Immune checkpoint inhibitor-related colitis in patients on immunotherapy for cancer.

OBJECTIVES: Immune checkpoint inhibitors, a revolutionary class of cancer immunotherapy drugs, have transformed cancer treatment by bolstering antitumor immunity for various advanced-stage solid cancers. The US Food and Drug Administration has approved 7 immune checkpoint inhibitors that target 3 major immune checkpoint proteins: cytotoxic T-lymphocyte-associated protein 4, programmed cell death 1 protein, and programmed cell death 1 ligand 1. In addition to their remarkable efficacy, however, these inhibitors have been observed causing immune-related adverse events, particularly immune checkpoint inhibitor-related colitis, which often results in severe or life-threatening clinical issues. METHODS: The diagnosis of immune checkpoint inhibitor-related colitis relies on incorporation of clinical evaluation as well as endoscopic and histopathologic examination, with exclusion of other potential etiologies. RESULTS: The common histopathologic manifestations of immune checkpoint inhibitor-related colitis are acute active colitis, chronic active colitis, microscopic colitis (collagenous or lymphocytic), and ischemic colitis, with patterns overlapping. Notably, enterocyte apoptosis is a unique feature of immune checkpoint inhibitor toxicity. The proposed mechanisms for the pathogenesis of immune checkpoint inhibitor-related colitis are primarily associated with autoimmune-type dysregulation and gut microbiome alteration. This review summarizes the clinical and pathologic characteristics of immune checkpoint inhibitor-related colitis and elucidates its underlying pathogenic mechanisms. CONCLUSIONS: Future successful management of this form of colitis relies on our comprehension of the intricate interplay between tumoral and systemic immune responses to immune checkpoint inhibitors and innovative approaches to modify these responses, along with specific immune cell populations, to preclude immune-related adverse events while achieving antitumor therapeutic outcomes.

Renal Medullary Carcinoma.

Renal medullary carcinoma, also referred to as the seventh sickle cell nephropathy, typically affects young African Americans with sickle cell trait, or, less frequently, patients with sickle cell disease. The existence of renal medullary carcinoma without a concomitant hemoglobinopathy is a topic of controversy. The typical patient is a young male of African or Mediterranean descent, with hematuria and/or flank pain. Most patients have metastatic disease at the time of presentation. The tumor is characteristically a poorly circumscribed mass in the medullary region, commonly showing variable amounts of hemorrhage and necrosis. Microscopically, a characteristic reticular or cribriform pattern with a striking desmoplastic stromal response and a robust mixed inflammatory infiltrate is observed. Collecting duct carcinoma, malignant rhabdoid tumor, urothelial carcinoma, and other subtypes of renal cell carcinoma are in the differential diagnosis. Because of the advanced stage of disease at presentation and the aggressive nature of this malignant neoplasm, survival is poor even with chemotherapy; however, isolated reports of prolonged survival have been documented.

Potential influence of p16 immunohistochemical staining on the diagnosis of squamous cell lesions in cervical biopsy specimens: observation from cytologic-histologic correlation.

BACKGROUND: The p16 immunohistochemical (IHC) marker has been used increasingly as an adjunct to morphologic assessment of cervical biopsies in which the differential diagnoses include high-grade squamous intraepithelial lesion (HSIL) and its mimics. The objective of this study was to assess the potential influence of p16 IHC staining on the evaluation of cervical biopsy as observed through cytologic-histologic correlation (CHC). METHODS: Cervical biopsy samples that had cytologic diagnoses of either low-grade squamous intraepithelial lesion (LSIL) or HSIL and also had histologic follow-up were retrieved from the department database. CHC and the use of p16 IHC from 2 periods (group 1, 2008; group 2, 2014-2016) were compared and analyzed. RESULTS: Histology on 452 samples from patients who had prior LSIL cytology in group 1 yielded 126 benign (27.9%), 272 LSIL (60.2%), and 54 HSIL (11.9%) diagnoses. By comparison, 491 samples from the patients in group 2 yielded 106 benign (21.6%), 277 LSIL (56.4%), and 108 HSIL (22.0%) diagnoses. The difference in CHC discrepancies between the 2 groups was significant (P = .0001), mainly because of the increased diagnosis of HSIL in group 2. Although p16 IHC was not applied to any sample from group 1, it was performed on 141 of 491 samples (28.7%) from group 2. Further follow-up of patients who had histologic HSIL revealed that residual HSIL was identified significantly more often in those who did not have p16 IHC applied in the preceding cervical biopsy than in those did (P = .0004). A similar comparison was performed between 113 patients from group 1 and 152 patients from group 2 who had a prior diagnosis of HSIL cytology, and the difference was statistically insignificant. CONCLUSIONS: The use of p16 IHC on cervical biopsies in patients who had a prior cytologic diagnosis of LSIL may lead to greater detection and upgrading of HSIL, thereby compounding the discrepancy in CHC.