A Unique Presentation of Nodular Masses in Infancy

We present a case of a male neonate delivered at 35 weeks and 6 days to a 37-year-old gravida 4 para 4 mother. The birthweight of the neonate was 2,590 g. Maternal cell-free DNA testing is low risk, and invasive genetic testing is not pursued. Midpregnancy anatomy scan reveals right forearm edema. Serial growth scans are performed for surveillance. At 35 weeks, ultrasonography reveals new growth lag in both abdominal circumference and estimated fetal weight, accompanied by bilateral enlargement of lower extremities and persistent thickening of the right forearm. Soft tissue abnormalities include scattered heterogeneous thickening with echogenic and hypoechoic areas. The appendicular skeleton shows preservation with normal ossification, except for some remodeling of the right proximal ulna. Prenatal consultants include neonatology and pediatric orthopedics, leading to a scheduled cesarean delivery to mitigate potential dystocia risk because of extremity enlargement.After delivery, the infant briefly needs positive pressure ventilation, transitioning to nasal continuous positive airway pressure. Apgar scores are 5 and 8 at 1 and 5 minutes, respectively. Physical examination reveals a 14-cm firm right forearm mass with ventral skin ulceration, right-sided finger contractures, and mobile nodules (4 − 30 mm) on lower extremities, abdomen, neck, and back (Fig 1 A−C). The infant is admitted to the NICU for comprehensive evaluation.After initial radiography (Fig 2 A) and ultrasonography (Fig 2 B, Fig 3 A and B), whole body MRI (with and without contrast) reveals multiple masses in various regions, demonstrating peripheral enhancement and central necrosis (Fig 3 C and D). Biopsy confirms the diagnosis, leading to a collaborative, multidisciplinary approach involving neonatology, radiology, pediatric surgery, dermatology, and hematology-oncology, and chemotherapy is initiated for treatment.Soft tissue overgrowth and tumors in neonates encompass a wide range of differential diagnoses such as cysts, lipomas, neuromas, fibrous hamartomas, neurofibromas, congenital teratoma, infantile myofibromatosis (IM), vascular anomalies, and a spectrum of borderline and malignant lesions including histiocytosis, stage MS neuroblastoma, congenital infantile fibrosarcoma, and rhabdomyosarcoma. (1) Accurate diagnosis of the underlying etiology requires thorough consideration of clinical examination findings, including associated features, chronology, and assessment of both histologic and imaging findings.Histopathologic examination demonstrated a hypocellular myoid nodule with immature mesenchymal cells and branching vessels (Fig 4 A−D). Myoid areas exhibited strong and diffuse immunoreactivity for smooth muscle actin (SMA). Initial tumor profiling genetic laboratory tests yielded negative results for genes linked to IM, hereditary cancer syndromes, and connective tissue disorders. However, the extended gene analysis revealed a variant in the platelet-derived growth factor receptor beta (PDGFRB) gene (p.Cys835_Gly837dup). The presence of multiple nodules raised suspicion of multicentric or generalized myofibromatosis with visceral involvement. Biopsy results played a crucial role in confirming the diagnosis of IM.IM is a rare mesenchymal tumor that primarily affects the neonatal and pediatric populations in the first few years of age. It has an estimated incidence of 1 in 150,000 to 400,000 live births (2) and predominantly affects males. (3) Cutaneous manifestations are most common, with tumors presenting in the skin, subcutaneous tissue, or underlying muscle. They can be solitary, multicentric, or generalized, each requiring tailored therapeutic approaches. (2)(4)The presentation varies with lesion location and extent. Solitary lesions manifest as firm subcutaneous masses, occurring in various locations such as the skull, cervical vertebrae, long bones, and bone marrow. (3)(5)(6) Multicentric IM involves nodules affecting the skin, tissues, muscles, and bones. (7) The generalized form includes both cutaneous and visceral involvement, affecting organs. (8) Nodules vary in color and size, displaying features such as lobulation, ulceration, or hemangiomalike characteristics, and, rarely, pedunculated, multilobulated lesions may develop ischemic necrosis. (5)(9)Diagnosis relies on precise histopathologic examination, revealing myofibroblastic spindle cell proliferation encircling polygonal cells with central zone necrosis and calcifications. (5) Immunohistochemical staining shows positive reactivity to vimentin and SMA. (5)(10) Multicentric and generalized forms exhibit higher cellular division, skin erosions, ulceration, and long-lasting inflammation compared to the solitary form. (5) Imaging studies including ultrasonography, CT, and whole body MRI allow visualization of tumor growth and progression, which aid in diagnosis and surgical planning. (1)(5)Recent studies have linked IM with mutations in specific genes. The PDGFRB gene plays a vital role in stimulating mesenchymal cells; sporadic mutations in this gene have been recognized as the most prevalent cause of IM. (11) Genetic aberrations in NOTCH3 and the serum response factor (SRF) have similarly been linked to the PDGFRB pathway. (12)(13)(14) In our patient, whole exome sequences failed to show a variant in either gene. Further investigations are required to further elucidate the intricate pathogenesis of this condition. (15)The management hinges upon several key factors, including tumor location, extent, and clinical presentation. For suspected solitary lesions, additional evaluation is crucial to rule out visceral involvement. (16) Genetic counseling is strongly advised, particularly for patients with PDGFRB germline mutations. (17) Treatment strategies range from surveillance of asymptomatic solitary lesions to a comprehensive multidisciplinary approach, including surgery, chemotherapy, and radiation, for aggressive, recurrent, or symptomatic cases. (5)(9)Some lesions may regress spontaneously 18 to 24 months after diagnosis. (17) Optimal surveillance potentially involves rapid whole body MRI scans every 3 to 6 months for 2 years, depending on tumor extent. (18) A mid-adolescence screening brain magnetic resonance angiography is advisable if PDGFRB mutations are present. (10)(17) Family members of a patient with IM should consult with a geneticist for potential surveillance. Solitary lesions generally have a favorable prognosis, but the generalized form with visceral involvement carries increased morbidity and rare instances of fatality due to mass effect. (15)(17) Mortality risk increases with cardiac and gastrointestinal complications. (15)In summary, IM should be considered as a potential diagnosis in cases of soft tissue masses in newborns and pediatric patients. It is crucial to establish a multidisciplinary team to ensure accurate diagnosis, therapeutic management, and future surveillance and counseling for both the infant and the family.Neonates with soft tissue enlargement on prenatal ultrasonography should be closely monitored, and IM should be considered in the differential diagnosis.Diagnosis should be confirmed through histopathological analysis and immunohistochemistry.Focused genetic investigation and counseling are necessary for patients with IM.