Abstract
Gorham-Stout syndrome (GSS) is a rare lymphatic malformation with fewer than 400 documented cases, characterized by progressive osteolysis and multisystem involvement. Its refractory management to conventional therapies represents a significant clinical challenge. This systematic review, following PRISMA 2020, synthesizes current evidence on pathophysiological mechanisms, diagnosis, and emerging therapeutic strategies for refractory multisystem GSS, with emphasis on robotic surgery, vascular microsurgery, and immunotherapy. PubMed, Scopus, Web of Science, and Orphanet were searched up to May 2026, including 74 studies. The results suggest that robotic surgery offers precision advantages for spinal stabilization and complex reconstructions; vascular microsurgery controls lymphatic leakage; and immunotherapy with interferon-alpha, sirolimus, and bisphosphonates stabilizes the disease in selected cases. Management requires a multidisciplinary approach, but the lack of clinical trials and heterogeneity limit high-quality evidence. Prospective registries and validated diagnostic criteria are needed.
References
[1] Z. Zhou, T. Qiu, J. Zhou, Z. Zhang, X. Gong, X. Zhang, Y. Lan, C. Yang, Y. Zhang, S. Xiang, and Y. Ji, "Clinical features and current management experience in Gorham-Stout disease: a systematic review," Orphanet J. Rare Dis., vol. 20, p. 134, Mar. 2025. doi: 10.1186/s13023-025-03649-9.
[2] A. B. Burke, C. Dong, and S. R. Chandra, "Updates to the Management of Gorham-Stout Disease and Osseous Vascular Lesions in the Head and Neck," Oral Maxillofac Surg Clin North Am, vol. 36, no. 1, pp. 93-102, Feb. 2024. doi: 10.1016/j.coms.2023.09.006.
[3] A. Takahashi, C. Ogawa, T. Kanazawa, H. Watanabe, M. Suzuki, N. Suzuki, Y. Tsuchida, A. Morikawa, and H. Kuwano, "Remission induced by interferon alfa in a patient with massive osteolysis and extension of lymph-hemangiomatosis: a severe case of Gorham-Stout syndrome," J. Pediatr. Surg., vol. 40, no. 3, pp. E47-E50, Mar. 2005. doi: 10.1016/j.jpedsurg.2004.11.015.
[4] H. Di, B. Zhang, N. Xu, Y. Yin, X. Han, Y. Zhang, and X. Zeng, "Refractory serositis in Gorham–Stout syndrome," Orphanet J. Rare Dis., vol. 17, p. 152, Apr. 2022. doi: 10.1186/s13023-022-02307-8.
[5] M. Rossi, I. Rana, P. S. Buonuomo, G. Battafarano, V. De Martino, M. D’Agostini, et al., "Stimulation of Treg cells to inhibit osteoclastogenesis in Gorham-Stout disease," Front. Cell Dev. Biol., vol. 9, p. 706596, 2021. doi: 10.3389/fcell.2021.706596.
[6] Y. S. Park, J. M. Goo, and J. G. Im, "Gorham-Stout syndrome (GSS): A rare disease characterized by localized bone resorption," Korean J. Radiol., vol. 26, no. 10, pp. 951-958, Oct. 2025. doi: 10.3348/kjr.2025.0264.
[7] M. J. Page, J. E. McKenzie, P. M. Bossuyt, I. Boutron, T. C. Hoffmann, C. D. Mulrow, L. Shamseer, J. M. Tetzlaff, E. A. Akl, S. E. Brennan, R. Chou, J. Glanville, J. M. Grimshaw, A. Hróbjartsson, M. M. Lalu, T. Li, E. W. Loder, E. Mayo-Wilson, S. McDonald, and D. Moher, "The PRISMA 2020 statement: An updated guideline for reporting systematic reviews," BMJ, vol. 372, p. n71, 2021. doi: 10.1136/bmj.n71.
[8] S. Liu, X. Zhou, A. Song, X. Kong, Y. Wang, and Y. Liu, "Successful treatment of Gorham-Stout syndrome in the spine by vertebroplasty with cement augmentation: A case report and literature review," Medicine (Baltimore), vol. 97, no. 29, p. e11555, Jul. 2018. doi: 10.1097/MD.0000000000011555.
[9] E. Grigoriou, M. B. Transtrum, S. Oishi, C. E. Johnston, and M. E. Johnson, "Tibiopelvic rotational arthroplasty for pediatric Gorham-Stout disease: A case report and surgical technique," JBJS Case Connect., vol. 14, no. 4, p. e24.00172, Oct.-Dec. 2024. doi: 10.2106/JBJS.CC.24.00172.
[10] M. Kose, S. Pekcan, D. Dogru, C. Akyuz, U. Ozcelik, Y. Ozsurekci, B. Gulhan, M. Demircin, and N. Kiper, "Gorham-Stout Syndrome with chylothorax: successful remission by interferon alpha-2b," Pediatr. Pulmonol., vol. 44, no. 6, pp. 613-615, Jun. 2009. doi: 10.1002/ppul.20849.
[11] N. Morimoto, H. Ogiwara, K. Suzuki, M. Oya, T. Hori, and T. Otsuki, "Gorham-Stout syndrome affecting the temporal bone with cerebrospinal fluid leakage," Int. J. Pediatr. Otorhinolaryngol., vol. 77, no. 9, pp. 1596-1600, Sep. 2013. doi: 10.1016/j.ijporl.2013.06.001.
[12] D. K. Kuriyama, S. C. McElligott, D. W. Glaser, and K. S. Thompson, "Treatment of Gorham-Stout disease with zoledronic acid and interferon-α: a case report and literature review," J. Pediatr. Hematol. Oncol., vol. 32, no. 8, pp. 579-584, Nov. 2010. doi: 10.1097/MPH.0b013e3181edb464.
[13] L. Cramer, S. Wei, A. C. Merrow, and J. G. Pressey, "Gorham-Stout Disease Successfully Treated With Sirolimus and Zoledronic Acid Therapy," J. Pediatr. Hematol. Oncol., vol. 38, no. 3, pp. e129-e132, Apr. 2016. doi: 10.1097/MPH.0000000000000514.
[14] T. Mao, L. Xu, Y. Yu, Z. Li, and J. Sheng, "Use of zoledronic acid combined with thalidomide in the treatment of Gorham–Stout disease," Rheumatology (Oxford), vol. 57, no. 6, pp. 1122-1124, Jun. 2018. doi: 10.1093/rheumatology/key055.
[15] D. A. Ramaroli, P. Cavarzere, M. Cheli, M. Provenzi, M. Barillari, G. Rodella, R. Gaudino, and F. Antoniazzi, "A Child with Early-Onset Gorham-Stout Disease Complicated by Chylothorax: Near-Complete Regression of Bone Lesions with Interferon and Bisphosphonate Treatment," Horm. Res. Paediatr., vol. 91, no. 6, pp. 406-410, 2019. doi: 10.1159/000495364.
[16] K. Stawarz, A. Galazka, F. Kissin, and J. Zwolinski, "A new therapeutic approach in Gorham–Stout disease: a case report," Front. Surg., vol. 10, p. 1225209, Sep. 2023. doi: 10.3389/fsurg.2023.1225209.
[17] G. M. Quille Chuisaca, M. C. Ortiz Vega, B. L. Patiño López, J. L. Nugra Sanchez, J. L. Castillo Lopez, and J. J. Ayora Muñoz, "Síndrome de Gorham Stout: Reporte de Caso y Revisión de la Literatura," iberociencias, vol. 4, no. 4, pp. 2956-2969, Dec. 2025. doi: 10.63371/ic.v4.n4.a535.
[2] A. B. Burke, C. Dong, and S. R. Chandra, "Updates to the Management of Gorham-Stout Disease and Osseous Vascular Lesions in the Head and Neck," Oral Maxillofac Surg Clin North Am, vol. 36, no. 1, pp. 93-102, Feb. 2024. doi: 10.1016/j.coms.2023.09.006.
[3] A. Takahashi, C. Ogawa, T. Kanazawa, H. Watanabe, M. Suzuki, N. Suzuki, Y. Tsuchida, A. Morikawa, and H. Kuwano, "Remission induced by interferon alfa in a patient with massive osteolysis and extension of lymph-hemangiomatosis: a severe case of Gorham-Stout syndrome," J. Pediatr. Surg., vol. 40, no. 3, pp. E47-E50, Mar. 2005. doi: 10.1016/j.jpedsurg.2004.11.015.
[4] H. Di, B. Zhang, N. Xu, Y. Yin, X. Han, Y. Zhang, and X. Zeng, "Refractory serositis in Gorham–Stout syndrome," Orphanet J. Rare Dis., vol. 17, p. 152, Apr. 2022. doi: 10.1186/s13023-022-02307-8.
[5] M. Rossi, I. Rana, P. S. Buonuomo, G. Battafarano, V. De Martino, M. D’Agostini, et al., "Stimulation of Treg cells to inhibit osteoclastogenesis in Gorham-Stout disease," Front. Cell Dev. Biol., vol. 9, p. 706596, 2021. doi: 10.3389/fcell.2021.706596.
[6] Y. S. Park, J. M. Goo, and J. G. Im, "Gorham-Stout syndrome (GSS): A rare disease characterized by localized bone resorption," Korean J. Radiol., vol. 26, no. 10, pp. 951-958, Oct. 2025. doi: 10.3348/kjr.2025.0264.
[7] M. J. Page, J. E. McKenzie, P. M. Bossuyt, I. Boutron, T. C. Hoffmann, C. D. Mulrow, L. Shamseer, J. M. Tetzlaff, E. A. Akl, S. E. Brennan, R. Chou, J. Glanville, J. M. Grimshaw, A. Hróbjartsson, M. M. Lalu, T. Li, E. W. Loder, E. Mayo-Wilson, S. McDonald, and D. Moher, "The PRISMA 2020 statement: An updated guideline for reporting systematic reviews," BMJ, vol. 372, p. n71, 2021. doi: 10.1136/bmj.n71.
[8] S. Liu, X. Zhou, A. Song, X. Kong, Y. Wang, and Y. Liu, "Successful treatment of Gorham-Stout syndrome in the spine by vertebroplasty with cement augmentation: A case report and literature review," Medicine (Baltimore), vol. 97, no. 29, p. e11555, Jul. 2018. doi: 10.1097/MD.0000000000011555.
[9] E. Grigoriou, M. B. Transtrum, S. Oishi, C. E. Johnston, and M. E. Johnson, "Tibiopelvic rotational arthroplasty for pediatric Gorham-Stout disease: A case report and surgical technique," JBJS Case Connect., vol. 14, no. 4, p. e24.00172, Oct.-Dec. 2024. doi: 10.2106/JBJS.CC.24.00172.
[10] M. Kose, S. Pekcan, D. Dogru, C. Akyuz, U. Ozcelik, Y. Ozsurekci, B. Gulhan, M. Demircin, and N. Kiper, "Gorham-Stout Syndrome with chylothorax: successful remission by interferon alpha-2b," Pediatr. Pulmonol., vol. 44, no. 6, pp. 613-615, Jun. 2009. doi: 10.1002/ppul.20849.
[11] N. Morimoto, H. Ogiwara, K. Suzuki, M. Oya, T. Hori, and T. Otsuki, "Gorham-Stout syndrome affecting the temporal bone with cerebrospinal fluid leakage," Int. J. Pediatr. Otorhinolaryngol., vol. 77, no. 9, pp. 1596-1600, Sep. 2013. doi: 10.1016/j.ijporl.2013.06.001.
[12] D. K. Kuriyama, S. C. McElligott, D. W. Glaser, and K. S. Thompson, "Treatment of Gorham-Stout disease with zoledronic acid and interferon-α: a case report and literature review," J. Pediatr. Hematol. Oncol., vol. 32, no. 8, pp. 579-584, Nov. 2010. doi: 10.1097/MPH.0b013e3181edb464.
[13] L. Cramer, S. Wei, A. C. Merrow, and J. G. Pressey, "Gorham-Stout Disease Successfully Treated With Sirolimus and Zoledronic Acid Therapy," J. Pediatr. Hematol. Oncol., vol. 38, no. 3, pp. e129-e132, Apr. 2016. doi: 10.1097/MPH.0000000000000514.
[14] T. Mao, L. Xu, Y. Yu, Z. Li, and J. Sheng, "Use of zoledronic acid combined with thalidomide in the treatment of Gorham–Stout disease," Rheumatology (Oxford), vol. 57, no. 6, pp. 1122-1124, Jun. 2018. doi: 10.1093/rheumatology/key055.
[15] D. A. Ramaroli, P. Cavarzere, M. Cheli, M. Provenzi, M. Barillari, G. Rodella, R. Gaudino, and F. Antoniazzi, "A Child with Early-Onset Gorham-Stout Disease Complicated by Chylothorax: Near-Complete Regression of Bone Lesions with Interferon and Bisphosphonate Treatment," Horm. Res. Paediatr., vol. 91, no. 6, pp. 406-410, 2019. doi: 10.1159/000495364.
[16] K. Stawarz, A. Galazka, F. Kissin, and J. Zwolinski, "A new therapeutic approach in Gorham–Stout disease: a case report," Front. Surg., vol. 10, p. 1225209, Sep. 2023. doi: 10.3389/fsurg.2023.1225209.
[17] G. M. Quille Chuisaca, M. C. Ortiz Vega, B. L. Patiño López, J. L. Nugra Sanchez, J. L. Castillo Lopez, and J. J. Ayora Muñoz, "Síndrome de Gorham Stout: Reporte de Caso y Revisión de la Literatura," iberociencias, vol. 4, no. 4, pp. 2956-2969, Dec. 2025. doi: 10.63371/ic.v4.n4.a535.
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