Patients sister was later offered risk-reducing strategies including prophylactic total hysterectomy and bilateral salpingo-oophorectomy and colonoscopies. Discussion Checkpoint inhibitors (Anti PD-1 drugs) are approved in a variety Eslicarbazepine Acetate of cancers, including sound tumors with a microsatellite instability phenotype.21 The side effects of anti-PD-1 are similar to autoimmune conditions.4 The hematological immune-related side effects were reported in few cases, such as bicytopenia,6 two cases of immune thrombocytopenias within two weeks and after 42 days of immunotherapy. loss of nuclear expression of MLH-1 and PMS-2. Based on a strong predictor of response to immunotherapy, pembrolizumab was tried. However, within a few days of the single dose of pembrolizumab, immune thrombocytopenia followed by pancytopenia, recurrent seizures, visual hallucination, and cerebellar indicators Eslicarbazepine Acetate consistent with limbic encephalitis developed, which were not responding to steroid and intravenous immunoglobulin. Conclusion We are presenting a case of a CCE with deficient mismatch repair that developed two autoimmune side effects, pancytopenia and limbic encephalitis, within a few days of a single injection of pembrolizumab. strong class=”kwd-title” Keywords: pancytopenia, limbic encephalitis, obvious cell endometrial malignancy, obvious cell carcinoma of the endometrium, microsatellite instability-high, MSI-H, pembrolizumab Introduction A frequent mismatch repair protein deficiency can be seen in mixed endometrial and obvious cell carcinoma of the endometrium (CCE).1 Mismatch-repair status can predict clinical benefit from immune checkpoint blockade.2 Different immune checkpoint inhibitors had been investigated in advanced endometrial malignancy including PD-1 inhibitors as pembrolizumab and PDL-1 inhibitors as atezolizumab and avelumab.3 Immune-related adverse events complicating immunotherapy can mimic autoimmune conditions, affecting the thyroid, lung, colon and liver.4 With the broad use of anti-PD1 in clinical practice, rarer side effects are emerging. To date, hematological immune-related adverse events remain occasionally explained;5 for instance, bi-cytopenia (severe anemia and thrombocytopenia) possibly induced after the sixth cycle of injection of Nivolumab (anti-PD-1 antibody), given to a patient with primary malignant melanoma of the esophagus with inefficiency of high-dose intravenous methylprednisolone,6 immune-mediated thrombocytopenia,7 immune-mediated agranulocytosis,8 immunotherapy-associated hemolytic anemia with pure red-cell aplasia,9 immune medicated pancytopenia,10 and even central Lum immune cytopenia. 11 Limbic encephalopathy due to checkpoint inhibitor has also been reported,12C18 and as with encephalitis from other causes, the most frequent signs and symptoms are fever, headache, confusion, memory impairment, gait ataxia, seizures, and hallucinations. The onset was typically acute to sub-acute over days to a few weeks.19 Case Statement A 53-year-old female patient, known to have diabetes mellitus, and hypothyroidism, and no family history of malignancy, was diagnosed in 1999, with endometrial malignancy and was treated with hysterectomy and left salpingo-oophorectomy, relapsed few months later, as left pelvic mass, excised with sigmoidectomy, without Eslicarbazepine Acetate adjuvant chemotherapy. She was well until May 2016, when she presented with few months history of abdominal pain and rising CA 125. MRI and PET CT scan showed retroperitoneal mass that invaded substandard vena cava with no distant metastasis (Physique 1A). Open in a separate window Physique 1 (A) Initial PET scan showing retroperitoneal mass invading substandard vena cava. (B) PET scan showing retroperitoneal mass progression with right hydronephrosis and lung metastasis post 3 lines of chemotherapy. The mass was excised together with substandard vena cava angioplasty and the pathology showed lymph node metastasis with poorly differentiated carcinoma, forming cribriform/papillary growth pattern (Physique 2: image 1) and focal obvious cell changes (Physique 2: image 2) in favor of endometrial main. The excisional margin was positive. The tumor table made the decision either adjuvant chemotherapy or radiotherapy, which was declined by the patient. Open in a separate window Physique 2 H&E of the excised retroperitoneal lymph node showing poorly differentiated carcinoma, forming cribriform/papillary growth pattern [image 1] and focal obvious cell changes [image 2]. Complete loss of nuclear expression of MLH-1 [image 3] and PMS-2 [image 4]. Intact expression of MSH-6 [image 5] and MSH-2 [image 6]. Low power section demonstrates invasive malignant tumor-infiltrating tissue by a solid sheet of tumor cells with obvious voluminous obvious cytoplasm (hematoxylin and eosin stain, 4, [image 7]. High power section demonstrates malignant tumor composed of large voluminous obvious cytoplasm, unique margins, enlarged angulated pleomorphic hyperchromatic bizarre nuclei with prominent nucleoli (hematoxylin and eosin stain, 40, [image 8]. In September 2016, the tumor relapsed Eslicarbazepine Acetate in the retroperitoneal lymph node between L3-4 and in the lungs. Since then until April 2017, the patient received three lines of chemotherapy: Carboplatin/Paclitaxel/Bevacizumab, Topotecan and then Liposomal Adriamycin that were poorly tolerated. The Eslicarbazepine Acetate disease progressed further locally causing mass effect.