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.

Identification of human MHC-I HPV18 E6/E7-specific CD8 + T cell epitopes and generation of an HPV18 E6/E7-expressing adenosquamous carcinoma in HLA-A2 transgenic mice.

BACKGROUND: Human Papillomavirus type 18 (HPV18) is a high-risk HPV that is commonly associated with cervical cancer. HPV18 oncogenes E6 and E7 are associated with the malignant transformation of cells, thus the identification of human leukocyte antigen (HLA)-restricted E6/E7 peptide-specific CD8 + T cell epitopes and the creation of a HPV18 E6/E7 expressing cervicovaginal tumor in HLA-A2 transgenic mice will be significant for vaccine development. METHODS: In the below study, we characterized various human HLA class I-restricted HPV18 E6 and E7-specific CD8 + T cells mediated immune responses in HLA class I transgenic mice using DNA vaccines encoding HPV18E6 and HPV18E7. We then confirmed HLA-restricted E6/E7 specific CD8 + T cell epitopes using splenocytes from vaccinated mice stimulated with HPV18E6/E7 peptides. Furthermore, we used oncogenic DNA plasmids encoding HPV18E7E6(delD70), luciferase, cMyc, and AKT to create a spontaneous cervicovaginal carcinoma model in HLA-A2 transgenic mice. RESULTS: Therapeutic HPV18 E7 DNA vaccination did not elicit any significant CD8 + T cell response in HLA-A1, HLA-24, HLA-B7, HLA-B44 transgenic or wild type C57BL/6 mice, but it did generate a strong HLA-A2 and HLA-A11 restricted HPV18E7-specific CD8 + T cell immune response. We found that a single deletion of aspartic acid (D) at location 70 in HPV18E6 DNA abolishes the presentation of HPV18 E6 peptide (aa67-75) by murine MHC class I. We found that the DNA vaccine with this mutant HPV18 E6 generated E6-specific CD8 + T cells in HLA-A2. HLA-A11, HLA-A24 and HLA-b40 transgenic mice. Of note, HLA-A2 restricted, HPV18 E7 peptide (aa7-15)- and HPV18 E6 peptide (aa97-105)-specific epitopes are endogenously processed by HPV18 positive Hela-AAD (HLA-A*0201/Dd) cells. Finally, we found that injection of DNA plasmids encoding HPV18E7E6(delD70), AKT, cMyc, and SB100 can result in the development of adenosquamous carcinoma in the cervicovaginal tract of HLA-A2 transgenic mice. CONCLUSIONS: We characterized various human HLA class I-restricted HPV18 E6/E7 peptide specific CD8 + T cell epitopes in human HLA class I transgenic mice. We demonstrated that HPV18 positive Hela cells expressing chimeric HLA-A2 (AAD) do present both HLA-A2-restricted HPV18 E7 (aa7-15)- and HPV18 E6 (aa97-105)-specific CD8 + T cell epitopes. A mutant HPV18E6 that had a single deletion at location 70 obliterates the E6 presentation by murine MHC class I and remains oncogenic. The identification of these human MHC restricted HPV antigen specific epitopes as well as the HPV18E6/E7 expressing adenosquamous cell carcinoma model may have significant future translational potential.

Single-cell RNA-sequencing dissects cellular heterogeneity and identifies two tumor-suppressing immune cell subclusters in HPV-related cervical adenosquamous carcinoma.

The intratumor heterogeneity of human papillomavirus (HPV)-related cervical cancer remains poorly defined. We performed single-cell RNA sequencing on 18 046 individual cells derived from two HPV-related cervical adenosquamous carcinoma samples to analyze the transcriptional heterogeneity of both epithelial and immune constituents, identifying seven epithelial (Epi1-7) and 11 immune subclusters. Based on expression of known cervical cancer markers, Epi1-2 primarily displayed features of adenocarcinoma, whereas Epi3-6 were instead characterized by features of squamous carcinoma. Our analyses also revealed that hypoxia and Kirsten rat sarcoma viral oncogene signaling were highly represented within Epi1; metabolic pathways mediating glycolysis and oxidative phosphorylation were enriched in Epi2-4; while Epi5 was enriched in p53 pathway components and features of epithelial-mesenchymal transition. Moreover, CD8+ FGFBP2+ T cells and FGFBP2+ natural killer cells were found to display high levels of cytotoxic effectors (GZMA, GZMB, GNLY, and PRF1) and low levels of inhibitory markers (PDCD1, TIGIT, and CTLA4), such that tumor infiltration by these populations was positively associated with survival in a cohort of n = 165 patients with HPV-related cervical cancer from The Cancer Genome Atlas database (p = 0.017 and 0.014, respectively). These results shed new light on the intratumor heterogeneity of HPV-related cervical adenosquamous carcinoma, which will help to refine diagnostic and treatment approaches.

Epstein-Barr virus-associated gastric adenosquamous carcinoma with concurrent gastric carcinoma with lymphoid stroma: a case report and review of the literature.

BACKGROUND: Adenosquamous carcinoma (ASC)with concurrent gastric carcinoma with lymphoid stroma (GCLS) are extremely rare tumors. There are only limited cases reported in the literature. Epstein-Barr virus (EBV) infection was found in the concomitant GCLS, but none in the ASC. Here, we report the first case of gastric cancer with EBV infection detected in both ASC and GCLS. CASE PRESENTATION: A 59-year-old man complained of intermittent upper abdominal pain. The gastric endoscopy revealed a type IIc tumor located in the gastric body near the fundus of the stomach. Histological examination of the gastric tumor showed the coexistence of ASC and GCLS. Both components were positive for EBV-encoded RNA (EBER) in situ hybridization. Neoplastic nests of the former were positive for p63, p40 and CK5/6. The glandular components showed positive acid mucus in the Alcian-blue periodic-acid-schiff (AB-PAS) staining. There was significant difference in the expression of epidermal growth factor receptor (EGFR) between adenocarcinoma and squamous carcinoma, but not in other proteins such as human epidermal growth factor receptor 2 (HER2), p53 and mismatch repair proteins. The role of EGFR signaling pathway needs to be further explored in the differentiation of squamous carcinoma in the gastric ASC. Finally, a diagnosis of early EBV associated gastric ASC with concurrent GCLS (pT1bN1) was made. The patient took a single-drug S1 periodically for half a year after the surgery and has been disease free during 8 months of medical follow-up. CONCLUSIONS: This is the first case of EBV associated gastric ASC with concurrent GCLS, and pathologists and clinicians should recognize and pay attention to this type of tumor.

Pancreatic panniculitis in a patient with pancreatic adenosquamous carcinoma.

Pancreatic panniculitis is a rare complication of pancreatic diseases. We aimed to evaluate a case of pancreatic panniculitis. A 58-year-old woman was referred to our hospital with complaints of painful cutaneous nodules on her limbs. Various diagnostic tests confirmed pancreatic panniculitis and pancreatic adenosquamous carcinoma. We diagnosed pancreatic panniculitis by a skin nodule biopsy that revealed fine basophilic material within anucleate cells and neutrophil infiltration. Abdominal imaging detected a tumor with necrosis on the pancreas and endoscopic ultrasound-guided fine-needle aspiration revealed it as an adenocarcinoma. The patient underwent pancreatoduodenectomy after neoadjuvant chemotherapy. The tumor was composed of differentiated adenocarcinoma and squamous cell carcinoma and diagnosed as adenosquamous carcinoma. This is the first report of pancreatic panniculitis in a patient with adenosquamous cell carcinoma of the pancreas.

Primary adenosquamous carcinoma of the liver detected during cancer surveillance in a patient with primary sclerosing cholangitis.

Primary sclerosing cholangitis (PSC) is associated with significant risk for hepatobiliary cancers. Primary hepatic adenosquamous carcinoma (ASC), a rare subtype of cholangiocarcinoma, is composed of both adenocarcinoma and squamous cell carcinoma components. We herein report the case of a patient with PSC who was diagnosed with ASC of the liver during cancer surveillance. A 74-year-old male patient was diagnosed with PSC based on blood chemistry and magnetic resonance cholangiopancreatography findings, and regular surveillance for hepatobiliary cancers was initiated. Four years later, the level of carbohydrate antigen 19-9 rapidly increased, and abdominal imaging studies revealed a cystic mass, 40 mm in diameter, containing a solid component in the right liver lobe. Right lobectomy was performed with a pre-operative diagnosis of cholangiocarcinoma; however, the definitive diagnosis was ASC based on the presence of adenocarcinoma and squamous cell carcinoma components in the resected tumor. The patient did not receive post-operative chemotherapy, but was alive for more than 4 years without recurrence at last follow-up. The present case illustrates that regular surveillance and curative resection might achieve long-term survival in hepatic ASC, which has a poor prognosis.

Metabolic syndrome affects the long-term survival of patients with non-endometrioid carcinoma of the uterine corpus.

OBJECTIVE: To probe the influence of metabolic syndrome (MS) on the long-term survival of patients with non-endometrioid adenocarcinoma. METHODS: Between January 2003 and December 2012, 139 Chinese patients with non-endometrial adenocarcinoma were analyzed in a retrospective study. Patients who had received any treatment before surgery were excluded. Survival times were compared between patients with and without MS. RESULTS: Overall, 41 (29.5%) patients had MS; the highest incidence of MS was observed in those with uterine serous carcinoma (19/45, 42.2%). For uterine serous carcinoma or adenosquamous carcinoma, MS was an independent predictive factor of morbidity (P=0.023 and 0.016, respectively). For the overall population, those with MS had a significantly lower survival rate than those without MS (P=0.008), and the median overall survival (mOS) was 15 months versus 55 months (P<0.001, hazard ratio [HR] 0.45, 95% confidence interval [CI] 0.29-0.69). Similarly, a lower survival rate (P=0.020) and shorter mOS (19 months vs 55 months, P=0.007, HR 0.41, 95% CI 0.20-0.83) were also found in the uterine serous carcinoma population with MS. Multivariate Cox regression analyses showed that disease stage (P=0.023) and MS (P=0.008) were independent prognostic factors for uterine serous carcinoma. CONCLUSION: The present study suggests that MS is a prognostic factor for non-endometrioid adenocarcinoma, especially uterine serous carcinoma.

A case of melanocytic cervical adenosquamous carcinoma complicated with Cushing's syndrome.

BACKGROUND: To date, cervical carcinoma complicated with Cushing's syndrome were all diagnosed as small cell carcinoma histo- logically, but not adenosquamous carcinoma. Here the authors present the diagnosis, management, and prognosis of a case of melanocytic cervical adenosquamous carcinoma complicated with Cushing's syndrome. CASE: A 28-year-old woman was admitted with the chief complaint of post-coital bleeding for one month. Gynecological examination revealed a nodular yellowish-pigmented vegetation (6x5 cm) on the cervix. Laboratory findings proved the diagnosis of Cushing's syndrome. Histopathological diagnosis showed the adenosquamous carcinoma with melanoma differentiation. Immunohistochemical stainings for melanoma A and anti- adrenocorticotropic hormone (ACTH) were positive in the majority of the tumor cells, which indicated that this melanocytic cervical carcinoma lesion was the source of ectopic ACTH production resulting in Cushing's syndrome. CONCLUSION: This is a unique case of a rare type of cervical carcinoma.

Utility of dysphagia grade in predicting endoscopic ultrasound T-stage of non-metastatic esophageal cancer.

Patients with non-metastatic esophageal cancer routinely undergo endoscopic ultrasound (EUS) for loco-regional staging. Neoadjuvant therapy is recommended for ≥T3 tumors while upfront surgery can be considered for ≤T2 lesions. The aim of this study was to determine if the degree of dysphagia can predict the EUS T-stage of esophageal cancer. One hundred eleven consecutive patients with non-metastatic esophageal cancer were retrospectively reviewed from a database. Prior to EUS, patients' dysphagia grade was recorded. Correlation between dysphagia grade and EUS T-stage, especially in reference to predicting ≥T3 stage, was determined. The correlation of dysphagia grade with EUS T-stage (Kendall's tau coefficient) was 0.49 (P < 0.001) for the lower and 0.59 (P = 0.008) for the middle esophagus. The sensitivity and specificity of dysphagia grade ≥2 (can only swallow semi-solids/liquids) for T3 cancer were 56% (95% confidence interval [CI] 43-67%) and 93% (95% CI 79-98%), respectively. The sensitivity, specificity, and positive predictive value of dysphagia grade ≥3 (can only swallow liquids or total dysphagia) for T3 lesions were 36% (95% CI 25-48%), 100% (95% CI 89-100%), and 100% (95% CI 83-100%), respectively. Overall, there was a significant positive correlation between dysphagia grade and the EUS T-stage of esophageal cancer. All patients with dysphagia grade ≥3 had T3 lesions. This may have clinical implications for patients who can only swallow liquids or have complete dysphagia by allowing for prompt initiation of neoadjuvant therapy, especially in countries/centers where EUS service is difficult to access in a timely manner or not available.

Evaluation of histologically confirmed carcinoma of the cervix in Nnewi Nigeria: A five year review.

Background: Cervical cancer is the commonest gynaecological cancer in developing countries. It is a major cause of cancer related deaths among women in our subregion. Objective: To determine the incidence, mode of presentation, associated risk factors and management of histologically confirmed carcinoma of the cervix at the Nnamdi Azikiwe University Teaching Hospital, Nnewi. Method: This was a retrospective study of all the cases of histologically confirmed carcinoma of the cervix at the Nnamdi Azikwe University Teaching Hospital, Nnewi, between first of August 2009 and 31st July 2014. Data collected was analysed with SPSS version 20.0 software and presented in tables and charts. Results: Sixty two patients with histological confirmation of cervical cancer were managed in the hospital over a five year period. Forty five of these patients with adequate information in their folders constitute the study group. There was an incidence of 9.2% of all gynaecological admissions. The highest incidence(31.2%) was found in age group 50-59 years. Conclusion: The incidence of cervical cancer is very high in our environment. Majority of the presentations were at the advanced stage of the disease.

Effect of hydronephrosis on survival in advanced stage cervical cancer.

BACKGROUND: Hydronephrosis is frequently encountered in advanced stage cervical cancers, and may be associated with mortality. In the present study, we aimed to demonstrate the effect of hydronephrosis on survival in patients with inoperable advanced stage cervical cancer. MATERIALS AND METHODS: The study data were acquired by retrospective analysis of the patient records belonging to 165 women with FIGO (International Federation of Gynecology and Obstetrics) stage-IIIB or more advanced cervical cancer, which were not surgical candidates. Parameters including patient age, pathological diagnosis, disease stage, pelvic sidewall extension, presence of hydronephrosis and administration of chemoradiation were analyzed. Further, the effects of these variables on survival were assessed. P values less than 0.05 were considered statistically significant. RESULTS: The distribution of the study patients according to disease stage was as follows: 131 (79.4%) had stage-IIIB, 18 (10.9%) had stage-IVB and 16 (% 9.7) patients had stage-IVA disease. Hydronephrosis was not evident in 91 (55.2%) of these patients, whereas 41 (24.8%) had unilateral and 33 (20%) patients had bilateral hydronephrosis. When compared to mean survival in patients who did not have hydronephrosis, survival was significantly shortened in patients who had bilateral and unilateral hydronephrosis (p<0.05). There was no significant survival difference between patients with unilateral and bilateral hydronephrosis (p>0.05). Although patient age, pathological type, pelvic involvement, and chemotherapy treatment rates were similar (p>0.05), radiotherapy requirement rate and disease stage were significantly different among the study groups (p<0.05). CONCLUSIONS: Hydronephrosis was found to be a significant predictor of poor survival in patients with advanced stage cervical cancer, irrespective of unilateral or bilateral involvement.While waiting for future studies with larger sample sizes, we believe that the FIGO stages in advanced cervical cancer could further be stratified into subgroups according to presence or absence of hydronephrosis.

Pre- and post- transplantation lung cancer in heart transplant recipients.

Heart transplantation after lung cancer surgery can be questionable because of the high risk of cancer recurrence. We report the results of two patients. The first underwent right lobectomy in 2008 for pT1N0 adenocarcinoma, heart-transplantation in 2010, and surgery for synchronous adenocarcinoma and squamous-cell carcinoma in 2012. The second underwent left segmentectomy for pT1aN0 adenosquamous carcinoma and transplantation in 1995 and then surgery for pT1aN1 adenocarcinoma in 2013. Posttransplantation lung cancer histologic analysis results were different in both cases, demonstrating the absence of metastatic recurrence. Thus, early stage lung cancer might not be a contraindication to heart transplantation, nor are long delays be necessary before registering on a waiting list.

Tumor thrombus in left atrium from pulmonary adenosquamous carcinoma.

We report a case of pulmonary adenosquamous carcinoma with a tumor thrombus in the left atrium. The left atrial tumor thrombus and lung cancer were removed via a right pneumonectomy and atriotomy under cardiopulmonary bypass. Simultaneous resection of a left atrial tumor thrombus and lung cancer can prevent systemic embolization, mitral obstruction, and sudden death, and improve the prognosis in selected patients.

Fever as a first manifestation of advanced gastric adenosquamous carcinoma: a case report.

Gastric adenosquamous carcinoma (ASC) is a rare type of gastric cancer. It is a mixed neoplasm, consisting of glandular cells and squamous cells. It is often diagnosed at an advanced stage, thus carrying a poor prognosis. We describe a case of a 73-year-old male, who presented with refractory fever and an intra-abdominal mass on imaging. He underwent a laparoscopic exploration followed by a successful totally laparoscopic total gastrectomy with D2 lymphadenectomy for gastric cancer. Postoperative pathology revealed primary gastric ASC (T4aN0M0). The patient received adjuvant radiotherapy and chemotherapy with S1 and is alive 20 mo after surgery without recurrence. This is the first case of advanced gastric ASC with fever as the initial presentation treated with totally laparoscopic total gastrectomy reported in the English literature.

Tubular duplication of the oesophagus presenting with dysphagia.

Duplications of the alimentary tract are rare congenital malformations, with the ileum being the most commonly affected site, followed by the oesophagus. Among oesophageal duplications, cystic duplication is the most common and the tubular variety, the rarest. Herein, we report a rare case of tubular oesophageal duplication, complicated by adenosquamous carcinoma at the lower end of the oesophagus, in a 32-year-old man who presented with progressive dysphagia. Although proton pump inhibitors may relieve dysphagia, oesophagectomy and gastric interpositioning should be the first-line treatment for patients with tubular oesophageal duplication, in order to reduce the risk of malignant transformation at the lower end of the oesophagus.

Primary urinary bladder adenosquamous carcinoma complicated with lower limb deep venous thromboses: a case report.

Primary urinary bladder adenosquamous carcinoma is extremely rare and only a few cases have been reported in English literatures. Its biological behavior remains unclear. Here we reported a 60-year-old male patient with lower limb deep venous thromboses associated with primary urinary bladder adenosquamous carcinoma. A color ultrasonography showed right stock total venous thrombosis and right great saphenous vein thrombosis of lower limb. Contrast-enhanced computed tomography (CT) scan confirmed a 3.17 × 3.33 × 3.84 cm enhancing mass within the urinary bladder along the right lateral and posterior wall. Histopathological examination revealed adenosquamous carcinoma of urinary bladder, with extensive infiltration of the muscle layer. To the best of our knowledge, this is the first report of primary urinary bladder adenosquamous carcinoma complicated with deep venous thromboses in lower limb.