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

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

The table below summarizes the findings that differentiate Leiomyosarcoma from other conditions that may cause similar signs and symptoms.

Diseases	Clinical manifestations		Para-clinical findings					Gold standard	Additional findings
	Symptoms	Physical examination
			Lab Findings	Imaging			Histology
				Ultrasound	CT scan	MRI
Uterine Leiomyosarcoma	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)	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)	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	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	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	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