Leiomyosarcoma differential diagnosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief:  Nima Nasiri, M.D.[2]

## Overview

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Leiomyosarcoma must be differentiated from other soft tissue tumors, some variants of leiomyoma resembles malignant tumor. Other possible differential diagnosis of leimyosarcoma include, epithelioid endometrial stromal sarcoma, epithelioid angiosarcoma.

## Differentiating Leiomyosarcoma from other Diseases

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The table below summarizes the findings that differentiate Leiomyosarcoma from other conditions that may cause similar signs and symptoms.[1][2][3]

Diseases  | Clinical manifestations | Para-clinical findings  | Gold standard | Additional findings

|
|
|
|

Symptoms | Physical examination
Lab Findings  | Imaging  | Histology
Ultrasound  | CT scan  | MRI
Uterine Leiomyosarcoma[4][5][6] |

* Abnormal vaginal bleeding (Postmenopausal or intermenstrual bleeding or bleeding from uterus or vagina)
* Pressure or pain pelvic or abdomen
* Vaginal discharge
* Change in bladder or bowel habits
* Fatigue
* Fever
* Malaise
* Weight loss

* Lump protruding from vagina

* Mass in abdomen or pelvic

* Tenderness on palpating pelvic or abdomen

* Lymphadenopathy

* ↓ RBC or Hemoglobin may be seen on CBC.
* In uterine leiomyosarcomas (LMSs) p16 is overexpressed compared with leiomyoma.

* Deep myometrial invasion

* Massive uterine enlargement
* Irregular central zones of low attenuation,
* Extensive necrosis and hemorrhage

* Features such as tumor localization, irregular or nodular margins, necrosis, rapid growth, intense contrast enhancement, and restriction at diffusion-weighted imaging can suggest the diagnosis and help differentiate from more common leiomyomas and endometrial carcinoma.

* Gross histology:
* Large, solitary, poorly circumscribed masses (average 10 cm)
* Typically display a fleshy variegated cut surface with areas of hemorrhage or necrosis

* Histology and biopsy

* Women with sarcoma vs women with fibroids, tend to be older
* More likely to be postmenopausal
* More likely to have a history of another nonuterine malignancy
* Women with sarcoma were more likely to have masses that are subserosal
* Solitary rather than multiple uterine mass

Leiomyoma (mitotically active type)[7][8][9][10][11][12] |

* Vaginal bleeding

* Pelvic pain
* Urinary retention
* Constipation
* Infertility
* Bowel obstruction
* Vaginal discharge

* Large,irregular pelvic mass

* CBC suggestive of anemia
* Bcl-2 expression is more frequent and strong marker in leiomyomas compared with leiomyosarcoma.

* Enlarged uterus with multiple whorled mass lesions, largest of size 8.6×7.1 cm, not extending into the abdomen

* An enlarged uterus and a deformed uterine contour are the most common CT findings of leiomyomas
* Leiomyomas usually have a uniformly solid consistency

T2-weighted MRI:

* Hypointense masses
* Homogeneous

enhancement

* Red degeneration

* Abscence of cytologic atypia

* Mild nuclear atypia, up to 10-20 mitosis

* No tumor cell necrosis

* Biopsy and histology

Hemorrhagic cellular leiomyomas (apoplectic leiomyoma)[13][14] |

* Abdominal pain
* Vaginal bleeding

* Pelvic pain
* Urinary retention
* Constipation
* Infertility
* Bowel obstruction
* Vaginal discharge

* Large,irregular pelvic mass

* ↓ RBC or Hemoglobin on CBC

* Irregularly enlarged uterus, usually hypoechoic but can be isoechoic and even hyperechoic as well.

* Enlarged uterus with irregular border

| T2-weighted MRI:

* Hypointense masses

| On microscopic analysis:

* Zones of recent hemorrhage within nodules of hypercellular smooth muscle.

* Coagulative necrosis (red degeneration)

Mitotic figure not exceeding 2/10 HPF, mostly located in the perihemorrhagic areas

On gross examination:

* Features of multiple hemorrhagic area
* Necrosis
* Cyst formation
* Softening, or color different than the usual leiomyoma

* Biopsy specimen and histology

PEComa[15][16][17] |

* Palpable abdominal masses
* Abnormal vaginal bleeding
* Flank pain (kidneys)
* Dull abdominal pain in right upper quadrant (liver)

* Lower abdominal pain with a palpable mass

* PECs typically stain for melanocytic markers (HMB-45, HMSA-1, Melan A (Mart 1), micro-ophthalmia transcription factor (Mitf), myogenic markers (actin), and less commonly desmin

* Granulomatous ovoid uterine tumor with a rich vascular network

* Mean tumor diameter of 5 cm, well-defined margins, hypodense mass

* Low and high signal intensity on T1- and T2-weighted MRI
* Strong, heterogeneous enhancement

| Microscopic analysis:

* Perivascular location
* Epithelioid, elongated and spindle shaped, or vacuolated (adipocyte-like).
* Clear to granular, lightly eosinophilic cytoplasm
* Nuclear atypia

* Biopsy

* Association with lymphangiomyomatosis and tuberous sclerosis

Epitheloid angiosarcoma[18][19][20] |

* Painful, enlarging soft tissue masses

* Long bone fractures
* Arteriovenous shunting and subsequent high-output cardiac failure symptoms such as dyspnea on exertion.

* Peritoneal bleeding in some cases
* Painful, enlarging soft tissue masses

* Strongly positive for vimentin
* Positive for cytokeratin
* CD31, CD34

* Nonspecific

* Bulky or normal size uterus

* Intratumoral blood flow on Doppler

* Enhanced huge enhanced round heterogenous solid mass with internal multifocal cysts on CT scan

| T2-weighted MRI:

* Focal areas of high signal intensity, known as the “cauliflower-like appearance” on gadolinium-enhanced MRI

| Microscopic histology:

* Nodules, and trabeculae of infiltrative epithelioid to spindled cells
* Eosinophilic cytoplasm.

* Biopsy and histology

* Epithelioid angiosarcoma has a male predilection
* Most often arises in the deep soft tissues (usually intramuscular) of the extremities, but a variety of primary sites, including the thyroid gland can be involved.
* Early nodal and solid organ metastasis, especially to the lungs, bone, soft tissue, and skin.

Intravenous leiomyomatosis[21][22][23] |

* Symptoms varies depending on tumor location.
* Symptoms related to uterine leiomyoma such as abdominal pain, abnormal uterine bleeding, and abdominal distension
* Dyspnea, lower extremity edema in case of cardiac involvement

* Jugular venous distension
* Lower extremity edema
* Abdominal mass

* No specific lab finding

* Vascularized thrombi within the pelvic veins and inferior vena cava

* Irregular mass exhibiting heterogeneous enhancement with extension into adjacent veins

* Leiomyomatous lesion or a distorted uterus with projections into vasculature.

* Benign, well-differentiated tumor with smooth muscle growing within veins as worm-like projections.

* Biopsy and Histology

* Echocardiography may show hyperechoic elongated mobile mass extending from the IVC and an irregular lesion in the right atrium with protrusion into the right ventricle

## References

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1. ↑ Cotton PB, Shorvon PJ (1984) Analysis of endoscopy and radiography in the diagnosis, follow-up and treatment of peptic ulcer disease. Clin Gastroenterol 13 (2):383-403. PMID: 6378443
2. ↑ Wanebo HJ, Kennedy BJ, Chmiel J, Steele G, Winchester D, Osteen R (1993) Cancer of the stomach. A patient care study by the American College of Surgeons. Ann Surg 218 (5):583-92. PMID: 8239772
3. ↑ Kimura T, Kamiura S, Yamamoto T, Seino-Noda H, Ohira H, Saji F (2004) Abnormal uterine bleeding and prognosis of endometrial cancer. Int J Gynaecol Obstet 85 (2):145-50. DOI:10.1016/j.ijgo.2003.12.001 PMID: 15099776
4. ↑ Santos, Pedro; Cunha, Teresa Margarida (2015). "Uterine sarcomas: clinical presentation and MRI features". Diagnostic and Interventional Radiology. 21 (1): 4–9. doi:10.5152/dir.2014.14053. ISSN 1305-3825.
5. ↑ Hata, Kohkichi; Hata, Toshiyuki; Makihara, Ken; Aoki, Showa; Takamiya, Osamu; Kitao, Manabu; Harada, Yuji; Nagaoka, Saburo (1990). "Sonographic Findings of Uterine Leiomyosarcoma". Gynecologic and Obstetric Investigation. 30 (4): 242–245. doi:10.1159/000293278. ISSN 1423-002X.
6. ↑ Rha, Sung Eun; Byun, Jae Young; Jung, Seung Eun; Lee, Soo Lim; Cho, Song Mee; Hwang, Seong Su; Lee, Hae Giu; Namkoong, Sung-Eun; Lee, Jae Mun (2003). "CT and MRI of Uterine Sarcomas and Their Mimickers". American Journal of Roentgenology. 181 (5): 1369–1374. doi:10.2214/ajr.181.5.1811369. ISSN 0361-803X.
7. ↑ Woźniak, Andrzej; Woźniak, Sławomir (2017). "Ultrasonography of uterine leiomyomas". Menopausal Review. 16 (4): 113–117. doi:10.5114/pm.2017.72754. ISSN 1643-8876.
8. ↑ Bodner, Klaus; Bodner-Adler, Barbara; Kimberger, Oliver; Czerwenka, Klaus; Mayerhofer, Klaus (2016). "Bcl-2 Receptor Expression in Patients With Uterine Smooth Muscle Tumors: An Immunohistochemical Analysis Comparing Leiomyoma, Uterine Smooth Muscle Tumor of Uncertain Malignant Potential, and Leiomyosarcoma". Journal of the Society for Gynecologic Investigation. 11 (3): 187–191. doi:10.1016/j.jsgi.2003.10.003. ISSN 1071-5576.
9. ↑ Adaikkalam J (April 2016). "Lipoleiomyoma of Cervix". J Clin Diagn Res. 10 (4): EJ01–2. doi:10.7860/JCDR/2016/16505.7531. PMID 27190823.
10. ↑ Houser, L. Murray; Carrasco, C. H.; Sheehan, C. R. (1979). "Lipomatous tumour of the uterus: radiographic and ultrasonic appearance". The British Journal of Radiology. 52 (624): 992–993. doi:10.1259/0007-1285-52-624-992. ISSN 0007-1285.
11. ↑ Keriakos, Remon; Maher, Mark (2013). "Management of Cervical Fibroid during the Reproductive Period". Case Reports in Obstetrics and Gynecology. 2013: 1–3. doi:10.1155/2013/984030. ISSN 2090-6684.
12. ↑ Coronado GD, Marshall LM, Schwartz SM (May 2000). "Complications in pregnancy, labor, and delivery with uterine leiomyomas: a population-based study". Obstet Gynecol. 95 (5): 764–9. PMID 10775744.
13. ↑ Myles JL, Hart WR (November 1985). "Apoplectic leiomyomas of the uterus. A clinicopathologic study of five distinctive hemorrhagic leiomyomas associated with oral contraceptive usage". Am. J. Surg. Pathol. 9 (11): 798–805. PMID 4073354.
14. ↑ . doi:10.1097/PAS.0000000000000569. Check `|doi=` value (help). Missing or empty `|title=` (help)
15. ↑ Tan, Y.; Zhang, H.; Xiao, E.-H. (2013). "Perivascular epithelioid cell tumour: Dynamic CT, MRI and clinicopathological characteristics—Analysis of 32 cases and review of the literature". Clinical Radiology. 68 (6): 555–561. doi:10.1016/j.crad.2012.10.021. ISSN 0009-9260.
16. ↑ Kang, Jeong Ba; Seo, Jin Won; Park, Young-Han; Jang, Pong Rheem (2014). "Malignant Perivascular Epithelioid Cell Tumor of the Uterus with Lung Metastasis". The Korean Journal of Pathology. 48 (6): 454–457. doi:10.4132/KoreanJPathol.2014.48.6.454. ISSN 1738-1843.
17. ↑ "PEComa of the Uterus: A Rare Mesenchymal Tumor Displaying a ≪Snowstorm≫ Pattern at Magnetic Resonance Imaging". Journal of the Belgian Society of Radiology. 100 (1). 2016. doi:10.5334/jbr-btr.926. ISSN 1780-2393.
18. ↑ . doi:10.1043/1543-2165-135.2.268. Check `|doi=` value (help). Missing or empty `|title=` (help)
19. ↑ Hwang, Jae Pil; Lim, Sang Moo (2013). "Uterine Epithelioid Angiosarcoma on F-18 FDG PET/CT". Nuclear Medicine and Molecular Imaging. 47 (2): 134–137. doi:10.1007/s13139-013-0191-y. ISSN 1869-3474.
20. ↑ Chen, Innie; Firth, Bianca; Hopkins, Laura; Bougie, Olga; Xie, Ri-hua; Singh, Sukhbir (2018). "Clinical Characteristics Differentiating Uterine Sarcoma and Fibroids". JSLS : Journal of the Society of Laparoendoscopic Surgeons. 22 (1): e2017.00066. doi:10.4293/JSLS.2017.00066. ISSN 1086-8089.
21. ↑ Nakayama Y, Kitamura S, Kawachi K, Kawata T, Fukutomi M, Hasegawa J; et al. (1994). "Intravenous leiomyomatosis extending into the right atrium". Cardiovasc Surg. 2 (5): 642–5. PMID 7820530.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
22. ↑ Kang LQ, Zhang B, Liu BG, Liu FH (January 2012). "Diagnosis of intravenous leiomyomatosis extending to heart with emphasis on magnetic resonance imaging". Chin. Med. J. 125 (1): 33–7. PMID 22340462.
23. ↑ Fasih, Najla; Prasad Shanbhogue, Alampady K.; Macdonald, David B.; Fraser-Hill, Margaret A.; Papadatos, Demetrios; Kielar, Ania Z.; Doherty, Geoffrey P.; Walsh, Cynthia; McInnes, Matthew; Atri, Mostafa (2008). "Leiomyomas beyond the Uterus: Unusual Locations, Rare Manifestations". RadioGraphics. 28 (7): 1931–1948. doi:10.1148/rg.287085095. ISSN 0271-5333.

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