Keywords
Mammography - magnetic resonance imaging - primary breast lymphoma - ultrasound
Introduction
The most common malignant lesion presenting as lump in the breast is carcinoma breast,
and the most common benign lesion affecting the breast is fibroadenoma. Primary lymphoma
as a cause of lump breast is very rare and accounts for about 0.4%–0.7% of all neoplastic
lesions of breast.[[1]] Primary lymphoma of the breast has no tell-tale imaging characteristics, but the
possibility of lymphoma should be considered if the lesion looks high grade but does
not fit into classical description of carcinoma breast. We present here one such case
which presented as diagnostic dilemma on imaging.
Case History
A 48-year-old postmenopausal lady presented with history of enlargement of the right
breast since the past 1 month which was painless. She felt heaviness and vague lump
in the right breast and noticed scanty watery discharge 10 days before she presented
to the hospital. There was no history of trauma, fever, or weight loss. There was
no family history of carcinoma breast in immediate relatives. On general examination,
her vitals were stable, and there was no generalized lymphadenopathy or organomegaly.
Local examination revealed asymmetrical enlargement of the right breast with ill-defined
palpable lump of approximately 9 × 10 cm in size, which was firm in consistency. The
overlying skin and nipple areolar complex were normal. Her laboratory investigations
including the total and differential leucocyte counts were normal. Mammography was
done, and it showed well-defined round hyperdense mass lesion measuring 10 × 6 × 9
cm in the superolateral quadrant, there was no architectural distortion of adjacent
breast parenchyma or any micro- or macrocalcification [[Figure 1]]A and [[Figure 1]]B. There was right axillary lymphadenopathy with loss of fatty hilum (arrow). Ultrasound
(USG) of breast revealed a large hyperechoic lesion in the right breast with multiple
round to oval hypoechoic nodules [[Figure 2]]A. The right axillary nodes were enlarged, round, hypoechoic, and showed loss of
normal fatty hilum or slit-like configuration of hilum [[Figure 2]]B and [[Figure 2]]C. Based on mammography and breast USG imaging, diagnosis of BI-RADS IV lesion (breast
imaging reporting and data system) with possibility of phyllodes tumor was given.
Following this, USG-guided trucut biopsy of the mass was done. Histopathological examination
revealed diffuse sheets of large pleomorphic malignant lymphoid cells. These cells
had high N:C ratio with scant cytoplasm, vesicular nuclei, and inconspicuous nucleoli
which were CD45- and CD20-positive. Proliferation index by Ki-67 was high >90%; the
findings were suggestive of diffuse large B-cell lymphoma (DLBL) (high grade) [[Figure 3]].
Figure 1 (A and B): (A) MLO and (B) CC view of right breast showing well-defined large hyperdense mass
in the superolateral quadrant without architectural distortion. Note the enlarged
node in the right axilla (arrow)
Figure 2 (A-C): (A) Ultrasound showing a large hyperechoic lesion in the right breast with multiple
round to oval hypoechoic nodules. (B) Round, hypoechoic, enlarged axillary nodes with
loss of normal fatty hilum, and (C) a few nodes with slit-like configuration of hilum
Figure 3: Histopathological examination showed a diffuse growth pattern of medium to large
lymphoid cells with vesicular chromatin and inconspicuous nucleoli (H and E). These
lymphoid cells were positive for CD45 and CD20 and negative for ER, PR, and CK
Thereafter, magnetic resonance imaging (MRI) of breast was done to screen the contralateral
breast and to detect any other similar smaller lesions. MRI showed a solitary well-defined,
smoothly marginated lesion measuring 10 × 5.4 × 9 cm (AP × TR CC) in size which was
iso- to hypointense on T1W and hyperintense on short TI inversion recovery (STIR)
sequence with few hypointense nodules [[Figure 4]]A and [[Figure 4]]B. On dynamic contrast MRI study, the mass showed enhancement with hyper-enhancing
nodules. There was early enhancement with plateau followed by slow washout of contrast
on time–intensity curve (type 2 kinetic curve) [[Figure 4]]C and [[Figure 4]]D.
Figure 4 (A-D): MRI of breast showing a well-defined, smoothly marginated mass in right breast iso-
to hypointense on T1W (A) and hyperintense on STIR with few hypointense nodules (B).
On dynamic contrast study, the lesion shows heterogeneous enhancement (C) with plateau
and slow washout of contrast in time-intensity curve (D)
Positron emission tomography/computed tomography (PET/CT) was done to stage the disease.
It showed well-defined rounded large soft tissue density mass with increased 2-fluorodeoxyglucose
(FDG) uptake in the mass (SUVmax of 9.4) (standardized uptake value) and right axillary nodes [[Figure 5]]. No uptake of radiotracer was seen in any other lymph nodal groups.
Figure 5: PET/CT image showing increased FDG uptake in the mass in the right breast with SUVmax of 9.4
Discussion
Involvement of breast in lymphoma can be primary or secondary to metastatic disease
process. Pathological criteria for diagnosis of primary breast lymphoma (PBL) given
by Wiseman and Liao are presence of lymphoma cells in breast tissue in a patient with
no history of earlier or simultaneous lymphoma at another site; however, involvement
of ipsilateral axillary lymph nodes may be seen.[[2]]
The majority of PBL are of the non-Hodgkin’s lymphoma type with most cases of B-cell
lineage, with 60% being the diffuse large B-cell type.[[3]] Most of the affected patients present in their fifth or sixth decade of life. Clinically,
it presents with painless lump in the breast or in some cases as asymmetric enlargement
of the breast as was seen in this case.
The basic work-up of any lump breast includes mammography and USG of the breast. There
are no pathognomonic imaging features of PBL on mammography; however, findings such
as solitary mass with well-defined margins, lack of micro- or macrocalcification,
and absence of distortion of the normal breast architecture with axillary lymphadenopathy
should raise the suspicion of PBL.[[4]] This case had typical mammographic features of PBL such as well-circumscribed large
mass, absent calcification, preserved breast architecture, and axillary adenopathy
[[Figure 1]]; however, these features are nonspecific and the diagnosis of PBL cannot be made
on the basis of mammographic findings alone.
The most common USG feature of PBL has been described as a solitary round or oval
hypoechoic mass. Other findings which can be seen in PBL are heteroechoic mass with
ill-defined margins or masses with an echogenic center and surrounding hypoechogenicity.
Surov et al.[[5]] in their study found 67% of the lesions to be oval in shape, 15% were anechoic,
46% were hypochoic, and mixed echogenicity was seen in 39% with posterior enhancement
noted in 52% of the lesions. The USG in our case showed an echogenic mass which merged
with the normal breast tissue and had multiple round to oval hypoechoic areas within
[[Figure 2]]A; these focal round to oval lesions are akin to lymphoma deposits seen in other
organs such as spleen or liver. This round to oval hypoechoic lymphoma deposits in
breast have not been described in literature; more studies will be required before
it can be considered specific for PBL, although this USG characteristic is not seen
in any other breast lump. The USG also showed multiple enlarged ipsilateral axillary
nodes; these nodes had variable appearance with round to oval shape and appeared hypoechoic;
a few showed loss of normal fatty hilum, whereas others showed slit-like appearance
of hilum. Metastatic nodes are round and show loss of fatty hilum [[Figure 2]]B or the hilum is displaced to the side, whereas reactive nodes maintain their reniform
shape and have preserved fatty hilum. Slit-like appearance of hilum is often seen
in metastatic disease than reactive nodes, as was seen in this case [[Figure 2]]C.
MRI findings of PBL show well-circumscribed masses which are isointense on T1W and
hyperintense on T2W/STIR images. Post contrast administration, the lesions show marked
heterogeneous enhancement. Time–intensity curve or kinetics study on MRI in PBL shows
a rapid early enhancement and plateau or a slow washout in delayed phase. The lesion
in this case was isointense on T1W, hyperintense on STIR, and showed heterogeneous
enhancement with a few nodular hyper-enhancing areas within. It showed type 2 kinetic
curve [[Figure 4]]D. Unlike breast carcinoma which typically shows early enhancement and rapid washout
(type 1 curve), lymphomas tend to show type 2 curve. Surov et al. in their study of 23 lesions of PBL found type 2 and type 1 kinetic curves in 90%
and 5% of the lesions, respectively.[[5]]
Lymphomas show increased FDG uptake on PET/CT which can be focal or diffuse depending
on the involvement of the breast, as was seen in our case with SUVmax of 9.4 [[Figure 5]]. PET/CT has a role in staging and in evaluation of treatment response and detection
of recurrence on follow-up.[[6]]
The differential diagnosis of PBL should include phyllodes tumor, fibroadenoma, breast
hamartoma, primary breast cancer, and metastatic lesions. Phyllodes tumor presents
as painless rapidly growing mass which occurs most commonly between 40 and 60 years
in the perimenopausal age. On mammography, it appears as large rounded oval or lobulated,
well-circumscribed mass lesion with even margins. Micro- or macrocalcification is
not a typical feature of phyllodes. On USG, it may mimic a large fibroadenoma in appearance.
Breast hamartomas also present as painless lump with asymmetrical enlargement of breast,
but they typically occur in relatively younger age group of 35–50 years, unlike lymphomas
that occur in 50–60 years age group. On mammography, they are seen as inhomogeneous,
round to oval mass with well-defined margins surrounded by thin halo. On USG, they
are compressible and show internal echotexture mixed with both hyperechoic and hypoechoic
components which may mimic the appearance of large lymphoma. On MRI, the hamartoma
appears as encapsulated mass with intralesional fat and fibroglandular signal intensity
without abnormal contrast enhancement;[[7]] lymphoma, in contrast, appears hyperintense on STIR/T2W imaging and shows avid
contrast enhancement.
Pathologically, PBLs are mostly B-cell lymphomas with up to half being DLBL mostly
CD 20+, as was seen in our case. Other lymphomas that can present in breast are follicular
lymphoma, MALT lymphoma, Burkitt’s lymphoma, and Burkitt-like lymphoma.[[8]]
The management of PBL includes radiotherapy and chemotherapy, which depends on the
stage and histologic grade of disease. It is vital to make a correct diagnosis, as
surgical resection is generally not required in these cases.
Conclusion
Primary lymphoma of breast is rare but an important differential in patient presenting
with lump breast as it can be treated without surgical resection by chemotherapy.
Therefore, radiologically one should keep in mind this differential diagnosis especially
in elderly patient presenting with well-defined radiodense lump with ipsilateral enlarged
nodes on mammography or USG. The trucut biopsy should be done in these cases as histopathological
and immunocytohistochemistry conclusively diagnose this entity.
Acknowledgement
The authors would like to thank Dr. Neeraj Kumar, Asst. Prof., Department of Nuclear
Medicine, Command Hospital, for permitting them to use the PET/CT image.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms.
In the form the patient(s) has/have given his/her/their consent for his/her/their
images and other clinical information to be reported in the journal. The patients
understand that their names and initials will not be published and due efforts will
be made to conceal their identity, but anonymity cannot be guaranteed.
