QUIZ PAGE FEBRUARY 2014 Swollen Kidneys and a Pancreatic Mass CLINICAL PRESENTATION
QUIZ PAGE
A 46-year-old man presented with progressive generalized weakness, arthralgias of the large joints, and an unintentional 4-kg weight loss over 6 months. Physical examination showed the patient to be hypertensive (blood pressure, 152/ 105 mm Hg) with a body mass index of 21 kg/m2. Cardiac, pulmonary, and abdominal examinations produced normal results. There were no signs of arthritis or edema. Eczema was present. Laboratory test results included an elevation in serum creatinine level from 1.40 to 2.62 mg/dL, with a corresponding decrease in estimated glomerular filtration rate from 65 to 31 mL/min/1.73 m2 (using the 4-variable MDRD [Modification of Diet in Renal Disease] Study equation) in 2 months. Other results included the following values: sodium, 143 mEq/L; potassium, 4.5 mEq/L; calcium, 9.42 mg/dL; phosphate, 3.25 mg/dL; an inflammatory response with erythrocyte sedimentation rate, 46 (normal, ,15) mm/h; C-reactive protein, 16 (normal, ,10) mg/L; leukocytes, 10.8 3 103/ mL; eosinophils, 0.8 3 103/mL; albumin, 3.1 g/dL; total protein, 8.5 g/dL; and increased liver enzyme levels: bilirubin, 0.29 mg/dL; alkaline phosphatise, 220 U/L; g-glutamyl transferase, 179 U/L; aspartate aminotransferase, 40 U/L; and alanine aminotransferase, 97 U/L. Urine dipstick tested positive for erythrocytes and proteinuria (protein excretion, 1.0 g in 24-hour urine collection), but no erythrocyte casts were observed in fresh urine. Ultrasonography and computed tomography were performed (Fig 1) and showed an enlarged corpus and tail of the pancreas suspicious for pancreatic cancer, enlarged kidneys (left, 16 cm; right, 13 cm), and bilateral lung consolidations in the lower lobes. A diagnostic biopsy of the left kidney was performed (Fig 2).
xviii
Figure 1. Abdominal computed tomographic scan shows an enlarged corpus and tail of the pancreas (arrow) and enlarged kidneys.
- Describe the biopsy findings. - What is your diagnosis? - What other organs may be involved in this
condition? - What is the treatment for this patient?
Am J Kidney Dis. 2014;63(2):xviii-xxi
Figure 2. Kidney biopsy. (A) David Jones stain; original magnification, 320. (B) Hematoxylin and eosin stain; original magnification, 320. (C) Detailed image of interstitium (hematoxylin and eosin stain; original magnification, 340). (D) Tri-Pas stain; original magnification, 310. (E) Arrow indicates wall vein. David Jones stain; original magnification, 310. (F) Immunoglobulin G stain; original magnification, 340. Abbreviations: g, glomerulus; i, interstitium; t, tubule; v, vein.
xix
QUIZ PAGE
Am J Kidney Dis. 2014;63(2):xviii-xxi
QUIZ PAGE FEBRUARY 2014
ANSWERS
DISCUSSION - Describe the biopsy
findings
QUIZ PAGE
Morphologic analysis of the kidney biopsy specimen (Fig 2) showed glomeruli with intact thin glomerular basement membranes, no mesangial or endocapillary proliferation, and no glomerular crescents (Fig 2A). Fluorescence microscopy (results not shown) did not reveal depositions. The interstitium contained dense lymphoplasmacytic infiltrate (Fig 2B) with numerous plasma cells, lymphocytes, and eosinophils, as seen in the detailed image of the infiltrate (Fig 2C). Interstitial fibrosis also was a prominent feature (Fig 2D). Furthermore, phlebitis with near-complete obliteration of a vein by infiltration of lymphocytes and plasma cells within the wall of the venous channel was easily appreciated (Fig 2E). On immunohistochemical staining, there was polyclonal staining of plasma cells for k and l (results not shown). Stains for immunoglobulin heavy chains in plasma cells showed predominance for immunoglobulin G (IgG) over IgD and IgA, with only little expression of IgM. The high number of IgG-positive plasma cells can be appreciated clearly in Fig 2F. IgG4 subtyping was performed, with the number of IgG41 plasma cells per high-power field greatly exceeding the accepted number of 10/high-power field.1 This can be seen in Fig 3. - What is your diagnosis?
The diagnosis is IgG4-related disease with localization in the xx
Figure 3. Kidney biopsy. Immunoglobulin G4 stain; original magnification, 340 (equals 1 high-power field).
kidneys, pancreas, lungs, and skin. IgG4-related disease is a relatively rare but increasingly recognized entity with a wide range of manifestations. It is characterized by inflammatory swelling in affected organs and allergic manifestations (eg, eczema, asthma, and mild eosinophilia). In the kidney, key histopathologic findings include dense lymphoplasmacytic infiltrates, fibrosis (usually in a storiform pattern), and obliterative phlebitis.2 The radiologic features are easily mistaken for malignancy, as they initially were in this patient. The pathophysiology is incompletely understood, but an interleukin 10–mediated (“modified”) type 2 helper T cell is involved. The majority of patients are men and older than 50 years. Serum IgG4 concentration usually is elevated. Decreased serum complement C3 or C4 levels, peripheral-blood eosinophilia, and positive antinuclear antibody also may be present.1
In our patient, the diagnosis was suggested by the increased total serum protein level caused by increased serum IgG4 levels (11.00 [reference range, 0.081.40] g/L) and confirmed by the kidney biopsy. - What other organs may
be involved in this condition? In addition to the kidneys, pancreas, and skin, virtually any organ can be affected in IgG4-related disease. Organs that frequently are involved include the bile duct (sclerosing cholangitis), gallbladder (cholecystitis), salivary glands (sclerosing sialadenitis), retroperitoneum (retroperitoneal fibrosis), and thyroid gland (presenting as Riedel goiter and sometimes Hashimoto thyroiditis).3,4 - What is the treatment for
this patient? First-line treatment consists of glucocorticoids. Prednisolone in a Am J Kidney Dis. 2014;63(2):xviii-xxi
dosage of 0.6 mg/kg of body weight per day for 2-4 weeks usually is effective. The dosage then can be tapered to 5 mg/d over several months. Azathioprine, mycophenolate mofetil, or methotrexate may serve as alternative treatments.3
FINAL DIAGNOSIS IgG4-related disease with IgG4related tubulointerstitial nephritis.
REFERENCES 1. Saeki T, Nishi S, Imai N, et al. Clinicopathological characteristics of patients with IgG4-related tubulointerstitial nephritis. Kidney Int. 2010;78(10):1016-1023.
CASE PROVIDED AND AUTHORED BY Dinette E. Agterhuis, MD,1 Edwin P. Schuurmans, BSc,1 Marieke C.H. Hogenes, MD,2 and Gozewijn
D. Laverman, MD, PhD,1 Department of Internal Medicine, ZGT Hospital, Almelo; and 2 Laboratory for Pathology East Netherlands, Enschede, the Netherlands. Address correspondence to Dinette Agterhuis, MD, Zilvermeeuw 1, 7609 PP Almelo, the Netherlands. E-mail: [email protected] Ó 2014 by the National Kidney Foundation, Inc. http://dx.doi.org/10.1053/j.ajkd.2013. 06.030 SUPPORT: None. FINANCIAL DISCLOSURE: The authors declare that they have no relevant financial interests. 1
xxi
QUIZ PAGE
Am J Kidney Dis. 2014;63(2):xviii-xxi
2. Deshpande V, Zen Y, Chan JK, et al. Consensus statement on the pathology of IgG4-related disease. Mod Pathol. 2012;25(9):1181-1192. 3. Vaglio A, Zwerina J. IgG4related disease [letter]. N Engl J Med. 2012;366(17):1646. author reply 1646-1647. 4. Fervenza FC, Downer G, Beck LH Jr, Sethi S. IgG4-related tubulointerstitial nephritis with membranous nephropathy. Am J Kidney Dis. 2011;58(2):320-324.
QUIZ PAGE
A 46-year-old man presented with progressive generalized weakness, arthralgias of the large joints, and an unintentional 4-kg weight loss over 6 months. Physical examination showed the patient to be hypertensive (blood pressure, 152/ 105 mm Hg) with a body mass index of 21 kg/m2. Cardiac, pulmonary, and abdominal examinations produced normal results. There were no signs of arthritis or edema. Eczema was present. Laboratory test results included an elevation in serum creatinine level from 1.40 to 2.62 mg/dL, with a corresponding decrease in estimated glomerular filtration rate from 65 to 31 mL/min/1.73 m2 (using the 4-variable MDRD [Modification of Diet in Renal Disease] Study equation) in 2 months. Other results included the following values: sodium, 143 mEq/L; potassium, 4.5 mEq/L; calcium, 9.42 mg/dL; phosphate, 3.25 mg/dL; an inflammatory response with erythrocyte sedimentation rate, 46 (normal, ,15) mm/h; C-reactive protein, 16 (normal, ,10) mg/L; leukocytes, 10.8 3 103/ mL; eosinophils, 0.8 3 103/mL; albumin, 3.1 g/dL; total protein, 8.5 g/dL; and increased liver enzyme levels: bilirubin, 0.29 mg/dL; alkaline phosphatise, 220 U/L; g-glutamyl transferase, 179 U/L; aspartate aminotransferase, 40 U/L; and alanine aminotransferase, 97 U/L. Urine dipstick tested positive for erythrocytes and proteinuria (protein excretion, 1.0 g in 24-hour urine collection), but no erythrocyte casts were observed in fresh urine. Ultrasonography and computed tomography were performed (Fig 1) and showed an enlarged corpus and tail of the pancreas suspicious for pancreatic cancer, enlarged kidneys (left, 16 cm; right, 13 cm), and bilateral lung consolidations in the lower lobes. A diagnostic biopsy of the left kidney was performed (Fig 2).
xviii
Figure 1. Abdominal computed tomographic scan shows an enlarged corpus and tail of the pancreas (arrow) and enlarged kidneys.
- Describe the biopsy findings. - What is your diagnosis? - What other organs may be involved in this
condition? - What is the treatment for this patient?
Am J Kidney Dis. 2014;63(2):xviii-xxi
Figure 2. Kidney biopsy. (A) David Jones stain; original magnification, 320. (B) Hematoxylin and eosin stain; original magnification, 320. (C) Detailed image of interstitium (hematoxylin and eosin stain; original magnification, 340). (D) Tri-Pas stain; original magnification, 310. (E) Arrow indicates wall vein. David Jones stain; original magnification, 310. (F) Immunoglobulin G stain; original magnification, 340. Abbreviations: g, glomerulus; i, interstitium; t, tubule; v, vein.
xix
QUIZ PAGE
Am J Kidney Dis. 2014;63(2):xviii-xxi
QUIZ PAGE FEBRUARY 2014
ANSWERS
DISCUSSION - Describe the biopsy
findings
QUIZ PAGE
Morphologic analysis of the kidney biopsy specimen (Fig 2) showed glomeruli with intact thin glomerular basement membranes, no mesangial or endocapillary proliferation, and no glomerular crescents (Fig 2A). Fluorescence microscopy (results not shown) did not reveal depositions. The interstitium contained dense lymphoplasmacytic infiltrate (Fig 2B) with numerous plasma cells, lymphocytes, and eosinophils, as seen in the detailed image of the infiltrate (Fig 2C). Interstitial fibrosis also was a prominent feature (Fig 2D). Furthermore, phlebitis with near-complete obliteration of a vein by infiltration of lymphocytes and plasma cells within the wall of the venous channel was easily appreciated (Fig 2E). On immunohistochemical staining, there was polyclonal staining of plasma cells for k and l (results not shown). Stains for immunoglobulin heavy chains in plasma cells showed predominance for immunoglobulin G (IgG) over IgD and IgA, with only little expression of IgM. The high number of IgG-positive plasma cells can be appreciated clearly in Fig 2F. IgG4 subtyping was performed, with the number of IgG41 plasma cells per high-power field greatly exceeding the accepted number of 10/high-power field.1 This can be seen in Fig 3. - What is your diagnosis?
The diagnosis is IgG4-related disease with localization in the xx
Figure 3. Kidney biopsy. Immunoglobulin G4 stain; original magnification, 340 (equals 1 high-power field).
kidneys, pancreas, lungs, and skin. IgG4-related disease is a relatively rare but increasingly recognized entity with a wide range of manifestations. It is characterized by inflammatory swelling in affected organs and allergic manifestations (eg, eczema, asthma, and mild eosinophilia). In the kidney, key histopathologic findings include dense lymphoplasmacytic infiltrates, fibrosis (usually in a storiform pattern), and obliterative phlebitis.2 The radiologic features are easily mistaken for malignancy, as they initially were in this patient. The pathophysiology is incompletely understood, but an interleukin 10–mediated (“modified”) type 2 helper T cell is involved. The majority of patients are men and older than 50 years. Serum IgG4 concentration usually is elevated. Decreased serum complement C3 or C4 levels, peripheral-blood eosinophilia, and positive antinuclear antibody also may be present.1
In our patient, the diagnosis was suggested by the increased total serum protein level caused by increased serum IgG4 levels (11.00 [reference range, 0.081.40] g/L) and confirmed by the kidney biopsy. - What other organs may
be involved in this condition? In addition to the kidneys, pancreas, and skin, virtually any organ can be affected in IgG4-related disease. Organs that frequently are involved include the bile duct (sclerosing cholangitis), gallbladder (cholecystitis), salivary glands (sclerosing sialadenitis), retroperitoneum (retroperitoneal fibrosis), and thyroid gland (presenting as Riedel goiter and sometimes Hashimoto thyroiditis).3,4 - What is the treatment for
this patient? First-line treatment consists of glucocorticoids. Prednisolone in a Am J Kidney Dis. 2014;63(2):xviii-xxi
dosage of 0.6 mg/kg of body weight per day for 2-4 weeks usually is effective. The dosage then can be tapered to 5 mg/d over several months. Azathioprine, mycophenolate mofetil, or methotrexate may serve as alternative treatments.3
FINAL DIAGNOSIS IgG4-related disease with IgG4related tubulointerstitial nephritis.
REFERENCES 1. Saeki T, Nishi S, Imai N, et al. Clinicopathological characteristics of patients with IgG4-related tubulointerstitial nephritis. Kidney Int. 2010;78(10):1016-1023.
CASE PROVIDED AND AUTHORED BY Dinette E. Agterhuis, MD,1 Edwin P. Schuurmans, BSc,1 Marieke C.H. Hogenes, MD,2 and Gozewijn
D. Laverman, MD, PhD,1 Department of Internal Medicine, ZGT Hospital, Almelo; and 2 Laboratory for Pathology East Netherlands, Enschede, the Netherlands. Address correspondence to Dinette Agterhuis, MD, Zilvermeeuw 1, 7609 PP Almelo, the Netherlands. E-mail: [email protected] Ó 2014 by the National Kidney Foundation, Inc. http://dx.doi.org/10.1053/j.ajkd.2013. 06.030 SUPPORT: None. FINANCIAL DISCLOSURE: The authors declare that they have no relevant financial interests. 1
xxi
QUIZ PAGE
Am J Kidney Dis. 2014;63(2):xviii-xxi
2. Deshpande V, Zen Y, Chan JK, et al. Consensus statement on the pathology of IgG4-related disease. Mod Pathol. 2012;25(9):1181-1192. 3. Vaglio A, Zwerina J. IgG4related disease [letter]. N Engl J Med. 2012;366(17):1646. author reply 1646-1647. 4. Fervenza FC, Downer G, Beck LH Jr, Sethi S. IgG4-related tubulointerstitial nephritis with membranous nephropathy. Am J Kidney Dis. 2011;58(2):320-324.
