An injury to the vas deferens during inguinal herniorrhaphy from possible tethering of the vas has not, to our knowledge, previously been described in the surgical literature. We report a case of iatrogenic injury of the vas deferens that occurred during elective hernia repair in a 28-year-old man who had previously sustained blunt trauma to the abdomen and pelvis.

Intravascular large cell lymphoma (IVLCL) is a rare disease characterized by proliferation of malignant lymphocytes within the small blood vessel lumens. The association of IVLCL with autoimmune hemolytic anemia (AIHA) has been described in a single case report, but the true prevalence of this co-occurrence is not known because of declining autopsy rates. Here, we report a case of a 41-year-old woman who carried a diagnosis of AIHA for 2 years, with repeated hemolytic episodes that were initially well controlled with immunomodulatory treatment. At her last presentation, the patient developed rapidly progressive neurologic symptoms and leukoencephalopathy on MRI; she died 4 weeks later with a clinical impression of thrombotic microangiopathy, a known complication of AIHA. At autopsy, the brain showed widespread platelet thrombi and intraparenchymal hemorrhages characteristic of this disorder. In addition, there was evidence of a clinically unsuspected IVLCL, most likely of B-cell lineage. This case illustrates a potential association between IVLCL and AIHA, highlights the need for broad differential diagnosis in cases with atypical disease presentation or progression, and underlines the importance of autopsy in establishing the full cause of morbidity and mortality.

Background

The optimal therapeutic approach for patients with AIDS-related primary central nervous system lymphoma (AR-PCNSL) remains undefined. While its incidence declined substantially with combination antiretroviral therapy (cART), AR-PCNSL remains a highly aggressive neoplasm for which whole brain radiotherapy (WBRT) is considered a standard first-line intervention.

Methods

To identify therapy-related factors associated with favorable survival, we first retrospectively analyzed outcomes of AR-PCNSL patients treated at San Francisco General Hospital, a public hospital with a long history of dedicated care for patients with HIV and AIDS-related malignancies. Results were validated in a retrospective, multicenter analysis that evaluated all newly diagnosed patients with AR-PCNSL treated with cART plus high-dose methotrexate (HD-MTX).

Results

We provide evidence that CD4+ reconstitution with cART administered during HD-MTX correlates with long-term survival among patients with CD4 <100. This was confirmed in a multicenter analysis which demonstrated that integration of cART regimens with HD-MTX was generally well tolerated and resulted in longer progression-free survival than other treatments. No profound differences in immunophenotype were identified in an analysis of AR-PCNSL tumors that arose in the pre- versus post-cART eras. However, we detected evidence for a demographic shift, as the proportion of minority patients with AR-PCNSL increased since advent of cART.

Conclusion

Long-term disease-free survival can be achieved in AR-PCNSL, even among those with histories of opportunistic infections, limited access to health care, and medical non-adherence. Given this, as well as the long-term toxicities of WBRT, we recommend that integration of cART plus first-line HD-MTX be considered for all patients with AR-PCNSL.

There is an unmet need for effective biological therapies for relapsed central nervous system (CNS) lymphoma. Lenalidomide is active in activated B-cell type diffuse large B-cell lymphoma and rituximab is effective in CNS lymphoma. These observations are the basis for this first trial of an immunomodulatory drug as monotherapy in CNS lymphoma, and, in patients with inadequate responses to lenalidomide, with rituximab. In an independent cohort, we evaluated lenalidomide maintenance after salvage with high-dose methotrexate or focal irradiation in relapsed primary CNS lymphoma (PCNSL). We determined safety, efficacy, and cerebrospinal fluid (CSF) penetration of lenalidomide at 10-, 15-, and 20-mg dose levels in 14 patients with refractory CD20⁺ CNS lymphoma. Nine subjects with relapsed, refractory CNS lymphoma achieved better than partial response with lenalidomide monotherapy, 6 maintained response ≥9 months, and 4 maintained response ≥18 months. Median progression-free survival for lenalidomide/rituximab was 6 months. In the independent cohort, response duration with lenalidomide maintenance after complete responses 2 through 5 were significantly longer than response durations after standard therapy. The CSF/plasma partition coefficient of lenalidomide was ≥20% at 15- and 20-mg dose levels. Change in CSF interleukin-10 at 1 month correlated with clinical response and response duration to lenalidomide. Metabolomic profiling of CSF identified novel biomarkers, including lactate, and implicated indoleamine-2,3 dioxygenase activity with CNS lymphoma progression on lenalidomide. We conclude that lenalidomide penetrates ventricular CSF and is active as monotherapy in relapsed CNS lymphomas. We provide evidence that maintenance lenalidomide potentiates response duration after salvage in relapsed PCNSL and delays whole brain radiotherapy (WBRT). This trial was registered at www.clinicaltrials.gov as #NCT01542918.