INTRODUCTION
Papillary lesions of the breast encompass a heterogeneous group of diseases which are characterized by the presence of epithelial proliferation supported by fibrovascular cores. These may be benign or malignant. Papillary carcinoma of the breast is a rare malignant tumor, constituting 1%–2% of all breast carcinomas in women.[1] While intraductal papillomas are benign lesions that are characterized by finger-like fibrovascular cores covered by an epithelial and myoepithelial cell layer, papillary carcinomas include intraductal papillary carcinoma which is a malignant noninvasive neoplastic epithelial proliferation, encapsulated papillary carcinoma (with or without invasion), solid papillary carcinoma (in situ or with invasion), and invasive papillary carcinoma.[2] It is important to differentiate between invasive and noninvasive types of papillary carcinomas because of the difference in prognosis.
Papillary carcinomas are defined by the complete or almost complete absence of myoepithelial cells in the papillary fronds of the intraductal proliferations.[3] Myoepithelial cells are frequently absent in encapsulated papillary carcinoma and solid papillary carcinoma (80% of the cases) and always absent in invasive papillary carcinoma.[4] In encapsulated papillary carcinoma, myoepithelial cells are not usually seen in the interstitium of the vascular pedicles and among the tumor cells, although myoepithelial markers such as p 63, calponin and CD10 sometimes confirm a small number of myoepithelial cells on the tumor margin.[5] Thus, the pathologic characterization of papillary lesions of the breast is based primarily on morphologic considerations. Histopathological examination with immunohistochemistry as an adjunct is essential in correctly characterizing these lesions. Excisional biopsy is also necessary because invasive papillary carcinoma is more difficult to diagnose than common breast cancer preoperatively; fine needle aspiration and core needle biopsy are not sufficient many a times.
In a 3-year study of breast cancer cases which came for histopathological examination in a tertiary care center in Northeast India, we came across 6 cases of papillary carcinoma breast. Due to the rarity of this type of cancer and the limited studies available, we have presented our experience of papillary carcinoma breast in our institute to add to the existing body of literature.
MATERIALS AND METHODS
After going through 3 years of archival data, the cases of papillary carcinoma breast were identified. The clinical records of the patients, the complaints. Presentation, demographic features, gross findings of the cases were studied. The hematoxylin and eosin-stained sections were retrieved, and the microscopic features were reassessed based on current knowledge. The results of immunohistochemical study were also noted.
RESULTS
A total of 6 cases of papillary cancer breast were noted during this period. Of these, five were in female patients, and one was a male patient. The median age of the patients was 45.5 years. Of the five female patients, three were menopausal, while two were premenopausal. The youngest was 26 years old [Table 1]. In five cases, the tumors were seen in the left breast with only one case having right breast mass.
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Table 1: Clinico demographic profile of the patients
Grossly, the size of the tumors ranged from 2 cm × 2 cm × 1.5 cm to as large as 6 cm × 10 cm × 4 cm. The mass was cystic in three of the cases. Three of the cases had positive axillary nodes [Table 2].
Table 2: Pathological characteristics of the tumors
Case 1
Patient was a 55-year-female who presented with breast lump of 6 months duration. Lump was rapidly progressive in size, with mild pain radiating to the axilla. History of weight loss was positive. The patient had attained menopause 10 years back. There was no significant medical or family history. On gross examination, a modified radical mastectomy (MRM) specimen was received with a growth of size 3 cm × 3 cm × 2 cm in upper outer quadrant of the left breast.
On microscopic examination, invasive carcinoma with papillary architecture comprising of fibrovascular cores lined by malignant epithelial cells was seen. A diagnosis of invasive papillary carcinoma of breast (Modified-Bloom-Richardson Grade 3) was made [Figure 1].
Figure 1: Invasive papillary carcinoma (×10, H and E)
Immunohistochemistry was positive for Estrogen receptor (ER), progesterone receptor (PR), and negative for Her2 neu.
Case 2
The patient was a 60-year-female with lump in the left breast for 9 months and left axilla for 1 month. Growth was insidious in onset with mild pain in the later months. There was no history of nipple discharge. The patient complained of loss of appetite and weight loss. There was no other significant history.
On gross examination, an MRM specimen measuring 10 cm × 6 cm × 4 cm with an ill-defined thickened area involving the whole of the excised breast was noted.
Microscopy revealed the presence of invasive papillary carcinoma breast with ductal carcinoma in situ (DCIS). Three axillary nodes showed metastatic disease. Immunohistochemistry was negative for ER, PR while Her2 neu was 3+.
Case 3
A 40-year-old female presented with lump in the left breast for 1 year. The swelling was insidious in onset, gradually progressive, painless. Occasional nipple discharge was noted. History of weight loss was present. There was no significant medical or family history of disease. Menstruation was normal. History of oral contraceptive use was present. MRM was performed, and a mass of size 3 cm × 2 cm × 2 cm was noted beneath the nipple.
Microscopic examination revealed the presence of papillary structures with a fibrovascular core lined by neoplastic cells with mild pleomorphism and high nucleocytoplasmic ratio with occasional nucleoli. A diagnosis of invasive papillary carcinoma breast was given (modified bloom Richardson Grade 3). The tumor was negative for ER, PR, and Her2neu. Two axillary nodes showed metastatic carcinoma.
Case 4
This was a 44-year-old male with lump in the left breast for 3 months. There was no associated pain; however, nipple discharge was present along with a history of weight loss. No other significant history was present. Ultrasonography revealed a cystic septic SOL below left nipple measuring 3.5 cm × 3.5 cm. Fine-needle aspiration of the lump revealed cells in papillary pattern and in cords. Individual cells showed mild nuclear atypia with moderate amount of cytoplasm in a background of macrophages and cyst fluid. Gross examination of the surgically resected specimen revealed a cyst measuring 2 cm × 2 cm × 1.5 cm with some solid areas showing irregular grayish-white mass from the cyst wall. Microscopic examination showed the presence of papillary structure with a fibrovascular core lined by neoplastic cells which were pleomorphic with high nucleocytoplasmic ratio and prominent nucleoli in some of the cells. A diagnosis of intracystic papillary carcinoma or encapsulated papillary carcinoma was made [Figure 2a and b].
Figure 2: (a) Intracystic papillary carcinoma of breast (×10, H and E). (b) Higher magnification. Fibrovascular cores lined by neoplastic cells (×40, H and E)
The tumor cells were positive for ER, PR and negative for Her2neu.
Case 5
A 47-year-old woman presented with lump in the left breast of 2 years’ duration. The lump was painless, gradually increasing in size. The patient was menopausal; there was no significant medical or family history. MRM was done. On gross examination, a growth measuring 4.5 cm × 3 cm × 2.5 cm located 1 cm from the lateral margin was seen. On cut section, the growth was solid to cystic.
Microscopy revealed multiple circumscribed cellular masses comprised of closely apposed, expanded, and solidified rounded duct-like structures in a contiguous pattern embedded in dense fibrous stroma. Fine fibrovascular cores could be delineated. The myoepithelial cell layer was absent. Other areas showed invasive ductal carcinoma with DCIS. Thus a diagnosis of solid papillary carcinoma with invasive duct carcinoma and DCIS was made [Figure 3]. Immunohistochemistry was not done in this patient. Four axillary nodes showed metastatic disease.
Figure 3: Solid variant of papillary carcinoma. Papillary architecture can be appreciated in some areas (×10, H and E)
Case 6
A 26-year-old female presented with swelling in the right breast for 2 years. The swelling was insidious in onset, gradually progressive with no associated pain. There was no significant medical history or family history of malignancy. The patient was having regular menstruation. The patient underwent MRM. On gross examination, a growth of size 3 cm × 8 cm × 8 cm was noted 1 cm above the nipple with involvement of the skin. Cut section showed solid and cystic areas with areas of hemorrhage and necrosis.
On microscopic examination, a fibrous capsule was evident on low power. Tumor cells with fibrovascular cores lined by monomorphic population of neoplastic cells with intermediate-grade nuclei were seen. Myoepithelial cells were absent. However, areas of frank invasion beyond the encapsulated tumor were seen. A diagnosis of encapsulated papillary carcinoma with invasion was made [Figure 4]. The tumor was Modified Bloom Richardson Grade 2. All the harvested lymph nodes were negative.
Figure 4: Encapsulated papillary carcinoma of breast. Other areas of the same tumor showed invasion into the surrounding stroma (×40, H and E)
Immunohistochemistry could not be done in this tumor.
DISCUSSION
The term “papillary carcinoma” has been used in the literature to describe a heterogeneous group of malignant neoplasms which include both noninvasive and invasive carcinomas.[2] It can be present as an isolated lesion or associated with conventional nonpapillary in situ or invasive carcinoma. Invasive papillary carcinoma has a low incidence as compared to infiltrating duct carcinoma, and prognosis is better as compared to other malignant entities of the breast.[3]
We came across three cases of invasive papillary carcinoma, one case of encapsulated papillary carcinoma without invasion, one case of encapsulated papillary carcinoma with invasion, and a solid papillary carcinoma. Interestingly, all our cases except one occurred in the left breast.
True invasive papillary carcinomas do not have any specific or known clinical characteristics. On the other hand, intraductal papillary carcinoma present with clear or bloodstained nipple discharge or as a mass when located peripherally[6] while solid papillary carcinoma presents as a mammographic abnormality or a palpable mass and sometimes with bloody nipple discharge.[7] Encapsulated papillary carcinoma presents as a circumscribed round mass with or without nipple discharge.[8] In our study, nipple discharge was seen in 2 of the 6 cases. All cases complained of lump in the breast. While breast cancer is usually said to be painless, two of our patients complained of mild pain.
Diagnosis of papillary carcinoma is difficult because of mixed findings in mammography and cytology. Mammography usually shows a relatively well-circumscribed and homogeneous mass, though margins may be obscured. The sensitivity of mammography is low at 67%, while its specificity is <10% in differentiating benign papillary lesions from malignancy.[9] On ultrasonography, the lesion may show an indistinct border or microlobulation, which might suggest that it is malignancy. Differentiation between benign and malignant papillary lesions may be difficult on fine-needle aspiration cytology (FNAC) also because FNAC targets the center of the lesion while invasion occurs at the periphery. Therefore histopathological examination is essential for correct diagnosis with immunohistochemistry as an adjunct to see the hormone receptor status and to look for the presence or absence of myoepithelial cells. A study by Zheng, et al.[10] summarized the clinicopathological characteristics of invasive papillary carcinoma breast and found that this histological type was associated with a lower grade, a smaller tumor size, reduced lymph node involvement, earlier stages, higher hormone expression positivity, and lower HER2 amplification rates than were IDCs. Four of our cases presented with small tumors, and the tumor which was largest in size was Her2neu positive. In another case which presented with a large growth, hormone receptor status could not be done. One tumor was triple negative while two others were ER, PR positive, and Her2neu negative. Only three out of six cases had positive axillary nodes. Both cases of encapsulated papillary carcinoma (one without invasion and one with invasion) were node-negative.
In another study of six cases of papillary carcinoma in Northeastern India, 4 cases were ER, PR positive, one was positive for ER, PR and Her2 Neu and one was triple negative.[11] In a study of Encysted papillary carcinoma breast by Spyrou et al., 18% of patients had evidence of metastasis in the axillary nodes, and vast majority (96%) were ER positive.[12]
Several studies have reported a greater incidence of papillary carcinomas in males among the different tumour subtypes in the breast,[13] which is mainly related to encapsulated papillary carcinoma and solid papillary carcinoma with or without the associated stromal invasive disease. One of our cases was a tumor in male breast which showed a cystic lesion, and a diagnosis of intracystic papillary carcinoma was made.
Prognosis of papillary carcinoma is usually excellent with disease-free 10-year survival rates being reported as 91% and overall survival at 10 years as 100% in one study.[14] All our cases are currently doing well postsurgery.
CONCLUSION
Papillary carcinoma is a rare variant of breast tumor. As this lesion has a better prognosis and biomarker profile as compared to Infiltrating duct carcinoma breast, it is important to be aware of the different subtypes and diagnostic pitfalls of this tumor to correctly diagnose it. A histopathological examination with immunohistochemistry is important to correctly identify the lesion.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient (s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initial s will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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