Diseases Of Testes Flashcards
What are the presents features of testicular tumors?
- Metates to lymph node / lung/ met to bone
2.gynecomastia —> because testicular tumors produce estrogen - Retroperitoneal mass
- Swelling of testis
- Secondary hydrocele
Patient with met to lung will present with?
—> shortness of breath
How we monitor patients with testicular disease?
By palpation
Can we detect swelling in such tumors?
Swelling cannot be detected unless tumor is large enough
What causes hydrocele?
Blockage of drainage
What are the most common testicular tumors?
Germ cell tumors
What is the most common germ cell tumor?
50% of germ cell tumors are seminomas
How we divide testicular tumors?
- Germ cell tumors
2. Stroma tumors
What are examples of germ cell tumors?
- Seminomas
- Non seminomas
A.teratoma
B. Yolk sac
C. Embryonak carcinoma
What are the stroma testicular tumors?
Sertoli cell tumor
Leydig cell tumors
What is the difference between seminomas and non-seminomas?
Seminomas —> treated by radiotherapy
Non-seminomas —> chemotherapy
Are testicular tumors curable?
Yes, testicular tumors are highly curable even if advanced
What is a characteristic of sex-stroma tumors and with what are they associated?
They are mostly benign
They may be associated with hormonal syndromes
Where do lymphatic spread of testicular tumor goes?
- Para-aortic
- Iliac
- Mediastinal
- Supraclavicular nodes
To where hematogenous spread of testicular tumor?
- Liver
- Lungs
- Brain
- Bones
Notes metasis differ from primary lesion histologically
For what we use serum tumor markers?
They are used for staging
What serum tumor marker assess the tumor burden?
Lactate dehydrogenase LDH
What tumor markers as the response to therapy?
Alpha fetoprotein (AFP) Human chorionic gonadotropin (hCG)
What germ cell tumors produce alpha fetoprotein?
Yolk sac tumors
Do we use genetics in testicular tumors?
Yes, but they are not specific
What majority of testicular tumours have? (Genetics)
Majority of testicular tumours have a preneoplastic stage which is called an intratubular cell neoplasia and this is happening by alteration of P53 —> exception is the yolk sac tumor
What are the genetics involved in testicular tumor?
- Specific genetic marker —> isochromosome of the short arm of chromosome 12 - i(12p) in all germ cell tumors
- Intratubular germ cell neoplasia —> alteration in p53 locus 66%
- Familial cases linked to the receptor tyrosine kinase KIT and BAK which are involved in gonadal development and the transcription factors OCT3/4 and NANOG which maintain pluripotent stem cells (Rare)
What are risk factors for testicular tumours?
- Cryptorchidism (10% of tumors, higher position in abdomen increases risk)
- Genetics (white have 5* risk of blacks
- Siblings of affected patients have 10* risk
- Testicular dysgenesis (testicular feminization > Klinefelter)
- Li-fraumeni syndrome
- Prior testicular germ cell tumor —> have higher chance of recurrence
- Prior intratubular germ cell neoplasia
It is in situ stage of germ cell neoplasia
Seen in 90% to 100 % of testes adjacent to germ cell tumors
Intratubular germ cell neoplasia (IGCN)
Where is intratubular germ cell neoplasia less often seen ?
- Yolk sac tumors
2. Childhood teratoma
What do u see under the microscope patient with intratubular germ cell neoplasia (IGCN)
This as an abnormal tubule completely filled with abnormal cells and we don’t see sperm
What are the main categories of tumors of testes?
Germ cell tumors 5 1. Seminoma 2. Embryonal carcinoma 3. Yolk sac tumor 4. Choriocarcinoma 5.teratoma Sex cord - stromal tumors 1. Leydig cell tumour 2. Sertoli cell tumor 3.gonzdoblastoma, rare associated with testicular dysgenesis - cryptorchidism Hypospadis Poor sperm quality
Mixed germ cell - gonadal stromal tumors
It is a tumor identical to ovarian dysgerminoma ?
Seminoma
It account for 50% of GCTs?
Seminoma
What are characteristics of seminoma?
Most common tumor in men 25-29 years
1-2 % are bilateral
15% are bilateral if 2 undescended testes
Arises from intratubular germ cell neoplasia (ITGCN) except the adult spermatocytic seminoma variant
What is the seminoma that doesn’t originate from the ITGCN?
Adult spermatocytic seminoma variant
What genes seminoma contains?
Contains isochromosome 12p and expresses OCT3/4 and NANOG while 25% have KIT activating mutations
What is the gross description of seminoma?
- Bulky
- Homogenous gray-white
- Well-circumscribed with lobulated and building cut surface
- 50% involve the entire testis
- Invasion of tunica albuginea in less than 10T with rare extension to epididymis, spermatic cord or scrotal sac
Note: Usually No hemorrhage No cystic changes No extensive necrosis
Usually we don’t see hemorrhage, cystic change or necrosis unlike non-seminomas where we can see hemorrhage and necrosis
The tumor is homogeneously yellow and lobulated
Fresh bulky multi lobular
Testis is replaced by a solid and relatively homogeneous neoplasm
Seminoma
Do we remove the entire testis in seminoma and why?
Yes, we remove the entire testis in seminoma because we can have small area that we can not see and these are cancers
What is the microscopic appearance of seminomas?
- Sheets of relatively uniform tumor cells
- Divided into poorly demarcated lobules by delicate fibrous septa with lymphocytes and plasma cells
- Cells are large, round-polyhedral with distinct cell membranes, abundant clear/ watery cytoplasm (glycogen)
- Large central nuclei
- 1-2 prominent often elongated and irregular nucleoli
- Usually minimal mitotic figures
Seminoma are positive for what?
They are positive for KIT
PLAP (placental alkaline phasphatase)
OCT4
Histology showing the characteristic combination of the large neoplasticism cells with
clear cytoplasm
the lymphocyte-rich stroma
Seminoma
Clear tumor cells form nests surrounded by fibrous strands infiltrated with lymphocytes + positive alkaline phosphates is demonstrated in tumor cells
Seminoma
A man presents with a tumor that is homogeneous grey-white, has a bulging cut surfaces, and no necrosis, hemorrhage, or cystic change? A) teratoma B) embryonal carcinoma C) seminoma D) choriocarcinoma
C) seminoma
It is a non seminoma and very bad disease which metasize, some present as pure embryonal carcinoma and some are mixed with seminomas
65% presents metastasas at diagnosis
Frequent extension through the tunica albuginea to the epididymis and cord
Positive for OCT3/4 PLAP CD30 Cytokeratin Negative for KIT
Embryonal carcinoma
What is the gross appearance of embryonal carcinoma?
Usually replaces only a portion of testes ( unlike seminoma which replaces the entire thin)
Variegated or pale-gray
Poorly demarcated with hemorrhage and necrosis
Often invades tunica albuginea —> mean size 2.5 cm
What is the microscopic findings of embryonal carcinoma?
Solid
Pseudo glandular
Alveolar
Tubular or papillary patterns
High grade features of large cells with prominent nucleoli
In distinct cell borders with nuclear overlapping
Pleomorphism
Frequent mitosis
What type of cell is seen in embryonal carcinoma?
Primitive epithelial type cells
What are the pattern embryonal carcinoma show?
Solid pattern —> you can see sheets of malignant cells and necrosis
Alveolar pattern —> this is the pattern of invasion called the alveolar pattern you don’t need to know it
Most common testicular tumor at age 3 years or younger
Often pure
Good prognosis at this age
Adult: usually part of a mixed tumor, has prognosis of embryonal carcinoma
Yolk sac tumor
What is the difference between yolk sac tumor in adults and children?
In adults —> usually part of a mixed tumor, has prognosis of embryonal carcinoma
In children —> most common testicular tumor at age 3 years or younger
Often pure / good prognosis at this age
95% of this patients with this tumor contain —> have elevated serum alpha fetoprotein ( AFP)
Yolk sac tumours
What is alpha fetoprotein?
It is a major serum protein of early fetus, produced by fetal gut, hepatocytes, yolk sac
What is the gross appearance of pure yolk sac tumor in a child?
Mucoid soft appearance covering the entire testis but has a good prognosis and 100% cure rate
Nonencapsulated, homogeneous, yellow-white, mutinous, soft, multicystic
Adult cases often have hemorrhage and necrosis, 2-6 cm
What are the two important microscopic features of yolk sac?
- Cystic spaces
- Schiller-Duvall bodies —> which looks like glomeruli, they have capillaries in center surrounded by primitive epithelial cells
What are the microscopic features of yolk sac?
- Lace like (reticular), papillary or cord-like pattern of cuboidal/ elongated cells
- Cells have low grade nuclei
- 50% of tumors have Schiller-Duvall bodies (with central capillary and visceral and parietal layer of cells resembling primitive glomeruli)
- Tumor cells have eosinophilia hyaline globules
- Intratubular germ cell neoplasia not present in young patients but are often present after puberty
Yolk sac tumors?
Histology showing the characteristic arrangement of tumor cells around a blood vessels (Schiller- Duval body)
Glomeruli in the middle and around it the primitive epithelial cells
Yolk sac tumor
15 year old female with ovarian tumor that has alpha fetoprotein as a marker and a lot of Schiller duval bodies
Yolk sac tumor
Tumors contain cellular components derived from 2 or 3 germ layers
Teratoma
Most commonly seen in children but can also happen in adults
The most important thing about this tumor is that it has derivatives from 3 germ cell layers (endoderm, ectoderm, mesoderm)
Yolk sac tumor
It is a tumor that is benign in pre-pubertal children
Malignant post-pubertal email patients regardless of differentiation
Not associated with intratubular germ cell neoplasia
Usually are pure in infants and children
Teratoma
Is a tumor that u can see epithelium from respiratory tract
Epithelium from the colonic gastrointestinal tract which are endoderm
Can also see skin which is ectoderm
U can see cartilage and bone which are mesoderm
Teratoma
Is a tumor of testicles that is benign in children and malignant in adults
Teratoma
What is the gross appearance of teratoma?
Large 5-10 cm
Multi nodular
Heterogenous (solid, cartilaginous, cystic)
May have hair, bone, or teeth
How can we divide teratoma?
Teratoma are divided into mature and immature teratoma
What is the difference between mature teratoma and immature teratoma?
Mature teratomas —> we have elements that we can recognize like osteocytes / chondrocytes/ bones
Immature teratomas —> we don’t have elements that we can recognize it is poorly differentiated - poorly recognized
What can u see in mature teratomas?
Mixture of elements of ectoderm, endoderm, and mesoderm
What do u see in immature teratomas?
Neuroepithelium, have Fock resembling embryonic or fetal structures, usually without cytology condition atypia
Includes
- primitive neuroectoderm
- Poorly formed cartilage
- Neuroblasts
- Loose mesenchyme
- Primitive glandular structures
High of low grade terminology based on cellularity and mitotic activity used for immature teratomas
Which type of teratoma has higher chance for metases?
Immature teratomas
What is significance about immature teratomas?
Hard to recognize and we can see neuroepithelium and remember it can metastasize
What we call the feature in teratoma where we have Ros setting appearance and around it is mature fibers resembling the epithelium?
Primitive neuroepithelium
A testicular tumor with primitive neuroectodermal cells and Fock of fetal tissue ? A. Mature teratoma B. Immature teratoma C) seminoma D) embryonal carcinoma
Immature teratoma
Cystic tumor containing elements derived from all 3 germ layers?
Mature teratoma
Tumor with collection of tissues derived from all three germ layers?
Teratoma
Is a testicular tumor that may present initially with metastasis (Liver, lung, mediastinum, retroperitoneum, brain) with normal testis or small tumor but with increased serum hCG
Usually fatal when pure (in contrast to gestational CC which is curable with chemotherapy)
Choriocarcinoma
Is very aggressive and rare can also happen in women after delivery
It can be treated in women but hardest treated in men
Increased serum HCG is a good marker to use for monitoring this patient
Choriocarcinoma
What is the gross appearance of choriocarcinoma?
Hemorrhagic and necrotic mass
Small
May be replaced by fibrous scar with hemosiderin because it outgrows blood supply
Resembles disintegrating clot
What is the microscopic finding of choriocarcinoma?
Hemorrhage and necrosis common
Cytotrophoblast —> polygonal/round cells with distinct cell borders / clear cytoplasm / single bland
Syncytiotrophoblast —> large multi nuclear cell with eosinophilia and vacuolalated cytoplasm
Do we see intratubular germ cell neoplasia in choriocarcinoma?
Yes, it is common
What is the difference between cells present in choriocarcinoma?
Cytotrophoblast —> small / clear cells
Syncytiotrophoblast —> giant / esoniphillic/ vacuolated cytoplasm
We can see necrosis in choriocarcinoma
Section of endometrium showed necrosis associated with syncytiotrophoblast and cytotrophoblast. What will be increased?
Human chorionic gonadotropin —> choriocarcinoma
A tumor composed entirely of proliferating cytotrophoblasts and no chronic villi?
Choriocarcinoma
A tumor composed entirely of proliferating cytotrophoblasts and syncytiotrophoblast with areas of hemorrhage but no chronic villi. What is the diagnosis?
Choriocarcinoma
A women who had a recent delivery developed a cancer that showed cytotrophoblasts and syncytiotrophoblast proliferation with no villi formation. What is the diagnosis ?
A. Yolk sac
B. Hydatitiform mole
C. Gestational choriocarcinoma
C. Gestation choriocarcinoma
What does increased levels of BHCG indicate?
Choriocarcinoma
Is a placental tumor that showed hemorrhagic necrosis. Which one is that?
Choriocarcinoma
What are sex cord-stromal tumours?
These are testicular tumors but are not found in the seminiferous tubules they are found in the stroma
What are examples of sex cord - stromal tumours?
- Sertoli cell tumour
- Leydig cell tumour
Both of these cells produce sex hormones so we expect this tumors to highly secrete them
If a patient who is 5-6 years old presented with sertoli or leydig cell tumors what will u see?
Precocious puberty because of high testosterone secretion
Precocious puberty is when the child changes into adult to soon
What is the most common sex cord stromal tumours?
Leydig cell tumor is the most common
Are tumors that sometimes arise in setting of androgen insensitivity syndrome or adrenogenital syndrome (AGS); designate as tumor- like lesion occurring in specific syndrome
Stromal sex cord tumors
A patient presents with precocious puberty in children or gynecomastia, but most often presents as testicular swelling like other testicular tumors
Produce testosterone , dehydroepuandrosterone, androstenedione , and estrogen
10% are malignant
No predilection based on ethnicity or race
1-3 % of testicular tumors
Majority of leydig cells are benign
Leydig (interstitial) cell tumors
What is the gross appearance of leydig cell tumor?
Because this tumour produces hormones we expect them to be yellow in color
Well circumscribed, often encapsulated
3a-5 cm in size
Cut surface is homogeneous yellow or mahogany brown hyallinization and calcification may be identifiable
Where can we see reindeer crystalloids?
Leydig cell tumor
The tumor is composed of solid nests of uniform cells that have vesicular round nuclei, prominent nucleoli and well developed eosinophilia cytoplasm
Leydig cell tumor
In what type of tumors can reinvent crystalloids can be seen?
Leydig cell tumors
A 23 year old male came with gynecomastia and testicular mass showing reined crystals
Leydig cell tumors
Is a tumor the majority is benign and can be part of petunia-jegher syndrome?
Sertoli cell tumour
The majority are benign
They can produce testosterone and estrogen so the male will be presented with feminization and gynecomastia
Can occur as part of androgen insensitivity syndrome
Carney’s complex
Peutz-jegher’s syndrome
Sertoli cell tumour
It is a testicular tumor 25 to 30 % of cases have feminization and gynecomastia ?
Sertoli cell tumour
What is the gross of Sertoli cell tumor?
Spherical, lobulated, well circumscribed tumors
Cut surface usually homogenous tan yellow or grayish white
Areas of necrosis usually not evident
Hemorrhage may be seen
The tumor forms cords and groups that resemble tubules?
Sertoli cell tumor
Cord like appearance testicular tumor?
Sertoli cell tumor
They are tumors that produce hormones and causes precocious puberty ?
Sertoli and leydig cell tumors
Cystic tumor containing elements derived from all 3 germ layers?
Mature teratoma
A testicular tumor with primitive neuroectodermal cells and Fock of fetal tissue. What is it? A. Mature teratoma B. Immature teratoma C. Seminoma D. Embryonal carcinoma
B immature teratoma
A man presents with a tumor that is homogenous grey-white, has bulging cut surface and no necrosis, hemorrhage, or cystic change? A. Teratoma B. Embryonal carcinoma C. Seminoma D. Choriocarcinoma
C. Seminoma
A 23-year old male came with gynectomastia and testicular mass showing Reinke crystals. Diagnose?
A) leydig cell tumor
Note: while both leydig and sertoli can lead to gynectomastia as a result of increase estrogen
Reinke’s crystals are characteristic of leydig cells
What is seen next to most germ cell tumors?
Intratubular germ cell tumors
A case about tumor with Reinke’s crystals?
Leydig cell tumor
Which is associated with alpha fetoprotein protein?
Yolk sac tumor
What is the microscopic finding of Sertoli cells?
Tumor cells are typically arranged in solid or hollow tubules separated by basement membrane
Cytoplasm is pale eosinophilic to vacuolated due to extensive lipid
Tumor cells are bland and uniformly round with oval, elongated nuclei; no prominent nucleoli, no nuclear grooves , no inclusions
Rarely mild nuclear atypia and pleomorphism