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Male Genital Tract Pathology-2
      Dr.CSBR.Prasad, M.D.
Testicular tumors


      CSBRP-July-2012
Pathologic Classification of Common
        Testicular Tumors
       Germ Cell Tumors
           Seminomatous tumors
                Seminoma
                Spermatocytic seminoma
           Non-seminomatous tumors
                Embryonal carcinoma,
                Yolk sac (endodermal sinus) tumor
                Choriocarcinoma
                Teratoma
       Sex cord-Stromal Tumors
                Leydig cell tumor
                Sertoli cell tumor


                   CSBRP-July-2012
Figure 22-47 Histogenesis and interrelationships of tumors of germ cell origin.

                                CSBRP-July-2012
Germ cell tumors
Hence germ cell tumors can be divided into:

  1-Those that continue to resemble germ cells
         ex: Seminoma / Dysgerminoma
  2-Those that resemble protions of the embryo
         ex: Teratomas
  3-Those that resemble portions of the
  extraembryonic tissue
         ex: Yolk sac tumor, Choriocarcinoma
                    CSBRP-July-2012
Pathogenesis – testicular tumors

• Cryptorchidism (10% of testicular tumors)
• Testicular dysgenesis
     (testicular feminization, Klinefelter’s)
• Genetic factors
  –   Low incidence in blacks
  –   Familial clustering
  –   Occuring in sibs
  –   i(12p)
                      CSBRP-July-2012
Seminoma
•Most common type of germ cell tumor
•Peak in 30s
•Types: classic type, spermatocytic type, anaplasitc type.
•Spermatocytic seminoma: distinct both clinically,
histologically,
       Uncommon
       >60yrs
       No metastasis (excellent prognosis)
                          CSBRP-July-2012
Seminoma
Seminoma of the testis. A small rim of remaining normal testis appears at the far
right (arrow). The tumor is composed of lobulated soft tan to brown tissue.
                                   CSBRP-July-2012
Seminoma
CSBRP-July-2012
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Pathology Pearls
Name some RADIOSENSITIVE tumors
 •   Seminoma
 •   Medulloblastoma / Myeloma
 •   Wilms’ tumor
 •   Lymphomas esp. Hodgkin’s
 •   Ewing’s tumor
              CSBRP-July-2012
                                SMILE
Spermatocytic Seminoma



        CSBRP-July-2012
CSBRP-July-2012
CSBRP-July-2012
Spireme chromatin

CSBRP-July-2012
Special features of
       Spermatocytic Seminoma
•   Do not arise from intratubular germ cell neoplasm
•   Uncommon 1-2% of all testicular tumors
•   Occurs in old age >60yrs
•   Slow growing; No mets to regional lymphnodes
•   Surgery is the mode of Tx
•   No lymphocytic infiltration
•   Three types of cells in histology
•   Excellent prognosis

                      CSBRP-July-2012
Embryonal carcinoma
•20-30yrs
•More aggressive
•Variegated appearance
•Histologically: ALVEOLAR, TUBULR, &
PAPILLARY patterns


                   CSBRP-July-2012
Here is an embryonal carcinoma of the testis. There is a rim of normal testis superiorly.
The tumor is soft and much more variegated than the seminoma, with red to tan to
brown areas, including prominent hemorrhage and necrosis
Embryonal carcinoma, but there are scattered firmer white areas that
histologically are teratoma. Thus, this testicular neoplasm is mixed embryonal
          carcinoma plus teratoma (sometimes called teratocarcinoma).
This is the histologic pattern of embryonal carcinoma. Sheets of blue
               cells are trying to form primitive tubules.
CSBRP-July-2012
CSBRP-July-2012
Teratoma
• Infants and young children
• In adults pure teratomas are rare
• Gross: Large, heterogenous areas
          Cystic and solid areas
• Micro: collection of tissue derived from
  different germ layers
Terms:
1. Teratoma with malignant transformation
2. Teratocarcinoma
                  CSBRP-July-2012
CSBRP-July-2012
A small testicular carcinoma is shown here. There is a mixture of bluish cartilage (Blue
arrow) with red and white tumor tissue. This neoplasm microscopically contained
mainly teratoma, but areas of embryonal carcinoma were also present.
Here is an embronal carcinoma mixed with teratoma in which islands of bluish white
cartilage from the teratoma component are more prominent. A rim of normal brown
testis appears at the left.         CSBRP-July-2012
Here is a testicular neoplasm that is mostly teratoma, but embryonal carcinoma and
seminoma were found microscopically. In contrast with the ovary, pure benign
teratomas of the testis are very rare.
CSBRP-July-2012
Immature teratoma


Presence of primitive neuroepithelium




              CSBRP-July-2012
Immature teratoma




     CSBRP-July-2012
Immature teratoma




     CSBRP-July-2012
Teratocarcinoma

     Teratoma
            +
Embryonal carcinoma


       CSBRP-July-2012
Teratocarcinoma
At the bottom is a focus of cartilage. Above this is a primitive mesenchymal stroma and
to the left a focus of primitive cells most characteristic for embryonal carcinoma. This is
embryonal carcinoma mixed with teratoma.
Pathology Pearls
     “An important point to remember”
           Testicular Teratoma

        in Pre-pubertal males: Benign
      in Post-pubertal males: Malignant

This rule will not apply to OVARIAN teratomas
                  CSBRP-July-2012
Choriocarcinoma
• Highly malignant neoplasm
• Composed of both cyto and
  syncytiotrophoblastic cells
• Pure form is rare, most common is mixed
  patterns
• Gross: small lesions rarely exceed 5cms,
  hemorrhages and necrosis are very common
• HCG can be demonstrated in
  syncytiotrophoblasts
                 CSBRP-July-2012
Choriocarcinoma




CSBRP-July-2012
CSBRP-July-2012
Choriocarcinoma




    CSBRP-July-2012
Choriocarcinoma




    CSBRP-July-2012
Choriocarcinoma - IHC




                         ß-HCG
       CSBRP-July-2012
Yolk sac tumor
• Also known as infantile embryonal carcinoma or
  endodermal sinus tumor
• It is the most common testicular tumor in infants
  and children up to 3 years of age
• It has a very good prognosis in infants and young
  children
• In adults, the pure form of this tumor is rare;
  instead, yolk sac elements frequently occur in
  combination with embryonal carcinoma

                     CSBRP-July-2012
Yolk sac tumor




    CSBRP-July-2012
An endodermal sinus tumor (yolk sac tumor) of the testis is shown composed of primitive germ
cells that form glomeruloid or embryonal-like structures. These tumors are most frequent in
children, but overall they are rare.
YST - Schiller–Duval body
YST - Hyaline globules
         CSBRP-July-2012
Sex cord-Stromal Tumors




         CSBRP-July-2012
Leydig cell tumor
• Functional tumor: Androgens, Estrogens, Corticosteroids
• Any age (usually between 20 & 60yrs)
• Presenting feature: Testicular swelling
                     Gynecomastia
                     Precocious masculanization
• Morphology: Cicumscribed nodules <5cms
               Golden brown cut surface
• Histologically: Leydig cells with Reinke crystals
                ~10% are malignant
                        CSBRP-July-2012
CSBRP-July-2012
CSBRP-July-2012
CSBRP-July-2012
Reinke’s crystalloids
             Van Gieson’s stain
CSBRP-July-2012
Gynecomastia in a 25yo male. Secondary to Leydig cell tumor of testis.
Pathology Pearls
Gynecomastia - Causes:
1. Cirrhosis of the liver
2. Functioning testicular tumor (leydig cell tumor,
   sertoli cell tumor)
3. Anabolic steroids
4. Alcoholism
                                          LIVER
5. Antipsychotic agents
6. Antiretroviral drugs
7. Marijuana / heroin
                                      3   DRUGS
                                          TESTIS
                    CSBRP-July-2012
Pathology Pearls
Name some FUNCTIONAL TUMORS
All hormone secreting tumors are functional
1.   Somatostatinoma            1.   Leydig cell tumors
2.   Glucagonoma                2.   Sertoli cell tumor
3.   Insulinoma
                                3.   Granulosa cell tumors
4.   Adrenocortical tumors
5.   Parathyroid adenoma        4.   Theca cell tumors




                       CSBRP-July-2012
Sertoli cell tumor
                 (Androblastoma)
•   Functional tumor: may elaborate estrogens or androgens
     (precocious masculanization or feminization)
•   Occasionally it may induce gynecomastia
•   Most of them are benign
•   ~10% may pursue malignant course
•   Morphology: firm nodules, g/w to yellow
•   Histology: cells are arranged in trabaculae and structures
    resembling spermatic cord.
                          CSBRP-July-2012
CSBRP-July-2012
CSBRP-July-2012
Gonadoblastoma
• Rare
• Tumors composed of
      Germ cells + stromal elements
• Arise in dysgenetic gonads (100%)
• In some tumors, germ cell component
  may become malignant giving rise to an
  invasive Seminoma
                CSBRP-July-2012
Testicualr Lymphoma
• Most common neoplasm in men >60yrs
• At presentation it’s advanced disease
• It’s almost always NHL – Diffuse large
  cell lymphoma
• Prognosis is very poor



                CSBRP-July-2012
CSBRP-July-2012
CSBRP-July-2012
CSBRP-July-2012
Epidermoid cyst



     CSBRP-July-2012
Epidermoid cyst of testis




          CSBRP-July-2012
Mixed germ cell tumors

• ~60% of testicular tumors composed of more
than one pattern
• Prognosis is worsened by the presence of an
aggressive element



                 CSBRP-July-2012
CF of Testicular tumors
• Painless enlargement of the testis
• Spread: Lymphatics: Retroperitoneal para-aortic nodes
          Hematogenous: Lungs, brain, liver.
          Mets may have different histology
• Tumors are divided in to Seminoma and NSGCT
• Prognosis depends on
    --- clinical stage
    --- histological type
• Distant mets if present, usually occur within first 2yrs after Tx.


                           CSBRP-July-2012
Differences between Seminoma and NSGCTs

               SEMINOMA                     NSGCT

Presentation 70% in stage-I           60% in stage-II, III.

Mets         LN                       Hematogenous

Tx           Extremely                Radioresistant
             radiosensitive
Prognosis    Less aggressive          More aggressive
             Good prognosis           Poor prognosis
                    CSBRP-July-2012
Markers

Biological:                     Molecular:
• AFP                           • OCT3/4 gene
• hCG                           • Inactivation X
• PAP                             chromosome
• Placental lactogen            These can be detected by
• LDH                             immunoperoxidase
                                  and PCR


                       CSBRP-July-2012
Value of serum markers
         (HCG, AFP, LDH)
1.   In the evaluation of testicular masses
2.   Staging testicular germ cell tumors
3.   To assess tumor burden
4.   To monitor response to Tx and relapse




                  CSBRP-July-2012
Pathology Pearls
Important practical points to remember
•   All testicular masses are neoplastic, unless proven otherwise
•   Most of the neoplasms are malignant
•   No testicular biopsy if tumor is suspected
•   Hence, in case of solid testicular mass, orchiectomy is
    performed with a presumption of malignancy
•   Mets may have different histology: Embryonal carcinoma
    May present a teratomatous picture in the secondary deposits
    Explanation:
     A.   Forward and backward differentiation
     B.   Primary tumor is mixed and that minor component in the primary
          lesion, that were unresponsive to chemotherapy survived
          resulting in the dominant metastatic pattern
                            CSBRP-July-2012
E N D

 CSBRP-July-2012
Contact:
Dr.CSBR.Prasad, M.D.,
Associate Professor of Pathology,
Sri Devaraj Urs Medical College,
Kolar-563101,
Karnataka,
INDIA.

CSBRPRASAD@REDIFFMAIL.COM

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Male genitaltract 2

  • 1. Male Genital Tract Pathology-2 Dr.CSBR.Prasad, M.D.
  • 2. Testicular tumors CSBRP-July-2012
  • 3. Pathologic Classification of Common Testicular Tumors Germ Cell Tumors Seminomatous tumors Seminoma Spermatocytic seminoma Non-seminomatous tumors Embryonal carcinoma, Yolk sac (endodermal sinus) tumor Choriocarcinoma Teratoma Sex cord-Stromal Tumors Leydig cell tumor Sertoli cell tumor CSBRP-July-2012
  • 4. Figure 22-47 Histogenesis and interrelationships of tumors of germ cell origin. CSBRP-July-2012
  • 5. Germ cell tumors Hence germ cell tumors can be divided into: 1-Those that continue to resemble germ cells ex: Seminoma / Dysgerminoma 2-Those that resemble protions of the embryo ex: Teratomas 3-Those that resemble portions of the extraembryonic tissue ex: Yolk sac tumor, Choriocarcinoma CSBRP-July-2012
  • 6. Pathogenesis – testicular tumors • Cryptorchidism (10% of testicular tumors) • Testicular dysgenesis (testicular feminization, Klinefelter’s) • Genetic factors – Low incidence in blacks – Familial clustering – Occuring in sibs – i(12p) CSBRP-July-2012
  • 7. Seminoma •Most common type of germ cell tumor •Peak in 30s •Types: classic type, spermatocytic type, anaplasitc type. •Spermatocytic seminoma: distinct both clinically, histologically, Uncommon >60yrs No metastasis (excellent prognosis) CSBRP-July-2012
  • 9. Seminoma of the testis. A small rim of remaining normal testis appears at the far right (arrow). The tumor is composed of lobulated soft tan to brown tissue. CSBRP-July-2012
  • 11.
  • 20. Pathology Pearls Name some RADIOSENSITIVE tumors • Seminoma • Medulloblastoma / Myeloma • Wilms’ tumor • Lymphomas esp. Hodgkin’s • Ewing’s tumor CSBRP-July-2012 SMILE
  • 21. Spermatocytic Seminoma CSBRP-July-2012
  • 25. Special features of Spermatocytic Seminoma • Do not arise from intratubular germ cell neoplasm • Uncommon 1-2% of all testicular tumors • Occurs in old age >60yrs • Slow growing; No mets to regional lymphnodes • Surgery is the mode of Tx • No lymphocytic infiltration • Three types of cells in histology • Excellent prognosis CSBRP-July-2012
  • 26. Embryonal carcinoma •20-30yrs •More aggressive •Variegated appearance •Histologically: ALVEOLAR, TUBULR, & PAPILLARY patterns CSBRP-July-2012
  • 27. Here is an embryonal carcinoma of the testis. There is a rim of normal testis superiorly. The tumor is soft and much more variegated than the seminoma, with red to tan to brown areas, including prominent hemorrhage and necrosis
  • 28. Embryonal carcinoma, but there are scattered firmer white areas that histologically are teratoma. Thus, this testicular neoplasm is mixed embryonal carcinoma plus teratoma (sometimes called teratocarcinoma).
  • 29. This is the histologic pattern of embryonal carcinoma. Sheets of blue cells are trying to form primitive tubules.
  • 32. Teratoma • Infants and young children • In adults pure teratomas are rare • Gross: Large, heterogenous areas Cystic and solid areas • Micro: collection of tissue derived from different germ layers Terms: 1. Teratoma with malignant transformation 2. Teratocarcinoma CSBRP-July-2012
  • 34. A small testicular carcinoma is shown here. There is a mixture of bluish cartilage (Blue arrow) with red and white tumor tissue. This neoplasm microscopically contained mainly teratoma, but areas of embryonal carcinoma were also present.
  • 35. Here is an embronal carcinoma mixed with teratoma in which islands of bluish white cartilage from the teratoma component are more prominent. A rim of normal brown testis appears at the left. CSBRP-July-2012
  • 36. Here is a testicular neoplasm that is mostly teratoma, but embryonal carcinoma and seminoma were found microscopically. In contrast with the ovary, pure benign teratomas of the testis are very rare.
  • 38.
  • 39. Immature teratoma Presence of primitive neuroepithelium CSBRP-July-2012
  • 40. Immature teratoma CSBRP-July-2012
  • 41. Immature teratoma CSBRP-July-2012
  • 42. Teratocarcinoma Teratoma + Embryonal carcinoma CSBRP-July-2012
  • 44. At the bottom is a focus of cartilage. Above this is a primitive mesenchymal stroma and to the left a focus of primitive cells most characteristic for embryonal carcinoma. This is embryonal carcinoma mixed with teratoma.
  • 45. Pathology Pearls “An important point to remember” Testicular Teratoma in Pre-pubertal males: Benign in Post-pubertal males: Malignant This rule will not apply to OVARIAN teratomas CSBRP-July-2012
  • 46. Choriocarcinoma • Highly malignant neoplasm • Composed of both cyto and syncytiotrophoblastic cells • Pure form is rare, most common is mixed patterns • Gross: small lesions rarely exceed 5cms, hemorrhages and necrosis are very common • HCG can be demonstrated in syncytiotrophoblasts CSBRP-July-2012
  • 49. Choriocarcinoma CSBRP-July-2012
  • 50. Choriocarcinoma CSBRP-July-2012
  • 51. Choriocarcinoma - IHC ß-HCG CSBRP-July-2012
  • 52. Yolk sac tumor • Also known as infantile embryonal carcinoma or endodermal sinus tumor • It is the most common testicular tumor in infants and children up to 3 years of age • It has a very good prognosis in infants and young children • In adults, the pure form of this tumor is rare; instead, yolk sac elements frequently occur in combination with embryonal carcinoma CSBRP-July-2012
  • 53. Yolk sac tumor CSBRP-July-2012
  • 54. An endodermal sinus tumor (yolk sac tumor) of the testis is shown composed of primitive germ cells that form glomeruloid or embryonal-like structures. These tumors are most frequent in children, but overall they are rare.
  • 56. YST - Hyaline globules CSBRP-July-2012
  • 57. Sex cord-Stromal Tumors CSBRP-July-2012
  • 58. Leydig cell tumor • Functional tumor: Androgens, Estrogens, Corticosteroids • Any age (usually between 20 & 60yrs) • Presenting feature: Testicular swelling Gynecomastia Precocious masculanization • Morphology: Cicumscribed nodules <5cms Golden brown cut surface • Histologically: Leydig cells with Reinke crystals ~10% are malignant CSBRP-July-2012
  • 62.
  • 63. Reinke’s crystalloids Van Gieson’s stain CSBRP-July-2012
  • 64.
  • 65. Gynecomastia in a 25yo male. Secondary to Leydig cell tumor of testis.
  • 66. Pathology Pearls Gynecomastia - Causes: 1. Cirrhosis of the liver 2. Functioning testicular tumor (leydig cell tumor, sertoli cell tumor) 3. Anabolic steroids 4. Alcoholism LIVER 5. Antipsychotic agents 6. Antiretroviral drugs 7. Marijuana / heroin 3 DRUGS TESTIS CSBRP-July-2012
  • 67. Pathology Pearls Name some FUNCTIONAL TUMORS All hormone secreting tumors are functional 1. Somatostatinoma 1. Leydig cell tumors 2. Glucagonoma 2. Sertoli cell tumor 3. Insulinoma 3. Granulosa cell tumors 4. Adrenocortical tumors 5. Parathyroid adenoma 4. Theca cell tumors CSBRP-July-2012
  • 68. Sertoli cell tumor (Androblastoma) • Functional tumor: may elaborate estrogens or androgens (precocious masculanization or feminization) • Occasionally it may induce gynecomastia • Most of them are benign • ~10% may pursue malignant course • Morphology: firm nodules, g/w to yellow • Histology: cells are arranged in trabaculae and structures resembling spermatic cord. CSBRP-July-2012
  • 71. Gonadoblastoma • Rare • Tumors composed of Germ cells + stromal elements • Arise in dysgenetic gonads (100%) • In some tumors, germ cell component may become malignant giving rise to an invasive Seminoma CSBRP-July-2012
  • 72. Testicualr Lymphoma • Most common neoplasm in men >60yrs • At presentation it’s advanced disease • It’s almost always NHL – Diffuse large cell lymphoma • Prognosis is very poor CSBRP-July-2012
  • 76. Epidermoid cyst CSBRP-July-2012
  • 77. Epidermoid cyst of testis CSBRP-July-2012
  • 78.
  • 79. Mixed germ cell tumors • ~60% of testicular tumors composed of more than one pattern • Prognosis is worsened by the presence of an aggressive element CSBRP-July-2012
  • 80.
  • 81.
  • 82. CF of Testicular tumors • Painless enlargement of the testis • Spread: Lymphatics: Retroperitoneal para-aortic nodes Hematogenous: Lungs, brain, liver. Mets may have different histology • Tumors are divided in to Seminoma and NSGCT • Prognosis depends on --- clinical stage --- histological type • Distant mets if present, usually occur within first 2yrs after Tx. CSBRP-July-2012
  • 83. Differences between Seminoma and NSGCTs SEMINOMA NSGCT Presentation 70% in stage-I 60% in stage-II, III. Mets LN Hematogenous Tx Extremely Radioresistant radiosensitive Prognosis Less aggressive More aggressive Good prognosis Poor prognosis CSBRP-July-2012
  • 84. Markers Biological: Molecular: • AFP • OCT3/4 gene • hCG • Inactivation X • PAP chromosome • Placental lactogen These can be detected by • LDH immunoperoxidase and PCR CSBRP-July-2012
  • 85. Value of serum markers (HCG, AFP, LDH) 1. In the evaluation of testicular masses 2. Staging testicular germ cell tumors 3. To assess tumor burden 4. To monitor response to Tx and relapse CSBRP-July-2012
  • 86. Pathology Pearls Important practical points to remember • All testicular masses are neoplastic, unless proven otherwise • Most of the neoplasms are malignant • No testicular biopsy if tumor is suspected • Hence, in case of solid testicular mass, orchiectomy is performed with a presumption of malignancy • Mets may have different histology: Embryonal carcinoma May present a teratomatous picture in the secondary deposits Explanation: A. Forward and backward differentiation B. Primary tumor is mixed and that minor component in the primary lesion, that were unresponsive to chemotherapy survived resulting in the dominant metastatic pattern CSBRP-July-2012
  • 87. E N D CSBRP-July-2012
  • 88. Contact: Dr.CSBR.Prasad, M.D., Associate Professor of Pathology, Sri Devaraj Urs Medical College, Kolar-563101, Karnataka, INDIA. CSBRPRASAD@REDIFFMAIL.COM