Final Diagnosis -- Intravascular NK/T-Cell Lymphoma with Associated Multifocal Microinfarcts

FINAL DIAGNOSIS

INTRAVASCULAR NK/T-CELL LYMPHOMA WITH ASSOCIATED MULTIFOCAL MICROINFARCTS

DISCUSSION

This is a highly unusual case both from the clinical, neuroradiological and neuropathological perspectives. At autopsy, neuropathologic examination showed intravascular lymphoma that was immunophenotypically of an NK/T-cell type. Intravascular large cell lymphoma (IVLCL), a rare variant of extranodal non-Hodgkin lymphoma, is thought to remain localized within vessels due to the absence of certain adhesion molecules, preventing diapedesis, although the exact mechanism is not well characterized (2). IVLCL is most commonly of a B-cell immunophenotype, but T-cell and natural killer (NK)-cell variants have been described in < 30 reports in the literature (1). Because precise determination of lineage requires flow cytometric and gene rearrangement studies, the paucity of tumor cells in cases of IVLCL precludes further subtyping beyond what can be determined by immunohistochemistry as a generic "NK/T-cell" phenotype. As opposed to B-cell IVLCL, the NK/T-cell phenotype is frequently positive by in-situ hybridization for Epstein-Barr virus encoding RNA (EBER) (2, 3). Clinical behavior is usually aggressive, but varies depending on the stage, and extent of disease.

There is no stereotypic radiological presentation for intravascular lymphoma. In the current case, the radiologic differential diagnosis initially included embolic disease given the multifocal punctate infarcts. However, the favorable symptomatic response to steroid therapy and recurrent infarcts involving multiple vascular territories made a more chronic steroid-responsive process, such as lupus cerebritis, primary angiitis of the central nervous system (CNS), and intravascular lymphoma, more likely. When she re-presented with new symptoms and radiologic findings, as well as a positive, high-titer, nucleolar pattern ANA, the clinical suspicion shifted to include lupus cerebritis, given a reported history of lupus in the patient's mother, and malignancy, specifically intravascular lymphoma, although no systemic involvement was found on antemortem pathology examinations of skin, muscle, and bone marrow biopsies. A brain biopsy was scheduled, but the patient expired prior to surgery.

While NK/T-cell IVLCL often shows systemic involvement, particularly in the skin, a subset of cases are also detected in the brain, most commonly at autopsy (1). CNS involvement may account for the primary symptomatic presentation (5), and is often associated with the presence of microinfarcts (4), as in our case. Finally, although only a limited antemortem workup was performed, this case may represent the sole report of apparently exclusive CNS involvement by NK/T cell IVLCL, with the caveat of a lack of complete autopsy.

REFERENCES

1. Cerroni L, Massone C, Kutzner H, Mentzel T, Umbert P, Kerl H. Intravascular large T-cell or NK-cell lymphoma: a rare variant of intravascular large cell lymphoma with frequent cytotoxic phenotype and association with Epstein-Barr virus infection. (2008) Am J Surg Pathol 32:891-8.
2. Nakamichi N, Fukuhara S, Aozasa K, Morii E. (2008) NK-cell intravascular lymphomatosis--a mini-review. Eur J Haematol. 81:1-7.
3. Song DE, Lee MW, Ryu MH, Kang DW, Kim SJ, Huh J. (2007) Intravascular large cell lymphoma of the natural killer cell type. J Clin Oncol. 25:1279-82.
4. Wu H, Said JW, Ames ED, Chen C, McWhorter V, Chen P, et al. (2005) First reported cases of intravascular large cell lymphoma of the NK cell type: clinical, histologic, immunophenotypic, and molecular features. (2005) Am J Clin Pathol. 123(4):603-11.
5. Xie J, Zhou X, Zhang X, Zheng Y, Yue B. Primary intravascular natural killer/T cell lymphoma of the central nervous system. Leuk Lymphoma. 2015 Apr;56(4):1154-6.

Contributed by Katherine E. Schwetye, MD, PhD, David Rodriguez, MD, Robert E. Schmidt, MD, PhD, Sonika Dahiya, MD