Uterus

Smooth muscle tumors

Intravenous and diffuse leiomyomatosis



Last author update: 30 August 2023
Last staff update: 30 August 2023

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PubMed Search: Intravenous leiomyomatosis / diffuse leiomyomatosis

See Also: Leiomyoma

João Costa, M.D.
Sabrina Croce, M.D., Ph.D.
Page views in 2023: 4,172
Page views in 2024 to date: 2,625
Cite this page: Costa J, Croce S. Intravenous and diffuse leiomyomatosis. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/uterusleiomyomaintravascular.html. Accessed June 16th, 2024.
Definition / general
  • Intravenous leiomyomatosis
    • Rare entity characterized by an intravenous proliferation of benign smooth muscle cells; may coexist with leiomyoma
    • May present with pelvic and extrapelvic spread along venous vasculature
  • Diffuse leiomyomatosis
    • Rare entity characterized by a symmetrical uterine enlargement with innumerable poorly defined, confluent smooth muscle nodules that replace most of the myometrium
Essential features
  • Intravenous leiomyomatosis
    • Intravascular proliferation of tumor plugs composed by bland smooth muscle cells
    • Most cases are confined to the uterus but may present with pelvic and extrapelvic extension through the venous circulatory system
    • Clinical presentation is varied, nonspecific and dependent on tumor extension
    • Despite being a benign tumor, it may cause remarkable systematic complications and has a relatively high risk of recurrence
  • Diffuse leiomyomatosis
    • Diffuse, symmetrical thickening of the myometrium with innumerous poorly defined, coalescent nodules of bland smooth muscle cells
    • Clinical presentation is varied and nonspecific
    • Benign tumor, patients usually do not experience recurrence
Terminology
  • Intravenous leiomyomatosis: intravascular leiomyomatosis
  • Diffuse leiomyomatosis: diffuse uterine leiomyomatosis
ICD coding
  • Intravenous leiomyomatosis
    • ICD-O: 8890/1 - intravenous leiomyomatosis
    • ICD-11: 2E86.0 & XH60C2 - leiomyoma of uterus & intravascular leiomyomatosis
  • Diffuse leiomyomatosis
    • ICD-O: 8890/0 - leiomyoma, NOS
    • ICD-11: 2E86.0 - leiomyoma of uterus
Epidemiology
Sites
Pathophysiology
Etiology
Clinical features
  • Intravenous leiomyomatosis
    • Clinical manifestations are usually diverse, nonspecific and dependent on its location and extension
    • According to one group of authors, clinically, intravenous leiomyomatosis can be divided into 4 stages (Medicine (Baltimore) 2016;95:e4902)
      • Stage I: tumors invading the uterine vein and limited to the pelvis
      • Stage II: tumors extending to the abdominal cavity but without involvement of the renal vein
      • Stage III: tumors invading the renal vein and inferior vena cava and extending further up to the right atrium but without reaching the pulmonary arteries
      • Stage IV: tumors reaching the pulmonary arteries or metastasizing to the lungs
    • ~29.7% of patients reported in literature present in stages I / II and 65.6% in stages III / IV but patients with early lesions or asymptomatic patients may be underreported (Front Surg 2023;9:1020004)
    • When confined to the uterus, most patients are asymptomatic (J Obstet Gynaecol Res 2021;47:4357 Mod Pathol 2016;29:500, Medicine (Baltimore) 2016;95:e4902)
    • Some patients present with nonspecific symptoms suggestive of a pelvic mass and similar to uterine leiomyomas: hypermenorrhea, menostaxis, irregular vaginal bleeding, abdominal swelling or pelvic pain (J Obstet Gynaecol Res 2021;47:4357 Mod Pathol 2016;29:500, Medicine (Baltimore) 2016;95:e4902)
    • Cases with extrapelvic extension may present with edema and heaviness of the lower extremities (J Obstet Gynaecol Res 2021;47:4357)
    • In cases with cardiac and pulmonary extension, chest discomfort, dyspnea and syncope, congestive heart failure, pulmonary embolism and sudden death have been reported (J Obstet Gynaecol Res 2021;47:4357)
  • Diffuse leiomyomatosis
Diagnosis
Radiology description
  • Intravenous leiomyomatosis
    • The most typical CT features of intravenous leiomyomatosis described are (Clin Radiol 2018;73:503.e1, BMC Cancer 2016;16:73)
      • Continuous pelvic and intravenous masses, with heterogeneous enhancement and occasionally, presence of blood vessels in the lesion
      • Lesions in the inferior vena cava that are continuous and shaped like sausages
      • In cases with involvement of the right cardiac chambers, the cardiac imaging findings show a snake head or walking stick head appearance
      • No invasion or adhesion to the vessel wall
      • May present with calcifications
    • Cases invading the inferior vena cava may have a characteristic feature on contrast enhancing CT and MRI: the growth pattern and the small vessels within the tumor create an appearance similar to a sieve on axial images and a luffa sponge on coronal images (Clin Radiol 2018;73:503.e1)
  • Diffuse leiomyomatosis
    • Imaging techniques reveal symmetrical and uniform enlargement of the uterus, with innumerable coalescing nodules of different sizes with indistinct borders in the myometrium (World J Clin Cases 2022;10:8797)
    • Typical leiomyomas are well circumscribed masses with an asymmetrical involvement of the uterus and usually demonstrate low / intermediate signal intensity on T2 weighted images, which can be difficult to appreciate in diffuse leiomyomatosis (Radiol Case Rep 2022;17:1536, Eur Radiol 2018;28:3125)
Radiology images

Images hosted on other servers:

Intravenous leiomyomatosis
Intravenous leiomyomatosis - Contrast enhancing CT

Contrast enhancing CT

Intravenous leiomyomatosis - Magnetic resonance imaging

MRI

 
Diffuse leiomyomatosis
Diffuse leiomyomatosis - Magnetic resonance imaging

MRI

Prognostic factors
Case reports
  • Intravenous leiomyomatosis
    • 31 year old woman with a history of myomectomy presented with abnormal uterine bleeding, anemia and multiple uterine nodules (Radiol Case Rep 2022;17:4203)
    • 49 year old woman presented with dyspnea, abdominal distension and a large uterine mass extending to the right parauterine veins, right ovarian vein and the inferior vena cava (Taiwan J Obstet Gynecol 2021;60:367)
    • 52 year old woman presented with lower abdominal pain, a 270 mm uterine mass and a 78 x 47 mm mass in the right atrium (Diagn Pathol 2020;15:4)
  • Diffuse leiomyomatosis
    • 27 year old woman presented with heavy vaginal bleeding and a regularly enlarged uterus (World J Clin Cases 2022;10:8797)
    • 36 year old woman presented with a 1 year history of lower abdominal discomfort and dysmenorrhea and a markedly enlarged uterus replaced by innumerable nodules (Radiol Case Rep 2022;17:1536)
    • 38 year old nulliparous woman presented with abdominal distension and an enlarged uterus of size 250 x 200 x 130 mm (Cureus 2022;14:e29595)
Treatment
  • Intravenous leiomyomatosis
    • Surgery is the main treatment option (J Obstet Gynaecol Res 2021;47:4357, Medicine (Baltimore) 2021;100:e24228, J Int Med Res 2020;48:300060519896887, Front Surg 2023;9:1020004)
      • Complete removal of the lesion is crucial to obtain a favorable prognosis
      • Controversy surrounding the selection of the different surgical approaches
      • Hysterectomy is recommended for most patients
      • Bilateral oophorectomy has also been recommended for patients who are menopausal / perimenopausal or with extrauterine extension but recent studies questioned its usefulness
      • Myomectomy has been proposed as an option for young women who wish to preserve fertility but it has been associated with an increased risk of recurrence
      • Multidisciplinary surgical approach is required in cases of extrapelvic extension
      • 1 stage or 2 stage surgery may be employed, depending on several factors, such as patient's tolerance and tumor extension
      • Complete tumor resection is achieved in 56 - 92.1% of patients
    • Use of postoperative hormone treatment is controversial (J Obstet Gynaecol Res 2021;47:4357, Medicine (Baltimore) 2021;100:e24228)
      • Gonadotropin releasing hormone agonist was previously recommended as a postoperative approach to reducing the risk of recurrence in cases with preservation of both ovaries or impossibility of complete resection but recent studies have questioned its effectiveness
      • Use of tamoxifen and aromatase inhibitors has also been reported
  • Diffuse leiomyomatosis
Gross description
Gross images

Contributed by Sabrina Croce, M.D., Ph.D.

Intravenous leiomyomatosis
Tumor plugs

Tumor plugs

 
Diffuse leiomyomatosis
Diffuse myometrial expansion

Diffuse myometrial expansion

Numerous coalescing nodules

Numerous coalescing nodules

Symmetrical myometrial enlargement

Symmetrical myometrial enlargement



Images hosted on other servers:

Intravenous leiomyomatosis
Intravenous leiomyomatosis Intravenous leiomyomatosis

Tumor plugs

Involvement of myometrial vessels

Microscopic (histologic) description
Microscopic (histologic) images

Contributed by Sabrina Croce, M.D., Ph.D.

Intravenous leiomyomatosis
Tumor plugs Tumor plugs

Tumor plugs

Tumor plugs

Tumor plugs

Plexiform appearance

Plexiform appearance


Coexisting leiomyoma

Coexisting leiomyoma

Estrogen receptor

Estrogen receptor

Desmin

Desmin

Desmin

CD34



Diffuse leiomyomatosis
Numerous confluent nodules Numerous confluent nodules

Numerous confluent nodules

Poorly defined nodules Poorly defined nodules

Poorly defined nodules


Well defined contours

Well defined contours

Progesterone receptor

Progesterone receptor

Progesterone receptor

Caldesmon

Virtual slides

Images hosted on other servers:
Intravenous leiomyomatosis

Intravenous leiomyomatosis

Diffuse leiomyomatosis

Diffuse leiomyomatosis

Positive stains
Negative stains
Molecular / cytogenetics description
  • Intravenous leiomyomatosis
    • Some cases of intravenous leiomyomatosis demonstrate balanced translocations t(12;14)(q14-15;q23-24), commonly observed in uterine leiomyomas (Hum Pathol 2022;120:18, Mod Pathol 2016;29:500, Cancer Med 2020;9:4581)
      • Breakpoint on 12q14-15 typically results in overexpression of HMGA2, as evidenced by high levels of HMGA2 staining
      • HMGA2 overexpression and t(12;14)(q15;q24) likely have important roles in tumorigenesis but additional genetic alterations might explain the quasimalignant behavior of intravenous leiomyomatosis
    • Recurrent 22q and 1p regional losses and 12q gains have been reported (Cancers (Basel) 2022;14:2907, Mod Pathol 2016;29:500, Int J Gynecol Pathol 2015;34:169)
    • Unlike leiomyomas, MED12 mutations have been rarely reported in intravenous leiomyomatosis (Cancers (Basel) 2022;14:2907, Mod Pathol 2016;29:500, Int J Gynecol Pathol 2015;34:169)
    • X chromosome inactivation analysis confirmed the monoclonal origin of intravenous leiomyomatosis (Mod Pathol 2002;15:351, Mod Pathol 2016;29:500)
    • Comparative genomic hybridization analysis on a benign metastasizing leiomyoma of the lung and uterine intravenous leiomyomatosis suggested that these entities may represent different points from the same neoplastic continuum (Pathol Res Pract 2018;214:871, Mod Pathol 2002;15:351)
    • RNA sequencing shows that intravenous leiomyomatosis appears to have higher expression of angiogenesis and antiapoptotic factors when compared to uterine leiomyomas (Cancer Med 2020;9:4581)
      • These factors may be associated with the characteristic continuous extension growth and proliferation rate of intravenous leiomyomatosis
      • Gene expression profile of intravenous leiomyomatosis is more complex than that of leiomyomas
    • Comparative proteomic profiling study of intravenous leiomyomatosis and other smooth muscle tumors described the selective enrichment of coregulated splicing factors, which may be associated with distinct biological pathways (Cancers (Basel) 2022;14:2907)
  • Diffuse leiomyomatosis
Videos

Intravenous leiomyomatosis

Sample pathology report
  • Uterus, hysterectomy:
    • Intravenous leiomyomatosis (see comment)
    • Comment: Microscopic examination reveals several tumor plugs inside dilated vessels. The tumor plugs are comprised of smooth muscle cells with a fascicular and plexiform architecture and are lined by endothelial cells. The mitotic activity is estimated at 2 mitoses/10 high power fields. No cytologic atypia or tumor cell necrosis is observed. The tumor plugs present with extension to the broad ligament vessels. Additionally, an intramural uterine leiomyoma is observed. Intravenous leiomyomatosis is a benign smooth muscle tumor, albeit with the potential for locoregional and distant recurrence. Clinical and imagiological correlation to determine the presence of intravenous extension beyond the uterus and broad ligament, as well as postoperative residual lesions, is advised. Close clinical follow up is recommended.

  • Uterus, hysterectomy:
    • Diffuse leiomyomatosis (see comment)
    • Comment: Microscopic examination reveals numerous poorly circumscribed, coalescent nodules within the myometrium, composed of smooth muscle cells, organized into interlacing fascicles. The mitotic activity is estimated at 1 mitosis/10 high power fields. No cytologic atypia or tumor cell necrosis is observed. The morphology is consistent with diffuse leiomyomatosis.
Differential diagnosis
  • Intravenous leiomyomatosis
    • Uterine lymphangioleiomyomatosis:
    • Leiomyoma with vascular invasion:
    • Dissecting (cotyledonoid) leiomyoma:
      • Characterized by tongues and broad fascicles of smooth muscle cells, dissecting the myometrium
      • May have varying degrees of hydropic change and numerous blood vessels (Hum Pathol 2011;42:1240)
      • No atypia or necrosis
      • No intravascular growth (Hum Pathol 2011;42:1240)
    • Uterine leiomyosarcoma:
      • Moderate / marked cytologic atypia, presence of tumor cell necrosis or numerous mitotic figures, including atypical mitosis
      • Recurrences of intravenous leiomyomatosis may lead to suspicion of a missed diagnosis of a leiomyosarcoma
        • Bland nuclear features, low mitotic activity and lack of tumor cell necrosis favor intravenous leiomyomatosis
        • History of hysterectomy / myomectomies and histological review of previous uterine specimens (if possible) may also aid in the diagnosis
        • Consultation services should be considered for difficult cases
    • Low grade endometrial stromal sarcoma:
      • Composed of cells resembling proliferative phase endometrium
      • Infiltrative / permeative growth in the myometrium
      • May be associated with lymphovascular invasion, with numerous intravascular tumor plugs, grossly detected
      • Most cases show diffuse, strong expression of ER, PR, CD10 and IFITM1
      • Immunohistochemical panel of at least 2 smooth muscle markers (desmin and caldesmon) and CD10 may be helpful in the differential diagnosis
      • May show areas with smooth muscle differentiation, which may be positive for caldesmon, desmin, ER, PR and variably positive for CD10
        • Searching for areas with the classical morphological and immunohistochemical features and molecular testing may aid in the diagnosis
      • Differential diagnosis with intravenous leiomyomatosis may be challenging, especially with intravenous adenomyomatosis comprised only of endometrial stroma
  • Diffuse leiomyomatosis
    • Multiple leiomyomas:
      • Asymmetrical involvement of the myometrium and sharp circumscription of the individual leiomyomas, unlike diffuse leiomyomatosis
    • Intravascular leiomyomatosis:
      • May also have a multinodular appearance
      • Presence of coalescing nodules without associated intravascular involvement allows the diagnosis of diffuse leiomyomatosis
      • Some cases of diffuse leiomyomatosis may present with concomitant intravenous leiomyomatosis
    • Endometrial stromal sarcoma:
      • Multinodular appearance and permeative growth may raise this differential diagnosis
      • Morphological, immunohistochemical and molecular features allow for this diagnosis
    • PEComatosis:
Board review style question #1

A 42 year old woman with metrorrhagia, abdominal pain and imaging findings suggestive of multiple leiomyomas was submitted to a hysterectomy. A representative microscopic image is shown above. Which of the following hypotheses is true?

  1. CD10 is consistently negative in these tumors
  2. High mitotic rates are frequently observed in these tumors
  3. These are benign tumors, without risk of spread beyond the uterus
  4. These lesions are associated with tuberous sclerosis complex
  5. These lesions may coexist with leiomyomas
Board review style answer #1
E. These lesions may coexist with leiomyomas. Presence of a coexisting uterine leiomyoma has been estimated to be 38.9 - 61.5% of cases. Answer D is incorrect because intravenous leiomyomatosis has not been associated with tuberous sclerosis complex, unlike lymphangioleiomyomatosis, an important differential diagnosis. Answer A is incorrect because CD10 is weakly positive in some cases and strongly positive in cases of intravascular adenomyomatosis. Answer B is incorrect because these tumors present with no or occasional mitotic figures (< 2/10 high power fields). Answer C is incorrect because intravenous leiomyomatosis is a benign tumor that may present with pelvic and extrapelvic spread along venous vasculature.

Comment Here

Reference: Intravenous and diffuse leiomyomatosis
Board review style question #2
Which of the following observations is true regarding diffuse uterine leiomyomatosis?

  1. Cytologic atypia and high mitotic counts are typical of this tumor
  2. It is a benign condition with a relatively high risk of recurrence
  3. It is often characterized by an asymmetrical thickening of the myometrium
  4. Numerous well defined, confluent nodules are present in the myometrium
  5. X chromosome inactivation analysis suggests a polyclonal origin of the different nodules
Board review style answer #2
E. X chromosome inactivation analysis suggests a polyclonal origin of the different nodules. X chromosome inactivation analysis supports the hypothesis of an independent clonal origin of the different nodules (Hum Pathol 2000;31:1429). Answers C and D are incorrect because diffuse leiomyomatosis classically is characterized by a diffuse, symmetrical thickening of the myometrium with numerous poorly defined, confluent nodules. Answer B is incorrect because patients usually do not experience recurrence (only 2 cases of recurrence after conservative surgery have been reported). Answer A is incorrect because diffuse leiomyomatosis does not show significant cytologic atypia and only demonstrates low mitotic activity.

Comment Here

Reference: Intravenous and diffuse leiomyomatosis
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