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Merkel cell tumor and chronic lymphocytic leukemia - coincidence or a possible association?

  • Author(s): Ben-David, Aya
  • Lazarov, Aneta
  • Lev, Silvia
  • Nussbaum, Bela
  • et al.
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Merkel cell tumor and chronic lymphocytic leukemia - coincidence or a possible association?
Aya Ben-David MD1,Aneta Lazarov MD 2, Silvia Lev MD3, Bela Nussbaum4
Dermatology Online Journal 11 (3): 16

1. Department of Family Medicine, Clalit Health Services, Jerusalem. lazarova@clalit.org.il2. Dermatology Clinic, 3. Pathology Department, 4. Oncology Department, Meir Hospital, Kfar Saba, Israel and Sackler School of Medicine, Tel Aviv University.

Chronic lymphocytic leukemia (CLL) is a B-cell tumor associated with an increased incidence of secondary malignant neoplasms, such as brain tumors, melanomas, and gastrointestinal-tract carcinomas [1]. The risk of developing skin cancers, such as basal and squamous cell carcinomas, in patients with CLL is eight-fold compared to a control population [2].

Only seven instances of patients with a previous diagnosis of CLL who developed aggressive Merkel cell tumor (MCT) have been reported in literature [3, 4, 6, 7]. We describe a similar case recently seen in our clinic.


Clinical synopsis


Figure 1

A 92-year old woman diagnosed with CLL in august 2001, was referred by her family physician to our Dermatology Clinic in October 2004 with a diagnosis of recurrent cellulitis of her right leg for evaluation and further treatment. The patient had not received any treatment for her CLL.

The patient presented with two dome-shaped erythematous nodules on her right shin; these lesions had shiny surfaces and rubbery consistencies. The larger nodule measured 3 cm and the smaller one measured 1 cm in diameter (Fig. 1). Lymphadenopathy was palpable in the right inguinal area. The differential diagnosis of the skin tumors included dermatological manifestation of CLL, B-cell lymphoma, and Kaposi sarcoma.


Figure 2 Figure 3
Fig.2 Merkel cell tumor. HE × 100. The tumor cells show a diffuse and insular growth pattern, as sheets and solid nests, infiltrating the entire dermis.
Fig. 3 H&E × 200. Tumor cells demonstrating atypical features and multiple mitoses.

The skin nodule was biopsied and the histological examination showed monomorphic, medium-sized cells with scant cytoplasm, uniform hyperchromatic nuclei with episodical molding, and multiple small nucleoli (Fig. 2). The tumor cells displayed a diffuse and insular growth pattern, sheets and solid nests infiltrating the entire dermis and extending into the subcutis. The overlying epidermis was without ulceration. The tumor showed high mitotic index and atypical and apoptotic cells (Fig. 3). Immunohistochemical staining with CK and CK-20 demonstrated paranuclear globules (Fig. 4). The tumor cells also stained with NSE (Fig. 5). These findings were consistent with the diagnosis of a Merkel cell carcinoma.


Figure 4 Figure 5
Fig.4 Immunohistochemical staining CK-20 × 400. Paranuclear dots are depicted.
Fig. 5 Immunohistochemical stain NSE × 400. Strong positive reaction of the tumor cells stained with NSE.

Laboratory investigations demonstrated hemoglobin of 11 g/dL, WBC of 15 × 109/L (neutrophils 51 %), and platelet count 235, 000 /L. Blood chemistry was within normal limits. Computerized tomography of the chest, abdomen and pelvis did not revealed metastases.

The patient was treated with palliative radiotherapy. Despite treatment, 3 months after the diagnosis the patient died.


Discussion

CLL patients are at higher risk of developing skin cancers such as basal cell carcinoma and squamous cell carcinoma [5]. Agnew et al. [6] evaluated 21 patients with CLL and found 75 premalignant and malignant skin tumors. The incidence of the tumors observed in their series was as follows: Of the 75 tumors noted, there were 33 basal cell carcinomas (44 %), 23 squamous cell carcinomas (31 %), 2 basosquamous lesions (2.7 %), 2 T-cell lymphomas (2.7 %), 2 malignant melanomas (2.7 %), 8 actinic keratoses (11 %), 3 leukemia cutis (4 %), and 2 Merkel cell tumors (2.7 %). In the literature there are altogether only 7 cases of association of CLL with MCT [3, 4, 6, 7]. This patient is the eighth case.

The pathogenic relationship between CLL and skin neoplasia is not clearly understood. Possible explanations include immunological impairment, individual genetic susceptibility, immunosuppressive treatment, and exposure to ultraviolet radiation. A large study using population-based tumor registries found that the risk of skin cancer did not vary according to initial CLL treatment [8].

The association of CLL and MCT could be coincidental taking into account the relative high frequency of CLL and the increased risk for the development of skin cancers in CLL patients. Nevertheless it is possible that the abnormal T and B cell functions in CLL may have a role in the development of MCT in CLL patients [9].

Although the development of MCT in CLL patients is unusual, this neuroendocrine tumor should be recognized and promptly treated because of its aggressive behavior.

References

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2.Manusow D &Weinerman BH. Subsequent neoplasia in chronic lymphocytic leukemia. JAMA 1975; 232: 267 9

3. Ziprin P, Smith S, Salerno G, Rosin RD. Two cases of Merkel cell tumour arising in patients with chronic lymphocytic leukemia. Br J Dermatol 2000; 142: 525 8.

4.D.R.Warakaulle E. Rytina N.P. Burrows. (2001) Merkel cell tumour associated with chronic lymphocytic leukemia. British Journal of Dermatology 144:1, 216-216

5.Levi F, Randimbison L, Te V-C, La Vecchia C. Non-HodgkinÕs lymphomas, chronic lymphocytic leukemias and skin cancers. Br J Cancer 1996;

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6.K.L. Agnew, R.Ruchlemer, D.Catovsky, E.Matutes and C.B. Bunker. (2004) Cutaneous findings in chronic lymphocytic leukaemia. British Journal of Dermatology 150:6, 1129-1135

7.Yun Gu, Sara S. Strom, Susan Lerner, Michael J. Keating. Second Cancers after CLL Diagnosis. Blood 2004; 104:9a

8.Travis LB, Curtis RE, Hankey BF et al. Second cancers in patients with chronic lymphocytic leukemia. J Natl Cancer Inst 1992; 84:1422-7

9. Scrivener S, Kaminski ER, Demaine A, Prentice AG. Analysis of the expression of critical activation/interaction markers on peripheral blood T cells in B-cell chronic lymphocytic leukemia: evidence of immune dysregulation. Br J Haematol 2001; 112: 959-64.

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