Outcome and Prognostic Factors in Adenosquamous Carcinoma of the Head and Neck - a Multicenter Rare Cancer Network Study

Background: Adenosquamous carcinoma (AC) of the head and neck is a distinct entity first described in 1968. Its natural history is more aggressive than squamous-cell carcinoma. The aim of this study was to assess the clinical profile, patterns of failure, and prognostic factors in patients with AC of the head and neck treated by radiation therapy (RT) with or without chemotherapy (CT).Materials and Methods: Data from 19 patients with stage I (n = 3), II (n = 1), III (n = 4), or IVa (n = 11) AC, treated between 1989 and 2009, were collected in a retrospective multicenter Rare Cancer Network study. Median age was 60 years (range, 48−73). Fifteen patients were male, and 4 female. Risk factors, including perineural invasion, lymphangitis, vascular invasion, positive margins were present in the majority (83%) of the patients. Tumour sites included oral cavity in 4, oropharynx in 4, hypopharynx in 2, larynx in 2, salivary glands in 2, nasal vestibule in 2, maxillary sinus in 2, and nasopharynx in 1 patient. Surgery (S) was performed in all but 5 patients. S alone was performed in only 1 patient, and definitive RT alone in 3 patients. Fifteen patients received combined modality treatment (S+RT in 11, RT+CT in 2, and all of the three modalities in 2 patients). Median RT dose to the primary and to the nodes was 66 Gy (range, 50−72) and 53 Gy (range, 44−66), respectively (1.8−2.0 Gy/fr., 5 fr./week). In 4 patients, the planning treatment volume included the primary tumour site only. Eight patients were treated with 2D RT, 7 with 3D conformal RT, and 2 with intensity-modulated RT.Results: After a median follow-up period of 39 months (range, 9−62), 9 patients developed distant metastases (lung, bone, mediastinum, and liver), 7 presented nodal recurrences, and only 4 had a local relapse at the primary site (all in-field recurrences). At last follow-up, 7 patients were alive without disease, 1 alive with disease, 9 died from progressive disease, and 2 died from intercurrent disease. The 3-year and median overall survival, disease-free survival (DFS), and locoregional control rates were 55% (95% confidence interval [CI]: 32−78%) and 39 months, 34% (95% CI: 12−56%) and 22 months, and 50% (95% CI: 22−78%) and 33 months, respectively. In multivariate analysis (Cox model), DFS was negatively influenced by the presence of extracapsular extension (p = 0.01) and advanced stage (IV versus I−III, p = 0.002).Conclusions: Overall prognosis of locoregionally advanced AC remains poor, and distant metastases and nodal relapse occur in almost half of the cases. However, local control is relatively better, and early stage AC patients had prolonged DFS when treated with combined-modality treatment.

Adenosquamous carcinoma of the head and neck: report of 20 cases and review of the literature.

PURPOSE: To assess the clinical profile and prognostic factors in patients with adenosquamous carcinoma (ASC) of the head and neck treated by surgery and/or radiation therapy with or without chemotherapy. METHODS: Data from 20 patients with stage I-II (n = 4), III (n = 5), or IVA (n = 11) head and neck ASC, treated between 1989 and 2010 were collected in a retrospective multicenter Rare Cancer Network study. Surgery was performed in 16 patients. Seventeen patients received combined modality treatment. RESULTS: After a median follow-up of 15.5 months, 12 patients recurred. The 3-year and median overall survival, disease-free survival (DFS), and loco-regional control were 52% and 39 months, 32% and 12 months, and 47% and 33 months respectively. In multivariate analysis, DFS was negatively influenced by the presence of extracapsular extension and advanced stage. CONCLUSION: Overall prognosis of locoregionally advanced ASC remains poor. However, early stage ASC patients managed with combined modality treatment may have prolonged DFS.

Outcome and Prognostic Factors in Adenosquamous Carcinoma of the Head and Neck: A Multicenter Rare Cancer Network Study

Purpose/Objective(s): Adenosquamous carcinoma (AC) of the head and neck is a distinct entity first described in 1968. Its natural history is more aggressive than squamous cell carcinoma but this is based on very small series reported in the literature. The goal of this study was to assess the clinical profile, outcome, patterns of failure and prognostic factors in patients with AC of the head and neck treated by radiation therapy (RT) with or without chemotherapy (CT).Materials/Methods: Data from 18 patients with Stage I (n = 3), II (n = 1), III (n = 4), or IVa (n = 10) AC, treated between 1989 and 2009, were collected in a retrospective multicenter Rare Cancer Network study. Median age was 60 years (range, 48 - 73 years). Fourteen patients were male and 4 female. Risk factors, including perineural invasion, lymphangitis, vascular invasion, positive margins, were present in 83% of the patients. Tumor sites included oral cavity in 4, oropharynx in 4, hypopharynx in2, larynx in 2, salivary glands in 2, nasal vestibule in 2, nasopharynx in 1, and maxillary sinus in 1 patient. Surgery (S) was performed in all but 5 patients. S alone was performed in only 1 patient, and definitive RT alone in 3 patients. Fourteen patients received combined modality treatment (S+RT in 10, RT+CT in 2, and all of the three modalities in 2 patients). Median RT dose to the primary and to the nodes was 66 Gy (range, 50 - 72 Gy) and 53 Gy (range, 44 - 66 Gy), respectively (1.8 - 2.0 Gy/fr., 5 fr./ week). In 4 patients, the planning treatment volume included the primary tumor site only. Seven patients were treated with 2D RT, 7 with 3D conformal RT, and 2 with intensity-modulated RT.Results: After a median follow-up period of 38 months (range, 9 - 62 months), 8 patients developed distant metastases (lung, bone, mediastinum, and liver), 6 presented nodal recurrences, and only 4 had a local relapse at the primary site (all in-field recurrences). At last follow-up, 6 patients were alive without disease, 1 alive with disease, 9 died from progressive disease, and 2 died from intercurrent disease. The 3-year and median overall survival, disease-free survival (DFS) and locoregional control rates were 52% (95% confidence interval [CI]: 28 - 76%) and 39 months, 36% (95% CI: 13 - 49%) and 12 months, and 54% (95% CI: 26 - 82%) and 40 months, respectively. In multivariate analysis (Cox model), DFS was negatively influenced by the presence of extracapsular extension (p = 0.02) and advanced stage (IV versus I-III, p = 0.003).Conclusions: Overall prognosis of locoregionally advanced AC remains poor, and distant metastases and nodal relapse occur in almost half of the cases. However, local control is relatively good, and early stage AC patients had prolonged DFS when treated with combined modality treatment.

Adenosquamous carcinoma of the head and neck: report of 20 cases and review of the literature

PURPOSE To assess the clinical profile and prognostic factors in patients with adenosquamous carcinoma (ASC) of the head and neck treated by surgery and/or radiation therapy with or without chemotherapy. METHODS Data from 20 patients with stage I-II (n = 4), III (n = 5), or IVA (n = 11) head and neck ASC, treated between 1989 and 2010 were collected in a retrospective multicenter Rare Cancer Network study. Surgery was performed in 16 patients. Seventeen patients received combined modality treatment. RESULTS After a median follow-up of 15.5 months, 12 patients recurred. The 3-year and median overall survival, disease-free survival (DFS), and loco-regional control were 52% and 39 months, 32% and 12 months, and 47% and 33 months respectively. In multivariate analysis, DFS was negatively influenced by the presence of extracapsular extension and advanced stage. CONCLUSION Overall prognosis of locoregionally advanced ASC remains poor. However, early stage ASC patients managed with combined modality treatment may have prolonged DFS.

Molecular profiling of lung adenosquamous carcinoma: hybrid or genuine type?

Lung adenosquamous carcinoma is a particular subtype of non-small cell lung carcinoma that is defined by the coexistence of adenocarcinoma and squamous cell carcinoma components. The aim of this study was to assess the mutational profile in each component of 16 adenosquamous carcinoma samples from a Caucasian population by a combination of next generation sequencing using the cancer hotspot panel as well as the colon and lung cancer panel and FISH. Identified mutations were confirmed by Sanger sequencing of DNA from cancer cells of each component collected by Laser Capture microdissection. Mutations typical for adenocarcinoma as well as squamous cell carcinoma were identified. Driver mutations were predominantly in the trunk suggesting a monoclonal origin of adenosquamous carcinoma. Most remarkably, EGFR mutations and mutations in the PI3K signaling pathway, which accounted for 30% and 25% of tumors respectively, were more prevalent while KRAS mutations were less prevalent than expected for a Caucasian population. Surprisingly, expression of classifier miR-205 was intermediate between that of classical adenocarcinoma and squamous cell carcinoma suggesting that adenosquamous carcinoma is a transitional stage between these tumor types. The high prevalence of therapy-relevant targets opens new options of therapeutic intervention for adenosquamous carcinoma patients.

Adenosquamous carcinoma of the esophagogastric junction. Case report

Adenosquamous carcinoma is a rare tumor with coexisting elements of infiltrating squamous cell carcinoma and adenocarcinoma. This tumor is reported to arise in different organs but rarely in the oesophagus. In most cases, it shows highly aggressive biological behaviour with high propensity to regional lymph-node metastasis and poor prognosis. We describe the management of a patient with an aggressive adenosquamous carcinoma of the esophagogastric junction.

Carcinoma Adenoescamoso primário de fígado

Adenosquamous carcinoma of the liver is a rare type of hepatic tumor first described in 1975. It is characterized by both glandular and squamous compounds. We describe a case of adenosquamous carcinoma of the liver. It was discovered in a 42-yr-old female with a 2-month history of vomiting, weight loss (7 kg). A left hepatic lobectomy disclosed an 11 x 9 x 7,5 cm tumor located at I, II, III, IV segments. This tumor is rare entity and is a variant of cholangiocarcinoma whose etiology and prognostic are not well known.

Human papillomavirus prevalence among women with cervical intraepithelial neoplasia III and invasive cervical cancer from Goiânia, Brazil

This study estimated the prevalence and distribution of human papillomavirus (HPV) types among women with cervical intraepithelial neoplasia (CIN) grade III and invasive cervical cancer from Goiás (Brazil Central Region). Seventy-four cases were analyzed and consisted of 18 CIN III, 48 squamous cell carcinomas, 4 adenocarcinomas, 1 adenosquamous carcinoma and 3 undifferentiated carcinomas. HPV-DNA sequences were examined in formalin-fixed and paraffin-embedded tissues using primers from L1 region GP5+/GP6+. Polymerase chain reaction products were typed with dot blot hybridization using probes for HPV 16, 18, 31, 33, 45, 54, 6/11, 42/43/44, 51/52, 56/58. The prevalence of HPV was estimated to be 76% (56/74). HPV 16 was the most frequently found type, followed by HPV 33, 18 and 31. The prevalence of untyped HPV was 6%; 79% percent of the squamous cell carcinoma cases and 61% percent of the CIN III were positive for HPV and the prevalence rate of HPV types was the same for the total number of cases. According to other studies, HPV type 16 is the most prevalent virus in all Brazilian regions, but there is variation regarding to other types. Type 18 is the second most prevalent HPV in North, Southeast and South Brazil regions and types 31 and 33 are the second most prevalent HPV in Northeast and Central Brazil, respectively.

Endoscopic band ligation without resection in selected patients for small and superficial upper gastrointestinal tract lesions

Background and aim: The aim of this study was to evaluate the efficacy of endoscopic band ligation (EBL) in carefully selected patients who would benefit from this method of resection. Methods: Patients with early upper gastrointestinal and small (< 15 mm) lesions treated with EBL (Duette® Multi-Band Mucosectomy) were prospectively recruited and retrospectively analyzed between 2010 and 2015. All cases were discussed in a multidisciplinary cancer committee and it was concluded that, owing to patient conditions, surgery was not possible and that not conducting histology would not change the clinical management. A first endoscopic control with biopsies was planned at 4-8 weeks. If there was no persistence of the lesion, new controls were programmed at 6 and 12 months. Results: The group (n = 12) included 5 esophagus lesions (adenosquamous carcinoma, n = 1; carcinoma squamous, n = 2; adenocarcinoma, n = 2); 4 gastric lesions (high grade dysplasia, n = 1; adenocarcinoma, n = 2; neuroendocrine tumor [NET], n = 1), and 3 duodenal lesions (NETs) (n = 3). The mean tumor diameter was 9.6 ± 2.8 mm (range 4-15). Only one minor adverse event was described. At first follow-up (4-8 weeks), there was 91.6% and 75% of endoscopic and histological remission, respectively. At 6-month follow-up there was 70% of both endoscopic remission and negative biopsies. And at 12 months, there was 100% and 75% of endoscopic and histological remission, respectively. Persisting lesions were T1 cancers. The median follow-up was 30.6 months. Conclusion: EBL without resection is an easy and safe technique that should be considered in patients with multiple morbidities and small superficial UGI lesions.

Integrated Proteomics Identified Up-regulated Focal Adhesion-mediated Proteins In Human Squamous Cell Carcinoma In An Orthotopic Murine Model.

Understanding the molecular mechanisms of oral carcinogenesis will yield important advances in diagnostics, prognostics, effective treatment, and outcome of oral cancer. Hence, in this study we have investigated the proteomic and peptidomic profiles by combining an orthotopic murine model of oral squamous cell carcinoma (OSCC), mass spectrometry-based proteomics and biological network analysis. Our results indicated the up-regulation of proteins involved in actin cytoskeleton organization and cell-cell junction assembly events and their expression was validated in human OSCC tissues. In addition, the functional relevance of talin-1 in OSCC adhesion, migration and invasion was demonstrated. Taken together, this study identified specific processes deregulated in oral cancer and provided novel refined OSCC-targeting molecules.

Stathmin 1, A Therapeutic Target In Esophageal Carcinoma?

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Histologic Correlation Of Expression Of Ki-67 In Squamous Cell Carcinoma Of The Glottis According To The Degree Of Cell Differentiation.

Squamous cell carcinoma is the most common neoplasm of the larynx and glottis, and its prognosis depends on the size of the lesion, level of local invasion, cervical lymphatic spread, and presence of distant metastases. Ki-67 (MKI67) is a protein present in the core, whose function is related to cell proliferation. To evaluate the expression of marker Ki-67 in squamous cell carcinoma of the larynx and glottis and its correlation to pathological findings. Experimental study with immunohistochemistry analysis of Ki-67, calculating the percentage of the cell proliferation index in glottic squamous cell carcinomas. Sixteen cases were analyzed, with six well-differentiated and 10 poorly/moderately differentiated tumors. There was a correlation between cell proliferation index and degree of cell differentiation, with higher proliferation in poorly/moderately differentiated tumors. The cell proliferation index, as measured by Ki-67, may be useful in the characterization of histological degree in glottic squamous cell tumors.

Stromal Myofibroblasts In Squamous Cell Carcinoma Of The Tongue In Young Patients - A Multicenter Collaborative Study.

The purpose of this study was to evaluate the presence of myofibroblasts, frequently associated with a more aggressive neoplastic behavior, in oral tongue squamous cell carcinoma (TSCC) of young patients and to compare with the distribution observed in older patients. Tumor samples from 29 patients younger than 40 years old affected by TSCC were retrieved and investigated for the presence of stromal myofibroblasts by immunohistochemical reactions against α smooth muscle actin, and the results obtained were compared to TSCC cases affecting older patients. No positive reaction could be found in the stromal areas devoid of neoplastic tissue, whereas myofibroblasts were present in 58.6% of the lesions in young patients and in 75.9% of the older ones. No significant difference was found when comparing the invasive front and the overall stroma of both groups, and no correlation could be obtained with stromal α smooth muscle actin expression, higher tumor grades or clinical stage (P > .05). There was no significant difference between the presence of stromal myofibroblasts of TSCC affecting young and old individuals.

Intraductal Carcinoma Of The Prostate: Interobserver Reproducibility Survey Of 39 Urologic Pathologists.

The diagnosis of intraductal carcinoma (IDC) of the prostate remains subjective because 3 sets of diagnostic criteria are in use. An internet survey was compiled from 38 photomicrographs showing duct proliferations: 14 signed out as high-grade prostatic intraepithelial neoplasia (HGPIN), 17 IDC, and 7 invasive cribriform/ductal carcinoma. Each image was assessed for the presence of 9 histologic criteria ascribed to IDC. Thirty-nine respondents were asked to rate images as (1) benign/reactive, (2) HGPIN, (3) borderline between HGPIN and IDC, (4) IDC, or (5) invasive cribriform/ductal carcinoma. Intraclass correlation coefficient was 0.68. There was 70% overall agreement with HGPIN, 43% with IDC, and 73% with invasive carcinoma (P < .001, χ(2)). Respondents considered 19 (50%) of 38 cases as IDC candidates, of which 5 (26%) had a two-thirds consensus for IDC; two-thirds consensus for either borderline or IDC was reached in 9 (47%). Two-thirds consensus other than IDC was reached in the remaining 19 of 38 cases, with 15 supporting HGPIN and 4 supporting invasive carcinoma. Findings that differed across diagnostic categories were lumen-spanning neoplastic cells (P < .001), 2× benign duct diameters (P < .001), duct space contours (round, irregular, and branched) (P < .001), papillary growth (P = .048), dense cribriform or solid growth (both P = .023), and comedonecrosis (P = .015). When the 19 of 38 images that attained consensus for HGPIN or invasive carcinoma were removed from consideration, lack of IDC consensus was most often attributable to only loose cribriform growth (5/19), central nuclear maturation (5/19), or comedonecrosis (3/19). Of the 9 histologic criteria, only 1 retained significant correlation with a consensus diagnosis of IDC: the presence of solid areas (P = .038). One case that attained IDC consensus had less than 2× duct enlargement yet still had severe nuclear atypia and nucleomegaly. Six fold nuclear enlargement was not significant (P = .083), although no image had both 6× nuclei and papillary or loose cribriform growth: a combination postulated as sufficient criteria for IDC. Finally, 20.5% of respondents agreed that an isolated diagnosis of IDC on needle biopsy warrants definitive therapy, 20.5% disagreed, and 59.0% considered the decision to depend upon clinicopathologic variables. Although IDC diagnosis remains challenging, we propose these criteria: a lumen-spanning proliferation of neoplastic cells in preexisting ducts with a dense cribriform or partial solid growth pattern. Solid growth, in any part of the duct space, emerges as the most reproducible finding to rule in a diagnosis of IDC. Comedonecrosis is a rarer finding, but in most cases, it should rule in IDC. Duct space enlargement to greater than 2× the diameter of the largest, adjacent benign spaces is usually present in IDC, although there may be rare exceptions.

Clinicopathological And Immunohistochemical Evaluation Of Oral And Oropharyngeal Squamous Cell Carcinoma In Chilean Population.

In oral and oropharyngeal squamous cell carcinoma (OCSCC and OPSCC) exist an association between clinical and histopathological parameters with cell proliferation, basal lamina, connective tissue degradation and surrounding stroma markers. We evaluated these associations in Chilean patients. A convenience sample of 37 cases of OCSCC (n=16) and OPSCC (n=21) was analyzed clinically (TNM, clinical stage) and histologically (WHO grade of differentiation, pattern of tumor invasion). We assessed the expression of p53, Ki67, HOXA1, HOXB7, type IV collagen (ColIV) and carcinoma-associated fibroblast (α-SMA-positive cells). Additionally we conducted a univariate/bivariate analysis to assess the relationship of these variables with survival rates. Males were mostly affected (56.2% OCSCC, 76.2% OPSCC). Patients were mainly diagnosed at III/IV clinical stages (68.8% OCSCC, 90.5% OPSCC) with a predominantly infiltrative pattern invasion (62.9% OCSCC, 57.1% OPSCC). Significant association between regional lymph nodes (N) and clinical stage with OCSCC-HOXB7 expression (Chi-Square test P < 0.05) was observed. In OPSCC a statistically significant association exists between p53, Ki67 with gender (Chi-Square test P < 0.05). In OCSCC and OPSCC was statistically significant association between ki67 with HOXA1, HOXB7, and between these last two antigens (Pearson's Correlation test P < 0.05). Furthermore OPSCC-p53 showed significant correlation when it was compared with α-SMA (Kendall's Tau-c test P < 0.05). Only OCSCC-pattern invasion and OPSCC-primary tumor (T) pattern resulted associated with survival at the end of the follow up period (Chi-Square Likelihood Ratio, P < 0.05). Clinical, histological and immunohistochemical features are similar to seen in other countries. Cancer proliferation markers were associated strongly from each other. Our sample highlights prognostic value of T and pattern of invasion, but the conclusions may be limited and should be considered with caution (small sample). Many cases were diagnosed in the advanced stages of the disease, which suggests that the diagnosis of OCSCC and OPSCC is made late.