Intracystic breast carcinoma. An important differential diagnosis in postmenopausal patients presenting with a rapidly growing breast cyst. Management and literature review

Abstract

Intracystic breast carcinoma is a rare clinical entity accounting for 0.5–2% of all breast cancers. It represents a distinctive clinical form rather a histological subtype of breast cancer and can either be in situ or invasive tumor. We herein describe a rare case of intracystic breast carcinoma arising from the wall of a cyst in a postmenopausal patient, who presented with a rapidly growing complex breast cyst. Diagnostic evaluation and management of the patient are discussed along with a review of the literature. Complex breast cysts may represent a diagnostic and therapeutic challenge. An underlying malignancy has been reported in 21–31% of the cases. Preoperative diagnosis is challenging. Complex breast cysts with thick wall, thick inner septations, and intracystic solid components should undergo histological evaluation in order to rule out an underlying malignancy. The cytological analysis may be inconclusive. Ultrasound-guided biopsy is the diagnostic modality of choice. The correlation of clinical features, with imaging and histopathological findings is very important for the optimal treatment. In cases of discordance, a complete surgical excision is necessary with careful assessment of the extent of the disease and appropriate treatment.

Introduction

Intracystic breast carcinoma (IBC), is a rare clinical entity accounting for 0.5–2% of all breast cancers [1,5,9,10,17,25,27] and 5–7% of all breast malignancies in men [26]. It represents a distinctive clinical form rather a histological subtype of breast cancer and can be either invasive or in situ tumor. In most cases, IBCs are of papillary or medullary subtype whereas infiltrative ductal carcinomas are uncommon [1]. Clinical situations that can lead to the development of IBC may include: arising of a tumor from the wall of a cyst, invasion of a carcinoma into a preexisting cyst, cystic degeneration of a rapidly growing poorly differentiated breast carcinoma or very rarely sarcoma, and dilatation of a duct due to obstruction from an encysted papillary tumor  [15,18,26]. Complex breast cysts have been associated with the presence of an underlying malignancy in 21–31% of the cases [2,7,16,21,27]. We herein present a rare case of intracystic breast carcinoma in a premenopausal patient who presented with a rapidly growing giant breast cyst and was diagnosed with a ductal invasive breast cancer originating from the cyst wall. Diagnostic evaluation and management of the patient are discussed along with a review of the literature on complex breast cysts and underlying malignancy.

Case presentation

An 89 -year- old woman presented with a four-month history of a rapidly growing left breast mass which had been doubled in size over the previous 2 months. Her past medical history was significant for coronary artery disease and atrial fibrillation but she had no family history of breast or ovarian cancer.

Clinical examination revealed a large well defined and partially cystic left breast mass measuring 12 × 8  cm (Fig. 1). There was no axillary, cervical or supraclavicular lymphadenopathy. The mammogram was not diagnostic and classified as ACR 4, but ultrasound revealed a predominantly cystic complex mass with solid component projecting into the cystic lumen and thick internal septa (Fig. 2). Computed tomography scan of the chest, that was performed as a part of the staging evaluation, showed a large left breast complex cystic mass measuring 12 × 8  cm (Fig. 3). Aspiration of the cyst yielded 150 ml of bloodstained fluid and cytological analysis showed malignant cells. Staging investigations revealed no distant metastases. Magnetic resonance imaging was not used in this setting.

Due to the severity of heart disease, a resection of the large complex cyst was performed. Gross examination the hemorrhagic cyst, measuring 12 cm in diameter, revealed a whitish mass clearly originating from the cyst wall without evidence of invasion from the adjacent breast parenchyma. The histological examination revealed a grade III invasive ductal carcinoma measuring 5.2 × 3.5 × 2.3  cm . The tumor originated from the cyst wall and the neoplastic elements were projecting into the cyst cavity lining a small area of its surface with the presence of micropapillary formations and apical hobnail nuclei. (Fig. 4). A high mitotic rate ≥20 mitotic figures per 10 high power fields was noted. At the periphery of the tumor, a small area of cribriform and micropapillary ductal carcinoma in situ was detected along with a few lymph vessel tumor emboli. Surgical margins were free of tumor cells. On immunohistochemical analysis, the tumor cells were stained negative for estrogen and progesterone receptors and c-erbB2. Sentinel node biopsy was not considered because of the patient’s age and severity of heart disease. In addition, clinical examination and ultrasonography of the axilla were unremarkable. The patient received adjuvant radiotherapy. She remained well for 4 years after surgery but was then lost to follow-up.

Discussion

Intracystic breast cancer (IBC) originating from the wall of a cyst is very rare clinical entity accounting for less than 1.2% of all breast cancers [1,9,10,14,17]. It most commonly affects postmenopausal women in their fifth and sixth decades of life [15,17,26], but extremely rare cases have also been reported in men [6,14,15,19,24]. There is no general consensus regarding the pathogenesis of the tumor and regional lymphatic spread [14].

The most common presentation is that of a relatively large palpable breast lump [14,18,26]. Patients with IBC present at an older age than patients with other forms of breast cancer. In the study by Kitada et al. [14], the mean age of patients with IBC was 73.3 years compared to 53.6 years of patients with other forms of breast cancer. In addition, van den Wildenberg [28], reported that the 17 patients with IBC were ten years older compared to the other breast cancer patients.

There are no pathognomonic imaging findings of IBC thus making preoperative diagnosis difficult [14,24]. On mammography, the tumor may appear as a high-density mass with well circumscribed or partially circumscribed margins depending on the extension of the tumor to the adjacent breast parenchyma [26,28]. Microcalcifications are uncommon [28]. On ultrasonography, the tumor may appear as a well defined predominantly cystic, heterogeneous hypoechoic mass with projections arising from the cyst wall [18]. On gross examination, the tumor appears as a mural lesion protruding from the cyst wall filling a variable volume of the cyst [26].

Cysts are one of the most common types of breast mass in women attending breast clinics [20] and may occur in up to 10% of women during their lifetime [24]. They are most commonly encountered between 35 and 50 years of age, especially during the perimenopausal years [16,17]. Conversely, breast cysts are rare in older women with only 5% of them occurring in women over 59 years of age [24]. Breast cysts are divided into simple cysts that are classified as ACR2 according to the BI-RADS lexicon, complicated cysts classified as ACR3 and complex cysts classified as ACR 4 [2]. In 25% of the cases, the cysts are simple, consisting of smooth thin wall and require no intervention. Only 0.2–0.8% of all breast cysts are found to harbor an intracystic tumor [16].

Complex cystic masses are defined as those with cystic and solid components with a thick wall (>0.5 mm) and thick internal septa (>0.5 mm), an intracystic mass or solid mass with cystic areas [4]. They are detected in 5% of women undergoing ultrasound examination [11,21].

Yao et al. [29], reviewed 79 complex cysts and classified them into four types according to their ultrasonographic features; type I, masses with a thick wall, thick internal septa, or both; type II, intracystic masses with one or more discrete solid mural lesions within a cyst; type III, masses containing mixed cystic and solid components and are at least 50% cystic portion in a mass; and type IV, predominantly (at least 50%) solid masses with eccentric or central cystic foci. The authors found that the incidence of malignancy was higher among III and IV lesions. Factors that have been associated with higher probability of malignancy include lesion diameter >2 cm, ill-defined lesion, resistance index higher of 0.7, suspicious mammographic findings and axillary node abnormalities [12,29].

The most common benign etiologies for a complex cystic mass include hematoma, abscess, fat necrosis, phyllodes tumor and papilloma. A malignant etiology has been reported in 23–31% of the complex cystic masses and mainly includes encapsulated papillary carcinoma, solid papillary carcinoma, poorly differentiated ductal invasive carcinoma, mucinous carcinoma, medullary carcinoma, metaplastic carcinoma, breast sarcoma and very rarely metastases [2].

Encapsulated or intracystic papillary carcinoma (EPC) is a rare breast malignancy, representing 0.6% to 1% of breast cancers [2]. On gross examination, the tumor is friable or lumpy inside a cyst whereas microscopically, it consists of one or more papillary carcinoma nodules surrounded by a thick capsule [2]. EPC has been associated with an indolent clinical course and excellent prognosis and can be treated with adequate local therapy [22]. However, a distinct proportion of EPCs may show high cytonuclear grade features. Rakha et al. [23], reported that 3% of EPCs are associated with high-grade features. These tumors tend to be of larger size, are often hormone receptor negative and are more often associated with stromal invasion. Patients with high-grade EPCs should be treated similarly to patients with conventional invasive carcinomas [23].

Complex cystic breast masses may represent a diagnostic challenge for the interventional radiologist [2]. There is no consensus on the optimal management of incidentally found complex cysts [11]. On the mammogram, complex cysts may appear as lesions with indistinct margins and higher density than surrounding breast parenchyma [4]. Ultrasonography findings include thick wall, thick internal septa an intracystic mass and in most cases posterior acoustic enhancement [2,11]. They are classified as BI-RADS 4 lesions requiring histological verification by percutaneous biopsy [2].

Magnetic resonance imaging (MRI) findings of complex breast cystic masses may include enhancement of the solid component and fluid signal characteristics of the cystic portion. Washout enhancement and irregular wall are indicators of malignancy [4]. Popli et al. [20] studied 50 patients with complex breast cysts with advanced MRI techniques such as dynamic imaging, diffusion-weighted sequences, and MR spectroscopy. The authors found that heterogeneous contrast enhancement, type III kinetic curve, diffusion restriction and tall choline peak were strong predictors of malignancy.

Various diagnostic approaches have been reported for complex breast cysts including fine needle aspiration (FNA) biopsy, core needle biopsy, vacuum assisted percutaneous biopsy and total excision [7,16]. The choice of the biopsy technique must be individualized for each patient and each tumor on the basis of clinical and radiographic features [2].

Ultrasound-guided percutaneous biopsy is the diagnostic modality of choice of a complex breast cyst, but this may be challenging [7]. Aspiration of the fluid may result in more difficult detection of the solid component [4,7,8]. Ultrasonography-guided core needle biopsy from the solid component should be performed immediately after aspiration [2,6,7,16]. Factors such as internal echostructure and presence of vascularity are useful in differentiating a benign from a malignant intracystic lesion [7,8]. For predominantly solid lesions a 14-gauge needle should be used, while for predominantly cystic lesions a vacuum-assisted macro biopsy system with 8–10 gauge needle is preferable [2,8,27]. Placement of a post-biopsy marker should be considered for future interventions [2,7,8]. Criteria associated with higher incidence of malignancy are age, the character of fluid and residual mass after aspiration [17].

The size of a complex cyst is a good predictor of malignancy. Jales et al. [13], studied 48 complex cystic masses and found that all lesions with a maximum diameter less than 3 cm were benign, whereas all lesions larger than 3 cm were malignant. In another study, Berg et al. [3], studied 79 cases of complex breast cysts and found that the presence of a thick wall, thick inner septations, intracystic masses and predominantly solid masses with eccentric foci were associated with higher incidence of malignancy. Another study by Chang et al. [5] including 175 symptomatic breast lesions, reported that 50% of the cases with cystic masses with a thick wall/septa or nodules, and complex solid and cystic masses were malignant. The authors suggested that these lesions require a biopsy even if they have well-defined margins.

Cytological analysis of the aspirated fluid from complex cystic breast masses may not be diagnostic [4,7–10,15,18,25] and the method is associated with false negative results in 22–37.5% of the cases [15,28]. Main reasons include sparse cellularity, necrotic debris, presence of blood and degenerative cell changes [15]. The aspirated fluid is usually hemorrhagic whereas cytology class IV/V findings have been reported in 63–65% of the cases [14].

High levels of the carcinoembryonic antigen of the aspirated cystic fluid may indicate the presence of malignancy [28]. Matsuo et al. [18], reported that in their patient the CEA level in the aspirated fluid was 5.5 times higher than the serum CEA level. Many authors have however suggested that aspirated fluid should be discarded due to low diagnostic value [16]. Hemorrhagic aspiration, however, should always be sent for cytological analysis [2]. The characteristics of the fluid may indicate a suspicious lesion, as a bloodstained fluid is yielded in the majority of patients with cancer [17,25].

The correlation of clinical features, with imaging and histopathological findings, is essential [4,7,15] for the optimal treatment. In cases with discordance, a complete surgical excision of the lesion should be performed [1,2,9,14,27]. A thorough investigation is mandatory to rule out an extramural invasion of the tumor. Kitada et al. [14], reported a 66.7% incidence of extramural invasion among six cases of IBC. Patients with extramural invasion are at increased risk for lymph metastases and therefore apart from the local therapy of the primary tumor, a sentinel node biopsy should also be considered for staging and definitive treatment [14].

Patients with IBC originating from the wall of the cyst have a more favorable prognosis [1,14,17,26] than patients with other forms of breast carcinoma. Patients with poorly differentiated carcinomas with cystic degeneration have a poor prognosis, whereas in patients with intracystic papillary carcinoma the prognosis is excellent [5,17,25]. Invasion beyond the cyst wall has been associated with an up to 30% incidence of lymph node metastases [25].

Conclusions

Intracystic breast carcinoma arising from the wall of a cyst is a rare form of breast cancer. It should always be considered in the differential diagnosis in postmenopausal women presenting with a rapidly growing complex breast cyst. Preoperative diagnosis is challenging. Complex breast cysts with thick wall, thick inner septations, and intracystic solid components should undergo histological evaluation. The cytological analysis may be inconclusive. Ultrasound-guided biopsy is the diagnostic modality of choice. The correlation of clinical features, with imaging and histopathological findings, is essential for the optimal treatment. In cases of discordance, a complete surgical excision is necessary with careful evaluation of the extent of the disease and appropriate treatment.