Brain Pathology Case of the Month - February 2018

FINAL DIAGNOSIS

CD8+ Cytotoxic T-Cell Lymphoma .

DISCUSSION

Primary cutaneous aggressive intraepidermal cytotoxic T-cell lymphoma is a rare (comprising <1%) subtype of cutaneous T-cell lymphoma (CTCL) and follows a more rapid clinical course. In this particular patient, a right forearm biopsy taken approximately 4 months prior to the brain biopsy showed an intraepidermal as well as a dermal lymphoid infiltrate with marked adnexotropism, composed of medium-sized lymphocytes with perinuclear haloes; less than 30% were enlarged. Among other markers, the tumor cells were positive for CD3, CD8, CD7, and CD4, with <50% of cells positive for CD5, and negative for CD30 and EBER. Given the similar morphology and immunophenotype in the brain biopsy material, we favored these tumors to represent the same lymphoma.

Rapid progression with extracutaneous dissemination to extranodal sites (lung, testis, central nervous system, and oral cavity) is typical. As described in one of the original studies, aggressive intraepidermal cytotoxic T-cell lymphoma involved the central nervous system (CNS) in 2 of 8 patients with a distinct clinical course. The results of a recent task force workshop further distinguished this entity from other CD8+ lymphomas, including mycosis fungoides with CD8+ phenotype, lymphomatoid papulosis, and solitary pagetoid reticulosis. Aggressive intraepidermal cytotoxic T-cell lymphoma occurred in 11 men and 7 women (18 cases total), ranging in age from 27-87 years (average, 54.5 years). The median survival in 13 fatal cases was 12 months. All cases were CD8 positive and expressed either or both TIA-1 and granzyme B, while 14/18 cases lacked CD2 and/or CD5; 8/10 cases tested were positive for beta-F1. All cases were negative for CD30, CD56, and EBER in-situ hybridization.

CNS involvement by peripheral T-cell lymphomas generally portends poor prognosis. A recent review from a single institution documented 15 of 231 patients with CNS involvement by a peripheral T-cell lymphoma over a 17-year time period, of which 8 cases were pathologically confirmed. CNS disease typically presented early (median, 3.44 months from diagnosis of lymphoma to CNS involvement), and survival thereafter was a median of 2.63 months.

REFERENCES

  1. Berti E, Tomasini D, Vermeer MH, Meijer CJ, Alessi E, Willemze R. Primary cutaneous CD8-positive epidermotropic cytotoxic T cell lymphomas. A distinct clinicopathological entity with an aggressive clinical behavior. Am J Pathol. 1999 Aug;155(2):483-92.
  2. Robson A, et al. Aggressive epidermotropic cutaneous CD8+ lymphoma: a cutaneous lymphoma with distinct clinical and pathological features. Report of an EORTC Cutaneous Lymphoma Task Force Workshop. Histopathology. 2015 Oct;67(4):425-41.
  3. Gurion R, et al. Central nervous system involvement in T-cell lymphoma: A single center experience. Acta Oncol. 2016 May;55(5):561-6.

Contributed by Alireza Shams, MD and Katherine Schwetye, MD, PhD

International Society of Neuropathology