P16 and HPV status in head and neck sarcomas and sarcomatoid carcinomas.

Human papillomavirus (HPV)-positive oropharyngeal carcinoma is a distinct type of head and neck carcinoma with improved prognosis. p16 immunostaining is often used as a surrogate marker for HPV infection in this particular setting. The aim of this study is to estimate the prevalence of p16 staining and HPV infection in head and neck sarcomatoid carcinomas as well as head and neck sarcomas. 21 sarcomatoid carcinomas and 28 head and neck sarcomas were tested for p16 positivity using immunohistochemical staining, and for high-risk HPV infection using In situ hybridization (ISH). 24 % of sarcomatoid carcinomas and 21 % of sarcomas were positive for p16 staining. All 49 cases were negative for HPV ISH. The results confirm that p16 staining is not specific and may not be associated with HPV infection in non-oropharyngeal head and neck sites. They also indicate that non-oropharyngeal head and neck sarcomatoid carcinomas are not likely to be HPV related.

Utility of artificial intelligence in a binary classification of soft tissue tumors.

Soft tissue tumors (STTs) pose diagnostic and therapeutic challenges due to their rarity, complexity, and morphological overlap. Accurate differentiation between benign and malignant STTs is important to set treatment directions, however, this task can be difficult. The integration of machine learning and artificial intelligence (AI) models can potentially be helpful in classifying these tumors. The aim of this study was to investigate AI and machine learning tools in the classification of STT into benign and malignant categories. This study consisted of three components: (1) Evaluation of whole-slide images (WSIs) to classify STT into benign and malignant entities. Five specialized soft tissue pathologists from different medical centers independently reviewed 100 WSIs, representing 100 different cases, with limited clinical information and no additional workup. The results showed an overall concordance rate of 70.4% compared to the reference diagnosis. (2) Identification of cell-specific parameters that can distinguish benign and malignant STT. Using an image analysis software (QuPath) and a cohort of 95 cases, several cell-specific parameters were found to be statistically significant, most notably cell count, nucleus/cell area ratio, nucleus hematoxylin density mean, and cell max caliper. (3) Evaluation of machine learning library (Scikit-learn) in differentiating benign and malignant STTs. A total of 195 STT cases (156 cases in the training group and 39 cases in the validation group) achieved approximately 70% sensitivity and specificity, and an AUC of 0.68. Our limited study suggests that the use of WSI and AI in soft tissue pathology has the potential to enhance diagnostic accuracy and identify parameters that can differentiate between benign and malignant STTs. We envision the integration of AI as a supportive tool to augment the pathologists' diagnostic capabilities.

Endogenous Pancreatic Cancer Cell PD-1 Activates MET and Induces Epithelial-Mesenchymal Transition to Promote Cancer Progression.

We recently demonstrated that immune checkpoint PD-1 was endogenously expressed in pancreatic ductal adenocarcinoma (PDAC) cells. Our data indicated that PD-1 proteins are not exclusive to immune cells and have unrecognized signal transduction cascades intrinsic to cancer cells. Building on this paradigm shift, we sought to further characterize PD-1 expression in PDAC. We utilized a phospho-explorer array to identify pathways upregulated by PD-1 signaling. We discovered PD-1-mediated activation of the proto-oncogene MET in PDAC cells, which was dependent on hepatocyte growth factor (MET ligand) and not secondary to direct protein interaction. We then discovered that the PD-1/MET axis in PDAC cells regulated growth, migration, and invasion. Importantly, the PD-1/MET axis induced epithelial-to-mesenchymal transition (EMT), a well-established early oncogenic process in PDAC. We observed that combined targeting of PDAC cell PD-1 and MET resulted in substantial direct tumor cell cytotoxicity and growth inhibition in PDAC cell lines, patient-derived organoids, and patient-derived xenografts independent of cytotoxic immune responses. This is the first report of PDAC-endogenous PD-1 expression regulating MET signaling, which builds upon our growing body of work showing the oncogenic phenotype of PD-1 expression in PDAC cells is distinct from its immunogenic role. These results highlight a paradigm shift that the tumor-specific PD-1 axis is a novel target to effectively kill PDAC cells by antagonizing previously unrecognized PD-1-dependent oncogenic pathways.

Xantho-granulomatous mastitis preceded by cysts on ultrasound: Two cases with review of literature.

Xantho-granulomatous mastitis (XGM) is a rare entity, only recently described in 2005. These lesions are often biopsied due to their clinical and radiological resemblance to breast cancer. With limited clinical experience, the etiopathogenesis and natural history of XGM remains unknown. We present two cases of pathologically proven XGM that were imaged at two time-points, with the findings alluding to the possibility of a precursor stage of cyst formation. In addition, we present a thorough review of all cases published to date and discuss the differential considerations and management implications of XGM.

Development of a Single-Cell Technique to Increase Yield and Use of Gastrointestinal Cancer Organoids for Personalized Medicine Application.

BACKGROUND: Organoids are excellent 3-dimensional in vitro models of gastrointestinal cancers. However, patient-derived organoids (PDOs) remain inconsistent and unreliable for rapid actionable drug sensitivity testing due to size variation and limited material. STUDY DESIGN: On day10/passage 2 after standard creation of organoids, half of PDOs were dissociated into single-cells with TrypLE Express Enzyme/DNase I and mechanical dissociation; and half of PDOs were expanded by the standard technique. Hematoxylin and eosin and immunohistochemistry with CK7 and CK20 were performed for characterization. Drug sensitivity testing was completed for single-cells and paired standard PDOs to assess reproducibility. RESULTS: After 2 to 3 days, >50% of single-cells reformed uniform miniature PDOs (∼50 µm). We developed 10 PDO single-cell lines (n = 4, gastric cancer, [GC]; and n = 6, pancreatic ductal adenocarcinoma, [PDAC]), which formed epithelialized cystic structures and by IHC, exhibited CK7(high)/CK20(low) expression patterns mirroring parent tissues. Compared with paired standard PDOs, single-cells (n = 2, PDAC; = 2, GC) showed similar architecture, albeit smaller and more uniform. Importantly, single cells demonstrated similar sensitivity to cytotoxic drugs to matched PDOs. CONCLUSIONS: PDO single-cells are accurate for rapid clinical drug testing in gastrointestinal cancers. Using early passage PDO single-cells facilitates high-volume drug testing, decreasing time from tumor sampling to actionable clinical decisions, and provides a personalized medicine platform to optimally select drugs for gastrointestinal cancer patients.

In Situ Bioprinting of Autologous Skin Cells Accelerates Wound Healing of Extensive Excisional Full-Thickness Wounds.

The early treatment and rapid closure of acute or chronic wounds is essential for normal healing and prevention of hypertrophic scarring. The use of split thickness autografts is often limited by the availability of a suitable area of healthy donor skin to harvest. Cellular and non-cellular biological skin-equivalents are commonly used as an alternative treatment option for these patients, however these treatments usually involve multiple surgical procedures and associated with high costs of production and repeated wound treatment. Here we describe a novel design and a proof-of-concept validation of a mobile skin bioprinting system that provides rapid on-site management of extensive wounds. Integrated imaging technology facilitated the precise delivery of either autologous or allogeneic dermal fibroblasts and epidermal keratinocytes directly into an injured area, replicating the layered skin structure. Excisional wounds bioprinted with layered autologous dermal fibroblasts and epidermal keratinocytes in a hydrogel carrier showed rapid wound closure, reduced contraction and accelerated re-epithelialization. These regenerated tissues had a dermal structure and composition similar to healthy skin, with extensive collagen deposition arranged in large, organized fibers, extensive mature vascular formation and proliferating keratinocytes.

Differentiating Intrarenal Ectopic Adrenal Tissue From Renal Cell Carcinoma in the Kidney.

BACKGROUND: Adrenal rest (AR) is the presence of ectopic adrenal cortical tissue, often identified incidentally during autopsy (20% of postmortem examination). In the kidney, AR can be found in 6% of the general population. Ectopic adrenal tissue is of no functional significance but may in some cases, pose a diagnostic challenge for the pathologist, especially in the context of renal clear cell renal cell carcinoma (RCC) and small needle biopsies. AIM: To investigate the utility of immunohistochemical stains in distinguishing AR from RCC. METHODS: Archival cases of AR, in our institution, were reviewed and compared with a cohort of RCC cases using a panel of immunohistochemical stains, including PAX2, PAX8, calretinin, and inhibin. RESULTS: Nine of 10 (90%) cases of AR showed positive staining for inhibin and negative staining for calretinin, PAX2 and PAX8. One AR case was positive for PAX2 and PAX8 in addition to inhibin. All (100%) RCC cases were positive for PAX2 and PAX8, but negative for inhibin and calretinin. CONCLUSIONS: A panel of PAX2, PAX8 and inhibin may be useful markers for distinguishing AR from RCC. Calretinin was noncontributory in our study.

Routine Hematoxylin and Eosin Stain Is Specific for the Diagnosis of Cytomegalovirus Infection in Gastrointestinal Biopsy Specimens.

BACKGROUND: Gastrointestinal cytomegalovirus (CMV) infection is a serious complication in immunocompromised patients; clinicians often expect expedited results for biopsy specimens. Our goal is to determine the accuracy of identification of CMV on hematoxylin and eosin (H&E) stain. METHODS AND RESULTS: A total of 361 biopsy specimens from 273 patients with suspicion for CMV infection were retrieved. CMV was detected by immunohistochemistry (IHC) in 37 specimens acquired from 33 individual patients (average age = 54 years). Among the CMV-positive patients, 29 (88%) were reported to be immunosuppressed. Colon was the most common affected location. Of 37 CMV-positive specimens by IHC, 28 were positive by H&E (76%), 6 were negative (16%), and 3 were suspicious (8%). Of the 29 positive specimens on H&E, 28 were confirmed by IHC (97%) and 1 was indeterminate (3%). The sensitivity and specificity of H&E were 84% and 94%, respectively; the positive predictive value was 97%, and the negative predictive value was 93% ( P < .00001). CONCLUSION: Our results show that a preliminary diagnosis of CMV infection, based on H&E stains, can be reported with high specificity and low risk for false-positive results. Suspicious cases should be deferred pending the result of IHC stains.

Mutational Landscapes of Smoking-Related Cancers in Caucasians and African Americans: Precision Oncology Perspectives at Wake Forest Baptist Comprehensive Cancer Center.

Background: Cancers related to tobacco use and African-American ancestry are under-characterized by genomics. This gap in precision oncology research represents a major challenge in the health disparities in the United States. Methods: The Precision Oncology trial at the Wake Forest Baptist Comprehensive Cancer Center enrolled 431 cancer patients from March 2015 to May 2016. The composition of these patients consists of a high representation of tobacco-related cancers (e.g., lung, colorectal, and bladder) and African-American ancestry (13.5%). Tumors were sequenced to identify mutations to gain insight into genetic alterations associated with smoking and/or African-American ancestry. Results: Tobacco-related cancers exhibit a high mutational load. These tumors are characterized by high-frequency mutations in TP53, DNA damage repair genes (BRCA2 and ATM), and chromatin remodeling genes (the lysine methyltransferases KMT2D or MLL2, and KMT2C or MLL3). These tobacco-related cancers also exhibit augmented tumor heterogeneities. Smoking related genetic mutations were validated by The Cancer Genome Atlas dataset that includes 2,821 cases with known smoking status. The Wake Forest and The Cancer Genome Atlas cohorts (431 and 7,991 cases, respectively) revealed a significantly increased mutation rate in the TP53 gene in the African-American subgroup studied. Both cohorts also revealed 5 genes (e.g. CDK8) significantly amplified in the African-American population. Conclusions: These results provide strong evidence that tobacco is a major cause of genomic instability and heterogeneity in cancer. TP53 mutations and key oncogene amplifications emerge as key factors contributing to cancer outcome disparities among different racial/ethnic groups.

Circulating mutational portrait of cancer: manifestation of aggressive clonal events in both early and late stages.

BACKGROUND: Solid tumors residing in tissues and organs leave footprints in circulation through circulating tumor cells (CTCs) and circulating tumor DNAs (ctDNA). Characterization of the ctDNA portraits and comparison with tumor DNA mutational portraits may reveal clinically actionable information on solid tumors that is traditionally achieved through more invasive approaches. METHODS: We isolated ctDNAs from plasma of patients of 103 lung cancer and 74 other solid tumors of different tissue origins. Deep sequencing using the Guardant360 test was performed to identify mutations in 73 clinically actionable genes, and the results were associated with clinical characteristics of the patient. The mutation profiles of 37 lung cancer cases with paired ctDNA and tumor genomic DNA sequencing were used to evaluate clonal representation of tumor in circulation. Five lung cancer cases with longitudinal ctDNA sampling were monitored for cancer progression or response to treatments. RESULTS: Mutations in TP53, EGFR, and KRAS genes are most prevalent in our cohort. Mutation rates of ctDNA are similar in early (I and II) and late stage (III and IV) cancers. Mutation in DNA repair genes BRCA1, BRCA2, and ATM are found in 18.1% (32/177) of cases. Patients with higher mutation rates had significantly higher mortality rates. Lung cancer of never smokers exhibited significantly higher ctDNA mutation rates as well as higher EGFR and ERBB2 mutations than ever smokers. Comparative analysis of ctDNA and tumor DNA mutation data from the same patients showed that key driver mutations could be detected in plasma even when they were present at a minor clonal population in the tumor. Mutations of key genes found in the tumor tissue could remain in circulation even after frontline radiotherapy and chemotherapy suggesting these mutations represented resistance mechanisms. Longitudinal sampling of five lung cancer cases showed distinct changes in ctDNA mutation portraits that are consistent with cancer progression or response to EGFR drug treatment. CONCLUSIONS: This study demonstrates that ctDNA mutation rates in the key tumor-associated genes are clinical parameters relevant to smoking status and mortality. Mutations in ctDNA may serve as an early detection tool for cancer. This study quantitatively confirms the hypothesis that ctDNAs in circulation is the result of dissemination of aggressive tumor clones and survival of resistant clones. This study supports the use of ctDNA profiling as a less-invasive approach to monitor cancer progression and selection of appropriate drugs during cancer evolution.

Activation of the c-Met Pathway Mobilizes an Inflammatory Network in the Brain Microenvironment to Promote Brain Metastasis of Breast Cancer.

Brain metastasis is one of the chief causes of mortality in breast cancer patients, but the mechanisms that drive this process remain poorly understood. Here, we report that brain metastatic cells expressing high levels of c-Met promote the metastatic process via inflammatory cytokine upregulation and vascular reprogramming. Activated c-Met signaling promoted adhesion of tumor cells to brain endothelial cells and enhanced neovascularization by inducing the secretion of IL8 and CXCL1. Additionally, stimulation of IL1ß secretion by activation of c-Met induced tumor-associated astrocytes to secrete the c-Met ligand HGF. Thus, a feed-forward mechanism of cytokine release initiated and sustained by c-Met fed a vicious cycle that generated a favorable microenvironment for metastatic cells. Reinforcing our results, we found that pterostilbene, a compound that penetrates the blood-brain barrier, could suppress brain metastasis by targeting c-Met signaling. These findings suggest a potential utility of this natural compound for chemoprevention. Cancer Res; 76(17); 4970-80. ©2016 AACR.

Prognostic Molecular Subtypes of Low-Grade Cancer of the Appendix.

BACKGROUND: Appendiceal cancer (AC) patients treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) often demonstrate an unpredictable variability in their survival outcomes. Biomarkers predictive of CRS/HIPEC efficacy could better guide treatment decisions. We hypothesized that variation in the transcriptional programming of AC tumors might distinguish molecular subtypes with differential outcomes after CRS/HIPEC. STUDY DESIGN: Gene expression profiles of 2 AC cohorts were analyzed using Affymetrix whole-genome expression microarrays. Hierarchical clustering methods, Kaplan-Meier analysis, and Cox regression models were used to discover and validate prognostic molecular subtypes of AC. Gene set enrichment analysis was used to infer pathologic attributes of the molecular subtypes. RESULTS: Unsupervised hierarchical clustering analysis of tumor expression profiles revealed a 139-gene cassette that distinguished 2 molecular subtypes (based on low vs high expression of the gene cassette) with statistically significant survival differences (disease-specific survival, p = 0.0075; progression-free survival, p = 0.0072). In a second AC cohort, the 139-gene cassette reproducibly partitioned tumors into subtypes with significant survival differences. Tumors showing high relative expression of the genes comprising the cassette associated with poor survival outcomes (disease-specific survival, p = 0.047; progression-free survival, p = 0.0079), and exhibited gene expression patterns enriched for oncogenic processes and pathways. The prognostic value of the molecular subtypes was specific for low-grade appendiceal tumors (disease-specific survival, p = 0.028; progression-free survival, p = 0.0016), and remained significant in the presence of conventional prognostic markers, including grade, surgical resection score, Eastern Cooperative Oncology Group status, and age. CONCLUSIONS: The 139-gene cassette can have actionable clinical utility for identifying low-grade appendiceal tumor molecular subtypes predictive of therapeutic efficacy of CRS/HIPEC.

Local control of brain metastases after stereotactic radiosurgery: the impact of whole brain radiotherapy and treatment paradigm.

PURPOSE: We investigate clinical, pathologic, and treatment paradigm-related factors affecting local control of brain metastases after stereotactic radiosurgery (SRS) with or without whole brain radiotherapy (WBRT). METHODS AND MATERIALS: Patients with brain metastases treated with SRS alone, before or after WBRT were considered to determine predictors of local failure (LF), time to failure and survival. RESULTS: Among 137 patients, 411 brain metastases were analyzed. 23% of patients received SRS alone, 51% received WBRT prior to SRS, and 26% received SRS followed by WBRT. LF occurred in 125 metastases: 63% after SRS alone, 20% after WBRT then SRS, and 22% after SRS then WBRT. Median time to local failure was significantly less after SRS alone compared to WBRT then SRS (12.1 v. 22.7 months, p=0.003). Tumor volume was significantly associated with LF (HR:5.2, p<0.001, 95% CI:3.4-7.8). CONCLUSIONS: WBRT+SRS results in reduced LF. Local control was not significantly different after SRS as salvage therapy versus upfront SRS.

Ossifying fibromyxoid tumor: report of a case with cytomorphologic description.

Ossifying fibromyxoid tumor (OFMT) is a rare soft tissue neoplasm with uncertain histogenesis. Most cases behave in a clinically benign fashion; however, a small percentage of tumors may locally recur or metastasize. Herein we present a case of a 56-year-old man who presented with an enlarging left groin mass, left inner thigh numbness, burning paresthesia and discomfort in his left groin. The mass sampled by fine- needle aspiration and needle core biopsy. Cytology showed bland-appearing epithelioid cells with round nuclei and fine chromatin, with fragments of fibromyxoid stroma in the background. Immunohistochemical stains performed on the core biopsy showed that the lesional cells were focally positive for S100 protein and negative for desmin, smooth muscle actin, CD34 and cytokeratin AE1/AE3. A benign neoplasm was favored with ossifying fibromyxoid tumor as the main entity in the differential diagnosis. A subsequent resection showed a well-circumscribed 5 cm mass with firm consistency and focal areas of calcifications. Histologically, the tumor had a nodular growth pattern with relatively bland spindle cells containing round to oval nuclei suspended in a variably collagenous to myxoid stroma. Significant ossification and bone formation was also noted. There was no significant atypia, necrosis or increased mitoses. Ossifying fibromyxoid tumors have distinct cytologic features and should be considered in the differential diagnosis of soft tissue tumors with prominent ossification.

En bloc spondylectomy for primary malignant fibrous histiocytoma of the thoracic spine with aortic involvement: case report.

In this article, the authors describe a 48-year-old man who initially presented with progressively worsening back pain. Magnetic resonance imaging revealed a soft-tissue mass involving the T10-11 vertebral bodies with extension anteriorly into the aorta as well as epidural extension without spinal cord compression. A biopsy of the mass showed findings consistent with a malignant fibrous histiocytoma (MFH). A total en bloc spondylectomy with resection and reconstruction of the involved aorta using a vascular graft was performed. The patient received postoperative radiation therapy and is neurologically intact at 18 months postoperatively. To the authors' knowledge, this is the first reported case of a spinal MFH resection with aortic reconstruction.

Roles of the cyclooxygenase 2 matrix metalloproteinase 1 pathway in brain metastasis of breast cancer.

Brain is one of the major sites of metastasis in breast cancer; however, the pathological mechanism of brain metastasis is poorly understood. One of the critical rate-limiting steps of brain metastasis is the breaching of blood-brain barrier, which acts as a selective interface between the circulation and the central nervous system, and this process is considered to involve tumor-secreted proteinases. We analyzed clinical significance of 21 matrix metalloproteinases on brain metastasis-free survival of breast cancer followed by verification in brain metastatic cell lines and found that only matrix metalloproteinase 1 (MMP1) is significantly correlated with brain metastasis. We have shown that MMP1 is highly expressed in brain metastatic cells and is capable of degrading Claudin and Occludin but not Zo-1, which are key components of blood-brain barrier. Knockdown of MMP1 in brain metastatic cells significantly suppressed their ability of brain metastasis in vivo, whereas ectopic expression of MMP1 significantly increased the brain metastatic ability of the cells that are not brain metastatic. We also found that COX2 was highly up-regulated in brain metastatic cells and that COX2-induced prostaglandins were directly able to promote the expression of MMP1 followed by augmenting brain metastasis. Furthermore, we found that COX2 and prostaglandin were able to activate astrocytes to release chemokine (C-C motif) ligand 7 (CCL7), which in turn promoted self-renewal of tumor-initiating cells in the brain and that knockdown of COX2 significantly reduced the brain metastatic ability of tumor cells. Our results suggest the COX2-MMP1/CCL7 axis as a novel therapeutic target for brain metastasis.

Esophageal eosinophilia in pediatric patients with celiac disease: is it a causal or an incidental association?

OBJECTIVES: Celiac disease (CD) and eosinophilic esophagitis (EoE) are 2 distinct disease entities affecting the gastrointestinal tract of pediatric patients. Recently it has been suggested that EoE is more prevalent in patients with celiac disease than in the general population. We studied the association between these 2 disease entities in our pediatric patients. METHODS: We reviewed our hospital files for suspected or confirmed cases of CD. Only cases with both duodenal and esophageal biopsies in pediatric patients were included. A total of 120 patients who met these criteria were included as the disease group. We also selected 100 patients with no clinical suspicion of CD and included them as a control group. Slides were reviewed using established criteria for diagnosis of both conditions. Duodenal biopsies were categorized as positive, negative, and suspicious for CD, whereas esophageal biopsies were classified as either positive or negative for esophageal eosinophilia (EE). Serologic and clinical data were additionally collected. RESULTS: Sixty-two (62) cases were considered positive for CD in the disease group; among those 4 (6.5%) showed EE. In the control group, 91 cases were negative for CD, histologically, and 7 of those had EE (7.7%). Although 6 patients in the control group were histologically suspicious for CD, none of them had evidence of EE. CONCLUSIONS: Our findings show that, in our patient population, patients with CD are not more likely to have EE than patients undergoing upper endoscopy for other reasons. Therefore, we suggest that the association between CD and EE is likely incidental and not causal.

Changing prognostic factors in osteosarcoma: analysis of 381 cases from two institutions.

Osteosarcoma occurs most commonly in children and young adults, with a historic second incidence peak in the elderly. Most studies have focused on those occurring in adolescence. Detailed information on descriptive features and prognostic factors in patients of different age groups is lacking. We analyzed 381 osteosarcomas diagnosed between 1973 and 2012 to identify factors significantly associated with survival in various age groups. The peak incidence was seen in patients age <25, followed by a steady incidence rate thereafter until the sixth decade, when it started to decline. In the early onset diseases, significant factors for recurrence-free survival (RFS) were tumor site and size; whereas those for overall survival (OS) were gender, tumor site, type, grade and size. In patients age 25 to 54, tumor type and grade were significant for RFS, and the pathologic type was significant for OS. In those age ≥55, race and tumor size were significant for RFS; tumor site and size were significant for OS. In multivariate analysis, tumor size remained significant for RFS; gender, tumor site and size maintained their significance for OS in patients age <25. While no independent factor was identified in patients age 25 to 54, tumor size remained significant for RFS in those age ≥55. Chemotherapy-induced tumor necrosis was a prognosticator for RFS in patients age 25 to 54 by univariate analysis, but not as an independent factor in any stratified age group. Our data indicate that the distinctive prognostic factors differed significantly among different age groups, thus providing a rationale for age-based management strategies.

Practical approach to MRI of female pelvic masses.

OBJECTIVE: Female pelvic masses have a broad differential diagnosis, including benign and malignant neoplasms and nonneoplastic entities. CONCLUSION: By using a systematic approach to the evaluation of a complex pelvic mass, including incorporating the clinical and surgical history, and by using multiparametric MRI to identify the anatomic origin, morphologic features, and tissue composition of a mass, a short meaningful differential diagnosis or definitive diagnosis can often be established.