Metaplasia means ‘change in form’.

It is the reversible replacement of one differentiated

cell type with another differentiated cell type. It causes precursor cells to change their cell fate,
and do not change existing differentiated cells.

Our internal body system is constantly at work and innumerable activities such as cell
division, repairing damage cells, building new cells, exchange and breakdown of energy as well
as transformation of tissues and cells in various types owing to different chemical reactions are
going on in a non ceasing manner. Some such changes are beneficial for our body whereas some
might create problems. Metaplasia too is a natural process which can be beneficial or
problematic depending upon whether it is normal or abnormal.

Metaplasia usually occurs in response to chronic irritation and inflammation and allows for
substitution of cells that are better able to survive under circumstances in which a more fragile
cell type might succumb. It may represent an adaptive substitution of cells that are sensitive to
stress by cell types better able to withstand the adverse environment. The process is usually
reversible, mostly when the stimulus for metaplasia is removed or treated.

Examples:
Squamous Metaplasia
Apocrine Metapasia
Oncocytic Metaplasia
Intestinal Metaplasia
Pyloric Metaplasia
Osseous Metaplasia
Tubal Metaplasia

Metaplasia and Carcinogenesis:

Metaplasia is not synonymous with dysplasia and is not considered as directly
carcinogenetic. However, the factors that predispose to metaplasia, if persistent, may
induce malignant transformation in metaplastic epithelium. Thus, the common form of cancer in
 the respiratory tract is composed of squamous cells, which arise in areas of metaplasia of the
normal columnar epithelium into squamous epithelium.

Metaplasia Common Causes:

 Cigarette Smoking
 Body being exposed to harmful radiation.
 When the person is experiencing myelodysplasia myelodysplastic syndrome.
 When the person is having a chronic type of myelogenous leukemia.
 When the person has polycythemia Vera.
 When the person is suffering from several bone marrow disorders.
 When the person is suffering from a disease called myeloproliferative.
 When the person is suffering from primary myelfibrosis.
 When the person is having chemotherapy for cancer.

Metaplasia General Symptoms:

 Anemia
 Difficulty in breathing. The person is only having short breathes.
 The person is feeling fatigue.
 The person’s immune system is weakening.
 The person is prone to different types of infection.
 The person is over stressed.
 Bleeding.
 The person is developing larger spleens.
 The person is likely to sweat a lot during night time.
 The person suddenly feels drastic weight loss.
 The person suddenly feels bone and joint pains.

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Metaplasia At Different Locations In Human Body:

Every cell in our body has its own responsibilities and functions to do in order for the body
to function well and be healthy at the same type. If the cell changes and they go back to its
normal state while being in the wrong place, this may cause harmful effects on the human body,
and it is also said to be one of the most common source of malignancy if they are left undetected
for a long time without proper medication.

Tissue Normal Metaplasia

Esophagus Squamous epithelium Columnar epithelium
Cervix Glandular epithelium Squamous epithelium
Urinary bladder Transitional epithelium Squamous epithelium
Airways Pseudostratified columnar Squamous epithelium
epithelium

Endometrial Epithelial Metaplasias:

The endometrial epithelial metaplasia refers to the process in which the surface and /or cryptic
epithelium is replaced by other cellular types which are either absent or very rarely seen at this
level. Hendrickson and Kempson first described this phenomenon in 1980.

The endometrial metaplastic changes may be the consequence of two processes:

 True metaplastic process, involving most frequently a phenomenon of mullerian

differentiation, in which the columnar epithelium can be replaced with a mucosecretory,
squamous or ciliated tubal epithelium
 Degenerative or regenerative /reparative processes with subsequent changes involving
either the surface (most frequently) or glandular epithelium.
Factors influencing endometrial epithelial metaplasia:

The endometrial epithelial metaplasias /changes arise almost always in certain conditions,
affecting more often either perimenopausal women or younger women with exogenous or
endogenous hyperestrogenism. These endometrial changes may be seen in association with a
dishormonal status (anovulatory cycle, polycystic ovaries) or with hormonal therapy (estrogens
or tamoxifen), in chronic endometritis or mechanical irritations (IUD); associated with
metroragy; associated with endometrial polyps or in endometrial hyperplasias and carcinomas.

Classification:

The most comprehensive classification of endometrial epithelial changes include metaplastic and
related endometrial changes grouped in 10 distinctive categories

1) Squamous /morular metaplasia

2) Mucinous metaplasia

3) Ciliated (tubal) metaplasia

4) Eosinophilic cell change

5) Hobnail cell change

6) Clear cell change

7) Secretory change

8) Surface sincitial change

9) Papilary proliferation

10) Arias Stella change

Barrett's esophagus

Barrett's esophagus is a serious complication of GERD, which stands for gastroesophageal

reflux disease. In Barrett's esophagus, normal tissue lining the esophagus changes to tissue that
resembles the lining of the intestine. About 10% of people with chronic symptoms of GERD
develop Barrett's esophagus

Risk Factors

It can only be diagnosed with an upper endoscopy and biopsy. Guidelines from the
American Gastroenterological Association recommend screening in people who have multiple
risk factors for Barrett’s esophagus. Risk factors include age over 50, male sex, white race, hiatal
hernia, long standing GERD, and overweight, especially if weight is carried around the middle.

A diagnosis of Barrett's esophagus is not a cause for major alarm. Barrett's esophagus,
however, can lead to precancerous changes in a small number of people and has an increased risk
for cancer.

Treatment
The most common treatment that will be advised by the doctor will be the methods to control
the reflux made by acids inside your body, surgical anti air flux therapy, and chemoprevention
tests.
Gastric Intestinal Metaplasia:

Gastric intestinal metaplasia is defined as the replacement of the surface, foveolar, and
glandular epithelium in the oxyntic or antral mucosa by intestinal epithelium. IM of the stomach
is associated with a very small increased risk of developing gastric cancer

Subtypes

As gastric intestinal metaplasia is heterogenous, several classification systems have been

proposed . The most widely used and clinically useful classification is based on the histologic
appearance with hematoxylin and eosin staining into the following subtypes:

Complete intestinal metaplasia is defined by the presence of small intestinal-type mucosa

with goblet cells, a brush border, and eosinophilic enterocytes.
Risk Factors
 Helicobacter pylori infection.
 High salt intake.
 Smoking.
 Alcohol consumption.
 Chronic bile reflux.
Treatment
For the intestinal metaplasia, where the person is likely to suffer from acids in the stomach,
the common treatment would be: antibiotics, proton pump inhibitors, endoscopy, and tests to
check the H Pylori in your body.

Cervical Metaplasia
It is usually an adaptive change that occurs in in reaction to chronic irritation, or in response
to hormonal stimuli. As the female goes through puberty and reaches maturation, hormonal
changes cause the cervix to avert, which in turn causes the fragile glandular epithelium to be
exposed to a harsher, more acidic environment in the vagina. A similar process occurs during
pregnancy.
  From birth until puberty, the endocervical epithelium is composed of columnar cells
and the ectocervical epithelium of native squamous cells. The interface between the
two is termed the original squamocolumnar junction.
 During puberty and at the first pregnancy the cervix increases in volume in response
to hormonal changes. The endocervical epithelium everts onto the ectocervix
exposing it to the acid pH of the vagina. This provides a stimulus for metaplastic
change of the columnar epithelium.
 The process of metaplasia is a patchy one: it starts initially in the crypts and at the tips
of the endocervical villae, which gradually fuse. Eventually the whole of the everted
endocervical epithelium may be replaced by squamous epithelium.

Clinical significance of squamous metaplasia in the cervix

In the cervix, the area of the epithelium that has undergone metaplastic change is called the
transformation zone. Numerous studies have shown that high-grade Cervical intraepithelial
neoplasia primarily involves the immature metaplastic epithelial cells of the TZ where most, if
not all cervical cancers arise.
Treatment

For the Squamous metaplasia, wherein the target is the cervix, the most common treatment
will depend on the smear test that will be conducted wherein most of the time, antibiotics and
other medications will be given in order to treat infection.

Breast Apocrine Metaplasia

Apocrine Metaplasia is a particular kind of cellular change associated with a variety of

breast cystic disorders. It is a completely benign condition which in itself does not increase risk
for subsequent breast cancer. Apocrine metaplasia is sometimes described as a
‘benign epithelial alteration’ of breast tissue, which means that epithelial cells are undergoing an
unexpected change

Apocrine metaplasia is believed to arise from the lobular cells located in the terminal
ductal-lobular units (TDLU) of the breast. Usually, these metaplasic cells will show up in the
epithelial lining of breast cysts which are developing or have already developed.

Incidence Of Apocrine Metaplasia

Apocrine Metaplasia is most commonly associated with older, post menopausal

women.Microscopic apocrine metaplasia is not uncommon with women in their 30s, but
generally speaking the condition is associated with older, post-menopausal women, and is most
common in women in their 50s. By the time women reach their 80s and 90s, about 50% will
have developed apocrine metaplasia.

Agnogenic Myeloid Metaplasia

Agnogenic myeloid metaplasia usually develops slowly. It most often occurs in people 50
years old and older. Agnogenic myeloid metaplasia leads to progressive bone marrow failure
with severe anemia.Most people with agnogenic myeloid metaplasia become dependent on blood
transfusions for survival.

Symptoms
The most common symptoms of Agnogenic myeloid metaplasia are:
 Rapid heart beat
 Paleness
 Enlarged spleen
 Night sweats
 Weight loss
 Stuffed feeling after eating
Treatments options:
Medications can help treat Agnogenic myeloid metaplasia but an allogeneic stem cell
transplantation is needed for a cure
Bronchial Epithelial Metaplasia:
When an air passage is irritated like from smoking or infection, the cells lining it can
change from being like rectangles standing up next to each other to be flatter and stacked on top
of each other. This change is called squamous metaplasia . When the irritation disappears, for
example when you stop smoking or the infection clears, the lining cells return to their normal
appearance.
Chronic Obstructive Pulmonary Disease (COPD) is associated with bronchial epithelial
changes, including squamous cell metaplasia and goblet cell hyperplasia. These features are
partially attributed to activation of the epidermal growth factor receptor (EGFR). Whereas
smoking cessation reduces respiratory symptoms and lung function decline in COPD,
inflammation persists.

Risk Factors
In the habitual cigarette smoker, the normal ciliated columnar epithelial cells of the trachea
and bronchi are often replaced focally or widely by stratified squamous epithelial cells.
Deficiency of vitamin A (retinoic acid) induces squamous metaplasia in the respiratory
epithelium.Although the metaplastic squamous cells in the respiratory tract, for example, are
capable of surviving, an important protective mechanism-mucus secretion-is lost.
Connective Tissue Metaplasia
It is the formation of cartilage, bone, or adipose tissue in tissues that normally do not contain
these elements.
 Bone formation in muscle, designated myositis ossificans, occasionally occurs after bone
fracture. This type of metaplasia is less clearly seen as an adaptive response.
 In synovial chondromatosis, cells of the synovial membrane undergo metaplasia to
become cartilage-producing chondrocytes.

Mechanism Behind Metaplasia:

Metaplasia does not result from a change in the phenotype of a differentiated cell type;
instead it is the result of a reprogramming of stem cells that are known to exist in normal tissues,
or of undifferentiated mesenchymal cells present in connective tissue. In a metaplastic change,
these precursor cells differentiate along a new pathway.

 The differentiation of stem cells to a particular lineage is brought about by signals

generated by cytokines, growth factors, and extracellular matrix components in the cell’s
environment. Tissue-specific and differentiation genes are involved in the process, and an
increasing number of these are being identified.
 Bone morphogenetic proteins (BMPs), members of the TGF-β superfamily, induce
chondrogenic or osteogenic expression in stem cells while suppressing differentiation
into muscle or fat. These growth factors, acting as external triggers, then induce specific
transcription factors that lead the cascade of phenotype-specific genes toward a fully
differentiated cell.
 In the case of vitamin A deficiency or excess, it is known that retinoic acid regulates cell
growth, differentiation, and tissue patterning and may thus influence the differentiation
pathway of stem cells.
 Certain cytostatic drugs cause a disruption of DNA methylation patterns and can
transform mesenchymal cells from one type (fibroblast) to another (muscle, cartilage).
Interesting Research Regarding Metaplasia:
Study conducted by a group of Chinese scientists published in American Journal of
physiology in 2011 , comprising affects of Human AM that was obtained at the time of a
Cesarean section from a healthy human placenta on ocular surface squamous epithelium
metaplasia. There is no effective treatment for this abnormality. In the study, they established an
ex vivo conjunctival squamous metaplasia model by culturing human conjunctival tissues at an
air-liquid interface for durations of up to 12 days. Then, they investigated the effects of amniotic
membrane (AM) on squamous metaplasia through coculture of conjunctival tissues with AM or
AM extract. They found that metaplasia features such as hyperproliferation and abnormal
epidermal differentiation of conjunctival epithelium could be inhibited by AM or its extract.
In addition, existing squamous metaplasia of conjunctival epithelium could be reversed to
a nearly normal phenotype by AM. The mechanism by which AM prevents squamous metaplasia
may involve downregulation of p38 mitogen-activated protein kinase and Wnt signaling
pathways, which were activated in conjunctival explants cultured with an airlift technique. In
conclusion, AM can inhibit and reverse squamous metaplasia of conjunctival epithelium. This
finding may shed new light on prevention and treatment of diseases that involve epithelial
squamous metaplasia.

References

Slack, J.M. 2007. Metaplasia and transdifferentiation: from pure biology to the clinic. Nat Rev
Mol Cell Biol., 8(5):369-78.
Lugo, M. and P.B Putong, 1984. Metaplasia: an overview.Arch Pathol Lab Med., 108:185.

Tosh D and Slack J.M, 2002. How cells change their phenotype:Nat Rev Mol Cell Biol., 3:187.

Firoiu, C., C. Simionsecu, D. Stanculescu, F.Cheznoiu and A.Stepan., 2009. Histopathological

Study of Epithelial Metaplasias in Endometrial Hyperplasia:Current Health Science Journal.,
53(1).

MedlinePlus Medical Encyclopedia:"Barrett's esophagus."

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