Introduction

The reported incidence of the rare neuroendocrine breast tumors comprises 2–5% of all breast carcinomas. The diagnosis depends mainly on the radiologically and histopathologically detected criteria [1, 2]. The World Health Organization categorized these tumors as a subtype of invasive breast cancer based on endocrine features [3].

NENs of the breast (Br-NENs) are the rarest of all NENs (accounting for less than 1% of all NENs) [4–6], and comprise a heterogeneous group of tumors. All Br-NENs are invasive carcinomas, by definition.

Neuroendocrine differentiation is observed in up to 20% of mammary carcinomas, so the real incidence of NEBCs is difficult to evaluate because immunohistochemical neuroendocrine markers are not usually used in the diagnosis of breast cancer [5].

The clinical and radiological features may not differ from other invasive cancers; however, the diagnosis is solely made on the discovery features similar to neuroendocrine tumors arising from the gastrointestinal tract or lungs. These tend to express neuroendocrine markers in >50% of cases [7]

Case Report

A 58-year-old female, a mother of 1 noticed a mass in left breast since 6-month duration. There were no associated pain, discharge, skin changes, or systemic manifestations. Gynecological history was unremarkable with regular menstrual cycles and intermittent use of oral contraceptive pills. There was no family history of breast cancer or similar a presentation.

General Examination Was Unremarkable

Local examination revealed breast asymmetry, with a 3-fold increase in the left breast size. A 7 × 7-cm mass occupied both lower and lateral quadrants extending from 2 and 5 o’clock. The overlying skin was normal. Nipple and the areola complex were stretched but uncompromised. No lymph node was palpated in the ipsilateral axilla (Fig. 1).

The primary clinical impression was locally advanced breast cancer. Initial standard investigations included mammogram (Fig. 2), followed by core needle biopsy. Core biopsy was Suggestive of Invasive Ductal carcinoma. (Grade -1)

Ultrasound of Abdomen and nuclear bone scans both demonstrated the breast lesion with no evidence of distal metastasis.

Patient underwent Modified Radical Mastectomy with Axillary Lymphnode dissection.

Discussion

NEBC was first described in 1963 by Feyrter and Hartmann as carcinoid growth pattern within two cases of breast cancer [8]. Later, in 1977, Cubilla and Woodruff classified eight cases of breast cancers as “carcinoid” [9]. Only several years later, in 2003, the World Health Organization (WHO) recognized

NEBC as a separate entity of breast cancer, showing morphological characteristics similar to gastrointestinal and pulmonary neuroendocrine tumors (NETs), with the expression of a neuroendocrine marker in at least 50% of tumor cells [10]. In the subsequent updates WHO further classified these tumors based on their expression of neuroendocrine markers.

Table 1. WHO classifications from 2003 , 2012 and 2019

A NET of breast is a subtype of breast cancer with similar morphological characteristics to gastrointestinal/lung NETs while displaying some degree of heterogeneity, including certain features that are usually difficult to identify from IBCNST. Therefore, NECB may be misdiagnosed as metastatic breast cancer, carcinomas of IDC-NST, or breast carcinoma with neuroendocrine differentiation.

As the incidence of NECB is low, there is limited knowledge about the specific clinical characteristics of NECB. Most of the data comes from case reports and retrospective studies. The clinical feature of NECB is mainly characterized by a solitary breast lump, probably accompanied by skin ulceration, bloody nipple discharge, skin retraction, palpable axillary mass, and breast discomfort. Some people may have complications such as bone pain, respiratory symptoms, abnormal liver function, hematuria, and neuralgia caused by metastasis. While some people have no symptoms, they occasionally discover the disease due to routine mammographic screening. A few patients may suffer from carcinoid syndrome or hormonal hypersecretion. Patient age at diagnosis is mainly between the fifth and seventh decade of life (majority aged >60 years), ranging from 26 to 99 years, and most patients are postmenopausal women with higher clinical stage and histologic grade.[11]

Compared to IDC-NST, NECB patients are more likely to present systematic metastasis at initial diagnosis, and the most common metastatic sites are bone, liver, lungs, brain, bone marrow, and pleura, and several cases involve skin (12-15). In addition, Kawasaki et al. reported peculiar endovascular spread (16).

There are no specific radiological features of primary Br-NENs [17], and the diagnosis is confirmed on the basis of the histopathological findings. Gallo et al. recently reviewed the mammographic findings in case reports and case series of Br-NENs and reported that the most common mammographic appearance was a hyperdense, irregularly shaped solitary mass without calcifications [18]. Computed tomography (CT) is performed to detect distant metastases and the possibility of the breast tumor being a metastasis from primitive NETs arising in other organs. It is reasonable to perform somatostatin receptor scintigraphy or positron emission tomography (PET)-CT with gallium-68-labeled somatostatin analogues to evaluate the disease location in cases of well-differentiated NETs and indication of peptide receptor radionuclide therapy (PRRT). PET-CT with 18-fluorodeoxyglucose can be performed in patients with poorly differentiated tumors or high-grade carcinomas.[19]

Currently, there is a lack of clinical trials specifically on NE breast cancers, and surgery remains the mainstay of treatment, with supplementary hormonal therapy. Chemotherapy is reserved for those with high risk of recurrence. The choice of treatment for NE breast cancers is based on the main prognostic factors (including TNM stage, Nottingham histologic grade, ER, PR and HER2 status) as for the other types of breast cancer. NE breast cancers appear to have a worse prognosis than other breast cancers. Data on treatment response of NE breast cancers are scarce. A trend of better outcome for NE breast cancers (basing on WHO 2003 classification) receiving hormonal therapy and radiotherapy has been demonstrated, but an opposite trend for chemotherapy has been shown in one report. However, the data did not reach statistical significance.

Endocrine therapies may have an advantage in susceptible tumors. Somatostatin analogues are suggested for tumors with somatostatin receptor expression [20,21]. The diagnosis of primary poorly differentiated invasive neuroendocrine carcinoma is an uncommon challenging entity that requires diligent multimodality management.

References

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