Cystic hypersecretory ductal carcinoma (CHDC): a rare distinctive variant of ductal carcinoma

Abstract

Cystic hypersecretory ductal carcinoma (CHDC) is a rare distinctive variant of ductal carcinoma that behaves in a low-grade fashion. This rare form of breast malignancy has only been reported a handful of times in the surgical literature. This article outlines the clinical presentation, workup and management of a 43-year-old woman who presented with a bilobed cystic mass of the right breast diagnosed as CHDC.

Background

In this article, we outline the clinical presentation, workup and management of a case of cystic hypersecretory ductal carcinoma (CHDC)—a rare form of breast malignancy.

Case presentation

A 43-year-old woman presented with a bilobed cystic mass in the 9 o’clock position of the right breast near the areola. The lesion had grown from 24×17 mm to 33×25 in 18 months by ultrasound imaging. She had no family history of breast cancer, was nulliparous, premenopausal, had a menarche age of 13 and she was otherwise healthy.

On examination, there was a large firm mass in the retroareolar position of her A-cup breast. The mass was not fixed to the underlying pectoralis major, but it was close to the skin. Axillary examination was unremarkable as was the left breast and axillary examination.

A needle core biopsy was performed which showed a low grade invasive ductal carcinoma with papillary features and intermediate grade Ductal-carcinoma in-situ (DCIS). The disease was strongly Estrogen-receptor (ER) positive, strongly Progesterone-receptor (PR) positive, and Human epidermal growth factor receptor 2 (Her2) negative.

The patient underwent a right total mastectomy with sentinel lymph node biopsy. She chose not to undergo immediate breast reconstruction.

Histopathology of the tumour showed cystically dilated ducts within bland fibrous stroma (figure 1). Cysts were lined by mild to moderately atypical cuboidal to columnar cells with rare mitoses. Many cysts contained abundant oeosinophilic colloid-like material with a minority containing acellular mucin. There was extensive DCIS with papillary and cribriform morphologies.

Figure 1.

H&E staining of cystic hypersecretory ductal carcinoma: (A) ×1.25 magnification (B) ×10 magnification.

Immunohistochemical stains including p63, SMM/p63 and PANK/p63 confirmed the loss of myoepithelial cells around the cystic components (figure 2). Features were consistent with invasive cystic hypersecretory carcinoma with T2 (24 mm), N0 (0/4 sentinel lymph nodes), M0, grade 1 disease. Prognostic markers were ER positive, PR positive and Her2/neu negative. The specimen was negative for lymphovascular invasion and had clear surgical margins less than 1 mm.

Figure 2.

Immunohistochemistry staining of cystic hypersecretory ductal carcinoma: (A) p63 at ×2.5 magnification (B) SMM/p63 at ×5 magnification (C) panK/p63 at ×5 magnification (D) panK/p63 at ×10 magnification.

Outcome and follow-up

The patient recovered well from surgery with no complications. She was recommended 10 years of tamoxifen. To date, she remains on tamoxifen and shows no evidence of recurrence with routine surveillance.

Discussion

CHDC was first described in 1984 by Rosen and Scott.¹ It is a rare distinctive variant of ductal carcinoma that behaves in a low-grade fashion, but it has the potential for invasive growth and development of distant metastasis. It is thought to evolve from cystic hypersecretory hyperplasia (CHH), which is a benign breast lesion that is characterised by cystically dilated ducts of various sizes lined with bland columnar epithelium. Histologically, CHDC resembles CHH but its epithelium shows atypical cells and usually contains micropapillary DCIS.²

Invasive disease has been reported in approximately 20% of CHDC cases. Invasive disease tends to show poorly differentiated disease with a solid growth pattern and no secretory activity.² In the English literature, only a few cases of invasive CHDC have been reported so far.^{3 4} Previous case reports have highlighted the heterogeneous nature of these specimens and the need for extensive sampling to ensure invasive disease is not overlooked.⁴ The literature reports a total of five CDHC cases diagnosed with lymph node metastasis.^{3 4} And in one case, a patient developed invasive lobular carcinoma of the contralateral breast 10 years after mastectomy.² Guerry et al observed 29 patients with CHDC for up to 23 years.⁵ Twenty‐five of these were well or died of other causes during follow-up. Of the other four patients, one died 9 months after being diagnosed with systemic metastases, and the other three remained disease‐free. This series demonstrates the low‐grade clinical course of CHDC.

The usual clinical presentation of CHDC is a painful palpable lump.² Up to 10% of reported cases also presented with nipple discharge.^{4 6} There are no known genetic mutations or syndrome associations, and radiological findings vary but often show microcalcifications.²

The characteristic gross appearance demonstrates 1–10 cm lesions with the presence of dilated ducts or cysts containing a thyroid/colloid-like viscid, gelatinous substance.^{1 2} Histologically, these lesions show cystically dilated ducts containing homogeneous eosinophilic secretion the resemble thyroid follicles. The secretions often retract from the surrounding epithelium. The epithelial lining of these cysts range from flattened cells to cuboidal or columnar cells.⁷ The characteristic feature that differentiates CHH from CHDC is the presence of neoplastic epithelial proliferation producing areas of micropapillary intraductal carcinoma.⁵ The classic bridging pattern frequently seen in other forms of micropapillary DCIS in uncommon in CHDC. Extravasation of cyst material into the stroma is not considered as invasion. Invasive foci have solid nests that are poorly differentiated and lack cyst formation or secretion.^{2 3}

Positive reactions for Periodic acid–Schiff, carcinoembryonic antigen, alpha-lactalbumin have been observed in the cyst contents. Cyst contents are consistently negative for thyroglobulin. CHDC tumours are usually ER positive, PR positive and Her-2/neu positive.²

The differential diagnosis for CHDC includes mucin-producing colloid carcinoma of the breast, juvenile papillomatosis and juvenile secretory carcinoma, and metastatic follicular thyroid carcinoma. However, cystic hypersecretory carcinoma has pathognomonic gross and microscopic features which differentiates the disease from the above-mentioned pathology.

CHDC is differentiated from mucin-producing colloid carcinoma of the breast by the presence of basophilic mucin which frequently contains clusters of malignant cells⁸

CHDC is differentiated from Juvenile Papillomatosis by its pattern of duct papillomatosis, papillary hyperplasia, sclerosing adenosis and epithelial atypia.⁹ Juvenile secretory carcinoma has only focal areas of cyst formation and the cells are characterised by prominent vacuoles in the cytoplasm.⁹ The presentation of both these juvenile entities in a younger age group also helps in the differential diagnosis.

Metastatic follicular thyroid carcinoma may need immunohistochemical diagnosis for the presence of thyroglobulin in thyroid carcinoma to differentiate it from CHDC.¹⁰

Our case highlights another example of this rare breast entity. We can use this case along with the others reported to help better understand the prognosis and biological behaviour of CHDC. A better understanding will help clarify the best way to classify and treat these rare lesions.

Learning points.

• Cystic hypersecretory ductal carcinoma (CHDC) is a rare form of ductal carcinoma.

• It is low grade, but invasive disease is reported in approximately 20% of CHDC cases and it has the potential to metastasise.

• CHDC be treated like invasive ductal carcinoma.

Ethics statements

Patient consent for publication

Obtained.