Acute lymphoblastic leukemia presenting as a breast lump: A report of two cases.

Extra-medullary leukemic infiltration of the breast by acute lymphoblastic leukemia (ALL) is very rare. We report two cases of ALL presenting as breast masses and diagnosed on fine-needle aspiration (FNA). Our first patient, a post-partum 30-year-old female, developed bilateral breast lumps in her last trimester of pregnancy and complained of easy fatigability. Our second patient, a 14-year-old girl, presented with a right-breast lump of 1-week duration. She had received treatment for ALL 1 year back and had been in complete remission for the last 1 year. FNA of the breast nodules done in both the cases revealed diffuse infiltration by lymphoblasts. Subsequent hematological investigations confirmed bone marrow involvement by ALL in the first case and extra-medullary relapse in the second case. Fine-needle aspiration cytology (FNAC) is an easy and cost effective method for the early diagnosis of metastatic leukemic infiltration, avoiding unnecessary excisional biopsies in such cases.

Introduction

Leukemic infiltration of breast is rare and may occur as an isolated tumor or as extra-medullary manifestation in systemic disease.[1] We recently came across two cases of acute lymphoblastic leukemia (ALL) presenting as breast masses. Breast infiltration was diagnosed on fine-needle aspiration cytology (FNAC) and later confirmed with other investigations. These cases are reported on account of their rarity, variable presentation, and the fact that there have been few case reports of similar nature elucidating their FNAC.

Case Reports

Case 1

A 30-year-old female, 6 weeks after delivery, presented with bilateral painless breast-swellings which she had developed in her 9 month of pregnancy. She complained of early fatigability but had no history of bleeding tendency, weight loss, or loss of appetite. Her general physical examination revealed pallor but was otherwise unremarkable. On local examination, a 3 × 3 cm, firm, irregular, non-tender and partly mobile swelling was felt in the left breast and a similar swelling, 2 × 2 cm in the right. There was no axillary lymphadenopathy. A complete blood-count revealed a total leukocyte count of 1.21 × 103/mm3 with a differential leukocyte count showing 90% blasts, a hemoglobin level of 5.3 mg/dL, and a platelet count of 180 × 103/μL. A mammography was advised and showed diffuse nodular infiltration in both breasts [Figure 1]. No focal mass was seen. Breast ultrasound revealed a coarse echo pattern with no fixity to any structure and normal ducts. FNAC was performed on both breast lumps. Microscopy revealed benign groups of ductal cells, clumps of degenerated cells along with scattered round cells with scanty cytoplasm and inconspicuous nucleoli (lymphoblasts) [Figure 2]. Some of the blasts showed nuclear indentation. Features were in favor of leukemic infiltration in both breasts — most likely ALL.

Figure 1

Mammography showing diffuse dense areas in upper and outer quadrants of both breasts but no well-defined mass

Figure 2

Smears showing abundant round cells with scanty cytoplasm and inconspicuous nucleoli (lymphoblasts) amidst a few benign duct cells (MGG, ×400)

A bone marrow aspirate obtained was hypercellular with >25% blasts having coarse chromatin, inconspicuous nucleoli and scant cytoplasm. An impression of acute lymphoblastic leukemia–L2 (ALL-L2) was made. Flow cytometry of bone marrow was positive for CD19, CD10, CD22, CD33, CD45, terminal deoxynucleotidyl transferase (TdT), HLA DR4, CD34 and negative for T-cell markers. The aberration detected was CD33. Scatter parameters and antigen expression as studied by flow cytometry were suggestive of a B-cell ALL, common acute lymphoblastic leukemia antigen (CALLA) -positive with myeloid co-expression. Her cerebrospinal fluid examination was unremarkable.

The patient received chemotherapy — modified Berlin — Frankfurt — Munich (BFM) protocol. She went into remission and her breast nodules regressed. She is on regular follow-up and remains disease-free 1 year later.

Case 2

A 14-year old female presented with a 1-week history of a painless swelling in the right breast. She was diagnosed with ALL-L2 a year-and-a-half back; flow cytometry had shown CALLA positive B-Cell ALL with breakpoint cluster region–abelson gene (BCR–ABL) fusion in 98% cells. The patient received chemotherapy (UK ALL XII protocol with CNS prophylaxis), and stem cell transplant was declined for financial reasons. The patient responded and had been in remission for the last 1 year.

On general physical examination, the patient looked healthy. There was no pallor, lymphadenopathy or organomegaly. Clinical examination of her breast swelling revealed a 1.5 cm firm, painless, mobile swelling, in the right breast. There was no axillary lymphadenopathy. A complete blood count revealed a total leukocyte count of 9.4 × 103/mm3, a hemoglobin level of 14.2 mg/dL, and a platelet count of 184 × 103/μL. A clinical diagnosis of fibroadenoma was made. An aspirate obtained from the lump using a 22-gauge syringe was stained with May-Grünwald-Giemsa (MGG). Microscopic examination revealed highly cellular smears, showing diffuse infiltration by round cells with inconspicuous nucleoli and scanty cytoplasm (lymphoblasts) [Figure 3]. Abundant mitotic figures were seen. The findings were consistent with those of infiltration by ALL.

Figure 3

Smears show abundant lymphoblasts with some mitotic figures (MGG, ×400)

Discussion

Leukemic infiltration of breast is rare and may occur as an isolated tumor or as an extra-medullary manifestation in systemic disease.[123] Only very rarely, is this the primary manifestation of an ALL.[4] Involvement of the breast in extra-medullary relapse is also very infrequent.[5] Breast malignant tumors are uncommon in children and adolescent females.[6]

Patients with leukemic infiltration of breast usually are present with a palpable lesion that is generally well-circumscribed and rapidly enlarging. The lesion may be bilateral or multi-nodular simulating a fibroadenoma.[4]

The mammographic findings are variable and can be unremarkable or reveal an enlarged breast with diffusely coarse breast parenchyma. An irregular mass or a mass with well-defined borders and a benign appearance may also be seen.[2] On ultrasonography, most masses are homogenously hypoechoic with micro-lobulated or indistinct margins.[3]

Various case reports on fine needle aspiration (FNA) of ALL infiltration of the breast describe a common cytological picture. The aspirates exhibit dispersed monomorphic blastic cells ranging from small, medium-to-large cells having a high nuclear: cytoplasmic (N:C) ratio. Nuclei are round or convoluted with dispersed chromatin and inconspicuous nucleoli. Cytoplasm is scanty. Mitotic figures may be present and variable in number.[78] Ninety percent are T-cell neoplasms and stain for these markers and the remaining 10% are B-cell type. ALL is the only lymphoma that shows TdT positively.[9]

In the absence of a suggestive clinical picture, other small round cell tumors should be considered in the differential diagnosis. These include non-Hodgkin's lymphoma, rhabdomyosarcoma, granulocytic sarcoma, lobular carcinoma, neuroblastoma and endocrine carcinoma.[7]

Our cases had cellular aspirates comprising monomorphic small-to-medium size round cells having high N:C ratio, immature chromatin, inconspicuous nucleoli and scanty cytoplasm. Few ductal cells were intermingled between lymphoid cells in the aspirates from the postpartum female. Both cases were B-cell CALLA positive. Our first case showed myeloid co-expression (CD33) and our second case was BCR-ABL positive.

In conclusion, breast infiltration by ALL is rare. It should be considered in the differential diagnosis of breast lumps of sudden onset, especially when there is a significant past history. FNAC gives an easy and early diagnosis. In combination with flow cytometry or immunocytochemistry, a definitive diagnosis can be made, avoiding an excisional biopsy and allowing the initiation of early treatment.