Intratumoral, rather than stromal, CD8+ T cells could be a potential negative prognostic marker in invasive breast cancer patients

BACKGROUND: Tumor infiltrating lymphocytes (TILs) are widely considered a key sign of the immune interaction between host and tumor, and potentially prognostic biomarkers of good or bad outcome in many cancers, included invasive breast cancer (BC). However, results about the association between TIL typology, location and BC prognosis, are controversial. The aim of the study was to evaluated the prognostic significance of TIL subtypes (CD4+, CD8+, FOXP3+ T cells) and their location (stromal “s” and intratumoral “i” CD4+ and CD8+) in BC patients, focusing on the association between these markers and immunocheckpoint molecules such as cytotoxic T lymphocyte antigen 4 (CTLA-4), programmed cell death ligand 1 (PD-L1) and its receptor (PD-1). METHODS: CD4+, CD8+, FOXP3+, CTLA4+, PD-L1+ and PD-1+ expression was examined by immunohistochemistry on tissue microarrays (TMAs) from 180 BC patients. Univariate and Kaplan–Meier analyses of disease free survival (DFS) were performed to evaluate the prognostic significance of marker expression. RESULTS: Total CD8+ T cells were not significantly associated with DFS. Differently, patients with iCD8+ and sCD8+ overexpression showed a trend toward respectively a worse (P = .050) and a better 5-years DFS (P = .064). Interestingly, TIL expression of both PD-1+ and PD-L1+, was significantly associated with iCD8+ (P = .0004; P < .0001 respectively), while only TIL expression of PD-1 was associated with sCD8+ (P = .001). CONCLUSION: Our data show that iCD8+ T cells, but no sCD8+ T cells identify a subgroup of patients with poor DFS and this could be due to the overexpression of PD-L1/PD-1 pathway

Rapidly-growing hemangioma of the testicle clinically simulating an aggressive neoplasm. A case report

We present a case of intraparenchymatous capillary-type hemangioma of the testicle in an adult. The patient was a 37-year-old man who showed a rapidly enlarging and palpable mass in left testicle. Radical orchiectomy was performed, and histological examination revealed an unencapsulated lobulated tumour with wide hemorrhagic portions. To our knowledge, the occurrence of rapid enlargement in a testicular hemangioma has not been previously reported, which might be explained by the development of intra-tumoural haemorrhage

EGFR polysomy in squamous cell carcinoma of the thyroid. Report of two cases and review of the literature

AIMS AND BACKGROUND:Primary squamous cell carcinoma of the thyroid gland (PSCCT) is an uncommon malignancy characterized by a poor prognosis. A radical surgical approach combined with radiotherapy or chemotherapy is the generally accepted treatment for this tumor. The epidermal growth factor receptor (EGFR) is a transmembrane tyrosine kinase receptor modulating the cell proliferation and biological progression of many human epithelial tumors. The EGFR overexpression in PSCCT suggests an additional therapeutic option for the treatment of this tumor.METHODS AND STUDY DESIGN:The clinicopathological features and immunohistochemical profiles of two cases of primary squamous cell carcinoma of the thyroid in a 66-year-old and an 83-year-old woman are presented. EGFR status was valued in both cases.RESULTS:Overexpression of EGFR protein was detected in 50% and 75% of the tumor cell membranes. EGRF gene polysomy was detected in both tumors.CONCLUSIONS:Pharmaceuticals targeting EGFR may help to provide the rationale for an additional, novel therapeutic option for this rare tumor, especially when other therapeutic options have been exhausted

Downstream Signaling of Inflammasome Pathway Affects Patients&rsquo; Outcome in the Context of Distinct Molecular Breast Cancer Subtypes

Inflammasomes are protein complexes involved in the regulation of different biological conditions. Over the past few years, the role of NLRP3 in different tumor types has gained interest. In breast cancer (BC), NLRP3 has been associated with multiple processes including epithelia mesenchymal transition, invasion and metastization. Little is known about molecular modifications of NLRP3 up-regulation. In this study, in a cohort of BCs, the expression levels of NLRP3 and PYCARD were analyzed in combination with CyclinD1 and MYC ones and their gene alterations. We described a correlation between the NLRP3/PYCARD axis and CyclinD1 (p &lt; 0.0001). NLRP3, PYCARD and CyclinD1&rsquo;s positive expression was observed in estrogen receptor (ER) and progesterone receptor (PgR) positive cases (p &lt; 0.0001). Furthermore, a reduction of NLRP3 and PYCARD expression has been observed in triple negative breast cancers (TNBCs) with respect to the Luminal phenotypes (p = 0.017 and p = 0.0015, respectively). The association NLRP3+/CCND1+ or PYCARD+/CCND1+ was related to more aggressive clinicopathological characteristics and a worse clinical outcome, both for progression free survival (PFS) and overall survival (OS) with respect to NLRP3+/CCND1&minus; or PYCARD+/CCND1&minus; patients, both in the whole cohort and also in the subset of Luminal tumors. In conclusion, our study shows that the NLRP3 inflammasome complex is down-regulated in TNBC compared to the Luminal subgroup. Moreover, the expression levels of NLRP3 and PYCARD together with the alterations of CCND1 results in Luminal subtype BC&rsquo;ss poor prognosis

Discordance between FISH, IHC, and NGS Analysis of ALK Status in Advanced Non–Small Cell Lung Cancer (NSCLC): a Brief Report of 7 Cases

BACKGROUND: Anaplastic lymphoma kinase (ALK) rearrangement represents a landmark in the targeted therapy of non–small cell lung cancer (NSCLC). Immunohistochemistry (IHC) is a sensitive and specific method to detect ALK protein expression, possibly an alternative to fluorescence in situ hybridization (FISH). In this study, the concordance of FISH and IHC to determine ALK status was evaluated, particularly focusing on discordant cases. MATERIALS AND METHODS: ALK status was tested by FISH and the IHC validated method (Ventana ALK (D5F3) CDx Assay) in 95 NSCLCs. Discordant cases were analyzed also by next-generation sequencing (NGS). The response to crizotinib of treated patients was recorded. RESULTS: Seven (7.3%) discordant cases were ALK FISH positive and IHC negative. They showed coexistent split signals pattern, with mean percentage of 15.4%, and 5′ deletions pattern, with mean percentage 31.7%. Two cases had also gene amplification pattern. In three cases (42.8 %), the polysomy was observed. The NGS assay confirmed IHC results. In these patients, the treatment with crizotinib was ineffective. CONCLUSIONS: In our discordant cases, a coexistent complex pattern (deleted, split, and amplified/polysomic) of ALK gene was observed by FISH analysis. These complex rearranged cases were not detectable by IHC, and it could be speculated that more complex biological mechanisms could modulate protein expression. These data highlight the role of IHC and underscore the complexity of the genetic pattern of ALK. It could be crucial to consider these findings in order to best select patients for anti-ALK treatment in daily clinical practice

Thyroglobulin determination in fine needle aspiration biopsy washout of suspicious lymph nodes in thyroid carcinoma follow up

Background: Differentiated thyroid carcinomas (DTCs) account for about 1% of all human malignancies. Cervical lymph nodes metastases and recurrences in the thyroid bed frequently occur. Furthermore, about 10-15% of patients develop distant metastases. Therefore, patients must undergo life-long follow-up. Objective: The aim of this study was to evaluate the usefulness of Thyroglobulin measurement in FNAB washout (FNAB-Tg) in the detection of local metastasis in patients affected by or evaluated for thyroid cancer. Materials and Methods: In a 3-year period, a total of 83 consecutive patients coming to our attention at the Ear-Nose-Throat (ENT) Outpatients Service of the National Cancer Research Center "Istituto Tumori Giovanni Paolo II" of Bari, Italy, because of the finding of one or more cervical lymph node(s), were enrolled in the study. After collection of the cytological specimen, the needle used for performing FNAB was then washed in 1 ml of normal saline. 89 FNAB washouts were collected from the same number of lymph nodes and subsequently investigated for Thyroglobulin levels using a sequential chemiluminescent-immunometric assay. Results: Comparing the cytological or, when performed, histological diagnoses with the results of FNAB-Tg, we found that in 24 cases of lymph node metastases from PTC (19 lymph nodes from patients at the first diagnoses and 5 lymph nodes from PTC patients in follow up) the mean level of Thyroglobulin was 1840.11 ng/ml; range: &lt;0,2 to 11440 ng/ml. In the group of PTC patients (27 lymph nodes) with lymph nodes negative for metastatic involvement at cytology (i.e. no lymph node recurrence at follow-up), as well as in the cases of subjects without PTC and submitted to FNAB because of the appearance of lymph node(s) classified as reactive at cytology (37 lymph nodes), FNAB-Tg was lower than or equal to 0.2 ng/ml. As expected, the Thyroglobulin level was not detectable (&lt; 0.2 ng/ml) also in a lymph node FNAB from a case of anaplastic thyroid carcinoma. Conclusion: In our study, FNAB-Tg was not detectable in all node negative patients showing, when considering together all the lymph node metastases, a 96% sensitivity and 100% specificity

ARGO, Automatic Record Generator for Oncology: a natural language process-based tool to capture pathology features from onco-hematological reports (Preprint)

Background: The unstructured nature of medical data from Real-World (RW) patients and the scarce accessibility for researchers to integrated systems restrain the use of RW information for clinical and translational research purposes. Natural Language Processing (NLP) might help in transposing unstructured reports in electronic health records (EHR), thus prompting their standardization and sharing. Objective: We aimed at designing a tool to capture pathological features directly from hemo-lymphopathology reports and automatically record them into electronic case report forms (eCRFs). Methods: We exploited Optical Character Recognition and NLP techniques to develop a web application, named ARGO (Automatic Record Generator for Oncology), that recognizes unstructured information from diagnostic paper-based reports of diffuse large B-cell lymphomas (DLBCL), follicular lymphomas (FL), and mantle cell lymphomas (MCL). ARGO was programmed to match data with standard diagnostic criteria of the National Institute of Health, automatically assign diagnosis and, via Application Programming Interface, populate specific eCRFs on the REDCap platform, according to the College of American Pathologists templates. A selection of 239 reports (n. 106 DLBCL, n.79 FL, and n. 54 MCL) from the Pathology Unit at the IRCCS - Istituto Tumori “Giovanni Paolo II” of Bari (Italy) was used to assess ARGO performance in terms of accuracy, precision, recall and F1-score. Results: By applying our workflow, we successfully converted 233 paper-based reports into corresponding eCRFs incorporating structured information about diagnosis, tissue of origin and anatomical site of the sample, major molecular markers and cell-of-origin subtype. Overall, ARGO showed high performance (nearly 90% of accuracy, precision, recall and F1-score) in capturing identification report number, biopsy date, specimen type, diagnosis, and additional molecular features. Conclusions: We developed and validated an easy-to-use tool that converts RW paper-based diagnostic reports of major lymphoma subtypes into structured eCRFs. ARGO is cheap, feasible, and easily transferable into the daily practice to generate REDCap-based EHR for clinical and translational research purposes