A 32-Year-Old Man With Recurrent Kidney Stones and an Abnormal Chest Radiograph

Abstract

A 32-year-old man presented to the hospital with hypertensive urgency and painless hematuria. He had no medical symptoms until 8 years previous when he began experiencing recurrent kidney stones that necessitated multiple lithotripsies. The patient denied abdominal pain, fever, and weight loss. On examination, he appeared comfortable despite a BP of 200/110 mm Hg. Reduced chest wall expansion and gynecomastia were noted. There was no renal bruit. The rest of his physical examination, including fundoscopy, was normal. The patient's medical history, social history, and review of systems were otherwise unremarkable. Blood work revealed the following values: sodium, 139 mmol/L; potassium, 3.0 mmol/L; bicarbonate, 19 mmol/L; BUN, 19 mg/dL; creatinine, 2.4 mg/dL; calcium, 10.7 mg/dL (8.4-10.4 mg/dL); albumin, 2.9 g/dL; phosphorus, 2.5 mg/dL (2.5-4.9 mg/dL); magnesium, 1.2 mg/dL; and hemoglobin, 11 g/dL (mean corpuscular volume, 93%). The patient's serum bilirubin and transaminases levels were normal. His urinalysis showed microscopic hematuria. His pulmonary function tests demonstrated moderate restriction, with a total lung capacity of 4.22 L (69% predicted), an FEV1/FVC ratio of 0.78, an FEV1 of 2.40 L (72% predicted), and an FVC of 3.08 L (78% predicted). The patient was admitted for hypertensive urgency, and adequate BP control was achieved with two oral antihypertensive agents. His prolactin level was normal, so the gynecomastia was probably idiopathic. The patient's posteroanterior and lateral chest radiographs are shown in Figure 1. CT images of the chest (axial view) are shown in Figure 2. A biopsy specimen of the iliac bone was obtained and is shown in Figure 3.Figure 2CT scan of the chest showing many expansile lytic lesions of the ribs with no intraparenchymal masses or nodules. A, Lung window. B, Mediastinal window.View Large Image Figure ViewerDownload Hi-res image Download (PPT)Figure 3Biopsy specimen of the iliac bone showing mononuclear cells with round to oval nuclei and sarcomatoid features consisting of numerous spindle cells in a hypercellular, storiform configuration, which is a harbinger for more-destructive tumor behavior, along with scattered multinucleated giant cells with nuclei similar to those seen in the mononuclear cells. Abundant hemosiderin deposits indicate relatively recent hemorrhage. The lesion has replaced the bone marrow and surrounds normal-appearing trabecular bone. A, Hematoxylin-eosin, original magnification ×20. B, Hematoxylin-eosin, original magnification ×40.View Large Image Figure ViewerDownload Hi-res image Download (PPT) What is the diagnosis? Diagnosis: Multiple brown tumors Brown tumor, also known as generalized osteitis fibrosa cystica or Von Recklinghausen disease of the bone, comprises only a small percentage of osteolytic bony pathologies.1Khalil PN Heining SM Huss R et al.Natural history and surgical treatment of brown tumor lesions at various sites in refractory primary hyperparathyroidism.Eur J Med Res. 2007; 12: 222-230PubMed Google Scholar It usually develops in the third to fourth decade of life and is more prevalent in women.2Meydan N Barutca S Guney E et al.Brown tumors mimicking bone metastases.J Natl Med Assoc. 2006; 98: 950-953PubMed Google Scholar Eighty percent of brown tumors occur as a complication of primary parathyroid adenoma.3Heath III, H Hodgson SF Kennedy MA Primary hyperparathyroidism. Incidence, morbidity, and potential economic impact in a community.N Engl J Med. 1980; 302: 189-193Crossref PubMed Scopus (818) Google Scholar The patient's parathyroid hormone level was 2,165 pg/mL (15-65 pg/mL). His 25-hydroxy vitamin D level was <4 ng/mL (32-100 ng/mL), and his serum protein electrophoresis was normal. Because of earlier diagnosis and treatment of hyperparathyroidism, brown tumors have become very rare,4Yilmazlar S Arslan E Aksoy K Tolunay S Sellar-parasellar brown tumor: case report and review of literature.Skull Base. 2004; 14: 163-168Crossref PubMed Scopus (22) Google Scholar and they represent a challenge for the clinician because they can mimic bone metastases. Hypercalcemia, as seen in this patient, is due to primary hyperparathyroidism. Table 1 lists common causes of hypercalcemia.Table 1Causes of HypercalcemiaPrimary hyperparathyroidismMalignancy related Osteolytic hypercalcemia (breast cancer, multiple myeloma, lymphoma) Humoral hypercalcemia of malignancy (lung, kidney) Ectopic production of calcitriol (lymphoma, leukemia)Hypercalcemia of granulomatous disease [↑1,25(OH)2D] (sarcoidosis)Chronic renal failure with aplastic bone diseaseTertiary hyperparathyroidismAcute renal failureFamilial hypercalcemic hypocalciuriaLithium-associated hypercalcemiaVitamin D intoxicationHigh bone turnover related Hyperthyroidism Immobilization Vitamin A intoxication ThiazidesMultiple endocrine neoplasia (I, IIA)Milk-alkali syndrome Open table in a new tab Although brown tumors are classically found with slightly greater incidence in patients with severe untreated primary hyperparathyroidism, they also may occur with secondary and tertiary hyperparathyroidism.5Buchanan WW Kraag GR Palmer DG Cockshott WP The first recorded case of osteitis fibrosa cystica.Can Med Assoc J. 1981; 124: 812-815PubMed Google Scholar, 6Keyser JS Postma GN Brown tumor of the mandible.Am J Otolaryngol. 1996; 17: 407-410Abstract Full Text PDF PubMed Scopus (101) Google Scholar The pathogenesis of primary, secondary, and tertiary hyperparathyroidism varies. Primary hyperparathyroidism is characterized by increased serum calcium as well as parathyroid hormone (PTH) concentration. Secondary hyperparathyroidism is characterized by increased serum PTH but low or normal calcium concentration. Tertiary hyperparathyroidism refers to hypercalcemia caused by excessive PTH secretion in the setting of longstanding secondary hyperparathyroidism.7Schlomo M Polansky KS Larsen PR Kronenberg HM Williams Textbook of Endocrinology. 12th ed. Saunders Elsevier, Philadelphia, PA2011: 1274Google Scholar Hyperparathyroidism frequently is caused by the development of a parathyroid adenoma and less often by hyperplasia or carcinoma. Increased secretion of intact PTH from the parathyroid adenoma activates osteoclasts and causes increased bone turnover, leading to multiple osteolytic lesions, destruction of cortical bone, formation of fibrous cysts, and generalized skeletal demineralization. The subperiosteal bone resorption and formation of osteoclastomas lead to cortical thinning, lytic lesions, and bone cysts that can disrupt the overlying cortex.8Syed Z Khan A Skeletal effects of primary hyperparathyroidism.Endocr Pract. 2000; 6: 385-388Crossref PubMed Google Scholar On radiographic imaging, brown tumors appear as lytic lesions with thinned cortical bone that may progress further and cause gross lytic destruction. Concurrent changes that also may suggest brown tumor are osteopenia, a “salt and pepper” bone appearance seen on spine radiographs, and subperiosteal bone resorption. The margin of the tumors in this case are partially sharp and partially indistinct, giving rise to the incomplete border sign seen on chest radiography, which is an attribute of an extrapulmonary mass. The lesions are convex toward the lung and form obtuse angles with the chest wall. An ultrasonograph of the patient's neck (Fig 4) revealed a heterogeneous, predominantly cystic mass consistent with a parathyroid adenoma. A sestamibi scan (Fig 5) showed increased radiotracer uptake at the level of the right lower neck compatible with localization of the right-side parathyroid gland along with scattered uptake in the bone. Multiple brown tumors can coexist throughout the skeleton. They may arise in the mandible, maxilla, pelvis, ribs, clavicle, spine, and extremities.9Blinder G Hiller N Gatt N Matas M Shilo S Brown tumor in the cricoid cartilage: an unusual manifestation of primary hyperparathyroidism.Ann Otol Rhinol Laryngol. 1997; 106: 252-253Crossref PubMed Scopus (15) Google Scholar, 10Mourelatus Z Goldberg H Sinson G Quan D Lavi E Case of the month: March 1998—48 year old man with back pain and weakness.Brain Pathol. 1998; 8: 589-590PubMed Google Scholar Only a few cases have been reported of rib lesions as the initial manifestation of brown tumor. MRI appearance of brown tumor has been described in the literature as intense enhancement on T1-weighted images and variable intensities on T2-weighted images. These findings, however, are not specific.11Gould CF Ly JQ Lattin Jr, GE Beall DP Sutcliffe III, JB Bone tumor mimics: avoiding misdiagnosis.Curr Probl Diagn Radiol. 2007; 36: 124-141Abstract Full Text Full Text PDF PubMed Scopus (72) Google Scholar, 12Takeshita T Tanaka H Harasawa A Kaminaga T Imamura T Furui S Brown tumor of the sphenoid sinus in a patient with secondary hyperparathyroidism: CT and MR imaging findings.Radiat Med. 2004; 22: 265-268PubMed Google Scholar MRI may be better for determining the presence of cysts or fluid levels, a finding that may suggest brown tumor.13Takeshita T Takeshita K Abe S Takami H Imamura T Furui S Brown tumor with fluid-fluid levels in a patient with primary hyperparathyroidism: radiological findings.Radiat Med. 2006; 24: 631-634Crossref PubMed Scopus (31) Google Scholar Ectopic parathyroid adenomas are observed in ∼10% of cases and may be located within the thymus, thyroid, or pericardium or behind the esophagus. The diagnosis of hyperparathyroidism depends on laboratory evaluation of the serum. Localization studies as well as intraoperative PTH testing are used to guide the surgeon toward a minimally invasive procedure and are helpful for localizing ectopic adenomas. Sestamibi scan and neck ultrasonography are the preferred modalities to pinpoint parathyroid adenomas.14Nichols KJ Tomas MB Tronco GG et al.Preoperative parathyroid scintigraphic lesion localization: accuracy of various types of readings.Radiology. 2008; 248: 221-232Crossref PubMed Scopus (75) Google Scholar, 15Haber RS Kim CK Inabnet WB Ultrasonography for preoperative localization of enlarged parathyroid glands in primary hyperparathyroidism: comparison with (99m)technetium sestamibi scintigraphy.Clin Endocrinol (Oxf). 2002; 57: 241-249Crossref PubMed Scopus (186) Google Scholar In this patient, localization studies confirmed the presence of an adenoma, and intraoperative reduction of the PTH level by >50% from baseline following resection supported successful excision of the tumor. Brown tumor is not a true neoplasm, but it is the result of a reparative cellular process. In some areas where bone loss is particularly rapid, hemorrhage, reparative granulation tissue, and a vascular, actively proliferating fibrous tissue replace the normal marrow content.16Enneking WF Clinical Musculoskeletal Pathology. 3rd ed. University of Florida Press, Gainesville, FL1990Google Scholar Hemorrhages, with accumulation of hemosiderin within the vascular fibrous tissue, are common and give the lesion its typical reddish-brown color.17Parisien M Silverberg SJ Shane E Dempster DW Bilezikian JP Bone disease in primary hyperparathyroidism.Endocrinol Metab Clin North Am. 1990; 19: 19-34PubMed Google Scholar The patient was referred for parathyroidectomy, and the pathology was compatible with localized parathyroid cancer (Fig 6). Parathyroid cancer has an estimated incidence of 0.015 per 100,000 population, an estimated prevalence of 0.005% in the United States, and is one of the rarest of all human cancers.18Fraker DL Parathyroid tumors.in: DeVita Jr, VT Hellman S Rosenberg SA Cancer: Principles and Practice of Oncology. 7th ed. Lippincott Williams & Wilkins, Philadelphia, PA2005: 1521-1527Google Scholar, 19Hundahl SA Fleming ID Fremgen AM Menck HR The American College of Surgeons Commission on Cancer and the American Cancer Society Two hundred eighty-six cases of parathyroid carcinoma treated in the U.S. between 1985-1995: a National Cancer Data Base Report.Cancer. 1999; 86: 538-544Crossref PubMed Scopus (335) Google Scholar In benign parathyroid disease, it is unusual to have both renal and bone symptoms documented at the time of diagnosis.20Vetto JT Brennan MF Woodruf J Burt M Parathyroid carcinoma: diagnosis and clinical history.Surgery. 1993; 114: 882-892PubMed Google Scholar These symptoms are present simultaneously at diagnosis in ≤50% patients with parathyroid cancer.18Fraker DL Parathyroid tumors.in: DeVita Jr, VT Hellman S Rosenberg SA Cancer: Principles and Practice of Oncology. 7th ed. Lippincott Williams & Wilkins, Philadelphia, PA2005: 1521-1527Google Scholar This case study shows an unusual presentation of benign metabolic bone pathology that is rarely seen with localized parathyroid cancer and severe hyperparathyroidism. The striking radiographic abnormalities may resemble metastatic bone disease.