Publications by authors named "Renato Franco"

250 Publications

Primary Extra-Nodal DLBCL of Glands: Our Experiences outside Guidelines of Treatment.

Healthcare (Basel) 2021 Mar 5;9(3). Epub 2021 Mar 5.

Division of Pathology, Department of Mental Health and Preventive, University of Campania "Luigi Vanvitelli", 80138 Naples, Italy.

Lymphomas usually involve lymph nodes and other lymphoid tissues, but sometimes occur in non-lymphoid organs, called extra-nodal sites. Primary diffuse extra-lymph node large B-cell lymphoma (DLBCL) of the thyroid and parotid gland have been observed rarely. According to the most accredited guidelines, primary extra-nodal DLBCL of the parotid and thyroid glands should be treated with three cycles of R-CHOP followed by radiotherapy of the involved site (ISRT). Surgery alone is not enough to treat DLBCL. We describe two unusual cases of primary extra-nodal DLBCL in elderly patients treated exclusively with surgical resection, given the inability to apply chemotherapy. Both patients achieved clinical recovery, which was maintained after a follow-up of more than 18 months, despite not having performed the indicated chemotherapy protocol. The two cases presented here, and a few others reported in the literature, should be considered exceptions to the rule, and do not allow the conclusion that surgery alone might be sufficient for complete remission.
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http://dx.doi.org/10.3390/healthcare9030286DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8002204PMC
March 2021

Treatment of Cutaneous Melanoma Harboring SMO p.Gln216Arg Mutation with Imiquimod: An Old Drug with New Results.

J Pers Med 2021 Mar 14;11(3). Epub 2021 Mar 14.

Dermatology Unit, Department of Mental and Physical Health and Prevention Medicine, Università degli Studi della Campania "Luigi Vanvitelli", 80131 Naples, Italy.

Melanoma is the most lethal form of skin cancer and its incidence is growing worldwide. In the last ten years, the therapeutic scenario of this disease has been revolutionized by the introduction of targeted therapies and immune-checkpoint inhibitors. However, in patients with many lesions and bulky tumors, in which surgery is no longer feasible, there is a need for new treatment options. Here we report, for the first time to our knowledge, a clinical case where a melanoma patient harboring the SMO p.Gln216Arg mutation has been treated with imiquimod, showing a complete and durable response. To better explain this outstanding response to the treatment, we transfected a melanoma cell line (MeWo) with the SMO p.Gln216Arg mutation in order to evaluate its role in response to the imiquimod treatment. Moreover, to better demonstrate that the antitumor activity of imiquimod was due to its role in suppressing the oncogenic SMO signaling pathway, independently of its immune modulating function, an in vivo experiment has been performed. This clinical case opens up a new scenario for the treatment of melanoma patients identifying a new potentially druggable target.
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http://dx.doi.org/10.3390/jpm11030206DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8000647PMC
March 2021

Discrepancy of p16 immunohistochemical expression and HPV RNA in penile cancer. A multiplex in situ hybridization/immunohistochemistry approach study.

Infect Agent Cancer 2021 Mar 31;16(1):22. Epub 2021 Mar 31.

Pathology Unit, Department of Mental and Physical Health and Preventive Medicine, University of Campania "L. Vanvitelli", Complesso di Santa Patrizia, Via Luciano Armanni, 5, 80138, Naples, Italy.

Background: The high-risk human papillomavirus (HPV) infection represents one of the main etiologic pathways of penile carcinogenesis in approximately 30-50 % of cases. Several techniques for the detection of HPV are currently available including Polymerase chain reaction-based techniques, DNA and RNA in situ hybridization (ISH), p16 immunohistochemistry (IHC). The multiplex HPV RNA ISH/p16 IHC is a novel technique for the simultaneous detection of HPV E6/E7 transcripts and p16INK4a overexpression on the same slide in a single assay. The main aim of this study was to evaluate the discrepancy of p16 IHC expression relatively to HPV RNA ISH in penile cancer tissue.

Methods: We collected a series of 60 PCs. HPV has been analysed through the RNA ISH, p16 IHC and the multiplex HPV RNA ISH/p16 IHC.

Results: The multiplex HPV RNA ISH /p16 IHC results in the series were in complete agreement with the previous results obtained through the classic p16 IHC and HPV RNA scope carried out on two different slides. The multiplex HPV RNA ISH /p16 IHC showed that HPV positivity in our series is more frequently in usual squamous cell carcinoma than in special histotypes (19 out of 60 - 15 %- versus 6 out of 60 - 10 %-), in high-grade than in moderate/low grade carcinomas (6 out of 60 - 10 %- versus 4 out of 60 - 6.7 %-). In addition, our data revealed that in 5 out of 20 cases with p16 high intensity expression is not associated with HPV RNA ISH positivity.

Conclusions: Our findings emphasize that the use of p16 as a surrogate of HPV positivity was unsuccessful in approximatively 8 % of cases analysed in our series. Indeed, p16 IHC showed a sensitivity of 100 % and a specificity of 71 %, with a positive predictive value (PPV) of 54 % and a negative predictive value of 100 %; when considering high intensity, p16 IHC showed a sensitivity of 100 %, a specificity of 89 %, with a PPV of 75 % and NPV of 100 %. Since HPV positivity could represent a relevant prognostic and predictive value, the correct characterization offered by this approach appears to be of paramount importance.
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http://dx.doi.org/10.1186/s13027-021-00361-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011184PMC
March 2021

High performance of multiplex fluorescence in situ hybridization to simultaneous detection of BCL2 and BCL6 rearrangements: useful application in the characterization of DLBCLs.

Virchows Arch 2021 Mar 25. Epub 2021 Mar 25.

Pathology Unit, Department of Mental and Physical Health and Preventive Medicine, Università degli Studi della Campania "L Vanvitelli", Via Luciano Armanni, 5, 80138, Naples, Italy.

Chromosomal rearrangements involving BCL2, BCL6 and MYC are commonly found in the most frequent B cell lymphomas, namely follicular lymphomas (FLs) and diffuse large B-cell lymphomas (DLBCLs). Particularly, BCL2-rearrangement represents a diagnostic hallmark in FLs, whereas MYC translocation can occur simultaneously with BCL2 and/or BCL6 rearrangements, defining a specific category of DLBCLs with a poorer prognosis. In this study, we aim to validate the diagnostic performance of multiplex BCL2/BCL6 FISH approach in formalin-fixed paraffin-embedded FLs and DBCLs and cytological samples of DLBCL comparing to the classic set of single break-apart probes. We collected a series of lymphomas, including 85 DLBCLs, 45 FLs and 36 other B-cell lymphoma histotypes and 16 cytological samples of DLBCLs. MYC, BCL2 and BCL6 rearrangements were previously assessed by a classic FISH test using single break-apart probes. All samples were analysed by a multiplex FISH assay. In the FL series, 38 cases showed BCL2-R; in the DLBCLs series, MYC-R was detected in 21 out of 85 DLBCL patients, BCL2-R in 10 out of 85 and BCL6-R in 33 out of 85. In the DLBCL cytological series, MYC-R was detected in 4 out of 16, BCL2-R in 4 out of 16 and BCL6-R in 1 out of 16. Notably, in FFPE, 13 double-hit lymphomas (DHLs) and 3 triple-hit lymphomas (THLs) were detected; in the cytological series, only 3 DHL cases were observed. The dual BCL2/BCL6 FISH probe test results were fully concordant with the results obtained using classic BCL2 and BCL6 single break apart. Particularly, multiplex FISH to simultaneously detect BCL2-R and BCL6-R on a single slide could find a wide application in the characterisation of double- and triple-hit DLBCLs.
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http://dx.doi.org/10.1007/s00428-021-03084-8DOI Listing
March 2021

Dermatological Considerations in the Diagnosis and Treatment of Marginal Zone Lymphomas.

Clin Cosmet Investig Dermatol 2021 8;14:231-239. Epub 2021 Mar 8.

Pathology Unit, Department of Mental and Physical Health and Preventive Medicine, Università degli Studi della Campania "Luigi Vanvitelli", Naples, 80138, Italy.

Primary cutaneous marginal zone lymphoma (PC-MZL) is a B-cell lymphoma arising in the skin. Although it is a rare disease, PC-MZL accounts for 20-40% of all primary cutaneous B-cell lymphoma in Western Countries. The aetiology and the pathogenesis of PC-MZL are poorly understood, as it generally lacks the chromosomal translocations most typically present in marginal zone lymphomas of other sites. The diagnosis of PC-MZL may be challenging, due to the rarity of the disease, and needs the competence of different professional figures, including the dermatologist and the pathologist. Furthermore, the management of the patient after the diagnosis is complex and involves the dermatologist, the haematologist, the surgeon, the radiotherapist and the radiologist. The aim of this review is to describe the clinical and histological findings for the diagnosis of PC-MZL, and the state of art for the management of the patient.
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http://dx.doi.org/10.2147/CCID.S277667DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7954031PMC
March 2021

Fusion proteins in lung cancer: addressing diagnostic problems for deciding therapy.

Expert Rev Anticancer Ther 2021 Mar 30:1-14. Epub 2021 Mar 30.

Pathology Unit, Department of Mental and Physical Health and Preventive Medicine, University of Campania 'Luigi Vanvitelli', Naples, Italy.

: Gene fusions are frequent chromosomal aberrations in solid tumors. In Lung cancer (LC) several druggable-fusions involving tyrosine kinase receptor genes have been described, including ALK, ROS1, RET and NTRK. In non-small cell lung cancer, testing for targetable fusions has become a part of routine clinical practice, greatly impacting therapeutic choice for patients with these aberrations. Although substantial technologies for gene fusion detection have been implemented over time including; cytogenetic, Fluorescence in situ hybridization (FISH), Immunohistochemistry (IHC), Retro-transcription Real-Time PCR (RT-qPCR), to Next Generation Sequencing (NGS), nCounter system (Nanostring technology), several critical issues remain. To date, only the companion diagnostic tests FISH and IHC for ALK-rearrangements and NGS for ROS1-rearrangments were approved. Other fusion approved tests are currently unavailable.: In this review, we explore current diagnostic problems of gene fusion detection relative to the technologies available, in order to clarify future standardization of analyses which determine therapeutic choices.: The establishment of a gold standard, an effective diagnostic algorithm, and a standardized interpretation for the analysis of each druggable-fusions in lung cancer is essential for adequate therapeutic management.
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http://dx.doi.org/10.1080/14737140.2021.1903875DOI Listing
March 2021

RNAScope Hybridization as a Novel Technique for the Assessment of c-KIT mRNA Expression in Canine Mast Cell Tumor.

Front Vet Sci 2021 16;8:591961. Epub 2021 Feb 16.

Department of Veterinary Medicine and Animal Production, University of Naples Federico II, Naples, Italy.

RNA is considered as an indicator of the dynamic genetic expression changes in a cell. RNAScope is a commercially available hybridization assay for the detection of RNA in formalin-fixed paraffin-embedded tissue. In this work, we describe the use of RNAScope as a sensitive and specific method for the evaluation of messenger RNA (mRNA) in canine mast cell tumor. We investigated the expression of mRNA with RNAscope in 60 canine mast cell tumors (MCTs), comparing it with the histological grade and KIT immunohistochemical expression patterns. Our results showed an overall good expression of mRNA in neoplastic cells if compared with control probes. We also observed a statistically significant correlation between histological grade and mRNA expression. No correlations were found between KIT protein immunohistochemical distribution pattern and mRNA expression or histological grade. Our results provide a reference basis to better understand mRNA expression in canine MCTs and strongly encourage further studies that may provide useful information about its potential and significant role as a prognostic and predictive biological marker for canine MCTs clinical outcome.
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http://dx.doi.org/10.3389/fvets.2021.591961DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921150PMC
February 2021

Innovative granular formulation of Metarhizium robertsii microsclerotia and blastospores for cattle tick control.

Sci Rep 2021 Mar 2;11(1):4972. Epub 2021 Mar 2.

Department of Animal Parasitology, Veterinary Institute, Federal Rural University of Rio de Janeiro, Seropédica, Rio de Janeiro, 23897-000, Brazil.

The tick Rhipicephalus microplus poses a serious threat to the cattle industry, resulting in economic losses aggravated by tick resistance to chemical acaricides. Strains of Metarhizium spp., a well-known group of entomopathogenic fungi, can contribute to managing this ectoparasite. We explored two novel granular, microsclerotia- or blastospores-based formulations of Metarhizium robertsii for R. microplus control under semi-field conditions. Fungal persistence in soil was also observed for 336 days. The experiment used pots of Urochloa decumbens cv. Basilisk grass, treated with 0.25 or 0.5 mg of granular formulation/cm (25 or 50 kg/ha) applied to the soil surface prior to transferring engorged tick females onto the treated soil. The fungal granules yielded more conidia with subsequent sporulation under controlled indoor conditions than in the outdoor environment, where the levels of fungus rapidly declined over time. Metarhizium-root colonization ranged from 25 to 66.7% depending on the propagule and rate. Fungal formulations significantly reduced the number of tick larvae during the humid season, reaching at least 64.8% relative efficacy. Microsclerotia or blastospores-granular formulations of M. robertsii can reduce the impact of R. microplus, and thus prove to be a promising tool in the control of ticks.
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http://dx.doi.org/10.1038/s41598-021-84142-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7925645PMC
March 2021

Second Diagnostic Opinion by Experienced Dermatopathologists in the Setting of a Referral Regional Melanoma Unit Significantly Improves the Clinical Management of Patients With Cutaneous Melanoma.

Front Med (Lausanne) 2020 4;7:568946. Epub 2021 Feb 4.

Pathology Unit, Department of Mental and Physical Health and Preventive Medicine, University of Campania "Luigi Vanvitelli," Naples, Italy.

The diagnosis of cutaneous melanoma and melanocytic neoplasms in general is one of the most challenging fields in pathology, and the reported interobserver diagnostic agreement in the evaluation of melanocytic lesions is poor. Nevertheless, a correct histopathological diagnosis is crucial to ensure a good clinical management of the patients. The institution of multidisciplinary teams has recently modified the approach to the patients with cutaneous melanoma. Patients referred to a multidisciplinary melanoma unit after receiving a diagnosis of melanoma elsewhere are encouraged to have their histopathological diagnosis confirmed by a second opinion from the experienced pathologist of the team before any treatment is initiated. We performed a retrospective analysis on a series of 121 histopathological revisions required for melanocytic neoplasms in the context of a multidisciplinary team, in order to evaluate the effects of second diagnostic opinion (SDO) on the clinical management of the patients. We defined three types of diagnostic discrepancies between the first diagnosis and the second opinion, according to the greatness of their clinical impact. Overall, the incidence of diagnostic discrepancies of any type was quite high in our series (56%). Interestingly, the SDO determined relevant changes in the clinical management of the patients in 33 out of 121 (27.3%) cases. This study confirms that SDO by expert pathologists significantly affects the course of treatment of melanoma patients and helps improving the diagnostic accuracy and clinical outcome.
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http://dx.doi.org/10.3389/fmed.2020.568946DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890120PMC
February 2021

Multitarget fluorescence in situ hybridization diagnostic applications in solid and hematological tumors.

Expert Rev Mol Diagn 2021 Feb 22;21(2):161-173. Epub 2021 Feb 22.

Department of Mental and Physic Health and Preventive Medicine, Pathology Unit, University of Campania Luigi Vanvitelli, Napoli, Italy.

: Multitarget FISH (mFISH) is a technique allowing for simultaneous detection of multiple targets sequences on the same slide through the choice of spectrally distinct fluorophore labels. The mFISH could represent a useful tool in the field of precision oncology.: This review discusses the potential applications of mFISH technology in the molecular diagnosis of different solid and hematological tumors, including non-small cell lung cancers, melanomas, renal cell carcinomas, bladder carcinomas, germ cell tumors, and multiple myeloma, as commonly required in the clinical practice.: In this emerging era of the tailored therapies and newer histo-molecular classifications, there are increasing numbers of predictive and diagnostic biomarkers required for effective clinical care. The mFISH approach may have several applications in the common clinical practice, improving the molecular diagnosis in terms of time, cost and preservation of biomaterial for tumors with a limited amount of tumor available. The mFISH provides several advantages compared to other high-throughput technologies; however, it requires high level of expertise required to interpret complex results.
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http://dx.doi.org/10.1080/14737159.2021.1887733DOI Listing
February 2021

How Fear of COVID-19 Can Affect Treatment Choices for Anaplastic Large Cell Lymphomas ALK+ Therapy: A Case Report.

Healthcare (Basel) 2021 Jan 31;9(2). Epub 2021 Jan 31.

Pathology Unit, Department of Mental and Physical Health and Preventive Medicine, University of Campania "Luigi Vanvitelli", 80138 Naples, Italy.

Background: The t (2; 5) chromosomal rearrangement of the ALK gene with nucleophosmin 1 gene (NPM1), resulting in an NPM1-ALK fusion, was first demonstrated in 1994 in anaplastic large cell lymphoma, (ALCL), a T-cell lymphoma responsive to cyclophosphamide, abriblastine, vincristine and prednisone in approximately 80% of cases; refractory cases usually respond favorably to brentuximab vedotin. These treatments are regarded as a bridge to allogeneic hematopoietic stem cell transplantation (allo-SCT). Nowadays, transplant procedures and the monitoring of chemotherapy patients proceed very slowly because the SARS-CoV-2 pandemic has heavily clogged the hospitals in all countries.

Results: A 40-year-old Caucasian woman was first seen at our clinical center in June 2020. She had ALCL ALK+, a history of failure to two previous therapeutic lines and was in complete remission after 12 courses of brentuximab, still pending allo-SCT after two failed donor selections. Facing a new therapeutic failure, we requested and obtained authorization from the Italian drug regulatory agency to administer 250 mg of crizotinib twice a day, a drug incomprehensibly not registered for ALCL ALK +.

Conclusions: The response to crizotinib was optimal since no adverse event occurred, and CT-PET scans persisted negative; this drug has proved to be a valid bridge to allo-SCT.
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http://dx.doi.org/10.3390/healthcare9020135DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7912420PMC
January 2021

Dual inhibition of TGFβ and AXL as a novel therapy for human colorectal adenocarcinoma with mesenchymal phenotype.

Med Oncol 2021 Feb 11;38(3):24. Epub 2021 Feb 11.

Medical Oncology, Department of Precision Medicine, Università Degli Studi Della Campania Luigi Vanvitelli, Napoli, Campania, Italy.

A subset of colorectal cancer (CRC) with a mesenchymal phenotype (CMS4) displays an aggressive disease, with an increased risk of recurrence after surgery, reduced survival, and resistance to standard treatments. It has been shown that the AXL and TGFβ signaling pathways are involved in epithelial-to-mesenchymal transition, migration, metastatic spread, and unresponsiveness to targeted therapies. However, the prognostic role of the combination of these biomarkers and the anti-tumor effect of AXL and TGFβ inhibition in CRC still has to be assessed. To evaluate the role of AXL and TGFβ as negative biomarker in CRC, we conducted an in-depth in silico analysis of CRC samples derived from the Gene Expression Omnibus. We found that AXL and TGFβ receptors are upregulated in CMS4 tumors and are correlated with an increased risk of recurrence after surgery in stage II/III CRC and a reduced overall survival. Moreover, we showed that AXL receptor is differently expressed in human CRC cell lines. Dual treatment with the TGFβ galunisertib and the AXL inhibitor, bemcentinib, significantly reduced colony formation and migration capabilities of tumor cells and displayed a strong anti-tumor activity in 3D spheroid cultures derived from patients with advanced CRC. Our work shows that AXL and TGFβ receptors identify a subgroup of CRC with a mesenchymal phenotype and correlate with poor prognosis. Dual inhibition of AXL and TGFβ could represent a novel therapeutic strategy for patients with this aggressive disease.
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http://dx.doi.org/10.1007/s12032-021-01464-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7878213PMC
February 2021

Diagnostic performance of melanocytic markers for immunocytochemical evaluation of lymph-node melanoma metastases on cytological samples.

J Clin Pathol 2021 Jan 28. Epub 2021 Jan 28.

Pathology Unit, Department of Mental and Physical Health and Preventive Medicine, Università degli Studi della Campania "Luigi Vanvitelli", Naples, Italy.

Aims: The diagnosis of metastatic cutaneous melanoma (CM) on lymph node fine needle aspiration samples may be challenging and usually requires confirmation by immunocytochemistry. However, the cytological material could be too scant to order a broad panel of markers. In this case, the pathologist is forced to choose the most advantageous antibodies. The most commonly used melanocytic markers include S100, Melan-A, HMB45 and SOX10 but their diagnostic yield on cytological samples has been poorly studied. The current work aimed to evaluate the diagnostic performance of melanocytic markers when applied to cell blocks obtained from fine needle aspiration cytology (FNAC) of lymph node metastases from CM.

Methods: S100, Melan-A, HMB45 and SOX10 were tested on cell block sections of 38 lymphnode metastases from CM diagnosed by cytology. A combined score was built to evaluate each immunostaining, considering the intensity of the staining and the percentage of stained neoplastic cells.

Results: S100 and SOX10 revealed a higher sensitivity (100%) than Melan-A and HMB45 for the diagnosis of metastatic CM. Furthermore, SOX10 emerged as the melanocytic marker with the best staining performance.

Conclusion: SOX10 has a 100% detection rate and the most easily interpretable staining pattern compared with other melanocytic markers. Therefore, it is strongly recommended that SOX10 is included in the minimal immunocytochemical panel for the diagnostic evaluation of lymph node FNAC in patients with suspected CM metastasis.
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http://dx.doi.org/10.1136/jclinpath-2020-206962DOI Listing
January 2021

Rescue Therapy of Refractory Diffuse Large B-Cell Lymphomas BCL2 with Venetoclax: Case Report.

Chemotherapy 2020 21;65(5-6):161-165. Epub 2021 Jan 21.

Department of Mental and Physical Health and Preventive Medicine, Pathology Unit, University of Campania "Luigi Vanvitelli", Naples, Italy.

Eleven years ago, a 64-year-old Caucasian man had LNH Follicular 3a, IV A stage, FLIPI 2 as a prognostic index of follicular lymphoma. He received 8 cycles of RCHOP followed by rituximab maintenance, with complete remission. Due to a systemic recurrence, a new treatment schedule (RCOMP, 6 cycles) was introduced with partial remission persisting during a long-term maintenance treatment with rituximab. Three years ago, LNH Follicular 3a progressed into GC type diffuse large B-cell lymphomas (DLBCL); 6 cycles of rituximab and bendamustine were followed by R-ICE and R OXALI DHAP treatments without beneficial effect. Due to the worse general condition (ECOG 3-4), the patient was treated with pixantrone (6 cycles) until July 10, 2019, with a partial response. On Jan 13, 2020, an extreme compassioned treatment with venetoclax alone was started; this drug was well tolerated and provided a satisfactory clinical and laboratory improvement. In June 2020, however, he developed bone marrow toxicity and septic fever. Nasal and pharyngeal secretions were SARS-CoV-2 RNA negative. Blood cultures for mycotic agents and Gram-positive, Gram-negative, and anaerobic bacteria were negative, but few days later, the patients died of sepsis due to unidentified agents. The use of venetoclax as a single drug to treat DLBCL BCL2 patients deserves further investigation.
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http://dx.doi.org/10.1159/000512541DOI Listing
March 2021

Extranodal B-cell marginal zone lymphoma arising in the context of a lympho-epithelial cyst of the parotid gland in a patient with clonal B-cell lymphocytosis: report of the first case.

Minerva Stomatol 2020 Dec 16. Epub 2020 Dec 16.

Pathology Unit, Department of Mental and Physical Health and Preventive Medicine, University of Campania L. Vanvitelli, Naples, Italy.

Background: Primary salivary gland lymphomas are unusual, accounting for 2.5% to 4.5% of salivary gland tumours. More than 90% are non-Hodgkin lymphomas (NHLs) and extranodal marginal zone lymphoma (EMZL) is the most common histotype.

Methods: A patient with a history of CD5-negative and CD23-negative clonal B-cell lymphocytosis presented a nodule in the deeper left parotid region, discovered accidentally during a follow-up for the lymphocytosis. Ultrasounds and Magnetic resonance imaging showed multiple nodules, the biggest of about 1.5 centimetres, partly solid and partly cystic. US-guided fine needle aspiration cytology and flow cytometry were executed. Final diagnosis of a monoclonal B-cell lymphoproliferative disorder was rendered, and the patient underwent to partial left parotidectomy.

Results: Histological examination and immunohistochemistry allowed to formulate the final diagnosis of an extranodal non-Hodgkin B-cell marginal zone lymphoma (MZL) occurring in the context of a lympho-epithelial cyst was rendered. The 2 years clinical and instrumental follow-up was uneventful.

Conclusions: The diagnostic evaluation of a LEC has to include the possibility of a concurrent EMZL, mainly in case of high risk biological and clinical conditions like CBL.
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http://dx.doi.org/10.23736/S0026-4970.20.04441-6DOI Listing
December 2020

Lymph node fine needle aspiration cytology (FNAC) in paediatric patients: Why not? Diagnostic accuracy of FNAC in a series of heterogeneous paediatric lymphadenopathies.

Pathol Res Pract 2021 Jan 22;217:153294. Epub 2020 Nov 22.

Division of Pathology, Department of Mental and Physical Health and Preventive Medicine, Università Degli Studi Della Campania "Luigi Vanvitelli", Naples, Italy.

Fine needle aspiration cytology (FNAC) can be a precious tool for the evaluation of lymphadenopathies in children and adolescents. The purpose of this study was to analyse the diagnostic accuracy of FNAC in a paediatric lymph node series. We report a series of 76 patients, aged up to 19 years, who underwent lymph node FNAC. In our series, 57 cases were diagnosed as non-neoplastic, including benign reactive hyperplasia and other inflammatory lesions, 18 cases were diagnosed as malignant and 1 case was diagnosed as suspicious for lymphoproliferative process, not otherwise specified. Sensitivity, specificity, positive predictive value and negative predictive value were 93 %, 100 %, 100 % and 98 %, respectively. Diagnostic accuracy resulted 98.6 %. FNAC is an accurate, minimally invasive method with minimal complications that allows evaluation of paediatric lymphadenopathies and a correct triage of reactive/inflammatory and neoplastic lymphadenopathies. The application of rapid on-site evaluation, the realization of a cell block and the application of ancillary diagnostic tests, including at least immunocytochemistry and flow cytometry, allows to achieve an excellent diagnostic performance.
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http://dx.doi.org/10.1016/j.prp.2020.153294DOI Listing
January 2021

Added value of assessing medical students' reflective writings in communication skills training: a longitudinal study in four academic centres.

BMJ Open 2020 11 6;10(11):e038898. Epub 2020 Nov 6.

Internal Medicine, University of Minho School of Medicine, Braga, Portugal

Objectives: This study describes the development and implementation of a model to assess students' communication skills highlighting the use of reflective writing. We aimed to evaluate the usefulness of the students' reflections in the assessment of communication skills.

Design: Third-year and fourth-year medical students enrolled in an elective course on clinical communication skills development were assessed using different assessment methods.

Setting And Participants: The communication skills course was offered at four universities (three in Brazil and one in Portugal) and included 69 students.

Outcome Measures: The students were assessed by a Multiple-Choice Questionnaire (MCQ), an objective structured clinical examination (OSCE) and reflective writing narratives. The Cronbach's alpha, dimensionality and the person's correlation were applied to evaluate the reliability of the assessment methods and their correlations. Reflective witting was assessed by applying the Reflection Evaluation for Enhanced Competencies Tool Rubric (Reflect Score (RS)) to measure reflections' depth, and the Thematic Score (TS) to map and grade reflections' themes.

Results: The Cronbach alpha for the MCQ, OSCE global score, TS and RS were, respectively, 0.697, 0.633, 0.784 and 0.850. The interobserver correlation for the TS and RS were, respectively, 0.907 and 0.816. The assessment of reflection using the TS was significantly correlated with the MCQ (r=0.412; p=0.019), OSCE (0.439; p=0.012) and RS (0.410; p=0.020). The RS did not correlate with the MCQ and OSCE.

Conclusions: Assessing reflection through mapping the themes and analysing the depth of reflective writing expands the assessment of communication skills. While the assessment of reflective themes is related to the cognitive and behavioural domains of learning, the reflective depth seems to be a specific competence, not correlated with other assessment methods-possibly a metacognitive domain.
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http://dx.doi.org/10.1136/bmjopen-2020-038898DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7651724PMC
November 2020

Clinical management of squamous cell carcinoma of the tongue: patients not eligible for free flaps, a systematic review of the literature.

Expert Rev Anticancer Ther 2021 Jan 4;21(1):9-22. Epub 2020 Nov 4.

Department of Multidisciplinary Medical, Surgical and Dental Specialties, University of Campania "Luigi Vanvitelli" , Naples, Italy.

Introduction: The management of squamous cell carcinoma (SCC) of the tongue represents the most demanding treatment planning in head and neck surgery. Ablation followed by free flap reconstruction is considered the gold standard, but not all patients are suitable for this strategy. The aim of this review is to provide a comprehensive view of surgical reconstruction possibilities in patients not eligible for free flaps.

Methods: Following PRISMA recommendations, a systematic literature review was conducted searching for original papers that investigated outcomes of patients treated by surgical ablation for tongue SCC followed by reconstruction with local or pedicled flaps. Selected papers were read and data extracted for qualitative analysis.

Results: Twenty articles met the inclusion/exclusion criteria. The study design was case series in sixteen papers, cohort study in the remaining four. Four different local flaps (BMM, FAMM, NLIF, SMIF) and four regional flaps have been discussed in included studies (IHF, SFIF, SCM, PMMC).

Conclusion: The improved anatomical knowledge makes local flaps a reliable alternative to free tissue transfer in cases requiring small-/medium-sized defects. Regional flaps still represent cornerstones in reconstruction of the tongue. Ease of execution, costs-to-benefit ratio, low-rate complications, minimal donor site morbidity represent the best advantages choosing local/regional flaps.
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http://dx.doi.org/10.1080/14737140.2021.1840359DOI Listing
January 2021

Massive squamous differentiation and anaplastic features in eccrine porocarcinoma as rare and confounding elements.

Australas J Dermatol 2020 Sep 27. Epub 2020 Sep 27.

Division of Pathology, Department of Mental and Physical Health and Preventive Medicine, University of Campania "L. , Naples, Italy.

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http://dx.doi.org/10.1111/ajd.13472DOI Listing
September 2020

Giant cell-rich extrapleural solitary fibrous tumor: Cytological findings and differential diagnosis of a rare neoplasm.

Diagn Cytopathol 2021 Mar 17;49(3):E113-E118. Epub 2020 Sep 17.

"Centro Barberio" Pathology Laboratory, Naples, Italy.

Extrapleural solitary fibrous tumor (ESFT) is a rare neoplasm with a variable biological behavior that may occur almost everywhere in the body, as it has been reported in head and neck, back, retroperitoneum, inguinal region and more. The diagnosis of ESFT may be challenging, especially in case of its morphological rare variants such as giant cell-rich ESFT. Fine-needle aspiration cytology (FNAC) is a rapid, poorly invasive, safe diagnostic technique, which is recently proving useful for the preoperative diagnosis of mesenchymal neoplasms. Herein we report a case of a FNAC diagnosis of giant cell-rich ESFT, focusing on its morphological and immunocytochemical characteristics, and showing how cytology may be an effective tool in the preoperative diagnosis of mesenchymal neoplasms, allowing the correct surgical management of the patient.
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http://dx.doi.org/10.1002/dc.24610DOI Listing
March 2021

Myoepithelial sialadenitis with metachromatic matrix: A diagnostic pitfall. A case of salivary gland swelling in a paediatric patient evaluated by fine needle aspiration cytology.

Cytopathology 2021 Mar 11;32(2):257-260. Epub 2020 Oct 11.

Division of Pathology, Department of Mental and Physical Health and Preventive Medicine, Università degli Studi della Campania "Luigi Vanvitelli", Naples, Italy.

Fine needle aspiration cytology (FNAC) is generally characterized by a high diagnostic accuracy in differentiating non-neoplastic/inflammatory lesions from neoplastic lesions of the salivary glands. Lymphoepithelial sialadenitis/myoepithelial sialadenitis is exceedingly rare in paediatric patients and is characterized by a diffuse, often bilateral, salivary gland enlargement and the differential diagnosis may sometimes be difficult. We report the case of a 10-year-old boy who presented with a swelling of the left parotid gland investigated by ultrasound salivary gland FNAC.
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http://dx.doi.org/10.1111/cyt.12916DOI Listing
March 2021

Double-staining Immunohistochemistry Reveals in Malignant Pleural Mesothelioma the Coexpression of ERCC1 and RRM1 as a Frequent Biological Event Related to Poorer Survival.

Appl Immunohistochem Mol Morphol 2021 03;29(3):231-238

Pathology Unit, University of Campania "Luigi Vanvitelli".

Malignant pleural mesothelioma (MPM) is a rare cancer with a poor prognosis. To date, standard MPM therapy is still limited to surgery, radiotherapy, and chemotherapy, including pemetrexed and platinum compounds. The main mechanisms of platinum resistance are associated with DNA repair pathways. Excision repair cross-complementing group 1 (ERCC1) and ribonucleotide reductase subunit M1 (RRM1) are important components of the DNA repair, considered as prognostic and predictive biomarkers in various cancer types. The main goal of the present study was to investigate the ERCC1 and RRM1 expression and their potential impact on outcome in this tumor. A series of 73 MPM, mainly treated with a platin-based regimen, was collected and the immunohistochemistry tests were performed to assess ERCC1 and RRM1 expression. In addition, a multiplex immunohistochemistry has been validated to detect simultaneously the 2 proteins on the same slide. In our series, 36 of 73 cases showed ERCC1 expression and 55 of 73 showed RRM1 expression. The double immunohistochemical staining showed the coexpression of ERCC1/RRM1 in 34 of 73 cases. A significant association between ERCC1 and RRM1 expression was observed in our series (P<0.05). Patients with ERCC1/RRM1 coexpression experienced shorter median overall survival (6.6 vs. 13.8 mo, log-rank=7688; P=0.006). Our results suggest that the coexpression of ERCC1/RRM1 could define a group of MPM patients with the worst prognosis who should need likely alternative treatment. In conclusion, we propose the putative usefulness of ERCC1/RRM1 coexpression as prognostic biomarkers for overall survival in MPM.
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http://dx.doi.org/10.1097/PAI.0000000000000869DOI Listing
March 2021

Primary and secondary cutaneous angiosarcoma: Distinctive clinical, pathological and molecular features.

Ann Diagn Pathol 2020 Oct 15;48:151597. Epub 2020 Aug 15.

Pathology Unit, Department of Mental and Physical Health and Preventive Medicine, Università degli Studi della Campania "Luigi Vanvitelli", via Luciano Armanni 20, 80100 Naples, Italy. Electronic address:

Angiosarcomas are ubiquitous neoplasms involving both cutaneous and soft tissue and visceral locations. Accumulating biomolecular evidences suggest that cutaneous angiosarcomas are distinctive entities with molecular, clinical and pathological peculiarities. Despite several ongoing clinical trials with promising therapeutic agents, the prognosis of cutaneous angiosarcomas is dismal and survival still rely on early diagnosis and surgery. An accurate diagnosis and the knowledge of the underlying molecular landscape are therefore essential to improve the prognosis. We detail the molecular, clinical, dermoscopic, morphological and prognostic features of cutaneous angiosarcoma. Although the molecular landscape of cutaneous angiosarcoma is not completely understood, accumulating evidences suggest that there are characteristic molecular alterations including dysregulation of angiogenesis and several complex molecular pathways. Secondary cutaneous angiosarcomas, arising in correlation with chronic lymphedema and ionizing radiation, have different molecular hallmarks, which are also leading to the first diagnostic applications. The diagnosis of cutaneous angiosarcoma may be challenging, as well-differentiated forms can be hard to distinguish from benign and low-grade vascular neoplasms, while poorly differentiated forms can be easily confounded with other non-vascular high-grade neoplasms. An accurate and early diagnosis, which is mandatory to ensure the best survival for the patients, is mainly based on morphological hallmarks.
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http://dx.doi.org/10.1016/j.anndiagpath.2020.151597DOI Listing
October 2020

AXL is a predictor of poor survival and of resistance to anti-EGFR therapy in RAS wild-type metastatic colorectal cancer.

Eur J Cancer 2020 10 17;138:1-10. Epub 2020 Aug 17.

Department of Precision Medicine, Università Degli Studi Della Campania "Luigi Vanvitelli", Naples, Italy. Electronic address:

Background: RAS mutations are the only validated biomarkers in metastatic colorectal cancer (mCRC) for anti-epidermal growth factor receptor (EGFR) therapy. Limited clinical information is available on AXL expression, marker of epithelial to mesenchymal transition, in mCRC.

Methods: AXL was retrospectively assessed by immunohistochemistry in 307 patients. RAS wild-type (WT) patients (N = 136) received first-line anti-EGFR-based therapy; RAS mutant patients (N = 171) received anti-angiogenic-based regimens. Preclinical experiments were performed using human RAS WT CRC cell lines and xenograft models. AXL RNA levels were assessed in a cohort of patients with available samples at baseline and at progression to anti-EGFR treatment and in the GSE5851 dataset.

Results: AXL was expressed in 55/307 tumour tissues, correlating with worse survival in the overall population (AXL-positive, 23.7 months; AXL-negative, 30.8 months; HR, 1.455, P = 0.032) and in RAS WT patients (AXL-positive, 23.0 months; AXL-negative, 35.8 months; HR,1.780, P = 0.032). Progression-free survival (PFS) in the RAS WT cohort was shorter in the AXL-positive cohort (6.2 months versus 12.1 months; HR, 1.796, P = 0.013). Three-dimensional cultures obtained from a patient following anti-EGFR therapy resulted AXL-positive, showing resistance to anti-EGFR drugs and sensitivity to AXL inhibition. AXL transfection in CRC cell lines induced AXL overexpression and resistance to the EGFR blockade. At progression to cetuximab, 2/10 SW48-tumour xenograft mice showed AXL expression. Consistently, AXL RNA levels increased in 5/7 patients following anti-EGFR therapy. Moreover, in the GSE5851 dataset higher AXL RNA levels correlated with worse PFS with cetuximab in KRAS-exon2 WT chemorefractory patients.

Conclusions: AXL is a marker of poor prognosis in mCRC with consistent clinical and preclinical evidences of involvement in primary and acquired resistance to anti-EGFR drugs in RAS WT patients.
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http://dx.doi.org/10.1016/j.ejca.2020.07.010DOI Listing
October 2020

Cytological diagnosis of Xp11 translocation renal cell carcinoma: An unusual suspect in bone metastases from unknown primary malignancies.

Diagn Cytopathol 2021 Jan 18;49(1):11-17. Epub 2020 Aug 18.

Pathology Unit, Department of Mental and Physical Health and Preventive Medicine, Università della Campania "Luigi Vanvitelli", Naples, Italy.

Background: Renal cell carcinoma (RCC) constitutes 3% of all cancers, with a higher incidence in patients with age between 60 and 70 years. RCC frequently present as a metastatic tumor at diagnosis, and bones represent one of the most frequent sites. Many cases, mainly in young patients, includes the Xp11 translocation RCC. The cytological diagnosis of Xp11 translocation RCC in adult population it is rarely performed, likely for the morphological overlap with other adult renal cell carcinoma subtypes.

Methods: We retrospectively analyze a series of 92 adult patients with metastatic bone tumors, diagnosed on fine-needle aspiration cytology (FNAC) samples, focusing mainly on the cytological, immunophenotypic and molecular features of Xp11 translocation RCC.

Results: In our series 6 of 92 (6.5%) cases were metastatic RCC (mRCC), among them 2 cases were metastasis from Xp11translocation RCC. Those cases showed a bloody background, with several groups of atypical cells arranged in syncytial groups or in papillary groups composed by atypical cells with abundant cytoplasm, with scattered clear cells. TFE3 was positive on immunocytochemical analysis and specific translocation t(Xp11.23) was detected by FISH analysis.

Conclusions: In adult patients with mRCC, it is necessary to consider also Xp11 translocation RCC among the diagnostic hypotheses. FNAC represents a valid tool to investigate bone lesions but cytological features of Xp11 translocation RCC are still poorly described and must necessarily be better defined.
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http://dx.doi.org/10.1002/dc.24587DOI Listing
January 2021

Multiplex HPV RNA in situ hybridization/p16 immunohistochemistry: a novel approach to detect papillomavirus in HPV-related cancers. A novel multiplex ISH/IHC assay to detect HPV.

Infect Agent Cancer 2020 14;15:46. Epub 2020 Jul 14.

Pathology Unit, Department of Mental and Physical Health and Preventive Medicine, University of Campania "L. Vanvitelli", 80138 Naples, Italy.

Background: High-risk human papillomavirus (HR-HPV) is notoriously associated with tumor progression in a broad spectrum of malignancies. Detection of HR-HPV is clinically important in the management of HPV-related carcinomas, particularly in cervical cancer and oropharyngeal squamous cell carcinoma (OPSCC). Several methods for HPV detection are currently available including Polymerase chain reaction (PCR)-based techniques, DNA in situ hybridization (ISH), RNA ISH, and p16 immunohistochemistry (IHC). Currently, the guidelines for HPV detection in cervical carcinoma are available, while no clear consensus has not yet been reached on the gold standard for HPV testing in OPSCC. Multimodality testing could help to reliably identify patients with transcriptionally active high-risk HPV-positive.

Methods: We propose a multiplex approach carrying out HPV RNA ISH and p16 IHC on the same slide to detect simultaneously HPV E6/E7 transcripts and p16INK4a overexpression. We tested this assay in two different series one of the cervical cancers with p16-positive, as control, and the other of oropharyngeal squamous cell carcinomas with blind p16 status.

Results: The multiplex HPV RNA ISH /p16 IHC results in the series both of the cervical cancers and the oral-oropharyngeal cancers were fully concordant with the previous results achieved through the classic p16 IHC and HPV RNA scope carried out on two different slides.

Conclusions: Our results suggesting several advantages of this technical approach, namely an easy interpretation fully in the light field, the feasibility in formalin-fixed paraffin-embedded tissue sections, complete automation and a potential wide spreadable for routine testing in several clinical laboratories.
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http://dx.doi.org/10.1186/s13027-020-00310-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7362547PMC
July 2020

Unproductive Effects of ALK Gene Amplification and Copy Number Gain in Non-Small-Cell Lung Cancer. ALK Gene Amplification and Copy Gain in NSCLC.

Int J Mol Sci 2020 Jul 12;21(14). Epub 2020 Jul 12.

Department of Mental and Physical Health and Preventive Medicine, Pathology Unit, University of Campania "L. Vanvitelli", 80138 Naples, Italy.

The Anaplastic Lymphoma Kinase (ALK) gene is known to be affected by several genetic alterations, such as rearrangement, amplification and point mutation. The main goal of this study was to comprehensively analyze amplification (-A) and gene copy number gain () in a large cohort of non-small-cell lung cancer (NSCLC) patients in order to evaluate the effects on mRNA and protein expression. locus number status was evaluated in 578 NSCLC cases by fluorescence in situ hybridization (FISH). In addition, ALK immunohistochemistry and ALK mRNA in situ hybridization were performed. Out of 578 cases, 17 cases showed -A. In addition, 14 cases presented K-CNG and 72 cases presented chromosome 2 polyploidy. None of those carrying -A and -CNG showed either ALK immunohistochemical expression or ALK mRNA expression through in situ hybridization. We observed a high frequency of extra copies of the gene. : Our findings demonstrated that -A is not involved in mRNA production and consequently is not involved in protein production; these findings support the hypothesis that -A might not play a role in the pathogenesis of NSCLC, underlining the absence of a specific clinical application.
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http://dx.doi.org/10.3390/ijms21144927DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7404032PMC
July 2020

Interventional cytopathology in the COVID-19 era.

Cytopathology 2020 11 9;31(6):509-513. Epub 2020 Aug 9.

Division of Pathology, Department of Mental and Physical Health and Preventive Medicine, Università degli Studi della Campania "Luigi Vanvitelli", Naples, Italy.

Introduction: The dramatic spread of COVID-19 has raised many questions about cytological procedures performed in and out of the laboratories all over the world.

Methods: We report a heterogeneous series of fine needle aspirations performed during the period of phase 1 of the lockdown for the COVID-19 pandemic to describe our experience and measures taken during this period.

Results: A total of 48 fine needle aspirations (ultrasound, computed tomography and endoscopic ultrasound guided) were processed and reported.

Conclusions: Pre-existing procedures have been modified to allow healthcare professionals to work safely ensuring patients the necessary assistance with samples suitable for cellularity, fixation and staining for an accurate cytological diagnosis.
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http://dx.doi.org/10.1111/cyt.12886DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7404649PMC
November 2020

A case of primary cutaneous B-cell lymphoma with immature features in an old man. Diffuse large B-cell lymphoma with immature features or B-cell lymphoblastic lymphoma?

J Cutan Pathol 2021 Apr 9;48(4):535-540. Epub 2020 Sep 9.

Oncology and Hematology Unit, Department of Precision Medicine, University of Campania "Luigi Vanvitelli", Naples, Italy.

Primary cutaneous B-cell lymphomas are a heterogeneous group of lymphoid neoplasms primarily occurring in the skin. Although most cases are represented by primary cutaneous follicle center cell lymphoma, primary cutaneous marginal zone lymphoma and leg-type diffuse large B-cell lymphoma, other diffuse large B-cell lymphomas and B-cell lymphoblastic lymphoma may rarely present primarily in the skin. In this setting, the presence of histopathologic and immunohistochemical features of cellular immaturity is exceedingly rare and may represent a diagnostic challenge. We present the first case of a primary cutaneous diffuse large B-cell lymphoma characterized by diminished expression of CD45, expression of TdT and rearrangement of MYC gene. The differential diagnosis mainly included B-cell lymphoblastic lymphoma, and required the genetic analysis of heavy chain (IGH) gene rearrangements.
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http://dx.doi.org/10.1111/cup.13795DOI Listing
April 2021