These findings expand the literature of immune-related toxicities of PD-L1 and PD-1 blockade to include lichenoid dermatitis and lichenoid mucositis. Of note, these cutaneous side effects were amenable to topical treatment, without the need for medication dose reduction or discontinuation.

Guanosine derivatives with a nucleophilic group at the 5' position (G-5') are oxidized by the Pt (IV) complex Pt( d, l)(1,2-(NH 2) 2C 6H 10)Cl 4 ([Pt (IV)(dach)Cl 4]). The overall redox reaction is autocatalytic, consisting of the Pt (II)-catalyzed Pt (IV) substitution and two-electron transfer between Pt (IV) and the bound G-5'. In this paper, we extend the study to improve understanding of the redox reaction, particularly the substitution step. The [Pt (II)(NH 3) 2(CBDCA-O,O')] (CBDCA = cyclobutane-1,1-dicarboxylate) complex effectively accelerates the reactions of [Pt (IV)(dach)Cl 4] with 5'-dGMP and with cGMP, indicating that the Pt (II) complex does not need to be a Pt (IV) analogue to accelerate the substitution. Liquid chromatography/mass spectroscopy (LC/MS) analysis showed that the [Pt (IV)(dach)Cl 4]/[Pt (II)(NH 3) 2(CBDCA-O,O')]/cGMP reaction mixture contained two Pt (IV)cGMP adducts, [Pt (IV)(NH 3) 2(cGMP)(Cl)(CBDCA-O,O')] and [Pt (IV)(dach)(cGMP)Cl 3]. The LC/MS studies also indicated that the trans, cis-[Pt (IV)(dach)( (37)Cl) 2( (35)Cl) 2]/[Pt (II)(en)( (35)Cl) 2]/9-EtG mixture contained two Pt (IV)-9-EtG adducts, [Pt (IV)(en)(9-EtG)( (37)Cl)( (35)Cl) 2] and [Pt (IV)(dach)(9-EtG)( (37)Cl)( (35)Cl) 2]. These Pt (IV)G products are predicted by the Basolo-Pearson (BP) Pt (II)-catalyzed Pt (IV)-substitution scheme. The substitution can be envisioned as an oxidative addition reaction of the planar Pt (II) complex where the entering ligand G and the chloro ligand from the axial position of the Pt (IV) complex are added to Pt (II) in the axial positions. From the point of view of reactant Pt (IV), an axial chloro ligand is thought to be substituted by the entering ligand G. The Pt (IV) complexes without halo axial ligands such as trans, cis-[Pt(en)(OH) 2Cl 2], trans, cis-[Pt(en)(OCOCF 3) 2Cl 2], and cis, trans, cis-[Pt(NH 3)(C 6H 11NH 2)(OCOCH 3) 2Cl 2] ([Pt (IV)(a,cha)(OCOCH 3) 2Cl 2], satraplatin) did not react with 5'-dGMP. The bromo complex, [Pt (IV)(en)Br 4], showed a significantly faster substitution rate than the chloro complexes, [Pt (IV)(en)Cl 4] and [Pt (IV)(dach)Cl 4]. The results indicate that the axial halo ligands are essential for substitution and the Pt (IV) complexes with larger axial halo ligands have faster rates. When the Pt (IV) complexes with different carrier ligands were compared, the substitution rates increased in the order [Pt (IV)(dach)Cl 4] < [Pt (IV)(en)Cl 4] < [Pt (IV)(NH 3) 2Cl 4], which is in reverse order to the carrier ligand size. These axial and carrier ligand effects on the substitution rates are consistent with the BP mechanism. Larger axial halo ligands can form a better bridging ligand, which facilitates the electron-transfer process from the Pt (II) to Pt (IV) center. Smaller carrier ligands exert less steric hindrance for the bridge formation.

Adenoviruses are common pathogens that usually cause self-limited infections. However, in the immunocompromised host they can cause severe infections involving multiple organs including the liver. A search of the pathology database at Stanford University Medical Center (1995 to 2016) identified 12 cases of adenovirus hepatitis including biopsy and autopsy specimens. There were 8 pediatric patients, 7 of which had received orthotropic liver transplants and 1 of which was receiving chemotherapy for lymphoblastic leukemia. There were 4 adult patients, of which 1 was actively receiving chemotherapy for chronic lymphocytic leukemia and 2 had undergone hematopoietic stem cell transplantation for hematologic malignancies. One patient had lymphoplasmacytic lymphoma and had received chemotherapy over a year prior but was not receiving therapy at the time he contracted adenovirus hepatitis. In all cases, histologic sections showed nonzonal coagulative hepatocyte necrosis and characteristic intranuclear inclusions. Hepatocyte necrosis ranged from spotty to massive. The majority of cases (7/12; 58%) had no associated inflammation. If present, inflammation was focal and lymphohistiocytic. In 1 case, findings were focal within the liver, requiring an image-guided biopsy. This patient underwent a simultaneous nontargeted liver biopsy that lacked histologic evidence of adenovirus. Among the pediatric patients, 63% (5/8) died secondary to organ failure, while there was 100% (4/4) mortality in the adult population.

Objectives To evaluate the significance of increasing depth of invasion (DOI) as the sole risk factor for recurrence in patients with low‐risk early‐stage oral cavity squamous cell carcinoma (OCSCC). Methods We retrospectively reviewed 560 patients with OCSCC treated at our institution between 2003 and 2013. Patients were included if they had low‐risk early‐stage OCSCC treated with surgical resection ± neck dissection and no adjuvant therapy. Low risk was defined as absence of positive or close margins, lymphovascular invasion, perineural invasion, and positive lymph nodes. Patients with tumor (T)3‐T4 disease were excluded. Pathology specimens were independently re‐reviewed by two board‐certified pathologists to confirm proper measurement of DOI. Kaplan‐Meier and Cox proportional hazards regression analyses were performed to identify factors predictive for recurrence as well as progression‐free survival (PFS) and overall survival (OS). Results A total of 126 patients with low‐risk early‐stage T1‐2N0 OCSCC were included. Median follow‐up time was 42.5 months and median DOI was 4 mm. There was no significant difference in incidence of local (P = 0.95), regional (P = 0.81), or distant recurrence (P = 0.96) among patients with DOI < 4 mm versus ≥4 mm. On multivariable analysis, DOI was significant for both PFS (P = 0.03) and OS (P = 0.002). Conclusion In this study, we show that in the absence of other high‐risk pathologic features, DOI ≥ 4 mm does not portend for increased incidence of local, regional, or distant relapse in patients treated with surgery alone; however, increasing DOI is a marker for worse PFS and OS in patients with low‐risk, early‐stage OCSCC. Level of Evidence 4 Laryngoscope, 129:2082–2086, 2019

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Pancreatic intraductal papillary mucinous neoplasms (IPMNs) are subclassified into gastric, intestinal, pancreatobiliary, and oncocytic subtypes based on histologic features. The WHO classification scheme suggests use of immunohistochemical stains to help subtype IPMNs with ambiguous histology. Seventy-two pancreatic IPMN resections between 2008 and 2014 were retrospectively evaluated. Immunohistochemistry for CDX2, MUC2, and MUC5AC was performed on cases where the histologic subtype could not be determined on routine hematoxylin and eosin (H&E) sections. There were 41 gastric (57%), 8 intestinal (11%), 4 pancreatobiliary (6%), and 1 oncocytic (1%) IPMNs. Eighteen (25%) IPMNs were either unclassifiable due ambiguous morphology or contained distinct epithelium from >1 subtype (i.e., "mixed"). Two IPMNs initially unclassifiable strictly by H&E morphology were definitively classified as intestinal after positive immunohistochemical staining with CDX2, MUC2, and MUC5AC. Immunohistochemistry for another 7 IPMNs unclassifiable by H&E did not indicate a clear subtype and often contained discordant results (e.g., discordant CDX2 and MUC2 staining). In our experience, a considerable number of IPMNs are either unclassifiable or contain epithelium from >1 subtype. Furthermore, among those IPMNs initially unclassifiable by H&E morphology, application of immunohistochemical stains to aid in subtyping allow for definite classification in only a small subset of cases. These data, when taken in context with the significant ranges in the reported prevalence of specific histologic subtypes, suggest that accurate IPMN subtyping is poorly reproducible in up to 25% of cases, and in these problematic cases, immunohistochemistry adds little value.

The second order measure entropy is preferable to that of the first order average pixel intensity as a measure of image texture to characterize ultrasound images of extremity lymphedema.

Intraosseous schwannomas are rare benign tumors that most often occur at the mandible or sacrum. We present an unusual case of a bilobed schwannoma of the distal humerus with both intraosseous and extraosseous components. The extraosseous component was non-enhancing on initial MRI and enhanced on a subsequent MRI obtained after biopsy. We hypothesize that this change was attributable to decreased intra-tumoral pressure secondary to biopsy-related disruption of the tumor capsule.