Table of Contents  
CASE REPORT
Year : 2015  |  Volume : 8  |  Issue : 1  |  Page : 108-110  

A rare case of chronic lymphocytic leukemia in a patient with recurrent metastatic breast carcinoma


Department of Pathology, Shrimati Kashibai Navale Medical College and General Hospital, Pune, Maharashtra, India

Date of Web Publication8-Jan-2015

Correspondence Address:
Siddhi Khandeparkar
E-517, The Island, Wakad, Pune - 411 057, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0975-2870.148871

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  Abstract 

The hematological malignancy is a well-known complication following breast carcinoma (BC), but the type of malignancy that occurs and treatment regimens followed are still under evaluation. The literature mostly describes therapy-related acute myeloid leukemia and myelodysplastic syndrome associated with BC. Chronic lymphocytic leukemia (CLL) is extremely rare following BC and is mostly described in patients treated with radiotherapy. Herein, we present a rare case of CLL detected at the time of recurrence in a 61-year-old female patient with a previous history of BC solely treated with surgery. She presented simultaneously with metastatic recurrent carcinoma and CLL.

Keywords: CLL, metastatic breast carcinoma, recurrent breast carcinoma, secondary malignancy


How to cite this article:
Khandeparkar S, Bhatt NC, Deshmukh SV, Joshi A. A rare case of chronic lymphocytic leukemia in a patient with recurrent metastatic breast carcinoma. Med J DY Patil Univ 2015;8:108-10

How to cite this URL:
Khandeparkar S, Bhatt NC, Deshmukh SV, Joshi A. A rare case of chronic lymphocytic leukemia in a patient with recurrent metastatic breast carcinoma. Med J DY Patil Univ [serial online] 2015 [cited 2024 Mar 28];8:108-10. Available from: https://journals.lww.com/mjdy/pages/default.aspx/text.asp?2015/8/1/108/148871


  Introduction Top


Certain malignancies may occur synchronously or metachronously. Our patient presented with breast carcinoma (BC) followed 2 years later by metachronous chronic lymphocytic leukemia (CLL) with recurrent metastatic BC. The development of secondary malignancies after the treatment of BC has been well studied. [1] However, development of CLL following surgically treated BC is rarely documented.

The BRCA1 gene, located on chromosome 17q21, and the BRCA2 gene, located on chromosome 13q12-13, are both tumor suppressor genes. Subjects with germline mutation of BRCA1 and BRCA2 genes are known to have a very high risk of developing breast and ovarian cancer. [2] CLL is defined as clonal expansion of neoplastic B lymphocytes in the blood, bone marrow, lymph node and spleen. Few studies mention a presence of previous history of other cancers in these patients of CLL, with an incidence of 16%. [3] Majority of these patients exhibit somatic deletions of the chromosome 13q12.3 locus encompassing BRCA2. [4]

Herein, we present an unusual case of CLL noticed at the time of recurrence in a 61-year-old female patient with a previous history of surgically treated BC.


  Case Report Top


A 61-year-old female, a known case of infiltrating ductal carcinoma (IDC) of left breast surgically treated 2 years back, came to the surgery outpatient department with a complaint of recurrent lump in the same breast. Two years back, she was diagnosed histopathologically with IDC of the left breast with clinical staging of pT3N0M0 (Stage IIb). The surgically resected margins, base and skin, nipple and areola were free of tumor. She did not receive chemotherapy, radiotherapy or hormonal therapy. She is also a known case of hypertension diagnosed 3 years back. She had developed cerebrovascular infarct with left hemiplegia 3 years back.

On examination, she was found to have a left breast lump measuring 4 cm × 4 cm with ulceration along and above the scar of previous mastectomy and axillary lymph node measuring 2 cm × 2 cm, which was firm and mobile [Figure 1]. Clinical examination showed cervical and axillary lymphadenopathy and mild splenomegaly. She was asked to undergo fine needle aspiration (FNA) of both the breast lump and the axillary lymph node. FNA from the left breast lump showed paucicellular smears with clusters of loosely cohesive and singly scattered malignant ductal epithelial cells. FNA from the axillary lymph node showed loosely cohesive clusters and sheets of malignant epithelial cells in the background of lymphoid cells [Figure 2]a. A diagnosis of recurrent IDC with metastasis to the axillary lymph node was offered. On immunohistochemical analysis (IHC), the tumor was found to be strongly positive for estrogen [Figure 2]b and progesterone receptors [Figure 2]c. Complete hemogram showed hemoglobin of 11.0 gm/dL and total leukocyte count of 126,000/cmm, with a differential leukocyte count of polymorphs 7%, lymphocytes 93% and platelet count of 175,000/cmm. Peripheral blood smear showed marked leukocytosis with the presence of mature lymphocytes suggestive of chronic lymphoproliferative disorder [Figure 3]]. Bone marrow aspiration (BMA) showed preponderance of mature lymphocytes (93%) with few erythroid and myeloid series cells and adequate megakaryocytes [Figure 3]b. IHC on bone marrow aspiration showed lymphoid cells to be CD 20 positive [Figure 3]d and CD 3 negative [Figure 3]e. In addition were seen clusters of malignant epithelial cells in the BMA giving evidence of metastasis most likely from IDC [Figure 3]c. A diagnosis of B cell CLL with metastasis of recurrent IDC to the bone marrow was made. Her serum lactate dehydrogenase level was increased to 800 IU/L. Liver function test, renal function test, HbsAg, anti-HIV antibody and chest X-ray were normal. Because the patient had Rai stage II CLL, she was treated symptomatically for the same. She was referred to the oncosurgeon for management of recurrent BC (stage IV).
Figure 1: Clinical photograph of the patient showing the scar of the previous surgery: Lump along the scar and ulceration of the skin

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Figure 2: (a) Fine needle aspiration showing metastasis of infiltrating ductal carcinoma to the axillary lymph node. (Pap, 400X) Immunohistochemistry analysis: Strong nuclear positivity for estrogen (b) and progesterone (c) receptors (400×)

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Figure 3: (a) PS– chronic lymphocytic leukemia (Leishman, 40×), (b) bone marrow aspiration (BMA) showing markedly cellular smears composed of small lymphocytes (Leishman, 100×), (c) BMA showing metastatic epithelial cells from infi ltrating ductal carcinoma (Leishman, 400×), (d) immunohistochemistry (IHC) of BMA - tumor cells showing strong membrane positivity for CD 20 and (e) IHC of BMA - tumor cells showing CD 3 negativity

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  Discussion Top


A second malignant neoplasm has been found to be more frequent than might be expected from the general population rates, particularly after a first case in childhood. [5] The second malignancy may present as an unexpected finding during the investigation of the previous malignancy, as in our case. [6]

The literature mostly describes acute myeloid leukemia (AML) as second malignancy in BC patients solely treated with surgery. It is hypothesized that development of secondary AML after a previous BC is related to genetically determined inherited alterations. This hypothesis is supported by the various studies that report a seven-to 30-times higher risk of development of leukemia in surgically treated BC patients. [1]

It has recently been suggested that there is a tumor suppresser locus in CLL at 13q12.3 near or at the BRCA2 locus. Deletion of regions on chromosome 13q containing the BRCA2 and RB1 genes has also been reported in sporadic BC. These observations suggest that there may be a link between these two diseases acting through chromosome 13. [4] The association of CLL/small lymphocytic lymphoma with another primary malignancy has been noted by several authors. Impairment of the immune system caused by CLL is regarded as a predisposing factor. [6]

A synchronous malignant tumor is defined as the occurrence of two tumors within a 6-month period in the same patient, which is a rare circumstance. The occurrence of multiple, primary tumors in the same individual is well recognized. [6] The present case exhibited simultaneous malignancies (metastatic adenocarcinoma and CLL) on bone marrow examination. But, as the preceding history of the primary tumor was 2 years ago, it strictly did not qualify for synchronous malignancies. Various factors have been suggested to contribute to the occurrence of synchronous neoplasms (not related to treatment). These include genetic susceptibility, advanced age of the patients, depressed cellular immunity (immunosuppression produced by the first tumor) and exposure to a common inducing agent. [6]

The literature mostly describes therapy-related AML and myelodysplastic syndrome associated with BC. Very few case studies mention AML associated with surgically treated BC patients. [1] CLL following surgically treated BC cases is exceedingly rare. When comparing patients treated by surgery alone with those who received chemo ± radiotherapy, a significantly higher median age and high number of cytogenetic abnormalities was observed in surgically treated patients. However, the significance of these data need to be further assessed. [1]

In conclusion, we think that large prospective studies on patients with breast cancer, observed for long-term follow-up, associated with molecular biology studies performed on BC tissues and, possibly, on leukemic cells at onset of CLL are necessary to answer the remaining questions regarding the development of secondary leukemia and to confirm the possible biological predisposition of BC patients to CLL.

 
  References Top

1.
Pagano L, Pulsoni A, Mele L, Tosti ME, Cerri R, Visani G, et al. Acute myeloid leukemia in patients previously diagnosed with breast cancer: Experience of the GIMEMA group. Ann Oncol 2001;12:203-7.  Back to cited text no. 1
    
2.
Fruscalzo A, Damante G, Calcagno A, Di Loreto C, Marchesoni D. Four primary malignancies successively occurred in a BRCA2 mutation carrier: A case report. Cancer Invest 2006;24:611-4.  Back to cited text no. 2
    
3.
Tsimberidou AM, Wen S, McLaughlin P, O'Brien S, Wierda WG, Lerner S, et al. Other malignancies in chronic lymphocytic leukemia/small lymphocytic lymphoma. J Clin Oncol 2009;27:904-10.   Back to cited text no. 3
    
4.
Shousha S, Costello C, Luqmani YA, Sinnett HD. CD5 positive breast carcinoma in a patient with untreated chronic lymphocytic leukaemia: Molecular studies of chromosome 13q. J Clin Pathol 1998;51:862-4.  Back to cited text no. 4
    
5.
Bhatia P, Das R, Ahluwalia J, Malhotra P, Varma N, Varma S, et al. Acute leukemia/myelodysplastic syndrome as a sequelae of carcinoma breast: A report of five cases from north India. Indian J Pathol Microbiol 2009;52:167-70.  Back to cited text no. 5
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6.
Pandey U, Naraynan M, Karnik U, Sinha B. Carcinoma metastasis to unexpected synchronous lymphoproliferative disorder: Report of three cases and review of literature. J Clin Pathol 2003;56:970-1.  Back to cited text no. 6
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]



 

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