Modern Cytopathology: An evolving field Troncone, Giancarlo; Roy‐Chowdhuri, Sinchita
Cytopathology (Oxford),
September 2021, 2021-09-00, 20210901, Volume:
32, Issue:
5
Journal Article
Peer reviewed
The modern‐day cytopathologist is equipped with an armamentarium of useful tools that have refined cytological diagnoses, provided predictive and prognostic information to guide patient care, and ...enabled more therapeutic options for patients. This Special Issue aims to highlight some of the aspects that are inherent to the role of Modern Cytopathology for diagnosis and therapeutic management of patients with cancer.
Background
NUT carcinoma (NC) is an aggressive neoplasm that often presents with alarge tumor burden and metastases; cytology is frequently one of the primary diagnostic modalities. Primary pulmonary ...NCs are very rare and cytology descriptions are limited. The current study was performed to analyze the cytomorphological features of primary pulmonary NCs in different cytology samples and preparations.
Methods
A total of 15 cytology specimens from 10 patients with primary pulmonary NCs diagnosed primarily on histology were retrieved and reviewed.
Results
Fifteen cytology samples, including aspirates from primary (5 samples) and metastatic (5 samples) sites, sputum (1 sample), and effusions (4 samples), that were prepared as direct smears, centrifuged smears, and cell blocks were reviewed. Aspirate smears from all cases were cellular and demonstrated fragments and cohesive clusters of primitive tumor cells with scant cytoplasm, ovoid nuclei with coarse granular chromatin, and consistently conspicuous single nucleoli in a frequently neutrophil‐rich necrotic background with dispersed bare tumor nuclei. In fluid cytology, tight, 3‐dimensional tumor clusters and singly lying tumor cells were observed. Squamous differentiation in the form of sheets and singly lying polygonal tumor cells with abundant dense cytoplasm was noted focally in rare cases. The diagnoses during original sign‐outs were poorly differentiated carcinoma, poorly differentiated squamous cell carcinoma, and malignant small round cell tumor. NUT‐1 (NUT family member 1 protein) immunocytochemistry performed on cell blocks demonstrated characteristic speckled nuclear staining in tumor cells.
Conclusions
Pulmonary NC presents as a poorly differentiated carcinoma with focal to absent squamous differentiation on cytology. Cellular fragments of primitive tumor cells with conspicuous nucleoli should raise suspicion of NUT carcinoma and prompt ancillary testing.
Pulmonary NUT carcinomas appear as fragments and cohesive clusters in aspiration specimens and as tight 3‐dimensional balls in fluid specimens. They are composed of primitive tumor cells with ovoid nuclei, coarse granular chromatin, consistently conspicuous single nucleoli, and scant cytoplasm in a frequently neutrophil‐rich inflammatory background with dispersed bare nuclei. A high index of suspicion with the judicious use of immunocytochemistry (p40, NUT) is necessary for an early and accurate diagnosis on cytology.
Intratumoral heterogeneity (ITH) is a fundamental property of cancer; however, the origins of ITH remain poorly understood. We performed single-cell transcriptome profiling of peritoneal ...carcinomatosis (PC) from 15 patients with gastric adenocarcinoma (GAC), constructed a map of 45,048 PC cells, profiled the transcriptome states of tumor cell populations, incisively explored ITH of malignant PC cells and identified significant correlates with patient survival. The links between tumor cell lineage/state compositions and ITH were illustrated at transcriptomic, genotypic, molecular and phenotypic levels. We uncovered the diversity in tumor cell lineage/state compositions in PC specimens and defined it as a key contributor to ITH. Single-cell analysis of ITH classified PC specimens into two subtypes that were prognostically independent of clinical variables, and a 12-gene prognostic signature was derived and validated in multiple large-scale GAC cohorts. The prognostic signature appears fundamental to GAC carcinogenesis and progression and could be practical for patient stratification.
Background
Current national guidelines do not include hyperthermic intraperitoneal chemoperfusion (HIPEC) as treatment for gastric cancer, and there are no completed clinical trials of cytoreduction, ...gastrectomy, and HIPEC from the US.
Methods
Patients with gastric adenocarcinoma and positive peritoneal cytology or carcinomatosis who had completed systemic chemotherapy and laparoscopic HIPEC underwent cytoreduction, gastrectomy, and HIPEC with 30 mg mitomycin C and 200 mg cisplatin. The primary endpoint was overall survival (OS), with a secondary endpoint of postoperative complications (NCT02891447).
Results
We enrolled 20 patients from September 2016 to March 2019. Six patients had positive cytology only and 14 had carcinomatosis. All patients were treated with systemic chemotherapy with a median of eight cycles (range 5–11 cycles) and at least one laparoscopic HIPEC. The median peritoneal carcinomatosis index at cytoreduction/gastrectomy/HIPEC was 2 (range 0–13). After surgery, the 90-day morbidity and mortality rates were 70% and 0%, respectively. Median length of hospital stay was 13 days (range 7–23 days); median follow-up was 33.5 months; median OS from the date of diagnosis of metastatic disease was 24.2 months; and median OS from the date of cytoreduction, gastrectomy, and HIPEC was 16.1 months. 1-, 2-, and 3-year OS rates from the diagnosis of metastatic disease were 90%, 50%, and 28%, respectively.
Conclusions
Survival rates for patients with gastric adenocarcinoma and peritoneal disease treated with cytoreduction, gastrectomy, and HIPEC are encouraging; our early results are similar to those of recent prospective registry studies. Multi-institutional and cooperative group trials should be supported to confirm survival and safety outcomes.
Background
Immune checkpoint inhibitors targeting the programmed cell death protein 1 (PD‐1)/programmed cell death ligand 1 (PD‐L1) pathway have recently emerged as a frontline treatment for head and ...neck squamous cell carcinoma (HNSCC). The evaluation of PD‐L1 expression by immunohistochemistry in histologic samples is used to determine the eligibility of patients with HNSCC for immunotherapy. Patients with newly diagnosed HNSCC are frequently diagnosed by fine‐needle aspiration (FNA) of lymph nodes with metastatic disease. However, the evaluation of PD‐L1 expression with the proposed combined positive score (CPS) has not been well established in cytology specimens.
Methods
This study retrospectively identified 21 HNSCC patients with a known PD‐L1 status from histologic specimens and matched FNA specimens with tumor cells on cell blocks (CBs). The CB sections were stained with a PD‐L1 antibody (22C3 clone). All cases were scored with CPS and the tumor proportion score (TPS).
Results
The data showed substantial concordance between cytologic and histologic specimens for CPS (agreement, 76.2%; κ = 0.607) and TPS (agreement, 76.2%; κ = 0.607). With histology used as a reference standard, the positive predictive value was 100% for both CPS and TPS, whereas the negative predictive value was 57.1% for CPS assessments and 50% for TPS assessments.
Conclusions
PD‐L1 expression in HNSCC cytology samples has high concordance with paired histologic samples. PD‐L1 CPS evaluation is feasible in HNSCC cytology CBs and can act as a surrogate for determining eligibility for immunotherapy in cases in which a histologic specimen is not readily available.
Programmed cell death ligand 1 (PD‐L1) expression in head and neck squamous cell carcinoma (HNSCC) cytology samples has substantial concordance with paired histologic samples. PD‐L1 evaluation using the combined positive score is feasible in HNSCC cytology cell blocks and can act as a surrogate for determining eligibility for immunotherapy in cases in which a histologic specimen is not readily available.
Many patients with non‐small cell lung cancer do not receive guideline‐recommended, biomarker‐directed therapy, despite the potential for improved clinical outcomes. Access to timely, accurate, and ...comprehensive molecular profiling, including targetable protein overexpression, is essential to allow fully informed treatment decisions to be taken. In turn, this requires optimal tissue management to protect and maximize the use of this precious finite resource. Here, a group of leading thoracic pathologists recommend factors to consider for optimal tissue management. Starting from when lung cancer is first suspected, keeping predictive biomarker testing in the front of the mind should drive the development of practices and procedures that conserve tissue appropriately to support molecular characterization and treatment selection.
When lung cancer is first suspected, all stakeholders must consider that predictive biomarker testing will likely be required, which, in turn, should drive practices to conserve tissue appropriately. Optimal tissue management allows complete biomarker testing and fully informed treatment decisions to be made for the ultimate benefit of the patient.
Peritoneal carcinomatosis (PC; malignant ascites or implants) occurs in approximately 45% of advanced gastric adenocarcinoma (GAC) patients and associated with a poor survival. The molecular events ...leading to PC are unknown. The yes-associated protein 1 (
) oncogene has emerged in many tumour types, but its clinical significance in PC is unclear. Here, we investigated the role of YAP1 in PC and its potential as a therapeutic target.
Patient-derived PC cells, patient-derived xenograft (PDX) and patient-derived orthotopic (PDO) models were used to study the function of YAP1 in vitro and in vivo. Immunofluorescence and immunohistochemical staining, RNA sequencing (RNA-Seq) and single-cell RNA-Seq (sc-RNA-Seq) were used to elucidate the expression of YAP1 and PC cell heterogeneity. LentiCRISPR/Cas9 knockout of YAP1 and a YAP1 inhibitor were used to dissect its role in PC metastases.
YAP1 was highly upregulated in PC tumour cells, conferred cancer stem cell (CSC) properties and appeared to be a metastatic driver. Dual staining of YAP1/EpCAM and sc-RNA-Seq revealed that PC tumour cells were highly heterogeneous, YAP1
PC cells had CSC-like properties and easily formed PDX/PDO tumours but also formed PC in mice, while genetic knockout YAP1 significantly slowed tumour growth and eliminated PC in PDO model. Additionally, pharmacologic inhibition of YAP1 specifically reduced CSC-like properties and suppressed tumour growth in YAP1
PC cells especially in combination with cytotoxics in vivo PDX model.
YAP1 is essential for PC that is attenuated by YAP1 inhibition. Our data provide a strong rationale to target YAP1 in clinic for GAC patients with PC.
Introduction
The diagnosis of solid pseudopapillary neoplasm (SPN) on fine needle aspiration specimens can be challenging because of morphological overlap with other pancreatic neoplasms, including ...pancreatic neuroendocrine tumour (PanNET). SRY‐related high‐mobility group box 11 (SOX11) is a recently described sensitive and specific marker for SPN diagnosis. However, SOX11 immunocytochemistry on cytological smears has not been reported. We evaluated the utility of SOX11 for diagnosis of SPN on cytological preparations.
Methods
SOX11 immunocytochemistry was performed on Papanicolaou‐stained smears and/or corresponding cell blocks from aspirates of 7 SPN and 10 PanNET cases identified between 2005 and 2020. Findings were compared with those for beta‐catenin, a frequently used diagnostic marker for SPN.
Results
Six smears and 6 cell blocks from SPN cases and 8 smears and 10 cell blocks from PanNET cases were available for immunostaining. For SPN, nuclear staining for SOX11 was seen in 6 of 6 (100%) smears and 5 of 6 (83%) cell blocks, with equivocal staining in 1 cell block. In contrast, 7 of 8 (88%) smears and 9 of 10 (90%) cell blocks were negative for SOX11 for PanNet, with equivocal staining seen in 1 case. Beta‐catenin immunocytochemistry showed nuclear staining in 6 of 7 (86%) SPN cases and no staining in all 10 (100%) PanNET cases.
Conclusions
SOX11 detected by immunocytochemistry can serve as a useful diagnostic marker for SPN, in addition to beta catenin, and can be performed on cytological smears in cases without a cell block preparation.
SOX11 is a sensitive and specific marker for the diagnosis of solid pseudopapillary neoplasm on cytological fine needle aspiration samples and can be assayed on both direct smears and cell block preparations. This is especially useful in specimens with limited amounts of tissue, in which the morphology is not definitive, and the cell block is inadequate for an extensive immunohistochemical work‐up.
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