Abberant Cell Growth

Introduction to Aberrant cell
growth
Mehdi Hayat Khan
Senior Nursing Instructor
BSN,M.Phil Physiology,MSN*
mehdisnc05@gmail.com
Objectives
By the end of this session the learners will be able to,
• Define the characteristics of the normal cell
• Describe the characteristics if the cancer cells
• Discuss the predisposing factors of the aberrant cell
growth
• Differentiate between malignant and benign tumor
• Describe the TNM system
• Explain proto oncogene and anti oncogene.
Copyright © 2017 by Mehdi Hayat Khan

Homeostasis
• The “steady state” that cell exists in normally.
• An equilibrium of the cells with their environment for

adequate function.

Normal cell
• Cells are the smallest functional unit of the body
• They contain structures that are strikingly similar to
those needed to maintain total body function
• The nucleus is the control center for the cell. It also
contains most of the hereditary material.
• The organelles, which are analogous to the organs of the
body, are contained in the cytoplasm.
• The cell membrane encloses the cell and provides for
intracellular and intercellular communication, transport
of materials into and out of the cell.

Characteristics of the Normal cell
• Normal body cells have a number of important
characteristics.
• They can Reproduce themselves exactly
• Stop reproducing at the right time
• There is proper cell communication in between the cells
• Stick together in the right place
• Self destruct if they are damaged
• Become specialized or 'mature

Normal cell cycle

Cellular Adaptation
Cellular adaptation refers to changes made by a cell in
response to adverse environmental change
The adaptation may be
• physiologic(al) (normal)
• Pathologic(al) (abnormal)
Adaptation can involve:
✓ change in cell size or number
✓ change to different type of cell

On application of Stress
Stress, ADAPTATION
demand
NORMAL Fails to
CELL adapt
Injurious
stress CELL INJURY
CELL DEATH

NORMAL <--->ABNORMAL
Cellular Adaptations
• Atrophy • Metaplasia: simple
• Hypertrophy columnar to stratified
squamous (lungs)
• Hyperplasia • Dysplasia: some loss of

control as in cervix

Types of Cellular Adaptation
Types of adaptation:
1. Atrophy
2. Hypertrophy
3. Hyperplasia
4. Dysplasia
5. Metaplasia.

TYPES OF ADAPTATION

Atrophy: (cells shrink)
• Muscle atrophy is defined as a decrease in the mass of
the muscle;
•  workload or adverse environmental conditions
– Is adaptive and reversible
– results in a decrease in cell size
• Types and Causes
– Disuse atrophy (paralysis)
– Ischemic atrophy (kidney, heart)
– Malnutrition atrophy (starvation)
– Loss of endocrine stimulation (uterine, breast)
– Denervation
– Senile Atrophy (old age)

HYPERTROPHY:( size of cells)
o In the size of cells which results in enlargement of the
organs , without any change in the no. of cells
o  workload requirement of an organ part

o Results in an increase in tissue mass
o Seen in cardiac, skeletal, and muscle tissue
o May be a normal physiologic response
o as seen in an increase in muscle size with exercise
o May be a pathological response as in myocardial
hypertrophy from HTN or valve disease.

HYPERPLASIA:( # of cells)
• Occurs due to a response from appropriate stimulus and
ceases when stimulus is removed
– An increase in NUMBER of cells
• Restricted to cells capable of mitosis
• Physiological hyperplasia
– uterus and breast enlarge in pregnancy

METAPLASIA
o Transformation or replacement of one adult cell type to
another adult cell type (e.g., the change from columnar
to squamous cells in respiratory tract, from squamous to
columnar in Barrett esophagitis).
o With continued smoke exposure, ciliated columnar cells
are changed to stratified squamous cells
o Metaplastic changes usually result from chronic
irritation.
o Metaplastic changes seem to the development of cancer,
in some instances.

DYSPLASIA:(ATYPICAL HYPERPLASIA)
• Deranged cell growth resulting in cells of varying size, shape,
and appearance
– May be associated with chronic irritation or inflammation
– May be reversible if offending agent is removed
• Dysplasia is considered A STRONG PRECURSOR OF CANCER!!!
– Example: Cervical dysplasia
– However, dysplasia is an adaptive process – may or may
not lead to cancer
• Decrease risk if irritation is removed or inflammation
treated.

Important Terminology
• Anaplasia: cells that lack normal cellular characteristics
and differ in shape and organization with respect to their
cells of origin; usually, anaplastic cells are malignant
• apoptosis: programmed cell death
• Oncology: Branch of medicine that deals with the study,
detection, treatment and management of cancer

Aberrant cell Growth
Mehdi Hayat Khan

Senior Nursing Instructor
BSN,M.Phil Physiology,MSN*
mehdisnc05@gmail.com
Cancer
• A disease resulting from the uncontrolled
growth of cells, which causes malignant
cellular tumors.
• The second leading cause of death in
developed countries.

Cancer cells Cancer (Neoplasia)
• Cancer is a disorder of altered cell differentiation and
growth.
• The resulting process is called neoplasia, meaning “new
growth,” and the new growth is called a neoplasm.

Most Common Cancers
• In men, most common cancers are prostate, lung, and
colorectal.
• In women, they are breast, colorectal, lung, and uterine.

Etiology/ Risk Factors of cancer
• Heredity (A hereditary predisposition to approximately 50 types of
cancer has been observed in families. Breast cancer, for example,
occurs more frequently in women whose grandmothers, mothers,
aunts, or sisters also have experienced a breast malignancy)
• Hormones (Hormones have received considerable research
attention with respect to cancer of the breast, ovary, and
endometrium in women and of the prostate and testis in men)
• Immunological mechanisms (There is substantial evidence for
the immune system’s participation in resistance against the
progression and spread of cancer. The central concept, known as the
immune surveillance hypothesis)

• Chemical agents (chemical carcinogens can be divided
into two groups)
1. Direct-reacting agents, which do not require activation in the body
to become carcinogenic.
2. Indirect-reacting agents, called procarcinogens or initiators, which
become active only after metabolic conversion
• Radiations (The effects of ionizing radiation in carcinogenesis have
been well documented in atomic bomb survivors, in patients
diagnostically exposed, and in industrial workers, scientists, and
physicians who were exposed during employment).

4. Genetics and Family History
1. PHYSICAL AGENTS • Colon Cancer
– Radiation • Breast cancer
– Exposure to 5. Dietary Habits
• Low-Fiber
irritants
• High-fat
– Exposure to • Processed foods
sunlight • alcohol
2. CHEMICAL AGENTS 6. Viruses and Bacteria
• DNA viruses- Hepa B, Herpes,
– Smoking
EBV, CMV, Papilloma Virus
– Dietary • RNA Viruses- HIV,
ingredients • Bacterium- H. pylori
– Drugs 7. Hormonal agents
• DES
• OCP especially estrogen

Normal Tissue renewal
• Normal tissue renewal and repair involves cell
proliferation, differentiation, and apoptosis.

Proliferation
• Proliferation, or the process of cell division, is an inherent
adaptive mechanism for cell replacement when old cells
die or additional cells are needed.
• Cell proliferation is the process of increasing cell numbers
by mitotic cell division.
• In normal tissue, cell proliferation is regulated so that the
number of cells actively dividing is equivalent to the
number dying or being shed.
• In humans, there are two major categories of cells:
gametes and somatic cells.

Apoptosis
• Apoptosis is a form of programmed cell death that
eliminates senescent cells, cells with damaged DNA, or
unwanted cells.

Cell differentiation
• Cell differentiation is the process whereby proliferating
cells become progressively more specialized cell types.
This process results in a fully differentiated, adult cell that
has a specific set of structural, functional, and life
expectancy characteristics.
• For example, the red blood cell is a terminally
differentiated cell that has been programmed to develop
into a concave disk that functions as a vehicle for oxygen
transport and lives approximately 120 days.

Differentiation
Body cells can be divided into two large groups:
• The well differentiated neurons and cells of skeletal and
cardiac muscle that rarely divide and reproduce,
• Second is the progenitor or parent cells that continue to
divide and reproduce, such as blood cells, skin cells, and
liver cells.
• A third category of cells are the stem cells that remain
quiescent until there is a need for cell replenishment, in
which case they divide, producing other stem cells and
cells that can carryout the functions of differentiated
cells.

Differentiation
• Cells can be well differentiated, moderately
differentiated, or poorly differentiated Grade of the
cancer cell
• The more normal a cancer cell looks, the lower its grade,
• The more abnormal or less well developed a cancer cell is,
the higher its grade
• Low, medium or high grade. It is also called grades 1, 2, or
3, where grade 1 is low grade.

Characteristics of Cancer Cells
• Cancer cells are different to normal cells in several ways.
They don't die if they move to another part of the body
and
• Cancer cells don't stop reproducing (Unlike normal cells,
cancer cells do not stop reproducing after they have
doubled 50 or 60 times.

Characteristics of Cancer Cells
• Cancer cells don't obey signals from other cells
(Something in the cancer cells overrides the normal
signaling system.
• This may be because the genes that tell the cell to
reproduce keep on and on firing. Or because the genes
that normally tell the cell to stop reproducing have been
damaged or lost. So the cancer cell keeps on doubling,
regardless of the damage the extra cells cause to the part
of the body where the cancer is growing)
• Cancer cells don't stick together.
• Cancer cells don't specialize, but stay immature.

Tumors
• Tumor is a swelling that can be caused by a number of
conditions, including inflammation and trauma, but more
recently the term has been used to define a mass of cells
that arises because of overgrowth.
• Although not synonymous, the terms tumor and
neoplasm often are used interchangeably.

Tumor Growth
Once cells have an adequate blood supply, the rate of tissue
growth in normal and cancerous tissue depends on three
factors:
1. The number of cells that are actively dividing or moving
through the cell cycle,
2. The duration of the cell cycle, and
3. The number of cells that are being lost relative to the
number of new cells being produced. One of the
reasons cancerous tumors often seem to grow so
rapidly relates to the size of the cell pool that is actively
engaged in cycling.

Carcinogenesis
Malignant transformation, or carcinogenesis, is the process
by which carcinogenic (cancer-causing) agents cause normal
cells to become cancer cells is hypothesized to be a
multistep mechanism that can be divided into three stages:
1. Initiation,
2. Promotion
3. Progression

Carcinogenesis
Initiation: Involves the exposure of cells to appropriate
doses of a carcinogenic agent that makes them
susceptible to malignant transformation.)
– Mutation of genetic structure
– Has potential to develop into clone of neoplastic cells

Carcinogenesis
Promotion: involves the induction of unregulated
accelerated growth in already initiated cells by various
chemicals and growth factors. Promotion is reversible if
the promoter substance is removed.
– Characterized by the increased proliferation of altered
cells
– Latent period
• Initial genetic alteration to clinical evidence of
cancer.

Carcinogenesis
Progression (the process whereby tumor cells acquire
malignant phenotypic changes that promote
invasiveness, metastatic competence, autonomous
growth tendencies, and increased karyotypic instability)
– Characterized by increased growth rate of tumor as
well as its invasiveness and metastasis

Carcinogenesis

Proto oncogenes
• “Proto-oncogenes are a group of genes that cause normal cells
to become cancerous when they are mutated “(Adamson, 1987;
Weinstein & Joe, 2006).
• Mutations in proto-oncogenes are typically dominant in
nature,
• Mutated version of a proto-oncogene is called an oncogene.
• Often, proto-oncogenes encode proteins that function to
stimulate cell division, inhibit cell differentiation, and halt cell
death.
• All of these processes are important for normal human
development and for the maintenance of tissues and organs.

Oncogenes
• Oncogenes, however, typically exhibit increased
production of these proteins,
• Thus leading to increased cell division, decreased cell
differentiation, and inhibition of cell death; taken
together, these phenotypes define cancer cells.
• Thus, oncogenes are currently a major molecular target
for anti-cancer drug design.

Spread of Cancer
• Malignant disease processes have the ability to allow
the spread or transfer of cancerous cells from one organ
or body part to another by
1. Invasion
2. Metastasis

1. Invasion:
• Invasion, which refers to the growth of the primary
tumor into the surrounding host tissues, occurs in several
ways.
• Mechanical pressure exerted by rapidly proliferating
neoplasms may force fingerlike projections of tumor cells
into surrounding tissue and interstitial spaces.

2. Metastasis
• spread of cancer from primary (initial) site to distant
site
• Tumor cells travel through blood or lymph circulation
to other body areas and invade tissues and organs
there.
• Primary tumor: The original site of the malignancy
• Secondary tumor (sites): Areas where malignancy has
spread i.e. metastasis (metastatic tumor)
• Common sites of metastasis are lymph nodes, liver,
lungs, bones, brain.

2. Metastasis
• 50 – 60 % of tumors have metastasized by time
primary tumor identified
• Lymph(most common) and blood are key mechanisms
by which cancer cells spread.
• Angiogenesis

The steps of metastasis

Main Classifications of Cancer
• Lymphomas (cancers occurring in infection-fighting
organs, such as lymphatic tissue).
• Leukemia's (cancers occurring in blood-forming organs,
such as the spleen, and in bone marrow).
• Sarcomas (cancers occurring in connective tissue, such
as bone).
• Carcinomas (cancers occurring in epithelial tissue, such
as the skin).

Classification of the Tumor
• Neoplasm is an abnormal growth of tissue, and, when it
also forms a mass, is commonly referred to as a tumor
• Types of Neoplasm
1. Benign
2. Malignant

Malignant and Benign

Cancer Prevention and Detection
1. Primary Prevention
2. Secondary Preventions

• Reduce or avoid exposure to known or suspected
carcinogens
• Eat balanced diet
• Exercise regularly
• Adequate rest
• Health examination on a regular basis
• Eliminate, reduce, or change perceptions of stressors and
enhance ability to cope

• Enjoy consistent periods of relaxation and leisure
• Know 7 warning signs of cancer
• Self-examination
• Seek medical care if cancer is suspected

Warning Signs of Cancer
Utilize the American Cancer Society 7 Warning Signals
CAUTION
• Change in bowel or bladder habits
• A sore throat that does not heal
• Unusual bleeding or discharge from body orifice
• Thickening or lump in breast or elsewhere
• Indigestion of difficulty in swallowing
• Obvious change in wart or mole
• Nagging cough or hoarseness

Staging and Grading of Tumors
• Staging determines the extent of the spread of cancer.
• Grading evaluates tumor cells in comparison to normal
cells.

TNM staging system
It is the system that classifies the various cancers into
different anatomical forms, its regional lymph node
involvement and distant metastasis.
T: It is defined as the size of the primary tumor
N: It tells the presence or absence of the tumor in the
regional lymph nodes and lymph node drainage.
M: It is the absence or presence to the distant spread or
metastasis.

TNM staging system
“T” Primary tumor:
T0: No evidence of primary tumor
T: Carcinoma in situ
T1: Tumor < 2mm
T2: Tumor >20 mm but less than 50mm
T3: > 50mm
T4: tumor of any size /to the chest wall or skin
Tx: Primary tumor can not be assessed

TNM Staging system
“N” Regional lymph nodes
N0: No regional lymph nodes involvement
N1: Movable level( axiliary involvement)
N2: Mammary lymph nodes,( not palpable axillary)
N3: additionally supraclavical lymph nodes are involved
Nx: can not be assessed

TNM staging system
“M” Distant Metastasis
Mo: No distant metastasis
M1: Metastasis present

Tumor Grading or histological
classification
• Grade 1: Differ slightly from normal; well differentiated
• Grade 2: More abnormal; moderately differentiated
• Grade 3: Very abnormal; poorly differentiated
• Grade 4: Immature, primitive and undifferentiated cells;
difficult to determine cell of origin

Tumor Staging

Detection and diagnosis of Cancer
The earlier cancer is detected, the more likely it is to be
controlled.
• Tumor marker identification
1. PSA (Prostatic-specific antigen): prostate cancer
2. CEA (Carcinoembryonic antigen): colon cancer
3. Alkaline Phosphatase: bone metastasis
• Fluoroscopy
• Magnetic resonance imaging
• Computed tomography
• Ultrasonography

Detection and diagnosis of Cancer
Direct Visualization
a) Sigmoidoscopy
b) Cystoscopy
c) Endoscopy
d) Bronchoscopy
• PET Scan
• Invasive Diagnostic Techniques
• Biopsy is the most accurate diagnostic test for cancer.

Goals of Cancer Therapy
1. To cure the cancer
– Complete eradication of malignant disease
2. To control the cancer
– Prolonged survival and containment of cancer cell
growth
– Continued surveillance
3. To ease cancer symptoms (sometimes called palliation)
– May involve terminal care if client’s cancer is not
responding to treatment
– Relief of symptoms associated with the disease

Treatment Modalities for Cancer
Factors that determine treatment modality
– Cell type
– Location and size of tumor
– Extent of disease
– Grading and Staging of Cancer

Treatment Modalities for Cancer
A variety of approaches, including
1. Surgery
2. Radiation therapy
3. Chemotherapy
4. Other therapies

1. Surgery
• Surgical removal of the entire cancer remains the ideal
and most frequently used treatment method
Types of Cancer Surgeries:
1. Diagnostic Surgery
– Biopsy
• Excisional,
• Incisional, and
• Needle methods

1. Surgery
2. Prophylactic Surgery:
• Prophylactic surgery involves removing nonvital tissues or
organs that are at increased risk to develop cancer.
• Colectomy, mastectomy, and oophorectomy are examples
of prophylactic surgeries.
3. Palliative Surgery:
• When cure is not possible, the goals of treatment are to
make the patient as comfortable as possible and to
promote quality of life
4. Reconstructive Surgery

Prophylactic Surgery

Surgery

2. Radiation Therapy
– Emission and distribution of energy
1. Curative
– as in thyroid carcinomas, localized cancers of the
head and neck, and cancers of the uterine cervix.
2. Control
– when a tumor cannot be removed surgically or when
local nodal metastasis is present, or it can be used
neoadjuantly (prior to local definitive treatment) with
or without chemotherapy to reduce the size of a
tumor to enable surgical resection.

3. Prophylactic
– to prevent the spread of a primary cancer to a distant
area (eg, irradiating the brain to prevent leukemic
infiltration or metastatic lung cancer).
4. Palliative
– to relieve the symptoms of metastatic disease.

Two types of ionizing radiation
1. Electromagnetic radiation (x-rays and gamma rays)
2. Particulate radiation (electrons, beta particles, protons,
neutrons, and alpha particles)
Administration of Radiation
Teletherapy (external beam radiation)
Brachytherapy (internal radiation), Systemic
(radioisotopes), contact or surface molds. Combination
of internal and external radiation can also be used.

2. Radiation Therapy (Side Effects)
• Altered skin integrity is a common effect and can include
alopecia
• Alterations in oral mucosa secondary to radiation therapy
include stomatitis (inflammation of the oral tissues),
xerostomia (dryness of the mouth),\
• The entire gastrointestinal mucosa may be involved, and
esophageal irritation with chest pain and dysphagia may result
• radiation field, anemia, leukopenia (decreased white blood
cells [WBCs]), and thrombocytopenia (a decrease in platelets)
may result
• The patient is then at increased risk for infection and bleeding
until blood cell counts return to normal.
• Systemic side effects include fatigue, malaise, and anorexia

3. Chemotherapy
• Chemotherapy, antineoplastic agents are used in an
attempt to destroy tumor cells by interfering with cellular
functions, including replication.
• Chemotherapy is used primarily to treat systemic disease
rather than localized lesions that are amenable to
surgery or radiation. Chemotherapy may be combined
with surgery, radiation therapy, or both to reduce tumor
size preoperatively (neoadjuvant), to destroy any
remaining tumor cells postoperatively (adjuvant), or to
treat some forms of leukemia or lymphoma (primary).

3. Chemotherapy
Classes of Chemotherapy Drugs
a. Alkylating agents
• 1. Action: create defects in tumor DNA
• 2. Examples: Nitrogen Mustard, Cisplatin
b. Antimetabolites
• 1. Action: specific for S phase
• 2. Examples: Methotrexate; 5 fluorouracil
• 3. Toxic Effects: nausea, vomiting, stomatitis, diarrhea,
alopecia, leukopenia
c. Antitumor Antibiotics
• 1. Action: interfere with DNA
• 2. Examples: Actinomycin D, Bleomycin
• 3. Toxic Effect: damage to cardiac muscle
3. Chemotherapy
d. Miotic inhibitors
• 1. Action: Prevent cell division during M phase
• 2. Examples: Vincristine, Vinblastine
• 3. Toxic Effects: affects neurotransmission, alopecia,
bone marrow depression
e. Hormones
• 1. Action: stage specific G1
• 2. Example: Corticosteroids
f. Hormone Antagonist
• 1. Action: block hormones on hormone-binding tumors
(breast, prostate, endometrium; cause tumor regression
• 2. Examples: Tamoxifen (breast); Flutamide (prostate)
• 3. Toxic Effects: altered secondary sex characteristics

Toxicity and side effects
• Acute toxicity • Alopecia (hair loss)

– Vomiting – Generally reversible
– Allergic reactions – New hair often different
color and texture
– Arrhythmias
– Wigs
• Delayed effects – Anorexia
– Mucositis • Fatigue
– Alopecia • Nausea & vomiting
– Bone marrow
• Mucositis
suppression

4. Other Therapies
• Targeted therapies or Biotherapies seek to minimize the
negative effects on healthy tissues by disrupting specific
cancer cell functions .
• Other Therapies
– Bone Marrow Transplantation
– Gene Therapy
– Unproven and Unconventional Therapies
– Complementary and Alternative Medicine (CAM)

Oncological Emergencies
A. Pericaridal Effusion and Neoplastic Cardiac Tamponade
1. Concern: compression of heart by fluid in pericardial sac,
compromised cardiac output
2. Treatment: pericardiocentesis
B. Superior Vena Cava Syndrome
1. Concern: obstruction of venous system with increased
venous pressure and stasis; facial and neck edema with
slow progression to respiration distress
2. Treatment: respiratory support; decrease tumor size with
radiation or chemotherapy

C. Sepsis and Septic Shock
1. Concern: Early recognition of infection
2. Treatment: prompt
D. Spinal Cord Compression
1. Concern: pressure from expanding tumor can cause
irreversible paraplegia; back pain initial symptom with
progressive paresthesia and leg pain and weakness
2. Treatment: early detection and radiation or surgical
decompression
E. Obstructive Uropathy
1. Concern: blockage of urine flow; undiagnosed can result
in renal failure
2. Treatment: restore urine flow

Hypercalcemia
1. Concern: high calcium from ectopic parathyroid hormone
or metastases.
2. Behaviors: fatigue, muscle weakness, polyuria,
constipation progressing to coma, seizures.
3. Treatment: restore fluids with intravenous saline; loop
diuretics; more definitive treatments

G. Hyperuricemia
1. Concern: occurs with rapid necrosis of tumor cells as
with chemotherapy; can result in renal damage and
failure
2. Prevention and treatment with fluids and Alopurinol
(Zyloprim)
H. SIADH (Syndrome of Inappropriate Antidiuretic Hormone
Secretion)
1. Concern: ectopic ADH production from tumor leads to
excessive hyponatremia
2. Treatment: restore sodium level

References
• Porth, C., Matfin, G., & Porth, C. (2009). Pathophysiology:
Concepts of altered health states (8th ed.). Philadelphia,
PA:Wolters Kluwer Health/Lippincott Williams & Wilkins.
• Smeltzer, S.C.C., Bare, B.G., Hinkle, J.L. and Cheever, K.H.
eds., 2010. Brunner & Suddarth's textbook of medical-
surgical nursing (Vol. 1). Lippincott Williams & Wilkins.
• Grossman, S., Porth, C.M., Conelius, J., Gerard, S.O.,
Moriber, N., O'Shea, E.R. and Wheeler, K., 2014. Porth's
pathophysiology: Concepts of altered health states.
• LeMone, P., Burke, K., Dwyer, T., Levett-Jones, T.,
Moxham, L. and Reid-Searl, K., 2015. Medical-surgical
nursing. Pearson Higher Education AU.

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Abberant Cell Growth

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Introduction to Aberrant cell

Copyright © 2017 by Mehdi Hayat Khan

• The “steady state” that cell exists in normally.

• An equilibrium of the cells with their environment for

Copyright © 2017 by Mehdi Hayat Khan

Copyright © 2017 by Mehdi Hayat Khan

Copyright © 2017 by Mehdi Hayat Khan

Copyright © 2017 by Mehdi Hayat Khan

Copyright © 2017 by Mehdi Hayat Khan

Copyright © 2017 by Mehdi Hayat Khan

• Hyperplasia • Dysplasia: some loss of

Copyright © 2017 by Mehdi Hayat Khan

Copyright © 2017 by Mehdi Hayat Khan

Copyright © 2017 by Mehdi Hayat Khan

Copyright © 2017 by Mehdi Hayat Khan

o  workload requirement of an organ part

Copyright © 2017 by Mehdi Hayat Khan

Copyright © 2017 by Mehdi Hayat Khan

Copyright © 2017 by Mehdi Hayat Khan

Copyright © 2017 by Mehdi Hayat Khan

Copyright © 2017 by Mehdi Hayat Khan

Mehdi Hayat Khan

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