Lung metastasis in secretory carcinoma breast – Rare presention

Secretory carcinoma is a rare breast cancer with mean age of 25 years. It was initially thought to be a tumour of children but can also occur in adults and old age. Tumour cells are cytologically bland and form glands and microcystic spaces containing abundant secretion. They are triple negative tumours but with good prognosis and excellent response to surgery. However, the patients should be kept on long term follow up as late occurrence of metastasis isknown. Here we report a patient with diagnosis of Secretory carcinoma breast who developed lung metastasis four years later.


Introduction
Secretory carcinoma breast (SCB) is a rare breast cancer with indolent clinical behavior. It is seen primarily in children but can also occur in adults. The tumor cells have characteristic abundantintra-and extracellular secretions and granular eosinophilic cytoplasm [1]. It accounts for <0.1% of all cases of invasive breast cancer [2]. It has a less aggressive behavior and a much better prognosis than other variants observed in adults. Axillary metastasis is rare and distant metastases are even rarer [3]. Here we report a patient with diagnosis of SCB who developed lung metastasis four years later.

Case Report
A 62 years old female presented with cough and hemoptysis of 6 weeks duration. She gave history of breast carcinoma 4 years ago which was surgically resected. Computerised Tomography (CT) scan of chest revealed an ill defined heterogeneously enhancing soft tissue mass lesion in right upper lung lobe measuring 10.3x4x6.3cm. It extended from the chest wall deep to the mediastinum and right hilar region encasing the right main pulmonary artery and its upper lobar branch alongwith right main bronchus with small intrabronchial extension. Few mildly enlarged paratracheal and subcarinal lymph nodes were seen largest measuring 1.3 cm in diameter.
Tracheobronchial biopsy of the mass showed malignant cells exhibiting mild pleomorphism, having vesicular nuclei with prominent nucleoli forming small glandular structures surrounded by fibrous stroma (Figure 1A,B). Immunohistochemistry (IHC)-Cytokeratin (CK) and S100 positive ( Figure 1C,D) whereas thyroid transcription factor 1(TTF1), CK20, synaptophysin, estrogen receptor (ER), progesterone receptor (PR), carcinoembryonic antigen (CEA) were negative. A diagnosis of metastatic adenocarcinoma (well differentiated) of breast origin was made. She presented 4 years ago with breast mass whose trucut biopsy revealed to be invasive ductal carcinoma (IDC)-secretory versus apocrine type. She underwent modified radical mastectomy (MRM) with size of tumor being 3x3x1.5cm and diagnosis of secretory variant of IDC was reached ( Figure 2).
There was vascular invasion but all axillary lymphnodes (17) resected were found to be free of tumor. Histological grading according to Nottingham score (modified Bloom Richardson grade) was II/III. It was ER, PR, Androgen receptor (AR), human epidermal growth factor receptor (HER-2/Neu) negative and S100 positive on IHC. Currently the patient is receiving hormonal therapy and is on followup.

Discussion
Secretory carcinoma is a rare tumor with frequency less than 0.15% of all breast cancers.Mean age in a study was found to be 25 years with female predominance [4]. However a recent study conducted on 246 invasive secretory carcinomas showed mean age of 56.4 years [5]. This goes against the previous view that it is found predominantly in children.
This entity was initially termed "Juvenile breast cancer" by Mc Divitt and Stewart, based on the fact that the average age of the seven patients described in their series was nine years with range of three to fifteen years [6]. Subsequently more cases in children and adults were described. Therefore, it was recommended that the descriptive term SCB replace the designation "juvenile carcinoma".
Grossly, it is well circumscribed and usually small. The margins are of the 'pushing' type withprominent hyalinization seen in the central portion [1].
Microscopically the tumor cells, glands, and microcystic spaces contain abundant secretion, which is usually pale pink or amphophilic with hematoxylin and eosin (H&E) staining. It is often vacuolated or "bubbly," reacting variably for mucin and with the periodic acid-Schiff (PAS) reaction, and is diastase resistant.
In microcystic areas the secretion resembles the material that accumulates in cystic hyper secretory lesions. Strong positive staining has been reported for α-lactalbumin, S-100 protein and CEA (polyclonal). No reactivity was observed for gross cystic disease fluid protein 15 (GCDFP-15) or for monoclonal CEA.
Secretion sometimes in membrane-bound vacuoles, can be found ultra structurally within the cytoplasm of tumor cells and in intracytoplasmic lumina [7]. SCB are negative for hormone receptors ER, PR and do not express HER-2/neu [8]. Our case was also triple Pathology Update: Tropical Journal of Pathology & Microbiology Available online at: www.pathologyreview.in 558 | P a g e negative. However a recent study showed they are frequently hormone receptor-positive [5]. Tognon et al were the first to report that SCB expresses the ETV6-NTRK3 gene fusion characterized by a balanced genetic translocation, t(12;15) in 12 out of 13 of their cases [9].
SBC with the ETV6-NTRK3 fusion gene belonged to the phenotypic spectrum of basal-like breast carcinomas and immunohistochemical as well as genetic features of SCB distinguished them from other basal-like breast cancers. Prognostic significance of expression of basal markers is not known [10].
While IDC of the breast that is triple negative is associated with a poor prognosis, SCB has been reported to be a low-grade carcinoma with an indolent course and excellent prognosis. Tumor size (less than 2 cm), age (less than 20 years at the time of diagnosis), and circumscribed margins of the tumor are favorable prognosis indicators [4]. SCB in adults is potentially more aggressive than in childhood.
Nodal metastases are more frequentwith the lungs and bones being frequent sites of breast cancer metastasis.Slow growth and delayed recurrence are characteristic of many of these tumours. Death from systemic metastases is rare, but may ensue either rapidly or following a long latent period after treatment.
Prolonged follow-up is needed to assess accurately the biological behaviour of this tumour [11]. The reported incidence rate of axillary lymph node metastasis ofSCB is 15-30% [12]. Our patient presented with lung metastasis after being in remission for 4 years after treatment.
Treatment modalities are not very well defined because of its rarity. For patients over 20 years old an initial simple mastectomy with axillary node dissection is considered adequate [4].
Our patient underwent MRM with axillary dissection. Surgery is associated with good long-term survival. In a study conducted by Jacob et al SCB's were frequently hormone positive in contrast to previous reports where they were hormone negative.
They compared treatment modalities of SBC with IDC and found breast conserving surgery and hormonal therapy rates were similar in both.Systemic chemotherapy was used less often for SCBand overall survival of patients with SCB being better than with IDC [5].

Conclusion
SCB is a rare indolent malignancy with good prognosis. The patients should be kept on long term followup as later on chances of metastasis areknown.