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|Year : 2011 | Volume
| Issue : 1 | Page : 55-56
An unusual case of chronic lymphocytic leukemia following primary breast carcinoma on chemotherapy
H Chandra1, S Chandra1, SK Verma2, VP Pathak1
1 Department of Pathology, Himalayan Institute of Medical Sciences, Doiwala, Dehradun, Uttarakhand, India
2 Department of Medicine, Himalayan Institute of Medical Sciences, Doiwala, Dehradun, Uttarakhand, India
|Date of Web Publication||31-Jan-2011|
Department of Pathology, Himalayan Institute of Medical Sciences, Doiwala, Dehradun, Uttarakhand
|How to cite this article:|
Chandra H, Chandra S, Verma S K, Pathak V P. An unusual case of chronic lymphocytic leukemia following primary breast carcinoma on chemotherapy. J Postgrad Med 2011;57:55-6
|How to cite this URL:|
Chandra H, Chandra S, Verma S K, Pathak V P. An unusual case of chronic lymphocytic leukemia following primary breast carcinoma on chemotherapy. J Postgrad Med [serial online] 2011 [cited 2014 Mar 8];57:55-6. Available from: http://www.jpgmonline.com/text.asp?2011/57/1/55/74294
The secondary leukemia following breast carcinoma is well documented but is rare, and literature mostly describes acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) associated with it. , Chronic lymphocytic leukemia (CLL) is extremely rare following breast cancer with usually long course of development and seen in cases who have not received chemotherapy. 
Three years back, a 69-year-old female was histopathologically diagnosed with infiltrating ductal carcinoma of breast after surgery with stage of T2N0M0 [Figure 1]. All the resected surgical margins, skin, subareolar margin and left axillary level I and level II lymph nodes were free of tumor. Immunohistochemistry showed negativity for estrogen receptors (ER), progesterone receptors (PR) and Her-2/neu receptors. Her hemogram at that time showed hemoglobin (Hb) 141 g/L, total leukocyte count (TLC) 8.7×10 9 /L, differential leukocyte count (DLC) polymorphs 44%, lymphocytes 49%, eosinophils 7% and platelet count (PC) 180×10 9 /L. The biochemical and radiological investigations were within normal limits and radioisotope bone scan showed no evidence of skeletal metastasis. She received chemotherapy comprising six cycles every 28 days of doxorubicin (60 mg/m 2 ) and paclitaxel (200 mg/m 2 ) without any endocrine or radiation therapy. On follow-up after 1 year of completion of chemotherapy, her hematological investigations showed bicytopenia with leukocytosis (Hb 66 g/L, TLC 282×10 9 /L, and PC 86Χ10 9 /L). DLC showed 97% lymphocytes, 2% polymorphs and 1% prolymphocytes with features suggestive of chronic lymphoproliferative disorder [Figure 1]. On clinical examination, there was multiple cervical, axillary and inguinal lymphadenopathy with mild hepatosplenomegaly. In addition, there was no evidence of any recurrence of breast carcinoma. Bone marrow aspiration showed preponderance of mature lymphocytes (95%) along with few myeloid and erythroid precursors and reduced megakaryocytes. Immunophenotyping on flow cytometry showed CD5/CD19 coexpression (96.41% of gated region R1), CD23 (96.30% of gated region R1) CD20 (89.01% of gated region R1), FMC-7 (0.51% of gated region R1) and thus findings were consistent with B-cell CLL. Cytogenetic studies could not be performed due to patient's reluctance and condition of the patient deteriorated rapidly and she succumbed to her illness within 2 months.
|Figure 1: (a) Peripheral blood smear showing lymphocytosis suggestive of CLL (Jenner Giemsa, ×100); (b) microphotograph showing infiltrating ductal carcinoma of breast (H and E, ×40)|
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The hematological malignancy is a well-known complication following breast carcinoma but the types of leukemia that occur and treatment regimens (chemotherapy/radiotherapy) followed are still under evaluation. Kaplan et al. reported an incidence rate of 0.28% for crude leukemia after diagnosis of breast carcinoma, with an incidence of 0.11% for AML/MDS.  Singhal et al. have also described a case of T-cell prolymphocytic leukemia which they reported to be not described earlier following breast cancer chemotherapy.  The rarity of secondary lymphoid malignancies may be attributed to the effect of chemotherapy on telomere length shortening observed more in myeloid cells in comparison to lymphoid cells after autologous hematopoietic stem cell transplant.  Radiotherapy has been considered as an important leukemogenic factor, and Kaplan et al. observed in their study that no patient who received chemotherapy without radiotherapy developed any type of leukemia.  In addition, they concluded that there is no evidence of increased post-treatment leukemia in association with chemotherapy including doxorubicin based chemotherapy.  In contrast, the present case reports CLL following breast cancer in a patient who had received only adjuvant chemotherapy comprising doxorubicin and paclitaxel without any radiotherapy. The length and intensity of chemotherapy may also play an important role in treatment related leukemia, and Praga et al. concluded that patients receiving standard cumulative doses of epirubicin and cyclophosphamide have lower probability of secondary leukemia than patients treated with higher cumulative doses for breast cancer.  However, in the present case, CLL developed even when the patient was treated with standard dose of doxorubicin and paclitaxel. The authors would however lay emphasis that as the differential count showed 49% lymphocytes initially at the time of diagnosis of infiltrating ductal carcinoma of breast, a rare possibility of co-existing CLL in early phase cannot be completely ruled out. The case also showed an aggressive course with development of CLL followed by death within 2 years of primary carcinoma diagnosis. This is in contrast to the study which showed long period of development of CLL of about 5-6.5 years after primary breast carcinoma diagnosis.  This aggressive course may be related to the underlying genetic abnormality but definite opinion is not possible as cytogenetic studies were not performed.
To conclude the case highlights the variable spectrum of leukemia that can occur after breast carcinoma which may possibly arise as secondary leukemia following chemotherapy or may rarely co-exist as another malignancy. Although the exact pathogenesis of the leukemia following breast carcinoma cannot be clearly defined, the authors emphasize that close hematological follow-up is essential in every case of breast cancer irrespective of the therapy (radiotherapy/chemotherapy) provided. It also lays the importance of balance between the benefits of breast cancer chemotherapy and the risk of secondary leukemia.
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