T-Cell Lymphoblastic Lymphoma Presenting with a Breast

Mass

PERRAN FULDEN YUMUKa,*, ADNAN AYDINERa, ERKAN TOPUZa, NESLIHAN CABIOGLUb andONER DOGANc

aIstanbul University, Istanbul Oncology Institute, Capa, Istanbul, Turkey; bIstanbul Faculty Of Medicine, Department Of General Surgery, Capa,Istanbul, Turkey; cIstanbul Faculty Of Medicine, Department Of Pathology, Capa, Istanbul, Turkey

(Received 10 August 2003)

Lymphomas secondarily involving the breast are uncommon, although they do represent the largestgroup of tumors metastatic to breast. A 20-year-old female with lymphoblastic lymphoma (LBL)presented here with 3 month history of weight loss, night sweats, fatigue and a mass in her left breast.Her physical examination revealed a left breast mass, lympadenopathy, bilateral pleural effusion andhepatomegaly. WBC count was 17,710/mm3 and LDH was mildly elevated. Breast ultrasound showeda 1.7 cm mass in the inner lower quadrant of left breast. Biopsy of the breast mass showed diffuseinfiltration with small, round atypical cells which did not stain with CD20, CD43, CD34, cytokeratineand were positive for CD3. She was diagnosed as leukemic phase of a precursor T-cell LBL andtreated with 6 cycles of CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone),intrathecal methotrexate and cranial radiotherapy, achieving a complete response. She then wasstarted on maintenance therapy. Four months later she returned with CNS involvement and wasstarted on induction treatment. She had a very aggressive course of disease and died only 12 monthsafter diagnosis. Breast involvement is very rarely seen in precursor T-cell LBL/ALL and in this patientoccurred secondarily as part of widespread disease.

Keywords: Breast; Lymphoma; Non-Hodgkin; High-Grade; T-cell; Lymphoblastic

INTRODUCTION

Non-Hodgkin’s lymphoma (NHL) presenting as a breast

mass is very uncommon. Primary breast lymphoma

accounts for 0.05 – 0.5% of all breast tumors and most

of these are MALToma (lymphoma of mucosa associated

lymphoid tissue) group of extranodal lymphomas.

Lymphoblastic lymphoma (LBL) is a distinct clinical

entity included in high-grade category of NHL. Impor-

tant clinical features include an increased incidence in

men, adolescents, and young adults, a predilection for

mediastinal involvement, and high incidence of bone

marrow involvement during the course of disease.

Morphologically, the disease is indistinguishable from T

lymphocyte-derived acute lymphocytic leukemia (ALL).

Despite reports of long-term disease-free survivors among

pediatric patients, LBL was associated with a poor

prognosis, especially in patients with bone marrow

involvement. Central nervous system (CNS) was a

frequent site of disease progression. More aggressive

therapy, beginning CNS prophylaxis during the induction

period, and attention to prognostic features, this

subgroup of LBL now ranks among curable lymphomas

[1]. Here we present a case of T-cell LBL who presented

with a breast mass.

CASE PRESENTATION

A 20-year-old Caucasian female was seen in 1997 with a 3

month history of weight loss, night sweats, fatigue and a

mass in her left breast. She had been started on anti-

tuberculosis treatment because of suspicious clinical signs

(fatigue, cough, shortness of breath, weight loss and

sweating), 2 months before she was seen in our clinic. Her

past medical history and family history was negative. Her

physical examination revealed red, tender left breast with

a mass 2 cm in diameter, in inner lower quadrant,

palpable, firm thyroid gland, lympadenopathy, bilateral

decreased breathing sounds and dullness to percussion,

*Corresponding author. Address: Caddebostan, Iskeleyolu C, Selin S 6/6 Erenkoy, 81060 Istanbul, Turkey. Tel./Fax: (90) (216) 327 5181. E-mail:fuldenyumuk@superonline.com, fuldenyumuk@yahoo.com

Leukemia & Lymphoma, April 2004 Vol. 45 (4), pp. 833–836

ISSN 1042-8194 print/ISSN 1029-2403 online # 2004 Taylor & Francis LtdDOI: 10.1080/10428190310001617277

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tacchycardia and hepatomegaly (3 cm beneath the costal

margin).

Routine chemistry showed normal renal, liver and

thyroid function tests and electrolytes, except hypoalbu-

minemia and lactate dehydrogenase (LDH) level was

mildly elevated. Complete blood count showed white

blood cell (WBC) count of 17,710/mm3, with 25.1%

neutrophils, 68.1% lymphocytes, 1.8% monocytes, 0.5%

eosinophiles, 0.9% basophiles and 3.6% undefined cells,

hemoglobin (Hb) of 9.8 g/dl and platelets of 243,000/

mm3.

Breast ultrasound showed a single 1.7 cm mass in inner

lower quadrant of left breast and lymphadenopathy in

left axilla (Figs. 1A and 1B). Abdominal ultrasound

revealed hepatomegaly and pleural effusion. Thorax CT

revealed bilateral pleural effusion, pericardial effusion,

mediastinal mass and bilateral axillary lympadenopathy.

Thyroid ultrasonography showed bilateral thyroid hyper-

plasia with multiple, small heterogeneous degenerative

areas of necrosis and cysts in the gland. Diffuse

adenomateous hyperplasia was seen in nuclear thyroid

scan. Echocardiography showed pericardial effusion with

EF of 61%. Fine needle aspiration of the thyroid showed

increased lymphocytes. Pleural tap was characterized as a

transudate. Cerebrospinal fluid sample was suspicious

with few atypical cells being seen.

Excisional biopsy of the breast mass showed

diffuse infiltration with small, round atypical cells

(Fig. 2). These cells did not stain with CD 20, CD

43, CD 34, lysosome, CD 68 EMA (epithelial

membrane antigen), vimentin, cytokeratine, S100,

cromogranin and NSE (neuron specific enolase).

These results ruled out any epithelial or mesenchymal

malignancies. Staining focally with monoclonal anti-

CD 3, diffusely with polyclonal anti-CD 3 and

cytologic appearance was compatible with T-cell

LBL/ALL. Bone marrow aspiration and biopsy

showed leukemic infiltration with mild increase in

reticulin (Figs. 3A, 3B and 3C).

She was diagnosed with leukemic phase of precursor T-

cell LBL and treated with 6 cycles of CHOP (cyclopho-

sphamide 600 mg/m2 day 1, doxorubicin 50 mg/m2 day 1,

vincristine 2 mg day 1, prednisolone 60 mg/m2 days 1 to

5, every 4 weeks) [1], intratechal methotrexate (12 mg)

and cranial radiotherapy (started on the 3rd week to a

total of 2,400 rad), achieving a complete response. Her

general health was good with no systemic symptoms

except mild fatigue. Then she was started on maintenance

therapy with 6-mercaptopurine (75 mg/m2/day) and

methotrexate (30 mg/m2/week) for 30 weeks. Four

months later she returned to clinic with signs of CNS

involvement. In peripheral blood flowcytometry 100% of

the cells were positive for CD 45, 73% for CD 5, 65% for

CD 7, 31% for HLA-DR, 7% for CD 3, 5% for CD 33

and 3% for CD 13. CD 34, CD 19 and CD 20 were

positive only in 1% of the cells. She had no breast

involvement this time. She was started on induction

treatment for T-cell ALL (methylprednisolone 60 mg/

m26 4 weeks, L-asparaginase 5,000 U/m26 14 days,

vincristine 2 mg/week6 4, daunorubicin 45 mg/m2/

week6 4) and intratechal cytosine arabinoside. She had

a

b

FIGURE 1 (A) Ultrasonography of the left breast. (B) Ultrasono-graphy of the enlarged left axillary lymph nodes.

FIGURE 2 Leukemic infiltration in breast biopsy (hematoxylin andeosin staining, original magnification6 500).

834 P. FULDEN YUMUK et al.

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a very aggressive course of disease and died only 12

months after the diagnosis was established, despite very

intensive treatment.

DISCUSSION

LBL demonstrates considerable histological, immuno-

phenotypic, cytogenic and clinical similarities with T-cell

ALL. They are clearly biologically related. Lymphadeno-

pathy predominates in LBL, while higher percentage of

blasts in bone marrow and blood is seen in ALL.

Lymphoblasts have a more immature thymic phenotype

in T-cell ALL, while more mature level of intrathymic T-

cell differentiation involvement is seen in LBL. Usually it

is difficult to distinguish between a leukemic conversion

of LBL and de novo ALL, as seen in this patient.

Precursor T-cell LBL is a highly aggressive disease. In

lymphomas, T-cell phenotype, independent of other

adverse clinical prognostic factors, is associated with

poor prognosis relative to B-cell phenotype. Multivariate

analysis established 4 adverse factors: T-cell phenotype,

LDH level, serum albumin level, and the number of

extranodal sites [2]. Patients with LBL can be stratified

into 2 prognostic groups [1]. Low risk patients (Ann

Arbor stage 5 IV or stage IV non-bone marrow

involvement, non-CNS, LDH 5 300 IU/l) may have

prolonged disease free interval after intensive multiagent

treatment. High risk patients are stage IV with bone

marrow or CNS disease, or stage IV with other disease

sites or LDH 4 300 IU/l at presentation and they have a

very aggressive course of disease. Coleman et al. reported

in their series of 44 LBL patients that although 42

patients (95%) had a complete remission (CR) 72% in the

high-risk group and 5% of low risk patients relapsed [1].

The case presented here also had very poor prognosis at

presentation.

The results of ALL treatment protocols were similar to

NHL protocols (CHOP) (1,3). Starting CNS prophylaxis

early in the disease (on the 3rd week) reduces the rate of

CNS recurrence from 31% to 3%, but no improvement in

total patient survival could be demonstrated with this

approach [1]. Bone marrow transplantation after first CR

is also important in the treatment of high-risk LBL

patients [3]. In our case, in spite of CNS prophylaxis, she

relapsed in CNS.

Breast involvement is very rarely seen in precursor T-

cell LBL/ALL. To best of our knowledge there are only

14 cases reported in the literature [3 – 9] and in this patient

it occurred secondarily as a part of widespread disease.

References

[1] Coleman, C.N., Picozzi, V.J., Cox, R.S., McWhirter, K., Weiss,L.M., Cohen, J.R., et al. (1986) ‘‘Treatment of lymphoblasticlymphoma in adults’’, Journal of Clinical Oncology, 4, 1628 – 1637.

[2] Coiffier, B., Brousse, N., Peuchmaur, M., Berger, F., Gisselbrecht,C., Bryon, P.A., et al. (1990) ‘‘Peripheral T-cell lymphomas have aworse prognosis than B-cell lymphomas: a prospective study of 361immunophenotyped patients treated with the LNH-84 regimen. TheGELA (Groupe d’Etude des Lymphomes Agressives)’’, Annals ofOncology, 1, 45 – 50.

[3] Morel, P., Lepage, E., Brice, P., Dupriez, B., D’Agay, M.F., Fenaux,P., et al. (1992) ‘‘Prognosis and treatment of lymphoblasticlymphoma in adults: A report on 80 patients’’, Journal of ClinicalOncology, 10, 1078 – 1085.

a

b

c

FIGURE 3 (A) Acute leukemic infiltration in bone marrow biopsy(hematoxylin and eosin staining, original magnification6 600). (B) TdTimmunoreactivity in bone marrow infiltrates (AEC cromogen, Mayerhematoxylin, original magnification6 600). (C) CD 3 immunoreactivityin bone marrow infiltrates (AEC cromogen, Mayer hematoxylin, originalmagnification6 600).

835BREAST T-CELL LYMPHOBLASTIC LYMPHOMA

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[4] Arber, D.A., Simpson, J.F., Weiss, L.W. and Rappaport, H. (1994)‘‘Non-Hodgkin’s lymphoma involving the breast’’, American Journalof Surgical Pathology, 18, 288 – 295.

[5] Cohen, P.L. and Brooks, J.J. (1991) ‘‘Lymphomas of the breast: Aclinicopathologic and immunohystochemical study of primary andsecondary cases’’, Cancer; 67, 1359 – 1369.

[6] Hugh, J.C., Jackson, F.I., Hanson, J. and Poppema, S. (1990)‘‘Primary breast lymphoma: An immunologic study of 20 new cases’’,Cancer, 66, 2602 – 2611.

[7] Poros, A., Hollan, S.R., Natonek, K., Lelkes, G. and Gyodi, E.(1981) ‘‘T acute lymphoblastic leukemia with breast tumor: A briefreport’’, Haematologia, 14, 215 – 218.

[8] Au, W.Y., Chan, A.C., Chow, L.W. and Liang, R. (1997)‘‘Lymphoma of the breast in Hong Kong Chinese’’, HematologicalOncology, 15, 33 – 38.

[9] Pettinato, G., Manivel, J.C., Petrella, G. and De Chiara, A. (1991)‘‘Primary multilobated T-cell lymphoma of the breast diagnosed byfine needle aspiration cytology and immunocytochemistry’’, ActaCytologica, 35, 294 – 299.

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