Case Letter

Chronic Lymphocytic Leukemia and Infiltrates Seen During Excision of Nonmelanoma Skin Cancer

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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.



To the Editor:

Specific characteristics of a lymphocytic infiltrate noted on frozen section histologic examination during Mohs micrographic surgery (MMS) tumor excision should raise suspicion of an underlying chronic lymphocytic leukemia (CLL). This infiltrate may be the presenting sign of the underlying leukemia and has variable presentation that may mimic aggressive features. The following 3 cases highlight this phenomenon.

A 74-year-old man (patient 1) with a medical history of multiple nonmelanoma skin cancers (NMSCs) presented for definitive treatment of a biopsy-proven infiltrative basal cell carcinoma involving the right infra-auricular region. Mohs section histologic evaluation revealed patches of lymphocytic infiltrates so dense they obscured the tumor margins. The lymphocytic infiltrates persisted even after 3 MMS stages, though they were moderately less dense compared to the initial MMS stage. Clinical interpretation determined no relationship between the lymphocytic infiltrates and residual tumor. Due to concerns that this lymphocytic infiltrate may indicate an underlying leukemic process, preoperative laboratory tests were ordered prior to closure of the surgical wound, which demonstrated an elevated white blood cell count of 65,000/µL (reference range, 4500–11,000/µL) with 93% lymphocytes. A follow-up complete blood cell count (CBC) and blood smear confirmed the diagnosis of CLL. The patient was referred to a hematologist/oncologist.

An 84-year old man (patient 2) with a medical history of numerous precancerous lesions and 1 squamous cell carcinoma (SCC) presented for a biopsy, which determined moderately differentiated SCC. Mohs micrographic surgery was performed. The initial stage of MMS histologic examination demonstrated basosquamous carcinoma in the specimen margins, including perineural growth, with an extensive lymphoid infiltrate surrounding the tumor (Figure 1). A second stage of MMS was performed, and although margins appeared to be clear of the basosquamous histology, complete assessment was difficult due to areas of dense inflammatory infiltrate (Figure 2), including perineural infiltration that remained and appeared to extend deeper into the tissues. Pathology was consulted and it was determined that the perineural infiltration was unlikely related to tumor spread but rather secondary to an unknown cause. Further investigation of the patient’s medical history revealed previously diagnosed CLL, which had been omitted by the patient, as he had forgotten this diagnosis and denied a history of cancer, lymphoma, and even leukemia. A query to the patient’s primary care physician found the most recent CBC demonstrated an elevated white blood cell count of 37,600/µL with 78% lymphocytes.

Figure 1. Histologic examination showed perineural wrapping by the tumor with a lymphocytic infiltrate at the center of this view (H&E, original magnification ×40).

Figure 2. Histologic examination of this Mohs micrographic surgery specimen’s margins was difficult due to the persistent lymphoid infiltrate, which appeared quite close to a nerve (H&E, original magnification ×40).

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