Giant Intracystic Papillary Carcinoma of the Breast Report of a Case and Review of the Literature

Introduction

Intracystic papillary carcinoma (IPC) is a distinctive variant of a papillary ductal neoplasm confined to a dilated cystic space and surrounded by a fibrous capsule.^1–4 This rare mammary tumor comprises between 0.5% and 2% of all breast cancer specimens and typically appears as a discrete solitary mass in the central region of the breast in a postmenopausal woman.^5–8 Parallel hemorrhagic nipple discharge may be noted.^4,8 Subsequent mammography depicts a round, oval, or circumscribed mass due to the appearance of the dilated duct rather than the tumor within it. ⁹

Because of its relevant growth pattern and indolent clinical behavior, IPC is conventionally regarded as a variant of an intraductal papillary carcinoma with the absence of myoepithelial cells, both within the papillae as well as around the periphery of the lesion.^2,5,6 This lack of a myoepithelial layer resulted in the hypothesis that IPC might present as a relatively less-aggressive lesion with expansile invasion rather than being a category of ductal carcinoma in situ (DCIS).^1,4 Differential diagnosis on mammography includes colloid or medullary carcinoma, invasive ductal carcinoma, hematoma, benign cyst, or adenofibroma. ⁹ There have been several cases that indicated a slow evolution of the mass, verifying the perception that IPC is associated with favorable clinical outcome.^10,11 Axillary lymph-node metastases and markers related to invasion have been documented in some patients.^5,12,13 Due to the rarity of the tumor and variability noted in treatment strategies, only a few surveys have assessed the significance of lymph-node status and the role of adjuvant treatment.

This article presents the case of a female patient with a giant IPC. Relevant literature is reviewed briefly. Clinical features, histogenesis, and morphologic and immunochemical findings are discussed, while the role of current diagnostic and therapeutic management of this neoplasm is emphasized.

Case

A 65-year-old-woman was admitted to the ATTIKON University Hospital, in Chaidari, Athens, Greece, for the management of a palpable mass of the left breast. The lesion was discovered by the patient by palpation 4 years prior and was growing gradually over the months. Comorbidities were absent, while her family history was irrelevant. On clinical examination, the entire left breast was noted to be replaced by an extremely large, irregularly shaped, relatively mobile lesion. The mass was almost fixed to surrounding tissues, including skin and pectoral muscle (Fig. 1A). Regional lymphadenopathy was not detected on physical examination. Due to the size of the lesion, mammography could not be performed. Computed tomography (CT) revealed a giant, mainly cystic, cavity with various intracystic components characterized by irregular shapes and rough borders (Fig. 1B). Subsequent fine-needle aspiration (FNA) produced results that were not indicative of malignancy. Due to the size of the tumor and disease duration, the patient underwent a left modified radical mastectomy (MRM; Fig. 2)

OPEN IN VIEWER

FIG. 1.

(A) Clinical figure of an extremely large, irregularly shaped, relatively mobile intracystic papillary carcinoma of the breast (B) Computed tomography findings of an intracystic papillary carcinoma of the breast indicative of a giant mainly cystic cavity with various intracystic components characterized by irregular shape and rough borders.

OPEN IN VIEWER

FIG. 2.

Surgical specimen (A) and bioptical sample (B) from a modified radical mastectomy for a giant intracystic papillary carcinoma of the breast.

Macroscopically, the cut surface of the mass seemed elastic and soft in consistency with mixed solid and lobulated features, and had a primarily white and less brown appearance. Maximal cyst diameter was estimated at 20 cm. Tumor dimensions were ∼7 × 4 × 2 cm, and wall thickness was up to 0.6 cm. The skin was not infiltrated by the mass. A tissue sample was fixed in 10% formalin. Paraffin sections were prepared and stained with hematoxylin and eosin. Additional immunostaining with anti-p63 antibody, E-carderin, estrogen receptor (ER), progesterone receptor (PR), HER-2/neu oncogene (Cerb-B2), anti-p53 antibody and anti-ki67 antibody was accomplished.

Results

Pathology examination revealed an encapsulated mass with expansive, multiloculated growth, and filled with hemorrhagic elements, fibrin, and necrotic debris. The tumor, which was mostly solid and focally of a micropapillary type, presented with low-grade nuclear malignancy and moderate pleomorphism in the carcinomatous structure. Within the cystic wall, an extensive granulomatous reaction—with the presence of epithelial cells, histiocytes, and polynuclear giant cells, along with cholesterol crystals—was apparent. Concomitant vascular invasion or metastasis to 19 removed lymph nodes was not noted. A hormonal receptor assay in the carcinomatous component included ER (70%) and PR activity (10%). Nucleus p53 stain as well as Ki-67 proved to be weakly positive (1% and 5%, respectively). C-erbB2 assessment was not clear (with a score of 2+).

Additional immunohistochemical staining showed a positive reaction in the epithelial element for cytokeratin p63, which explained the absence of an intact myoepithelial layer. E-cadherin staining was also positive. The final histopathologic diagnosis was an IPC. The patient underwent systemic screening for distant metastasis, which was negative. Secondary hematogenous infiltrations were not defined. She had an uneventful recovery and was administered a hormone therapy.

Discussion

Breast IPC is extremely rare and accounts of <2% of all retrospectively diagnosed breast cancers.^7,8 Histologically, this kind of tumor is encysted within a dilated duct with arborization of the fibrovascular stroma and contains nodules of papillary carcinoma (PC) surrounded by a thick fibrous capsule. Hence, many investigators favor the term encapsulated papillary carcinoma.^14,15 Recent information within the literature was indicative of IPC being a variant of DCIS, with some lesions actually being referred to as low-risk invasive tumors. ¹⁶ These cases are often clinically considered as breast cysts, for which the tumors can be easily mistaken. Although less common, axillary lymph or distant metastases have been noted even without frank invasion. ⁵ As most studies published in the past were case reports, there is a lack of guidelines for this unusual but distinct subtype of PC. Nevertheless, current data represent further evidence of the theory that IPC runs a very slow course and has an excellent prognosis. Associated cumulative 5-year survival rate is estimated as being between 81.8% and 100%.^4,17

IPC usually affects postmenopausal women (median age: 67–68 years), but there have been reports of IPC in younger women or men.^18–21 It clinically presents as a painless breast lump, with or without hemorrhagic nipple discharge, which grows bigger slowly.^22,23 On mammography, the tumor appears as a round calcific opacity that is well-circumscribed. Therefore this tumor should be distinguished from other types of breast tumors, including colloid or medullary carcinoma, invasive ductal carcinoma, hematoma, benign cyst, or adenofibroma. Ultrasonography (US) usually shows a cystic mass with septa and a notable intramural blood flow. ⁶ Subsequent cytologic diagnosis with FNA could be mistakenly reassuring, as the physician may aspirate only fluid. ²⁴ Diagnosis should only be established with a US-guided core biopsy, which may be more accurate due to aspiration of tumor cells. ²⁵

The current patient was a 65-year-old woman. Her tumor grew for several months and, eventually, it developed unusually enormous dimensions and, thus, mammography could not be performed. CT indicated the presence of a cystic cavity with solid components. FNA results were inconclusive.

There are genomic lesions considered to be associated with IPC; these lesions resemble those connected with DCIS. One focal change within 1q seems to be important. There are two localized genes—NTRK1 [neutrotophic tyrosine kinase receptor type 1] and PRCC [papillary renal cell carcinoma]—that are also connected with papillary carcinomas of the kidney and thyroid gland. This genomic change is not detected in DCIS. ² Usually, IPCs are strongly ER- and PR-positive and HER2/neu-negative.^4,5,20 Immunohistochemical staining shows positivity of the epithelial part for specific membrane antigens (epithelial membrane antigen), cytokeratins, DF3, and p63. Further investigation of the myoepithelial cell layer reveals expression of smooth-muscle actin, p63, S-100, CD10, SMM-HC, 34βE12, collagen IV, maspin, and calponin when the tumor is deprived of an invasive pattern.^26,27 In the current case, immunohistochemical examination showed strongly positive reactions for ER and E-cadherin and weakly positive expression of PR, p53 and Ki67 staining. Locally, an absence of p63 detection has been assessed.

Treatment strategies for IPC resemble those for typical breast cancer, including MRM with axillary dissection. ²⁸ However, as a consequence of the infrequency of IPC tumor, specific guidelines considering its management are lacking. In accordance with recent recommendations, IPC is to be treated as an invasive ductal carcinoma, with wide local excision and adjuvant radiotherapy or mastectomy.^4,5,29 Axillary lymph nodes are not frequently involved, as according to studies, nodal involvement have been between 0% and 11%. Therefore, some investigators have judged that lymph-node evaluation is not necessary. ³⁰ Adjuvant radiotherapy is still controversial with respect to IPC cases due to the lack of effect it seems to have in local recurrences.^1,9 Although data interpretation has been that IPC is a hormonal-positive and a HER-2-negative tumor, the option of endocrine therapy has not been clarified fully as needed, and there are questions regarding its outcome.^{4, 9,16} Recent studies have suggested that endocrine therapy should be given only in cases when surgery cannot be performed, when there is a recurrence, or when there is a high-risk morphology tumor. ⁶ In the current case, a MRM was performed and the patient's postoperative course was uneventful. Additional tumor metastases along the lymphogenous route were absent, and administration of tamoxifen was warranted.

Conclusions

Because of its relevant growth pattern and indolent clinical behavior, IPC is conventionally regarded as a variant of intraductal papillary carcinoma with an absence of myoepithelial cells. Several cases have indicated a slow evolution of this type of mass, verifying the perception that IPC is associated with a favorable clinical outcome. Differential diagnoses include colloid or medullary carcinoma, invasive ductal carcinoma, hematoma, benign cyst, or adenofibroma. Axillary lymph-node metastases and markers related to invasion have been documented.