Metastatic spread to the salivary glands is rare, occurring primarily from head and neck tumors to the parotid gland. So far, only one sublingual gland metastasis has been reported in the literature. We herein report the second case of metastasis to this gland occurring in a woman in her 50s, previously diagnosed with HER2-positive metaplastic breast carcinoma (MpBC) with chondroid differentiation, with lymph node and diffuse organ metastases. The sublingual lesion presented as a tumefaction on the floor of the mouth, causing masticatory discomfort. Histologically it was formed by epithelial cells with high-grade cytomorphological features with a large central area of chondroid differentiation. The case was clinically and pathologically challenging, given the rarity of the primary MpBC and the improbable secondary location. Alternative primary salivary gland tumors with chondroid differentiation were considered, but ultimately the clinical integration was crucial in establishing the diagnosis of MpBC metastasis to the sublingual gland.

The One Step Nucleic Acid Amplification (OSNA) is being adopted worldwide for sentinel lymph nodes (SLNs) staging in breast cancer (BC). As major disadvantage, OSNA precludes prognostic information based on structural evaluation of SLNs. Our aim is to identify biomarkers related to tumor-microenvironment interplay exploring gene expression data from the OSNA remaining lysate. This study included 32 patients with early stage hormone receptors-positive BC. Remaining OSNA lysates were prepared for targeted RNA-sequencing analysis. Identification of differentially expressed genes (DEGs) was performed by DESeq2 in R and data analysis in STATA. The results show that, in metastatic SLNs, several genes were upregulated: KRT7, VTCN1, CD44, GATA3, ALOX15B, RORC, NECTIN2, LRG1, CD276, FOXM1 and IGF1R. Hierarchical clustering analysis revealed three different clusters. The identified DEGs codify proteins mainly involved in cancer aggressiveness and with impact in immune response. The overexpression of the immune suppressive genes VTCN1 and CD276 may explain that no direct evidence of activation of immune response in metastatic SLNs was found. We show that OSNA results may be improved incorporating microenvironment-related biomarkers that may be useful in the future for prognosis stratification and immunotherapy selection. As OSNA assay is being implemented for SLNs staging in other cancers, this approach could also have a wider utility.

Lynch syndrome (LS) is a prevalent genetic condition associated with colorectal cancer (CRC). Accurate identification of LS patients is challenging, and a universal tumor screening approach has been recommended. We present the methodology and results of universal LS screening in our hospital’s Pathology Department. This retrospective study analyzed CRC tumors from a 5-year period (2017-2021). Immunohistochemistry was used to assess MMR protein expression, followed by BRAF V600E analysis and MLH1 promoter methylation. Statistical analysis examined associations between clinicopathologic variables MMR status and LS-suspected tumors. The study analyzed 939 colorectal carcinomas, with 8.7% exhibiting mismatch repair (MMR) deficiency, significantly lower than previous research. After applying the algorithm, 24 LS-suspected cases were identified, accounting for 2.6% of tested patients and 29.3% of MMR-deficient tumors. Our study establishes the feasibility of universal testing for all new cases of CRC in detecting individuals at risk for LS, even in the absence of clinical information. To gain a comprehensive understanding of the MMR status in our population, further investigations are warranted.

In the management of early-stage breast cancer (BC), lymph nodes (LNs) are typically characterised using the One-Step Nucleic Acid Amplification (OSNA) assay, a standard procedure for assessing subclinical metastasis in sentinel LNs (SLNs). The pivotal role of LNs in coordinating the immune response against BC is often overlooked. Our aim was to improve prognostic information provided by the OSNA assay and explore immune-related gene signatures in SLNs. The expression of an immune gene panel was analysed in SLNs from 32 patients with Luminal A early-stage BC (cT1-T2 N0). Using an unsupervised approach based on these expression values, this study identified two clusters, regardless of the SLN invasion: one evidencing an adaptive anti-tumoral immune response, characterised by an increase in naive B cells, follicular T helper cells, and activated NK cells; and another with a more undifferentiated response, with an increase in the activated-to-resting dendritic cells (DCs) ratio. Through a protein—protein interaction (PPI) network, we identified seven immunoregulatory hub genes: CD80, CD40, TNF, FCGR3A, CD163, FCGR3B, and CCR2. This study shows that, in Luminal A early-stage BC, SLNs gene expression studies enable the identification of distinct immune profiles that may influence prognosis stratification and highlight key genes that could serve as potential targets for immunotherapy.

Hepatoid adenocarcinoma of the lung (HAL) is a rare pulmonary malignancy that resembles hepatocellular carcinoma morphologically and poses diagnostic challenges, particularly when alpha‐fetoprotein (AFP) is absent. We report a man in his 50s with chronic obstructive pulmonary disease and a solitary 1.9‐cm right upper lobe nodule. Percutaneous biopsy identified non‐small cell carcinoma without establishing the subtype. Video‐assisted thoracoscopic right upper lobectomy with mediastinal lymphadenectomy revealed a hepatoid tumour expressing HepPar‐1 and CK7 but not AFP, arginase‐1 or glypican‐3. The absence of a hepatic lesion on staging imaging supported a pulmonary primary. The tumour was pT1bN0 with no clinically detected metastases. At 6 months after resection, there was no evidence of recurrence. This case illustrates the limitations of small biopsies and isolated immunohistochemical markers in diagnosing an AFP‐negative pulmonary hepatoid tumour.

Recent studies suggest that ultrasound-guided fine-needle aspiration biopsy (iFNAb) enhances diagnostic accuracy for palpable lesions. This study evaluates the efficacy of palpation-guided FNAb (pFNAb) performed at Unidade Local de Saúde de Coimbra, Portugal, compares findings to existing literature, and identifies lesions that could benefit from ultrasound guidance. A retrospective review of 278 pFNAb cases from 2021 to 2023 was conducted, collecting data on lesion characteristics, procedural details, and operator expertise. Diagnostic accuracy was determined through concordance with histopathology, flow cytometry, or clinical follow-up. Statistical analyses included Fisher's exact test, chi-square tests, and logistic regression. A Preferred Reporting Items for Systematic reviews and Meta-Analyses-guided literature review was also performed to contextualize findings. Diagnostic accuracy was achieved in 84% of pFNAb cases. Lesions less than 1 cm exhibited significantly lower diagnostic rates compared to larger lesions. Diagnostic accuracy improved with additional needle passes, reaching 87% with 3 attempts. Anatomical location significantly influenced outcomes, with scalp lesions having the lowest diagnostic rate (33%) compared to skin and soft tissue lesions (85.7%). Literature review findings corroborated the data, emphasizing the superior accuracy of iFNAb for smaller or anatomically challenging lesions. pFNAb is effective for diagnosing most palpable lesions and provides a standard of care in settings without imaging resources. However, iFNAb is recommended for specific cases, such as small or scalp lesions, to enhance diagnostic accuracy. Tailoring biopsy approaches based on lesion characteristics can improve outcomes, reduce repeat procedures, and enhance patient care.