Hyperplasia Uterus Causes and Diagnosis

Hyperplasia Uterus

Cells can respond to excessive physiologic stresses or pathologic stimuli by undergoing a number of physiologic and morphologic cellular adaptations, in which a new but altered steady state is achieved, preserving the viability of the cell and modulating its function as a response to such stimuli.

Some of these adaptations involve changes in cellular growth, size, or differentiation and include:

• Hyperplasia is an increase in cell number
• Hypertrophy, an increase in cell size
• Atrophy is a decrease in the size and function of cells
• Metaplasia and dysplasia, an alteration of cell differentiation.

Diagnosis of cancer Hyperplasia

It is an increase in the number of parenchymal cells which results in the enlargement of organs or tissue.

Hyperplasia Causes:

• Physiologic hyperplasia: It is of two types
  • Hormonal hyperplasia: It occurs under the influence of hormonal stimulation, e.g. hyperplasia of the female breast during pregnancy, puberty, and lactation; prostatic Hyperplasia in old age.
  • Compensatory hyperplasia: Hyperplasia occurs the removal of a part or an organ, For Example. regeneration of the liver following partial hepatectomy, regeneration of skin epidermis after, skin abrasion.
• Pathologic hyperplasia: It is due to excessive stimulation of hormones or growth factors, For Example. endometrial hyperplasia following estrogen excess. In wound healing, there is the formation of granulation tissue due to the proliferation of fibroblasts and endothelial cells.

Diagnosis of cancer Hypertrophy

It is the increase in the size of parenchymal cells resulting in the enlargement of organs or tissue without any change in the number of cells.

Hypertrophy Causes

• Physiologic: The best example is the enlarged size of the uterus in pregnancy.
• Pathologic: Examples of certain diseases which are associated with hypertrophy are—hypertrophy of cardiac muscles in aortic valve disease and hypertrophy of smooth muscles in pyloric stenosis.

Diagnosis of cancer Atrophy

Reduction in the number and size of parenchymal cells of an organ or its parts is known as atrophy.

Atrophy Causes

• Physiologic: Atrophy is a normal process of aging in some tissues which could be due to loss of endocrine stimulation or arteriosclerosis, e.g. atrophy of lymphoid tissue in lymph nodes, or atrophy of the brain.
• Pathologic: Causes are:
  • Starvation atrophy: There is a depletion of carbohydrates and fat stores followed by protein catabolism, for example, in Cancer and severely ill patients.
  • Ischemic atrophy: Gradual diminish in blood supply lead to shrinkage of the affected organ, e.g. atrophic kidney in atherosclerosis, atrophy of the brain in cerebral atherosclerosis.
  • Disuse atrophy: Prolonged diminish functional activity is associated with disused atrophy of organs, for example, the Wasting of muscles of a limb immobilized in a cast.
  • Neuropathic atrophy: Interruption of nerve supply lead to wasting of muscles, e.g. poliomyelitis
  • Endocrine atrophy: Loss of endocrine regulatory mechanism lead to reduced metabolic activity of tissues and lead to atrophy, for example, Hypopituitarism lead to atrophy of the thyroid, adrenals, and gonads.
  • Pressure atrophy: Prolonged pressure from benign tumors or cysts may cause compression and atrophy of tissues, For Example. erosion of the spine by a tumor in the nerve root.
  • Idiopathic atrophy: In this causes are not defied, e.g. myopathy and testicular atrophy.

Diagnosis of Cancer Metaplasia

• Meta means transformation and plasma means growth.
• Metaplasia is defined as a reversible change of one type of epithelial or mesenchymal adult cells to another type of adult epithelial or mesenchymal cells usually in response to an abnormal stimulus.

Metaplasia is divided into two types:

• Epithelial
• Mesenchymal.

Epithelial Metaplasia

• This is a more common type.
• The metaplastic change may be patchy or diffuse. Some common types of epithelial metaplasia are:

Squamous metaplasia:

There is the transformation of various types of epithelium into squamous epithelium due to chronic irritation.

• In bronchus (normally lined by stratified columnar ciliated epithelium) in chronic smokers.
• In the gallbladder, in prostrate in chronic prostatitis.

Columnar metaplasia:

There is the transformation of various epitheliums into columnar epithelium.

• Intestinal metaplasia in healed chronic gastric ulcer.
• Conservation of pseudostratified columnar epithelium into chronic bronchitis to columnar type.

Mesenchymal Metaplasia:

There is the transformation of one adult type of mesenchymal tissue into another.

Osseous metaplasia:

Osseous metaplasia is the formation of bone in fibrous tissue, cartilage, and myeloid tissue.

• Arterial wall in old age
• In the fibrous stroma of the tumor.
• In cartilage of larynx and bronchi in old age.
• Cartilaginous metaplasia: In the healing of the fracture.

Diagnosis of cancer Dysplasia:

Dysplasia means “disordered cellular development”.

• It is also referred to as atypical hyperplasia.
• Dysplasia occurs most often in epithelial cells.
• Epithelial dysplasia is characterized by cellular proliferation and cytological changes.
• These changes include:
  • Increased number of layers of epithelial cells.
  • Disorderly arrangement of cells.
  • Loss of basal polarity, i.e. nuclei lying away from the basement membrane.
  • Cellular and nuclear pleomorphism.
  • Increased N: C ratio.
  • Nuclear hyperchromatism.
  • Increased mitotic activity.
• Dysplasia occurs due to chronic irritation or prolonged inflammation.
• Dysplasia progresses into carcinoma.
• The two most common examples of dysplastic changes are:
  • Uterine cervix and respiratory tract.

Investigations for Diagnosis of Cancer

1. Histological Methods

Paraffin Embedding Technique:

• Histological methods are based on microscopic examination of properly fied tissue supported with complete clinical and investigated data.
• A biopsy of the lesion is done and tissue is filled in 10% formalin and processed in a tissue processor get paraffin-embedded, cryostat machine is employed and is examined under a light microscope.
• Histological diagnosis is made on the basis that cytological features of benign tumors resemble normal tissue and they are unable to invade and metastasize while malignant tumors are identified by lack of differentiation in cancer cells known as cellular atypia and these tumors may invade and metastasize.

Frozen Section:

• In this technique, an unfied tissue is used and the procedure is generally carried out when the patient is undergoing surgery and is still under anesthesia. Here, instead of a tissue processor and paraffin embedding, a cryostat machine is employed and fresh unified tissue is used.
• The tissue biopsy is quickly frozen to the ice at about —25°C acts as an embedding medium and then sectioned. Sections are then ready for rapid H & E or toluidine blue staining.
• A frozen section is a rapid intraoperative diagnostic procedure for tissues before proceeding to major radical surgery or may be used to know the extent of the presence of cancer at the surgical margin.

2. Cytological Methods

In cytological methods, there is the study of cells that shed off into the body cavities.

The following are the cytological methods:

Exfoliative Cytology: In this method, microscopic identification of characteristics of malignant cells which are incohesive and loose and shed off or exfoliated is done.

Findings in exfoliative cytology:

• Class 1 (Normal): It indicates that only normal cells are present in the smear.
• Class 2 (Atypical): It indicates the presence of minor cellular atypia.
• Class 3 (Intermediate): This is in-between cytology that separates cancer from non-cancer diagnosis, the cells which display wider atypia are suggestive of cancer. A biopsy is recommended for further diagnosis.
• Class 4 (Suggestive Cancer): It indicates that in the lesion there is the presence of few cells with malignant characteristics. A biopsy is mandatory.
• Class 5 (Positive of Cancer): The cells exhibit definite features of malignancy. A biopsy is mandatory.

Fine Needle Aspiration Cytology: It is the method in which there is the study of cells are obtained by a fine needle introduced under vacuum into the lesion and is called fine needle aspiration cytology.

As aspiration is done, the smear is made and it is filled in 95% ethanol. PAP staining is done on the field smear and is diagnosed under a light microscope. The presence of dysplastic cells is suggestive of cancer. This method has diagnostic reliability between 80 and 97%.

3. Histochemistry and Cytochemistry:

Histochemistry and cytochemistry are additional diagnostic tools that help the pathologist in identifying the chemical composition of cells, their constituents, and their products by special staining methods.

Some of the common examples are:

4. Immunohistochemistry:

• This is an immunological method of recognizing a cell by one or more of its specific components in the cytoplasm, cell membrane, or nucleus. These cell components (called antigens) combine with specific antibodies on the formalin-fixed paraffin sections or cytological smears.
• The complex of antigen-antibody on the slide is made visible for light microscopic identification by either florescent dyes (’ fluorochromes) or by enzyme system (’chromogens’).
• The specific antibody against a particular cellular antigen is nowadays obtained by the hybridoma technique for monoclonal antibody production.
• These monoclonal antibodies, besides being specific against antigens, are highly sensitive in the detection of antigenic components, and, therefore, impart objectivity to the subjective tumor diagnosis made by the surgical pathologist.

Immunohistochemistry Uses

• Categorization of undifferentiated neoplasms
• Specific typing of leukemias/lymphomas
• Determination of the site of origin of a metastatic tumor
• Detection of molecules that have prognostic or therapeutic significance
• Expression of protein products of oncogenes
• Differentiating benign from malignant lesions.

5. Intermediate Filaments:

• Intermediate filaments are a family of related proteins that share common structural features. They have an average diameter of 10 nanometers, which is between that of microfilaments (which are smaller) and microtubules (which are larger).
• Most types of intermediate filaments are cytoplasmic except lamins, which are unclear. The most important function of intermediate filaments is to provide mechanical support for the plasma membrane. Where they come in contact with other cells or with the extracellular matrix. Unlike microfilaments and microtubules

Intermediate filaments and their significance in the diagnosis of tumor

6. Electron Microscopy:

By electron microscopy confirmation of the tumor, diagnosis is done which is arrived by light microscopy and immunohistochemistry. Some of the features of malignant tumors by electron microscopic examination are:

• Cell junctions—their presence and type Cell surface For Example. presence of microvilli
• Cell shape and cytoplasmic extensions
• Nucleoli-size and density
• Cytoplasmic organelles—their number is reduced.

7. Tumor Markers:

• Tumor markers are biochemical assays of products elaborated by tumor cells in blood or other body fluids.
• These methods lack sensitivity and specificity and are only used as an adjunct to pathological diagnosis arrived at by other methods and not for primary diagnosis of cancer.
• Secondly, it is used for prognostic and therapeutic purposes, For Example. are alpha-fetoprotein for hepatocellular carcinoma and carcinoembryonic antigen for breast cancer.

Modern Aids in Tumor Diagnosis:

• Flow Cytometry:
  • This is a computerized technique by which the detailed characteristics of individual tumor cells are recognized and quantified and the data can be stored for subsequent comparison too.
  • Since for flow cytometry single cell, suspensions are required to ’ flow’ through the ’cytometer’, it can be employed on blood cells and their precursors in bone marrow aspirates and body fluids, and sometimes on fresh frozen unfixed tissue.
  • The method employs either identification of cell surface antigen or DNA content analysis.
• In situ hybridization:
  • This is a molecular technique by which nucleic acid sequences (cellular/viral DNA and RNA) can be localized by specifically—labeled nucleic acid probe directly in the intact cell (in situ) rather than by DNA extraction (see below).
  • situ, hybridization may be used for the analysis of certain human tumors by the study of oncogenes aside from its use in the diagnosis of viral infection.
• Cell Proliferation Analysis: Besides flow cytometry the degree of proliferation of cells is determined by various other methods, i.e.
  • Mitotic count: It is the oldest method. A number of cells in mitosis are counted as per high power field, for example,  In categorizing various smooth muscle cells.
  • Radioautography: In this method, proliferating cells are labeled in vitro with thymidine and then the tissue is processed for paraffin embedding. Thymine-labeled cells are then counted per 2000 tumor cell nuclei and expressed as a thymine labeling index. It is employed as a prognostic marker in breast carcinoma.
  • Microspectrophotometric analysis: The section is stained with Feulgen reaction which imparts staining to the DNA content of a cell, then DNA content is measured by microspectrophotometry. It has limited usage.
  • IHC proliferation markers: Nuclear antigen is specific for cell growth and division and is stained by immunohistochemical method and then positive cells are counted under a microscope or by an image analyzer.
  • Nucleolar organizer region: Nucleolus contains ribosomal components which are formed at chromosomal regions containing DNA called NORs. NORs have an affinity for silver.
• Image Analyzer and Morphometry:
  • An image analyzer is a software system in a computer attached to a microscope that is a field in an image capture board. It performs measurements of architectural, cellular, and nuclear features of tumor cells. It can be used for the following purposes, i.e.
  • Morphometric study of tumor cells by measurement of architectural, cellular, and nuclear features.
  • Quantitative DNA nuclear DNA ploidy measurement.
  • Quantitative valuation of immunohistochemical staining.
• Molecular diagnostic techniques:
  • The group of molecular biologic methods in the tumor diagnostic laboratory are a variety of DNA/RNA-based molecular techniques in which the DNA/RNA are extracted (compared from in situ above) from the cell and analyzed.
  • These techniques are highly sensitive, specialized, and rapid and have revolutionized diagnostic pathology in neoplastic as well as non-neoplastic conditions. Molecular diagnostic techniques include DNA analysis by Southern blot, RNA analysis by Northern blot, and polymerase chain reaction (PCR).
• DNA microarray analysis of tumors:
  • Currently it is possible to perform molecular profiling of a tumor by use of gene chip technology which allows measurement of levels of expression of several thousand genes (up-regulation or down-regulation) simultaneously. Fluorescent labels are used to code the cDNA synthesized by a trigger from RNA.

The conventions of DNA probes are substituted by a silicon chip which contains the entire range of genes and high-resolution scanners are used for the measurement.