[Immunocompromised HIV patient with lymphadenopathy and fever]. / Adénopathies et fièvre chez une patiente VIH positive.

The case of a immunocompromised HIV patient with fever and lymphadenopathy discussed in an anatomo-pathological round. This complex clinical case was used as an opportunity to discuss the broad differential diagnosis of fever in an immunocompromized individual with multiples lymphadenopathies. Clinical reasoning leading to the probable diagnosis based on clinical, biological and radiological informations is not only a difficult task for the speaker but also a rich source of learning opportunities for our medical community.

[Predictive pathology of lymphomas]. / Pathologie prédictive des lymphomes.

The predictive pathology in the diagnosis of B-cell lymphomas is a field in evolution. As our understanding of these tumours progresses so does our ability to predict their evolution. This is true not only in the wider and traditional sense where a given marker identifies a group of tumors with a better or worse prognosis but also with reference to specific patients. Here the development of new therapeutic agents whose activity depends on the expression within the tumour of specific proteins has begun to bring the long awaited era of "personalised therapy" a little closer to reality.

Cervical chordoma with retropharyngeal extension presenting with impaired voice.

AIMS AND BACKGROUND: We report an extremely rare case of cervical chordoma presenting with impaired voice. METHOD: Case report and a review of the literature concerning the presentation, diagnosis, and treatment of a cervical chordoma. RESULTS: A singing teacher complaining of dysphonia was examined and surgically treated for a retropharyngeal extension of a cervical chordoma. A local recurrence was treated with proton beam therapy. Among primary malignant tumors of bone, chordomas account for 3-4% of all cases. Chordoma is typically a locally aggressive tumor with a high propensity for local recurrence. Its management involves surgery, radiotherapy, or both. CONCLUSION: To our knowledge this is the first report in the world literature of a retropharyngeal extension of a cervical chordoma presenting with impaired voice. This case indicates that bony tumors of the spine may present first to voice-disorder clinicians. Increased awareness of this neoplasm may lead to earlier diagnosis and better treatment.

EBV+ cutaneous B-cell lymphoproliferation of the leg in an elderly patient with mycosis fungoides and methotrexate treatment.

A 77-year-old man with a 5-year history of mycosis fungoides (MF) who had received several lines of therapy, including intravenous courses of Methotrexate (MTX) for the past 2 years, went on to develop several ulcerated cutaneous nodules on the left leg. Biopsy revealed diffuse sheets of EBV-positive large B cells (CD20+ CD30 ± IgM Lambda), with an angiocentric distribution and a monoclonal IGH gene rearrangement. Although the pathological features were diagnostic for an EBV-positive diffuse large B-cell lymphoma (DLBCL), several possibilities could be considered for assignment to a specific entity: EBV-positive DLBCL of the elderly, methotrexate-induced lymphoproliferative disorder (LPD), lymphomatoid granulomatosis, or the more recently described EBV-positive mucocutaneous ulcer. The development of EBV+ lymphoproliferations has been reported in two other patients with MF under MTX, and occurred as skin lesions of the leg in one of these and in the current case, which may question the relatedness to primary cutaneous DLCBL, leg-type.

Inhibition of the Kit ligand/c-Kit axis attenuates metastasis in a mouse model mimicking local breast cancer relapse after radiotherapy.

PURPOSE: Local breast cancer relapse after breast-saving surgery and radiotherapy is associated with increased risk of distant metastasis formation. The mechanisms involved remain largely elusive. We used the well-characterized 4T1 syngeneic, orthotopic breast cancer model to identify novel mechanisms of postradiation metastasis. EXPERIMENTAL DESIGN: 4T1 cells were injected in 20 Gy preirradiated mammary tissue to mimic postradiation relapses, or in nonirradiated mammary tissue, as control, of immunocompetent BALB/c mice. Molecular, biochemical, cellular, histologic analyses, adoptive cell transfer, genetic, and pharmacologic interventions were carried out. RESULTS: Tumors growing in preirradiated mammary tissue had reduced angiogenesis and were more hypoxic, invasive, and metastatic to lung and lymph nodes compared with control tumors. Increased metastasis involved the mobilization of CD11b(+)c-Kit(+)Ly6G(high)Ly6C(low)(Gr1(+)) myeloid cells through the HIF1-dependent expression of Kit ligand (KitL) by hypoxic tumor cells. KitL-mobilized myeloid cells homed to primary tumors and premetastatic lungs, to give rise to CD11b(+)c-Kit(-) cells. Pharmacologic inhibition of HIF1, silencing of KitL expression in tumor cells, and inhibition of c-Kit with an anti-c-Kit-blocking antibody or with a tyrosine kinase inhibitor prevented the mobilization of CD11b(+)c-Kit(+) cells and attenuated metastasis. C-Kit inhibition was also effective in reducing mobilization of CD11b(+)c-Kit(+) cells and inhibiting lung metastasis after irradiation of established tumors. CONCLUSIONS: Our work defines KitL/c-Kit as a previously unidentified axis critically involved in promoting metastasis of 4T1 tumors growing in preirradiated mammary tissue. Pharmacologic inhibition of this axis represents a potential therapeutic strategy to prevent metastasis in breast cancer patients with local relapses after radiotherapy.