Cutaneous granulocytic sarcoma arising at the site of radiotherapy for breast carcinoma

ARTICLE

Cutaneous granulocytic sarcoma is an uncommon leukemia cutis, composed of immature granulocytic precursor cells [1]. It usually occurs in association with acute myelocytic leukemia (AML) or myeloproliferative disorders. It may also be isolated, and the term of aleukemic leukemia cutis has been given to this rare condition [2]. We describe a patient with cutaneous granulocytic sarcoma in the right mammary area, six months after radiotherapy for breast cancer.

Case report

A 44-year-old woman presented in October 1999 for evaluation of multiple papules and nodules which had appeared one month previously in the right mammary area (Fig. 1). Local examination revealed erythematous, firm and nontender papules and nodules measuring 5 to 15 mm in diameter (Fig. 2). There were two similar nodules on the trunk. Past medical history revealed that the patient was treated six months earlier for adenocarcinoma of the right breast. She had lumpectomy, axillary lymph node dissection and radiation therapy. She received 45 Grays to the breast and 45 Grays to the internal mammary node field and to the supraclavicular and axillary area. Clinical examination did not detect adenopathy or hepatosplenomegaly. Histologic examination of a papular lesion showed a dermal infiltration of large cells with irregularly shaped nuclei (Fig. 3). Immunohistologically, pan-B, pan-T, and CD30 stains were negative. Anticytokeratine antibodies, anti-EMA and hormonal receptors were also negative. Lysozyme, CD11, CD14, CD15, CD33, CD43 and CD68 stains were positive (Fig. 4). Cytogenetic analysis of a cutaneous lesion was a failure. Final diagnosis was granulocytic sarcoma. Histologic re-examination of the breast tumor confirmed the diagnosis of ductal adenocarcinoma. The blood cell count, bone marrow aspiration, bone marrow karyotype, and bone marrow biopsy were normal. The patient underwent induction chemotherapy with cytarabine and mitoxantrone. All nodules disappeared after the first induction cycle. She received consolidation chemotherapy with high dose cytarabine and central nervous system prophylaxis with intrathecal cytarabine. She remained in complete cutaneous and haematological remission in February 2000.

Discussion

Granulocytic sarcoma is an extramedullary tumor composed of immature granulocytic precursor cells [1, 3]. It may involve any site of the body but most commonly develops in the bone, periosteum, soft tissue, lymph nodes and skin [1, 4]. Clinically, cutaneous granulocytic sarcomas appear as rapidly growing, firm nodular masses, that most commonly occur on the trunk, scalp and face [4, 5]. Unusual presentations include development of tumors of the chest wall at the implantation site of a central catheter and infiltration similar to cutis verticis gyrata [6, 7]. Granulocytic sarcoma has been reported to occur in three clinical situations: (i) in patients with known AML; (ii) in patients with myelodysplastic disorders with leukemic transformation or chronic myelogenous leukemia with impending blast crisis; and (iii) in patients without known haematologic disease [1, 5, 8, 9].

In our patient's case, the clinical diagnosis suspected was cutaneous metastases of breast carcinoma. First histological findings were suggestive of large cell lymphoma and the diagnosis of granulocytic sarcoma was confirmed with immunohistochemical stains. The histologic diagnosis of granulocytic sarcoma may be difficult and an initial misdiagnosis rate of up to 75% has been reported [8]. The most commonly confused tumors include different types of non Hodgkin's lymphoma and Ewing's sarcoma [1, 8].

Carcinogenic effects of radiotherapy for breast cancer are well-known. The occurrence of secondary malignancies in women treated with radiation therapy is increased [10]. However, the leukemogenic effect of radiotherapy is very debated [10, 11]. Several studies indicate a slightly elevated risk of non-lymphocytic leukemia following adjuvant radiotherapy in breast carcinoma [10-12]. Whole breast irradiation, as currently employed following breast conserving surgery, may raise the risk of leukemia, particularly in association with certain types of adjuvant chemotherapy [10, 13]. It appears that most, if not all, cases of secondary leukemia associated with radiation therapy occur after regional radiation therapy that includes an internal mammary node field, which may expose the thoracic spine to a relativity high radiation dose [10]. In all cases, the mean interval from diagnosis of breast cancer to leukemia is approximately 5 years [10, 11]. In our patient's case, the responsibility of radiation in the occurrence of granulocytic sarcoma is debatable, since the delay was very short. Nevertheless the localization of skin lesions in an irradiated area is surprising, and may be compared to the development of skin metastases within a field of previous irradiation [14, 15]. Several studies have demonstrated that the endothelial cell alteration caused by radiation may lead to increased tumor cell trapping [16]. The impairment of lymphatic drainage in the irradiated area, in addition to the axillary lymph node dissection, may also explain why the skin lesion occurred primarily and mainly in the irradiated area.

Article accepted on 22/2/01

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