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Spontaneous Partial Regression Of Fetal Lung Interstitial Tumor With A2m::alk Rearrangement In A Neonate

Tan-Garcia, A. 2024Lung cancer

Tan-Garcia, A., Lee, Y. T., Kuick, C. H., Soh, S. Y., Chang, K. T., & Merchant, K. (2024). Spontaneous Partial Regression of Fetal Lung Interstitial Tumor With A2M::ALK Rearrangement in a Neonate. Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society, 27(2), 187–192. https://doi.org/10.1177/10935266231189929

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Abstract

The differential diagnosis for neonatal primary lung masses includes developmental anomalies and congenital lung tumors. Fetal lung interstitial tumor (FLIT) is a rare benign mesenchymal lesion which presents either antenatally or within the first 3 months of age. FLIT is a circumscribed solid-cystic mass which histologically resembles the fetal lung during the canalicular stage at 20-24 weeks of gestation. It is composed of immature mesenchymal cells expanding the interstitium and irregular airspace-like structures. Of all published cases, only 1 identified an α2-macroglobulin (A2M)::anaplastic lymphoma kinase (ALK) fusion and all cases underwent surgical resection in the neonatal or infancy period. We present the second case of FLIT with an A2M::ALK fusion diagnosed postnatally in a neonate which partially regressed spontaneously during conservative management with interim resection at 39 months of age, and provide a review of the literature.

Case Details

Disease Location

Fetal lung

Personal Characteristics

39-month-old male, he was born premature at 36 weeks gestation via emergency cesarean section for non-reassuring fetal status.

Clinical Characteristics

At birth, he was noted to have hydrops fetalis with bilateral pleural effusion, ascites, and truncal and peripheral edema. A chest radiograph showed bilateral white-out of the lungs. Ultrasonography showed a solid-cystic mass in the right middle to lower thorax measuring 6.1 cm. The hydrops fetalis was not diagnosed antenatally and was assessed to be secondary to the intrathoracic tumor and anemia. Chest drains were inserted and pleural fluid analysis showed a transudative profile. The right intrathoracic mass was further evaluated by MRI which showed a heterogeneous ovoid mass measuring 6.5 cm × 4.6 cm × 4.2 cm and causing left-sided displacement of the heart. The patient underwent a thoracoscopic-assisted, mini-thoracotomy and resection of the lesion. Macroscopically, the solid circumscribed mass was centered within the lung parenchyma, measuring 1.5 cm × 1 cm × 1 cm. Microscopically, the lesion was unencapsulated and composed of haphazardly oriented bland spindle to ovoid cells expanding the interstitium in a fibrocollagenous and focally myxoid stroma. Gene fusion analysis identified an a2m (exon 23)::alk (exon 19) fusion. The final diagnosis was fetal interstitial lung tumor with a2m::alk gene fusion

Remission Characteristics

Serial monitoring showed gradual reduction in the size of the intrathoracic mass and normal urine hva and vma.

Treatment & Mechanisms

Proposed Remission Mechanisms

The genomic breakpoint of a2m was within intron 23, resulting in the retention of exon 23 in the fusion gene, inactivates de tumorigenesis capability of the alk kinase domain

Clinical Treatment

Thoracotomy and resection of the lesion

Non-Clinical Treatment

None reported