Transbronchial cryo‐nodal biopsies in children: A case series

When evaluating pediatric hilar lymphadenopathies, sampling can be challenging due to the location and size of the lymph nodes. Transbronchial needle aspiration (TBNA) face challenges related to sample size and adequacy, particularly when diagnosing lymphoma and sarcomas.1 The recent introduction of a 1.1 mm cryoprobe allows clinicians to perform cryoextraction, tissue devitalization, and cryobiopsies to evaluate and treat various pediatric airway diseases.2 While adult literature highlights the diagnostic benefits of transbronchial cryo-nodal biopsies, there is currently no data on cryo-nodal biopsies in pediatric cases.3, 4 To our knowledge, this is the first case series describing this novel technique in pediatrics. This case series was conducted at Cincinnati Children's Medical Center focusing on patients diagnosed with hilar lymphadenopathies who underwent Endobronchial Ultrasound (EBUS) or Cone Beam CT (CBCT) and transbronchial biopsies. This study has been determined to be exempt from IRB review in accordance with applicable regulations and institutional policy (IRB # 2024-0360), with a waiver of informed consent. A 16-year-old previously healthy male presented for acute on chronic abdominal pain, hypertension with proteinuria, and weight loss. Endoscopy was initially concerning for Inflammatory bowel disease. However, biopsies showed only lymphocytic infiltration, and CT scan of the abdomen was notable for pancreatitis, ascites, lymphadenopathy in the chest and abdomen, and multiple bone lesions. The cytology of ascites was negative for malignant cells. Broad inflammatory and infectious work-up did not reveal an obvious cause. Mediastinal lymph nodes were determined to be the most accessible nodes. He underwent EBUS with TBNA and cryo-nodal biopsy of the 11 L lymph node (see Image 1). Both biopsies were consistent with signet ring cell adenocarcinoma. The cryobiopsy provided substantially larger tissue samples which permitted various stains to be performed by the pathology team. The patient had no complications from this procedure and was transferred to the oncology floor to initiate chemotherapy. A 13-year-old female with a known Hodgkin's Lymphoma with partial response to initial chemotherapy underwent surveillance positron emission tomography (PET) scan, which showed interval progression with increased size and metabolic activity of mediastinal and supraclavicular lymph nodes. She, then, underwent bronchoscopy for lymph node biopsy. EBUS guided cryo-nodal biopsy of 10 R and subcarinal lymph nodes were performed. The 11 RI lymph node could not be reached with EBUS due to small airway size and CBCT guided biopsies were obtained. The biopsies showed large, atypical cells consistent with Reed-Sternberg cells positive for CD30, partial CD15, and dim PAX5, diagnostic of recurrence of classic Hodgkin Lymphoma. She had no complications from the procedure. A 10-year-old previously healthy male initially presented to an outside hospital with abdominal pain in the setting of prolonged malaise and 10 pounds weight loss. The months before admission also included intermittent rib pain and a febrile illness treated as group A streptococcus pharyngitis. CT scans showed nodules scattered throughout the lungs and pancreas. He began to have worsening respiratory status and fevers. He was started on antibiotics for concerns of community acquired pneumonia and pancreatitis and was subsequently transferred to our facility. The patient underwent bronchoscopy that revealed a large mass obscuring the right upper lobe (RUL) and 90% of the bronchus intermedius. EBUS-TBNA was taken of the 10 R lymph node. Forceps and cryo-nodal biopsies were obtained. All samples showed infiltrates of large neoplastic cells positive for DC3, CD7, CD4, CD8, CD30, ALK, and MUM1, diagnostic for anaplastic Large Cell Lymphoma. The bronchus intermedius patency was re-established, but RUL bronchus could not be recanalized. The patient underwent no complications of the procedure, but he was admitted to the PICU for post-op monitoring and required brief escalation of respiratory support due to bronchial compression. A 15-year-old male with a history of asthma was admitted for prolonged cough, weight loss, and globus sensation. Initial work-up revealed extensive mediastinal and hilar lymphadenopathy with superior vena cava and esophageal compression. Blood count showed microcytic anemia. He underwent a broad infectious and inflammatory work-up as well as EBUS. TBNA, forceps biopsies, and cryo-nodal biopsies of the station 7 and 4 R lymph nodes were negative for lymph node malignancy and showed fungal elements and necrotizing granuloma. Blood work resulted in a histoplasma CF positive at 1:256 despite a negative histoplasma antigen. The patient had no complications postoperatively and began treatment for histoplasma infection with clinical improvement. A 3-year-old female with history of neuroblastoma, status-post two bone marrow transplants presented with new left hilar and subcarinal soft tissue masses. A PET scan was performed which confirmed FDG avidity of the new lesions and were concerning for recurrent disease. She underwent CBCT in the operating room and subcarinal mass was mapped with augmented fluoroscopy. The subcarinal lymph node was biopsied with TBNA, forceps, and cryoprobe. The TBNA and forceps did not provide adequate specimen; however, the cryo-nodal biopsy demonstrated poorly differentiated neuroblastoma. A 2-year-old infant with history of multifocal mesenchymal hamartoma of the chest wall was monitored with serial scans. Her Magnetic Resonance Imaging (MRI) revealed a new mass in the right hilum. A PET scan was obtained which showed FDG avid right anterior chest wall mass lesion, with FDG avid mediastinal lymphadenopathy and large right perihilar conglomerated nodal lesion. CBCT imaging was performed in the operative room and the lesion was localized and segmented by the interventional radiology (IR) team. The airway evaluation revealed an endobronchial lesion in the right middle lobe bronchus, which was compressing distal bronchi. EBUS could not be utilized in this case given the small age and size of the patient. The endobronchial lesion was initially biopsied with cryoprobe and forceps under fluoroscopic guidance (see Image 2). The pathological results showed necrotizing granuloma without malignant transformation of her hamartoma. In pediatrics, we present an innovative approach to obtaining minimally invasive lymph node samples through transbronchial cryo-nodal biopsies in patients as young as 2-years-old. The cryobiopsies were performed either under EBUS or CBCT with augmented fluoroscopic guidance in patients too small to accommodate the EBUS scope. The procedure involves creating a needle puncture adequate to pass the 1.1 mm cryoprobe. The transbronchial cryobiopsies helped retrieve larger biopsy specimens when compared to regular TBNA and facilitate histopathologic evaluation. The cryo-nodal sampling was successful, leading to an end diagnosis for all patients. Minimal complications were observed, limited to mild bleeding (Nashville Grade 1 & 2), and no patients were diagnosed with pneumothorax or required chest tube placement (see Table 1). In addition, none of the patients in this case series necessitated additional invasive procedures such as mediastinoscopy or VATS. Our study is limited by sample size. Further extensive clinical trials are necessary before routine use can be recommended. 6.4 cm × 4.3 cm (S7) 4.7 cm × 5 cm (4 R) 19 G needle, 2.0 mm forceps and 1.7 mm cryoprobe 21 G Peri flex needle, 1.15 mm forceps and 1.1 mm cryoprobe 1.1 mm cryoprobe and 2.0 mm forceps Necrotic granuloma with few yeast forms. Histo CF + 1:256 Grade 2 bleeding controlled with >1 min suctioning Kubra Melike Bozkanat: Conceptualization; investigation; writing—original draft; writing—review and editing; resources; project administration; visualization. Robert Wendroth: Conceptualization; investigation; writing—original draft. Christopher Radchenko: Conceptualization; writing—review and editing. Gregory Burg: Conceptualization; writing—review and editing. Erik Hysinger: Conceptualization; investigation; writing—original draft; resources; writing—review and editing; visualization. The authors declare no conflicts of interest. The data that support the findings of this study are available from the corresponding author upon reasonable request.