Ovarian mature cystic teratomas

Ovarian dermoid cysts or mature cystic teratomas (MCT) are benign ovarian neoplasms arising from an unfertilized oocyte. They are composed of tissue derived from two or three embryonic layers, i.e. combinations of either mature endodermal, mesodermal or ectodermal tissue.

 ICD-10-CM D27.9

Ovarian MCTs are the most common ovarian neoplasms. They annually affect 8.9/100 000 women(2). MCTs comprise about 20% of ovarian pathology and account for more than 50% of neoplasms diagnosed in women younger than 20 years(3-4). Cases have been documented at all ages, but most MCTs are diagnosed in the third or fourth decade(3-7).  

Genetic studies comparing teratoma cells to somatic cells have unveiled a parthenogenetic inception from germ cells after the first meiotic division(8). 

Macroscopic features
MCTs usually have a smooth outer surface. Sometimes the external contour is lobulated.  Most MCTs are unilocular, some are multilocular. The cyst contents - composed of sebum, keratin and hair - are liquid at body temperature and solid at room temperature.   A nodule consisting of fat, teeth and/or hair often protrudes into the cyst lumen(3). In up to 15% of cases, MCTs are bilateral(3,7). Most MCTs are smaller than 10 cm but some may be as large as 20 cm or more(3,7). 

Microscopic features
MCTs are composed of adult tissue derived from two or three embryonic layers, i.e. different combinations of mature endodermal, mesodermal and ectodermal tissue. They often contain hair and other skin derivatives (ectoderm) but may also contain, for example, thyroid or gastro-intestinal tissue (endoderm), bone, fat, cartilage (mesoderm), or neural tissue(7). It is important to distinguish MCTs from benign monodermal teratomas. The latter are derived from a single embryonic layer, e.g. struma ovarii (consisting of only thyroid tissue), carcinoid tumors (composed of neuroendocrine cells), and neuroectodermal type tumors (e.g. ependymomas)(7).  
 

Most MCTs are detected incidentally at gynecologic or ultrasound examination performed routinely or for symptoms unrelated to the MCT(5,9). However, painful complications may occur, e.g. adnexal torsion, infection or cyst rupture(3). 

Sonography has proven its value in diagnosing ovarian teratomas. Efforts to extract typical features pathognomonic of this pathology are ample and have lead to several suggestive signs. On grayscale two-dimensional ultrasound, one or more of the following typical features can be identified (1).
-    Dots and/or lines (by some called ’dermoid mesh’), appearing hyperechogenic in the cyst(10,11).
-    Echogenic white ball, is recognizable by its smooth surface, the absence of vascularity on color/power Doppler imaging, the fact that it may or may not cast extensive acoustic shadows and may or may not be mobile upon dynamic scanning(12). The nodule is not to be considered as solid tissue according to the International Ovarian Tumor Analysis (IOTA) group criteria(13).
-    Fat- fluid level, seen as a straight, sharp demarcation between hyperechoic and less echogenic cyst fluid. The hyperechoic cyst fluid is sometimes mobile upon shift in decubital position or when pushed upon(10,14).
-    Tip of the iceberg sign, signifying a retro-lesional shadow that obscures visibility of any structure lying beyond the proximal lesion border(10,15). However, this sign is hard to define and is dependent on machine settings(11,15).
-    Cotton wool tufts, poorly demarcated hyperechogenic lesions in the cyst content. (1)
-    ‘Mushroom cap sign’ may be seen as a variation of the ‘fat-fluid level’. It is characterized by a static, sharp, curvilinear demarcation between hypo- or anechoic and hyperechoic substances(1). 
-    Completely hyperechogenic lesion, in which the sebacious and/or adipose content completely fills the cyst without irregularities(1). 
-    Starry sky sign, seen as anechoic cystic content with floating hyperechogenic particulate matter (1).

Only a small proportion of MCTs manifest no typical features. Vascularized solid tissue is present in a small minority  of MCTs (1).

Expectantly managed, (usually asymptomatic) MCTs vary in growth rate(9,16). One study showed that sonographically detected mature teratomas (dermoid cysts) smaller than 6 cm grew on average 1.8 mm per year in premenopausal women, whereas they annually shrunk by 1.6 mm per year in postmenopausal patients(16). Another study reported the median growth rate for MCTs (irrespective of initial size or menopausal status) to be 0.09 mm per month(17). With increasing size, the risk of torsion rises(18). 
The probability of recurrence within 2 years after laparoscopic resection of a MCT (cystectomy) has been reported to be 7.6% (recurrence defined as surgical re-intervention)(19). Cyst removal without spill is important because spill may cause granulomatous peritonitis mimicking tuberculosis or peritoneal carcinomatosis(7,20).

MCTs may also be associated with peritoneal gliomatosis, i.e. peritoneal implants of glial tissue (7,21). The etiology of gliomatosis is unknown(22). If the implants consist entirely of mature glial tissue, the prognosis is good(7,21). 

Even though MCTs are generally benign, malignant transformation may occur. It has been described in 0.3-0.7% of surgically removed MCTs(23,24). Squamous cancers account for 80% of malignancies in MCTs(7,23). An unusually large cyst with adhesions and necrosis or hemorrhage should raise suspicion of malignancy(7). 

Extremely rare complications of MCTs are auto-immune hemolytic anemia (AIHA) and anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis(7,25,26). In AIHA, red blood cells are targeted by auto-immune antibodies. The mechanisms by which MCTs induce antibody production against red blood cells is not known, but cyst removal is a successful remedy(7,25). Anti-NMDAR encephalitis is potentially lethal. Due to its rarity, the association between Anti-NMDAR encephalitis and MCTs has only recently been well established(27). MCTs of patients affected with Anti-NMDAR encephalitis contain more neuroglial components and lymphocytic inflammatory infiltrates than those of women without anti-NMDAR encephalitis (27). Delay in diagnosis and in surgical removal of the MCT may result in more neurological sequelae and longer convalescence (26). Cystectomy is enough for patients to be cured, but some patients have recovered without surgical intervention(26). Treatment also involves immunotherapy(7,26,27). 

Overall, MCTs are associated with few complications. Therefore, a conservative, fertility sparing approach should be offered to children and women of childbearing age(9,16,18,19)).  If the ovarian mass can be reliably identified as a benign MCT (for example with transvaginal ultrasound), conservative management with follow-up is an alternative to surgery(9,16,18). If surgery is required because of symptoms or is requested by the patient, cystectomy or adnexectomy is appropriate. Complete removal of the MCT is desirable because incomplete removal of the cyst wall could lead to recurrence(19).

Differential Diagnosis                                                  ICD-10-CM
- Echogenic bowel                                                         n/a
- Perforated appendix with abscess/appendicolith        K35.33
- Ovarian (cystadeno)fibromas                                      D27.9
- Endometrioma                                                             N80.1
- Immature ovarian teratoma                                         C56.9
- Ovarian malignancy NOS                                            C56.9    

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