Lymphoma of the female genital tract is a rare condition that accounts for 0.5 to 1% of all extranodal lymphomas. The prevalence of lymphoma of the cervix is less than 1% among all cervical cancers (1). In total, 185 cases with primary cervical lymphoma were reported according to the literature review of the MEDLINE database (2).
The primary malignant lymphoma of the uterine cervix is localized cervical cancer with no evidence of other sites of involvement or systemic leukemia (3). The most common clinical features of this condition are abnormal vaginal bleeding, perineal discomfort, persistent vaginal discharge, less frequently abdominal masses, dyspareunia, and urinary retention (4); however, routine cervical screening tests are not diagnostic in most cases. It seems that the best treatment option for primary malignant lymphoma of the uterine cervix should be directed to the individual person and the case reports showed no widely accepted consensus on its management (4).
However, the chemotherapy treatment with a regimen of four drugs known as cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) with or without rituximab has been shown to be effective (5).
Cubo et al. reported a 51-year-old female with a primary lymphoma who was successfully treated with combined rituximab chemotherapy (6). Kosari et al. treated a primary lymphoma of the uterine cervix with a combination of
CHOP chemotherapy regimen and radiotherapy. However, central nervous system involvement led to the patient’s death 20 months after diagnosis (3). Moreover, multimodality therapy may be utilized which is either chemotherapy or the combination of more than one method of cancer treatment.
Stroh et al. used chemotherapy and radiation for the treatment of 16 cases with lymphoma of the cervix. According to the results, 12 cases had received radiation and 90% of patients with low-risk factors were disease-free at 5 years follow-up (7).
Due to the scarce number of reported cases, there is no established therapeutic protocol; however, different cancer treatments, including radiotherapy, chemotherapy, and surgery are described in the literature. With this background in mind, the aim of this report was to introduce a case of primary malignant lymphoma of the uterine cervix which was misdiagnosed as an ovarian cyst on ultrasonography.
A 31-year-old female referred to the Oncology Department of a teaching hospital affiliated to Mashhad University of Medical Sciences, Mashhad, Iran in 2017. Her chief complaint was abnormal uterine bleeding for the past 6 months. The ultrasound findings showed a suspicious malignant ovarian mass. On gynecological examination, an obvious fragile exophytic mass was observed in the cervix which resulted in diffuse enlargement of the cervix without parametrial involvement.
The gynecologist requested ultrasonography imaging without a pelvic examination. According to the obtained results, an 8 cm solid multicystic adnexal mass was detected as a suspected ovarian malignancy. In addition, based on the results of the patient’s examination, the presence of a large cervical mass was detected and the patient underwent cervical biopsy. The findings of clinically suspicious looking cervix resulted in the possible diagnosis of stage IB2 of cervical cancer.
On the other hand, the computed tomography scans demonstrated a bulky mass in the uterine cervix with no other sites
of metastases (Figure 1). According to the radiological and clinical findings, the initial diagnosis was cervical cancer (FIGO stage IB2).
Surprisingly, the pathological report of the patient’s cervical biopsy revealed non-Hodgkin's diffuse B cell lymphoma. Immunohistochemical studies demonstrated that CD-20 and LCA were intensely positive. However, there was negative staining for CK, CD 3, CD 10, Tdt, human
papillomavirus (HPV), and Epstein-Barr virus (EBV). Moreover, the positive rate of the Ki67 index was obtained at 30% (Figure 2). As a result, the definitive diagnosis was non-Hodgkin's B cell lymphoma of the cervix and the tumor was classified as stage IE.
Therefore, the therapeutic protocol was CHOP chemotherapy plus rituximab every 3 weeks for 6 cycles. After 18 months of close surveillance, the patient was in good condition without any relapse. The written informed consent was obtained from the patient for
the publication of this case report and accompanying images.
Lymphoma of the female genital tract is a rare condition. Before any lymph node detection, tumor involvement of other sites was found in the majority of patients at the time of diagnosis, which is known as extralymphatic invasion (stage IE) that was similar to our case.
Although the age at presentation ranges from 20 to 80 years, the median age was closer to 40-60 years (8). The most common clinical presentations are abnormal vaginal bleeding, vaginal discharge, perineal discomfort, and dyspareunia. Moreover, the patients may also be presented with an asymptomatic pelvic mass (9).
Cervical erosion, nodules in the Pouch of Douglas (cul de sac), and contact bleeding can be detected on pelvic examination. However, friable exophytic lesions can be obviously palpable (10). In addition, the infiltration of the tumor within the cervical stroma is not common. As a result, specific cytological diagnosis of primary malignant lymphoma of the uterine cervix with Pap smear is considered less useful and is commonly negative (59%) (11). Moreover, this type of cancer is rarely diagnosed by cervical screening, because it originates in the cervical stroma, and the overlying squamous epithelium is usually remained unaffected (12). The differential diagnosis of this malignancy includes precancerous lesions, HPV, EBV, and associated lymphoma, such as lesions of the cervix, small cell carcinoma of the cervix, endometrial stromal sarcoma, and granulocytic sarcoma (13). Immunohistochemistry (IHC) is a routinely used methodology that is useful for correct diagnosis. Accordingly, due to the wide range of IHC staining methods that are currently available on paraffin sections, the definitive diagnosis of these tumors is broadly accessible.
The most common definition of the immunohistochemical profile is positivity of LCA, vimentin, CD20, CD30, Bcl6, Bcl2, IgMk, and Ki-67 index as well as the negativity of CD10, MUM1, and BCL2. All of the above-mentioned markers are pivotal in the subcategorization of PCL (14, 15). In the present case, IHC studies of CD-20 and LCA were intensely positive. However, the staining for CK, CD 3, CD 10, Tdt, HPV, and EBV were negative. In contrast, the Ki-67 index was positive. The best standard treatment option for primary malignant lymphoma of the uterine cervix should be directed to the individual person; however, surgery, chemotherapy, or radiotherapy
are the therapeutic choices. The CHOP chemotherapy regimen with or without rituximab has been shown to be effective in the improvement of the survival rate (16). A combined chemotherapy regimen, such as CHOP has proven to be an effective treatment for this disease due to its advantages regarding the prevention of micrometastasis and fertility preservation (17).
The present patient also received CHOP chemotherapy. The primary treatment of patients with cervical lymphoma who undergo chemotherapy has led to favorable prognosis which results from early detection of the disease. In addition, a 5-year survival rate of 81% was estimated in case of detection of early-stage disease (18). However, in a study conducted by Stroh et al. on 16 cases of primary malignant lymphoma of the uterine cervix, 5-year disease-free survival rate was obtained at 90% (7).
Some other reports achieved similar results (19). Heredia et al. reported two cases of cervical lymphoma treated with CHOP and radiotherapy. In the mentioned study, one case had 61 months of disease-free survival after the initial diagnosis and the other one benefited from 15-monthsrelapse-free survival (19).
The clinical appearance of primary cervical lymphoma of the cervix often mimics squamous cell carcinoma. Therefore, cytology may be non-contributory to achieve a correct diagnosis. Consequently, careful history taking and pelvic examination are important.
A pelvic examination in patients with vaginal bleeding, vaginal discharge, and pelvic discomfort should be considered as the first step after taking the patient's medical history.
We would like to acknowledge the staff of the Gynecology Oncology department of Gahem Hospital of Mashhad University of Medical Sciences.
Conflicts of Interest
The authors declare no conflicts of interest.