Abstract
A 46-year-old woman of Asian origin presented with heavy intermenstrual and postcoital bleeding caused by the rare entity of primary non-Hodgkin’s lymphoma of the cervix uteri, with no evidence of disease elsewhere. Prompt diagnosis by biopsy avoided unnecessary surgery, and instead appropriate treatment with chemoradiotherapy was administered.
BACKGROUND
Primary malignant lymphoma of the female genital tract is an extremely rare clinical entity;1 involvement of the cervix by lymphoma as part of widespread disease is more common.2–4 Clinical symptoms are often non-specific and mimic other more common gynaecological pathology, both benign and malignancies such as squamous cell carcinoma of the cervix or endometrial adenocarcinoma.1 Clinical awareness of this rare possibility is important to achieve early diagnosis and appropriate management.
CASE PRESENTATION
The patient is a mother of three (all delivered by lower segment caesarean section), with no other significant medical history. She was referred to the gynaecology clinic due to intermenstrual and postcoital bleeding. Examination revealed an irregular firm mass measuring 7–8 cm in diameter, which appeared to arise from the cervix. The cervix could be felt anteriorly and extended laterally. The surface was smooth with no ulceration. Her smear history was all negative, with the most recent being 1 year earlier. The clinical diagnosis was of a cervical fibroid. The patient was booked for an examination under anaesthesia with hysteroscopy and excision or biopsy of the mass.
In theatre examination showed a large solid mass measuring 7–8 cm arising from the substance of the cervix uteri posteriorly. There was no stalk or line of cleavage between the mass and the cervical canal. Hysteroscopy showed a small normal endometrial cavity above the elongated cervical canal. The clinical impression was of a large cervical fibroid. Two superficial punch biopsies from the mass and an endometrial biopsy were taken and sent for histopathological analysis.
INVESTIGATIONS
Histopathology
Histology revealed follicular non-Hodgkin’s lymphoma of the cervix, diffuse in nature (figs 1–3). There was a mixture of small cells with triangular shaped nuclei and large blasts. Immunostains showed expression of CD 20, CD 10, BCl6 and CD 23, with a proliferation index of 40% (as per MIB-1). FISH analysis showed no evidence of IGH/BCL-2 rearrangement (20–30% can show no rearrangement).
Figure 1.
Normal endocervical tissue (left) infiltrated by the neoplastic lymphoid cells with crushing artefact.
Figure 2.
Higher power showing the neoplastic lymphoid cells.
Figure 3.
The cells showing strong CD 20 positivity.
Subsequent investigations
Staging CT showed no other lymphadenopathy, and a bulky uterus. Bone marrow studies showed no evidence of infiltration with lymphoma, and the LDH, b2 microglobulin and immunoglobulin were normal.
DIFFERENTIAL DIAGNOSIS
The clinical diagnosis was of a cervical fibroid.
TREATMENT
In view of the bulk of the disease combined chemoradiotherapy treatment was chosen.
The patient received six courses of chemotherapy with RCVP, as well as localised radiotherapy to the cervix. She required 12 fractions for local control.
OUTCOME AND FOLLOW-UP
Post-treatment CT scan and hysteroscopic biopsy showed no evidence of disease. An MR scan of the pelvis did not show any evidence of disease. The patient is under regular follow-up in the gynaecology and haematology clinics and remains relapse free 1 year on.
DISCUSSION
Primary malignant lymphoma of the female genital tract is an extremely rare clinical entity. Gynaecological sites for non-Hodgkin’s lymphoma include the cervix, vagina and uterus. Until now, about 130 cases of primary cervical non-Hodgkin’s lymphoma of the cervix have been reported and primary cervical lymphoma accounts for less than 1% of the extra-nodal lymphomas.1 Involvement of the cervix by lymphoma as part of widespread disease is more common.2
Non-Hodgkin’s lymphoma usually presents with lymphadenopathy, fever, night sweats and weight loss.5 The median age at presentation is 44 years, ranging from 27 to 80 years.6,7
Clinical symptoms of female genital tract lymphoma are often non-specific and mimic other much more common gynaecological pathology, including benign conditions, as in this case, and malignancies such as squamous cell carcinoma of the cervix or endometrial adenocarcinoma.1 Diagnosis is only confirmed by histology, and this case highlights the importance of the role of biopsy in the diagnosis of this rare entity.1
Because the neoplasm originates in the submucosal cervical stroma and the overlying squamous epithelium is unaffected, cervical smears are usually normal, as in this case.1,8
Cervical biopsy and immunophenotyping are necessary to differentiate primary cervical non-Hodgkin’s lymphoma from benign and malignant disease of the cervix.1,2
The most common histological subtype is diffuse large B-cell lymphoma, but can also be follicular lymphoma, as found in this case.1,6
The management strategy for primary cervical non-Hodgkin’s lymphoma of the cervix is not clear because of rarity of the disease, different histopathological subtypes and limited experiences. According to several case reports and a few case series, treatment options for primary cervical non-Hodgkin’s lymphoma of the cervix include chemotherapy alone, radiotherapy alone, or radiotherapy combined with either chemotherapy or surgery.1,2,5,6,9
In cases of relapse, some keep surgical treatment in the form of a hysterectomy as an option.10
Overall cervical lymphoma has a good prognosis, particularly in cases of low grade disease. The extent of the disease, the size of the primary tumour and the type of lymphoma (low or high grade) are important prognostic features.1 Cases tend to have a remitting and relapsing nature. Hence the need for close gynaecological monitoring, including cervical biopsies if indicated as cervical smear, routine pelvic examination and CT scan have low specificity and sensitivity.2
LEARNING POINTS
Primary non-Hodgkin’s lymphoma of the cervix is rare.
Clinical awareness is important as distinguishing this rare condition from more common gynaecological conditions is difficult and requires appropriate investigation.
This case illustrates the importance of taking a biopsy, as without this an inappropriate and difficult hysterectomy would have been undertaken.
Close gynaecological follow-up is required, including examination and further cervical biopsies if indicated.
Acknowledgments
Dr Alison Uku, Dr Emir Salmo.
Footnotes
Competing interests: none.
Patient consent: Patient/guardian consent was obtained for publication.
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