Chronic Lymphocytic Leukemia and Infiltrates Seen During Excision of Nonmelanoma Skin Cancer
Practice Points
- Chronic lymphocytic leukemia (CLL) may be seen during histologic examination of specimens during Mohs micrographic surgery as a monomorphic infiltrate of small mature lymphocytes with dense nuclei. Patients may be unaware of their diagnosis, which can be the presenting feature.
- An infiltrate of CLL may mimic aggressive behavior of nonmelanoma skin cancers including perineural invasion. A leukemic infiltrate may appear more dense and monomorphic. If needed, immunohistochemical staining of leukemic cells will show CD5 and CD23 positivity.
- Anecdotally, patients with CLL may not remember this pertinent medical history. Whether due to its asymptomatic nature or lack of treatment in early stages, direct questioning about CLL may be warranted if this characteristic infiltrate is encountered.
When evaluating a patient with suspected CLL, laboratory tests should include a CBC with differential and examination of the peripheral smear. If abnormal, immunophenotyping of lymphocytes by flow cytometry will rule out other lymphoproliferative diseases and verify CLL as the diagnosis.3 Diagnosis of CLL requires the presence of monoclonal B lymphocytes (≥5×109/L) in the peripheral blood as confirmed by flow cytometry.3 Clonality of circulating B lymphocytes must be confirmed, and immunophenotyping will establish a diagnosis with leukemic cells having positive expression of CD20 (Figure 3A) and CD23 (Figure 3B)(characteristic of B-cell lineage) with coexpression of CD43 and CD5 (Figure 3C)(characteristic of T-cell lineage).7,9 This pattern of immunohistochemical markers can be differentiated from the normal immune response to cutaneous malignancies, which have the pattern of being CD3+, CD5+, and CD43+ with absence of B-cell markers (ie, CD20, CD23)(Table).7
The pathogenesis of this peritumoral infiltrate is unknown, though multiple theories exist. One theory is that the neoplastic lymphocytes are responding as a dysfunctional arm of the immune system to tumor-specific antigens. In patients with CLL, leukemic lymphocytes comprise a large portion of the circulating leukocyte population and this peritumoral infiltrate may simply be a reflection of the circulating leukocytic population. Another theory contends that neoplastic lymphocytes are simply nonspecific aggregations secondary to tumor neovascularization and increased vascular permeability.10
,This neoplastic infiltrate seen incidentally during MMS excision of NMSCs not only provides a unique opportunity to diagnose and intervene in those with unknown CLL but also to be aware of complicating features that can spare the patient from unnecessary tissue removal, thereby maximizing the benefit of MMS. This infiltrate can obscure tumor margins; is unusually dense and patchy, with or without infiltrating perineural or perivascular components; and persists beyond what would seem to be an adequate margin to clear a tumor. These cases show these findings, which exemplify the peritumoral infiltrate of CLL and should prompt further workup.
