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Clinical and genetic analysis of idiopathic normophosphatemic tumoral calcinosis in 19 patients

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Abstract

Purpose

Tumoral calcinosis is a rare clinicopathological entity characterized by ectopic soft-tissue calcification, typically periarticular. Normophosphatemic tumoral calcinosis is seldom reported in East Asian populations, and the preoperative diagnosis is often elusive. This study was performed to characterize the clinical profile of normophosphatemic tumoral calcinosis and investigate the presence of the SAMD9 gene mutation.

Methods

The clinical features, pathological examination findings, and outcomes of 19 subjects were retrospectively reviewed. All patients were analyzed for SAMD9 gene mutation using paraffin-embedded tumoral calcinosis specimens.

Results

Nineteen subjects were analyzed (7 males, 12 females). Their mean age at surgery, mean age at symptom onset, and median disease duration was 51.9 ± 17.3 (range 7–75) years, 49.1 ± 17.2 (range 7–74) years, and 1.3 (interquartile range 0.5–3.0) years, respectively. Lesions were located in the hand in 8 (42.1%) subjects; wrist in 5 (26.3%); shoulder in 2 (10.5%); and hip, knee, buttock, and scrotum in 1 (5.3%) subject each. The lesions in 17 (89.5%) subjects were located around the joints [small joints (hand and wrist) in 13 (68.4%) and large joints (shoulder, hip, and knee) in 4 (21.1%)]. Lesions occurred in the upper limbs in 15 (78.9%) subjects and in the lower limbs in 2 (10.5%). Multiple-lesion involvement (distal right index finger and middle finger) occurred in one (5.3%) subject. Symptoms included pain in 15 (78.9%) subjects, impaired mobility in 5 (26.3%), swelling in 5 (26.3%), numbness in 2 (10.5%), and an asymptomatic mass in 2 (10.5%). The serum inorganic phosphorus concentration was normal in all 19 subjects (mean 1.17 ± 0.15 mmol/L). The serum calcium concentration was normal in 18 subjects and low in 1. The serum alkaline phosphatase concentration was normal in all 19 subjects. Pathological examination indicated multiple nodules of calcified materials that manifested an amorphous or granular blue-purple crystal and were surrounded by proliferation of mononuclear or multinuclear macrophages, osteoclastic-like giant cells, fibroblasts, and chronic inflammatory cells. Notably, different phases of pathological manifestations were observed in the same microscopic field. During follow-up (0.5–65.0 months), no recurrence of tumoral calcinosis was observed in 18 (94.7%) subjects, but 1 subject developed in situ recurrence of an asymptomatic subcutaneous mass after 6 months postoperatively. Genetic analysis in all 19 subjects revealed no SAMD9 gene mutations.

Conclusions

Most subjects were females and developed calcinosis in adulthood. Small joints (hand and wrist) and the upper limbs were frequently involved. The presence of different phases of pathological features in the same subject suggests that about half of the study participants had been misdiagnosed with another condition (such as gout, osteoarthritis, etc.). Complete surgical excision led to cure without recurrence during follow-up in majority of the study participants.

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Availability of data and materials

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Acknowledgements

We thank all of the subjects for participating in this study.

Funding

This study was funded by National Key R&D Program of China (2017YFC0909600), the Beijing Municipal Administration of Hospitals’ Youth Programme (QML20170205), and Science & Technology Project of Beijing, China (No. D171100002817005 and No. D17110700280000).

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Author notes

  1. Qing-Yao Zuo and Xi Cao contributed equally to this paper.

Authors and Affiliations

  1. Beijing Diabetes Institute, Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, China

    Q.-Y. Zuo, X. Cao, Z. Xin & J.-K. Yang

  2. Department of Endocrinology, Beijing Jishuitan Hospital, Beijing, 100035, China

    Q.-Y. Zuo & W. Deng

  3. Department of Pathology, Beijing Jishuitan Hospital, Beijing, 100035, China

    B.-Y. Liu

  4. Department of Radiology, Beijing Jishuitan Hospital, Beijing, 100035, China

    D. Yan

  5. Department of Orthopaedic Oncology, Beijing Jishuitan Hospital, Beijing, 100035, China

    X.-H. Niu

  6. Department of Hand Surgery, Beijing Jishuitan Hospital, Beijing, 100035, China

    C. Li

  7. Department of Nephrology, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center of Kidney Diseases, Chinese PLA General Hospital, Beijing, 100039, China

    Z.-Y. Dong

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Contributions

Qing-Yao Zuo and Xi Cao contributed to developing research methodology, analysis, and writing the manuscript. Bao-Yue Liu, Dong Yan, Zhong Xin, Xiao-Hui Niu, Chun Li, and Wei Deng coordinated to collect and analyze research data. Zhe-Yi Dong coordinated to collect research data and revised the manuscript. Jin-Kui Yang contributed to the design of the study, research data analysis, and wrote manuscript, and coordinated submission.

Corresponding author

Correspondence to J.-K. Yang.

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The authors declare that they have no conflict of interest.

Ethics approval

The study was approved by the Beijing Jishuitan Hospital Institutional Review Board (201803-06). All procedures in the study were performed in accordance with the 1964 Helsinki declaration and its later amendments.

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Informed consent was obtained from all participants included in the study.

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Zuo, QY., Cao, X., Liu, BY. et al. Clinical and genetic analysis of idiopathic normophosphatemic tumoral calcinosis in 19 patients. J Endocrinol Invest 43, 173–183 (2020). https://doi.org/10.1007/s40618-019-01097-4

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  • DOI: https://doi.org/10.1007/s40618-019-01097-4

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