Pathology – Research and Practice 210 (2014) 318–320
Contents lists available at ScienceDirect
Pathology – Research and Practice journal homepage: www.elsevier.com/locate/prp
Teaching Cases
Pulmonary rhabdomyomatous dysplasia of the newborn in neurofibromatosis type 1 Kazuhito Hatanaka, Takako Yoshioka, Takashi Tasaki, Akihide Tanimoto ∗ Department of Molecular and Cellular Pathology, Kagoshima University Graduate School of Medical and Dental Sciences, Japan
a r t i c l e
i n f o
Article history: Received 10 July 2013 Received in revised form 2 October 2013 Accepted 29 October 2013 Keywords: Lung New born Rhabdomyomatous dysplasia Neurofibromatosis type 1
a b s t r a c t Proliferation of non-neoplastic striated muscle cells in the lung is rare and has been frequently observed in cases of cardiovascular and pulmonary congenital malformations. We present an extremely rare case of pulmonary rhabdomyomatous dysplasia (RD) in neurofibromatosis type 1 (NF-1). A male neonate was born at 35 weeks’ gestation after normal pregnancy. Postnatally, besides patent ductus arteriosus and posterior mediastinal mass, abnormal cystic lesions in the left upper and lower lung were detected. No bronchial atresia and stenosis were identified. Partial lobectomy specimens showed hypoplastic lung parenchyma with cystic lesions resembling terminal bronchioles and distinctive proliferation of non-neoplastic striated muscle fibers in the interstitium. The posterior mediastinal mass consisted of neurofibroma. Considering that café au lait spots and freckling occurred at 2 months of age, a diagnosis of NF-1 was made. The patient died of aspiration pneumonia at the age of 30 months. To the best of our knowledge, this is the first case of pulmonary RD in NF-1. © 2013 Elsevier GmbH. All rights reserved.
Introduction The presence of non-neoplastic striated muscle fibers in the lung is an extremely rare finding, and only few reports have described non-neoplastic striated muscle proliferation in the lung [1]. In 1974, Remberger reported an autopsy case of a 4-month-old male infant with diffuse involvement of cross-striated muscle tissue of a different maturity grade in the alveolar septa and bronchial wall of the hypoplastic lung as pulmonary rhabdomyomatous dysplasia (RD) [11]. A few similar cases have been subsequently reported [7–10]. Most cases are associated with multiple visceral abnormalities, including major cardiovascular and pulmonary malformations, with usually poor prognoses. Here, we present an exceedingly rare case of RD of the lung in a newborn with no other pulmonary malformations; the patient remained free of disease at age of 30 months after partial lobectomy. Moreover, the infant was found to have neurofibromatosis type 1 (NF-1). Case report A 2824 g male infant was born at 35 weeks’ gestation after a normal pregnancy and delivery. No relevant family history was
∗ Corresponding author at: 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan. Tel.: +81 99 275 5263; fax: +81 99 264 6348. E-mail address: [email protected] (A. Tanimoto). 0344-0338/$ – see front matter © 2013 Elsevier GmbH. All rights reserved. http://dx.doi.org/10.1016/j.prp.2013.10.008
found. Routine antenatal examinations revealed no abnormalities. At 11 days of age, the infant presented with tachypnea and cyanosis. Chest computed tomographic images showed ill-defined parenchymal lesions showing cystic structures in the left upper and lower lobes. A posterior mediastinum mass-like lesion was also detected. No bronchial atresia and stenosis were identified. No other abnormalities were detected, except for patent ductus arteriosus (PDA). Partial lobectomy and mediastinal mass resection were performed. The infant made an uneventful postoperative recovery. At 2 months of age, more than 6 café au lait spots larger than 5 mm in greatest diameter were identified in the trunk and lower extremities, and freckling was also detected in the inguinal regions. Although an analysis for NF-1 gene was not performed, NF-1 was diagnosed according to the criteria of NF-1 in postnatal testing [13]. The patient received follow-up care at an outpatient clinic, and intervention treatment for PDA was not performed. He died because of aspiration pneumonia at the age of 30 months. Death due to aspiration pneumonia in this age group is considered rather unusual. However, the details were unclear because autopsy was not performed. Materials and methods Resected specimens were fixed in 10% buffered formalin, embedded in paraffin, and cut into 4 m sections. In addition to hematoxylin and eosin (H&E) staining and phosphotungstic acid hematoxylin (PTAH) staining, desmin, muscle-specific actin, myoglobin, smooth muscle actin and S-100 protein
K. Hatanaka et al. / Pathology – Research and Practice 210 (2014) 318–320
319
Fig. 1. Macroscopic and loupe images. (a) The firm area located on one edge of the resected lower lung (dotted line). (b) The firm area is composed of abnormal parenchyma including the bronchus (H&E). (c) No apparent fibrotic lesion is present in the firm area (Elastica-Masson trichrome). (d) Immunohistochemistry for muscle-specific actin showing the proliferation of muscle tissue in the firm area.
immunohistochemical studies were performed using mouse monoclonal antibodies D33 (Dako, Glostrup, Denmark), HHF35 (Enzo, New York, USA), MYO18 (Novocastra, Newcastle Upon Tyne, UK), ␣sm-1 (Novocastra) and the rabbit polyclonal antibody Z0311 (Dako), respectively. Results The resected left upper and lower lobes showed similar findings. Macroscopically, a firm area, approximately 3.5 cm in diameter, was observed at one edge of the resected lower lung (Fig. 1a). Loupe images revealed that the firm area was composed of abnormal parenchyma including bronchus (Fig. 1b), and fibrosis was unclear (Fig. 1c). Moreover, the proliferation of muscle tissue was recognized in the firm area (Fig. 1d). No abnormal vessels were identified. Microscopic examination revealed that the firm area consisted of hypoplastic parenchyma and multiple cystic lesions resembling terminal bronchioles. The irregularly shaped cystic lesions were lined by ciliated cuboidal to columnar respiratorytype epithelium. In the broadening interstitium, abundant bundles of striated muscle fibers were present (Fig. 2), which were fairly uniform in thickness but varied in length (Fig. 3a). The muscle fiber had eosinophilic cytoplasm, and well-developed cross striations were revealed by PTAH staining (Fig. 3b). Most nuclei were located peripherally, but some were located centrally. No cytological atypia, mitotic figures and necrosis were identified. Small lymphocyte and plasma cell infiltration were observed in the interstitium. Immunohistochemical staining demonstrated desmin, muscle-specific actin, and myoglobin positivity in the muscle fibers, and the striking features of the widespread distribution of the striated muscle fibers in the interstitium (Fig. 4). The posterior mediastinal mass was composed of loosely arranged spindle-shaped cells showing a fascicular and wavy growth
Fig. 2. Numerous strands of striated muscle fibers distributed in the hypoplastic lung parenchyma (H&E; ×100).
pattern with fibroblasts and collagen fibers. The tumor cells showed no cytological atypia and mitosis. In the immunohistochemical study, the tumor cells were found to be positive for S-100 protein. These features were considered to be neurofibroma (not shown). Discussion Only a few cases of pulmonary RD or similar disorders have been reported in the English literature [7–11], and these cases showed multiple visceral malformations, including cardiovascular and/or lung abnormalities, except two cases [7,10]. On the other hand, it is questionable to make a diagnosis of RD by the existence of striated
Fig. 3. (a) Large numbers of irregular bundles of striated muscle fibers localized in the pulmonary interstitium (H&E; ×200). (b) The muscle fibers had well-developed cross striations (PTAH; ×400).
320
K. Hatanaka et al. / Pathology – Research and Practice 210 (2014) 318–320
Fig. 4. Striated muscle fibers exhibiting immunopositivity with muscle-specific actin and striking features of widespread distribution in the interstitium (×200).
muscle cells [5], as the proliferation of striated muscle tissues was identified in abnormal congenital lungs, such as horseshoe lung, incomplete lobation, hypoplasia, and hypoplastic lung of congenital diaphragmatic hernia [6]. Moreover, Fraggetta reported 5 cases of striated muscle cell proliferation in a review of a series of 31 cases of congenital non-neoplastic lung abnormalities, including congenital cystic adenomatoid malformation (CCAM) type II and pulmonary sequestration [6]. In the cases reviewed by Fraggetta, striated muscle cell proliferation was diffused in 3 and focal in 2 cases. Our case had no other pulmonary malformations, and histological examination demonstrated numerous bundles of striated muscle fibers distributed in a random manner in the lung interstitium, not isolated muscle strands in the pulmonary parenchyma between the cysts and alveolus-like structures as seen in CCAM [7]. Although the exact number of striated muscle cells needed to distinguish RD from a simple presence of striated muscle cells in the lung interstitium remains unclear, the presence of RD as a distinct entity is supported by its association with multiple visceral malformations [5]. It is of interest that no other lung abnormalities were observed in the present case. The origin of the striated muscle cells in the lung interstitium is also unclear. It has been proposed that it originates from the misplaced striated muscle tissue of the pharynx, esophagus, or diaphragm as a developmental error [11]. The possibility of cardiac origin was also suggested; however, it was denied by immunohistochemical and electron microscopic analyses [3]. Some authors favor the hypothesis of myoblastic differentiation of primitive mesenchymal cells or metaplastic transformation of pluripotent mesenchymal cells, which develop into rhabdomyomatous cells in postnatal life [12]. Our case was complicated with NF-1. To the best of our knowledge, no other case reports on RD and similar disorders of striated muscle cells proliferation in the non-neoplastic lung interstitium associated with NF-1 have been published. Diffuse lung disease is known as a pulmonary manifestation in NF-1, characterized by upper lobe cystic and bullous disease and basilar fibrosis [15]. Moreover, the occurrence of primary pulmonary rhabdomyosarcoma in childhood is suggested to be associated with NF-1 [14]. Although the pathogenesis of primary pulmonary rhabdomyosarcoma in NF-1 is unknown [2], myoblastic differentiation of primitive mesenchymal cells in the lung interstitium is suggested to be associated with rhabdomyosarcoma in NF-1 [4]. Aside from NF-1, the presence of striated muscle tissues was proposed as the origin of rhabdomyosarcoma, which may be the result of
displacement from adjacent organs such as the esophagus or pharynx in early fetal life, and the presence of striated smooth muscle fibers, including RD, may present as the first stage in the development of a primary pulmonary rhabdomyosarcoma [6,9]. We were unable to prove the definite relationship between RD and NF-1 in this case; however, our case is notably interesting when we consider the pathogenesis of primary pulmonary rhabdomyosarcoma associated with NF-1. Among the previously reported cases of RD, most were associated with major pulmonary and/or cardiovascular malformations, which are life threatening. Only one case survived after partial lobectomy, and the rhabdomyomatous lung was not associated with other abnormalities [7]. Although our patient died of aspiration pneumonia, he survived free of disease until the age of 30 months, and physical examination revealed no other visceral abnormalities except PDA. Based on clinicopathological considerations of the previously reported cases and our case, we suggest that the presence of striated muscle tissue in the lung does not always indicate the existence of lethal congenital malformations and that resection of the affected pulmonary parenchyma might be curative. We experienced an extremely rare case of RD of a neonatal lung in NF-1 and suggest the possibility of an association between the two diseases. However, further study is necessary to evaluate the diagnostic criteria and pathogenesis of RD and the relationship between these disorders. Acknowledgements This work was supported by a grant from the Kodama Memorial Fund for Medical Research. References [1] K. Aterman, S. Patel, Striated muscle in the lung, Am. J. Anat. 128 (1970) 341–358. [2] H. Brems, E. Beert, T. de Ravel, E. Legius, Mechanisms in the pathogenesis of malignant tumours in neurofibromatosis type 1, Lancet Oncol. 10 (2009) 508–515. [3] M.E. Chen, R. Onerheim, N.S. Wang, I. Hüttner, Rhabdomyomatosis of newborn lung: a case report with immunohistochemical and electronmicroscopic characterization of striated muscle cells in the lung, Pediatr. Pathol. 11 (1991) 123–129. [4] J.S. Choi, J.S. Choi, E.J. Kim, Primary pulmonary rhabdomyosarcoma in an adult with neurofibromatosis-1, Ann. Thorac. Surg. 88 (2009) 1356–1358. [5] F. Fraggetta, S. Cacciaguerra, M. Davenport, A tumorous type of pulmonary rhabdomyomatous dysplasia. By A. Ramaswany et al. (in: Pathol. Res. Pract. 194: 639-642, 1998), Pathol. Res. Pract. 195 (1999) 199–200. [6] F. Fraggetta, M. Davenport, G. Magro, S. Cacciaguerra, R. Nash, Striated muscle cells in non-neoplastic lung tissue: a clinicopathologic study, Hum. Pathol. 31 (2000) 1477–1481. [7] D. Hardisson, J.A. García-Jiménez, J.A. Jiménez-Heffernan, M. Nistal, Rhabdomyomatosis of the newborn lung unassociated with other malformations, Histopathology 31 (1997) 474–479. [8] U. Lienicke, H. Hammer, M. Schneider, K. Heling, R.R. Wauer, H. Mau, M. Vogel, Rhabdomyomatous dysplasia of the newborn lung associated with multiple congenital malformations of the heart and great vessels, Pediatr. Pulmonol. 34 (2002) 222–225. [9] N. Orpen, R. Goodman, C. Bowker, K. Lakhoo, Intralobar pulmonary sequestration with congenital cystic adenomatoid malformation and rhabdomyomatous dysplasia, Pediatr. Surg. Int. 19 (2003) 610–611. [10] A. Ramaswamy, I. Weyers, V. Duda, K. Bock, P.J. Barth, A tumorous type of pulmonary rhabdomyomatous dysplasia, Pathol. Res. Pract. 194 (1998) 639–642. [11] K. Remberger, G. Hübner, Rhabdomyomatous dysplasia of the lung, Virchows Arch. A Pathol. Anat. Histol. 363 (1974) 363–369. [12] J.T. Stocker, J.E. Madewell, R.M. Drake, Congenital cystic adenomatoid malformation of the lung: classification and morphologic spectrum, Hum. Pathol. 8 (1977) 155–171. [13] V.C. Williams, J. Lucas, M.A. Babcock, D.H. Gutmann, B. Korf, B.L. Maria, Neurofibromatosis type 1 revisited, Pediatrics 123 (2009) 124–133. [14] P. Yang, S. Grufferman, M.J. Khoury, A.G. Schwartz, J. Kowalski, F.B. Ruymann, H.M. Maurer, Association of childhood rhabdomyosarcoma with neurofibromatosis type 1 and birth defects, Genet. Epidemiol. 12 (1995) 467–474. [15] A.C. Zamora, H.R. Collard, P.J. Wolters, W.R. Webb, T.E. King, Neurofibromatosisassociated lung disease: a case series and literature review, Eur. Respir. J. 29 (2007) 210–214.
Contents lists available at ScienceDirect
Pathology – Research and Practice journal homepage: www.elsevier.com/locate/prp
Teaching Cases
Pulmonary rhabdomyomatous dysplasia of the newborn in neurofibromatosis type 1 Kazuhito Hatanaka, Takako Yoshioka, Takashi Tasaki, Akihide Tanimoto ∗ Department of Molecular and Cellular Pathology, Kagoshima University Graduate School of Medical and Dental Sciences, Japan
a r t i c l e
i n f o
Article history: Received 10 July 2013 Received in revised form 2 October 2013 Accepted 29 October 2013 Keywords: Lung New born Rhabdomyomatous dysplasia Neurofibromatosis type 1
a b s t r a c t Proliferation of non-neoplastic striated muscle cells in the lung is rare and has been frequently observed in cases of cardiovascular and pulmonary congenital malformations. We present an extremely rare case of pulmonary rhabdomyomatous dysplasia (RD) in neurofibromatosis type 1 (NF-1). A male neonate was born at 35 weeks’ gestation after normal pregnancy. Postnatally, besides patent ductus arteriosus and posterior mediastinal mass, abnormal cystic lesions in the left upper and lower lung were detected. No bronchial atresia and stenosis were identified. Partial lobectomy specimens showed hypoplastic lung parenchyma with cystic lesions resembling terminal bronchioles and distinctive proliferation of non-neoplastic striated muscle fibers in the interstitium. The posterior mediastinal mass consisted of neurofibroma. Considering that café au lait spots and freckling occurred at 2 months of age, a diagnosis of NF-1 was made. The patient died of aspiration pneumonia at the age of 30 months. To the best of our knowledge, this is the first case of pulmonary RD in NF-1. © 2013 Elsevier GmbH. All rights reserved.
Introduction The presence of non-neoplastic striated muscle fibers in the lung is an extremely rare finding, and only few reports have described non-neoplastic striated muscle proliferation in the lung [1]. In 1974, Remberger reported an autopsy case of a 4-month-old male infant with diffuse involvement of cross-striated muscle tissue of a different maturity grade in the alveolar septa and bronchial wall of the hypoplastic lung as pulmonary rhabdomyomatous dysplasia (RD) [11]. A few similar cases have been subsequently reported [7–10]. Most cases are associated with multiple visceral abnormalities, including major cardiovascular and pulmonary malformations, with usually poor prognoses. Here, we present an exceedingly rare case of RD of the lung in a newborn with no other pulmonary malformations; the patient remained free of disease at age of 30 months after partial lobectomy. Moreover, the infant was found to have neurofibromatosis type 1 (NF-1). Case report A 2824 g male infant was born at 35 weeks’ gestation after a normal pregnancy and delivery. No relevant family history was
∗ Corresponding author at: 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan. Tel.: +81 99 275 5263; fax: +81 99 264 6348. E-mail address: [email protected] (A. Tanimoto). 0344-0338/$ – see front matter © 2013 Elsevier GmbH. All rights reserved. http://dx.doi.org/10.1016/j.prp.2013.10.008
found. Routine antenatal examinations revealed no abnormalities. At 11 days of age, the infant presented with tachypnea and cyanosis. Chest computed tomographic images showed ill-defined parenchymal lesions showing cystic structures in the left upper and lower lobes. A posterior mediastinum mass-like lesion was also detected. No bronchial atresia and stenosis were identified. No other abnormalities were detected, except for patent ductus arteriosus (PDA). Partial lobectomy and mediastinal mass resection were performed. The infant made an uneventful postoperative recovery. At 2 months of age, more than 6 café au lait spots larger than 5 mm in greatest diameter were identified in the trunk and lower extremities, and freckling was also detected in the inguinal regions. Although an analysis for NF-1 gene was not performed, NF-1 was diagnosed according to the criteria of NF-1 in postnatal testing [13]. The patient received follow-up care at an outpatient clinic, and intervention treatment for PDA was not performed. He died because of aspiration pneumonia at the age of 30 months. Death due to aspiration pneumonia in this age group is considered rather unusual. However, the details were unclear because autopsy was not performed. Materials and methods Resected specimens were fixed in 10% buffered formalin, embedded in paraffin, and cut into 4 m sections. In addition to hematoxylin and eosin (H&E) staining and phosphotungstic acid hematoxylin (PTAH) staining, desmin, muscle-specific actin, myoglobin, smooth muscle actin and S-100 protein
K. Hatanaka et al. / Pathology – Research and Practice 210 (2014) 318–320
319
Fig. 1. Macroscopic and loupe images. (a) The firm area located on one edge of the resected lower lung (dotted line). (b) The firm area is composed of abnormal parenchyma including the bronchus (H&E). (c) No apparent fibrotic lesion is present in the firm area (Elastica-Masson trichrome). (d) Immunohistochemistry for muscle-specific actin showing the proliferation of muscle tissue in the firm area.
immunohistochemical studies were performed using mouse monoclonal antibodies D33 (Dako, Glostrup, Denmark), HHF35 (Enzo, New York, USA), MYO18 (Novocastra, Newcastle Upon Tyne, UK), ␣sm-1 (Novocastra) and the rabbit polyclonal antibody Z0311 (Dako), respectively. Results The resected left upper and lower lobes showed similar findings. Macroscopically, a firm area, approximately 3.5 cm in diameter, was observed at one edge of the resected lower lung (Fig. 1a). Loupe images revealed that the firm area was composed of abnormal parenchyma including bronchus (Fig. 1b), and fibrosis was unclear (Fig. 1c). Moreover, the proliferation of muscle tissue was recognized in the firm area (Fig. 1d). No abnormal vessels were identified. Microscopic examination revealed that the firm area consisted of hypoplastic parenchyma and multiple cystic lesions resembling terminal bronchioles. The irregularly shaped cystic lesions were lined by ciliated cuboidal to columnar respiratorytype epithelium. In the broadening interstitium, abundant bundles of striated muscle fibers were present (Fig. 2), which were fairly uniform in thickness but varied in length (Fig. 3a). The muscle fiber had eosinophilic cytoplasm, and well-developed cross striations were revealed by PTAH staining (Fig. 3b). Most nuclei were located peripherally, but some were located centrally. No cytological atypia, mitotic figures and necrosis were identified. Small lymphocyte and plasma cell infiltration were observed in the interstitium. Immunohistochemical staining demonstrated desmin, muscle-specific actin, and myoglobin positivity in the muscle fibers, and the striking features of the widespread distribution of the striated muscle fibers in the interstitium (Fig. 4). The posterior mediastinal mass was composed of loosely arranged spindle-shaped cells showing a fascicular and wavy growth
Fig. 2. Numerous strands of striated muscle fibers distributed in the hypoplastic lung parenchyma (H&E; ×100).
pattern with fibroblasts and collagen fibers. The tumor cells showed no cytological atypia and mitosis. In the immunohistochemical study, the tumor cells were found to be positive for S-100 protein. These features were considered to be neurofibroma (not shown). Discussion Only a few cases of pulmonary RD or similar disorders have been reported in the English literature [7–11], and these cases showed multiple visceral malformations, including cardiovascular and/or lung abnormalities, except two cases [7,10]. On the other hand, it is questionable to make a diagnosis of RD by the existence of striated
Fig. 3. (a) Large numbers of irregular bundles of striated muscle fibers localized in the pulmonary interstitium (H&E; ×200). (b) The muscle fibers had well-developed cross striations (PTAH; ×400).
320
K. Hatanaka et al. / Pathology – Research and Practice 210 (2014) 318–320
Fig. 4. Striated muscle fibers exhibiting immunopositivity with muscle-specific actin and striking features of widespread distribution in the interstitium (×200).
muscle cells [5], as the proliferation of striated muscle tissues was identified in abnormal congenital lungs, such as horseshoe lung, incomplete lobation, hypoplasia, and hypoplastic lung of congenital diaphragmatic hernia [6]. Moreover, Fraggetta reported 5 cases of striated muscle cell proliferation in a review of a series of 31 cases of congenital non-neoplastic lung abnormalities, including congenital cystic adenomatoid malformation (CCAM) type II and pulmonary sequestration [6]. In the cases reviewed by Fraggetta, striated muscle cell proliferation was diffused in 3 and focal in 2 cases. Our case had no other pulmonary malformations, and histological examination demonstrated numerous bundles of striated muscle fibers distributed in a random manner in the lung interstitium, not isolated muscle strands in the pulmonary parenchyma between the cysts and alveolus-like structures as seen in CCAM [7]. Although the exact number of striated muscle cells needed to distinguish RD from a simple presence of striated muscle cells in the lung interstitium remains unclear, the presence of RD as a distinct entity is supported by its association with multiple visceral malformations [5]. It is of interest that no other lung abnormalities were observed in the present case. The origin of the striated muscle cells in the lung interstitium is also unclear. It has been proposed that it originates from the misplaced striated muscle tissue of the pharynx, esophagus, or diaphragm as a developmental error [11]. The possibility of cardiac origin was also suggested; however, it was denied by immunohistochemical and electron microscopic analyses [3]. Some authors favor the hypothesis of myoblastic differentiation of primitive mesenchymal cells or metaplastic transformation of pluripotent mesenchymal cells, which develop into rhabdomyomatous cells in postnatal life [12]. Our case was complicated with NF-1. To the best of our knowledge, no other case reports on RD and similar disorders of striated muscle cells proliferation in the non-neoplastic lung interstitium associated with NF-1 have been published. Diffuse lung disease is known as a pulmonary manifestation in NF-1, characterized by upper lobe cystic and bullous disease and basilar fibrosis [15]. Moreover, the occurrence of primary pulmonary rhabdomyosarcoma in childhood is suggested to be associated with NF-1 [14]. Although the pathogenesis of primary pulmonary rhabdomyosarcoma in NF-1 is unknown [2], myoblastic differentiation of primitive mesenchymal cells in the lung interstitium is suggested to be associated with rhabdomyosarcoma in NF-1 [4]. Aside from NF-1, the presence of striated muscle tissues was proposed as the origin of rhabdomyosarcoma, which may be the result of
displacement from adjacent organs such as the esophagus or pharynx in early fetal life, and the presence of striated smooth muscle fibers, including RD, may present as the first stage in the development of a primary pulmonary rhabdomyosarcoma [6,9]. We were unable to prove the definite relationship between RD and NF-1 in this case; however, our case is notably interesting when we consider the pathogenesis of primary pulmonary rhabdomyosarcoma associated with NF-1. Among the previously reported cases of RD, most were associated with major pulmonary and/or cardiovascular malformations, which are life threatening. Only one case survived after partial lobectomy, and the rhabdomyomatous lung was not associated with other abnormalities [7]. Although our patient died of aspiration pneumonia, he survived free of disease until the age of 30 months, and physical examination revealed no other visceral abnormalities except PDA. Based on clinicopathological considerations of the previously reported cases and our case, we suggest that the presence of striated muscle tissue in the lung does not always indicate the existence of lethal congenital malformations and that resection of the affected pulmonary parenchyma might be curative. We experienced an extremely rare case of RD of a neonatal lung in NF-1 and suggest the possibility of an association between the two diseases. However, further study is necessary to evaluate the diagnostic criteria and pathogenesis of RD and the relationship between these disorders. Acknowledgements This work was supported by a grant from the Kodama Memorial Fund for Medical Research. References [1] K. Aterman, S. Patel, Striated muscle in the lung, Am. J. Anat. 128 (1970) 341–358. [2] H. Brems, E. Beert, T. de Ravel, E. Legius, Mechanisms in the pathogenesis of malignant tumours in neurofibromatosis type 1, Lancet Oncol. 10 (2009) 508–515. [3] M.E. Chen, R. Onerheim, N.S. Wang, I. Hüttner, Rhabdomyomatosis of newborn lung: a case report with immunohistochemical and electronmicroscopic characterization of striated muscle cells in the lung, Pediatr. Pathol. 11 (1991) 123–129. [4] J.S. Choi, J.S. Choi, E.J. Kim, Primary pulmonary rhabdomyosarcoma in an adult with neurofibromatosis-1, Ann. Thorac. Surg. 88 (2009) 1356–1358. [5] F. Fraggetta, S. Cacciaguerra, M. Davenport, A tumorous type of pulmonary rhabdomyomatous dysplasia. By A. Ramaswany et al. (in: Pathol. Res. Pract. 194: 639-642, 1998), Pathol. Res. Pract. 195 (1999) 199–200. [6] F. Fraggetta, M. Davenport, G. Magro, S. Cacciaguerra, R. Nash, Striated muscle cells in non-neoplastic lung tissue: a clinicopathologic study, Hum. Pathol. 31 (2000) 1477–1481. [7] D. Hardisson, J.A. García-Jiménez, J.A. Jiménez-Heffernan, M. Nistal, Rhabdomyomatosis of the newborn lung unassociated with other malformations, Histopathology 31 (1997) 474–479. [8] U. Lienicke, H. Hammer, M. Schneider, K. Heling, R.R. Wauer, H. Mau, M. Vogel, Rhabdomyomatous dysplasia of the newborn lung associated with multiple congenital malformations of the heart and great vessels, Pediatr. Pulmonol. 34 (2002) 222–225. [9] N. Orpen, R. Goodman, C. Bowker, K. Lakhoo, Intralobar pulmonary sequestration with congenital cystic adenomatoid malformation and rhabdomyomatous dysplasia, Pediatr. Surg. Int. 19 (2003) 610–611. [10] A. Ramaswamy, I. Weyers, V. Duda, K. Bock, P.J. Barth, A tumorous type of pulmonary rhabdomyomatous dysplasia, Pathol. Res. Pract. 194 (1998) 639–642. [11] K. Remberger, G. Hübner, Rhabdomyomatous dysplasia of the lung, Virchows Arch. A Pathol. Anat. Histol. 363 (1974) 363–369. [12] J.T. Stocker, J.E. Madewell, R.M. Drake, Congenital cystic adenomatoid malformation of the lung: classification and morphologic spectrum, Hum. Pathol. 8 (1977) 155–171. [13] V.C. Williams, J. Lucas, M.A. Babcock, D.H. Gutmann, B. Korf, B.L. Maria, Neurofibromatosis type 1 revisited, Pediatrics 123 (2009) 124–133. [14] P. Yang, S. Grufferman, M.J. Khoury, A.G. Schwartz, J. Kowalski, F.B. Ruymann, H.M. Maurer, Association of childhood rhabdomyosarcoma with neurofibromatosis type 1 and birth defects, Genet. Epidemiol. 12 (1995) 467–474. [15] A.C. Zamora, H.R. Collard, P.J. Wolters, W.R. Webb, T.E. King, Neurofibromatosisassociated lung disease: a case series and literature review, Eur. Respir. J. 29 (2007) 210–214.
