Subject:

  Pathology   Second  Semester  A.Y.  2013-­‐2014  

Topic:   Male  Genital  Tract  Diseases  
Lecturer:   Dr.  Carina  P.  Villamayor  
  Date:   January  8,  2015    
 
OUTLINE   o Interferes   with   cleanliness   and   permits   accumulation   of  
I.  Penis   secretion   and   detritus   under   the   prepuce   →Prone   to  
  A.  Congenital   repeated   infection   (deposition   of   smegma:   desquamated  
  B.  Inflammation   epithelial  cells,  sweat,  debris)  and  carcinoma  
C.  Tumors      
o May   result   from   anomalous   development   or   from   repeated  
II.  Testis/Epididymis  
A. Congenital  
attacks  of  infection  causing  scaring  of  the  preputal  ring.  
B. Regressive    
C. Inflammation  
D. Vascular  diseases  
E. Tumors  
III.  Prostate  
  A.  Inflammation  
  B.  Benign  Enlargement    
  C.  Malignancy  
 
PENIS          
A. CONGENITAL   Figure  3.  Phimosis  
PARAPHIMOSIS  
• Malformations  of  the  penis  
o Phimotic  prepuce  is  forcibly  retracted  over  the  glans  penis  
o Abnormal   location   of   the   urethral   orifice   along   the   penile  
o Extremely  painful  
shaft  
o Cause  urethral  constriction  and  serious  acute  urinary  
o Malformation   of   the   urethral   groove   and   urethral   canal  
retention  
creating  abnormal  openings  on  the  penis  
 
o May   be   associated   with   failure   of   normal   descent   of   the  
B. INFLAMMATION  
testes  and  with  malformation  of  the  urinary  tract  
• Invariably  involves  the  glans  and  prepuce  and  include  a  variety  
o Abnormal   opening   is   usually   constricted   and   may   result   in  
of  specific  infection  (  sexually  transmitted  disease)  and  
urinary   obstruction   and   increase   in   risk   of   ascending   urinary  
nonspecific  infection  
tract  infection  
 
o Normal   ejaculation   and   insemination   may   be   hampered   or  
BALANOSPOSTHITIS  
blocked  →  result  in  sterility  
  • Infection  of  the  glans  and  prepuce  caused  by  a  variety  of  
HYPOSPADIAS  (Ventral  Aspect)   organisms:  
-­‐  More  common  (1/300  live  male  births)   o Candida  albicans  
EPISPADIAS  (Dorsal  Aspect)   o Anaerobes  
  o Gardnerella  
o Pyogenic  
• Occurs  as  a  consequence  of  poor  local  hygiene  in  uncircumcised  
males,  causing  the  accumulation  of  smegma  beneath  the  
prepuce.  

       
Figure  1.  Hypospadias  

       
Figure  4.  Balanosposthitis  
 
C. TUMORS  (NEOPLASIA)  
I. BENIGN  
CONDYLOMA    ACUMINATA  “Venereal  or  Genital  warts”  
o Benign  sexually  transmitted  tumor  caused  by  HPV  types  6  
  and  11  
Figure  2.  Epispadias   o Exactly  the  same  appearance  and  etiology  as  on  the  female  
  external  genitalia  
PHIMOSIS   o May  occur  on  any  moist  mucocutaneous  surface  of  the  
o Abnormal  small  opening  which  prevents  normal  retraction  of   External  genitalia  and/or  perineum  
the  prepuce   o Recur,  rarely  progress  to  carcinoma  

Trans  Group:  Sadaya,  Saligan,  Salindong,  Salise   Page  1  of  11  

Edited  By:    
Gross      
o Occurs  in  the  external  genitalia  and  perineum,  often  on  the  
coronal  sulcus  and  inner  surface  of  the  prepuce  
o Single  or  multiple  sessile  or  pednculated,  red  papillary  
exrescence  that  vary  from  1mm  to  several  mm  in  diameter  

 
Figure   7.   Bowen   Disease(Gross   and   Histology).   Right:   note   “loss   of   maturation  
pattern”  where  surface  cells  not  much  different  from  base  cells,  quite  typical  
of  squamous  CJS  everywhere  
           
Figure  5.  Condyloma  Acuminatum:  multiple  pedunculated  red  papillary  
excrescence  
BOWENOID  PAPULOSIS  
Histology   o Sexually  active  adults;  younger  patients  
o Branching,   villous     papillary   CT   stroma   that   may   have   o Presence  of  multiple  pigmented  reddish-­‐  papular  lesions  
superficial   hyperkeratosis   and   acanthosis   (   thickening   of   o Never  develops  to  invasive  CA,  can  spontaneously  regress  
 
underlying  epidermis)  
Table  1.  Bowen’s  Disease  vs.  Bowenoid  Papulosis  
o Koilocytosis:   perinuclear   cytoplasmic   vacuolization   of   the  
Bowen’s  Disease   Bowenoid  Papulosis  
squamous  cells,  classical  for  HPV   Associated  with  HPV  16  
o May  have  a  viral  atypia  but  true  dysplasia  is  rare   History  of  promiscuous  sexual  activity  
o Intact  basement  membrane   Solitary  lesions   Multiple  lesions  
Older  patients   Younger  patients  
Usually  progress  to  SCCA  in  10  %  of   Never  develops  into  invasive  CA  
cases  (high  grade  CIS)  
 
B. INVASIVE    
SQUAMOUS  CELL  CARCINOMA  
o Infiltrating  or  invasive  
o US:  Uncommon  (<1%  CA  in  male)  
o Asia,  Africa,  S.  America:  10-­‐20%  of  male  malignancies  
    o Usually    this  is  present  in  patients  with  poor  local  hygiene  
Figure  6.Condylomata  Acuminata  (histo):  Left:  Papillary  (villous)  architecture   o Ages  40-­‐70  years  old  
and  thickening  of  epidermis.  Right:  Koilocytosis;  nuclei  appear  raisin-­‐like.   o Circumcision  confers  protection  
  o Association  with  genital  hygiene  and  HPV  16  and  18  
II. MALIGNANT   o HPV  16  most  frequent  culprit  and  HPV  DNA  can  be  detected  
A. In-­‐situ     o Cigarette  smoking  increases  risk  of  developing  CA  of  the  penis  
BOWEN  DISEASE   o Bowen  disease  may  transform  into  SCCA  in  10%  of  patients  
o Squamous  cell  carcinoma-­‐in-­‐situ  of  the  skin  of  the  shaft  of    
the  penis  and  scrotum   Gross  
o Occurs  in  the  genital  region  of  both  men  and  women,  usually   o Papillary  lesion  stimulate  condyloma  acuminata  producing  a  
over  35  years  old   verrucous  cauliflower-­‐like  fungating  masses  
Gross   o Flat  lesions  appear  as  areas  of  epithelial  thickening  
o Solitary,  thickened  gray-­‐white,  shiny,  opaque,  and  velvety   accompanied  by  graying  and  fissuring  of  the  mucosal  surface  
plaque  with  shallow  ulceration  and  crusting   o Progress  to  ulcerated  papule  
o Single  or  multiple  shiny  red  velvety  plaques  on  the  glans  and    
prepuce  –  Erythroplasia  of  Queyrat  
 
Histology  
o  Epidermal  proliferation  with  numerous  mitosis,  dysplastic  
cells  with  lack  of  orderly  maturation  and  large  
hyperchromatic  nuclei  
o Dermal-­‐epidermal  border  is  markedly  delineated  by  intact  
Basement  Membrane  
o Over  the  span  of  years,  10%  may  develop  infiltrating      
squamous  carcinoma  and  visceral  cancer   Figure  8.  Squamous  Cell  Carcinoma  of  the  Penis  
Histology  
o Differentiation  and  can  have  connection  or  no  connection  to  
the  epidermis.  
 

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 2. Endocrine  factors,  or  
3. Mechanical  factors  that  prevent  passage  of  the  fetal  
testis  thru  the  inguinal  canal  
o Epidemiology:  
§ 1%  of  all  births  
§ Unilateral    >>  bilateral  (25%  cases)  
§ Associated   with   significantly   increased   incidence   of   germ  
cell   tumors   (recall   that   major   lesions   in   the   testis   are  
tumors)  
  o Clinical  significance:  (from  Essentials  of  Rubin’s  Pathology)  
Figure   9.   Note   the   presence   of   keratin   pearls   and   large   cells   with   pleomorphic   § Related   to   an   increased   incidence   of   infertility   and   germ  
nuclei   and   prominent   nucleoli.   Intercellular   bridging:   even   if   it   is   neoplastic  
cell  neoplasia  
you  could  still  see  the  distinct  demarcation  of  the  cells  from  each  other.  There  
§ Bilateral  cryptorchidism  à  azoospermia  (infertile)  
is  presence  of  abundant  pink  cytoplasm.  
  § Unilateral   cryptorchidism   à   oligospermia   (sperm   count  
<20  million.mL)  in  40%  of  cases  
o Characterized   by   an   arrest   in   the   development   of   germ   cells  
associated   with   marked   hyalinization   and   thickening   of   the  
basement  membrane  of  the  spermatic  tubules  
 

 
Figure   10.   Slowly   growing,   locally   invasive.     Lesions   are   non-­‐painful   until  
ulceration  and  infection  develop.  Presence  of  atypia  or  angry  looking  nucleus  
with  coarse  chromatin.  Metastasis  to  inguinal  and  iliac  nodes.  
 
VERRUCOUS   CARCINOMA   (Giant   Condyloma   or   Bushke-­‐Lowenstein  
tumor)    
o Uncommon,   exophytic   well   differentiated   variant   with   low   Figure   11.   (L)   Normal   testis   shows   tubules   with   active   spermatogenesis.   (R)  
malignant  potential;  locally  invasive  but  rarely  metastasize.   Testicular   atrophy   in   cryptorchidism.   The   tubules   show   Sertoli   cells   but   no  
o Believed   to   be   caused   by   HPV   16   due   to   koilocytic   changes   spermatogenesis.   There   is   thickening   of   basement   membranes   and   an  
apparent  increase  in  interstitial  Leydig  cells.  
insuperficial   layer;   papillary   appearance   like   condyloma  
 
acuminatum.  
o No  spermatogenic  activity  
 
o Asymptomatic   but   undescended   testes   are   palpable   in   the  
II.  TESTIS/EPIDIDYMIS  
inguinal  canal  
• Epididymis:  mostly  inflammatory  diseases  
o Requires  surgical  correction  (orchiopexy)  
• Testis:  mostly  tumors  
 
 
OTHER  CONGENITAL  ANOMALIES:  
A.  Congenital  Anomalies   o absence  of  one  or  more  testes  
CRYPTORCHIDISM   o fusion  of  the  testes  (synorchism)  
o Complete   or   incomplete   failure   of   the   intra-­‐intra-­‐abdominal    
testes  to  descend  into  the  scrotal  sac   NOTE  
 
Congenital   anomalies   are   extremely   rare,   EXCEPT   for  
RECALL   cryptorchidism.  
Testicular  descent  occurs  in  2  phases:    
1. Transabdominal  phase  
B.  Regressive  Changes    
• the   testis   comes   to   lie   within   the   lower  
TESTICULAR  ATROPHY  
abdomen  or  brim  of  pelvis  
o regressive  change  that  affects  the  testis  
• controlled  by  müllerian-­‐inhibiting  substance   o Can  have  several  causes,  including:  
2. Inguinoscrotal  phase   1. atherosclerotic  narrowing  of  the  blood  supply  in  old  age  
• testes   descend   thru   the   inguinal   canal   into   2. end   stage   of   an   inflammatory   orchitis,   whatever   the  
the  scrotal  sac   etiologic  agent  
• controlled  by  androgen   3. Cryptorchidism  (undescended  testes  are  sterile)  
• more  commonly  affected  in  cryptorchidism   4. hypopituitarism    
  5. generalized  malnutrition  or  cachexia    
  6. irradiation  
o Pathogenesis:  (from  Essentials  of  Rubin’s  Pathology)   7. prolonged   administration   of   female   sex   hormones,  
§ The  causes  of  testicular  maldescent  are  usually  unknown,   (treatment   of   patients   with   carcinoma   of   the   prostate  
but  theoretically  the  condition  could  be  related  to:   and  cirrhosis)  
1. Developmental  disorders  of  the  gonad,   8. exhaustion   atrophy   (produce   high   levels   of   follicle-­‐

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 stimulating  pituitary  syndrome)   o Clinical  significance:  
o Atrophy   occasionally   occurs   as   a   primary   failure   of   genetic   § Such  inflammatory  involvement  of  the  epididymis  and  
origin,  such  as  in  Klinefelter  syndrome.   testis  is  often  followed  by  fibrous  scarring,  which  in  many  
o An   end-­‐stage   pattern   of   testicular   injury,   i.e.   it   occurs   after   cases  leads  to  sterility.  
several  other  patterns  associated  with  decreased  fertility  (such   § However,  usually  the  interstitial  cells  of  Leydig  are  not  
as   hypospadias,   maturation   arrest,   vas   deferens   obstruction)   totally  destroyed,  so  sexual  activity  is  not  disturbed.  
have  been  manifested     o Epididymitis  
o In   some   cases,   if   a   specific   cause   for   testicular   injury   can   be   § Acute   or   chronic   inflammation   of   the   epididymis   usually  
found  and  removed  before  development  of  atrophy,  then  test   caused  by  bacteria  
function  can  be  restored.   § Cause  varies  with  patient’s  age:  
  Childhood  (uncommon)   congenital   genitourinary  
abnormality   and   infection  
with  Gram  (-­‐)  rods  
sexually  active  <35  y/o       Chlamydia   trachomatis,  
Neisseria  gonorrhoeae    
(STD  pathogens)  
>35  y/o   E.  coli,  Pseudomonas    
(UTI  pathogens)  
 
o Orchitis  
§ Acute  of  chronic  inflammation  of  the  testis  
§ May  occur  as  part  of  epididymo-­‐orchitis  or  be  an  isolated  
testicular  inflammation  
  § Often   secondary   of   UTI;   typically   associated   with  
Figure   12.   Testicular   atrophy,   classical   pattern,   showing   ghosting   or   fibrosis   of   epididymis.  
tubules  (arrow),  NO  spermatogenesis,  INCREASED  interstitial  cells  of  Leydig.    
  SPECIFIC  INFLAMMATIONS  
C.  Inflammatory  Lesions  of  the  Testis   o Three   major   specific   inflammatory   states   that   affect   the  
• Inflammations   are   more   common   in   the   epididymis   than   in   the   testis/epididymis:  
testis   1. Gonorrhea  –  arises  in  epididymis  
• Inflammatory   lesions   of   the   testis   usually   involve   the   epididymis   2. Tuberculosis  –  arises  in  epididymis  
first.  These  include:   3. Syphilis  –  arises  in  testis  
o Sexually  transmitted  diseases  e.g.  syphilis   o Mumps  
o Nonspecific  epididymitis  and  orchitis   § A   systemic   viral   disease   of   the   parotid   glands   that   most  
o Mumps   commonly   affects   school   children.   But   at   this   age   group,  
o Tuberculosis   testicular  involvement  is  uncommon.  
o Autoimmune  granulomatous  orchitis   § Only  20%  of  adult  males  present  with  mumps  
  • 20-­‐30%   of   these   postpubertal   males   may   develop  
associated  orchitis  
§ Morphology:    
• Edema  and  congestion  
• Chronic  inflammatory  infiltrate  
• May  cause  atrophy  and  sterility  
o Tuberculosis  
§ TB  begins  in  the  epididymis  and  may  spread  to  the  testis  
§ Infection  invokes  the  characteristic  granulomatous  
inflammation  and  caseous  necrosis  

 
Figure  13.    (L)  Scrotal  swelling.  (R)  Huge  collection  of  neutrophils.  
 
NONSPECIFIC  EPIDIDYMITIS  AND  ORCHITIS  
o Epididymitis  and  possible  subsequent  orchitis  are  commonly  
related  to  UTIs  (cystitis,  urethritis,  prostatitis)  
§ Infections  in  the  urinary  tract  may  reach  the  epididymis  
and  testis  thru  either:  (1)  vas  deference  or  (2)  lymphatics  
of  the  spermatic  cord.  
o Pathogenesis:  
§ Bacterial  invasion  à  nonspecific  acute  inflammation  
(congestion,  edema,  and  infiltration  by  neutrophils,    
Figure  14.  Tuberculous  orchitis,  showing  granulomatous  cheesy  material.  
macrophages,  and  lymphocytes)  
 
§ Infection  spreads  from  interstitial  connective  tissue  à  
tubules  à  frank  abscess  formation  or  complete  
suppurative  necrosis  of  entire  epididymis  à  testis  

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 o Either  in  utero  or  shortly  after  birth  
o Lacks   any   associated   anatomic   defect   that   allows  
excessive  mobility  of  testis  
2. Adult  Torsion  
o Typically  seen  in  adolescence  
o Presents  as  sudden  onset  of  testicular  pain  
o Often  occurs  without  any  inciting  injury  
o May  even  occur  during  sleep  
o Results  from  a  bilateral  anatomic  defect  where  the  testis  
has   increased   mobility   (bell-­‐clapped   abnormality—i.e.  
the   testis   is   free   to   swing,   much   like   the   gong/clapper  
inside  a  bell)  
 
Figure  15.  (L)  Areas  of  necrosis.  (R)  Presence  of  Langans  giant  cells.   o If  one  testis  becomes  twisted,  the  unaffected  one  can  be  
  saved   from   subsequent   twisting   by   surgically   fixing   it   to  
AUTOIMMUNE  GRANULOMATOUS  ORCHITIS   the  scrotum  (orchiopexy)  
o Rare  finding  in  middle  aged  men    
o Presents  in  middle  age  as  a  moderately  tender  testicular  mass   E.  Testicular  Neoplasms  
of  sudden  onset  sometimes  associated  with  fever   • Epidemiology:  
o Distinguished  by  granulomas  restricted  to  spermatic  tubules   o Most  important  cause  of  painless  enlargement  of  testis  (since  
o Although   an   autoimmune   basis   is   suspected,   the   cause   of   painless,   patients   usually   present   with   the   later   stage   of   the  
these  lesions  remains  unknown   disease)  
  o 2/100,000  males,  whites  >  blacks  (US)  
NOTES   o Increased  frequency  in  siblings  
• Often,   Inflammations   in   the   testicle   ALSO   involve   the   o Peak  incidence  15-­‐34  yrs  
epididymis,   and   vice   versa.   Commonly,   urinary   tract   o Most  are  malignant  
gram  negatives  infect  BOTH   o Associated  with  germ  cell  maldevelopment  
• However,     § Cryptorchidism  (most  important  risk  factor)  
1.  Mumps  and  TB  are  the  most  common  agents  of   § Testicular  dysgenesis(XXY)  syndrome  
primarily  orchitis,  and   • Pathogenesis:  
2.  CHLAMYDIA  and  TORSION  are  the  most  common   o 95%  arise  from  germ  cells  
causes  of  primarily  epididymitis.   § Isochromosome  12,  i(12p),  is  a  common  finding  
  § Intratubular  germ  cell  neoplasms  
D.  Vascular  Disorders   § Most   germ   cell   tumors   are   aggressive   cancers   capable   of  
TORSION  OF  THE  TESTIS   rapid,   wide   dissemination,   although   with   current   therapy  
o Twisting  of  the  spermatic  cord  cuts  off  venous  drainage  to  the   most  can  be  cured.  
testis;   thick-­‐walled   arteries   remain   patent,   allowing   vascular   o Rarely  arise  from  Sertoli  cells  or  Leydig  cells  
engorgement  followed  by  hemorrhagic  infarction.   § These  are  often  benign  
  o Lymphoma   –   5%   of   testicular   neoplasms   are   secondary   to  
aggressive  Non-­‐Hodgkin’s  lymphoma  
§ Most  common  testicular  neoplasm  in  men  >  60  y/o    
• Try  to  rule  out  lymphoma  first  before  considering  other  
testicular  neoplasms  for  patients  in  this  age  
§ Diffuse  large  cell  lymphoma    
• most   common   testicular   neoplasm   in   men,   regardless  
of  age  
 
• WHO  Classification  of  Testicular  Tumors:  
o One  histologic  pattern  (40%)  –  pure  forms  
  § Seminomas  (30%)  –  best  prognosis  because  it  is  extremely  
Figure   16.   Infarcted,   purple   testicle   &   epididymis   due   to   torsion;   with  
radiosensitive;   one   of   the   most   common   testicular  
hemorrhagic  infarction.  
neoplasms  
 
§ Embryonal  carcinoma  
o If   complete   torsion,   severe   pain   and   infarction   of   testicular  
§ Yolk  sac  tumor  
germ  cells  occur  within  a  few  hours  
§ Choriocarcinoma  
o Often  presents  after  vigorous  physical  activity    
§ Teratoma  
o May   be   associated   with   a   congenital   abnormality   that   allows  
o Multiple   histologic   patterns   (60%)   –   combination   of   different  
excess  mobility  of  the  testis  
forms  
o Reduction   of   torsion   within   6   hours   can   lead   to   complete  
§ Embryonal  CA  +  teratoma  
recovery;  delay  by  12-­‐24  hours  may  cause  severe  or  total  loss  
§ Choriocarcinoma  +  other  
of  testicular  viability.  
§ Other  combinations  
o Torsion  is  one  of  the  few  urologic  emergencies  
 
2  Types  of  Testicular  Torsion    
1. Neonatal  Torsion    

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Figure  18.  Seminoma  of  the  Testis  appears  as  a  fairly  well  circumscribed  pale,  
fleshy,  homogenous  mass  
 
Histology  
  o Clear  seminoma  cells,  delicate  septa,  lymphocytic  infiltrate    
Figure  17.  Histogenesis  of  Testicular  Neoplasms.  See  text  below  for  
explanation.   o The   classic   seminoma   cell  is   large   and   round   to   polyhedral   and  
  has   a   distinct   cell   membrane;   a   clear   or   watery-­‐appearing  
• Histogenesis  of  Testicular  Neoplasms:   cytoplasm;   and   a   large,   central   nucleus   with   one   or   two  
1. Neoplasms  arising  from  germ  cell  precursors  are  divided  into   prominent  nucleoli.    
either  the  seminomatous  or  nonseminomatous  group:   o Approximately   15%   of   seminomas   contains   synctiotrophoblasts  
a. If  the  neoplasm  undergoes  gonadal  differentiation   resulting   in   elevated   levels   of   human   chorionic   gonadotropin  
(seminomatous  group):   (HCG)  though  not  to  the  extent  of  those  with  choriocarcinoma    
§ it  is  a  seminoma,  which  is  usually  found  in  40-­‐ o May   also   be   accompanied   by   ill-­‐defined   granulomatous  
50  year  olds.     reaction   (in   contrast   to   well-­‐formed   discrete   granulomas   seen  
§ Another   example   of   gonadal   differentiation   is   in  TB)    
spermatocytic  seminoma  which  is  very  rare.     o Anaplastic   Seminoma   is   used   to   indicate   greater   cellular   and  
b. When   the   neoplasm   undergoes   totipotential   nuclear   irregularity   with   more   frequent   tumor   giant   cells   and  
differentiation,  it  is  nonseminomatous.     many  mitoses  but  is  not  associated  with  worse  prognosis  
2. Nonseminomas  are  called  embryonal  CA.      
a. If   embryonal   neoplasms   undergo   trophoblastic  
differentiation,  it  is  called  choriocharcinoma.    
§ Choriocarcinoma   is   heralded   by   an   increase   in  
beta-­‐hCG,  which  can  also  be  found  in  females.    
b. If  it  undergoes   yolk   sac   differentiation,  it  is  called  a  
yolk  sac  tumor.    
§ This  is  the  most  common  tumor  in  infants  and  
children  less  than  3  years  old.    
§ It  is  usually  alpha-­‐feto-­‐protein  (AFP)  positive.    
c. For   somatic   differentiation,   there   is   the   teratoma  
which  affects  all  ages.    
§ Teratomas   can   either   be   mature,   immature   or    
Figure  19.  Seminoma  Left:  Low  magnifiation  shows  clear  seminoma  cells  
have  malignant  differentiation.     divided  into  poorly  demarcated  lobules  by  delicate  septa.  Right:  Microscopic  
  examination  reveals  large  cells  with  distinct  cell  borders,  pale  nuclei,  
NOTES   prominent  nucleoli,  and  a  sparse  lymphocytic  infiltrate.  The  larger  cells  are  
• Females   also   have   choriocarcinoma,   yolk   sac   tumors,   GERM  cells  and  they  often  do  look  like  spermatocytes  from  normal  histology.  
and  teratoma.   The  smaller  cells  look  like  typical  lymphocytes  because  they  are  typical  
lymphocytes.  Usually,  there  are  good  numbers  of  BOTH  kinds  of  cells  
• Seminomas  in  females  are  called  dysgerminoma  (they  
 
have  the  same  histologic  picture)  
EMBRYONAL  CARCINOMA  
 
o Keywords:   Hemorrhagic   mass,   alveolar/tubular   patterns,   AFP  
SEMINOMA  
elevated    
o Keywords:  Clear  seminoma  cells,  delicate  septa,  lymphocytic  
o These   cells   are   usually   described   as   “primitive,”   but   usually  
infiltrates  
show  kind  of  a  GLANDULAR  pattern,  which  is  why  in  the  old  days  
o Most  common  type  of  germ  cell  tumor  (50%)    
they   were   often   called   adenocarcinomas.   But   remember   they  
o Peak  incidence  at  third  decade  and  almost  never  in  infants    
are  GERM  cells,  NOT  glandular  epithelial  cells    
o Identical  tumor  in  ovary:  dysgerminoma    
o Occurs  mostly  in  20  to  30-­‐year  age  group    
o Seminomas  produce  bulky  masses,  sometimes  10  times  the  
o More  aggressive  than  seminomas    
size  of  the  normal  testis  
 
Gross  
Gross  
o Typical  seminoma  has  a  homogenous,  gray-­‐white,  lobulated  cut  
o Tumor  is  smaller  than  seminoma  and  usually  does  not  replace  
surface,  usually  devoid  of  hemorrhage  or  necrosis    
entire  testis    
o Tunica  albuginea  is  not  penetrated  but  occasionally  extension  
o Variegated,  poorly  demarcated  on  margins,  punctuated  by  foci  
to  epididymis,  spermatic  cord,  or  scrotal  sac  occurs  
of  hemorrhage  or  necrosis  
 
 

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Figure  20.  Embryonal  carcinoma:  Hemorrhagic  mass.    
Histology   Figure  22.  Choriocarcinoma  
o Cells   grow   in   alveolar   or   tubular   patterns,   sometimes   with   YOLK  SAC  TUMOR  
papillary  convolutions     o AKA  endodermal  sinus  tumor    
o Lack   well-­‐formed   glands   with   basally-­‐situated   nuclei   and   apical   o Most  common  testicular  tumor  in  infants  and  children  up  to  3yo  
cytoplasm  seen  in  teratomas     (good  prognosis  in  this  age  group)  
o More  differentiated  lesions  may  display  sheets  of  cells      
o Epithelial  appearance:  large,  anaplastic,  and  have  hyperchromatic   Gross  
nuclei  with  prominent  nucleoli     o Tumor  is  nonencapsulated    
o In   contrast   to   seminoma:   indistinct   cell   borders   and   there   is   o Cross  section:  homogenous,  yellow  white,  mucinous  appearance  
considerable  variation  in  cell  and  nuclear  size  and  shape      
o Mitotic  figures  and  tumor  giant  cells  frequently  seen     Histology  
  o Lacelike   (reticular)   network   of   medium-­‐sized   cuboidal   or  
flattened  cells  
o Papillary  structures,  solid  cords  of  cells  may  be  seen    
o In  approximately  50%,  structures  resembling  endodermal  sinus,  
SCHILLER-­‐DUVAL   BODIES,   may   be   seen;   these   consist   of  
mesodermal   core   with   a   central   capillary   and   a   visceral   and  
parietal  layer  of  cells  resembling  primitive  glomeruli    
o Present   within   and   outside   cytoplasm   are   eosinophilic,   hyaline  
like   globules   in   which   alpha-­‐fetoprotein   (AFP)   and   alpha1-­‐
antitrypsin   can   be   demonstrated   by   immunocytochemical  
staining    
o AFP   in   tumor   cells   is   highly   characteristic   and   it   underscores  
 
Figure  21.  Embryonal  carcinoma  shows  sheets  of  undifferentiated  cells  as  well   their  differentiation  into  yolk  sac  cells.    
as   primitive   glandular   differentiation.   The   nuclei   are   large   and    
hyperchromatic.  
 
CHORIOCARCINOMA  
o Keywords:  trophoblastic  differentiation,  HCG,  hemorrhage  and  
necrosis    
o Highly  malignant  form  of  testicular  cancer  (ST  and  CT  cells)    
o In  its  “pure”  form  it  is  rare,  <1%  of  all  germ  cell  tumors    
 
Gross  
o They  cause  no  testicular  enlargement  and  are  detected  only  as  a  
 
small  palpable  nodule     Figure  23.  Schiller-­‐Duval  bodies  
o Tumors  are  small  and  rarely  larger  than  5cm  in  diameter      
o Hemorrhage  and  necrosis  extremely  common  
 
Histology  
o Two  cell  types:    
• Syncytiotrophoblastic   cells   –   large   and   have   many   lobular  
or   hyperchromatic   nuclei   and   an   abundant   eosinophilic  
vacuolated   cytoplasm.   HCG   readily   demonstrated   in   the  
cytoplasm    
• Cytotrophoblastic   cells   –   more   regular   and   tend   to   be  
polygonal,   with   distinct   borders   and   clear   cytoplasm.   They  
grow   in   cords   or   masses   and   have   a   singly,   fairly   uniform  
nucleus    
Figure  24.  Yolk  sac  tumor  with  lacelike  reticular  network  
 
 
TERATOMA,  MALIGNANT  TERATOMA,  TERATOCARCINOMA  
o Conglomeration   of   tissue   arising   from   ectoderm,   mesoderm,   and  
endoderm  (more  than  one  germ  layer)    

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o Most  testicular  teratomas  are  malignant.  Most  ovarian  teratomas  
are  benign  (e.g.  dermoid  cyst)    
o In  post-­‐pubertal  males,  teratomas  are  usually  malignant   whether  
immature  or  mature  (bad  prognosis)    
o Clusters  of  squamous  epithelium,  hair,  skin  glands  (most  common  
thing   that   is   found   in   teratoma)   composed   of   a   heterogenous,  
helter-­‐skelter  collection  of  differentiated  cells    
• Neural   tissue,   retina,   muscle   bundles,   islands   of   cartilage,  
structures   reminiscent   of   thyroid   gland,   bronchial   or  
bronchiolar   epithelium,   bits   of   intestinal   wall   or   brain  
substance  
 

 
Figure  27.  HYPERPLASIAS:  TZ;  CARCINOMAS:  PZ.  
Carcinomas/neoplasias   (e.g.   prostate   cancer):   usually   in   peripheral   zone.  
Hyperplasia   (e.g.   BPH):   usually   in   transitional   zone.   Usual   screening   for  
prostate   cancer:   Digital   Rectal   Examination   (DRE)   is   used;   posterior   part   of  
peripheral  zone  of  prostate  is  usually  affected.  
 
A. INFLAMMATION  
  (Not  extensively  discussed  by  the  lecturer.  Info  lifted  from  Robbins)  
Figure   25   .   Teratoma   of   the   testis   (Immature   teratoma)   -­‐   the   variegated   cut    
surfaces   with   cysts   reflects   the   multiplicity   of   tissue   found   histologically.   PROSTATITIS  
Heterogenous,  with  solid,  sometimes  cartilaginous  and  cystic  areas.  
 
 
I.  ACUTE  BACTERIAL  PROSTATITIS  
o Usually  same  as  Urinary  Tract  Pathogens  
o Most   common   are   various   strains:   E.coli,   Gram(-­‐)   rods,  
enterococci  and  staphylococci  
o Become   implanted   by   intraprostatic   reflux   of   urine   from   the  
posterior   urethra   or   from   the   urinary   bladder   OR   seed   the  
prostate   by   lymphohematogenous   routes   from   distant   foci   of  
infection  
o May  usually  follow  a  surgical  manipulation  of  urethra  or  prostate  
gland  itself.  (e.g.  catheterization)  
o DRE:  tender  and  boggy  
o Clinical  manifestations:  fevers,  chills  and  dysuria  
  o Diagnosis:  urine  culture  and  clinical  features  
Figure   26.   Teratoma   of   the   Testis-­‐   consisting   of   a   disogranized   collection   of  
glands,  cartilage,  smooth  muscle,  and  immature  stroma    
  Morphology  
PROSTATE   o Minute,  disseminated  abscesses  
o Large,  coalescent  focal  areas  of  necrosis  
• Normal  adult  prostate  weighs  20gm;  has  a  chestnut  structure  
o Diffuse   edema,   congestion   and   boggy   suppuration   of   entire  
• Retroperitoneal   organ   encircling   the   neck   of   the   bladder   and  
gland.  
urethra,  and  is  devoid  of  a  distinct  capsule  
• Enlargement  of  the  prostate  will  constrict  the  urethra.  Most  
patients  will  complain  of  urinary  incontinence  and  present  with  a  
distended  bladder.  Just  insert  a  catheter  to  relieve  it.  
• Some  patients  will  have  no  idea  that  their  prostate  is  enlarged  
unless  they  already  present  urinary  problems.  
• 3  pathologic  processes:  inflammation,  benign  nodular  
enlargement  (most  common),  tumors  
• The  normal  prostate  has  several  different  zones  
o Central  Zone  (CZ)  –  nearest  the  urethra  
o Peripheral  Zone  (PZ)  –  nearest  the  capsule  
o Transitional  Zone  (TZ)  –  between  the  two  
o Periurethral  zone  

 
Figure  28.    Acute  Prostatitis.  With  a  lot  of  Neutrophils.  
 

    Page  8  of  11  

 
II.  CHRONIC  PROSTATITIS   leads  to  urethral  obstruction.  
o Usually  abacterial  but  also  often  are  recurrent  or  persistent  from   • Hypertrophy  =  enlargement  of  the  prostate  
acute;  most  common  form   • Hyperplasia  =  increase  in  the  number  of  glands  and  increased  
prostatic  stroma  
• Secondary  to  the  hypertrophy  and  hyperplasia,  they  can  form  
nodules  which  can  be  palpated  during  DRE  
• Associated  with  old  age  (Common  disorder  in  men  over  age  50  
years)  
• Associated  with  urinary  obstruction,  frequency,  bladder  
hypertrophy  and  bladder  trabeculations  
• Not  considered  to  be  a  premalignant  lesion  
 
Morphology  
  • Prostate  weighs  between  60-­‐100gm  
Figure  29.  Chronic  Prostatitis;  due  to  Lymphocytes  seen.   • Hyperplasia  originates  in  the  transition  zone  
  • The  hallmark  of  BPH  is  nodularity  due  to  glandular  proliferation  
1.  CHRONIC  BACTERIAL  PROSTATITIS   or  dilation  and  to  fibrous  or  muscular  proliferation  of  the  stroma  
o Difficult  to  diagnose  and  treat   • Common  location  of  BPH:  Median  lobe  (median  lobe  
o Clinical  symptoms:  Low  back  pain,  dysuria  and  perineal  and   hypertrophy)  and  lateral  lobes  
suprapubic  discomfort   • Androgen-­‐related  (DHT  produced  by  the  stromal  cells)  
o Usually  present  with  recurrent  urinary  tract  infections  (cystitis,  
 
and  urethritis)  caused  by  the  same  organism  →  continuation  of   Clinical  Features  
infection  
• Increased  gland  size  and  smoothe  ms-­‐mediated  contraction  of  
 
the  prostate  leading  to  obstruction,  increased  resistance  to  
o Diagnosis:  
urinary  outflow,  inability  to  fully  empty  bladder  creating  a  
o Leukocytosis  in  the  expressed  prostatic  secretions  
possible  site  of  infection,  increased  urinary  frequency,  nocturia,  
o Positive  bacterial  culture  
difficulty  in  starting  and  stopping  the  stream  of  urine,  overflow  
 
dribbling,  dysuria.  
2.  CHRONIC  ABACTERIAL  PROSTATITIS  
 
o Most  common  form  of  prostatitis  
o Indistinguishable  from  the  bacterial  type.  
o No  history  of  recurrent  urinary  tract  infection  
o Expressed  prostatic  secretions:  >10  leukocytes/HPF  
o Bacterial  cultures  (-­‐)  
 
III.  GRANULOMATOUS  PROSTATITIS  
o Tuberculosis  or  non-­‐tuberculosis  
o May  be  specific  or  non-­‐specific  
o Fungal  prostatitis  is  seen  in  immunocompromised  patients  
o Nonspecific  granulomatous  prostatitis  is  relatively  common;  
presents  secretions  from  ruptured  prostatic  ducts  and  acini;    
 
o (-­‐)  Bacteria   Figure  31.  Left:  Cross  Section  of  prostate:  blue  arrows:  nodules,  can  weigh  as  
much   as   100gm;   due   to   increased   number   of   epithelial   cells   and   stromal  
components  in  the  periurethral  area  of  the  prostate.  Right:  Prostate  chips.  
 

   
Figure  30.    Granulomatous  Prostatitis.   Figure   32.   Nodular   hyperplasia.   Forms   nodules   or   trabeculations.   Normal  
  gland   has   a   basal   cell   layer   made   up   of   columnar   cells;   double   layer;   can   be  
B. BENIGN  ENLARGEMENT   columnar  or  cuboidal.  Has  increased  number  of  glands.  The  glands  are  lined  by  
• BPH  (H  =  Hypertrophy)  or  BPH  (  H  =  Hyperplasia)   a  two  cell  layer:  Basal  and  Columnar  layers.  
• Glandular  and  Stromal  Hyperplasia    
• “Nodular”  Hyperplasia  –  aka  Benign  Prostatic  Hyperplasia,  
where  nodules  compress  and  narrow  the  urethral  canal  which  

    Page  9  of  11  

 
 CLINICAL  COURSE  
o Often  clinically  silent  
o Earliest  symptom:  change  in  urinary  frequency  
o Monitoring  through  Digital  Rectal  Exam  (DRE)  
o Prostate  Specific  Antigen  (PSA)  –  most  important  test  used  in  the  
diagnosis  and  management  of  prostate  CA;  organ-­‐specififc,  not  
cancer-­‐specific  
o 4  ng/ml  in  peripheral  blood  
o Free  PSA  <  25%  (<10%  in  Robbins)  
o Transrectal  ultrasound-­‐  determine  the  size  
o Needle  Biopsy  –  required  to  confirm  the  diagnosis  
o Prostatism  –  presents  like  BPH  ie.  Urinary  incontinence  
o Osteoblastic  metastases  –  presents  with  bone  pain  
o Usually  in  the  vertebra  (lumbar  spine  >  proximal  femur  >  pelvis  >  
 
Figure   33.   BPH.   Dilatation   and   proliferation   of   the   acini,   hyperplasia   of   the   thoracic  spine  >  ribs)  
acini.   Glandular   hyperplasia,   note   ABSENCE   of   nucleoli.   Also   note   nuclei   are    
where  they  should  be,  i.e.,  basal.  Also  note  glands  are  NOT  back  to  back,  but   MORPHOLOGY  
each  one  is  separated  by  thin  fibrous  tissue.   • In  approx.  70%  of  cases,  carcinoma  of  the  prostate  arises  in  the  
  peripheral  zone.  
• THREE  conditions  favor  a  BENIGN  process:   • On  cross  section,  neoplastic  tissue  is  gritty  and  firm,  but  when  
o Glandular  hyperplasia,  note  ABSENCE  of  nucleoli.   embedded  within  prostatic  substance  it  may  be  difficult  to  
o Also  note  nuclei  are  where  they  should  be,  i.e.,  basal.   visualize  and  be  more  readily  apparent  on  palpation.  
o Also  note  glands  are  NOT  back  to  back,  but  each  one  is   • May  commonly  involve  periprostatic  tissue,  seminal  vesicles,  
separated  by  thin  fibrous  tissue.   and  base  of  the  urinary  bladder.  
  • Histologically,  most  lesions  are  adenoCAs  that  produce  well-­‐
C. MALIGNANCY   defined  gland  patterns.  The  glands  are  typically  smaller  than  
ADENOCARCINOMA   benign  glands  and  are  lined  by  a  single  uniform  layer  of  cuboidal  
EPIDEMIOLOGY   or  low  columnar  epith.  
o Most  common  cancer  in  men   • The  outer  basal  cell  layer  is  absent.  
o About  70/100,00  men  in  US;  about  29%  of  cancer  in  the  US    
(2007)   TREATMENT:  Surgery,  radiation,  hormones,  chemotherapy  
o 200,000  new  cases/year  in  US    
o 20%  are  lethal  
Note:   Prostate  CA:  AdenoCA  
o Second  most  common  cause  of  cancer  death  in  men  
Penis  CA:  Squamous  Cell  CA  
o Peak  incidence  of  clinical  cancer  is  65-­‐75  yo    
o Latent  CA  is  even  more  prevalent;  latency  is  due  to  its    
asymptomatic  presentation  
o >50%  in  men  >  80  yo  
o 20%  in  men  in  their  50s;  70%  in  men  70-­‐80  y/o  
o Uncommon  in  Asians;  frequent  in  blacks  
 
PATHOGENESIS  
• Hormonal  Factors  
o Androgens  –  Bind  with  androgen  receptor  in  the  neoplastic  
cell  and  induce  the  expression  of  pro-­‐growth  and  pro-­‐
survival  gene  factors  in  the  neoplastic  cells  
o Does  not  occur  in  eunuchs  (castrated)  
o Orchiectomy  and/or  estrogen  treatment  inhibits  growth  of  
the  cancer  
• Genetic  Factors    
Figure  34.  (Left)  Local  extension  to  periprostatic  tissue  Metastases  spread  via  
o Increased  risk  in  first  order  relatives  
lymphatics   first:   obturator   and   para-­‐aortic   nodes.   Hematogenous:   bones.  
o Blacks  >  Whites  (but  symptomatic  CA)   (Right)  Glands  are  smaller  than  benign  glands  and  are  lined  by  cuboidal  or  low  
• Environmental  Factors   columnar;   outer   basal   cell   layer   is   absent;   fused   glands,   no   more   septa  
o Geographic  differences  in  incidence  of  clinical  cancer  (not   separating   them.   Note   the   various   sized   glands   with   almost   no   stroma   in  
of  latent  CA)   between.  
o Change  in  incidence  with  migration    
• Diet  and  lifestyle  
o More  westernized  (increased  consumption  of  fats),  increase  
in  incidence  of  prostate  cancer.  Dietary  products  that  
inhibit,  prevent,  delay  progression  of  prostate  cancer  
include  lycopenes,  vitamin  A,  Vitamin  E,  selenium  and  soy  
products  
 

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Figure  38.  Gleason  Score.  Grade  1  -­‐  most  well-­‐differentiated  tumors  in  which  
the   neoplastic   glands   are   uniform   and   round   in   appearance   and   are   packed  
into   well-­‐circumscribed   nodules.  Grade   5   -­‐   no   glandular   differentiation,   tumor  
cells   infiltrate   the   stroma   in   the   form   of   cords,   sheets   and   nests  
 
  • A  Gleason’s  final  SCORE  is  the  SUM  of  the  predominant  pattern  
Figure   35.   NUCLEOLI   separate   benign   from   malignant   prostate   glands!!!   Of  
(1-­‐5)  and  the  secondary  pattern  (1-­‐5).  
course  there  are  other  differentiating  features,  but  this  is  the  MOST  RELIABLE  
one.   The   presence   of   NUCLEOLI   in   most   of   these   cells   almost   nails   the   • So  a  Gleason  GRADE  ranges  from  1-­‐5,  and  a  Gleason  SCORE  
diagnosis  of  malignancy.   ranges  from  2-­‐10.  
• Grading  is  of  particular  importance  in  prostatic  cancer  because  
grade  and  stage  are  the  best  prognostic  predictors.  
 
STAGING  
• Staging  of  prostatic  cancer  is  important  in  the  selection  of  
appropriate  form  of  therapy  
o A(T1)  MICROSCOPIC  ONLY  
o B(T2)  MACROSCOPIC  (PALPABLE)  
o C(T3  &T4)  EXTRACAPSULAR  
o D(N1-­‐3,M1)  METASTATIC  
• Prognosis  dependent  on  stage  and  histologic  grade  
o 90%  10  YR  survival  for  A  AND  B  
o 10-­‐40%  10  YR  survival  for  C  AND  D  
   
Figure  36.  Perineural  Invasion.  Even  if,  theoretically,  the  prostate  gland  cells   Table  2.  Staging  of  Prostate  CA  using  the  TNM  System  
look  100%,  if  they  surround  nerve  spaces,  they  are  malignant  
TNM  
ANATOMIC  FINDINGS  
DESIGNATION  
Extent  of  primary  Tumor  (T)  
T1   CLINICALLY  INAPPARENT  LESION  (BY  
PALPATION/IMAGING  STUDIES)  
T1a   Involvement  of  ≤5%  of  resected  tissue  
T1b   Involvement  of  >5%  of  resected  tissue  
T1c   Carcinoma  present  on  needle  biopsy  (following  
elevated  PSA)  
T2   PALPABLE/VISIBLE  CANCER  CONFINED  TO  
PROSTATE  
T2a   Involvement  of  ≤5%  of  one  lobe  
  T2b   Involvement  of  >5%  of  one  lobe,  but  unilateral  
Figure  37.  TIP:  Multiple  bone  metastases  in  males  is  usually  carcinoma  of  the  
prostate.  (Commonly  affects  lumbar  spine>femur>pelvis>thoracic  spine>ribs)   T2c   Involvement  of  both  lobes  
  T3   LOCAL  EXTRAPROSTATIC  EXTENSION  
GRADING  (GLEASON  SYSTEM)   T3a   Extracapsular  extension  
• Gleason  Score:  Predominant  pattern  (1-­‐5)  +  Secondary  pattern   T3b   Seminal  vesical  invasion  
(1-­‐5)   T4   INVASION  OF  CONTIGUOUS  ORGANS  AND/OR  
o Grades  2-­‐4:  well-­‐differentiated   SUPPORTING  STRUCTURES  INC  BLADDER  NECK,  
o Grades  5-­‐6:  intermediate  grade   RECTUM,  EXTERNAL  SPHINCTER,  LEVATOR  MS,  
o Grade  7:  moderate  to  poorly  differentiated  CA   OR  PELVIC  FLOOR  
o Grades  8-­‐10:  high  grade  tumor   Status  of  Regional  Lymph  Nodes  (N)  
• BEST  Score  =  2;  WORST  SCORE  =  10   N0   NO  REGIONAL  NODAL  METASTASES  
• Prostate  CA  are  stratified  into  5  grades  based  on  glandular   N1   METASTASIS  IN  REGIONAL  LYMPH  NODES  
patterns  of  differentiation.   Distant  Metastases  (M)  
• Most  tumors  form  more  than  1  pattern.  One  assigns  a  primary   M0   NO  DISTANT  METASTASES  
grade  to  the  dominant  pattern  and  a  secondary  grade  to  the   M1   DISTANT  METASTASES  PRESENT  
second  most  frequent  pattern.  The  two  numeric  grades  are  then   M1a   Metastases  to  distant  lymph  nodes  
added  to  obtain  a  combined  Gleason  score.   M1b   Bone  metastases  
• Exception  to  the  rule:  If  three  patterns  are  present  on  biopsy,   M1c   Other  distant  sites  
the  most  common  and  highest  grades  are  added  together.    

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