Primary primitive neuroectodermal tumor of the cervix confirmed with molecular analysis in a pregnant woman: A case report and literature review

Introduction

Primary primitive neuroectodermal tumor (PNET) is a highly malignant tumor characterized by neuroectodermal and neural crest cells’ origin, most of which arise from the central nervous system, soft tissues, and bones (Rajwanshi et al., 2009). In more than 90% of PNET cases, chromosomal translocations result in the fusion between the EWS gene (also known as EWSR1, Ewing sarcoma breakpoint region 1) and a member of the ETS family of transcription factors, such as FLI1 and ERG (Song et al., 2012).

In this article, we presented a case of cervical PNET diagnosed during pregnancy whose tumor grew very rapidly. The patient terminated her pregnancy, and was treated with surgical resection, adjuvant chemotherapy, followed by pelvic radiotherapy. To gain a deeper understanding of this rare disease, we reviewed PNET-related literature and found 26 cases of primary cervical PNET, including 5 cases occurring during pregnancy.




Case report

A 29-year-old female, gravida 1 para 0, was referred to her obstetrician at the 7th week of gestation. An ultrasonography examination revealed a cystic-solid mass measuring 5 cm × 4 cm in the cervix. Her medical and family history were not significant. No additional examinations or treatments were performed because of her pregnancy. During follow-up, the ultrasonography examination demonstrated that the mass grew rapidly, and at the 20th week, the patient was admitted to our department because she began to complain of low back pain. An MRI was performed and it was found that the mass grew to 11 cm × 10 cm × 10 cm in just 2 months. The levels of CA-125, CEA, SCC, and NSE were normal. Considering the pregnancy, the patient refused biopsy and chose to continue observation.
However, at the 22nd week of gestation, the patient was referred to the emergency department because of vaginal watery discharge. Gynecological examination showed that there was a rupture on the surface of the tumor and fluid was flowing out of the rupture, which was thicker than amniotic fluid. The result of amniotic fluid crystallization was negative. In addition, MRI showed the cystic-solid mass was smaller (10 cm × 8 cm × 7 cm) than before. Bimanual pelvic examination revealed the tumor was in the cervix, without invading the vagina, or adjacent organs (Figure 1). The patient underwent a biopsy of the cervical mass, and it was found that the tumor consisted of small round cells and had extensive necrosis. IHC showed that tumor cells expressed CD99, synaptophysin (SYN), friend leukemia integration 1 (FLI1), and P16. However, no expression of cytokeratin (CAM5.2), P53, chromogranin A (CgA), CD56, or neuron specific enolase (NSE) was detected. Ki-67 proliferation index was about 80% (Figure 2). A pathological diagnosis of cervical PNET was suspected. Next, we performed FISH to detect the presence of the chromosomal translocation t (11;22, q24;q12). A section of 4 μm was cut from paraffin-embedded biopsy blocks and stained with hematoxylin-eosin in order to confirm the presence of tumor cells and to choose the appropriate area for the hybridization procedures. A specific translocation separation probe kit (Vysis, United States ) was used, which consisted of two probes; one directly labeled with red fluorescence and bound to 3′ end of the FLI1 (11q24) gene, and the second directly labeled with green fluorescence and bound to 5′ end of the EWSR1 (22q12) gene. According to the manufacturer’s instructions, 200 nuclei with fluorescence signal were randomly selected to observe the number of nuclei with hybridization signal by using a Zeiss Axioplan fluorescence microscope (Zeiss, Germany). Nuclei with the EWS-FLI1 fusion gene showed yellow signals, while nuclei without gene translocation showed separate red and green signal. The criterion for a positive result of the EWS-FLI1 fusion gene was that more than 10% of the nuclei showed a fusion signal. FISH demonstrated that more than 35% of the cells were positive, indicating the presence of the EWS-FLI1 fusion gene (Figure 3A). In order to clarify the type of fusion, we performed RT-PCR test. Total RNA was isolated using TRIzol (Gibico, United States ) and the concentrations were measured by NanoDrop-2000c (Thermo Fisher Scientific, United States ). Transcriptor high fidelity cDNA synthesis kit (Takara, Japan) was used for reverse transcription of 1 μg of RNA from the sample. RT-PCR was carried out using SYBR Green Master Mix (Roche, Switzerland) in a Quantstudio3 real-time thermal cycler (Thermo Fisher Scientific, United States ). Expression data were normalized to GAPDH. The primer sequences used for RT-PCR analysis of EWS-FLI1 were as follows; 5′- CCA​AGT​CAA​TAT​AGC​CAA​CAG-3′ and 5′-GGC​CAG​AAT​TCA​TGT​TAT​TGC-3’. RT-PCR products were analyzed on a 2% agarose gel electrophoresis. The results showed the RT-PCR product of the tumor was 166bp, which indicated that the 7th exon of EWS was fused to the 5th exon of FLI1 (Figures 3B,C). These results confirmed the diagnosis of cervical PNET.

Chest computed tomography, abdominal and pelvic MRI did not reveal lymph nodes or distant metastases. The patient and her family were informed of the highly invasive nature and poor prognosis of the disease, and they decided to terminate the pregnancy and receive surgical treatment. Subsequently, the patient underwent a type C1 radical hysterectomy, bilateral salpingo-oophorectomy, and pelvic lymphadenectomy. There was a complete fetus in the uterine cavity, and the cervical tumor was 9 cm × 8 cm × 8 cm in stereoscopic size, invading more than two-thirds of the cervical interstitium and extending to the parametrium. No lymph node metastasis was found. However, there was lymphovascular invasion. Histological and IHC staining supported the previous diagnosis of PNET, and according to the International Federation of Gynecology and Obstetrics, the clinical stage was determined asⅡB. After surgery, the patient received adjuvant chemotherapy with pirarubicin, ifosfamide, and cisplatin for six cycles, followed by pelvic radiotherapy of 50 Gy. She remained free of disease for thirty-one months after the diagnosis.

Conclusion

PNET in the female reproductive tract is an extremely rare disease. In this article, we reported a case of cervical PNET complicated by pregnancy. The diagnosis of PNET depends on pathology, immunohistochemistry, and genetic analysis. Molecular analysis may significantly contribute to the final diagnosis of PNET occurring in this unusual location. In addition, the type of EWS-FLI1 fusion may be related to clinical outcomes. At present, the effective treatment for PNET is surgery combined with chemotherapy and radiotherapy. The rapid growth of PNET during pregnancy may be related to hormonal changes and further research is needed.

#FutureOfNeuroscience, #Neurotechnology, #BrainResearch, #Neurobiology, #CognitiveScience, #BrainHealth, #Neuroplasticity, #Neurodiversity, #NeuroInnovation, #Neurodevelopment, #Neuropharmacology, #Neuroanatomy, #Neurophysiology, #BrainTraining, #Neuropsychology,

https://molecularbiologist.org/

Follow on:

Comments

Post a Comment

Popular posts from this blog

Why Vitamin D Deficiency Can Raise Autoimmune Disease Risk

Image
  The body can naturally produce vitamin D when skin is exposed to sunlight, but this process declines significantly in winter. There also aren't many food sources of vitamin D. But vitamin D is very important to the body. The  vitamin D receptor  can be found in many different tissues, and while the vitamin's roles in bone health and calcium level maintenance are  well known , less is understood about its other functions, such as how it relates to immunity. Several immune cells have vitamin D receptors and gene activity in those cells can be affected by the vitamin. Low levels of vitamin D have also been associated with a variety of autoimmune disorders including inflammatory bowel disease, multiple sclerosis, psoriasis vulgaris, rheumatoid arthritis, and type 1 diabetes. Studies  have also shown  that vitamin D supplements can help lower the risk of autoimmune disease. A new study  reported in  Science Advances  has provided new insights in...
Read more

Uncovering the molecular drivers of liver cancer

Image
  Researchers discover that inflammation and aging contribute to non-viral liver cancer development. Green tea's role in reversing some of the pathway dysregulation that may contribute to the cancer development and other therapies explored. Liver cancer can arise spontaneously from healthy liver tissue. Recently, however, researchers have discovered an increasing correlation between some liver cancers and non-viral chronic liver disease (CLD). One liver cancer, hepatocellular carcinoma (HCC), is associated with CLD in about 15–25% of cases. While increasing awareness and screening of cancers has improved the ability to detect liver cancer at earlier stages when it is more effectively treated, cancer prevention is always a primary goal of both healthcare providers and biomedical researchers. The increasing prevalence of CLD with HCC suggests that this underlying condition predisposes liver tissue to cancer development. In order to investigate how healthy liver tissue differs from th...
Read more

New Hybrid Cell Discovery Shakes Up Neuroscience

Image
Neuroscientists have unveiled a new hybrid cell, straddling the line between the well-known neurons and glial cells in the brain.Previously, glial cells, especially astrocytes, were believed to merely support neuron functions. However, recent research highlights the ability of these cells to release neurotransmitters and directly influence neural circuits.This groundbreaking discovery challenges traditional beliefs about brain cell functionality and paves the way for novel therapeutic strategies. Key Facts: A new hybrid cell type, located between neurons and astrocytes, has been identified that can release neurotransmitters. Modern molecular biology techniques confirmed that astrocytes possess machinery necessary for the rapid secretion of glutamate. Disruption of these hybrid cells’ functionality impacts memory, has links with epilepsy, and offers therapeutic insights for Parkinson’s disease. Source: University of Lausanne Neuroscience is in great upheaval. The two major families of c...
Read more