Case 21: Middle aged female with metastatic melanoma develops crescentic proliferative GN while on immunomodulatory therapy
To preserve patient privacy and for didactic purposes, case descriptions and pathology reports have been anonymized and partially fictionalized. The pathology images are representative images from a mixture of similar cases.
Daniel LandryCase Presenter | Baystate Medical Center, Springfield, MA, USA | No conflict of interest reported
Ali Poyan MehrNephrology Discussant | Beth Israel Deaconess Medical Center, Boston, MA, USA | Conflict of interest reported: Mallinckrodt - Glomerular Disease Consultant and Research Grant
Patient is a 50-year-old female originally sent to the office for consultation regarding a creatinine of 1.8 mg/dL, new-onset resistant hypertension, and subnephrotic-range proteinuria of 2.5 grams/day.
Medical history: History of recurrent, metastatic melanoma 2013 (original excision 1985). She began therapy for her metastatic melanoma with with ipilimumab/nivolumab (“Checkpoint Inhibitors”) 2 years prior to current presentation. However, therapy was discontinued after approximately 8 months due to hepatitis (treated with steroids). In light of persistent disease, an alternative regimen was started with MAPK inhibitors dabrafenib and trametinib, which she has been now been using for approximately one year.
Physical Exam: Overweight 2+ lower extremity edema but no rash or pulmonary findings.
Laboratory and other data: Normal creatinine couple months after ipilimumab/nivolumab discontinuation. She presented to nephrology with creatinine of 1.8 mg/dL six months after that, while on dabrafenib and trametinib. UA with dysmorphic RBCs and 2.5 gram proteinuria by spot ratio. Negative SPEP/IFE, ANCA, anti-GBM, C3/C4, ANA. Hb 10 mg/dl, platelets normal, haptoglobin normal. Chest X-ray normal.
Pathology images pending
Focal crescentic, proliferative, and sclerosing glomerulonephritis. Less than 10% of glomeruli with focal cellular crescents, and focal endocapillary proliferation. Focal sclerosis, and global sclerosis is present in few glomeruli. Acute and chronic tubular injury with moderate interstitial inflammation and interstitial fibrosis involving of approximately 30% of the cortical area.
On immunofluorescence: Global and diffuse linear staining of capillary loops dominant for IgG (3+), also for IgA (2+), Kappa (2+), and Lambda (1+). C3 demonstrates nonspecific granular staining within mesangial and hilar areas. IgM, C1q and Fibrinogen are negative.
Ultrastructural examination of the three glomeruli demonstrates areas with open capillary loops and preserved foot processes. Other areas demonstrate diffuse effacement of foot processes with variable thickening and wrinkling of glomerular basement membranes. A segmental area of endocapillary proliferation and a small cellular crescent are identified. No immune complex disease is identified. There are no tubuloreticular structures.
Questions posed & summary of key discussion points
1. How would you treat this patient? 2. Is there a potential mechanism behind the patient’s cancer immunotherapy that could describe this pathologic finding?
Author(s) of case summary:
Case summary pending
If you would like to be a contributing author for the creation of didactic materials and case summaries, please contact us at [email protected].