- Email: [email protected]
Langerhans cell histiocytosis with disseminated skeletal involvement in a neonate
European Journal of Radiology Extra 77 (2011) e85–e88
Contents lists available at ScienceDirect
European Journal of Radiology Extra journal homepage: intl.elsevierhealth.com/journals/ejrex
Langerhans cell histiocytosis with disseminated skeletal involvement in a neonate Da-Mi Kim a , Kyu Soon Kim a,∗ , Hyun Young Han a , Tong Jin Chun a , Seoung Oh Yang a , In Kyu Yu a , Hye Kyung Lee b a b
Department of Radiology, Eulji University Hospital, 1306 Dunsan-dong, Seo-gu, Daejeon 302-799, South Korea Department of Pathology, Eulji University Hospital, 1306 Dunsan-dong, Seo-gu, Daejeon 302-799, South Korea
a r t i c l e
i n f o
Article history: Received 9 November 2010 Accepted 22 December 2010
Keywords: Langerhans cell histiocytosis Neonate Bone scintigraphy Thymus
a b s t r a c t A female baby was admitted to our hospital with an immobilized right arm. The baby had multiple osteolytic lesions without sclerotic borders in the metaphyses and diaphyses in long bones of both arms, but she had not any mucocutaneous symptoms and signs at all. In this case report, we discuss the differential diagnoses of neonatal multiple osteolytic lesions, and osseous and extraosseous imaging features of neonatal Langerhans cell histiocytosis (LCH). © 2011 Elsevier Ireland Ltd. All rights reserved.
1. Introduction Multiple osteolytic lesions in a neonate is a rare finding with a poor prognosis [1]. Until now, neonatal LCH with disseminated skeletal involvement without skin lesions has not been reported in the literature. Therefore, we report a rare case of a multiple skeletal form of LCH in a neonate without mucocutaneous lesions. 2. Case report The baby girl was born by normal vaginal delivery at 38 weeks gestation to a healthy mother. The birth weight was 2700 g. The baby was brought to our hospital at 55 days of life with an immobilized right arm, which had been injured when her older sister pulled on her forearm. Radiographs showed multiple osteolytic lesions in the metaphyses and diaphyses in both arms and clavicles, as well as a pathologic fracture with callus formation in the right proximal humerus (Fig. 1a). Radiographs of the femurs showed multifocal osteolytic lesions involving the pelvis and femurs with diffuse periosteal reaction along the both femoral shafts (Fig. 1b). Radiographs of the skull revealed three osteolytic lesions in the parietal bones bilaterally, and the right anterior frontal bone (Fig. 1c). The vital signs were normal and there was no fever,
∗ Corresponding author. Tel.: +82 42 611 3565; fax: +82 42 611 3590. E-mail address: [email protected] (K.S. Kim). 1571-4675/$ – see front matter © 2011 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ejrex.2010.12.015
mucocutaneous lesions, hepatosplenomegaly, or lymphadenopathy. The results of the initial laboratory evaluation were as follows: white blood cell (WBC), 13,560/L; platelet count, 4,851,000/L; aspartate aminotransferase (AST)/alanine aminotransferase (ALT), 64/194 IU/L; alkaline phosphatase (ALP), 796 IU/L; and lactate dehydrogenase (LDH), 538 IU/L. We considered that the common causes of multifocal, permeative, osteolytic lesions in early childhood included neuroblastoma metastasis, leukemia/lymphoma, and LCH. Therefore, an abdominal computed tomography (CT) was performed to rule out a neuroblastoma, and showed normal findings, including both kidneys, the liver, and spleen. A routine chest radiograph showed mediastinal widening and a few focal osteolytic lesions in the right 7th, 9th ribs (Fig. 1d). To clarify this finding, a chest CT was done, which showed a huge, lobulated contoured, mildly enhancing mass in the anterior mediastinum with no internal calcifications or co-existing pulmonary abnormalities (Fig. 1e). The anterior mediastinal mass had similar attenuation of the normal thymus, which was draped over the anterior cardiac border. These CT scan findings were consistent with thymic involvement of LCH. Bone scintigraphy showed multifocal increased radiotracer uptake in the humeri, radii, ulnas, pelvis, femurs, tibias, and multiple ribs, but there was no increased uptake in the osteolytic lesion of skull (Fig. 2a). A bone biopsy from the right proximal humerus was performed. Histopathologic examination of the biopsy specimen revealed proliferation of histiocytes with infiltration of multiple inflammatory cells (mainly eosinophils and macrophages). Based on an immunohistochemical study, Langer-
e86
D.-M. Kim et al. / European Journal of Radiology Extra 77 (2011) e85–e88
Fig. 1. (a) Radiographs show multiple osteolytic lesions with nonsclerotic borders in the metaphyses and diaphyses of both arms. There are no remarkable periosteal reaction or epiphyseal involvement. Right proximal humeral meta-diaphysis with an osteolytic lesion (measuring approximately 2.0 cm × 1.1 cm) and pathologic fracture with callus formation were seen (arrow). (b) Radiograph shows multifocal osteolytic lesions without sclerotic margins involving the pelvis and femurs with diffuse periosteal reactions along the both femoral shafts. (c) Radiograph of the skull shows single lucent LCH lesion in the right anterior frontal bone. (d) Chest radiograph shows mediastinal widening (long arrows) and a few focal osteolytic lesions in the right 7th, 9th ribs (short arrows). (e) Enhanced chest CT scans (mediastinal window setting, window width, 400H; window level, 40H) shows a relatively homogeneous, smooth contoured, enhancing upper anterior mediastinal mass without internal calcifications, features suggestive of thymic involvement.
hans cells were immunoreactive for CD1a and S100 protein (Fig. 2b and c). After the pathologic diagnosis was established, the chemotherapeutic regimen, which consisted of prednisolone and vincristine, was administered for 3 months. Treatment was welltolerated. 3-month later, a follow-up chest and bone radiographs showed decreased size of osteolytic lesions with sclerotic rim compared with the initial radiograph, and there was no new mucocutaneous lesions. Laboratory findings, including ALP and LDH, showed improvement. We concluded that the baby girl is at low risk of long term sequelae or recurrence.
3. Discussion LCH, a rare disease that occurs mainly in children, may produce a wide range of manifestations, including osseous and extraosseous involvement. The peak age of onset is between 1 and 3 years of age [2]. In our case, we presumed that the age of onset was the neonatal period because the child could not complain of discomfort and the initial radiographs showed callus formation of the pathologic fracture involving the right humerus. Letterer–Siwe disease is an acute or subacute disseminated form of LCH that occurs in children < 2 years of age. There is an initially acute onset of skin eruptions, and later onset of generalized lymphadenopathy, hepatosplenomegaly,
D.-M. Kim et al. / European Journal of Radiology Extra 77 (2011) e85–e88
e87
Fig. 2. (a) Bone scintigraphy shows multifocal increased radiotracer uptake in the both humeri, radii, ulnas, pelvis, femurs, tibias, and multiple ribs, but there are no increased uptake in the skull lesion. It is postulated that small lesion (<1 cm) or pure osteolytic lesion without osteoblastic activity. (b) Photomicrograph (original magnification, 400×; hematoxylin–eosin stain) shows a proliferation of Langerhans cells, which are characterized by a moderate amount of eosinophilic cytoplasm, elongated kidney-shaped nuclei, and a nuclear groove. The Langerhans cells are associated with numerous eosinophils, occasional macrophages, and lymphocytes. (c) Photomicrograph obtained at immunohistochemical staining with antibodies to CD1a, a glycoprotein antigen at the cellular surface shows abundant Langerhans cells (brown-stained areas).
pulmonary involvement [1,3]. Although there was disseminated bone involvement in our case, there was no mucocutaneous involvement. The most commonly involved sites of LCH are the bones of the skull, long tubular bones of the extremities, ribs, vertebrae [4]. LCH rarely affects the epiphyses and the most commonly affected regions of long tubular bones in this disorder are metaphyses and diaphyses [4], with equal frequency in our case. The early phase of bone lesions depicted by scintigraphy more easily demonstrates the full extent of skeletal involvement. As in our case, failure to detect skull lesions has been reported occasionally. It has been postulated that the quiescent lesions or healed states of LCH are probably fibrous in nature without any activity of the histiocytic process [5,6]. Recognition of the extent of bone involvement is important in establishing a diagnosis and in determining management, therefore scintigraphy should be employed in the initial work-up [5,6]. Thymic involvement in LCH has been reported infrequently [2]. Typical radiologic features are diffuse, heterogeneous, hypoattenuated mass lesions with punctate or serpentine calcifications or enhancing internal septa [3,7,8]. In many cases of thymic involvement, there are co-existing pulmonary abnormalities [2]. In our case, atypical manifestations of thoracic involvement were noted, such as a smooth lobulated, extensively homogeneous, hypoattenuated thymic lesion without internal calcifications, cystic changes, or co-existing pulmonary involvement. Uninvolved lung parenchyma can be explained by the relatively early detection of the disease.
Treatment of LCH includes surgery, oral, topical, and intravenous medications and chemotherapy or radiation therapy, depending on the site and extent of disease [9]. The recommended duration of therapy is 6 months for patients who require chemotherapy for bone, skin, or lymph node involvement of LCH. If multifocal bone lesions are involved, standard treatment options area as follows: 6 months of treatment with weekly vinblastine for 7 weeks, then every 3 weeks to achieve a good response [10]. The prognosis depends chiefly upon involvement of multiple organ systems, and also upon the response to chemotherapy during the initial 6 weeks of treatment [10]. Early diagnosis for disseminated osseous lesions without characteristic mucocutaneous lesions in a neonate is a challenge. The sooner neonatal LCH is diagnosed, the better are the chances for overcoming it. Therefore, to facilitate diagnosis at an early stage of LCH, radiologists must recognize the individual clinical findings, as well as the relevance of imaging features of neonatal LCH. Conflict of interest None declared. References [1] Donnelly LF. Pediatric imaging. 1st ed. Saunders Elsevier; 2009. [2] Schmidt S, Eich G, Geoffray A, et al. Extraosseous Langerhans cell histiocytosis in children. Radiographics 2008;28:707–26. [3] Writing Group of the Histiocyte Society. Histiocytosis syndromes in children. Lancet 1987;1:208–9.
e88
D.-M. Kim et al. / European Journal of Radiology Extra 77 (2011) e85–e88
[4] Caballes RL, Caballes Jr RA, McKeon JJ. Langerhans cell histiocytosis involving epiphysis of al long bone. Ann Diagn Pathol 2004;8:91–5. [5] Van Nienwenhuyse JP, Clapuyt P, Malghem J, et al. Radiographic skeletal survey and radionuclide bone scan in Langerhans cell histiocytosis of bone. Pediatr Radiol 1996;26:734–8. [6] Howarth DM, Mullan BP, Wiseman GA, Wenger DE, Forstorm LA, Dunn WL. Bone scintigraphy evaluated in diagnosing and staging Langerhans cell histiocytosis and related disorders. J Nucl Med 1996;37: 1456–60.
[7] Junewick JJ, Fitzgerald NE. The thymus in Langerhans cell histiocytosis. Pediatr Radiol 1999;29:904–7. [8] Sumner TE, Auringer ST, Preston AA. Thymic calcifications in histiocytosis X. Pediatr Radiol 1993;23:204–5. [9] Allen CE, McCain KL. Langerhans cell histiocytosis: a review of past, current, and future therapies. Drugs Today 2007;43:627–43. [10] Elizabeth K, Satter MPH, High WA. Langerhans cell histiocytosis: a review of the current recommendations of the histiocyte society. Pediatric Dermatol 2008;25:291–5.
Contents lists available at ScienceDirect
European Journal of Radiology Extra journal homepage: intl.elsevierhealth.com/journals/ejrex
Langerhans cell histiocytosis with disseminated skeletal involvement in a neonate Da-Mi Kim a , Kyu Soon Kim a,∗ , Hyun Young Han a , Tong Jin Chun a , Seoung Oh Yang a , In Kyu Yu a , Hye Kyung Lee b a b
Department of Radiology, Eulji University Hospital, 1306 Dunsan-dong, Seo-gu, Daejeon 302-799, South Korea Department of Pathology, Eulji University Hospital, 1306 Dunsan-dong, Seo-gu, Daejeon 302-799, South Korea
a r t i c l e
i n f o
Article history: Received 9 November 2010 Accepted 22 December 2010
Keywords: Langerhans cell histiocytosis Neonate Bone scintigraphy Thymus
a b s t r a c t A female baby was admitted to our hospital with an immobilized right arm. The baby had multiple osteolytic lesions without sclerotic borders in the metaphyses and diaphyses in long bones of both arms, but she had not any mucocutaneous symptoms and signs at all. In this case report, we discuss the differential diagnoses of neonatal multiple osteolytic lesions, and osseous and extraosseous imaging features of neonatal Langerhans cell histiocytosis (LCH). © 2011 Elsevier Ireland Ltd. All rights reserved.
1. Introduction Multiple osteolytic lesions in a neonate is a rare finding with a poor prognosis [1]. Until now, neonatal LCH with disseminated skeletal involvement without skin lesions has not been reported in the literature. Therefore, we report a rare case of a multiple skeletal form of LCH in a neonate without mucocutaneous lesions. 2. Case report The baby girl was born by normal vaginal delivery at 38 weeks gestation to a healthy mother. The birth weight was 2700 g. The baby was brought to our hospital at 55 days of life with an immobilized right arm, which had been injured when her older sister pulled on her forearm. Radiographs showed multiple osteolytic lesions in the metaphyses and diaphyses in both arms and clavicles, as well as a pathologic fracture with callus formation in the right proximal humerus (Fig. 1a). Radiographs of the femurs showed multifocal osteolytic lesions involving the pelvis and femurs with diffuse periosteal reaction along the both femoral shafts (Fig. 1b). Radiographs of the skull revealed three osteolytic lesions in the parietal bones bilaterally, and the right anterior frontal bone (Fig. 1c). The vital signs were normal and there was no fever,
∗ Corresponding author. Tel.: +82 42 611 3565; fax: +82 42 611 3590. E-mail address: [email protected] (K.S. Kim). 1571-4675/$ – see front matter © 2011 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ejrex.2010.12.015
mucocutaneous lesions, hepatosplenomegaly, or lymphadenopathy. The results of the initial laboratory evaluation were as follows: white blood cell (WBC), 13,560/L; platelet count, 4,851,000/L; aspartate aminotransferase (AST)/alanine aminotransferase (ALT), 64/194 IU/L; alkaline phosphatase (ALP), 796 IU/L; and lactate dehydrogenase (LDH), 538 IU/L. We considered that the common causes of multifocal, permeative, osteolytic lesions in early childhood included neuroblastoma metastasis, leukemia/lymphoma, and LCH. Therefore, an abdominal computed tomography (CT) was performed to rule out a neuroblastoma, and showed normal findings, including both kidneys, the liver, and spleen. A routine chest radiograph showed mediastinal widening and a few focal osteolytic lesions in the right 7th, 9th ribs (Fig. 1d). To clarify this finding, a chest CT was done, which showed a huge, lobulated contoured, mildly enhancing mass in the anterior mediastinum with no internal calcifications or co-existing pulmonary abnormalities (Fig. 1e). The anterior mediastinal mass had similar attenuation of the normal thymus, which was draped over the anterior cardiac border. These CT scan findings were consistent with thymic involvement of LCH. Bone scintigraphy showed multifocal increased radiotracer uptake in the humeri, radii, ulnas, pelvis, femurs, tibias, and multiple ribs, but there was no increased uptake in the osteolytic lesion of skull (Fig. 2a). A bone biopsy from the right proximal humerus was performed. Histopathologic examination of the biopsy specimen revealed proliferation of histiocytes with infiltration of multiple inflammatory cells (mainly eosinophils and macrophages). Based on an immunohistochemical study, Langer-
e86
D.-M. Kim et al. / European Journal of Radiology Extra 77 (2011) e85–e88
Fig. 1. (a) Radiographs show multiple osteolytic lesions with nonsclerotic borders in the metaphyses and diaphyses of both arms. There are no remarkable periosteal reaction or epiphyseal involvement. Right proximal humeral meta-diaphysis with an osteolytic lesion (measuring approximately 2.0 cm × 1.1 cm) and pathologic fracture with callus formation were seen (arrow). (b) Radiograph shows multifocal osteolytic lesions without sclerotic margins involving the pelvis and femurs with diffuse periosteal reactions along the both femoral shafts. (c) Radiograph of the skull shows single lucent LCH lesion in the right anterior frontal bone. (d) Chest radiograph shows mediastinal widening (long arrows) and a few focal osteolytic lesions in the right 7th, 9th ribs (short arrows). (e) Enhanced chest CT scans (mediastinal window setting, window width, 400H; window level, 40H) shows a relatively homogeneous, smooth contoured, enhancing upper anterior mediastinal mass without internal calcifications, features suggestive of thymic involvement.
hans cells were immunoreactive for CD1a and S100 protein (Fig. 2b and c). After the pathologic diagnosis was established, the chemotherapeutic regimen, which consisted of prednisolone and vincristine, was administered for 3 months. Treatment was welltolerated. 3-month later, a follow-up chest and bone radiographs showed decreased size of osteolytic lesions with sclerotic rim compared with the initial radiograph, and there was no new mucocutaneous lesions. Laboratory findings, including ALP and LDH, showed improvement. We concluded that the baby girl is at low risk of long term sequelae or recurrence.
3. Discussion LCH, a rare disease that occurs mainly in children, may produce a wide range of manifestations, including osseous and extraosseous involvement. The peak age of onset is between 1 and 3 years of age [2]. In our case, we presumed that the age of onset was the neonatal period because the child could not complain of discomfort and the initial radiographs showed callus formation of the pathologic fracture involving the right humerus. Letterer–Siwe disease is an acute or subacute disseminated form of LCH that occurs in children < 2 years of age. There is an initially acute onset of skin eruptions, and later onset of generalized lymphadenopathy, hepatosplenomegaly,
D.-M. Kim et al. / European Journal of Radiology Extra 77 (2011) e85–e88
e87
Fig. 2. (a) Bone scintigraphy shows multifocal increased radiotracer uptake in the both humeri, radii, ulnas, pelvis, femurs, tibias, and multiple ribs, but there are no increased uptake in the skull lesion. It is postulated that small lesion (<1 cm) or pure osteolytic lesion without osteoblastic activity. (b) Photomicrograph (original magnification, 400×; hematoxylin–eosin stain) shows a proliferation of Langerhans cells, which are characterized by a moderate amount of eosinophilic cytoplasm, elongated kidney-shaped nuclei, and a nuclear groove. The Langerhans cells are associated with numerous eosinophils, occasional macrophages, and lymphocytes. (c) Photomicrograph obtained at immunohistochemical staining with antibodies to CD1a, a glycoprotein antigen at the cellular surface shows abundant Langerhans cells (brown-stained areas).
pulmonary involvement [1,3]. Although there was disseminated bone involvement in our case, there was no mucocutaneous involvement. The most commonly involved sites of LCH are the bones of the skull, long tubular bones of the extremities, ribs, vertebrae [4]. LCH rarely affects the epiphyses and the most commonly affected regions of long tubular bones in this disorder are metaphyses and diaphyses [4], with equal frequency in our case. The early phase of bone lesions depicted by scintigraphy more easily demonstrates the full extent of skeletal involvement. As in our case, failure to detect skull lesions has been reported occasionally. It has been postulated that the quiescent lesions or healed states of LCH are probably fibrous in nature without any activity of the histiocytic process [5,6]. Recognition of the extent of bone involvement is important in establishing a diagnosis and in determining management, therefore scintigraphy should be employed in the initial work-up [5,6]. Thymic involvement in LCH has been reported infrequently [2]. Typical radiologic features are diffuse, heterogeneous, hypoattenuated mass lesions with punctate or serpentine calcifications or enhancing internal septa [3,7,8]. In many cases of thymic involvement, there are co-existing pulmonary abnormalities [2]. In our case, atypical manifestations of thoracic involvement were noted, such as a smooth lobulated, extensively homogeneous, hypoattenuated thymic lesion without internal calcifications, cystic changes, or co-existing pulmonary involvement. Uninvolved lung parenchyma can be explained by the relatively early detection of the disease.
Treatment of LCH includes surgery, oral, topical, and intravenous medications and chemotherapy or radiation therapy, depending on the site and extent of disease [9]. The recommended duration of therapy is 6 months for patients who require chemotherapy for bone, skin, or lymph node involvement of LCH. If multifocal bone lesions are involved, standard treatment options area as follows: 6 months of treatment with weekly vinblastine for 7 weeks, then every 3 weeks to achieve a good response [10]. The prognosis depends chiefly upon involvement of multiple organ systems, and also upon the response to chemotherapy during the initial 6 weeks of treatment [10]. Early diagnosis for disseminated osseous lesions without characteristic mucocutaneous lesions in a neonate is a challenge. The sooner neonatal LCH is diagnosed, the better are the chances for overcoming it. Therefore, to facilitate diagnosis at an early stage of LCH, radiologists must recognize the individual clinical findings, as well as the relevance of imaging features of neonatal LCH. Conflict of interest None declared. References [1] Donnelly LF. Pediatric imaging. 1st ed. Saunders Elsevier; 2009. [2] Schmidt S, Eich G, Geoffray A, et al. Extraosseous Langerhans cell histiocytosis in children. Radiographics 2008;28:707–26. [3] Writing Group of the Histiocyte Society. Histiocytosis syndromes in children. Lancet 1987;1:208–9.
e88
D.-M. Kim et al. / European Journal of Radiology Extra 77 (2011) e85–e88
[4] Caballes RL, Caballes Jr RA, McKeon JJ. Langerhans cell histiocytosis involving epiphysis of al long bone. Ann Diagn Pathol 2004;8:91–5. [5] Van Nienwenhuyse JP, Clapuyt P, Malghem J, et al. Radiographic skeletal survey and radionuclide bone scan in Langerhans cell histiocytosis of bone. Pediatr Radiol 1996;26:734–8. [6] Howarth DM, Mullan BP, Wiseman GA, Wenger DE, Forstorm LA, Dunn WL. Bone scintigraphy evaluated in diagnosing and staging Langerhans cell histiocytosis and related disorders. J Nucl Med 1996;37: 1456–60.
[7] Junewick JJ, Fitzgerald NE. The thymus in Langerhans cell histiocytosis. Pediatr Radiol 1999;29:904–7. [8] Sumner TE, Auringer ST, Preston AA. Thymic calcifications in histiocytosis X. Pediatr Radiol 1993;23:204–5. [9] Allen CE, McCain KL. Langerhans cell histiocytosis: a review of past, current, and future therapies. Drugs Today 2007;43:627–43. [10] Elizabeth K, Satter MPH, High WA. Langerhans cell histiocytosis: a review of the current recommendations of the histiocyte society. Pediatric Dermatol 2008;25:291–5.