Anti-GBM Disease Following Ovarian Mesonephric-Like Adenocarcinoma: A Unique Insight Into Paraneoplastic Autoimmunity.

A 63-year-old woman presented to primary care with urinary frequency, brown vaginal discharge, and an abdominal mass. CA-125 concentration was 50 U/mL (reference range, 0-35 U/mL); ultrasound revealed a left-sided, multiloculated, 16 × 12 cm adnexal mass. Urea 4.1 mmol/L (reference, 2.5-7.8 mmol/L), creatinine 82 μmol/L (reference, 45-85 μmol/L, baseline ∼80 μmol/L), and sodium 135 mmol/L (reference, 133-146 mmol/L) were normal. Given her postmenopausal status, laparoscopic bilateral salpingo-oophorectomy with peritoneal washings was performed. Although both ovaries and fallopian tubes were removed, a small portion of the cyst remained adherent to the left pelvic side wall. All specimens were sent for histopathological analysis. Histology confirmed MLA of the left ovary with positive washings. Staging computed tomography of the chest, abdomen, and pelvis showed trace pelvic fluid only. One month after the surgery, the patient underwent laparoscopic total hysterectomy, cyst remnant excision, bilateral pelvic lymph node dissection, para-aortic lymph node sampling, and subcolic omentectomy. Final histology confirmed FIGO (Fédération Internationale de Gynécologie et d’Obstétrique) stage IIIA1(i) MLA on endometriosis in the cyst remnant and perinodal pelvic tissue; complete cytoreduction was achieved. The patient received 6 cycles of carboplatin-paclitaxel (administered on day 1 of a 21-day cycle). Dexamethasone premedication was reduced from 20 mg to 8 mg after cycle 1 as no infusion reaction occurred. Four months after chemotherapy, the patient developed fatigue, nausea, and anemia (hemoglobin 8.5 g/dL [reference, 11.5-16.5 g/dL]; other blood tests were not drawn at that stage). Dipstick revealed hematuria, and automated urine microscopy revealed a white cell count of 33/μL (no reference range is used for the automated analyzer, but values >40/μL are cultured routinely) and a red cell count of 1026/μL (no reference range is used for the automated analyzer, but values >10/μL may be considered significant). Urine was not sent for further analysis. Oral iron was started then stopped due to nausea. Computed tomography urogram and computed tomography of the chest were nonspecific except for a right renal cyst. Fourteen days after initial presentation, vomiting, abdominal pain, and oliguria accompanied stage 3 acute kidney injury (creatinine 1,899 μmol/L [reference, 45-85 μmol/L], urea 44.3 mmol/L [reference, 2.5-7.8 mmol/L]), hyperkalemia (potassium 7.3 mmol/L [reference, 3.5-5.3 mmol/L]), an unremarkable serum sodium of 138 mmol/L [reference, 133-146 mmol/L], and partially compensated metabolic acidosis. Dialysis was started for refractory hyperkalemia and acidosis. Due to progressive anemia (hemoglobin 7.1 g/dL [reference, 11.5-16.5 g/dL]), nonvisible hematuria, and dipstick-indicated low-grade proteinuria, an intrinsic kidney disease serum screen was undertaken, revealing positive anti-GBM (378.0 U/mL [reference, 0-7 U/mL]) and antimyeloperoxidase (MPO) antibodies (10 IU/mL [reference, 0-3.5 IU/mL]), consistent with a possible anti-neutrophil cytoplasmic antibody/GBM overlap glomerulonephritis. Antiproteinase 3 was <1 IU/mL (reference, 0-2 IU/mL). Urine was not sent for further analysis. Despite an unremarkable chest x-ray, a new supplemental oxygen requirement was managed as likely pulmonary congestion following erythrocyte transfusion during dialysis. Clinical suspicion for pulmonary hemorrhage persisted after an acute fall in hemoglobin concentration (7.1 g/dL to 5.4 g/dL [reference, 11.5-16.5 g/dL]) despite ultrafiltration and, in response to this, a single unit (300 mL) of leukodepleted red cells was administered (hemoglobin 7 g/dL [reference, 11.5-16.5 g/dL] 3 days later). Treatment comprised daily plasma exchange, thrice-weekly dialysis, and 500 mg intravenous methylprednisolone for 3 consecutive days, with the third day also coinciding with the administration of a single dose of cyclophosphamide 620 mg and rituximab 1 g. The methylprednisolone was immediately followed by tapering oral steroids starting at 40 mg prednisolone daily. A single further 1 g rituximab was administered 13 days after the first. After 8 days of daily plasma exchange and 3 dialysis sessions, anti-GBM IgG concentrations had reduced by over 50% ( Fig 1 ). A single additional unit (300 mL) of leukodepleted red cells was administered 2 weeks before the first in response to a hemoglobin concentration of 6 g/dL. Due to the kidney disease severity at presentation, kidney biopsy was not performed. Given the risk of cancer recurrence, the patient agreed to a strategy to limit exposure to any further immunosuppressive agents and, other than the tapering oral steroids, no further immunosuppression has been given. Figure 1 Variation of the anti-glomerular basement membrane (GBM) titer over time. Variation of the anti-glomerular basement membrane (GBM) titer over time. Outpatient review concluded anti-GBM disease, mindful of anti-MPO positivity and potential overlap syndromes. Three months after the initial screen, anti-MPO levels were normal (1.5 IU/mL [reference, 0-3.5 IU/mL]), antiproteinase 3 <1 IU/mL [reference, 0-2 IU/mL], sodium 136 mmol/L [reference,133-146 mmol/L], urea 8.5 mmol/L [reference, 2.5-7.8 mmol/L], creatinine 389 μmol/L [reference, 45-85 μmol/L]. Urine was not sent for further analysis at that stage. She continues under nephrology care, evaluated for a right brachiocephalic fistula for ongoing dialysis. The patient’s malignancy remains in remission, and no further chemotherapy has been administered since completing 6 cycles. The patient continues to be monitored by the oncology team, who have advised that a minimum of 6 years of cancer-free status is required before renal transplantation can be considered. Given the combination of the patient’s age, dialysis dependence, and elevated serum creatinine at presentation, significant recovery of kidney function is considered unlikely. As such, in the absence of a clear clinical benefit and due to the associated risks, the nephrology team is not currently pursuing a kidney biopsy.

This case represents a novel clinical observation and the first documented instance of anti-GBM disease after treatment for ovarian MLA, raising suspicion of a potential pathophysiological link. It highlights a compelling connection between chemotherapy, an exceptionally rare and aggressive malignancy, and the onset of autoimmune glomerular injury. 6 , 7 Circulating anti-GBM IgG, with specificity ∼99% and thus nearly diagnostic for anti-GBM disease, contrasts with anti-MPO/anti-neutrophil cytoplasmic antibodies, which, although ∼90% specific for small-vessel vasculitides such as microscopic polyangiitis, can also be present in malignancies and other inflammatory conditions. 8 , 9 Therefore, careful clinicopathologic correlation is imperative when both antibodies are detected. Although paraneoplastic kidney diseases typically emerge within 6 months after tumor resection or after completion of cytotoxic chemotherapy, there are notable exceptions. 10 Although anti-GBM disease has been observed with other malignancies, 11 , 12 , 13 , 14 this case raises specific questions regarding how MLA and/or its treatment may act as a trigger, possibly through immune dysregulation that exposes or modifies GBM antigens, prompting autoantibody production. Notably, paclitaxel, a key component of this patient’s chemotherapy, is known to impair regulatory T-cell function, which may reduce immune tolerance in predisposed individuals. 15 The concurrent positivity for anti-GBM and anti-MPO antibodies also hints at a possible anti-neutrophil cytoplasmic antibody/anti-GBM overlap syndrome, a phenomenon that may reflect the unique immune environment created by MLA-associated autoimmunity. This observation suggests that the pathophysiology of MLA may involve immune mechanisms not yet fully understood, highlighting the role of cancer biology in modifying autoimmune risk. Overall, this case emphasizes the need for vigilance in patients with rare malignancies undergoing chemotherapy, as such treatments may unveil autoimmune syndromes with unique characteristics. Furthermore, it underscores the value of continued research into paraneoplastic autoimmunity and the effect of chemotherapeutic agents on immune function. This case adds valuable data on paraneoplastic autoimmunity associated with an extremely rare malignancy, offering insights that may extend to other malignancies with immune-altering properties.

Antiglomerular basement membrane (GBM) disease is a rare autoimmune small vessel vasculitis that affects the glomerular and pulmonary capillaries. It is characterized by anti-GBM autoantibodies targeting the NC1 domain of the α3 chain of type IV collagen. 1 While the causative stimulus for these antibodies is not fully understood, several risk factors have been implicated, including infections and drugs. 2 Anti-GBM disease has been identified concurrently in cases of certain malignancies, as well as following treatment for various malignancies. 3 , 4 Any genuine relationship between anti-GBM disease and cancer or cancer treatment may be related to immune dysregulation and GBM antigen exposure. Kidney biopsy remains the gold standard for diagnosis. Mesonephric-like adenocarcinoma (MLA) is an extremely rare and aggressive adenocarcinoma predominantly affecting the uterine corpus and ovaries. MLA typically displays diverse architectural patterns and is immunohistochemically positive for markers such as PAX8, GATA3, and TTF1, whereas it is negative for estrogen and progesterone receptors. 5 Due to its rarity, optimal treatment and long-term prognosis remain under study. This case report documents the first known instance of anti-GBM disease following the development and treatment of ovarian MLA, further suggesting that pre-existing malignancy or its treatment may trigger the production of anti-GBM antibodies.