The majority of invasive breast carcinomas are categorized as ductal carcinoma. Invasive lobular carcinoma (ILC) is the second most common histological type of breast carcinoma, accounting for approximately 5%–15% of all invasive breast cancers [1, 2]. Classical ILC, by definition, is a low-grade tumor with little or no nuclear atypia and a low mitotic rate. ILCs are characterized by cytologically uniform cells with round nuclei and inconspicuous nucleoli, as well as discohesive architecture with a linear or non-linear growth pattern [3–6]. Lobular neoplasia and infiltrative lobular carcinoma may produce intracellular mucin. Tumor cells may appear in signet ring shapes owing to distension with mucus. Extracellular mucin secretion is known as a feature of ductal carcinoma [4].
Herein, we present a case of lobular carcinoma with extracellular mucin and signet ring component. Up to the now, only 2 cases of mammary invasive lobular carcinoma with extracellular mucin have been described in the English written literature [7, 8].
Case report
A 43-year-old premenopausal woman, who had no family history of breast cancer, presented with a mass in the right breast. No axillary adenopathy was detected upon examination. A vague palpable mass was identified in the 8 o’clock region of the right breast. The palpable mass was confirmed with mammographic and ultrasonographic findings. Two lesions were detected on mamography. A primary spiculated, irregular, radiodense mass lesion measuring 2.5x2 cm, located at mid-outer quadrant of the right breast causing retraction of areola-nipple complex and skin thickening was detected on craniocaudal (CC) and mediolateral (MLO) projection mammographies of the patient. BI-RADS category was assessed to be 4 C. A secondary radiodense lobulated lesion measuring about 1 cm in diameter, located superolaterally of the bigger mass, was also detected and presumed to represent a satellite lesion. A hypoechoic, spiculated solid lesion with posterior acoustic shadowing located at 8–9 radiant at the edge of areola and a second hypoechoic solid lesion located at 9 radiant 2 cm away from areola was detected with ultrasonography consistent with mammographic findings (Figure 1a,b).
No additional abnormality was detected in the left breast. A subsequent diagnostic biopsy revealed an invasive lobular carcinoma with extracellular mucin. The patient underwent modified radical mastectomy with ipsilateral axillary clearance.
The resected tissue was fixed in 10% formalin and embedded in paraffin. Three-micrometer-thick sections were cut and stained with H&E. Histochemical stains for Mucicarmine and Alcian-Blue were used to confirm the mucin production and its localization.
Further analysis was performed using the streptavidin – biotin – immunoperoxidase technique. Immunohistochemistry for E-cadherin (clone: 36B5, Neomarkers, ready to use), Estrogen receptor (clone: SP1 Neomarkers, ready to use), progesteron receptor (clone: SP2 Neomarkers, ready to use), HER2/neu (clone: E2-4001 + 3b5, Neomarkers, ready to use) chromogranin A(clone LK2H10+PHE5, Neomarkers, ready to use), synaptophysin (clone:SYP02, Neomarkers, ready to use) were performed. The reaction product was visualized by aminoethylcarbazole (AEC) chromogen (Thermo scientific, Fremont, USA)) and counterstained with Mayer’s haematoxylin.
On gross examination, two separate solid lesions, measuring 2.5 cm and 0.5 cm in maximal dimension with an intervening distance of 1 cm were identified and the tumors were located below nipple and areola complex (Figure 2). A third tumor mass measured 1x0.8x0.8 cm was observed close to the axillary region. The size of the largest invasive carcinoma was used for T classification. A cross section of the masses showed a grey white solid mucinous area. There was retraction of nipple and the skin over the lump was normal. Nineteen axillary lymph nodes were isolated.
Microscope examination showed that abundant extracellular mucin was accumulated around solid tumor cells. In the peripheral areas, morphology of classic lobular carcinoma was observed (Figure 3). Mucicarmine and, PAS-Alcian-blue demonstrated the presence of intracellular and extracellular mucin (Figure 4). The tumor cells were small to medium in size, relatively uniform and round, with small nucleoli and scant to moderate amount of cytoplasm. Signet ring cells with intracellular lumina were also present (Figure 5). These coexisted with lobular carcinoma in situ. No lympho vascular invasion was observed. No nipple or skin involvement was present. Only one axillary lymph nodes were involved with tumor cells which were histologically identical with those in the breast tumor. The tumor was staged as T2N1M0 and was estrogen receptor (ER) and progesterone receptor (PR) positive. Immunohistochemically, HER2/neu and E-cadherin were found negative in the carcinomatous cells (Figure 6). Chromogranin A and Synaptophysin, used to exclude neuroendocrine differentiation, were negative.
Informed consent was obtained from the patient.