AM ER IC AN JOURNAL OF OT OLARYNGOLOGY – H E A D A N D NE CK M E D IC IN E A ND S U RGE RY 3 6 (2 0 1 5) 1 03– 1 0 5
Available online at www.sciencedirect.com
ScienceDirect www.elsevier.com/locate/amjoto
Isolated adult lymphadenopathy: a rare presentation of Langerhans cell histiocytosis☆ Jonathan M. Melzer, MD, LT, MC, USN a,⁎, Jessica Winters, BS, ENS, MC, USN b , Allen O. Mitchell, MD, CAPT, MC, USN a, 1 a b
Department of Otolaryngology-Head and Neck Surgery, Naval Medical Center Portsmouth, 620 John Paul Jones Circle, Portsmouth, VA F. Edward Hebert School of Medicine, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Rd, Bethesda, MD
ARTI CLE I NFO
A BS TRACT
Article history:
Intro: Langerhans cell histiocytosis (LCH) is a rare disease involving the proliferation of
Received 25 September 2014
histiocytes in one or more organ systems. The presentation of LCH is more common in the pediatric population and rarely occurs within the adult population. Isolated lymph node involvement is an extremely rare presentation of the disease. The authors present a case of isolated lymph node LCH in an otherwise healthy adult female and discuss management strategies for these unusual findings. Methods: A case report of a patient at a tertiary care facility in June 2014 is discussed. Results/Discussion: The diagnosis, clinical course, and management strategies for isolated adult LCH are discussed and reviewed. Conclusion: Langerhans cell histiocytosis rarely presents with isolated lymph node involvement in adults. Management and surveillance algorithms are discussed in this unusual case of seemingly benign lymphadenopathy. Published by Elsevier Inc.
1.
Introduction
Langerhans cell histiocytosis (LCH) is a rare disease involving the proliferation of histiocytes in one or more organ systems. The presentation of LCH is more common in the pediatric population and rarely occurs within the adult population.
Clinical manifestations of the disease are variable, ranging from single organ involvement to disseminated disease. Common sites of involvement among adults include bone, skin, hypothalamus, liver, and lung. Isolated lymph node involvement is rare, with one large study of 314 patients showing only 7% incidence of lymph node involvement at all.
☆ The views expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the Department of the Navy, Department of Defense, or the United States government. There are no financial conflicts of interest to disclose. I am a military service member. This work was not prepared as part of my official duties. Title 17 U.S.C. 105 provides that ‘Copyright protection under this title is not available for any work of the United States Government.’ Title 17 U.S.C. 101 defines a United States Government work as a work prepared by a military service member or employee of the United States Government as part of that person's official duties. There are no academic or financial conflicts of interest for any of the listed authors. ⁎ Corresponding author at: Department of Otolaryngology-Head and Neck Surgery, Naval Medical Center Portsmouth, 620 John Paul Jones Circle, Portsmouth, VA, 23708. Tel.: +1 757 953 2800; fax: + 1 757 953 0166. E-mail addresses: [email protected], [email protected] (J.M. Melzer), [email protected] (J. Winters), [email protected] (A.O. Mitchell). 1 Tel.: + 1 757 953 2800; fax: +1 757 953 0166.
http://dx.doi.org/10.1016/j.amjoto.2014.10.016 0196-0709/Published by Elsevier Inc.
104
AM ER IC AN JOURNAL OF OT OLA RYNGOLOGY– H E A D A N D NE CK M E D ICI N E AN D S U RGE RY 3 6 (2 0 1 5) 1 03 – 1 0 5
Two percent of patients in that study presented with head/ neck lymphadenopathy as the dominant presenting feature, and only one patient had lymphatic system involvement alone [1]. The authors present a case of isolated lymph node LCH in an otherwise healthy adult female and discuss management strategies for these unusual findings.
2.
Case history
A 20-year-old female was referred to the ENT department with a two-year history of postauricular lymphadenopathy and intermittent tenderness to palpation. The patient denied any fevers, chills, or weight loss and had an otherwise unremarkable medical history. Physical exam revealed a 5 mm palpable mass in the right postauricular region without tenderness or skin involvement. Ultrasound imaging revealed two enlarged postauricular lymph nodes with normal morphology and a measurement axis of 1.3 cm. The patient was subsequently treated with a course of antibiotics without any decrement in size, and the patient elected to undergo excision of the palpable lymph node due to continued tenderness as well as for diagnostic purposes. She was taken to the operating room and underwent a successful and uneventful excisional biopsy but pathology review showed the lymph node to be consistent with LCH.
3.
Discussion
LCH is a rare disease of unknown etiology, characterized as a proliferative disorder of Langerhans cells (LCs) in one or more organ systems. LCs are bone marrow-derived dendritic cells, which normally reside in the skin and lymph nodes [2]. Definitive diagnosis of LCH as set forth by the Histiocyte Society classification criteria requires the presence of CD1a or CD207 antigenic determinants on the surface of cells in question [3]. LCH predominantly presents in the pediatric population and little information is available concerning LCH and adults; only a few reports have been published involving a series of adult patients diagnosed with LCH [4]. In a report published in 2003 based on data from the International Registry of the Histiocyte Society, the mean age at onset of disease was 33 years. This registry data included only adults 18 years or older, totaling 274 patients from 13 different countries, collected between January 2000 and June 2001 [5]. LCH may present with a variety of symptoms based on the organ systems involved. The most common sites of presentation amongst reports on adult LCH include bone, skin, and lung manifestations [1,4,6,7]. Symptoms may include bone pain, rash (often on the scalp), dyspnea, chronic cough, or spontaneous pneumothorax. Overall, lymph node involvement is infrequent, and most often manifests as enlargement of one or more the cervical nodes. In the IRHS report, the histological diagnosis of LCH was made from lymph nodes in only 6.3% of patients [3]. Additionally, Howarth et al. reported only 1 of 104 patients with non-osseous single-system LCH disease presenting with lymph node infiltration, and only 21 of 314 patients had any lymph node involvement at all [1].
Histopathologically, tissues involved in LCH often show effacement of the nodal architecture and sinuses markedly distended by histiocytes. Immunohistochemical staining of the histiocytes are positive for CD1a, S-100, and CD-68 (Figs. 1–4). Treatment of LCH is tailored according to the extent and severity of disease at diagnosis. The LCH Study Group adopted a stratification system in 1990 with the division of LCH into two major diagnostic categories: single system (SS) and multisystem (MS). Single-system LCH is further subdivided into single site (unifocal bone, skin or lymph node) and multiple site (multifocal bone or multiple lymph nodes) [8]. Multisystem is defined as involvement of two or more organs at diagnosis with or without organ dysfunction and subdivided into either ‘low risk’ or ‘high risk’ groups [8]. Low-risk patients have an excellent prognosis and are characterized by the absence of involvement of ‘high risk’ organs such as liver, lungs, spleen or hematopoietic system. Patients with involvement of the aforementioned systems have a significantly higher mortality rate and require more intensive management [8]. The presentation of LCH as isolated single lymph node enlargement is rare and appears to be of low risk for patients due to single system, unifocal involvement. Occasionally, cases of isolated LCH have resulted in spontaneous regression of the lesion [9]. However, due to the potential for occult multi-system involvement, further workup upon histopathologic diagnosis is recommended. Appropriate diagnostic evaluation for LCH includes a thorough physical exam, a complete blood count, blood chemistry, liver function tests, erythrocyte sedimentation rate (ESR), and coagulation studies [10]. Imaging of the chest by chest X-ray or CT to assess for potential lung involvement and a complete skeletal survey for evaluation of osseous LHC lesions are necessary for discovery of other involved organ systems. Historically, ultrasound has been used to assess liver, spleen and lymph nodes. However, PET/CT of whole body can be used in lieu of ultrasound, chest X-ray, and bone CT [10].
Fig. 1 – Low power magnification of dissected lymph node, H&E stain.
AM ER IC AN JOURNAL OF OT OLARYNGOLOGY – H E A D A N D NE CK M E D IC IN E A ND S U RGE RY 3 6 (2 0 1 5) 1 03– 1 0 5
Fig. 2 – High power magnification showing Langerhans cells, H&E stain.
Management of an isolated lymph node with confirmed LCH may include watchful waiting or surgical excision. Surgical excisional biopsy often serves as the primary method of diagnosis and treatment, as was the case with this patient. However, the proximity of this lymph node to the temporal bone in this case required additional consideration and vigilance. LCH has been reported to involve the temporal bone in up to 60% of LCH cases [11–13]. The Histiocyte Society has determined the temporal bone to be a special site due to the risk of involvement or spread to the central nervous system [2,10]. Subsequent imaging studies (chest CT, PET scan) were performed to evaluate for multi-system disease and once ruled out, the patient was diagnosed with single-system LCH disease and selected for periodic observation. This case serves to add to the differential diagnosis in otherwise unremarkable lymphadenopathy which may require additional diagnostic testing to optimize patient care.
Fig. 3 – Langerhans cells with CD1a staining.
105
Fig. 4 – Langerhans cells with s100 staining.
REFERENCES
[1] Howarth DM, Gilchrist GS, Mullan BP, et al. Langerhans cell histiocytosis: diagnosis, natural history, management, and outcome. Cancer 1999;85:2278–90. [2] Broadbent V, Gadner H. Current therapy for Langerhans cell histiocytosis. Hematol Oncol Clin North Am 1998;12:327–38. [3] Vaiselbuh SR, Bryceson YT, Allen CE, et al. Updates on histiocytic disorders. Pediatr Blood Cancer 2014;61:1329–35. [4] Arico M, Girschikofsky M, Genereau T, et al. Langerhans cell histiocytosis in adults report from the international registry of the histiocyte society. Eur J Cancer 2003;39:2341–8. [5] Aricò M. Langerhans cell histiocytosis in adults: more questions than answers? Eur J Cancer 2004;40:1467–73. [6] Kilpatrick SE, Wenger DE, Gilchrist GS, et al. Langerhans' cell histiocytosis (histiocytosis X) of bone. A clinicopathologic analysis of 263 pediatric and adult cases. Cancer 1995;76: 2471–84. [7] Malpas JS, Norton AJ. Langerhans cell histiocytosis in the adult. Med Pediatr Oncol 1996;27:540–6. [8] Abla O, Egeler RM, Weitzman S. Langerhans cell histiocytosis: current concepts and treatments. Cancer Treat Rev 2010;36: 354–9. [9] Lo WC, Chen CC, Tsai CC, et al. Isolated adult Langerhans' cell histiocytosis in cervical lymph nodes: should it be treated? J Laryngol Otol 2009;123(9):1055–7. [10] Girschikofsky M, Arico M, Castillo D, et al. Management of adult patients with Langerhans cell histiocytosis: recommendations from an expert panel on behalf of Euro-Histio-Net. Orphanet J Rare Dis 2013;8:72. http://dx.doi.org/10.1186/1750-1172-8-72. [11] Goldsmith AJ, Myssiorek D, Valderrama E, et al. Unifocal Langerhans' cell histiocytosis (eosinophilic granuloma) of the petrous apex. Arch Otolaryngol Head Neck Surg 1993;119: 113–6. [12] Hermans R, De Foer B, Smet MH, et al. Eosinophilic granuloma of the head and neck: CT and MRI features in three cases. Pediatr Radiol 1994;24:33–6. [13] McCaffrey V, McDonald TJ. Histiocytosis X of the ear and temporal bone: review of 22 cases. Laryngoscope 1979;89: 1735–42. Hermans R, De Foer B, Smet MH, Leysen J. Eosinophilic granuloma of the head and neck: CT and MRI features in three cases. Pediatr Radiol 1979;24:33–6.
Available online at www.sciencedirect.com
ScienceDirect www.elsevier.com/locate/amjoto
Isolated adult lymphadenopathy: a rare presentation of Langerhans cell histiocytosis☆ Jonathan M. Melzer, MD, LT, MC, USN a,⁎, Jessica Winters, BS, ENS, MC, USN b , Allen O. Mitchell, MD, CAPT, MC, USN a, 1 a b
Department of Otolaryngology-Head and Neck Surgery, Naval Medical Center Portsmouth, 620 John Paul Jones Circle, Portsmouth, VA F. Edward Hebert School of Medicine, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Rd, Bethesda, MD
ARTI CLE I NFO
A BS TRACT
Article history:
Intro: Langerhans cell histiocytosis (LCH) is a rare disease involving the proliferation of
Received 25 September 2014
histiocytes in one or more organ systems. The presentation of LCH is more common in the pediatric population and rarely occurs within the adult population. Isolated lymph node involvement is an extremely rare presentation of the disease. The authors present a case of isolated lymph node LCH in an otherwise healthy adult female and discuss management strategies for these unusual findings. Methods: A case report of a patient at a tertiary care facility in June 2014 is discussed. Results/Discussion: The diagnosis, clinical course, and management strategies for isolated adult LCH are discussed and reviewed. Conclusion: Langerhans cell histiocytosis rarely presents with isolated lymph node involvement in adults. Management and surveillance algorithms are discussed in this unusual case of seemingly benign lymphadenopathy. Published by Elsevier Inc.
1.
Introduction
Langerhans cell histiocytosis (LCH) is a rare disease involving the proliferation of histiocytes in one or more organ systems. The presentation of LCH is more common in the pediatric population and rarely occurs within the adult population.
Clinical manifestations of the disease are variable, ranging from single organ involvement to disseminated disease. Common sites of involvement among adults include bone, skin, hypothalamus, liver, and lung. Isolated lymph node involvement is rare, with one large study of 314 patients showing only 7% incidence of lymph node involvement at all.
☆ The views expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the Department of the Navy, Department of Defense, or the United States government. There are no financial conflicts of interest to disclose. I am a military service member. This work was not prepared as part of my official duties. Title 17 U.S.C. 105 provides that ‘Copyright protection under this title is not available for any work of the United States Government.’ Title 17 U.S.C. 101 defines a United States Government work as a work prepared by a military service member or employee of the United States Government as part of that person's official duties. There are no academic or financial conflicts of interest for any of the listed authors. ⁎ Corresponding author at: Department of Otolaryngology-Head and Neck Surgery, Naval Medical Center Portsmouth, 620 John Paul Jones Circle, Portsmouth, VA, 23708. Tel.: +1 757 953 2800; fax: + 1 757 953 0166. E-mail addresses: [email protected], [email protected] (J.M. Melzer), [email protected] (J. Winters), [email protected] (A.O. Mitchell). 1 Tel.: + 1 757 953 2800; fax: +1 757 953 0166.
http://dx.doi.org/10.1016/j.amjoto.2014.10.016 0196-0709/Published by Elsevier Inc.
104
AM ER IC AN JOURNAL OF OT OLA RYNGOLOGY– H E A D A N D NE CK M E D ICI N E AN D S U RGE RY 3 6 (2 0 1 5) 1 03 – 1 0 5
Two percent of patients in that study presented with head/ neck lymphadenopathy as the dominant presenting feature, and only one patient had lymphatic system involvement alone [1]. The authors present a case of isolated lymph node LCH in an otherwise healthy adult female and discuss management strategies for these unusual findings.
2.
Case history
A 20-year-old female was referred to the ENT department with a two-year history of postauricular lymphadenopathy and intermittent tenderness to palpation. The patient denied any fevers, chills, or weight loss and had an otherwise unremarkable medical history. Physical exam revealed a 5 mm palpable mass in the right postauricular region without tenderness or skin involvement. Ultrasound imaging revealed two enlarged postauricular lymph nodes with normal morphology and a measurement axis of 1.3 cm. The patient was subsequently treated with a course of antibiotics without any decrement in size, and the patient elected to undergo excision of the palpable lymph node due to continued tenderness as well as for diagnostic purposes. She was taken to the operating room and underwent a successful and uneventful excisional biopsy but pathology review showed the lymph node to be consistent with LCH.
3.
Discussion
LCH is a rare disease of unknown etiology, characterized as a proliferative disorder of Langerhans cells (LCs) in one or more organ systems. LCs are bone marrow-derived dendritic cells, which normally reside in the skin and lymph nodes [2]. Definitive diagnosis of LCH as set forth by the Histiocyte Society classification criteria requires the presence of CD1a or CD207 antigenic determinants on the surface of cells in question [3]. LCH predominantly presents in the pediatric population and little information is available concerning LCH and adults; only a few reports have been published involving a series of adult patients diagnosed with LCH [4]. In a report published in 2003 based on data from the International Registry of the Histiocyte Society, the mean age at onset of disease was 33 years. This registry data included only adults 18 years or older, totaling 274 patients from 13 different countries, collected between January 2000 and June 2001 [5]. LCH may present with a variety of symptoms based on the organ systems involved. The most common sites of presentation amongst reports on adult LCH include bone, skin, and lung manifestations [1,4,6,7]. Symptoms may include bone pain, rash (often on the scalp), dyspnea, chronic cough, or spontaneous pneumothorax. Overall, lymph node involvement is infrequent, and most often manifests as enlargement of one or more the cervical nodes. In the IRHS report, the histological diagnosis of LCH was made from lymph nodes in only 6.3% of patients [3]. Additionally, Howarth et al. reported only 1 of 104 patients with non-osseous single-system LCH disease presenting with lymph node infiltration, and only 21 of 314 patients had any lymph node involvement at all [1].
Histopathologically, tissues involved in LCH often show effacement of the nodal architecture and sinuses markedly distended by histiocytes. Immunohistochemical staining of the histiocytes are positive for CD1a, S-100, and CD-68 (Figs. 1–4). Treatment of LCH is tailored according to the extent and severity of disease at diagnosis. The LCH Study Group adopted a stratification system in 1990 with the division of LCH into two major diagnostic categories: single system (SS) and multisystem (MS). Single-system LCH is further subdivided into single site (unifocal bone, skin or lymph node) and multiple site (multifocal bone or multiple lymph nodes) [8]. Multisystem is defined as involvement of two or more organs at diagnosis with or without organ dysfunction and subdivided into either ‘low risk’ or ‘high risk’ groups [8]. Low-risk patients have an excellent prognosis and are characterized by the absence of involvement of ‘high risk’ organs such as liver, lungs, spleen or hematopoietic system. Patients with involvement of the aforementioned systems have a significantly higher mortality rate and require more intensive management [8]. The presentation of LCH as isolated single lymph node enlargement is rare and appears to be of low risk for patients due to single system, unifocal involvement. Occasionally, cases of isolated LCH have resulted in spontaneous regression of the lesion [9]. However, due to the potential for occult multi-system involvement, further workup upon histopathologic diagnosis is recommended. Appropriate diagnostic evaluation for LCH includes a thorough physical exam, a complete blood count, blood chemistry, liver function tests, erythrocyte sedimentation rate (ESR), and coagulation studies [10]. Imaging of the chest by chest X-ray or CT to assess for potential lung involvement and a complete skeletal survey for evaluation of osseous LHC lesions are necessary for discovery of other involved organ systems. Historically, ultrasound has been used to assess liver, spleen and lymph nodes. However, PET/CT of whole body can be used in lieu of ultrasound, chest X-ray, and bone CT [10].
Fig. 1 – Low power magnification of dissected lymph node, H&E stain.
AM ER IC AN JOURNAL OF OT OLARYNGOLOGY – H E A D A N D NE CK M E D IC IN E A ND S U RGE RY 3 6 (2 0 1 5) 1 03– 1 0 5
Fig. 2 – High power magnification showing Langerhans cells, H&E stain.
Management of an isolated lymph node with confirmed LCH may include watchful waiting or surgical excision. Surgical excisional biopsy often serves as the primary method of diagnosis and treatment, as was the case with this patient. However, the proximity of this lymph node to the temporal bone in this case required additional consideration and vigilance. LCH has been reported to involve the temporal bone in up to 60% of LCH cases [11–13]. The Histiocyte Society has determined the temporal bone to be a special site due to the risk of involvement or spread to the central nervous system [2,10]. Subsequent imaging studies (chest CT, PET scan) were performed to evaluate for multi-system disease and once ruled out, the patient was diagnosed with single-system LCH disease and selected for periodic observation. This case serves to add to the differential diagnosis in otherwise unremarkable lymphadenopathy which may require additional diagnostic testing to optimize patient care.
Fig. 3 – Langerhans cells with CD1a staining.
105
Fig. 4 – Langerhans cells with s100 staining.
REFERENCES
[1] Howarth DM, Gilchrist GS, Mullan BP, et al. Langerhans cell histiocytosis: diagnosis, natural history, management, and outcome. Cancer 1999;85:2278–90. [2] Broadbent V, Gadner H. Current therapy for Langerhans cell histiocytosis. Hematol Oncol Clin North Am 1998;12:327–38. [3] Vaiselbuh SR, Bryceson YT, Allen CE, et al. Updates on histiocytic disorders. Pediatr Blood Cancer 2014;61:1329–35. [4] Arico M, Girschikofsky M, Genereau T, et al. Langerhans cell histiocytosis in adults report from the international registry of the histiocyte society. Eur J Cancer 2003;39:2341–8. [5] Aricò M. Langerhans cell histiocytosis in adults: more questions than answers? Eur J Cancer 2004;40:1467–73. [6] Kilpatrick SE, Wenger DE, Gilchrist GS, et al. Langerhans' cell histiocytosis (histiocytosis X) of bone. A clinicopathologic analysis of 263 pediatric and adult cases. Cancer 1995;76: 2471–84. [7] Malpas JS, Norton AJ. Langerhans cell histiocytosis in the adult. Med Pediatr Oncol 1996;27:540–6. [8] Abla O, Egeler RM, Weitzman S. Langerhans cell histiocytosis: current concepts and treatments. Cancer Treat Rev 2010;36: 354–9. [9] Lo WC, Chen CC, Tsai CC, et al. Isolated adult Langerhans' cell histiocytosis in cervical lymph nodes: should it be treated? J Laryngol Otol 2009;123(9):1055–7. [10] Girschikofsky M, Arico M, Castillo D, et al. Management of adult patients with Langerhans cell histiocytosis: recommendations from an expert panel on behalf of Euro-Histio-Net. Orphanet J Rare Dis 2013;8:72. http://dx.doi.org/10.1186/1750-1172-8-72. [11] Goldsmith AJ, Myssiorek D, Valderrama E, et al. Unifocal Langerhans' cell histiocytosis (eosinophilic granuloma) of the petrous apex. Arch Otolaryngol Head Neck Surg 1993;119: 113–6. [12] Hermans R, De Foer B, Smet MH, et al. Eosinophilic granuloma of the head and neck: CT and MRI features in three cases. Pediatr Radiol 1994;24:33–6. [13] McCaffrey V, McDonald TJ. Histiocytosis X of the ear and temporal bone: review of 22 cases. Laryngoscope 1979;89: 1735–42. Hermans R, De Foer B, Smet MH, Leysen J. Eosinophilic granuloma of the head and neck: CT and MRI features in three cases. Pediatr Radiol 1979;24:33–6.
