male genital system Flashcards

1
Q

describe the basic anatomy of testes?

A

Testes have a membrane sheath covering it –> TUNICA ALBUGINEA

theres a layer more outer to tunica albuginea called tunica vaginalis

below the tunical albuginea we have a TUNICA VASCULOSA

So from outside to inside –> T. vaginlais –> T. albuginea —> T. vaginalis

The testes also have fibrous septum dividing them internally dividing them to lobules

inside the testes :

Lobules formed of seminiferous tubules which then make a network of ductules ( Mediastinal testes ) which then goes through the epididymis which has a head , body , tail that then continue upward as vas deferens to convey sperm

Vas deferens joins the seminal veiscles ( posterior to the bladder ) to form ejaculatory duct that opens into the urethra

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2
Q

whats the function of prostate?

A

its located inferior to the neck of the bladder

Secrete alkaline fluid that will neutralize the vaginas acidity later

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3
Q

what are the layers from inside to outside in tests?

A

Tests

1- T. vasculosa

2- T. albuginea

3- T. Viganalis

4- Internal spermatic fascia

5- Cremasteric muscle and fascia

6- External spermatic fascia

7- Dartos fascia and muscle

8- Skin

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4
Q

what are testicular lesions ?

A

Cryptochidism

Inflammatory lesions

Vascular disturbances

Male infertility

Tumors

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5
Q

what is the function of seminiferous tubules?

A

Make mature sperm :

Spermaogonia 1 —> Spermatocyte 2 —> Spermatocyte spermatids

the main cells here are GERM cells

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6
Q

what are the other supporting cells ?

A

Steroli cells

Leydig cells

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7
Q

describe steroli cells ?

A

Epithelium cells

Connected by tight junctions

Contain cytoplasmic filaments = CHACOT BOTTCHER CRYSTALS

Secrete inhibin, anti mullerian hormone and ESTROGEN

THESE NOURISH THE GROWING SPERM

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8
Q

describe leydig cells?

A

supporting cells found outside the tubules in the interstitial

in the cytoplasm they contain :

Lipid droplet

Rod shaped crystals –> REINKE CRYSTALS( function of the crystals is unkown
BUT ANY TUMOR ARISE FROM LEYDIG CELLS WILL HAVE THESE CRYSTALS in the cytoplasm

secrete testosterone mainly and little bit of estrogen

( male with a tumor and female manifestation think of leydig or steroli cells cuz they secrete estrogen )

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9
Q

what is cryptorchidism ?

A

Crypt = testes

Orchid = hidden

So hidden testes

Failure of testicular descent into scrotum

MOST COMMON CONGINETAL ABNORMALTIY OF GENITO TRACT

Bilateral in 10% of patients ( both sides )

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10
Q

describe the descent of testes?

A

Develops at T10-T12 segments in post abdominal wall from genital ridge and subsequently descend to reach scrotum

Begin at 2 month intrauterine life

3th month reach iliac fossa

4-6 month reach deep inguinal ring

7 month –> inguinal canal

8–> superifical inguinal ring

9 —> scrotum

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11
Q

what stops and what continues in cryptorchidism?

A

Sperm production stop cuz not idea temp

BUT

Hormone production continue normally ( Testosterone )

SO spermatogenesis stops but testosterone continue and SECONDARY SEXUAL CHARACTERISTICS DEVELOP

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12
Q

what is the etiology of crytporchidism ?

A

no one knows

UNKOWN

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13
Q

what are the complications of cryptorchidism ?

A

Undescended tests become atrophic ( cuz no production = no function )

Bilateral cryptorchidism results in sterility ( sterility = uncurable infertility, infertility = inability to conceive but curable )

In unilateral cases of cryptorchidism = even the normal descent testes will get atrophied even though it produces sperm ( unknown why )

3-5 fold increase risk of testicular cancer

Increased risk of cancer even in the normal descent testes will have high chance —> SEMINOMA –> the most common malignancy

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14
Q

what is the treatment of cryptorchidism ?

A

Surgical placement of undedescended testis into scrotum ( orchiopexy ) by 18 month

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15
Q

what are the mircoscopic features of testicualr atrophy resulted from cryptorchidism ?

A

Small tubules –> No germ cells, thick basement membrane

Interstitial FIBROSIS

Increased leydig cells ( more room to get bigger and produce hormones )

Germ cell neoplasia in situ —> IF it appears it will show :

Large cells with clear cytoplasm

Largue nuclei

Prominent nucleoli

PLAP+ PROTEIN SHOWN UNDER STAIN

if you see PLAP+ = CANCER

Pretty large and prominent = P = PLAP L = large cells A = abdundant clear cytoplasm , P = prominent nucleoli

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16
Q

where does the testicular inflammation happen?

A

More common in epididymis

than the testis

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17
Q

what is etiology of testitcular inflammation ?

A

STD

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18
Q

when mumps rare and when is it common?

A

Before puberty –> MUMPS ORCHITIS is rare –> cuz HPA axis is not working yet so less blood supply going to the testes

After puberty —> Common and usually one testicle ( one week after parotidits )

Common cuz now the HPA is working and more blood supply is going to the testes

Orchitis = inflammation of testis

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19
Q

what is varicocele ?

A

Tortuous and dilated veins of PAMPININIFORM PLEXUS OR TESTICULAR VEIN

testies draiange is

Pampiniform then testicular vein then IVF if right or Left renal vein if left

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20
Q

why varicocele more common in left side?

A

Cuz the right testicular vein drains into the IVF ( huge so no much pressure )

but

Left side testicular vein drains into left renal vein which is a small vein so much pressure n its a bit harder

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21
Q

what causes varicocele ?

A

incompetent valves of vein

why ?

now one knows IDIOPATHIC

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22
Q

why is varicocele associated with Infertility ?

A

cuz of the blood pooling

The blood pooling will raise the temp affecting the production in both testes

Another theory

Increase Reactive oxygen species production = damage DNA of sperm in both

Another theory :

Disrupt HPA axis

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23
Q

how do we diagnose Varicocele ?

A

Doppler ultra sound of the scrotum

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24
Q

what is torsion of testis ?

A

Twisting of the spermatic cord with all of its contents

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25
what results from this twisting of the spermatic cord?
Obstruction of the veins ( cause veins are easily obstructed ) The arteries remain patent cuz they have thick walls This obstruction of veins and continuation of blood coming from arteries will lead to : INTENSE vascular engorgement ---> Infarction
26
what are the 2 types of torsion of testicular?
Neonatal torsions = Not associated to anatomical defect ( mostly due to problems during labor Adult torsion : DUE TO BILATERAL CONGINETAL ANOMALY = bell clapper abnormality
27
what is bell clapper abnormality ?
congenital problem where the testis are no longer oblique they come transversally free floating in the sac so easily twisted if patient come with adult testicular torsion and has bell clapper you have to check on the other testy too CUz the bell clapper affect both testis not one
28
what are the complications testicular torsion ?
Infarction = if the cord is not fixed/untiwsted within 6 hours = gg = rip testis Infertility
29
why infertility happen in torsion ?
When torsion happen = damage = release of testicular antigens into blood Since the testis are outside the immune system doesnt know they are part of the body will recognize the antigen and then go the attack both testis
30
what is the clinical presentation of testicular torsion ?
Severe sudden pain TO diagnose = doppler ultra sound like varicocele
31
what is the treatment?
surgically fix the twisted one Then go the other one that is not twisted and fix the congenital anomaly ( bell clapper ) b4 it gets twisted
32
what is male infertility ?
Male = in male POV Infertility = inability to conceive after 1 year of trying with the same partner without contraception Sterility = incurable infertility Impotence = erectile dysfunction
33
what are the causes of male infertility ?
Supra-pre-testicular Testicular infertility Post-testicular infertility in all cases its js not being able to produce sperm
34
what are supra-pre-testicular causes ?
Injuries of hypothalamic pituitary area --> disrupt HPA axis
35
what are testicular causes ?
Chromosomal abnormalities --> KLINEFELTER non chromosmal causes--> Varicocele , cryptorchidism, chemo/radio therapy
36
what are post-testicular causes ?
Blockage of excretory ducts through which sperm reach urethra
37
what is steroli only syndrome ?
Germ cell aplasia So in the tubules u only find the steroli cells inside the tubules no germ cells ( hence the name steroli only) Results in Azoospermia = no sperm in the semen sample of patient
38
what causes steroli only syndrome ?
Y chromosome microdeletion Chemical or toxin radiation therapy Severe testicular trauma/injury
39
what do you do when patient come with enlarged scrotum ?
History + clinical picture Examination Transillumination test : If positive = illuminate = fluid not solid = hydrocele or spermatocele IF negative = doesnt illuminate = solid = TUMOR
40
what is spermatocele ?
Cyst containing sperm Dilation of efferent ductules in the rete testis or head of epididiymis Usually on the upper pole where we find efferent tubules and vas deferes
41
what causes spermatocele ?
idiopathic no one knows
42
what is the clinical presentation of spermatocele ?
painless mass
43
How do we diagnose spermatocele ?
Positive trans-illumination test Ultra sound = Cyst , displaces testes if large
44
what is hydrocele ?
accumulation of fluid in tunica vaginalis
45
what causes hydrocele?
no one knows
46
what is the clinical presentation ?
painless mass
47
how do we diagnose hydrocele?
Positive trans illumination test Ultra sound = CYST but it ENVELOPES surrounds the testis instead of displacing ( spermatocele displaces it )
48
what are the characteristics of testicular tumors?
happen in POST pubertal males ( after 20+ ) 95% of testicular tumors arise from GERM cells ( post pubertal males go to GYM = GERM ) Sometimes follow germ cell neoplasia in situ ( cryptorchidia ) ( large cells, large cytoplasm, prominent nucleus, express PALP1 MOST OF THEM ARE MALIGNANT AGE IS IMPORTANT
49
what are the ages of which testicular peaks in ?
2-4 20-40 above 60 Above 60 if you see tumor in scrotum = its either Lymphoma = 1st differential diagnosis Spermatocytic tumor
50
what are testicular tumor associated with ?
Specific serum markers no need for biopsy if u see marker its enough Its contraindicated to take biopsy from testis or ova cuz after biopsy the tumor spreads more
51
where can testicular tumors arise from ?
Germ cells tumors Steroli cells Ledy cells
52
where do germ cell tumors arise from ?
Seminiferous epithelium ( EXCLUDING THE STEROLI CELLS )
53
what are the environmental risk factors for germ cell tumors?
Development of cancer in one testis Male infertility History of mumps orchitis Inguinal hernia
54
what are genetics risk factors for germ cell tesitcular cancer?
Cryptorchidism Gonadal dysgenesis Klinefelter syndrome ( XXY) Family history of testicular cancer
55
what is the pathogenesis in genetic abnormalities?
Chromosome 12 become isochromosome 12 ---> Loses a long arm and replace it with a short arm so it becomes with 2 short arms Mutation in KIT gene
56
what are the classifications of testicular tumors?
1- Germ cell tumors ( aggressive ) 2- Sex cord stromal tumor ( generally benign ) 3- Others ---> non hodking lymphoma, mesothelioma, para testicular , metastatic
57
what are the classification of Germ cell tumors?
1- Derived from Germ cell neoplasia in situ ( Cryptorchidism ) 2- Unrelated to GCNIS the germ cell tumors are aggressive
58
What are the tumors derived from GCNIS?
Seminoma Embryonal carcinoma Yolk sac tumor --> POST TYPE Trophoblastic tumors Teratoma --> POST TYPE Teratoma with somatic type malignancies Mixed germ cell tumor ---> POST type YTM --> if it was derived from GNICS its post pubertal
59
what are the tumors unrelated to GCNIS?
Spermatocytic tumor ( 2nd differential in old males ) Yolk sac tumor ---> PRE Teratoma --> Pre Mixed ---> Pre YTM --> if it wasnt related to GNICS = pre pubertal So non related ones are = YTM ( pre ) + S ( spermatocytic tumor )
60
so when are YTM post and when they are pre?
YTM Y= YOLK SAC T= TERATOMA M= Mixed If they were related to GCNIS = POST PUBERTAL if they were NOT related to GCNIS = Pre pubertal
61
what are the sex cord stromal tumors?
Leydig cell tumor (K body ) Stertoli cell tumor ( Charcot body) Granulosa cell tumor Thecoma/fibroma they are usually benign
62
what is seminoma ?
most common germ cell tumor in males Germ cystic neoplasia in situ derivates Arise from Seminiferous tubules Could be Pure ( alone ) or Mixed ( with other tumors )
63
what is the age group for seminoma ?
30-40 10 years older than other tumor age group ( other tumors happen in younger age )
64
what are proteins seen in seminoma?
Since its GCNIS derivate : it has PLAP1 + CD117
65
what is the treatment of seminoma?
orchiectomy + Radiation --> Respond well to
66
what are the grossly features of seminoma ?
Soft well defined Grey-white Multinodular Replace entire testis
67
what are the microscopic features of seminoma ?
MONOTONUS = all the cells are the same ( no variation in anything ) all the cells are : Large, clear, Glycogen rich cytoplasm, prominent nuclei ( similar to GCNIS but here it invades) In Nest shape with fibrous septa with lymphocyte Also similar to CLEAR CELL RCC ( but remember in clear cell there was vessels cuz of VHL mutation)
68
what is spermatocytic tumor?
tumor arising from seminal epithelium BUT NOT DERIVED FROM GCNIS
69
what age group where spermatocytic tumor happen?
above 50 years remember old patient = tumor = 2 differentials 1- lymphoma 2- spermatocytic
70
what are the characteritics of spermatocytic tumor?
NOT mixed with any other Germ cell tumor Not associated with GCNIS Not metastasize
71
what proteins are shown in Spermacytic tumor?
non it doesnt have PLAP cuz its not GCNIS dervative
72
what is the treatment of spermacytic tumor?
orchiectomy alone
73
what are the grossly features of spermatocytic tumor ?
Similar to seminoma ( Soft , well defined, white, multinodular, replace testis ) but with mucoid material and cysts
74
what are the microscopic features of spermatocytic tumor?
Polymorphic ( opposite to seminoma ) many shapes, sizes, different nucleous in everything variable in anything --> Small cells with scant cytoplasm, Intermediate cells , granular chromatic, GIANT CELLS maybe mutinucleation arranged in sheets NO LYMPHOCYTE INFILRTATION ( in seminoma there was infiltration )
75
what is embryonal carcinoma?
Very malignant and aggressive tumor Common component of mixed germ cell tumor RARELY COMES ALONE it usually have many other components
76
at what age does embyronal carcinoma appear?
10 years younger than seminoma ( so at 20 ) in seminoma was 30-40
77
what is the serum marker of embryonal carcinoma ?
high LDH
78
What protein is positive in embryonal carcinoma?
CD30 --> Very imp
79
what is the treatment of embryonal carcinoma ?
Orchiectomy and chemotherapy
80
what are the grossly features of embryonal carcinoma ?
poorly circumscribed ( HIGHLY AGGRESSIVE ) Gray white mass with hemorrhage and necrosis Does not replace the entire testis only one nodule
81
what are the microscopic features of embryonal carcinoma ?
ANPLASTIC EPITHELIUM CELLS --> most imp Arranged in solid sheets or tubules or glands or papillary Necrosis
82
what is Yolk sac tumor ?
Endodermal sinus tumor Called yolk sac cuz it has similar histo structure to yolk sac in children : MOST COMMON primary testicular tumor ( cuz its unrelated to GCNIS ) In adults : Common component of mixed germ cell tumor ( CUZ RELATED TO GCNIS )
83
what are the 2 types of yolk sac tumors?
post pubertal --> related to GNCIS - part of MGCT Pre pubertal --> unrelated to GNCIS --> pure
84
whats the serum marker for Yolk sac tumor ?
AFP
85
what the protein seen in yolk sac tumor ?
AFP
86
what are the grossly features of Yolk sac tumor ?
MULTICYSTIC ( full of cysts ) yello whitish mucinous soft
87
what are the microscopic features of Yolk sac tumor features?
Cuboidal to columnar epithelial cells that FORM MANY AND HUNDREDS OF SHAPES : Microcysts ( most imp, remember gross was multicystic ), glands, sheets ,papillae, dumbell , etc SCHILLER DUVAL BODY --> reason why its called yolk sac ( present in normal yolk sac ) HYALINE GLOBULES
88
describe schiller duval body in yolk sac tumor ?
Papillary projection with Central blood vessel The blood vessel is surrounded by a thick layer of basement membrane Covered by a layer of embryonic epithelium cells
89
describe hyaline globules found yolk sac tumor ?
Eosinophilic PAS positive globules --> AFP These represent the AFP Mnemonic --> yolk SAC tumor S = schiller duval body A= AFP C: children
90
what is teratoma ?
Germ cell tumor Composed of cell types derived from all 3 germ layers Ectoderm --> skin, neural tissue Endoderm--> glandular tissue Mesoderm -> fibrous tissue, muscle,s fat, cartilage
91
what are the 2 types of teratome ?
Prepubertal Post pubertal
92
describe prepubertal?
Before 6 y/o NOT associated with GCNIS NOT ASSOCIATED WITH isochromosome 12 BENIGN --> less likely to metastasize or reoccur
93
describe post pubertal ?
Associated with GCNIS associated with isochromosome 12 Malignant
94
what are the grossly features of teratoma ?
Lobulated Cysts of Mucinous/ Gelatinous/ Serous material
95
what are the microscopic features of POST pubertal type teratoma?
Post pubertal = Malignant TISSUES ARE HAPHZARADLY ARRANGED =not organized You will see GCNIS features = large cells, clear cyto, large nuclei, PLAP, prominent nuclie
96
what are the microscopic features Pre puberal teratoma ?
Its benign So you will see ORGANIZED ORGANOID ARRANGEMENT ( grouped together ) No GCNIS features cuz its not associated with it if it was pre pube
97
what are the microscopic features of teratoma malignant ?
Third type its teratoma but somatic type malignancy it turns into adenocarcinoma, squamous cell carcinoma, neuroendocrine , etc
98
what is choriocarcinoma ?
cancer arising from chorionic villi Mixed Germ cell tumor HIGHLY MALIGNANT
99
what is the serum indicator for Choriocarcinoma ?
hCG
100
what is the protein found in choriocarcinoma ?
hCG
101
what are the characteristics of choriocarcinoma ?
Most aggressive NSGCT May not cause enlargement testicular Spread rapidly by blood Treated by surgery and chemotherapy
102
what are the grossly features of choiocarcinoma?
solid sheats --> no villi hemorrhage Irregular necrosis
103
what are the histological features of choriocarcinoma ?
varying amount of Syncytiotrophoblast cells :large multinucleated cells with large irregular nuclei Cytotrophoblasts : Pale cytoplasm with single large nucleus and prominent nucleus Intermediate trophoblasts
104
what leydig cell tumor?
sex cord stromal tumor affect leydig cells --> hormone producing cells
105
what is the clinical presentation of leydig cell tumor?
since its hormone producing tumor : it produces androgens and may produce estrogn IN children : Precocious puberty ( cuz much hormones ) In adults : Gynecomastia, infertility, etc ( estrongen will be produced more )
106
what are the grossly features of leydig cell tumor?
Well circumscribed Brown mahogany cut surface --> LIKE ONCOCYTOMA AND CHROMPHOBE RCC
107
what are the microscopic features of leydig cell tumor ?
Solid sheets Polygonal cells with abundant eosinophilic cytoplasm Cytoplasm contains : Red rods =Reinke crystals Lipofuscin droplet --> pigment
108
what does steroli cell tumor secrete ?
Estrogen only cuz it has aromatase enzyme ( convert testosterone into estrogen , testosterone come from leydig cells )
109
what is the clinical manifestation stertoli cell tumor ?
it produces estrogen only so estrogen manifestation Gynecomastia , infertility, loss of libido, erectile dysfunction
110
what are the grossly features of sertoli cells tumor?
Well circumscribed , solid , WHITE NODULE
111
what are the microscopic features of sertoli cell tumor?
Tubules in shape ( in leydig was sheet ) Cells with clear or pale eosinophilic cytoplasm cytoplasm contain : Lipids Filaments = Charcto bottcher filaments
112
what is the clinical presentation of all testicular tumor?
painless testicular mass negative transillumination test
113
what is special about metastasize of testicular tumors?
they spread by lymph, blood, but These are pluripotent cells when it metastasize it can become a different testicular tumor for example start off as seminoma --> meta ---> become embryonal w hakaza
114
what is the most common tumor for epididymis ?
Adenomatoid tumor Tubular structure ( glands ) lined cuboidal cells
115
what is the most common tumor of spermatic cord?
lipoma
116
what is most common MALIGNANT tumor of spermatic cord?
Rhabdomyosarcoma
117
what are 3 zones of prostate ?
the prostate itself is below the bladder surrounding the urethra Centra zone ---> urethra and bladder Peripheral zone --> away from the bladder In between them transitional zone
118
what happens to transitional zone at 50?
expands causing nodular prostatic hyperplasia
119
what is the source of prostatic tumors?
Peripheral zone 80% of tumors come from it
120
what are types of cells in prostate?
Secretory cells Basal cells
121
describe secretory cells ?
Along glandular lumen Nucleus is DARK
122
describe basal cells ?
Betweeen secretory cells and basement membrane Nucleus is lighter blue Their presence distinguishes benign from maligancy if it was present = benign Not present = malignant
123
what causes prostatic inflammation?
Bacteria to the prostate from urethra by : Infected urine Stool from rectum STDS
124
What are the risk factors for inflammation ?
Following surgical manipulation --> cather Prostatic enlargement Recent bladder infection
125
how do we diagnose inflammation ?
Urine and prostatic secretions no need for biopsy
126
what are the forms of prostatic inflammation?
Acute bacterial prostatitis --> Same bacteria as UTI Chronic bacterial prostatitis ---> Recurrent UTI Chronic nonbacterial prostatitis / Chronic pelvic pain syndrome (90%)-->Similar to chronic bacterial prostatitis but negative culture--> ASSOCIATED WITH CHLAMYDIA TROCHAMTIS, UREAPLASMA UREALYTICUM Granulomatous prostatitis
127
what is benign prostatic hyperplasia?
Most common benign prostatic disease more than 50 years old NON CANCEROUS Hyperplasia of transitional zone doesnt predispose to cancer Compress urethra
128
What does it raise the lvl of?
PSA But its not cancerous u take a biopsy in case of elevation to tell if cancer or not
129
what causes this benign hyperplasia ?
Testosterone is the main cause Naturally present in males It will get convered to DHT by type 2 5a reducatse This DHT bind to androgen receptor ( AR ) it release growth factors causing proliferation in the stormal cells these new cells will travel to the lining of the epithelium decreasing apoptosis So you have increased proliferation +Accumulation = hyperplasia
130
what are the grossly features of benign prostatic hyperpalsia ?
Enlarged prostate with multiple nodules as they enlarge they compress the centrally located urethra some papillary form because of accumulation of epithelial cells
131
what are the microscopic features of BPH?
Well circumscribed non capsulated nodules Proliferation of epithelial cells Glands are lined by 2 layers of cells Papillary structures -project into lumen are present Corpora amylaceae present Proliferation of stroma BASAL CELLS ARE PRESENT
132
what is the clinical presentation of BPH?
Elder with difficulty in starting urine Intermittent interruption of stream while voiding Urine retention
133
what are the complications of BPH?
Hypertrophy of bladder---> Trabeculation of wall --> diverticula Infection --> cystitis or pyelonephritis if it goes up Prolonged obstruction results in hydroureter , hydronephrosis --> renal failure
134
what is High grade PIN?
High grade prostate intra-epithelium neoplasia its premalignant condition WE DONT HAVE LOW GRADE
135
what are the grossly features of high grade PIN?
nothing its microscopic feature
136
what are the microscopic features of high grade PIN?
Cells become enlarge nuclei --> NUCLEOMEGALY Prominent nucleoli ---> NUCELOLOMEGALY these are found in all cancers of prostate Basal cells are present but less amount and gone in some places
137
what is special about high grade PIN?
IT DOESNT LEAD TO : ELEVATED SERUM PSA ( DOESNT AFFECT IT ) NOR ABNORMAL DIGITAL EXAMINATION FINDINGS OR RADIOLOGICAL
138
what is the prognosis of High grade PIN?
focal --> one area = follow up by PSA every 6-24 month Multifocal --> multiple areas with HGPIN -> re do biopsy No therapy needed
139
what is prostatic carcinoma ?
MOST COMMON FORM OF CANCER IN MEN Wide variation in natural history of prostate cancer ( someone could die without it even doing anything or could die from it being so aggressive )
140
what are the risk factors for prostatic carcinoma ?
age - 65 and 75 Family history Hereditary factors --> MUTATION OF BRCA2
141
what is the site of prostatic carcinoma?
Prostatic apex more involved than base Peripheral zone is often more involved
142
what are the pathogenesis dependent on AR signaling?
ANDROGEN BIND TO AR- --> pro-growth and survival genes
143
what are the genetic mutations of prostatic carcinoma ?
Mutation of BRCA2 Chromosomal rearrangement : ETS IS AKA ERG ETS next to TMPRSS2 promoter gene ETS gene under the control of TMPRSS2 promoter ETS overexpression PCA3 overexpression its aka DD3 so BRCA2, ETS (ERG ), PCA3 ( DD3)
144
what is the grossly morphology of prostatic carcinoma ?
Multifocal -> we need to take from one site we take from multiple Neoplastic tissue is firm, gritty, show focal yellow discoloration
145
what are the microscopic features of prostatic carcinoma?
different than normal adenocarcinoma Crowded small acini ( gland ) ( smaller than the normal gland) Formed by SINGLE LAYER of epithelial cells NO BASAL CELLS Nucleo and nucleolo megaly Crystalloids --> composed of inorganic sulfar, deeply eosinophilic, rhomboid Mucin : Acidic mucin looks basophilic or deeply eosinophilic
146
how do we grade prostatic carcinoma?
Gleason grading
147
describe the gleason grading ?
Based on architecture classified into 5 patterns ( 5 grades ) Gleason score is sum of 1ry and 2nd pattern
148
describe how the grading works?
grade 1 = cancer forms well define nodules with clear acini ( glands ) the more you go down in grades the more the distorded the acini and nodules are in grad3 = they start moving away from each others in 4 or 5 they start fusing together and forming large abnormal structures that are no longer acini ( lose ability to form acini )
149
how do we score the grading ?
we take from multiple areas and then whatever we find the most of we put in the first and then followed by the second most abundant type For example : 3+2 = means most of the tumor was 3 and then there are areas that are 2 2+3 = most areas were 2 w hakaza if all the areas ( focals ) = we js put the same number twice For example 3+3= all tumor was 3
150
how to differentiate betwen grade 3 and 4 and 5 in microscope ?
if u can see the acini ( Gland ) and draw a circule around it = grade 3 if you see them start fusing = grade 4 grade 5 = u wont see acini all are fused
151
how does prostatic cancer spread?
Local --> invade prostatic capsulse , vesiclaes , bladder neck , perineural tumor Lymphatic --> Obturator nodes and eventually to para aortic Blood --> MAINLY BONES PROSTATE LOVES BONES --> LUMBAR SPINE, PROXIMAL FEMUR, PELVIS, RIBS Both osteoclastic and osteoblastic activities are affected but mainly obsteoblast = bone formation = if you see old pateint with bone metastasis that stimulates osteoblast = prostatic cancer
152
what are is clinical course of prostatic cancer?
Early stage --> asymptomatic , discovered by PSA and rectal Transrectal ultrasenography + biopsy Multiparametic MRI
153
what are the categories of prostate cancer ?
Pathology T category = based on pathological examination of RESECTED PROSTATE Clinical T category cT= based on rectal examination and imaging of prostate biopsy
154
what are the biomarkers of prostate cancer?
1- PSA = raising in prostatic cancer ( produced by epithelium of prostate and its normally present but low ) we have density of PSA = high density = higher malignancy ( density = PSA serum / Volume of prostate measured by TRUS ) 2- Prostatic acidic phosphatase ( PAP ) PAP Only elevate when prostate metastasize not specific , could be elevated in renal ,liver, bone malignancies ) 3- AP, ( also raise in liver and bone metast ) DD3 ( PCA3)-> was one of the risk factors 4- in urine : PCA3 (DD3) mRNA TMPRSS2 ERG ( ETS) DNA fusions was also risk factors