Unusual metastatic microcalcification in an IgG4-related disease detected by Tc-99m MDP SPECT/CT：a case report

Unusual metastatic microcalcification in an IgG4-related disease detected by Tc-99m MDP SPECT/CT：a case report | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Unusual metastatic microcalcification in an IgG4-related disease detected by Tc-99m MDP SPECT/CT：a case report Rui-Xue Dong, Jian-Hua Jin This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3513080/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background IgG4-related disease (IgG4RD) is a systemic disease affects nearly every organ. More than 90% of hypercalcemia is caused by primary hyperparathyroidism or malignancy, and rarely by IgG4RD. Case presentation A 60-year-old Chinese male was admitted urgently to the hospital with hypercalcemia and renal insufficiency. Tc-99m Methylene diphosphonate single photon emission computed tomography/computed tomography (Tc-99m MDP SPECT/CT) images showed a significantly increased uptake of tracer in the stomach and lung. After tracheoscopy, lymph node and renal biopsy,the final diagnosis of this case was IgG4RD. The patient's condition improved significantly after treatment with methylprednisolone, and renal function and blood calcium returned to normal. Conclusions IgG4RD combined with hypercalcemia is rare. For patients with renal insufficiency of unknown etiology with hypercalcemia, we should consider the possibility of IgG4RD on the basis of excluding primary hyperparathyroidism and tumor.Tc-99m MDP SPECT/CT examination can be timely detected metastatic calcification and contribute to appropriate treatment. IgG4-related disease Hypercalcemia IgG4-related tubulointerstitial nephritis Metastatic calcification Tc-99m MDP SPECT/CT Figures Figure 1 Figure 2 Background IgG4RD can affected one or multiple organs, such as pancreas, kidneys, salivary glands, lungs, lymph nodes and skin, however, combine with hypercalcemia is infrequent[ 1 ]. Here we report a rare case of IgG4RD complicated with hypercalcemia. Tc-99m MDP SPECT/CT showed metastatic calcification was developing extensively in lungs and stomach. Further tracheoscopy, lymph node and renal biopsy confirmed the diagnosis of metastatic microcalcification of IgG4RD combined with hypercalcemia. The new treatment protocol was administered and the patient recovered well. Case presentation A 60-year-old Chinese man was admitted urgently because of severe hypercalcemia and renal insufficiency. The patient complained weakness and physical examination suggested appearance of anemia.Laboratory findings showed renal dysfunction and severe hypercalcemia (blood urea nitrogen of 18.31 mmol/L, serum creatinine of 330 µmol/L, serum Ca of 3.67 mmol/L). Serum IgG was 2533.0 mg/dL (reference range, 860.0-1740.0 mg/dL) and serum IgG4 subclass was 241 mg/dL (reference range, 3-201 mg/dL). Serum whole Parathyroid Hormone (PTH) decreased to 9.2 pg/mL (reference range, 15–65 pg/mL). Chest Computed tomography(CT) showed exudative changes in both lungs and multiple slightly larger lymph nodes in bilateral axilla and mediastinum, which considered was inflammation, so anti-infection therapy was provided.Tc-99m MDP SPECT/CT scan was performed for further evaluation. Imaging was acquired 180 minutes after intravenous injection of 740 MBq (20 mCi) of Tc-99m MDP and showed increased MDP uptake in the stomach and lungs (Fig. 1 ). These findings suggested that metastatic calcification was developing extensively in the affected lesions. For diagnosis, tracheoscopy and lymph node biopsy were performed. Bronchoscopy and microscopy showed chronic inflammation is accompanied by more eosinophil infiltration and diffuse small focal calcification in the bronchial mucosa(Fig. 2 ). Left axillary enlarged lymph node biopsy was ruled out a hematologic malignancy, and immunohistochemistry demonstrated an increased presence of IgG4 + plasma cells (about 40/high power field), and the IgG4+/IgG + ratio of the plasma cells was high (> 40%) (Fig. 2 ). The results from a renal biopsy showed about 25% of glomeruli were globally sclerosed. Multiple microcalcifications in renal tubular epithelial cells. Multifocal plasma cell infiltration and multifocal fibrous tissue hyperplasia were seen in the renal interstitium. Electron microscopy showed diffuse and irregular thickening of the basement membrane, occasional deposition of electron dense material in the mesangial region, and diffuse fusion of foot processes between epithelial cells. Immunostaining showed abundant IgG4 + plasma cells infiltration (༞10/HPF). All these findings met the diagnostic criteria for IgG4-related tubulointerstitial nephritis(IgG4-RD TIN). Other diseases such as lymphoma, cancer, sarcoidosis, and Castleman’s disease were excluded from the differential diagnosis. The final diagnosis of this case was IgG4-related disease (IgG4RD), accompanied by hypercalcemia and renal insufficiency. Subsequent intravenous drip of methylprednisolone (20mg/day) was administered. The patient's condition improved significantly and renal function and blood calcium returned to normal (serum urea nitrogen of 10.06 mmol/L, serum creatinine of 118 µmol/L, and serum Ca of 2.27mmol/L). Discussion and conclusions IgG4RD is a systemic disease characterized by infiltration of IgG4 immunopositive plasma cells,elevated serum IgG4 concentrations, and swelling of multiple organs, as well as nice response to treatment with glucocorticoids[ 2 , 3 ]. The main laboratory findings are elevated serum IgG4, hypergammaglobulinemia, and eosinophilia. The pathogenesis is currently unknown, and the main idea is that autoimmunity and infection are potential immune triggers for IgG4-RD, and that a central element of the etiopathogenesis of IgG4-RD involves antigen presentation by B cells to CTLs. Interactions between B cells and other CD4 T lymphocytes, such as follicular T helper cells, drive the class switch to IgG4, leading to overexpression of cytokines represented by type 2 helper T(Th 2) cells and activation of regulatory T (Treg) cell, which promotes massive infiltration of inflammatory cells, that can lead to organ damage[ 4 ]. Patients usually present with nonspecific symptoms and are referred to various departments. When IgG4-RD affects organs such as the lungs, kidneys, and digestive tract, it presents as tumor-like swelling and needs to be differentiated from malignancy or other autoimmune diseases (including antineutrophil cytoplasmic antibody-associated vasculitis, idiopathic multicenter Castleman disease (iMCCD), and Rosai-Dorfman disease. When IgG4-RD affects the lungs, it is called IgG4-related lung disease (IgG4 RLD). Lymphoplasmacytic infiltration occurs in both IgG 4-RLD and iMCCD, and the lungs of patients with IgG4-RLD present with fibrosis and eosinophilic infiltration of the perivascular stromal area with obliterative phlebitis, while iMCCD lung lesions are seen in the alveoli adjacent to the perilymphatic stromal area[ 5 ]. Rosai-Dorfman disease can present with lymphadenopathy whose histopathology shows a predominance of histiocytes with large amounts of cytoplasm in which lymphocytes are engulfed (also known as emperipolesis or Rosai-Dorfman cells). This pathology also shows positive staining for S-100 protein and negative CD1a marker. Both IgG4-RD and Rosai-Dorfman disease possess hypergammaglobulinemia,and there is a degree of speculation of an overlap[ 6 ]. When IgG4-RD affects the kidneys, the most common manifestation is plasma cell-rich tubulointerstitial nephritis (TIN), called IgG4-related TIN (IgG4-TIN) [ 7 – 10 ]. Features include eosinophil infiltration, specific distribution of renal parenchymal lesions(the margin between affected and unaffected areas is very clear) immunoglobulins, and complement deposition in the tubular basement membrane (TBM) [ 8 – 11 ]. Corticosteroids can distinguished IgG4-RD from other disorders by their therapeutic effects. IgG4-RD responds rapidly to glucocorticoid therapy, and patients with idiopathic multicenter Castleman disease (iMCCD) respond partially to steroid therapy and respond to immunosuppressant and/or anti-IL-6 therapy. More than 90% of hypercalcemia is caused by primary hyperparathyroidism and malignancy. IgG4RD is rarely combined with hypercalcemia. To our knowledge, only several cases of IgG4RD with hypercalcemia were previously reported. The PTH level is an important node in the diagnosis of hypercalcemia. Hypercalcaemia can be divided into PTH-dependent hypercalcaemia and non-PTH-dependent hypercalcaemia. PTH-dependent hypercalcemia is usually caused by parathyroid adenoma and hyperplasia. Cansu et al. reported that a woman with IgG4RD was combined with parathyroid adenoma with high PTH and blood calcium,pathological manifestations of lymphoplasmacyte infiltration after parathyroidectomy, and IgG4/IgG ratio was > 50%[ 12 ]. PTH-dependent hypercalcemia can also be caused by antibodies that inactivate the parathyroid calcium-sensitive receptor, a woman with multiple autoimmune processes, elevated serum calcium and PTH levels, response to glucocorticoid administration, pathology after subtotal parathyroidectomy,patchy lymphocyte infiltration of normal glands, considered the presence of IgG4 autoantibodies to calcium-sensitive proteins, resulting in hypocalciuria hypercalcemia[ 13 ] . Hasegawa et al.reported a patient with IgG4RD involving systemic lymph nodes, liver, and salivary glands with elevated calcium and serum levels of intact PTH, and no abnormalities on Tc-99m methoxyisobutylisonitrile(MIBI) scintigraphy, thyroid ultrasonography, ultimately considering transient hypercalcemia associated with IgG4 disease[ 14 ]. Kawakita et al. presented a 40-year-old male who was hospitalized with renal impairment and severe hypercalcemia, and Tc-99m MDP SPECT showed increased ectopic uptake in the heart, lungs, stomach, and kidneys, finally, autopsy revealed an increase in osteoclasts in the bone marrow, and IgG4-RD with osteolytic hypercalcemia is considered[ 15 ]. The cause of non-PTH-dependent hypercalcemia is unknown. In the present case, the patient's PTH is below normal, suggesting non-PTH-dependent hypercalcemia and the next should be to evaluate for potential malignancy[ 16 ]. Through various laboratory, radiological, and histological examinations, we ruled out other causes of hypercalcemia, such as solid tumors, lymphomas, multiple myeloma, and drug side effects. Therefore, the etiology of IgG4RD with high blood calcium needs to be further studied. Hypercalcemia, abnormal calcium metabolism, easy to precipitate in an alkaline environment, so metastatic calcification is easy to occur in lung, kidney, stomach, and other soft tissues with high pH values[ 17 – 19 ].Tc-99m MDP SPECT/CT can detect extraosseous metastatic calcifications promptly, not only assess the degree of metastatic calcifications, but also help diagnose the disease and avoid the need for invasive biopsy, and may be the most sensitive technique for early detection of metastatic calcifications. For patients with renal insufficiency, unknown etiology hypercalcemia and elevated serum IgG4; we should carefully assess the possibility of IgG4RD. Tc-99m MDP SPECT/CT examination can timely detected metastatic calcification and contribute to appropriate treatment. Abbreviations IgG4RD IgG4-related disease Tc-99m MDP SPECT/CT Tc-99m Methylene diphosphonate single photon emission computed tomography/computed tomography CT Computed tomography PTH Parathyroid Hormone MIBI methoxyisobutylisonitrile iMCCD idiopathic multicenter Castleman disease IgG4 RLD IgG4-related lung disease TIN tubulointerstitial nephritis Declarations Acknowledgements The authors thank the patient for allowing us to publish this case report. Author Contributions RXD wrote the manuscript and compared the current case with the literature;JHJ critically revised the manuscript. All authors read and approved the final manuscript. Funding None. Availability of data and materials The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. Ethics approval and consent to participate Not applicable. Consent for publication Informed consent was obtained in both written and verbal format from then patient to publish this case report and any accompanying images. Competing interests The authors declare that they have no competing interests. Author details Rui-Xue Dong 1 ,Department of Nuclear Medicine, First Hospital of Shanxi Medical University, Taiyuan 030000, China. E-mail:d4655ong @126.com Jian-Hua Jin 2 , Department of Nuclear Medicine, First Hospital of Shanxi Medical University, Taiyuan 030000, China.E-mail: [email protected] References Stone JH, Zen Y, Deshpande V. IgG4-related disease. N Engl J Med. 2012;366:539–51. Sánchez-Oro R, Alonso-Muñoz EM, Martí Romero L. Revisión de la enfermedad relacionada con la IgG4. Gastroenterología y Hepatología. 2019;42(10):638–47. Goto H, Takahira M, Azumi A. Diagnostic criteria for IgG4-related ophthalmic disease. Jpn J Ophthalmol. 2015;59:1–7. Kubo S, Nakayamada S, Zhao J, Yoshikawa M, Miyazaki Y, Nawata A, Hirata S, Nakano K, Saito K, Tanaka Y. Correlation of T follicular helper cells and plasmablasts with the development of organ involvement in patients with IgG4-related disease. Rheumatology. 2018;57(3):514–24. Terasaki Y, Ikushima S, Matsui S, Hebisawa A, Ichimura Y, Izumi S, Ujita M, Arita M, Tomii K, Komase Y, et al. Comparison of clinical and pathological features of lung lesions of systemic IgG4-related disease and idiopathic multicentric Castleman's disease. Histopathology. 2017;70(7):1114–24. de Jong WK, Kluin PM, Groen HM. Overlapping immunoglobulin G4-related disease and Rosai-Dorfman disease mimicking lung cancer. Eur Respir Rev. 2012;21(126):365–7. Saeki T, Nishi S, Imai N, Ito T, Yamazaki H, Kawano M, Yamamoto M, Takahashi H, Matsui S, Nakada S, et al. Clinicopathological characteristics of patients with IgG4-related tubulointerstitial nephritis. Kidney Int. 2010;78(10):1016–23. Kawano M, Saeki T, Nakashima H, Nishi S, Yamaguchi Y, Hisano S, Yamanaka N, Inoue D, Yamamoto M, Takahashi H, et al. Proposal for diagnostic criteria for IgG4-related kidney disease. Clin Exp Nephrol. 2011;15(5):615–26. Raissian Y, Nasr SH, Larsen CP, Colvin RB, Smyrk TC, Takahashi N, Bhalodia A, Sohani AR, Zhang L, Chari S, et al. Diagnosis of IgG4-Related Tubulointerstitial Nephritis. J Am Soc Nephrol. 2011;22(7):1343–52. Yamaguchi Y, Kanetsuna Y, Honda K, Yamanaka N, Kawano M, Nagata M. Characteristic tubulointerstitial nephritis in IgG4-related disease. Hum Pathol. 2012;43(4):536–49. Yamada K, Kawano M. IgG4-Related Kidney Disease and IgG4-Related Retroperitoneal Fibrosis. Semin Liver Dis. 2016;36(03):283–90. Üsküdar Cansu D, Cansu GB, Yildirim R, Dinler M, Tekin E, Ak Sivrikoz İ, Korkmaz C. Hypercalcemia in IgG4-related disease: coincidental or associated? Case based review. Rheumatol Int. 2022;42(7):1297–305. Pallais JC, Kifor O, Chen YB, Slovik D, Brown EM. Acquired hypocalciuric hypercalcemia due to autoantibodies against the calcium-sensing receptor. N Engl J Med. 2004;351(4):362–9. Hasegawa S, Mine S, Hagiwara S. IgG4-Related Disease Combined with Autoimmune Hemolytic Anemia and Steroid-Responsive Transient Hypercalcemia. Clin Med Insights Case Rep. 2015;8:51–5. Kawakita C, Kinomura M, Gon Y, et al. A case of fatal osteolytic hypercalcemia complicated with IgG4-related ophthalmic disease leading to renal failure. CEN Case Reports. 2019;8:23–30. Auron A, Alon US. Hypercalcemia: a consultant's approach. Pediatr Nephrol. 2018;33:14751488. Zagzag J, Hu MI, Fisher SB, et al. Hypercalcemia and cancer: Differential diagnosis and treatment. CA Cancer J Clin. 2018;68:377–86. Pallais JC, Kifor O, Chen Y, et al. Acquired Hypocalciuric Hypercalcemia Due to Autoantibodies against the Calcium-Sensing Receptor. N Engl J Med. 2004;351:362–9. Morris C, Drinkwater K, Varshney N. Hepatic Sarcoidosis Presenting as Hypercalcemia. Am J Med. 2020;133:e727–8. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3513080","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":263669992,"identity":"ea07ad0a-761a-435e-baf7-ea2f66281e4b","order_by":0,"name":"Rui-Xue Dong","email":"","orcid":"","institution":"First Hospital of Shanxi Medical University","correspondingAuthor":false,"prefix":"","firstName":"Rui-Xue","middleName":"","lastName":"Dong","suffix":""},{"id":263669993,"identity":"1aebc81c-52e4-4aef-942a-14a178292e0a","order_by":1,"name":"Jian-Hua Jin","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAu0lEQVRIiWNgGAWjYBACxoYzDAc+VPyTY2NvPkC0FsaDM84cMObjOZZArD08zId52w4kzpPIUSBOA3Pj2QMHeNjupLcx5DAw/KjYRozDziUckOB5ltvGcPYAY8+Z28RoOWNwwECCObeNsS+BmbGNWC0JBszpbMw8BiRoOZBwOIGNjRQtBxsOpBm28bAlHCTKL4Yzzhh//vvPRl5+/uODD35UEKXlAIJzAJcqFCDP30CUulEwCkbBKBjJAADhxUUuHi8g7AAAAABJRU5ErkJggg==","orcid":"","institution":"First Hospital of Shanxi Medical University","correspondingAuthor":true,"prefix":"","firstName":"Jian-Hua","middleName":"","lastName":"Jin","suffix":""}],"badges":[],"createdAt":"2023-10-30 15:30:24","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3513080/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3513080/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":49078494,"identity":"7ed7368e-618c-41e5-b4fc-86375df4088c","added_by":"auto","created_at":"2024-01-02 19:16:52","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":850338,"visible":true,"origin":"","legend":"\u003cp\u003eThe whole-body bone imaging (A, anterior; B, posterior), transversal (D) and coronal (F) SPECT/CT images showed increased MDP uptake in the stomach and lungs. Transversal CT of the chest showed diffuse ground glass opacity of the lung fields (C) and thickening of the gastric wall associated with a slightly higher density (E).\u003c/p\u003e","description":"","filename":"Figure1..png","url":"https://assets-eu.researchsquare.com/files/rs-3513080/v1/dda3c4f9c4209c03d8f4f4c9.png"},{"id":49078492,"identity":"a22644e5-bd34-4340-b9c8-0241fa892c3a","added_by":"auto","created_at":"2024-01-02 19:16:52","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":2025620,"visible":true,"origin":"","legend":"\u003cp\u003eBronchoscopy revealed an uneven nodular uplift in the bronchial mucosa (\u003cstrong\u003eA\u003c/strong\u003e), and microscopy showed chronic inflammation is accompanied by more eosinophil infiltration and diffuse small focal calcification. Left axillary enlarged lymph node ( B ) biopsy indicated lymph tissue reactive hyperplasia with a marked increase in IgG4-positive cells, and immunohistochemistry demonstrated an increased presence of IgG4-positive plasma cells (about 40/high power field) , and the IgG4+/IgG+ ratio of the plasma cells was high (\u0026gt; 40%) (C，D).\u003c/p\u003e","description":"","filename":"Figure2..png","url":"https://assets-eu.researchsquare.com/files/rs-3513080/v1/3b13111302ad209d70e0369b.png"},{"id":56558555,"identity":"1e150ef6-8fe1-4595-a645-d47f3cdb1bbd","added_by":"auto","created_at":"2024-05-15 19:11:12","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3039547,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3513080/v1/555ef851-2435-4a7e-a589-7326d30f56a9.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Unusual metastatic microcalcification in an IgG4-related disease detected by Tc-99m MDP SPECT/CT：a case report","fulltext":[{"header":"Background","content":"\u003cp\u003eIgG4RD can affected one or multiple organs, such as pancreas, kidneys, salivary glands, lungs, lymph nodes and skin, however, combine with hypercalcemia is infrequent[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Here we report a rare case of IgG4RD complicated with hypercalcemia. Tc-99m MDP SPECT/CT showed metastatic calcification was developing extensively in lungs and stomach. Further tracheoscopy, lymph node and renal biopsy confirmed the diagnosis of metastatic microcalcification of IgG4RD combined with hypercalcemia. The new treatment protocol was administered and the patient recovered well.\u003c/p\u003e"},{"header":"Case presentation","content":"\u003cp\u003eA 60-year-old Chinese man was admitted urgently because of severe hypercalcemia and renal insufficiency. The patient complained weakness and physical examination suggested appearance of anemia.Laboratory findings showed renal dysfunction and severe hypercalcemia (blood urea nitrogen of 18.31 mmol/L, serum creatinine of 330 \u0026micro;mol/L, serum Ca of 3.67 mmol/L). Serum IgG was 2533.0 mg/dL (reference range, 860.0-1740.0 mg/dL) and serum IgG4 subclass was 241 mg/dL (reference range, 3-201 mg/dL). Serum whole Parathyroid Hormone (PTH) decreased to 9.2 pg/mL (reference range, 15\u0026ndash;65 pg/mL).\u003c/p\u003e \u003cp\u003eChest Computed tomography(CT) showed exudative changes in both lungs and multiple slightly larger lymph nodes in bilateral axilla and mediastinum, which considered was inflammation, so anti-infection therapy was provided.Tc-99m MDP SPECT/CT scan was performed for further evaluation. Imaging was acquired 180 minutes after intravenous injection of 740 MBq (20 mCi) of Tc-99m MDP and showed increased MDP uptake in the stomach and lungs (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). These findings suggested that metastatic calcification was developing extensively in the affected lesions. For diagnosis, tracheoscopy and lymph node biopsy were performed. Bronchoscopy and microscopy showed chronic inflammation is accompanied by more eosinophil infiltration and diffuse small focal calcification in the bronchial mucosa(Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Left axillary enlarged lymph node biopsy was ruled out a hematologic malignancy, and immunohistochemistry demonstrated an increased presence of IgG4\u0026thinsp;+\u0026thinsp;plasma cells (about 40/high power field), and the IgG4+/IgG\u0026thinsp;+\u0026thinsp;ratio of the plasma cells was high (\u0026gt;\u0026thinsp;40%) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe results from a renal biopsy showed about 25% of glomeruli were globally sclerosed. Multiple microcalcifications in renal tubular epithelial cells. Multifocal plasma cell infiltration and multifocal fibrous tissue hyperplasia were seen in the renal interstitium. Electron microscopy showed diffuse and irregular thickening of the basement membrane, occasional deposition of electron dense material in the mesangial region, and diffuse fusion of foot processes between epithelial cells. Immunostaining showed abundant IgG4\u0026thinsp;+\u0026thinsp;plasma cells infiltration (༞10/HPF). All these findings met the diagnostic criteria for IgG4-related tubulointerstitial nephritis(IgG4-RD TIN).\u003c/p\u003e \u003cp\u003eOther diseases such as lymphoma, cancer, sarcoidosis, and Castleman\u0026rsquo;s disease were excluded from the differential diagnosis. The final diagnosis of this case was IgG4-related disease (IgG4RD), accompanied by hypercalcemia and renal insufficiency. Subsequent intravenous drip of methylprednisolone (20mg/day) was administered. The patient's condition improved significantly and renal function and blood calcium returned to normal (serum urea nitrogen of 10.06 mmol/L, serum creatinine of 118 \u0026micro;mol/L, and serum Ca of 2.27mmol/L).\u003c/p\u003e"},{"header":"Discussion and conclusions","content":"\u003cp\u003eIgG4RD is a systemic disease characterized by infiltration of IgG4 immunopositive plasma cells,elevated serum IgG4 concentrations, and swelling of multiple organs, as well as nice response to treatment with glucocorticoids[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. The main laboratory findings are elevated serum IgG4, hypergammaglobulinemia, and eosinophilia. The pathogenesis is currently unknown, and the main idea is that autoimmunity and infection are potential immune triggers for IgG4-RD, and that a central element of the etiopathogenesis of IgG4-RD involves antigen presentation by B cells to CTLs. Interactions between B cells and other CD4 T lymphocytes, such as follicular T helper cells, drive the class switch to IgG4, leading to overexpression of cytokines represented by type 2 helper T(Th 2) cells and activation of regulatory T (Treg) cell, which promotes massive infiltration of inflammatory cells, that can lead to organ damage[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Patients usually present with nonspecific symptoms and are referred to various departments. When IgG4-RD affects organs such as the lungs, kidneys, and digestive tract, it presents as tumor-like swelling and needs to be differentiated from malignancy or other autoimmune diseases (including antineutrophil cytoplasmic antibody-associated vasculitis, idiopathic multicenter Castleman disease (iMCCD), and Rosai-Dorfman disease. When IgG4-RD affects the lungs, it is called IgG4-related lung disease (IgG4 RLD). Lymphoplasmacytic infiltration occurs in both IgG 4-RLD and iMCCD, and the lungs of patients with IgG4-RLD present with fibrosis and eosinophilic infiltration of the perivascular stromal area with obliterative phlebitis, while iMCCD lung lesions are seen in the alveoli adjacent to the perilymphatic stromal area[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eRosai-Dorfman disease can present with lymphadenopathy whose histopathology shows a predominance of histiocytes with large amounts of cytoplasm in which lymphocytes are engulfed (also known as emperipolesis or Rosai-Dorfman cells). This pathology also shows positive staining for S-100 protein and negative CD1a marker. Both IgG4-RD and Rosai-Dorfman disease possess hypergammaglobulinemia,and there is a degree of speculation of an overlap[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. When IgG4-RD affects the kidneys, the most common manifestation is plasma cell-rich tubulointerstitial nephritis (TIN), called IgG4-related TIN (IgG4-TIN) [\u003cspan additionalcitationids=\"CR8 CR9\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Features include eosinophil infiltration, specific distribution of renal parenchymal lesions(the margin between affected and unaffected areas is very clear) immunoglobulins, and complement deposition in the tubular basement membrane (TBM) [\u003cspan additionalcitationids=\"CR9 CR10\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Corticosteroids can distinguished IgG4-RD from other disorders by their therapeutic effects. IgG4-RD responds rapidly to glucocorticoid therapy, and patients with idiopathic multicenter Castleman disease (iMCCD) respond partially to steroid therapy and respond to immunosuppressant and/or anti-IL-6 therapy.\u003c/p\u003e \u003cp\u003eMore than 90% of hypercalcemia is caused by primary hyperparathyroidism and malignancy. IgG4RD is rarely combined with hypercalcemia. To our knowledge, only several cases of IgG4RD with hypercalcemia were previously reported. The PTH level is an important node in the diagnosis of hypercalcemia. Hypercalcaemia can be divided into PTH-dependent hypercalcaemia and non-PTH-dependent hypercalcaemia. PTH-dependent hypercalcemia is usually caused by parathyroid adenoma and hyperplasia. Cansu et al. reported that a woman with IgG4RD was combined with parathyroid adenoma with high PTH and blood calcium,pathological manifestations of lymphoplasmacyte infiltration after parathyroidectomy, and IgG4/IgG ratio was \u0026gt;\u0026thinsp;50%[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. PTH-dependent hypercalcemia can also be caused by antibodies that inactivate the parathyroid calcium-sensitive receptor, a woman with multiple autoimmune processes, elevated serum calcium and PTH levels, response to glucocorticoid administration, pathology after subtotal parathyroidectomy,patchy lymphocyte infiltration of normal glands, considered the presence of IgG4 autoantibodies to calcium-sensitive proteins, resulting in hypocalciuria hypercalcemia[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e] .\u003c/p\u003e \u003cp\u003eHasegawa et al.reported a patient with IgG4RD involving systemic lymph nodes, liver, and salivary glands with elevated calcium and serum levels of intact PTH, and no abnormalities on Tc-99m methoxyisobutylisonitrile(MIBI) scintigraphy, thyroid ultrasonography, ultimately considering transient hypercalcemia associated with IgG4 disease[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Kawakita et al. presented a 40-year-old male who was hospitalized with renal impairment and severe hypercalcemia, and Tc-99m MDP SPECT showed increased ectopic uptake in the heart, lungs, stomach, and kidneys, finally, autopsy revealed an increase in osteoclasts in the bone marrow, and IgG4-RD with osteolytic hypercalcemia is considered[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe cause of non-PTH-dependent hypercalcemia is unknown. In the present case, the patient's PTH is below normal, suggesting non-PTH-dependent hypercalcemia and the next should be to evaluate for potential malignancy[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Through various laboratory, radiological, and histological examinations, we ruled out other causes of hypercalcemia, such as solid tumors, lymphomas, multiple myeloma, and drug side effects. Therefore, the etiology of IgG4RD with high blood calcium needs to be further studied. Hypercalcemia, abnormal calcium metabolism, easy to precipitate in an alkaline environment, so metastatic calcification is easy to occur in lung, kidney, stomach, and other soft tissues with high pH values[\u003cspan additionalcitationids=\"CR18\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e].Tc-99m MDP SPECT/CT can detect extraosseous metastatic calcifications promptly, not only assess the degree of metastatic calcifications, but also help diagnose the disease and avoid the need for invasive biopsy, and may be the most sensitive technique for early detection of metastatic calcifications. For patients with renal insufficiency, unknown etiology hypercalcemia and elevated serum IgG4; we should carefully assess the possibility of IgG4RD. Tc-99m MDP SPECT/CT examination can timely detected metastatic calcification and contribute to appropriate treatment.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eIgG4RD\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eIgG4-related disease\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eTc-99m MDP SPECT/CT\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eTc-99m Methylene diphosphonate single photon emission computed tomography/computed tomography\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eCT\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eComputed tomography\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003ePTH\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eParathyroid Hormone\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eMIBI\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003emethoxyisobutylisonitrile\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eiMCCD\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eidiopathic multicenter Castleman disease\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eIgG4 RLD\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eIgG4-related lung disease\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eTIN\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003etubulointerstitial nephritis\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors thank the patient for allowing us to publish this case report.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eRXD wrote the manuscript and compared the current case with the literature;JHJ critically revised the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eInformed consent was obtained in both written and verbal format from then patient to publish this case report and any accompanying images.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor details\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eRui-Xue Dong\u003csup\u003e1\u003c/sup\u003e ,Department of Nuclear Medicine, First Hospital of Shanxi Medical University, Taiyuan 030000, China. E-mail:d4655ong @126.com\u003c/p\u003e\n\u003cp\u003eJian-Hua Jin\u003csup\u003e2\u003c/sup\u003e, Department of Nuclear Medicine, First Hospital of Shanxi Medical University, Taiyuan 030000, China.E-mail: [email protected]\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eStone JH, Zen Y, Deshpande V. IgG4-related disease. N Engl J Med. 2012;366:539\u0026ndash;51.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eS\u0026aacute;nchez-Oro R, Alonso-Mu\u0026ntilde;oz EM, Mart\u0026iacute; Romero L. Revisi\u0026oacute;n de la enfermedad relacionada con la IgG4. Gastroenterolog\u0026iacute;a y Hepatolog\u0026iacute;a. 2019;42(10):638\u0026ndash;47.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGoto H, Takahira M, Azumi A. Diagnostic criteria for IgG4-related ophthalmic disease. Jpn J Ophthalmol. 2015;59:1\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKubo S, Nakayamada S, Zhao J, Yoshikawa M, Miyazaki Y, Nawata A, Hirata S, Nakano K, Saito K, Tanaka Y. Correlation of T follicular helper cells and plasmablasts with the development of organ involvement in patients with IgG4-related disease. Rheumatology. 2018;57(3):514\u0026ndash;24.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTerasaki Y, Ikushima S, Matsui S, Hebisawa A, Ichimura Y, Izumi S, Ujita M, Arita M, Tomii K, Komase Y, et al. Comparison of clinical and pathological features of lung lesions of systemic IgG4-related disease and idiopathic multicentric Castleman's disease. Histopathology. 2017;70(7):1114\u0026ndash;24.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ede Jong WK, Kluin PM, Groen HM. Overlapping immunoglobulin G4-related disease and Rosai-Dorfman disease mimicking lung cancer. Eur Respir Rev. 2012;21(126):365\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSaeki T, Nishi S, Imai N, Ito T, Yamazaki H, Kawano M, Yamamoto M, Takahashi H, Matsui S, Nakada S, et al. Clinicopathological characteristics of patients with IgG4-related tubulointerstitial nephritis. Kidney Int. 2010;78(10):1016\u0026ndash;23.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKawano M, Saeki T, Nakashima H, Nishi S, Yamaguchi Y, Hisano S, Yamanaka N, Inoue D, Yamamoto M, Takahashi H, et al. Proposal for diagnostic criteria for IgG4-related kidney disease. Clin Exp Nephrol. 2011;15(5):615\u0026ndash;26.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRaissian Y, Nasr SH, Larsen CP, Colvin RB, Smyrk TC, Takahashi N, Bhalodia A, Sohani AR, Zhang L, Chari S, et al. Diagnosis of IgG4-Related Tubulointerstitial Nephritis. J Am Soc Nephrol. 2011;22(7):1343\u0026ndash;52.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYamaguchi Y, Kanetsuna Y, Honda K, Yamanaka N, Kawano M, Nagata M. Characteristic tubulointerstitial nephritis in IgG4-related disease. Hum Pathol. 2012;43(4):536\u0026ndash;49.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYamada K, Kawano M. IgG4-Related Kidney Disease and IgG4-Related Retroperitoneal Fibrosis. Semin Liver Dis. 2016;36(03):283\u0026ndash;90.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e\u0026Uuml;sk\u0026uuml;dar Cansu D, Cansu GB, Yildirim R, Dinler M, Tekin E, Ak Sivrikoz İ, Korkmaz C. Hypercalcemia in IgG4-related disease: coincidental or associated? Case based review. Rheumatol Int. 2022;42(7):1297\u0026ndash;305.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePallais JC, Kifor O, Chen YB, Slovik D, Brown EM. Acquired hypocalciuric hypercalcemia due to autoantibodies against the calcium-sensing receptor. N Engl J Med. 2004;351(4):362\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHasegawa S, Mine S, Hagiwara S. IgG4-Related Disease Combined with Autoimmune Hemolytic Anemia and Steroid-Responsive Transient Hypercalcemia. Clin Med Insights Case Rep. 2015;8:51\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKawakita C, Kinomura M, Gon Y, et al. A case of fatal osteolytic hypercalcemia complicated with IgG4-related ophthalmic disease leading to renal failure. CEN Case Reports. 2019;8:23\u0026ndash;30.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAuron A, Alon US. Hypercalcemia: a consultant's approach. Pediatr Nephrol. 2018;33:14751488.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZagzag J, Hu MI, Fisher SB, et al. Hypercalcemia and cancer: Differential diagnosis and treatment. CA Cancer J Clin. 2018;68:377\u0026ndash;86.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePallais JC, Kifor O, Chen Y, et al. Acquired Hypocalciuric Hypercalcemia Due to Autoantibodies against the Calcium-Sensing Receptor. N Engl J Med. 2004;351:362\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMorris C, Drinkwater K, Varshney N. Hepatic Sarcoidosis Presenting as Hypercalcemia. Am J Med. 2020;133:e727\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"IgG4-related disease, Hypercalcemia, IgG4-related tubulointerstitial nephritis, Metastatic calcification, Tc-99m MDP, SPECT/CT","lastPublishedDoi":"10.21203/rs.3.rs-3513080/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3513080/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIgG4-related disease (IgG4RD) is a systemic disease affects nearly every organ. More than 90% of hypercalcemia is caused by primary hyperparathyroidism or malignancy, and rarely by IgG4RD.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase presentation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA 60-year-old Chinese male was admitted urgently to the hospital with hypercalcemia and renal insufficiency. Tc-99m Methylene diphosphonate single photon emission computed tomography/computed tomography (Tc-99m MDP SPECT/CT) images showed a significantly increased uptake of tracer in the stomach and lung. After tracheoscopy, lymph node and renal biopsy,the final diagnosis of this case was IgG4RD. The patient's condition improved significantly after treatment with methylprednisolone, and renal function and blood calcium returned to normal.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIgG4RD combined with hypercalcemia is rare. For patients with renal insufficiency of unknown etiology with hypercalcemia, we should consider the possibility of IgG4RD on the basis of excluding primary hyperparathyroidism and tumor.Tc-99m MDP SPECT/CT examination can be timely detected metastatic calcification and contribute to appropriate treatment.\u003c/p\u003e","manuscriptTitle":"Unusual metastatic microcalcification in an IgG4-related disease detected by Tc-99m MDP SPECT/CT：a case report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-01-02 19:16:47","doi":"10.21203/rs.3.rs-3513080/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"2f4b45d8-a2d8-4084-9654-dbbcabd358eb","owner":[],"postedDate":"January 2nd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-05-15T19:03:04+00:00","versionOfRecord":[],"versionCreatedAt":"2024-01-02 19:16:47","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3513080","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3513080","identity":"rs-3513080","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}