remnants of thymic tissue can be implanted along the cervical pathway, later appearing as a cervical mass representing the so-called ectopic or aberrant cervical thymus. On the other hand, hyperplasia of the thymus secondary to infection, or rarely displacement of the incompletely descended thymus toward the neck (due to increased intrathoracic pressure), may also give the appearance of a mass in the lower neck region. These two conditions, congenital and acquired, take part in the pathogenesis of the persistent cervical thymus. Fewer than seventy clinical cases of cervical thymus have been reported in the English literature, mostly isolated case reports. Thirty cases were ectopic solid thymic masses, whereas thirty-eight were of cystic nature. We have lately encountered six such cases and believe the lesion to be far more common than previously suggested. Our cumulated experience in the diagnosis and treatment of this entity is reported herein. Basic knowledge of the embryologic de\relopment of the cervical region is absolutely essential in understanding the pathogenesis of this entity and in evaluating the young patient with a cervical mass and its associated symptoms. Case Reports Case I. A three year old male infant was admitted because of a soft tissue mass in the upper anterior triangle of the right neck. According to t,he mother, the lump had been
Frorr the Departments of Ear, Nose, and Throat and Pediatric Surgery, Soroka Medical Center, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer-Sheva, Israel. Reprint requests should be addressed to Abraham J. Mares, MD. Department of Pediatric Surgery, Soroka Medical Center, Ben Gurion University, Faculty of Health Sciences, PO Box 151, Beer-Sheva. Israel
Volume 136, November 1976
present on and off since birth. However, the diagnosis was somewhat elusive. On one outpatient clinic examination, deep palpation of the neck suggested a lymph node consistency, whereas on another occasion the possibility of a branchial cleft cyst or cystic hygroma had been raised. The rest of the physical examination and routine laboratory tests were within normal limits. At surgery, a solid mass, 4 by 3 by 2 cm, was excised deep to the sternocleidomastoid muscle and anterior to it, in the vicinity of the carotid bifurcation along the deep jugular lymph nodes. It was surrounded by hyperplastic lymph nodes. Recovery was uneventful. Histologic diagnosis confirmed the presence of ectopic thymus presenting scattered cystic degeneration of Hassall’s bodies. Case II. A ten year old female was admitted because of dyspnea of one day’s duration without associated fever. The child was also quadriplegic due to trauma to the neck one year prior to the present admission. On chest x-ray films, an enlargement of the upper mediastinum was noted, extending towards the right side of the neck. Exploration of the base of the neck revealed a soft tissue mass in continuity with the mediastinal mass. It proved to be thymic tissue. Her postoperative course was complicated by atelectasis and pneumonia which responded well to chest physiotherapy and antibiotic administration. Histologic examination of the partially resected mass revealed necrosis and acute inflammation of Hassall’s bodies, areas of demarcation between the medulla and cortex of the thymic gland, and scattered germinal centers in the medulla of the thymic glands. Case III. A twenty-six year old man was hospitalized for surgery upon diagnosis of a cold nodule in the left lobe of the thyroid. Surgical exploration revealed a thyroid nodule as well as a 1 by 1 by 0.5 cm mass in the lower jugular vein. Hemithyroidectomy and excision of the mass were performed. Histopathologic analysis revealed a benign colloid nodular goiter, while the mass near the thyroid lohe was thymic tissue. Recovery was uneventful. Case IV. A four month old male infant was admitted with a lump appearing in the central portion 01’ the lower neck, evident mostly when crying. Episodes of dysphagia
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limits. The neck exploration revealed an 18 by 5 by 5 cm cystic mass that extended from the mediastinum to the basis cranii along the jugular vein and was in continuity with the mediastinal thymic structure. The mass was excised. Pathologic examination showed it to be multilocular, cystic, and containing brown gelatinous fluid. (Figure 2.) Microscopically, the walls of the cysts were fibrous, intermittently lined with simple squamous, cuboid, and in some areas pseudostratified cuboid epithelium. Some areas were devoid of epithelium altogether. (Figure 3A.) In addition, rich lymphoid infiltration, scattered Hassall’s bodies, and fibrosis were present in the subepithelial layer. (Figure 3B.) Some areas included cholesterol granulomas and secondary cystic formations. In one area cords of parathyroid cells and thyroid tissue were found in the cystic wall. (Figure 4.) Her postoperative course was unremarkable. Embryology, Pathogenesis, and Anatomic Presentation For better orientation and understanding of the pathogenesis and clinical significance of the thymic tissue in the neck, the embryologic development and anatomic borderlines of this structure should be considered. Embryology of the Normal Thymus
Figure 1. Case IV. lntraoperative findings of mass adherent to the incompletely descended thymus.
and dyspnea preceded his admission for one month. A superficial hemangioma of the overlying skin was observed. Chest x-ray films revealed a large mass at the thoracic inlet, thought to be a deep component of the hemangioma. However, on exploration, a solid mass adherent to the incompletely descended thymus was found on the right side of the lower neck. (Figure 1.) There was compression of the trachea by the mass. Immediately after resection the dyspnea and dysphagia disappeared. The histologic findings were consistent with aberrant thymic tissue. Case V. A nine month old female infant was hospitalized because of a lump that appeared on the right lower side of the neck while crying. The general physical examination, routine laboratory data, and chest x-ray results revealed no abnormalities. Neck exploration revealed a 3 by 1.5 by 1 cm mass adherent to the right thymic lingula. This mass was excised, and histopathologic analysis showed aberrant thymic tissue. The postoperative course was uneventful.
Case VI. An eleven year old girl was admitted because of a large lump in the right neck which appeared only the day before admission, On physical examination a large lump was found on the right side of the neck sensitive to palpation. Chest x-ray films showed enlargement of the mediastinum. Routine laboratory tests were within normal
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The third and fourth pharyngeal pouches in the embryo are characterized at their distal extremity by so-called dorsal and ventral wings. The thymus develops mainly from the ventral wing (sacculation) of the third pharyngeal pouch on each side. (Figure 5.) The dorsal wings of the same pouch give rise to the inferior parathyroid glands. The thymic primordia that develop from the fourth pharyngeal pouch, even at the time of its formation, are likely to be quite small and rudimentary. They may give rise only to vestigial tissue masses. The superior parathyroid glands develop from the dorsal wings (sacculations) of the same pouches. The primordial thymus appears in the beginning of the sixth week of fetal life. By the end of this week the connections of the primordia with the pharyngeal pouches are severed. Each primordium ‘elongates caudally and medially as a tubular structure (thymopharyngeal tract) which soon begins a process of obliteration by epithelial proliferation. By the eighth week, the bilateral thymic primordia fuse in the midline and start to slide down under the sternum in the superior mediastinum, where they lie in contact with the parietal pericardium. The fusion of the right and left thymic primordia is never really complete, so that the organ never loses entirely its paired character (this makes surgical extirpation of one lobe easier, if deemed necessary). At the end of the descent, the upper end of the thymus becomes drawn
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Figure 2. Case VI. Transection of the fresh operative specimen. Multilocular cystic thymus on righi side of the neck.
in and generally vanishes. The final location of the thymus is usually entirely in the anterior mediastinum, between the sternum, parietal pericardium, and thoracic inlet. .4t birth the thymus is large relative to total body weight (average weight, 13 gm). That is why in the early years of life a distinctive radiographic shadow of the thymus normally appears in the upper anterior mediastinum. Its absolute weight increases in the two years after birth and at approximately eleven years reaches a maximum weight of 30 to 40 gm. After this age its weight begins to decrease to an adult weight of approximately 15 gm or less. Pathogenesis of the Cervical Thymus
Until 1962, only thirty-two cases of cervical thymic masses had been described [I]. Most of them were diagnosed at necropsy; only eleven clinical cases were reported. Wenglowsky, cited by Bieger and McAdams [Z], using serial sections of the neck, demonstrated thymic rests in two of ten adults and twenty-one of sixty-five children at autopsy. Small cervical thymic cysts were verified during routine postmortem examinations [2,3]. Barrick and O’Kell [4], in their review of the literature, described thirty cases of cervical thymus, the majority of which were cysts found mostly in children. Considering that the thymus reaches its greatest absolute size at puberty and its greatest relative size between the second and fourth years of life, they found it unsurprising that the diagnosis was made mostly in children. The recognition of this entity has increased lately, as evidenced by a relative abundance of isolated case reports [1-191. Thymic tissue becomes implanted in the neck by a process of sequestration from the main gland during its normal fetal descent. In this case the tissues form a solitary mass which in essence is a true ectopic
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(aberrant) thymus in the neck (cases I and III are examples of this anomaly). Other possibilities occur, however, in the pathogenesis of cervical thymic tissue. Sometimes after descent, the upper ends of the gland, instead of involuting, form separate accessory lobes or persistent cords (cases II and V). Rarely, the thymus fails to descend [20] or descends incompletely. Naturally, it then remains wholly or partially in the cervical region (cases IV and VI). Failure of the complete descent of the thymus may locate the structure at the thoracic inlet [15]. Increased intrathoracic pressure, such as an infant’s crying, may force the gland upwards into the neck, presenting the appearance of a lower cervical mass. This was actually the presenting symptom in cases IV and V. It is usually prominent in infancy due to the small size and proportions of the infant’s chest and thoracic inlet. Other similar examples have been cited [15,21,22]. Another presentation of cervical thymus is hyperplasia of the normally situated thymus gland (case II). Hyperplasia of the thymus gland may occur secondary to infections or vaccinations. It is not merely a matter of volume. The histologic findings demonstrate increased cellularity of the cortex and medulla of the thymus, delineating a clear demarcation between these two zones 1201. The presence of germinal centers or lymphoid folliculi in the medulla is one of the most reliable criteria of this entity [23,24]. Mitchelson and Sender [25] reported a case in which hyperplasia of the cervical thymus appeared during an upper respiratory tract infect,ion and involuted immediately after antibiotic therapy, somewhat similar to the situation in case II. The pathogenesis of cyst formation within the thymus tissue is still a matter of controversy. Speer [26] in 1938 suggested that cysts may originate from: (1) embryologic remnants in the neck; (2) seques-
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Figure 3. Case VI. A, wall of the thymic cyst lined with simple squamous and pseudostratified cuboid epithelium. A large cholesterol granuloma is seen on the left side. (Magnification X 32; reduced 12 per cent). 6, normal and calcified Hassall’s bodies surrounded by lymphoid infiitrafion. (Magnification X 125; reduced 33 per cent).
tration products in pathologic involution of the thymus; (3) neoplastic processes; (4) degeneration of Hassall’s bodies; or (5) mesenchymal elements. Ellis [3] in 1967 suggested that most cysts of the thymus arise as a result of cystic degeneration of Hassall’s bodies, but he pointed out that the cause is obscure. He based his argument on the concept that progres-
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sive cystic change in Hassall’s bodies and the epithelial reticulum is an acquired and not a developmental defect. On the other hand, he accepted the fact that occasionally congenital cervical thymic remnants can undergo cystic changes. About the same time, Bieger and McAdams [2] concluded that these cysts arise from persistent thymopharyngeal ducts. Fahmy [19] in 1974 suggested that the thymic cysts arising from the vestigial remnants of the thymopharyngeal ducts should be considered a variant of branchial cleft cysts, affecting generally the youngest age group. The similarity of the epithelial lining of the branchial cyst to that of the thymic cyst [27], the presence of subepithelial lymphatic infiltration in both types of cyst, and their similar localization support the concept that they are both derived from the same vestigial structure. It may be of interest to mention at this point that in case VI we found histologic evidence of both thyroid and parathyroid tissue within the wall of the large thymic cystic mass. (Figure 5.) Gilmour [28,29] and Behring and Bergman [ll] also described the occurrence of parathyroid tissue in thymic remnants. The parathyroid glands and the anlage of the thymus are adjacent structures in the third pharyngeal pouch. The anlage of the thymus may produce parathyroid tissue under certain circumstances according to the multipotentiality of certain cells in a given region at a certain early stage of embryologic formation. Willis [30], along Van Dyke’s theory of the formation of accessory thyroid tissue in the thymus, suggested the possibility of metaplastic interconversion of the thymus and thyroid because of their similar developmental origins. This theory may explain the thyroid tissue in the wall of cystic cervical thymus. However, we think that it is more likely that due to their proximity, clusters of thyroid cells were “imprisoned” in the thymopharyngeal remnant. Hence, in the process of cystic degeneration and formation of cystic cervical thymus, we find them as well. The size and extent of the cystic mass in case VI make it likely that the mass originated from a congenital branchial remnant, as suggested by Fahmy ]191. Clinical Presentation and Implications of Cervical Thymus
Generally, most of these ectopic and aberrantly located thymic masses remain dormant. They may be found incidentally during thyroid surgery (as in case III) or after surgery on histologic examination of the resected specimen and during explorations of the neck for other causes, such as parathyroid ade-
The American Journal of Surgery
Aberrant Cervical Thymus
Figure 48. Case VI. Subepithelial layer showing parathyroid cords. ( Magnification X 725).
Figure 4A. Case VI. 7’hyroidand parathyroid tissue in thymic cyst wall. (Magnification X 60).
nomas [31]. However, occasionally, the symptomless cervical tissue tends to grow during childhood just like the main thymus gland. Thus, any time during ch:ldhood and prepubertal age it may reach proportions that will make it easily recognizable by mere inspection, palpation, or both. X-ray films may also be of help in identifying the mass or suggesting the diagnosis. The cervical thymus is mostly localized along a line extending from the angle of the mandible to the manubrium sterni [18] or around the thyroid gland [32]. Some authors suggest predominance of the left side [I]. This was not corroborated in our patients, in whom most of the masses were on the right side. Extraordinary cases with intratracheal or hypopharyngeal locations were cited by Lewis [I] in his review of the literature. Thymic cysts can occur both in the neck and in the mediastinum [33]. Diagnosis of these anomalies in the neck are obviously predominant due to the relative ease in examining the cervical region [4]. Sometimes the cervical cysts may extend into the mediastinum. Although it is claimed [34] that the thymic gland,
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no matter how large, does not compress or displace normal structures, cases of ectopic thymus causing compression, displacement, or deviation of neighboring structures have been described [ 15,21,25,35]. Some of these phenomena were quite obvious in case IV as well. Location of the gland in the thoracic inlet has the potential to compress the trachea [35], and it may also compress the esophagus. This may give rise to the appropriate symptoms, namely dyspnea, stridor, and dysphagia. The diagnosis of cervical thymus has never been made preoperatively and always came somewhat as a surprise, either during the operative procedure or after sectioning the surgical specimen and the histopathologic examination. This is due to the fact that cervical thymus is far from being a well known entity; therefore, it is not readily considered in the differential diagnosis of neck cysts and masses, particularly in infants and children. Since the neck is a common site for the occurrence of congenital anomalies, one has to consider and differentiate the thymic cysts and other ectopic or aberrant thymic tissue from more familiar anomalies, such as thyroglossal or branchial cleft, dermoid and hygroma coli cysts, as well as thyroid [9,14], parathyroid, and other cervical lymph node lesions. Solid and cystic thymic lesions may mimic benign tumors, such as hemangiomas and lymphangiomas, as well as malignant neoplasms, such as lymphoproliferative disease and other metastatic neoplasms in cervical lymph nodes. During workup of a patient with a neck mass (suspected of being of thymic origin), the familiar routine should be followed: (1) thorough physical examination with particular emphasis on the anterior triangles of the neck and oropharyngeal regions; (2) complete blood analysis; (3) x-ray films of the chest
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PHARVNGEAL
POUCHES
i-
i
Jthymlc
I
-\L---thVmlc
primordia
prlmordia
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5
Figure 5. Embryologic development of the branch/al system.
and soft tissues of the neck (both in the posteroanterior and lateral projections); (4) thyroid scanning to rule out possible thyroid involvement (unfortunately, to date we do not have a good isotope scan available for the thymus); and (5) esophagography if deemed necessary. Hurley [7] recently advised direct contrast radiographic demonstration of cystic lesions. We do not believe that this should be a routine approach to this problem. The primary therapeutic approach to cervical thymus should be identical to the approach to any other neck mass, namely surgical. Frozen section analysis during surgery will sometimes facilitate the decision as to how much of the thymus to remove. At times it may save total thymic excision, particularly in those patients in whom complete failure of descent has occurred. This is especially true in infants and young children, in whom the thymus still plays a very important role in the development of immune mechanisms. Therefore, it should not be totally removed unless it is causing severe symptoms by interfering with neighboring structures. In all cases of cervical thymus that are in continuity with the mediastinally placed portion, partial excision of the cervical and thoracic inlet portion of the thymus usually suffices in eliminating the local pressure and related symptoms. Malignant thymic neoplasms in cervical thymus are extremely rare. Neoplastic degeneration of a solid cervical thymic mass was described by Pirkey [35] in 1954 and was mentioned by Lewis [I] in 1962. Thy-
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mic cysts, on the other hand, have never been found to behave in that manner. Consequently, a solid solitary aberrant thymus should be totally removed, particularly when the presence of a normally placed mediastinal thymus can be reaffirmed by chest x-ray films or at the time of surgery. Sease [36] in 1965 described a patient with myasthenia gravis and a low cervical mass diagnosed histologically as a benign thymoma. The patient recovered completely -after removal of this neoplasm. Here also, no cysts were present histologically. The prognosis after removal of a cervical thymus (partially or totally, as mentioned) is excellent. If the lesion was symptomless, the fear of an unfavorable lesion (thymic or otherwise) is eliminated by its removal. On the other hand, if the lesion was symptomatic, certainly the indication for its removal was anywhere from moderate to urgent, and the results are just as good upon removal: all symptoms disappear immediately. In only one type of cervical thymus-hyperplasia-can there be an argument as to the necessity of surgical intervention in the face of a recent intercurrent infection. The enlarged hyperplastic thymus with a cervical projection may shrink after appropriate therapy to control the infection. Decision in favor of exploration may be momentarily deferred based on individual consideration of each such case. The general approach to this and all other thymic cervical lesions must basically remain, like that to all other neck masses, in the hands of the surgeon.
The American Journal 01 Surgery
Aberrant
Summary Cervical thymic anomalies are not as rare as previously suggested. Six cases were encountered over a relatively short period of time, prompting us to report them and emphasize the importance of this entity. Five of the six patients were children, two of them infants less than one year old. The occurrence oft hymic remnants in the neck of young children is not surprising, considering the nature and behavior of the thymus at different stages of life. After a brief embryologic survey, the various types of cervical thymus (solitary ectopic, cystic, or partially arrested descent) and their pathogenesis are discussed. The rare occurrence of thyroid and parathyroid tissue within the mass of a large cervical thymic cyst is reported and evaluated. Cervical thymic lesions can either be symptomless or cause severe dyspnea and dysphagia, especially in the young infant. Accurate diagnosis and an intelligent surgical approach in the child with a cervical mass can avoid the obvious parental apprehension and lead to the correct treatment. Symptoms due to pressure on neighboring structures are promptly elirninated after excision, and prognosis is excellent. References 1. Lewis MR: Persistence of the thymus in the cervical area. J fediatr Surg61: 887, 1962. 2. Bieger RC, McAdams AJ: Thymic cysts. Arch Pathol82: 535, 1966. 3. Ellis HA: Cervical thymic cysts. Br J Surg 54: 17, 1967. 4. Barrick B. O’Kell RT: Thymic cysts and remnant cervical thymus. J Pediatr Surg 4: 355, 1969. 5. Johnsen NJ, Bretlau P: Cervical thymic cysts. Acta Oto/aryngo/ Scand82: 143, 1976. 6. Thorrens SJ, Panzer JG, Bennett JE: Cervical thymus gland. Plast Reconstr Surg 44: 86, 1969. 7. Hurley F: Cervico mediastinal thymic cyst. Cyst puncture and contrast radiologic demonstration. Br J Radio/ 50: 676, 1977. 8. Gaeckle DY, Gerber ML: Thymic cyst in the neck. Am J Surg 103: 755, 1962. 9. Movitz D, Lum CL: Thymic cyst of the neck simulating goiter surgery. Surgery51: 456, 1962. 10. Ozlo C, Allen JD: Unilateral thymic cyst of the neck. J Ky Med Assoc 60: 743, 1962.
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Thymus
11. Behrino CH. Beraman F: Thvmic cvst of the neck, reoort of a case: Acia Patho/ Micro&o/ S&d 59: 45, 1962. 12. Fielding JF, Farmer AW, Lindsay WK, Conen PE: Cystic degeneration in persistent cervical thymus: a report of four cases in children. Can J Surg 6: 178, 1963. 13. Simons JN, Robinson DW, Masters FW: Cervical thymic cyst. Am J Surg 108: 578, 1964. 14. Stanley M: Cervical thymic cyst. Case report and review of the literature. Arch Surg 109: 558, 1974. 15. Shalkelford GD, McAllister WNM: The aberrently positional thymus. A cause of mediastinal or neck area masses. Am J Roentgenol Rad Ther Nucl Med 120: 291, 1974. 16. Strome M, Eraklis A: Thymic cysts in the neck. Laryngoscope 87: 1645, 1977. 17. Hinds EA, Linkner LM, Cloud DT, Trump DS: Ectopic thymic tissue of the neck. J Pediatr Surg 5: 460, 1970. 18. Ratnesar P: Unilateral cervical thymic cysts. J Laryngol Otol 85: 293, 1971. 19. Fahmy S: Cervical thymic cysts. Their pathogenesis and relationship to branchial cysts. J Laryngol Otol88: 47, 1974. 20. Castleman B: Atlas of tumor pathology, sect V fast 19, p 15, 16. Tumors of the Thymus Gland. Washington DC, Armed Forces Institute of Pathology, 1955. 21. Arnheim EE, Gemson BL: Persistent cervical thymus gland: thymectomy. Surgery 27: 603, 1950. 22. Mosely JC, Som M: Cervical thymus gland. J Mt Sinai Hasp 21: 289, 1954. 23. Anderson WAB: Pathology, vol 2. St. Louis, C. V. Mosby, 1971, p 1397. 24. Robbins SL: Pathologic Basis of Diseases: Philadelphia, WB Saunders, 1974, p 1367. 25. Michelson H, Sender B: Cervical thymus. Arch Surg 72: 265, 1956. 26. Speer FD: Thymic cysts. NY Med Co// and flower Hasp Bull 1: 142, 1938. 27. Rickles NH, Little JW: The histogenesis of the branchial cyst. A study of the lining epithelium. Am J fatho/ 50: 765, 1967. 28. Gilmour JR: The embryology of parathyroid glands: the thymus and certain associated rudiments. J Pathol Bacterial 45: 507, 1937. 29. Gilmour JR: Some developmental anomalies of the thymus and parathyroids. J Pathol Bacterial 52: 2 13, 1941. 30. Willis RA: The Borderline of Embryology and Pathology, 2nd edition. London, Butterworth, 1958, p 313. 31. lndeglia RA, Shea MA, Grage TB: Congenital cysts of the thymus gland. Arch Surg 94: 149, 1967. 32. Batsakis JG: Tumors of the head and neck: clinical and pathological considerations. Baltimore, Williams & Wilkins, 1974, p 162. 33. Ackerman LV, Rosai J: Surgical Pathology, 5th edition. St. Louis, CV Mosby, 1974, p 255. 34. Dunbar S: Upper respiratory tract obstructions in infants and children. Am Roentgenol Rad Ther Nucl Med 109: 227, 1970. 35. Pirkey WP: Epithelioma of undescended thymus in a child. Arch Otolaryngol59: 237, 1954. 36. Sease Cl: Cervical thymoma. Va Med 83: 345, 1956.
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