Congenital Bilateral and Multifocal Mesenchymal hamartoma of the chest wall: A Case in a Neonate and Differential Diagnosis

Background: Mesenchymal hamartoma of the chest wall(MHCW) is a rare benign extrapleural lesion that arises from rib or spine of neonates or early infancy, and commonly presents as a unilateral mass. Here, we describe a rare case of bilateral and multifocal MHCW in the right 5th rib and the left 11-12th thoracic and 1st lumbar vertebrae. Case presentation: A male neonate of 3700g weight transferred to our hospital with mild respiratory distress and an asymptomatic, progressively enlarging intra-thoracic mass. Computed tomography scan(CT) and magnetic resonance imaging(MRI) indicated a large well-circumscribed, heterogeneous enhancing mass, arising from the posterior-medial aspect of the right chest wall, involving 3-5th posterior ribs. Other smaller sizes lesions observed in vertebral arch and transverse process of the left 11-12th thoracic and 1st lumbar vertebrae. The thoracotomy with en bloc resection of the mass and the 5th rib was performed. Microscopically, the lesion was cystic and solid, consisted of hyaline cartilages, mesenchymal cells, and various-sized hemorrhagic spaces. Immunohistochemically, the cartilages and mesenchymal cells were positive for S-100, Smooth Muscle Actin(SMA), CD163 and CD68. The epithelium cells of aneurysmal bone cyst(ABC)-like were negative for CD34. Ki-67 estimated at 5%-10%. Fluorescence in situ hybridization(FISH) was negative for USP6 gene break-apart probe, which ruled out primary ABC. At 8-month follow-up postoperatively, the right chest walls with no sign of recurrence and the lesions of left vertebral arch and transverse process were stable, no increased in size.

arising from the posterior-medial aspect of the right chest wall, involving 3-5th posterior ribs. Other smaller sizes lesions observed in vertebral arch and transverse process of the left 11-12th thoracic and 1st lumbar vertebrae. The thoracotomy with en bloc resection of the mass and the 5th rib was performed. Microscopically, the lesion was cystic and solid, consisted of hyaline cartilages, mesenchymal cells, and various-sized hemorrhagic spaces. Immunohistochemically, the cartilages and mesenchymal cells were positive for S-100, Smooth Muscle Actin(SMA), CD163 and CD68. The epithelium cells of aneurysmal bone cyst(ABC)-like were negative for CD34. Ki-67 estimated at 5%-10%. Fluorescence in situ hybridization(FISH) was negative for USP6 gene break-apart probe, which ruled out primary ABC. At 8month follow-up postoperatively, the right chest walls with no sign of recurrence and the lesions of left vertebral arch and transverse process were stable, no increased in size.

Conclusion:
The bilateral and multifocal MHCW is considerably rare and related clinical research is limited. Fortunately, we clearly observed the tumor's origin, growth process from the earlier pregnancy to delivery, different effects during the fetal periods, and differential diagnosis. This report may raise awareness regarding the MHCW.

Background
Mesenchymal hamartoma of the chest wall(MHCW), also known as chondromesenchymal hamartoma, is a rare benign extrapleural lesion that arises from rib [1] . It has an incidence of about 0.03% among primary bone tumors [2,3] , and mostly occurs in fetal life, neonates or early infancy [4] . Multifocal or/and bilateral lesions are extremely rare. Herein, we present the imaging and pathological features, treatment and prognosis of a male neonate with bilateral and multifocal MHCW, and a brief review of the literature.

Case Presentation
A 30-year-old pregnant woman gravida 2 para 1 at the 22nd gestation week, accepted routine pregnancy US at a local hospital. Examination showed a fetus of a weight of 744g and head-rst presentation and normal amniotic uid volume. Moreover, there was a hyper-echoic mass of 14×11mm at the right posterior chest wall of the fetus (Fig. 1A). Afterwards, the woman transferred to a local 3A hospital, accepted fetal Ultrasound(US) and MRI at the 26th gestation week. US showed a fetus of a weight of 1113g ± 162g with a heterogeneous hyper-echoic mass of 24×12mm situated at the posterior 4-5th ribs of the right posterior-medial chest wall (Fig. 1B). MRI showed a well-de ned lobulated, mixed mass of 19×16mm at lower lobe of right lung. Both radiologist and obstetrician more considered that this mass was a teratoma or neurogenic tumor, and suggested the woman reviewing periodically. At the 37th gestation week, the woman delivered a male baby of 3700g weight and the medical examination was normal except for mild respiratory distress. The neonate transferred to our hospital with an asymptomatic, progressively enlarging intra-thoracic mass. CT showed a large well-circumscribed, heterogeneous enhancing mass, measuring approximately 56×50mm, with several speckled and multiple strip vascular internal shadows, arising from the posterior-medial aspect of the right chest wall, involving 3-5th posterior ribs (Fig. 1C). The cortical and medullary of 5th rib were observed the destructive-expansile changes. The 3-4th ribs were compressed and deformed. Other lesions of similar nature but of smaller sizes were also observed in vertebral arch and transverse process of the left 11-12th thoracic and 1st lumbar vertebrae (Fig. 1D). MRI showed that the mass was solid-cystic with multiple uid-uid levels( Fig. 1E and 1F), which was suspected to be a benign chondrogenic tumor. A month later, the baby underwent thoracotomy with en bloc resection of the mass and the 5th rib. Furthermore, any evidence of invasion or metastatic disease by the mass have been not observed. Gross examinations showed a grayred mass connected to partial rib with unclear boundary, measuring approximately 75×41×35mm( Fig. 2A). The cut surface was solid-cystic, gray white and dark red. The solid area was gray white, soft to hard. The cystic area was various-sized cysts with dark red liquid owing out (Fig. 2B). Microscopically, the solid area consisted of mature or immature irregular hypercellular hyaline cartilages with foci of endochondral calci cation and ossi cation, isolated by fascicles of immature spindle-shaped mesenchymal cells (Fig. 2C). Scattered woven bones were observed (Fig. 2D). The cystic area was composed of various-sized hemorrhagic spaces enclosed by brous cyst walls with multinucleated osteoclastic giant cells and scattered osteoid trabeculae, as secondary aneurysmal bone cyst(ABC)-like structures (Fig. 2C). Abnormal mitoses and atypia were not seen. Immunohistochemically, the cartilaginous areas were positive for S-100 (Fig. 2E). Mesenchymal spindle-shaped cells were immunoreactive for SMA, CD163. Osteoclastic giant cells were positive for CD68. The epithelium cells of ABC-like were negative for CD34, but interstitial blood vessels were positivity (Fig. 2F). Ki-67 proliferation index was approximately 5%-10%. Fluorescence in situ hybridization(FISH) revealed the negativity of USP6 gene break-apart probe (Fig. 2G), which con rmed the nal diagnosis of MHCW and ruled out primary ABC. Subsequently, the thoracic tube drain was removed in the 7th day after surgery (Fig. 1G), and the infant was discharged from the hospital in the 2nd postoperative week. Post-operative follow-up at one month and six months showed the patient to be developmentally well. CT scan at 6 months postoperatively showed the right chest walls with no sign of recurrence and a normal lung appearance, and the lesions of left vertebral arch and transverse process were stable, no increased in size (Fig. 1H).

Discussion And Conclusions
MHCW is a rare benign nature lesion composed of non-neoplastic skeletal tissues, with incidence of less than 1 per million in the general population [5] . It commonly presents as unilateral mass and locates in the right thoracic cavity [6] . Occasionally a few cases of multifocal and/or bilateral lesions have been reported [4,7−10] , only 5 multifocal cases and 10 bilateral cases in the previous literatures. In terms of our case, we clearly observed the growth of MHCW from the earlier pregnancy to delivery, obviously, the tumor was congenital and had different effects during the fetal periods. In the earlier days, it was too small to be found and to affect the lungs, thorax, spine. As the tumor grew larger and multifocal, it gradually compressed the lung and caused deformation of the ribs and spine, especially in the late fetal period. Subsequently, in neonate, the tumor presented the clinical symptoms as the results of long term occupancy and destruction: respiratory distress, cough, fever, scoliosis, and chest wall deformity. Therefore, we considered that MHCW gradually evolved into a diverse structure from the fetus, and mainly affected neonate and early infant.
In the diagnosis of MHCW, different imaging methods have their own advantages and disadvantages. On US, it is very helpful and useful in early detecting the site, size, density, enlargement, adjacent structures and margin, but it can't differentiate the origin from rib or soft tissue, benign or malignant [11,12] . CT scan clearly reveals the extrapleural origin, osteoid, chondroid, osseous expansion and destruction, and hemorrhagic cystic regions [13] , but which can't make differential diagnosis with malignant chest wall tumors such as Ewing sarcoma, rhabdomyosarcoma, osteosarcoma, chondrosarcoma or metastasis of leukemia, neuroblastoma and lymphoma [14] . MRI also observes the characteristics of MHCW like CT, especially in ABC-like uid-uid levels, but it is di cult to distinguish between the primary and secondary ABC [7] .
It is noteworthy that MHCW is commonly accompanied with the ABC-like structures [15] , which easily makes misdiagnosis with primary ABC. Immunohistochemical markers such as S-100,SMA,CD68,CD163 and CD34, all of those substantiate the characteristics of histological diversity of MHCW. Furthermore, USP6 rearrangement is found in almost 69% of primary ABC [16] , but not in secondary ABC of MHCW.
According to the literatures, there are two main treatment approaches for MHCW. For the patients of unilateral and larger volume of MHCW, with clinical respiratory symptoms, the surgical resection is a very suitable treatment [4] . For the smaller asymptomatic patients, the conservative management with imaging modality is recommended [17] . The prognosis of most patients is favorable [18] , only a few cases have recurrence at the post-operative period, and even one with malign transformation [19] . In our case, we chose the surgical resection for right thoracic lesion in the 5th rib, and the conservative management for the smaller sizes lesions in the vertebral arch and transverse process of the left 11-12th thoracic and 1st lumbar vertebrae. By post-operative follow-up and imaging modality, we didn't observe the sign of recurrence, and the other lesions were stable and stopped growing. The prognosis was good and consistent with a few literatures about multifocal lesions [20,21] . We will keep following up.
In conclusion, MHCW is a rare congenital benign lesion that usually originates from the rib of the fetus, and presents the clinical symptoms in neonates or early infancy. It is extremely rare to observe the multifocal and/or bilateral lesions. This report may raise awareness regarding the presentation, diagnosis, and treatment of MHCW among pathologists, radiologists, and clinicians.