Large cell neuroendocrine carcinoma of the breast
A breast neoplasm is classified as ‘neuroendocrine’ if a majority of the cells involved are of neuroendocrine origin.
Naturally, these cells are part of the overall neuroendocrine system. This system basically refers to the way in which the brain communicates with certain cells in order to produce hormones.
Hormones are ‘regulatory chemicals’ with many different functions. They stimulate the growth of some cells and restrict the growth of others.
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A “large cell” neuroendocrine breast carcinoma is a particular type of cancer whereby new cells are simply larger than normal.
Nonetheless, it is a distinctive form of breast cancer, with a unique histology and somewhat predictable behavior in terms of cancer aggressiveness and metastasis.
Based on the clinical evidence, it appears that large cell neuroendocrine breast carcinomas tend to occur in older women, often around 70 years of age.
Large cell neuroendocrine carcinoma can occur in various areas of the body. One would naturally expect a greater frequency of this type of tumor in body regions that are highly dependent upon hormonal activity.
The lung and the mid-gut region, for example, are highly prone to neuroendocrine carcinomas.
There are some neuroendocrine cells in breast tissue, but not that many, and as such the diagnosis of primary neuroendocrine breast carcinoma is extremely rare.
The incidence of breast neuroendocrine breast carcinoma is very small. Some studies place the frequency in the range of less than 0.3%, but others show a general frequency of about 2% to 5% of all breast cancers.
In any event, large cell neuroendocrine breast carcinomas would be a subset of these very infrequent neuroendocrine breast carcinomas. In actual fact, up to 97% of all neuroendocrine tumors occur in the gastrointestinal or respiratory system.
Large cell neuroendocrine carcinoma of the breast could result from metastasis from cancer elsewhere in the body
Of course, there is a distinct possibility that the development of large cell neuroendocrine breast carcinoma is a result of metastasis from a primary site somewhere else in the body.
So a conclusive diagnosis of ‘primary‘ large cell neuroendocrine breast carcinoma is only made if all non-mammary sites are quite confidently excluded.
There is also a very small possibility that large cell neuroendocrine carcinoma can be found at an ‘in situ‘ stage.
Histological features of large cell neuroendocrine carcinoma of the breast
One of the ways in which a diagnosis of neuroendocrine breast carcinoma is confirmed, (including for large cell) is through the histological evidence of neuroendocrine markers.
As a rule of thumb, the neuroendocrine markers should be present in at least 50% of the cell population in order to have a ‘neuroendocrine‘ differentiation.
Some of the most common ‘positive‘ neuroendocrine markers are chromogranin, synaptophysin, and NSE (Neuron-specific enolase, although NSE is relatively non-specific).
Nests of tumor cells, separated by collagen bundles
Upon histological evaluation, large cell neuroendocrine breast carcinomas tend to show small nests of large tumor cells with faint, granular cytoplasm or vesicular cytoplasm, often separated by dense collagen bundles.
Nuclei tend to be polygonal and prominent. Large cell neuroendocrine breast carcinoma cells are also frequently arranged in a kind of ‘pallisading‘ pattern. Mitoses is quite a common feature, and evidence of necrosis is to be expected.
Imaging features common to large cell neuroendocrine breast cancers
On mammography, a large cell neuroendocrine breast tumor will likely appear as a high density round mass, possibly with a spiculated or lobulated margin.
On ultrasound, one will typically find a gently lobulated, heterogeneous, round or oval low-echoic mass.
The margin will likely be slightly irregular, and there will probably be some posterior acoustical shadowing.
Sometimes a CT scan is used to find large cell neuroendocrine breast carcinomas, in which case it will tend to appear as a well-defined, highly-enhancing mass.
Outlook and treatment for women with large cell neuroendocrine breast carcinoma
The outlook for women with large cell neuroendocrine breast cancer is far from conclusive.
Large cell neuroendocrine breast carcinomas tend at times to mimic the behavior of small cell neuroendocrine breast tumors, which are quite aggressive.
Metastasis is common, and local recurrence is also an unfortunate feature of this disease.
The prognosis for patients with large cell neuroendocrine breast carcinoma is significantly worse than for patients with ‘large cell carcinoma‘ (without a neuroendocrine differentiation).
But due to the very small number of cases of large cell neuroendocrine breast carcinoma, it is difficult to make any generalizations.
Treatment is often by surgical excision with chemotherapy
Treatment of a large cell neuroendocrine breast cancer tumor is usually by local surgical excision, with adjuvant chemotherapy.
Anthracyclines have been shown to be somewhat effective against neuroendocrine differentiated breast cancers.
Some patients are also treated with postoperative radiation therapy. And, surgical removal of any metastatic lesions will generally lead to a durable disease-free status.
But generally speaking, large cell neuroendocrine breast carcinomas show limited responsiveness to treatment and have a relatively poor prognosis when compared to other types of breast cancer.
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