Neurofibroma of the breast
A neurofibroma is an uncommon neoplastic tumor which can from due to changes in the peripheral nervous system. Is is one of two types of peripheral nerve sheath tumors which occasionally develop within the breast, the other being breast schwannoma. They may effect multiple organ systems, and mostly develop in the skin, but a rare few do develop within the breast.
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They are considered to be 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).
Breast neurofibromas tend to be associated with neurofibromatosis
Neurofibromatosis is a genetically-inherited disorder which causes nerve tissue to grow into tumors. Neurofibromatosis is autosomal dominant, (affecting males and females equally, and requiring only one copy of an affected gene), and comes in two major forms.
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 association with benign tumor development, but more likely to cause balance problems, headaches, possibly tinnitus, but may also develop into very serious brain or spinal tumors.
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 2 (NF2) affects about 1 in 40000 people, while neurofibromatosis type 1, (which includes breast neurofibromas) is more common, effecting 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) element in breast neurofibromas are Schwann cells (though unlike with breast schwannomas, there are other kinds of cells involved 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, and it is thought that the non-myelinating variety are 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‘, it would only be considered a ‘benign neoplasm‘. If however the neurofibroma initiates a malignant transformation into a ‘malignant peripheral nerve sheath tumor‘ (MPNST), then yes it would be called cancer.
‘Tumor suppressor‘ functions might be suppressed by the proliferations of fibroblasts and Schwann cells
No one knows what causes malignant cancer, but it is generally thought 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 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 tumor suppressing genes are either lost or inhibited, the tumor can grow in an uncontrolled way. The concern with breast neurofibroloma is that the hyperplastic growth of Schwann cells and fibroblasts could impair the tumor suppression functions, allowing it to grow into a malignant peripheral nerve sheath tumor, or a ‘cancer‘, within the breast.
Inherited versus ‘sporadic‘ breast neurofibromas
Breast neurofibromas may either develop as a result of the inherited autosomal dominant trait, or, they may develop randomly at a later time due to unexpected 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 are generally thought to have a more benign course.
While they are no firm statistics in this regard, about 40% of breast neurofibromas are of the ‘sporadic‘ variety, occuring 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, while a ‘neoplasm‘ is growth in a new or unexpected type of cell altogether.
Mammographic aspects of neurofibroma of the breast
Breast neurofibromas usually appear 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
Neurofibromas of the breast may be classified in two basic types; dermal and plexiform. Dermal neurofibromas are associated with a single peripheral nerve, while 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 and itching, pain, and possibly dis-figuration if left untreated. Dermal breast neurofibromas usually do not lead to subsequent malignant transformation, but, 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 are typically composed 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. Most breast neurofibromas are non-encapsulated.
Treatment and prognosis for neurofibroma of the breast
Because of the latent possibility of malignant transformation, most neurofibromas are treated by surgical excision anyways. For breast neurofibromas this usually means either 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 when associated with NF type 1 is about 10%.
For further reading, I suggest you go to this page which has some information about breast schwannoma.
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