COVID-19 Pandemic: Huge Stress Test for Health System Could Be a Great Opportunity to Update the Workflow in a Modern Surgical Pathology.

BACKGROUND: On December 2019, an outbreak of atypical pneumonia, known as COVID-19, was identified in Wuhan, China. This disease, characterized by the rapid human-to-human transmission of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread rapidly in more than 200 countries. Northern Italy's regions have been hit hard in terms of deaths. Here, we report the experience of the Pathology Department of the Fondazione IRCCS Istituto Nazionale Tumori (INT) in Milan, the first Italian public cancer center, in the period of the lockdown that took place in Lombardy from March to May 2020. METHOD: The variation in terms of exams was calculated in two different timeframes: December 2019-February 2020 (pre-COVID-19) and March-May 2020 (COVID-19). During these periods, Turn-Around-Time (TAT) metrics released by the Lombardy Region were calculated to assess if changes applied to guarantee the safeguarding of workers affected the average diagnosis time. RESULTS: In the COVID-19 period, there was a decrease for all the performed exams. The most considerable decrease was observed for PAP tests (-81.6%), followed by biopsies (-48.8%), second opinions (-41.7%), and surgical (-31.5%), molecular (-29.4%) and cytological (-18.1%) tests. Measures applied within the Pathology Department, such as digital pathology, remote working, rotations and changes in operating procedures, improved the diagnostic performance as required by the guidelines of the Lombardy Region in terms of TAT. At the same time, the measures applied for the safeguarding of the personnel turned out to be feasible and did not affect the overall performance of the Pathology Department. CONCLUSIONS: The sharp slowdown in cancer screening during the first wave of COVID-19 could seriously endanger cancer prevention in the near future.

Fluorescence in situ hybridization analysis and immunophenotyping of c-Kit/PDGFRA and Bcl-2 expression in gastrointestinal stromal tumors.

OBJECTIVE: To investigate c-Kit/PDGFRA genomic alterations, KIT-PDGFRA coexpression in gastrointestinal stromal tumors (GISTs) and the role of Bcl-2. STUDY DESIGN: We analyzed 70 primary tumors, 6 recurrences, 4 metastases and 1 recurrence plus metastasis, all molecularly characterized. Alterations in gene copy number were detected by fluorescence in situ hybridization (FISH) and expression of KIT, PDGFRA and Bcl-2 by immunohistochemistry. RESULTS: c-Kit/PDGFRA gene alterations affected 38% of all cases and 39% of primary tumors, with major changes accounting for 15% in both all the cases and primary tumors. Cytoplasmic KIT/PDGFRA coexpression was present in 96.5% of the c-Kit-mutated cases, 100% of the wt c-Kit/PDGFRA cases and 66.6% of the PDGFRA-mutated cases. Bcl-2 immunoreactivity was present in 70% of cases, with expression levels of +++ in 29%, ++ in 38% and + in 33%. CONCLUSION: FISH confirmed cytogenetic alterations in about 40% of primary GISTs at the onset. The high rate of c-Kit/PDGFRA coexpression suggests that both receptors are involved in oncogenicity and may affect imatinib efficacy. The assumption that Bcl-2 expression is supported by the KIT pathway and that its imatinib-mediated down-regulation contributes to autophagic cell death, although attractive, needs to be further confirmed.

Primary giant clear cell sarcoma (soft tissue malignant melanoma) of the sternum.

One case of a primary clear cell sarcoma of the sternum (also called soft tissue melanoma) is reported. This neoplasm represents a rare occurrence, and as a rule, differential diagnosis with melanoma often requires detailed immunohistochemistry and cytogenetic analysis (ie, rearrangement of EWS gene localized on 22q12 chromosome). Because wide resection is recommended, chest wall reconstruction may pose challenging technical issues. In our patient, we elected not to proceed to clavicular stabilization. Nevertheless, acceptable shoulder girdle mobility was observed after surgery.

Expression of ligand-activated KIT and platelet-derived growth factor receptor beta tyrosine kinase receptors in synovial sarcoma.

PURPOSE: The use of tyrosine kinase receptor inhibitors is increasingly becoming a valuable therapeutic alternative in tumors carrying activated tyrosine kinase receptors. In a previous study, we described a coexpression of KIT and stem cell factor (SCF) mRNA in Synovial sarcomas, (SS) and in a limited number of cases, we demonstrated the presence of an activated receptor. Here, in a wider number of cases, we investigated the expression level and phosphorylation status of two structurally related tyrosine kinase receptors, KIT and platelet-derived growth factor receptor beta (PDGFRbeta), at the light of their role as possible targets of tyrosine kinase receptors inhibitor molecules. EXPERIMENTAL DESIGN: Forty-three SS cases were analyzed for KIT and PDGFRbeta expression/activation by immunoprecipitation/Western blotting experiments. The cognate ligands, SCF and PDGFB, were detected by reverse transcription-PCR. RESULTS: KIT was observed in 48 and 41% (45% total) whereas PDGFRbeta in 54 and 33% (45% total) of monophasic and biphasic SS cases, respectively. With respect to the fusion transcript type SYTSSX1 and SYTSSX2, KIT was more expressed in SYTSSX1 carrying cases (48 versus 38%), whereas PDGFRbeta resulted more frequently expressed in SYTSSX2 ones (54 versus 37%). When expressed, the receptors were phosphorylated. Their ligands were detected in all of the activated cases. CONCLUSIONS: About 70% of the cases express one of the two activated tyrosine kinase receptors with a mutually exclusive expression trend. Coexpression is not frequent and seems to be restricted to monophasic subtype. These data indicate that a consistent fraction of this tumor type could represent a good candidate for kinase inhibitor molecules effective on KIT and PDGFRbeta where their activation is sustained by an autocrine loop.