Malignant lesions of uterus

imaging Malignant lesions of the uterus

1. Imaging in Malignant lesions of uterus Dr. Gobardhan Thapa Resident, MD Radiodiagnosis NAMS Bir hospital , Kathmandu

2. Presentation outline Relevant anatomy of uterus. Carcinoma of cervix. Malignant lesions of the uterine body. Endometrial Carcinoma Other rare entities. conclusions

3. Fig. Female pelvis: sagittal section showing pelvic floor Fig. Uterus and fallopian tubes: coronal section to show blood supply and ureter relative to uterine artery, cervix and vaginal fornices .

4. Fig. Support ligaments of female pelvis Fig. Transverse ultrasound of uterus and broad ligament. The broad ligament is outlined by fluid, and therefore can be seen The right ovary lies in its anterior surface.

5. ultrasound Fig. Ultrasound of uterus and vagina (A) Longitudinal image; (B) Transverse image; (C) Endovaginal sagittal image The ultrasound probe is in the posterior fornix of the vagina, directed anteriorly so that the transducer is parallel to the long axis of the uterus and cervix .

6. Fig. CECT of female pelvis showing uterus and ovaries.

7. Fig. MRI of female pelvis: (A) transverse T 2 -weighted image showing lower body of uterus and both ovaries Note the high signal of endometrium and ovarian follicles; (B) Sagittal section midline.

8. Gynecological Cancers: epidemiology in Nepal Histological patterns of gynecological cancers, Dhakal et al

9. CARCINOMA OF THE UTERINE CERVIX Typically in younger women, average age at onset: 45 years. Clinical presentation: vaginal bleeding vaginal discharge subclinical: abnormal cervical cancer screening test

10. Risk factors: human papillomavirus (HPV) 16 and 18 infections: for most types of Ca cervix. Multiple sexual partners or a male partner with multiple previous or current sexual partners. Young age at first intercourse. High parity. Immunosuppression . Certain HLA subtypes oral contraceptives nicotine/smoking 

11. Pathogenesis: Cervix: endocervix and the ectocervix . The ectocervix is covered with stratified squamous epithelium whereas the endocervix is covered by columnar mucin secreting endocervical epithelium. The junction of these two epithelia is called the squamocolumnar junction (SCJ).

12. During puberty and reproductive years of a woman, the squamocolumnar junction moves up and the epithelium between the old and the new SCJ is referred to as the ‘ transitional zone’ (TZ). most cervical carcinomas originate in the Transitional Zone. Precancerous state of Ca cervix - cervical intraepithelial neoplasia or CIN . Papanicolaou smear - Screening for cervical cancer.

13. Human papilloma virus infection (genotypes 16 and 18 ) - cervical cancer and precancer .

14. Microscopically, squamous cell carcinoma is most common followed by adenocarcinoma . The squamous cell carcinomas may be keratinizing or nonkeratinizing and may be well, moderately or poorly differentiated. Adenocarcinoma - Endocervical , endometrioid and other subtypes.

15. Role of imaging Ultrasound – first line assessment. Trans vaginal ultrasound.

16. CT: limited use in local staging Able to depict extra uterine spread of disease – enlarged lymph nodes, fistulation into the bladder or rectum, and distant metastases. Contrast CT: variable enhancement. Identification of primary cervical tumor often difficult of CT - 50% of tumors isodense to cervical stroma .

17. MRI: Excellent soft tissue contrast resolution and Defines local extent of primary tumor and metastatic spread. Angled trans-axial and sagittal T2 W images are useful for tumor extension and detection of cervical cancer.

18. Fig. Correct imaging plane for evaluation of cervical cancer with MR imaging a) Sagittal T2-weighted image, obtained to localize the cervix, shows an imaging plane (dashed lines) that is axial to the cervix.  (b)  MR image obtained in the plane indicated by the dashed lines in  a  shows the cervix ( TRILAMINAR )as a “ doughnut ” with the endocervical canal in the center. Normal cervical stroma is dark on T2-weighted images with a rim of intermediate SI smooth muscle.

19. Cervical cancer : appears as T2 hyperintense lesion in T2 hypointense cervical stroma . Mostly isointense in T1 WI May demonstrate areas of necrosis or blood products. Enlarged barrel shaped cervix with an abnormal intermediate to high T2 signal intensity mass that replaces the low signal intensity cervical stroma . Tumors enhance earlier than adjacent cervical stroma . May be restricted on DWI/ADC maps.

20. Fig. Cervical cancer in a 47-year-old patient. A, T2-weighted image shows a mass larger than 4 cm in diameter (arrow) in the posterior aspect of the cervix, protruding into the vagina. The vagina shows high signal intensity (asterisk) due to opacification with ultrasound gel. The normal low signal intensity of the posterior cervix is replaced by the intermediate-signal-intensity mass. B, Axial T2-weighted image shows a small peripheral rim of normal cervical stroma of low signal intensity (arrows), ruling out parametrial invasion.

21. Stage I. A rim of surrounding T2 low-intensity cervical stroma should remain intact at this stage to indicate tumor confinement within the cervix. Fig. Cervical Carcinoma-Stage IA-MR. This T2 WI MR image was obtained in an oblique coronal plane to the patient in order to image the cervix in transverse orientation. The tumor (T) appearing dark gray has nearly completely replaced the normal cervix seen only as a black rim (arrowheads). No parametrial invasion is evident. Free intraperitoneal fluid (ff) is seen in the culde - sac. B, bladder.

22. Stage II extend beyond the uterus and involve the upper two thirds of the vagina but do not extend to the pelvic side wall or the lower one third of the vagina. Involvement of the upper two thirds of the vagina is characterized by a T2-hyperintense lesion disrupting the T2-hypointense vaginal wall.

23. Parametrial invasion disruption of the low-signal-intensity cervical stromal ring, with nodular or irregular tumor extending into the parametrium . Additional features suggesting parametrial invasion include segmental disruption with a spiculated tumor- parametrium interface, soft tissue extension into the parametrium , and encasement of the periuterine vessels. Conversely, parametrial invasion can be confidently excluded if the T2-hypointense cervical stromal rim is thicker than 3 mm, with a specificity of 99%.

24. Fig. Cervical Carcinoma---Stage IIB-CT. Heterogeneous tumor (T) has completely replaced the cervix on this CT scan. Stranding densities (arrowheads) into the paracervical fat indicate parametrial invasion by tumor. Fig. Parametrial extension of cervical cancer. T2-weighted MR image shows that an intermediate-signal-intensity tumor has replaced all of the normal low-signal-intensity cervical stroma . Fingerlike projections of the tumor (arrows) extend into the parametrial fat.

25. Stage III IIIA, tumors extend to the lower one third of the vagina but not the pelvic sidewall. IIIB - extension to the pelvic sidewall or involvement of the ureters , which causes hydronephrosis .

26. Stage IVA: local pelvic organ invasion, which is characterized by infiltration of the rectal mucosa or urinary bladder. T2-weighted images: rectal invasion indicated by segmental disruption of the hypointense muscularis layer by the hyperintense tumor. S tage IVB: tumors spread beyond the pelvis to distant organs.

27. Stage IVA cervical cancer. A, Bulky enlargement of the cervix by a large mass of intermediate signal intensity is seen on the sagittal T2-weighted image. It extends to the middle third of the anterior vagina. Disruption of the low signal intensity of the posterior deep bladder wall and the irregular surface of the bladder (B) wall over a distance of 2.5 cm is shown (arrow). B, Angulated transaxial T2-weighted image shows an enlarged left iliac lymph node suggestive of metastasis (arrow). Cystoscopy confirmed mucosal bladder wall invasion.

28. Invasive Cervical Carcinoma Grossly: P olypoid , predominantly exophytic tumors with a cauliflower-like appearance or may be endophytic , deeply infiltrative resulting in a hard cervix, which is only slightly enlarged. Evaluation of a surgical specimen - extent of circumferential involvement, upper and lower limits of the tumor and depth of stromal involvement. As cervical cancer spreads locally into the parametrium , this also needs careful evaluation.

29. Role of Radiologists Imaging more important for staging rather than detection. {detection: Pap smear} Checklist for a Ca cervix report : Tumor size, depth of stromal invasion, presence of parametrial invasion, hydronephrosis , lymphadenopathy , distant mets . MR best for assessment of local tumor extent. PET/CT: rapidly upcoming tool

30. Fig. PET image shows uptake in the supraclavicular region (arrow), a known site of skip metastases from cervical cancer. PET depicts distant nodal disease that would not be evident at clinical examination.

31. Imaging of complications of treatment : Can be evaluated with CECT. MRI to distinguish local recurrence from post operative scarring and fibrosis.

32. Fig. Radiation enteritis in a patient who was treated for cervical cancer. Contrast-enhanced CT scan shows thick-walled small bowel loops of increased permeability, hence the ascites . Fig. Local recurrence after hysterectomy for cervical cancer. T2-weighted MR image shows a mass in the anterior vaginal wall (arrow), a finding that represents a local recurrence of cervical cancer. The vagina is distended with surgical lubricant, which allows better delineation of the walls.

33. Malignant lesions of uterus include tumors of the endometrium and of the myometrium . Endometrial cancers include endometrial carcinoma, endometrial stromal sarcoma and malignant mixed Müllerian tumors (MMMT). Leiomyosarcoma arises from the smooth muscle of the myometrium .

34. Endometrial carcinoma most common gynecological malignancy in developed countries. It typically occurs in elderly postmenopausal women. 6 and 7 decades of life, with the mean age of patients being 65 years.

35. Clinically: Abnormal uterine bleeding in a post menopausal patient. Endometrial thickness: if > 4 mm – tissue biopsy

36. Based on the pathogenesis, two distinct types are noted: Type I , which occurs in a background of excess estrogenic stimulation and develops against a background of endometrial hyperplasia; and Type II , which occurs de novo. Obesity, hypertension, diabetes and nulliparity are risk factors for type I carcinomas. Other predisposing conditions include polycystic ovarian disease (PCOD), dysfunctional uterine bleeding (DUB), long standing estrogen users, tamoxifen usage and those with functioning granulosa cell tumors.

37. Type I: Endometrioid Adenocarcinoma Gross appearance: polypoidal , predominantly exophytic growth arising from the uterine cavity or as diffusely infiltrating tumors. Microscopically: like the usual adenocarcinomas and are divided into grade I-III tumors based on their degree of differentiation. Aspects to be evaluated: depth of myoinvasion . vertical extent of involvement and involvement of the cervix.

38. Type II Carcinoma includes serous carcinoma and clear cell carcinoma. highly aggressive and occur in older women. Serous carcinoma characterized by a complex papillary growth pattern. The lining cells show moderate to severe pleomorphism and atypia with mitotic figures and sometimes psammoma bodies. Usually deep myoinvasion is present.

39. Clear cell carcinoma composed of large clear cells with distinct cellular margins and abundant cytoplasm containing abundant glycogen.

40. Staging and role of imaging

41. Imaging Ultrasound: Vary from moderate endometrial thickening to an irregularly hypoechoic intracavitary mass. Enlarged diffusely infiltrated uterus. Endovaginal ultrasound: good at differentiating early stage disease. Fig. TVS: poorly defined intrauterine mass due to endometrial carcinoma.

42. MRI T1 isointense and T2 hypointense relative to normal endometrium , with relatively less enhancement compared to normal myometrium . Restricted diffusion on DWI and ADC mappings.

43. Fig. Endometrial cancer. A, T2-weighted image demonstrates a T2-hypointense mass filling the majority of the endometrial cavity, which demonstrates T1-isointense signal (B). C, Mild postcontrast enhancement of the endometrial lesion. D and E, Sagittal DWI and corresponding ADC map demonstrate restricted diffusion.

44. Stage I: Confined to uterus and further subdivided by the amount of invasion into the myometrium ( ≤50 % invasion).

45. Fig. Stage IB endometrial cancer in a 68-year-old female with. (A) Sagittal T2W MR image, (B) T1W post-contrast image, and (C) DW image show endometrial tumor with more than 50% of myometrial invasion in the anterior wall (arrows) indicating stage IB disease Fig. Stage IA - Sagittal contrast-enhanced image 6 minutes after contrast injection shows a hypointense endometrial tumor (asterisk) invading the posterior and anterior myometrium in less than 50% of the entire myometrial thickness.

46. Stage II: Stromal invasion of cervix Fig. A 65-year-old female with endometrial cancer. (A) Sagittal T2W MR image, (B) T1W post-contrast image, (C) DW image, and (D) ADC map image show a large and irregular endometrial mass (white arrows) which disrupts the cervical stroma (black arrowheads), but does not extend beyond the uterus indicating stage II disease. Note normal posterior cervical lip (white arrowheads)

47. Stage III: Defined by local or regional tumor spread beyond the uterus but not outside the true pelvis Further subdivided by the extent of locoregional invasion and presence of lymphadenopathy .

48. IIIA: tumors invade through the serosa , disrupts the contour of the outer myometrium or involves the adnexa . IIIB: extension into the parametrium or vaginal involvement.

49. IIIC: lymph node involvement. Nodal characters: short axis > than 10 mm, multiplicity, irregular contours, internal necrosis, or abnormal signal within the lymph node that is similar to the primary tumor .

50. Stage IV: IVA: extension into normally T2 hyperintense bladder or rectal mucosa. IVB: distant metastasis includes peritoneal spread ( omental caking, malignant ascites ), paraaortic lymphadenopathy , and inguinal lymph node metastases.

51. Fig. stage IVB endometrial cancer in 75-year-old female. (A) Axial contrast-enhanced computed tomography image of the pelvis shows the thick hypodense endometrium (black arrow). (B) Axial contrast-enhanced CT image shows peritoneal implants (white arrows) in this patient with clear cell endometrial carcinoma Fig. Endometrial cancer in a 71-year-old female. Sagittal T2W MR image shows focal loss of low signal intensity wall of the bladder (arrow) suggestive of bladder involvement.

52. Role of radiologists Ultrasound (esp. TVS) – acceptable modality for first line assessment of postmenopausal bleeding. {endometrial thickness threshold: 5 mm}. Sonohysterography : in evaluation of postmenopausal bleeding with abnormal USG results with negative blind biopsy. CT/MRI – to assess extent of endometrial cancer esp in locally advanced cases.

53. Follow up imaging : CECT: routine surveillance, can demonstrate ascites , adenopathy and distant mets . MR imaging: differentiation of soft tissue masses from bowel, incisional hernia and hypertrophic scar.

54. Fig. Tumor recurrence in a patient who underwent hysterectomy for endometrial cancer. The patient experienced pelvic pain for several months after surgery; because palpation was compromised by body habitus , MR imaging was performed to evaluate for recurrence. Sagittal MR image shows implantation of endometrial cancer (arrowhead) in the hysterectomy scar. 

55. Rare uterine malignancies Rare heterogeneous groups of tumors of mesenchymal origin and represents ~8% of uterine malignancies. Can be classified into Epithelial or mixed epithelial- nonepithelial tumors . Leiomyosarcoma : most common pure histologic subtype

56. Leiomyosarcoma occurs in older women Grossly is seen as a large fleshy intramural mass with submucous and subserosal extension. Areas of hemorrhage and necrosis.

57. Microscopically, Highly cellular with large areas of coagulative tumor necrosis. Cellular atypia is obvious and mitoses.  Fig. uterine leiomyosarcoma , CT: large lobulated heterogenous mass lesion seen replacing uterus, with hypodense necrotic areas and some calcifications within.

58. <0.2% - from sarcomatous transformation of a benign leiomyoma . MRI: Infiltrating heterogeneously enhancing uterine mass with T1 heterogenously hypointense and irregular and ill-defined margins. T2: intermediate to high signal intensity May have areas of central necrosis, hemorrhage or foci of calcifications.

59. Leiomyosarcoma . T2WI shows a huge heterogeneous tumor mass (arrowheads) arising from the anterior wall of the retroflexed uterus (arrow). Note that the uterine cavity is intact. The exophytic myometrial origin and heterogeneity of the mass is indicative of either a degenerated leiomyoma or a leiomyosarcoma . The latter diagnosis was confirmed at surgery.

60. Endometrial Stromal Sarcoma In the 5th decade of life and present clinically with vaginal bleeding. Gross appearance: Sharply circumscribed nodule with no permeation of the surrounding tissue, when they are designated Endometrial stromal nodule.

61. Microscopy: These tumors are composed of small ovoid cells resembling the endometrial stromal cells. They are individually enveloped by reticulin fibers.

62. Fig. 42 year old female with endometrial stromal sarcoma  Coronal T2WI showing a large heterogeneous hyperintense mass in the endometrial cavity extending from the fundal region up to the vagina, causing distension of the cervical canal (white arrows). Uterus appears superiorly displaced by the mass.

63. MMMT (malignant mixed mullerian tumors) Carcinosarcoma always seen in postmenopausal women. They present with uterine bleeding and enlargement. Grossly, soft, polypoidal masses filling the cavity with areas of hemorrhage and necrosis.

64. Microscopically admixture of carcinoma and sarcoma-like elements. The carcinoma resembles endometrioid , clear cell or papillary serous types. The sarcomatous component may be homologous or heterologous in nature. Homologous refers to a sarcoma resembling endometrial stromal sarcoma or a spindle cell sarcoma resembling leiomyosarcoma or fibrosarcoma . Heterologous elements may be chondrosarcoma , osteosarcoma or rhabdomyosarcoma in nature.

65. MMMTs are highly aggressive neoplasms . Extension into the pelvis, lymphatic and vascular permeation and blood-borne metastases are common. Extension of the tumor to the serosa and beyond is a sign of even worse prognosis.

66. Müllerian Adenosarcoma usually presents in the elderly as a bulky polypoidal growth filling the endometrial cavity. Microscopically, E pithelial and stromal elements. The epithelial component has a benign appearance whereas the stromal component is malignant and resembles a sarcoma. Müllerian adenosarcoma with a sarcomatous overgrowth (MASO) is an aggressive variant of this neoplasm with a poor prognosis.

67. Fig. Müllerian adenosarcoma in a 20-year-old-woman. A, Color Doppler image showing diffuse enhancement of the uterus. There is a polypoid lesion within the endometrial canal (arrow). B, T2-weighted MRI showing a polypoid lesion within the endocervical canal (arrow). There are high T2 signal regions shown within the thickened junctional zone. C, Contrast-enhanced CT of the uterus showing a heterogeneous appearance to the uterus with a region of low density and slight bulging of the surface of the uterus, shown on the right side (arrow).

68. Conclusions Diagnostic imaging is critical in the staging of all gynecologic neoplasms and can help ensure that the proper therapy is administered. Surgical staging is necessary unless the patient is not a surgical candidate; that is, if the performance status is so poor that the patient could not withstand a laparotomy .

69. References Anatomy for diagnostic imaging, 3/e; Ryan Diagnostic Imaging Genitourinary imaging, 3/e Berry series. CT and MRI of the whole body, 6/e; John Haaga . Ovarian, Cervical, and Endometrial Cancer, Viswanathan et al, RadioGraphics 2008; 28:289–307. Imaging in endometrial carcinoma, Faria et al; Indian J Radiol Imaging. 2015 Apr-Jun; 25(2): 137–147.

70. Thank you !!