Secondary Logo

Journal Logo

Adult Langerhans’ cell histiocytosis with multisystem involvement

A case report

Kim, Seung Soo, MDa,*; Hong, Soon Auck, MD, PhDb; Shin, Hyeong Cheol, MD, PhDa; Hwang, Jeong Ah, MDa; Jou, Sung Shick, MD, PhDa; Choi, Seo-Youn, MDc

Section Editor(s): NA.,

doi: 10.1097/MD.0000000000013366
Research Article: Clinical Case Report
Open
SDC

Rationale: Langerhans’ cell histiocytosis (LCH), also called histiocytosis X, is an uncommon disorder manifesting in a variety of ways. Although LCH can involve various organs including bone, skin, and lymph nodes, multisystem involvement of LCH is rare in adults.

Patient concerns: A 31-year-old woman first presented to our hospital with left leg pain. She had a history of a 20-kg weight gain over three months.

Diagnoses: X-ray, magnetic resonance imaging (MRI), computed tomography (CT), and bone scan images revealed enhancing lesions in the left femur and right temporal bone, multiple cystic lesions in the lung, enhancing mass in the pituitary stalk, and fat density lesions in the liver. The patient underwent excisional biopsy for the femoral lesion and histologic examination confirmed the diagnosis of LCH.

Interventions: Excisional biopsy was performed for the bony lesion in the left femur. She received chemotherapy with vinblastine and prednisolone.

Outcomes: The patient expired after 21 months from initial admission following recurrent episodes of pneumothorax, pneumonia, and sepsis.

Lessons: Our case showed LCH involvement in bone, lung, central nervous system (CNS), and liver. Although it is occasionally difficult to discriminate LCH from other disorders, systemic evaluation might be helpful for differential diagnosis. Familiarity with the various multisystemic involvements of LCH on imaging is vital for diagnosing and managing patients in daily practice.

aDepartment of Radiology, Soonchunhyang University College of Medicine, Cheonan Hospital, Cheonan-si

bDepartment of Pathology, Soonchunhyang University College of Medicine, Cheonan Hospital, Cheonan-si

cDepartment of Radiology, Soonchunhyang University College of Medicine, Bucheon Hospital, Bucheon, Republic of Korea.

Correspondence: Seung Soo Kim, Department of Radiology, Soonchunhyang University College of Medicine, Cheonan Hospital, 31 Soonchunhyang6-gil, Dongnam-gu, Cheonan-si, Chungcheongnam-do 330–721, Republic of Korea. (e-mail: radiology2008@hanmail.net).

Abbreviations: CNS = central nervous system, CT = computed tomography, DI = diabetes insipidus, LAM = lymphangioleiomyomatosis, LCH = Langerhans’ cell histiocytosis, MRI = magnetic resonance imaging, SI = signal intensity.

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sector. This work was supported by the Soonchunhyang University Research Fund.

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors.

Verbal informed consent was obtained from the patient's family.

The authors declare that they have no conflicts of interest.

This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0

Received May 29, 2018

Accepted October 31, 2018

Back to Top | Article Outline

1 Introduction

Langerhans’ cell histiocytosis (LCH), which is also known as histiocytosis X, refers to a clonal proliferative disorder characterized by infiltration of Langerhans cells.[1,2] Although LCH is a rare disorder, multisystem involvement of LCH is relatively common in children; however, it is very rare in adults.[3,4] It has been described using various terms according to the clinical and pathologic findings. Since 1987, Langerhans’ cell histiocytosis has been considered the precise term to present a conglomeration of previous conditions.[3,5,6] The bone is the most common site of LCH involvement, and lung, skin, lymph node, central nervous system (CNS), and liver can also be involved.[7–9] Here, we report a case of LCH that showed the involvement of multiple organs including bone, lung, CNS, and liver in a 31-year-old woman.

Back to Top | Article Outline

2 Case description

This study was approved by the institutional review board of the First Affiliated Hospital of Soonchunhyang University (Cheonan, Republic of Korea). Verbal informed consent was obtained from the patient's family for publication of the case details and the accompanying images. A 31-year-old female presented with left leg pain. She had a history of 20-kg weight gain over 3 months and did not reveal other specific clinical history. Serum levels of eosinophils (7.5%) and C-reactive protein (6.8 mg/L) were elevated. Other laboratory studies were in the normal range: white blood cell count, 8,500/mm3; hemoglobin, 13.6 g/dL; hematocrit, 42.6%; platelet count, 272,000/mm3; total protein, 7.2 g/dL; albumin, 4.4 g/dL; AST, 24 IU/mL; ALT 30 IU/mL; and γ-GTP, 85 IU/mL. The initial X-ray examination showed a well-defined osteolytic lesion in the cortex of the left femur (Fig. 1A). The lesion showed high signal intensity (SI) on T1- and T2-weighted images of magnetic resonance imaging (MRI), respectively (Fig. 1B). Differential diagnoses of the bony lesion were osteoid osteoma, metastasis, and eosinophilic granuloma. Bone scan showed increased activity in the left femur and right temporal bone (Fig. 2), and chest computed tomography (CT) showed multiple cystic lesions with nodules in both lungs (Fig. 3A). The bony lesion was thought to be eosinophilic granuloma associated with LCH due to cystic lesions in the lung. The patient underwent excisional biopsy for the femoral lesion, and a histologic examination demonstrated diffuse infiltration of histiocytes with destruction of bony structure (Fig. 4A). The Langerhans cell was a large cell with indented, grooved, or folded nuclei and eosinophilic cytoplasm. A high level of eosinophils was also noted (Fig. 4B). S-100 (Fig. 4C) and CD1a (Fig. 4D) immunohistochemical staining highlighted the presence of Langerhans cells, and LCH was diagnosed. After histopathological confirmation, systemic evaluation was conducted. Brain MRI demonstrated an enhancing soft tissue in the right temporal bone, which showed increased activity on the bone scan and another enhancing mass in the pituitary stalk (Fig. 5). These lesions were supposed to be due to involvement of LCH. A hormonal examination revealed diabetes insipidus (DI), and previous history of rapid weight gain was considered to be caused by pituitary involvement of LCH. The patient received chemotherapy with vinblastine and prednisolone. Follow-up CT after 6 months showed pneumothorax (Fig. 3B) and 2 fat density lesions were newly discovered in the liver, which were located around the portal vein (Fig. 6A and B). The fat density lesions decreased in size during the follow-up and finally disappeared (Fig. 6C and D). The patient expired after 21 months from initial admission following recurrent episodes of pneumothorax, pneumonia, and sepsis.

Figure 1

Figure 1

Figure 2

Figure 2

Figure 3

Figure 3

Figure 4

Figure 4

Figure 5

Figure 5

Figure 6

Figure 6

Back to Top | Article Outline

3 Discussion

LCH is a rare proliferative disorder, with an incidence 2.6–5.4 cases per million in children; however, the precise incidence of LCH in the general population is not known due to its low prevalence in adults.[3,4] There are 3 clinical variants of LCH according to the involved organ: eosinophilic granuloma, the most common form characterized by a solitary bony lesion; Hand-Schuller-Christian disease, the chronic recurrent form, which classically shows the triad of skull lesion, exophthalmos, and DI; and Letterer-Siwe disease, the fulminant form with multiple organ involvement.[5] LCH is also subdivided into single- and multi-system types according to the number of involved organs.[10] In our case, although only one enhancing lesion in the left femur was pathologically confirmed, typical imaging findings of LCH were observed in lung, pituitary gland, temporal bone, and liver without exophthalmos. Therefore, the LCH in the subject was considered to be the multisystem and fulminant form among clinical variants.

Bone is the most common site of involvement in LCH. Any bone can be involved, but in the majority of cases, LCH involves the skull, rib, spine, and long bone.[5] Osseous LCH usually presents as swelling or pain. Although it typically appears as a lytic bony lesion, radiologic features of LCH depend on the phase of the disease. In the early phase, LCH shows a more aggressive pattern of osteolysis, and the lesion becomes sharply demarcated in the later phase. Remodeling of the bone may cause an expanded appearance, as in our case.[5,11] Bony LCH is relatively common in children; thus, if there is an osteolytic lesion in children and young adults, LCH should be included in the differential diagnosis.

Lung involvement is not a common form of LCH and is associated with smoking.[12] Pulmonary LCH presents as multiple nodules and cysts on high-resolution CT, and these lesions affect the upper and middle lung zones with sparing of lung bases. A previous study described that predominance of the nodular pattern is an early manifestation of pulmonary LCH, whereas a predominant cystic pattern is typically noted in the later phase.[13] According to that study, pulmonary LCH progresses from a cellular nodule to a cavitary nodule and will change into a cyst. In our case, cystic lesions were predominant; therefore, our subject may have been in the later stage of pulmonary LCH. Pneumothorax occurs in about 10% of patients with pulmonary LCH.[12] The differential diagnoses of pulmonary LCH includes lymphangioleiomyomatosis (LAM), which also shows cystic destruction of the lung. However, LAM shows an even distribution of cystic lesions without pulmonary nodules, in contrast, LCH reveals sparing of lung bases.[14]

Our case showed involvement of the pituitary gland, although CNS is an uncommon site of involvement with LCH.[9] The pituitary stalk is the most common site of CNS involvement and is usually associated with DI.[15,16] The imaging finding of hypothalamic involvement varies from mild thickening of the pituitary stalk to a hypothalamic mass.[16] However, sarcoidosis, leukemia, and brain tumors also show a hypothalamic lesion, and it is difficult to differentiate LCH from these disease entities.[16,17] Further evaluation such as bone scan or chest CT may be helpful for discrimination of LCH from other diseases involving the pituitary stalk because isolated CNS involvement is rare in patients with LCH.[16]

Hepatic involvement of LCH is observed in patients with extensive LCH but is rare in adults.[8] There are 4 histologic phases of hepatic LCH with different imaging features: proliferative, granulomatous, xanthomatous, and fibrous phases.[9,11,18] The proliferative and granulomatous phases show periportal infiltration of histiocytes and inflammation, and they present as a hypodense lesion on CT and show low and high SI on T1- and T2-weighted images of MRI, respectively.[19] The xanthomatous phase is characterized by periportal fatty lesion due to the lipid-rich character of histiocytes, therefore CT demonstrates fat density lesions in the xanthomatous phase.[8] In the fibrous phase, biliary cirrhosis develops owing to sclerosing cholangitis.[18] Our case was considered to be in the xanthomatous phase of hepatic LCH. Hepatic involvement is usually seen in patients with extensive LCH and is a poor prognostic factor.[20] Our subject expired 15 months after the detection of hepatic fat density lesions, although fat density lesions had disappeared during follow-up.

In summary, we describe a case of LCH involving the bone, lung, CNS, and liver. In each imaging feature in 1 organ, it is occasionally difficult to discriminate LCH from other disorders. Therefore, systemic evaluation is needed when LCH is suspected. Familiarity with the various features of LCH on imaging is paramount for diagnosing and managing patients in daily practice.

Back to Top | Article Outline

Author contributions

All authors contributed to the patient care, had access to the data, and played a role in writing this manuscript.

Conceptualization: Seung Soo Kim

Data curation: Seung Soo Kim and Soon Auck Hong

Investigation: Seung Soo Kim and Soon Auck Hong

Methodology: Jeong Ah Hwang

Resources: Sung Shick Jou

Supervision: Hyeong Cheol Shin

Writing – original draft: Seung Soo Kim

Writing – review & editing: Seung Soo Kim, Seo-Youn Choi

Seung Soo Kim orcid: 0000-0002-1763-8217.

Back to Top | Article Outline

References

[1]. Osband M, Histiocytosis X. Langerhans’ cell histiocytosis. Hematol Oncol Clin North AmV 1 1987;737–51.
[2]. Heerde P, Egeler R. The cytology of Langerhans cell histiocytosis (histiocytosis X). Cytopathology 1991;2:149–58.
[3]. Broadbent V, Egeler R, Nesbit M Jr. Langerhans cell histiocytosis--clinical and epidemiological aspects. Br J Cancer Suppl 1994;23:S11–6.
[4]. Bhatia S, Nesbit ME, Egeler M, et al. Epidemiologic study of Langerhans cell histiocytosis in children. J Pediatr 1997;130:774–84.
[5]. Stull MA, Kransdorf MJ, Devaney K. Langerhans cell histiocytosis of bone. Radiographics 1992;12:801–23.
[6]. Broadbent V, Gadner H, Komp DM, et al. Histiocytosis syndromes in children: II. Approach to the clinical and laboratory evaluation of children with Langerhans cell histiocytosis. Medical Pediatr Oncol 1989;17:492–5.
[7]. Mampaey S, Warson F, Van Hedent E, et al. Imaging findings in Langerhans’ cell histiocytosis of the liver and the spleen in an adult. Eur Radiol 1999;9:96–8.
[8]. Radin DR. Langerhans cell histiocytosis of the liver: imaging findings. AJR Am J Roentgenol 1992;159:63–4.
[9]. Schmidt S, Eich G, Hanquinet S, et al. Extra-osseous involvement of Langerhans’ cell histiocytosis in children. Pediatr Radiol 2004;34:313–21.
[10]. Abla O, Egeler RM, Weitzman S. Langerhans cell histiocytosis: current concepts and treatments. Cancer Treat Rev 2010;36:354–9.
[11]. Kilborn T, Teh J, Goodman T. Paediatric manifestations of Langerhans cell histiocytosis: a review of the clinical and radiological findings. Clin Radiol 2003;58:269–78.
[12]. Vassallo R, Ryu JH, Schroeder DR, et al. Clinical outcomes of pulmonary Langerhans’-cell histiocytosis in adults. N Engl J Med 2002;346:484–90.
[13]. Brauner M, Grenier P, Mouelhi M, et al. Pulmonary histiocytosis X: evaluation with high-resolution CT. Radiology 1989;172:255–8.
[14]. Abbott GF, Rosado-de-Christenson ML, Frazier AA, et al. Lymphangioleiomyomatosis: radiologic-pathologic correlation 1. Radiographics 2005;25:803–28.
[15]. Grois N, Prayer D, Prosch H, et al. Neuropathology of CNS disease in Langerhans cell histiocytosis. Brain 2005;128:829–38.
[16]. Prayer D, Grois N, Prosch H, et al. MR imaging presentation of intracranial disease associated with Langerhans cell histiocytosis. Am J Neuroradiol 2004;25:880–91.
[17]. Saleem SN, Said A-HM, Lee DH. Lesions of the hypothalamus: MR imaging diagnostic features 1. Radiographics 2007;27:1087–108.
[18]. König CW, Pfannenberg C, Trübenbach J, et al. MR cholangiography in the diagnosis of sclerosing cholangitis in Langerhans’ cell histiocytosis. Eur Radiol 2001;11:2516–20.
[19]. Wong A, Ortiz-Neira CL, Reslan WA, et al. Liver involvement in Langerhans cell histiocytosis. Pediatr Radiol 2006;36:1105–7.
[20]. Donadieu J. A multicentre retrospective survey of Langerhans’ cell histiocytosis: 348 cases observed between 1983 and 1993. The French Langerhans’ cell histiocytosis study group. Arch Dis Child 1996;75:17–24.
Keywords:

bone and bones; histiocytosis, Langerhans’ cell; liver; lung; pituitary gland

Copyright © 2018 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.