Publications by authors named "Massimo Mascolo"

142 Publications

Detection of CAF-1/p60 in peripheral blood as a potential biomarker of HNSCC tumors.

Oral Oncol 2021 Jul 5;120:105367. Epub 2021 Jul 5.

Department of Advanced Biomedical Sciences, Pathology Section, University of Naples "Federico II", Naples, Italy.

To date, a very small number of serum biomarkers have been identified for clinical use in squamous carcinomas of the head and neck region. Chromatin Assembly Factor-1 (CAF-1) heterotrimeric complex subunit CAF1/p60 expression levels have been reported to be of prognostic value in Oral Squamous Cell Carcinoma (OSCC), as well as in other human solid tumors. Here our aim was to detect and quantify CAF1/p60 in the peripheral blood of Head and Neck Squamous Cell Carcinoma (HNSCC) patients, and to investigate the possible associations between serum concentration of CAF-1/p60 and HNSCC tumors. A total of 63 HNSCC patients (51 OSCC, 8 OPSCC, 3 laryngeal SCC, and 1 rhinopharynx SCC) and 30 healthy controls were enrolled. The serum levels of CAF-1/p60 were measured by ELISA assay before and after surgery. Serum CAF-1/p60 concentration resulted significantly higher in cancer patients, compared with healthy controls, in pre-surgery samples (P < 0.05). Serum levels of CAF-1/p60 significantly decreased in serum samples taken after surgery (P < 0.05). Our results demonstrated that CAF-1/p60 may be detected in serum, suggesting a role for CAF-1/p60 as potential soluble biomarkers in HNSCC tumors.
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http://dx.doi.org/10.1016/j.oraloncology.2021.105367DOI Listing
July 2021

Bilateral Chilblain-like Lesions of the Toes Characterized by Microvascular Remodeling in Adolescents During the COVID-19 Pandemic.

JAMA Netw Open 2021 06 1;4(6):e2111369. Epub 2021 Jun 1.

Department of Translational Medical Sciences, Section of Pediatrics, University of Naples Federico II, Naples, Italy.

Importance: Chilblain-like lesions have been one of the most frequently described cutaneous manifestations during the COVID-19 pandemic. Their etiopathogenesis, including the role of SARS-CoV-2, remains elusive.

Objective: To examine the association of chilblain-like lesions with SARS-CoV-2 infection.

Design, Setting, And Participants: This prospective case series enrolled 17 adolescents who presented with chilblain-like lesions from April 1 to June 30, 2020, at a tertiary referral academic hospital in Italy.

Main Outcomes And Measures: Macroscopic (clinical and dermoscopic) and microscopic (histopathologic) analysis contributed to a thorough understanding of the lesions. Nasopharyngeal swab, serologic testing, and in situ hybridization of the skin biopsy specimens were performed to test for SARS-CoV-2 infection. Laboratory tests explored signs of systemic inflammation or thrombophilia. Structural changes in peripheral microcirculation were investigated by capillaroscopy.

Results: Of the 17 adolescents (9 [52.9%] male; median [interquartile range] age, 13.2 [12.5-14.3] years) enrolled during the first wave of the COVID-19 pandemic, 16 (94.1%) had bilaterally localized distal erythematous or cyanotic lesions. A triad of red dots (16 [100%]), white rosettes (11 [68.8%]), and white streaks (10 [62.5%]) characterized the dermoscopic picture. Histologic analysis revealed a remodeling of the dermal blood vessels with a lobular arrangement, wall thickening, and a mild perivascular lymphocytic infiltrate. SARS-CoV-2 infection was excluded by molecular and serologic testing. In situ hybridization did not highlight the viral genome in the lesions.

Conclusions And Relevance: This study delineated the clinical, histologic, and laboratory features of chilblain-like lesions that emerged during the COVID-19 pandemic, and its findings do not support their association with SARS-CoV-2 infection. The lesions occurred in otherwise healthy adolescents, had a long but benign course to self-resolution, and were characterized by a microvascular remodeling with perivascular lymphocytic infiltrate but no other signs of vasculitis. These results suggest that chilblain-like lesions do not imply a concomitant SARS-CoV-2 infection. Ongoing studies will help clarify the etiopathogenic mechanisms.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.11369DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193438PMC
June 2021

Expression Profile of Stemness Markers CD138, Nestin and Alpha-SMA in Ameloblastic Tumours.

Int J Environ Res Public Health 2021 04 8;18(8). Epub 2021 Apr 8.

Melbourne Dental School, University of Melbourne, 720 Swanston Street, Carton, VIC 3053, Australia.

Ameloblastic carcinoma is a rare malignant odontogenic neoplasm with a poor prognosis. It can arise de novo or from a pre-existing ameloblastoma. Research into stemness marker expression in ameloblastic tumours is lacking. This study aimed to explore the immunohistochemical expression of stemness markers nestin, CD138, and alpha-smooth muscle actin (alpha-SMA) for the characterisation of ameloblastic tumours. Six cases of ameloblastoma and four cases of ameloblastic carcinoma were assessed, including one case of ameloblastic carcinoma arising from desmoplastic ameloblastoma. In all tumour samples, CD138 was positive, whilst alpha-SMA was negative. Nestin was negative in all but one tumour sample. Conversely, the presence or absence of these markers varied in stroma samples. Nestin was observed in one ameloblastic carcinoma stroma sample, whilst CD138 was positive in one ameloblastoma case, one desmoplastic ameloblastoma case, and in two ameloblastic carcinoma stroma samples. Finally, alpha-SMA was found positive only in the desmoplastic ameloblastoma stroma sample. Our results suggest nestin expression to be an indicator for ameloblastic carcinoma, and CD138 and alpha-SMA to be promising biomarkers for the malignant transformation of ameloblastoma. Our data showed that nestin, CD138, and alpha-SMA are novel biomarkers for a better understanding of the origins and behaviour of ameloblastic tumours.
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http://dx.doi.org/10.3390/ijerph18083899DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8068135PMC
April 2021

Rituximab-Containing Risk-Adapted Treatment Strategy in Nodular Lymphocyte Predominant Hodgkin Lymphoma: 7-Years Follow-Up.

Cancers (Basel) 2021 Apr 7;13(8). Epub 2021 Apr 7.

Department of Clinical Medicine and Surgery, Hematology Section, University of Naples "Federico II", Via Sergio Pansini, 5, 80131 Naples, Italy.

Background: Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is a rare variant of HL that accounts for 5% of all HL cases. The expression of CD20 on neoplastic lymphocytes provides a suitable target for novel treatments based on Rituximab. Due to its rarity, consolidated and widely accepted treatment guidelines are still lacking for this disease.

Methods: Between 1 December 2007 and 28 February 2018, sixteen consecutive newly diagnosed adult patients with NLPHL received Rituximab (induction ± maintenance)-based therapy, according to the baseline risk of German Hodgkin Study Group prognostic score system. The treatment efficacy and safety of the Rituximab-group were compared to those of a historical cohort of 12 patients with NLPHL who received Doxorubicin, Bleomycin, Vinblastine, Dacarbazine (ABVD) chemotherapy followed by radiotherapy (RT), if needed, according to a similar baseline risk. The primary outcome was progression-free survival (PFS) and secondary outcomes were overall survival (OS) and side-effects (according to the Common Terminology Criteria for Adverse Events, v4.03).

Results: After a 7-year follow-up (range, 1-11 years), PFS was 100% for patients treated with the Rituximab-containing regimen versus 66% for patients of the historical cohort ( = 0.036). Four patients in the latter group showed insufficient response to therapy. The PFS for early favorable and early unfavorable NLPHLs was similar between treatment groups, while a better PFS was recorded for advanced-stages treated with the Rituximab-containing regimen. The OS was similar for the two treatment groups. Short- and long-term side-effects were more frequently observed in the historical cohort. Grade ≥3 neutropenia was more frequent in the historical cohort compared with the Rituximab-group (58.3% vs. 18.7%, respectively; = 0.03). Long-term non-hematological toxicities were observed more frequently in the historical cohort.

Conclusion: Our results confirm the value of Rituximab in NLPHL therapy and show that Rituximab (single-agent) induction and maintenance in a limited-stage, or Rituximab with ABVD only in the presence of risk factors, give excellent results while sparing cytotoxic agent- and/or RT-related damage. Furthermore, Rituximab inclusion in advanced-stage therapeutic strategy seems to improve PFS compared to conventional chemo-radiotherapy.
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http://dx.doi.org/10.3390/cancers13081760DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8067750PMC
April 2021

Tissue Expression of Carbonic Anhydrase IX Correlates to More Aggressive Phenotype of Basal Cell Carcinoma.

Front Oncol 2021 25;11:659332. Epub 2021 Mar 25.

Pathology Unit, Department of Advanced Biomedical Sciences, University of Naples "Federico II", Naples, Italy.

Basal cell carcinoma (BCC) is the most common cancer in the white-skinned population accounting for about 15% of all neoplasms. Its incidence is increasing worldwide, at a rate of about 10% per year. BCC, although infrequently metastasizing, very often causes extensive tissue losses, due to the high propensity toward stromal infiltration, particularly in its dedifferentiated forms, with disfiguring and debilitating results. To date, there still is limited availability of therapeutic treatments alternative to surgery. We evaluated the immunohistochemical expression of the carbonic anhydrase IX (CAIX), one of the main markers of tissue hypoxia, in a set of 85 archived FFPE BCC tissues, including the main subtypes, with different clinical outcomes, to demonstrate a possible relationship between hypoxic phenotype and biological aggressiveness of these neoplasms. Our results showed that the expression level of the CAIX protein contributes to the stratification of BCC in the different risk classes for recurrence. We hypothesize for CAIX a potential therapeutic role as a target therapy in the treatment of more aggressive BCCs, thus providing an alternative to surgical and pharmacological therapy with Hedgehog inhibitors, a promising example of target therapy in BCCs.
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http://dx.doi.org/10.3389/fonc.2021.659332DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027352PMC
March 2021

Mycosis fungoides (CTCL) associated with colorectal adenocarcinoma. A rare case of combined response to neoadjuvant therapy.

Ann Ital Chir 2021 Mar 26;10. Epub 2021 Mar 26.

Mycosis fungoides (MF) is a well-known and common form of cutaneous T-cell lymphoma (CTCL), composed of malignant proliferation of CD4+CD45Ro+helper memory T cells. In the patient with MF, the incidence of secondary malignancies is higher than general population but very few cases with both MF and colorectal adenocarcinoma have been reported. Herein we describe a case of MF occurring in a 64-year-old man and followed, five months later, by a diagnosis of colorectal adenocarcinoma. Of notice, simultaneous regression of both rectal mass and cutaneous MF manifestations was observed after administration of chemioradiation therapy prior to rectal surgery. The patient is alive and in stable clinical remission at eight years from the diagnosis. KEY WORDS: CTCL, Colorectal adenocarcinoma, Mycosis fungoides, PUVA.
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March 2021

Prognostic Significance of CD30 in Transformed Mycosis Fungoides.

Am J Clin Pathol 2021 Mar 26. Epub 2021 Mar 26.

Department of Advanced Biomedical Sciences, Pathology Section  Naples, Italy.

Objectives: Several studies suggested that CD30 expression is a favorable prognostic marker in transformed mycosis fungoides (tMF). However, evidence in this field is still unclear. This systematic review and meta-analysis aimed to evaluate the prognostic significance of CD30 in tMF.

Methods: Electronic databases were searched from their inception to June 2020 for all studies assessing the prognostic value of CD30 in tMF. Pooled hazard ratio (HR) for death was calculated; a P value less than .05 was considered significant. Inconsistency index (I2) was used to assess statistical heterogeneity among studies.

Results: Seven studies with 323 patients were included. CD30 expression in tMF was significantly associated with a decreased hazard of death both on univariate (HR, 0.459; 95% confidence interval [CI], 0.319-0.660; P < .001) and multivariate analysis (HR, 0.503; 95% CI, 0.345-0.734; P < .001), and the statistical heterogeneity among studies was null in all analyses (I2 = 0%).

Conclusions: tMF cases with CD30 expression in large cells have a hazard of death two times lower than CD30-negative cases.
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http://dx.doi.org/10.1093/ajcp/aqaa261DOI Listing
March 2021

Does endometrial morular metaplasia represent odontogenic differentiation?

Virchows Arch 2021 Mar 5. Epub 2021 Mar 5.

Pathology Unit, Department of Advanced Biomedical Sciences, University of Naples "Federico II", Naples, Italy.

The nature of endometrial morular metaplasia (MorM) is still unknown. The nuclear β-catenin accumulation and the not rare ghost cell keratinization suggest a similarity with hard keratin-producing odontogenic and hair matrix tumors rather than with squamous differentiation. We aimed to compare MorM to hard keratin-producing tumors. Forty-one hard keratin-producing tumors, including 26 hair matrix tumors (20 pilomatrixomas and 6 pilomatrix carcinomas) and 15 odontogenic tumors (adamantinomatous craniopharyngiomas), were compared to 15 endometrioid carcinomas with MorM with or without squamous/keratinizing features. Immunohistochemistry for β-catenin, CD10, CDX2, ki67, p63, CK5/6, CK7, CK8/18, CK19, and pan-hard keratin was performed; 10 cases of endometrioid carcinomas with conventional squamous differentiation were used as controls. In adamantinomatous craniopharyngiomas, the β-catenin-accumulating cell clusters (whorl-like structures) were morphologically similar to MorM (round syncytial aggregates of bland cells with round-to-spindled nuclei and profuse cytoplasm), with overlapping squamous/keratinizing features (clear cells with prominent membrane, rounded squamous formations, ghost cells). Both MorM and whorl-like structures consistently showed positivity for CD10 and CDX2, with low ki67; cytokeratins pattern was also overlapping, although more variable. Hard keratin was focally/multifocally positive in 8 MorM cases and focally in one conventional squamous differentiation case. Hair matrix tumors showed no morphological or immunophenotypical overlap with MorM. MorM shows wide morphological and immunophenotypical overlap with the whorl-like structures of adamantinomatous craniopharyngiomas, which are analogous to enamel knots of tooth development. This suggests that MorM might be an aberrant mimic of odontogenic differentiation.
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http://dx.doi.org/10.1007/s00428-021-03060-2DOI Listing
March 2021

Prognostic value of Bcl2 and p53 in Hodgkin lymphoma: A systematic review and meta-analysis.

Pathol Res Pract 2021 Mar 8;219:153370. Epub 2021 Feb 8.

Department of Advanced Biomedical Sciences, Pathology Section, University of Naples "Federico II", Naples, Italy. Electronic address:

Aims: Several studies suggested that high expression of Bcl2 and/or p53 in Hodgkin/Reed-Sternberg cells is an unfavorable prognostic factor in Hodgkin lymphoma (HL). However, results in this field appear contrasting. We aimed to assess the prognostic value of p53 and Bcl2 in HL through a systematic review and meta-analysis.

Methods: Electronic databases were searched from January 2000 to December 2020 for all studies assessing the prognostic value of p53 and Bcl2 in HL. The association of high p53 or Bcl2 expression with overall survival (OS), progression-free survival (PFS) and response to treatment was assessed by using hazard ratio (HR) and odds ratio (OR).

Results: Eighteen studies were included. Bcl2 overexpression was significantly associated with decreased PFS (HR = 2.202; p < 0.0001), while the associations with decreased OS (HR = 1.565; p = 0.257) and refractoriness to treatment (OR = 0.482; p = 0.068) were non-significant. p53 overexpression was not significantly associated with refractoriness to treatment (OR = 0.904; p = 0.155); the analysis of OS and PFS was not feasible, but published data suggested the absence of a significant association.

Conclusions: In HL, Bcl2 overexpression is associated with decreased PFS, while a significant prognostic value could not be demonstrated for p53. Defining optimal criteria for interpreting Bcl2 and p53 immunostaining is necessary to draw definitive conclusions.
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http://dx.doi.org/10.1016/j.prp.2021.153370DOI Listing
March 2021

A rare case of bilateral conjunctival Kaposi's sarcoma in a HIV-negative patient.

Am J Ophthalmol Case Rep 2021 Mar 31;21:101024. Epub 2021 Jan 31.

Department of Neurosciences, Reproductive Sciences and Dentistry, University of Naples Federico II, Naples, Italy.

Purpose: Kaposi's sarcoma (KS) is a rare multi-centric vascular neoplasm, first described by Moritz Kaposi in 1872. It can appear in four different forms: classic, endemic, HIV-related and post-transplant form. We present an uncommon case of seronegative HIV infection patient with skin KS involving conjunctiva of both eyes.

Observations: Firstly, right eye lesions were surgically removed. Subsequently, the patient was administered with systemic chemotherapy (doxorubicin) to treat both skin and left eye lesions. No signs of recurrence were observed at 20 months' follow-up.

Conclusions: Both eyes involvement in KS is rarely described in scientific literature. Both surgery and chemotherapy could be considered valid treatment options for conjunctival KS.
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http://dx.doi.org/10.1016/j.ajoc.2021.101024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7868732PMC
March 2021

Chemotherapy-Induced Remission of Steroid-Dependent Ulcerative Colitis Associated With Rectal Hodgkin Lymphoma.

Inflamm Bowel Dis 2021 Jun;27(7):e81-e82

Gastroenterology, Department of Clinical Medicine and Surgery, University Federico II of Naples, Naples, Italy.

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http://dx.doi.org/10.1093/ibd/izab010DOI Listing
June 2021

Borrelia burgdorferi in primär kutanen Lymphomen: eine systematische Übersicht und Metaanalyse.

J Dtsch Dermatol Ges 2020 Dec;18(12):1379-1386

Pathology Section, Department of Advanced Biomedical Sciences, University of Naples "Federico II", Naples, Italy.

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http://dx.doi.org/10.1111/ddg.14289_gDOI Listing
December 2020

Hysteroscopic Intact Removal of Angular and Caesarean Scar Pregnancy: A Novel and Markedly Less Invasive Surgical Treatment.

Gynecol Obstet Invest 2021 10;86(1-2):55-62. Epub 2020 Dec 10.

Gynecology and Obstetrics Unit, Department of Medicine, Surgery and Dentistry "Scuola Medica Salernitana", University of Salerno, Baronissi (SA), Italy.

Introduction: Ectopic pregnancy is the most common cause of mortality during the first trimester of pregnancy, and intrauterine ectopic pregnancies show significantly higher morbidity and mortality than extrauterine ones. Despite being less invasive, safety and effectiveness of the hysteroscopic treatment are still unclear. Moreover, such approach is not standardized. We aimed to evaluate safety and effectiveness of hysteroscopic intact removal of angular or cesarean section scar pregnancies, defining a novel and markedly less invasive hysteroscopic technique with a 5-mm Bettocchi hysteroscope or a 3.5-mm Versascope hysteroscope.

Materials And Methods: Medical records and video archives were reviewed for all the patients with angular or caesarean scar pregnancies treated with hysteroscopic intact removal technique from January 2000 to December 2018 at our Department. Success and complication rates were assessed.

Results: Four patients with angular (n = 1) or cesarean scar pregnancy (n = 3) met inclusion criteria. Case #1 was treated with bipolar resectoscope, cases #2 and #3 with 5-mm Bettocchi hysteroscope, and case #4 with 3.5-mm Versascope hysteroscope. Cases #2-4 did not require cervical dilatation. Before hysteroscopic treatment, cases #2-4 underwent unsuccessful medical therapy with multiple-dose methotrexate. Hysteroscopic treatment success rate was 100%, while complication rate was 0%. All patients were treated with a novel technique: hysteroscopic intact removal of angular or cesarean scar pregnancies. Such technique was described step-by-step.

Conclusions: Hysteroscopic treatment of angular and cesarean scar pregnancies may be a safe and effective minimally invasive option. The novel technique of hysteroscopic intact removal technique may allow a markedly less invasive approach.
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http://dx.doi.org/10.1159/000510510DOI Listing
May 2021

Expression of P16INK4a in Uveal Melanoma: New Perspectives.

Front Oncol 2020 13;10:562074. Epub 2020 Oct 13.

Department of Advanced Biomedical Sciences, Pathology Section, University of Naples Federico II, Naples, Italy.

Uveal melanoma (UM) is the most common intraocular tumor in adults. Despite sharing the name and similar morphological features with cutaneous melanoma (CM), it is an entirely different neoplasia with a particular genetic background and clinical behavior. CDKN2A is a gene located at chromosome 9p21, encoding for P16INK4a and P14(ARF) proteins, whose role as a tumor suppressor has been clearly defined in many malignant tumors. CDKN2A frequently presents germline mutations in familial CM and epigenetic downregulation in a considerable percentage of sporadic CM. It has been hypothesized that CDKN2A alterations are early events in CM development, playing a central role in the malignant transformation of melanocytes. Alterations of the CDKN2A gene reduce the expression of P16INK4a in most CM subtypes. Immunohistochemical evaluation of P16INK4a is currently used, in association with Ki67 and HMB45, in pathology practice to discriminate between dysplastic nevi and melanoma. On the other hand, CKDN2A is rarely mutated in UM, and the immunohistochemical expression of P16INK4a has only been reported in small case series. We tested P16INK4a expression on paraffin-embedded tissue sections from 9 tissue microarrays (TMAs), built with 2 mm cores derived from 133 uveal melanoma FFPE blocks, collected from 1990 to 2018, and from selected paraffin-blocks of 3 UM liver metastases. The immunohistochemical expression of P16INK4a was assessed with a visual evaluation by light microscopy and then with a digital approach. Both approaches, with an acceptable concordance rate, revealed P16INK4a expression in a large proportion of UM cases and all liver metastases, opening new possibilities of using it in the differential diagnosis between cutaneous and uveal melanoma metastases in cases of unknown primary tumor or patients with two different primary melanomas.
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http://dx.doi.org/10.3389/fonc.2020.562074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7590828PMC
October 2020

Role of chromatin assembly factor-1/p60 and poly [ADP-ribose] polymerase 1 in mycosis fungoides.

Virchows Arch 2021 May 24;478(5):961-968. Epub 2020 Oct 24.

Department of Advanced Biomedical Sciences, Pathology Section, School of Medicine, University of Naples "Federico II", Via Sergio Pansini, 5, 80131, Naples, Italy.

Mycosis fungoides (MF) represents the most common type of cutaneous lymphoma. In the majority of patients, the disease has a slow evolution and a protracted course; however, a subset of patients shows poor oncologic outcomes. Unfortunately, there are no reliable prognostic markers for MF, and the currently available treatments are only effective in a minority of patients. This study aimed to evaluate the expression and clinical significance of PARP-1 and CAF-1/p60 in MF. Sixty-four MF representatives of the different stages of disease were assessed by immunohistochemistry for PARP-1 and CAF-1/p60. The association of PARP-1 and CAF-1/p60 with the MF stage and outcome was assessed by using Fisher's exact test and Kaplan-Meier survival analysis with the Log-rank test; a p value < 0.05 was considered significant. PARP-1 was overexpressed in 57.9% of MF and was significantly associated with a MF stage > II (p = 0.034) but not with the risk of death (p = 0.237). CAF-1/p60 was overexpressed in 26.8% of MF and was significantly associated with decreased overall survival (p < 0.001) but not with the MF stage (p = 1). A significant association was found between PARP-1 overexpression and CAF-1/p60 overexpression (p = 0.0025). Simultaneous overexpression of PARP-1 and CAF-1/p60 was significantly associated with decreased overall survival (p < 0.001), although less strongly than CAF-1/p60 alone (χ = 14.916 vs 21.729, respectively). In MF, PARP-1 is overexpressed in advanced stages, while CAF-1/p60 is overexpressed in the cases with shorter overall survival, appearing as a significant prognostic marker. A role for PARP-1 inhibitors and anti-CAF-1/p60 targeted therapy may be reasonably hypothesized in MF.
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http://dx.doi.org/10.1007/s00428-020-02952-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099834PMC
May 2021

A rare evolution of porokeratosis.

G Ital Dermatol Venereol 2020 Oct 21. Epub 2020 Oct 21.

Pathology Section, Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy.

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http://dx.doi.org/10.23736/S0392-0488.20.06630-4DOI Listing
October 2020

Borrelia burgdorferi in primary cutaneous lymphomas: a systematic review and meta-analysis.

J Dtsch Dermatol Ges 2020 Dec 8;18(12):1379-1384. Epub 2020 Oct 8.

Pathology Section, Department of Advanced Biomedical Sciences, University of Naples "Federico II", Naples, Italy.

Background: The association between Borrelia burgdorferi and primary cutaneous lymphoma is still unclear. This systematic review and meta-analysis aims to define the association of Borrelia burgdorferi with primary cutaneous lymphoma and its different entities.

Methods: Electronic databases were searched for all studies that assessed the presence of Borrelia burgdorferi DNA in specimens of primary cutaneous lymphoma. The association between Borrelia and primary cutaneous lymphomas was assessed with an odds ratio (significant p < 0.05); cutaneous specimens with no lymphoproliferative disorders were used as controls. A secondary analysis was performed to assess the prevalence of Borrelia infection in different lymphoma entities.

Results: Ten studies with 506 primary cutaneous lymphomas and 201 controls were included. The prevalence of Borrelia DNA positivity was highly heterogeneous among studies from different regions. Borrelia DNA positivity was significantly associated with primary cutaneous lymphomas (odds ratio = 10.88; p < 0.00001). The prevalence of Borrelia DNA positivity was similar among different entities (marginal zone: 7.3 %; follicular: 8.1 %; diffuse large B-cell: 7.5 %; mycosis fungoides: 8 %).

Conclusions: Borrelia burgdorferi is significantly associated with primary cutaneous lymphomas, with no differences among the several lymphoma entities (both B-cell and T-cell), but with strong geographical differences. Molecular testing for Borrelia would be justified in patients with primary cutaneous lymphoma from endemic areas.
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http://dx.doi.org/10.1111/ddg.14289DOI Listing
December 2020

Primary cutaneous anaplastic large-cell lymphoma of the eyelid: report of two cases and review of the literature.

Orbit 2020 Oct 1:1-7. Epub 2020 Oct 1.

Department of Neurosciences, Reproductive Sciences and Dentistry, University of Naples Federico II, Naples, Italy.

Purpose: Two new cases of primary cutaneous CD30+ anaplastic large-cell lymphoma (cALCL) of the eyelid are reported; these are analysed alongside existing cases to identify challenges relating to the diagnosis and management of such rare lesions.

Material And Methods: A review of existing literature on the PubMed database is conducted using the keywords: 'eyelid lymphoid proliferations', 'lymphoma of the eyelid', and 'primary cutaneous CD30+, ALK-anaplastic large-cell lymphoma of the eyelid'. Two new cases of cALCL are reported. Cases where patients present solely with a nodular periocular lesion are analysed for recurrence and survival rate.

Results: Two new patients with a painless ulcerated nodule on the upper eyelid receive a confirmed diagnosis of cALCL after undergoing an excisional biopsy. The first, elderly patient has spontaneous remission; the second patient, with a concomitant chronic infection of hepatitis C virus (HCV), presents a more diffuse disease at the onset and requires radiotherapy. Together with 13 patients a primary cALCL identified from 11 previous studies, this constitutes a cohort of 15 patients. Of these, 10 present with an exclusively nodular lesion of the eyelid and four experience disease recurrence; no deaths from cALCL are reported.

Conclusion: Differential diagnosis between primary cALCL and lymphomatoid papulosis is essential and requires careful consideration of clinical and pathologic features. Radiologic staging examination is crucial in order to exclude systemic ALCL, particularly for patients with comorbidity. Though cALCL has the pathological features of a malignant lesion, the prognosis seems favourable for patients; a relatively high percentage even experience spontaneous resolution.
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http://dx.doi.org/10.1080/01676830.2020.1826543DOI Listing
October 2020

HIV prevalence in primary central nervous system lymphoma: A systematic review and meta-analysis.

Pathol Res Pract 2020 Nov 6;216(11):153192. Epub 2020 Sep 6.

Department of Advanced Biomedical Sciences, Pathology Section, Federico II University of Naples, Naples, Italy. Electronic address:

HIV infection is considered a major risk factor for primary central nervous system lymphoma (PCNSL). However, the percentage of PCNSL that occurs in HIV + patients is not well defined. We aimed to assess the prevalence of HIV infection in patients with PCNSL through a systematic review and meta-analysis. Electronic databases were searched for studies assessing the presence of HIV infection in series of patients with PCNSL. Pooled prevalence of HIV infection in PCNSL was calculated, with a subgroup analysis based on the geographic area. Twenty-seven studies with 6422 patients were included. Overall, pooled prevalence of HIV infection among PCNSL patients was 6.1 % with high heterogeneity. In the subgroup analysis, pooled prevalence was 3.6 % in India with low heterogeneity, 30.2 % (overall) and 16.5 % (after 2000) in the USA with high heterogeneity, 5.7 % in Europe with high heterogeneity, 2.2 % in East Asia with null heterogeneity, 7.3 % in South America with moderate heterogeneity. In conclusion, only a minor part of PCNSL occurs in patients with HIV. The results stratified by geographic area reflect the different prevalence of HIV infection in the general population, except for India, probably due to the shorter life expectancy of HIV + patients.
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http://dx.doi.org/10.1016/j.prp.2020.153192DOI Listing
November 2020

Clinical management of extrapleural septal solitary fibrous tumor: A case report.

Oncol Lett 2020 Sep 30;20(3):2465-2468. Epub 2020 Jun 30.

Department of Neuroscience, Reproductive and Odontostomatological Sciences-ENT Section, University of Naples 'Federico II', I-80131 Naples, Italy.

Solitary fibrous tumor (SFT) is a rare neoplasm arising from the pleura, although it can sometimes affect extrapleural sites, including the head and neck. The sinonasal involvement is exceptional. Recent literature defines the SFT as a single spectrum of mesenchymal tumors, including hemangiopericytoma, which is currently considered a cellular phenotypic variant. The current case describes a rare case of a nasal septal SFT. The mass was embolized and then removed through endonasal endoscopic surgery. Histopathologic examination demonstrated positive immunoreactivity for CD34, and negative for keratin and S100 protein confirming the diagnosis of benign nasal SFT. After two years of follow-up, no relapse was observed. Diagnostic assessment of SFT requires nasal endoscopy, imaging and histopathological examination and a long time follow up is mandatory.
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http://dx.doi.org/10.3892/ol.2020.11789DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7400225PMC
September 2020

Orbital myeloid sarcoma (chloroma): Report of 2 cases and literature review.

Am J Ophthalmol Case Rep 2020 Sep 11;19:100806. Epub 2020 Jul 11.

King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia.

Purpose: Myeloid sarcoma (MS) of the orbit is an uncommon condition in occurring in children, generally coupled to myeloproliferative neoplasms.

Observations: We describe two rare cases of orbital MS in young boys with aggressive local symptoms but without evidence of acute myeloid leukemia (AML), both patients underwent orbitotomy for gross-tumor resection and biopsy. At follow up, there was no evidence of recurrence nor evolution of the myeloproliferative neoplasms clinically and by radiological and laboratory work-up. We also provide a detailed description of the magnetic resonance imaging presentation, with an extensive pathological analysis correlation.

Conclusions And Importance: A comprehensive revision of the literature on isolated orbital MS was carried out with particular emphasis on clues for differential diagnosis and treatment options, stressing the need to consider MS even in the absence of sign and symptoms of an underlying myeloproliferative disorders.
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http://dx.doi.org/10.1016/j.ajoc.2020.100806DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7397738PMC
September 2020

Papillary thyroid carcinoma arising in ectopic thyroid tissue within sternocleidomastoid muscle: a review of current literature.

Minerva Endocrinol 2020 Dec 3;45(4):318-325. Epub 2020 Aug 3.

Unit of Endocrinology, Department of Clinical Medicine and Surgery, Federico II University Medical School, Naples, Italy.

The prevalence of ectopic thyroid tissue as consequence of an aberrant migration of thyroid during embryogenesis ranges up to 10% in autopsy studies. The differential diagnosis between the relatively rare occurrence of a primary carcinoma arising in ectopic thyroid tissue and the more frequent presence of cervical lymph node metastasis from papillary thyroid carcinoma (PTC) might represent a difficult challenge in the clinical practice. The clinical relevance of these lesions lies in their risk of hidden primary thyroid cancer. Our intention is to provide in this review the current limited data available and to report an unusual localization of primary PTC arising from an extra-thyroid area, responsible for a solitary cervical mass as initial manifestation. The tumor developed in an ectopic thyroid tissue embedded within the clavicular head of the sternocleidomastoid muscle and was completely separated from the thyroid. Surgical excision of ectopic thyroid tissue with clavicular head of sternocleidomastoid muscle along with total thyroidectomy and central and selective lateral neck dissection were carried out. Histopathology was diagnostic for ectopic PTC and no primary lesions in the thyroid gland neither metastatic lymph nodes were found. Tumor cells were positive for thyroid transcription factor-1and thyroglobulin, and negative for CD56. A postoperative adjuvant radioiodine ablation was given after recombinant human thyroid-stimulating hormone (TSH) stimulation and the post-treatment whole body scan was negative. After the evaluation at six months showing negative neck ultrasound and undetectable thyroglobulin levels, while TSH suppressed and after recombinant human TSH stimulation, the patient was re-evaluated every six months. At two years, the patient remained completely free of disease and is currently on substitutive dose of l-thyroxine. Endocrinologists and neck surgeons must be aware of the rare possibility of primary PTC arising from ectopic thyroid tissue within the sternocleidomastoid muscle.
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http://dx.doi.org/10.23736/S0391-1977.20.03167-3DOI Listing
December 2020

Involvement of Helicobacter Pylori in Ocular Adnexa Lymphoma.

Pathol Oncol Res 2020 Oct 18;26(4):2075-2081. Epub 2020 Jun 18.

Department of Advanced Biomedical Sciences, Pathology Section, Anatomic Pathology Unit, University of Naples "Federico II", Via Sergio Pansini, 5, 80131, Naples, Italy.

Helicobacter pylori has been proposed as a possible etiologic factor of ocular adnexa lymphoma (OAL), although with conflicting results. To assess the involvement of H. pylori in OAL, as (1) H. pylori DNA positivity on OAL specimens, and (2) prevalence of H. pylori gastric infection in patients with OAL. A systematic review of studies assessing H. pylori in patients with OAL was conducted by searching electronic databases from their inception to May 2019. Pooled positivity for H. pylori in OAL specimens detected by polymerase chain reaction, and pooled prevalence of H. pylori gastric infection, were calculated with 95% confidence interval (CI). Eleven studies with 308 patients were included. Pooled positivity for H. pylori was 16.8% in all OALs and 22.7% in MALT OAL, with high heterogeneity among studies. Pooled prevalence of H. pylori gastric infection in patients with OAL was 34.7%, with low statistical heterogeneity. In conclusion, H. pylori seems to be involved in a subset of OAL, but the heterogeneity found needs to be investigated in further studies. The prevalence of H. pylori gastric infection in patients with OAL does not seem to differ from that of the general population.
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http://dx.doi.org/10.1007/s12253-020-00848-6DOI Listing
October 2020

A Machine-learning Approach for the Assessment of the Proliferative Compartment of Solid Tumors on Hematoxylin-Eosin-Stained Sections.

Cancers (Basel) 2020 May 25;12(5). Epub 2020 May 25.

Department of Advanced Biomedical Sciences, Pathology Unit, University of Naples Federico II, 80131 Naples, Italy.

We introduce a machine learning-based analysis to predict the immunohistochemical (IHC) labeling index for the cell proliferation marker Ki67/MIB1 on cancer tissues based on morphometrical features extracted from hematoxylin and eosin (H&E)-stained formalin-fixed, paraffin-embedded (FFPE) tumor tissue samples. We provided a proof-of-concept prediction of the Ki67/MIB1 IHC positivity of cancer cells through the definition and quantitation of single nuclear features. In the first instance, we set our digital framework on Ki67/MIB1-stained OSCC (oral squamous cell carcinoma) tissue sample whole slide images, using QuPath as a working platform and its integrated algorithms, and we built a classifier in order to distinguish tumor and stroma classes and, within them, Ki67-positive and Ki67-negative cells; then, we sorted the morphometric features of tumor cells related to their Ki67 IHC status. Among the evaluated features, nuclear hematoxylin mean optical density (NHMOD) presented as the best one to distinguish Ki67/MIB1 positive from negative cells. We confirmed our findings in a single-cell level analysis of H&E staining on Ki67-immunostained/H&E-decolored tissue samples. Finally, we tested our digital framework on a case series of oral squamous cell carcinomas (OSCC), arranged in tissue microarrays; we selected two consecutive sections of each OSCC FFPE TMA (tissue microarray) block, respectively stained with H&E and immuno-stained for Ki67/MIB1. We automatically detected tumor cells in H&E slides and generated a "false color map" (FCM) based on NHMOD through the QuPath measurements map tool. FCM nearly coincided with the actual immunohistochemical result, allowing the prediction of Ki67/MIB1 positive cells in a direct visual fashion. Our proposed approach provides the pathologist with a fast method of identifying the proliferating compartment of the tumor through a quantitative assessment of the nuclear features on H&E slides, readily appreciable by visual inspection. Although this technique needs to be fine-tuned and tested on larger series of tumors, the digital analysis approach appears to be a promising tool to quickly forecast the tumor's proliferation fraction directly on routinely H&E-stained digital sections.
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http://dx.doi.org/10.3390/cancers12051344DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281627PMC
May 2020

Amyloidoma of the Tongue: Case Report, Surgical Management, and Review of the Literature.

J Oral Maxillofac Surg 2020 Sep 27;78(9):1572-1582. Epub 2020 Apr 27.

Full Professor and Department Head, Oral Medicine Unit, Department of Neuroscience, Reproductive Sciences and Dentistry, University of Naples Federico II, Naples, Italy.

Purpose: Localized amyloidosis of the tongue is a benign condition in which surgical management may be considered. The aim of the study was to review the current literature and report a case.

Materials And Methods: We searched the PubMed database for all relevant articles reporting cases of localized tongue amyloidosis published between 1980 and February 2020. In addition, we updated 1 case diagnosed and treated in our department.

Results: A 49-year-old male patient presented with an asymptomatic tongue nodule of the dorsum mimicking median rhomboid glossitis. The results of an incisional biopsy showed an amyloid on Congo red staining and positive findings for the κ light chain by immunohistochemical analysis. The findings of the systemic workup were negative. Therefore, a diagnosis of localized κ light-chain amyloidosis was made. The patient underwent a resection of the lesion, and no recurrence or progression was observed during a period of 18 months. The literature review showed 12 reports describing 21 patients (11 men, 52.3%) with localized tongue amyloidosis. The most common clinical presentation was nodular with a single lesion of the tongue dorsum (15 patients, 71.4%). All cases showed positive findings on Congo red staining. Immunohistochemical analysis findings were available for only 9 patients (42.8%) and showed light-chain amyloidosis. No case showed any systemic involvement or the development of systemic disease. Surgical excision was performed in 9 cases, with recurrence at the site of operation in 2 cases.

Conclusions: Localized amyloidosis of the tongue is a rare disease in which surgical excision may be therapeutic when a multidisciplinary evaluation does not show any systemic disease. We recommend an excision when the lesion is persistent or shows an enlargement or when discomfort is reported. In the case of any further local recurrence, resection may be repeated.
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http://dx.doi.org/10.1016/j.joms.2020.04.022DOI Listing
September 2020

Hepatitis C virus in MALT-lymphoma of the ocular adnexa.

Pathol Res Pract 2020 Apr 20;216(4):152864. Epub 2020 Feb 20.

Department of Advanced Biomedical Sciences, Pathology Section, Federico II University of Naples, Naples, Italy. Electronic address:

Objective: Hepatitis C virus (HCV) has been proposed as a possible etiologic factor in ocular adnexal marginal zone lymphoma (OAML). We aimed to assess the prevalence of HCV infection in patients with OAML through a systematic review and meta-analysis.

Methods: Electronic databases were searched from their inception to August 2019 for studies assessing HCV seroprevalence in patients with OAML. Pooled prevalence of HCV infection was calculated with 95 % confidence interval (CI). Statistical heterogeneity among studies was quantified via the inconsistency index (I). Funnel plot symmetry was used to assess the risk of bias across studies.

Results: Nine studies with 360 patients were included. Overall pooled prevalence of HCV in OAML was 12.7 %, with low statistical heterogeneity (I = 17.4 %) and with asymmetrical funnel plot. The studies clustered into two groups: 5 studies (3 from Italy and 2 multicenter with a major Italian contribution) showed a higher HCV prevalence in OAML (15.6 %), while the other 4 (from countries other than Italy) showed a lower prevalence (4.7 %); in both subgroups, statistical heterogeneity was null (I = 0%) and funnel plot was symmetrical.

Conclusion: HCV might be a significant etiologic factor of OAML in Italy.
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http://dx.doi.org/10.1016/j.prp.2020.152864DOI Listing
April 2020

Sjögren Syndrome in Primary Salivary Gland Lymphoma.

Am J Clin Pathol 2020 05;153(6):719-724

Department of Advanced Biomedical Sciences, Pathology Section, Federico II University of Naples, Naples, Italy.

Objectives: Sjögren syndrome (SS) is considered as a major etiologic factor for primary salivary gland lymphoma (SGL). However, the percentage of SGL that is caused by SS (and thus the real impact of SS on SGL epidemiology) is unclear. We aimed to assess the prevalence of SS in patients with SGL through a systematic review and meta-analysis.

Methods: Electronic databases were searched for studies assessing the presence of SS in patients with SGL. Pooled prevalence of SS in SGL was calculated, with a subgroup analysis based on histotype (mucosa-associated lymphoid tissue [MALT] vs non-MALT).

Results: Sixteen studies with 665 SGLs were included. Pooled prevalence of SS in SGL was 18.2%, with high heterogeneity among studies. In MALT SGL, the prevalence of SS was 29.5%, with moderate heterogeneity. In non-MALT SGL, the prevalence of SS was 0%, with null heterogeneity.

Conclusions: SS seems to be responsible for a significant but minor portion of SGLs. SS appears involved in MALT-type SGL but not in other histotypes.
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http://dx.doi.org/10.1093/ajcp/aqaa005DOI Listing
May 2020
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