Endometrial cancer differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Qurrat-ul-ain Abid, M.D.[2]; Monalisa Dmello, M.B,B.S., M.D. [3]Roukoz A. Karam, M.D.[4]

Overview

In early stages endometrial cancer must be differentiated from diseases that cause abnormal uterine bleeding and endometrial thickening on ultrasound, such as endometrial hyperplasia, endometrial polyp, and submucosal uterine leiomyoma. In advanced stages endometrial cancer must be differentiated from uterine sarcoma and uterine lymphoma.

Differentiating Endometrial Cancer From Other Diseases

Diseases Clinical manifestations Para-clinical findings Gold standard
Symptoms Physical examination
Lab Findings Imaging Pap Smear Histopathology
Bleeding Pelvic Pain/pressure/

discomfort

Other Abdomino-pelvic examination Hb B-HCG CA-125 Ultrasound MRI
Endometrial cancer[2][3][4][5] ± ↓ – +
  • Atypical glandular cells
 Endometrial malignant cells
  • Low grade Type I
  • High grade Type II
Uterine

leiomyosarcoma[6][7][8][9]

± ↓ – +
  • Shows details of uterine mass boundaries, extent and spread
  • Negative
Diseases Bleeding Pelvic Pain/pressure/

discomfort

Other Pelvic examination Hb B-HCG CA-125 Ultrasound MRI Pap Smear Histopathology Gold standard
Uterine leiomyoma[10][11][12] + ↓ or Nl – –
  • Hypoechoic, well-circumscribed round masses
  • Location of fibroid: Submucosal, intramural, subserosal, and cervical fibroids
  • Normal
  • Imaging and histologic analysis
Uterine carcinosarcomas (Malignant mixed mullerian tumour (MMMT) of the uterus)[13][14][15][16] ± ↓ – +
  • Heterogenous bulky polypoid mass with intense enhancement
  • Biphasic:
Cervical cancer[17][18] ±

Pressure-related bowel and bladder symptoms

↓ – ±
  • To evaluate tumor size, extent and parametrial invasion
  • Usually not needed for diagnosis
  • To evaluate tumor size, local extent and staging
  • Low-grade squamous intraepithelial lesions (LSILs)
  • High-grade squamous intraepithelial lesions (HSILs)
  • Atypical glandular cells (AGC)
  • Endocervical adenocarcinoma in situ (AIS)
Diseases Bleeding Pelvic Pain/pressure/

discomfort

Other Pelvic examination Hb B-HCG CA-125 Ultrasound MRI Pap Smear Histopathology Gold standard
Metastasis ± ↓ – –
  • Not recommended
  • It may show the malignant cells of the primary site
Endometrial polyp[19][20] –
  • Asymptomatic
  • Endometrial polyp prolapses (visible on speculum examination protruding through cervical os)
  • Normal sized uterus with smooth surface
 ↓ – + or Nl
  • MRI will show polyp size and dimension in detail
  • Not required for diagnosis
  • Normal
Endometrial hyperplasia[21][22][23][24] –
  • Asymptomatic
 ↓ – +
  • Determines endometrial thickness
  • Rules out other abnormalities
  • Non-neoplastic changes:
  • Disordered endometrial growth
  • Benign hyperplasia
  • Simple hyperplasia
  • Complex hyperplasia without atypia
  • Precancerous changes:
  • Endometrial intraepithelial neoplasms
  • Atypical complex hyperplasia
Uterine adenomyosis[25][26][27] – ±
  • Diffusely enlarged tender boggy uterus with smooth surface
  • Uterus may develop masses
 ↓ – +
Diseases Bleeding Pelvic Pain/pressure/

discomfort

Other Pelvic examination Hb B-HCG CA-125 Ultrasound MRI Pap Smear Histopathology Gold standard
Hematometra (blood within the uterine cavity)

[28][29]

– +

Cramping cyclic pain

↓ – –
  • Not required
  • Normal
  • Biopsy is not required for diagnosis
Gestational trophoblastic disease[30][31] + ↓ ± +
  • Dilated grape like structures
  • Diffuse hydropic swelling
  • Multiples echoes
  • Cystic spaces invading edometrium and myometrium (in case of invasive disease)
  • MRI defines the extent of primary lesion, invasion and distant metastasis
  • Trophoblastic cells
  • Dilated grape like villous structures
  • Invasive malignant lesions
  • Imaging
  • Histologic diagnosis
Incomplete abortion + N/↓ ± +↓
  • Not required for the diagnosis
  • Not required for the diagnosis
  • Imaging
  • Histologic diagnosis
Pregnancy
  • Absent menstrual cycle
  • May have intermenstrual bleeding
 + – + –
  • Normal or may show cervical cells
Uterine lymphoma[1][32][33][34] + ↓ - -
Diseases Bleeding Pelvic Pain/pressure/

discomfort

Other Pelvic examination Hb B-HCG CA-125 Ultrasound MRI Pap Smear Histopathology Gold standard

References

  1. ↑ 1.0 1.1 Hippisley-Cox J, Coupland C (2011). "Identifying women with suspected ovarian cancer in primary care: derivation and validation of algorithm". BMJ. 344: d8009. doi:10.1136/bmj.d8009. PMC 3251328. PMID 22217630.
  2. ↑ "ACOG practice bulletin, clinical management guidelines for obstetrician-gynecologists, number 65, August 2005: management of endometrial cancer". Obstet Gynecol. 106 (2): 413–25. August 2005. PMID 16055605.
  3. ↑ Boruta DM, Gehrig PA, Fader AN, Olawaiye AB (October 2009). "Management of women with uterine papillary serous cancer: a Society of Gynecologic Oncology (SGO) review". Gynecol. Oncol. 115 (1): 142–153. doi:10.1016/j.ygyno.2009.06.011. PMID 19592079.
  4. ↑ Bokhman JV (February 1983). "Two pathogenetic types of endometrial carcinoma". Gynecol. Oncol. 15 (1): 10–7. PMID 6822361.
  5. ↑ Felix AS, Weissfeld JL, Stone RA, Bowser R, Chivukula M, Edwards RP, Linkov F (November 2010). "Factors associated with Type I and Type II endometrial cancer". Cancer Causes Control. 21 (11): 1851–6. doi:10.1007/s10552-010-9612-8. PMC 2962676. PMID 20628804.
  6. ↑ Nordal RR, Thoresen SO (May 1997). "Uterine sarcomas in Norway 1956-1992: incidence, survival and mortality". Eur. J. Cancer. 33 (6): 907–11. PMID 9291814.
  7. ↑ Goto A, Takeuchi S, Sugimura K, Maruo T (2002). "Usefulness of Gd-DTPA contrast-enhanced dynamic MRI and serum determination of LDH and its isozymes in the differential diagnosis of leiomyosarcoma from degenerated leiomyoma of the uterus". Int. J. Gynecol. Cancer. 12 (4): 354–61. PMID 12144683.
  8. ↑ Bell SW, Kempson RL, Hendrickson MR (June 1994). "Problematic uterine smooth muscle neoplasms. A clinicopathologic study of 213 cases". Am. J. Surg. Pathol. 18 (6): 535–58. PMID 8179071.
  9. ↑ Karpathiou G, Sivridis E, Giatromanolaki A (2010). "Myxoid leiomyosarcoma of the uterus: a diagnostic challenge". Eur. J. Gynaecol. Oncol. 31 (4): 446–8. PMID 20882892.
  10. ↑ Stewart EA (April 2015). "Clinical practice. Uterine fibroids". N. Engl. J. Med. 372 (17): 1646–55. doi:10.1056/NEJMcp1411029. PMID 25901428.
  11. ↑ Dueholm M, Lundorf E, Hansen ES, Ledertoug S, Olesen F (March 2002). "Accuracy of magnetic resonance imaging and transvaginal ultrasonography in the diagnosis, mapping, and measurement of uterine myomas". Am. J. Obstet. Gynecol. 186 (3): 409–15. PMID 11904599.
  12. ↑ Omary RA, Vasireddy S, Chrisman HB, Ryu RK, Pereles FS, Carr JC, Resnick SA, Nemcek AA, Vogelzang RL (November 2002). "The effect of pelvic MR imaging on the diagnosis and treatment of women with presumed symptomatic uterine fibroids". J Vasc Interv Radiol. 13 (11): 1149–53. PMID 12427815.
  13. ↑ Chaffer CL, San Juan BP, Lim E, Weinberg RA (December 2016). "EMT, cell plasticity and metastasis". Cancer Metastasis Rev. 35 (4): 645–654. doi:10.1007/s10555-016-9648-7. PMID 27878502.
  14. ↑ Zhao S, Bellone S, Lopez S, Thakral D, Schwab C, English DP, Black J, Cocco E, Choi J, Zammataro L, Predolini F, Bonazzoli E, Bi M, Buza N, Hui P, Wong S, Abu-Khalaf M, Ravaggi A, Bignotti E, Bandiera E, Romani C, Todeschini P, Tassi R, Zanotti L, Odicino F, Pecorelli S, Donzelli C, Ardighieri L, Facchetti F, Falchetti M, Silasi DA, Ratner E, Azodi M, Schwartz PE, Mane S, Angioli R, Terranova C, Quick CM, Edraki B, Bilgüvar K, Lee M, Choi M, Stiegler AL, Boggon TJ, Schlessinger J, Lifton RP, Santin AD (October 2016). "Mutational landscape of uterine and ovarian carcinosarcomas implicates histone genes in epithelial-mesenchymal transition". Proc. Natl. Acad. Sci. U.S.A. 113 (43): 12238–12243. doi:10.1073/pnas.1614120113. PMC 5087050. PMID 27791010.
  15. ↑ Callister M, Ramondetta LM, Jhingran A, Burke TW, Eifel PJ (March 2004). "Malignant mixed Müllerian tumors of the uterus: analysis of patterns of failure, prognostic factors, and treatment outcome". Int. J. Radiat. Oncol. Biol. Phys. 58 (3): 786–96. doi:10.1016/S0360-3016(03)01561-X. PMID 14967435.
  16. ↑ Teo SY, Babagbemi KT, Peters HE, Mortele KJ (July 2008). "Primary malignant mixed mullerian tumor of the uterus: findings on sonography, CT, and gadolinium-enhanced MRI". AJR Am J Roentgenol. 191 (1): 278–83. doi:10.2214/AJR.07.3281. PMID 18562759.
  17. ↑ "Pap and HPV Testing - National Cancer Institute".
  18. ↑ Benedet JL, Bender H, Jones H, Ngan HY, Pecorelli S (August 2000). "FIGO staging classifications and clinical practice guidelines in the management of gynecologic cancers. FIGO Committee on Gynecologic Oncology". Int J Gynaecol Obstet. 70 (2): 209–62. PMID 11041682.
  19. ↑ Kim KR, Peng R, Ro JY, Robboy SJ (August 2004). "A diagnostically useful histopathologic feature of endometrial polyp: the long axis of endometrial glands arranged parallel to surface epithelium". Am. J. Surg. Pathol. 28 (8): 1057–62. PMID 15252313.
  20. ↑ Salim S, Won H, Nesbitt-Hawes E, Campbell N, Abbott J (2011). "Diagnosis and management of endometrial polyps: a critical review of the literature". J Minim Invasive Gynecol. 18 (5): 569–81. doi:10.1016/j.jmig.2011.05.018. PMID 21783430.
  21. ↑ Emons G, Beckmann MW, Schmidt D, Mallmann P (February 2015). "New WHO Classification of Endometrial Hyperplasias". Geburtshilfe Frauenheilkd. 75 (2): 135–136. doi:10.1055/s-0034-1396256. PMC 4361167. PMID 25797956.
  22. ↑ Wright TC, Massad LS, Dunton CJ, Spitzer M, Wilkinson EJ, Solomon D (October 2007). "2006 consensus guidelines for the management of women with abnormal cervical screening tests". J Low Genit Tract Dis. 11 (4): 201–22. doi:10.1097/LGT.0b013e3181585870. PMID 17917566.
  23. ↑ Espindola D, Kennedy KA, Fischer EG (December 2007). "Management of abnormal uterine bleeding and the pathology of endometrial hyperplasia". Obstet. Gynecol. Clin. North Am. 34 (4): 717–37, ix. doi:10.1016/j.ogc.2007.09.001. PMID 18061866.
  24. ↑ Montgomery BE, Daum GS, Dunton CJ (May 2004). "Endometrial hyperplasia: a review". Obstet Gynecol Surv. 59 (5): 368–78. PMID 15097798.
  25. ↑ McElin TW, Bird CC (1974). "Adenomyosis of the uterus". Obstet Gynecol Annu. 3: 425–41. PMID 4608783.
  26. ↑ Maheshwari A, Gurunath S, Fatima F, Bhattacharya S (July 2012). "Adenomyosis and subfertility: a systematic review of prevalence, diagnosis, treatment and fertility outcomes". Hum. Reprod. Update. 18 (4): 374–92. doi:10.1093/humupd/dms006. PMID 22442261.
  27. ↑ Byun JY, Kim SE, Choi BG, Ko GY, Jung SE, Choi KH (October 1999). "Diffuse and focal adenomyosis: MR imaging findings". Radiographics. 19 Spec No: S161–70. doi:10.1148/radiographics.19.suppl_1.g99oc03s161. PMID 10517452.
  28. ↑ McCausland AM, McCausland VM (2007). "Long-term complications of endometrial ablation: cause, diagnosis, treatment, and prevention". J Minim Invasive Gynecol. 14 (4): 399–406. doi:10.1016/j.jmig.2007.04.004. PMID 17630156.
  29. ↑ U Nayak A, Swarup A, G S J, N S (April 2010). "Hematometra and acute abdomen". J Emerg Trauma Shock. 3 (2): 191–2. doi:10.4103/0974-2700.62117. PMC 2884455. PMID 20606801. Vancouver style error: name (help)
  30. ↑ Bakri YN, Berkowitz RS, Khan J, Goldstein DP, von Sinner W, Jabbar FA (March 1994). "Pulmonary metastases of gestational trophoblastic tumor. Risk factors for early respiratory failure". J Reprod Med. 39 (3): 175–8. PMID 8035373.
  31. ↑ Lurain JR (December 2010). "Gestational trophoblastic disease I: epidemiology, pathology, clinical presentation and diagnosis of gestational trophoblastic disease, and management of hydatidiform mole". Am. J. Obstet. Gynecol. 203 (6): 531–9. doi:10.1016/j.ajog.2010.06.073. PMID 20728069.
  32. ↑ Samama M, van Poelgeest M (September 2011). "Primary malignant lymphoma of the uterus: a case report and review of the literature". Case Rep Oncol. 4 (3): 560–3. doi:10.1159/000334852. PMC 3251245. PMID 22220150.
  33. ↑ Shen CJ, Tsai EM, Tsai KB, Wu CH, Hsu SC (March 2007). "Primary T-cell lymphoma of the uterine corpus". Kaohsiung J. Med. Sci. 23 (3): 138–41. doi:10.1016/S1607-551X(09)70388-2. PMID 17389178.
  34. ↑ Heeren JH, Croonen AM, Pijnenborg JM (April 2008). "Primary extranodal marginal zone B-cell lymphoma of the female genital tract: a case report and literature review". Int. J. Gynecol. Pathol. 27 (2): 243–6. doi:10.1097/PGP.0b013e3181569a0a. PMID 18317217.
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