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Male Genital System and Lower Urinary Tract (STDs (Nongonococcal…

- - - - in contrast to most cancers: Bone metastases, particularly to axial skeleton
      - tumor marker: PSA
        
        serum PSA level of 4 ng/mL is cutoff between normal and abnormal [although some guidelines designate values above 2.5 ng/mL as abnormal]; if above 4--> biopsy to see if cancer or nodular hyperplasia
        
        percentage of free PSA (the ratio of free PSA to total PSA) is lower in men w/ prostate cancer than in men w/ benign prostatic diseases (over 25%: less risk of cancer)
    - - histologic
        
        [most lesions: moderately differentiated adenocarcinomas that produce well-defined glands]
        malignant glands differences w/ benign ones: typically smaller + lined by a single uniform layer of cuboidal or low columnar epithelium, lacking basal cell layer, crowded together and characteristically lack branching and papillary infolding.
        
        cytoplasm of tumor cells ranges from pale-clear (as in benign glands) to a distinctive amphophilic (dark purple) appearance. Nuclei enlarged and often contain one or more prominent nucleoli
      - Gleason system
        
        5 grades on basis of glandular patterns of differentiation
        
        infiltrative ، با اندازه متفاوت، هنوز نمیتوانیم غدد را مشخص کنیم.
        
        fuse gland غدد به هم میچسبند و حالت غربالی پیدا میکنند.
        
        اندازه غدد کمی متفاوت و حدودش به اندازه مورد یک دقیق نیست.
        
        غدد را نمیبینیم یا وسطشان نکروز وسیع وجود دارد
        
        تومور دارای حدود مشخص و بدون ترشح.
        
        Since most tumors contain >one pattern, a primary grade is assigned to the dominant pattern and a secondary grade to the next most frequent pattern--> two grades added to obtain a combined Gleason score. Tumors w/ only one pattern are treated as if their primary and secondary grades are the same, and, hence, number is doubled. Thus the most differentiated tumors have a Gleason score of 2 (1 + 1) and the least differentiated tumors merit a score of 10 (5 + 5); Typical Gleason Scores range from 6-10
        
        7--> intermediate risk for aggressive cancer.
        
        >=8--> likely to spread more rapidly, these cancers are often referred to as poorly differentiated or high grade.
        
        =<6--> cancer cells look similar to normal cells and suggest that cancer is likely to grow slowly
      - gross: Most detected clinically not visible grossly. More advanced lesions appear as firm, gray-white lesions w/ ill-defined margins that infiltrate adj gland
- - - - males, gonorrhea is manifested by the presence of dysuria, urinary frequency, and a mucopurulent urethral exudate; Untreated infections may ascend to involve the prostate, seminal vesicles, epididymis, and testis
      - female: may be asymptomatic or associated with dysuria, lower pelvic pain, and vaginal discharge. Untreated cases may be complicated by ascending infection, leading to acute inflammation of the fallopian tubes (salpingitis) and ovaries. Scarring of the fallopian tubes--> resultant infertility and an increased risk of ectopic pregnancy.
      - Gonococcal infection may be transmitted to infants during
        passage through the birth canal. The affected neonate may develop purulent infection of the eyes
  - - - gross:irregular ulcer, painful; shaggy, yellow-gray exudate regional lymph nodes, particularly in the inguinal region, become enlarged --> erode overlying skin to produce chronic, draining ulcers
      - superficial zone of neutrophilic debris and fibrin, with an underlying zone of granulation tissue containing areas of necrosis and thrombosed vessels. A dense, lymphoplasmacytic inflammatory infiltrate is present beneath the layer of granulation tissue
  - - - raised, papular lesion--> ulceration--> abundant granulation tissue; Regional lymph nodes typically are spared or show only nonspecific reactive changes, in contrast with chancroid
      - epithelial hyperplasia at borders of ulcer, sometimes mimicking carcinoma (pseudoepitheliomatous hyperplasia)
        mixture of neutrophils and mononuclear inflammatory cells is present at base of the ulcer and beneath the surrounding epithelium.
        organisms demonstrable in Giemsa-stained smears of the exudate as minute coccobacilli within vacuoles in macrophages (Donovan bodies). Silver stains (e.g., the Warthin-Starry stain) also may be used
  - - - Tertiary (late latent): u. after a latent period of 5 years or more. Complications:
        
        cardiovascular syphilis: syphilitic aortitis and accounts for more than 80% of cases of tertiary disease; it is much more common in men than in women
        
        neurosyphilis: 10% of cases of tertiary syphilis overall but occurs at increased frequency in those with concomitant HIV infection
        
        benign tertiary syphilis: an uncommon form marked by the development of gummas in various sites
      - Secondary: generalized lymph node enlargement and a variety of mucocutaneous lesions. Skin lesions u. symmetrically distributed and may be maculopapular, scaly, or pustular; In moist skin areas, (anogenital region, inner thighs, and axillae) broad-based, elevated lesions termed condylomata lata may appear (not to be confused with condyloma acuminata caused by HPV; mucocutaneous lesions of
        secondary syphilis resolve over several weeks, at which point the disease enters its early latent phase, which lasts approximately 1 year. Lesions may recur at any time during this latent period, and these lesions are also highly infectious.
      - Primary : “hard chancre,” to distinguish it from “soft chancre” of chancroid caused by Haemophilus ducreyi; chancre begins as a small, firm papule, which gradually enlarges to produce a painless ulcer with well-defined, indurated margins and a “clean,” moist base; Regional lymph nodes often are slightly enlarged; Even w/o therapy, primary chancre resolves over a period of several weeks to form a subtle scar
      - Congenital
        
        stillborn: hepatomegaly, bone abnormalities, pancreatic fibrosis, and pneumonitis. The liver often shows extramedullary hematopoiesis and portal tract inflammation.
        
        Infantile: liveborn infants that is clinically manifest at birth or within the first few months of life; chronic rhinitis (snuffles) and mucocutaneous lesions similar to those seen in secondary syphilis in adults. Visceral and skeletal changes resembling those seen in stillborn infants also may be present
        
        Late, or tardive: untreated congenital syphilis of more than 2 years’ duration. Classic manifestations include the Hutchinson triad: notched central incisors, interstitial keratitis with blindness, and deafness from eighth cranial nerve injury. Other: so-called saber shin deformity caused by chronic inflammation of the periosteum of the tibia, deformed molar teeth (“mulberry molars”), chronic meningitis, chorioretinitis, and gummas of the nasal bone and cartilage with a resultant “saddlenose” deformity
      - Serologic Tests for Syphilis
        
        Nontreponemal: screening; measure antibody to cardiolipin, an antigen that is present in both host tissues and the treponemal cell wall; rapid plasma reagin (RPR) and Venereal Disease Research Laboratory (VDRL) tests. Nontreponemal antibody tests are usually positive by 4 to 6 weeks of infection
        
        treponemal
- - - - morpho
        
        Microscopic evidence of tubular atrophy evident by age of 5 to 6 years, and hyalinization present by time of puberty.
        
        Foci of intratubular germ cell neoplasia may be present in cryptorchid testes and likely precursors of subsequent germ cell tumors.
        
        Atrophic changes similar to those in cryptorchid testes may be caused by several other insults: chronic ischemia, trauma, irradiation, and antineoplastic chemotherapy, as well as conditions associated with chronically elevated estrogen levels (e.g., cirrhosis). Intratubular germ cell neoplasia is not a feature of these conditions, however
      - patho: majority: cause unknown
      - clinical course
        
        undescended testes--> atrophic, bilateral cryptorchidism--> sterility; even unilateral may be a. w/ atrophy of contralateral descended gonad--> sterility!
        
        3-5x incr risk of testicular cancer; unilateral also at increased risk for development of cancer in contralateral, normally descended testis,
        
        Surgical placement of undescended testis into scrotum (orchiopexy) before puberty (jozveh: 18 mahegi) reduces but does not eliminate the risk of cancer and infertility
      - definition: failure of testicular descent into scrotum. (norm: testes descend from abdominal cavity into pelvis by third month of gestation and then through inguinal canals into scrotum during last 2 months of intrauterine life)
        diagnosis: only established with certainty after age of 1 year, particularly in premature infants (bc testicular descent into scrotum not always complete at birth)
        affects 1% of male population; bilateral in 10% of affected
  - - - Embryonal carcinomas
        
        gross: ill-defined, invasive masses containing foci of hemorrhage + necrosis; primary lesions may be small, even in patients w/ systemic metastases.
        
        micro: cells large and primitive looking, w/ basophilic cytoplasm, indistinct cell borders, and large nuclei with prominent nucleoli
        
        In most cases: mixed; Pure embryonal carcinomas: only 2% to 3% of all testicular germ cell tumor
      - Yolk sac tumors
        
        most common primary testicular neoplasm in children < 3 yrs; in this age group it has a very good prognosis. In adults, most often seen mixed w/ embryonal carcinoma.
        
        gross: large and may be well demarcated.
        
        micro: low cuboidal to columnar epithelial cells forming microcysts, lacelike (reticular) patterns, sheets, glands, and papillae; A distinctive feature: structures resembling primitive glomeruli (Schiller-Duvall bodies).
        
        often have eosinophilic hyaline globules in which α1 -antitrypsin + AFP can be demonstrated by immunohistochemical techniques. AFP can also be detected in serum
      - spermatocytic seminoma
        
        uncommon tumor; occurs in much older individuals than other testicular tumors (>65 yrs)
        
        In contrast w/ classic seminomas: lack lymphocytic infiltrates, granulomas, and syncytiotrophoblasts; not admixed w/ other germ cell tumor histologies; not a. w/ intratubular germ cell neoplasia; and do not metastasize.
        
        tumor u. comprises polygonal cells of variable size
      - Choriocarcinomas
        
        pluripotential neoplastic germ cells differentiate along trophoblastic lines.
        
        Gross: primary tumors often small, nonpalpable lesions, even those with extensive systemic metastases.
        
        Micro: [composed of sheets of small cuboidal cells irregularly intermingled with or capped by] large, eosinophilic syncytial cells containing multiple dark, pleomorphic nuclei; these represent cytotrophoblastic and syncytiotrophoblastic differentiation, respectively
        
        HCG within syncytiotrophoblasts can be identified by immunohistochemical staining + elevated in the serum
      - Seminomas
        
        gross: soft, well-demarcated, gray-white tumors that bulge from cut surface of affected testis
        
        micro
        
        large, uniform cells w/ distinct cell borders, clear, glycogen-rich cytoplasm, and round nuclei with conspicuous nucleoli
        
        cells often arrayed in small lobules w/ intervening fibrous septa
        
        lymphocytic infiltrate u. present
        
        may also be accompanied by an ill-defined granulomatous reaction.
        
        15% of cases: syncytiotrophoblasts present--> minimally elevated serum hCG (presence has no bearing on prognosis)
      - Teratomas
        
        neoplastic germ cells differentiate along somatic cell lines.
        
        may occur at any age from infancy to adult life. Pure forms fairly common in infants and children; In adults, pure teratomas rare; prepubertal: teratomas typically benign, whereas in postpubertal males are malignant, being capable of metastasis regardless of whether they are composed of mature or immature elements.
        
        gross: firm masses that on cut surface often contain cysts and recognizable areas of cartilage
      - Dermoid + epidermoid cysts, common in ovary, rare in testis;
      - Rarely, non–germ cell tumors may arise in teratoma: “teratoma with malignant transformation.”
        may take form of a focus of squamous cell carcinoma, mucin-secreting adenocarcinoma, or sarcoma.
        importance : when non–germ cell component spreads outside of testis--> does not respond to chemotherapy
    - - Seminomas and nonseminomatous tumors differ
        
        Seminomas: often remain confined to testis for long intervals and may reach considerable size before diagnosis. Metastases most commonly encountered in iliac and paraaortic lymph nodes
        
        nonseminomatous: tend to metastasize earlier, by lymphatic as well as hematogenous routes.
      - tumor markers helpful diagnostically + following response to therapy
        
        hCG: always elevated in choriocarcinoma and, as noted, can be minimally elevated in persons with other germ cell tumors containing syncytiotrophoblastic cells without cytotrophoblasts.
        
        AFP incr in setting of a testicular neoplasm: a yolk sac tumor component.
        
        levels of LDH: correlate with the tumor burden.
      - present most frequently w/ a painless testicular mass that (unlike enlargements caused by hydroceles) is non-translucent; Biopsy not allowed--> standard management of a solid testicular mass is radical orchiectomy
      - treatment
        
        seminoma: extremely radiosensitive and tends to remain localized for long periods, has best prognosis
        
        nonseminomatous: chemo + radiotherapy
    - - RFs:
        
        more common in whites than in blacks
        
        Intersex syndromes (androgen insensitivity syndrome and gonadal dysgenesis)
        
        Family hx important (first degree relatives have an 8-10x increased risk)
        
        An isochromosome of short arm of chromosome 12, i(12p), found in virtually all histologic types
        
        [Most testicular tumors in postpubertal males arise from
        the in situ lesion] intratubular germ cell neoplasia [present in conditions associated with a high risk of developing germ cell tumors (e.g., cryptorchidism, dysgenetic gonads)]
      - 6 per 100,000 males; a heterogeneous group of neoplasms that include
        
        germ cell tumors: In postpubertal males, 95% of testicular tumors arise from germ cells, and all are malignant (REMAINDER OF DISCUSSION ABOUT GERM CELL TUMORS)
        
        seminomas: account for 50% of testicular germ cell neoplasms; most common; histologically identical to ovarian dysgerminomas and to germinomas occurring in CNS + other extragonadal sites
        
        nonseminomatous
        
        sex cord– stromal tumors (derived from Sertoli or Leydig cells): uncommon and u.benign
- - - - gross: solitary plaque on shaft of penis.
      - micro: morphologically malignant cells throughout the epidermis with no invasion of the underlying stroma; gives rise to infiltrating squamous cell carcinoma in 10% of patients