Block 15 Step Pathology Prt 2

SEMINOMA make up to 30%-40% of testicular tumors and is the most common type of germ cell tumors. The seminomas are divided into 2 major categories; classical, and spermatocytic seminomas. The classic seminomas are of moderate size, solid, homogenous, light yellow, and may contain sharply circumscribed zones of necrosis. Areas of cystic change or hemorrhage are usually not seen. Microscopically, the individual tumor cells are uniformly large, round to polyhedral cells. There is a distinct cell membrane with abundantly clear cytoplasm and large central nucleus with one or two prominent nucleoli. The tumor cells are characteristically arranged in nests outlined by fibrous bands and these bands are infiltrated by lymphocytes and plasma cells.
SPERMATOCYTIC SEMINOMAS occur in the elderly age group over 65 years of age. They have a soft gelatinous appearance. Microscopically, they are composed of cells with perfectly round nuclei and prominent variation in size. Bizarre giant forms are common, together with small cells with a lymphocyte -like appearance. Mitoses are numerous. Areas of lymphocytic infiltration are absent. Ultrastructurally, the cells show clear-cut evidence of spermatocytic differentiation. The prognosis is excellent.
YOLK-SAC TUMOR also called an endodermal sinus tumor and is the most common testicular tumor in infants and children up to 3 years of age. It has a very good prognosis. In adults, the pure form is rare, but yolk sac elements occur in combination with embryonal carcinoma. Grossly, the tumor is non-encapsulated. The cut surface is homogenous, yellow-white, and mucinous in appearance. Microscopically, it consists of a lace like network of medium sized cuboidal or elongated cells. In addition, papillary structures or solid cords of cells may be found. Yolk sac elements are recognized by the intermingling of epithelial and mesenchymal elements in characteristic organoid formation. A mesodermal core with a central capillary and a visceral and parietal layer of cells resembling primitive glomeruli, known as Schiller-Duval bodies, are generally present. Also present within and outside the cytoplasm are eosinophik hyaline-like globules in which AFP and alpha-1-antitrypsin can be demonstrated by
immunocytochemical staining.
EMBRYONAL CARCINOMA is more aggressive than seminoma and generally occurs In the age group of 20-30 years old. They have a more variegated appearance with poorly demarcated margins and areas of hemorrhage and necrosis. Extensions to epididymis and cord are not infrequent. Microscopically, the cells are arranged in a glandular, alveolar, papillary, or tubular pattern. The individual cells have an epithelial appearance and are large and anaplastic with angry looking hyperchromatic nuclei having prominent nucleoli. The cell borders are indistinct. Mitotic figures are frequent. Giant cells are frequent.
TESTICULAR LYMPHOMAS constitute only 5% of all testicular malignancies, but are the most common testicular tumors in elderly persons over 60 years of age. They are generally bilateral and in most cases dissemination is present at the time of diagnosis. Microscopically, there is predominantly interstitial proliferation of malignant cells ,which surrounds and infiltrates the seminiferous tubules. Most are diffuse large cell lymphomas and carry a poor prognosis.

LEYDIG CELL TUMORS comprise between 1% and 3% of all testicular tumors and about 3% are bilateral. Most occur in adults with a palpable testicular mass. They may produce endocrine changes because of increased production of androgens and/or estrogens. Gynecomastia is the most common symptom. In children, it manifests as sexual precocity. Grossly, they are circumscribed nodules less than 5cm In diameter with a cut surface showing a distinct golden brown homogenous appearance. Microscopically, the tumor cells are large to polygonal with round to oval nucleus and deeply acidophilic abundantly granular cytoplasm. The cell boundaries are often Indistinct. The cytoplasm shows lipochromic pigment and rod shaped crystalloids of Reinke. Most are benign, but 10% are invasive and metastasize.
SERTOLI CELL TUMORS occur in all age groups and present with gynecomastia in 1/3 of all cases. Grossly, the tumors are well-circumscribed, white or yellow, and firm, with focal cystic areas. Microscopically, the diagnostic feature is the presence of tubular formations lined by elongated cells having the appearance of Sertoli cells. In other areas, the tumor is solid and can be confused with seminomas. Most are benign with 10% pursuing a malignant course.
SEMINOMAS make up to 30%-40% of testicular tumors and are the most common type of germ cell tumors. The seminomas are divided into 2 major categories: classical and spermatocytic seminomas. The classic seminomas are of moderate size, solid, homogenous, light yellow, and may contain sharply circumscribed zones of necrosis. Areas of cystic change or hemorrhage are usually not seen. Microscopically, the individual tumor cells are uniform, large, round to polyhedral cells. There is a distinct cell membrane with abundantly clear cytoplasm and large central nucleus with 1 or 2 prominent nucleoli. The tumor cells are characteristically arranged In nests outlined by fibrous bands and these bands are infiltrated by lymphocytes and plasma cells.
TERATOCARCINOMA is composed of a mixture of adult teratoma and embryonal carcinoma. Its gross appearance depends on the relative amount of these 2 components: multicystic in areas of adult teratoma, and solid with hemorrhagic and necrotic foci in the areas of embryonal carcinoma. The appearance of teratomatous foci ranges from mature to immature.
MATURE TERATOMAS constitute 5% to 10% of all the testicular tumors. It is predominantly cystic and multiloculated. Foci of cartilage are usually evident, but the presence of bone is infrequent. Microscopically, all types of tissues may be seen, with the most common being nerve, cartilage, and various types of epithelium. To diagnose adult teratoma, all the tissues that are present should be well differentiated or mature.
Immature teratomas show some areas of tissue immaturity, which may be in the stroma, the epithelial, or in the neural component. This may range from a slight hypercellularity of the stroma around the glandular component to large foci of primitive glands or neuroepithelium.

Most endonnetnal polyps are represented as benign endonnetrial hyperplastic processes. Endonnetrial polyps occur most frequently in perimenobausal women, when the ovary is characterized by unopposed estrogen production. The most common presenting symptom is abnormal bleeding.
If the polyps are large, then surgical removal is necessary in order to reduce the amount of bleeding. Less than 5% of postmenopausal women are likely to be associated with endometrial carcinoma.

This woman is suffering from Stein-Leventhal syndrome (polycystic ovary syndrome). Her ovaries are enlarged because they contain many atretic follicles. They also have stromal hyperplasia. These numerous ovarian cysts are due to increased LH production. LH binds to cells of the theca interna, stimulating them to grow, then synthesize and secrete testosterone, the substrate for the follicular aromatase. The testosterone is then metabolized into estrogens In the peripheral tissues. These estrogens suppress FSH secretion and stimulate LH secretion. Inhibition of FSH production leads to lower amounts of aromatase production by granulosa cells and thus abnormally low amounts of estradiol. The increased LH leads to hypertrophy of follicles and excessive androgen secretion. Because of the lack of aromatase, the androgens are not converted to estrogens but instead cause abnormal hirsutism. These women as often exhibit endometrial hyperplasia and are at increased risk for endometrial carcinoma.

LEYDIG CELL TUMORS comprise between 1% and 3% of all testicular tumors and about 3% are bilateral. Most occur in adults with a palpable testicular mass. They may produce endocrine changes because of increased production of androgens and/or estrogens. Gynecomastia is the most common symptom. In children, it manifests as sexual precocity. Grossly, they are circumscribed nodules less than 5cm In diameter with a cut surface showing a distinct golden brown homogenous appearance. Microscopically, the tumor cells are large to polygonal with round to oval nucleus and deeply acidophilic abundantly granular cytoplasm. The cell boundaries are often Indistinct. The cytoplasm shows lipochromic pigment and rod shaped crystalloids of Reinke. Most are benign, but 10% are invasive and metastasize.
SERTOLI CELL TUMORS occur in all age groups and present with gynecomastia in 1/3 of all cases. Grossly, the tumors are well-circumscribed, white or yellow, and firm, with focal cystic areas. Microscopically, the diagnostic feature is the presence of tubular formations lined by elongated cells having the appearance of Sertoli cells. In other areas, the tumor is solid and can be confused with seminomas. Most are benign with 10% pursuing a malignant course.
SEMINOMAS make up to 30%-40% of testicular tumors and are the most common type of germ cell tumors. The seminomas are divided into 2 major categories: classical and spermatocytic seminomas. The classic seminomas are of moderate size, solid, homogenous, light yellow, and may contain sharply circumscribed zones of necrosis. Areas of cystic change or hemorrhage are usually not seen. Microscopically, the individual tumor cells are uniform, large, round to polyhedral cells. There is a distinct cell membrane with abundantly clear cytoplasm and large central nucleus with 1 or 2 prominent nucleoli. The tumor cells are characteristically arranged In nests outlined by fibrous bands and these bands are infiltrated by lymphocytes and plasma cells.
TERATOCARCINOMA is composed of a mixture of adult teratoma and embryonal carcinoma. Its gross appearance depends on the relative amount of these 2 components: multicystic in areas of adult teratoma, and solid with hemorrhagic and necrotic foci in the areas of embryonal carcinoma. The appearance of teratomatous foci ranges from mature to immature.
MATURE TERATOMAS constitute 5% to 10% of all the testicular tumors. It is predominantly cystic and multiloculated. Foci of cartilage are usually evident, but the presence of bone is infrequent. Microscopically, all types of tissues may be seen, with the most common being nerve, cartilage, and various types of epithelium. To diagnose adult teratoma, all the tissues that are present should be well differentiated or mature.
Immature teratomas show some areas of tissue immaturity, which may be in the stroma, the epithelial, or in the neural component. This may range from a slight hypercellularity of the stroma around the glandular component to large foci of primitive glands or neuroepithelium.

Endometriosis is a presence of endometrial tissue outside the cavity of the uterus. GnRH analogs produce a hypogonadotrophic-hypogonadic state by down-regulation of the pituitary gland. When used continuously for periods of longer than 2 weeks, they stop the production of estrogen. This deprives the endometrial implants of estrogen, causing them to become inactive and degenerate. The return of ovulation and menstruation is very variable, depending on the drug used, way of delivery, and patient hormonal status.
ESTROGEN is the most important known factor that stimulates the growth of endometriosis. Estrogens will therefore worsen the condition of your patient.
MEGLITINIDES are a class of antidiabetic drugs. Therefore, they have no role in treatment of endometriosis. These short-acting secretagogues act on the potassium channels: by closing the potassium channels of the pancreatic beta cells, they open the calcium channels, hence enhancing insulin secretion.
HUMAN CHORIONIC GONADOTROPIN (HCG) is a glycoprotein produced in pregnancy that is made by the
developing embryo after conception and later by the syncytiotrophoblast of the placenta. hCG also plays a role
in cellular differentiation, proliferation, and may activate apoptosis. It is extensively used as an ovulation inducer. In endonnetriosis, the ovulation is present and is painful if endonnetrial tissue has grown on the ovaries. Therefore, hCG is not indicated in endometriosis.
PROSTAGLANDINS are autocrine and paracrine mediators and locally acting messengers involved in the pain mechanism, inflammation, cell growth, thernnoregulation, constriction or dilation in vascular smooth muscle cells, aggregation or disaggregation of platelets, hormone regulation, glomerular filtration, etc. Their presence is increased in painful states, including endonnetriosis. They are not indicated in this patient.

Solid mass with irregular borders are suspect of carcinoma. Stellate projections in an immobile mass greatly increases the probability of malignancy. A biopsy should be performed to confirm the imaging diagnosis.

This patient most probably has an infiltrating ductal carcinoma, which is the most common breast carcinoma in males. A total of 93.7% of male breast cancers are ductal or unclassified carcinomas.
Breast cancer Is relatively rare in males (less than 1% of all breast cancers), but is similar to breast cancer in females when considering etiology, family history, prognosis, and treatment. Nearly 30% of males with breast carcinoma have a positive family history. The etiology of male breast cancer is unclear, but hormonal levels may play a role in the etiology.
It typically presents as a painless retroareolar mass, often eccentric to the nipple. Nipple discharge is uncommon, but when present is suggestive of malignancy. A hard, ill-defined, nontender mass is felt beneath the nipple or areola on examination.
MAMMOGRAPHY alone can diagnose breast carcinoma with reasonable accuracy. Fine-needle aspiration guided by palpation and/or excisional biopsy can be used to confirm a diagnosis of breast carcinoma.
Treatment consists of modified radical mastectomy with axillary lymph node dissection or sentinel node biopsy in most patients. Adjuvant chemotherapy is used to treat male patients who have a considerable risk of recurrence and death from breast cancer. Tamoxifen is primarily used for management of advanced breast cancer in men. Radiation therapy is effective in preventing local recurrences and treating localized metastases in the skin, lymph nodes, or skeleton that are causing symptoms. Breast cancer is more frequently hormone receptor postive in men and hence may be more sensitive to hormonal therapy.
LOBULAR CARCINOMA IN SITU and INFILTRATING LOBULAR CARCINOMA (1.5%) are rare because lobules are typically absent in the male breast, which is primarily composed of fat tissue with a few branching ducts and connective tissue.
PAPILLARY AND MUCINOUS CARCINOMA account for 2.6 and 1.8 % of male breast carcinomas, respectively.

FIBROADENOMA is one of the most common causes of benign lump in the breast. Microscopically, these tumors show loose cellular connective tissue, which surrounds a variable number of ductular structures. The stromal nuclei are spindle shaped and normally exhibit little pleomorphism with infrequent mitosis. The ductules vary In configuration. Two classical patterns are described, intracanalicular when the ductules are compressed by the stroma into clefts, and pencanalicular when the stroma appears to surround ductules in a circumferential pattern. Both the patterns may be seen in the same lesion. However, this has no prognostic significance. PHYLLODES TUMOR derived its name from the Greek word phyllodes, which means leaflike due to their gross leaflike pattern. Based on the histological appearances, phyllodes tumor is classified into benign or malignant. Microscopically, benign phyllodes tumor shows 2 major elements, clefts lined by epithelial cells and an associated cellular stroma. The epithelial element consists of the layers of myoepithelial and secretory epithelial cells. The stroma is cellular consisting of spindle cells. These spindle cells do not exhibit pleomorphism, although an occasional bizarre giant cell may be present. Malignant phyllodes show frank sarcomatous change, hypercellular stroma, nuclear atypia, and increased mitotic count. Metastasis is generally rare and if it does metastasize, it consists of only stromal component. SCLEROSING ADENOSIS is a proliferative lesion arising from the terminal duct lobular unit. It is infrequently found as a microscopic component of fibrocystic change, but more rarely as a mass lesion, which may be palpable. Microscopically, the normal configuration of a group of lobules is distorted by a disorderly proliferation of acini and intra-lobular stromal cells giving a whorled appearance. Compressed microtubular structures may be seen but acinar lumina are frequently obliterated. A two-layered acinar structure is usually visible. Nuclei are small and regular, usually without atypia, and mitosis is frequent. FIBROCYSTIC CHANGE is the term used for a combination of breast changes including cyst formation, apocrine metaplasia, blunt duct adenosis, and various other forms of adenosis. Microscopically, the cysts are lined by a single layer of cuboiclal epithelium or flattened epithelium or metaplastic apocrine epithelium. In apocrine metaplasia, the type of epithelium resembles the epithelium of the apocrine sweat glands with large columnar cells having abundant granular eosinophilic cytoplasm and basally placed nuclei. Blunt duct adenosis is characterized by replacement of the normal luminal epithelial layer by a single layer of tall columnar epithelial cells with basally placed nuclei and cytoplasmic apical snouts in the individual terminal duct lobular unit. The normal rounded acinar configuration is changed to larger, irregular, branching, and blind-ended duct-like structures.

SEMINOMA make up to 30%-40% of testicular tumors and is the most common type of germ cell tumors. The seminomas are divided into 2 major categories; classical, and spermatocytic seminomas. The classic seminomas are of moderate size, solid, homogenous, light yellow, and may contain sharply circumscribed zones of necrosis. Areas of cystic change or hemorrhage are usually not seen. Microscopically, the individual tumor cells are uniformly large, round to polyhedral cells. There is a distinct cell membrane with abundantly clear cytoplasm and large central nucleus with one or two prominent nucleoli. The tumor cells are characteristically arranged in nests outlined by fibrous bands and these bands are infiltrated by lymphocytes and plasma cells.
SPERMATOCYTIC SEMINOMAS occur in the elderly age group over 65 years of age. They have a soft gelatinous appearance. Microscopically, they are composed of cells with perfectly round nuclei and prominent variation in size. Bizarre giant forms are common, together with small cells with a lymphocyte -like appearance. Mitoses are numerous. Areas of lymphocytic infiltration are absent. Ultrastructurally, the cells show clear-cut evidence of spermatocytic differentiation. The prognosis is excellent.
YOLK-SAC TUMOR also called an endodermal sinus tumor and is the most common testicular tumor in infants and children up to 3 years of age. It has a very good prognosis. In adults, the pure form is rare, but yolk sac elements occur in combination with embryonal carcinoma. Grossly, the tumor is non-encapsulated. The cut surface is homogenous, yellow-white, and mucinous in appearance. Microscopically, it consists of a lace like network of medium sized cuboidal or elongated cells. In addition, papillary structures or solid cords of cells may be found. Yolk sac elements are recognized by the intermingling of epithelial and mesenchymal elements in characteristic organoid formation. A mesodermal core with a central capillary and a visceral and parietal layer of cells resembling primitive glomeruli, known as Schiller-Duval bodies, are generally present. Also present within and outside the cytoplasm are eosinophik hyaline-like globules in which AFP and alpha-1-antitrypsin can be demonstrated by
immunocytochemical staining.
EMBRYONAL CARCINOMA is more aggressive than seminoma and generally occurs In the age group of 20-30 years old. They have a more variegated appearance with poorly demarcated margins and areas of hemorrhage and necrosis. Extensions to epididymis and cord are not infrequent. Microscopically, the cells are arranged in a glandular, alveolar, papillary, or tubular pattern. The individual cells have an epithelial appearance and are large and anaplastic with angry looking hyperchromatic nuclei having prominent nucleoli. The cell borders are indistinct. Mitotic figures are frequent. Giant cells are frequent.
TESTICULAR LYMPHOMAS constitute only 5% of all testicular malignancies, but are the most common testicular tumors in elderly persons over 60 years of age. They are generally bilateral and in most cases dissemination is present at the time of diagnosis. Microscopically, there is predominantly interstitial proliferation of malignant cells ,which surrounds and infiltrates the seminiferous tubules. Most are diffuse large cell lymphomas and carry a poor prognosis.

LEYDIG CELL TUMORS comprise between 1% and 3% of all testicular tumors and about 3% are bilateral. Most occur in adults with a palpable testicular mass. They may produce endocrine changes because of increased production of androgens and/or estrogens. Gynecomastia is the most common symptom. In children, it manifests as sexual precocity. Grossly, they are circumscribed nodules less than 5cm In diameter with a cut surface showing a distinct golden brown homogenous appearance. Microscopically, the tumor cells are large to polygonal with round to oval nucleus and deeply acidophilic abundantly granular cytoplasm. The cell boundaries are often Indistinct. The cytoplasm shows lipochromic pigment and rod shaped crystalloids of Reinke. Most are benign, but 10% are invasive and metastasize.
SERTOLI CELL TUMORS occur in all age groups and present with gynecomastia in 1/3 of all cases. Grossly, the tumors are well-circumscribed, white or yellow, and firm, with focal cystic areas. Microscopically, the diagnostic feature is the presence of tubular formations lined by elongated cells having the appearance of Sertoli cells. In other areas, the tumor is solid and can be confused with seminomas. Most are benign with 10% pursuing a malignant course.
SEMINOMAS make up to 30%-40% of testicular tumors and are the most common type of germ cell tumors. The seminomas are divided into 2 major categories: classical and spermatocytic seminomas. The classic seminomas are of moderate size, solid, homogenous, light yellow, and may contain sharply circumscribed zones of necrosis. Areas of cystic change or hemorrhage are usually not seen. Microscopically, the individual tumor cells are uniform, large, round to polyhedral cells. There is a distinct cell membrane with abundantly clear cytoplasm and large central nucleus with 1 or 2 prominent nucleoli. The tumor cells are characteristically arranged In nests outlined by fibrous bands and these bands are infiltrated by lymphocytes and plasma cells.
TERATOCARCINOMA is composed of a mixture of adult teratoma and embryonal carcinoma. Its gross appearance depends on the relative amount of these 2 components: multicystic in areas of adult teratoma, and solid with hemorrhagic and necrotic foci in the areas of embryonal carcinoma. The appearance of teratomatous foci ranges from mature to immature.
MATURE TERATOMAS constitute 5% to 10% of all the testicular tumors. It is predominantly cystic and multiloculated. Foci of cartilage are usually evident, but the presence of bone is infrequent. Microscopically, all types of tissues may be seen, with the most common being nerve, cartilage, and various types of epithelium. To diagnose adult teratoma, all the tissues that are present should be well differentiated or mature.
Immature teratomas show some areas of tissue immaturity, which may be in the stroma, the epithelial, or in the neural component. This may range from a slight hypercellularity of the stroma around the glandular component to large foci of primitive glands or neuroepithelium.

SEMINOMA is the least malignant germinal neoplasm of the testes, and its pure form constitutes about 40 percent of such tumors. Grossly, the affected testis is partly or completely replaced by a firm, resilient, gray or tan mass with a glistening, bulging cut surface. Foci of necrosis are common. Microscopically, the seminoma consists of sheets of polyhedral cells which uniformly measure about 201.lm in diameter. Fibrous trabeculae lobulate the neoplasm, and the fibrous stroma is typically infiltrated with lymphocytes. Metastases are most commonly to the periaortic and iliac lymph nodes, liver, and lungs. The 5-year survival rate is about 90 percent. Seminomas are highly sensitive to radiation.

LIGAMENTS OF COOPER are hollow conical projections of fibrous tissue, the apices of which are tethered to the superficial fascia. It is at these points that the pits appear.
LYMPHATIC VESSELS would not produce dimpling of the skin.
BREAST LOBULES do not open onto the skin directly. They empty via ductules into a lactiferous duct.
SUBCUTANEOUS FIBROSIS gives a firm feeiing with broad retraction of the skin.
Openings of sebaceous glands do not appear as pits.

FIBROADENOMA is one of the most common causes of benign lump in the breast. Microscopically, these tumors show loose cellular connective tissue, which surrounds a variable number of ductular structures. The stromal nuclei are spindle shaped and normally exhibit little pleomorphism with infrequent mitosis. The ductules vary In configuration. Two classical patterns are described, intracanalicular when the ductules are compressed by the stroma into clefts, and pencanalicular when the stroma appears to surround ductules in a circumferential pattern. Both the patterns may be seen in the same lesion. However, this has no prognostic significance. PHYLLODES TUMOR derived its name from the Greek word phyllodes, which means leaflike due to their gross leaflike pattern. Based on the histological appearances, phyllodes tumor is classified into benign or malignant. Microscopically, benign phyllodes tumor shows 2 major elements, clefts lined by epithelial cells and an associated cellular stroma. The epithelial element consists of the layers of myoepithelial and secretory epithelial cells. The stroma is cellular consisting of spindle cells. These spindle cells do not exhibit pleomorphism, although an occasional bizarre giant cell may be present. Malignant phyllodes show frank sarcomatous change, hypercellular stroma, nuclear atypia, and increased mitotic count. Metastasis is generally rare and if it does metastasize, it consists of only stromal component. SCLEROSING ADENOSIS is a proliferative lesion arising from the terminal duct lobular unit. It is infrequently found as a microscopic component of fibrocystic change, but more rarely as a mass lesion, which may be palpable. Microscopically, the normal configuration of a group of lobules is distorted by a disorderly proliferation of acini and intra-lobular stromal cells giving a whorled appearance. Compressed microtubular structures may be seen but acinar lumina are frequently obliterated. A two-layered acinar structure is usually visible. Nuclei are small and regular, usually without atypia, and mitosis is frequent. FIBROCYSTIC CHANGE is the term used for a combination of breast changes including cyst formation, apocrine metaplasia, blunt duct adenosis, and various other forms of adenosis. Microscopically, the cysts are lined by a single layer of cuboiclal epithelium or flattened epithelium or metaplastic apocrine epithelium. In apocrine metaplasia, the type of epithelium resembles the epithelium of the apocrine sweat glands with large columnar cells having abundant granular eosinophilic cytoplasm and basally placed nuclei. Blunt duct adenosis is characterized by replacement of the normal luminal epithelial layer by a single layer of tall columnar epithelial cells with basally placed nuclei and cytoplasmic apical snouts in the individual terminal duct lobular unit. The normal rounded acinar configuration is changed to larger, irregular, branching, and blind-ended duct-like structures.

The only dimorphic fungal infection that is endemic in the specified regions listed and producing large spherule forms containing endospores in infected tissues is Coccidioidomycosis. The disease is caused by Coccidioides spp of soil molds.
Cell-mediated immune response of the host to the fungal antigens is of critical importance in resistance to the infection.
Other choices are not associated with pathogenesis of coccidioidomycosis.
Main mode of entry of the fungal spores into the host is by inhalation. Entry through inoculation is very rare and usually associated with accidental infections in the laboratory. Most common lesions produced are pulmonary. After primary infection, about 60% of individuals remain asymptomatic. Coccidioides spp does not possess capsule.
Virulence factors of Coccidioides spp include the spherule outer wall glycoprotein (SOWgp) which helps the survival of the fungus in the host as well as boosting urease production that contributes to host tissue damage.
Studies based on molecular markers have recognized 2 species as causative agents of human coccidioidomycosis: Coccidioides immitis mainly from Central California and C.posadasil mostly responsible for infections in South Arizona. These species are phenotypically indistinguishable.
Primary infection occurs mainly by inhalation of airborne arthrospores of the fungus from soil sites. After entering the host tissues, each arthrospore develops into a multi-nucleated spherule. The spherule grows and divides internally producing uninucleated endospores. The mature thick-walled spherule measures 60-100 microns and endospores are 2-5 microns in size. Endospores are liberated by rupture of mature spherules and in the tissue; each endospore further develops into a spherule. The spherules and endospores are seen within the granulomatous lesions of coccidioidonnycosis.
Within 2-4 weeks after primary infection, humoral and cell-mediated immune responses develop in the host. Both IgM and IgG antibodies are produced by infection, but neither is protective. Persons in whom primary infection is asymptomatic develop a positive skin test indicating cell-mediated immune response and with rare exceptions develop life-long immunity.
In clinical forms of the disease, CMI to the fungal antigens is associated with good prognosis, whereas high titer of specific IgG antibody is associated with poor prognosis. In most persons, a positive delayed hypersensitivity skin test elicited by either coccidioidin or spherulin signifies strong CMI. CMI gives protection against re-infection and reactivation of the infection.
During primary infection, only 40% are found to develop symptomatic disease. Symptoms develop within 7-21 days after primary exposure.
Early manifestations (Valley fever) can be variable ranging from mild influenza-like illness to self-limited or severe pneumonia. Hypersensitivity reactions with cutaneous, ocular or joint involvement and complications like chronic progressive pneumonia or pulmonary cavitary disease can develop. Residual pulmonary nodules may occur.
When CMI is inadequate to contain the pulmonary foci of infection, dissemination occurs. AIDS patients, women in third trimester of pregnancy, and those under immunosuppression are at risk of developing life-threatening disseminated infections. Host genetic and ethnic factors are also thought to be of importance in the severity and dissemination of coccidioides infection.
Case clusters due to exposure of a group of susceptible individuals to wind-borne
dust in endemic areas, travel-associated infections, and outbreaks among military personnel have been reported. Both Coccidioides species are considered by the federal government to be select agents of bioterrorism.
There is ongoing research for development of an effective vaccine against coccidioidomycosis by investigators of the
Valley Fever Vaccine Project (VFVP) in California

SEMINOMA make up to 30%-40% of testicular tumors and is the most common type of germ cell tumors. The seminomas are divided into 2 major categories; classical, and spermatocytic seminomas. The classic seminomas are of moderate size, solid, homogenous, light yellow, and may contain sharply circumscribed zones of necrosis. Areas of cystic change or hemorrhage are usually not seen. Microscopically, the individual tumor cells are uniformly large, round to polyhedral cells. There is a distinct cell membrane with abundantly clear cytoplasm and large central nucleus with one or two prominent nucleoli. The tumor cells are characteristically arranged in nests outlined by fibrous bands and these bands are infiltrated by lymphocytes and plasma cells.
SPERMATOCYTIC SEMINOMAS occur in the elderly age group over 65 years of age. They have a soft gelatinous appearance. Microscopically, they are composed of cells with perfectly round nuclei and prominent variation in size. Bizarre giant forms are common, together with small cells with a lymphocyte -like appearance. Mitoses are numerous. Areas of lymphocytic infiltration are absent. Ultrastructurally, the cells show clear-cut evidence of spermatocytic differentiation. The prognosis is excellent.
YOLK-SAC TUMOR also called an endodermal sinus tumor and is the most common testicular tumor in infants and children up to 3 years of age. It has a very good prognosis. In adults, the pure form is rare, but yolk sac elements occur in combination with embryonal carcinoma. Grossly, the tumor is non-encapsulated. The cut surface is homogenous, yellow-white, and mucinous in appearance. Microscopically, it consists of a lace like network of medium sized cuboidal or elongated cells. In addition, papillary structures or solid cords of cells may be found. Yolk sac elements are recognized by the intermingling of epithelial and mesenchymal elements in characteristic organoid formation. A mesodermal core with a central capillary and a visceral and parietal layer of cells resembling primitive glomeruli, known as Schiller-Duval bodies, are generally present. Also present within and outside the cytoplasm are eosinophik hyaline-like globules in which AFP and alpha-1-antitrypsin can be demonstrated by
immunocytochemical staining.
EMBRYONAL CARCINOMA is more aggressive than seminoma and generally occurs In the age group of 20-30 years old. They have a more variegated appearance with poorly demarcated margins and areas of hemorrhage and necrosis. Extensions to epididymis and cord are not infrequent. Microscopically, the cells are arranged in a glandular, alveolar, papillary, or tubular pattern. The individual cells have an epithelial appearance and are large and anaplastic with angry looking hyperchromatic nuclei having prominent nucleoli. The cell borders are indistinct. Mitotic figures are frequent. Giant cells are frequent.
TESTICULAR LYMPHOMAS constitute only 5% of all testicular malignancies, but are the most common testicular tumors in elderly persons over 60 years of age. They are generally bilateral and in most cases dissemination is present at the time of diagnosis. Microscopically, there is predominantly interstitial proliferation of malignant cells ,which surrounds and infiltrates the seminiferous tubules. Most are diffuse large cell lymphomas and carry a poor prognosis.