Cytodiagnosis of papillary carcinoma of the breast: Report of a case with histological correlation.

Papillary lesions of the breast pose diagnostic challenges on aspiration cytology due to overlapping features of benign and malignant entities. Accurate cytologic diagnosis of papillary breast carcinoma cannot usually be made pre-operatively. We present the case of an adult female who underwent fine-needle aspiration (FNA) of a left breast lump. FNA smears were highly cellular showing cohesive clusters, complex papillary fragments and few singly dispersed intact cells. The tumor cells had hyperchromatic nuclei, prominent nucleoli and mild nuclear pleomorphism. A cytologic impression of papillary lesion, possibly malignant (in view of high cellularity, complex papillae and single intact cells) was rendered. The lesion proved to be a papillary carcinoma with microscopic foci of stromal invasion on histologic examination. Papillary carcinoma, an uncommon subtype of breast carcinoma, should be considered while evaluating a papillary lesion with complex branching papillae containing delicate fibrovascular cores and singly lying intact atypical cells.

Introduction

Papillary lesions of the breast include benign (papilloma) as well as malignant (papillary carcinoma) entities. Both the ends of the spectrum are characterized by the presence of fibrovascular cores lined by epithelial proliferation with varying degrees of atypia.[1] Though a definite diagnosis of the nature of tumor is possible on an excision biopsy, the distinction is not easy on aspiration cytology. This is due to the overlapping of cytologic features between benign and malignant as well as other entities containing papillary component.[2]

Earlier authors have attempted to define the differentiating cytologic features between benign and malignant papillary breast lesions.[23] Features like high cellularity, complex branching papillary fragments and single atypical intact cells have been suggested to point toward the malignant nature of the tumor. However, these features have not been found to be restricted to the malignant tumors.[2] Hence, a definite diagnosis of papillary breast carcinoma on aspiration cytology is usually not possible.

We describe the cytologic and histopathologic features of a case of papillary carcinoma of the breast in an adult female.

Case Report

A 50-year-old female presented with history of painless lump in the left breast. The lump was detected 6 months ago and had been increasing in size. There was no associated nipple discharge or changes in the overlying skin. No significant medical or surgical history could be elicited.

Local examination revealed a well-circumscribed lump in the lower outer quadrant of left breast. The lump measured 4 cm in diameter and was firm and mobile. The overlying skin and underlying muscle were free from the lump. Axillary lymphadenopathy was not present. Mammography of the left breast showed a well-defined mass in the left breast with BIRADS score of 4 (suspicious for malignancy). Considering the age and mammographic findings, a possibility off carcinoma of left breast was considered and fine-needle aspiration (FNA) performed.

FNA smears, stained by May-Grünwald-Giemsa, showed high cellularity composed of cohesive clusters and few singly dispersed cells. Numerous papillary fragments with finger-like branching were also seen [Figure 1a,b]. Some of the papillary fragments were three dimensional with delicate fibrovascular cores. The cells were round to oval ith moderate amount of basophilic cytoplasm, hyperchromatic nuclei with prominent nucleoli [Figure 1c]. There was mild nuclear pleomorphism. Background showed few singly-lying intact tumor cells [Figure 1d] along with cystic macrophages and apocrine cells. A cytologic impression of papillary lesion, suspicious for malignancy was rendered.

Figure 1

(a) Aspirate showing papillary fragments of tumor (Giemsa, ×40). (b) Smooth margins of the fragment (Giemsa, ×100). (c) The tumor cells have moderate cytoplasm, hyperchromatic nuclei and small nucleoli (Giemsa, ×400). (d) Few singly-lying intact tumor cells seen in the background (Giemsa, ×400)

The patient underwent left simple mastectomy. On gross examination, a grey-white tumor, 4 × 3.5 × 2 cm was seen in the lower outer quadrant. The tumor was well circumscribed, unencapsulated and firm in consistency. No hemorrhage or necrosis was seen. Histologic examination showed features of a papillary carcinoma with microscopic foci of stromal invasion [Figure 2a,b]. The resected margins were not involved by the tumor.

Figure 2

(a) Histologic photomicrograph of the resected tumor showing a papillary tumor with complex papillae (H and E, ×100). (b) Focus of stromal invasion (H and E, ×200)

The patient has been recurrence-free after 1 year of follow up.

Discussion

Papillary lesions of the breast encompass a complete spectrum including benign lesions (papilloma) to noninvasive (intraductal papillary carcinoma) to invasive papillary carcinoma. These lesions are characterized by epithelial proliferation overlying a fibrovascular core with the presence or absence of a myoepithelial cell layer.[1] Papillary carcinoma involves male breast more frequently than women. Hence, it is suggested that papillary lesions would be encountered more frequently in FNA of male breast.[1]

Accurate diagnosis of papillary lesions by FNA is fraught with complications largely because of the overlapping cytologic features of benign and malignant lesions as also between true papillary lesions and other entities with papillary component.[2] The latter include fibrocystic change, fibroadenomas, invasive ductal carcinoma and phyllodes tumor.[2] The cytologic features of fibroadenoma, fibrocystic change and papilloma of the breast may be similar. However, the presence of numerous oval bare nuclei in the background, isolated stromal fragments (not associated with epithelial fragments) without fibrovascular cores and absence of columnar epithelial cells favor a cytological diagnosis of fibroadenoma.[2] Fibrocystic change, on the other hand, shows lesser cellularity than papillomas. Three-dimensional branched epithelial cell sheets may be seen, however fibrovascular cores are not usually present. Benign columnar cells, if present in fibrocystic change, are less in quantity than papillomas.[2]

Among the malignant lesions, ductal carcinoma-in-situ (papillary, micropapillary and cribriform), invasive duct carcinoma, intraductal papillary carcinoma and invasive papillary carcinoma need to be differentiated. Papillary and cribriform DCIS are low nuclear grade lesions that may or may not be associated with an invasive component. Invasive ductal carcinoma with focal papillary areas usually shows highly cellular smears with complex crowded epithelial cell sheets displaying nuclear atypia and irregularities. There is usually the absence of bare nuclei in the background. Micropapillary carcinoma, an uncommon histologic type, lacks true fibrovascular cores and shows angulated papillary and tubuloalveolar pattern of cellular aggregates with single atypical cells.[4] Smears from intracystic papillary carcinoma are highly cellular composed predominantly of discohesive epithelial cells with minimal to mild cytological atypia. Aspiration of cyst fluid may dilute the cellularity, leading to errors in diagnosis.[5]

The National Cancer Institute (NCI)-sponsored conference for formulating guidelines for breast FNA placed the papillary lesions in the indeterminate category since the criteria for distinction of benign and malignant lesions on cytology are not well established.[6] There have been studies to delineate the distinctive cytologic features of benign and malignant papillary lesions of the breast.[23] It has been suggested from these and other studies that malignant papillary lesions have high cellularity, complex branching papillary fragments, single intact atypical cells, absence of bland columnar cells and lack of foamy or hemosiderin-laden macrophages in the background. Though these features are said to be diagnostic of papillary carcinoma, single intact cells with moderate nuclear atypia may be seen in infarcted papilloma or cases of atypical papillomas.[2] The atypical papillomas, in addition, show high cellularity with complex papillae and single atypical cells, making the distinction from carcinoma difficult.[1] In addition, the differentiation of noninvasive intraductal papillary carcinoma from frankly invasive papillary carcinoma is problematic due to identical cytologic features.[7] Though the cytological features of papillary carcinoma are well described, distinction from papilloma may not be possible in some cases on cytology alone and histopathology offers the accurate diagnosis. In the present case, a papillary pattern was noted on FNA smears. A malignant lesion was considered due to the high cellularity with 3D papillary fragments, delicate fibrovascular cores and single intact tumor cells. The lesion was confirmed as an invasive papillary carcinoma on histopathologic examination.

In conclusion, papillary carcinoma is an uncommon histologic subtype of breast carcinoma. Cytologic diagnosis of the lesion is difficult due to overlap with benign entity and other mimics. Hence, cytopathologists need to be aware of the features helpful in distinction between benign and malignant papillary lesions. Also, all lesions seen as papillary on FNA should be excised completely to allow accurate classification.