A 55-year-old woman with no significant medical history initially presented with several months of right-sided flank pain. A computed tomography (CT) of the abdomen and pelvis revealed severe right-sided hydroureteronephrosis and right cortical atrophy of the right kidney. A CT urogram demonstrated a soft tissue mass involving the distal right ureter near the ureterovesical junction as well as enlarged right external iliac lymph nodes. She underwent cystoscopy which identified tumor arising from the right ureteral orifice. A transurethral resection of bladder tumor (TURBT) was performed which revealed invasive high-grade, poorly differentiated papillary urothelial carcinoma that extended into the lamina propria but did not invade into the muscularis propria. A biopsy of the right external iliac lymph node was positive for malignancy. The patient was thus initially diagnosed with stage IIIA disease (pT1N1M0) and started on neoadjuvant dose dense methotrexate, vinblastine, doxorubicin, and cisplatin (ddMVAC). She eventually underwent a radical nephroureterectomy, partial cystectomy, and pelvic lymph node dissection. At the time of surgery, she was found to have microscopic foci of malignancy with negative surgical margins and negative lymph nodes in the nine total lymph nodes examined. Adjuvant therapy was not indicated given the pathologic findings of pTaN0Mx, and the patient proceeded with surveillance.
Four months after surgery, she was found to have a new 3.1 cm right inguinal lymph node and 1.3 cm anterior aortocaval lymph node on re-staging CT imaging. Biopsy of the right inguinal lymph node was positive for recurrent urothelial carcinoma. There was concern for platinum resistance given her prior neoadjuvant ddMVAC therapy. The patient was therefore started on intravenous pembrolizumab 200 mg every 3 weeks instead of a cisplatin-based regimen. Re-staging CT imaging after approximately three months of pembrolizumab indicated decreasing size of the inguinal and pelvic lymph nodes. After five months of pembrolizumab (eight cycles), repeat imaging indicated no evidence of disease. However, CT chest imaging at this time revealed interval development of bilateral ground glass opacities in the lungs. At this time, the patient did not report any respiratory symptoms such as shortness of breath, dyspnea on exertion, or cough. However, pembrolizumab was held given the concern for immune-mediated pneumonitis. She eventually developed acute-onset shortness of breath and fever for which she presented to the hospital where she was found to have progressive bilateral ground glass opacities involving all of the lobes. Infectious workup including Pneumocystis jirovecii was negative. She was then started on a prolonged steroid taper for grade 3 immune-mediated pneumonitis. One month after starting steroids, she had improvement in respiratory symptoms. An interval CT chest at this time demonstrated improvement in the bilateral opacities. The patient completed her steroids over two months with complete resolution of her pulmonary symptoms.
Approximately 4 weeks later (3 months after her last dose of pembrolizumab), she developed several recurrent episodes of red eyes, styes, and eyelid tenderness involving both eyes. She had pre-existing myopia and age-related presbyopia but did not have any changes in visual acuity. The patient did not have any blurry vision or ocular pain. Given that her symptoms persisted despite conservative measures, she was evaluated by an optometrist. Visual acuity examination was stable. Tear breakup time (TBUT) was low suggesting tear film instability. The patient was also noted to have thin tear meniscus in both eyes. Digital expression of the meibomian glands revealed thick, turbid meibum. Infrared meibography revealed bilateral grade 2 meibomian gland atrophy (Figure 2). Taken together, she was diagnosed with meibomian gland dysfunction (MGD). Management was started with warm compresses, lid massages, oil-based eye drops, as well as dietary omega-3 fatty acid supplementation. With these measures, the patient had significant improvement in her eye symptoms. Pembrolizumab was not continued after eight cycles given that her interval staging scans did not show any evidence of cancer or recurrence and since she had experienced severe pulmonary toxicity. At a follow-up two years after completing pembrolizumab, the patient was doing well clinically without evidence of cancer on repeat imaging. She continued to have mild eye symptoms and persistent meibomian gland atrophy on meibography. However, her symptoms were well-managed with continued MGD therapies.