リンパ管腫症／ゴーハム病

UNLABELLED: Specialised skeletal blood-vessel subtypes have established the importance of angiogenesis-osteogenesis coupling in bone development, homeostasis and repair. Emerging evidence further indicates that bone-associated lymphatics contribute to interstitial fluid drainage, immune trafficking, inflammatory resolution, damage-associated molecular pattern clearance and regenerative signalling. However, how vascular and lymphatic compartments are coordinated in the skeletal microenvironment remains incompletely defined.In this review, we propose an evidence-graded working model of skeletal vascular-lymphatic dual circulation. We distinguish established observations from logical extensions and author-proposed analytical constructs. Current evidence is organised into shared upstream cues, blood-vessel-biased programmes, lymphatic identity and functional programmes, proposed coupling interfaces, and disease-integration modules. We discuss their context-dependent relevance across osteoporosis, glucocorticoid-associated skeletal injury, osteoarthritis, rheumatoid arthritis, bone metastasis, Gorham-Stout disease and heterotopic ossification.Finally, we evaluate therapeutic directions aimed at restoring pro-osteogenic vascular competence, lymphatic drainage and clearance, and vascular-lymphatic-immune coordination. This framework is intended to organise current evidence, define knowledge gaps and guide future validation rather than to assert a validated disease taxonomy or clinical stratification system. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: This review offers an evidence-graded translational framework for skeletal repair and bone disease by integrating vascular niche competence, lymphatic drainage and clearance, osteoimmune regulation, and stromal repair. It highlights functional endpoints, including perfusion quality, lymphatic transport, inflammatory resolution, pathological osteoclastogenesis, and repair quality, that may improve preclinical study design and therapeutic evaluation. Vascular-skewed and lymphatic-skewed features are used as heuristic descriptors rather than diagnostic categories. After validation of skeletal vascular-lymphatic biomarkers, imaging tools, and functional endpoints, this framework may inform future stratification and network-informed combination therapy.

This narrative review summarizes contemporary diagnosis and management of aneurysmal bone cysts (ABCs) of the spine and sacrum, emphasizing axial-specific risks, decision thresholds, and adjunctive therapies. A PubMed/MEDLINE review was performed focusing on the last 10 years, with selective inclusion of earlier foundational studies. Search terms combined "aneurysmal bone cyst" with anatomy-specific modifiers ("spine," "vertebral," and "sacrum") and domains relevant to axial care, including molecular diagnostics such as ubiquitin-specific peptidase 6, imaging, biopsy, differential diagnosis, operative strategies, embolization, percutaneous therapies, and recurrence. ABCs are benign but locally aggressive lesions that frequently involve posterior elements, extend toward the canal, and threaten neurologic function and stability. Imaging may demonstrate expansile osteolysis and fluid-fluid levels but lacks specificity in axial disease; biopsy remains essential to exclude malignant mimics and secondary ABC-like change. Management is individualized based on neurologic compromise, instability, deformity, and lesion extent. Surgical options range from intralesional curettage to more extensive excision with stabilization, while adjuncts such as selective arterial embolization, doxycycline sclerotherapy, and denosumab may support hemorrhage control and local control in selected cases. Recurrence remains most strongly associated with incomplete resection and younger age. Prospective, spine-specific comparative studies are needed to standardize treatment selection, define the sequencing of adjuncts, and clarify long-term outcomes.

A recent study reported the existence of lymphatic vessels in normal bone and suggested their involvement in bone regeneration after injury. However, this conclusion was based on approaches that do not allow unequivocal identification of the spatial localization of lymphatic endothelial cells (LECs). Here, we employed a Prox1-based genetic tool and a dual-recombinase-mediated LEC-specific labeling system to trace lymphatic vessels with high specificity. We found that LECs are present in the connective tissues, including the periosteum surrounding the bone. However, they do not reside within the bone itself, nor do they penetrate the periosteum to facilitate bone regeneration after injury. By contrast, hyperplastic LECs on the bone surface breach the periosteum and invade bone tissue in mouse models of generalized lymphatic anomaly and Gorham-Stout disease. These data demonstrate that lymphatic vessels are absent from bone during homeostasis and regeneration after injury but invade bone during disease. This Matters Arising paper is in response to Biswas et al. (2023), published in Cell. See also the response by Yang et al. (2026), published in this issue.

Rare bone diseases, though uncommon, present significant diagnostic and therapeutic challenges due to their clinical variability and overlapping symptoms with more prevalent conditions. This article describes a clinical case series of three patients with bone fragility fractures caused by rare bone diseases - primary hyperparathyroidism with brown tumor, Gorham-Stout disease, and alkaptonuria - treated at the Department of Orthopedic and Traumatology of Pisa University Hospital between 2018 and 2023. Each case highlights the diagnostic complexities, including inconclusive biopsies, nonspecific imaging findings, and the necessity of a multidisciplinary approach for accurate diagnosis and management. Advanced imaging techniques, such as MRI, CT, and PET, alongside genetic and biochemical analyses, were instrumental in guiding treatment. The cases underscore the importance of early differential diagnosis, which is critical for optimizing both surgical and non-surgical interventions, preventing long-term complications, and improving the patient outcomes. This study emphasizes the need for a collaborative, multidisciplinary approach to effectively diagnose and manage rare bone diseases, ensuring that patients receive timely and appropriate care.

BACKGROUND: Gorham-Stout disease (GSD) is an extremely rare osteolytic disorder characterized by progressive bone resorption associated with nonneoplastic vascular or lymphatic proliferation. Craniovertebral junction involvement is particularly uncommon and may cause life-threatening instability or neurological compromise. To the authors' knowledge, bow hunter syndrome caused by craniovertebral GSD has not been reported. OBSERVATIONS: A 71-year-old woman presented with dizziness and inability to stand. Brain MRI and MR angiography demonstrated a left cerebellar infarction and left vertebral artery occlusion. CT and MRI showed extensive C1-3 osteolysis and cranial settling of the osteolytic C2 vertebral body. CT angiography in the neutral head position demonstrated vertebral artery recanalization, suggesting dynamic occlusion consistent with bow hunter syndrome. Additional osteolytic lesions in the L1 vertebral body, left seventh rib, and phalanges suggested GSD. After halo vest immobilization, occipitocervical (O-C7) fusion was performed using an autologous fibular strut graft, with angiographic confirmation of vertebral artery patency. Histopathological analysis confirmed GSD. No progression of the C1-3 osteolytic lesions was observed during 4 years of follow-up. LESSONS: Craniovertebral GSD can cause bow hunter syndrome and cerebellar infarction. Angiographic confirmation of vertebral artery patency, rigid fixation, and a fibular graft potentially resistant to osteolysis may be important for stabilization. https://thejns.org/doi/10.3171/CASE26576.