Repro Patho Jared PDF

Non Neoplastic: Inflammatory disorders -​ Rare outside lactational period 1.​ Acute mastitis -​ Common in lactating breast -​ Bacteria (Staphylococci) from infant during breastfeeding -​ Travels via ducts or erosions due to sucking -​ Proliferation in stagn...

Non Neoplastic: Inflammatory disorders -​ Rare outside lactational period 1.​ Acute mastitis -​ Common in lactating breast -​ Bacteria (Staphylococci) from infant during breastfeeding -​ Travels via ducts or erosions due to sucking -​ Proliferation in stagnant milk, acute inflammation (neutrophils), acute abscess formation -​ TREATMENT: Antibiotics 1st choice, if not then excise 2.​ Idiopathic granulomatous mastitis: -​ Rare inflammatory condition in parous women (women who have given birth) -​ Unknown etiology (maybe hypersensitivity) -​ Presents as hard mass, mimics malignancy -​ Histologically mimics TB with epithelioid granulomas and MNCs -​ TREATMENT: steroids, immunosuppressives, surgery 3.​ Paraffinoma: -​ Hardened lump (fibrosis) due to paraffin injections for breast augmentation -​ Can mimic cancer -​ Foreign body type MNC reaction Non Neoplastic: Benign epithelial conditions 1.​ Fibrocystic changes: -​ Common non proliferative lesion, presents as lump/lumpiness -​ Hormone sensitive lesion, occurs during reproductive age and worsens during period -​ CHARACTERISTIC MICROSCOPIC FEATURES: 1)​ Fibrosis 2)​ Cysts 3)​ Apocrine metaplasia 4)​ Epithelial hyperplasia - determines risk of malignancy Benign Neoplasms 1.​ Fibroadenoma: -​ Common, most in young women (~25yrs) -​ Firm well circumscribed lump (1-6 cm) -​ Multiple or bilateral -​ Can recur or regress spontaneously -​ HISTO: proliferation of glandular and stromal elements 2.​ Phyllodes tumor: -​ Another fibroepithelial tumor → Leaflike architecture -​ Usually bigger than fibroadenoma, and stromal proliferation is more common -​ Can be benign, borderline or malignant (also KEY difference from fibroadenoma) Malignant Neoplasms -​ Clinical presentations: ➔​ Palpable mass ➔​ Nipple discharge ➔​ Mammographic density ➔​ Mammographic calcifications -​ Breast Carcinoma gross features: ​ Sites: upper outer > subareolar > other sites ​ Growth pattern: Comedo, circumscribed, infiltrating ​ Consistency: scirrhous, encephaloid (brain/jelly like), mucinous Malignant Neoplasms: non invasive in situ ® 1.​ Ductal Carcinoma In Situ (DCIS) -​ Calcification and necrosis -​ Larger cells than LCIS -​ Comedo, cribriform patternHigher risk of invasion than LCIS 2.​ Lobular Carcinoma In Situ (LCIS) -​ Arise in terminal duct, lobular areas -​ Solid pattern Malignant Neoplasms: Invasive 1.​ No Special Type -​ Tumor morphology is distinct, every tumor has a different morphology -​ MAJORITY of invasive breast carcinomas SPECIAL TYPES: (2-5) 2.​ Tubular carcinoma -​ One of the BEST tumors to have → extremely good prognosis -​ Tries to mimic normal ducts 3.​ Mucinous carcinoma: -​ Radiologically – rounded, dense mass due to lots of mucin -​ Low grade, good prognosis -​ Well circumscribed, soft mucinous in nature -​ On histo slide → invasive tumor floating in a backdrop of mucin 4.​ Medullary carcinoma -​ Tumor arranged in sheaths -​ High grade histologically but responds well to chemotherapy -​ Grossly well circumscribed -​ Intervening stroma has lymphoplasmacytic immune response 5.​ Lobular carcinoma -​ Loss of cellular adhesion due to loss of E-cadherin mutation (used as a diagnostic test) -​ Characteristically arranged in discohesive or single file patterns -​ Concentric arrangement around duct 6.​ Paget’s disease: -​ Proliferation of malignant glandular epithelial cells in nipple areolar epidermis -​ Generally patients will have underlying DCIS, tumor cells then migrate into stratified squamous regions of alveolar complex -​ Presents as nipple erosion or ulceration or redness Pathology of the prostate gland 1.​ Benign Prostatic Hyperplasia -​ Nodular Hyperplasia of both prostatic stromal and epithelial cells; common over 50 -​ PATHOPHYSIOLOGY: ➔​ Type 2 5a reductase in stromal cells convert test to DHT ➔​ DHT binds to androgen receptors in epithelial + stromal cells → induce growth factor production ➔​ = proliferation of stromal cells + reduced death of epithelial cells  -​ OCCURS IN TRANSITIONAL ZONE, can cause urinary obstruction (+ a1 adrenergic receptor mediated prostatic smooth muscle tone) -​ SSx: Lower UT symptoms: nocturia, terminal dribbling, urinary retention, incontinence, increased frequency -​ IMPORTANT COMPLICATIONS: 1)​ Acute urinary obstruction (emergency) 2)​ Chronic urinary obstruction: -​ Recurrent UTI (Due to stasis of urine) -​ Bladder hypertrophy -​ CKD -​ TREATMENT: Medical: a blockers to reduce SM tone and 5a reductase inhibitors 2.​ Prostatic cancer: -​ Top 3 most common cancers in men, usually over 50 -​ Wide range of biological behavior: from indolent lesions to metastatic fatal tumors -​ ADENOCARCINOMA is most common, and under it ACINAR type is most common (95%) -​ SSx: ➔​ ASYMPTOMATIC ➔​ LUTS due to obstruction to urethra ➔​ Symptoms of metastases, eg back pain due to bone metastasis (prostate cancer is osteoblastic = more bone formation) ➔​ Enlarged hard prostate in rectal exam ➔​ Elevated PSA but not diagnostic -​ HISTO: infiltrative malignant glands with nuclear atypia and absent basal cell layers -​ When tumor invades extra prostatic fat (extends) OR PNI, severity of cancer is higher -​ Treatment: FOR LOCALIZED: radical prostatectomy or radiotherapy, FOR ADVANCED: androgen deprivation therapy, with drugs or surgery Pathology of the penis/scrotum 1.​ Condyloma acuminatum: -​ Sexually transmitted wart caused by HPV 6 and 11 -​ Papillary tumors on coronal sulcus and inner surface of prepuce -​ HISTO: papillary proliferation of thickened epidermis with koilocytosis: squamous cells with enlarged nuclei with perinuclear halos  2.​ Squamous cell carcinoma: -​ Associated with HPV 16 and 18 (Same as Cervical cancer) and smoking -​ HPV acts as carcinogen by coding for viral proteins E6 and E7 that target and inactivate TSGs E6 → p53, E7 → RB -​ Circumcision decreases risk -​ SLOW GROWING but locally invasive -​ May be preceded by non invasive precursor lesion - penile intraepithelial neoplasia (PeIN) -​ Metastasis to inguinal or iliac lymph nodes → poor prognosis Pathology of the testes 1.​ Hydrocoele: -​ Accumulation of serous fluid between the visceral and parietal layers of tunica vaginalis -​ Causes: primary (idiopathic), secondary (infections, tumor etc) -​ SSX: Painless + enlarged testis/scrotum + transillumination 2.​ Testicular torsion: -​ Twisting of spermatic cord cuts off venous drainage to the testis -​ Typically seen in adolescent males; presents with SUDDEN ONSET OF PAIN -​ Torsion of >24hrs will CERTAINLY cause INFARCTION = INFERTILITY -​ RISK FACTORS: ​ Congenital anatomy (bell clapper abnormality - 90%) ​ Larger testis ​ Cryptorchidism Bell Clapper Abnormality: abnormally high insertion of tunica vaginalis on spermatic cord, leading to increased mobility of the testis. Usually bilateral 3.​ Infections/inflammations: -​ Childhood: Gram negative rods, Sexually active young men: STI, Men >35yrs: E coli, UTI ​ Gonorrhea: Spread from urethra → prostate → seminal vesicles → epididymis ​ Mumps: Young children, acute orchitis 1 week after parotid gland swelling ​ Tuberculosis: Spreads from epididymis → testis, caseating granulomas seen ​ Syphilis: testis involved first Testicular tumors -​ Mainly germ cell tumors (95%), lymphomas can be seen in older patients 1.​ Testicular germ cell tumor -​ 50% are seminomas, rest are non seminomatous GCTs  Seminomatous GCTs Non-seminomatous GCTs Tumor cells resemble primordial germ cells Undifferentiated tumor cells SLOW GROWING, GOOD PROGNOSIS MORE AGGRESSIVE, POORER PROGNOSIS SENSITIVE TO RADIOTHERAPY RESISTANT TO RADIOTHERAPY Lymphatic mets Mets earlier, Haematogenous spread -​ Cryptorchidism is a predisposing factor -​ SSx: ​ Painless enlargement of testis ​ Elevated serum tumor markers: 1)​ Lactate Dehydrogenase (LDH): seminomas and lymphomas but can be elevated in any tumor w high turnover rate 2)​ Alpha Fetoprotein (AFP) - in yolk sac tumors 3)​ Beta HCG - in choriocarcinomas 2.​ Seminoma: -​ Commonest testicular germ cell tumor (50%) ~ 30-40yrs -​ SERUM LDH OFTEN ELEVATED (higher the LDH, more severe it is) -​ OCT4 immunostain used 3.​ Embryonal carcinoma -​ Second most common after seminoma -​ 15-34 yrs, peak at 30yrs -​ Not associated with elevated tumor markers; if elevated markers are found, search for other GCTs -​ HISTO: solid, glandular and papillary growth 4.​ Yolk sac tumor -​ Most common testicular tumor in infants -​ GOOD PROGNOSIS -​ Serum AFP elevated in 95-98% BUT neonates physiologically have elevated AFP of up to 6 months of age -​ HISTO: heterogeneous in pattern, Schiller - Duval bodies: papillary structures comprising central vessel surrounded by cuboidal/columnar tumor cells (seen in 50% of tumors) → 5.​ Choriocarcinoma: -​ Arises from trophoblastic tissue -​ Increased serum Beta HCG: histologically has nests and sheets of multinucleated syncytiotrophoblast -​ Early hematogenous metastasis -​ Hemorrhagic and necrotic tumor  6.​ Teratoma: -​ Pre pubertal type: benign, not associated with GCNIS -​ Post pubertal type: malignant, derived from GCNIS 7.​ Sex cord stromal tumors: (non germ cell tumor) -​ Rare, mostly benign -​ LEYDIG CELL TUMORS: secrete androgens → cause hormonal effects (eg in children) -​ SERTOLI CELL TUMORS: testicular mass, hormonally silent. 10% malignant 8.​ Lymphomas -​ Usually older patients -​ Typically non hodgkin b cell lymphoma -​ Serum LDH elevated Pathology of the vulva: 1.​ Lichen sclerosus (epithelial disorder): -​ Autoimmune -​ Atrophic skin (thinned epidermis), whitish plaque that spreads 2.​ Lichen simplex chronicus -​ Thickened epidermis secondary to pruritus (skin itch) Cancer of the vulva Benign: condylomas (papillary projections due to HPV), hidradenoma Malignant: VIN, SCC, Paget’s -​ 30% of vulvar cancers → HPV 16 associated -​ 70% are not HPV related and develop from lichen sclerosus or premalignant lesion 1.​ Paget’s disease: malignant carcinoma -​ In situ glandular neoplasm that originates from primitive epithelial progenitor cells (since vulva has no gland) -​ Treatment is to excise affected area or vulvectomy 2.​ Squamous cell carcinoma: -​ Majority of malignant tumors of vulva Malignancy of the vagina: 1.​ Clear Cell Adenocarcinoma (CCA) -​ In young women (15-20) whose mothers were treated with(DES) during pregnancy -​ PRECURSOR: vaginal adenosis → when vaginal epithelium undergoes neoplasia to form benign glands  2.​ Sarcoma Botryoides (AKA embryonal rhabdomyosarcoma) -​ Infants and children -​ Grape like clusters -​ Surgery + chemotherapy Malignancy of the cervix: HPV features: -​ Multinucleation -​ Perinuclear halos -​ Crinkled nuclei 3 Steps necessary for cervical cancer development: -​ HPV infection → progression to Cervical Intraepithelial Neoplasia (CIN) → invasion (takes abt 10-15 yrs) Cervical carcinoma features: -​ Fungating, ulcerating or infiltrative -​ Cervix is replaced by cauliflower growth -​ SSx: intermenstrual bleed, post coital bleed, post menopausal bleed, dyspareunia 1)​ Squamous cell carcinoma (75-90%) : large cell keratinizing and non keratinizing, small cell(