Clinical implications of heterogeneity in PD-L1 immunohistochemical detection in hepatocellular carcinoma: the Blueprint-HCC study.

Programmed cell death ligand-1 immunohistochemical detection (PD-L1 IHC) is a putative predictor of response to PD-1/PD-L1-targeted checkpoint inhibitors. However, there is no gold standard assay in hepatocellular carcinoma (HCC). We evaluated 5 PD-L1 IHC assay platforms (E1LN3, 28-8, 22c3, SP263 and SP142) in 100 HCCs reporting PD-L1 expression in malignant (M) and tumour-infiltrating immune cells (TICs) and non-tumorous cirrhotic tissues (NTICs). We found substantial inter-assay heterogeneity in detecting PD-L1 expression in M (R2 = 0.080-0.921), TICs (Cohen's κ = 0.175-0.396) and NTICs (κ = 0.004-0.505). Such diversity may impact on the reliability and reproducibility of PD-L1 IHC assays as a predictor of response to immune checkpoint inhibitors.

Primary Malignant Melanoma of The Endocervix Uteri and Outpatient Hysteroscopy as a Diagnostic Tool: Case Report and Literature Overview.

Mucosal malignant melanoma has a low incidence and only 2% are diagnosed in the gynecological tract. Diagnosis of primary cervical malignant melanoma is often challenging. The clinical presentation mimics other malignant cervical tumors, usually with abnormal bleeding or discharge. Cervical screening tests, such as cytology, often fail to detect malignant melanomas because of the rarity of the disorder, and histological evaluation of lesions is of paramount importance. The treatment is often based on regimens used for cutaneous malignant melanoma. We present the first case in the literature of primary malignant melanoma of the endocervix diagnosed by outpatient hysteroscopy and we have performed a narrative review of the literature on PubMed, Scopus and Web of Science from 1980 to December 2023, identifying 137 cases. The most common initial symptom was vaginal bleeding in 82.8% of cases, and 84.8% of patients were menopausal at the time of diagnosis. The first diagnostic modality was biopsy in 67.7%; 90% of patients underwent surgery and 64.5% of the deaths occurred within the first 12 months after diagnosis. Primary malignant melanoma of the cervix is extremely rare and difficult to diagnose at an early stage which is due to the aggressiveness of the disease and the non-specificity of the symptoms. To improve survival, early diagnosis is essential and hysteroscopy could be a useful tool in achieving it. It is crucial to increase the attention of gynecologists on primary malignant melanoma of the cervix to also perform a diagnostic hysteroscopy in case of doubtful symptoms.

KRAS mutation testing on all non-malignant diagnosis of pancreatic endoscopic ultrasound-guided fine-needle aspiration biopsies improves diagnostic accuracy.

Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is the procedure of choice for the cytologic diagnosis of pancreatic masses. The specificity of EUS-FNA approaches 100%, but the sensitivity is still low, and the high rate of indeterminate (atypical and suspicious) and false-negative results needs improvement. KRAS gene is frequently mutated in pancreatic ductal adenocarcinoma (PDAC) (up to 90%), and mutation analysis of KRAS has been proposed as diagnostic biomarker of PDAC. In most laboratories, KRAS mutation testing is performed by Sanger sequencing or real time-quantitative polymerase chain reaction (RT-qPCR), but these methods may give false-negative results in routine samples, mainly due to low cellularity. In order to increase the sensitivity of EUS-FNA, we propose a sequential approach for detecting KRAS mutations using mutant enriched-PCR (ME-PCR, sensitivity up to 0.1%) in cytologically indeterminate and negative samples tested wild-type by RT-qPCR. EUS-FNA specimens from 107 patients with pancreatic masses (51 males, 56 females, mean age 67 years) were cytologically examined. According to the Papanicolaou Society of Cytopathology guidelines, 50 cases (47%) were classified malignant, 15 (14%) suspicious, 13 (12%) atypical and 10 (9%) negative for malignancy; 18 cases (17%) were non-diagnostic. The overall specificity and sensitivity of cytological examination were 100% and 61%, respectively, when only negative and positive cases were considered; when atypical and suspicious were added to positive cases, the sensitivity increased to 95.1% and the specificity decreased to 85.7%. In all the cases, DNA was extracted from the cell-block and KRAS mutations were investigated by RT-qPCR, followed by ME-PCR in non-amplifiable and negative cases. The overall sensitivity and specificity of KRAS mutation testing alone were 79.3% and 100%; when KRAS mutation testing was performed in indeterminate and negative cytology, the sensitivity increased to 90% with specificity to 100%. Our data indicate that conventional cytology from EUS-FNA samples is highly specific for the diagnosis of pancreatic cancer. Indeterminate and negative cases need to be screened for KRAS mutations; this two-step approach may greatly improve the diagnostic accuracy of this method.