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A story of a pimple: Newly diagnosed chronic lymphocytic leukemia in a basal cell carcinoma biopsy

CLL is the most common form of leukemia in the United States. The majority of CLL patients are asymptomatic or have painless lymphadenopathy at the time of presentation. The suspicion of CLL is often raised during a routine peripheral blood evaluation with an incidental finding of an absolute lymphocytosis. Flow cytometry and molecular studies usually confirm the diagnosis. The dermatological manifestations of CLL usually present months or years after the diagnosis of CLL has been rendered. BCC and SCC are the most common skin manifestation in patients with CLL, but malignant melanoma has also been described in a small subset of cases. However, the association of BCC with a newly diagnosed CLL is an extremely rare coincidence which has not been reported previously. Only two cases of SCC associated with newly diagnosed CLL have been reported previously. Here, we present a patient with an undiagnosed CLL associated with a newly diagnosed BCC. A 65-year-old woman presented with a skin growth on her upper back for the past several months. The patient's medical history was significant for hypertension and hypothyroidism. Physical exam revealed a 10 mm pink dome-shaped papule on her upper back (Figure 1) with the clinical impression of BCC. A shave biopsy of the lesion demonstrated a nodular BCC associated with a mirroring dense dermal infiltrate of lymphocytes. The lymphoid infiltrate spared the epidermis, and was composed of small cells with clumped chromatin and no distinctive nucleoli. A large cell component was not identified (Figure 2). Immunohistochemistry of the lymphoid infiltrate demonstrated immunoreactivity for CD5, CD20, CD43, and CD23 (Figure 3). CD3 was expressed in the background T-cells. The Ki-67 (MIB) index was very low (<3%). The malignant lymphoid cells were negative for cyclin D1 and SOX-11. These findings were most consistent with a diagnosis of chronic lymphocytic leukemia. The patient was successfully referred to Hematology-Oncology for further evaluation. Recent flow cytometric evaluation showed a small population of B-cells (9% of the total cells) with surface dim lambda light-chain restriction, in addition to CD5, CD43, and CD23 co-expression. The total lymphocyte count was 2.59 cell/μL. Several months after the skin biopsy, he also developed slowly progressive thrombocytopenia. A CT scan of abdomen and pelvis showed sub centimeter retroperitoneal and pelvic lymph nodes not suspicious for nodal involvement by lymphoma. Given these findings, the patient was diagnosed with CLL/SLL Rai Stage 0. The association of cutaneous CLL with epithelial cutaneous malignancies has been previously described. However, the initial diagnosis of CLL in association with a BCC biopsy has not been reported. Only two cases of a newly diagnosed CLL infiltrating a squamous cell carcinoma have been reported previously. Recognition of CLL in these cases has clinical and prognostic relevance considering that CLL patients have increased risk for recurrence and metastasis of these cutaneous epithelial malignancies. Referral to a Mohs surgeon should be considered. Although CLL affects the prognosis of BCC/SCC; the diagnosis of BCC/SCC does not appear to affect the prognosis of CLL. T-lymphocytes commonly constitute the primary inflammatory cells in patients with cutaneous malignancies. The reason why B-cells (ie, CLL) are attracted to these cutaneous malignancies is not entirely clear. Possible explanations of this phenomenon have been hypothesized: It is possible that this leukemic infiltrate simply reflects the immune dysregulation that is seen in patients with CLL. Another possible explanation is that atypical B-lymphocytes respond to antigenic stimuli from the cutaneous neoplasm resulting in reactive migration. A contrast to these ideas is the possibility of increased vascular permeability stemming from neovascularization causing lymphocytes to accumulate around the neoplasm. From a differential diagnosis, other cutaneous lymphoproliferative disorders, that are CD5+ should also be included in the differential diagnosis: to this extent, mantle cell lymphoma (MCL) is a systemic form of B-cell malignancy that can sometimes involve the skin. As opposed to CLL, mantle cell lymphoma is typically CD23 and CD43 negative. Mantle cell lymphoma also shows a specific translocation F IGURE 1 A pink, small, round papule is present in the upper back Received: 10 March 2020 Revised: 21 April 2020 Accepted: 29 April 2020