Un Caso di linfoma a grandi linfociti granulosi (LGL) in un cavallo: caratterizzazione istochimica ed immunofenotipica = Large granular lymphoma (LGL) in a horse: histochemical and immunophenotype characterization

The aim of this study is to confirm lymphoma diagnosis, characterize the neoplasia immunophenotype and observe cell typologies by histochemical staining

Prima segnalazione di un caso di tumore misto mulleriano dell’ovaio in un cane = First report of canine malignant mixed mullerian tumor of the ovary

Adenocarcinoma is the most represented histotype of primary ovarian neoplasms in aged bitch. In woman, adenocarcinomas are quite common, whereas mixed forms as carcinosarcomas, or malignant mixed mullerian tumors [MMMTs] are rarely reported. The aim of the present study is to describe light and immunohistochemical findings of canine heterologous ovarian MMMT

HPV infection and triple-negative breast cancers: an Italian case-control study

Background: Breast cancer is one of the most important neoplasia among women. To reduce its incidence and mortality impact it would be desirable to early identify risk factors associated with its development. It was recently suggested that biological agents could be the etiological cause, particularly Human Papilloma Virus (HPV). No specific relationship with different breast cancer types has been demonstrated until now. In particular, the triple-negative breast cancer (TNBC), characterized by a receptor negative pattern (ER/PgR/HER2–negative) and poor prognosis, can represent one of the most relevant clinical and public health priority in terms of observational research. Findings: Aim of the study was to evaluate the HPV-positivity prevalence in two breast cancer series (TNBC vs. non-TNBC) in Northern Sardinia, Italy. The sample size of each group was represented by 40 formalin-fixed and paraffin-embedded specimens. The mean age was 60.3 years. The majority of the cancers were ductal (84%). The grading distribution was different: G2 was the most prevalent grade in the non-TNBC series, whereas G3 was the most frequent in the TNBC series (70% and 72%, respectively). Six biological samples were HPV-positive (7.5%): the positivity was assessed only in the TNBC group (15%; p-value: 0.026). The isolated genotypes were: 16, 31, 45, 52, 6, and 66. Only one co-infection was found (i.e., HPV-6 and -66). Conclusions: The prevalence of HPV-positivity in TNBC specimens was 15%. On the basis of its carcinogenetic ability, an etiological role in the pathogenesis of the cancer could be supposed. This association should be confirmed with longitudinal studies to better assess the role of the HPV infection in TNBC and non-TNBC tumors

Analysis of PIK3CA mutations and activation pathways in <i>triple negative</i> breast cancer

Background: Triple Negative Breast Cancer (TNBC) accounts for 12–24% of all breast carcinomas, and shows worse prognosis compared to other breast cancer subtypes. Molecular studies demonstrated that TNBCs are a heterogeneous group of tumors with different clinical and pathologic features, prognosis, genetic-molecular alterations and treatment responsivity. The PI3K/AKT is a major pathway involved in the regulation of cell survival and proliferation, and is the most frequently altered pathway in breast cancer, apparently with different biologic impact on specific cancer subtypes. The most common genetic abnormality is represented by PIK3CA gene activating mutations, with an overall frequency of 20–40%. The aims of our study were to investigate PIK3CA gene mutations on a large series of TNBC, to perform a wider analysis on genetic alterations involving PI3K/AKT and BRAF/RAS/MAPK pathways and to correlate the results with clinical-pathologic data. Materials and Methods: PIK3CA mutation analysis was performed by using cobas® PIK3CA Mutation Test. EGFR, AKT1, BRAF, and KRAS genes were analyzed by sequencing. Immunohistochemistry was carried out to identify PTEN loss and to investigate for PI3K/AKT pathways components. Results: PIK3CA mutations were detected in 23.7% of TNBC, whereas no mutations were identified in EGFR, AKT1, BRAF, and KRAS genes. Moreover, we observed PTEN loss in 11.3% of tumors. Deregulation of PI3K/AKT pathways was revealed by consistent activation of pAKT and p-p44/42 MAPK in all PIK3CA mutated TNBC. Conclusions: Our data shows that PIK3CA mutations and PI3K/AKT pathway activation are common events in TNBC. A deeper investigation on specific TNBC genomic abnormalities might be helpful in order to select patients who would benefit from current targeted therapy strategies

Long-lasting responses with chemotherapy followed by T-cell therapy in recurrent or metastatic EBV-related nasopharyngeal carcinoma

BackgroundRefractory or metastatic nasopharyngeal carcinoma (NPC) patients have a poor prognosis due to the lack of effective salvage treatments and prolonged survival by means of combination chemotherapy being described only for a minority of younger patients with oligometastatic disease. Targeting the Epstein - Barr virus (EBV) proteins expressed in NPC cells has been shown to be a feasible strategy that could help control systemic disease.Patients and MethodsBetween 2011 and 2014, 16 patients with recurrent/metastatic EBV-NPC received first-line chemotherapy (CT) followed by 2 doses of autologous cytotoxic EBV specific T-lymphocytes (15-25 x 107 total cells/dose, 2 weeks apart), based on our previous studies showing the feasibility and efficacy of this infusion regimen. Cumulative overall survival (OS) and median OS were analysed in the whole population and according to specific clinical and biological parameters.ResultsAll patients received the planned T-cell therapy schedule, 9 after reaching partial (n=5) or complete (n=4) disease remission with CT, and 7 after failing to obtain benefit from chemotherapy. No severe adverse events were recorded. Patients who received cytotoxic T-lymphocytes (CTLs) had a cumulative 10-year OS of 44%, with a median OS of 60 months (95% CI 42-62). Patients responding to CT, with oligometastatic disease (&lt;3 disease sites), and plasma EBV-DNA &lt;1000 copies/mL had a better outcome.ConclusionsAutologous EBV-specific CTLs transplanted following conventional first-line CT demonstrated promising efficacy with several patients obtaining long-lasting disease control. The rationale provided by this study, with the crucial role likely played by the timing of CTL administration when trying to induce synergy with conventional treatment needs to be confirmed in a prospective controlled trial

Management of Germ Cell Tumors During the Outbreak of the Novel Coronavirus Disease-19 Pandemic:A Survey of International Expertise Centers

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has become a public health emergency affecting frail populations, including patients with cancer. This poses the question of whether cancer treatments can be postponed or modified without compromising their efficacy, especially for highly curable cancers such as germ cell tumors (GCTs). MATERIALS AND METHODS: To depict the state-of-the-art management of GCTs during the COVID-19 pandemic, a survey including 26 questions was circulated by e-mail among the physicians belonging to three cooperative groups: (a) Italian Germ Cell Cancer Group; (b) European Reference Network-Rare Adult Solid Cancers, Domain G3 (rare male genitourinary cancers); and (c) Genitourinary Medical Oncologists of Canada. Percentages of agreement between Italian respondents (I) versus Canadian respondents (C), I versus European respondents (E), and E versus C were compared by using Fisher's exact tests for dichotomous answers and chi square test for trends for the questions with three or more options. RESULTS: Fifty-three GCT experts responded to the survey: 20 Italian, 6 in other European countries, and 27 from Canada. Telemedicine was broadly used; there was high consensus to interrupt chemotherapy in COVID-19-positive patients (I = 75%, C = 55%, and E = 83.3%) and for use of granulocyte colony-stimulating factor primary prophylaxis for neutropenia (I = 65%, C = 62.9%, and E = 50%). The main differences emerged regarding the management of stage I and stage IIA disease, likely because of cultural and geographical differences. CONCLUSION: Our study highlights the common efforts of GCT experts in Europe and Canada to maintain high standards of treatment for patients with GCT with few changes in their management during the COVID-19 pandemic. IMPLICATIONS FOR PRACTICE: Despite the chaos, disruptions, and fears fomented by the COVID-19 illness, oncology care teams in Italy, other European countries, and Canada are delivering the enormous promise of curative management strategies for patients with testicular cancer and other germ cell tumors. At the same time, these teams are applying safe and innovative solutions and sharing best practices to minimize frequency and intensity of patient contacts with thinly stretched health care capacity

Recurrent/metastatic head and neck squamous cell carcinoma in older patients : are new agents bringing new hope?

Head and neck cancer is a broad family of diseases, most of which are of squamous cell origin, affecting the epithelial mucosa lining the upper aerodigestive tract. They often recur or are progressive despite multimodality treatment approaches, resulting in a poor prognosis. Given the progressive aging of the global population, the probability to plan an active and eventually toxic treatment for an older patient, with either curative or palliative intent, can no longer be considered as an uncommon occurrence. A crucial point in offering a systemic treatment to older patients with head and neck squamous cell carcinoma is that they are underrepresented in randomised clinical trials, and evidence-based guidelines are lacking, while, from a clinical point of view, these patients may have varying grades of resilience to anticancer treatments due to differences in their health, social and/or economic status. Our aim is to draw attention to the older patient population suffering from recurrent and/or metastatic head and neck squamous cell carcinoma and to address some open questions, such as possible differences in epidemiology and biology compared with their younger counterparts; to highlight frailty and its components by discussing how to measure and use it to personalise treatment; to evaluate which outcomes should be best achieved in the older adult setting; finally, in the era of immunotherapy, to examine whether there are differences to be addressed when considering new treatments for older patients

Rectal endometrial stromal sarcoma arising in endometriosis

PURPOSE: Endometriosis of the rectovaginal septum can harbor different types of secondary tumors that may involve the rectal wall and protrude into its lumen, thus making diagnosis difficult. Extrauterine low-grade endometrial stromal sarcoma may rarely arise in endometriosis. The purpose of this article was to present the third case of this association. METHOD: This was a clinicopathologic study. RESULTS: A 42-year-old female presented with abdominal pain and fever. Laparotomy revealed a large pelvic mass involving the rectovaginal septum and the colonic wall and which protruded into the lumen forming endoluminal polypoid masses. Concomitant peritoneal nodules and a metastatic paracolic lymph node were also found. Histopathologically, primary endometriotic foci were found in close relationship with an endometrial stromal sarcoma which invaded the rectal wall. The female genital tract had no endometriotic lesions. The patient was treated by surgery and subsequent chemotherapy and was alive and well 20 months later. CONCLUSIONS: Endometriosis and its possible malignant changes should be taken into account in the differential endoscopic diagnosis of rectal masses in females