Primary Cervical Adenocarcinoma Research Articles

A Population-based Study Investigating the Incidence of Human Papillomavirus-Associated and Human Papillomavirus-Independent Cervical Adenocarcinomas.

Cervical adenocarcinomas are now classified as human papillomavirus (HPV)-associated and HPV-independent types with the former being more common. However, population-based studies regarding the relative incidences of the 2 types are few. This study investigates the incidence of cervical adenocarcinomas in Northern Ireland (a country with a relatively stable population of ~1.8 million) over a recent 9-year period (2015-2023). Overall, there were 146 primary cervical adenocarcinomas, 130 HPV-associated (89%) and 16 HPV-independent (11%). The median age was 43 years (range: 24-82) for HPV-associated and 62.5 years (range: 31-84) for HPV-independent neoplasms; this was statistically significant (P < 0.001). The calculated age-adjusted incidence of the patients with HPV-associated and HPV-independent neoplasms was 1.68 and 0.20 per 100,000 person-years, respectively. The HPV-independent neoplasms were more often advanced stage at diagnosis; 97 of 130 (75.4%) of the HPV-associated cases were diagnosed at Stage I compared with 5 of 16 (31.3%) of the HPV-independent cases. The HPV-independent neoplasms were mostly gastric-type (56.3%) with smaller numbers of clear cells and mesonephric. Despite the relatively short follow-up, the mortality of patients with HPV-independent adenocarcinomas was significantly higher than patients with HPV-associated neoplasms (56.3% vs 5.4%) with a median survival of just over a year (13.2mo) in the former for those who died.

Analysis of primary synchronous breast invasive ductal carcinoma and lung adenocarcinoma with next-generation sequencing: A case report.

Multiple primary cancers (MPCs) have an increasing incidence rate due to the detection of early stages of cancer and the development of effective therapeutic strategies. MPCs are less common compared with metachronous cancers. Therefore, distinguishing synchronous primary tumors from metastasis and developing an individualized treatment strategy can be challenging. In the present study, the case of a 70-year-old female who was referred to The First Hospital of Jilin University (Changchun, China) with an enlarged left cervical lymph node and no other clinical manifestations is reported. Radiography revealed distinct lesions in the left breast, left cervical lymph node and bilateral lungs. Subsequently, a biopsy was performed in all three lesions and then each specimen was subjected to immunohistochemistry, fluorescence in situ hybridization, amplification refractory mutation system-PCR and next-generation sequencing (NGS). Disease-related enrichment of lymph node mutant genes and Gene Ontology Biological Process enrichment of breast, as well as lung, mutant genes were performed using the Database for Annotation, Visualization and Integrated Discovery. Based on the molecular assessment, the patient was finally diagnosed with breast invasive ductal carcinoma, primary lung adenocarcinoma and cervical lymph node metastatic lung adenocarcinoma. Since primary synchronous breast and lung cancer (SBLC) is rare, a molecular assessment, particularly using NGS, could provide important information for both the diagnosis and treatment of SBLC.

Testing Algorithms for the Diagnosis of Malignant Glandular Tumors of the Uterine Cervix Histotyped per the International Endocervical Adenocarcinoma Criteria and Classification (IECC) System.

The International Endocervical adenocarcinoma Criteria and Classification (IECC) categorizes tumors into human papilloma virus (HPV) associated (HPVA), not associated (NHPV), and invasive adenocarcinoma not otherwise specified (IA NOS). HPVA and NHPV encompass 11 histotypes and an algorithm of mucin content, HPV ribonucleic acid (RNA), estrogen receptor and GATA3 is proposed for the diagnosis of most. In this study, the IECC algorithm's diagnoses were compared with hematoxylin and eosin (H&E) based IECC histotyping. Kappa statistics measured performance agreement. With additional markers, hierarchical clustering by random forest (RF) classification identified the most discriminating between tumor types, and investigated other algorithms. Three pathologists independently reviewed digitized H&E images of n=152 primary cervical adenocarcinomas for IECC histotype and mucin content, and tissue microarrays for expression of HPV RNA by in situ hybridization and 16 antibodies by immunohistochemistry. Results were finalized by consensus. There were n=113 HPVA, n=22 NHPV, and n=17 IA NOS. Mucin was obvious in n=36 and limited in n=116. Among n=124 with satisfactory test results, HPV RNA was positive in n=96, estrogen receptor in n=72, and GATA3 in n=15. The IECC algorithm diagnosed n=99 which agreed with H&E histotyping in n=64 for a fair κ of 0.36 (95% confidence interval, 0.21-0.50): n=12 were undiagnosed and n=13 were IA NOS. Small sample sizes restricted RF to HPVA versus NHPV which were discriminated by p16, HPV RNA, and MUC6 with an area under the curve of 0.74 (95% confidence interval, 0.58-0.90). The IECC algorithm for histotyping under-performed. The RF algorithmin for categorization was favorable, but validation in larger studies and investigation of additional algorithms to discriminate between all IECC histotypes are needed.

Endocervical adenocarcinoma in situ with ovarian metastasis: a case report

Background: Ovarian metastases, which may simulate primary ovarian neoplasms, can occur in advanced stage primary cervical adenocarcinoma (AC). However, such tumors are very rarely observed in cases of endocervical adenocarcinoma in situ (AIS) with early or even no obvious signs of tumor invasion. Case: We present a case of ovarian metastasis occurring in a 37-year-old triparous premenopausal woman with a diagnosed case of endocervical AIS. The patient presented with a rapidly growing and painful abdominal mass 22 months after a cold knife cone biopsy and 19 months after a simple extrafascial hysterectomy. She was subsequently treated with a combination of surgery and chemotherapy and is currently free of disease seven years after the initial diagnosis of endocervical AIS lacking unequivocally recognizable stromal invasion. Conclusion: Endocervical AIS with early or even no obvious detectable invasion may spread to the ovaries, but this situation is exceptionally rare. We propose that, in such cases, ovary sparing surgery is justifiable for initial treatment. Medical care strategies for patients affected by rare diseases largely depend on experience gained from reported cases in published literature, this is what compelled us to report this particular case.

Prior cervical cytology and high-risk HPV testing results for 311 patients with invasive cervical adenocarcinoma: a multicenter retrospective study from China\u2019s largest independent operator of pathology laboratories

BackgroundHigh-risk human papillomavirus (HR-HPV) testing is more sensitive than cytology for the detection of cervical cancer and its precursors. However, limited and inconsistent data are available about the efficacy of the combination of these two methods for screening cervical adenocarcinoma. This multicenter retrospective study investigated the screening results of a cohort of Chinese patients who were subsequently diagnosed with invasive cervical adenocarcinoma, with the goal of identifying the optimal cervical adenocarcinoma screening method.MethodsWe retrospectively retrieved and analyzed the data from patients with histologically confirmed primary invasive cervical adenocarcinoma from eight local pathology laboratories operated by KingMed Diagnostics, the largest independent operator of pathology laboratories in China, over a 2-year period. Only patients who underwent cytology and/or HR-HPV testing within 6 months before the adenocarcinoma diagnosis were included. HR-HPV DNA was detected using one of two HPV test kits: the Hybrid Capture 2 (HC2) assay (Qiagen, Hilden, Germany) and an HPV genotyping panel (Yaneng Bio, Shenzhen, China).ResultsOf the 311 patients, 136 underwent cytology alone, 106 underwent HR-HPV testing alone, and 69 underwent cytology and HR-HPV co-testing. The sensitivities of cytology alone (64.0, 95% confidence interval [CI]: 55.9–72.0) and HR-HPV testing alone (66.0, 95% CI: 57.0–75.1) were similar (P = 0.738). The sensitivity of cytology and HR-HPV co-testing (87.0, 95% CI: 79.0–94.9) was significantly higher than that of either cytology (P = 0.001) or HR-HPV testing alone (P = 0.002).ConclusionsBoth cytology alone and HR-HPV testing alone showed poor screening efficiency, whereas the combination of the two clearly increased the efficiency of primary cervical adenocarcinoma screening. Thus, cytology and HR-HPV co-testing might be the most efficient cervical adenocarcinoma screening method.

Tumor-suppressor gene SOX1 is a methylation-specific expression gene in cervical adenocarcinoma.

The present study is to analyze the difference of gene methylation in early cervical adenocarcinoma and to find molecular markers for predicting the occurrence and development of cervical adenocarcinoma.A total of 15 cases of primary cervical adenocarcinoma and 10 cases of primary cervical squamous cell carcinoma at stages IB1 or IIA1 were included in the study. Infinium MethylationEPIC BeadChip (850K) was used to screen specifically expressed genes in cervical adenocarcinoma tissues. Bisulfite sequencing polymerase chain reaction (BSP) and quantitative real-time polymerase chain reaction (qRT-PCR) were used to verify the methylation levels in cervical adenocarcinoma, cervical squamous cell carcinoma, and normal cervical tissues.Sex determining region Y-box 1 (SOX1) and cyclin D1 (CCND1) genes participated in multiple signaling pathways, being the central nodes of gene regulatory networks. SOX1 gene, but not CCND1 gene, was a specifically methylated gene in cervical adenocarcinoma according to BSP. According to qRT-PCR, methylation level of SOX1 in cervical adenocarcinoma tissues is significantly different from that in cervical squamous cell carcinoma tissues or normal cervical tissues, and the methylation level of CCND1 in cervical adenocarcinoma tissues or cervical squamous cell carcinoma tissues is significantly different from that in normal cervical tissues.The present study demonstrates that tumor-suppressor gene SOX1 is a methylation-specific expression gene of cervical adenocarcinoma and is expected to become a specific molecular marker for the diagnosis of cervical adenocarcinoma. However, CCND1 gene was not proven to be a specific methylation expression gene in cervical adenocarcinoma in the present study.

Expression of Markers of Müllerian Clear Cell Carcinoma in Primary Cervical and Vaginal Gastric-type Adenocarcinomas.

The incidence of cervical adenocarcinoma, both absolute and relative to squamous cell carcinoma, is increasing. Most cervical adenocarcinomas are human papillomavirus associated, although non-human papillomavirus-associated neoplasms exist; the latter include gastric-type adenocarcinoma (GAS) and clear cell carcinoma (CCC). Histologically, these 2 tumors may superficially resemble one other and although morphologic evaluation usually permits a correct diagnosis, immunohistochemistry may be required to resolve diagnostic uncertainty, especially in a small biopsy specimen. Markers of CCC include hepatocyte nuclear factor 1 beta (HNF1β) and Napsin A. In order to explore the utility of these markers in distinguishing between GAS and CCC, we stained 24 cases of GAS (19 cervical, 5 vaginal), 3 of cervical gastric-type adenocarcinoma in situ (gAIS) and 14 CCCs (13 cervical, 1 vaginal) with these antibodies. We found HNF1β expression in 21 of 23 cases of GAS (91.3%; there was no material available for staining in 1 case), 3/3 cases of gAIS (100%) and 10 of 14 (71.4%) CCCs. Napsin A was expressed in 4 of 24 (16.7%) cases of GAS, 0 of 3 (0%) gAIS, and 11 of 14 (78.6%) CCC. On the basis of these findings, Napsin A is of value in resolving diagnostic confusion between GAS and CCC, whereas HNF1β lacks specificity and its use in this setting is discouraged.

Metastatic Adenocarcinoma to the Uterine Cervix Versus Primary Cervical Adenocarcinoma

Abstract Adenocarcinoma metastases to the cervix can originate from the endometrium, the upper müllerian tract, or from extramüllerian sites such as the gastrointestinal and pancreatobiliary tract, bladder, breast, lung, or even the salivary gland. In some cases, the metastatic lesions have signet-ring morphology, infiltrative pattern, and/or extensive lymphovascular spread. In others, however, the distinction between a primary cervical lesion and a metastasis to the cervix is more challenging because metastases may mimic endocervical adenocarcinoma in situ by colonizing the native endocervical mucosa through intraepithelial spread. Careful morphologic interpretation, combined with immunohistochemistry, human papillomavirus molecular testing, and clinical correlation, is required in order to arrive at the correct diagnosis.

Primary Adenocarcinoma of the Uterine Cervix: Classification and Grading

Abstract Cervical adenocarcinomas are a group of malignancies with several distinct histologic tumor types, which include endocervical usual type, endometrioid, intestinal, villoglandular, gastric, signet ring, serous, clear cell, and mesonephric. Diagnosis of cervical adenocarcinoma, in particular early diagnosis, and classification of the tumor type may pose a significant challenge. The goal of this article is to review the current classification, diagnostic criteria, adjunct markers, and differential diagnosis of various subtypes of cervical adenocarcinomas. The article presents up-to-date summary of such problematic issues as differentiating glandular tumors from benign mimics, differentiating early invasive lesions from adenocarcinoma in situ, determining the tumor type, and, finally, differentiating primary cervical adenocarcinoma from uterine endometrioid adenocarcinoma. Discussion of human papillomavirus detection in different tumor types is provided.

Cervical Adenocarcinoma: Diagnosis of Human Papillomavirus-Positive and Human Papillomavirus-Negative Tumors.

- Cervical adenocarcinomas span a diverse group of tumors with several distinct histologic tumor types, which include endocervical, endometrioid, intestinal, villoglandular, gastric, signet ring, serous, clear cell, and mesonephric. Diagnosis of cervical adenocarcinoma, especially early diagnosis, poses a significant challenge. - To review the pathogenesis, diagnostic criteria, immunohistochemical markers, and differential diagnosis of various subtypes of human papillomavirus (HPV)-positive and HPV-negative cervical adenocarcinomas. The paper presents a concise summary of the issues that may be particularly difficult in histopathologic diagnosis, such as differentiating neoplastic lesions from benign mimics, determining the tumor type, differentiating early invasive lesions from adenocarcinoma in situ, measuring the depth of invasion, and, finally, differentiating primary cervical adenocarcinoma from uterine endometrioid adenocarcinoma and tumors metastatic from other primary sites. - The study employed a PubMed search of recently published reports. - Early detection of HPV-positive tumor types may be aided with the expansion of HPV testing; however, early diagnosis of HPV-negative cervical adenocarcinomas will continue to pose a challenge and may require the development of additional molecular testing techniques.

Mixed Lineage Leukemia 5 (MLL5) Protein Stability Is Cooperatively Regulated by O-GlcNac Transferase (OGT) and Ubiquitin Specific Protease 7 (USP7).

Mixed lineage leukemia 5 (MLL5) protein is a trithorax family histone 3 lysine 4 (H3K4) methyltransferase that regulates diverse biological processes, including cell cycle progression, hematopoiesis and cancer. The mechanisms by which MLL5 protein stability is regulated have remained unclear to date. Here, we showed that MLL5 protein stability is cooperatively regulated by O-GlcNAc transferase (OGT) and ubiquitin-specific protease 7 (USP7). Depletion of OGT in cells led to a decrease in the MLL5 protein level through ubiquitin/proteasome-dependent proteolytic degradation, whereas ectopic expression of OGT protein suppressed MLL5 ubiquitylation. We further identified deubiquitinase USP7 as a novel MLL5-associated protein using mass spectrometry. USP7 stabilized the MLL5 protein through direct binding and deubiquitylation. Loss of USP7 induced degradation of MLL5 protein. Conversely, overexpression of USP7, but not a catalytically inactive USP7 mutant, led to decreased ubiquitylation and increased MLL5 stability. Co-immunoprecipitation and co-immunostaining assays revealed that MLL5, OGT and USP7 interact with each other to form a stable ternary complex that is predominantly located in the nucleus. In addition, upregulation of MLL5 expression was correlated with increased expression of OGT and USP7 in human primary cervical adenocarcinomas. Our results collectively reveal a novel molecular mechanism underlying regulation of MLL5 protein stability and provide new insights into the functional interplay among O-GlcNAc transferase, deubiquitinase and histone methyltransferase.

Human papillomavirus detected in a colonic metastasis of cervical adenocarcinoma

In this letter, we report a case of a 57-year-old woman referred to our Coloproctology Division with symptoms of progressive constipation and a colonoscopy showing a rigid stenosis of the sigmoid colon, without any mucosal lesion. She had a history of a radical hysterectomy, performed 5 years earlier, due to a well-differentiated villoglandular cervical adenocarcinoma (Fig 1a). After a preoperative workup without additional findings, she underwent a sigmoid resection. Histopathologic examination of the surgical specimen revealed a well-differentiated glandular malignant tumor (3 9 3 cm) within the intestinal wall (Fig. 1b), without extension to the mucosal layer, but showing tumor emboli within subserosal vessels (Fig 1c). This glandular pattern was very similar to that previously seen in the cervical adenocarcinoma. Immunohistochemical analysis of the tumor confirmed the diagnosis of adenocarcinoma originating in the cervix. The immunohistochemical profile was as follows: strong intensity staining for CEA, CA125 and CK7 in 100 % of the tumor cells; strong staining for CK20 in 70 % of the cells; and negative staining for p53, k-ras and progesterone receptor. Considering the well-known etiological correlation of human papillomavirus (HPV) and cervical cancer, we decided to analyze tumor tissues through MY/GP-nested polymerase chain reaction (PCR) and through GP5?/ GP6? auto-nested PCR. Specific primer sets targeting the E6/E7 region of the HPVs 16, 18, 33, 45 were used for typing. The molecular analyses revealed the presence of HPV18 in both the primary cervical adenocarcinoma and the metastatic tumor. Metastatic lesions involving the colon are rare, being usually related to carcinomas of the breast and kidney or to melanoma. Colonic metastases of cervical cancers are exceedingly rare. To date, there are only 9 cases reported in the literature (eight squamous carcinomas) [1–5]. There is only one report of a cervical adenocarcinoma metastasizing to the large bowel, which also involved the sigmoid colon with extension to the subserosa [5]. HPV has been definitely implicated in the process of cervical carcinogenesis. Its role in development of primary colorectal cancer has also been demonstrated [6]. Some authors have reported the identification of HPV deoxyribonucleic acid (DNA) in bone, lung, liver and lymph node metastasis from squamous cell carcinoma of the cervix [4]. However, to the best of our knowledge, the present article is the first to report the detection of HPV within a metastastic adenocarcinoma of the cervix involving the colon. Our findings confirm the importance of HPV in cervical carcinogenesis and reinforce prior data indicating that viral integration into host cell DNA represents a crucial step for development of the malignant phenotype and tumor dissemination. A. P. Damin G. Agnes Laboratory of Molecular Biology, Federal University of Health Science of Porto Alegre, Porto Alegre, Brazil

Clinical outcome of pelvic exenteration in patients with advanced or recurrent uterine cervical cancer

Pelvic exenteration has attained an important role in the treatment of advanced or recurrent cervical cancer for obtaining a complete cure or longer disease-free survival. The purpose of this study was to evaluate patients undergoing pelvic exenteration and to determine the clinical features associated with outcome and survival. We retrospectively analyzed the records of 12 patients who underwent pelvic exenteration for uterine cervical cancer between July 2002 and August 2011. Two patients had primary stage IVA cervical adenocarcinoma and 10 patients had recurrent cervical cancer. Eight patients underwent anterior pelvic exenteration, 3 patients underwent total pelvic exenteration, and 1 patient underwent posterior pelvic exenteration. With a median duration of follow-up of 22 months (range 3-116 months), 5 patients were alive without recurrence. Of 5 patients with no evidence of disease, 4 were recurrent or residual tumor, all of whom had common factors, such as a tumor size ≤ 30 mm, negative surgical margins, complete resection, and no lymph node involvement. The 5-year overall survival rate for 12 patients was 42.2 %. Ileus was the most common complication (42 %) and post-operative intestinal anastomosis leaks developed in 3 patients, but no ureteral anastomosis leaks occurred. Pelvic exenteration is a feasible surgical procedure in advanced and/or recurrent cervical cancer patients with no associated post-operative mortality, and the only therapeutic option for complete cure or long-term survival; however, post-operative complications frequently occur.

New developments in endocervical glandular lesions

McCluggage W G (2012) Histopathology New developments in endocervical glandular lesions There is evidence that the prevalence of premalignant and malignant endocervical glandular lesions is increasing in real as well as in apparent terms. In this review, new developments and selected controversial aspects of endocervical glandular lesions are covered, concentrating mainly on premalignant and malignant lesions. The terminology of premalignant endocervical glandular lesions is discussed with a comparison of the World Health Organization classification and the cervical glandular intraepithelial neoplasia (CGIN) system, which is in widespread use in the United Kingdom. Primary cervical adenocarcinomas comprise a heterogeneous group of different morphological types, and while it is known that the majority of these are associated with high-risk human papillomavirus (HPV), it has become clear in recent years that most of the more uncommon morphological types are unassociated with HPV, although they may sometimes be p16-positive. A spectrum of benign, premalignant and malignant cervical glandular lesions exhibiting gastric differentiation is now recognized; these include type A tunnel clusters, typical and atypical lobular endocervical glandular hyperplasia, adenoma malignum and gastric-type adenocarcinoma. The latter is a recently described variant of primary cervical adenocarcinoma which has a different morphological appearance to the usual endocervical type and which is probably associated with different patterns of spread and a worse prognosis. There is accumulating evidence that 'early invasive' cervical adenocarcinomas have an excellent prognosis and are suitable for conservative management. Immunohistochemical markers of value in the distinction between a primary cervical and endometrial adenocarcinoma are discussed. While it is well known that a panel of markers comprising oestrogen receptor (ER), vimentin, p16 and monoclonal carcinoembryonic antigen (CEA) is useful, several major pitfalls are pointed out and this panel of markers is predominantly of value in 'low-grade' adenocarcinomas. A related group of lesions, including cervical ectopic prostatic tissue and vaginal tubulosquamous polyp, are probably derived from para-urethral Skene's glands and may be positive with prostatic markers. Recent developments in cervical neuroendocrine neoplasms are discussed, as these are associated not uncommonly with a premalignant or malignant endocervical glandular lesion.

A Case Of Two Synchronous Tumour Of Different Histology - Advanced Cervical Adenocarcinoma With Borderline Mucinous Ovarian Tumour In A 22 Year Old Virgin.

We report a case of synchronous cervical adenocarcinoma with borderline mucinous ovarian tumourin a 22 year old virgin who presented with prolonged bleeding and dysmenorrhoea of four months duration. A transabdominal ultrasound demonstrated fluid in the endometrial cavity. This was confirmed by MRI pelvisrevealing adistended endometrial cavity with cervical stenosis. Evacuation revealed hematometra and the post evacuation uterine cavity is empty. She was discharged and subsequently presented at three months with acute urinary retention and heavy bleeding. A CT pelvisshowed complex bilateral ovarian cyst with minimal ascites, an enlarged paraaortic node at L2 and hematometrawith cervical stenosis. An exploratory laparotomy was performed with cystectomy, supracolicomentectomy with uterine and cervical biopsy. The histopathology shows bilateral borderline mucinous tumor of the ovary with metastatic omental nodules and primary well differentiated adenocarcinoma of the cervix. The subsequent CT thorax revealed metastatic pulmonary nodules. In view of advanced cervical adenocarcinoma, she was advised palliative chemotherapy with carboplatin and paclitaxel for six cycles. She has currently completed one cycle of chemotherapy. Conclusion:This case is one of the rare presentations of synchronous tumours of different histology with primary cervical adenocarcinoma and bilateral borderline ovarian tumour occurring in a virgin with atypical clinical presentation and rapid progression.

A Case Of Two Synchronous Tumour Of Different Histology - Advanced Cervical Adenocarcinoma With Borderline Mucinous Ovarian Tumour In A 22 Year Old Virgin.

We report a case of synchronous cervical adenocarcinoma with borderline mucinous ovarian tumourin a 22 year old virgin who presented with prolonged bleeding and dysmenorrhoea of four months duration. A transabdominal ultrasound demonstrated fluid in the endometrial cavity. This was confirmed by MRI pelvisrevealing adistended endometrial cavity with cervical stenosis. Evacuation revealed hematometra and the post evacuation uterine cavity is empty. She was discharged and subsequently presented at three months with acute urinary retention and heavy bleeding. A CT pelvisshowed complex bilateral ovarian cyst with minimal ascites, an enlarged paraaortic node at L2 and hematometrawith cervical stenosis. An exploratory laparotomy was performed with cystectomy, supracolicomentectomy with uterine and cervical biopsy. The histopathology shows bilateral borderline mucinous tumor of the ovary with metastatic omental nodules and primary well differentiated adenocarcinoma of the cervix. The subsequent CT thorax revealed metastatic pulmonary nodules. In view of advanced cervical adenocarcinoma, she was advised palliative chemotherapy with carboplatin and paclitaxel for six cycles. She has currently completed one cycle of chemotherapy. Conclusion:This case is one of the rare presentations of synchronous tumours of different histology with primary cervical adenocarcinoma and bilateral borderline ovarian tumour occurring in a virgin with atypical clinical presentation and rapid progression.

Ovarian Low-grade Serous Carcinoma Involving the Cervix Mimicking a Cervical Primary

We describe the clinicopathologic and immunohistochemical features of the first reported case of an ovarian low-grade serous carcinoma metastatic to the cervix mimicking a cervical primary. The patient, a 55-year-old woman, was found to have an abnormal cervix and an abnormal Pap smear during a preoperative workup for a rectocele repair. A subsequent cervical biopsy contained moderately differentiated adenocarcinoma and the patient underwent a cold knife conization. An infiltrating adenocarcinoma was found in the anterior cervical lip, the neoplasm reached the surface of the endocervical canal and was composed of mildly to moderately atypical, eosinophilic or amphophilic columnar cells arranged in glands and papillae. Mitotic figures were rare and no apoptotic bodies were seen. Psammoma bodies and intraglandular mucinous material were also noted. There was extensive vascular/lymphatic invasion. The tumor extended to all margins and was interpreted as a moderately differentiated (grade 2) adenocarcinoma of the uterine cervix with a linear spread of at least 1.4 cm and a depth of at least 0.6 cm (FIGO stage 1B1). The patient was treated with radiotherapy and cisplatin. Six months later, surveillance imaging studies showed that the patient's ovaries seemed to be enlarging. The patient underwent exploratory laparotomy, bilateral salpingo-oophorectomy, right pelvic lymph node sampling, omentectomy, peritoneal biopsies, and pelvic washings. The ovaries contained bilateral cystic tumors. There was gross tumor involving multiple peritoneal sites. Microscopic examination of the ovaries showed the typical features of low-grade serous carcinoma associated with a serous neoplasm of low malignant potential with a cribriform pattern. Metastatic low-grade serous carcinoma was detected in multiple peritoneal sites and in the pelvic washings. A consultation was obtained, with the consultant concurring that the tumors represented independent primaries. The patient received carboplatin and taxol. Two and 4 years after the initial diagnosis, she experienced recurrences and was treated with carboplatin and taxol each time. After the second recurrence, the patient decided to seek additional advice about treatment options. The latter prompted a re-review of her histologic material. Upon this re-review, it was noted that the tumor in the cervix had some rather unusual features for a primary cervical adenocarcinoma, such as the lack of conspicuous mitotic activity, extensive vascular/lymphatic invasion in the context of a tumor with no solid areas, and only mild-to-moderate cytologic atypia. In addition, the tumor in the cervix had areas that were similar to the metastatic tumor present in the omentum. Immunoperoxidase staining for WT-1, estrogen receptor, and p16 was performed on the tumor in the cervix and on the ovarian tumor. The neoplastic cells in both tumors stained in a similar manner; the tumor cells were diffusely positive for WT-1 and estrogen receptor (90%) and focally positive for p16. No detectable signal for high-risk human papillomavirus was seen in the in-situ hybridization performed on the section of the tumor in the cervix. In summary, the histologic and immunohistochemical features and the in-situ hybridization results were in keeping with a diagnosis of metastatic ovarian low-grade serous carcinoma involving the cervix. This case underscores the importance of attentive histopathologic examination and the use of ancillary tests to ensure the recognition of the site of origin of a neoplasm involving the cervix.

Diagnose und Differenzialdiagnose des zervikalen Adenokarzinoms

This overview summarizes pathogenetic and practical aspects of (sub-)classification of cervical glandular (pre-)neoplasias and, inter alia, calls into question the usefulness of grading. In the context of the differential diagnosis of benign "imitations", the phenotypic variability of glandular precancerous lesions and carcinomas is described as well as the use of special tests to distinguish them. With regard to carcinomas, the differential diagnosis of well-differentiated neoplasias is addressed including "minimal deviation" adenocarcinoma (MDA, malignant adenoma), carcinomas with endometrioid or villoglandular morphology, and mesonephric hyper- and neoplasias. Furthermore, knowledge of HPV-negative glandular (pre-)neoplasias is covered including "gastric-type" adenocarcinomas and diagnostic algorithms for discriminating between primary and secondary cervical adenocarcinomas. Finally, comments are offered on the difficulties in recognizing early invasive adenocarcinomas, especially also the pitfalls inherent in determining the depth of invasion.

Metastatic Carcinomas in the Cervix Mimicking Primary Cervical Adenocarcinoma and Adenocarcinoma in Situ: Report of a Series of Cases

Metastatic Carcinomas in the Cervix Mimicking Primary Cervical Adenocarcinoma and Adenocarcinoma in Situ: Report of a Series of Cases

Diverse facets of cervical adenocarcinoma: comprehensive review of clinicopathologic features and diagnostic criteria

Cervical adenocarcinomas span a diverse group of tumours in terms of their pathogenesis, morphology and patients’ prognosis. The diagnostic challenges are numerous and arise with virtually every case. The issues that may be particularly difficult in histopathologic evaluation of cervical adenocarcinomas include 1) differentiating in-situ and invasive tumours from their benign mimics, 2) differentiating adenocarcinoma in-situ from an early invasive lesion, 3) measuring the depth of invasion, 4) differentiating primary cervical adenocarcinoma from uterine endometrial adenocarcinoma or tumours metastatic from other primary sites such as colon. The paper reviews the pathogenesis, clinical characteristics, diagnostic criteria, immunohistochemical markers, differential diagnosis and prognosis of various subtypes of cervical adenocarcinoma.