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Pathology of cervix &uterus

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Pathology of cervix &uterus

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Pathology of cervix &uterus

  1. 1. Pathology of the Cervix & Uterus Dr. Aye Aye Tun Senior Lecturer, Pathology Unit RCMP,UniKL
  2. 2. Learning Objective  Etiopathogenesis  Morphological features  Clinical features  Complications  Investigations and
  3. 3. Learning Objective The aetiopathogenesis, morphological features, clinical features, investigations and complications of  CARCINOMA CERVIX  Congenital anomalies of the uterus  Endometrial hyperplasia  Endometriosis & adenomyosis  Uterine tumors: benign & malignant
  4. 4. PATHOLOGY OF CERVIX  INFLAMMATION  METAPLASIA  POLYPS  DYSPLASIA  CIN  INFILTRATING CARCINOMA
  5. 5. Endocervical Polyps  Benign exophytic growths  Occur in 2% to 5% of adult women  Irregular vaginal “spotting” or bleeding Treatment - Simple curettage or surgical excision effects a cure
  6. 6. Site: within the endocervical canal Size: small and sessile to large (5-cm masses that protrude through the cervical os) Consistency: soft& mucoid
  7. 7. Microscopic - fibromyxomatous stroma mucus secreting endocervical glands often accompanied by inflammation Endocervical Polyps
  8. 8. Premalignant and Malignant Neoplasms CERVICAL INTRAEPITHELIAL NEOPLASIA Nearly all invasive cervical squamous cell carcinomas arise from precursor epithelial changes referred to as CIN
  9. 9. CERVICAL INTRAEPITHELIAL NEOPLASIA Not all cases of CIN progress to invasive cancer persist without change or even regress
  10. 10. Classification Systems for Premalignant Squamous Cervical Lesions Dysplasia CIN Squamous Intraepithelial Lesion (SIL) Mild dysplasia CIN I Low-grade SIL (LSIL) Moderate dysplasia CIN II High-grade SIL (HSIL) Severe dysplasia CIN III High-grade SIL (HSIL) Carcinoma in situ CIN III High-grade SIL (HSIL)
  11. 11. Papanicolaou (Pap) smear Cytologic examination (Papanicolaou (Pap) smear) can detect CIN long before any abnormality can be seen grossly The Pap smear - the most successful cancer screening test In populations that are screened regularly, cervical cancer mortality is reduced by as much as 99%
  12. 12. The cytology of CIN as seen on the Papanicolaou smear Normal exfoliated superficial squamous epithelial cells CIN I CIN II CIN III
  13. 13. DYSPLASIA / CIN (CERVICAL INTRAEPITHELIAL NEOPLASIA ) Spectrum of cervical intraepithelial neoplasia: A. normal squamous epithelium for comparison B. CIN I with koilocytotic atypia C. CIN II with progressive atypia in all layers of the epithelium D. CIN III (carcinoma in situ) with diffuse atypia and loss of maturation
  14. 14. Carcinoma Cervix second most common cancer in women  Squamous cell carcinomas (75%)  Adenocarcinomas & adenosquamous carcinomas (20%)  Small-cell neuroendocrine carcinomas (<5%)
  15. 15. Nobel Prize in 2008 HARALD ZUR HAUSEN was awarded For discovery of HPV as a cause of cervical cancer
  16. 16. Pathogenesis of Carcinoma Cervix High oncogenic risk HPVs are currently considered to be the single most important factor in cervical oncogenesis HPV 16 and HPV 18
  17. 17. Pathogenesis of Carcinoma Cervix The risk factors for cervical cancer are related to both host and viral characteristics HPV exposure viral oncogenicity inefficiency of immune response presence of co-carcinogens
  18. 18. Risk Factors 1. Multiple sexual partners 2. A male partner with multiple previous or current sexual partners 3. Young age at first intercourse 4. High parity 5. Persistent infection with a high oncogenic risk HPV, e.g., HPV 16 or HPV18 6. Immunosuppression 7. Certain HLA subtypes 8. Use of oral contraceptives 9. Use of nicotine
  19. 19. Smoking, Hormone, Oral contr. parity, Altered immune response etc. Cervical Transformation Zone Sexual Exposure HPV Infection Squamous Ep Columnar Ep Squamous Ca Adeno Ca High Risk Types (16,18) Low Risk-6,11 PATHOGENESIS
  20. 20. Role of HPV in carcinoma cervix How does HPVtransform cells? Viral oncoproteins E6 and E7  E6 binds - the product of tumor suppressor gene TP53 and inactivates it  E7 binds - the retinoblastoma gene (RB) protein
  21. 21. MORPHOLOGY pink-tan, friable Fungating (exophytic) lesion on the anterior cervical lip
  22. 22. Squamous cell carcinoma of the cervix Microinvasive squamous cell carcinoma with invasive nest breaking through the basement membrane of HSIL MORPHOLOGY Invasive nest of tumor cells
  23. 23. squamous cell carcinomas are composed of nests and tongues of malignant squamous epithelium either keratinizing or non keratinizing invading the underlying cervical stroma MORPHOLOGY
  24. 24. MORPHOLOGY Adencarcinoma in situ Adenocarcinomas are characterized by proliferation of glandular epithelium composed of malignant endocervical cells with large, hyperchromatic nuclei and relatively mucin-depleted cytoplasm, resulting in dark appearance of the glands as compared with the normal endocervical epithelium Invasive adencarcinoma
  25. 25. CLINICAL FEATURES  Asymptomatic  unexpected vaginal bleeding  Leukorrhea  painful coitus (dyspareunia)  Dysuria
  26. 26. BODY OF UTERUS AND ENDOMETRIUM The uterus has two major components: Myometrium - composed of tightly interwoven bundles of smooth muscle that form the wall of the uterus Endometrium - composed of glands embedded in a cellular stroma
  27. 27. BODY OF UTERUS AND ENDOMETRIUM Diseases of uterus result from  endocrine imbalances  complications of pregnancy  neoplastic proliferation
  28. 28. BODY OF UTERUS AND ENDOMETRIUM  D.U.B. (Dysfunctional Uterine Bleeding)  Inflammation  Adenomyosis/Endometriosis  Polyps/Hyperplasia  Malignant Tumors of the Endometrium  Tumors of the Endometrium with Stromal Differentiation  Tumors of the Myometrium
  29. 29. Adenomyosis/Endometriosis Endometriosis presence of endometrial tissue both endometrial glands and stroma outside of the uterus It occurs in the following sites (1) Ovaries (2) uterine ligaments (3) rectovaginal septum (4) cul de sac (5) pelvic peritoneum (6) large and small bowel and appendix (7) mucosa of the cervix, vagina, and fallopian tubes (8) laparotomy scars
  30. 30. Adenomyosis characterizedby functional endometrial nests within the myometrium producing foci of hemorrhagic cysts within the uterine wall
  31. 31. Endometrosis in ovary cystic and contains dark blood and debris resembling chocolate described as “chocolate cysts
  32. 32. Polyps/Hyperplasia Endometrial Polyps Exophytic masses of variable size that project into the endometrial cavity Asymptomatic or cause abnormal bleeding (intramenstrual, menometrorrhagia, or postmenopausal) if they ulcerate or undergo necrosis
  33. 33. single or multiple usually sessile, measuring from 0.5 to 3 cm in diameter occasionally large and pedunculated MORPHOLOGY
  34. 34. Endometrial Hyperplasia defined as an increased proliferation of the endometrial glands relative to the stroma resulting in an increased gland-to-stroma ratio when compared with normal proliferative endometrium an important cause of abnormal bleeding
  35. 35. Endometrial Hyperplasia associated with prolonged estrogen stimulation of the endometrium Have the malignant potential of endometrial hyperplasia endometrial hyperplasia and carcinoma share specific molecular genetic alterations inactivation of the PTEN tumor suppressor gene
  36. 36. MORPHOLOGY Simple hyperplasia without atypia with architectural abnormalities including mild glandular crowding cystic glandular dilatation
  37. 37. MORPHOLOGY Complex hyperplasia without atypia increased glandular crowding with areas of back-to-back glands cytologic features similar to proliferative endometrium
  38. 38. MORPHOLOGY Complex hyperplasia with atypia similar to complex hyperplasia without atypia the cytologic features have changed
  39. 39. MORPHOLOGY High magnification of complex hyperplasia with atypia showing rounded, vesicular nuclei with prominent nucleoli
  40. 40. Malignant Tumors of the Endometrium Carcinoma of the endometrium peak incidence is in 55 - 65 year classification of endometrial carcinoma two broad categories type I and type II
  41. 41. Characteristics of Type I and Type II Endometrial Carcinoma Characteristics Type I Type II Age 55–65 yr 65–75 yr Clinical setting Unopposed estrogen Atrophy Thin physique Obesity Hypertension Diabetes Morphology Endometrioid Serous Clear cell Mixed m?llerian
  42. 42. Characteristics of Type I and Type II Endometrial Carcinoma Characteristics Type I Type II Precursor Hyperplasia Endometrial intraepithelial carcinoma Molecular genetics PTEN p53 PIK3CA Aneuploidy KRAS PIK3CA MSI β-catenin p53
  43. 43. Characteristics of Type I and Type II Endometrial Carcinoma Characteristics Type I Type II Behavior Indolent Aggressive Spreads via lymphatics Intraperitoneal and lymphatic spread
  44. 44. Schematic diagram depicting the development of type I endometrial carcinoma arising in the setting of hyperplasia molecular genetic alterations are shown at the time during the progression of the disease Type I Adenocarcinoma endmetrium
  45. 45. MORPHOLOGY Sagittal section of the uterus shows a friable, tan-yellow tumor that is filling the uterine cavity and extending into the myometrium
  46. 46. MORPHOLOGY Endometrial adenocarcinoma a fungating mass in the fundus of the uterus Well-differentiated (grade 1) endometrioid adenocarcinoma preserved glandular architecture lack of intervening stroma Moderately differentiated (grade 2) endometrioid adenocarcinoma glandular architecture admixed with solid areas Poorly differentiated (grade 3) endometrioid adenocarcinoma with predominantly solid growth
  47. 47. Schematic diagram of the development of type II endometrial carcinoma. Type II Adenocarcinoma endmetrium
  48. 48. MORPHOLOGY Endometrial intraepithelial carcinoma Strong, diffuse expression of p53 as detected by immunohistochemistry in endometrial intraepithelial carcinoma Serous carcinoma of the endometrium with papillary growth pattern Strong, diffuse expression of p53 as detected by immunohistochemistry in serous carcinoma endometrium
  49. 49. Clinical course of adenocarcinoma of the endometrium irregular or postmenopausal vaginal bleeding excessive leukorrhea Uterine enlargement may be absent in the early stages The diagnosis of endometrial cancer must ultimately be established by biopsy or curettage and histologic examination of the tissue
  50. 50. Staging of types I and II of endometrial adenocarcinoma Stage I Carcinoma is confined to the corpus uteri itself Stage II Carcinoma involves the corpus and the cervix Stage III Carcinoma extends outside the uterus but not outside the true pelvis Stage IV Carcinoma extends outside the true pelvis or involves the mucosa of the bladder or the rectum
  51. 51. Tumors of the Myometrium Leiomyoma(commonly called fibroids)  most common tumor in women  benign smooth muscle neoplasms approximately 40% have a simple chromosomal abnormality Several cytogenetic subgroups have been recognized t(12;14)(q14–q15;q23–q24)), del(7)(q22–q32)), trisomy 12 rearrangements of 6p, 3q, and 10q The rearrangements of 12q14 and 6p involving the HMGIC and HMGIY genes
  52. 52. Morphology  Site – Leiomyoma can occur within the myometrium - intramural just beneath endometrium - submucosal beneath the serosa - subserosal  Size - varying in size from small to massive tumors that fill the pelvis  Number – single or most often multiple
  53. 53. Morphology  Shape - sharply circumscribed, discrete, round  Color & Consistency - firm, gray-white tumors  on cut section - characteristic whorled pattern of smooth muscle bundles  red degeneration- areas of yellow-brown to red softening in large tumors
  54. 54. Morphology On histologic examination leiomyoma is composed of whorled bundles of smooth muscle cells that resemble the uninvolved myometrium the individual muscle cells - uniform in size and shape - have the characteristic oval nucleus - long, slender bipolar cytoplasmic processes
  55. 55. Leiomyomas of the myometrium The uterus is opened to reveal multiple tumors in submucosal (bulging into the endometrial cavity) intramural, and subserosal locations a firm white appearance on sectioning MORPHOLOGY well-differentiated, regular spindle-shaped smooth muscle cells associated with hyalinization
  56. 56. Leiomyosarcoma A large hemorrhagic tumor mass distends the lower corpus is flanked by two leiomyomas MORPHOLOGY Leiomyosarcoma

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