An inflammatory myofibroblastic tumor (IMT) is a neoplasm composed of myofibroblastic and fibroblastic spindle cells accompanied by inflammatory cells, including lymphocytes and eosinophils. It is an ultra-rare tumor, the optimal management of which remains to be defined. Surgery is the treatment of choice for localized tumors. The treatment of advanced disease is not precisely defined. Chemotherapy regimens result in an overall response rate of approximately 50% based on retrospective data. The latest pathophysiological data highlight the role played by tyrosine kinase fusion genes in IMT proliferation. Anaplast lymphoma kinase (ALK) oncogenic activation mechanisms have been characterized in approximately 80% of IMTs. In this context, data regarding targeted therapies are most important. The aims of this article are to review the latest published data on the use of systematic therapy, particularly the use of molecular targeted therapy, and to publish an additional case of an IMT with Ran-binding protein 2 (RANPB2)-ALK fusion showing a long response to a tyrosine kinase inhibitor.

Dasatinib, a second-generation tyrosine kinase inhibitor (TKI), used as treatment for chronic myeloid leukemia, BCR::ABL1-positive (CML), is complicated by pleural or pericardial effusions in about one-third of patients. Besides, in exceptional instances, effusion-based neoplastic B-cell lymphoproliferations have been described. Here, we report an HHV8-negative, EBV-positive large B-cell lymphoma presenting as a pericardial effusion in a patient with CML treated with dasatinib for 23 months, without associated tumor mass or lymphadenopathies. Large tumor cells showed a B-cell phenotype (CD20+, CD79+), with evidence of EBV infection (EBER-ISH+), but HHV8 (LANA-1) negative. Monoclonal IG gene rearrangements were identified. BCL2, BCL6, and MYC genes were not rearranged. Despite the aggressive cytomorphology the patient was in complete remission after 4 cycles of R-CHOP after 8 months followup. Four other cases of large B-cell effusion-based lymphomas developed in the setting of dasatinib therapy for CML have been reported in the literature. The four cases were HHV8-negative and one case was EBV-positive. Three of the four patients experienced a benign clinical course, which is in contrast to HHV8-positive primary effusion lymphoma (PEL). The mechanisms of development of these effusion-based B-cell lymphoproliferations in patients receiving TKI are not completely elucidated. Acute or relapsing effusions during TKI treatment in the setting of CML should be cytologically examined to exclude clonal B-cell lymphoproliferations.

Anal squamous cell carcinoma (ASCC) is a rare malignancy with a rising incidence associated with human papillomavirus (HPV) infection. The locally advanced disease is associated with a 30% rate of treatment failure after standard chemoradiotherapy (CRT). We aimed to elucidate the prognostic factors for ASCC after curative CRT. A retrospective multicenter study of 176 consecutive patients with ASCC having completed CRT treated between 2010 and 2017 at two centers was performed. Complete response (CR), disease-free survival (DFS), and overall survival (OS) were analyzed by Kaplan–Meier estimates with log-rank tests. The hierarchical clustering on principal components (HCPC) method was employed in an unsupervised and multivariate approach. The CR rate was 70% and was predictive of DFS (p < 0.0001) and OS (p < 0.0001), where non-CR cases were associated with shorter DFS (HR = 16.5, 95% CI 8.19–33.21) and OS (HR = 8.42, 95% CI 3.77–18.81) in a univariate analysis. The median follow-up was 38 months, with a 3-year DFS of 71%. The prognostic factors for DFS were cT1-T2 (p = 0.0002), N0 (p = 0.035), HIV-positive (p = 0.047), HIV-HPV coinfection (p = 0.018), and well-differentiated tumors (p = 0.037). The three-year OS was 81.6%. Female sex (p = 0.05), cT1-T2 (p = 0.02) and well-differentiated tumors (p = 0.003) were associated with better OS. The unsupervised analysis demonstrated a clear segregation of patients in three clusters, identifying that poor prognosis clusters associated with shorter DFS (HR = 1.74 95% CI = 1.25–2.42, p = 0.0008) were enriched with the locally advanced disease, anal canal location, HIV-HPV coinfection, and non-CR. In conclusion, our results reinforce the prognostic value of T stage, N stage, sex, differentiation status, tumor location, and HIV-HPV coinfection in ASCC after CRT.

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