Systemic mastocytosis is a multisystem disease that can affect various organs in a number of ways. Its pathophysiology is driven by the release of mast cell mediators or infiltrates into human tissues, causing toxic buildup in one or more visceral organs. 

One of the more prominent manifestations of this disease is skeletal; patients diagnosed with systemic mastocytosis are likely to be diagnosed with osteoporosis at some point of their lives. Oftentimes, the first sign of skeletal pathology is a fracture (particularly at the vertebrae). Osteosclerosis is another skeletal manifestation of systemic mastocytosis, although it is slightly less common. 

When skeletal pathology is detected in a patient with systemic mastocytosis, physicians typically perform a number of bone tests, including histomorphometric analysis and bone biopsy, to quantify the extent of bone disease. Physicians are interested in ruling out bone malignancies, especially if there are reasons for clinical suspicion to be raised. 

Read more about systemic mastocytosis etiology 

In a subset of patients, bone pathology is diagnosed before systemic mastocytosis is discovered. In circumstances in which a patient presents with bone disease and other features consistent with systemic mastocytosis, physicians are encouraged to conduct a thorough assessment and elicit a detailed history to conjecture on the likelihood of this diagnosis. 

Case Study: An Unexpected Fall and a Diagnosis of Systemic Mastocytosis 

In the Journal of the American Academy of Orthopedic Surgeons, Shah and colleagues write about the case of a patient who presented with symptoms of bone disease and was subsequently diagnosed with systemic mastocytosis. 

The case details a 54-year-old woman who experienced a fall that caused pain in her left hip and an inability to bear weight on her left lower limb. History-taking revealed that she had bisphosphonate-intolerant osteopenia; a bone density scan 4 months ago revealed a lumbar spine and proximal femur T score of -1.7. In addition, she was allergic to nonsteroidal anti-inflammatory drugs.

A physical examination revealed a shortened, externally rotated, and abducted left lower extremity. In addition, her physicians detected swelling and ecchymosis of the proximal thigh. 

An X-ray revealed a comminuted and displaced intertrochanteric left femoral fracture. A computed tomographic scan showed unexpected lytic lesions in the pelvis, ipsilateral femur, and the contralateral femur. Lytic lesions were also seen in the ribs and the sternum. These lesions prompted a full malignancy workup, which returned inconclusive. 

The patient’s surgeons decided to perform an open biopsy and intramedullary fixation with a trochanteric femoral nail. Frozen sections obtained intraoperatively were inclusive, prompting a secondary biopsy, which revealed large aggregates of spindled and round mast cells positive for CD117 (cKIT) with metachromatic granules. 

Further immunostaining investigations were positive for CD25 (mast cells) and CD2 (T cells). In addition, KIT mutation evaluations revealed a D816V mutation in exon 17. 

“The presence of clonal population of [mast cells] in bone marrow, with more than 25% spindle mast cells (morphology and immunostains) and detection of cKIT (D816V) mutation on exon 17 by polymerase chain reaction is consistent with systemic mastocytosis,” the authors wrote.

Postsurgery, the patient was started on vitamin D and calcium, which allowed her to ambulate without any assistance by the third month. A 5-month postsurgery bone density scan revealed a T score of -1.8, which indicated stable bone density. 

Thirty months after her surgery, radiographic studies revealed a healed intertrochanteric fracture with intact implants. No complications were detected. 

Uncovering the Etiology of Bone Pathology

In this case study, the patient presented with a fall from a standing height. This, of course, could have been an accident. However, it is unusual for a woman in her 50s to experience a fall from a standing height without the presence of bone pathology. 

In either case, her physicians rightfully sought to rule out the presence of a fracture, which led them to conduct a number of physical and radiological evaluations. These investigations ultimately led to a diagnosis of systemic mastocytosis. 

“One of the most common manifestations of systemic mastocytosis in adults is bone involvement,” the authors write. “For bone involvement, the spectrum of the clinical picture is wide ranging from fragility fractures due to osteoporosis and pathologic fractures from the neoplastic lesions of the skeleton, bone pain from osteopenia to asymptomatic osteolysis, and foci of diffused osteosclerosis.” 

Read more about systemic mastocytosis treatment 

In the case of this patient, calcium and vitamin D supplementation was sufficient to promote bone health, which resulted in improved mobility a few months after the initiation of treatment. Biphosphonates are sometimes recommended to deal with bone loss associated with systemic mastocytosis; however, the patient had a history of bisphosphonate intolerance, thus they were not prescribed. 

The main takeaway from this case study is that falls, bone fractures, and bone pathology ideally should be thoroughly investigated until a source is discovered. Although the outcome can be and is often benign, it is still important to establish a likely cause to ensure that serious causes such as systemic mastocytosis are not missed. If systemic mastocytosis is discovered to be the driver of bone pathology, physicians will be better equipped to treat both the bone disease and its underlying cause. 

References

Bouvard B, Pascaretti-Grizon F, Legrand E, Lavigne C, Audran M, Chappard D. Bone lesions in systemic mastocytosis: bone histomorphometry and histopathological mechanismsMorphologie. 2020;104(345):97-108. doi:10.1016/j.morpho.2020.01.004

Shah A, Bhan R, Pey EP, Riordan H, Khan F. Systemic mastocytosis presenting as pathologic intertrochanteric femur fractureJ Am Acad Orthop Surg Glob Res Rev. 2022;6(1):e21.00137. doi:10.5435/JAAOSGlobal-D-21-00137