Rare Breast Cancers: Section 5.d.

CONTENTS:

5.16 Rare Breast Cancer: Tumor Types
5.16.1 Neuro-endocrine Carcinoma
5.16.2 Secretory Carcinoma
5.16.3 Acinic Cell Carcinoma
5.16.4 Muco-epidermoid Carcinoma
5.16.5 Glycogen-rich Carcinoma
5.16.6 Lipid-rich Carcinoma

5.17 Malignant Mesenchymal Tumors of the Breast
5.17.1 Liposarcoma
5.17.2 Malignant Schwannoma
5.17.3 Angiosarcoma
5.17.4 Leiomyosarcoma
5.17.5 Rhabdomyosarcoma

5.18 Lymphoma of the Breast
5.18.1 B-cell Lymphoma
i. MALT / Marginal Zone Lymphoma
ii. Burkitt’s Lymphoma
iii. Diffuse, Large B-Cell Lymphoma (DLBCL)
5.18.2 T-cell Lymphoma
i. Anaplastic, Large Cell Lymphoma (ALCL)

Forward to section 5E male breast cancer. Back to 5C on papillary types.

5.16 Rare Breast Cancer: Tumor Types

So, rare breast cancer derives from tissues other than the breast ducts or lobules.

The cells and tissues that are not ductal or lobular include neuro-endocrine cells, ‘salivary-type’ glands, sebaceous glands, fat, muscle, endothelial cells, mesenchymal cells and lymphocytes.

If you get a biopsy showing a rare breast cancer type, it’s natural to be researching it on the internet. Want a free tip?

Absolutely.

Ask for an oncologist with grey hair. Whatever the cancer, even those rare breast cancer on a web page, the oncologist will be Very Familiar with it. They’ll know how to handle it, so you can let some anxiety fall away.

5.16.1 Neuro-endocrine Carcinoma

Neuro-endocrine carcinoma is a rare breast cancer. Indeed, features of this cancer are either as scattered cells, that are recognized by their expression of neuro-endocrine cell markers (as ‘breast carcinoma with neuro-endocrine features’), or as a special type of tumor where the vast majority of the cells display neuro-endocrine characteristics (‘neuro-endocrine differentiated carcinoma’).

There can be a spectrum of neuro-endocrine change in tumors, from benign to low-grade malignant (neuro-endocrine carcinoma) to high-grade malignant (‘small cell’ carcinoma).

The prognosis is related to conventional tumor grading, so in the breast, these tumors are neuro-endocrine carcinoma, well -, moderately- or poorly-differentiated.

Figure 5.30 Neuro-endocrine Carcinoma

A. ‘Small cell’ neuro-endocrine carcinoma is a high-grade malignancy consisting of
small, dark cells with little cytoplasm (sometimes called ‘oat cell’ carcinoma).
B. Large cell neuro-endocrine carcinoma consists of large cells with large, pale nuclei
and varying amounts of cytoplasm. (H&E x40)

Do these small purple cells look like oats?

Do I look like a farmer?

5.16.2 Secretory Carcinoma: Another rare Breast Cancer

Secretory carcinoma is a rare breast cancer but is also a distinct sub-type of breast carcinoma, with characteristic histology and a favorable prognosis.

Just out of interest, an earlier medical name for secretory carcinoma of the breast was ‘juvenile’ breast carcinoma.

The diagnostic histology of secretory carcinoma of the breast shows the presence of a large amount of intracellular and extracellular, eosinophilic (pink-staining) secretion.

The secretions are positive for histochemical stains (such as periodic acid-Schiff – PAS). These cancers are ‘triple negative‘ tumors that are negative for estrogen receptor (ER), progesterone receptor (PR), and HER2 (ERB-B2).

The prognosis is good.

Figure 5.31 Secretory Carcinoma

Photomicrograph of the histology from a breast biopsy shows rather
bland cells that contain pink secretions. (H&E x 20)

5.16.3 Rare Breast Cancer: Acinic Cell Carcinoma

Acinic cell carcinoma (ACC) of the breast is another rare breast cancer. However, ACC is similar to tumors that occur in the salivary glands and that show acinic cell differentiation.

Acinic cell carcinoma is a low-grade carcinoma and is an extremely rare tumor in the breast.

5.16.4 Muco-epidermoid Carcinoma

Muco-epidermoid carcinoma of the breast is another rare breast cancer. This type of breast cancer, again, is of the ‘salivary’ type. The incidence of this rare breast cancer is only between 0.2% to 0.3% of all breast carcinomas.

The histology of the tumor is similar to its salivary gland counterpart with a mixture of rather bland, pink cells, areas of extracellular mucin and sometimes, areas of cartilaginous metaplasia.

Figure 5.32 Acinic Cell and Muco-epidermoid Carcinoma

Photomicrographs of breast histology show A. the appearances of acinic cell
carcinoma, with bland, pink cells and B. muco-epidermoid carcinoma with
larger pink cells and areas of extracellular mucin. (H&E x 10 & x 20)

5.16.5 Glycogen-rich Carcinoma

Glycogen-rich breast tumors are rare breast cancers. On histology, their microscopic appearance is of pink tumor cells of varying grade.

Going by the cell morphology alone, these tumors have a wide differential diagnosis, including lipid-rich carcinoma, secretory carcinoma and carcinoma with apocrine-change.

On histology, glycogen-rich breast tumors show PAS-positivity.

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5.16.6 Lipid-rich Carcinoma

Lipid-rich carcinoma of the breast is also a rare breast cancer. On histology, these tumor cells have cytoplasmic lipid droplets that stain positively for oil-red-O (ORO).

Both lipid-rich and glycogen-rich cells can be found in the same breast tumo

Figure 5.33 Lipid-rich and Glycogen-rich Carcinoma

Photomicrograph of the histology of a moderate grade breast cancer (IDC)
showing combined lipid-filled cells (empty spaces) and glycogen-rich cells
(dark pink cytoplasm). (H&E x40)

Fig 5-33 Lipid-rich and Glycogen-rich carcinoma

5.17 Malignant Mesenchymal Tumors of the Breast

With the exception of fibro-epithelial tumors, primary malignant mesenchymal tumors of the breast, particularly sarcoma of the breast, are also a very rare breast cancer. (Beatty et al., 2006).

Primary breast sarcoma accounts for less than 1% of all breast malignancy and less than 5% of all soft tissue sarcomas. The estimated annual incidence is 17 new cases per 1,000,000 women.

Sarcoma in a breast, is just a rare, freak, bad luck surprise.

But look at the excellent survival numbers. Or take my word for it.

Other than radiation-induced angiosarcoma, no definitive etiologic relationship exists between sarcomatous and non-sarcomatous mesenchymal tumors.

A 90-year search of the Mayo Clinic database reveals that primary breast sarcoma accounted for 0.06% of all breast cancers (Adem, 2004). Tumor size was the most valuable prognostic factor, with 91% overall survival for women with breast sarcomas less than or equal to 5 cm and 50% for those with breast sarcomas greater than 5 cm.

With regard to the breast, liposarcoma, malignant schwannoma, angiosarcoma, leiomyosarcoma and rhabdomyosarcoma are most commonly found in the breast.

Wow! I wonder who did the 90 year search of the cinic’s database.

I don’t know but they must be getting on a bit!

5.17.1 Liposarcoma

The breast consists mainly of fat; although liposarcomas are rare tumors, they must be considered when discussing mesenchymal breast tumors.

Liposarcomas consist of ‘lipoblasts,’ when examined microscopically. The neoplastic lipoblasts have a characteristic morphology.

Liposarcoma has four histological types: myxoid (low-grade), round cell (high-grade), pleomorphic (high-grade), and well-differentiated (low-grade).

I’m reading a book about anti-gravity. It’s impossible to put down.

Unlike the benign lipoma, liposarcoma does not always present as a mass, but tends to be more infiltrative. A magnetic resonance imaging (MRI) scan may be more sensitive than mammographic X-ray in identifying the boundaries of liposarcoma. Higher-grade liposarcomas are more vascular than low-grade liposarcomas.

The diagnosis may be made by core needle biopsy (CNB) or incision breast biopsy. Treatment is by wide excision followed by radiation therapy. For tumors greater than 8 cm in diameter, pre-operative radiotherapy and chemotherapy may be considered (Austin & Dupree, 1986).

Figure 5.34: Types of Rare Breast Cancer

A. Photomicrograph of Liposarcoma with lipoblasts which are typical of this tumor.
B. Photomicrograph of the histology of Malignant Schwannoma shows atypical
spindle cells with abundant mitoses.

Fig 5-34 lipoblast and malignant schwannoma

5.17.2 Malignant Schwannoma

Malignant schwannoma is a soft tissue tumor that involves the peripheral nerves. It is also known as ‘neurofibrosarcoma’ or ‘fibrosarcoma of nerve sheath.’

Malignant schwannoma may arise from within a pre-existing benign schwannoma, especially in women with neurofibromatosis.

Speaking of birds, what do you call a very rude bird?

A schwann is not a bird, but go on.

A mocking bird.

Of all soft tissue sarcomas, 10 % are malignant schwannomas; half of them are related to neurofibromatosis (von Recklinghausen’s disease).

The histology of malignant schwannoma shows ‘comma-shaped’ tumor cells.

Wide excision with radiation and chemotherapy is the usual treatment (Silver & Tavassoli, 1998).

Did you notice Von Recklinghausen’s disease? That’s a fun name.

5.17.3 Angiosarcoma

Only between 1% and 2% of soft tissue sarcomas are of vascular origin. Benign and malignant vascular tumors can arise from the skin of the breast. The main vascular malignancy that arises from the breast tissue is angiosarcoma.

Primary angiosarcoma of the breast is rare and represents about 0.05% of all primary malignant breast tumors (Nascimento et al. 2008). It affects relatively younger patients and has an overall clinical course that is similar to angiosarcoma arising in the skin or soft tissue.

Angiosarcoma of the breast carries a moderate risk of local recurrence and a high risk of metastasis.

In a review of forty-nine cases of primary angiosarcoma of the breast, the peak incidence was found to be between the ages of 30 and 50 years (Nascimento et al. 2008). The right breast was more commonly affected than the left breast; the tumor was bilateral at presentation in 4.5 %.

In this study, tumor size varied from 0.7 to 25 cm (mean 6.7 cm). In this study, most patients presented with a palpable, painless breast mass; 4 % of patients had a history of prior radiation treatment for breast carcinoma. Histologically, 35.4% were low-grade, 35.4% as intermediate-grade and 29.2% as high- grade; 58.5% developed metastases, which were most commonly to lung, liver, skin, and bone.

In this large study by Nascimento and colleagues, there was no correlation between histologic grade and patient outcome; this is similar to angiosarcomas that arise at other sites in the body (Nascimento et al. 2008).

I hate jokes that rely on visual imagery; I’ve had it right up to here with them.

Figure 5.35 Angiosarcoma of the Breast

A. Mammographic X-ray shows a linear breast density. B. Photomicrograph of
the histology of this excised breast lesion shows malignant spindle cells
that are ‘vaso-formative’ with ill-formed vascular channels containing red
blood cells. (H&E x 60)

Fig 5-35 rare breast cancer Angiosarcoma

5.17.4 Leiomyosarcoma

Leiomyosarcoma is a malignant tumor of smooth muscle and arises from smooth muscle of vessels in the breast or smooth muscle beneath the breast nipple.

Leiomyosarcoma is a high-grade soft tissue sarcoma that usually occurs in adults, especially women. The histology of the breast biopsy shows spindle cells with varying degrees of pleomorphism but that express smooth muscle actin.

Treatment is by surgical excision with or without radiation, and occasionally chemotherapy.

Figure 5.36 A. Leiomyosarcoma of the Breast

Photomicrograph of the histology shows spindle cells with elongated
nuclei with round, blunt ends. B. Rhabdomyosarcoma
of the Breast. Photomicrograph of the histology can show round,
‘rhabdoid’ cells with pink cytoplasm. (H&E x 20 & x 40)

5.17.5 Rhabdomyosarcoma

Rhabdomyosarcoma is the most common soft tissue sarcoma in children; in adults, 15 % to 20 % of all soft tissue sarcomas are rhabdomyosarcomas. In the adult breast, these tumors arise from the striated muscle of the chest wall but are extremely rare.

Histology of rhabdomyosarcoma shows four patterns: embryonal, boytroid, alveolar and pleomorphic.

Treatment for rhabdomyosarcoma includes Adjuvant systemic therapy (chemotherapy and/or radiation therapy) and wide margin excision. The local recurrence rate for this sarcoma is very high if surgical margins are not adequate.

Why does a bird bring toilet paper to the party? Because he is a party pooper.

5.18 Lymphoma of the Breast

The breast may be involved by leukemic infiltrates and by disseminated lymphoma (malignancy of lymphoid cells) (Joks et al., 2011).

Primary lymphoma of the breast is a rare breast cancer and accounts for 0.04 % to 0.5 % of all breast malignancy and approximately 1% to 2% of all extra-nodal lymphomas (Julen, 2009). Secondary involvement of the breast with lymphomas is more common than primary breast lymphoma.

Primary breast lymphoma is believed to arise from intra-mammary lymphocytes that are associated with breast ducts: mucosa-associated lymphoid tissue (MALT).

The majority of breast lymphoma presents as a unilateral painless breast mass in an older woman (average age at diagnosis 55 to 60 years). The right breast has been reported to be involved more often than the left. Ipsilateral axillary lymphadenopathy is present in 30% to 40% of cases (Joks et al., 2011).

There is some evidence that widespread mammographic screening for breast cancer is leading to increased incidental detection of lymphoma of the breast.

A less common but distinctive presentation is that of a young woman of child-bearing age who presents during or immediately after pregnancy. Breast lymphoma may be bilateral. Most of these women have highly aggressive, Burkitt’s lymphoma.

Breast lymphomas have been reported in men although they are rare.

The vast majority of primary breast lymphomas are https://www.cancer.gov/types/lymphoma (NHL).

Although a core biopsy is adequate to make a diagnosis of a breast lymphoma, an excision biopsy is preferable.

Radiographically, breast lymphomas appear as circumscribed masses that lack calcification or evidence of a desmoplastic reaction (i.e. retraction), but these features are non-specific.

Staging of Breast Lymphomas

As with other lymphomas, primary breast lymphomas are staged according to the Lugano revisions to the Ann Arbor staging system (Cheson et al., 2014). By definition, stage IE disease is limited to breast involvement only, and stage IIE disease involves the breast and ipsilateral axillary lymph nodes.

Staging of breast lymphoma is based upon clinical history and physical examination, imaging, bone marrow aspiration and biopsy, and laboratory studies (including a serum lactate dehydrogenase level). Assessment of the contralateral breast is essential since approximately 10 % of cases of primary breast lymphoma are bilateral.

Prognosis of primary lymphoma of the breast is dependent upon clinical stage and histologic type.

As with localized non-Hodgkin lymphoma (NHL) at other sites, poor prognostic indicators include: age greater than 60 years, elevated serum lactate dehydrogenase (LDH), stage II disease rather than stage I disease, and Eastern Cooperative Oncology Group (ECOG) performance status ≥ 2 (Oken, 1982).

The treatment of primary lymphoma of the breast is similar to lymphoma of the same stage and histology in other locations.

Figure 5.37. Lymphoma of the Breast

A. MALT Lymphoma. Photomicrograph of the histology of the breast shows a
‘lympho-epithelial’ lesion with atypical small lymphocytes infiltrating epithelial cells.
B. Burkitt’s Lymphoma. Photomicrograph of the histology shows the enlarged,
‘foamy’ Burkitt cells. C. Diffuse Large-Cell B-Cell (DLCBCL) Lymphoma.
Photomicrograph of the histology show enlarged lymphocties with large, angular
nuclei and a high mitotic rate. D. Anaplastic Large-Cell Lymphoma (ALCL).
Photomicrograph of the histology shows large, bizarre cells, a high mitotic rate
and high apoptotic rate. (H&E x 20, x 40 & x 60)

5.18.1 B-cell Lymphoma

Primary breast lymphomas are most commonly B-cell, non-Hodgkin lymphomas; approximately one-half are diffuse, large B-cell lymphoma (DLBCL). Follicular lymphoma or extra-nodal marginal zone (MALT) lymphoma, occur less commonly.

i. MALT / Marginal Zone Lymphoma

Lymphocytes within the breast are part of mucosa-associated lymphoid tissue (MALT). Marginal zone B-cell lymphomas (previously called mucosa-associated lymphoid tissue [MALT] lymphomas) may present with or develop bilateral breast involvement.

ii. Burkitt’s Lymphoma

Another rare breast cancer is Burkitt’s lymphoma of the breast. This lymphoma is associated with a distinctive clinical presentation.

Burkitt’s lymphoma is an aggressive B-cell lymphoma, characterized by translocation and de-regulation of the MYC gene on chromosome 8.

Patients with Burkitt’s lymphoma require intensive, multi-agent therapy, with CNS prophylaxis. There is no role for radiotherapy, even in patients with localized disease.

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iii. Diffuse, Large B-Cell Lymphoma (DLBCL)

Diffuse, large B-cell lymphoma (DLBCL) is a high-grade lymphoma. The presentation can be with a breast mass but is more likely to be with axillary lymph node involvement.

The histology is typical for high-grade lymphoma, with large, pleomorphic lymphocytes with a moderate to high mitotic count; there may be some lympho-plasmacytoid differentiation. Given the high incidence of central nervous system (CNS) recurrence in patients with DLBCL of the breast, CNS prophylaxis should be considered.

5.18.2 T-cell Lymphoma

T-cell lymphomas rarely arise in the breast, but when they do, they are associated with an aggressive clinical course.

i. Anaplastic, Large-Cell Lymphoma (ALCL)

Although this is a rare primary tumor of the breast, it is one that is reported to be associated with a history of silicone breast implants (Kellogg et al., 2014).

In a population-based, case-control study, the risk for primary breast anaplastic large-cell lymphoma (ALCL) in women with a cosmetic silicone breast prosthesis was estimated to be one to three cases per million; this is 18-fold higher than in women who did not have a silicone breast implant (Kellogg et al., 2014).

References

Beatty SD, Atwood M, Tickman R, Reiner M. Metaplastic breast cancer: clinical significance. Am J Surg. 2006;191:657–664. (Retrieved November 14^th 2014): https://www.ncbi.nlm.nih.gov/pubmed/16647355

Austin R.M., Dupree W.B. (1986). Liposarcoma of the breast: a clinocopathological study of 20 cases. Hum Pathol 17, 906-913. (Retrieved November 14th 2014): http://www.ncbi.nlm.nih.gov/pubmed/?term=Hum+Pathol++1986%3B+17%3A906-913.

More references for this section are on this page.

Patient Information

Breast Cancer Org Types of Breast Cancer. (Retrieved February 6^th2015): 2015): http://www.cancer.org/cancer/breastcancer/detailedguide/breast-cancer-breast-cancer-types

National Cancer Institute Non-Hodgkin Lymphoma. (Retrieved February 6^th2015): https://www.cancer.gov/types/lymphoma

More patient information for this section is on this page.

Forward to section 5E male breast cancer. Back to 5C on papillary types.