B Fisher

B Friedenson

C Praga

CE Dearden

E Diamandidou

J Mercieca

Manish Singhal

MC Le Deley

Prasenjit Das

R Tadeusz

RE Curtis

RE Smith

Ritu Gupta

S Chakraborty

Vinod Raina

English

PubMed

Crossref

T cell-prolymphocytic leukemia detected in a patient of breast cancer at the time of recurrence: a case report

Springer - Publisher Connector

BioMed CentralCases Journal
ssOpen AcceCase Report
T cell-prolymphocytic leukemia detected in a patient of breast 
cancer at the time of recurrence: a case report
Manish Singhal*1, Vinod Raina2, Ritu Gupta2 and Prasenjit Das3
Address: 1Department of Medical Oncology, Institute Rotary Cancer Hospital (IRCH), All India Institute of Medical Sciences (AIIMS), New Delhi, 
India, 2Department of Lab Oncology, IRCH, AIIMS, New Delhi, India and 3Department of Pathology, AIIMS, New Delhi, India
Email: Manish Singhal* - singhaloncocare@yahoo.co.in; Vinod Raina - vinodraina@hotmail.com; Ritu Gupta - drritugupta@hotmail.com; 
Prasenjit Das - dr_prasenpgi@yahoo.co.in
* Corresponding author    
Abstract
Introduction: Therapy related second malignancy of the hematological system is small but real risk after
adjuvant chemotherapy for breast cancer. It includes acute myeloid leukemia (AML) and myelodysplastic
syndrome (MDS); however T-cell prolymphocytic leukemia (T-PLL) has not been described earlier in
relation to breast cancer and its therapy. T-PLL is a rare chronic T-cell lymphoproliferative disease with a
mature post-thymic T-cell immunophenotype and aggressive clinical course.
Case presentation: A 45 year old Indian female of Nordic origin presented 5 years back with a lump in
the right breast and the axilla. She underwent modified radical mastectomy. Histophotomicrograph of the
excised breast lesion showed a 2.1 cm duct carcinoma, positive for ER and PR with 1 out of 25 lymph
nodes positive for metastasis. She received 6 cycles of chemotherapy with cyclophosphamide, epirubicin,
and 5-fluorouracil. This was followed by tamoxifen 20 mg per day for five years. She was doing well on
follow up until the completion of fifth year of her disease, when she presented with complaints of mild
fever and weakness. Examination revealed generalized lymph node enlargement along with hepatomegaly.
Hemogram showed mild anemia, normal platelet count and a leukocyte count of 1.2 × 1011/L. Peripheral
blood examination revealed medium sized lymphoid cells, constituting almost 75% of total nucleated cell
population. Immunophenotying, established a diagnosis of post thymic T-cell prolymphocytic leukemia.
Contrast-enhanced computed tomography of the chest and abdomen was done which revealed an anterior
mediastinal mass with destruction of sternum along with multiple small nodular shadows in bilateral lung
fields suggestive of lung metastasis. Fine needle aspiration cytology of the mass showed atypical ductal cells
with nuclear pleomorphism, which were positive for ER, PR and Her2neu protein. This confirmed a co-
existent metastatic breast carcinoma. She was started on chemotherapy for T-PLL along with hormonal
therapy with aromatase inhibitor. Unfortunately, both her malignancies progressed after an initial stable
disease of two months.
Conclusion: Our case describes the potential of breast chemotherapy to cause grave second
hematological malignancies of the T-cell lymphoid lineage, not described earlier. Such events highlight the
importance to identify those patients of breast cancer in whom chemotherapy can safely be avoided.
Published: 4 January 2010
Cases Journal 2010, 3:4 doi:10.1186/1757-1626-3-4
Received: 19 October 2009
Accepted: 4 January 2010
This article is available from: http://www.casesjournal.com/content/3/1/4
© 2010 Singhal et al; licensee BioMed Central Ltd. 
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), 
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Page 1 of 5
(page number not for citation purposes)
Cases Journal 2010, 3:4 http://www.casesjournal.com/content/3/1/4Introduction
Therapy related second malignancy of the hematological
system is small but real risk after adjuvant chemotherapy
for breast cancer. It includes acute myeloid leukemia
(AML) and myelodysplastic syndrome (MDS); however T-
cell prolymphocytic leukemia (T-PLL) has not been
described earlier in relation to breast cancer and its ther-
apy. T-PLL is a rare chronic T-cell lymphoproliferative dis-
ease with a mature post-thymic T-cell immunophenotype
and aggressive clinical course.
Case Presentation
A-45-year old Indian female of Nordic origin presented 5
years back with a lump in the right breast and the axilla.
She was detected to have carcinoma of the right breast
with clinical stage as T2N1. Investigations ruled out any
metastatic site and she underwent modified radical mas-
tectomy. The tumor measured 2.1 cm with 1 out of 25
lymph nodes positive for tumor deposits. Histophotomi-
crograph of the excised breast lesion showed a duct carci-
noma, not otherwise specified. (Figure. 1C).
Immunohistochemistry showed positivity for estrogen
receptor(ER) and progesterone receptor (PR). She
received 6 cycles of chemotherapy with cyclophospha-
mide (500 mg/m2), epirubicin (50 mg/m2), and 5-fluor-
ouracil (500 mg/m2) on day1 and day15 every 4 weeks.
This was followed by tamoxifen 20 mg per day for five
years. She was doing well on follow up until the comple-
tion of fifth year of her disease, when she presented with
complaints of mild fever, weakness and swelling in the
neck and elbow. Examination revealed bilateral cervical,
epitrochlear, inguinal and right axillary lymph node
enlargement along with hepatomegaly. Hemogram
showed mild anemia, normal platelet count and a leuko-
cyte count of 1.2 × 1011/L. Lactate dehydrogenase level
was elevated (746 IU/L). Peripheral blood examination
revealed medium sized lymphoid cells (Figure 2), consti-
tuting almost 75% of total nucleated cell population, sug-
gestive of a chronic lymphoproliferative disorder.
Findings were confirmed on bone marrow examination.
The lymphoid cells showed, dot-like staining with acid
phosphatase (Figure 2. inset) and immunophenotying,
A. Low power photomicrograph of the FNA smear from anterior mediastinal mass showing atypical ductal cells arranged in trabecular pattern (PAP ×100)Figure 1
A. Low power photomicrograph of the FNA smear from anterior mediastinal mass showing atypical ductal 
cells arranged in trabecular pattern (PAP ×100). B. The same ductal cells showing moderate nuclear pleomorphism, 
overlapping and prominent nucleoli (PAP × 400). C. Histophotomicrograph of the excised primary breast lesion showing malig-
nant ductal cells arranged in trabeculae (H&E × 200). D. Ductal cells form the FNA of anterior mediastinal mass showing 
nuclear positivity for ER protein (IHC-ER×100). E. Same ductal cells showing positivity for PR protein (IHC-PR × 200). F. Same 
ductal cells showing grade 3 positivity for erb-B2 (Her2neu) stain (IHC-ERBB2 × 200).
A B C
D E FPage 2 of 5
(page number not for citation purposes)
Cases Journal 2010, 3:4 http://www.casesjournal.com/content/3/1/4depicted positivity for CD2, CD3, CD4, CD5, CD7, CD45,
CD38 and ZAP70 and negative for CD8, CD10, CD19,
CD20, CD103, CD11c, CD23, surface immunoglobulin
and TdT. Based on these findings, a diagnosis of post
thymic T-cell prolymphocytic leukemia was made. Con-
ventional cytogenetics did not reveal any abnormality.
Contrast-enhanced computed tomography (CECT) of the
chest and abdomen was done which revealed an anterior
mediastinal mass with destruction of sternum and right
coastal margin (Figure. 3A arrow) along with multiple
small nodular shadows in bilateral lung fields suggestive
of lung metastasis (Figure. 3B arrow). In the background
of breast carcinoma, recurrence of the primary breast can-
cer was kept as a differential and fine needle aspiration
(FNA) cytology of the anterior mediastinal mass was
done. Low power photomicrograph of the FNA smear
showed atypical ductal cells arranged in trabecular pattern
(Figure. 1A). The ductal cells showed moderate nuclear
pleomorphism, overlapping and prominent nucleoli (Fig-
ure. 1B). Immunohistochemical stains performed on
aspiration smears showed nuclear positivity for ER pro-
tein (Figure. 1D), PR protein (Figure. 1E) and grade 3 pos-
itivity for erb-B2 (Her2neu) stain (Figure. 1F). This
confirmed a metastatic carcinoma consistent with a breast
primary. She was started on chemotherapy for T-PLL with
fludarabine and cyclophosphamide along with hormonal
therapy with aromatase inhibitor (letrozole 2.5 mg per
day) for metastatic carcinoma of the breast. Unfortu-
nately, both her malignancies progressed after an initial
stable disease of two months.
Discussion
Leukemia is not an important factor in the natural history
of breast cancer, though its association with breast cancer
therapy has frequently been reported. There are reports of
therapy related hematological malignancies in breast can-
cer dated as early as 1980's describing the incidence as
1.68 ± .33% at 10 years with chemotherapy vis a vis 0.06%
to 0.27% with surgery alone [1]. In 1992, a large case-con-
trol study of 82,700 women with breast cancer demon-
strated a relative risk of developing AML as 2.4 for
radiotherapy, 10 for therapy with alkylating agents and
17.4 when the two were used in combination [2] The
chemotherapy regimens employed during these studies
used mainly melphalan as alkylating agent and that for
long durations (12 to 24 months) [1,2]. Though over the
last decade anthracyclines along with safer alkylating
agents have formed the main core of the breast cancer
therapy; the modern chemotherapy is not entirely safe.
The more recent reports in the background of anthracy-
cline and alkylator based chemotherapy have described
the risk as, 0.5% estimated leukemia rate at 10 years with
relative higher risk for more intense regimens (RR, 6.16; P
< 0.0001) [3,4]. Studies have also remarked on a dose risk
relation in respect to exposure to anthracycline as well as
alkylators; the risk increasing with increasing cumulative
doses [5].
Interestingly, the reports on second hematological malig-
nancies after treatment for breast cancer mostly describe
myeloid malignancies/MDS in contrast to lymphoid
malignancies [1,5,6]. While therapy related lymphoid
malignancies are relatively rare, T-PLL has never been
listed as a possible therapy related second malignancy
after treatment for breast cancer. This may have several
attributes such as more pronounced impact of cytotoxic
therapy in respect to telomere length dynamics and its
accelerated shortening observed in myeloid lineage as
opposed to lymphoid lineage before the development of
MDS/AML after hematopoietic stem cell transplant [7].
However, the risk of therapy related lymphoid malignan-
cies is not deniable. T-PLL is a disease of the elderly with
median age 65-70 years and our patient was much
younger to be at a natural risk for this disease [8]. Absence
of family history of breast cancer and other malignancies,
undermined the possibility of a common genetic abnor-
mality or pathway for such an occurrence [9]. Also the dis-
ease appeared at 5 years after the completion of therapy
which is the median latency time described for therapy
related second malignancies of the hematopoietic system
[1,3]. She also seemed to be at a relatively higher risk,
being exposed to higher cumulative doses of anthracy-
cline (600 mg/m2 of epirubicin) and alkylating agent (6
gm/m2 of cyclophosphamide) [5]. Our patient was dis-
covered to have disease recurrence simultaneously with
the detection of leukemia. Similar situation has also been
Peripheral blood smear showing medium sized lymphoid c lls, with oval nucleus, a visible nucleolus and moderateamount of as philic granular cytoplas  (Jenner-Giemsa, 1000×)Figur 2
Peripheral blood smear showing medium sized lym-
phoid cells, with oval nucleus, a visible nucleolus and 
moderate amount of basophilic agranular cytoplasm 
(Jenner-Giemsa, 1000×). Inset Lymphoid cells showing, 
dot-like staining with acid phosphatase, 1000×).Page 3 of 5
(page number not for citation purposes)
Cases Journal 2010, 3:4 http://www.casesjournal.com/content/3/1/4reported by Fisher et al wherein 2 of 34 patients with ther-
apy related hematological malignancy had simultane-
ously developed disease recurrence and
myeloproliferative disorder [1]. This however, largely
seems to be just a coincidence than otherwise.
T-cell PLL is an aggressive leukemia with median survival
of 7-8 months [8,10]. Nucleoside analogues have been
used with overall and complete response rates of 50% and
10% respectively [11]. Alemtuzumab which is a human-
ized IgG1 antibody that targets CD52, expressed at high
density on the malignant T-cells, has been shown to be
particularly effective with overall and complete response
rates of 76% and 60% respectively [10]. However,
responses are transient and further disease progression
inevitable and the only possibility of cure lies in an allo-
geneic stem cell transplant [8]. Our patient was initially
asymptomatic from the recurrence of her primary disease
and was hence, prescribed hormonal therapy (letrozole)
alone for breast carcinoma, along with fludarabine based
chemotherapy for T-PLL. However, she progressed early in
regard to both her malignancies, and this posed a major
therapeutic challenge.
Conclusion
Our case describes the potential of breast cancer chemo-
therapy to cause grave second hematological malignan-
cies of the T-cell lymphoid lineage, not described earlier;
and underscores the therapeutic dilemma posed by the
co-existence of two aggressive malignancies. While breast
cancer chemotherapy improves survival, events like this,
reminds us of the importance to identify those who are at
low-risk and in whom breast cancer chemotherapy can
safely be avoided.
Abbreviations
AML: Acute myeloid leukemia; MDS: Myelodysplastic
syndrome; T-PLL: T-cell prolymphocytic leukemia; IU:
International unit; ER: Estrogen receptor; PR: Progestrone
receptor; T: Tumor stage; N: Nodal stage; CD: Cluster dif-
ferentiation; ZAP: Zeta-associated protein; TdT: Terminal
transferase detection; FNA: Fine needle aspiration; CECT:
Contrast enhanced computed tomography; RR: Relative
risk.
Consent
Written informed consent was obtained from the patient
for publication of this case report and accompanying
images. A copy of the written consent is available for
review by the Editor-in-Chief of this journal.
Competing interests
The authors declare that they have no competing interests.
Authors' contributions
MS was involved in immediate care of the patient, con-
ducting planned investigations, and writing of the manu-
script. VR was involved in concept and final approval of
the manuscript. RG and PD were involved in establishing
diagnosis, planning investigations and RG also helped
with the manuscript. All authors read and approved the
final manuscript.
References
1. Fisher B, Rockette H, Fisher ER, Wickerham DL, Redmond C, Brown
A: Leukemia in Breast Cancer Patients Following Adjuvant
Chemotherapy or Postoperative Radiation: The NSABP
Experience.  J Clin Oncol 1985, 3:1640-1658.
2. Curtis RE, Boice JD Jr, Stovall M, Bernstein L, Greenberg RS, Flannery
JT, Schwartz AG, Weyer P, Moloney WC, Hoover RN: Risk of
A. CECT of chest showing anterior mediastinal mass with destruction of sternum and right coastal marginFigure 3
A. CECT of chest showing anterior mediastinal mass with destruction of sternum and right coastal margin. B. 
CECT of chest showing multiple small nodular shadows in bilateral lung fields.
A BPage 4 of 5
(page number not for citation purposes)
Cases Journal 2010, 3:4 http://www.casesjournal.com/content/3/1/4Publish with BioMed Central   and  every 
scientist can read your work free of charge
"BioMed Central will be the most significant development for 
disseminating the results of biomedical research in our lifetime."
Sir Paul Nurse, Cancer Research UK
Your research papers will be:
available free of charge to the entire biomedical community
peer reviewed and published immediately upon acceptance
cited in PubMed and archived on PubMed Central 
yours — you keep the copyright
Submit your manuscript here:
http://www.biomedcentral.com/info/publishing_adv.asp
BioMedcentral
leukemia after chemotherapy and radiation treatment for
breast cancer.  N Engl J Med 1992, 326:1745-1751.
3. Diamandidou E, Buzdar AU, Smith TL, Frye D, Witjaksono M, Horto-
bagyi GN: Treatment-related leukemia in breast cancer
patients treated with fluorouracil-doxorubicin-cyclophos-
phamide combination adjuvant chemotherapy: The Univer-
sity of Texas M.D. Anderson Cancer Center experience.  J
Clin Oncol 1996, 14:2722-2730.
4. Smith RE: Risk for the development of treatment-related
acute myelocytic leukemia andmyelodysplastic syndrome
among patients withbreast cancer: Review of the literature
and theNational Surgical Adjuvant Breast and Bowel Projec-
texperience.  Clin Breast Cancer 2003, 4:273-279.
5. Praga C, Bergh J, Bliss J, Bonneterre J, Cesana B, Coombes RC, Far-
geot P, Folin A, Fumoleau P, Giuliani R, Kerbrat P, Hery M, Nilsson J,
Onida F, Piccart M, Shepherd L, Therasse P, Wils J, Rogers D: Risk of
acute myeloid leukemia and myelodysplastic syndrome in
trials of adjuvant epirubicin for early breast cancer: Correla-
tion with doses of epirubicin and cyclophosphamide.  J Clin
Oncol 2005, 23:4179-4191.
6. Le Deley MC, Suzan F, Cutuli B, Delaloge S, Shamsaldin A, Linassier
C, Clisant S, de Vathaire F, Fenaux P, Hill C: Anthracyclines,
mitoxantrone, radiotherapy, and granulocyte colony-stimu-
lating factor: Risk factors for leukemia and myelodysplastic
syndrome after breast cancer.  J Clin Oncol 2007, 25:292-300.
7. Chakraborty S, Sun CL, Francisco L, Sabado M, Li L, Chang KL, For-
man S, Bhatia S, Bhatia R: Accelerated telomere shortening pre-
cedes development of therapy-related myelodysplasia or
acute myelogenous leukemia after autologous transplanta-
tion for lymphoma.  J Clin Oncol 2009, 27:791-798.
8. Tadeusz R, Paweł R: Current treatment options in prolym-
phocytic leukemia.  Med Sci Monit 2009, 13:RA69-80.
9. Friedenson B: The BRCA1/2 pathway prevents hematologic
cancers in addition to breast and ovarian cancers.  BioMed Cen-
tral Cancer 2007, 7:152-163.
10. Dearden CE, Matutes E, Cazin B, Tjønnfjord GE, Parreira A, Nomde-
deu B, Leoni P, Clark FJ, Radia D, Rassam SM, Roques T, Ketterer N,
Brito-Babapulle V, Dyer MJ, Catovsky D: High remission rate in T-
cell prolymphocytic leukemia with CAMPATH-1H.  Blood
2001, 98:1721-1726.
11. Mercieca J, Matutes E, Dearden C, MacLennan K, Catovsky D: The
role of pentostatin in the treatment of T-cell malignancies:
analysis of response rate in 145 patients according to disease
subtype.  J Clin Oncol 1994, 12:2588-2593.Page 5 of 5
(page number not for citation purposes)


A: Leukemia in Breast Cancer Patients Following Adjuvant Chemotherapy or Postoperative Radiation: The NSABP Experience. J Clin Oncol

Accelerated telomere shortening precedes development of therapy-related myelodysplasia or acute myelogenous leukemia after autologous transplantation for lymphoma.

Anthracyclines, mitoxantrone, radiotherapy, and granulocyte colony-stimulating factor: Risk factors for leukemia and myelodysplastic syndrome after breast cancer.

B: The BRCA1/2 pathway prevents hematologic cancers in addition to breast and ovarian cancers. BioMed Central Cancer

Catovsky D: High remission rate in Tcell prolymphocytic leukemia with CAMPATH-1H. Blood

Catovsky D: The role of pentostatin in the treatment of T-cell malignancies: analysis of response rate in 145 patients according to disease subtype.

Current treatment options in prolymphocytic leukemia. Med Sci Monit

Hortobagyi GN: Treatment-related leukemia in breast cancer patients treated with fluorouracil-doxorubicin-cyclophosphamide combination adjuvant chemotherapy: The University of Texas M.D. Anderson Cancer Center experience.

Risk for the development of treatment-related acute myelocytic leukemia andmyelodysplastic syndrome among patients withbreast cancer: Review of the literature and theNational Surgical Adjuvant Breast and Bowel Projectexperience. Clin Breast Cancer

Risk of acute myeloid leukemia and myelodysplastic syndrome in trials of adjuvant epirubicin for early breast cancer: Correlation with doses of epirubicin and cyclophosphamide.

file:///data/remote/core/dit/data/Springer-OA/pdf/19c/aHR0cDovL2xpbmsuc3ByaW5nZXIuY29tLzEwLjExODYvMTc1Ny0xNjI2LTMtNC5wZGY=.pdf

T cell-prolymphocytic leukemia detected in a patient of breast cancer at the time of recurrence: a case report

Abstract

Similar works

Full text

Available Versions

Crossref

Springer - Publisher Connector

Springer - Publisher Connector