Nabothian Cyst

Etiology

Proliferation of the squamous epithelium of the uterine cervix covers the columnar epithelium of the endocervical glands. This process occurs when chronic inflammation affects the cervix, typically due to healing from chronic cervicitis, childbirth, trauma, or surgical procedures (such as cervical cauterization or cryotherapy), or as part of physiological metaplasia. The columnar epithelium secretes mucus, leading to the formation of retention cysts, known as Nabothian cysts. These cysts are usually only a few millimeters in diameter, but they can grow to 4 cm or larger.[2] Although these cysts are benign and occur naturally, factors such as recurrent inflammation or infection may cause them to enlarge, occasionally leading to clinical symptoms.

Epidemiology

The epidemiology of Nabothian cysts has not been extensively studied. However, a study conducted in a hospital in the United States between 2010 and 2011 examined the spectrum of pigmented lesions in the uterine cervix using 2118 hysterectomy specimens. The researchers found that hemorrhagic Nabothian cysts had an incidence of 3%.[3]

The prevalence of Nabothian cysts varies, but they are generally considered a normal physiological change rather than a pathological condition. These cysts are more commonly observed in multiparous women due to cervical remodeling after childbirth. A recent study by Xu et al reported an association between low whole-blood nicotinamide adenine dinucleotide (NAD+) levels and an increased risk of Nabothian cysts.[4] Despite their widespread occurrence, Nabothian cysts have no known association with malignancy or significant long-term health risks.

Pathophysiology

Nabothian cysts form when mucus-secreting columnar epithelial cells of the endocervical glands become trapped beneath an overlying layer of squamous epithelium, leading to mucus retention and cyst development. This process often results from squamous metaplasia, where squamous epithelium replaces columnar cells at the cervix's transformation zone. Trauma or inflammation can further contribute to this epithelial overgrowth and glandular obstruction.[5] The trapped mucus gradually accumulates, resulting in cyst formation of varying sizes. 

Histopathology

During a Pap smear, superficial Nabothian cysts may rupture upon contact with the spatula, causing the mucoid content to adhere to the brush and be transferred onto the slides in conventional cytology or mixed with the preserving solution in liquid-based cytology (LBC) preparations. In LBC, mucus rarely persists, as it typically dissolves in the preserving solution and is removed during centrifugation before slide preparation.

Macroscopically, a Nabothian cyst appears as a cervical cyst containing mucinous liquid.[2] In rare cases, mucus within Nabothian cysts may become impregnated with neutrophils, giving it a granular appearance visible on LBC slides. Nabothian cyst content is identifiable on conventional Pap smears but can sometimes be mistaken for a tumor diathesis pattern associated with invasive carcinoma.[1] Microscopically, Nabothian cysts are lined by a single layer of columnar or flattened epithelium without cellular mitosis or atypia.[5]

History and Physical

Patients with Nabothian cysts are often asymptomatic, and the cysts are typically discovered incidentally during routine pelvic examinations or cervical screenings. However, if the cyst is large or complex, it may be mistaken for a malignancy or a tumor. In such cases, it can cause symptoms such as dyspareunia, pelvic pain, irregular vaginal bleeding, and vaginal discharge. A Nabothian cyst may also present with pressure symptoms if it compresses nearby organs, leading to issues like urinary retention, amenorrhea, and lower abdominal pain.[6][7][8] 

If the cyst presses on the rectum, it may cause abnormal defecation and tenesmus. A history of childbirth, chronic cervicitis, or cervical trauma may be relevant, as these factors contribute to cyst formation. On physical examination, Nabothian cysts appear as small, smooth, dome-shaped nodules on the cervix that are either translucent or opaque. They typically range from a few millimeters to several centimeters in size. In rare cases, significantly enlarged cysts can cause cervical enlargement or obstruction, requiring further evaluation through imaging or colposcopy.

Evaluation

The evaluation of Nabothian cysts typically involves a thorough clinical assessment during routine pelvic examinations. No additional testing is required in most cases, as their benign nature is easily recognized. However, further evaluation may be needed if the cysts are unusually large, multiple, symptomatic, or suspected to resemble other cervical lesions. A colposcopy can provide a magnified view of the cervix to confirm the diagnosis.

Transvaginal ultrasound and magnetic resonance imaging (MRI) can be used to evaluate deeper or hemorrhagic Nabothian cysts and to rule out other cervical or uterine pathologies. MRI is beneficial for distinguishing between endophytic and exophytic growths and differentiating normal from abnormal conditions. Nabothian cysts typically appear as high T2 signal intensity on MRI. A recent case report described a patient with a large Nabothian cyst measuring 10 cm by 15 cm on MRI.[9]

If cancer is suspected and MRI cannot exclude it, biopsy, conization, and endocervical curettage are effective diagnostic tools to rule out neoplastic processes. Despite the availability of these modern techniques, exploratory laparotomy and hysterectomy may still be necessary in cases of unusually large and deep intracervical cysts when malignancy cannot be definitively excluded.[2] Proper evaluation is crucial for ensuring an accurate diagnosis, appropriate management, and the avoidance of unnecessary interventions.

Treatment / Management

Nabothian cysts typically require no treatment if they are asymptomatic and have no malignant potential. Treatment is recommended for symptomatic cases, particularly when pain is present or when malignancy cannot be excluded. In such cases, treatment primarily involves drainage. One concern with surgical intervention is the risk of scar tissue formation, which may lead to future pain.[2] In cases of obstructed labor, simple drainage is also used to facilitate vaginal delivery. If a diagnosis remains uncertain, or if the cysts are large or deep and symptomatic, excision is necessary to assess histopathology and rule out other cervical tumors or adenoma malignum.[5](B3)

A study conducted in Japan proposed a management protocol involving an interprofessional diagnostic approach using cytology, MRI, gastric-type mucin analysis, and subsequent treatment and follow-up. The protocol’s effectiveness was evaluated in 94 patients with multicystic cervical lesions between 1995 and 2014. Using the protocol, the researchers achieved correct diagnoses in 90% of cases. The study concluded that the proposed approach was both accurate and effective in diagnosing and treating multicystic cervical lesions.[10](B2)

Differential Diagnosis

The differential diagnoses of Nabothian cysts include various cervical and gynecological conditions with similar cystic or nodular features. Cervical endometriosis can resemble Nabothian cysts, particularly when the lesions appear dark or hemorrhagic. Gartner duct cysts, along with mesonephric or paramesonephric cysts, are congenital anomalies that may be mistaken for Nabothian cysts, especially if located deep within the cervical stroma. Cystic degeneration of uterine leiomyomas can also cause cervical enlargement and require further evaluation. Additionally, microglandular hyperplasia and squamous papilloma are other benign cervical conditions to consider in the differential diagnosis.[5] A recent case report described giant Nabothian cysts that resembled the appearance of a genitourinary fistula.[11] 

More concerning differential diagnoses include cervical neoplasms, such as adenocarcinoma or squamous cell carcinoma, which may present as atypical cystic or solid cervical lesions. Adenoma malignum, a well-differentiated, multicystic form of mucinous adenocarcinoma, and other glandular malignant cervical lesions can mimic Nabothian cysts. However, these malignant lesions are typically located deeper in the cervix. Endocervical adenocarcinoma should also be considered, as it may present with a prominent cystic component.[2] Imaging modalities such as transvaginal ultrasound and MRI, along with colposcopy and biopsy when indicated, can help distinguish Nabothian cysts from these other conditions and ensure accurate diagnosis.

Pertinent Studies and Ongoing Trials

Trials evaluating Nabothian cysts primarily focus on optimal detection techniques. Although multiple randomized trials have assessed various diagnostic methods, no definitive gold standard has been established. Recent case reports suggest that MRI can be effective when transvaginal ultrasound and computed tomography yield inconclusive results.[12] 

Prognosis

The prognosis for Nabothian cysts is excellent, as they are non-neoplastic and typically do not cause complications or require treatment. Most cysts remain asymptomatic and show minimal growth over time. They are usually small, measuring 0.2 to 0.3 cm in diameter, although they may exceed 1 cm and rarely reach sizes greater than 4 cm.[5][7] In rare cases, large or multiple cysts can cause cervical enlargement or discomfort, which can be effectively managed with simple drainage or minor procedures. Nabothian cysts do not increase the risk of cervical cancer or other serious conditions, so routine monitoring during gynecological exams is generally sufficient.

Complications

Complications of Nabothian cysts are rare. Cervical enlargement from large or multiple cysts can cause discomfort, pelvic pain, dyspareunia, or obstruction of the cervical canal, potentially affecting menstrual flow or complicating childbirth. In some cases, multiple or giant cysts may cause significant issues such as hematometra, labor passage obstruction, rectal compression, or abnormal uterine bleeding. Large cysts can also lead to chronic urinary retention by restricting the bladder outlet or compressing the pudendal and sacral nerves, disrupting the nerve supply to the detrusor muscle.[5][8][13][14]

Additionally, Nabothian cysts have been identified as a common cause of false-positive iodine uptake in whole-body scans using iodine-131. MRI is a useful diagnostic tool in such cases.[15] Misdiagnosis as a malignant cervical pathology can lead to unnecessary anxiety and interventions. Proper clinical evaluation, including imaging and colposcopy when necessary, is crucial to differentiate Nabothian cysts from other cervical abnormalities and ensure appropriate management if symptoms develop.