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Indian Journal of Cancer, Vol. 48, No. 3, July-September, 2011, pp. 380-381 Letter to Editor Leukemic relapse masquerading as a breast lump: An unusual manifestation CS Premalata1, CR Rao1, DS Madhumathi1, L Lakshmidevi1, D Lokanatha2 1 Department of Pathology, Kidwai Memorial Institute of Oncology, Bangalore, India Code Number: cn11106 PMID: 21921352 DOI: 10.4103/0019-509X.84931 Sir, A 21-year-old female came to the hospital with a history of fever, generalized weakness, and weight loss since 3 months. On examination, the patient was pale with evidence of gum bleeding. Multiple cervical lymphnodes were enlarged and there was mild hepatosplenomegaly. Complete blood count showed pancytopenia. Bone marrow aspiration was markedly hypercellular with sheets of blasts forming 80% of the nucleated marrow cells. Cytochemical stains for myeloperoxidase and periodic acid Schiff (PAS) were negative. Routine cytogenetic analysis showed the karyotype - 52XX, +X ,+1, -2, +12, +14, +15, +19, +20, suggestive of hyperdiploid acute lymphoblastic leukemia. A morphological diagnosis of acute lymphoblastic leukemia (ALL) - L2 (FAB classification) was rendered. Cerebrospinal fluid examination was normal. The patient was started on multi agent combination chemotherapy for ALL with intrathecal methotrexate as CNS prophylaxis. While on maintenance therapy, the patient conceived and the pregnancy was terminated at 6 weeks. After completion of therapy, the patient was disease free for two years, the bone marrow being in remission throughout. Two years later, she developed a mobile, 3 × 4 cm 2 lump in the left breast which gradually increased in size, which on histological examination showed sheets of monotonous cells infiltrating the breast tissue around the mammary ducts and lobules [Figure - 1], with high mitotic activity showing focal starry sky pattern [Figure - 2]a. On immunostaining, the neoplastic cells were positive for TdT [Figure - 2]b, CD10 [Figure - 2]c, CD43, and CD79a and were negative for CD 117, CD68, CD 20, and CD3. Many of the blasts also showed distinct positive staining for MPO [Figure - 2]d. The blood counts, peripheral smear, bone marrow, and CSF examination were normal. A diagnosis of isolated breast relapse of ALL was made with the possibility of it being a mixed phenotypic leukemia. The patient was started on multi drug combination chemotherapy again but the patient succumbed to treatment-related complications 2 months after the initiation of therapy. Despite advances in chemotherapy, about 30%-40% of ALL relapse. Breast relapse as an isolated manifestation of ALL is very rare. Ellegaard et al., first described breast tumors as a manifestation of extramedullary relapse in ALL, followed by scattered reports in the literature. [1] ALL can involve the breast at presentation or as a site of extramedullary relapse after successful chemotherapy and allogenic bone marrow transplantation. [2],[3],[4] Breast involvement in ALL can be diffuse and bilateral or may present as well defined unilateral or bilateral masses simulating fibroadenoma. [3] The patient in the present case, presented with a lump in the breast, 2 years after successful chemotherapy with a history of terminated pregnancy during maintenance therapy. Immunohistochemistry on the excised breast mass, showed pre-B phenotype with additional positivity for MPO, and the disease relapsing as mixed phenotypic leukemia, i.e., B/myeloid leukemia was considered (WHO 2008). As immunophenotyping of the blasts was not done at presentation, we are not sure whether the blasts expressed myeloid markers at presentation or the relapse was as a result of emergence of a more aggressive biphenotypic/bilineal clone which escaped therapy. Pregnancy may have played a role in the localization of relapse in the breast, as there is sex hormone dependent increase in homing of lymphoblasts to breast and genital tract during pregnancy and lactation. [5] Burkitt leukemia/lymphoma most often involves the breasts during pregnancy and lactation, causing bilateral diffuse often massive breast enlargement, [5] though similar evidence is lacking for localization of ALL in the breasts, during pregnancy. In conclusion, we present a rare case of isolated breast relapse of ALL which had certain unique features like association with pregnancy and expression of myeloid markers and recommend that breast examination should be part of the follow up of female patients with ALL. References
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