Slide of the Week: Severe Uterine Hemorrhage, November 28th, 2011

A 48 YO African American female presents with severe uterine bleeding.  She states that she has been bleeding very heavily for the past two days and the flow is increasing.  She also is diabetic and hypertensive. Pelvic examination revealed an enlarged irregularly shaped uterus.  A large mass was noted by ultrasonography and the uterus was removed.  A section of the mass is evaluated.

 

Uterine Hemorrhage

 

 

Click here to see the whole slide image.

Examine the H&E stained section.  What is your diagnosis?

  1. Leiomyosarcoma
  2. Adenocarcinoma
  3. Leiomyoma
  4. None of the above

 

 

Click here for the comparative pathology.

Scroll below for answers.


 

 

 

 

 

 

 

 

 

 

 

 

Answer: 3, Leiomyoma.

 

Comment:

Leiomyomas (fibroids) are very common benign uterine tumors.  It is estimated that 25% of women in their reproductive years will develop fibroids.  They rarely progress into a malignancy.  Until recently, it was thought that both progesterone and estrogen were the prime influencing factors in fibroid formation and there is considerable evidence that supports their involvement.  Recent studies, however, indicate that other factors may also play key roles. These include an inherited component and also growth factors such as: transforming growth factor-beta, fibroblast growth factor, epidermal growth factor and platelet-derived growth factor.  The exact inherited component is unknown at this time but the fact that fibroids run in families is an indicator that one or more will be found.  Further, a recent study demonstrated that 70% of fibroids exhibited mutations in MED-12.  These studies, and others, provide the current working hypothesis on fibroid development.  There are most likely several factors involved:  1) A genetic predisposition, 2) hormones (including those of environmental origin), and 3) growth factors.  Risk factors also include: obesity, diabetes, nulliparity, hypertension and being of African American descent.

 

References:

“MED12, the Mediator Complex Subunit 12 Gene, is Mutated at High Frequency in Uterine Leiomyomas”.  Makinen, N. et al. (2011).  Science. doi:10.1126/science.1208930. PMID 21868628.

Rein, MS (2000). “Advances in uterine leiomyoma research: the progesterone hypothesis”. Environmental health perspectives 108 Suppl 5: 791–3. PMID 11035984.

Maruo, T.; Ohara, N.; Wang, J.; Matsuo, H. (2004). “Sex steroidal regulation of uterine leiomyoma growth and apoptosis”. Human reproduction update 10 (3): 207–220. doi:10.1093/humupd/dmh019. PMID 15140868

Estradiol-dependent uterine leiomyomas in transgenic mice. Romagnolo, B, et al. J Clin Invest. 1996;98(3):777–784.   doi:10.1172/JCI118850.

Memy 1: a novel murine model for uterine leiomyoma using adenovirus-enhanced human fibroid explants in severe combined immune deficiency mice. Am J Obstet Gynecol. 2008 Aug;199(2):156.e1-8. Epub 2008 May 12 Hassan MH et al.

Constitutive Activation of Beta-Catenin in Uterine Stroma and Smooth Muscle Leads to Development of Mesenchymal Tumors in Mice.  Tanwar P.S. et al,  Biol of Reprod 81, 545-552 (2009). DOI 10.1095/biolreprod.108.075648

Establishment of a Novel Xenograft Model for Human Uterine Leiomyoma in Immunodeficient Mice.  Tsuiji, K. et al.  Tohoku Journal of Experimental Medicine. 222: pp55-61 (2010).

 

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