Mucinous carcinoma or mucosal colloid (MC) is a rare histological form of mammary tumor  . It represents 1 to 4% of all breast cancers  . According to the World Health Organization (WHO), it is defined by the presence of extracellular mucus in which mucosecreting malignant tumor cells float  . Histologically, there are two types of MC: the pure MC and the mixed MC that associate foci of infiltrating ductal carcinoma next to the mucinous component. This distinction is crucial because of its prognostic value  . The positive diagnosis of these tumors is provided by echomammography and confirmed by ultrasound-guided microbiopsy or surgical excision. It is a mild cancer. Relapses are rare and usually late   . Through a retrospective study of 14 cases of breast MC and a review of the literature, we will try to discuss the main features of this rare form of breast cancer.
2. Materials and Methods
This is a retrospective study of 14 patients with a breast MC including eight pure MC and six mixed MC, treated at Monastir Maternity and Neonatal Center over a period of 9 years from January 2009 to December 2017. We selected all patients with MC defined by the presence of extracellular mucin in which carcinomatous cells are bathed with or without the presence of non-specific ductal carcinoma component (CCnsp). Data was collected from patient records and transcribed on a pre-established computerized form. These data were relevant to demographic, anatomo-clinical and radiological characteristics.
In our series we collected 14 patients with a breast MC from 728 patients diagnosed and treated for breast cancer at the Maternity and Neonatal Center of Monastir between January 2009 and December 2017. This rate represents 1.9% of cancers treated in the center during the same study period. The average age of our patients was 55 years (38 - 82 years). Only one patient in our series had a history of contra-lateral breast SCCs. A family history of breast cancer was noted in two patients (14%). In 71.4% of the cases, the patients had consulted for appearance of a mammary mass, one had consulted for inflammatory breast and only one as part of a control balance (CCnsp of the contra-lateral breast). Both breasts were equally affected. The tumor was unique in 13 patients (92%). A bifocal tumor was found in a patient with pure MC. The average clinical tumor size was 40 mm (20 - 80 mm). Mucinous carcinoma of the breast was pure in 8 cases, mixed in 6 cases. Table 1 summarizes a comparison of clinical presentation of pure CM versus mixed CM.
Mammograms showed multifocal lesions in 3 cases. Pure CMs had an average size of 26 mm versus 29 mm for mixed CM without significant difference (p = 0.17). They were 83% oval-shaped with microlobulated contours in half of the cases, while mixed CMs had an irregular shape in 57% of cases with indistinct contours in 85% of cases, as shown in Figure 1. The difference was significant (p = 0.01/p = 0.04). Microcalcifications were present in both subtypes (p = 0.13).
On ultrasound, pure CMs had a homogeneous hypoechogenic oval mass appearance with microlobulated contours enhancing ultrasound. Mixed CMs had an irregular shape of non-geometric contours and heterogeneous hypoechogenic appearance with posterior attenuation of ultrasound without any notable difference as shown in Figure 2 (p = 0.06).
Our patients were classified according to the 1986 TNM classification. Three
Table 1. Clinical presentation of pure CM versus mixed CM.
Figure 1. Mammography snapshot external oblique ((a), (b)): (a) Mass with microlobulated contours by location (arrows); (b) Retro-polar mass with indistinct contours (thick arrows).
Figure 2. Mammary echography ((a), (b)): (a) Oval-shaped hematogenous mass (star); (b) Non-geometric hypoechoic mass (arrow).
(21%) patients were classified as T1. Stage T2 represented a rate of (28%). The T3 stage was found in three patients (14%) and the 1/3 of the patients (35%) were classified T4. The radical surgery was performed on 13 patients. It consisted of a mastectomy with axillary dissection. Conservative surgery was performed in a case of pure MC. Pure MCs were classified as SBR I and SBR II in 50% of cases respectively. Mixed MCs were rated SBR I, SBR II and SBR III in equal ways. The average number of lymph nodes sampled was 12 (range 1 to 27). Ganglionic invasion was noted in 5 patients. Hormonal receptors were positive in 12 patients. HER2 was sought in all our patients. It was over-expressed at (3 +) in a single patient who had a pure MC and not expressed in the rest of the patients. Table 2 illustrates a comparison of histological presentation between pure CM versus mixed CM.
Chemotherapy was performed in 9 patients. This consisted of adjuvant chemotherapy in two patients (22%) and neo-adjuvant chemotherapy in seven patients (78%). Radiotherapy was performed in 10 patients (71.4%). Hormone therapy was prescribed in 11 patients. Two patients developed metastases during the course of the progress. Overall survival at 5 years was 100% and survival recurrence free rate was 72% at 5 years. Overall survival for pure mucinous carcinoma is 74% while survival for mixed carcinoma is 59%.
Table 2. Histological presentation of pure CM versus mixed CM.
Note that the pure variant has a better survival compared to the mixed variant (p = 0.045).
MC is a particular histological form of breast carcinoma, first described in 1826 by Geschickter  . This is a rare entity that preferentially affects women over sixty years of age. It accounts for 7% of all malignant breast tumors after age 75 and 1% before age 35   . The average age at diagnosis is 65 years (48 to 82 years)    . In the literature, there were few studies that examined the influence of conventional breast cancer risk factors on MC. In terms of risk factors, no significant difference was found between MC, tubular carcinoma, and breast ITC  . Self-examination of a breast nodule was the most common telltale sign    , and this was the case in our series. Bilateral character is rarely described in the literature, while multi-focality remains exceptional     . Both mammography and ultrasound findings correlate with the histological type of the tumor and the extracellular mucin volume    . For pure MC it is a nodular mass circumscribed and multi-lobed with well-defined contours. The well-defined limits are correlated with the volume of extracellular mucin, so that they can be mistaken for benign formations   . The mammographic aspect of mixed MC is nevertheless more suspect. It appears as a mass of irregular contours with ill-defined boundaries, or even speculated with the glandular tissue. The MRI aspect of the PMC is characteristic. Indeed, the signal intensity in T1 sequence after gadolinium injection varies according to the tumor concentration in extracellular mucin. In T2 sequence, the lesion is characterized by intense and homogenous contrast enhancement and dynamic analysis by a fine increase of the signal and then plateau, unlike CCI and mixed mucinous carcinoma which presents a heterogeneous enhancement with a Wash out appearance. However, the problem arises with phyllode tumors, medullary carcinomas, cysts, and abscesses that exhibit comparable behavior  -  . The interest of the extension assessment is not recommended by the majority of authors for the early stages    . However, the authors always recommend the extension assessment in patients with stage III breast cancer   . In the literature, the majority of patients (92% - 97%) were classified as T1 or T2 according to the TNM classification     . The breast MC is subdivided into two subtypes: Pure MC: characterized by the presence of tumor tissue completely surrounded by abundant extracellular mucus, with no infiltrating ductal component or when it is present, it does not exceed 10% of the overall tumor volume. The transition between mucus and surrounding connective tissue is abrupt. Mixed MC: characterized by the presence, in addition to the mucinous component, of an infiltrating ductal component. This constitutes more than 10% of the total tumor volume; the transition between extracellular mucus and adjacent carcinomatous tissue is progressive   . The ER and positive PR rates reported in the literature in pure breast MC are 77% and 50%, respectively, versus 74% and 52% for mixed MC  . In our series, hormone receptors were positive in 12 patients (85%). For the surgical treatment, a radical treatment (a mastectomy with axillary dissection) is advisable on the other hand, there are consensually agreed indications concerning the conservative treatment such as unifocal invasive tumors, of size less than or equal to 3 cm. distance from the nipple and without skin invasion    . Axillary dissection is an integral part of surgical treatment whether radical or conservative. The therapeutic value of cleaning is controversial. The ganglionic invasion in the pure MC of the breast is rare, it varies from 0 to 21% against 45% to 64% for the mixed MC and is relayed to the tumor size   . Regarding chemotherapy, its indications in the breast MC are restricted     . There is no consensus on protocols and number of courses. The data from the literature have identified some peculiarities specific to MC. The chemotherapy protocols are modeled on those used for other types of breast cancer. Trastuzumab has a place in the management of these tumors, in fact the efficacy of trastuzumab has been observed as an adjuvant, alone or in combination with concomitant or sequential chemotherapy, in patients with or without lymph node involvement. It improves overall survival, recurrence-free survival, and event time     . Overall survival at 5 years ranges from 80% to 100%     ; at age 10 it ranges from 72.8% to 100%     . Most authors have found better survival for MC compared with other infiltrating cancers. Recurrence-free survival at 5 years ranges from 81% to 91.6%    ; at 10 years ranges from 75.3% to 90%    . For prognostic factors, the young age tumor size greater than 30 mm, a tumor of high cellularity and ganglion invasion are factors of poor prognosis     . However, no conclusions could be drawn about the impact of HER2 on prognosis    .
Mucinous Carcinoma of the breast is a rare variety, occurring mainly after menopause. It is important to distinguish between the two pure and mixed forms, because the therapeutic attitude and the prognosis depend on it. The pure form remains a favorable prognosis, whereas that of the mixed form matches that of infiltrating ductal carcinomas.
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