Ajit Paintal

Context.—: Pembrolizumab is used in patients with metastatic head and neck squamous cell carcinoma contingent upon the programmed death ligand-1 (PD-L1) combined positive score (CPS). Objective.—: To compare PD-L1 CPS scores derived from paired resected primary tumors (PTs) and lymph node metastases (LMs) in patients with p16+ oropharyngeal squamous cell carcinoma (OPSCC). Design.—: We identified 38 resected p16+ OPSCCs for which paired PTs and LMs were available. PD-L1 immunohistochemistry using the SP263 antibody clone was done on both the PT and the LM. CPS scoring was performed by 4 observers, and data were analyzed at the CPS cut points of greater than or equal to 1 and 20 in regard to interobserver and interspecimen agreement. Results.—: Overall agreement between consensus CPS scoring of PT and LM was seen in 76% of paired specimens (κ = 0.53). No specimen received a negative consensus score. Interobserver agreement for both PT and LM was fair to substantial (κ = 0.54 and 0.51, respectively) and was inferior to that seen in a prospective series of unselected head and neck squamous carcinoma cases evaluated at our institution (κ = 0.84). Conclusions.—: Given the high rates of interobserver and interspecimen variability, evaluation of additional material or by additional observers may be of value in performing CPS scoring in cases of p16+ OPSCC. This is particularly the case when a negative or low-positive result is being evaluated in a patient who is otherwise a good candidate for immunotherapy.

Genetic alterations involving NF2 occur at low frequencies in renal cell carcinoma across all of the major histologic subtypes and have been associated with adverse outcomes. To better characterize tumors harboring these alterations, we identified 14 cases with NF2 mutations that had been previously diagnosed as papillary renal cell carcinoma; renal cell carcinoma, unclassified; or translocation associated renal cell carcinoma. These tumors were characterized by a tubulopapillary architecture, sclerotic stroma, microscopic coagulative necrosis, and psammomatous calcifications. All the cases displayed eosinophilic cytology as well as a high nuclear grade (World Health Organization/International Society of Urological Pathology [WHO/ISUP] grade 3 to 4) in all but 1 case. A subset of cases shared features with the recently described biphasic hyalinizing psammomatous renal cell carcinoma. Next-generation sequencing demonstrated mutations involving NF2 gene in all cases. In 10 cases, this was paired with the loss of chromosome 22. Additional mutations involving PBRM1 were found in 5 cases that were associated with a more solid growth pattern. Eight patients presented with metastatic disease including all 5 with PBRM1 mutations. Despite the aggressive disease course seen in many of the patients in our series, 2 patients exhibited a dramatic response to immunotherapy. Our results support the existence of a distinct group of cases of renal cell carcinoma characterized by distinct although admittedly nonspecific morphology, an aggressive disease course, and NF2 mutations, often paired with the loss of chromosome 22.

To evaluate the performance characteristics of PD-L1 immunohistochemistry (IHC) combined positive scoring (CPS) in core biopsies and aspirate cell blocks from patients with head and neck squamous cell carcinoma (HNSqCCa). PD-L1 IHC using the SP263 antibody was performed on 20 paired cases which consisted of a small biopsy and an excisional specimen. The scores were compared at both the 1% and 20% cutpoints. Using the CPS result obtained from the resected specimen or excisional biopsy as the gold standard, PD-L1 IHC performed on the core biopsy or cell block identified 4 of 6 positive cases (66%) at the 20% cutpoint and 12 of 17 (70%) positive patients at the 1% cutpoint. False positive cases were uncommon at both cutpoints. CPS scoring should be used with caution in small biopsies from patients with HNSqCCa. A negative result should prompt consideration of an excisional biopsy and repeat testing.

Background: Given the lack of recent literature regarding the aspiration cytology of immunohistochemically confirmed malignant mesothelioma (MM), we were interested in reviewing the experience of our institution and establishing useful morphologic criteria.Methods: Seventeen aspiration and touch preparation specimens with a diagnosis of MM obtained between 2002‐2013 were reviewed along with 20 cases of adenocarcinoma and 16 cases of squamous cell carcinoma. The utility of a number of morphologic features was evaluated.Results: In most cases of MM, a consistent pattern emerged. Aspirates and touch preps were cellular with irregularly shaped 2 and 3 dimensional clusters. The individual cells were predominantly angulated and had dense cytoplasm with eccentric nuclei. In every case, a minority of tumor cells contained prominent microvacuoles. The chromatin pattern tended to be fine with small nucleoli. While most cases were cytologically monotonous, five cases displayed striking pleomorphism and three cases contained occasional large atypical cells. Two cases contained metachromatic background material. Features which were most useful in discriminating MM from adenocarcinoma were angulated cell shape(P = 0.0002), dense cytoplasm(P = 0.0001), and cytoplasmic microvacuoles(P = 0.0001). In our material, cases of squamous cell carcinoma were often difficult to distinguish from MM. Useful discriminatory features present in squamous cell carcinoma included ink dot nuclei(P = 0.0003), a “dirty” cystic, necrotic background (P = 0.0027) and tumor balls with peripheral spindling(P = 0.0041).Conclusion: Most cases of MM have a consistent appearance in core biopsy touch preps and FNAs. Distinguishing MM from adenocarcinoma and squamous cell carcinoma can be facilitated by evaluating a few key morphologic features. Diagn. Cytopathol. 2016;44:14–19.