Diseases of the liver and pancreas



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PROSTATE - Inflammation

Acute and chronic prostatitis:

  • Extend from the bladder or urethra

  • Nonspecific infection caused by

  • Coliform bacteria

  • Gonococci

  • Chlamydia

Granulomatous prostatitis:

  • May be caused by specific infections such as tuberculosis or syphillis

  • Nonspecific inflammatory reaction to inspissated secretion/ autoimmune causation


Benign nodular hyperplasia (BNH) / Benign prostatic hyperplasia (BPH)

  • Extremely common disorder in men over 50

  • Gross - distinct circumscribed grey white nodules in the periurethral zone

  • Histology - proliferation of both glandular and fibromuscular stromal elements + infarct, infection, squamous metaplasia



Benign prostatic hyperplasia (BPH)

  • Proliferation of glands, some cystically dilated within a well defined nodule

Benign prostatic hyperplasia (BPH)

  • High power view showing hyperplastic glands with two layers

  • Inner columnar

  • Outer cuboidal

Clinical Features & Complications

  • Asymptomatic

  • Compression of urethra - difficulty in urination, frequency or dribbling

  • Retention of urine

  • Bladder distention and hypertrophy

  • Hydroureters and hydronephrosis

  • Prostatitis

  • Cystitis


Prostatic carcinoma

Incidence:

  • Marked geographical and racial difference: common in American males (more prevalent in blacks) but uncommon in orientals

Etiology:

  • Role of androgen in the growth of the tumor



Clinical presentation

  • Clinical symptoms (prostatism) is present, hard mass find during rectal examination.

  • Incidental finding during microscopic examination of the tissue surgically removed for non-malignant disease, particularly BPH.

  • Present with signs and symptoms of metastasis (e.g. back pain due to vertebral metastasis)

  • Tumors of the prostate detected during autopsy on patients that showed no clinical evidence of prostatic cancer


Tumour markers:

  • Prostatic acid phosphatase

  • Prostatic specific antigen

Gross:

  • Yellowish, hard, gritty tissue

Histology:

  • Adenocarcinoma, usually microacini

  • Perineural invasion

Modes of spread:

  • Local - causing prostatic urethra obstruction and may infiltrate into periphery adjacent tissue

  • Lymphatics - presacral in pelvis, iliac and paraaortic lymph nodes

  • Blood - vertebra, osteoblastic, widespread metastasis

Treatment: Surgery + hormonal therapy
Staging of Prostatic Cancer

Testicular Tumors



St Christopher’s College of Medicine
Testicular tumors - Objectives

  • Germ Cell Tumors:

  • know the classification of testicular germ cell tumors and how they originate

  • know the commonest type

  • be able to describe clinical and histologic features

  • know which tumor produces which marker

  • predict possible clinical outcomes and response to treatment

GERM CELL TUMORS

Epidemiology:

  • More common in whites than blacks

  • Peak incidence is between 20 and 34 years when it is the most common malignancy in males.

  • Mean age

  • Seminoma is about 40 years

  • Teratoma is about 30 years.

  • Are uncommon after 50 years of age.




  • Cause of germ cell tumors is unknown.

  • Cryptorchidism significantly increases the risk, 4 to 10 fold, of subsequent development of germ cell tumors.

  • Development of a germ cell tumor in one testis increases the risk of developing a tumor in the contralateral testis.


GERM CELL TUMORS

  • GCTs have the following subtypes and frequencies:

  • seminoma (40%),

  • embryonal (25%),

  • teratocarcinoma (25%),

  • teratoma (5%),

  • choriocarcinoma (pure) (1%).

  • The most important clinical distinction is between seminoma and nonseminoma, 2 broad categories with different treatment algorithms:

  • (1) seminoma as a classification refers to pure seminoma upon histopathologic review, and

  • (2) any nonseminomatous elements (even if seminoma is prevalent) change the classification to nonseminoma.




  • After a radical orchiectomy, testicular seminoma is a pathologic diagnosis in which

  • only seminomatous elements are observed upon histopathologic review and

  • serum alpha-fetoprotein (AFP) is normal.

  • Any elevation of AFP or nonseminomatous elements in the testis specimen mandates diagnosis of nonseminomatous GCT (NSGCT) and an appropriate change in treatment


Seminoma

  • Commonest type of primary testicular tumor.

  • Accounts for 35 - 70% of testicular neoplasms

  • Types:

  • Classic (or conventional)

  • Anaplastic

  • Spermatocytic seminomas.




  • Does not develop before puberty

Classic seminoma

  • A nodular tumor completely replaces the testis

Classic seminoma

Classic seminoma

  • The tumor is composed of sheets of uniform undifferentiated germ cells

  • with clear or fine granular cytoplasm,

  • well-defined cell border and round nuclei, frequently with prominent nucleoli.

  • Sheets of tumor cells are separated by slender fibrous septa.

  • Diffuse or focal intense lymphoid infiltrate is seen in most tumors.

  • Glycogen may be demonstrated in the cytoplasm of the tumor cells.

Classic seminoma

Seminoma – “fried-egg” appearance



Classic seminoma

  • Mitotic figures are usually infrequent.

  • Approx 35% cases, noncaseating granulomatous areas containing small giant cells are found.



  • Tumor giant cells that mimic syncytiotrophoblasts in appearance and which may contain intracytoplasmic ß-hCG are present in some tumors.

  • This may lead to a mild increase in serum ß-hCG.

Mitotic figure in intestinal epithelial cell

Classic seminoma

  • Left panel shows multinucleate giant cells of foreign body type.

  • Right panel shows syncytiotrophoblast-like tumor giant cell.

Classic seminoma - syncytiotrophoblast-like tumor giant cell

ANAPLASTIC SEMINOMAS

  • In some seminomas, the neoplastic cells are more pleomorphic and have more mitotic figures than in typical seminoma.

  • These tumors have been called anaplastic seminomas.

  • Although these tumors tend to occur at higher stages than classical seminoma, stage for stage this subgroup has the same prognosis as the classical type.


SPERMATOCYTIC SEMINOMA

  • Is a rare but distinct clinicopathologic variant of seminoma

  • Occurs only in the descended testes of elderly men

  • Forming about 5% of seminomas.

  • The tumor is bilateral in about 6% of cases compared to about 2% in classic seminoma.

SPERMATOCYTIC SEMINOMA

  • The tumor tends to be poorly demarcated, usually soft with a gelatinous or mucoid appearance.

  • Cystic areas, especially in the center, are common but hemorrhage or necrosis is almost always absent.


Histology - Spermatocytic seminomas

  • Forms solid sheets of cells without the nesting pattern of classical seminoma.

  • Three populations of tumor cells, separated according to size, are seen:

  • small cells that superficially resemble lymphocytes,

  • intermediate or medium-sized cells, the commonest cell type, have round nuclei and finely granular chromatic pattern,

  • large or giant cells.




  • Mitotic figures are usually abundant

  • Lymphocytic infiltrate and granulomas seen in classic seminoma are absent.

  • Spermatocytic seminoma is an extremely indolent tumor with rather limited malignant potential and rarely if ever metastasizes.



EMBRYONAL CARCINOMA

  • This subtype of GCTs represents the most primitive form of the NSGCTs.

  • Accounts for about 15-35% of testicular GCTs.


EMBRYONAL CARCINOMA

  • Grossly, the tumors are large, often hemorrhagic and necrotic producing a variegated cut surface.


Embryonal Cell Carcinomas

  • Sheets of undifferentiated cells and glandular differentiation


EMBRYONAL CARCINOMA

  • Extremely pleomorphic

  • Show a variety of patterns forming glands, tubules, and even primitive embryo-like structures.

  • Many mitotic figures are present.

EMBRYONAL CARCINOMA

  • Anaplastic and solid undifferentiated areas may present as sheets of cells with large, hyperchromatic nuclei, prominent nucleoli and poorly-defined cell borders.

EMBRYONAL CARCINOMA

  • Poorly differentiated area in embryonal carcinoma.

EMBRYONAL CARCINOMA

  • Metastasizes early and widely via both lymphatic and hematogenous routes.

  • Radiation is not as effective as with seminoma, but newer chemotherapeutic agents have greatly improved prognosis.

  • Tumors confined to the testis now have a prognosis essentially identical to that of seminoma (95% 5-year survival).


YOLK SAC TUMOR (ENDODERMAL SINUS TUMOR)

  • Is a distinct entity from embryonal carcinoma of which it was considered a variant in the past.

  • Noted for its:

  • Resemblance to rat fetal yolk sac

  • Presence of microscopically distinctive structures known as Schiller-Duval bodies.

YOLK SAC TUMOR

  • Testicular yolk sac tumors occur in two forms:

  • A pure form in young children

  • A focal differentiation within other NSGCTs, mainly embryonal carcinoma, in adults.

YOLK SAC TUMOR

  • The cut surface is gray-white and may be cystic

YOLK SAC TUMOR

  • Tumor shows a variety of patterns,

  • Commonest: loose meshwork of small spaces and cysts (producing a sieve-like appearance) lined by either flattened cells or vacuolated cells with nuclei that protrude in a "hobnail" fashion.

YOLK SAC TUMOR

  • In some tumors, Schiller-Duval bodies (endodermal sinus) are seen.

  • These are glomerulus-like structures with a central core of blood vessel surrounded by an inner layer of epithelial-like cells, a space and an outer layer of similar cells.

YOLK SAC TUMOR

  • Almost invariably associated with production of large amounts of alpha-fetoprotein (AFP)

  • AFP may be followed as a marker of disease progression in the patient's serum.

  • Antibodies directed against AFP may also be used to stain the tumors and aid in their diagnosis.

YOLK SAC TUMOR

  • Yolk sac tumor stained with antibodies against AFP. Note the brown staining of the epithelium indicating the presence of AFP

TERATOMA

  • In the WHO classification (used in the US) the term is restricted to a tumor typically composed of several tissues representing two or more germinal layers.

  • Are further subdivided into

  • Mature

  • Immature

  • Teratoma with malignant transformation.

Mature Teratoma

  • The tumor is composed exclusively of well-differentiated tissues and by definition, contains no malignant-looking tissue.

  • Some may consist of nests of mature cartilage, smooth muscle and squamous or mucous epithelial-lined cysts.

  • In others, more complex and organoid arrangement is seen and abortive gastrointestinal tract, brain, eye, pancreas, salivary gland, and other organs can easily be recognized.

Mature Teratoma

  • Showing cysts lined by mucous epithelium (left) and keratinizing squamous epithelium (right).

Mature Teratoma

  • Mature cartilage (left) and spaces lined by mucus secreting glandular epithelium (right) are present

Mature Teratoma

Mature Teratoma

Mature Teratoma



  • Although the tumor has a benign histologic appearance, its clinical course in the adult is unpredictable and it can metastasize.

  • The metastases show the same well-differentiated picture as the primary tumor.

  • In children, teratomas whatever their histological appearances behave in a benign fashion.

  • Teratoma is the 2nd most common testicular germ cell tumor in children (after Yolk Sac Tumor).

Immature Teratoma

  • In this type of teratoma there are incompletely differentiated, fetal-appearing tissues, often of neural differentiation.

Immature Teratoma

  • Primitive brain tissue (upper left corner)

  • Well-differentiated glands (lower half)

Choriocarcinoma

  • This is a highly malignant neoplasm that is usually widely disseminated and frequently fatal.

  • The cells differentiate in the direction of trophoblastic (placental) tissue

  • Both cytotrophoblast and syncitiotrophoblast must be present for the diagnosis to be made.

  • Pure choriocarcinoma of the testis is extremely rare, and the tumor is much more common as a component of mixed GCTs.

Choriocarcinoma

  • The tumor typically presents in adolescent or young adults with widespread disease, and an often small, painless primary lesion in the testis.

  • It is extensively hemorrhagic and necrotic and, sometimes, may be reduced to a fibrous scar, leaving widespread metastases with no apparent testicular mass.

  • On occasion, the tumor may be large and bulky.

  • Hemoptysis due to pulmonary involvement is common.

Choriocarcinoma



Choriocarcinoma

  • Tumor is composed of two types of cells:

  • Syncytiotrophoblasts: large multinucleate cells with abundant vacuolated cytoplasm containing hCG

  • Cytotrophoblasts: polygonal cells with distinct cell borders and single nuclei, which grow in clusters and are surrounded by the syncytiotrophoblasts.




  • Choriocarcinoma, left panel, and placenta, right panel.

  • Note similarity in histologic appearances.

Choriocarcinoma

  • Sheet of cytotrophoblasts surrounded by syncytiotrophoblasts.

Choriocarcinoma

  • This image shows admixture of polygonal cells with clear cytoplasm (cytotrophoblast) and large multinucleated cells with smudged nuclear chromatin (syncytiotrophoblast).

Choriocarcinoma

  • In classic cases of choriocarcinoma, syncytiotrophoblasts form a “cap” around clusters of cytotrophoblasts in an attempt to mimic the architecture of immature placental villi

Age Incidences of Germ-Cell Tumors


  • Question:


  • What is the commonest malignant testicular tumor after 50 years of age?




  • Malignant lymphoma




  • Question:




  • Choriocarcinoma is one of the very few carcinomas that metastasize more frequently via bloodstream than lymphatics. What are the others?




  • Follicular carcinoma of the thyroid

  • Renal cell carcinoma.

Tumour Markers

Human chorionic gonadotrophin (HCG)

  • Secreted by syncytiotrophoblastic cells in the placenta

  • Elevated levels are seen in most choriocarcinomas, some embryonal carcinomas and some seminoma containing syncytiotrophoblasts.

Alpha-fetoprotein (AFP)

  • Secreted in yolk sac tumors and some embryonic carcinoma.

Significance of Tumour Markers

  • Detection of non-seminomatous elements

  • Detection of recurrence

  • Detection of metastasis


Non-Germ Cell Tumors

Leydig (Interstitial) Cell Tumors

  • Tumors of Leydig cells may elaborate

  • Androgens

  • Androgens + estrogens

  • Corticosteroids

  • They arise at any age

  • Majority between 20 - 60 years of age

  • The most common presenting feature is testicular swelling

  • In some patients gynecomastia may be the first symptom

  • In children, hormonal effects, manifested primarily as sexual precocity, are the dominating features


Morphology

  • Most are benign tumors

  • Form circumscribed nodules <5 cm in size

  • Have golden-brown, homogeneous cut surface

Histologically:

  • Tumorous Leydig cells are large and round or polygonal, and they have an abundant granular eosinophilic cytoplasm with a round central nucleus.

  • The cytoplasm frequently contains lipid granules, vacuoles, or lipofuscin pigment, but, most characteristically, rod-shaped crystalloids of Reinke occur in about 25% of the tumors


Leydig (Interstitial) Cell Tumors

  • Sheets of large polygonal cells with round nuclei, single prominent nucleolus and abundant eosinophilic cytoplasm

Leydig (Interstitial) Cell Tumors

  • Several plump rod-shaped intracytoplasmic crystals of Reinke can be seen in the center of the photomicrograph.

Leydig (Interstitial) Cell Tumors

  • The smear was alcohol-fixed and stained with H&E. Several intact and fragmented Reinke’s crystalloids can be seen

Sertoli Cell Tumors (Androblastoma)

  • Tumors of Sex Cord - Gonadal Stroma

  • Composed entirely of Sertoli cells or may have a component of granulosa cells

  • Some induce endocrinologic changes

  • Estrogens or androgens may be elaborated

  • Only infrequently in sufficient quantity to cause precocious masculinization or feminization.

  • As with Leydig cell tumors - gynecomastia may appear


Sertoli Cell Tumors (Androblastoma) - Morphology

  • Appear as firm, small nodules with a homogeneous gray-white to yellow cut surface.

Histologically:

  • Tumor cells arranged in distinctive trabeculae

  • Tendency to form cord-like structures resembling immature seminiferous tubules

  • Majority of Sertoli cell tumors are benign



Testicular Lymphoma

  • Lymphomas account for 5% of testicular neoplasms

  • Most common form of testicular cancer in men over the age of 60.

  • In most cases, disseminated disease is already present at the time of detection of the testicular mass

  • Only rarely does it remain confined to the testis

  • Histologic type in almost all cases is the diffuse large cell lymphoma

  • The prognosis is extremely poor.

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