Cervix Uteri Carcinoma



Cervix Uteri Carcinoma


Maryam Rezvani, MD






























































































































(T) Primary Tumor


Adapted from 7th edition AJCC Staging Forms.


TNM


FIGO


Definitions


TX


Primary tumor cannot be assessed


T0


No evidence of primary tumor


Tis1


Carcinoma in situ (preinvasive carcinoma)


T1


I


Cervical carcinoma confined to uterus (extension to corpus should be disregarded)



T1a2


IA


Invasive carcinoma diagnosed only by microscopy; stromal invasion with a maximum
depth of 5.0 mm measured from the base of the epithelium and a horizontal spread of ≤ 7.0 mm; vascular space involvement, venous or lymphatic, does not affect classification




T1a1


IA1


Measured stromal invasion ≤ 3.0 mm in depth and ≤ 7.0 mm in horizontal spread




T1a2


IA2


Measured stromal invasion > 3.0 mm and ≤ 5.0 mm with a horizontal spread ≤ 7.0 mm



T1b


IB


Clinically visible lesion confined to the cervix or microscopic lesions greater than T1a/IA2




T1b1


IB1


Clinically visible lesion ≤ 4.0 cm in greatest dimension




T1b2


IB2


Clinically visible lesion > 4.0 cm in greatest dimension


T2


II


Cervical carcinoma invades beyond uterus but not to pelvic wall or to lower 1/3 of
vagina



T2a


IIA


Tumor without parametrial invasion




T2a1


IIA1


Clinically visible lesion ≤ 4.0 cm in greatest dimension




T2a2


IIA2


Clinically visible lesion > 4.0 cm in greatest dimension



T2b


IIB


Tumor with parametrial invasion


T3


III


Tumor extends to pelvic wall &/or involves lower 1/3 of vagina, &/or causes
hydronephrosis or nonfunctioning kidney



T3a


IIIA


Tumor involves lower 1/3 of vagina, no extension to pelvic wall



T3b


IIIB


Tumor extends to pelvic wall &/or causes hydronephrosis or nonfunctioning kidney


T4


IVA


Tumor invades mucosa of bladder or rectum, &/or extends beyond true pelvis (bullous
edema is not sufficient to classify a tumor as T4)


(N) Regional Lymph Nodes


NX


Regional lymph nodes cannot be assessed


N0


No regional lymph node metastasis


N1


IIIB


Regional lymph node metastasis


(M) Distant Metastasis


M0


No distant metastasis


M1


IVB


Distant metastasis (including peritoneal spread, involvement of supraclavicular,
mediastinal, or paraaortic lymph nodes, lung, liver, or bone)


1 FIGO no longer includes stage 0 (Tis).

2 All macroscopically visible lesions, even with superficial invasion, are T1b/IB.
































































































































AJCC Stages/Prognostic Groups


Adapted from 7th edition AJCC Staging Forms.


Stage


T


N


M


0


Tis


N0


M0


I


T1


N0


M0



IA


T1a


N0


M0




IA1


T1a1


N0


M0




IA2


T1a2


N0


M0



IB


T1b


N0


M0




IB1


T1b1


N0


M0




IB2


T1b2


N0


M0


II


T2


N0


M0



IIA


T2a


N0


M0




IIA1


T2a1


N0


M0




IIA2


T2a2


N0


M0



IIB


T2b


N0


M0


III


T3


N0


M0



IIIA


T3a


N0


M0



IIIB


T3b


Any N


M0





T1-3


N1


M0


IVA


T4


Any N


M0


IVB


Any T


Any N


M1








H&E stain shows high-grade squamous intraepithelial lesion. Cells have hyperchromatic nuclei, lack maturation, lack normal organization, and show indistinct cell membranes. Neoplastic cells are limited by the intact eosinophilic basement membrane image, leading to the term “preinvasive carcinoma.”






A. The depth of invasion is measured from the origin of invasion to the last cell of the invasion focus. B. Invasion is measured from the basement membrane to the last cell of the invasion focus. C. Invasion is measured from the site of origin to the last cell of the invasion focus.






Low-power magnification H&E of cervix shows there is loss of squamous epithelium on the right image with underlying moderately differentiated carcinoma characterized by irregular nests of squamous cells invading the stroma. Nests image extend to a depth of 1.5 mm from basement membrane image.






Higher power magnification shows the invasive squamous nests image with mitotic figures image and prominent surrounding inflammatory infiltrate. (Original magnification 400x.)







H&E section of the cervix with stromal depth of invasion of 3.5 mm is characteristic of tumor stage T1a2. (Original magnification 40x.)






H&E stain shows invasive squamous cell carcinoma with a microscopic depth of invasion of 6 mm. Clinically, this lesion was visible; however, it was confined to the cervix and less than 4 cm in greatest dimension. (Original magnification 20x.)






Low-power magnification of H&E stained slide shows cervical squamous cell carcinoma involving the lower 1/3 of the vagina. (Original magnification 40x.)






Higher power magnification shows uninvolved nonkeratinized vaginal surface epithelium with the subepithelial cords and nests of neoplastic cells image. (Original magnification 100x.)







Stage T1a1 cervical carcinoma is defined as microscopic tumor with stromal invasion of ≤ 3 mm in depth and ≤ 7 mm in horizontal spread.






Stage T1a2 cervical carcinoma is microscopic tumor with stromal invasion of 4-5 mm in depth and ≤ 7 mm in horizontal spread.






Stage T1b1 cervical carcinoma is a microscopic or clinically visible lesion. Microscopic tumors have stromal invasion > 5 mm in depth or > 7 mm in horizontal spread. Clinically visible tumors are ≤ 4 cm in size. All lesions at this stage are confined to the cervix.






Stage T1b2 cervical carcinoma is a clinically visible lesion > 4 cm in size. Tumors at this stage are confined to the cervix. Tumor may be exophytic extending into the vaginal vault; however, there is no invasion of adjacent structures.







Stage T2a tumor extends beyond the cervix to invade the upper 2/3 of the vagina. Graphics are sagittal views of the pelvis showing tumor invading the upper vagina. Left graphic depicts stage T2a1 with tumor ≤ 4 cm in size. Right graphic depicts stage T2a2 with tumor > 4 cm in size.






Stage T2b tumor extends beyond the cervix to invade the parametrium. Graphic looks into the pelvic bowl and depicts tumors invading the parametrium including fat, uterine ligaments, and paracervical vessels.






Stage T2b tumor extends beyond the cervix to invade the parametrium. Graphic is a view in the coronal plane depicting tumor invading the parametrium including fat, uterine ligaments, and paracervical vessels. There is encasement of the ureter; however, no hydronephrosis is present.






Stage T3a tumor invades the lower 1/3 of the vagina. Graphic is a sagittal view of the pelvis showing tumor invading the lower vagina.







Stage T3b tumor extends to the pelvic sidewall or causes hydronephrosis. Graphics are views looking into the pelvic bowl. Left graphic depicts tumor extending to the pelvic sidewall to encase the iliac vessels and invade the musculature. Right graphic depicts tumor invading the ureter, resulting in hydronephrosis.






Stage T3b tumor extends to the pelvic sidewall or causes hydronephrosis. Graphic is a view in the coronal plane showing tumor extending to the pelvic sidewall to encase the external iliac vessels and invade the musculature. Tumor invades the ureter, causing hydronephrosis (not shown).






Stage T4 tumor invades the urinary bladder or rectal mucosa. Graphic looks into the pelvic bowl and shows tumors invading the urinary bladder mucosa anteriorly and the rectal mucosa posteriorly.






Stage T4 tumor invades the urinary bladder or rectal mucosa. Graphic is a sagittal view of the pelvis showing tumor invading the urinary bladder mucosa anteriorly and the rectal mucosa posteriorly.







Frontal view of the female pelvis depicts lymph node chains. Regional lymph nodes in cervical carcinoma are highlighted and include parametrial, obturator, internal iliac, external iliac, common iliac, sacral, and presacral lymph nodes.






Lateral view of the pelvis shows the presacral and hypogastric routes of lymphatic drainage more clearly. The obturator lymph node, often the sentinel node in cervical carcinoma, is also shown.































image


METASTASES, ORGAN FREQUENCY


Liver


33%


Pulmonary


33-38%


Bone


15-29%


Adrenal gland


15%


Paraaortic lymph nodes


15%


Supraclavicular nodes


7%


Abdominal cavity


5-27%



Reported organ frequency of metastatic disease is based on
findings at autopsy in patients with recurrent cervical cancer.




OVERVIEW


General Comments



  • 3rd most common gynecologic malignancy


  • 80% are squamous cell carcinoma


Classification



  • Histopathologic types



    • Cervical intraepithelial neoplasia, grade III


    • Squamous cell carcinoma in situ


    • Squamous cell carcinoma



      • Invasive


      • Keratinizing


      • Nonkeratinizing


      • Verrucous


    • Adenocarcinoma in situ


    • Invasive adenocarcinoma


    • Endometrioid adenocarcinoma


    • Clear cell adenocarcinoma


    • Adenosquamous carcinoma


    • Adenoid cystic carcinoma


    • Adenoid basal cell carcinoma


    • Small cell carcinoma


    • Neuroendocrine


    • Undifferentiated carcinoma


PATHOLOGY


Routes of Spread



  • Contiguous spread



    • Most common mode of spread


    • Caudally to invade



      • Vagina


    • Anteriorly to invade



      • Vesicouterine ligament


      • Urinary bladder


    • Laterally to invade



      • Cardinal ligaments


      • Paracervical tissues



        • Fat, vessels, ureters, lymphatics


      • Pelvic sidewall in advanced disease



        • Iliac vessels, pelvic musculature


    • Posteriorly to invade



      • Uterosacral ligaments


      • Rectum


  • Lymphatic spread



    • Significant prognostic indicator


    • ↑ incidence with advancing stage of disease


    • Correlates with ↓ disease-free survival


    • ↑ incidence of recurrence at each stage with lymphatic invasion


    • Lymphatic drainage of cervix



      • Parametrial → obturator → internal/external iliac


    • 3 pathways of lymphatic drainage of cervix



      • Lateral route



        • Parallels external iliac vessels


        • Tumor drains 1st to medial external iliac chain, then to middle and lateral chains


        • Deep inguinal lymph nodes drain via lateral route


      • Hypogastric route



        • Parallels internal iliac vessels


        • Lymph nodes along internal iliac branches drain to junctional lymph nodes


        • Junctional lymph nodes lie between internal and external iliac vessels


      • Presacral route



        • Along uterosacral ligament


        • Uterosacral ligament → lymphatic plexus anterior to sacrum


    • All 3 routes of lymphatic drainage of cervix drain to common iliac chains


    • Common iliac chains drain to paraaortic lymph nodes


    • Depth of invasion of cervix and adjacent structures may affect nodal involvement



      • Parametrial and pelvic sidewall invasion



        • Drainage by external iliac lymph nodes


      • Invasion of lower 1/3 of vagina



        • Inguinal lymph node metastases


      • Rectal wall invasion



        • Drainage by inferior mesenteric lymph nodes


  • Peritoneal seeding



    • Peritoneal metastasis varies from 5-27% in autopsy series


    • Mesenteric or omental metastases are uncommon


    • “Sister Joseph” nodule



      • Umbilical metastasis


      • Direct extension of tumor from anterior peritoneal surface


  • Hematogenous spread



    • Liver is most common abdominal organ with metastases


    • Adrenal gland is 2nd most common metastatic site in abdomen


    • Pulmonary metastases are relatively common in autopsy series (33-38%)



      • May be present for significant period of time; however, may remain asymptomatic


      • 1/3 will have mediastinal or hilar adenopathy


      • Lymphangitic carcinomatosis occurs in < 5%


General Features



  • •Comments



    • Cervical cancer originates at squamocolumnar junction (SCJ)



      • SCJ is originally located in ectocervix (intravaginal)


      • SCJ moves to endocervix with advancing age


      • Cancer arises in transformation zone between old and new SCJ


    • Migration of SCJ accounts for age-related change in tumor growth pattern



      • Young women: Exophytic growth


      • Older women: Endophytic growth


    • Adenocarcinoma and small cell cervical cancer



      • Aggressive histologic subtypes


      • More often advanced at presentation


    • Adenoma malignum



      • Subtype of adenocarcinoma (3%)


      • Arises from columnar epithelium of endocervical canal


      • Composed of well-differentiated endocervical glands


      • History of copious watery discharge


      • Prognosis is poor



        • Early peritoneal metastases



        • Poor response to chemoradiation therapy


      • Associated with Peutz-Jeghers syndrome


    • Clear cell adenocarcinoma



      • Rare histologic subtype of adenocarcinoma


      • Associated with in utero diethylstilbestrol (DES) exposure


      • Case reports suggest possible association with cervical endometriosis


  • Etiology



    • Risk factors for cervical cancer



      • High-risk strains of human papilloma virus (HPV)


      • Sexual activity at early age


      • Multiple sexual partners


      • Sexually transmitted disease


      • Multiparity


      • Low socioeconomic status


      • Cigarette smoking


      • Immunosuppression


      • Long-term use of oral contraceptives


      • In utero DES exposure



        • Clear cell adenocarcinoma


    • 70% of cervical cancer is caused by HPV 16 and 18


    • 27% of women in USA age 14-59 years are positive for at least 1 strain of HPV



      • 15.2% are positive for 1 of high-risk strains


    • Women with HIV/AIDS have poor prognosis, often rapidly progressive cancer


  • Epidemiology & cancer incidence



    • 3rd most common gynecologic malignancy following endometrial and ovarian cancer


    • Decreased incidence since introduction and widespread use of Papanicolaou smear


    • Estimated 11,270 women diagnosed in 2009 in the USA


    • Estimated 4,070 cervical cancer-related deaths in 2009 in the USA


Gross Pathology & Surgical Features



  • Gross appearance



    • Poorly circumscribed granular or eroded appearance


    • Nodular, ulcerated lesion or exophytic mass


    • Diffuse enlargement and hardening of cervix



      • Endophytic infiltrative lesion in cervical canal


    • Barrel-shaped cervix



      • Diffusely enlarged, bulky, and > 6 cm


      • Most common with adenocarcinoma


Microscopic Pathology



  • H&E



    • Large-cell keratinizing squamous cell carcinoma



      • Sheets & nests of malignant squamous cells invade stroma


      • Abundant cytoplasm


      • Large pleomorphic nuclei & inconspicuous nucleoli


      • Keratin pearls & intercellular bridges


      • Occasional mitotic figures


      • Infiltrative growth pattern


    • Large-cell nonkeratinizing squamous cell carcinoma



      • Large cells of similar size and shape


      • Moderate cytoplasm


      • May have individual cell keratinization


      • Keratin pearls are absent


      • Prominent nucleoli


      • Mitotic figures are common


      • Invasive edge is smooth


    • Histologic grade



      • Degree of differentiation of tumor cells


      • Based on amount of keratin, degree of nuclear atypia, mitotic activity


      • Correlates with frequency of pelvic nodal metastasis


      • Grade 1: Well differentiated



        • Abundant intercellular bridging


        • Cytoplasmic keratinization


        • Keratin pearls


        • Cells are uniform with minimal nuclear pleomorphism


        • Mitotic rate is < 2 mitotic figures per high-power field


      • Grade 2: Moderately differentiated



        • Individual cell keratinization


        • Moderate nuclear pleomorphism


        • Mitotic rate is ≤ 4 mitotic figures per high-power field


      • Grade 3: Poorly differentiated



        • Minimal evidence of squamous differentiation


        • Cells are immature with marked nuclear pleomorphism and scant cytoplasm


        • Mitotic rate is > 4 mitotic figures per high-power field


IMAGING FINDINGS


Detection



  • Ultrasound



    • Inadequate for diagnosis, staging, and surveillance for recurrence


    • Technically limited by body habitus, low signal-to-noise ratio, and lack of tissue characterization


  • CT



    • 92% accuracy for assessment of stage IIIB-IVB disease


    • CT can demonstrate



      • Pelvic sidewall extension


      • Ureteral obstruction


      • Advanced bladder and rectal invasion


      • Adenopathy


      • Extrapelvic spread of disease


    • May see distention of uterine cavity with fluid/blood if tumor obstructs endocervical canal


    • CT can guide lymph node biopsy and radiation planning


    • CT has high sensitivity and specificity for detection of recurrent tumor



      • Soft tissue mass with variable degrees of necrosis


      • Cystic mass with minimal soft tissue


    • Limitations of CT



      • Limited visualization of primary tumor



        • Hypodense or isodense to normal cervical stroma


        • Tumor detection and depth of invasion difficult


      • Inaccurate for detection of parametrial invasion



        • Only 30-58% accuracy


        • Parametrial inflammation can mimic parametrial tumor infiltration


        • Paracervical ligaments and vessels may be mistaken for soft tissue strands



  • MR



    • Ideal for local cervical cancer staging



      • Superior soft tissue contrast


      • Multiplanar capability


    • Superior to clinical evaluation and other imaging modalities with regard to tumor characteristics that determine prognosis and stage



      • Tumor size


      • Parametrial invasion


      • Vaginal wall invasion


      • Pelvic sidewall extension


    • Accuracy of MR is 94% in selecting operative candidates



      • Compared with 76% for CT


    • Including MR in pre-treatment work-up significantly decreases number of procedures and invasive studies


    • Typical MR findings of cervical cancer



      • T2 hyperintense mass disrupting normal hypointense cervical stroma


      • Endophytic: Arises from endocervical canal


      • Exophytic: Arises from ectocervix and extends into vaginal vault


    • MR technique



      • T2WI best for visualization of tumor and local staging



        • FSE, small field of view (FOV), high resolution


      • Coronal oblique T2WI: Long & short (donut view) axis of cervix



        • Evaluation of depth of cervical stromal invasion


        • Evaluation of parametrial invasion


      • Sagittal T2WI



        • Depth of cervical stromal invasion


        • Visualization of invasion of vagina and urinary bladder


        • Helpful to distend vagina with gel


      • Axial T2WI



        • Parametrial invasion


        • Pelvic sidewall invasion


        • Rectal invasion


      • T2WI with fat saturation



        • Helpful if prominent paracervical venous plexus


      • IV contrast reportedly not helpful for depth of stromal invasion or parametrial involvement



        • Loss of soft tissue contrast due to enhancement of normal cervical stroma and variable tumor enhancement


        • May result in overestimation of tumor size


      • IV contrast is useful in advanced disease to evaluate



        • Rectal, urinary bladder, pelvic sidewall invasion


        • Pelvic fistulas


        • Recurrent/residual disease post radiation or surgery


    • Characteristic features of adenoma malignum



      • Multicystic mass extending from superficial to deep cervical wall


      • Mass may be nodular or annular


      • Mass invades deep into cervical stroma


      • Cystic components are hyperintense on T2WI with intervening low signal septations


      • Solid enhancing components help differentiate adenoma malignum from benign entities


    • Limitations of MR



      • Differentiating tumor recurrence from early radiation change and infection


      • May overestimate parametrial invasion with large tumors



        • Due to surrounding stromal edema from tumor compression or inflammation


  • PET/CT



    • Excellent for detection of lymphadenopathy and distant metastatic disease



      • 100% sensitivity and 99.6% specificity for lymph nodes > 5 mm in short axis


      • 100% sensitivity and 94% specificity for distant metastatic disease


    • PET is superior to MR and CT for depiction of adenopathy



      • Metabolic changes may precede morphologic changes


      • Moderate to marked increase FDG uptake relative to normal structures


      • SUV is not helpful when characterizing lymph node lesions


    • Limitations



      • Lower spatial resolution compared to CT and MR


      • Cannot differentiate malignant from reactive adenopathy


      • Cannot differentiate malignant, infectious, or inflammatory processes


    • Poor anatomic resolution of PET is overcome by fusion with CT


Staging



  • General comments



    • Accurate staging is critical for guiding management


    • Important to avoid upstaging at time of surgery



      • Significant increase in morbidity when surgery and radiotherapy are combined


    • International Federation of Gynecology and Obstetrics (FIGO)

Sep 18, 2016 | Posted by in OBSTETRICS & GYNAECOLOGY IMAGING | Comments Off on Cervix Uteri Carcinoma
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