Pediatr Blood Cancer 2015;62:1491–1492
LETTER TO THE EDITOR Suspected Early Onset of Congenital Langerhans Cell Histiocytosis Involving Ectopic Cervical Thymus and Mediastinal Thymus, Simultaneously
To the Editor: Langerhans cell histiocytosis (LCH) is a rare histiocytic disorder characterized by accumulation of Langerhans cells [1,2]. Congenital LCH chiefly affects the skin and is selfhealing (Hashimoto–Pritzker disease), but rare involvements of the lung, bone, or liver have been reported [3]. Thymus is one of the uncommon organs involved by LCH [4]. Ectopic thymus is an extremely rare etiology of a neck mass in an infant which results from abnormal embryogenesis of the thymus [5,6]. We present a case of congenital LCH with simultaneous involvement of ectopic cervical thymus and mediastinal thymus. A 2-month-old female without any significant medical history through the prenatal and neonatal period was brought to a physician complaining of left submandibular swelling. On physical examination, there was an elastic, soft, and poorly movable mass in the
left submandibular area. The mass was 3 cm in diameter and had a smooth surface. Computed tomography (CT) revealed cystic and solid components in the mass (Fig. 1A). An open biopsy of the mass was performed. The mass was well demarcated from surrounding tissues and was resected without macroscopic leaving residues. The pathological examination showed proliferation of CD1a positive cells with a round nuclear and rich cytoplasm in an eosinophil rich background (Fig. 1B–D). Diagnosis of LCH was made. Moreover, the resected mass contained ectopic thymic tissue whose architecture was partly effaced by infiltration of Langerhans cells (Fig. 1B and E). Reconfirmation of the CT image revealed the enlarged mediastinal thymus with multiple cysts and punctate calcifications which are specific findings of the thymic involvement of LCH (Fig. 1A) [7]. Although biopsy of the mediastinal thymic LCH
Fig. 1. (A) CT image showing a submandibular mass with cysts (arrowhead) and the enlarged mediastinal thymus with a punctate calcification (arrow). (B) Hematoxylin and eosin stain of the resected submandibular specimen showing proliferated cells with round nuclear and rich cytoplasm, and microscopic thymic tissue (asterisks). (C) High-power magnification showing grooved, folded, or indented nuclear contours of the proliferated cells, known as a “twisted towel“ or “coffee bean“ appearance. (D) Immunostain for CD1a highlighting Langerhans cells. (E) Architecture of ectopic thymic tissues is effaced by infiltration of Langerhans cells. Hassall’s corpuscles are seen (arrow).
Conflict of Interest: Nothing to declare.
Correspondence to: Akira Shimada, Department of Pediatrics, Okayama University Hospital, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan. E-mail: [email protected] Received 2 February 2015; Accepted 5 February 2015
C
2015 Wiley Periodicals, Inc. DOI 10.1002/pbc.25496 Published online 25 March 2015 in Wiley Online Library (wileyonlinelibrary.com).
1492
Kanamitsu et al.
lesion was not performed to avoid serious complications, we diagnosed this case as having a single-system disease with multiple involvements. She received the induction chemotherapy under Japan LCH Study Group (JLSG)-02 therapeutic protocol [8], resulting in a remarkable reduction of the mediastinal thymus. Now she is alive and well with maintenance therapy on outpatient basis. The ectopic thymus has been rarely reported [5,6]. The primordial thymus originates chiefly from the third pharyngeal pouches on each side in the early 6th week of gestational age. By the end of the 8th week, the primordium from each side fuses in the midline and begins descending toward the sternum. Abnormal sequestration of thymic tissue is considered to be one of the etiologies of ectopic thymus [5]. Neoplastic diseases except for thymoma have not been associated with ectopic thymus. In this case, we speculated that proliferation of Langerhans cells might begin in thymic primordia because there was no infiltrated organ except for thymus. During descent of thymic primordia, a sequestration of thymic tissue with proliferated. Langerhans cells were arrested in the submandibular area. The Langerhans cells continued proliferation both in mediastinal and ectopic thymus, finally forming the enlarged mediastinal thymus and the submandibular swelling, simultaneously. Although, we do not know precisely when Langerhans cells start to proliferate, this case suggests it occurs early in embryogenesis. Kiichiro Kanamitsu, MD Kana Washio, MD Megumi Oda, MD, PhD Akira Shimada, MD, PhD* Department of Pediatrics Okayama University Hospital Okayama, Japan
Pediatr Blood Cancer DOI 10.1002/pbc
Takuo Noda, MD, PhD Takanori Oyama, MD, PhD Terutaka Tanimoto, MD Department of Pediatric Surgery Okayama University Hospital Okayama, Japan Takehiro Tanaka, MD, PhD Department of Pathology Okayama University Hospital Okayama, Japan Kentaro Ida, MD, PhD Department of Radiology Okayama University Hospital Okayama, Japan
REFERENCES 1. Haupt R, Minkov M, Astigarraga I, Sch€afer E, Nanduri V, Jubran R, Egeler RM, Janka G, Micic D, Rodriguez-Galindo C, Van Gool S, Visser J, Weitzman S, Donadieu J. Langerhans cell histiocytosis (LCH): Guidelines for diagnosis, clinical work-up, and treatment for patients till the age of 18 years. Pediatr Blood Cancer 2013;60:175–184. 2. Morimoto A, Oh Y, Shioda Y, Kudo K, Imamura T. Recent advances in Langerhans cell histiocytosis. Pediatr Int 2014;56:451–461. 3. Nakashima T, Onoe Y, Tashiro A, Yamashita H. Congenital self-healing LCH: A case with lung lesions and review of the literature. Pediatr Int 2010;52: 224–226. 4. Ducassou S, Seyrig F, Thomas C, Lambilliotte A, Marec-Berard P, Berger C, Plat G, Brugiere L, Ouache M, Barkaoui M, Armari-Alla C, Lutz P, Leverger G, Rialland X, Mansuy L, Pacquement H, Jeziorski E, Gandemer V, Chalard F, Chateil JF, Tazi A, Emile JF, Donadieu J. Thymus and mediastinal node involvement in childhood Langerhans cell histiocytosis: Long-term follow-up from the French national cohort. Pediatr Blood Cancer 2013;60:1759–1765. 5. Tovi F, Mares AJ. The aberrant cervical thymus. Embryology, pathology, and clinical implications. Am J Surg 1978;136:631–637. 6. Wang J, Fu H, Yang H, Wang L. He Y. Clinical management of cervical ectopic thymus in children. J Pediatr Surg 2011;46: 33–36. 7. Lakatos K, Herbr€uggen H, P€otschger U, Prosch H, Minkov M. Radiological features of thymic langerhans cell histiocytosis. Pediatr Blood Cancer 2013;60:E143–E145. 8. Imashuku S, Kinugawa N, Matsuzaki A, Kitoh T, Ohki K, Shioda Y, Tsunematsu Y, Imamura T, Morimoto A. Langerhans cell histiocytosis with multifocal bone lesions: Comparative clinical features between single and multi-systems. Int J Hematol 2009;90:506–512.
LETTER TO THE EDITOR Suspected Early Onset of Congenital Langerhans Cell Histiocytosis Involving Ectopic Cervical Thymus and Mediastinal Thymus, Simultaneously
To the Editor: Langerhans cell histiocytosis (LCH) is a rare histiocytic disorder characterized by accumulation of Langerhans cells [1,2]. Congenital LCH chiefly affects the skin and is selfhealing (Hashimoto–Pritzker disease), but rare involvements of the lung, bone, or liver have been reported [3]. Thymus is one of the uncommon organs involved by LCH [4]. Ectopic thymus is an extremely rare etiology of a neck mass in an infant which results from abnormal embryogenesis of the thymus [5,6]. We present a case of congenital LCH with simultaneous involvement of ectopic cervical thymus and mediastinal thymus. A 2-month-old female without any significant medical history through the prenatal and neonatal period was brought to a physician complaining of left submandibular swelling. On physical examination, there was an elastic, soft, and poorly movable mass in the
left submandibular area. The mass was 3 cm in diameter and had a smooth surface. Computed tomography (CT) revealed cystic and solid components in the mass (Fig. 1A). An open biopsy of the mass was performed. The mass was well demarcated from surrounding tissues and was resected without macroscopic leaving residues. The pathological examination showed proliferation of CD1a positive cells with a round nuclear and rich cytoplasm in an eosinophil rich background (Fig. 1B–D). Diagnosis of LCH was made. Moreover, the resected mass contained ectopic thymic tissue whose architecture was partly effaced by infiltration of Langerhans cells (Fig. 1B and E). Reconfirmation of the CT image revealed the enlarged mediastinal thymus with multiple cysts and punctate calcifications which are specific findings of the thymic involvement of LCH (Fig. 1A) [7]. Although biopsy of the mediastinal thymic LCH
Fig. 1. (A) CT image showing a submandibular mass with cysts (arrowhead) and the enlarged mediastinal thymus with a punctate calcification (arrow). (B) Hematoxylin and eosin stain of the resected submandibular specimen showing proliferated cells with round nuclear and rich cytoplasm, and microscopic thymic tissue (asterisks). (C) High-power magnification showing grooved, folded, or indented nuclear contours of the proliferated cells, known as a “twisted towel“ or “coffee bean“ appearance. (D) Immunostain for CD1a highlighting Langerhans cells. (E) Architecture of ectopic thymic tissues is effaced by infiltration of Langerhans cells. Hassall’s corpuscles are seen (arrow).
Conflict of Interest: Nothing to declare.
Correspondence to: Akira Shimada, Department of Pediatrics, Okayama University Hospital, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan. E-mail: [email protected] Received 2 February 2015; Accepted 5 February 2015
C
2015 Wiley Periodicals, Inc. DOI 10.1002/pbc.25496 Published online 25 March 2015 in Wiley Online Library (wileyonlinelibrary.com).
1492
Kanamitsu et al.
lesion was not performed to avoid serious complications, we diagnosed this case as having a single-system disease with multiple involvements. She received the induction chemotherapy under Japan LCH Study Group (JLSG)-02 therapeutic protocol [8], resulting in a remarkable reduction of the mediastinal thymus. Now she is alive and well with maintenance therapy on outpatient basis. The ectopic thymus has been rarely reported [5,6]. The primordial thymus originates chiefly from the third pharyngeal pouches on each side in the early 6th week of gestational age. By the end of the 8th week, the primordium from each side fuses in the midline and begins descending toward the sternum. Abnormal sequestration of thymic tissue is considered to be one of the etiologies of ectopic thymus [5]. Neoplastic diseases except for thymoma have not been associated with ectopic thymus. In this case, we speculated that proliferation of Langerhans cells might begin in thymic primordia because there was no infiltrated organ except for thymus. During descent of thymic primordia, a sequestration of thymic tissue with proliferated. Langerhans cells were arrested in the submandibular area. The Langerhans cells continued proliferation both in mediastinal and ectopic thymus, finally forming the enlarged mediastinal thymus and the submandibular swelling, simultaneously. Although, we do not know precisely when Langerhans cells start to proliferate, this case suggests it occurs early in embryogenesis. Kiichiro Kanamitsu, MD Kana Washio, MD Megumi Oda, MD, PhD Akira Shimada, MD, PhD* Department of Pediatrics Okayama University Hospital Okayama, Japan
Pediatr Blood Cancer DOI 10.1002/pbc
Takuo Noda, MD, PhD Takanori Oyama, MD, PhD Terutaka Tanimoto, MD Department of Pediatric Surgery Okayama University Hospital Okayama, Japan Takehiro Tanaka, MD, PhD Department of Pathology Okayama University Hospital Okayama, Japan Kentaro Ida, MD, PhD Department of Radiology Okayama University Hospital Okayama, Japan
REFERENCES 1. Haupt R, Minkov M, Astigarraga I, Sch€afer E, Nanduri V, Jubran R, Egeler RM, Janka G, Micic D, Rodriguez-Galindo C, Van Gool S, Visser J, Weitzman S, Donadieu J. Langerhans cell histiocytosis (LCH): Guidelines for diagnosis, clinical work-up, and treatment for patients till the age of 18 years. Pediatr Blood Cancer 2013;60:175–184. 2. Morimoto A, Oh Y, Shioda Y, Kudo K, Imamura T. Recent advances in Langerhans cell histiocytosis. Pediatr Int 2014;56:451–461. 3. Nakashima T, Onoe Y, Tashiro A, Yamashita H. Congenital self-healing LCH: A case with lung lesions and review of the literature. Pediatr Int 2010;52: 224–226. 4. Ducassou S, Seyrig F, Thomas C, Lambilliotte A, Marec-Berard P, Berger C, Plat G, Brugiere L, Ouache M, Barkaoui M, Armari-Alla C, Lutz P, Leverger G, Rialland X, Mansuy L, Pacquement H, Jeziorski E, Gandemer V, Chalard F, Chateil JF, Tazi A, Emile JF, Donadieu J. Thymus and mediastinal node involvement in childhood Langerhans cell histiocytosis: Long-term follow-up from the French national cohort. Pediatr Blood Cancer 2013;60:1759–1765. 5. Tovi F, Mares AJ. The aberrant cervical thymus. Embryology, pathology, and clinical implications. Am J Surg 1978;136:631–637. 6. Wang J, Fu H, Yang H, Wang L. He Y. Clinical management of cervical ectopic thymus in children. J Pediatr Surg 2011;46: 33–36. 7. Lakatos K, Herbr€uggen H, P€otschger U, Prosch H, Minkov M. Radiological features of thymic langerhans cell histiocytosis. Pediatr Blood Cancer 2013;60:E143–E145. 8. Imashuku S, Kinugawa N, Matsuzaki A, Kitoh T, Ohki K, Shioda Y, Tsunematsu Y, Imamura T, Morimoto A. Langerhans cell histiocytosis with multifocal bone lesions: Comparative clinical features between single and multi-systems. Int J Hematol 2009;90:506–512.
