Invasive lobular carcinoma is a distinct type of breast carcinoma based on its characteristic histological pattern. It is more frequently hormone-receptor positive, displays a higher incidence of synchronous, contralateral primary tumors, more frequently presents with multicentric disease, and metastasizes to distinct sites such as the meninges, serosa, and retroperitoneum [4
]. These tumors arise from the lobular and terminal duct epithelium. They can occur throughout the entire age range of breast carcinoma in adult women and usually constitutes 5-15% of carcinomas. Besides the classical invasive lobular type, other variant forms are also seen [1
]. Histologically, the classical type of ILC is characterized by dyshesive cells with small nuclei, linear arrangements of cells infiltrating the stroma between collagen fascicles forming so-called ‘Indian files’ and low mitotic activity. Lobular carcinoma, both in situ and infiltrating, is a tumor that secretes acidic mucosubstances, that are intracellular in location [3
]. When the secretion is prominent, the cells have a signet ring configuration [4
]. The well-described variant ILCs include solid, alveolar, pleomorphic, tubulolobular, signet ring, and mixed types [3
Although generally accepted histological criteria serve to distinguish lobular from ductal carcinoma of the breast, this differential diagnosis may present a challenge in some variants of the tumors showing equivocal histological features [4
]. In breast tumors, extracellular mucin production is encountered as a feature of ductal phenotype [4
]. In our case report, lobular carcinoma with abundant extracellular mucin was detected.
It is important for pathologists to recognize invasive lobular carcinoma with extracellular mucin because of the differential diagnosis. The histological differential diagnosis of the tumor may include pure mucinous carcinoma, mixed mucinous-ductal carcinoma, mucinous carcinoma with neuroendocrine differentiation, mucinous papillary neoplasms, mucocel like tumor, and mixt carcinoma (lobular and ductal carcinoma). These tumors have ductal phenotype. The distinction is important for their prognosis and management. In the breast, E-cadherin is useful to distinguish between ductal and lobular neoplasia. Tumor cell of lobular carcinoma tends to have a loss of expression of E-cadherin. E-cadherin, a cell-cohesion protein encoded by a gene on chromosome 16q22.1, is the current marker of choice to help discriminate between lobular and ductal carcinoma [4
]. The majority of usual ductal carcinomas express membranous E-cadherin, whereas most in situ and invasive lobular carcinomas, both classic and pleomorphic types, lack its expression. In our case, The tumor was composed of small clusters of neoplastic cells disposed in large pools of mucin and classical lobular carcinoma areas. The complete loss of membranous E-cadherin in all areas of the tumor was detected. Ductal carcinoma in situ was not detected in any part of the tumor, but lobular carcinoma in situ was observed in many areas of the tumor. Also we used Chromogranin A and Synaptophysin to exclude the neuroendocrine differentiation of the tumor, where we observed that, these markers were negative.
The majority of invasive lobular carcinomas (ILCs) express estrogen receptor (ER) and progesterone receptor (PR). HER-2 overexpression and amplification are limited essentially to invasive ductal carcinomas of intermediate to high grade. Classical lobular carcinoma does not show HER-2 overexpression or amplification [6
]. Rosa and colleagues observed that the tumor did not overexpress HER2 protein in the first case of lobular carcinoma with extracellular mucin, similarly to our results [7
]. On the other hand, Yu and colleagues found overexpression of HER2 protein in lobular carcinoma with extracellular mucin in their case report. They thought that this tumor was between lobular and ductal carcinomas to the overlapping morphological features as well as molecular manifestation [8
]. Because number of cases of these tumors is limited, it is difficult to comment on the biological behavior and molecular profiles.
Lobular carcinoma with extracellular mucin secretion is a newly described extremely rare variant with only two cases reported in the English medical literature. Rosa and colleagues reported the first case, and Yu and colleagues reported the second case [7
]. These two cases are summarized in Table . The current report is the third documented case.
Summary of the reported case of lobular carcinoma with intra and extracellular mucin secretion
In conclusion, we have reported a very rare case of lobular carcinoma with intra and extracellular mucin secretion. Extracellular mucin secretion may not be an exlusive feature of ductal phenotype.