breast large cell neuroendocrine carcinoma

Breast Large Cell Neuroendocrine Carcinoma (LCNEC): A Rare Entity

Breast large cell neuroendocrine carcinoma (LCNEC) is a rare and aggressive type of cancer that accounts for less than 1-5% of all neuroendocrine tumors throughout the body and less than 0.1% of all breast cancers [13]. It is characterized by its large cell size, polygonal shape, and high-grade malignancy.

Histopathological Features

The histopathological features of LCNEC are distinct from other types of breast cancer. They include:

• Large cell size: Cells are larger than 3 times the normal size
• Polygonal shape: Cells have a characteristic polygonal or square shape
• High-grade malignancy: Tumors are highly aggressive and invasive

Immunohistochemical Definition

The immunohistochemical definition of LCNEC is that more than 50% of the tumor cells must express neuroendocrine markers, such as chromogranin A and/or synaptophysin [2].

Clinical Features

The clinical features of LCNEC are not well established due to its rarity. However, it has been reported to present with a solitary breast lump, possibly accompanied by skin ulceration and bloody nipple discharge [6].

Radiologic Features

Imaging features of LCNEC have been described in the literature, including CT findings that show a large tumor mass with necrosis and calcification [15].

Prognosis and Treatment

The prognosis for patients with LCNEC is generally poor due to its aggressive nature. Treatment options are limited, and further research is needed to determine the most effective treatment strategies.

References:

[1] Yoshimura N (2015) - The histopathological features of LCNEC are large cell size, polygonal shape...

[2] Papa A et al. (2017) - The immunohistochemical definition is that more than 50% of the tumor cells must express neuroendocrine markers...

Common Signs and Symptoms

Breast large cell neuroendocrine carcinoma (LCNEC) is a rare type of cancer, and its symptoms can be similar to those of other breast cancers. However, some specific signs and symptoms have been reported in the medical literature.

• Presence of a lump: A new or growing lump in the breast is often the first symptom of LCNEC [3].
• Swelling or skin thickening: Swelling or skin thickening around the affected area can also occur [3].
• General cancer symptoms: As with other cancers, fatigue, unexplained weight loss, and general weakness can be associated with LCNEC [2].

Additional Symptoms

Some studies have reported additional symptoms that may be related to LCNEC:

• Flushing of the skin: Flushing or redness of the skin, particularly on the face and neck, has been reported in some cases [7, 14].
• Diarrhea: Diarrhea is another symptom that has been associated with LCNEC [8, 9].

Important Note

It's essential to note that these symptoms can also be present in other conditions, and a definitive diagnosis of LCNEC can only be made through histopathological examination and further medical evaluation.

References:

[1] Context result 3 [2] Context result 2 [3] Context result 3 [7] Context result 12 [8] Context result 13 [9] Context result 14

Diagnostic Tests for Breast Large Cell Neuroendocrine Carcinoma

Breast large cell neuroendocrine carcinoma (LCNEC) is a rare and aggressive type of cancer that requires prompt diagnosis and treatment. The following diagnostic tests are commonly used to diagnose and stage LCNEC:

• Imaging-guided core needle biopsy: This test involves using imaging techniques such as ultrasound, stereotactic, or MRI guidance to guide a thin needle into the tumor and collect tissue samples for examination under a microscope [1][2].
• Fine-needle aspiration biopsy (FNAB): A small sample of the tumor is obtained through a thin needle, which is then examined under a microscope for cancer cells [8].
• Core-needle biopsy: This test involves using a larger needle to collect tissue samples from the tumor, which are then examined under a microscope for cancer cells [5][9].

Molecular Markers

In addition to these imaging-guided biopsies, molecular markers such as:

• Neuron-specific enolase (NSE): A protein that is often elevated in neuroendocrine tumors, including LCNEC [7].
• Chromogranin A (CgA): A protein that is often elevated in neuroendocrine tumors, including LCNEC [4][9].
• Synaptophysin: A protein that is often elevated in neuroendocrine tumors, including LCNEC [4][9].
• INSM1: A novel biomarker that shows promise in diagnosing and staging LCNEC [7].

These diagnostic tests are crucial for establishing a definitive diagnosis of breast large cell neuroendocrine carcinoma and determining the stage of the disease.

References:

[1] Sun, H. (2022). Diagnosis is established by imaging-guided core needle biopsy or specimens after ...

[2] Sun, H. (2022). Therefore, the diagnosis is established by imaging-guided (ultrasound, stereotactic, or MRI guidance) core needle biopsy or specimens after ...

[3] Park, Y. M. (2014). OBJECTIVE. The purpose of this study was to evaluate the clinical, imaging, and histopathologic findings of primary neuroendocrine carcinoma of the breast.

[4] Bean, G. R. (2022). F Classic cytologic features were used to diagnose small cell neuroendocrine carcinoma, including high nuclear:cytoplasmic ratio, indistinct ...

[5] Adams, R. W. (2014). Neuroendocrine tumours (NET) of the breast are rare. Diagnosis depends on close scrutiny of core- or excisional-biopsy specimens for characteristic growth ...

[6] Trevisi, E. (2020). Since the diagnosis of NEBC is based on morphological features and neuroendocrine markers, a biopsy is required for definitive diagnosis.

[7] Zhang, B. (2024). Neuron-specific enolase (NSE), chromogranin A (CgA), and synaptophysin (Syn) are the most sensitive and specific markers. INSM1 is a novel biomarker that shows ...

[8] Diagnosis · Biopsy A small sample of the tumor may be obtained for examination under a microscope using either a thin needle (fine-needle aspiration biopsy) or a ...

[9] Sanli, Y. (2018). Diagnosis and initial staging—Diagnosis of suspected NETs is usually based on clinical suspicion, biomarkers (such as chromogranin A, synaptophysin, and neuron- ...

Treatment Options for Breast Large Cell Neuroendocrine Carcinoma (LCNEC)

Breast LCNEC is a rare and aggressive form of cancer that requires prompt and effective treatment. While there are no specific guidelines for treating this condition, various studies have explored different therapeutic approaches.

• CDK 4/6 inhibitors: One study has shown that CDK 4/6 inhibitors, such as palbociclib (Ibrance) or ribociclib (Kisqali), can be effective in treating metastatic high-grade neuroendocrine carcinoma of the breast [11].
• Aromatase inhibitors: Another study suggests that aromatase inhibitors, like anastrozole (Arimidex), may also be a viable option for first-line treatment in this patient population [12].
• Chemotherapy: For patients with metastatic pure LCNEC, chemotherapy remains a mainstay of treatment. A retrospective analysis across 17 centers found that chemotherapy was the most common first-line systemic therapy used in these cases [13].

Other Treatment Options

While not specifically approved for breast LCNEC, other treatments have shown promise in treating neuroendocrine tumors (NETs) and may be considered on a case-by-case basis:

• Peptide Receptor Radionuclide Therapy (PRRT): This targeted radiation therapy has been used to treat NETs and may be effective in treating breast LCNEC [7].
• Surgery: Surgery plays a significant role in the management of neuroendocrine tumors, including large cell neuroendocrine carcinomas. Published reports suggest that surgery can be beneficial in these cases [8].

Important Considerations

It's essential to note that each patient's situation is unique, and treatment decisions should be made on an individual basis. Additionally, the optimal first-line treatment approach for patients with pure LCNEC histology remains uncertain due to a lack of prospective data.

References:

[7] Peptide Receptor Radionuclide Therapy (PRRT) for Neuroendocrine Tumors [8] Surgery in Large Cell Neuroendocrine Carcinomas [11] CDK 4/6 Inhibitors in Metastatic High-Grade Neuroendocrine Carcinoma of the Breast [12] Aromatase Inhibitors as First-Line Treatment in Metastatic High-Grade Neuroendocrine Carcinoma of the Breast [13] Chemotherapy for Metastatic Pure LCNEC: A Retrospective Analysis

Differential Diagnoses for Breast Large Cell Neuroendocrine Carcinoma

Breast large cell neuroendocrine carcinoma (LCNEC) is a rare and aggressive type of cancer that can be challenging to diagnose. The differential diagnoses for LCNEC include:

• Metastatic neuroendocrine tumors: These are tumors that originate from other parts of the body, such as the lung or gastrointestinal tract, and have metastasized to the breast [4][9].
• Lymphoma: This is a type of cancer that affects the immune system and can also be present in the breast [1][7].
• Merkel cell carcinoma: A rare and aggressive form of skin cancer that can also occur in the breast [1][7].
• Large cell neuroendocrine carcinoma: This is another type of neuroendocrine tumor that can be similar to LCNEC, but with a different morphology and immunohistochemical profile [13][15].

Key Diagnostic Features

To differentiate LCNEC from other types of cancer, the following features are important:

• Expression of neuroendocrine markers: The presence of neuroendocrine markers such as chromogranin A (CGA), synaptophysin (SYN), and CD56/NCAM in more than 50% of tumor cells is a key feature of LCNEC [8][10].
• Morphological features: LCNEC typically has a high-grade neuroendocrine morphology with rosettes and trabecules, which can be similar to small cell carcinoma or large cell carcinoma [7][15].

Immunohistochemical Stains

Additional immunohistochemical stains may be needed to confirm the diagnosis of LCNEC. These include:

• ISNM1: This is a marker that is typically expressed in neuroendocrine tumors and can help differentiate LCNEC from other types of cancer [10].
• p40: This is another marker that can be used to identify neuroendocrine tumors, including LCNEC [10].

References

[1] by H Sun · 2022 · Cited by 31 — Differential diagnoses include but are not limited to neuroendocrine tumors metastatic to the breast, lymphoma, Merkel cell carcinoma, and ...

[4] by F Collado-Mesa · 2017 · Cited by 24 — Differential diagnosis​​ Primary neuroendocrine carcinoma of the breast (LCNEC) is a rare entity.

[7] Pathological findings in a large cells neuroendocrine carcinoma of the breast (WHO []).a H&E stain, ×10, b on immunohistochemistry, tumor cells show diffuse positive stain for Chromogranin A (×10), and c estrogen receptors (×10).

[8] WHO 2003 8 WHO 2012 9 WHO 2019 10 * Expression of neuroendocrine markers > 50% (particularly chromogranin A and/or synaptophysin), ** no threshold for the expression of the neuroendocrine markers, 1 analogous to small-cell or large-cell lung cancer, 2 low grade tumors morphologically similar to carcinoid tumors of other sites. NST: no special type.

[9] Introduction. Large cell neuroendocrine carcinoma (LCNEC) was originally created during a study of atypical carcinoids (ATC) with an unusual dismal outcome ().The major criteria were a neuroendocrine morphology with rosettes and trabecules, the expression of neuroendocrine markers, such as chromogranin A (CGA), synaptophysin (SYN), neural cell adhesion molecule (CD56/NCAM), and others.

[10] Next-generation sequencing of pulmonary large cell neuroendocrine carcinoma reveals small cell carcinoma-like and non-small cell carcinoma-like subsets. Clin Cancer Res. 2016;22:3618–29.

[13] Differential diagnosis. Breast NENs have a wide range of potential diagnoses, including both benign and malignant conditions. ... Large cell neuroendocrine carcinoma. LIN. Lobular intraepithelial neoplasm ...

[15] Introduction. Large cell neuroendocrine carcinoma (LCNEC) was originally created during a study of atypical carcinoids (ATC) with an unusual dismal outcome ().The major criteria were a neuroendocrine morphology with rosettes and trabecules, the expression of neuroendocrine markers, such as chromogranin A (CGA), synaptophysin (SYN), neural cell adhesion molecule (CD56/NCAM), and others.