HPV-independent gastric type adenocarcinoma of the uterine cervix presenting as ovarian masses: A case report and review of literature

@#Adenocarcinoma, HPV-independent, gastric type of the uterine cervix comprises only 10-15% of all cervical adenocarcinomas. A rare case of which, with metastasis to the uterine corpus and bilateral ovaries, is described. A 43-year-old female (G0P0) presented with menorrhagia and right flank pain radiating to the hypogastrium. Physical examination revealed an immovable, tender mass at the right lower quadrant with a nodular, firm cervix. Transabdominal ultrasound revealed multiseptated ovarian masses. The right and left ovaries were sent for frozen section and was diagnosed as Mucinous Cystadenoma and Mature Cystic Teratoma, respectively. Hysterectomy revealed a detached and fragmented cervix with irregular, abnormally shaped glands lined by a single layer of columnar cells with bland, basally located nuclei and clear cytoplasm associated with desmoplasia, findings which were also seen in the endomyometrium and ovaries. These tumor cells were CK7 positive and negative for ER, PR, CK20 and CDX2. The patient died six months after surgery. The presence of benign appearing glands is a diagnostic challenge. Despite the appearance, they may be malignant and should be investigated rigorously.

Células glandulares atípicas: abordagem ginecológica / Atypical glandular cells: gynecological approach

As células glandulares atípicas representam 0,2% a 2,1% dos resultados dos testes de Papanicolaou. Mesmo com essa baixa prevalência, tem um significado importante no diagnóstico do câncer cervical e endometrial, tendo em vista que tais células e subcategorias, associadas à idade da paciente, podem prenunciar um número expressivo de doença intraepitelial, doença invasiva do endocérvix, endométrio e até neoplasias anexiais. E não se pode esquecer do importante número de resultados histológicos benignos, identificados no seguimento dessas pacientes, muitas vezes assintomáticas.(AU)

Atypical glandular cells represent 0,2% to 2,1% of Pap test results even with this low prevalence has an important significance in the diagnosis of cervical and endometrial cancer, considering that such cells and subcategories associated with the patient's age can predict a significant number of intraepithelial disease, invasive disease of the endometrium, endocervix and even adnexial neoplasms; no forgetting the important number of benign histological results, identified in the follow up of these patients, often asymptomatic.(AU)

Adenocarcinoma cervical in situ: abordagem na atenção primária e secundária à saúde / Cervical adenocarcinoma in situ: approach in primary and secondary health care

O adenocarcinoma cervical in situ é uma doença rara, totalmente curável, diagnosticada predominantemente por meio de rastreamento cervicouterino seguido de biópsia guiada por colposcopia e/ou conização. O tratamento em pacientes que desejam preservar a fertilidade pode ser realizado num contexto ambulatorial; aquelas com paridade definida deverão ser abordadas em nível terciário.(AU)

Cervical adenocarcinoma in situ is a rare, fully curable disease diagnosed predominantly through cervical-uterine screening followed by colposcopy-guided biopsy and/or conization. Treatment in patients wishing to preserve fertility may be performed in an outpatient setting; those with defined parity should be approached at the tertiary level.(AU)

Peritoneal metastasis in Stage IB1 adenocarcinoma cervix: A rare entity

The presence of ovarian or peritoneal metastasis in early-stage cervical malignancy is a rare entity. It often poses a diagnostic challenge whether it is a synchronous primary tumor or a metastatic lesion. A 63-year-old postmenopausal woman presented with Stage 1B1 carcinoma cervix with ascites, and a 5.8 cm × 4.2 cm × 3.5 cm left solid adnexal mass. She underwent Type III radical hysterectomy, excision of peritoneal mass, with bilateral pelvic and paraaortic lymphadenectomy and infracolic omentectomy. On histopathology, cervix showed features of adenocarcinoma, and the peritoneal mass revealed similar histomorphology as cervical growth with metastatic tumor deposits in omentum. Immunohistochemistry (IHC) was utilized to determine the origin of mass. The early stage disease and histology may not always predict the distant metastasis. Therefore, a thorough pretreatment evaluation, meticulous intraoperative assessment, and IHC are mandatory for optimum management and prognostication

Adenocarcinoma cervical: diagnóstico na atenção primária e secundária à saúde / Cervical adenocarcinoma: diagnosis in primary and secondary health care

O adenocarcinoma cervical é uma patologia grave cuja incidência tem aumentado, principalmente em pacientes jovens. Um diagnóstico oportuno, na assistência primária e secundária à saúde, com métodos convencionais, melhora sobremaneira o prognóstico da paciente, a um custo tolerável para países em desenvolvimento.(AU)

The cervical adenocarcinoma is a serious pathology whose incident has increased mainly in young patients. One opportunistic diagnosis, in primary and secondary health care, with conventional methods, greatly improves the prognosis of the patients, at a cost tolerable to developing countries.(AU)

Value of combined detection of cervical cytology and high-risk human papillomavirus in the diagnosis of cervical adenocarcinoma / 上海交通大学学报（医学版）

Objective • To investigate the diagnostic value of combined detection of cervical cytology and high-risk human papillomavirus (HPV) in cervical adenocarcinoma. Methods • The clinical data of patients diagnosed as cervical adenocarcinoma in the International Peace Maternal and Child Health Hospital, Shanghai Jiao Tong University School of Medicine from January 2006 to December 2017 were retrospectively collected and analyzed. A comparison among cytology detection, high-risk HPV test, and combined detection of both methods was performed. Results • A total of 2 291 cases of cervical cancer were collected, of which 480 cases were cervical adenocarcinoma patients. Finally, 409 cases of cervical adenocarcinoma were analyzed. The average age of all included patients was (46.8±11.4) years old. The proportion of the patients aged 35-55 was 59.2%. All the patients were divided into three groups, i.e., group A (cytology detection, n=208), group B (high-risk HPV test, n=103), and group C (cytology and high-risk HPV combined test, n=98). There were 142 (68.3%), 85 (82.5%), and 93 (94.9%) positive cases in group A, B, and C, respectively. There was a statistically significant difference among the three groups (P=0.000). In the patients with cervical in situ adenocarcinoma, the positive detection rates in group A, B and C were 70.6%, 100.0% and 100.0%, respectively (P=0.000). And in the patients with cervical invasive adenocarcinoma, the positive detection rates in group A, B, and C were 67.9%, 75.8% and 91.8%, respectively (P=0.000). Conclusion • Cervical cytology combined with high-risk HPV detection can significantly increase the positive detection rate of cervical adenocarcinoma.

Incidence Trend and Clinical Characteristic Changes of Inpatients with Cervical Adenocarcinoma in the Last Decade / 实用妇产科杂志

Objective:To evaluate the incidence trend and clinical characteristic changes of inpatients with cervical adenocarcinoma in the last decade.Methods:A retrospective analysis was performed.99 patients diagnosed with adenocarcinoma of cervix and hospitalized at Peking University First Hospital(PUFH) from January 2006 to May 2016 were included.Patients were divided into two groups according to the year and the results of screening.The clinical characteristics including basic information,diagnostic way and cancer stage were recorded and analysed.Results:①The incidence ratio of cervical adenocarcinoma had been significantly increased in the last decade,while clinical stage was statistically different.②The top three symptoms of cervical adenocarcinoma were irregular vaginal bleeding,bleeding after intercourse,abnormal vaginal discharge,accounting for 37.37％,34.34％ and 8.08％,respectively.There were significant differences in the stage of cervical cancer and the diameter of the lesion(P ＜0.05) after the comparison between the symptomatic group and the asymptomatic group,but there were no differences in differentiation degree,pathological type,lymph node metastasis and resection margin.③ Cytological screening of cervical adenocarcinoma was still dominated by squamous cell changes (42.19％).HPV18 ranked first in HPV detection,accounting for 36.21％ (21/58),however,29.31％ cases were negative in HPV test.There was no significant difference in the age,pathological type,differentiation degree,resection margin and lymph node metastasis between HPV negative and positive patients with cervical adenocarcinoma (P ＞ 0.05).Conclusions:The incidence of cervical adenocarcinoma is increasing year by year.Some patients with cervical adenocarcinoma have negative screening results for cytology and HPV,easy to be missed diagnosis,therefore,more attention should be put into the screening for cervical adenocarcinoma in order to find the cancer earlier.

Extrafascial hysterectomy after concurrent chemoradiotherapy in locally advanced cervical adenocarcinoma / 부인종양

OBJECTIVE: To evaluate whether adjuvant simple hysterectomy after concurrent chemoradiotherapy (CCRT) improves progression-free survival (PFS) compared with current standard care in locally advanced cervical adenocarcinoma (LACAC). METHODS: We reviewed a cohort of 55 patients with LACAC (International Federation of Gynecology and Obstetrics [FIGO] stage IB2, IIA2, IIB, III without distant metastasis) diagnosed and treated with radical CCRT at Peking Union Medical College Hospital between January 2004 and October 2014. We compared 34 patients who underwent adjuvant extrafascial hysterectomy with 21 patients with standard care after CCRT. The primary outcome was PFS. Overall survivals (OS) between the two groups were also compared. Surgery feasibility, operative complications, and pathologic features after radiation therapy were also analyzed. RESULTS: PFS was significantly improved in surgery group (log-rank p=0.0097; hazard ratio [HR], 0.3431; 95% CI, 0.152 to 0.772), as were OS (log-rank p=0.0419; HR, 0.3667; 95% CI, 0.139 to 0.964). Analysis of stage IIB demonstrates a similar result. There were no severe complications related to postradiation surgery in this series. The mean blood loss was less in laparoscopic group than those in the open group (87 mL vs. 208 mL, p=0.036, Mann-Whitney U-test). Approximately 47% patients (16/34) had pathologic residue tumor on hysterectomy specimens. About 94% patients (32/34) got complete remission after adjuvant surgery. CONCLUSION: Adjuvant hysterectomy after CCRT improves survival outcome for patients with LACAC compared with current standard care. Extrafascial hysterectomy is sufficient in tumor reduction and laparoscopic procedure may be more promising with lower blood loss and expedite recovery.

Extrafascial hysterectomy after concurrent chemoradiotherapy in locally advanced cervical adenocarcinoma / 부인종양

OBJECTIVE: To evaluate whether adjuvant simple hysterectomy after concurrent chemoradiotherapy (CCRT) improves progression-free survival (PFS) compared with current standard care in locally advanced cervical adenocarcinoma (LACAC). METHODS: We reviewed a cohort of 55 patients with LACAC (International Federation of Gynecology and Obstetrics [FIGO] stage IB2, IIA2, IIB, III without distant metastasis) diagnosed and treated with radical CCRT at Peking Union Medical College Hospital between January 2004 and October 2014. We compared 34 patients who underwent adjuvant extrafascial hysterectomy with 21 patients with standard care after CCRT. The primary outcome was PFS. Overall survivals (OS) between the two groups were also compared. Surgery feasibility, operative complications, and pathologic features after radiation therapy were also analyzed. RESULTS: PFS was significantly improved in surgery group (log-rank p=0.0097; hazard ratio [HR], 0.3431; 95% CI, 0.152 to 0.772), as were OS (log-rank p=0.0419; HR, 0.3667; 95% CI, 0.139 to 0.964). Analysis of stage IIB demonstrates a similar result. There were no severe complications related to postradiation surgery in this series. The mean blood loss was less in laparoscopic group than those in the open group (87 mL vs. 208 mL, p=0.036, Mann-Whitney U-test). Approximately 47% patients (16/34) had pathologic residue tumor on hysterectomy specimens. About 94% patients (32/34) got complete remission after adjuvant surgery. CONCLUSION: Adjuvant hysterectomy after CCRT improves survival outcome for patients with LACAC compared with current standard care. Extrafascial hysterectomy is sufficient in tumor reduction and laparoscopic procedure may be more promising with lower blood loss and expedite recovery.

Invasive villoglandular adenocarcinoma of the cervix with unusual clinical presentation: A rare case.

The incidence of cervical adenocarcinoma has increased over the last several decades. Villoglandular adenocarcinoma of the cervix (VGA) is a distinct subset of cervical adenocarcinoma, is very rare and occurs in young women. We report an extremely rare case of invasive villoglandular adenocarcinoma of the cervix in a 75 year old woman with unusual clinical presentation.

Genotipificación del virus papiloma humano en mujeres con adenocarcinoma cervical de la Región de La Araucanía-Chile / Human papillomavirus genotyping in cervical adenocarcinoma in the Region of La Araucanía-Chile

El virus papiloma humano (VPH) es el principal factor causal del cáncer cervicouterino (CCU). Así, detectar y genotipificar el VPH es importante para conocer la frecuencia de los genotipos presentes en la región. En este trabajo se estudiaron 44 biopsias de adenocarcinoma cervical (ACC). Para la detección del VPH se empleó una reacción de polimerasa en cadena anidada dirigida al gen L1 (RPCL1), para la genotipificación viral se utilizaron enzimas de restricción (Rsa I, Dde I, Pst I) y secuenciación. Se detectó ADN viral mediante RPCL1 anidada en 100 por ciento de las biopias. Se logró tipificar 38/44 casos: 81,6 por ciento VPH 16; 13,2 por ciento VPH 18; 2,6 por ciento VPH 33 y 2,6 por ciento VPH 18/33. Conclusiones: La metodología fue exitosa para identificar el tipo viral en 86 por ciento de las biopsias. Se observó una estrecha asociación ACC-VPH, especialmente con el tipo viral 16, detectado en 81,6 por ciento de los casos tipificados.

Human papillomavirus (HPV) is the main cause of cervical cancer. Thus, HPV detection and typing becomes important in order to know the frequency of genotypes present in the region. In this paper we studied 44 biopsies of cervical adenocarcinoma. For HPV detection nested polymerase chain reaction (PCR) was used to amplify the L1 gene. For viral typing restriction enzymes (Rsa I, Dde I, Pst I) and DNA sequencing were used. Viral DNA was detected by nested L1 PCR in 100 percent of biopsies; 38/44 cases could be typed: 81.6 percent HPV16; 13.2 percent HPV 18; 2.6 percent VPH 33 and 2.6 percent HPV 18/33. Conclusions: The technique was successful in identifying the virus type in 86 percent of biopsies. There was a strong association ACC-HPV, especially with the viral type 16, detected in 81.6 percent of established cases.

A case of advanced gynecologic pelvic tumors showing the diagnostic utility of HPV analysis / 부인종양

Gynecologic malignancies may have similar histological characteristics. This may lead to difficulties in determining the origin of the cancer and to distinguish a synchronous neoplasm from a metastatic cancer in advanced cases. Recently, we treated a 59-year-old patient with adenocarcinoma of the uterine cervix, endometrium, fallopian tubes, and ovaries. It was difficult to determine whether the cancer was a single origin metastatic cancer or a synchronous neoplasm. The patient was finally diagnosed with metastatic cancer that originated from the uterine cervix by human papillomavirus (HPV) test. Here we report the case and briefly review of the medical literature.

A case of clear cell carcinoma that is unrelated to diethystilbestrol of the uterine cervix / 대한산부인과학회지

Clear cell carcinoma of the uterine cervix is rare type of the uterine cervical adenocarcinoma. Although uterine cervical adenocarcinomas presently represent 20% to 30% of cervical cancers in the industrialized countries, the clear cell carcinoma of uterine cervix is very rare malignancy that accounts for 4% to 9% of the adenocarcinoma of uterine cervix. This malignancy occurs in two distinct age groups; those younger than 24 years and those older than 45 years. In younger patients, most of these malignancies are mainly related to prenatal diethylstilbestrol (DES) exposure, but older patients are unrelated to in utero DES-exposure. We experienced a case of clear cell carcinoma of the uterine cervix of 34 years old housewife who was not related to prenatal DES-exposure. We presented a case with a brief review of related literatures.

Clinicopathological Significance of FHIT Protein Expression in Cervical Adenocarcinoma / 대한산부인과학회지

OBJECTIVE: To investigate the expression of fragile histidine triad (FHIT) protein and the possible relationship between FHIT expression and clinicopathological indices in cervical adenocarcinoma. METHODS: FHIT protein expression was examined in 40 cases of cervical adenocarcinoma stage Ia to IIa and 28 cases of corresponding normal endocervical tissue by immunohistochemical method. We analyzed the relationship between the reduction of FHIT protein expression and several prognostic factors such as histological grade, lymph node metastasis, tumor size, cervical invasion depth and parametrial invasion. We used Fisher's exact test for statistical analysis. RESULTS: The FHIT protein expression was positive in 77.5% (31/40) of cervical adenocarcinoma tissue, and reduced its expression in 22.5% (9/40) whereas positive in 100% (28/28) cases of adjacent normal endocervical gland. The FHIT expression was decreased in 14.3% (4/28) of cancers without lymph node metastasis but 55.5% (5/9) of those with metastasis (p=0.023). And the reduction of FHIT expression was found in 34.8% (8/23) of grade II and III cancers and only 6.3% (1/16) of grade I (p=0.056). CONCLUSION: Loss of FHIT protein expression may be associated with metastasis and poor prognosis of cervical adenocarcinoma.

Clinicopathologic characteristics and prognostic factors of adenocarcinoma of the uterine cervix: a study of 80 cases / 부인종양

OBJECTIVE: The purpose of this study was to evaluate the clinicopathologic findings, treatment, and prognostic factors of adenocarcinoma of the uterine cervix. METHODS: This study retrospectively reviewed 80 patients with histologically proven stage I, II, and III cervical adenocarcinoma, at the Department of Obstetrics and Gynecology of Korea University Anam, Guro, and Ansan Hospitals, between January 1990 and December 2005, for clinical profiles and survival. Survival was analyzed according to the Kaplan-Meier method. Univariate analysis of prognostic factors was performed with the test of log rank. Cox regression model was used in multivariate analysis of prognostic factors. RESULTS: The mean age at the time of diagnosis was 48.5 years (range: 28-81 years) and the most common presenting symptom was uterine bleeding (51.3%). Fifty-eight patients (72.5%) presented with stage I, nineteen (23.7%) with stage II, and three (3.8%) with stage III. Surgery was the main treatment for stage I and IIa and radiation therapy for stage IIb or more. The 5-year survival rates for stages I, II, and III were 85.0%, 63.8%, and 0.0%, respectively. Univariate analysis showed that stage, lymph node metastasis, and lymph-vascular space invasion were significant prognostic factors (p or =50) were significant independent predictors for poor survival (OR 37.352, CI 3.167-440.579; OR 9.823, CI 1.808-53.354, respectively). CONCLUSION: The results suggest that FIGO stage and age are significant independent prognostic factors for patients with adenocarcinoma of the uterine cervix.

A Case of Primary Signet Ring Cell Adenocarcinoma of the Uterine Cervix / 대한산부인과학회지

Signet ring cell adenocarcinoma of the cervix is most commonly considered to be metastatic in origin. We describe one case of primary signet ring cell adenocarcinoma of the cervix occuring in 49-year-old patient. The lesion was located at the posterior lip of the cervix and about 3 cm in size. This case was parametrium thickening in pelvic examination and positive for HPV type 18. CCRT (concurrent chemoradiotherapy) was done for clinical FIGO stage II B adenocarcinoma of the cervix. The patient is alive for 6month since diagnosis and disappear lesion of the cervix. A upper gastroenteroscopy, colonoscopy, cystoscopy, intravenous pyelogram, abdominal pelvic CT, PET CT, mammogram were reported negative. Therefore we concluded this case for a primary cervical origin of signet ring cell adenocarcinoma of the uterine cervix.

A case of treatment of cervical adenocarcinoma associated with pregnancy by zinc-citrate compound (SeLava(R)) / 대한산부인과학회지

Cervical carcinoma is the second leading cause of death from cancer in women worldwide. It is well known that human papillomaviruses (HPVs) is the etiologic agent of cervical neoplasia and cervical cancer. Zinc has been shown to inhibit the growth of malignant cell lines by inducing apoptosis and cell cycle arrest. Recently it was reported that zinc-citrate compound (CIZAR(R)) has a cytotoxic effect on choriocarcinoma cell line and ovarian adenocarcinoma cell line and suppresses its proliferation inducing apoptosis. CIZAR(R) prevents the proliferation by inactivation of m-aconitase activity and induces apoptosis by increasing Bax expression and reducing Bcl-2 expression and inactivation of telomerase. We report one patient of cervical adenocarcinoma with HPV infection, who desires to continue pregnancy, treated by daily topical application of SeLava(R) which contains zinc-citrate compound (CIZAR(R)). We followed up the cytologic, pathologic and coloposcopic changes of healing process.

The efficacy of tumor markers SCC, CEA, and CA-125 in patients with cervical cancer / 대한산부인과학회잡지

OBJECTIVE: The aim of this study was to evaluate the positive rate of squamous cell carcinoma antigen (SCC), carcinoembryonic antigen (CEA), and CA-125 according to clinical stage and histology. We also determine the rate of normalization of SCC after surgical and radiation therapy. RESULTS: In 222 patients with cervical cancer, the pre-treatment positive rate of SCC, CEA, and CA- 125 were 38.7%, 24.3%, and 19.8%, respectively. The positive rate of SCC by clinical stage were 12.9% for stage I, 60.5% for stage II, 88.2% for stage III, and 87.5% for stage IV. The positive rate of CEA by stage were 7.8% for stage I, 36.4% for stage II, 83.3% for stage III, and 75% for stage IV. The positive rate of CA-125 by stage were 5.9% for stage I, 23.3% for stage II, 83.3% for stage III, and 75% for stage IV. The positive rates of SCC, CEA, and CA-125 were significantly increased by clinical stage. According to histology, the positive rate of SCC (39.8%) was more significantly higher than the positive rates of other tumor makers in squamous cell carcinoma of the uterine cervix. The positive rate of CA-125 was higher than the positive rate of other tumor markers in adenocarcinoma and adenosquamous carcinoma of the uterine cervix, but it was not statistically significant difference. CONCLUSION: SCC have been shown to be higher positive rate than any other tumor markers in patients with cervical cancer. The positive rates of SCC, CEA, and CA-125 were significantly increased by clinical stage. Concomitant measurement of SCC, CEA, and CA-125 may be more useful than measurement of SCC alone, and further study was needed.

Correlation between High Risk Human Papillomavirus Infection and p53 Protein Overexpression in Adenocarcinoma of Cervix / 대한산부인과학회잡지

OBJECTIVE: The aim of the present study was to analyze the relation between p53 mutation and cervical adenocarcinoma without HPV infection. METHODS: From 1998 to 2002, 54 patients were diagnosed with cervical adenocarcinoma and underwent radical hysterectomy at Seoul National University Hospital. Of them, 50 patients were available for review of medical records and histologic examination. Using ABC method, we performed immunohistochemical staining. If there is 10% or more of staining positive, it was read positive. And we used HPVDNAChip for detection of HPV. RESULTS: Of the 50 patients, 45 (90.0%) patients were positive for high risk HPV and 4 patients (8.0%) were p53 positive. In the patients with negative for p53, there were significantly more patient with HPV positive (p=0.04). Advanced stage of cervical adenocarcinoma was related to high rate of positivity of p53, but it was not statistically significant. CONCLUSION: In patients who diagnosed cervical adenocarcinoma without HPV infection, there were over expression of p53. This suggests that abnormality of p53 may be related to pathogenisis of cervical adenocarcinoma without HPV infection.

Spontaneous Urine Extravasation Caused by Ureteral Metastasis from a Cervical Adenocarcinoma / 대한비뇨기과학회지

Spontaneous urine extravasation due to metastatic cancer is extremely rare. We experienced a case of urine extravasation caused by ureteral metastasis from a cervical adenocarcinoma in a 69-year-old woman. On operating, a 3cm length ureter stricture was found in the upper third of the left ureter. There were no malignant cells in a frozen biopsy, and no urine leakage site was detected. An end-to-end ureteroureterostomy was performed by the tension-free method. The permanent histology of the ureterectomy specimen revealed a metastatic adenocarcinoma, identical to that obtained from the punch biopsy of the cervix. The urine leakage persisted following the end-to-end ureteroureterostomy, whereupon a nephroureterectomy was performed.