Gastric-Type Mucinous Adenocarcinoma of the Cervix in A Woman With Peutz-Jeghers Syndrome



Background: Peutz-Jeghers syndrome(PJS) is a very rare autosomal dominant disorder with predisposition to multiple neoplasms. Gastric-type adenocarcinoma (GAS) is a less common carcinoma of the cervix than squamous cell carcinoma, which is more aggressive and has lower 5 year survival rate than usual type endocervical adenocarcinoma (ECA), and unrelated to human papilloma virus(HPV) infection as well. We present a 32 year-old patient with Peutz-Jeghers syndrome who was found to have gastric-type adenocarcinoma of the cervix.

Case presentation: A 32-year-old woman without sexual life ever who was diagnosed Peutz-Jeghers syndrome when she was two years old presented with watery discharge for more than 6 months. A tumor around 6cm was found on the cervix and she was diagnosed gastric-type mucinous adenocarcinoma of the cervix clinical stage IB3. She was treated with artery intervention chemotherapy for one course followed by radical surgery and then systematic chemotherapy.

Conclusions: The case suggests more thorough cancer screening for patients with PJS as the disorder is rare and has high risk of malignancies. Young patients with Peutz-Jeghers syndrome, including those without sexual life, who have watery discharge or bleeding should be screened for cervical carcinoma even if cytologic results or human papilloma virus (HPV) is negative.


Peutz-Jeghers syndrome is a rare autosomal dominant disorder characterized by mucocutaneous pigmentation, multiple hamartomatous polyps in the gastrointestinal tracts and predisposition to certain neoplasm1. The estimated incidence ranges from 1 in 50,000 to 1 in 200,000 live births1,2. Previous reports3,4 shows that 11–17% of women with Peutz-Jeghers syndrome are found to have gastric-type adenocarcinoma (GAS). We report a case of adenocarcinoma of the cervix, diagnosed by cervical biopsy in a woman with Peutz-Jeghers syndrome, which was eventually histo-pathologically confirmed to be GAS after radical surgery.

Adenocarcinoma of the cervix is less common than squamous cell carcinoma of the cervix. However, the incidence of cervical adenocarcinoma has been increasing, especially in young women and is estimated to account for up to 10%-25% of all invasive cervical carcinomas5. Gastric-type adenocarcinoma (GAS) is a novel variant of endocervical mucinous adenocarcinoma according to the 2014 WHO classification6. It represents more aggressive disease and poorer prognosis than the usual-type endocervical adenocarcinoma (UEA)7,8.

Case Presentation

The institutional review board (International Peace Maternity and Child Health Hospital) approved this work. A 32-year-old woman without sexual life ever presented with a history of recurrent watery vaginal discharge for more than 6 months and prolonged menstrual periods over the preceding 3 months in August 2020. Pelvic magnetic resonance imaging (MRI) revealed a cervical mass 5.8*5.6*7.6 cm while enlarged lymph nodes were not seen (Fig. 1A and 1B). The patient was diagnosed Peutz-Jeghers syndrome at 2 months old at a tertiary hospital for mucocutaneous pigmentations over the lips. She had a history of colon polyps resection by colonoscopy when she was 12 years old and since then had colonoscopy and biopsy every year. In 2002 when she was 14 years old, she had an emergent surgery for bowl obstruction. In 2018 she had a surgery for breast tumor and pathology confirmed benign. No other family members were found with Peutz-Jeghers syndrome.

Physical examination revealed mucocutaneous pigmentations over the lips, especially the lower lip and nostrils (Fig. 2). Laboratory data showed no blood, urine, or stool changes. HPV test was negative. Tumor markers including carbohydrate antigen125(CA125), carbohydrate antigen199(CA199), squamous cell carcinoma antigen(SCC), carbohydrate antigen153(CA153), carbohydrate antigen724(CA724), carcino-embryonic antigen(CEA), alpha fetoprotein(AFP) and human epididymis protein4(HE4) were within normal range.

We proceeded with a gynecological examination under anesthesia. A tumor around 6 cm was found on the cervix, vagina and parametrium was not invaded on physical examination. Biopsy was taken and paraffin section pathology diagnosed moderate differentiated gastric-type mucinous adenocarcinoma of the cervix.

In accordance with the latest 2018 International Federation of Gynecology and Obstetrics criteria, gastric-type mucinous adenocarcinoma of the cervix clinical stage IB3 was diagnosed. We gave her artery intervention chemotherapy for one course9,10 (intravenous taxol 135 mg/m2 and bilateral uterine artery cis-platinum 80 mg/m2). MRI was taken 2 weeks later for tumor assessment. On the second MRI, the tumor shrinked to 4 + cm, and there were some dartoid tissue fell out of vagina one week after the artery intervention chemotherapy told by the patient.

Eventually, the patient underwent laparoscopic radical hysterectomy, bilateral salping-oophorectomy, bilateral pelvic lymph node dissection and para-aortic lymph node dissection 3 weeks after the artery intervention chemotherapy. The final histo-pathological analysis of the specimen from radical surgery confirmed moderate differentiated cervical gastric-type mucinous adenocarcinoma (Fig. 3A and Fig. 3B). No myometrial invasion or metastasis to pelvic lymph nodes was observed, no lymphovascular space invasion and clear vaginal resection margins. Immuno-histochemistry shows MUC6(+), MUC2(-), P16 patchy, ER and PR all negative(Fig. 4A-4F). A gene test was also taken and a mutation of STK11 was confirmed. The patient had adjuvant chemoradiation therapy after the radical surgery: intravenous taxol (135 mg/m2 every 21 days) and carboplatin (area under the curve of concentration*time[AUC] = 5 every 21 days). We plan to give her 6 courses of intravenous chemotherapy in total and right now she already has 5 courses and tolerates well.

Discussion And Conclusions

Peutz-Jeghers syndrome (PJS) is a clinical syndrome, occurring in sporadic and in autosomal dominant inherited forms, usually characterized by gastrointestinal, especially small bowel, hamartomatous polyposis, mucocutaneous melanin pigmentation and predisposition to certain neoplasms11. The first systematic descriptions of the inherited form of PJS are credited to Drs Jan Peutz and Harold Jeghers, who both described patients with gastrointestinal hamartomatous polyps and mucocutaneous melanin pigmentation—the latter distinguishing PJS from other gastrointestinal polyposis syndromes12,13. PJS affects about 1 in 50,000 to 200,000 individuals. Right now PJS is diagnosed by clinical criteria in a proband with one of the following, based on a European consensus statement14: Two or more histologically confirmed PJS-type hamartomatous polyps; Any number of PJS-type polyps detected in one individual who has a family history of PJS in at least one close relative; Characteristic mucocutaneous pigmentation in an individual who has a family history of PJS in at least one close relative; Any number of PJS-type polyps in an individual who also has characteristic mucocutaneous pigmentation.

PJS is a rare autosomal dominant syndrome defined by germline mutation of STK11 (chromosome 19p13.3) which encodes a serine/threonine kinase involved in cell polarity, metabolism and growth15. Germline mutation of STK11 is detected in 94% of PJS patients16,17. In this case, the patient was found STK11 mutation on chromosome 19 in exon 4. Until now a variety of deletion, insertion, inversion, and nonsense mutations have been described in nearly every coding exon, predominately in exons 1, 5, 6, and 718,19. However, right now data on genotype-phenotype correlation related to STK11 pathogenic variants are conflicting. The major source of morbidity and mortality, besides intestinal intussusception in young patients, is the increased lifetime risk of cancer, the most common being breast, colon, pancreatic, gastric, small intestine and lung cancer, the cumulative risks were seen in table 11. PJS-specific cancer surveillance guidelines exist, see table 21.

  1. If significant polyps are present at baseline, repeat upper endoscopy/colonoscopy every three years. If no significant polyps are present at baseline, repeat at age 18 years and then every three years.

  2. CT enterography may be used as an alternative. The use of MR enterography allows for simultaneous surveillance for pancreatic cancer.

  3. If few or no polyps at baseline, repeat at age 18 years.

  4.  Digital mammography if MRI not available

  5.  Discuss prophylactic mastectomy.

  6. Discuss prophylactic hysterectomy and oophorectomy.

Gynaecological tumours are not a major manifestation of PJS but there are two with distinct pathological features20: (1)gastric-type adenocarcinoma of the endocervix (GAS) and (2) ovarian sex cord tumour with annular tubules (SCTAT). Much less commonly, ovarian oxyphilic Sertoli cell tumour may occur in PJS patients21. One meta-analysis of the literature estimated the lifetime risk of cervical cancer in PJS to be 9% and mean age at diagnosis in the third decade20. Most cases were so-called adenoma malignum (also known as minimal deviation adenocarcinoma, MDA), which is now considered to be equivalent to a well-differentiated form of GAS in the 2014 World Health Organization(WHO) classification system. On the other hand, among those who have GAS, about 11–17% have PJS22,23. Ovarian tumors occur in about 21% of PJS patients, most of which are SCTAT24.

The diagnosis of gastric-type adenocarcinoma is based on the histological criteria25,26 : 1) clear or pale eosinophilic cytoplasm, 2) voluminous cytoplasm, and 3) distinct cell borders. The immune-phenotype of GAS is defined by the presence of pyloric gland mucin (positive MUC6 and HIK1083 staining) and by the absence of high risk HPV(hrHPV) 1627–30, MUC6 is more widely available than HIK1083, both of which mark pyloric gland mucin of the stomach and are positive in most GAS and lobular endocervical glandular hyperplasia(LEGH) but not in normal endocervix or usual type endocervical adenocarcinoma(ECA)8,11. p16 staining is usually patchy or negative. Most GAS lack estrogen receptors, and is unrelated to HPV infection, as shown in our case.

The presenting sign of GAS is often mucoid or watery discharge or vaginal bleeding, and typically shows widespread involvement and advanced stage at initial diagnosis. Ovarian involvement is not uncommon as well. GAS is more aggressive than usual type ECA; the 5 year survival rate is less than half of that for usual type ECA31,20. The prognosis of patients with GAS is worse than that of patients with HPV-related adenocarcinoma because patients with GAS tend to represent an advanced-stage disease and unusual metastatic organs. So in our case, we suggested and finally performed bi-oophorectomy for the patient under her consent. In the meanwhile, as according to the 2018 LACC clinical trial, we improved the surgical procedures of laparoscopic radical hysterectomy. In the surgery, a tape was used for uterus manipulation instead of cup-type uterine trans-cervical manipulator; In addition, colpotomy was done vaginally and the uterus was taken out from the vagina with the cervix wrapped in the vaginal wall cut.

Because of the high risk of malignancy in Peutz-Jeghers syndrome, a more thorough cancer screening has been proposed. Annual pelvic sonography and cervical screening test have been recommended for cancer screening in females with Peutz-Jeghers syndrome11,20,1. Although cytologic or HPV tests are usually negative in GAS, the presence of an enlarged cervix with multiple cysts in a patient with Peutz-Jeghers syndrome is an indication for cervical biopsy even if the patient has no sexual life.



Peutz-Jeghers syndrome


gastric-type adenocarcinoma


endocervical adenocarcinoma


human papilloma virus


usual-type endocervical adenocarcinoma


magnetic resonance imaging


carbohydrate antigen125


carbohydrate antigen199


squamous cell carcinoma antigen


carbohydrate antigen153


carbohydrate antigen724


carcino-embryonic antigen


alpha fetoprotein


human epididymis protein4


area under the curve of concentration


sex cord tumour with annular tubules


minimal deviation adenocarcinoma


World Health Organization


lobular endocervical glandular hyperplasia


The institutional review board (International Peace Maternity and Child Health Hospital) approved this work

Informed consent for publication of clinical data/details/images was obtained from patient. A copy of consent is available for review by the Editor of this journal

There is no dataset as this is a case report. Data/details of the patient available upon request

The authors declare that they have no competing interests

This research did not receive any specific grants or funding

TT: writing of the manuscript. FQ: providing the case details. SS: providing the case details. LYH: writing and editing of the manuscript. WYD: editing of the manuscript. The authors read and approved the final manuscript

We thank Professor Huijuan Zhang for providing pathology information and guidance of the case.


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Table 1

Cumulative Risk of Cancers in Peutz-Jeghers Syndrome

Cancer site

General population risk

Peutz-Jeghers syndrome


Mean age at diagnosis




42–46 years


< 1%


30–40 years

Small Bowel

< 1%


37–42 years

Ovarian(mostly SCTAT)



28 years

Cervix(adenoma malignum)

< 1%


34–40 years




43 years




41–52 years

Testicular(Sertoli cell tumor)

< 1%


6–9 years




47 years




37–59 years

SCTAT: sex cord tumour with annular tubules
Table 2

Screening and Surveillance Guidelines for Peutz-Jeghers Syndrome



Age at Initial Screening(yr)



Upper endoscopy

8, 181

3 yrs1

Small intestine

Capsule endoscopy or MRE2

8, 183

3 yrs

Large intestine


8, 181

3 yrs1


Breast self-examination



Clinical breast exam


6 mos

Breast MRI or digital mammography4,5,6


1 yr

Ovary, cervix,uterus

Transvaginal ultrasound & serum CA 125;pelvic exam w/pap smear6


1 yr


MRI-MRCP or endoscopic ultrasound


1–2 yrs


Testicular exam; ultrasound if symptomatic or abnormality on exam

Birth to teen yrs

1 yr

MRCP = magnetic resonance cholangiopancreatography; MRE = magnetic resonance enterography