The value of oestrogen receptor, progesterone receptor and keratins 5 and 14 immunohistochemistry in the evaluation of epithelial proliferations at cauterised margins in breast-conserving surgery specimens.

In breast conservative surgery, it is sometimes difficult to decide whether the cauterised tissue at the inked margin represents normal / hyperplastic or neoplastic tissue. We retrospectively assessed the value of ER, PR, CK5 and CK14 IHC in clarifying the nature of cauterised tissues at the margins concerning 34 lesions of 23 patients. 27 cases belonged to lesions that could not be adequately classified on the basis of the HE stains. Two thirds of them could be classified as non-neoplastic or neoplastic and two thirds of the remaining could be favourised as neoplastic or non-neoplastic, with 3/27 cases remaining uncertain. All 4 IHC reactions were helpful in classifying the lesions in almost half of the cases. However, 3 or 4 immunostains were supportive of the classification in 19/27. The most useful stains were the keratins, generally demonstrating a matching pattern of cell labelling with CK5 and CK14. ER and PR were somewhat less useful in classifying uncertain lesions. Considering all the 27 questionable lesions, IHC with ER, PR, CK5 and CK14 clarified the lesions at the cauterised margins in 23 cases. Taken all these considerations into account, CK5, CK14, PR and ER IHC may help in distinguishing between cautery damaged neoplastic and non-neoplastic tissues. All four IHC may yield the best support for decision making, but CK5 and/or CK14 may be sufficient in their own. The essential approach is that the results must be interpreted with caution, in the context of the given patient's disease, to avoid misinterpretations.

Cerebral manifestation and diagnostic dilemma of Rosai-Dorfman disease.

Rosai-Dorfman disease (RDD) is a rare, S100-positive histiocytic proliferation, that can cause both nodal and extranodal illness. We present a case of a 53-year-old male patient. Magnetic resonance imaging described a plaque-like meningeal lesion, and the preoperative diagnosis was meningioma. Histologically, dense infiltration of lymphocytes, plasma cells, and histiocytes was seen, furthermore, the presence of emperipolesis in the sample was pronounced. In the histiocytes nuclear and cytoplasmic positivity with S100 protein, and nuclear positivity with Cyclin D1 was observed. The case was concluded as RDD. Morphological appearance of intracranial RDD with imaging procedures can present a differential diagnostic challenge. The correct diagnosis is based on the presence of histiocytes with emperipolesis, and properly defined immunohistochemical characteristics.

Proposal of a grading system for squamous cell carcinoma of the lung - the prognostic importance of tumour budding, single cell invasion, and nuclear diameter.

The prognostic markers of lung squamous cell carcinoma (LSCC) are less investigated. The aim of our study was to evaluate tumour budding (TB), minimal cell nest size, nuclear diameter (ND), and spread through air spaces (STAS) among patients with resected LSCC, semi-quantitatively. Furthermore, we aimed to identify a grading system for the best prognostic stratification of LSCC. Patients who underwent surgical resection at the Department of Surgery, University of Szeged between 2010 and 2016 were included. Follow-up data were collected from medical charts. Morphological characteristics were recorded from histologic revision of slides. Kaplan-Meier analysis, log rank test and Cox proportional-hazards model, ROC curve analysis, and intraclass correlation were utilised. Altogether 220 patients were included. In univariate analysis, higher degree of TB, infiltrative tumour border, larger ND, the presence of single cell invasion (SCI) and STAS were associated with adverse prognosis. Based on our results, we proposed an easily applicable grading scheme focusing on TB, ND, and SCI. In multivariate analysis, the proposed grading system (pOS < 0.001, pRFS < 0.001) and STAS (pOS = 0.008, pRFS < 0.001) were independent prognosticators. Compared to the previously introduced grading systems, ROC curve analysis revealed that the proposed grade had the highest AUC values (AUCOS: 0.83, AUCRFS: 0.78). Each category of the proposed grading system has good (ICC: 0.79-0.88) reproducibility. We validated the prognostic impact of TB, SCI, ND, and STAS in LSCC. We recommend a reproducible grading system combining TB, SCI, and ND for proper prognostic stratification of LSCC patients. Further research is required for validation of this grading scheme.

TRPS1 expression in cytokeratin 5 expressing triple negative breast cancers, its value as a marker of breast origin.

The lack of oestrogen receptor, progesterone receptor and human epidermal growth factor receptor-2 expression in breast cancer (BC) is the basis for the categorization of the tumour as triple negative breast carcinoma (TNBC). The majority of TNBCs are aggressive tumours with common metastases and decreased expression of markers that could help in identifying the metastatic lesion as of mammary origin. Breast markers, such as gross cystic disease fluid protein-15 (GCDPF-15), GATA binding protein 3 (GATA3), mammaglobin (MGB) and SOX10, are not uniquely specific to BC. Our aim was to evaluate trichorhinophalangeal syndrome type 1 (TRPS1) protein as a breast marker in a series of cytokeratin-5-expressing TNBC, mostly corresponding to basal-like TNBCs, previously characterized for the expression of other breast markers. One hundred seventeen TNBCs in tissue microarrays were immunostained for TRPS1. The cut-off for positivity was ≥ 10%. The reproducibility of this classification was also assessed. TRPS1 positivity was detected in 92/117 (79%) cases, and this exceeded the expression of previously tested markers like SOX10 82 (70%), GATA3 11 (9%), MGB 10 (9%) and GCDFP-15 7 (6%). Of the 25 TRPS1-negative cases, 11 were positive with SOX10, whereas 5 to 6 dual negatives displayed positivity for the other makers. The evaluation showed substantial agreement. Of the five markers compared, TRPS1 seems the most sensitive marker for the mammary origin of CK5-expressing TNBCs. Cases that are negative are most often labelled with SOX10, and the remainder may still demonstrate positivity for any of the 3 other markers. TRPS1 has a place in breast marker panels.

Good practice: The experiences with the utilization of residual cancer burden-A single institution study.

INTRODUCTION: The use of neoadjuvant therapy (NAT) has been showing an incraesing tendency in the treatment of locally advanced breast cancer. The evaluation of residual cancer could be performed by Residual Cancer Burden (RCB) calculator. The prognostic system takes the two largest diameters of the tumor, the cellularity, the amount of in situ carcinoma, the number of metastatic lymph nodes, and the size of the largest metastatic deposit into account. The aim of our study was to examine the reproducibility of RCB in NAT treated patients. METHODS: Patients who were treated with NAT and had resection specimens between 2018 and 2021 were selected. Histological examination was performed by five pathologists. After assessment of the examined variables, RCB points and RCB classes were defined. For statistical analysis, interclass correlation was used (SPSS Statistics V.22.0 software). RESULTS: Altogether 100 patients were included in our retrospective, cohort study (average age: 57 years). In two-thirds of the cases, third generation chemotherapy was used, and mastectomy was performed. Significant concordance was found in the two largest diameters of the tumor (coefficients, 0.984 and 0.973), the cellularity (coefficient, 0.970), and the largest metastatic deposit (coefficient, 0.998). Although the amount of in situ carcinoma proved to be the least reproducible factor, it resulted in almost 90% of agreement (coefficient, 0.873). Regarding RCB points and classes, similar results were observed (coefficients, 0.989 and 0.960). CONCLUSIONS: Significant agreement was observed between examiners based on almost all RCB parameters, points, and classes, reflecting the optimal reproducibility of RCB. Therefore, we recommend the use of the calculator in routine histopathological reports in NAT cases.

The More Extensive the Spread through Air Spaces, the Worse the Prognosis Is: Semi-Quantitative Evaluation of Spread through Air Spaces in Pulmonary Adenocarcinomas.

INTRODUCTION: The extent of spread through air spaces (STAS) is less investigated among patients with lung adenocarcinoma who underwent sublobar resection. Therefore, we aimed to evaluate the extent of STAS semi-quantitatively, to assess its prognostic impact on overall survival (OS) and recurrence-free survival (RFS), and to investigate the reproducibility of this assessment. METHODS: The number of tumour cell clusters and single tumour cells within air spaces was recorded in three different most prominent areas (200x field of view). The extent of STAS was categorized into three groups, and the presence of free tumour cluster (FTC) was recorded. RESULTS: Sixty-one patients were included. Recurrence was more frequent with higher grade (p = 0.003), presence of lymphovascular invasion (p = 0.027), and presence of STAS of any extent (p = 0.007). In multivariate analysis, presence of FTC (HR: 5.89; 95% CI: 1.63-21.26; p = 0.005) and more pronounced STAS (HR: 7.46; 95% CI: 1.60-34.6; p = 0.01) had adverse impact on OS and RFS, respectively. Concerning reproducibility, excellent agreement was found among STAS parameters (ICC range: 0.92-0.94). DISCUSSION: More extensive STAS is an unfavourable prognostic factor in adenocarcinomas treated with sublobar resection. As the evaluation of extent of STAS is reproducible, further investigation is required to gather more evidence.

The prognostic value of stem cell markers in triple-negative breast cancer.

Among the many consecutive theories of cancer, the stem cell theory is currently the most accepted one. Cancer stem cells are located in small niches with specific environment, renew themselves and are believed to be responsible for many recurrences. They can be highlighted with stem cell markers, but often these markers also label tumor cells, and this may represent a phenotypical change associated with prognosis. In this study, we attempted to match tumor outcomes with the expression of the following stem cell markers: ALDH1, AnnexinA1, CD44, CD117, CD166, Nanog and oct-4. Tissue microarray blocks from triple-negative breast cancers were immunostained for the listed markers, and their expression by the majority of tumor cells (diffuse positivity) was correlated with prognosis. Of the 106 tumors investigated, diffuse positivity was seen in 7 (ALDH1), 33 (AnnexinA1), 53 (CD44), 44 (CD117 membranous only), 49 (CD117), 72 (CD166), 19 (Nanog), and 11 (oct-4) cases. With a median follow-up of 83 months, ALDH1 and CD117 expression was associated with DFS, whereas CD44, CD117 and CD166 were associated with OS estimates, based on Kaplan-Meier analyses. In the multivariate Cox proportional hazard models (including the examined markers and clinicopathological data which had a statistical impact in the univariate analysis), the pN category and the lack of ALDH1 expression were independent prognosticators for DFS, and the pN category and diffuse CD44 staining were independent prognosticators for OS. In the multivariate analysis including all of the examined clinicopathological data and markers, only CD117 showed a statistical impact on OS. We failed to demonstrate a prognostic impact for most stem cell markers tested in triple-negative breast cancer, but lack of ALDH1 staining and CD44 expression appears as of prognostic value, requiring further examination in independent studies.