Bone Marrow Failure and Extramedullary Hematopoiesis in Fibrous Dysplasia/Mccune-Albright Syndrome

Program: Abstracts - Orals, Poster Previews, and Posters
Session: FRI 368-390-Metabolic Bone Disease Case Reports (posters)
Friday, April 1, 2016: 1:15 PM-3:15 PM
Exhibit/Poster Hall (BCEC)

Poster Board FRI 377
Cemre Robinson*1, Andrea Estrada2, David E. Kleiner3, Alison Marie Boyce1, Revi P Mathew4, Robert Stanton5, Haydar Frangoul4 and Michael T Collins6
1Skeletal Clinical Studies Unit, Craniofacial and Skeletal Diseases Branch, Bethesda, MD, 2NIDCR/NICHD, NIH, Bethesda, MD, 3National Cancer Institute, Bethesda, MD, 4The Children's Hospital at TriStar Centennial, Nashville, TN, 5Nemours Children's Hospital, Orlando, FL, 6National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD
Background:  Fibrous dysplasia/McCune-Albright syndrome (FD/MAS) is a rare disorder caused by somatic activating mutations in Gsα.  In bone, this results in proliferation of skeletal stem cells with impaired differentiation towards mature osteoblasts, adipocytes, and hematopoiesis-supporting stroma.  Bone and bone marrow are replaced by fibro-osseous tissue typically devoid of hematopoietic marrow. Despite the potential for extensive marrow replacement in severely affected patients, there are no reports of bone marrow failure associated with FD/MAS.

Clinical case: The patient is a 15 year old girl with FD/MAS manifested by precocious puberty, hyperthyroidism (treated with total thyroidectomy), FGF-23-mediated hypophosphatemia, and extensive polyostotic FD requiring spinal fusion and intramedullary rod placement in both femora and tibiae.  Her course was complicated by long-standing secondary hyperparathyroidism related to hypophosphatemia treatment.  At age 14, she developed fatigue, weakness, and inability to walk.  Evaluation showed hepatosplenomegaly, pancytopenia, and iatrogenic thyrotoxicosis secondary to levothyroxine overtreatment.  Bone marrow biopsy was hypocellular with only 10% cellularity and fibrous tissue consistent with FD.  Liver biopsy revealed significant trilineage extramedullary hematopoiesis (EMH).  Evaluation showed no infectious or inherited causes of marrow failure.  Despite correction of hyperthyroidism and hyperparathyroidism, the patient remained pancytopenic, requiring multiple  red cell transfusions over the course of 8 months, and developed progressive massive painful splenomegaly (23.1 cm in longest dimension).  She underwent splenectomy 16 months after presentation with recovery of the pancytopenia and has since been transfusion independent.

Conclusion:  The etiology of this patient’s marrow failure, a complication previously not reported in FD/MAS, is likely related to loss of marrow reserve due to extensive polyostotic FD.  Compensatory EMH with massive splenomegaly and sequestration likely exacerbated her cytopenia, as evidenced by clinical improvement post-splenectomy.  Iatrogenic thyrotoxicosis and hyperparathyroidism, both of which can suppress bone marrow function, may have been exacerbatory factors.  Typically, patients with polyostotic FD have sufficient hematopoiesis-supporting cell niche to meet the demands of blood cell production. However, it is possible that at baseline, this patient’s hematopoiesis-supporting niche was barely adequate, and was worsened by uncontrolled endocrinopathies and intramedullary surgical instrumentation. This case demonstrates the complexity and multifactorial etiology of pancytopenia, and reports a novel complication of FD/MAS. 

Nothing to Disclose: CR, AE, DEK, AMB, RPM, RS, HF, MTC

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