Mammary Gland Mixed Cell Carcinomas

Overview

"Canine mammary tumors are the most common tumors in dogs and mainly affect middle-aged bitches. About 50% of the tumors are benign, with carcinomas constituting 40-45% of the malignant tumors. About 30% of carcinomas and 75% of sarcomas give rise to metastases." Eva Hellmen "The Pathogenesis of canine mammary tumors"

What is mixed is the type of cell that makes up the tumor: the epithelial cells that line the glandular tissue and the mesenchymal cells that make up the non-glandular portion. (Mixed does not refer to a mix of benign and malignant cells.) The mixed tumor can be either benign or malignant and the biopsy will indicate this. With a mixed cell carcinoma, either the epithellal or mesenchymal is abdormal, not both as seen in the carcinosarcoma.

Unspayed females have a fairly high chance (40%) of developing benign or malignant tumors of their mammary glands. If they were spayed before their first estrus (heat cycle), they have a 0.05% chance of development a mammary tumor. After their first heat cycle the risk is around 8%. After their second heat, the risk increases to 25%. You need to check your dogs mammary glands frequently.

Symptoms

Carcinomas generally develop rapidly, and they are detected by the owner in 26 months.

Canine mammary tumor usually appears as a single lump, a solid mass, or as multiple swellings in the mammary gland. They are easy to detect by palpating the gland. The tumor can feel soft or firm, could feel moveable or fixed to the skin or underlying tissue. You may notice a color change (red to purple). It can also become ulcerated. They can occure with or without the involvement of nipples. Some grow slow, others grow much faster. Since early treatment is so important in survival, if you feel anything suspious see your vet immediatly.

Female dogs typically have 5 sets of mammary glands - (10) nipples.
Starting at the top (towards the head)
  • row 1 is cranial thoracic
  • row 2 is caudal thoracic
  • row 3 is crandial abdominal
  • row 4 is caudal abdominal
  • row 5 is inguinal (this row is cloest to the groin).

Tumors can occur in any row. The normal glands should be soft, and pliant, especially towards the rear legs. About 70% of tumors occur in the caudal (row 4 and 5) mammary glands. Approximately 40% of all mammary tumors are located in the inguinal mammary glands and appear shortly after estrus. Tumors are found in glands 4 and 5, probably due to the more abundant parenchyma at this level. The most common types are tumors from the glandular tissues and include adenoma, carcinoma, and adenocarcinoma.

Because estrogen exposure over a lifetime promotes tumor growth, it is not uncommon to find more than one tumor. The key to successful treatment is to catch and treat these tumors early.

Diagnosis

The sooner you take your dog to the vet the better chance of having a good prognosis. They will start of with an exam. The two most common sites of metastases are lungs and regional lymph nodes. They can also spread to the liver and spleen. The exam will include evaluation of regional lymph nodes by palpation, exam the mass and the other mammary glands (50% of the time there is more than 1), complete blood count (CBC), blood panel, urinalysis, chest x-rays and an abdominal ultrasound. These test will be looking for metatisis as well as evaulating the overall health of you dog.

They may or may not take a fine need aspiration of the mass(es). Fine needle aspirates can tell if it is inflammation, a cyst, or an abnormal mass. Their accuracy can vary by the skill of the vet, as well as just a small sample is taken and observed. In most cases, a fine needle aspirate can not accuratly distinguish begnign from malignant tumors. Various test studies have showen rates from 60 to 80% accuracy, with many variables though. The only way to know for sure is to have the tumor removed and sent in for evaluation.

Histological evaulation of the biopsy remains the standard in recommendatoins for mammary tmor diagnosis.

Treatment

Surgical removal is the most effective way to deal with mammary tumors. Through testing, findings have been to help the surgeron know to remove the mass (typcally with 1-2cm margins), and/or affected lymph node(s).

Approximately 50% of malignant mammary tumors in the dog have receptors for either estrogen or progesterone. This means that the presence of these female hormones promotes the growth of these tumors. Benign tumors also have female hormone receptors and can also be stimulated by hormonal cycling of the female dog. This means that spaying is important even if a tumor has already developed; in one study, female dogs spayed at the time of mammary tumor removal or two years prior lived 45% longer than those who remained unspayed.

If surgery is successful, with clear histologic margins, and the patient has no evidence of lymph node involvement or metastasis, chemotherapy is not recommended. Chemotherapy does not seem to be effective when dealing with metastasis in this case.

After the tumor is removed, you will be told what type of cancer, the grade, and the prognosis. Most of the time it ends up in a keep a close eye on them, and hope it don't metastasis or reacure. Other tumors can show up not related to the first one as well. Each of those need to be examed by your vetrainian.

Staging

In order to incorporate prognostic factors, reclassification of canine mammary carcinoma has been attempted with statistical backups This staging is based on the size of the primary tumor, presence/absence of tumor metastasis to regional lymph nodes, and presence/absence of distant metastasis (Table 1). The greater the stage, the poorer the prognosis. Example: Dogs with smaller (less than 5 cm in diameter) malignant tumors have a better prognosis for long-term survival. Metastasis is observed in about half of malignant tumor cases. The definitive diagnosis is based on histopathology on excisional biopsy specimens. In addition to histological classification, WHO suggests tumor-node-metastasis (TNM) staging on canine mammary tumors to provide more practical prognostic information.

StageTumor SizeLymph NodeMetastasis
1< 3cm NoNo
23-5cm NoNo
3> 5cm NoNo
4AnyYesNo
5AnyYesYes


Another states features considered relevant to tumor grade include: cellular differenitation, and degree of invasiveness.

Histological StageFeaturesPrognosisProg. S simplified
1Lesions are non-infiltrative and resemble the tissue of origin. Tubular structures are evident High probability of surgical cureCurable
2Loss of tubular lumen and/or invasion of the surrounding stroma but no evidence of vascular or lymphatic invasionMedian survival time 380 days1 yr
3Presence of lymphatic or vascular invasionMedian survival time 108 days 3mths
4Evidence of metastasisMedian survival time 108 days3 mths


Grading

Grading of carcinomas refers to the employment of criteria intended to semi-quantify the degree of cellular and tissue maturity seen in the transformed cells relative to the appearance of the normal parent epithelial tissue from which the carcinoma derives.

Grade 1, or well differentiated: there is a close, or very close, resemblance to the normal parent tissue, and the tumor cells are easily identified and classified as a particular malignant histological entity;

Grade 2, or moderately differentiated: there is considerable resemblance to the parent cells and tissues, but abnormalities can commonly be seen and the more complex features are not particularly well-formed;

Grade 3, or poorly differentiated: there is very little resemblance between the malignant tissue and the normal parent tissue, abnormalities are evident, and the more complex architectural features are usually rudimentary or primitive;

Grade 4, or undifferentiated carcinoma: these carcinomas bear no significant resemblance to the corresponding parent cells and tissues, with no visible formation of glands, ducts, bridges, stratified layers, keratin pearls, or other notable characteristics consistent with a more highly differentiated neoplasm.

Positive points if you catch it early

It is not practical to biopsy all mammary masses, particularly those that are less than 1cm in diameter. For solitary small nodular masses, marginal 2mm excision will be diagnostic and may be curative.

The most important prognostic information is derived from the WHO staging system and histologic diagnosis. Size of the tumor is thought to be a good prognostic indicator. Dogs with smaller (less than 5 cm in diameter) malignant tumors have a better prognosis for long-term survival. Metastasis is observed in about half of malignant tumor cases.

Early surgical intervention and the method of surgery play important roles in prolonging survival.

Dogs with smaller (less than 5 cm in diameter) malignant tumors have a better prognosis for long-term survival.

Surgery for tumors that are low-to-intermediate grade carcinomas, have not spread, and are less than 3 cm is often curative.

This means that spaying is important even if a tumor has already developed; in one study, female dogs spayed at the time of mammary tumor removal or two years prior lived 45% longer than those who remained unspayed.

It is not practical to biopsy all mammary masses, par ticularly those that are less than 1 cm in diameter. For solitary small nodular masses, marginal (2 mm) excision will be diagnostic and may be curative

For small lesions (<1 cm diameter) it would be hard to justify the expense of radiography or ultrasonography, as the likelihood of malignancy is so low.

Histologically confirmed complete resection of canine mammary tumours should only be regarded to be likely to be predictive of clinical cure in cases of benign or histological stage 1 malignant cases.



Other Details

Mammary tumours are classified first according to their tissue of origin and whether they are benign or malignant. Originating tissues include glandular (adenoma/adenocarcinoma), ductular (papilloma/carcinoma), myoepithelial and pluripotential(mixed) cells, though some uncertainty about the histogenetic origin of many mammary tumour types remains.

Carcinoma is characterized by intact myoepithelial cell layer and basement membrane, and proliferation of epithelial cells. Normal breast duct is composed of a layer of epithelial cells and a layer of myoepithelial cells separated from the stroma by a basement membrane.

Carcinoma in a mixed tumor: Epithelial and mesenchymal tissue, one is neoplastic (abnormal)

What is mixed is the type of cell that makes up the tumor: the epithelial cells that line the glandular tissue and the mesenchymal cells that make up the non-glandular portion. (Mixed does not refer to a mix of benign and malignant cells.) The mixed tumor can be either benign or malignant and the biopsy will indicate this.

carcinoma is a cancer that begins in a tissue that lines the inner or outer surfaces of the body, Epithelial cells => carcinoma

carcinomas can coexist with benign tumors in the same gland and/or the neighboring glands.

11.3CARCINOSARCOMA Go to:

Carcinosarcoma is a malignant mixed tumor, formed by epithelium-like cells (epithelial, myoepithelial or both cells type) and connective tissue-like cells. Histological structure varies widely, from one tumor to another. A high percentage (30%) of mixed tumors contains fusiform cells, which are considered to originate in myoepithelial cells or connective tissue. The osteosarcomatous component is considered to originate from enchondral ossification (secondary bone) and from fibrous cells, primary bone.

Infiltrative growth and lymphatic metastases occur more rarely; it seems that these aspects only involve the carcinomatous component, less the sarcomatous component. Histological differentiation of carcinosarcoma is required from benign mixed tumors, and is sometimes difficult (Fig. 11.24.).

Malignant mixed tumors grow more slowly than carcinomas, with limits from 1 month to 1 year or more, the majority during of at least 6 months. Some of the mixed tumors histologically diagnosed as benign can be potentially and evolutionally malignant.

Metastases in malignant mixed tumors usually appear under the form of carcinomas and exceptionally as osteosarcomas, chondrosarcomas or myoepitheliomas. Metastases have been found in the lymph nodes, lungs, liver, kidneys and exceptionally in other organs.

*Epithelial cells that line the glandular tissue. Epithelial tissues line the cavities and surfaces of structures throughout the body, and also form many glands - One oncolgist described them to me as the cells making up the mammary gland tissue. Mammary epithelial cells could grow out of control and eventually result

*Myoepithelial cells (sometimes referred to as Myoepithelium) are cells usually found in glandular epithelium as a thin layer above the basement membrane but generally beneath the lumenal cells. Only rare cancers like adenoid cystic carcinomas contains myoepithelial cells as one of the malignant components.

*Mesenchyme, or mesenchymal connective tissue, is a type of undifferentiated loose connective tissue. mesenchymal cells around the epithelial bud get secrecting factors activated by PTHrP, such as BMP4, can transform into a dense, mammary-specific mesenchyme, which later develop into connective tissue with fibrous threads, forming blood vessels and the lymph system.[7] Basement membrane, mainly containing laminin and collagen, formed thereafter by differentiated myoepithelial cells keeps the polarity of this primary duct tree.

*alveoli (hollow cavities, a few millimetres large) lined with milk-secreting cuboidal cells and surrounded by myoepithelial cells. These alveoli join up to form groups known as lobules, and each lobule has a lactiferous duct that drains into openings in the nipple. The myoepithelial cells can contract under the stimulation of oxytocin thereby excreting milk secreted from alveolar units into the lobule lumen toward the nipple, where it collects in sinuses of the ducts



http://www.ncbi.nlm.nih.gov/books/NBK9542/
http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/112300.htm
http://www.peteducation.com/article.cfm?c=2+2087&aid=460
http://en.wikipedia.org/wiki/Mammary_gland
http://en.wikipedia.org/wiki/Mammary_tumor
http://genesdev.cshlp.org/content/15/1/50.long
www.revmedvet.com/artdes-us.php?id=1802
Cytology of Malignant Mammary Gland Tumors - www.revmedvet.com/2010/RMV161_212_218.pdf
http://www.ncbi.nlm.nih.gov/books/NBK9542/
http://www.ncbi.nlm.nih.gov/books/NBK9542/
http://veterinarynews.dvm360.com/dvm/Medicine/Prognosis-treatment-of-canine-mammary-tumors/ArticleStandard/Article/detail/520483
https://www.addl.purdue.edu/newsletters/2007/Fall/FinalDX.html
https://docs.google.com/viewer?a=v&q=cache:fWZOshjkd_kJ:www.vetcares.com/newsroom/wp-
content/uploads/canine_mammary_carcinoma.pdf+&hl=en&gl=us&pid=bl&srcid=ADGEESgYdJ3wv9J7vTA02CI11m5CmDpRlPlTaCB-Vk-
StHOB0YstSvvSs0qpo00MNDE3UquoxAtz0XGNaNN4I06ZIs82TcsTL7qlhggvL1ItY3EwXaHqx6yLHDXtw-vGUhlynnCzgfDV&sig=AHIEtbSxy6uBkys6-3Oa3oQiNwiH98C7ow
http://viplaserclinic-mauritius.com/breast_cancer
http://www.hindawi.com/journals/ijbc/2012/574025/
aleksabokarev.narod.ru/foreignarticle2/6.pdf
http://en.wikipedia.org/wiki/Mesenchyme
  Follow us on Facebook!
Terms of Use :: Site Map :: All Rights Reserved :: a Gruseldog Design
The purpose of this database is to provide online access to a Doberman registry/pedigree that aims to further gather and provide information that may help researchers in understand more about genetic health issues effecting our beloved Dobermans.
Member's Area: Submit Data :: Search Database