Pathology Notes

Testicular inflammation and injury   Updated: 01/28/2021 © Jun Wang, MD, PhD Infectious epididymitis and orchitis Sexually active men < 35 years of age: Commonly Chlamydia trachomatis and Neisseria gonorrhoeae > 35 years:   E. coli and Pseudomonas Gonorrhea : Extends from posterior urethra if untreated Mumps : 20 to 30% of postpubertal males one week after parotiditis, commonly unilateral, may cause infertility Tuberculosis : Begins in epididymis and spreads to testis Syphilis : Arises in testis before epididymis Granulomatous orchitis Rare Likely autoimmune process Tender testicular mass with sudden onset Need microbiology studies to rule out infection (AFB, fungal) Torsion May cause testicular infarct Usually occurs in first year of life May be caused by trauma or violent movement Associated with incomplete testicular descent, absent scrotal ligaments, absent gubernaculum testis or testicular atrophy causing testis to be abnormally mobile Treat

Testicle yolk sac tumor   Updated: 01/26/2021 © Jun Wang, MD, PhD General features Also called endodermal sinus tumor of Teilum Most common testicular tumor age 3 or less, often pure Adults: usually part of a mixed tumor, has prognosis of embryonal carcinoma May arise from seminoma Pathological findings Morphology same as ovarian yolk sac tumor Hemorrhage and necrosis Schiller-Duval body : central blood vessel enveloped by germ cells within a space similarly lined by germ cells, resembles glomerulus Marker Elevated serum AFP Positive: AFP , cytokeratin , variable PLAP Negative: hCG Management Orchiectomy with or without retroperitoneal lymph node dissection, chemo if with metastasis Good prognosis if < 3 years old Back to testicle tumors Back to pathology of male reproductive system Back to contents

Testicle teratoma   Updated: 01/28/2021 © Jun Wang,MD, PhD General features Tumors contain cellular components derived from 2 or 3 germ layers Second most common testicular tumor after yolk sac in children Most likely malignant if in adults More commonly as a component of mixed tumor Pathological findings Same microscopic morphology as ovarian teratoma Various differentiation, may have bone, cartilage , tooth or skin Management Orchiectomy Retroperitoneal lymph node dissection if positive for mets Chemotherapy Back to testicle tumors Back to pathology of male reproductive system Back to contents

Testicle sex cord-stromal tumor   Updated: 01/28/2021 © Jun Wang, MD, PhD Leydig cell tumor Most common sex cord stromal tumor Usually unilateral May be malignant Produce androgen May present with precocious puberty in children, or gynecomastia due to estrogen production Characteristic Reinke crystals : definitive feature, but present in only 30-40%; intracytoplasmic, nuclear or extracellular No respond to radiation or chemotherapy Treatment: surgery Sertoli cell tumor Rare Children or middle aged adults May be malignant May occur as part of androgen insensitivity syndrome, Carney’s complex and Peutz-Jegher’s syndrome May cause Feminization and gynecomastia Tumor cells have round to oval nuclei and moderate amount of pale, clear or eosinophilic cytoplasm Treatment: orchiectomy Gonadoblastoma Most before 30 Resembling immature granulosa cells and Sertolicells May be associated with disorders of sexual development, such as complete androgen insensit

Testicle choriocarcinoma   Updated: 01/28/2021 © Jun Wang, MD, PhD General features Most commonly a component of mixed tumor May present initially as metastasis to liver, lung, etc Pathological findings Morphology similar to ovarian or uterine choriocarcinoma Hemorrhage and necrosis Cytotrophoblast and syncytiotrophoblast Marker Elevated serum hCG Positive: hCG , cytokeratin , PLAP Negative: OCT ¾, AFP Management Orchiectomy with or without retroperitoneal lymph node dissection, chemo if with metastasis Back to testicle tumors Back to pathology of male reproductive system Back to contents

Testicle atrophy   Updated: 01/28/2021 © Jun Wang, MD, PhD General features Associated with various conditions, including Klinefelter syndrome, testicular regression syndrome, vasectomy, etc Testicular regression syndrome Possibly due to testicular infarct May be seen in cryptorchidism Testicular tissue replaced by fibrovascular nodule, calcification Rudimentary epididymis and spermatic cord with vas deferens Back to pathology of male reproductive system Back to contents

Spermatocytic tumor   Updated: 07/02/2023 © Jun Wang, MD, PhD General features Used to be called spermatocytic seminoma NOT related to classic seminoma NOT arise from intratubular germ cell neoplasia Most common in older population May occur in younger patients Only in descended testes Usually not part of mixed germ cell tumor Pathological findings Pale gray, mucoid, edematous 3 cell types ,  Small cells: scant eosinophilic cytoplasm, similar to lymphocytes Medium cells: Round nuclei, filamentous chromatin and eosinophilic cytoplasm, similar to spermatocyte Giant cells:One of more nuclei Marker Variable: KIT Negative: PLAP, OCT3/4, hCG, AFP  Management Orchiectomy Favorable prognosis unless presence of sarcomatoid components Back to testicle tumors Back to pathology of male reproductive system Back to contents

Prostatitis   Updated: 01/29/2021 © Jun Wang, MD, PhD General features Various etiology Chronic pelvic pain syndrome (CPPS): including prostatodynia, category III or abacterial prostatitis, is the most common urological diagnosis in men older than 50 years Diagnostic approaches Quantitative bacterial cultures and microscopic examination of fractionated urine specimens and expressed prostatic secretions Acute bacterial prostatitis Commonly due to Gram-negative bacteria Associated with reflux, surgical manipulation or sexually transmitted disease Usually localized, may cause obstruction, retention, abscess  Diagnosis: Symptoms, digital rectal exam for edematous prostate, urine Gram stain and culture Chronic bacterial prostatitis Chronic or recurrent urogenital symtoms Evidence of prostate bacterial infection Diagnosis: symptom, enlarged prostate, prostate fluid culture Chronic prostatitis/Chronic pelvic pain syndrome Pelvic pain or discomfort for

Benign prostatic hyperplasia   Updated: 01/29/2021 © Jun Wang, MD, PhD General features AKA benign prostatic hypertrophy (BPH) Incidence increases with age Considered a normal part of the aging process in men Hormonally dependent on testosterone and dihydrotestosterone production Periurethral (transitional zone) nodules likely compress urethra and cause obstructive symptoms May cause urinary retention, renal insufficiency, recurrent urinary tract infections, gross hematuria, and bladder calculi Pathogenesis Activation of androgen receptor Stromal type II 5-alpha-reductase convert testosterone to dihydrotestosterone (DHT) DHT promotes glandular and stromal hyperplasia Estrogen may increase quantity of androgen receptor Other growth factors Clinical features Due to chronic bladder outlet obstruction Urinary frequency Urinary urgency Hesitancy: Difficulty initiating the urinary stream; interrupted, weak stream Incomplete bladder emptying - The feeling of

Prostatic adenocarcinoma   Updated: 01/29/2021 © Jun Wang, MD, PhD General features Predominantly acinar type, less commonly ductal type Most common non cutaneous cancer in men in the United States Predominantly > 50 More common in North America, Australia and northern and central Europe Risk Factors Genetic factors Ashkenazi Jewish ancestry BRCA1, BRCA2 , Lynch syndrome CHEK, ATM, HOXB13, etc Environmental factors High animal fat diet Cigarette smoking Obesity, etc Hormones and growth factors Androgen Insulin and insulin-like growth factor Protective factors Lycopenes Coffee Soy products Vitamin D, etc   Pathogenesis Hormones, especially androgens and androgen receptor signaling Amplification/overexpression: Most common Mutation: Commonly in castrate-resistant cancers, most are gain-of-function mutation Splice variants: Active AR splice variants (SVs), created by gene splicing or genomic rearrangement Posttranslational modifications: Phosphorylation

Sexually transmitted penile infections   Updated: 04/15/2021 © Jun Wang, MD, PhD Syphilitic chancre Caused by Treponema pallidum Presentation of primary syphilis Usually solitary Painless hard chancre Commonly at inner foreskin, coronal sulcus, penile shaft and penile base Pathological features Same for syphilitic chancre at any location Sheets of plasma cells Spirochetes identified by silver stain (Warthin-Starry’s statin) Laboratory test   Screening tests :  Detect anti-cardiolipin antibodies in patient with syphilis Rapid plasma regain (RPR)  Venereal Disease Research Laboratory (VDRL) Toluidine Red Unheated Serum Test (TRUST) Confirmatory tests   May be used as initial tests due to automation  Fluorescent treponemal antibody-absorption (FTA-ABS)  Microhemagglutination test for antibodies to T. pallidum (MHA-TP) T. pallidum particle agglutination assay (TPPA) T. pallidum enzyme immunoassay (TP-EIA) Chemiluminescence immunoassay (CIA) Treatment: Penicil

Penile squamous neoplasia   Updated: 01/03/2023 © Jun Wang, MD, PhD Penile intraepithelial neoplasia (PeIN) Rare, precancerous lesion HPV associated Usually whitish discoloration with erythematous changes and ulceration Four variants Differentiated: Most common, more mature, atypia at bottom layers Basaloid: Monotonous small to intermediate sized cells Warty: Papillary growth with koilocytes Warty basaloid: Papillary growth with basaloid cells in middle and lower third of epithelium Common in HIV+ men with anal dysplasia Treatment: Laser, surgery Bowen’s disease Squamous cell carcinoma in situ Usually in elderly uncircumcised men Erythematous, scaly patch or plaque on the shaft of the penis Full thickness epithelial dysplasia with mitosis in upper third layer Overexpression of p16 Squamous cell carcinoma Most common penile neoplasms Risk factors: Phimosis , long foreskin, paraphimosis, HPV infection, lichen sclerosis, injury, smoking, psoriasis patients

Non-specific penile inflammation   Updated: 01/27/2021 © Jun Wang, MD, PhD Phimosis Failure of foreskin to be retracted due to a small orifice Associated with scarring from repeated infections, lichen sclerosis or congenitally abnormally long foreskin Risk for with secondary infections and possibly carcinoma due to accumulation of smegma May be physiological in young age, usually resolve by adolescence Pathological features:  fibrosis and nonspecific inflammation Treatment: Circumcision Balanoposthitis Infection of glans and foreskin Most common cause: pyogenic bacteria or Candida More common in uncircumcised men with poor hygiene and accumulation of smegma Can be sexually transmitted in adults May causes phimosis Treatment: Antibiotics Back to pathology of male reproductive system Back to contents

Intratubular germ cell neoplasia   Updated: 02/03/2022 © Jun Wang, MD, PhD General features AKA germ cell neoplasia in situ (GCNIS) Commonly in tissue adjacent to germ cell tumor Associated with gonadal dysgenesis, androgen insensitivity syndrome, infertility, cryptorchidism , contralateral testis in patients with prior testicular tumor May progress to germ cell tumor Usually incidental finding in biopsy for infertility evaluation Pathological findings Large cells (fried eggs, 3x normal) with clear cytoplasm Thickened tubular basement membrane Displaces Sertoli cells toward the lumen Spermatogenesis usually absent Marker PLAP Management Watchful waiting (clinical and ultrasound examination) Serum measurement of hCG, AFP, human placental lactogen (HPL) Back to testicle tumors Back to pathology of male reproductive system Back to contents

Embryonal carcinoma   Updated: 01/28/2021 © Jun Wang, MD, PhD General features Usually age 20-30's Most commonly a component of non seminoma germ cell tumor Aggressive Metastasis at diagnosis common May accompanied by gynecomastia May have elevated serum PLAP, LDH Pathological findings Tumor with hemorrhage and necrosis Solid, pseudoglandular, alveolar, tubular or papillary patterns Primitive epithelial type cells with minimal features of differentiation Marker Variable, likely AFP and hCG Positive: CD30 , cytokeratin , OCT ¾ Negative: EMA Management Orchiectomy with or without retroperitoneal lymph node dissection, chemo if with metastasis Back to testicle tumors Back to pathology of male reproductive system Back to contents

Seminoma   Updated: 02/03/2022 © Jun Wang, MD, PhD General features Counterpart of ovarian dysgerminoma Mean age 40 years vs. 25 years for nonseminomatous germ cell tumors (NSGCT) Rare in infants Also present in mediastinum, pineal gland (germinoma), retroperitoneum  Pathological findings Homogenous well demarcated gray-white with lobulated and bulging cut surface Uniform tumor cells with clear cytoplasm (glycogen contents), prominent cell border, and large nuclei with prominent nucleoli Marker Serum: PLAP, LDH (Less specific), hCG (probably) Tumor cells positive: KIT, OCT3/4, PLAP Tumor cells negative: cytokeratin Genetic abnormalities KRAS KIT OCT ¾ Others: CCND2, NANOG, etc Diagnosis Diagnosed if only seminomatous elements upon radical orchiectomy (Otherwise, mixed germ cell tumor) Normal AFP Management Orchiectomy Post operative radiation therapy if mets in regional lymph nodes (very radiosensitive) Cisplatin based chemotherapy, if di