- Email: [email protected]
Congenital peribronchial myofibroblastic tumor: Case report and review of literature
J Ped Surg Case Reports 3 (2015) 154e157
Contents lists available at ScienceDirect
Journal of Pediatric Surgery CASE REPORTS journal homepage: www.jpscasereports.com
Congenital peribronchial myofibroblastic tumor: Case report and review of literature Jolanta Jedrzkiewicz a, *, Eric Scaife b, Bo Hong c, Sarah South c, Mouied Alashari b a
University of Utah, Department of Pathology, 15 North Medical Drive East Ste. #1100, Salt Lake City, UT 84112, USA Primary Children’s Hospital, 100 N Mario Capecchi Drive, Salt Lake City, UT 84113, USA c ARUP Laboratories, 500 Chipeta Way, Salt Lake City, UT 84108, USA b
a r t i c l e i n f o
a b s t r a c t
Article history: Received 30 December 2014 Received in revised form 10 February 2015 Accepted 19 February 2015
Congenital peribronchial myofibroblastic tumor (CPMT) is a rare entity recognized in the WHO classification of pulmonary neoplasms. According to available literature, it is a benign tumor with a high mortality rate exceeding 50%. It is partially attributed to polyhydramnios, hydrops, prematurity, respiratory distress or adverse surgical outcomes due to intraoperative bleeding. Herein we present a case of congenital peribronchial myofibroblastic tumor in a premature male infant who was born at 31 weeks gestation due to polyhydramnios and premature rupture of membranes. Soon after birth, he required intubation due to worsening respiratory distress. Imaging demonstrated a large right chest mass causing mediastinal shift. Surgical intervention was attempted, which was challenging due to intraoperative bleeding and tumor retraction. The patient expired soon after the surgery. Hence, in this report we would like to share our experience with this difficult diagnosis and treatment of this rare tumor. Ó 2015 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Key words: Congenital peribronchial myofibroblastic tumor Pulmonary neoplasm Polyhydramnios
1. Case report A 27-year-old primigravida female at 31 weeks gestational age and previously uncomplicated pregnancy presented with premature rupture of membranes. Ultrasonogram demonstrated an intrauterine gestation with polyhydramnios and a fetus with a large solid and cystic mass in the right chest. After transfer to a tertiary care facility, a male infant weighting 2060 g was delivered vaginally with Apgar scores of 2 at 1 min, 3 at 5 min and 7 at 10 min. He required intubation with high frequency oscillator soon after the delivery. He was given surfactant to help with respirations. A chest CT scan demonstrated a homogenous round soft tissue density in the right hemithorax with a few small cystic spaces (Fig. 1A), compatible with a diagnosis of congenital pulmonary airway malformation (CPAM). Due to mass effect leading to progressive collapse of the left lung, urgent resection of the mass was pursued on the 2nd day of life. Right posterior lateral thoracotomy was performed with intent to perform a left lung lobectomy. Surgical intervention proved to be
* Corresponding author. Tel.: þ1 801 581 5207. E-mail addresses: [email protected], [email protected] (J. Jedrzkiewicz).
challenging. The tumor invaded the right mainstem bronchus and gave the bronchus the character of thin glass. The surgeons retracted the lung to provide exposure of the hilum and the mainstem bronchus completely fractured off the trachea. The tumor itself appeared to be growing into the hilum and after fracturing the bronchus through what appeared to be the tumor bed, the surgeon was forced to place a Satinsky clamp across the hilum. Moreover, a tear of the superior pulmonary vein back into the atrium was noted. To control the bleeding and the airways, an emergency completion pneumonectomy was performed. A pediatric cardiac surgeon was also involved to prevent injury to the pericardium. Unfortunately, the contralateral lung, which was suspected to be hypoplastic on antenatal ultrasound, proved to be insufficient to support the child. After completion of the procedure the child’s vital signs were heart rate of 130 bpm, blood pressure of 55/25 mmHg and oxygen saturation of 53%. The child was moved to the intensive care unit and required respiratory and vascular support. The patient passed away approximately 36 h after the operation due to inadequate pulmonary reserve. Pathologic examination revealed a grossly trabeculated solid mass without a cystic component measuring 5.3 4.5 3.4 cm (Fig. 1B). On microscopy, the mass partially involved all three lung lobes, particularly at the bronchovascular margins. No hemorrhage or necrosis was identified. The tumor cells had uniform spindle
2213-5766/Ó 2015 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). http://dx.doi.org/10.1016/j.epsc.2015.02.012
J. Jedrzkiewicz et al. / J Ped Surg Case Reports 3 (2015) 154e157
155
Fig. 1. A) Contrast CT of the chest, showing a large mostly solid and partially cystic right pulmonary mass; B) Gross photograph of the tumor showing trabecular solid cut surfaces.
morphology and showed bland nuclei with inconspicuous nucleoli and pink cytoplasm. They grew predominantly in broad fascicles, replacing normal lung parenchyma and abutting normal structures including bronchi and vessels (Fig. 2AeD). Brisk mitotic activity was present. The tumor cells were positive for smooth muscle actin, CD34, calponin and bcl2 immunohistochemical stains, supporting myofibroblastic differentiation (Fig. 2E and F). The AE1.3 cytokeratin cocktail (an epithelial marker) immunohistochemical stain is usually positive in the epithelial component of pleuropulmonary blastoma and CPAM but was negative in this case. The desmin (a muscle marker) immunohistochemical stain was also negative, ruling out leiomyosarcoma. The Ki-67 proliferation index was approximately 10%, which was consistent with a mitotically active tumor. Fluorescent in situ hybridization for the ETV6 rearrangement using a break apart probe was negative excluding congenital fibrosarcoma (congenital fibrosarcoma typically harbors an ETV6NTRK3 gene fusion). Additionally, a Formalin-Fixed ParaffinEmbedded (FFPE) Molecular Inversion Probe Array was performed using the Affymetrix OncoScan FFPE Assay. A 777 Kb deletion at
2q21.1, Chr2: 130,701,189e131,478,017 (hg19) was identified in the tumor tissue as well as in normal lung tissue. This deletion overlaps with a database of the Genomic Variant Region and therefore, this copy number change was predicted to be most likely constitutional or benign. Overall, the morphologic assessment and immunohistochemical stains supported a diagnosis of congenital peribronchial myofibroblastic tumor. 2. Discussion CPMT is a rare entity recognized in the WHO classification of pulmonary neoplasms of fetuses and infants. Only 23 reported cases are found in the literature (Fig. 3) [1]. Usually, this tumor presents with non-immune hydrops, polyhydramnios and premature rupture of membranes in the 3rd trimester. On imaging, a large solid mass in either left or right lung is identified that may exceed 5 cm [1]. There are no reports describing bilateral lung involvement. The differential diagnosis includes CPAM, bronchopulmonary blastoma, congenital fibrosarcoma and leiomyosarcoma. Prenatal
Fig. 2. A) Congenital peribronchial myofibroblastic tumor at low power, H and E stain 2; B) Tumor tracking along the pulmonary septa, H and E stain 10; C) Tumor abutting a larger bronchus, H and E stain 10; D) Neoplastic cells on high power, H and E 100; E) Positive vimentin immunohistochemical stain, 40; F) Positive smooth muscle actin immunohistochemical stain, 40.
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J. Jedrzkiewicz et al. / J Ped Surg Case Reports 3 (2015) 154e157
Fig. 3. Summary of available publications on CPMT. F e female, M e male, RD e respiratory distress, H e hydrops, PHA e polyhydramnios, PE e pleural effusion, MPB e massive perioperative bleeding, EM e electron microscopy, IHC e immunohistochemistry, Flow e flow cytometry, Karyo e karyotyping, R e right, L e left [2,5e8,12e27].
diagnosis of CPMT proves to be difficult, probably because of rarity of this neoplasm. Most reported cases were diagnosed during pathologic assessment with an aid of numerous adjunct studies including immunohistochemistry, electron microscopy and fluorescent in situ hybridization. CPAM is a most commonly encountered congenital pulmonary mass that may also present with hydrops, polyhydramnios, shift of the mediastinal structures and respiratory distress. Particularly the solid variant of CPAM can easily be confused with CPMT on imaging. However, Calvo-Garcia et al. report certain characteristic features of CPMT on magnetic resonance imaging. CPMT is hypointense on T2-W and hyperintense on T1-W relatively to the lung parenchyma with a thin peripheral rim of dark T2 signal [2]. These findings are not typical for solid type CPAM and these features are suggestive of a diagnosis of CPMT. Of note, the symptomatic patients with CPAM are usually treated by surgical resection [3]. According to the scant available literature, CPMT is a benign tumor and several successful resections have led to no evidence of metastasis or recurrences [4]. Unfortunately, the mortality rate is really high, exceeding 50% [1]. The large pulmonary mass most likely causes aberrant development of the normal respiratory parenchyma due to compression and shift of the mediastinal structures. Overall, surgical intervention is usually deemed to be necessary to alleviate mediastinal compression but the surgical outcomes are often poor due to reduced respiratory function [5]. Therefore, delivery by ex utero intrapartum treatment and utilization of extracorporeal membrane oxygenation could be of clinical consideration [2,6]. Means to support respiratory function should be prepared because severe respiratory distress is usually anticipated in these cases.
The resection of a bulky pulmonary mass in a child with respiratory insufficiency is a risky procedure. CPMT has a tendency to grow adjacent to large vessels and bronchi, which was seen grossly and confirmed microscopically in the current case. This tendency most likely caused these structures to be fragile during surgical manipulation. This probably led to the tear in the superior pulmonary vein and fracture of the mainstem bronchus from the trachea in the current case. Therefore, more extensive surgery with an emergent complete right pneumonectomy was attempted to save the child. This surgery was performed on an emergent basis without appropriate preparation for extracorporeal membrane oxygenation placement or lung transplantation. Massive perioperative bleeding and intraoperative death have also been reported as complications of CPMT resection [5,7,8]. Among the reported cases, patients with a diagnosis of a pulmonary mass prior to the development of severe hydrops and polyhydramnios treated with surgical resection had a tendency to have a better outcome (Fig. 3). More cases are needed to make more definitive conclusions about best practices for management and the prognosis of patients with CPMT. Overall, a prenatal diagnosis of a large pulmonary mass should trigger a referral to a tertiary care center and more extensive clinical work-up. Although some of the patients may choose to pursue an elective abortion, surgical resection may provide a successful treatment option (Fig. 3). Since CPMT is usually diagnosed in the 3rd trimester, the treatment may include earlier induction of delivery in order to provide the necessary interventions, antenatal corticosteroid therapy to enhance lung maturation or an open fetal surgery for tumor resection [5]. Perhaps as we expand our understanding of this rare neoplasm we might be able to make the diagnosis sooner and to have a better
J. Jedrzkiewicz et al. / J Ped Surg Case Reports 3 (2015) 154e157
chance of successful treatment. In order to expand our understanding of this tumor, we attempted to identify its driving molecular mutation. We have performed FFPE array analysis of this tumor, which to our knowledge has not been previously reported. We found a small deletion in the 2q21.1 region, which was determined to be constitutional as it was also present in the surrounding normal lung tissue uninvolved by the tumor. This deletion harbors at least 18 genes including RAB6C and PTPN18. Of note, RAB6C is a member of the RAS oncogene family and PTPN18 gene is a functional protein-tyrosine phosphatase gene [9e11]. Although, we do not think that this is a driving molecular mutation for CPMT, the link between constitutional deletion of 2q21.1 region and CPMT has not been previously described in the literature. Additional studies are needed to increase our understanding of the molecular mechanisms underlying this neoplasm. References [1] Travis WD, Brambilla E, Muller-Hermelink HK, Harris CC. WHO classification of tumors: pathology and genetics of tumours of the lung, pleura, thymus and heart. 3rd ed., 10; 2004. p. 102e3. [2] Calvo-Garcia M, Lim FY, Stanek J, Bitters C, Kline-Fath BM. Congenital peribronchial myofibroblastic tumor: prenatal imaging clues to differentiate from other fetal chest lesions. Pediatr Radiol 2014;44(4):479e83. [3] Schwartz MZ, Ramachandran P. Congenital malformations of the lung and mediastinumea quarter century of experience from a single institution. J Pediatr Surg 1997;32:44. [4] Dishop MK, Kuruvilla S. Primary and metastatic lung tumors in the pediatric population: a review and 25-year experience at a large children’s hospital. Arch Pathol Lab Med 2008;132(7):1079e103. [5] Chang C, Hung LY, Thanh TT, Lai CH, Chang KC. Congenital peribronchial myofibroblastic tumour with features of maturation in the older infant: report of two cases with a literature review. Histopathology 2014;64(5):755e7. [6] Huppmann AR, Coffin CM, Hoot AC, Kahwash S, Pawel BR. Congenital peribronchial myofibroblastic tumor: comparison of fetal and postnatal morphology. Pediatr Dev Pathol 2010;14(2):124e9. [7] McGinnis M, Jackobs G, el-Naggar A, Redline RW. Congenital peribronchial myofibroblastic tumor (so-called “congenital leiomyosarcoma”): a distinct neonatal lung lesion associated with nonimmune hydrops fetalis. Mod Pathol 1993;6:487e92. [8] Warren JS, Seo IS, Mirkin LD. Massive congenital mesenchymal malformation of the lung: a case report with ultrastructural study. Pediatr Pathol 1985;3: 321e8.
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[9] Tian K, Wang Y, Xu H. WTH3 is a direct target of the p53 protein. Br J Cancer 2007;96(10):1579e86. [10] Doody KM, Bottini N. “PEST control”: regulation of molecular barcodes by tyrosine phosphatases. Cell Res 2014;24(0):1027e8. [11] Gandhi T, Chandran S, Peri S, Saravana R, Amanchy R, Prasad TS, et al. A bioinformatics analysis of protein tyrosine phosphatases in humans. DNA Res 2005;12(2):79e89. [12] Açikalin A, Gümürdülü D, Baǧir E, Gönlüs¸en G, Iskit S. Congenital peribronchial myofibroblastic tumor: a case report and review of the literature. Balkan Med J 2013;30(3):329e32. [13] Hotokebuchi Y, Kohashi K, Toyoshima S, Matsumoto N, Nakashima T, Oda Y. Congenital peribronchial myofibroblastic tumor. Pathol Int 2014;64(4): 189e91. [14] Reiss A, Goldberg Y, Monichor M, Drugan A. Congenital pulmonary myofibroblastic tumordpathology and prenatal sonographic appearance. Prenat Diagn 2005;25(11):1064e6. [15] Alobeid B, Beneck D, Sreekantaiah C, Abbi RK, Slim MS. Congenital pulmonary myofibroblastic tumor: a case report with cytogenetic analysis and review of the literature. Am J Surg Pathol 1997;21:610e4. [16] Kim Y, Park HY, Cho J, Han J, Cho EY. Congenital peribronchial myofibroblastic tumor: a case study and literature review. Korean J Pathol 2013;47(2):172e6. [17] Jones CJ. Unusual hamartoma of the lung in a newborn infant. Arch Pathol (Chic) 1949;48:150e4. [18] Robb D. A case of neonatal fibrosarcoma of lung. Br J Surg 1958;46:173e4. [19] de Noronha L, Cecílio WA, da Silva TF, Maggio EM, Serapião MJ. Congenital peribronchial myofibroblastic tumor: a case report. Pediatr Dev Pathol 2010; 13(3):243e6. [20] Guccion JG, Rosen SH. Bronchopulmonary leiomyosarcoma and fibrosarcoma: a study of 32 cases and review of the literature. Cancer 1972;30:836e47. [21] Haller JO, Kauffman SL, Kassner EG. Congenital mesenchymal tumour of the lung. Br J Radiol 1977;50:217e9. [22] Horikoshi T, Kikuchi A, Matsumoto Y, Tatematsu M, Takae K, Oqiso Y, et al. Fetal hydrops associated with congenital pulmonary myofibroblastic tumor. J Obstet Gynaecol Res 2005;31(6):552e5. [23] Jimenez JF, Uthman EO, Townsend JW, Gloster ES, Seibert JJ. Primary bronchopulmonary leiomyosarcoma in childhood. Arch Pathol Lab Med 1986;110: 348e51. [24] Khong TY, Keeling JW. Massive congenital mesenchymal malformation of the lung: another cause of non-immune hydrops. Histopathology 1990;16: 609e11. [25] Kuhnen C, Harms D, Niessen KH, Diehm T, Müller KM. Congenital pulmonary fibrosarcoma: differential diagnosis of infantile pulmonary spindle cell tumors. Pathologe 2001;22:151e6. [26] Dishop MK. Congenital pulmonary myofibroblastic tumor [Internet]. Augusta: United States and Canadian Academy of Pathology. [cite 2012 Jul 5]. [27] Pettinato G, Manivel JC, Saldana MJ, Peyser J, Dehner LP. Primary bronchopulmonary fibrosarcoma of childhood and adolescence: reassessment of a low-grade malignancy. Clinicopathologic study of five cases and review of the literature. Hum Pathol 1989;20:463e71.
Contents lists available at ScienceDirect
Journal of Pediatric Surgery CASE REPORTS journal homepage: www.jpscasereports.com
Congenital peribronchial myofibroblastic tumor: Case report and review of literature Jolanta Jedrzkiewicz a, *, Eric Scaife b, Bo Hong c, Sarah South c, Mouied Alashari b a
University of Utah, Department of Pathology, 15 North Medical Drive East Ste. #1100, Salt Lake City, UT 84112, USA Primary Children’s Hospital, 100 N Mario Capecchi Drive, Salt Lake City, UT 84113, USA c ARUP Laboratories, 500 Chipeta Way, Salt Lake City, UT 84108, USA b
a r t i c l e i n f o
a b s t r a c t
Article history: Received 30 December 2014 Received in revised form 10 February 2015 Accepted 19 February 2015
Congenital peribronchial myofibroblastic tumor (CPMT) is a rare entity recognized in the WHO classification of pulmonary neoplasms. According to available literature, it is a benign tumor with a high mortality rate exceeding 50%. It is partially attributed to polyhydramnios, hydrops, prematurity, respiratory distress or adverse surgical outcomes due to intraoperative bleeding. Herein we present a case of congenital peribronchial myofibroblastic tumor in a premature male infant who was born at 31 weeks gestation due to polyhydramnios and premature rupture of membranes. Soon after birth, he required intubation due to worsening respiratory distress. Imaging demonstrated a large right chest mass causing mediastinal shift. Surgical intervention was attempted, which was challenging due to intraoperative bleeding and tumor retraction. The patient expired soon after the surgery. Hence, in this report we would like to share our experience with this difficult diagnosis and treatment of this rare tumor. Ó 2015 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Key words: Congenital peribronchial myofibroblastic tumor Pulmonary neoplasm Polyhydramnios
1. Case report A 27-year-old primigravida female at 31 weeks gestational age and previously uncomplicated pregnancy presented with premature rupture of membranes. Ultrasonogram demonstrated an intrauterine gestation with polyhydramnios and a fetus with a large solid and cystic mass in the right chest. After transfer to a tertiary care facility, a male infant weighting 2060 g was delivered vaginally with Apgar scores of 2 at 1 min, 3 at 5 min and 7 at 10 min. He required intubation with high frequency oscillator soon after the delivery. He was given surfactant to help with respirations. A chest CT scan demonstrated a homogenous round soft tissue density in the right hemithorax with a few small cystic spaces (Fig. 1A), compatible with a diagnosis of congenital pulmonary airway malformation (CPAM). Due to mass effect leading to progressive collapse of the left lung, urgent resection of the mass was pursued on the 2nd day of life. Right posterior lateral thoracotomy was performed with intent to perform a left lung lobectomy. Surgical intervention proved to be
* Corresponding author. Tel.: þ1 801 581 5207. E-mail addresses: [email protected], [email protected] (J. Jedrzkiewicz).
challenging. The tumor invaded the right mainstem bronchus and gave the bronchus the character of thin glass. The surgeons retracted the lung to provide exposure of the hilum and the mainstem bronchus completely fractured off the trachea. The tumor itself appeared to be growing into the hilum and after fracturing the bronchus through what appeared to be the tumor bed, the surgeon was forced to place a Satinsky clamp across the hilum. Moreover, a tear of the superior pulmonary vein back into the atrium was noted. To control the bleeding and the airways, an emergency completion pneumonectomy was performed. A pediatric cardiac surgeon was also involved to prevent injury to the pericardium. Unfortunately, the contralateral lung, which was suspected to be hypoplastic on antenatal ultrasound, proved to be insufficient to support the child. After completion of the procedure the child’s vital signs were heart rate of 130 bpm, blood pressure of 55/25 mmHg and oxygen saturation of 53%. The child was moved to the intensive care unit and required respiratory and vascular support. The patient passed away approximately 36 h after the operation due to inadequate pulmonary reserve. Pathologic examination revealed a grossly trabeculated solid mass without a cystic component measuring 5.3 4.5 3.4 cm (Fig. 1B). On microscopy, the mass partially involved all three lung lobes, particularly at the bronchovascular margins. No hemorrhage or necrosis was identified. The tumor cells had uniform spindle
2213-5766/Ó 2015 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). http://dx.doi.org/10.1016/j.epsc.2015.02.012
J. Jedrzkiewicz et al. / J Ped Surg Case Reports 3 (2015) 154e157
155
Fig. 1. A) Contrast CT of the chest, showing a large mostly solid and partially cystic right pulmonary mass; B) Gross photograph of the tumor showing trabecular solid cut surfaces.
morphology and showed bland nuclei with inconspicuous nucleoli and pink cytoplasm. They grew predominantly in broad fascicles, replacing normal lung parenchyma and abutting normal structures including bronchi and vessels (Fig. 2AeD). Brisk mitotic activity was present. The tumor cells were positive for smooth muscle actin, CD34, calponin and bcl2 immunohistochemical stains, supporting myofibroblastic differentiation (Fig. 2E and F). The AE1.3 cytokeratin cocktail (an epithelial marker) immunohistochemical stain is usually positive in the epithelial component of pleuropulmonary blastoma and CPAM but was negative in this case. The desmin (a muscle marker) immunohistochemical stain was also negative, ruling out leiomyosarcoma. The Ki-67 proliferation index was approximately 10%, which was consistent with a mitotically active tumor. Fluorescent in situ hybridization for the ETV6 rearrangement using a break apart probe was negative excluding congenital fibrosarcoma (congenital fibrosarcoma typically harbors an ETV6NTRK3 gene fusion). Additionally, a Formalin-Fixed ParaffinEmbedded (FFPE) Molecular Inversion Probe Array was performed using the Affymetrix OncoScan FFPE Assay. A 777 Kb deletion at
2q21.1, Chr2: 130,701,189e131,478,017 (hg19) was identified in the tumor tissue as well as in normal lung tissue. This deletion overlaps with a database of the Genomic Variant Region and therefore, this copy number change was predicted to be most likely constitutional or benign. Overall, the morphologic assessment and immunohistochemical stains supported a diagnosis of congenital peribronchial myofibroblastic tumor. 2. Discussion CPMT is a rare entity recognized in the WHO classification of pulmonary neoplasms of fetuses and infants. Only 23 reported cases are found in the literature (Fig. 3) [1]. Usually, this tumor presents with non-immune hydrops, polyhydramnios and premature rupture of membranes in the 3rd trimester. On imaging, a large solid mass in either left or right lung is identified that may exceed 5 cm [1]. There are no reports describing bilateral lung involvement. The differential diagnosis includes CPAM, bronchopulmonary blastoma, congenital fibrosarcoma and leiomyosarcoma. Prenatal
Fig. 2. A) Congenital peribronchial myofibroblastic tumor at low power, H and E stain 2; B) Tumor tracking along the pulmonary septa, H and E stain 10; C) Tumor abutting a larger bronchus, H and E stain 10; D) Neoplastic cells on high power, H and E 100; E) Positive vimentin immunohistochemical stain, 40; F) Positive smooth muscle actin immunohistochemical stain, 40.
156
J. Jedrzkiewicz et al. / J Ped Surg Case Reports 3 (2015) 154e157
Fig. 3. Summary of available publications on CPMT. F e female, M e male, RD e respiratory distress, H e hydrops, PHA e polyhydramnios, PE e pleural effusion, MPB e massive perioperative bleeding, EM e electron microscopy, IHC e immunohistochemistry, Flow e flow cytometry, Karyo e karyotyping, R e right, L e left [2,5e8,12e27].
diagnosis of CPMT proves to be difficult, probably because of rarity of this neoplasm. Most reported cases were diagnosed during pathologic assessment with an aid of numerous adjunct studies including immunohistochemistry, electron microscopy and fluorescent in situ hybridization. CPAM is a most commonly encountered congenital pulmonary mass that may also present with hydrops, polyhydramnios, shift of the mediastinal structures and respiratory distress. Particularly the solid variant of CPAM can easily be confused with CPMT on imaging. However, Calvo-Garcia et al. report certain characteristic features of CPMT on magnetic resonance imaging. CPMT is hypointense on T2-W and hyperintense on T1-W relatively to the lung parenchyma with a thin peripheral rim of dark T2 signal [2]. These findings are not typical for solid type CPAM and these features are suggestive of a diagnosis of CPMT. Of note, the symptomatic patients with CPAM are usually treated by surgical resection [3]. According to the scant available literature, CPMT is a benign tumor and several successful resections have led to no evidence of metastasis or recurrences [4]. Unfortunately, the mortality rate is really high, exceeding 50% [1]. The large pulmonary mass most likely causes aberrant development of the normal respiratory parenchyma due to compression and shift of the mediastinal structures. Overall, surgical intervention is usually deemed to be necessary to alleviate mediastinal compression but the surgical outcomes are often poor due to reduced respiratory function [5]. Therefore, delivery by ex utero intrapartum treatment and utilization of extracorporeal membrane oxygenation could be of clinical consideration [2,6]. Means to support respiratory function should be prepared because severe respiratory distress is usually anticipated in these cases.
The resection of a bulky pulmonary mass in a child with respiratory insufficiency is a risky procedure. CPMT has a tendency to grow adjacent to large vessels and bronchi, which was seen grossly and confirmed microscopically in the current case. This tendency most likely caused these structures to be fragile during surgical manipulation. This probably led to the tear in the superior pulmonary vein and fracture of the mainstem bronchus from the trachea in the current case. Therefore, more extensive surgery with an emergent complete right pneumonectomy was attempted to save the child. This surgery was performed on an emergent basis without appropriate preparation for extracorporeal membrane oxygenation placement or lung transplantation. Massive perioperative bleeding and intraoperative death have also been reported as complications of CPMT resection [5,7,8]. Among the reported cases, patients with a diagnosis of a pulmonary mass prior to the development of severe hydrops and polyhydramnios treated with surgical resection had a tendency to have a better outcome (Fig. 3). More cases are needed to make more definitive conclusions about best practices for management and the prognosis of patients with CPMT. Overall, a prenatal diagnosis of a large pulmonary mass should trigger a referral to a tertiary care center and more extensive clinical work-up. Although some of the patients may choose to pursue an elective abortion, surgical resection may provide a successful treatment option (Fig. 3). Since CPMT is usually diagnosed in the 3rd trimester, the treatment may include earlier induction of delivery in order to provide the necessary interventions, antenatal corticosteroid therapy to enhance lung maturation or an open fetal surgery for tumor resection [5]. Perhaps as we expand our understanding of this rare neoplasm we might be able to make the diagnosis sooner and to have a better
J. Jedrzkiewicz et al. / J Ped Surg Case Reports 3 (2015) 154e157
chance of successful treatment. In order to expand our understanding of this tumor, we attempted to identify its driving molecular mutation. We have performed FFPE array analysis of this tumor, which to our knowledge has not been previously reported. We found a small deletion in the 2q21.1 region, which was determined to be constitutional as it was also present in the surrounding normal lung tissue uninvolved by the tumor. This deletion harbors at least 18 genes including RAB6C and PTPN18. Of note, RAB6C is a member of the RAS oncogene family and PTPN18 gene is a functional protein-tyrosine phosphatase gene [9e11]. Although, we do not think that this is a driving molecular mutation for CPMT, the link between constitutional deletion of 2q21.1 region and CPMT has not been previously described in the literature. Additional studies are needed to increase our understanding of the molecular mechanisms underlying this neoplasm. References [1] Travis WD, Brambilla E, Muller-Hermelink HK, Harris CC. WHO classification of tumors: pathology and genetics of tumours of the lung, pleura, thymus and heart. 3rd ed., 10; 2004. p. 102e3. [2] Calvo-Garcia M, Lim FY, Stanek J, Bitters C, Kline-Fath BM. Congenital peribronchial myofibroblastic tumor: prenatal imaging clues to differentiate from other fetal chest lesions. Pediatr Radiol 2014;44(4):479e83. [3] Schwartz MZ, Ramachandran P. Congenital malformations of the lung and mediastinumea quarter century of experience from a single institution. J Pediatr Surg 1997;32:44. [4] Dishop MK, Kuruvilla S. Primary and metastatic lung tumors in the pediatric population: a review and 25-year experience at a large children’s hospital. Arch Pathol Lab Med 2008;132(7):1079e103. [5] Chang C, Hung LY, Thanh TT, Lai CH, Chang KC. Congenital peribronchial myofibroblastic tumour with features of maturation in the older infant: report of two cases with a literature review. Histopathology 2014;64(5):755e7. [6] Huppmann AR, Coffin CM, Hoot AC, Kahwash S, Pawel BR. Congenital peribronchial myofibroblastic tumor: comparison of fetal and postnatal morphology. Pediatr Dev Pathol 2010;14(2):124e9. [7] McGinnis M, Jackobs G, el-Naggar A, Redline RW. Congenital peribronchial myofibroblastic tumor (so-called “congenital leiomyosarcoma”): a distinct neonatal lung lesion associated with nonimmune hydrops fetalis. Mod Pathol 1993;6:487e92. [8] Warren JS, Seo IS, Mirkin LD. Massive congenital mesenchymal malformation of the lung: a case report with ultrastructural study. Pediatr Pathol 1985;3: 321e8.
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