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Neuroendocrine ductal carcinoma of the breast
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A 60-year-old white female presented to her primary care physician with a left breast lump, which she noticed while taking a shower. Her last mammogram was 5 years ago. Her past medical history was significant for bipolar disorder, hypothyroidism, stroke and seizure disorder.
Her medications included Ambien CR (Sanofi-Avantis), levothyroxine, paroxetine, lorazepam, and Motrin (McNeil) as needed. She is an active cigarette smoker who has smoked one-half a pack per day for 37 years. There was no family history of breast, ovarian or uterine cancers.
Physical examination revealed a 1 cm mass in the left upper outer quadrant of the breast. Her mammogram did not reveal any mass, but ultrasound showed an irregular hypoechoic nodule in the subareolar region over the area of palpable concern. Biopsy of that suspicious area showed invasive ductal carcinoma.
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She underwent lumpectomy and sentinel lymph node biopsy. Her sentinel lymph node was positive and, hence, she had an axillary dissection. Pathology showed an invasive neuroendocrine ductal carcinoma of the breast and low grade in situ ductal carcinoma.
Immunohistochemical staining for chromogranin and synaptophysin were positive in virtually 100% of tumor cells, supporting the diagnosis of neuroendocrine ductal carcinoma. The sentinel lymph node showed metastatic carcinoma involving the lymph node. It also showed neuroendocrine-like features and measured 3.3 mm in greatest extent and was seen only in frozen block.
The tumor size was 1.4cm × 1.2 cm. Axillary dissection of eight lymph nodes did not identify any metastatic tumor.
Final pathologic staging was pT1cN1a, ER/PR positive, HER2/neu negative (1+). The case was discussed in tumor board and the tumor was sent for oncotype testing. The recurrence score was low at 11, with 5-year recurrence risk of 7%. These results were discussed with the patient and it was decided not to administer adjuvant chemotherapy. Currently, the patient is receiving radiation to her left breast.
Case Discussion
Approximately 90% of breast cancers are either invasive ductal or lobular carcinomas. The less common pathologies include mucinous (2.4%), tubular (1.5%) and medullary (1.2%) type and have a favorable outcome. The other 5% comprise other rare subtypes such as apocrine, histiocytoid, inflammatory, invasive micropapillary, papillary, metaplastic, neuroendocrine, oncocytic, carcinoma with Paget’s disease and undifferentiated large cell variety.
Features of neuroendocrine small cell carcinoma similar to that of the lung has been reported in other sites such as larynx, trachea, breast, stomach, bladder, prostate and other tissues. Primary neuroendocrine carcinoma of the breast must be differentiated from small cell carcinoma of the lung or other neuroendocrine cancers with metastasis to the breast. The average age at diagnosis of these tumors is 60.
Low-grade breast carcinoma expressing predominant neuroendocrine differentiation are seen in less than 5% of breast cancers, depending on the definition. Histologically, they show the same features as neuroendocrine carcinomas with growth in solid sheets or insular pattern with small nuclei, scant cytoplasm, evenly distributed chromatin, no comedo necrosis and less frequent mitoses. They show immunoreactivity to neuroendocrine markers such as chromogranin and synaptophysin.
In general, 50% of tumor cells should exhibit neuroendocrine features to be classified as neuroendocrine ductal carcinoma. They are frequently associated with ductal carcinoma in situ. Estrogen receptor and progesterone receptor are important markers for directing therapy and determining prognosis. Steroid receptors are frequently positive (ER 80% and PR 35%)
Neuroendocrine carcinomas can be divided into low grade, high grade or unspecified. Low-grade neuroendocrine carcinoma have low-grade cytologic features with round, regular to mildly irregular nuclei up to two to three times the size of a red blood cells with no comedo necrosis. Neuroendocrine carcinoma not specified lack the specific features of the other two types. High-grade neuroendocrine carcinoma demonstrate features of small cell carcinoma.
Low grade tumors have good prognosis. These tumors are usually HER-2-negative. High grade tumors were considered aggressive with poor prognosis is some early reports. But the largest reported case series of nine patients with primary neuroendocrine carcinoma shows a variable prognosis. In this report by Shin and colleagues, early stage patients had a good prognosis indicating that the stage of the disease is a more important prognostic factor.
In conclusion, primary low-grade neuroendocrine tumors of the breast are uncommon neoplasms of the breast. They must be differentiated from metastatic tumors from other sites. Low-grade tumors are usually estrogen receptor-positive and HER-2 neu receptor-negative. The stage of the diagnosis may be a more important factor with regard to prognosis in low-grade neuroendocrine tumors than with high-grade small cell neuroendocrine tumors.
Ramya Varadarajan, MD, is a Medical Oncology Fellow at Roswell Park Cancer Institute, Buffalo, N.Y., and is a member of the HemOnc Today Editorial Board. Disclosure: Dr. Varadarajan reports no relevant financial disclosures.
For more information:
- Samli B. Arch Pathol Lab Med 2000; 124:296–8.
- Shin SJ. Am J Surg Pathol 2000; 24:1231-1239.