Generalized lymphatic anomalies and review of the current management landscape: a case report and review of the literature

Abstract

Background Generalized lymphatic anomaly previously known as diffuse systemic lymphangiomatosis is a rare multisystem congenital disease arising from the lymphatic system, and it is characterized by abnormal proliferation of the lymphatic channels in osseous and extraosseous tissues. It typically affects children or young adults. Although it is benign, it can be misdiagnosed as malignancy because of its diffuse and debilitating nature depending on the site of involvement. Due to its rarity, diagnosis is often delayed, leading to potential significant morbidity or mortality if vital organs are involved. Furthermore, its potential for multiorgan involvement with no curative treatment makes its management challenging. Case presentation We describe a case of a 35-year-old Caucasian female, who presented with epigastric pain and was subsequently extensively investigated at multiple tertiary centers by numerous specialists for query malignancy and metabolic bone disorder following incidental computed tomography imaging findings of multiple osteolytic lesions in the axial skeleton, and low-attenuating lesions in the axilla, spleen, and mediastinum. The diagnosis was confirmed with an axillary excisional biopsy. She was clinically stable with no end organ damage. She was monitored conservatively. Conclusions The case illustrates the importance of increased awareness among clinicians for this rare congenital disease to enable earlier diagnosis and to avoid unnecessary invasive investigations. Furthermore, this case highlights the potential need for multiple biopsies of affected sites to confirm diagnosis. We also discuss the emergence of interferon therapy, chemotherapy, immunosuppression, and immunotherapy as medical management for this condition.

Use of bevacizumab in a patient with Whipple’s disease: managing diagnostic uncertainty

“…Microbiology from bronchoalveolar lavage, which included culture, galactomannan antigen, and extended bacterial, viral (including SARS-CoV-2) and fungal nucleic acid testing, was negative. Further multidisciplinary discussion was undertaken to discuss options for therapy of GLA with multisystem involvement, given the absence of established guidelines for treatment, with most evidence derived from case reports or series 6. While most evidence exists for mTOR inhibitors, a decision was made to trial the anti-VEGF agent bevacizumab due to its intravenous delivery in the context of concurrent mesenteric involvement which might impair absorption, and promising case reports in the adult population for diffuse pulmonary lymphangiomatosis lead to clinical and objective improvements after first dose 7 8.…”

The Genetic Architecture of Vascular Anomalies: Current Data and Future Therapeutic Perspectives Correlated with Molecular Mechanisms

“…Milroy’s disease, the classic form of congenital lymphedema, is transmitted in an autosomal dominant manner and is determined by LOF of the VEGFR3 (vascular endothelial growth factor receptor 3 also called FLT4 ) gene, located on chromosome 5q35.3 [ 6 ]. Congenital lymphedema often presents at birth or childhood with swelling of both lower extremities [ 58 , 59 ].…”

“…GLA is a rare, benign congenital disorder characterized by abnormal proliferation of lymphatic vessels resulting in dilated and abnormally connected thin-walled lymphatic channels. The disease manifests itself in children and young adults, the lungs and skeleton being most frequently affected, in the latter case causing pain and impaired mobility [ 59 , 60 ].…”

Pathologic Fracture as Presentation of Generalized Lymphangiomatosis in an Eight-Year-Old: A Case Report and Literature Review

“…The incidence and clinical features of GLA are unknown, challenging even the most seasoned clinicians. A multidisciplinary team of pediatricians, orthopedists, and radiologists is needed to diagnose and manage patients with this disease [ 1 , 2 ].…”