Keywords
Axillary metastasis - distant metastasis - imaging features - juvenile carcinoma -
pediatric breast malignancy - secretory carcinoma breast
Introduction
The spectrum of conditions that affects pediatric breast differs significantly from
that of adults. The majority of breast masses in children and adolescents are benign,
fibroadenoma being the commonest diagnosis.[1] The malignant breast masses in children are exceedingly rare, most of them being
the metastatic or disseminated lesions.[1],[2],[3] Secretory carcinoma is a rare primary breast malignancy in pediatric age group.[1] Various investigators in past have reported the clinicopathological characteristics,
but there is paucity of literature on its imaging features.[4],[5],[6],[7] We report a case of secretory carcinoma breast, in an 11-year-old girl, with distant
and axillary metastasis. Distant metastases from secretory carcinoma are extremely
rare with only five cases reported, with ours being the sixth case, to the best of
our knowledge.[8] Moreover, this report is among the very few published reports, where the imaging
features of pediatric secretory carcinoma breast are emphasized, on various imaging
modalities including ultrasound, color Doppler, computed tomography (CT), magnetic
resonance imaging (MRI), and PET-CT.[6],[7],[8]
Case Report
An 11-year-old girl, presented to Surgery OPD, in 2014, with a painful lump and watery
discharge from right breast for 3–4 months. No significant past history was obtained.
There was a palpable firm to hard lump, in retroareolar area of right breast, adherent
to the overlying nipple, and underlying pectoralis muscles, with palpable right axillary
lymphadenopathy. Provisional diagnosis of suspicious malignant right breast mass with
axillary lymphadenopathy was made. After obtaining informed consent from the parents,
Ultrasound bilateral breasts was performed, which showed normal left breast [Figure 1]A. The right breast depicted a well-circumscribed retroareolar, oval shaped, homogeneously
hypoechoic mass, with partially microlobulated margins, and no internal calcifications
or necrosis or dirty edge shadows [Figure 1]B. The mass was seen to extend into skin anteriorly and abutting pectoralis major
muscle posteriorly [Figure 1]C. Ultrasound right axilla showed a round hypoechoic node with no fatty hilum [Figure 1]D. Color Doppler showed increased central and peripheral vascularity in the mass
and abnormal axillary node [Figure 2]A and [Figure 2]B. Diagnosis was made of a suspiciously malignant right breast mass, with likely
invasion of skin and pectoralis muscle with malignant right axillary lymphadenopathy.
MRI bilateral breasts was performed for better assessment of pectoralis involvement,
which revealed an irregular heterogeneously enhancing retroareolar right breast mass
with infiltration of skin and subcutaneous tissue. However, the intervening fat plane
with the pectoralis major was maintained [Figure 3]. The mass lesion showed a T1 hypointense and T2 heterogeneously hyperintense signal
intensity on MRI. US guided Biopsy showed tumor cells in diffuse sheets with minimal
pleomorphism, laden with Periodic Acidic Schiff (PAS)-positive secretions, suggesting
secretory carcinoma [Figure 4].
Figure 1 (A-D): Ultrasound images of bilateral breasts (A-C), show normal left breast (A), with a
well circumscribed, retroareolar, oval-shaped, homogeneously hypoechoic mass, in the
right breast (white arrow), with partially microlobulated margins and no internal
calcifications or necrosis or dirty edge shadows (B). The right breast mass is seen
to extend into the skin anteriorly (yellow open arrow) and abutting pectoralis major
muscle posteriorly (black arrow) (C). Ultrasound image of right axilla (D) shows a
round hypoechoic node with no fatty hilum (thick closed yellow arrow)
Figure 2 (A and B): Color Doppler images (A and B) show increased central and peripheral vascularity
in the mass (A) and abnormal axillary node (B)
Figure 3: Axial contrast enhanced T1 weighted magnetic resonance imaging image shows an irregular
heterogeneously enhancing retroareolar right breast mass (white arrow), with infiltration
of skin and subcutaneous tissue anteriorly and maintained fat plane with pectoralis
major posteriorly
Figure 4: Histopathology section shows tumor cells in diffuse sheets and tubules with minimal
pleomorphism (PAS × 200; black arrow). Inset shows PAS-positive secretions (×400;
black arrow)
On immunohistochemistry (IHC), the tumor was ER, PR, and HER2-neu negative (Triple
Negative). Genetic analysis was negative for BRCA 1, BRCA 2 genes. Staging CT revealed multiple bilateral fibro-nodular lung opacities suggesting
pulmonary metastasis [Figure 5]A,[Figure 5]B,[Figure 5]C,[Figure 5]D,[Figure 5]E. Whole body PET-CT showed hypermetabolic retroareolar right breast mass with multiple
bilateral FDG avid lung nodules. Final diagnosis was a triple negative secretory carcinoma,
right breast, with axillary and pulmonary metastasis (stage IV disease). The patient
was started on palliative chemotherapy. Follow-up CT after 2 years showed residual
retroareolar irregular heterogeneously enhancing right breast mass free from overlying
skin. CT chest showed post chemotherapy skin edema and reduction in number of lung
nodules [Figure 6]A,[Figure 6]B,[Figure 6]C. Follow-up PET-CT after 2 years showed a mass free from overlying skin, with multiple
bilateral lung nodules, showing mild FDG uptake [Figure 6]D. There was minimal reduction in size of the mass with significant resolution of
lung nodules. Following these investigations, the patient is on follow-up.
Figure 5 (A-E): Axial contrast enhanced computed tomography chest images in lung window (A-D) and
mediastinal window (E) show multiple bilateral fibro-nodular lung opacities (A-D),
with a heterogeneously enhancing irregular retroareolar right breast mass (yellow
arrow) (E)
Figure 6 (A-D): Axial contrast enhanced computed tomography chest images (postchemotherapy), in both
lung window (A, B) and mediastinal window (C), show reduction in number of bilateral
lung nodules (A-C), with an irregular heterogeneously enhancing retroareolar right
breast mass (yellow dotted arrow) with minimal reduction in size and postchemotherapy
skin edema (C). A 2-year follow-up PET CT image (D) shows mild FDG uptake in both
the retroareolar right breast mass and bilateral lung nodules (white arrow). The right
breast mass is now seen to be free from overlying skin (D)
Discussion
Carcinoma breast is extremely rare in children (<1% of all breast lesions).[3] BRCA1 and BRCA2 gene mutations are associated with pediatric breast cancers. Secretory
carcinoma is most common type of cancer seen in children, accounting for <0.1% of
all invasive breast cancers.[1] Other histological types less frequently encountered in children are medullary,
anaplastic, inflammatory, infiltrating lobular, and ductal carcinomas, which are more
aggressive, unlike favorable prognosis of secretory carcinoma.[1]
Secretory carcinoma was initially termed as juvenile breast carcinoma by McDivitt
and Stewart in 1966, owing to presentation, in young children.[9] Subsequently, Tavassoli and Norris coined the term “secretory carcinoma” based on
typical histopathology (vacuolated cytoplasm, intracellular, and extracellular secretory
material).[4] On IHC, these carcinomas are usually triple negative (ER, PR, and HER-2/neu negative),
with a recently identified balanced translocation t(12;15) ETV6-NTRK3 fusion gene.[8]
The patients present with a slow growing, well-circumscribed, retro-areolar mass,
with or without nipple discharge. There is lacuna in literature on specific imaging
characteristics of secretory breast carcinoma.[6],[7]
On ultrasound, a solitary, well-circumscribed, or partially microlobulated hypoechoic
or isoechoic mass is noted, mimicking a benign lesion.[1],[6],[7] The role of CT in pediatric breast masses is limited to staging.[8] MRI is important in assessment of chest wall infiltration.
The differentials in a sonographically solid pediatric breast lesion are benign and
malignant etiologies. The benign lesions include fibroadenomas, granular cell tumours,
juvenile papillomatosis, and pseudoangiomatous stromal hyperplasia (PASH). The malignant
lesions include primary breast malignancies like phylloides tumor and carcinomas and
breast secondaries. The imaging features of fibroadenomas, PASH, juvenile papillomatosis,
and phylloides tumor mimic each other on ultrasound and are seen as well circumscribed
homogeneously hypoechoic wider than taller masses. Presence of anechoic cysts and
clefts in phylloides may be a distinguishing feature. Juvenile papillomatosis shows
multiple tiny peripheral cysts. Granular cell tumor, though a benign tumor, masquerades
malignancy on ultrasound, with irregular spiculated hypoechoic mass, and dirty posterior
acoustic shadows. Breast carcinomas depict malignant features on sonography. Secretory
carcinoma may mimic a benign lesion on ultrasound. However, finally confirmation needs
histopathology. Sanders et al. have recently laid down guidelines, on when to perform biopsy, if encountered with
a pediatric solid breast mass.[1],[10],[11]
There is no consensus on ideal treatment strategy for secretory breast carcinoma.[1],[4],[5],[6],[7],[8] However, breast conservative surgery (BCS) is considered the mainstay of treatment.
Axillary metastasis is rare, with an incidence of about 30% in children. Involvement
of more than three lymph nodes may herald a risk for distant metastasis.[4],[5],[6],[7] The role of adjuvant chemotherapy and radiotherapy is not established, though their
administration following BCS, improves locoregional control.[5],[6],[7] Since, usually secretory tumors are triple negative, effectiveness of hormone therapy
is of little use. Recently, the identification of specific ETV6-NTRK3 fusion gene
mutation is considered to be a breakthrough in formulating targeted molecular therapies
for this disease in the near future.[8]
Conclusion
Since majority of breast lumps, in children mimic fibroadenomas, a high suspicion
is required to reach a diagnosis, thereby guiding appropriate management. Secretory
carcinoma, though a very rare pediatric breast malignancy, should be considered as
a differential diagnosis in slowly growing palpable mass, with solid benign looking
lesion on ultrasound. The awareness of possibility of malignancy in these masses can
be a great help in reaching an accurate diagnosis.
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.
