Diagnosis of Intracystic Papillary Carcinoma of the Breast by Preoperative Core Needle Biopsy: A Case Report Open Access

The patient was a 42-year-old Asian Japanese woman whose general condition was good. Her medical history was unremarkable, but a review of her family history revealed that her grandmother had gastric cancer. She found a tumor mass in the left inner breast 10 weeks before her initial visit to the Takahashi Breast and Gastroenterology Clinic, Osaka, Japan.

Mammography showed several mostly homogeneous tumor shadows with smooth margins in the left breast region. No calcification was observed (Fig. 1a, 1b). Ultrasonography showed cysts of 15.5 × 21.0 × 15.6 mm and 11.2 × 11.7 × 10.1 mm, accompanied by posterior echo enhancement and a papillary tumor of 15 × 10 × 10 mm, which protruded into the inner cavity. The tumors were accompanied by a lateral shadow and enhancement of posterior echo (Fig. 2a). Color Doppler of ultrasonography showed a surrounding vascular pattern (Fig. 2b).

The CNB needle was seen as a linear diagonal shadow from the right side to just before the tumor (Fig. 2c). The CNB needle was securely inserted into the solid tumor without being disturbed in the cyst (Fig. 2d).

CNB of the left tumor resulted in the diagnosis of intraductal (intracystic) carcinoma. Long cylindrical neoplastic cells, with elliptical cores stained with chromatin, showed papillary proliferation accompanied by interstitium and fine fibers in the cystic cavity. The core was atypical and mildly polymorphic. The resected segment showed no interstitial or vascular infiltration (Fig. 3a, 3b).

The patient was diagnosed with left breast cancer and underwent partial resection of the left breast. The histopathologic findings of the resected specimen were DCIS, intracystic carcinoma, estrogen receptor 80%, progesterone receptor 80%, MIB-1 (antibody) labeling index ≤2%, nuclear grade 1, and human epidermal growth factor receptor (EGFR)-2 score of 0.

ICPC is a breast cancer that protrudes and proliferates into the inner cavity of a cyst in a papillary form, and which reportedly accounts for 0.5% to 1% of all breast cancer cases.^1–3  A common symptom is recognition of a gradually enlarging breast tumor,⁴  and bloody nipple discharge is found in 22% to 34% of all cases.^5–7  It is generally classified as DCIS and rarely accompanied by infiltration. According to the latest version of the general rules for clinical and pathologic recording of breast cancer, it is defined as a state where a lesion is localized in a cyst, presenting as noninfiltrating intracystic carcinoma. However, there are reports of cases with infiltration outside the cyst, broad intraductal extension,⁸  or simultaneous liver metastasis.⁹  Differentiation from benign intracystic papilloma is considered difficult.

The patient's age is an important factor in predicting whether intracystic papilloma is benign or malignant. The mean age of patients with ICPC is 69.5 years, older than that of patients with ordinary breast cancer,⁶  whereas the mean age of patients with benign intracystic papilloma is 40.7 to 47 years.¹⁰  In this case, the age of the patient was 42 years, which was younger than that of mean ICPC. According to reports, breast cancer was found in 81% of patients 60 years or older who were diagnosed with an intracystic tumor.^2,10–15  In addition, mean diameters of tumors including cysts are reportedly 2.6 cm for ICPC and 1.9 cm for intracystic papilloma.¹³  Larger tumor diameters generally indicate malignancy rather than benignity. However, the diagnostic value of tumor size for differentiation between benignity and malignancy is considered low.^13,14  Ultrasonography often shows irregular margins for both benign and malignant intracystic tumors, and therefore, is ineffective for differential diagnosis.^14,15 

For diagnosis, it is essential to securely perform fine needle aspiration (FNA) or CNB of the intracystic solid part under ultrasound guidance. Moreover, many ICPCs are low grade and the determination of benignity or malignancy by cellular atypia alone is considered difficult. The rate of accurate diagnosis using FNA cytology is low, while diagnosis by CNB is believed to be more effective than cytology.¹⁶  CNB of the solid part of a cyst for preoperative diagnosis is difficult and has a sensitivity of 60%, whereas reportedly, preoperative diagnosis was not possible in 40% of ICPC patients.¹⁰  Therefore, biopsy by resection should be proactively considered in patients who cannot be diagnosed by FNA or CNB.^16–18  Papillary lesions of the breast pathology remain a challenging subject in diagnostic breast pathology, and it is still problematic about whether CNB is sufficiently accurate in the diagnosis of benign pathology to avoid surgical biopsy. Radiologic imaging, while it is helpful, cannot reliably distinguish between benign and potentially malignant papillary lesions revealed by CNB. All the more mammography is not reliable for distinction between benign and atypical papillary lesions. It is initially reported that all papillary lesions revealed on CNB required follow-up surgical excision to exclude DCIS or invasive carcinoma.^19,20  However, more recent data have suggested that benign papillary lesions can be diagnosed comfortably by means of CNB using particularly larger core needle to enable more samples and only ADH revealed by CNB need surgical excision²¹  because a significant proportion of these lesions contain DCIS or invasive carcinoma. By contrast, frozen section obtained from surgical excision is less reliable than permanent section, and it is often difficult to distinguish DCIS from ductal hyperplasia on frozen section because the tissue structure is not completely preserved. In the diagnosis of surgical margins on frozen section, it is reported that a diagnostic accuracy is 86%, sensitivity is 83%, and specificity is 86%.²² 

Cytokeratins (CKs) are generally thought to be the very important markers of epithelial differentiation because the specific composition of CKs in epithelial cells reflects not only cell type but also differentiation status. The use of CKs in the distinction of benign epithelial proliferations from DCIS has been previously investigated. It is reported that immunohistochemical expression of the 2 cytokeratins which are CK5/CK6 and CK14 can aid in evaluating papillary breast lesions to differentiate the benign papilloma from the malignant in situ papillary carcinoma.²³  Further study of CKs for papillary breast lesions might be expected well.

As for lymph node, generally DCIS cannot give axillary lymph node metastasis by definition. Therefore, axillary dissection is not indicated. Moreover, the role of the SLNB in the management of DCIS has not yet been established. SLNB should be considered in the case of DCIS where there exists a strong doubt of invasion at the definitive histology, such as large solid tumors or diffuse or pluricentric microcalcifications undergoing mastectomy. If the SLN is micrometastatic, complete axillary lymph node dissection is not essential.²⁴  Consequently, it is preferable to diagnose DCIS for ICPC preoperatively on the ground that not only axillary lymph node dissection but also SLNB might be avoidable.

According to the literature about the whole ICPC including DCIS and invasive carcinoma, the mean percentages for nuclear atypia in ICPC were 26% for grade 1, 51% for grade 2, and 23% for grade 3 tumors.²⁵  Furthermore, research suggests that ICPC is highly hormone-sensitive; 90% of patients with ICPC were shown to be estrogen receptor–positive, 100% were negative for human EGFR-2, and 10% were negative for these markers.²⁶ 

Although bloody intracystic fluid is seen in 88.9% of ICPC cases,²⁷  bloody fluid is also observed in 76% of intracystic papillomas,¹²  making differential diagnosis difficult. With regard to prognosis, the 5-year relative survival rate is reportedly 97.3% and the 10-year relative survival rate is 95.6%, with little difference between the noninfiltrating and infiltrating types.⁶  However, tumors with diameters of ≥4 cm have metastatic potential.²⁸  The frequency of lymph node metastases of ICPC ranges from 0% to 25%, which is lower than in ordinary breast cancer.^14,15  According to previous reports, infiltrating cancer is not rare. Intraductal progression of a tumor (≥2 cm) from the cystic wall in the mammary duct has been reported.¹²  Importantly, infiltrating cancer can be treated with the same modalities as those used to treat DCIS.

Intracystic papillary tumor of the breast is difficult to differentiate malignancy or benignity by imaging, so pathologic examination is necessary to diagnose it.

It is very important that DCIS for intracystic papillary tumor of the breast is preoperatively diagnosed because not only axillary lymph node dissection but also SLNB might be omitted.

FNA cytology is not effective to get the pathological diagnosis of DCIS for intracystic papillary tumor of the breast and also initial surgical excision prior to FNA and CNB is not recommended proactively.

This report suggests that the initial choice of CNB might be better recommended than both FNA and surgical resection to get the diagnosis of DCIS for ICPC on the first way of diagnosis.

A case of noninfiltrating ICPC was diagnosed based on a preoperative CNB, thus avoiding not only a biopsy by surgical resection and but also axillary lymph node dissection and SLNB.

Conflict of interest statement: Keiichi Takahashi who is the author declares that he has no conflict of interest. Keiichi Takahashi declares he has no source of support in the form of grants, equipment, drugs, or all of these.