Molecularly targeted therapy for advanced gastrointestinal noncolorectal cancer treatment: how to choose? Past, present, future.

Gastrointestinal cancer is a leading cause of death worldwide. Conventional cytotoxic chemotherapy has been the backbone of advanced gastrointestinal cancer treatment for decades and still represents a key element of the therapeutic armamentarium. However, only small increments in survival outcomes have been reached. New clinical trials are designed, including classic chemotherapy in association with either small-molecule inhibitors or mAb. During the past few years, remarkable progress in molecular biology of gastrointestinal noncolorectal cancers, the discovery of specific targets and the resulting development of systemic drugs that block critical kinases and several molecular pathways have all contributed to progress. New biological agents with molecularly targeted therapies are now available or currently included in clinical trials (EGFR inhibitors (i), antiangiogenic agents, c-METi, IDHi, FGFR2i, BRAFi, Pi3Ki/AKTi/mTORi, NTRKi). When we focus on the current state of precision medicine for gastrointestinal malignancies, it becomes apparent that there is a mixed history of success and failure. The aim of this review is to focus on the studies that have been completed to date with target therapies and to understand which of these are currently the accepted choice in clinical practice and which need further confirmation and approval for inclusion in guidelines. All these findings will enable to guide clinical practice for oncologists in the design of the next round of clinical trials.

Combination of radiation therapy for brain metastasis and anti-PD-1/PD-L1 treatment in non-small cell lung cancer: two cases and review of the literature.

Lung cancer is the most frequent cause of cancer-related death worldwide and is usually diagnosed in advanced stages. Among those, approximately 7.4% of non-small cell lung cancer (NSCLC) patients will have brain metastasis (BM) at presentation, and 25-30% will develop BM during the course of their disease. To date, patients with BMs are increasingly considered for combined treatment using systemic immune checkpoint inhibition (ICI) and cranial radiation therapy (RT); yet, there is limited data regarding the safety of this approach. Here, we report two cases of NSCLC patients treated with two different types of cranial RT and ICIs.

Dabrafenib and trametinib induced pancreatitis: a case report and review of the literature.

Approximately 50% of melanomas are characterized by BRAF mutation (V600E in 90% of cases), that predicts more aggressive behaviour. This mutation is the target of dabrafenib, an anti-BRAF tyrosine-kinase inhibitor (TKI), that together with trametinib, anti-MEK TKI, is approved for first-line treatment of metastatic melanoma due to significant benefit in overall and progression-free survival. Most common treatment-related adverse events are pyrexia, chills, fatigue, rash, nausea, vomiting, and diarrhoea. This case report aims to present another less common adverse event of combined anti-BRAF and anti-MEK treatment. Our patient, after 4 months on target-therapy, experienced sudden deep abdominal pain. At the initial work-out at the emergency department, increase in serum lipase was detected and radiological findings were consistent with acute pancreatitis. Admitted to the hospital, other causes were ruled out and target-therapy was discontinued with symptoms improvement. Radiological and clinical follow-up was performed and a diagnosis of drug-induced pancreatitis was made. After few days of medical support with analgesia and antibiotic, the patient felt better and was discharged; target-therapy was permanently interrupted. Searching the literature, not so many cases of iatrogenic pancreatitis are described with this TKI combination, therefore, we have reported it as a rare but life-threatening adverse event that should be investigated whenever conceivable.

Complete testicular remission after chemotherapy in a patient with advanced seminoma: is the testicle a real 'sanctuary'? A case report and review of the literature.

Testicular cancer is relatively uncommon, but at the same time, it is the most common solid tumor in men between the ages of 20 and 34 years. Seminoma represents the most frequently encountered germ cell tumors. Because orchiectomy is usually performed before chemotherapy, little is known about the effect of systemic chemotherapy on primary testicular tumors. Furthermore, the testis has always been considered a sanctuary site, an immune-privileged site in which inadequate exposure of the tumor to chemotherapy may occur. We report the case of a young patient with advanced seminoma with a complete testicular response after four cycles of cisplatin-based chemotherapy. Then, we performed a systematic review of the literature reporting the studies published to date on the topic.

COVID-19 in patients with thoracic malignancies (TERAVOLT): first results of an international, registry-based, cohort study.

BACKGROUND: Early reports on patients with cancer and COVID-19 have suggested a high mortality rate compared with the general population. Patients with thoracic malignancies are thought to be particularly susceptible to COVID-19 given their older age, smoking habits, and pre-existing cardiopulmonary comorbidities, in addition to cancer treatments. We aimed to study the effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on patients with thoracic malignancies. METHODS: The Thoracic Cancers International COVID-19 Collaboration (TERAVOLT) registry is a multicentre observational study composed of a cross-sectional component and a longitudinal cohort component. Eligibility criteria were the presence of any thoracic cancer (non-small-cell lung cancer [NSCLC], small-cell lung cancer, mesothelioma, thymic epithelial tumours, and other pulmonary neuroendocrine neoplasms) and a COVID-19 diagnosis, either laboratory confirmed with RT-PCR, suspected with symptoms and contacts, or radiologically suspected cases with lung imaging features consistent with COVID-19 pneumonia and symptoms. Patients of any age, sex, histology, or stage were considered eligible, including those in active treatment and clinical follow-up. Clinical data were extracted from medical records of consecutive patients from Jan 1, 2020, and will be collected until the end of pandemic declared by WHO. Data on demographics, oncological history and comorbidities, COVID-19 diagnosis, and course of illness and clinical outcomes were collected. Associations between demographic or clinical characteristics and outcomes were measured with odds ratios (ORs) with 95% CIs using univariable and multivariable logistic regression, with sex, age, smoking status, hypertension, and chronic obstructive pulmonary disease included in multivariable analysis. This is a preliminary analysis of the first 200 patients. The registry continues to accept new sites and patient data. FINDINGS: Between March 26 and April 12, 2020, 200 patients with COVID-19 and thoracic cancers from eight countries were identified and included in the TERAVOLT registry; median age was 68·0 years (61·8-75·0) and the majority had an Eastern Cooperative Oncology Group performance status of 0-1 (142 [72%] of 196 patients), were current or former smokers (159 [81%] of 196), had non-small-cell lung cancer (151 [76%] of 200), and were on therapy at the time of COVID-19 diagnosis (147 [74%] of 199), with 112 (57%) of 197 on first-line treatment. 152 (76%) patients were hospitalised and 66 (33%) died. 13 (10%) of 134 patients who met criteria for ICU admission were admitted to ICU; the remaining 121 were hospitalised, but were not admitted to ICU. Univariable analyses revealed that being older than 65 years (OR 1·88, 95% 1·00-3·62), being a current or former smoker (4·24, 1·70-12·95), receiving treatment with chemotherapy alone (2·54, 1·09-6·11), and the presence of any comorbidities (2·65, 1·09-7·46) were associated with increased risk of death. However, in multivariable analysis, only smoking history (OR 3·18, 95% CI 1·11-9·06) was associated with increased risk of death. INTERPRETATION: With an ongoing global pandemic of COVID-19, our data suggest high mortality and low admission to intensive care in patients with thoracic cancer. Whether mortality could be reduced with treatment in intensive care remains to be determined. With improved cancer therapeutic options, access to intensive care should be discussed in a multidisciplinary setting based on cancer specific mortality and patients' preference. FUNDING: None.

Microwave ablation of lung tumours: single-centre preliminary experience.

PURPOSE: This study was done to evaluate the feasibility, effectiveness and safety of microwave (MW) ablation of lung tumours. MATERIALS AND METHODS: Twenty-four patients underwent percutaneous MW ablation of 26 intraparenchymal pulmonary masses. All patients were judged to be inoperable on the basis of tumour stage, comorbidities, advanced age and/or refusal to undergo surgery. Ablation was performed using a microwave generator (Evident Microwave Ablation System, Covidien Ltd., Dublin). Lesions with a diameter ≤ 3 cm were treated with a single antenna, lesions with a diameter >3 cm were treated by positioning two or more antennae, simultaneously. All patients underwent computed tomography (CT) follow-up with and without contrast administration at 1, 3 and 6 months and then yearly in combination with complete blood and metabolic tests. RESULTS: Technical success was 100 %. No major complications were recorded. Asymptomatic grade-1 pneumothorax was recorded in 9 patients (37.5 %). One case of asymptomatic pleural effusion and one of haemoptysis, not requiring transfusion, were observed. No patients were diagnosed with a post-ablation syndrome. Complete necrosis was observed in 16 of 26 lesions (61.6 %). Partial necrosis was obtained in 30.8 % (8/26 lesions); in one case (3.8 %) a progression of the disease was recorded and in another case (3.8 %) a stability was observed. CONCLUSIONS: Our preliminary experience may be considered in accordance with literature dates, in terms of efficacy and safety.

Usefulness and safety of biliary percutaneous transluminal forceps biopsy (PTFB): our experience.

AIM: To evaluate the usefulness and safety of percutaneous transluminal forceps biopsy in patients suspected of having a malignant biliary obstruction. MATERIAL AND METHODS: Forty consecutive patients (21 men and 19 women; mean age, 71.9 years) underwent forceps biopsy through percutaneous transhepatic biliary access performed to drain bile. Lesions involved the common bile duct (n 8), common hepatic duct (n 18), hilum (n 6), ampullary segment of the common bile duct (n 8) and were biopsied with 7-F biopsy forceps. Final diagnosis was confirmed with pathologic findings at surgery, or clinical and radiologic follow-up. RESULTS: Twenty-one of 40 biopsies resulted in correct diagnosis of malignancy. Thirteen biopsy diagnosis were proved to be true-negative. There were six false-negative and no false-positive diagnoses. Sensitivity, specificity and accuracy in aspecific biliary obstructions were 85%, 100% and 88,7% respectively. Sensitivity of biopsy in malignancies was higher than in benign obstructions (100% vs 68,4%, CI = 95%). Sensitivity was lower in the hilum tract and in the common bile duct than in other sites (CI = 95%). No major complications related to biopsy procedures occurred. CONCLUSIONS: Percutaneous transluminal forceps biopsy is a safe procedure, easy to perform through a transhepatic biliary drainage tract, providing high accuracy in the diagnosis of malignant biliary obstructions.

Microwave ablation of liver metastases to overcome the limitations of radiofrequency ablation.

PURPOSE: The purpose of our study was to evaluate technical success, effectiveness and safety of microwave ablation (MWA) in patients with unresectable liver metastases, where radiofrequency ablation (RFA) presents some limits. MATERIALS AND METHODS: Twenty-five patients (17 men, 8 women) with 31 liver metastases >3 cm or located near vessels (>3 mm) were treated in a total of 29 sessions. Tumours were subdivided as follows: colorectal metastases (n=21) and no colorectal metastases (n=10). All procedures were performed percutaneously under ultrasound (US) guidance. Follow-up was performed with computed tomography (CT) scan at 1, 3, 6 and 12 months after treatment; mean follow-up period was 12.04 (range, 3-36) months. Technical success, mean disease-free survival, effectiveness and safety were evaluated. RESULTS: Technical success was obtained in all cases. Mean disease-free survival was of 20.5 months. Local recurrence was recorded in 12.9% of metastases treated (4/31). No major complications were recorded. The rate of minor complications was 44.8% (13/29 sessions). Mortality at 30 days was 0%. CONCLUSIONS: Percutaneous MWA of liver metastases >3 cm or located near vessels (>3 mm) can be considered a valid and safe option, probably preferable to RFA. Further studies are required to confirm these encouraging initial results.

Efficacy of Metronomic Oral Vinorelbine, Cyclophosphamide, and Capecitabine vs Weekly Intravenous Paclitaxel in Patients With Estrogen Receptor-Positive, ERBB2-Negative Metastatic Breast Cancer: Final Results From the Phase 2 METEORA-II Randomized Clinical Trial.

Importance: In spite of the effectiveness of endocrine therapy plus cyclin-dependent kinase (CDK) 4/6 inhibitors as the first-line treatment for estrogen receptor (ER)-positive, erb-b2 receptor tyrosine kinase 2 (ERBB2 [formerly HER2/neu])-negative (ER+/ERBB2-) metastatic breast cancer (MBC), patients eventually develop resistance, and eventually most will receive chemotherapy. The METEORA-II trial compared a metronomic all-oral treatment with intravenous (IV) chemotherapy. Objective: To compare the efficacy of the oral vinorelbine plus cyclophosphamide plus capecitabine (VEX) regimen vs weekly IV paclitaxel among patients with ER+/ERBB2- MBC who are candidates for chemotherapy. Design, Setting, and Participants: This phase 2 randomized clinical trial including 140 women 18 years and older (randomized 1:1) with ER+/ERBB2- MBC was carried out from September 13, 2017, to January 14, 2021 at 15 centers in Italy. Eligible patients could have received 1 prior line of chemotherapy for MBC and/or 2 lines of endocrine therapy (including CDK4/6 inhibitors). Interventions: In 4-week cycles, patients received either metronomic oral VEX or weekly IV paclitaxel. Main Outcomes and Measures: The primary end point was investigator-assessed time to treatment failure (TTF) defined as the interval between the date of randomization to the end of treatment (because of disease progression or lack of tolerability or because further trial treatment was declined). Secondary end points included progression-free survival (PFS), overall survival (OS), and disease control rate (complete or partial response or stable disease lasting for at least 24 weeks). Results: In total, 133 patients received either VEX (n = 70) or paclitaxel (n = 63) in 4-weekly cycles. The median age was 61 (range, 30-80) years. The VEX treatment significantly prolonged TTF vs paclitaxel (hazard ratio [HR], 0.61; 95% CI, 0.42-0.88; P = .008), median TTF was 8.3 (95% CI, 5.6-11.1) months for VEX vs 5.7 (95% CI, 4.1-6.1) months for paclitaxel, and the 12-month TTF was 34.3% for VEX vs 8.6% for paclitaxel. The median PFS was 11.1 (95% CI, 8.3-13.8) months vs 6.9 (95% CI, 5.4-10.1) months favoring VEX (HR, 0.67; 95% CI, 0.46-0.96, P = .03). The 12-month PFS was 43.5% for VEX vs 21.9% for paclitaxel. No difference in OS was found. The TF event for 55.6% of patients was progression of disease; for 23% it was AEs. More patients assigned to VEX had at least 1 grade 3 or 4 targeted adverse event (VEX, 42.9%; 95% CI, 31.1%-55.3% vs paclitaxel, 28.6%; 95% CI, 17.9%-41.3%), but essentially no alopecia. Conclusion and Relevance: This randomized clinical trial found significantly prolonged TTF and PFS for oral VEX but no improvement in OS compared with intravenous paclitaxel, despite increased but still manageable toxic effects. The VEX regimen may provide more prolonged disease control than weekly paclitaxel for ER+/ERBB2- MBC. Trial Registration: ClinicalTrials.gov Identifier: NCT02954055.

Adjuvant Exemestane With Ovarian Suppression in Premenopausal Breast Cancer: Long-Term Follow-Up of the Combined TEXT and SOFT Trials.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.The combined analysis of SOFT-TEXT compared outcomes in 4,690 premenopausal women with estrogen/progesterone receptor-positive (ER/PgR+) early breast cancer randomly assigned to 5 years of exemestane + ovarian function suppression (OFS) versus tamoxifen + OFS. After a median follow-up of 9 years, exemestane + OFS significantly improved disease-free survival (DFS) and distant recurrence-free interval (DRFI), but not overall survival, compared with tamoxifen + OFS. We now report DFS, DRFI, and overall survival after a median follow-up of 13 years. In the intention-to-treat (ITT) population, the 12-year DFS (4.6% absolute improvement, hazard ratio [HR], 0.79; 95% CI, 0.70 to 0.90; P < .001) and DRFI (1.8% absolute improvement, HR, 0.83; 95% CI, 0.70 to 0.98; P = .03), but not overall survival (90.1% v 89.1%, HR, 0.93; 95% CI, 0.78 to 1.11), continued to be significantly improved for patients assigned exemestane + OFS over tamoxifen + OFS. Among patients with human epidermal growth factor receptor 2-negative tumors (86.0% of the ITT population), the absolute improvement in 12-year overall survival with exemestane + OFS was 2.0% (HR, 0.85; 95% CI, 0.70 to 1.04) and 3.3% in those who received chemotherapy (45.9% of the ITT population). Overall survival benefit was clinically significant in high-risk patients, eg, women age < 35 years (4.0%) and those with > 2 cm (4.5%) or grade 3 tumors (5.5%). These sustained reductions of the risk of recurrence with adjuvant exemestane + OFS, compared with tamoxifen + OFS, provide guidance for selecting patients for whom exemestane should be preferred over tamoxifen in the setting of OFS.[Media: see text].

Long-term follow-up of rituximab plus bendamustine and cytarabine in older patients with newly diagnosed MCL.

The combination of rituximab, bendamustine, and low-dose cytarabine (R-BAC) has been studied in a phase 2 prospective multicenter study from Fondazione Italiana Linfomi (RBAC500). In 57 previously untreated elderly patients with mantle cell lymphoma (MCL), R-BAC was associated with a complete remission rate of 91% and 2-year progression-free survival (PFS) of 81% (95% confidence interval [CI], 68-89). Here, we report the long-term survival outcomes, late toxicities, and results of minimal residual disease (MRD) evaluation. After a median follow-up of 86 months (range, 57-107 months), the median overall survival (OS) and PFS were not reached. The 7-year PFS and OS rates were 55% (95% CI, 41-67), and 63% (95% CI, 49-74), respectively. Patients who responded (n = 53) had a 7-year PFS of 59% (95% CI, 44-71), with no relapse or progression registered after the sixth year. In the multivariate analysis, blastoid/pleomorphic morphology was the strongest adverse predictive factor for PFS (P = .04). Patients with an end of treatment negative MRD had better, but not significant, outcomes for both PFS and OS than patients with MRD-positive (P = 0.148 and P = 0.162, respectively). There was no signal of late toxicity or an increase in secondary malignancies during the prolonged follow-up. In conclusion, R-BAC, which was not followed by maintenance therapy, showed sustained efficacy over time in older patients with MCL. Survival outcomes compare favorably with those of other immunochemotherapy regimens (with or without maintenance), including combinations of BTK inhibitors upfront. This study was registered with EudraCT as 2011-005739-23 and at www.clinicaltrials.gov as #NCT01662050.

Concomitant Drugs Prognostic Score in Patients With Metastatic Renal Cell Carcinoma Receiving Ipilimumab and Nivolumab in the Compassionate Use Program in Italy: Brief Communication.

A concomitant drug-based score was developed by our group and externally validated for prognostic and predictive purposes in patients with advanced cancer treated with immune checkpoint inhibitors (ICIs). The model considers the use of three classes of drugs within a month before initiating ICI, assigning score 1 for each between proton pump inhibitor and antibiotic administration until a month before immunotherapy initiation and score 2 in case of corticosteroid intake. In the present analysis, the drug score was validated in a prospective population of 305 patients with metastatic renal cell carcinoma treated with ipilimumab plus nivolumab in the first-line setting. The value of the model in predicting overall survival and progression-free survival was statistically significant and clinically meaningful, with an overall survival rate at 12 months of 73% vs. 44% (P<0.0001), and median progression-free survival of 11.6 (95% CI: 9.1-14.1) months versus 4.8 (95% CI: 2.7-7.0) months (P=0.002), respectively, for patients belonging to the favorable group (score 0-1) versus the unfavorable (score 2-4). Further development will be represented by the gut microbiome analysis according to the drug-based model classification and to the outcome of patients to ICI therapy to demonstrate the link between drug exposure and immune sensitivity.

Metastatic basal cell carcinoma to the bone: A case of bone metastasis in uncommon sites.

Basal cell carcinoma (BCC) is the most common malignant tumor of the skin. Despite the indolent nature, metastatic BCC can occur, albeit rarely. Metastasis to the bone is very rare. From its approval, mBCC patients are treated with vismodegib, a selective hedgehog pathway inhibitor. Unfortunately, in recent period, it was demonstrated an emergence of drug resistance, due to Smoothened (SMO) mutation. To date, several groups are studying the effectiveness of immunotherapy in BCC. Clinical trials with Immune Checkpoint Inhibitors are ongoing. We report the rare case of a man with multiple bony metastasis, with a resistance to vismodegib, and we evaluated all manuscripts in literature reporting bone metastasis. Moreover, we review all the manuscripts in literature reporting bone metastasis, and we summarize the main therapeutic strategies, and the further perspectives.

Composite follicular lymphoma and "early" (in situ and mantle zone growth pattern) mantle cell neoplasia: A rare entity with peculiar cytogenetic and clinical features.

Composite follicular lymphoma (FL) and mantle cell lymphoma (MCL) is rare and not fully characterized from a genetic and clinicopathological point of view. We report a composite lymphoma (CL) in which a G1-2 FL was associated with an in situ mantle cell neoplasia (ISMCN) and a mantle zone growth pattern (MZGP) MCL, followed-up for six years after the first diagnosis, until the exitus of the patient. We performed a comprehensive immunohistochemical study and a detailed cytogenetic analysis, including conventional karyotyping, SKY FISH, FISH on metaphases and interphasic separated nuclei, and FISH on histological sections. The study was completed by the review of the 13 published composite FL and MCL. Our results show that this entity generally behaves like an indolent lymphoma, with the outcome of patients driven by the progression of the FL component. The MCL component generally does not evolve in an aggressive disease. Indeed, half of the cases present exclusively ISMCN. In our case, mantle cell neoplasia at diagnosis was represented by ISMCN and MZGP MCL and it was characterized by a simple karyotype, with t(11;14) as the sole cytogenetic abnormality. This cytogenetic aspect well correlates with the indolent behavior of the mantle cell component. Conversely, the complex karyotype of the FL component was associated with disseminated disease that influenced patient's outcome. Finally, we suggest that not only ISMCN, but also isolated MZGP MCL, may be considered as lesions with low potential of transformation in an aggressive MCL.

Diagnostic accuracy of contrast-enhanced spectral mammography for breast lesions: A systematic review and meta-analysis.

Breast cancer diagnosis and staging is based on mammography, ultrasound, and magnetic resonance imaging (MRI). Contrast enhanced spectral mammography (CESM) has gained momentum as an innovative and clinically useful method for breast assessment. CESM is based on abnormal enhancement of neoplastic tissue compared to surrounding breast tissue. We performed a systematic review of prospective trial to evaluate its diagnostic performance, following standard PRISMA-DTA. We used a bivariate random-effects regression approach to obtain summary estimates of both sensitivity and specificity of CESM. 8 studies published between 2003 and 2019 were included in the meta-analysis for a total of 945 lesions. The summary area under the curve obtained from all the study was 89% [95% CI 86%-91%], with a sensitivity of 85% [95% CI 73%-93%], and a specificity of 77% [95% CI 60%-88%]. With a pre-test probability of malignancy of 57% a positive finding at CESM gives a post-test probability of 83% while a negative finding a post-test probability of 20%. CESM shows a suboptimal sensitivity and specificity in the diagnosis of breast cancer in a selected population, and at present time, it could be considered only as a possible alternative test for breast lesions assessment when mammography and ultrasound are not conclusive or MRI is contraindicated or not available.

Cytomegalovirus infection of endocrine system in a patient with diffuse large B-cell lymphoma. Report of a case.

Cytomegalovirus (CMV) is an opportunistic pathogen causing different diseases in immunocompromised patients and leading to death in a high percentage of cases. CMV infection is also relatively frequent among patients with hematological malignancies, especially when treated with immunosuppressive agents. We describe the clinical history of a patient with stage IV diffuse large B-cell lymphoma (DLBCL) treated with eight courses of R-CHOP every two weeks, who presented clinical remission of the disease at the end of therapy. However, two months later he developed neurological symptoms due to cerebellar involvement and a subcutaneous dorsal lymphomatous infiltration. He had a partial response after chemotherapy and brain radiotherapy, but his clinical course was complicated by fever and hypotension. Although the fever resolved with broad-spectrum antibiotics, he presented progressive endocrine failure and died three weeks later. Autopsy confirmed disseminated multiorgan involvement by DLBCL associated with an unexpected CMV infection of the lungs and several endocrine organs including the pituitary gland, pancreatic islets and adrenals, a clinical association not previously reported in the English literature.

Poorly Differentiated Neuroendocrine Carcinoma of the Sigmoid Tract in Long-Standing Ulcerative Colitis: Report of a Case and Review of the Literature.

A 37-year-old male with long-standing and extensive ulcerative pancolitis developed a rapidly lethal poorly differentiated neuroendocrine carcinoma (NEC) in the sigmoid colon. Prior biopsies obtained from multiple sites of the colon during endoscopic surveillance showed minimal inflammatory changes and no sign of dysplasia. Patients with inflammatory bowel disease (IBD) are at increased risk of colorectal malignancies, and adenocarcinoma is the most common type of colorectal neoplasm associated with ulcerative colitis and Crohn's disease, but other types of epithelial and nonepithelial tumors have also been described in IBD. NECs arising in the setting of ulcerative colitis are very rare and are reported as anecdotic findings. We describe the clinicopathological features of an IBD-related NEC and review the previously reported cases.

Bcl-6 protein expression, and not the germinal centre immunophenotype, predicts favourable prognosis in a series of primary nodal diffuse large B-cell lymphomas: a single centre experience.

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease. The immunohistochemistry-based algorithms for the determination of the cell of origin of DLBCL have been proposed as a practical method to validate and surrogate results obtained by gene expression profiling. We studied 71 patients with primary nodal DLBCL at diagnosis, who received anthracycline-based therapy with or without rituximab. Immunohistochemistry was performed using anti-CD10, Bcl-6, MUM1 and Bcl-2 antibodies in order to assess the ontogenic profile of neoplastic cells and to verify its relation with clinical outcome. Survival data were analysed using an explorative Cox model. The immunohistochemistry-based algorithms for the determination of the cell of origin of DLBCL were not associated with prognosis. By contrast, Bcl-6 expression was associated with a longer lymphoma-free survival while immunoreactivities for MUM1 or Bcl-2 were not significantly related to patient outcome. Bcl-6 expression alone proved to be a prognostic marker in primary nodal DLBCL and seemed to be more reliable to predict clinical outcome in these disorders than the immunohistochemical algorithms for the detection of the germinal centre/non-germinal centre immunophenotype.

The modified International Prognostic Index can predict the outcome of localized primary intestinal lymphoma of both extranodal marginal zone B-cell and diffuse large B-cell histologies.

We have previously reported on the efficacy of a modified International Prognostic Index (MIPI) in predicting the outcome of patients with primary gastric lymphoma. This prompted the retrospective analysis of a large series of patients with primary intestinal lymphoma (PIL) of both diffuse large B-cell (DLCL) and low-grade (extranodal marginal zone B-cell lymphoma, MZL) histology. Clinical records of 122 patients with localized primary intestinal lymphoma of MZL (n=35) and DLCL (n=87) histology, confirmed by an ad hoc expert panel of pathologists, were reviewed. Forty-nine patients were treated with single therapy, while 72 received combined-modality treatment, which included surgery followed by a short-term chemotherapy. MIPI was included in a multivariate prognostic analysis for overall survival (OS) and event-free survival (EFS). Sixty-five patients (75%) with DLCL and 22 with MZL(65%) achieved complete remission. After a median follow-up of 42 months (range 6-163 months), 5-year estimates of OS and EFS were 68% and 50% for DLCL and 65% and 26% for MZL. OS varied according to MIPI, from, respectively, 86% and 87% for DLCL and MZL patients with 0-1 risk factor to 50% and 32% for patients with > 1 risk factor (P=0.01 and P=0.02). Similar results were obtained for EFS. Cox regression analysis showed an unfavourable MIPI to be the only independent predictor of shorter EFS. This retrospective study shows that stage-MIPI can be a reliable prognostic indicator for PIL of both low-grade MZL and diffuse large B-cell histology, enabling the early identification of patients at higher risk of failure.