Glassy Cell Carcinoma Research Articles

Uncommon Histopathological Subtypes and Variants of Cervical Carcinoma Diagnosed at a Tertiary Care Centre: A Case Series.

Introduction Cervical cancer ranks among the top gynaecological cancers worldwide. It is linked to lower socioeconomic status and high human papillomavirus (HPV) prevalence. This is a series of six cervical carcinoma cases analysed from 2021 to 2023 at our tertiary care centre to identify rare subtypes of cervical carcinoma. We document rare subtypes, which includeglassy cell carcinoma, small cell neuroendocrine carcinoma, papillary squamous-transitional variant,basaloid squamous cell carcinoma and serous carcinoma of the uterine cervix. Immunohistochemistry (IHC) was helpful in confirmation of the subtypes and in diagnosing HPV-associated cases. Materials and methods This case series comprises six cases, including raresubtypes and variants of cervical carcinomahistopathologically diagnosed by the Department of Pathology, Sri Ramachandra Institute of Higher Education and Research, Chennai, India, between 2021 and 2023. The demographic profile and patient details were obtained from the hospital information system and archival case files after obtaining informed consent from the patients. The H&E and relevant IHC slides along with histopathology reports of the included cases were analysed and studied. Results This series includes six cases of rare subtypes of cervical carcinoma, comprising glassy cell carcinoma, small cell neuroendocrine carcinoma, papillary squamous-transitional variant, basaloid squamous cell carcinoma (SCC), and serous carcinoma. Each subtype displays distinct clinicopathological features, emphasizing the need for specific diagnostic and treatment approaches, which are crucial in improving patient survival. Conclusion Six rare subtypes and variants of cervical carcinoma have been discussed in this case series, after correlating with histopathology reportsand clinical and radiological findings. Understanding the histopathological characteristics of these rarer subtypes is essential for accurate diagnosis and timely intervention. This series highlights the importance of comprehensive screening strategies, early diagnosis and awareness of rarer subtypes and variants of cervical carcinoma among healthcare professionals. These factors can tailor therapeutic options and improve patient outcomes.

A case of adenosquamous carcinoma, so-called glassy cell carcinoma, coexisting with small cell carcinoma of the uterine cervix

A case of adenosquamous carcinoma, so-called glassy cell carcinoma, coexisting with small cell carcinoma of the uterine cervix

A case of coexistent poorly differentiated adenosquamous carcinoma (glassy cell carcinoma), usual-type adenocarcinoma, and squamous cell carcinoma in situ of the cervix

Poorly differentiated adenosquamous carcinoma (glassy cell carcinoma) of the cervix is extremely rare, accounting for 1–2% of all cervical cancers. Herein, we report a case with coexistent poorly differentiated adenosquamous carcinoma (glassy cell carcinoma), “usual-type” adenocarcinoma, and squamous cell carcinoma in situ of the cervix. A female patient in her 60 s was referred to our hospital and diagnosed with poorly differentiated adenosquamous carcinoma based on cervical cytology and biopsy. The tumor was classified as clinical stage IB1 cervical cancer following magnetic resonance imaging; radical hysterectomy was performed. Histopathological examination revealed poorly differentiated adenosquamous carcinoma (glassy cell carcinoma), usual-type adenocarcinoma, and squamous cell carcinoma in situ, all coexisting. All carcinoma regions showed identical sizes to high-risk human papillomavirus (HPV) in fragment analysis. The patient is currently alive, without evidence of recurrence, 31 months post surgery. In this case, three different carcinomas coexisted. Fragment analysis of the patient’s HPV status suggested that all carcinomas were related to an infection with the same high-risk HPV type. To determine the precise mechanism of tumor development, i.e., whether the tumors were of the mixed or collision type, further studies are needed, including clonal analysis for the loss of heterozygosity pattern.

Glassy cell carcinoma of the cervix: Findings from a combined National Cancer Database analysis and single institution review of treatment patterns and outcomes

ObjectivesTo describe stage, treatment patterns, and survival for glassy cell carcinoma of the cervix (GCCC), a poorly understood rare tumor. MethodsClinical data and survival were compared between GCCC and more common histologic types using the National Cancer Database (NCDB) from 2004 to 2017. A retrospective review of GCCC cases at our institution from 2012 to 2020 was simultaneously performed with staging updated according to 2018 FIGO staging. Descriptive statistics and survival analyses were performed, and outcomes compared to historical references. Results143/89,001 (0.16%) NCDB cervical cancer cases were GCCC. Compared to other histologies, GCCC cases were younger, with 74.8% diagnosed before age 50. Stage distribution was similar. Stage I cases were less commonly treated with surgery alone (19/69, 27%). 79.4% of locally advanced (stage II-IVA) cases were treated with definitive chemoradiation. GCCC demonstrated worse OS for early-stage and locally-advanced disease. No survival differences were observed for patients with stage IVB disease.Our institutional review identified 14 GCCC cases. Median age at diagnosis was 34 years. All nine early-stage cases underwent radical hysterectomy. Adjuvant radiation was given for cases meeting Sedlis criteria (4/9, 44%). All five advanced stage cases were stage IIIC and received definitive chemoradiation. Recurrence rate was 0% (0/9) for early-stage and 60% (3/5) for advanced-stage cases. 3-year PFS was 100% for early-stage and 40% for advanced-stage. 3-year OS was 100% for early-stage and 60% for advanced-stage GCCC. ConclusionsGCCC presents at earlier ages than other cervical cancer histologic types. Although NCDB showed worse OS, our more contemporary institutional review, which incorporates updated staging and newer treatment modalities found outcomes more similar to historical references of more common histologic subtypes.

Abstract 6531: Point of care test for cervical cancer screening

Abstract Cervical cancer is a lethal gynecological malignancy and the fourth most common cancer among women. Most high-grade cervical pre-cancers and cancer cases are linked to infection with high-risk human papillomaviruses (HPV). There is an inequity between high-income countries (HICs) and low- and middle-income countries (LMICs) in cervical cancer burden; according to the World Health Organization, the estimated mortality rate of cervical cancer is 342,000 women worldwide in 2020, and 90% of these women reside in low- and middle-income nations where the human papillomavirus vaccine is unavailable and access to early detection testing are either unavailable or too expensive. This study aims to develop a simple and affordable point-of-care test based on four critical biomarkers for screening high-risk pre-cancer and invasive cervical cancer in collaboration with the biomedical engineering department. A cervical cancer swab will be used in the test. The swab will be placed on a paper-based device that looks for four protein biomarkers critical for the progression of noninvasive cervical cancer into invasive cervical cancer by combining two approaches using proteomics and lateral flow immunochromatography technology. We have validated the markers' expression in cervical cancer and precancerous tissues. The four markers were expressed in squamous cell carcinoma, glassy cell carcinoma, adenocarcinoma, clear cell carcinoma cancer tissues, and the high-grade cervical intraepithelial neoplasia. This point-of-care test will be affordable and implementable, especially in low and middle-income countries. Citation Format: Samrin Farouk Idris Habbani, Sayeh Jalali Dowlatshahi, Monisha Elumalai, Scott Charles Bolton, Lucy Teberh Tecle, Pankti Rajesh Thakkar, Jacqueline C Linnes, Sulma I Mohammed. Point of care test for cervical cancer screening [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6531.

Inmixed and Bellicose-Adenosquamous Carcinoma-Uterine Cervix

Adenosquamous carcinoma of uterine cervix is a preponderantly high grade neoplasm configured of admixed glandular articulations and squamous epithelium wherein glassy cell carcinoma emerges as an exceptional, aggressive variant. Adenosquamous carcinoma is posited to arise from sub-columnar reserve cells confined to endocervical basal epithelium. Cytological smears depict papillary articulations admixed with bland columnar epithelial cells and high grade squamous intraepithelial lesion. The biphasic tumour is composed of well defined, malignant components of glandular articulations and poorly differentiated squamous epithelium. Glassy cell carcinoma demonstrates solid cell nests comprised of pleomorphic, polygonal tumour cells pervaded with glassy, eosinophilic cytoplasm, enlarged, eosinophilic nuclei, prominent nucleoli and distinct cytoplasmic membrane. Neoplastic cells appear enmeshed within an intense inflammatory cell infiltrate with significant eosinophils. Glassy cell carcinoma appears immune reactive to MUC1, MUC2, epithelial membrane antigen (EMA), CAM5.2 or p63 with focal immune reactivity to carcinoembryonic antigen (CEA). Adenosquamous carcinoma requires segregation from neoplasms such as adenocarcinoma with coexisting squamous intraepithelial lesion (SIL), adenoid basal carcinoma, cervical extension of endometrial adenocarcinoma, and squamous cell carcinoma with focal mucin droplets, large cell non keratinizing squamous cell carcinoma or lymphoepithelioma-like carcinoma. Tumefaction may be appropriately treated by radical abdominal hysterectomy followed by adjuvant chemotherapy and radiation therapy.

Glassy cell carcinoma of the cervix (GCCC): a single institution review of treatment patterns and outcomes (184)

Glassy cell carcinoma of the cervix (GCCC): a single institution review of treatment patterns and outcomes (184)

Glassy cell carcinoma of cervix: A case report

Glassy cell carcinoma of the cervix is a rare subtype of adenosquamous carcinoma associated with aggressive course and poor prognosis. It is considered to originate from the subcylindrical reserve cells of the cervix and has been associated with human papillomavirus. Histologically glassy cell carcinoma is composed of nestes of large cells with ground glass cytoplasm and large vesicular nuclei with prominent nucleoli. Nuclear pleomorphism and tumor giant cells are frequently seen. Mitotic activity is brisk. Infiltration by eosinophils and plasma cells with admixture of lymphocytes is a characteristic feature. Focal squamous and glandular differentiation may be seen. The immunohistochemistry markers are positive for squamous cell carcinoma (p63, CK34) and adenocarcinoma(MUC1, MUC2, CEA).Here we present a case of 49 year old female diagnosed as glassy cell carcinoma histologically and immunohistochemically.

Immunohistochemical analysis of glassy cell carcinoma of the cervix reveals robust lymphocyte infiltrate and the expression of targetable inhibitory immune checkpoints.

To validate our previous findings of high-level EGFR expression in GCCC using an expanded cohort of specimens and to further examine the molecular and cellular features of this aggressive malignancy to identify potentially actionable therapeutic targets. The SEER database was queried to obtain the epidemiological data regarding the current national survival trends for GCCC. Immunohistochemistry (IHC) was used to examine the expression of EGFR, PD-1, and PD-L1. CiberSort analysis was used to analyze a previously published RNA-sequencing dataset obtained from a single patient diagnosed with GCCC. In comparison to squamous cell carcinomas and adenocarcinoma/adenosquamous carcinomas, GCCC was observed in younger patients (p < 0.001) and demonstrated inferior survival (p < 0.001). All (100%) of the specimens (8/8) exhibited immunoreactivity when stained for CD3ε (T-cell marker), EGFR, PD-1, and PD-L1 whereas CTLA4 expression was not detected. Analysis of RNA-sequencing data revealed that cetuximab and erlotinib altered the chemokine profile, lymphocyte abundance, and expression of inhibitory immune checkpoints in a single patient when combined with cytotoxic chemotherapy in a single patient. The data from this descriptive study suggests that immune checkpoint blockade, whether single agent or in combination, may be a suitable therapeutic option for a disease for which targeted approaches do not currently exist.

Trends in glassy cell cervical cancer in the United States from 1973-2015: Analysis based on SEER database.

e17502 Background: Glassy cell carcinoma of cervix (GCCC) is a rare histological subtype of cervical cancer which has historically been associated with rapidly progressive disease, early development of metastases and overall poor prognosis. We attempt to define real-world trends in GCCC in the United States based on data from SEER (Surveillance, Epidemiology and End Results) database. Methods: We extracted data from the US National Cancer Institute's SEER 2018 dataset using ICD-O code for ‘Cervix Uteri Glassy Cell Carcinoma’. All patients who were diagnosed between 1973-2015 were included. Statistical analysis was done using SPSS 26. Kaplan Meier curve was used for survival analysis. Results: Data for a total of 57 patients with GCCC was available from 1975 to 2017. Median age at diagnosis was 38 years (range 30.5-44.5). Increased frequency of cases was noted in white females (77.2%) as compared to black population (22.2%). Most cases initially presented with localized or regional spread (47.4% and 40.4% respectively) with distant metastasis seen in only 10.5% patients. Data analysis revealed that 63.2% patients had Grade III poorly differentiated carcinoma, 66.7% received radiation therapy, 57.9% underwent chemotherapy and 59.6% had cancer direceted surgery performed. Calculated mean overall survival was 121.9 months. We were unable to calculate 5 year and 10 year median overall survival due to small sample size and censored data. Conclusions: GCCC is a rare histologic type of cervical cancer that presents at a younger age, is more frequently seen in white females and is commonly associated with localized or regional spread at time of initial presentation.[Table: see text]

Glassy Cell Carcinoma of Cervix: A Rare Case Report

Glassy Cell Carcinoma of Cervix: A Rare Case Report

Glassy cell carcinoma of the uterine cervix: 20-year experience from a comprehensive cancer center

PurposeGlassy cell carcinoma (GCC) of the uterine cervix is a rare entity. This study aims at describing the clinical characteristics and outcomes of cervical GCC patients treated in a comprehensive cancer center. Material and methodsWe retrospectively reported patients and tumors characteristics, therapeutic management, overall survival (OS), progression-free progression (PFS), relapse rates, and toxicities. ResultsBetween 1994 and 2014, 55 patients were treated with curative intent. The median age at diagnosis was 41 years (range, 20–68). Among 22 patients with early stage tumors (IA2-IB1-IIA1), 17 had preoperative brachytherapy, followed by radical hysterectomy. Among 33 patients with locally advanced disease (≥IB2), 32 underwent chemoradiation±brachytherapy boost. After a median follow-up of 5.4 years (range, 0.15–21.7 years), 18/55 (33%) patients experienced tumor relapse. Local recurrence occurred in 2/22 (9%) patients with early disease (treated with upfront surgery) and in 3/32 (9%) patients with locally advanced disease. Most frequent relapses were distant, occurring in a total of 11/55 patients (20%). PFS rates at 5-year were 86.4% (95% CI: 63.4–95.4) for early stage versus 75.9% (95% CI: 55.2–89.2) for locally advanced stages, respectively (P=0.18). ConclusionLarge cohort data are warranted to guide the optimal management of GCC. From this retrospective analysis, a multimodal approach yielded to good disease control in early stages tumors. Given the high-risk of distant failure, consideration should be given to adjuvant chemotherapy in locally advanced disease.

PO-1135: Place of radiotherapy as part of multimodal management of cervical glassy cell carcinoma

PO-1135: Place of radiotherapy as part of multimodal management of cervical glassy cell carcinoma

Glassy cell carcinoma of cervix: an analysis for 20 cases and literatures review.

BackgroundGlassy cell carcinoma (GCC) of the cervix is defined as a rare subtype of adeno-squamous cell carcinoma (ASC) with poor prognosis. We presented our clinical data of patients with cervical GCC and reviewed the outcomes in recent years.MethodsFrom 2011.1 to 2019.7, 20 cases of cervical GCC diagnosed and treated in our institution were reviewed for clinicopathologic features, treatment strategies, and outcomes.Results(I) Twenty cases confirmed as cervical GCC were selected and represented 1.8% of all invasive cervical cancer diagnoses. The median age of all cervical GCC patients was 46 years (range from 33 to 69 years). The main clinical symptoms were abnormal vaginal bleeding and postcoital bleeding. The incidence of stage I, stage II, stage III was 75%, 20% and 5%. (II) Human papillomavirus (HPV) prevalence in cervical GCC was 44.4% (4/9). Of the HPV-positive tumors, HPV genotyping was variable. Tumors of 3 cases were found infected by HPV-18. Another tumor was infected by HPV-16 and HPV-31. Multiple infections were found in 1 case. (III) The disease-free survival (DFS) of early stage cervical GCC cases was 93%, and DFS of advanced stage cervical GCC cases was 67%. DFS of all cases was 85%. The median follow-up interval for surviving patients was 28 months. Three patients recurred, leading to an overall recurrence rate of 15% (3/20). One of 3 recurred cases was from multimodal treatment group who had one high risk factor (pelvic lymph node metastasis) and three intermediate risk factors lympho-vascular space involvement (LVSI), deep stromal invasion, and large tumor size (3.5 cm). Other 2 cases recurred were from radio-chemotherapy group.ConclusionsCervical GCC is associated with high-risk type HPV infection, especially HPV 18. The prognosis of GCC was not poor as depicted in previous studies. Early-stage GCC patients should receive multimodal treatment which reduced recurrence rate and improved survival rate. With the limitation of small sample size, we speculated surgery might play a key role in curing GCC. Patients whose pathology features includes at least two intermediate high risk recurrence or one high risk factor should accept adjuvant treatment after complete surgical management.

Glassy cell carcinoma: is surgical treatment with preservation of the uterus a therapeutic option

Glassy cell carcinoma (GCC) is a rare and aggressive type of adenoSquamous cervical carcinoma. It affects patients at a younger age compared to the general population of patients with cervical cancer. The five-year survival is inferior to that of the other histological types. The treatment is not standardized. Radiation therapy with concomitant chemotherapy is associated with a better local control and improves oncological results. The authors report here the clinical histories of two patients with an early GCC and a desire of fertility preservation treated with radical trachelectomy with an early recurrence. They conclude that considering the rarity and aggressivity of this histological type, and the lack of evidence in the literature for its management, it would be prudent to consider GCC at an early stage as a contraindication for a radical trachelectomy.

Glassy cell carcinoma du col de l’utérus : une maladie tumorale agressive

IntroductionCervical cancer is the twelfth most frequent cancer in women in France. Glassy cell carcinoma is a rare histological entity, rapidly aggressive, associated with a poor prognosis. Case reportA 30-year-old woman was admitted in an internal medicine department for polyarthralgia with high grade fever, evolving for 3 weeks. There was an inflammatory syndrome. The 18-FDG-PET-scan showed inflammatory lymph nodes as well as disseminated osteolytic lesions, and a primitive pelvic tumor. A 3cm tumor of the cervix was found during the gynaecologic examination. Histological analysis elicited a high-index mitotic carcinoma, glassy cell carcinoma type. Despite chemotherapy, the outcome was poor, with early death occurring after three months of follow-up. ConclusionThe glassy cell carcinoma of the cervix should be considered as an aetiology of bone metastases in young female patients.

Analysis of preventability of malignancy-related maternal death from the nationwide registration system of maternal deaths in Japan

Objective: We reviewed malignancy related maternal deaths in Japan to ascertain if there were avoidable factors.Methods: Malignancy-related maternal death in Japan reported to the Maternal Death Exploratory Committee, from 2010 to 2016 inclusive.Results: There were 12 cases of maternal death caused by malignancy. There were four gastric cancers (two poorly differentiated adenocarcinoma, one signet ring cell carcinoma with adenocarcinoma, one histology not available), 3 leukemia (two acute myeloid leukemia, one aggressive NK cell leukemia), two ureteral cancers (histology not available), one malignant lymphoma (diffuse large B-cell lymphoma with translocation), one brain tumor (gliomatosis cerebri), and one cervical cancer (glassy cell carcinoma). Two gastric cancer patients had chronic gastric pain before conception. In two cases the physicians commented that they had avoided computed tomography and the brain biopsy needed for diagnosis because the patient was pregnant. At diagnosis, the clinical stages were II–IV in 9, and the performance status was 3–5 in 8. Indication for delivery was exacerbated maternal condition in 5, for treatment in 3, spontaneous labor in 3, and one patient declined elective delivery. Median [interquartile rage] (range) gestational weeks of delivery was 29 [24–30] (19–40). One cervical cancer patient had a radical hysterectomy and chemotherapy for 10 months. However, three leukemia and one gastric cancer patients had chemotherapy within 10 d because they deteriorated rapidly. Another seven cases did not have any treatment because of poor general condition or because they remained undiagnosed. In all cases, the Committee considered that there was no evidence of substandard care.Conclusion: In these cases, both the clinical stages and biological degree of malignancy were high. In two-thirds of cases, early termination of the pregnancy was indicated because of deteriorating maternal condition. Chemotherapy was not effective because of short available time for therapy and the advanced stage of the cancers when diagnosed. Encouraging women to have a thorough medical assessment before conception, and early diagnosis and treatment before pregnancy, appears to be the only practical way to reduce deaths from malignancy while a woman is pregnant.

Cervical screening and risk of adenosquamous and rare histological types of invasive cervical carcinoma: population based nested case-control study

ObjectivesTo examine the association of cervical cytology screening with the risk of adenosquamous cell carcinoma (ASC) and rare histological types of invasive cervical carcinoma (RICC), using comprehensive registry data, and...

RETRACTED ARTICLE: Cervical adenosquamous carcinoma: detailed analysis of morphology, immunohistochemical profile, and clinical outcomes in 59 cases

Although 2014 World Health Organization criteria require unequivocal glandular and squamous differentiation for a diagnosis of cervical adenosquamous carcinoma, in practice, adenosquamous carcinoma diagnoses are often made in tumors that lack unequivocal squamous and/or glandular differentiation. Considering the ambiguous etiologic, morphological, and clinical features and outcomes associated with adenosquamous carcinomas, we sought to redefine these tumors. We reviewed slides from 59 initially diagnosed adenosquamous carcinomas (including glassy cell carcinoma and related lesions) to confirm an adenosquamous carcinoma diagnosis only in the presence of unequivocal malignant glandular and squamous differentiation. Select cases underwent immunohistochemical profiling as well as human papillomavirus (HPV) testing by in situ hybridization. Of the 59 cases originally classified as adenosquamous carcinomas, 34 retained their adenosquamous carcinoma diagnosis, 9 were reclassified as pure invasive stratified mucin-producing carcinomas, 10 as invasive stratified mucin-producing carcinomas with other components (such as HPV-associated mucinous, usual-type, or adenosquamous carcinomas), and 4 as HPV-associated usual or mucinous adenocarcinomas with benign-appearing squamous metaplasia. Two glassy cell carcinomas were reclassified as poorly differentiated usual-type carcinomas based on morphology and immunophenotype. There were significant immunophenotypic differences between adenosquamous carcinomas and pure invasive stratified mucin-producing carcinomas with regard to HPV (p < 0.0001), PAX8 (p = 0.038; more in adenosquamous carcinoma), p40 (p < 0.0001; more in adenosquamous carcinoma), p63 (p = 0.0018; more in adenosquamous carcinoma) and MUC6 (p < 0.0001; less in adenosquamous carcinoma), HNF-1beta (p = 0.0023), vimentin (p = 0.0003), p53 (p = 0.0004), and CK7 (p = 0.0002) expression. Survival outcomes were similar between all groups. Adenosquamous carcinomas should be diagnosed only in the presence of unequivocal malignant glandular and squamous differentiation. The two putative glassy cell carcinomas studied did not meet our criteria for adenosquamous carcinoma, and categorizing them as such should be reconsidered.

Role of DDX53 in taxol-resistance of cervix cancer cells in vitro

Cancer/Testis antigen DDX53 shows high expression level in various tumors and is involved in anti-cancer drug resistance. However, the functional study of DDX53 in cervix cancer remains unknown. In this study, the role of DDX53 in taxol-resistance of cervix cancer cells was investigated. In taxol-resistant HelaTR cells, DDX53 was significantly increased as compared to the parental HeLa cells. HelaTR cells also showed upregulation of multidrug resistant gene MDR1, invasive characteristics and decreased apoptosis. In addition, increased autophagy level was observed in HelaTR cells. Overexpression of DDX53 in HeLa and SiHa markedly led to greater resistance to taxol and cisplatin, whereas knockdown of DDX53 in HelaTR cells restored sensitivity, demonstrating that DDX53 regulated taxol resistance in cervix cancer cells. DDX53 overexpression in HeLa and SiHa cells enhanced invasion, migration and anchorage independent growth, DDX53 knockdown showed inverse effects in HeLaTR cells. When DDX53 expression was suppressed by siRNA, autophagic flux and drug resistance of HelaTR cells were decreased. In addition, DDX53 was upregulated in cervix cancer tissues from patient with a glassy cell carcinoma of cervix. Taken together, these results suggest that DDX53 plays a critical role in taxol-resistance by activating autophagy and a potential therapeutic target for the treatment of taxol-resistant cervix cancer.