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Journal of Clinical Gynecology & Obstetrics

Review

Volume 11, Number 4, December 2022, pages 89-100

Pyometrium as an Early Indicator of Cervical Squamous Cell Carcinoma: A Systematic Review

Pyometra, or pyometrium, is defined as the accumulation of pus in the uterine cavity due to an interference with drainage and occurs in 0.1-0.2% of all gynecological patients and 12.6% of elderly gynecological patients [1]. Pyometrium is uncommon, but is usually associated with advanced endometrial or cervical cancer. Pyometrium typically presents in postpartum or postmenopausal women with malodorous purulent vaginal discharge, bleeding, and pelvic pain, but can also be asymptomatic [2]. Manifestation of pyometrium is thought to be caused by the accumulation of pus in the uterine cavity resulting from bacteria ascending through the cervical canal with interference with its natural secretion drainage due to cervical stenosis [3]. It is imperative that in postmenopausal women diagnosed with pyometra gynecological malignancy be considered as an underlying cause until proven otherwise. Additionally, early diagnosis of pyometrium may decrease rates of spontaneous perforated pyometra (SPP). Although presentation of SPP predominantly presents with abdominal pain, vomiting and fever, there are no specific symptoms, making diagnosis difficult [4]. Here we describe a case of a postmenopausal female with pyometrium who was found to have underlying cervical squamous cell carcinoma. Additionally, we provide, to our knowledge, an original systematic review of case reports of pyometra focused on presenting symptoms, pathological results, and complications.

The patient was an 81-year-old G5P5 Caucasian female with a history of dementia, alcoholic hepatitis, anemia, hypertension, chronic obstructive pulmonary disease, gastroesophageal reflux disease, irritable bowel syndrome, gastritis, and dyslipidemia. Obstetrical history was significant for menopause at the age of 50 and normal pap smears, although she could not recall the date of her last pap smear. The patient presented to the emergency room for lower abdominal pain, bloating, and green-colored vaginal discharge for the past 3 weeks.

A computed tomography (CT) of the abdomen and pelvis showed a markedly distended endometrial cavity containing fluid and small air bubble concerning for cervical stenosis verses endometrial neoplasm/endometritis suggestive of pyometra. The patient underwent dilation and curettage with endometrial curette, of which pathology revealed abundant acute purulent inflammation consistent with clinical diagnosis of pyometra, and glandular epithelium with numerous plasma cells consistent with endometritis and multiple detached fragments of squamous cell carcinoma, which showed positive staining with p16, p63, and high Ki-67, that was consistent with cervical human papillomavirus (HPV)-related squamous cell carcinoma (Figs. 1-4). The endometrial tissue seen was negative for malignancy.

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Figure 1. Multiple detached fragments of squamous cell carcinoma in the curettage material (H&E, × 10). H&E: hematoxylin and eosin.

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Figure 2. Fragments of glandular epithelium with numerous plasma cells in the curettage material (H&E, × 40). H&E: hematoxylin and eosin.

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Figure 3. Residual minute microscopic focus of squamous cell carcinoma, hysterectomy material (H&E, × 10). H&E: hematoxylin and eosin.

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Figure 4. Endometrium with severe acute, histiocytic and plasmocytic inflammation, hysterectomy material (H&E, × 40). H&E: hematoxylin and eosin.

The patient underwent robotic-assisted total hysterectomy with bilateral salpingo-oophorectomy and sentinel, pelvic, and para-aortic lymph node dissection. Pathology revealed residual minute microscopic cervical squamous cell carcinoma (pT1a1 pN0) HPV associated in background of extensive high grade squamous intraepithelial lesion with glandular involvement and severe acute, histiocytic and plasmocytic inflammation consistent with endometritis. Based on various factors, including tumor, node and metastasis (TNM) staging, adjuvant treatment with radiation and chemotherapy was not deemed necessary.

Postoperative recovery was complicated by postoperative ileus which led to a small bowel obstruction. The patient removed her own nasogastric tube on multiple occasions which led to acute hypoxemic respiratory failure and intubation. Additionally, the patient formed a new right lateral abdominal wall hernia that contained incarcerated small bowel. The patient returned to the operating room for a diagnostic laparotomy with small bowel resection and reduction of the hernia. Following hernia repair, the patient was discharged to a skilled nursing facility.

We conducted an electronic-based search using the database PubMed. The medical subject heading of “pyometrium” was used. The search was limited to trials in humans and published in the English language from the 1990s to present day. We manually searched the reference lists of identified studies. We included all original case report articles and excluded pediatric cases.

Our search yielded 698 citations with exclusion criteria of non-English articles and date of completion prior to 1990s (Fig. 5). After excluding articles in non-humans, we obtained 206 articles. After eliminating pediatric cases, 113 articles remained. After further exclusion of articles that were abstracts only, picture only articles, articles that the authors were unable to obtain or not related to pyometra, 74 articles were eligible for review. Additionally, five articles reported on multiple cases, leading to the grand total of 80 patient case reports analyzed. Raw data are available in Table 1 [5-75].

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Figure 5. Flow diagram for article selection.

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Table 1. Characteristics of All Studies Included in the Systematic Review

Pyometrium has a reported incidence of 0.01-0.05% in all gynecological patients; however, this occurs more frequently in postmenopausal women, with an incidence of 13.6% in women over 60 years old [4]. The pooled average age of patients in our study population was 66 years (range 21-102 years). Of patients diagnosed with cancer, the average age of patients was 64.5 years (range 38-102). In patients not diagnosed with malignancy, the average age was 66.5 years (range 21-93 years). It has previously been shown that in younger patients, there is an increased incidence of pyometrium in those with diabetes, congenital cervical anomalies, cervicitis, large submucosal uterine fibroids, cervical cancer, recent vaginal surgery, or injection drug use [2]. When looking at possible risk factors of pyometra within the cases we analyzed, majority of the patients were multiparous; however, a majority of the studies did not report on the previous medical history of their patient, making it difficult to compare risk factors to those previously identified in the literature.

Known common presenting symptoms of pyometrium include abdominal pain, vomiting, nausea, and fever [9]. The most common presenting symptom within the cases we analyzed was abdominal pain, with 63.2% of patients exhibiting this complaint. The list of differential diagnosis of abdominal pain is vast and includes but is not limited to appendicitis, inflammatory bowel disease, diverticulitis, constipation, acute urinary retention, nephrolithiasis, ovarian torsion, pelvic inflammatory disease and complications of pregnancy including ectopic pregnancy [8]. Additional presenting symptoms within the cases we analyzed included vaginal bleeding and discharge, weight loss, constipation, vomiting, fever, and low back pain.

Diagnosis of pyometrium is traditionally made via imaging modalities including ultrasound (US), CT, or magnetic resonance imaging (MRI), which are required for confirmation or for evaluation of possible complications [5]. Findings from imaging suggestive of pyometra can include uterine enlargement and dilation, accumulation of discharge, and free air. Of the cases we analyzed, 93.6% of them used either US, CT, or MRI for diagnosis of pyometrium. Alternative methods of diagnosis included abdominal X-ray or exploratory laparotomy.

Pyometra has previously been reported to be associated with malignancy in 35% of cases in which pyometra was present [8], however this reported frequency has decreased to 13.6% in the last decade due to progress of cancer screening and diagnosis. Of cases reported, all the cases were diagnosed as squamous cell carcinoma of the cervix besides one reported by Vyas et al 2009 that was reported to be adenocarcinoma of the cervix [6].

Pyometra is often due to a polymicrobial cause, including both aerobic and anaerobic organisms [77] with the most common microorganisms including E. coli, Streptococcus spp., Bacteroides fragilis and Peptostreptococcus anaerobius [78]. Of the case reports we analyzed, there was a wide variety of causative microbes including Tuberculosis, Escherichia, Pseudomonas, Fusobacterium, Enterococcus, Pneumococcus, Clostridium, Sphenoides, Streptococcus, Staphylococcus, Bacteroides and Actinomyces. The microbes we identified were similar to those previously reported on.

Current literature supports basic pyometra treatment with transcervical drainage, irrigation of uterine cavity, and antibiotic therapy with emergency surgical intervention in cases of SPP [4]. In a previous case review of pyometra, treatment with hysterectomy was completed in 82% of cases [9]. Majority (61.6%) of the cases analyzed in our study were treated with hysterectomy. Of those treated with hysterectomy, 72.9% also underwent concurrent bilateral salpingo-oophorectomy. Average age of those treated with hysterectomy was 68.6 years old with a range of 23 to 92 years old. Additionally, only 9% of those treated with hysterectomy had diagnosis of squamous cell carcinoma of the cervix, with the rest having benign findings. Alternative treatment methods included antibiotic therapy and drainage of the pyometra.

If left untreated, pyometra can rarely result in the serious complication of SPP. Prognosis after SPP can be poor, especially in women of advanced age and those with poor general health. Current literature reports rates of SPP to be around 5% [4]; however, in our study group, uterine rupture was reported as a complication in 36.1% of cases. Additional complications reported included subcutaneous abscess, pneumonia, wound dehiscence, and respiratory insufficiency. Eight patients died following complications of the pyometra which included complications such as sepsis, pneumonia, colouterine fistula, organ failure and cancer progression due to refusal of treatment. No cases of recurrence were reported.

Preoperative diagnosis of pyometra is difficult but imperative, as early treatment may prevent from future uterine rupture and aid in identification of underlying cause including malignancy. Majority of cases in our analysis presented with abdominal pain and were treated with hysterectomy; however, a wide range of presentations and treatment modalities were identified in the reports included in this analysis. An increased number of cases were complicated by uterine rupture compared to previously reported research, in addition to an increased rate of underlying malignancy. With the presentation of our case and analysis of previously published case reports, we highlight the importance of considering malignancy as a differential diagnosis when presented with a postmenopausal patient with pyometrium, in addition to early intervention to prevent uterine rupture.

Highlight a case of pyometra in a postmenopausal woman with underlying gynecological malignancy.

Uterine perforation is a dangerous, and not uncommon consequence of prolonged pyometra, highlighting the importance of early diagnosis.

Underlying gynecological malignancy should be considered as an underlying cause of pyometrium in postmenopausal women.

Acknowledgments

None to declare.

Financial Disclosure

None to declare.

Conflict of Interest

None to declare.

Author Contributions

BD: literature search, introduction, discussion, abstract, and references. RM: case report, images, and literature search. GEK and MN: description of pathology findings, and images.

Data Availability

The authors declare that data supporting the findings of this study are available within the article.

Abbreviations

SPP: spontaneous perforated pyometra; US: ultrasound; CT: computed tomography; MRI: magnetic resonance imaging

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