Diagnostic challenges and individualized treatment of cervical adenocarcinoma metastases to the breast:A case report

BACKGROUND Cervical cancer is a rare primary tumor resulting in metastases to the breast with few cases reported in literature.Breast metastases are associated with poor prognosis.The following case highlights the diagnostic challenges associated with metastatic cervical cancer to the breast along with individualized treatment.CASE SUMMARY A 44-year-old G7P5025 with no significant past medical or surgical history presented with heavy vaginal to an outside emergency department where an exam and a pelvic magnetic resonance imaging showed a 4.5 cm heterogenous lobulated cervical mass involving upper two thirds of vagina,parametria and lymph node metastases.Cervical biopsies confirmed high grade adenocarcinoma with mucinous features.A positron emission tomography/computed tomography(PET/CT)did not show evidence of metastatic disease.She received concurrent cisplatin with external beam radiation therapy.Follow up PET/CT scan three months later showed no suspicious fluorodeoxyglucose uptake in the cervix and no evidence of metastatic disease.Patient was lost to follow up for six months.She was re-imaged on re-presentation and found to have widely metastatic disease including breast disease.Breast biopsy confirmed programmed death-ligand 1 positive metastatic cervical cancer.The patient received six cycles of carboplatin and paclitaxel with pembrolizumab.Restaging imaging demonstrated response.Patient continued on pembrolizumab with disease control.CONCLUSION Metastatic cervical cancer to the breast is uncommon with nonspecific clinical findings that can make diagnosis challenging.Clinical history and immunohistochemical evaluation of breast lesion,and comparison to primary tumor can support diagnosis of metastatic cervical cancer to the breast.Overall,the prognosis is poor,but immunotherapy can be considered in select patients and may result in good disease response.

Paired box proteins as diagnostic biomarkers for endocervical adenocarcinoma

In this editorial,we commented on the article by Akers et al published in the recent issue of the World Journal of Clinical Cases.We focused specifically on the role of the transcription factor paired box protein 8(PAX8)belonging to the family PAX in the carcinogenesis of a gynecologic tumor,endocervical adenocarcinoma,arising from the tissue of mesonephric origin,and the potential diagnostic value for the same type of neoplasms.The global vaccination program of human papillomavirus(HPV)has dramatically reduced the incidence of cervical cancer,including cases of adenocarcinoma.The type of adenoid epithelial origin has a lower frequency of HPV detection but tends to be more aggressive and fatal.Cases of endocervical adenocarcinoma occurring in females of menopause age have been described in the 2023 volume of the World Journal of Clinical Cases and in our study recently published in Oncol Lett.The histopathological findings and immunohistochemical assays showed that the lesions had glandular morphology,and the specimens in these two reports were immunohistochemically positive for the transcription factor PAX8,albeit that they had opposing expression profiles of tumor suppressor p16 and estrogen receptor and the presence of the HPV genome.The presence of a mucin protein,MUC 5AC,as revealed in both studies suggested target molecules for the diagnosis of mucinous adenoid type of uterine tumor and other histological origins.The clinical outcome was unfavorable due to metastasis and recurrence.This prompted the improvement of the antitumor modality,with the introduction of precise targeting therapy.Mucin has now been reported to be the therapeutic target for adenocarcinomas.

Detection and Identification of Human Papillomavirus in Cervical Adenocarcinoma

Objective： To evaluate the rate and types of human papillomavirus （HPV） infection in cervical adenocarcinoma. Methods： We detected and identified HPV in 67 lesions using PCR based reverse line blot hybridization and DNA sequencing. Among the 67 patients, 53 were diagnosed as cervical adenocarcinoma and 14 as cervical adenosquamous carcinoma. First a fragment of 150 bp was amplified from the L1 region of HPV with GP5/GP6 primers. If the result was negative, a short fragment of 65 bp was amplified from the L1 region with SPFI/SPF2 primers. Results： 6 cases were eliminated from the study because of unsatisfied DNA extraction. The total positive rate of HPV DNA detected by PCR in cervical adenocarcinoma and adenosquamous carcinoma was 91.8% （56/61）. Using general primer GP5/GP6, the positive rate was 50.8% （31/61）. Using SPF primers for the 30 negative cases, 25 additional HPV positive cases were founded. All the positive samples had at least one of the high risk types. HPV16 was the most preferential type followed by HPV18, 31, 39 and 45. The infection of HPV 16 and 18 accounted for about half of HPV-positive adenocarcinoma. Multiple HPV infections were found in 21.4% （12/56） of the cases. Conclusion： The high risk type of HPV is associated with cervical adenocarcinoma. Single infection is more frequently presented than multiple infections, no single type of HPV plays a predominated role even HPV16 and 18 are the major types.

Vaginal clear cell adenocarcinoma in Herlyn-Werner-Wunderlich syndrome:A case report

BACKGROUND Herlyn-Werner-Wunderlich(HWW)syndrome is a rare Müllerian duct anomaly,characterized by a combination of urogenital abnormalities.The occurrence of primary cervico-vaginal carcinomas in patients with HWW syndrome is excep-tionally rare,posing significant challenges for screening,early diagnosis,and effective management.CASE SUMMARY We report a rare case of primary clear cell carcinoma of the vagina complicated in a 40-year-old woman with HWW syndrome.The patient presented with irregular vaginal bleeding for 4 years.On gynecological examination,an oblique vaginal septum was suspected.Surgical resection of the vaginal septum revealed a com-municating fistula and a tumor on the left vagina and the left side of the septum,which was confirmed as clear cell carcinoma.One month later,she underwent a radical hysterectomy,vaginectomy,bilateral salpingo-oophorectomy,and pelvic lymph node dissection.Due to significant side effects,she completed only one course of chemotherapy.A year later,lung metastasis was detected and continued to grow.A thoracoscopic wedge resection of the right upper lobe was performed 4 years after the initial surgery.We also conducted a systemic review of the lite-rature on primary cervical or vaginal carcinoma in HWW syndrome to explore this rare entity.CONCLUSION Cervico-vaginal adenocarcinomas in patients with HWW syndrome are occult,and require early surgical intervention and regular imaging surveillance.

Ginsenoside Rh_2 Showing Ability to Induce Apoptosis in HeLa Cells

This paper deals with the inhibitory mechanisms of ginsenoside \{G Rh 2\} on the growth of tumor cells. \{G Rh 2\} significantly inhibited the proliferation of human cervical adenocarcinoma HeLa cells in a time and dose dependent manner. G Rh 2 induced apoptotic manifestations in HeLa cells as evidenced by the changes in the cell morphology, the DNA fragmentation and the activation of caspases. Caspase inhibitors, caspase family inhibitor, z Val Ala Asp fmk(z VAD fmk); caspase 1 inhibitor, Ac Tyr Val Ala Asp chloromethyl ketone(Ac YVAD cmk); caspase 3 inhibitor, z Asp Glu Val Asp fmk(z DEVE fmk) and caspase 8 inhibitor, \{z Ile \}Glu Asp fmk(z IETD fmk) effectively attenuated G Rh 2 induced cell death. The activities of caspase 1 and caspase 3 were increased in the G Rh 2 induced apoptotic process. However, caspase inhibitors can not inhibit G Rh - 2 induced cell death completely. These results suggest that G Rh 2 induced cell death is mediated by the activation of caspase cascade, but there might be some other pathways for induction of this apoptosis.

Phase 1/2 study of concurrent chemoradiotherapy with weekly irinotecan hydrochloride for advanced/recurrence uterine cancer:A multi-institutional study of Kansai Clinical Oncology Group

Objective:Concurrent chemoradiotherapy using cisplatin was thought to be standard treatment for squamous cell carcinoma of cervix,but it had not been effective for adenocarcinoma.Concurrent chemoradiotherapy using irinotecan hydrochloride(CPT-11)had been effective for colorectal cancer,thus,we chose CPT-11 as a candidate for gynecologic adenocarcinoma.To evaluate the maximum tolerated dose(MTD)of weekly CPT-11 with external pelvic radiotherapy,a phase 1/2 study was conducted according to modified Fibonacci method.Methods:Eligible patients were advanced uterine cancer with measurable diseases[performance score(PS):0-2].Study period was from August 1 st,2002 to December 31 st,2008.The starting dose level(DL)of CPT-11 was 30 mg/m2(DL1)given weekly for 4 weeks.Subsequently,dose escalation was scheduled in 10 mg/m2 increments to 60 mg/m^2(DL4).The fixed radiotherapy consisted of whole pelvic 1.8 Gy/d,once a day in weekday for five weeks and it amounted to 45 Gy(25 fractions)in total.Results:Seventeen patients were enrolled.As for toxicities,one(1/17:5.9%)grade(G)4 neutropenia lasting 7 days had been seen in DL4.G2 diarrhea was identified in 35.3%(6/17)of the patients,and 11.8%(2/17)G3 diarrhea was observed in DL3 and DL4.Thus,the MTD of CPT-11 was defined as dose of 60 mg/m^2.The recommended dose was decided as 50 mg/m^2.The response rate was 88.2%[9 complete response(CR),3 partial response(PR),3 stable disease(SD),2 not evaluable(NE)].Disease control rate at 1 month after treatment completion was 100%but distant metastases were found in 24%(4/17)in longer outcome.Conclusions:MTD was 60 mg/m^2 and recommended dose was set as 50 mg/m2.This concurrent chemoradiation using weekly CPT-11 was feasible at 50 mg/m^2,and it might be effective even in adenocarcinoma of the uterus.