Ch 10 Flashcards
(108 cards)
1
Q
Errors of morphogenesis in which there is an intrinsically abnormal developmental process.
A
Malformation
2
Q
Congenital heart defect and anencephaly are examples of: A. malformation B. disruption C. deformation D. Sequence
A
A. Malformation
3
Q
_ results from secondary destruction of an organ or body region that was previously normal in development; thus in contrast to malformation, this arise from an extrinsic disturbance in morphogenesis.
A
Disruption
4
Q
Amniotic bands - denoting rupture of amnion with formation of bands that encircle, compress or attach to parts of the developing fetus leading to an abnormality, is an example of: A. malformation B. Disruption C. Deformation D. sequence
A
B. Disruption
5
Q
_ represents an extrinsic disturbances of development rather than an intrinsic errors of morphogenesis.
A
deformation
6
Q
Around 35-38 weeks of development fetus outpaces the growth of the uterus and relative amount of amniotic fluid also decreases. this can lead to what kind of deformation: A. malformation B. Disruption C. Deformation D. Sequence
A
C. Deformation
7
Q
Club feet, fusion of orbits, cleft palate are examples of A. Malformation B. Deformation C. Disruption D. Sequence
A
C. Deformation
8
Q
Oligohydraminios is an example of A. Malformation B. Deformation C. Disruption D. Sequence
A
D. Sequence. it can lead to other formations like chronic leakage of amniotic fluid cuz of rupture of amnion, uteroplacental insufficiency, resulting from maternal hypertension or severe toxemia, renal agenesis in fetus. A sequence can lead to one of the other abnormalities, disruption, deformation or malformation
9
Q
Almost all chromosomal syndromes are associated with _
A
congenital malformation
10
Q
Holoprosencephaly is due to loss of function mutation of _
A
hedgehog
11
Q
fetal hyperinsulinemia resulting in fetal macrosomia (organomegaly and increased body fat and muscle mass; cardiac anomalies, neural tube defects, CNS malformation are all characteristics of _
A
diabetic embryopathy
12
Q
between what weeks is the embryo extremely susceptible to teratogen?
A
3rd and 9th weeks.
13
Q
_ is a plant teratogen that is an inhibitor of hedgehog and was shown in pregnant sheep who ate this plant developped cyclopia.
A
Cyclopamine
14
Q
_ , an antiepileptic and teratogen is known to disrupt expression of HOX.
A
Valproic acid
15
Q
In excess _ can act as a teratogen characterized by CNS, cardiac, craniofacial defects, cleft lip and cleft palate.
A
Vitamin A
16
Q
Risk factors for preterm premature rupture of placental membrane (PPROM) includes:
A
- prior hx of preterm delivery
- preterm labor and/or vaginal bleeding during current pregnancy
- maternal smoking
- low socioeconomic status
- poor maternal nutrition
17
Q
The most common microorganism that which causes intrauterine infection include:
A
Ureplasma urealyticum, cycoplasma hominis, gardnerlla vaginalis, trichomonas, gonorrhea, and chyamydia
18
Q
Which receptor is known to mediate responses to intrauterine infections and how does it risk of preterm premature rupture of placental membrane?
A
Toll-like receptors. TLR deregulates prostaglandin expression which induces uterine smooth muscle contraction
19
Q
What are some causes of prematurity?
A
- preterm premature rupture of placental membranes
- Intrauterine infection
- Uterine, cervical, placental structural abnormalities
- Multiple gestation
20
Q
What are some common examples of uterine, cervical, placental structural abnormalities which are associated with prematurity.
A
- Uterine distortion (uterine fibroids)
- cervical incompetence
- placenta previa
- abruptio placentae
21
Q
What are some common hazard to a newborn?
A
- neonatal respiratory distress syndrome aka hyaline membrane disease
- necrotizing enterocolitis
- sepsis
- intraventricular and germline matrix hemorrhage.
22
Q
Fetal growth restriction (GFR) is associated with fetal abnormalities that can be caused by a group of common fetal infection known as TORCH. What microorganism are associated with TORCH?
A
- Toxoplasmosis
- Other ..like syphillis
- Rubella
- Cytomegalovirus
- Herpesvirus
23
Q
What is meant by proportionate FGR?
A
Cause of Fetal growth restriction that which is intrinsic to the fetus. Such causes of SGA due to fetal factors usually have symmetric growth restriction termed proportionate GFR
24
Q
What are some common maternal abnormalities that is responsible for FGR?
A
- Decreased placental blood flow
- Vascular disease like preclampsia and chronic hypertension
- thrombophilias
- moms taking drugs like phenytin (dilatin) as chemo
- maternal manutrition
25
What are some common causes of respiratory distress syndrome?
- Hyaline membrane disease (most common)
- excessive sedation of mom
- fetal head injury during delivery
- aspiration of blood or amniotic fluid
- intrauterine hypoxia due to umbilical cord about the neck
26
What are the pathologic causes of RDS?
- Immature lungs
- inversely proportional to gestation age
- Fundamental defects in pulmonary surfactant
- poor
27
Congenital deficiency of surfactant can be associated with mutation in what genes?
SFTBP or SFTBC genes
28
At what week of gestation is surfactant production normally elevated?
35th week
29
Explain the pathophysiology of respiratory distress syndrome due to prematurity-linked reduced surfactant
With poor surfactant, infants has to work hard to get past the 40% of residual air volume even after the first breath. The problem with this stiff atelectatic lungs is compounded with soft thoracic wall that is pulled in as diaphragm descend. Progressive atelectasis and reduced lung compliance leads to protein-rich, fibrin rich exudation into the alveolar spaces with formation of hyaline membranes. The fibrin-hyaline membrane are barriers to gas exchange leading to carbon dioxide retention and hypoxemia which further impairs surfactant synthesis and a vicious cycle ensues.
30
Surfactant synthesis can be suppressed by compensatory high blood levels of _ in infants of diabetic moms which counters effects of steroid.
Insulin. That is why babies born to diabetic moms have higher risk of developing RDS
31
Historically, RDS neonates who received O2 after birth had two common sequelae associated with prolonged O2. Namely
1. During hyperoxic phase (Phase I) - expression of proangiogenic VEGF is markedly decreased causing endothelial cells apoptosis: VEGF levels rebound after return to relatively hypoxic room air ventilation (phase II), inducing retinal vessel proliferation (neovascularization) characteristic of the lesions in retina.
2. Bronchopulmonary dysplasia... striking decrease in alveolar septation and a dysmorphic capillary configuration.
32
There is no single bacteria linked to necrotizing enterocolitis, but a large number of inflammatory mediators are associated. Among them, one has been implicated in increasing mucosal permeability by promoting enterocyte apoptosis and compromising intercellular tight junctions, thus adding fuel to the fire What is this mediator?
Platelet activating factor (PAF).
33
In necrotizing enterocolitis the ultimate breakdown of mucosal barrier functions permits transluminal migration of gut bacteria leading to a vicious cycle of inflammation, mucosal necrosis and further bacterial entry. What the clinical course that follows?
Bloody stools, abdominal distention, and circulatory collapse
34
Morphologically, necrotizing enterocolitis involves what segment of the GI, how does it appear?
Usually involves terminal ileum, cecum, right colon. Involved segment is distended, friable and congested and can be gangrenous with intestinal perforation and accompanying peritonitis. Microscopically, mucosal transmural coagulative necrosis, ulceration bacterial colonization and submucosal gas bubbles
35
What are some common sequalae of transcervical infection?
Pneumonia, sepsis and meningitis
36
Most parasites, and viral infections and few bacterial infection gain access to fetal blood via what route?
transplacental (hematologic) route of infection
37
which virus causes erythema infectiosum aka fifth disease of childhood in immunocompetent older children, and can infect seronegative pregnant woman and is associated with spontaneous abortion, stillbirth, hydrops fetalis and congenital anemia? What viral inclusions can be seen in what kind of cells as a diagnostic marker?
Parvovirus B19. erythroid progenitor cells.
38
TORCH group of infections are grouped together cuz they evoke similar clinical and pathologic manifestation. They include:
- fever
- encephalitis
- chorioretinitis
- hepatosplenomegaly
- pneumonitis
- hemolytic anemia
- vascular or hemorrhagic skin lesions
39
What microorganism is commonly associated with perinatal early on-set sepsis? Late onset?
Early onset: Group B strep
| Late onset: Listeria and candida
40
What are the two major group of antigens known to cause immune hydrops?
Rh antigens and ABO blood groups
41
Which Rh antigen is the major cause of Rh incompatibility between mom and fetus?
The D antigen
42
If a fetus is Rh+ and mom is Rh- (a) what antibodies is initially produced and (b) why is this antibody protective for the first pregnancy? (c) What happens during subsequent pregnancy?
a. Initial exposure to Rh antigen evokes the formation of IgM antibodies.
b. unlike IgG antibodies , IgM do not cross the placenta and so does not attack the fetus.
c. exposure during a subsequent pregnancy generally leads to a brisk IgG antibody response and the risk of immune hydrops
43
Administration of what at 28 weeks and within 72 hours of delivery to Rh-negative moms significantly decreases the risk of hemolytic disease in Rh-positive neonates and in subsequent pregnancies?
Rhesus immune globulin containing anti-D antibodies which removes these Rh+ antibodies from the mother's circulation.
44
ABO incompatibility related fetal hemolysis occurs almost exclusively in fants of what blood group born to what blood group moms?
Infants of group A or B who are born to group O moms
45
What are the three major causes of nonimmune hydrops?
1. Cardiovascular defects both structural and functional such as congenital malformation and arrhythmias which can result in intrauterine cardiac failure and hydrops
2. Chromosomal anomalies such as 45,X (Turner syndrome)
3. Fetal anemia, not related to Rh or ABO. In some parts of world it can be due to homozygous a-thalaseemia. Parvovirus B19 is rapidly emerging as an important cause of hydrops.
46
The most serious threat in fetal hydrops is _
CNS damage known as kernicterus where the brain is enlarged and edematous and when sectioned a bright yellow color in the basal ganglia, thalamus, cerebellum, cerebral gray matter and spinal cord can be seen.
47
How would mildly affected and severely affected fetal hydrops present?
Mildly affected infants display pallor, maybe hepatosplenomegaly. Severely ill neonates present with intense jaundice, generalized edema and signs of neurologic injury
48
Classical PKU is caused by a severe deficiency of what enzyme?
Phenylalanine hydroxylase (PAH) resulting in hyperphenylalaninemia.
49
How does classical PKU infants present?
- normal at birth, but within few weeks develop a rising plasma phenylalanine level, which impairs brain development.
- Usually by 6 months of life severe mental retardation becomes evident
- one third of these children are never able to walk and two thirds cannot talk
- seizure,
- decreased pigmentation of hair and skin
- eczema
50
Explain the pathogenesis of maternal PKU
Infants born to moms with PKU. Mom's elevated phenylalanine acts as a teratogenic agent for the fetus and thus fetus develops abnormally and presents with mental retardation, microcephaly, and some with congenital heat disease.
51
The strong musty or mousy odor that imparts from PKU infants is due to _
When phenylalanine metabolism is blocked because of a lack of PAH enzyme, minor shunt pathways come into play, yielding several intermediates that are excreted in large amounts in the urine and in the sweat.
52
What's responsible for the light color of hair and skin as seen in PKU infants?
The biochemical abnormality in PKU is an inability to convert Phe into Tyr. Tyrosine is needed for melanin and so with no tyrosine, there's no melanin that's needed for the pigment seen in hair and skin.
53
A failure to thrive Infants presents with vomitting and diarrhea and is noted to have hepatomegaly, widespread scarring that closely resembles the cirrhosis of alcohol abuse, apacification of the lens is noted. Further studies shows loss of nerve cells, gliosis, and edema, particularl yin the dentate nuclei o the cerebellum and olivary nuceli of the medulla.
A. What is the diagnosis
B. What enzyme is defective?
C. What and where is the accumulated product
D. what are the products of the alternative metabolic pathways as activated due to this enzyme deficiency?
A. Galactosemia
B. Galactose-1-phosphate uridyl transferase (GALT)
C. accumulated product is galactose-1-phosphate that accumulates in liver, spleen, lens of eyes, kidneys, heart muscle, cerebral cortex, and erythorcytes.
D. Alternative pathway activation produces galactitol and galactonate both of which can also accumulate in tissues.
54
Infants with galactosemia, how soon do they show signs and symptoms?
Vomiting and diarrhea appears within a few day sof milk ingestion. Jaundice and hepatomegaly usually within first week of life. Cataracts within a few weeks. mental retardation within 6-12 months.
55
What are the main clinical features of cystic fibrosis?
- chronic lung disease secondary to recurrent infections
- pancreatic insufficiency
- steatorrhea,
- malnutrition
- hepatic cirrhosis
- intestinal obstruciton
- male infertility
56
What is the primary defect in cystic fibrosis?
Abnormal function of an epithelial chloride channel protein encoded by cystic fibrosis transmembrane conductance regulator (CFTR) gene on chromosome 7
57
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It is believed that one of the function of CFTR is regulation of multiple additional ion channels and cellular processes. Among the channels it regulates, which channels has the most pathophysiologic relevance to the disease?
A. Inwardly rectified K channel
B. Outwardly rectified K channel
C. epithelial Na channel
D. Epithelial Cl channel
E. Gap junction
```
C. Epithelial Na channel (ENaC).
ENaC is situated on the apical surface of exocrine epithelial cells and is responsible for Na uptake from the luminal fluid, rendering it hypotonic.
58
In a normal person, how does ENaC interact with CFTR?
Normally ENaC is inhibited by normally funcitonally CFTR; hence in systic fibrosis, ENaC activity is increased, markedly augmenting Na uptake across the acpical membrane and has profound significance in pathology in lung and GI of CF patients.
59
In the sweat ducts of CF patients, is ENaC activity decreased or increased? and what is the significance of this altered activity?
In the sweat duct, ENaC activity is decreased (unlike in GI and in lung where it's activity is increased due to CFTR mutation). With ENaC activity decreased in sweat duct, a hypertonic luminal fluid containing high sweat NaCl is formed. This is what mom's mean when they say their baby taste salty
60
In the respiratory and intestinal epithelium, CFTR is one of the most important avenues for active luminal secretion of what ion?
Chloride. CFTR mutation leads to loss or reduction of chloride secretion into the lumen and active lumminal Na absorption is increased due to loss of ENaC inhibition. and thus both of these ions changes increase passive water reabsorption from the lumen, lowering water content of the surface fluid layer coating mucosal cells.
61
The pathogenesis of respiratory and intestinal complications in CF seems to stem from an isotonic but low-volume surface fluid layer. Explain the significance of this in the lung.
In the lungs, this low volume surface fluid layer leads to defective mucociliary action and accumulation of hyperconcentrated viscous secretions that obstruct the air passage and predispose to recurrent infections.
62
Pancreatic insufficiency, a feature of classic CF is virtually always present when there are CFTR mutations with abnormal conductance of what compound?
bicarbonate. CFTR regulates transport of bicarbonate ions normally.
63
Which classes of CFTR defects and which one is most severe?
A combination of Class I, II, and III are most severe. with Class II mutation being the most common.
Class I: defective protein synthesis
Class II: abnormal protein folding processing and trafficking
Class III: defective regulation
Class IV: decreased conductance
Class V: reduced abundance
Class VI: altered function in regulation of ion channels
64
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Explain a distinctive feature seen in each of the following systems in patients with severe CF.
A. Lung
B. Pancreas
C. Small intestine
D. Liver
E. Reproductive
```
A. obstruction and infection of airways . bronchioles are distended with thick mucus. Prone to infections with s. aureus, H. influenzae, p.aeruginosa. p. aeruginosa causes chronic inflammation
B. pancreatic abnormalities in about 85-90% of CF patients. accumulation of mucus in ducts and some dilation of exocrine glands
C. Meconium ileus
D. Bile canaliculi are plugged by mucus accompanied by ductular proliferation and portal inflammation. Over time focal biliary cirrhosis develops
E. azoospermia and infertility
65
What are some parental risk factors associated with SIDS?
- young maternal age
- maternal smoking during pregnancy
- Drug abuse
- short intergestational intervals
- late or no prenatal care
- low socioeconomic group
- African and American Indian ethnicities
66
What are some infant risk factors associated with SIDS?
- brain stem abnormalities
- prematurity and/or low birth weight
- male
- product of multiple birth
- SIDS in prior sibling
- antecedent respiratory infections
- germline polymorphism in ANS genes
67
What are some environmental risk factors of SIDS?
- prone or side sleep position
- sleeping on a soft surface
- hyperthermia
- Co-sleeping in first 3 months of life
68
What are some examples of findings in postmortem cases of SUID?
- infections
- viral myocarditis
- bronchopneumonia
- unsuspected congenital anomaly
- congenital aortic stenosis
- anomalous roigin of the left coronary artery from pulmonary artery
- Traumatic child abuse
- intentional suffocation (filicide)
- genetic and metabolic defects
- long QT syndrome
- Fatty acid oxidation disorder
- Histiocytoid cardiomyopathy
69
In 80% of cases of SIDS, postmorten examination finding include _
multiple petechiae, usually present on the thymus, visceral and parietal pleura, and epicardium.
70
SIDS is deemed a multifactorial condition with a variable mixture of contirbuting factors. A triple risk model was proposed which postulates the intersection of three overlapping factors. What are they?
1 vulnerable infant such as delayed development of arousal and cardiorespiratory control. Abnormal serotonin-dependent signaling
2. A critical developmental period in homeostatic control. infants who are born before term or low birth weight are at risk
3. Exogenous stressor: prone or side sleeping or sleeping with parents in the first 3 months
71
Most SIDS babies have an immediate prior history of mild respiratory tract infection. These infections predispose an already vulnerable infant to even greater impairment of cardiorespiratory control and delayed arousal. In this context, what receptors emerged as a putative "missing link" between upper respiratory tract infections, the prone position, and SIDS?
Laryngeal chemoreceptors. When stimulated they elicit an inhibitory cardiorespiratory reflex and stimulation augments respiratory tract infection which increase volume of secretions, and by the prone position, impairs swallowing and clearing of the airways.
72
What is the single most common cause of sudden "unexpected" death (SUID)?
infections. followed by congenital anomalies.
73
what is choristoma?
aka heterotpia, microscopically normal cells or tissues that are present in abnormal locations. For example, pancreatic tissue found in the wall of he stomach or SI.
74
What is an hamartoma?
excessive, focal overgrowth of cells and tissues native to the organ in which it occurs. Everything in hamartoma looks the same as the normal cells, but they do not reproduce the normal architecture of the surrounding tissue. d
75
What are the most common sites of hemangioma in children?
Skin, mainly face and scalp where they form elevated, flat irregular, red-blue masses; some of the fat larger lesion are referred to as Port-wine stains
76
In addition to their cosmetic significance, they can represent one facet of the hereditary disorder von Hippel-Lindau disease. What disease is it?
Hemangioma
77
Cerebral cavernous malformation gene mutation can lead to this subset of CNS cavernous _
hemangioma
78
Where are lymphangiomas commonly found?
Neck, axilla, mediastinum, retroperitoneal tissues.
79
What are lymphagiomas?
hamartomatous or neoplastic, and usually are characterized by cystic and cavernous spaces.
80
What are lymphangiectasis
diffuse swelling of part or all of an extremity; considerable distortion and deformation may occur as a consequence of the spongy, dilated subcutaneous and deeper lyphmatics. Not progressive, most just causes cosmetic problems.
81
Congenital-infantile fibrosarcoma have been associated with what chromosomal translocation and what is the consequence of this translocation?
12;15 which results in generation of an ETV6-NTRK3 fusion transcript. ETV6 gene product is a TF and NTRK3 gene product is a tyrosine kinase. ETV6-TRKC is thus always active and stimulates signaling via RAS and PI-3K/AKT pathway
82
what marker is unique to infants fibrosarcomas and is an useful diagnostic marker?
ETV6-NTRK3
83
which neuroblastic tumors is the most common extracranial solid tumor?
Neuroblastoma
84
What mutation leads to neuroblastoma?
Germline mutation in anaplastic lymphoma kinase (ALK) gene. Somatic gain of function mutation of ALK mutation are also seen in 10% of sporadic neuroblastoma
85
The most common site of neuroblastoma is in_
adrenal medulla (40% of cases). 25% in paravertebral region of abd and 15% in mediastinum
86
Histology, Homer Right pseudorosette surrounding neutrophils are is characteristic of what childhood tumor?
Neuroblastoma
87
At what stage is neuroblastoma unresectable?
Stage 3.
88
explain the characteristic of stage 4s of neuroblastoma
localized primary tumor (stages 1, 2A or 2B) with dissemination limited to skin, liver, and/or bone marrow. Stage 4S is limited to infants younger than 1yr
89
90% of this type of tumor of these blueberry muffin baby, regardless of location produces catecholamines which are an important diagnostic feature.
Neurofibromatosis. blueberry muffin baby refers to the deep blue discoloration of the skin.
90
The prognostics of CF has several key factors of which age of infant is an important one. What age has emerged as a critical point of dichotomy in terms of prognosis.
18 months. Children under 18 months esp those in the first year of life have an excellent prognosis regardless of the stage of the neoplasm. Older than 18 falls in the intermediate risk category and others with higher stage or variable MYCN amplification is considered at higher risk.
91
What is the significance of presence of MYCN amplification in patients with neuroblastoma?
Amplification of MYCN oncogene in neuroblastoma is a molecular event that has possibly the most profound impact on prognosis. Those with this amplification bumps the tumor into a high risk category irrespective of age, stage, or histology.
92
What is chromothripsis and what does it implicate for the prognosis of neuroblastoma?
Chromothripsis is a form of segmental aberration involved in localized fragmentation of a chromosome segment followed by random assembly of the fragment. It's associated with poor prognosis.
93
In neuroblastoma, hemizygous deletion of distal short arm of chromosome 1 has a strong correlation with _ and thus is know to be associated with increased risk of disease prolapse and poor prognosis.
MYCN amplification
94
Expression of specific neurotrophin receptor is a prognostic marker for neuroblastoma. High levels of which tyrokinase kinase receptor expression is a favorable prognostic factor in neuroblastoma generally associated with low-stage tumor lacking MYCN amplification.
TrkA
95
What age group of kids does Wilm's tumor most commonly present in?
Peaks at 2-5. 95% occur before at 10.
96
The pathogenesis and genetics leading to wilms tumor is divided into three risk groups. The with the highest risk (90%) have what syndrome?
Denys-Rash - characterized by gonadal dysgenesis and early onset nephropathy leading to renal failure. Characteristic feature diffuse mesangial sclerosis
97
A group of patients with Wilms tumor fall under a risk group, all with WAGR syndrome (33%) of cases. What is WAGR syndrome characterized by?
Wilm's Tumor
Aniridia
Genital anomalies
Retardation (mental)
98
WAGR patients carry germline deletion of _
11p13
99
anirida as seen in WAGR is due to deletion of what gene?
PAX6
100
Kids with Wilm's tumor in the WAGR group, represents the two-hit phenomenon associated with WT1. what's the first hit and what's second hit?
1st: germline mutation
2nd: nonsense or frameshift mutation in the 2nd WT1 allele.
101
In Denys-Drash syndrome leading to Wilm's tumor, explain how mutation leads to the disease.
IN Denys-Drash there's a germline mutation in WT1, but it's a dominant-negative missense mutation in the zinc-finger region of the WT1 protein that affects its DNA-binding properties and it interferes with the remaining wild-type allele
102
Patients with Denys-Drash syndrome develop Wilm's tumor, but they are also at an increased risk of developing what other neoplasm?
gonadoblastoma
103
A patient presents with oraganomegaly, macroglossia, hemihypertrophy, omphalocele, and adrenal cytomegaly. You suspect these symptoms are associated with a disease with abnormalities localized to band 11p15.5. What other disease are these patients at greatest risk of developing?
Wilm's tumor. The clinical signs listed is of Reck-with Wiedemann syndrome (BWS). Patients with BWS have abnormalities in WT2 distal to the WT1 locus.
104
BWS leading to wilm's tumor serves as a model for what nonclassical mechanism of tumorigenesis?
genomic imprinting.
105
Imprinting abnormality of what growth factor has the strongest relationship to tumor predisposition in WBS?
IGF2
106
Sporadic Wilms tumors as seen in 10% of cases, is due to gain of function mutation of _
gene encoding beta-catenin. Beta catenin is developmentally important in the WNT signaling pathway.
107
In bilateral Wilm's tumor, in nearly 100% of cases, putative precursor lesions are seen in the renal parenchyma. These lesions are called _
nephrogenic rests
108
Microscopically, Wilms tumor are characterized by recognizable attempts to recapitulate different stages of nepherogenesis and identified by this classic triphasic combination of _
blastemal, stromal, and epitthelial cells types as observed in vas majority of the lesion.
