Invasive lobular carcinoma with extracellular mucin as a distinct variant of lobular carcinoma: a case report
© Haltas et al.; licensee BioMed Central Ltd. 2012
Received: 20 April 2012
Accepted: 21 May 2012
Published: 6 August 2012
The differences between invasive lobular and ductal carcinomas affect the diagnostic and therapeutic management for patients with breast cancer. In most cases, this can be accomplished because of distinct histomorphologic features. However, occasionally, this task may become quite difficult, in particular when dealing with the variants of infiltrating lobular carcinoma. Lobular carcinoma has been considered a variant of mucin-secreting carcinoma with only intracytoplasmic mucin. The presence of extracellular mucin is a feature of ductal carcinoma. Herein is presented a case of lobular carcinoma with extracellular and intracellular mucin in a 43-year-old female patient, and confirmed by immunohistochemistry. Up to the present, infiltrating lobular carcinoma displaying extracellular mucin has not been described in the literature except two case.
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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 .
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].
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.
Informed consent was obtained from the patient.
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 [4–6]. 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, 3, 4]. 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 . When the secretion is prominent, the cells have a signet ring configuration . The well-described variant ILCs include solid, alveolar, pleomorphic, tubulolobular, signet ring, and mixed types [3–6].
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 . In breast tumors, extracellular mucin production is encountered as a feature of ductal phenotype [4, 6]. 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, 6]. 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 . 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 . 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 . Because number of cases of these tumors is limited, it is difficult to comment on the biological behavior and molecular profiles.
Summary of the reported case of lobular carcinoma with intra and extracellular mucin secretion
Lobular Carcinoma In situ
Signet ring component
Positive lymph nodes
Rosa et al., 
axillary dissection not performed
synchronous ductal carcinoma in left breast
Yu et al. 
sentinel lymp node metastasis
modified radical mastectomy
axillary lymp node metastasis (1/19)
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.
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