Cervix
Carcinoma
Squamous cell carcinoma

Author: Branko Perunovic, M.D. (see Authors page)

Revised: 17 May 2017, last major update May 2007

Copyright: (c) 2007-2017, PathologyOutlines.com, Inc.

PubMed search: cervix Squamous cell carcinoma [title]

Related topics: Large cell keratinizing squamous cell carcinoma, Large cell nonkeratinizing squamous cell carcinoma, Papillary squamourothelial carcinoma, Small cell squamous cell carcinoma

Cite this page: Squamous cell carcinoma. PathologyOutlines.com website. http://pathologyoutlines.com/topic/cervixSCC.html. Accessed May 25th, 2017.
Definition / general
  • 4,500 deaths/year in US, #8 cause of cancer death in women in US (was #1 in 1940's); still #1 in other countries
  • Reduction due to Papanicolaou smear test to detect premalignant lesions (1 million cases of SIL detected per year in US, 13,000 new invasive carcinomas, Cancer 2004;100:1035)
  • Mean age 51 years, uncommon before age 30 years but most are ages 45 - 55 years
  • Risk factors: early age at first intercourse, multiple sexual partners (Br J Cancer 2003;89:2078), male partner with multiple prior sexual partners, history of HSIL; HLA associations in Mexican women (Hum Pathol 1999;30:626)
    • Oral contraceptives (some studies), cigarette smoking (Int J Cancer 2006;118:1481), parity, family history, associated genital infections, no circumcision in male partner
  • Human papillomavirus (HPV): causes vulvar condyloma acuminatum (sexually transmitted), found in DNA of 95% of cervical cancers, 90% of condylomas and premalignant lesions
  • High risk HPV types for cervical carcinoma: 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68 and others
  • Low risk HPV types for cervical carcinoma: 6, 11, 42, 44 (associated with condyloma)
  • HPV acts via E6 and E7 genes, which differ in high vs. low risk HPV types; HPV is integrated in premalignant lesions with tumor DNA vs. present in episomes (not integrated) in condylomas; in HPV 16 and 18, E6 binds to p53, causing its proteolytic degradation; E7 binds to retinoblastoma gene (Rb) and displaces transcription factors normally bound by Rb
  • Other cofactors are important, because (a) most with HPV don't get cervical cancer, (b) 10-15% of cervical cancer is NOT associated with HPV
  • HIV or HTLV - 1 infection adversely affect the prognosis, may be associated with rapidly progressive course
  • Detect clinically via white patches after application of acetic acid to cervix; cervix also has mosaic vascular patterns at colposcopy
Drawings:

Images hosted on other servers:

Evolution of invasive
carcinoma from SIL

Prognostic factors
  • Clinical stage, nodal status, size of largest node and number of involved nodes, tumor size, depth of invasion, endometrial extension, parametrial involvement, angiolymphatic invasion
  • HPV negative patients do poorer
  • Possibly S phase fraction
  • Possibly tissue associated eosinophilia (poorer survival in one study, Hum Pathol 1996;27:904)
  • Squamous cell carcinoma antigen serum level in patients with advanced disease (Int J Cancer 2006;118:1481)
  • Not relevant: microscopic tumor grade, tumor type, angiogenesis
  • Spreads usually through cervical lymphatics in sequential manner; via direct extension to vagina, uterus, parametrium, lower urinary tract, uterosacral ligaments; distant metastases to aortic and mediastinal lymph nodes, lung, bones, ovary (1%)
  • 2/3 are stage I or II when diagnosed
Case reports
Metastases:
Treatment
  • Surgery (note: trachelectomy means cervicectomy), radiation therapy, radioactive implants (for early lesions), pelvic extenteration (for postradiation therapy relapse; 5 year survival is 23%; frozen section may be necessary to rule out extra - pelvic spread)
  • 5 year survival of patients treated 1993 - 1995 by stage: Ia1 - Ib1: > 95%, Ib2 - IIb: 80 - 90%, III: 50%, IV: 25 - 35%
Gross description
  • Polypoid or deeply invasive
Gross images

Images hosted on PathOut server:

Barrel shaped cervix

Ulcerative tumor



Images hosted on other servers:

Stage I tumor

Tumor extending to vagina

Stage IV tumor with bladder extension


Invading lower uterine segment

Squamous tumor

Microscopic (histologic) description
  • Invasion characterized by desmoplastic stroma, focal conspicuous maturation of tumor cells with prominent nucleoli, blurred or scalloped epithelial-stromal interface, loss of nuclear polarity
  • May have pseudoglandular pattern due to acantholysis and central necrosis
  • Rare findings are amyloid (Arch Pathol Lab Med 1993;117:199), signet ring cells (Int J Gynecol Cancer 1992;2:152), melanin granules (Int J Gynecol Pathol 2003;22:285)
  • May have HSIL / CIN3 like growth pattern (Int J Gynecol Cancer 2000;10:95)
  • Grading does not correlate with prognosis and is optional
  • Well differentiated: predominantly mature squamous cells with abundant keratin pearls, occasional well developed intercellular bridges, minimal pleomorphism, minimal mitotic activity
  • Moderately differentiated: less distinct cell borders and less cytoplasm than well differentiated tumors; also more nuclear pleomorphism and more mitotic activity
  • Poorly differentiated: small primitive appearing cells with scant cytoplasm, hyperchromatic nuclei and marked mitotic activity; no / rare keratinization; resembles HSIL
Microscopic (histologic) images

Images hosted on PathOut server:

Moderately differentiated
with invasion by
nests and single cells

Poorly differentiated
spindled tumor with
focal keratinization

Poorly differentiated
with markedly
pleomorphic nuclei

Central keratinization

Resembling clear cell carcinoma


Contributed by Frank Melgoza MD and Mai Gui MD PhD, UC Irvine



Grading:

Well differentiated with
prominent keratin pearl



Images hosted on other servers:

Various images

Invasive tumor

Margin involvement

Cdc6, MIB - 1 (figures G, H)


Cytology description
Positive stains
Negative stains
Electron microscopy description
  • Well developed intracytoplasmic tonofilaments, desmoplastic - tonofilament complexes and intercellular microvilli in well differentiated tumors, lost with decreasing differentiation
Electron microscopy images

Images hosted on other servers:

Tumor cell in intratumoral vessel

Molecular / cytogenetics description
  • Aneuploid but tumor may exhibit heterogeneity
  • HPV16 is associated with 3q amplification
Differential diagnosis
  • Clear cell carcinoma: papillary and tubulocystic areas, hobnail cells, no squamous differentiation, may be associated with DES exposure
  • Immature squamous metaplasia: uniform cell size and shape, no significant nuclear atypia
  • Placental site nodule: well circumscribed nodules of intermediate trophoblast cells, no / rare mitotic activity, HPL+
  • Small cell neuroendocrine carcinoma: diffuse infiltration of small cells with scant cytoplasm and hyperchromatic nuclei; often rosettes, trabeculae or ribbons; often crush artifact; immunoreactive for neuroendocrine markers
  • Squamous metaplasia with extensive glandular involvement or marked decidual reaction: no atypia, no / rare mitotic figures; decidua is keratin-
Additional references