Fine needle aspiration (FNA) was performed in two separate areas of the nodule and smears were stained in accordance with the May-Gruenwald-Giemsa method. Both specimens showed an abundance of relatively monomorphic, atypical, epithelial-appearing cells without visible nucleoli, lying alone and in clusters. Occasional mitoses were evident. There were a few lymphoid cells in the background, very scant fibrous stroma and some peripheral blood. Nuclear molding was prominent in these cells and the cytoplasm was scant and rarely preserved (Figure 2A). Malignant cells showed strong staining with epithelial antigen (Ber-Ep4) (Figure 2B), while leukocyte common antigen (LCA) was used for leukocytes. Malignant cells showed strong positivity for epithelial marker, while LCA marked only a few scattered lymphoid cells in the background. Diagnosis of epithelial malignant tumor with neuroendocrine morphologic features indicated Merkel cell carcinoma.

Simultaneously with the FNA of the cutaneous tumor, a peripheral blood smear was analyzed. This showed a lymphocytosis (75% of lymphocytes). Bone marrow aspiration and flow cytometric analyses confirmed the diagnosis of a low-grade B-cell chronic lymphocytic leukemia. Right axillary region ultrasound indicated two enlarged lymph nodes which showed reactive changes on histopathological examinations. Further diagnostic tests did not reveal lymphadenopathy, hepatomegaly or splenomegaly. Whole body skeletal scintigraphy imaging did not indicate any irregularities. In our patient, CLL was in Rai stage 0, so there was no need for active treatment.

During 3 weeks of hospital treatment, we noticed the spontaneous regression of the tumor to half of its original size (Figure 1B). Surgical excision and sentinel lymph node biopsy were then carried out. Radical excision with 2 cm of tumor-free margins was performed under general anesthesia. The sentinel lymph nodes did not contain MCC.

Histopathological analysis of the regressed tumor, stained with hematoxylin and eosin, revealed that the tumor cells were completely replaced by mononuclear cells. An immunohistochemical study was performed with formalin-fixed and paraffin embedded material, using the avidin-biotin peroxidase method (all antibodies from Dako Japan, Co. Ltd, Kyoto). Immunolabeling of infiltrating lymphocytes was positive for CD3+ T cells (Figure 2C), while there were a few B cells. Infiltrating macrophages were positive for CD68+ (Figure 2D). Electronic microscopy of the excised tumor showed histiocytic infiltration, with no trace of epithelial cells (Figure 3).

The incidence of MCC is high (8%) among immunosuppressed patients [2], but the pathogenetic relationship between CLL and cutaneous neoplasia is still unclear. Both UV radiation and CLL are thought to cause immunosuppression which is associated with an increased incidence of cutaneous malignancies.

In our patient, these factors were combined with another possible trigger - an insect bite, generating an inflammatory milieu from which MCC could have derived. The fact that the tumor developed a few weeks after the insect bite, favors this line of thought.

A better prognosis has been associated with shorter intervals between the appearance of CLL and development of MCC, even though the outcome of MCC is possibly independent of the CLL stage [14]. Poor prognostic factors are young age, male sex, large tumor size, truncal site, nodal or distant disease and duration of the disease before presentation [2,15]. Considering these parameters, a favorable outcome would be expected in our patient.

Regression is a complete or partial disappearance of malignant cells without any treatment. It is mediated by T-lymphoid infiltration which induces apoptotic tumor cells [16]. A high proportion of MCC shows regression (1.7 to 3%) in MCC patients [17] so immunologic responses play an important role in this type of tumor.

It is still unclear how a mechanical stimulus (FNA) can be a trigger for activating the immune system toward macrophage mediated digestion of malignant cells. All previously described cases of MCC regression without any treatment were also noticed after needle biopsy. This procedure could stimulate the immune system toward tumor destruction. Our findings indicate that FNA is responsible for the activation of cell-mediated immunity, leading to clinical and histological regression of the tumor.

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