A diffuse large B cell lymphoma emerging with breast cancer relapse

The prevalence of secondary cancers associated with the breast cancer treatment has increased, which is due to the administration of cytotoxic/hormonal drugs as well as radiotherapy. A 54-year-old female patient with a history of breast cancer for 4 years and receiving tamoxifen the hematology clinic with fatigue and nosebleed. Laboratory parameters were revealed pancytopenia. The bone marrow biopsy finding was compatible with CD20 positive high-grade B cell lymphoma resembling diffuse large B cell lymphoma. The patient started to receive a chemotherapy. Her hemogram values displayed an improvement after the second cycle. However, interim PET-BT, performed after the fourth cycle, showed an incomplete response in cervical lymphatic nodes. Then, a tru-cut biopsy was performed resulting in breast cancer metastasis. This is an unusual case of secondary-DLBCL presenting with pancytopenia and occuring 4 years after the diagnosis of breast cancer. In conclusion, clinicians should carefully set the dosage of chemotherapy drugs to avoid the long-term side effects associated with such drugs.


Introduction
Breast cancer is among the most common tumors occurring in women, and recently, survival rates of the patients have progressively improved owing to neoadjuvant, adjuvant, endocrine and targeted therapies. However, chemotherapy-associated longterm side effects have gradually been on the rise in these patients.
Adjuvant chemotherapies comprising particularly alkylating agents and topoisomerase inhibitors may increase the risk of leukemia especially in patients with early-stage breast cancer [1][2][3].
Prophylactic or adjuvant chemotherapy administered due to earlystage breast cancer is demonstrated to increase 10-year hematological cancer risk by 0.5%, which is twice higher than those reported in previous studies [4]. While the most prevalent hematological cancers associated with the treatment are acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) [2,3], treatment-associated lymphomas constitute quite a rare clinical picture [5,6]. This report presents a secondary diffuse large B-cell lymphoma emerging with breast cancer relapse.

Patient and observation
A 54-year-old female patient referred to the hematology clinic with fatigue and nosebleed. She had a history of type-2 diabetes mellitus and breast cancer. The patient was diagnosed with breast cancer four years ago and underwent a mastectomy followed by radiotherapy and chemotherapy, and she has been receiving tamoxifen since that time. The chemotherapy protocol was inaccessible because the chemotherapy was administered in Syria.
The physical examination revealed a swollen right arm, ecchymoses in arms, and fixed, firm, painless cervical lymphadenopathies, the largest of which was 2x2cm in size and located on the right.
Laboratory parameters were as follows: white blood cell count: 3.62 x 10 9 /L with 0.84x10 9 /L neutrophils, hemoglobin: 11 g/dL, platelet count: 10x10 9 /L. Biochemical, liver and renal function test results were normal. HBsAg, Anti-HBS, Anti-HCV and Anti-HIV test results were negative. Platelet count by peripheral smear was compatible with the hemogram count without any atypical cells. The lymph node biopsy could not be performed since the platelet count did not rise despite transfusion. Instead, bone marrow aspiration and biopsy were performed for diagnostic purposes. The biopsy finding was compatible with CD20 positive high-grade B cell lymphoma resembling diffuse large B cell lymphoma (Figure 1 (A, B)). biopsy result showed breast cancer metastasis (Figure 1 (C, D)).
She underwent a bone marrow biopsy after six cycles of R-CHOP, which revealed that the lymphoma infiltration disappeared. The patient's breast cancer treatment continues.

Discussion
Breast cancer is one of the most common causes of cancer-related deaths in women. Although the mortality rate related to breast cancer has decreased lately with the development of early diagnosis and treatment techniques, the prevalence of secondary cancers associated with the treatment has increased due to the administration of cytotoxic/hormonal drugs as well as radiotherapy [2,3]. Regarding the hematological malignancies, lymphomas are encountered rarely compared to AML and MDS in those patients [2,3]. Given the high prevalence of breast cancer, these findings indicate that the number of patients under the risk of secondary cancer triggered by treatment might be actually higher than expected. The secondary cancers associated with breast cancer chemotherapy are largely associated with alkylating agents and topoisomerase II inhibitors [7]. Alkylating agents cause gene

Conclusion
Clinicians should carefully set the dosage of chemotherapy drugs, especially topoisomerase II inhibitors and alkylating agents, to avoid the long-term side effects associated with such drugs.

Competing interests
The authors declare no competing interests.

Authors' contributions
All the authors have read and agreed to the final manuscript.