Neuroendocrine tumors are tumors composed of neuroendocrine cells that are present throughout the nervous and endocrine or hormonal systems. These include carcinoid tumor, pancreatic endocrine tumor, paraganglioma, pheochromocytoma, medullary thyroid carcinoma and poorly differentiated small cell neuroendocrine carcinoma. As neuroendocrine cells are distributed widely throughout the body, tumors of these cells can occur at many sites, but they usually occur in the lungs or gastrointestinal tracts (1, 2). The origin of neuroendocrine carcinoma in the breast is still not clear, although its histogenesis is thought to arise from multipotential stem cells capable of divergent differentiation. Primary neuroendocrine carcinoma also occurs in other sites where neuroendocrine cells are normally absent or not readily identifiable, including the ovary and prostate (3). Primary neuroendocrine carcinoma of the breast is extremely rare with the first reported case in 1983 (4). Since then, fewer than 40 cases have been reported in the literature. The most frequent reported age varies from 40 to 70 years, with a higher incidence in women greater than 60 years (3). Prior to this case, the youngest documented case was in a 31-year-old woman (2). This rare tumor has also been reported in a 52-year-old man (5). To the best of our knowledge, the presented case is the youngest reported patient of primary neuroendocrine carcinoma of the breast in the literature.
This case presented with the uncommon clinical signs of inflammatory breast involvement similarly described by Samli et al. (5). In this age group, the common inflammatory breast pathologies are cellulitis, mastitis or breast abscess. However, apart from the breast edema and skin erythema, the patient displayed no other signs of infection such as fever, chills or leukocytosis. She also did not have risk factor for mastitis such as lactation. Furthermore, the axillary lymphadenopathy, with loss of fatty hilum seen on ultrasound was highly suspicious of a malignant etiology. Reactive nodes due to infection, though enlarged, should have preservation of the fatty hilum. Among those cases reported in the literature, mammographic findings have been frequently described (3, 4, 6-13), but ultrasonographic findings have been reported in a few studies only (4, 7-11). Mammographically, this condition has been reported as a dense, lobulated mass with a partially ill-defined margin (4, 10, 11, 13). Calcification and a spiculated border are also other documented mammographic findings (8, 11). Mammography was not performed in this case because of the patient’s young age and the high reliability of ultrasound in characterizing and detecting both solid and cystic components (4). The subsequent ultrasonographic findings reported by Rubini et al. also showed a cyst-containing mass with intracystic tracts (7). However, in the more recent papers, the lesions were generally described as solid hypoechoic masses with well or ill-defined borders and microlobulations of the tumor margin (8-11). Posterior acoustic shadowing, a sonographic feature typically associated with breast carcinoma, was not documented in previous literature. On the other hand, posterior acoustic enhancement was a common feature described by few authors (9-11). Mizukami et al. explained that the posterior acoustic enhancement reflects the high cellularity of the tumor cells (10). Our ultrasound examination revealed a solid, mildly lobulated hypoechoic mass with partially well-delineated borders. The mass contained few small cystic areas and few echogenic foci. The mass exhibited normal sound transmission (no acoustic phenomena). The cystic areas were probably the result of tissue necrosis which was revealed histologically, while the internal echogenic foci most likely represent air or hemorrhagic spots following the core biopsy performed just prior to the ultrasound examination. Doppler sonography has been helpful in differentiating between benign and malignant breast lesions. The greater number of vessels and presence of penetrating vessels are characteristic patterns of vascularity that are more commonly seen in malignant lesions (14, 15). However, these malignant characteristics were not elicited in the color-Doppler study of this case. Instead, we noted poor vascularity within the tumor and absence of penetrating vessels. The flow signals seen surrounding the tumor reflects increased vascularity of the surrounding breast stroma. To date, literature on Doppler sonography of the neuroendocrine tumor of the breast is not available for comparison or review and there has been only one reported MR finding of this rare tumor in the English literature. Bilgen et al. in their retrospective review of an MR examination performed on a non-palpable histologically proven primary neuroendocrine carcinoma of the breast, described the lesion as having irregular margins and showing homogeneous contrast enhancement with a time-intensity curve that showed early enhancement suggestive of malignancy (11). Immunohisto chemically, the cells of neuroendocrine tumor will show immunore activity for specific markers of endocrine differentiation. However, there is no consistent pattern of neuroendocrine marker expression in primary neuroendocrine breast carcinoma (2). In this case, the tumor showed a positive reaction to synaptophysin, chromogranin and cytokeratin MNF116. It also showed a high nuclear-to-cytoplasmic ratio, hyperchromatic nuclei and a high mitotic rate. Histologically, it is not possible to distinguish a metastatic and primary neuroendocrine tumor of the breast (6). The diagnosis of primary breast tumor is made on the basis of radiologic findings that exclude other non-mammary tumors and presence of an in situ component demonstrated within the breast histopathologically (2, 10). Generally, this tumor is considered clinically aggressive with dismal prognosis. As observed in this case, previous authors have also reported rapid progression or recurrence of this disease locally and distally, and a short survival period (1, 4, 6, 15). However, as in breast carcinoma of the usual type, size is a very important prognostic factor for this tumor (3). In more recent reports, it seems that the prognosis is better if the tumors are detected early and if there is no lymph node metastasis (3, 8). As for the management, there is still no established standard treatment protocol because so few cases have been described. As this entity resembles small cell lung carcinoma in morphology, clinical behavior and histiogenesis, it seems reasonable that their treatment should be similar (2). Thus, our patient was given chemotherapy using protocol for small cell lung carcinoma. Surgical excision may be implemented if the tumor responds well to chemotherapy and becomes operable. Unfortunately, in the presented case, chemotherapy failed to control the tumor and the disease followed a rapid and fatal course. The prognosis in this case is governed by the clinical stage of the disease at presentation.
In conclusion, primary neuroendocrine carcinoma of the breast is a rare entity. Reviewing the limited literature on this tumor, there is no age limit, classical presentation or specific imaging feature. It can occur in a 22-year-old young lady or even mimic an inflammatory breast condition. It displays some, but not the entire characteristic ultrasonographic features of a malignant breast lesion. Awareness of this type of breast tumor may help in the differential diagnosis. Although primary neuroendocrine carcinoma of the breast is regarded as clinically aggressive with poor outcome, early detection may lead to a more favorable prognosis.
LEAVE A COMMENT HERE: