Discussion:
The primary invasive breast carcinoma with neuroendocrine
differentiation is a very rare type of breast tumor. Most commonly the
neuroendocrine tumors are found in the gastrointestinal tract, pancreas,
and bronchopulmonary system but rarely found in the breast (6). These
tumors do not form the specific histopathological category of breast
carcinoma but there are groups of breast carcinoma like ductal, lobular
carcinoma, mucinous, and solid papillary carcinomas which can produce
ectopic hormonal substances (7). There are three categories of
neuroendocrine breast tumors as mentioned by the WHO in their
4th revised edition.
- Well-differentiated,
- Poorly differentiated neuroendocrine/ small cell carcinoma, and
- Invasive breast carcinoma with neuroendocrine differentiation.
There is no specific radiological or clinical sign to diagnose the
neuroendocrine tumor. Histopathological examination is the only means of
making a definitive diagnosis. Grossly, the tumor is usually
yellowish-colored with a firm consistency and multilobulated. (8) In
this case, we found the tumor to be a gray-white lobulated structure.
Histologically, the tumor usually shows similar features as
neuroendocrine tumors of the gastrointestinal tract with nuclear
palisading, cellular monotony, loss of cell cohesion, pesudorossete
formation, and abundant eosinophilic cytoplasm and nuclei with stippled
chromatin(9). Since the microscopic features are inconsistently present,
IHC markers like chromatin A or B, synaptophysin, neurospecific enolase
(NSE), CD-56, Ki-67, Leu 7(CD-57), INSM-1 are necessary for the
diagnosis [12]. INSM and CD-56 were focally positive, and Ki-67 is
around 40% with nuclear positivity.
This tumor should be differentiated from metastatic neuroendocrine
tumors from extramammary sites. They may show features similar to the
other primary tumors of the breast like lobular carcinoma and invasive
ductal carcinoma in situ (2). Some markers like CK-7 and caudal-type
homeobox-2(CD X-2) are useful to differentiate from GI neuroendocrine
tumors. Usually, the neuroendocrine breast tumors are positive for CK-7
and negative for CDX-2 whereas in gastrointestinal neuroendocrine tumors
CK-7 is negative and CDX-2 is positive (10).
Invasive breast carcinoma with neuroendocrine features is treated like
other invasive carcinoma breast carcinomas. The primary treatment option
is surgery depending upon the stage and location of the tumor. (1) The
combination of mastectomy, axillary lymph node dissection, and
metastasectomy is generally performed for surgical treatment. Like other
breast carcinomas, they are treated by chemotherapy and radiotherapy.
Immunohistochemistry helps to determine the type of adjuvant therapy
(8).
Prognosis in the patient with breast carcinoma with neuroendocrine
features generally depends upon the factors like age of the patient,
axillary lymph node involvement, clinical-stage, hormonal receptors.
(11) Neuroendocrine differentiation was said to be an independent
adverse prognostic factor according to the multivariant analysis based
on (Surveillance, Epidemiology, and End Results Program) SEER database.
(5) In a retrospective comparative study by Zang et al., the breast
carcinoma with neuroendocrine features showed a poorer survival rate,
lower recurrence-free survival rate, and a high rate of distant
metastasis. (12) Some literature reported that these tumors have a
similar prognosis with invasive breast carcinoma when the clinical stage
and grade of the tumors are compared. (13, 14)