Breast Neurofibroma

A neurofibroma is an uncommon neoplastic tumor which can form due to changes in the peripheral nervous system. Neurofibroma is one of two types of peripheral nerve sheath tumors which occasionally develop within the breast. The second type is breast schwannoma.

These tumors may affect multiple organ systems, but most develop in the skin. However, a rare few do develop within the breast.

A neurofibroma is usually a benign tumor, but a small percentage of neurofibromas have malignant cellular features which make them more likely to evolve into a malignant peripheral nerve sheath tumor (MPNST).

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Breast neurofibromas tend to be associated with neurofibromatosis

Neurofibromatosis is a genetically-inherited disorder which causes nerve tissue to grow into tumors. This disorder is autosomal dominant, (affecting males and females equally and requiring only one copy of an affected gene), and comes in two major forms:-

Breast neurofibromas are generally associated with NF type 1, while breast schwannomas are associated with NF type 2. NF1 also tends to be associated with the peripheral nerve system, while NF2 is associated with the central nervous system.

Neurofibromatosis Type 1 (NF1) tends to result in the development of multiple non-cancerous tumors (such as neurofibromas) and also spots of increased or decreased skin pigmentation (cafe-au-lait spots)
Neurofibromatosis type 2 (NF2) derives from a different chromosome and is much less commonly a benign tumor development. This tumor is likely to cause balance problems, headaches, possibly tinnitus. This tumor may also develop into very serious brain or spinal tumors.

Neurofibromatosis type 2 (NF2) affects about 1 in 40000 people, while neurofibromatosis type 1, (which includes breast neurofibromas) is more common, affecting approximately 1 in 4000 people.

Is a breast neurofibroma a kind of breast cancer?

It is a complex question. The short answer is no, as most breast cancers develop from epithelial cells found in the lining of the breast ducts. The main hyperplastic (rapidly growing) elements in breast neurofibromas are Schwann cells. Although, unlike breast schwannomas, there are other kinds of cells as well.

Breast neurofibromas can develop when Schwann cells exhibit biallelic inactivation of the NF1 gene that codes for the protein neurofibromin. There are both myelinating and non-myelinating Schwann cells. However, researchers believe that it is the non-myelinating variety that is responsible for both the initiation and progression of certain neurofibromas.

So, while the hyperplastic growth of Schwann and other cells with a breast neurofibroma remains typical, doctors consider it a ‘benign neoplasm’. If however, the neurofibroma initiates a malignant transformation into a ‘malignant peripheral nerve sheath tumor’ (MPNST), then yes it would be cancer.

‘Tumor suppressor’ functions in Neurofibroma

No one knows what causes malignant cancer, but researchers generally believe it to be the result of an accumulation of multiple genetic alterations.

Cancer researchers will often speak of an imbalance of genes which initiate malignant cell changes and also genes which suppress their development. Most of the genes responsible for hereditary cancers are tumor suppressor genes, which inhibit cell proliferation and growth (hormonal changes also play a role).

When these tumour-suppressing genes are either lost or inhibited, the tumor can grow in an uncontrollable way. The concern with breast neurofibroma is that the hyperplastic growth of Schwann cells and fibroblasts may impair the tumor suppression functions.

This allows the tumor to grow into a malignant peripheral nerve sheath tumor or cancer within the breast.

Genetic versus ‘sporadic’ breast Neurofibroma

Breast neurofibromas can develop either as a result of the inherited autosomal dominant trait or they may develop randomly at a later time due to genetic changes. These later developing, random neurofibromas will tend to occur alone, as sporadic tumors.

Sporadic breast neurofibromas tend to develop later in life (around middle age), are slower growing, and generally, have a more benign course. While they are no firm statistics in this regard, about 40% of breast neurofibromas are of the sporadic variety, occurring randomly and not associated with neurofibromatosis.

There is some speculation now that the more indolent clinical behavior typical of the sporadic neurofibromas in the breast, and the frequent absence of NF-1 association suggest that they are more hyperplastic or hamartomatous in nature, rather than a true neoplasm.

A hyperplasm suggests rapid growth of a cell native to the area, whilst a neoplasm is a growth in a new or unexpected type of cell altogether.

Mammographic aspects of neurofibroma of the breast

A breast neurofibroma usually appears as probably benign on mammography and ultrasound. Breast neurofibromas tend to be non-calcified, oval lesions with smooth and partially obscured margins. Neurofibroma breast masses can cause lobulations of cutaneous tissue and asymmetrical breast enlargement as well, particularly when they occur in multiples.

Ultrasound images of a breast neurofibroma will tend to show well-defined hypoechoic oval lesions, with mild posterior acoustic enhancement. Sometimes a breast neurofibroma can show distal acoustic enhancement which can resemble a breast cyst and result in misdiagnosis. Breast neurofibromas vary in size and shape to a degree but most are quite small, between 1 cm and 2 cm.

Two common types of breast neurofibroma

Doctors classify neurofibromas of the breast into two basic types:-

Dermal Neurofibromas usually occur within a single peripheral nerve.
Plexiform Neurofibromas are associated with multiple nerve bundles.

Both dermal breast neurofibromas can look like small lumps on or under the skin and can cause stinging, itching and pain. Sometimes, without treatment, a dermal breast neurofibroma can cause disfiguration.

Dermal breast neurofibromas usually do not lead to subsequent malignant transformation. However, about 10% of plexiform breast neurofibromas may transform into a malignant peripheral nerve sheath tumor.

Histological aspects of breast neurofibroma

The histological appearance of a breast neurofibroma will tend to show a proliferation of interlacing bundles of elongated cells (nerve fibers) and fibroblasts with dark, wavy, staining nuclei and narrow cytoplasmic processes.

Neurofibroma typically consists of a varied mixture of Schwann, fibroblastic, and perineurial-like cells, as well as cells with ‘intermediate‘ features between these various cells.

Cells are typically arranged closely together separated by small quantities of mucoid material. Of note, neurofibromas will usually lack any epithelial elements. Cell mitosis and atypia will tend to be absent, and their presence would suggest a more malignant tumor.

Treatment and prognosis for neurofibroma of the breast

Because of the latent possibility of malignant transformation, the treatment for most neurofibromas is surgical excision. For breast neurofibromas, this usually means either a modified or radical mastectomy.

When breast neurofibromas become malignant, they can grow very quickly. Unlike breast schwannomas, neurofibromas are more intimately attached to the nerve, making them somewhat more difficult to remove.

The prognosis will depend to a degree upon whether the breast neurofibroma developed as a result of neurofibromatosis type 1, or emerged randomly. The lifetime risk of developing a malignant peripheral nerve sheath tumor (NF type 1) is about 10%.

References

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