Solid Histologic Pattern Research Articles

Clinical outcomes in salivary adenoid cystic carcinoma.

6102 Background: Adenoid cystic carcinoma (ACC) is a rare salivary gland malignancy with a paucity of clinical outcome data. As such, evidence supporting and informing current guidelines remains limited. Methods: Inclusion criteria stipulated adults with adenoid cystic carcinoma treated at the University of Michigan between 1988 and 2019 with complete records (n=102). Clinical variables including demographics, disease stage, and treatment modality were abstracted. Pathologic variables analyzed included tumor grade, perineural invasion, lymphovascular invasion, and surgical margin status. Multivariate analyses were performed with disease recurrence calculated with Kaplan-Meier methodology as the primary outcome. Results: Mean age at diagnosis was 59 years; stage I and II disease accounted for 35 (38%) patients. Initial treatment was most commonly surgery with adjuvant radiation (77%). Median follow-up was 3 years. Distant metastatic disease developed in 34 (33%) patients. Most common sites included lung (68%), bone (21%), and brain (21%). Median time to distant metastases was 46 months with median overall survival of 58 months. Patients with locoregional recurrence experienced median survival of 91 months. Multivariate analysis adjusted for grade, perineural invasion, and surgical margin status (Table). Grade 3 tumors with predominantly solid histologic pattern pose higher risk of recurrence compared to grade 1 tubular histologic patterns as a reference (HR 3.69, 95% CI 1.15-11.88, p=0.028). Conclusions: Survival among patients with adenoid cystic carcinoma after locoregional recurrence is significantly better compared to those experiencing distant metastasis. Furthermore, tumor grade is most predictive of recurrence. Additionally, distant metastases may emerge over the course of many years. These data from one of the largest retrospective databases to date may inform the development of disease-specific surveillance guidelines and novel salvage treatment paradigms. [Table: see text]

Adenomatoid odontogenic tumor: A histopathologic profile of 43 cases with evidence supporting a mixed odontogenic origin

BackgroundAdenomatoid Odontogenic Tumor (AOT) accounts for 3% of all odontogenic tumors. It has been classified by WHO as an odontogenic tumor of purely epithelial origin. The current study attempts to establish the origin of the tumor along with detailed histopathological and clinicoradiographic analysis of 43 cases of AOT. Material and methodsForty-three cases were reviewed from the departmental archives for demographic data, radiographic features and histological features. Further, histopathological slides were stained with Picrosirius Red (PSR) and observed under polarised light. ResultsA majority of the cases were seen in the anterior jaws (76.7%), and were less than 3 cms (76.7%) in greatest dimension. Equal number of cases were of follicular and extra-follicular location while one was peripheral. Predominantly solid histological pattern was noted in 53.5%. Varied sub-patterns were observed with most cases exhibiting solid nodules and strands of tumor cells. Few cases showed melanin pigmentation. Over a third of cases (37.2%) showed dentigerous cyst like areas and one case each showed features of ossifying fibroma and focal cemento-osseous dysplasia. Tumor droplets, hyaline rings within duct-like structures, dentinoid material and osteodentin showed reddish yellow birefringence when observed under polarised microscopy post PSR staining. ConclusionThis study highlights the diverse histopathological variation of AOT with evidence to reclassify it as a mixed odontogenic tumor based on the polarising microscopic findings with PSR staining.

SPARC Is a Novel Positive Immunohistochemical Marker of Epithelioid Mesothelioma to Differentiate It From Lung Adenocarcinoma and/or Squamous Cell Carcinoma.

Epithelioid mesothelioma with a solid histologic pattern (solid epithelioid mesothelioma) is difficult to distinguish from a poorly differentiated squamous cell lung carcinoma and/or solid lung adenocarcinoma. Thus, immunohistochemical markers are essential for diagnosis; however, the sensitivity and specificity of pre-existing mesothelial markers are suboptimal, particularly for differentiation from squamous cell carcinoma. Using a cancer-dependency map, we analyzed gene expression data of pleural mesothelioma and non-small cell lung cancer cell lines (squamous cell carcinoma and adenocarcinoma) and identified secreted protein acidic and cysteine-rich (SPARC) as a promising candidate for the differential diagnosis of epithelioid mesothelioma from lung squamous cell carcinoma and/or lung adenocarcinoma. SPARC expression in mesothelioma and lung cancer cell lines was validated using reverse-transcription polymerase chain reaction, western blotting, and immunohistochemistry. Immunohistochemical staining was performed using anti-SPARC antibodies against solid epithelioid mesothelioma, solid lung adenocarcinoma, and poorly differentiated lung squamous cell carcinoma. SPARC positivity was seen in 42/45 (93.3%) of solid epithelioid mesothelioma, 2/40 (5%) solid lung adenocarcinoma, and 2/45 (4.5%) of lung squamous cell carcinomas. The sensitivity, specificity, and diagnostic accuracy for differentiating solid epithelioid mesothelioma from lung cancer (solid lung adenocarcinoma and poorly differentiated lung squamous cell carcinoma) were 93.3, 95.2, and 94.6%, respectively. In conclusion, SPARC is a novel mesothelial marker that can be used to differentiate epithelioid mesothelioma from squamous cell carcinoma and lung adenocarcinoma.

Comparison of 22C3-PD-L1 Expression Between Paired Tumor Paraffin Blocks of Surgical Resection Specimens of Nonsmall Cell Lung Cancer.

In this study, our aim was to evaluate the discordance of programmed cell death ligand 1 (PD-L1) expression between 2 paired paraffin blocks from surgical nonsmall cell lung cancer (NSCLC) specimens, thus providing recommendations for choosing paraffin blocks for PD-L1 immunohistochemistry detection. A total of 460 paired paraffin blocks of surgical NSCLC specimens were analyzed using the 22C3-PD-L1 assay. PD-L1 expression between 2 paired paraffin blocks was calculated using 3 classification schemes, tumor proportion score (TPS)-based 3-level classification and TPS-based binary classification using TPS ≥1% or TPS ≥50% as the cutoff. Clinicopathological characteristics were analyzed for cases with discordant PD-L1 expression. PD-L1 expression in 2 paired paraffin blocks of surgical NSCLC specimens was highly correlated from a single tumor ( R2 =0.89) in the overall trend. The overall discordance rates were 10.9%, 7.4%, and 3.5% respectively when using TPS-based 3-level classification or binary classification. No statistical differences were observed in PD-L1 expression discordance rates when patients were stratified by age, sex, smoking status, histologic types, TNM stage, or years of paraffin blocks ( P >0.05). The presence of a solid histologic pattern was associated with a higher PD-L1 expression discordance rate in adenocarcinomas ( P <0.05). Twenty-five cases with discordant PD-L1 expression were divided into 2 categories: spatial heterogeneity without recognizable morphology difference (76%) and spatial heterogeneity with significantly different morphology (24%). The discordance rate in TPS scores was much higher in cases with different morphology than those without different morphology. One representative paraffin block containing adequate neoplastic tissue may be adequate to determine PD-L1 expression in most of the surgical specimens of NSCLC. In cases that harbored different morphology in different paraffin blocks, the dual-block immunohistochemistry assessment method is recommended due to the intratumoral heterogeneity.

A Retrospective Study of Clinical and Histopathological Features of 81 Cases of Canine Apocrine Gland Adenocarcinoma of the Anal Sac: Independent Clinical and Histopathological Risk Factors Associated with Outcome.

Simple SummaryDogs can be affected by a tumour arising from the glands of the anal sacs. These tumours can grow aggressively and spread to other organs, resulting in disruption of bowel movements and/or organ function, ultimately leading to death or euthanasia. The reason why some tumours grow or spread more quickly is not well understood, and veterinarians are not able to distinguish between dogs likely to have better or worse survival times at the time of initial diagnosis. This study evaluates clinical, imaging, and tumour features of dogs with anal sac tumours and examines which features were linked to improved survival times. Smaller tumour size, smaller lymph node size, surgical removal, and treatment with radiotherapy were associated with better survival times. When examining the tumour tissue, the presence of closely packed tumour cells, dead tumour tissue, and invasion of vessels by tumour cells were each associated with worse survival times. Features that impacted survival were used to create two checklists that, when applied to an individual case, may indicate prognosis and therefore help clinicians and owners make more informed clinical decisions.Canine apocrine gland anal sac adenocarcinoma (AGASAC) is a malignant tumour with variable clinical progression. The objective of this study was to use robust multivariate models, based on models employed in human medical oncology, to establish clinical and histopathological risk factors of poor survival. Clinical data and imaging of 81 cases with AGASAC were reviewed. Tissue was available for histological review and immunohistochemistry in 49 cases. Tumour and lymph node size were determined using the response evaluation criteria in the solid tumours system (RECIST). Modelling revealed tumour size over 2 cm, lymph node size grouped in three tiers by the two thresholds 1.6 cm and 5 cm, surgical management, and radiotherapy were independent clinical variables associated with survival, irrespective of tumour stage. Tumour size over 1.3 cm and presence of distant metastasis were independent clinical variables associated with the first progression-free interval. The presence of the histopathological variables of tumour necrosis, a solid histological pattern, and vascular invasion in the primary tumour were independent risk factors of poor survival. Based upon these independent risk factors, scoring algorithms to predict survival in AGASAC patients are presented.

Vascular endothelial growth factor (VEGF) and hypoxia inducible factor-1 alpha (HIF-1ɑ) in lacrimal gland Adenoid cystic carcinoma: Correlation with clinical outcome

PurposeVEGF and HIF-1α are important regulators of angiogenesis, overexpressed in various tumors. Lacrimal gland Adenoid cystic carcinoma (ACC) is a malignant tumor whose angiogenic properties remain unexplored. This study was designed to evaluate the expression of HIF-1α and VEGF in lacrimal gland ACC. MethodsVEGF and HIF-1α immunoexpression was undertaken in 30 lacrimal gland ACC cases. mRNA expression of VEGF and HIF-1α was analysed in 17 cases by quantitative real time PCR. The results obtained were correlated with clinicopathological features and survival of the patients to determine the prognostic significance. ResultsImmunoexpression of HIF-1α and VEGF was seen in 36.6% and 46.6% ACC cases. HIF-1α expression showed significant association with advanced T-stage (P = 0.001) and VEGF with intracranial extension (P = 0.014) and solid histological pattern (P = 0.045). HIF-1α mRNA expression was seen in 29.4% cases and showed significant association with perineural invasion (P = 0.027). Recurrence occurred in 60%, distant metastasis in 20% and death in 20% cases. Survival analysis revealed that patients with HIF-1α, VEGF immunoexpression, solid histological pattern, perineural invasion, bone erosion, intracranial extension, metastasis, advanced T-stage, and exenteration had poor survival. On multivariate analysis VEGF immunoexpression (hazard ratio, 16.785; 95% confidence interval, 1.872–150.495; P = 0.012) was the most significant poor prognostic factor. ConclusionsThis study demonstrates that VEGF is a potential predictor for poor clinical outcome in lacrimal gland Adenoid cystic carcinoma.

Prognostic Value of Ki67 and Other Clinical and Histopathological Factors in Canine Apocrine Gland Anal Sac Adenocarcinoma.

Simple SummaryApocrine gland anal sac adenocarcinoma (AGASACA) is a locally aggressive tumor with a high metastatic rate to the regional ileo-sacral lymph nodes and later to distant sites. Clinical signs depend on the tumor and regional lymph nodes size or on the paraneoplastic hypercalcemia. Therefore, dogs are often referred for perineal swelling, tenesmus, constipation and/or polyuria, polydipsia. Surgical excision of both the neoplastic anal sac and the metastatic regional lymph nodes represents the standard of care. Adjuvant chemotherapy and/or radiotherapy are also indicated. Prognostic factors include tumor size, hypercalcemia, regional lymph nodes metastasis and tumor histologic features. The aim of the study was to retrospectively evaluate the prognostic significance of tumor Ki67 expression. The authors’ hypothesis was that higher Ki67 index correlated with decreased disease-free interval and overall survival time. Clinical data such as tumor size, regional lymph nodes metastasis and hypercalcemia at presentation and histological features such as tumor pattern, mitotic count, necrosis, inflammatory infiltration, vascular invasion, anisokaryosis, and anisocytosis were also investigated and correlated to the oncologic outcome in the dogs included in the study.Apocrine gland anal sac adenocarcinoma (AGASACA) is locally aggressive and highly metastatic to regional lymph nodes. The aim of this study was to evaluate the prognostic significance of Ki67 in surgically excised AGASACA. Prognostic impact of size, regional lymph nodes metastasis, hypercalcemia, histologic pattern, mitotic count, necrosis, inflammatory and lympho-vascular invasion, anisokaryosis and anisocytosis was also evaluated. Thirty-five dogs were included, twenty-four of which also had metastatic lymph nodes. When the entire population was evaluated, only metastatic disease spread to regional lymph nodes, and necrosis and inflammatory infiltration were correlated to prognosis. When only dogs with metastatic disease were evaluated, size, solid histologic pattern, presence of lymphatic and vascular invasion showed influence on prognosis. Ki67 index was not associated with survival time and disease free interval in any case. The results of this study showed that lymph nodes metastasis at diagnosis reduced disease free interval. Moreover, tumor size greater than 5.25 cm, presence of lymphatic and vascular invasion and a solid histologic pattern were associated with a shorter survival time in dogs with metastasis to regional lymph nodes. Ki67 expression was not significantly associated with prognosis, therefore it could not be considered as a prognostic factor in this tumor type, while the role of hypercalcemia remained unclear.

Prognostic impact of Notch1 receptor and clinicopathological High-Risk Predictors in lacrimal gland adenoid cystic carcinoma.

Adenoid Cystic Carcinoma (ACC) is an aggressive malignant lacrimal gland tumour associated with poor prognosis. Aberrant Notch signalling has been investigated in various tumours. However, very few studies on Notch signalling in lacrimal gland ACC are reported. The aim of the present study was to evaluate the status of Notch1 receptor and activated Notch1 (NICD1) in lacrimal gland ACC and to correlate it with high-risk clinicopathological features. A total of 23 cases of histopathologically proven lacrimal gland ACC, who underwent surgical treatment, were included in this study. Expression of Notch1 receptor and NICD1 was evaluated by immunohistochemistry on formalin fixed paraffin embedded tissues. The results obtained were correlated with clinicopathological high-risk features and survival of the patients. Kaplan-Meier survival and multivariate analysis was performed to determine the prognostic significance. Overexpression of Notch1 receptor and NICD1 was observed in 65% and 39% of lacrimal gland ACC cases, respectively. On Kaplan-Meier survival analysis, patients with Notch1 receptor overexpression had reduced disease free survival. On univariate analysis, male gender, bone erosion, perineural invasion, solid histologic pattern, intracranial extension and advanced tumour stage were also indicators of poor prognosis. On multivariate analysis bone erosion was the most significant poor prognostic indicator. Our study demonstrates that overexpression of Notch1 receptor plays a critical role in the biology and aggressive behaviour of lacrimal gland ACC. Bone erosion, solid histologic pattern, advanced T stage, perineural invasion and intracranial extension are other high-risk clinicopathological predictors of lacrimal gland ACC.

Prognostic importance of RUNX1 expression for head and neck adenoid cystic carcinoma.

In the present study, we aimed to investigate the prognostic value of RUNX1 expression in 76 patients with adenoid cystic carcinoma (ACC). All cases were arranged in tissue microarray blocks and submitted to immunohistochemistry against RUNX1. These results were statistically correlated with clinicopathologic features, including age, gender, tumour site, tumour size, lymph node status, AJCC clinical stage, distant metastasis, treatment, recurrences, follow-up, histologic pattern, vascular and neural invasion, all of which obtained from patient's medical records. RUNX1 was expressed in the nuclei of tumour cells, with a mean of 18.1% of positivity. Nuclear RUNX1 expression was significantly associated with AJCC clinical stage (p<.0001), solid histologic pattern (p<.0001), vascular invasion (p<.0001) and presence of local recurrence (p<.0001). Using univariate and multivariate analyses, RUNX1 nuclear expression was significantly associated with a lower disease-free survival (p<.0001 and p=.028, respectively) and disease-specific survival (p<.0001 and p=.018, respectively) rates. In summary, RUNX1 nuclear expression may represent an indicator of unfavourable outcome for patients affected by head and neck ACC.

Association with PD-L1 Expression and Clinicopathological Features in 1000 Lung Cancers: A Large Single-Institution Study of Surgically Resected Lung Cancers with a High Prevalence of EGFR Mutation.

Programmed cell death ligand 1 (PD-L1) expression is an important biomarker for predicting response to immunotherapy in clinical practice. Hence, identification and characterization of factors that predict high expression of PD-L1 in patients is critical. Various studies have reported the association of PD-L1 expression with driver genetic status in non-small cell cancer; however, the results have been conflicting and inconclusive. We analyzed the relationship between PD-L1 expression and clinicopathological factors including driver genetic alterations in 1000 resected lung cancers using a clinically validated PD-L1 immunohistochemical assay. PD-L1 expression was significantly higher in squamous cell carcinoma (SCC) compared to adenocarcinomas. PD-L1 expression in adenocarcinoma was associated with higher N-stage, solid histologic pattern, EGFR wild type, and ALK positive, but no significant association with the clinicopathological factors in SCC. EGFR mutant adenocarcinomas with distinctive clinicopathologic features, especially solid histologic pattern and higher stage showed higher PD-L1 expression. To the best of our knowledge, this study is the largest to evaluate the association between PD-L1 expression and clinicopathological and molecular features in lung cancer with a highly prevalent EGFR mutation. Therefore, our results are useful to guide the selection of lung cancer, even EGFR-mutated adenocarcinoma patients with PD-L1 expression, for further immunotherapy.

P2.09-008 Usefulness of Immunohistochemistry in the Differential Diagnosis of Epithelioid Mesothelioma and Lung Squamous Cell Carcinoma

The differential diagnosis between epithelioid mesothelioma (EM) showing a solid histological pattern (solid EM) and poorly differentiated squamous cell carcinoma (SCC) can be challenging with conventional light microscopy (haematoxylin and eosin-stained specimen) alone. The role of immunohistochemistry in distinguishing pleural EM from lung adenocarcinoma (LAC) has received much attention. Currently, many immunohistochemical markers are available for distinguishing pleural EM from LAC. . However, there are only a few reports on the immunohistochemical differential diagnosis of EM and lung SCC.

Cutaneous Angiosarcoma: Clinical and Pathology Study of 16 Cases

Background and objectivesPrimary cutaneous angiosarcoma is one of the most aggressive skin tumors and carries a very poor prognosis. Its initially indolent clinical presentation explains the frequently late diagnosis that, together with its typically multifocal pattern and poor delimitation, often makes surgery difficult. The low incidence of primary cutaneous angiosarcoma means that few large single-center series have been published. We review the clinical and pathologic characteristics of cutaneous angiosarcomas treated in our hospital, looking for prognostic factors and for possible diagnostic traits that could facilitate early diagnosis. Material and methodsThis was a retrospective observational study including all patients diagnosed with cutaneous angiosarcoma in Instituto Valenciano de Oncología in Valencia, Spain between January 2000 and December 2015. We recorded 16 clinical parameters, including age, sex, type of angiosarcoma, site, size, and time since diagnosis, and 8 histopathologic parameters. ResultsWe identified 16 patients (11 women and 5 men) with cutaneous angiosarcoma. Their mean age was 67 years (median, 71 years). The most common site was the trunk (10 cases), followed by the head and neck (5 cases). The mean size of the tumor was 10cm (median, 6.5cm). Fourteen patients underwent surgical excision. Six of the 16 patients were alive at the end of the study, after a mean follow-up period of 42.5 months. ConclusionsThe major determinants of survival among patients with cutaneous angiosarcoma are tumor size and patient age. Other characteristics associated with a poor prognosis were infiltration of deep planes (muscle), a predominantly solid histologic pattern, and a larger number of mitoses.

Angiosarcoma cutáneo: estudio clínico-patológico de 16 casos

Introduction and objectivesPrimary cutaneous angiosarcoma is one of the most aggressive skin tumors and carries a very poor prognosis. Its initially indolent clinical presentation explains the frequently late diagnosis that, together with its typically multifocal pattern and poor delimitation, often makes surgery difficult. The low incidence of primary cutaneous angiosarcoma means that few large single-center series have been published. We review the clinical and pathologic characteristics of cutaneous angiosarcomas treated in our hospital, looking for prognostic factors and for possible diagnostic traits that could facilitate early diagnosis. Material and methodsThis was a retrospective observational study including all patients diagnosed with cutaneous angiosarcoma in Instituto Valenciano de Oncología in Valencia, Spain between January 2000 and December 2015. We recorded 16 clinical parameters, including age, sex, type of angiosarcoma, site, size, and time since diagnosis, and 8 histopathologic parameters. ResultsWe identified 16 patients (11 women and 5 men) with cutaneous angiosarcoma. Their mean age was 67 years (median, 71 years). The most common site was the trunk (10 cases), followed by the head and neck (5 cases). The mean size of the tumor was 10cm (median, 6.5cm). Fourteen patients underwent surgical excision. Six of the 16 patients were alive at the end of the study, after a mean follow-up period of 42.5 months. ConclusionsThe major determinants of survival among patients with cutaneous angiosarcoma are tumor size and patient age. Other characteristics associated with a poor prognosis were infiltration of deep planes (muscle), a predominantly solid histologic pattern, and a larger number of mitoses.

P2.01-063 PDL1, JAK2 and PTEN Copy Number Alterations Synergistically Upregulate PD-L1 Expression in NSCLC

Predictive biomarkers research in anti-PD-1/PD-L1 immunotherapy treatment is still at an early stage of development. Recently, amplification of PDL1 gene (9p24.1) has been described in NSCLC in correlation with PD-L1 protein expression. In addition, other tumor-constitutive alterations such as JAK2 amplifications (322kb upstream of PDL1) or PTEN deletions are also known to modulate PD-L1 expression. We aimed to determine PDL1, JAK2 and PTEN copy number alterations (CNAs) and subsequent PD-L1 protein expression in NSCLC. A total of 171 NSCLC patients (121 ADC and 50 SCC) were included. Clinical, histopathological and molecular data were collected. In resected early-stage diseases, two distinct histologic areas from FFPE tumoral tissue were included for each patient in 8 tissue microarrays (TMAs). PD-L1 expression analysis was assessed by IHC using PD-L1 #SP142 clone (Ventana) and positive cut off was defined at >1%. Moreover, H-score semi-quantitative approach was used to generate a score from 0 to 300. PDL1, JAK2 and PTEN CNAs were studied by FISH using commercial and non-commercial probes hybridized with respective centromere enumeration probes. Amplifications were defined as mean gene by mean centromere ratio ≥2.0, deletions as mean gene by mean centromere ratio ≤0.8, gains as mean gene ≥2.5, and high gains as mean gene ≥4.0. PD-L1 expression was positive in 40 out of 171 cases (23.3%), with an average H-score of 177 and significantly associated with ADC solid histological pattern (p=0.012), KRAS mutations (p=0.001), the presence of TILs (p=0.001), and active smoking status (p=0.031). PDL1 gene CNAs were seen in 68/159 assessable cases (42.8%). We found 14 tumors with PDL1 amplification (8.8%), 21 PDL1 high gains (13%) and 33 PDL1 gains (20.8%). Twelve out of 14 FISH amplified cases had PD-L1 positive expression. Thus, FISH predicted positive PD-L1 IHC result with a low sensitivity (31.6%) but a high specificity (98.6%). Among PD-L1 expressing tumors (n=40), seven cases had JAK2 amplifications (6 of them with PDL1 gene coamplification) and eight showed PTEN deletions (3 of them were PDL1 amplified). Differences in H-score intensity between these groups were observed: JAK2-PDL1 coamplified cases had near 2-fold increase in PD-L1 expression than PDL1 alone (average H-score: 282 vs. 148). PDL1 gene amplification is synergistically regulating PD-L1 protein expression. In addition, JAK2 amplification upregulates PD-L1 expression, following the concept of cooperative oncogenic effects of genes within the PDJ amplicon. PDL1, JAK2 and PTEN CNAs analysis may be relevant for anti-PD-1/PD-L1 patient selection.

Pulmonary adenocarcinoma with signet ring features: Detailed cytomorphologic analysis.

Signet ring cell feature in lung adenocarcinoma is no longer considered a distinct subtype, but as a cytologic change that may occur in association with multiple histological patterns. Cases with signet ring cells show a strong association with Anaplastic Lymphoma Kinase (ALK) gene fusions and solid pattern. The cytomorphological findings of pulmonary adenocarcinoma with signet ring features (PASRF) was studied. Cases of pulmonary adenocarcinoma which showed presence of signet ring cells either on cytology or histology were included in the study. Out of 218 pulmonary adenocarcinomas diagnosed during the study period, 11 cases showed presence of signet ring cells (11/218). Out of the 11 cases, 7 had paired histology and cytology available, while the remaining 4 did not have a corresponding cytology sample. Majority of the cases (6/11) showed signet ring cells in more than 90% of the tumor area. All cases showed solid growth pattern. TTF-1 was positive in all the cases. Immunopositivity for ALK was seen in seven cases. The cytology smears showed single cells and clusters of signet ring cells, with either intracytoplasmic mucin vacuole and eccentric nucleus or histiocyte-like finely vacuolated cytoplasm with round nucleus and prominent nucleoli, the latter resembling alveolar macrophages. PASRF is commonly associated with a solid histologic pattern. Cases with predominant histiocyte-like pattern may be misdiagnosed on cytology; hence a high index of suspicion is required for an accurate diagnosis. Diagn. Cytopathol. 2016;44:607-611. © 2016 Wiley Periodicals, Inc.

Expression of SKA1 and MMP–9 in primary salivary adenoid cystic carcinoma: Correlation with tumor progression and patient prognosis

ABSTRACTConclusion The spindle and kinetochore-associated complex sub unit 1(SKA1) and matrix metalloproteinase-9 (MMP-9) are highly expressed in salivary adenoid cystic carcinoma (SACC), and SKA1 may be the novel, promising prognostic factor for clinical outcomes in head and neck adenoid cystic carcinoma patients. Objectives This study aimed to investigate the expression of SKA1 and MMP-9 in SACC tissues and the clinical significance. Methods SKA1 and MMP-9 expression in samples from 42 cases of SACC and 20 subjects with the normal tissue adjacent to carcinoma were detected by immunohistochemical analysis. Results The positive rate of SKA1 and MMP-9 staining was 78.6% and 66.7% in SACC, respectively, significantly higher than in normal salivary gland tissues (p < 0.001). Chi-square test showed that there was no significant correlation between SKA1 expression and MMP-9 expression in SACC tissues. However, SKA1 and MMP-9 expression was positively associated with advanced stage and solid histological pattern of SACC (p < 0.05). In addition, SKA1 and MMP-9 expression was positively associated with recurrence and perineural invasion, and survival time, respectively.

Hemangiosarcoma in a Free-living Rufous-bellied Thrush (Turdus rufiventris)

Background: Hemangiosarcoma is a malignant endothelial cell-derived neoplasm characterized by an intense cellular proliferation organized in a solid or cavernous pattern. Is characterized by intense cell proliferation, and organized in vascular slits, filled with blood, with fast grow and there is a high recurrence rate. This paper reports a case of multiple hemangiosarcoma in a Rufous-bellied Thrush (Turdus rufiventris).Case: A free-living Rufous-bellied Thrush (Turdus rufiventris), was attended at the veterinary hospital of the Federal University of Mato Grosso (UFMT) - Cuiabá, presenting prostration and three masses located in the following regions: left periorbital area, left lateral insertion of the beak and distal portion of the left tibia. The masses were blackened colored with an irregular aspect, and the cut surface was multiple cavity, filled with a blackened gelatinous material. The animal died during the surgical procedure and was sent to necropsy. Additionally, special immunohistochemistry staining was used in the tumors sections, with primary anti-S-100, anti-Von Willebrand Factor, anti-desmin, anti-actin, anti-cytokeratin and anti-vimentin. The three masses have rounded shape, multilobuled surface, deep red to blackened color, with skin adhered base, and, when cut, blackened color with multiple cavities filled with red to blackened gelatinous material and compressing the adjacent structures. Microscopically was observed a pronounced multifocal proliferation of the neoplastic endothelial cells, which are organized forming vessels with single cell layer and filled with red blood cells, giving a cavernous aspect to the section. Around these vessels were neoplastic areas with a more solid pattern with cells with elongated nuclei. The masses were partially surrounded by fibrous connective tissue, forming a pseudo capsule. In the immunohistochemical test, a strong positivity for the anti-actin antibody was founded, moderate positivity for anti-desmin, and weak positivity for anti-S-100 and anti- Von Willebrand. The test with anti-vimentin and for cytokeratin antibody was negative.Discussion: The clinical status of this bird was followed for seven days, but because is a free-living animal there are not much information about the clinical course of the neoplasm. Is known that it’s common that animals affected by the hem­angiosarcoma have an acute clinical course or asymptomatic, culminating in death, usually associated with hypovolemic shock. The three neoplasms gross aspect described here are compatible with hemangiosarcoma. The masses location were not uncommon although there is a predominance in the intra-coelomic area. In microscopic analysis of the three neoplasm, two histological patterns were observed, both with high cellularity: the cavernous pattern, with exuberant proliferation of blood vessels, and the solid pattern, with few vascular formations. The occurrence of both histological patterns is not uncommon, but the cavernous form being the most frequent. The diagnosis confirmation of hemangiosarcoma was performed by immunohistochemical. The Von Willebrand has low reactivity in avian tissue, as well as the desmin, both with an average to low positivity in this case. The anti-vimentin negative marking in this case generally is observed when the hemangiosarcoma has a more solid histological pattern. The anti-actin antibody is positive for the smooth muscle of the blood vessels, and the anti-S-100 mark nervous tissue, however, although both positive, there are no reports about the specificity of this antibodies to birds tissue. In the author’s knowledge, this is the first neoplasm report in a Turdus rufiventris (Rufous-bellied Thrush).Keywords: bird, tumors, tumor sanguine vessel, wild animals.

COPD-related adenocarcinoma presents low aggressiveness morphological and molecular features compared to smoker tumours

ObjectivesAdenocarcinoma comprises a group of diseases with heterogeneous clinical and molecular characteristics.COPD and lung cancer are strictly related; to date it is unknown if COPD-associated cancers have different features from tumours arising in non-COPD patients.Our aim was to study COPD-associated adenocarcinoma phenotypes mainly focusing on morphological and molecular aspects, in comparison to smoke-related cancer without COPD. Materials and methodsFrom 2010 to 2013, 54 patients with adenocarcinoma (20 COPD and 34 smokers) were prospectively studied. Each patient underwent a complete clinical and instrumental assessment.Morphological studies included analysis of growth pattern, cell proliferation (Ki-67/MIB1 expression) and parameters of intra- and peri-tumoral remodelling (inflammation, fibrosis and necrosis). Genetic analysis of EGFR and KRAS mutations was also performed. ResultsThe two groups were comparable for the main demographic and biohumoral parameters except for increased blood basophil cell count in the COPD group.Compared to COPD, tumours of smokers presented an increased percentage of solid component (median: 20% vs 5%, p=0.02), a reduced percentage of lepidic pattern (median: 0% vs 10%, p=0.06) and higher Ki-67/MIB1 median value (55% vs 30%, p=0.02).In multivariate analysis lepidic and solid histological pattern were significantly influenced by clinical group (p=0.03 and 0.05, respectively).Concerning EGFR mutation, no differences were found between groups while KRAS mutation presented a trend of higher percentage in smokers compared to COPD (41% vs 20%, p=NS).Adenocarcinoma with KRAS mutation showed a higher value of Ki-67/MIB1 (65% vs 35%, p=0.048) and prevalent solid pattern (35% vs 10%, p=0.019) in comparison to wild-type form. ConclusionsCOPD-related adenocarcinoma presents molecular and morphological features of lower aggressiveness (increased lepidic component, reduced solid pattern, lower cell proliferation and less frequent KRAS mutation) compared to smokers. Different molecular mechanisms could be associated with the development of COPD associated cancer.

193P - Heterogeneity of Met Assessed By Immunohistochemistry (Ihc) and Fluorescence-In-Situ Hybridization (Fish) in Nonsquamous Non-Small Cell Lung Cancer (Nsnsclc)

ABSTRACT Aim: Disappointing results have been observed in advanced NSCLC patients receiving MET inhibitors based on histological or immunohistochemical criteria. The aim of this study was to assess the impact of MET intratumor heterogeneity on MET evaluation and potentially on adequate selection of nsNSCLC patients for clinical trials. Methods: Samples were obtained from a cohort of 120 patients. Of these, 47 were incorporated in a tissue microarray (TMA), selecting 4 histologically distinct areas of the tumor for heterogeneity studies. Assessment of Met expression was performed by IHC (SP44 Ventana) using H-score and MetMab criteria. FISH was used to assess gene copy number (GCN) (MET and CEP7 probes from Vysis). Using different scoring methods, correlation with clinico-pathologic and molecular features (KRAS, EGFR) and between Met expression and GCN was investigated. Heterogeneity of Met status between different tumor cores was examined. Results: Seventy percent of the patients were male and 55% were current smokers. Median age was 66 years and 36% were stage IV nsNSCLC. Of 127 samples, 90% were adenocarcinomas. Nineteen per cent and 11% harbored KRAS and EGFR mutations, respectively. Forty-eight per cent were MET-High according to MetMab criteria, and median H-score was 140 (range 0-400). Increased Met expression was associated with advanced stage (p = 0.001) and with former or no smoking history (p = 0.038). Mean MET GCN was 2.8 and 9 cases were considered FISH-positive (GCN > =5). Increased MET GCN was associated with solid histological pattern. Met H-score was directly associated with GCN (p = 0.036). Intra-class correlation coefficient between 4 tissue cores was 0.57, both for Met H-score and GCN. In three patients considered FISH-positive, 4 out of 12 cores were FISH-negative. Conclusions: Classification of Met-driven tumors is challenging due to lack of robustness of methods and criteria for defining Met positivity. MET heterogeneity may hinder adequate patient selection for clinical trials with MET inhibitors. Disclosure: All authors have declared no conflicts of interest.

Clinicopathological Significance of L-type Amino Acid Transporter 1 (LAT1) Expression in Patients with Adenoid Cystic Carcinoma

The expression of L-type amino acid transporter 1 (LAT1) is correlated with tumor cell growth and survival. However, the clinicopathological significance of LAT1 expression in adenoid cystic carcinoma (ACC) remains to be elucidated. The aim of this study is to investigate the clinicopathological significance of LAT1 expression in ACC. A total of 30 patients with ACC were retrospectively reviewed. Tumor sections were stained by immunohistochemistry for LAT1, p53, and CD98, and cell proliferation and microvessel density (MVD) were determined by Ki-67 and CD34, respectively. High LAT1 and CD98 expression were observed in 27 % (8/30) and 23 % (7/30) of samples, respectively (p > 0.999). The high expression of LAT1 was significantly correlated with cell proliferation (Ki-67) and the cell cycle regulator p53. By univariate analysis, solid histological pattern, maxillary tumor site, LAT1, CD98, Ki-67 and p53 were significantly associated with poor prognosis. Multivariate analysis demonstrated that the high expression of LAT1 was an independent prognostic factor for predicting poor prognosis after surgical resection. LAT1 is a promising clinical marker to predict the outcome after surgery in patients with ACC.