Primary ovarian cancer combined with primary fallopian tube cancer: A case report

Abstract

BACKGROUND

Low grade serous carcinoma of the ovary (LGSOC) is a rare type of epithelial ovarian cancer with a low incidence rate. The origin of ovarian cancer has always been a hot topic in gynecological oncology research, and some scholars believe that the origin of ovarian malignant tumors is the fallopian tubes. Primary fallopian tube cancer is the lowest incidence of malignant tumors in the female reproductive system. There are only a few reports in the literature, but the mortality rate is very high. But in clinical practice, fallopian tube cancer is very common, but in most cases, it is classified as ovarian cancer.

CASE SUMMARY

We report a 54 years old postmenopausal woman who was hospitalized with a lower abdominal mass and underwent surgical treatment. The final pathological confirmation was low-grade serous carcinoma of the right ovary and low-grade serous carcinoma of the left fallopian tube. No special treatment was performed after the surgery, and the patient was instructed to undergo regular follow-up without any signs of disease progression.

CONCLUSION

The prognosis of LGSOC is relatively good, over 80% of patients still experience disease recurrence.

Key Words: Low grade serous carcinoma of the ovary, Primary fallopian tube cancer, Ovarian cancer, Epithelial ovarian cancer, Case report

Core Tip: Although the prognosis of low grade serous carcinoma of the ovary (LGSOC) is relatively good, over 80% of patients still experience disease recurrence. In most cases, these patients are relatively young and have the potential to receive active treatment and achieve a longer survival period. The treatment methods for LGSOC recurrence include re-tumor reduction surgery, chemotherapy, targeted therapy, hormone therapy and clinical trials. Currently, a large amount of research focuses on gene testing and targeted therapy. I hope that the progress of genome research and targeted therapy can change the therapeutic prospects of LGSOC and bring better therapeutic effects to patients with this disease.

INTRODUCTION

Low grade serous carcinoma of the ovary (LGSOC) is a rare type of epithelial ovarian cancer. Primary fallopian tube cancer is the lowest incidence rate among female reproductive system malignancies. The origin of ovarian cancer has always been a hot topic in gynecological oncology research, and some scholars believe that the origin of ovarian malignant tumors is the fallopian tubes.

We present a case of ovarian cancer combined with fallopian tube cancer in this manuscript.

CASE PRESENTATION

Chief complaints

A 54 years old postmenopausal woman visited our hospital on July 30, 2023 due to the discovery of a lower abdominal mass for half a month. She has no abnormal vaginal bleeding or discharge, and no abdominal pain. Her gynecological ultrasound showed a pelvic cyst (A liquid dark area of approximately 117 mm × 97 mm × 89 mm in size can be seen in front of the uterus, with good internal sound transmission. Several hyperechoic masses can be seen attached to the wall, with the larger area being approximately 28 mm × 31 mm × 19 mm in size) (Figure 1).

Figure 1 Gynecological ultrasound showed a pelvic cyst.

History of present illness

The patient has a history of good physical health and no history of chronic diseases.

History of past illness

Her menstrual cycle is regular, with a menarche age of 16 years old, a menstrual period of 5 d, and a menstrual cycle of 28-30 d. At the age of 52, she experienced menopause and had no history of dysmenorrhea or irregular vaginal bleeding. She had two children and had a history of induced abortion. Her body mass index (BMI) is 22.0. She has not undergone regular gynecological examinations before.

Personal and family history

There is no history of malignant tumors in her family.

Physical examination

After the patient checked into our department, we conducted a detailed physical examination on her, and no abnormalities were found in her cardiopulmonary and abdominal examinations. Her lymph nodes are not swollen. A gynecological examination was performed on her, and a cystic solid mass with a diameter of approximately 12 cm was palpable in her right adnexal area. The boundary of the mass was unclear, without tenderness, and the activity was poor.

Laboratory examinations

After the patient was admitted, all preoperative examinations were completed, and her female tumor markers showed no abnormalities, while the gastroscopy examination showed no abnormalities. The postoperative pathological report of this patient is as follows: (1) Low grade serous carcinoma of the right ovary, with no intravascular tumor thrombus or nerve infiltration. No cancer was found in the right fallopian tube. Immunohistochemical staining: P53 (wild-type), ER (partial+), PR (rarely+), CA125 (+), CK7 (+), CK20 (-), Ki-67 (about 20%+), P16 (-), WT-1 (+), Villin (-), HNF1-Beta (small focal weak+); (2) Low grade serous carcinoma of the left fallopian tube. No cancer was found in the left ovary; (3) No cancer was found in the greater omentum. No cancer was found in the peritoneum of the left and right pelvic walls, the peritoneum of the left and right colonic sulcus, the peritoneum of the rectal fossa, and the retroperitoneum of the bladder; (4) No cancer metastasis found in lymph nodes; and (5) No cancer cells were found in the peritoneal lavage solution.

Imaging examinations

Her pelvic computed tomography (CT) showed a circular cystic solid mass shadow on the right adnexal area of the pelvic cavity, with clear boundaries and a size of approximately 105 mm × 113 mm × 126 mm, no obvious enhancement was observed in the cystic part of the enhanced scan, and the local thickening of the cyst wall was not uniformly enhanced. Linear enhancement septa were visible inside the cyst, and the solid components inside the cyst showed obvious progressive enhancement (Figure 2).

Figure 2 Pelvic computed tomography showed a circular cystic solid mass.

FINAL DIAGNOSIS

The final diagnosis of this patient is: (1) Primary ovarian low-grade serous carcinoma stage IA; and (2) Primary fallopian tube low-grade serous carcinoma stage IA.

TREATMENT

On August 3, 2023, we performed surgical treatment on the patient. During the operation, we found no ascites in the abdominal cavity, the uterus was smaller than normal, and a tumor with a diameter of about 10 cm was visible in the right ovary, mainly cystic, with a smooth surface. There were no obvious abnormalities in the appearance of the right fallopian tube and left appendix. We removed the right accessory and opened it. After opening, we found solid cauliflower like tissue inside the cyst, which was sent for intraoperative frozen pathological examination. The frozen pathological result is a cystic adenoid tumor (right attachment), locally infiltrating carcinoma, to be further confirmed by paraffin section. During the surgery, we explored the omentum, colon, small intestine, appendix, bladder, liver, stomach, and spleen, but no cancer nodules were found on the surface. The diaphragm and peritoneum were smooth, and no lesions were found. During the surgery, we explained the patient's condition to the authorized person and obtained informed consent. After obtaining informed consent, we performed ovarian cancer staging surgery on the patient, including transabdominal total hysterectomy, bilateral ovarian and fallopian tube resection, greater omentum resection, pelvic and paraaortic lymph node resection, and peritoneal multipoint biopsy.

OUTCOME AND FOLLOW-UP

We didn't provide her with additional treatment after the surgery, we just suggested that she needs regular follow-up.

DISCUSSION

LGSOC is a rare type of epithelial ovarian cancer. Its incidence rate is low, accounting for 2% of all epithelial ovarian cancer and 4.7% of serous ovarian cancer[1]. It is reported that primary fallopian tube cancer is the lowest incidence rate among female reproductive system malignancies. There are only a few reports in the literature, but the mortality rate is very high. However, in reality, fallopian tube cancer is very common in clinical work, but in most cases, it is considered a type of ovarian cancer, resulting in limited reports on primary fallopian tube cancer. Because the incidence rate of LGSOC is low, there is no clear guidance and consensus at present. This article describes the LGSOC by providing a case of primary LGSOC with primary low-grade serous carcinoma of the fallopian tube.

LGSOC generally grows slowly and has a longer course. Its staging distribution is similar to that of high grade serous ovarian carcinoma (HGSOC), with 80% of patients diagnosed as advanced[2]. Compared with HGSOC, LGSOC has unique molecular biological characteristics and clinical manifestations, therefore, its treatment method is also different from HGSOC. With the establishment of the binary classification theory of ovarian serous cancer, many scholars have been prompted to study LGSOC as an independent rare disease. Due to its low incidence rate and limited number of cases reported at present, its etiology and prognostic factors are not completely clear. The onset age of LGSOC is relatively young, with a median onset age between 43 and 47 years old[3,4]. Currently, there are no clear genetic or environmental susceptibility factors for LGSOC. Some scholars believe that LGSOC may originate from benign ovarian serous tumors, then transform into borderline serous tumors, and ultimately develop into low-grade serous cancer[5], or it can itself be low-grade serous cancer. A comprehensive population study conducted by Vang et al[6] included 1042 cases of ovarian borderline tumors diagnosed in Denmark between 1978 and 2002, of which 4% developed ovarian cancer, 93% had low-grade serous cancer, and 7% had high-grade serous cancer. At present, several studies have found that age of first onset, BMI, and smoking status may be associated with the prognosis of LGSOC patients[3,4,7]. Among patients in stage II-IV, patients diagnosed after 35 years old have longer progression free survival and overall survival compared to patients diagnosed before 35 years old, and the likelihood of tumor progression and recurrence is also lower. Higher BMI (≥ 35 kg/m²) and smoking both increase the likelihood of disease progression and recurrence in LGSOC patients, shortening their survival time. The characteristic of LGSOC is the abnormal mitogen activated protein kinase (MAPK) pathway, which is a major intracellular signaling pathway responsible for regulating important cellular activities such as cell survival, proliferation, migration, and angiogenesis. MAPK mediates the transmission of growth signals to the nucleus. Mutations in upstream regulatory factors BRAF or KRAS of the MAPK pathway lead to constitutive activation of MAPK, thereby activating various downstream cellular and nuclear targets[8]. Compared with HGSOC, its sensitivity to chemotherapy is reduced. Approximately 20% to 40% of KRAS mutations, 5% of BRAF mutation frequencies, and very high estrogen and progesterone receptors positivity rates are present in LGSOC[9]. LGSOC rarely has BRCA gene mutations and is rarely associated with hereditary breast cancer ovarian cancer syndrome[10]. In contrast to HGSOC, LGSOC is mostly P53 wild-type and rarely undergoes P53 mutations[11,12]. Therefore, P53 immunohistochemistry is commonly used to distinguish between HGSOC and LGSOC. The cellular origin of ovarian cancer has always been a research hotspot of interest to researchers. Currently, some scholars believe that a certain proportion of ovarian cancer may be the result of malignant cells implanted into the ovary from fallopian tube cancer[13,14], but it is only speculated and has not been fully confirmed. Some researchers believe that the fallopian tubes are the origin of LGSOC.

In the early stages of LGSOC, there may be no symptoms. As the disease progresses, there may be abdominal distension, abdominal mass, pleural effusion, and other gastrointestinal symptoms, such as intestinal obstruction. Some patients may also exhibit cachexia such as weight loss and anemia, and it is generally rare for those with ascites[15]. In addition to routine medical history collection and detailed physical examination, it is also necessary to improve tumor marker carbohydrate antigen 125 (CA125), gynecological ultrasound, chest abdominal pelvic CT, and other examinations. Compared with HGSOC, there are fewer patients with elevated levels of CA125 in LGSOC. Analysis of GOG182 results showed that early normalization of CA125 levels is associated with a reduced risk of death, suggesting that CA-125 may be a sensitive biomarker for treatment response and can predict the outcome of LGSC[16].

Surgical treatment is the cornerstone of LGSOC treatment, and the most basic surgical methods for early patients without fertility requirements are total hysterectomy, bilateral fallopian tube oophorectomy, pelvic and paraaortic lymph node resection, omentectomy, and peritoneal multipoint biopsy. For advanced patients, tumor cell reduction surgery is necessary, and every effort must be made to remove all visible metastatic lesions. Many scholars have discussed the impact of residual diseases on the prognosis of LGSOC. In the auxiliary analysis of GOG182, Fader et al[15] published a study on the survival rate of 189 LGSOC patients, and only residual disease status was significantly correlated with survival rate. The median progression free survival (PFS) of residues smaller than 1 cm and larger than 1 cm under the microscope were 32.2 months, 14.65 months, and 14.1 months, respectively. Similarly, the median overall survival of microscopic residues smaller than 1 cm and larger than 1 cm were 96.6 months, 45 months, and 42 months, respectively. After controlling for other variables, the disease progression adjusted hazard ratio (HR) for LGSOC and measurable residual disease patients after initial cell reduction surgery was 2.28, and the death HR was 2.12, which is comparable to the results of HGSOC for measurable diseases[16,17]. In addition, Gershenson et al[3] concluded that compared to the absence of visible lesions at the end of the surgery, the presence of measurable lesions at the end of the initial cytoreductive surgery increases the risk of disease progression or recurrence, as well as the risk of death. Vatansever et al[18] also reached the same conclusion. For early patients with fertility requirements, surgery to preserve fertility function can preserve the patient's hope of pregnancy while treating the disease, and is suitable for patients of childbearing age from IA to IC1. Many scholars have conducted retrospective studies on the safety of fertility preserving surgery, and have concluded that it is safe and does not increase mortality for early patients[19,20]. Angiogenesis has been proven to play an important role in the occurrence and development of tumors. Bevacizumab is a monoclonal antibody that can inhibit vascular endothelial growth factor, but its application in the treatment of LGSOC has not yet been supported by high-level evidence, and further research on its therapeutic effect requires large-scale clinical trials. Hormone maintenance therapy after adjuvant chemotherapy can improve prognosis. Gershenson et al[21] retrospectively studied the results of hormone maintenance therapy in 203 patients with stage II-IV LGSOC. The study found that patients who added hormone maintenance therapy after surgery and chemotherapy had significantly longer PFS and lower risk of disease progression compared to those who chose to observe after surgery and chemotherapy[21].

CONCLUSION

Although the prognosis of LGSOC is relatively good, over 80% of patients still experience disease recurrence. In most cases, these patients are relatively young and have the potential to receive active treatment and achieve a longer survival period. The treatment options for LGSOC recurrence include re-tumor reduction surgery, chemotherapy, targeted therapy, hormone therapy and clinical trials. Currently, a large amount of research focuses on gene testing and targeted therapy. I hope that the progress of genome research and targeted therapy can change the therapeutic prospects of LGSOC and bring better therapeutic effects to patients with this disease.