Pathology Flashcards
1
Q
Paraneoplastic Cushing’s syndrome is most commonly associated with which malignancies?
A
Small cell lung cancer
2
Q
Acanthosis Nigricans is commonly appear with which malignancy?
A
Gastrointestinal malignancies
3
Q
Kind of necrosis found in acute pancreatitis
A
Fat necrosis
4
Q
3 clinical characteristics of PCO
A
- chronic anovulation (2ry amenorrheoa)
- hyperandrogegism (hirsutism, elevated LH, elevated free testosterone)
- necklace appearance in US
5
Q
laboratory characteristics of PCO
A
- High LH
- High androgen
- hyperinsulinemia
- high antimullerian hormone
- low SHBG
6
Q
Threshold of polycystic ovarian morphology (PCOM)
A
1.follicle number >20 (2-9mm)
2. Ovarian Vol >10ml
3. No corpus luteum, cysts or dominant follicle
8
Q
Commonest endocrine condition to affect women
A
PCO 10-15%
9
Q
the commonest epithelial ovarian tumor
A
Serous carcinoma
9
Q
commonest ovarian germ cell tumor
A
cystic teratoma (dermoid cyst) ~ usually benign
10
Q
Commonest malignant sex cord stromal tumor is
A
Adult type of granulosa cell tumor
11
Q
Commonest ovarian tumors that can lead to torsion
A
Germ cell tumor
12
Q
Commonest sites of endometriosis
A
- Ovaries
- Rectovaginal septum
3.pelvic peritoneum - laparotomy scars
13
Q
the classical example of metastatic GIT neoplasia to the ovaries
A
Krukenberg tumor
14
Q
Most common inherited bleeding disorder
A
Von Willebrand disease
15
Q
Percentage of Cx cancer which are HPV related
A
99.7%
16
Q
what is a complete mole?
A
Originates from fertilization of an empty ovum (has no chromosomes)
it will carry (paternal DNA only):
-Duplication of DNA of one sperm 90% -> 46XX
-Fertilization by 2 sperms 10% -> 46XX or 46XY
17
Q
What is partial mole?
A
originates from fertilization of normal ovum by 2 sperms –> triploidy
69XXX, 69XXY, 69XYY
18
Q
Partial Moles are misdiagnosed with
A
Hydropic Abortion and Complete mole
19
Q
Gross picture of Complete mole
A
grape-like vesicles
20
Q
Most common karyotype of Complete mole
A
46XX
21
Q
GTN metastasises to
A
Lungs 80%
Pelvic organs
Brain
22
Q
hCG status in GTD
A
Abnormal high hCG is the hall mark of GTD >100.000 IU/ml in the first 8 weeks
23
Q
What is the incidence of hyperthyroidism in complete molar pregnancy?
A
3%
24
Q
Low lying placenta
A
(less than 20mm from the cervix)
25
what is placenta previa?
placenta completely covering the cervix
26
What is Ovarian Theca lutein cyst?
commonly occurs in 25-60% of complete moles
in response to huge amounts of hCG secreted by proliferated cells
27
Placenta invaded through the full thickness of the myometrium.
Placenta Increta
28
How is obstetric cholestasis diagnosed?
when otherwise:
1. unexplained pruritus and
2. abnormal liver function tests (LFTs) and/or raised bile acids
occur in the pregnant woman and both resolve after delivery.
29
Percentage of pruritus in pregnancy
23% of pregnant women
30
when pruritus usually appears in pregnancy
in the 2nd half (3rd trimester- 80% after 30 weeks)
31
Risk factors of Obstetdriic cholestasis
1. +ve family history 35%
2. Estrogen
3. Multiple pregnancy
4. Carriage of hepatitis C
5. Presence of gallstones
32
Obstetric cholestasis pruritus is characterized by
• it is typically worse at night.
• widespread and may involve the palms of the hands &r the soles of the feet.
33
What is dermatographia artefacta?
skin trauma from intense scratching may be seen in obstetric cholestasis
34
How should obstetric cholestasis be monitored?
• Once obstetric cholestasis is diagnosed, measure LFTs weekly until delivery.
• A coagulation screen should be performed.
• Postnatally, LFTs should be deferred for at least 10 days (In normal pregnancy, LFTs may increase in the first 10 days of the puerperium).
35
Maternal Risks with Obstetric cholestasis
1. Vit. K deficiency
2. Increase rate of CS
3. Increase risk of postpartum hmge
36
Fetal Risks with Obstetric cholestasis
1. stillbirth
2. Intrapartum fetal distress
3. Amniotic fluid meconium
4. Preterm delivery
5. Intrauterine fetal death
6. Fetal intracranial haemorrhage
37
Causes of increased rates of placenta previa, accrete ..etc
d.t. rising rates of caesarean deliveries, increased maternal age and use of assisted reproductive technology (ART)
38
Incidence of Placenta Previa
1 in 200 Pregnancies
39
Placental villi adheres superficially to the myometrium without interposing decidua
Placenta Accrete
40
Placental villi penetrate deeply into the uterine myometrium down to the serosa
Placenta Increta
41
Placental villi perforates through the entire uterine wall and may invade the surrounding pelvic organs, such as the bladder.
Placenta Percreta
42
What is placental migration?
Apparent placental ‘migration’ following the development of the lower uterine segment during 3rd trimester of pregnancy results in the resolution of the low-lying placenta in 90% of the cases before term. This is less likely to occur in women with a previous caesarean delivery
43
Role of TVS in diagnosing Placenta previa
TVS for the diagnosis of placenta praevia or a low-lying placenta is superior to transabdominal and trans-perineal approaches, and is safe.
44
Endometrial thickness in reproductive age and premenopausal
5-14mm
45
Endometrial thickness in postmenopausal
4mm
46
The most common presentation of endometrial hyperplasia
Abnormal uterine bleeding.
This includes heavy menstrual bleeding, intermenstrual bleeding, irregular bleeding, unscheduled bleeding on hormone replacement therapy (HRT) and postmenopausal bleeding.
47
Risk of progression of endometrial cancer in hyperplasia without atypia
Less than 5% over 20 years
It will regress spontaneously during follow up
48
The main risk factor of endometrial hyperplasia
Unopposed estrogen exposure
49
Causes of skin pigmentation in pregnancy
Due to increase in estrogen, progesterone and melanocyte stimulating hormone levels.
50
Linea Nigra
a dark line on the abdomen, running straight down from the umbilicus, appears with pregnancy.
51
What is 2ry areola?
pigmented area around the 1ry areola appear during 5th month.
52
What is Melasma?
Brown, clearly defined patches on the face. Appear in forehead, malar distribution & cheekbones.
Occur in 75%, predominantly in 2nd or 3rd Trimester, Often persists for months & years postpartum.
53
Treatment of Melasma
treatment is of a limited response like
(topical bleaching creams, hydroquinones (not licensed in
the UK), retinoids and steroids, as well as chemical peels,
laser treatments and dermabrasion)
###All of the above treatments are contraindicated in pregnancy.
#Prevention: avoid of excessive sunlight exposure & use of
broad-spectrum sunscreens.
54
Cause of Striae Gravidarum
Caused by rupture of the dermal elastic fibers that explains their
irreversible nature
55
Cause of spider navel In pregnancy
Occur due to increased estrogen that cause dilatation, congestion & proliferation of bl. vessels that can be seen on or through the skin.
56
What is ACUTE TELOGEN EFFLUVIUM
a generalised hair shedding with diffuse non-scarring alopecia, characteristically occurs 3–6 months postpartum.
57
When will pregnant woman recover from ACUTE TELOGEN EFFLUVIUM?
Generally, recovery is spontaneous and occurs within 9–12 months, and rarely does hair density fail to recover completely.
58
Sweat glands changes during pregnancy?
Increased eccrine gland secretions towards 3rd trimester can cause prickly heat (miliaria) and hyperhidrosis which contribute to pruritus.
59
What is Impetigo Herpetiformis?
A form of generalized pustular psoriasis. Pus-filled blisters begins in groins, underarms & folds of knees & elbows.
60
timing of impetigo herpetiformis
typically presents in 3rd Trimester & disappears after delivery.
61
Presentation of impetigo herpetiformis
Rash always accompanied by severe illness (chills, fever, vomiting, diarrhea, joint pains & lymphadenopathy).
62
The four dermatoses of pregnancy are:
– atopic eruption of pregnancy (AEP)
– pemphigoid gestationis,
– polymorphic eruption of pregnancy (PEP/PUPP)
– intrahepatic cholestasis of pregnancy (ICP
63
The only known effective TTT of intrahepatic cholestasis (obstetric cholestasis)
Ursodeoxycholic acid
decrease maternal pruritus & improve liver function & prognosis for the fetus.
Dose: 15 mg/kg/day (≈1 gm/d) as a single dose or in 2 divided doses
64
Other name of Obstetric cholestasis
Intrahepatic Cholestasis of Pregnancy ICP
65
Other medications needed in treatment of Obstetric Cholestasis
Vitamin K: Prevent clotting abnormalities dt. the hepatic effects of obstetric cholestasis.
66
Most common dermatosis in pregnancy
Atopic eruption of pregnancy
67
Characteristics of Rash in polymorphic eruption of pregnancy
Starts in Abdomen
Spares Umbilicus, face, scalp, palms and soles
68
Characteristics of Rash in pemphigoid gestationis
Starts from umbilicus and spread to whole body.
**remission and exacerbation are characteristics
69
atopic eruption is commonly associated with
Multiparous
(has no serious risk on pregnancy)
70
polymorphic eruption is commonly associated with
Primigravida
(has no serious risk on pregnancy)
71
pemphigoid gesationis is commonly associated with
Autoimmune conditions (grave's dis. - IDDM)
(causes IUGR)
72
Is Intrahepatic Cholestasis of Pregnancy ICP associated with PPH?
True
73
When do you check LFTs postpartum, after ICP?
after 10 days (as biochemistry may worsen in the immediate postnatal period)
74
In treating ICP, What is the 2nd line after UDCA?
Rifampicin
75
The most common presentation of endometrial hyperplasia is
abnormal
uterine bleeding.
76
most common gynaecological malignancy in the Western world
Endometrial Cancer
77
How we perform Endometrial surveillance in case of End. Hyperplasia
endometrial sampling by outpatient endometrial biopsy (or by inpatient endometrial sampling, such as dilatation and curettage performed under general anaesthesia)
78
difference between End. hyperplasia and normal end. proliferation
Endometrial hyperplasia is defined as irregular proliferation of the endometrial glands with an increase in the gland to stroma ratio
79
incidence of endometrial hyperplasia
133/100.000 women with peak age 50-54 y
80
PCO association with End. hyperplasia
in women with PCO, if endometrial thickness is more than 7 mm, it is alarming for having endometrial hyperplasia
81
cut-off endometrial thickness in postmenopausal women for EH
Systematic reviews have suggested a cut-off of 3 mm or 4 mm for ruling out endometrial cancer
Propability reduced 1% when it's less than the cuts-off
82
Risk of EH without atypia to processing to End. cancer
less than 5% over 20 years
83
Treatment of EH without atypia
Follow-up and Progestagens (oral - LNG-IUS)
84
1st line ttt of EH without atypia
LNG-IUS
because compared with oral progestogens it has a higher disease regression rate with a more favourable bleeding profile and it is associated with fewer adverse effects.
85
Is cyclical progestogens effective in ttt of EH without atypia
should not be used because they are less effective in inducing regression of endometrial hyperplasia without atypia compared with continuous oral progestogens or the LNG-IUS
86
How long we continue the ttt of EH without atypia
minimum of 6 months.
In case of minimal adverse effects and no desire of fertility, LNG-IUS to be continued for 5 years
87
surveillance after EH without atypia ttt
End. biopsy every 6 months.
2 consecutive negative biopsies is needed to be discharged from the follow-up.
- if high risk patient to relapse, the latter is followed by annual biopsies.
88
When hysterectomy is indicated in ttt of EH without atypia
If endometrial hyperplasia persists for 12 months despite treatment, the risk of underlying cancer is high and the chances of disease regression are low, such that hysterectomy is advised
89
Hysterectomy indication in ttt of EH without atypia
1. Progression to atypical hyperplasia occurs during follow-up.
2. There is no histological regression of hyperplasia despite 12 months of treatment.
3. There is relapse of endometrial hyperplasia after completing progestogen treatment.
4. There is persistence of bleeding symptoms.
5. The woman declines to undergo endometrial surveillance or comply with medical treatment.
90
Type of Hysterectomy done in EH without atypia
in postmenopausal women, offer bilateral salpingo-oophirectomy
in pre-menopausal women. offer at least offer bilateral salpingectomy. and discuss ovaries removal
91
First line in ttt of atypical EH
Total Hysterctomy
92
How to manage EH with atypia in women who desire fertility/doesn't approve hysterectomy
End. biopsy every 3 months.
2 consecutive negative biopsies is needed to be discharged from the follow-up.
93
Does tamoxifen increases risk of EH
Yes, it inhibits proliferation of breast cancer
However, it has a partial agonist action on other tissues, including the vagina
and the uterus.
94
Alternative of tamoxifen if woman proven to have EH
Aromatase inhibitors
95
Rate of concomitant carcinoma when examining a uterus after hysterectomy in a woman with Atypical EH
43%
96
Best approach of TAH BSO in treating EH
Laparoscopic
97
What are the 4 variants of GTN
1. Invasive Mole (chorioadenoma destruens)
2. Epithelioid trophoblastic tumor
3. Choriocarcinoma
4. Placental site trophoblastic tumor
98
Most common site for Ectopic pregnancy
Falopian tube 95%
99
Incidence of Ectopic pregnancy
20 in 1000 pregnancy
100
Most common sites of ectopic pregnancy in fallopian tube
ampullary (55%)
isthmic (25%)
fimbrial (17%)
interstitial (2%)
101
What is heterotopic pregnancy
an ectopic pregnancy in combination with an intrauterine pregnancy following assisted reproduction treatment
102
Most common Presentation of Ectopic pregnancy
Unilateral or general pelvic pain
103
medical ttt of ectopic pregnancy
Methotrexate (with success rate of 90%)
104
Indication of methotrexate in Ectopic Pregnancy
Small <3.5 cm
no evidence of hemoperitoneum
HCG <1500 IU
no significant pain
CI in women with abnormal liver and renal function tests
105
Best surgical approach in ttt of ectopic pregnancy
Laparoscopy is gold standard
(laparotomy is indicated if patient is significantly compromised or laparoscopy is n't feasible)
106
In PV
• cervical movements tender.
• Posterior vaginal fornix may by bulging due to blood collection in pouch of Douglas
• A tender boggy mass may be felt on one side of uterus
107
Best diagnostic tool of Ectopic pregnancy
Transvaginal ultrasound (ring of fire appearance)
108
Indication of surgery in Ectopic Pregnancy
significant pain
Small >3.5 cm
HCG >5000 IU
109
Indication of Expectant management in Ectopic Pregnancy
Small <3.5 cm
no evidence of hemoperitoneum
HCG <1000 IU
no pain & clinical stable
110
Surgery options in ttt of Ectopic pregnancy
Salpingectomy (most preffered)
salpingotomy
salpingostomy
111
Response to methotrexate treatment
Assess bHCG in days 2,4,7
drop in bHCG 15% --> responding
if less than 15% ---> repeat
max. 3 doses --> surgery
112
contraindication of methotrexate
• Sensitivity to MTX
• Evidence of tubal rupture
• Breast feeding
• Intrauterine pregnancy
• Hepatic, renal, or hematological dysfunction
• Peptic ulcer disease
• Active pulmonary disease
• Evidence of immunodeficiency
113
Most common Presentation of HELLP syndrome
Epigastric pain and right upper quadrant tenderness (63%)
114
Ultrasound Criteria for Cervical Pregnancy called?
Paalman's criteria
115
What is Ultrasound Criteria for Cervical Pregnancy?
1, Echo-free uterine cavity or the presence of a false gestational sac only
2. Hourglass uterine shape
3. Ballooned cervical canal
4. Gestational sac in the endocervix
5. Placental tissue in the cervical canal
6. Closed internal os
116
Spielberg’s Criteria
is the criteria for diagnosing ovarian pregnancy
1. The fallopian tube on the affected side must be intact.
2. The fetal sac must occupy the position of the ovary.
3. The ovary must be connected to the uterus by the ovarian ligament
4. Ovarian tissue must be located in the sac wall.
117
Studdiford’s Criteria
criteria for Diagnosis of Primary Abdominal Pregnancy by u/s
1. Presence of normal tubes and ovaries with no evidence of recent or past pregnancy
2. No evidence of uteroperitoneal fistula
3. Presence of a pregnancy related exclusively to the peritoneal surface and early enough to eliminate the possibility of secondary implantation after primary tubal nidation.
118
Biggest risk factor of placenta previa
Caesarean delivery
incidence of placenta praevia increases from 10 in 1000 deliveries with one previous
caesarean delivery to 28 in 1000 with three or more caesarean deliveries.
119
Placenta previa Risk factors
-CS (most importnat)
- ART
-Smoking
-Advanced maternal age
120
Is there a place for cervical cerclage in women with placenta praevia or a
low-lying placenta?
The use of cervical cerclage to reduce bleeding and prolong pregnancy is not supported by sufficient evidence to recommend its use outside of a clinical trial
121
Anenatal corticosteroids in Placenta previa
A single course of antenatal corticosteroid therapy is recommended between 34+0 and 35+6 weeks of gestation for pregnant women with a low-lying placenta or placenta praevia and is appropriate prior to 34+0 weeks of gestation in women at higher risk of preterm birth.
It reduce all fetal risks of prematurity
122
success rare of vaginal delivery in low lying and placenta previa
Vaginal delivery in Low Lying:
10 mm from internal os: 56%
20mm from internal os: 93%
In case of previa or 3rd trimester with placenta less than 20mm from os, women should offer cesarian delivery
123
Which ovarian tumor is associated with LDH rumor marker
Dysgerminoma
124
What is the most likely histological subtype of ovarian cancer associated with endometriosis?
Clear cell carcinoma
125
Psammoma bodies are present in which ovarian tumors
serous cyst adenoma/cystadenocarcinoma
126
What hpv subtypes are vaccinated against with vaccine Gardasil
6,11,16 and 18
127
Which age group has the highest rates of chlamydia infection?
20‐24 year olds
128
The increase in size of endometrial cells during pregnancy is an example of
Hypertrophy
129
Karyotype of partial mole
69XXY
130
Renal cell carcinoma is associated with which type of metastasis?
Haematogenous
131
What is Exudate
an inflammatory extravascular fluid that has a high protein concentration and high specific gravity >1.02
132
What is Hageman factor
factor 12
133
What does Hageman factor activate
activates:
1. kinin system
2. clotting system
3. fibrinolytic system
4. complement system
134
Signs of inflammation
1. Raised ESR
2. Leucocytosis ~ increased number of immature neutrophils
3. Virchow's sign (loss of function)
+ 4 Cardinal Signs
1. Rubor (redness)
2. Tumor (swelling)
3. Calor (heat)
4. Dolor (pain)
135
Systemic acute phase response is predominantly induced by
1. interleukin-1
2. TNF
136
Risk of Lichen sclerosis to develop squamous cell carcinoma
<5%
137
Closure of PDA in preterm infant is typically by
NSAIDS; indomethacin
Ibuprofen could be used
138
Closure of PDA in term infant is typically by
Surgery is indicated
(Prostaglandin infusion maybe used but to keep it patent until surgery)
139
Closure of PDA in term infant is typically by
Surgery is indicated
(Prostaglandin infusion maybe used but to keep it patent until surgery)
140
Distinctive pattern of chronic inflammation
1. granulomas (focal area)
2. Epithelioid cells (activated macrophages)
141
when does cell injury occurs ?
when limits of adaptive responses are exceeded
(it may be reversible or irreversible)
142
Cell injury hallmarks include
1. decreased oxidative phosphorylation
2. Depleted ATP
3. Cellular swelling
143
Cell death is due to
irreversible cell injury
144
cell death hallmarks include
1. mitochondrial damage
2. loss of membrane permeability
145
Cell death characterized by
1. Pyknosis (condensation of chromatin)
2. Karyorrhexis (fragmentation of nuclear material)
3, Karyolysis (dissolution of nucleus)
146
Apoptosis characterized by
1. intact cell membrane
2. Degredation of nuclear DNA
147
Wound Healing has 3 phases
1. Inflammatory (2-3 days)
2. Proliferative (3 days- 3 weeks)
3. Remodeling
148
Predominat cells in wound healing process
Inflammatory phase (first 48 hours): PMNs
then it's got engulfed by macrophages
Next 3 days: Macrophages
149
In wound healing, fibroblast relay which type of collagen
Fibroblasts lay down type 3 collagen initially and subsequently type 1 collagen, which is strong collagen
(Remodelling)
150
Complete tensile strength of the wound take a period of what
12 weeks
151
What is carcinoma
malignancy of epithelial origin
152
What is sarcoma
malignancy of mesenchymal origin
153
What is teratoma
neoplasm that contains more than 1 germ cell layer
154
What is Hamartoma
non-malignant mass of disorganized but mature tissue indigenous to the site
155
A radiologically detectable tumor is
- 10 mm in size
- has 10`9 cells
156
All cancer can be metastasize except
Basal cell carcinoma and glioma
157
What is p53
- is a transcription factor regulates cell cycle
- is a tumor supressor
- located on chromosome 17
158
functions of p53
1. activates DNA repair
2. Initiates Apoptosis
159
Autosomal dominant syn. linked to mutation to p53
Li-Fraumeni Syn.
(has a 25 fold greater chance of developing malignancy by age of 50
160
The probability of sarcomatous change occurring in fibroid is?
0.1% ##
161
Midazolam is an effectve anxiolytc drug, used for preoperatve sedaton. Which receptor is responsible for its acton?
GABA
162
What histology constitutes the majority of vulvar cancers?
Squamous cell carcinoma
163
What is the most common congenital solid tumour of the mature newborn?
Neuroblastoma
164
What is the most common cause of the female urethral caruncle
Hypoestrogenism
165
Which is common malignant tumor in premature newborn?
Sarcococcygeal teratoma
166
Which pattern of endometrium do simple endometrial hyperplasia most likely
resemble?
Proliferative endometrium
167
Schiller Duval Bodies is found in
endodermal sinus tumor
168
What is the most common congenital solid tumor of the newborn?
Sacrococcygeal teratoma
169
Which ovarian tumor is associated with Meig's syndrome?
Fibroma
170
Which organ/system involved with Krukenberg tumor of the ovary?
GIT
171
what is the most common cause of the female urethral caruncle?
Hypoestrogenism
172
A woman has been diagnosed with carrying the BRCA1 gene. What is her life time risk of breast cancer and ovarian cancer?
80% Uterine
40% Ovarian
60-90% Breast
173
What type of epithelial tissue undergoes malignant change in the majority of bladder cancers?
Transitional
174
Which prominent cells are found in the tuberculosis granuloma?
Macrophages
175
Which neoplasm is characteristically associated with paraneoplastic syndrome of inappropriate antidiuretic hormone (SIADH)?
Small cell lung cancer
176
Incidence of leiomyoma to leiomyosarcoma
0.1%
177
Most common malignant tumor of the ovary
Papillary serous cystadenocarcinoma
178
Aria stella reaction effects on
Endometrium
179
Mismatch repair defect in Lynch syndrome is associated with most common
extraintestinal cancer
Endometrial cancer
180
What is lynch syndrome
Lynch syndrome used to be called hereditary nonpolyposis colorectal cancer (HNPCC). HNPCC is a term used to describe families with a strong history of colon cancer.
181
Inheritance pattern of lynch syndrome
Autosomal dominant
182
What type of cancer is linked to lichen planus
Squamous cell carcinoma
183
Most common degeneration of fibroid in non pregnant women
Hyaline degeneration
184
Psammoma bodies contain
Calcium
185
Which layer ablated for mennorrhegia
Basal layer of endometrium
186
Rate of gestational diabetes in pregnancy
2-5% of pregnancies
187
Presentation of acute fatty liver of pregnancy
Abdominal pain
lethargic
jaundice
deranged liver function
Coagulopathy
hypoglycemia
Hyperurecemia
188
Risk factors of acute fatty liver of pregnancy
Primigravida
male fetus
multiple pregnancy
obesity
189
Prevalence of acute fatty liver of pregnancy
1 in 10000 to 20000 pregnancies
190
Mortality rate of  Acute fatty liver of pregnancy
Fetal and maternal mortality = 20%
191
Cause of acute fatty liver of pregnancy
Fetal deficiency of long chain 3-hydroxyl COA dehydrogenase
192
Histological features of Lichen Sclerosus
- Epidermal atrophy or thinning
- hydropic degeneration of the basal layer (subepidermal hylainisation)
- dermal inflammation
193
Infertility rate in patients with endometriosis
40%
194
Risk of VIN to be developed into squamous cell carcinoma
15%
195
Most common degeneration of fibroid in pregnant women
Red degeneration
