Final Diagnosis -- Chronic Lymphocytic Leukemia and Metastatic Malignant Melanoma




This patient's bone marrow biopsy and aspirate were positive for both chronic lymphocytic leukemia (CLL) and metastatic malignant melanoma. The immunohistochemical stains demonstrated a lymphoid infiltrate of predominantly B-cells which were morphologically consistent with CLL. The tumor cells stained positively with S-100 and were consistent with metastatic melanoma.

Several studies have shown an association between skin cancer and other primary cancers and there is evidence of an association between hematologic neoplasms and skin cancer. In a study by Adami et al (1995), the relative risk for squamous cell carcinoma was 8.6 in patients with chronic lymphocytic leukemia (CLL) and 5.5 in patients with non-Hodgkin's lymphoma (NHL). These risks remained high for more than 15 years after diagnosis. In the same study, the relative risks for malignant melanoma were 3.1 in patients with CLL and 2.4 in patients with NHL. After the occurrence of squamous cell carcinoma, there was a two-fold increased risk of CLL and NHL.

Levi et al (1996) reported an increase in squamous cell and basal cell carcinomas in patients previously diagnosed with CLL or NHL. In the same study, there was an increase in NHL but not CLL after skin cancer diagnosis.

Gutman et al (1991) found a relative risk of 4.1 for the development of a second noncutaneous invasive cancer within six months of the diagnosis of malignant melanoma. These cases were considered to be "simultaneous malignancies". There was a 3.3 relative risk for the development of a second noncutaneous invasive malignancy beyond six months after the diagnosis of malignant melanoma. These increased relative risks were not related to the location of the primary tumor, level of invasion, stage, or treatment methods utilized.

The association and possible synergy between skin cancers and hematologic malignancies is not understood. The development of a first malignancy may be related to the patient's overall risk factors such as oncogenes, environmental exposures, or familial predisposition secondary to genetic defects. Tumor growth factors produced by the first malignancy, a skin cancer for example, may enhance proliferation of other cell lines.

There are known immunohistochemical similarities between cell lines and/or malignancies. For example, common leukocyte antigen (CALLA/CD10) a marker for precursor B-cells and germinal center B-cells is often, 30-100% of the time (Carrel et al , 1993), expressed by melanoma cells. The relevance of this with regard to an association between CLL and malignant melanoma is unknown.

CLL primarily affects elderly patients and does carry with it an increased risk of other primary malignancies, especially skin cancer. The studies cited in this case report help to quantify the association between skin cancer and hematologic neoplasms. This case is of particular interest because the two malignancies were simultaneously diagnosed.


Contributed by Debra L. Callahan, M.D.


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