Morphologic Mimics Research Articles

TRAF7-mutated Fibromyxoid Spindle Cell Tumors Are Associated With an Aggressive Clinical Course and Harbor an Undifferentiated Sarcoma Methylation Signature: A Molecular and Clinicopathologic Study of 3 Cases.

TRAF7 somatic mutations are rare and have been reported in meningiomas, intraneural perineuriomas, and mesotheliomas. Triggered by an index case of an unclassified low-grade mesenchymal tumor with TRAF7 mutation as the only genetic alteration, we searched our files and identified 2 additional cases with similar features. The tumors arose in 2 females and 1 male, aged 63 to 75 years old (median: 67y). They were infiltrative deep soft tissue masses involving the shoulder, chest wall, and thigh, measuring 7.0 to 9.1cm in greatest dimensions. One tumor was locally aggressive, and 2 were associated with lung and bone metastases. The tumors displayed alternating fibrous and myxoid stroma with mild to moderate cellularity and consisted of uniform spindle cells with open chromatin, inconspicuous nucleoli and scant cytoplasm. Significant mitotic activity or necrosis were not present. However, the metastatic tumor of 1 case showed an epithelioid morphology and brisk mitotic activity. Immunohistochemically, the tumors showed nonspecific and focal smooth muscle actin or CD34 expression. By DNA sequencing, all 3 cases harbored TRAF7 missense mutations involving the C-terminal WD40 domains as the only somatic mutations, showed nonrecurrent focal copy number alterations, and were negative for gene fusions by targeted RNA sequencing. On methylation profiling, the tumors clustered with the undifferentiated sarcoma and myxofibrosarcoma methylation classes and were distinct from morphologic mimics. On follow-up (5 to 36mo), 2 patients died of disease following aggressive chemotherapeutic regimens. We describe a novel TRAF7- mutated mesenchymal tumor characterized by aggressive clinical behavior despite the histologic appearance of a low-grade fibromyxoid spindle cell tumor.

How I Diagnose EBV-Positive B- and T-Cell Lymphoproliferative Disorders.

Epstein-Barr virus (EBV)-associated lymphoproliferative disorders (LPDs) encompass a group of well-defined entities of B-, T-, and natural killer (NK)-cell derivation. The diagnosis of these disorders is challenging because of clinical and morphologic features that may overlap with other benign and malignant EBV+ lymphoproliferations. This review describes our approach to the diagnosis of EBV-associated LPDs. Two cases are presented that illustrate how we diagnose EBV-associated LPDs. The first case represents a systemic EBV+ T-cell lymphoma of childhood and the second case an EBV+ mucocutaneous ulcer. The clinicopathologic features that help distinguish these entities from biological and morphologic mimickers are emphasized. The accurate diagnosis of EBV-associated LPDs requires the incorporation of histologic and immunophenotypic features, the assessment of the EBV latency program, and, most important, complete clinical findings. Clonality analysis is not helpful in distinguishing benign from malignant EBV+ LPDs. The better understanding of EBV-associated LPDs has resulted in the recognition of well-defined entities of B-, T-, and NK-cell derivation and consequently improvement of their treatment with curative intent. It is critical to distinguish benign from malignant EBV+ LPDs to avoid overtreatment.

Transcriptome-Wide Gene Expression Profiles from FFPE Materials Based on a Nuclease Protection Assay Reveals Significantly Different Patterns between Synovial Sarcomas and Morphologic Mimickers.

Simple SummaryThe following study aimed to validate and test the feasibility, reliability, technical applicability robustness, and reliability of a new commercially available transcriptome profiling assay, being performed on formalin-fixed, paraffin-embedded (FFPE) patient samples. The patients were suffering from either synovial sarcoma or spindle cell sarcoma, which are morphologically similar tumors, but differ in molecular characteristics. Transcriptome analysis of FFPE material is still challenging. However, it is the most available material in pathological routine and therefore valuable for translational research approaches. This new commercially available assay is based on a nuclease protection assay and has shown to be a feasible method for adequate transcriptome profiling with low sample input and therefore is suitable for further research of biomarkers. Background: Transcriptome profiling provides large data on tumor biology, which is particularly valuable in translational research and is becoming more and more important for clinical decision-making as well. RNA sequencing is considered to be the gold standard for this. However, FFPE material, as the most available material in routine pathology, has been an undefeatable obstacle for RNAseq. Extraction-free nuclease protection assays have the potential to be a reliable alternative method for large-scale expression profiling. The aim of this study was to validate and test the basic feasibility, technical applicability robustness, and reliability of the HTG transcriptome profiling (HTP) assay on clinical tumor samples. Methods: FFPE samples from 44 synovial sarcomas (SyS) and 20 spindle cell sarcomas (SpcS) were used. The HTP assay was performed on 10 µm thin FFPE slides. After nuclease protection in the HTG Edge Seq System, libraries were generated for sequencing on an Illumina NextSeq 500 platform. Fastq data were parsed and then analyzed by using the HTG analysis platform EdgeSeq REVEAL. Immunohistochemistry was performed to validate the expression of TLE1. Results: The technical application of the HTP Panel revealed robust and reliable results with 62 samples, and only 2 samples failed due to an incomplete digestion of gDNA. The analysis, performed at the analysis platform REVEAL, showed 5964 genes being significantly differentially expressed between SpcS and SyS. In particular, overexpression of the known marker TLE1 in synovial sarcoma could be recovered, which underlines the reliability of this system. Discussion: Transcriptome profiling gets more and more important for tumor research and diagnostics. Among other established technologies, the HTP Panel has shown to be a feasible method to get robust and reliable results. Thereby, this method needs very few sample-input by getting a success-rate of 96.88%, which indicates the upper average range, compared to other technologies working with FFPE tissue. Conclusion: The nuclease protection assay-based HTP Panel is a feasible method for adequate transcriptome profiling with low sample input and therefore is suitable for further research of biomarkers.

Mesonephric-Like Adenocarcinoma of the Endometrium: Review of the Literature and Practical Diagnostic Recommendations

Abstract Mesonephric-like adenocarcinomas are endometrial and ovarian neoplasms of müllerian origin with morphologic, immunophenotypic, and molecular evidence of mesonephric-type transdifferentiation, as well as considerable homology with endometrioid tumors. First described in 2016, mesonephric-like adenocarcinomas are morphologically indistinguishable from “true” mesonephric adenocarcinomas of the uterine cervix, but the latter are distinguished by (1) primary localization to the cervical wall, (2) frequent association with mesonephric remnants, and (3) in some cases, lack of mucosal involvement. Despite an overall low-grade morphology, mesonephric-like adenocarcinoma follows an aggressive clinical course, characterized by frequent and early recurrences, most often in the lung. Accordingly, accurate distinction of mesonephric-like adenocarcinoma from morphologic mimics—especially low-grade endometrioid adenocarcinoma—is critical. However, available evidence indicates that endometrial mesonephric-like adenocarcinomas are significantly underdiagnosed, likely due to their relative novelty, rarity, and considerable overlap with endometrioid neoplasia. Prospective recognition of characteristic morphologic features, a low threshold for application of diagnostic immunohistochemistry, and judicious use of molecular studies will permit accurate diagnosis in almost all cases.

MicroRNAs as Potential Biomarkers in the Differential Diagnosis of Lipomatous Tumors and Their Mimics.

Adipocytic tumors are the most common subtype of soft tissue tumors. In current clinical practice, distinguishing benign lipomas from well-differentiated liposarcomas (WDLPS), as well as dedifferentiated liposarcomas (DDLPS) from their morphologic mimics, remains a significant diagnostic challenge. This is especially so when examining small biopsy samples and without the aid of additional ancillary tests. Recognizing the important role that microRNAs (miRNAs) play in tumorigenesis and their potential utility in tumor classification, we analyzed routine clinical tissue samples of benign and malignant lipomatous tumors, as well as other sarcoma mimics, to identify distinguishing miRNA-based signatures that can aid in the differential diagnosis of these entities. We discovered a 6-miRNA signature that separated lipomas from WDLPS with high confidence (AUC of 0.963), as well as a separate 6-miRNA signature that distinguished DDLPS from their more aggressive histologic mimics (AUC of 0.740). Functional enrichment analysis unveiled possible mechanistic involvement of these predictive miRNAs in adipocytic cancer-related biological processes and pathways such as PI3K/AKT/mTOR and MAPK signaling, further supporting the relevance of these miRNAs as biomarkers for adipocytic tumors. Our results demonstrate that miRNA expression profiling may potentially be used as an adjunctive tool for the diagnosis of benign and malignant adipocytic tumors. Further validation studies are warranted.

NTRK -Rearranged Uterine Sarcomas: Clinicopathologic Features of 15 Cases, Literature Review, and Risk Stratification.

NTRK -rearranged uterine sarcomas are rare spindle cell neoplasms that typically arise in the uterine cervix of young women. Some tumors recur or metastasize, but features which predict behavior have not been identified to date. Distinguishing these tumors from morphologic mimics is significant because patients with advanced stage disease may be treated with TRK inhibitors. Herein, we present 15 cases of NTRK- rearranged uterine sarcomas, the largest series to date. Median patient age was 35 years (range: 16 to 61). The majority arose in the uterine cervix (n=14) and all but 2 were organ-confined at diagnosis. Tumors were composed of an infiltrative, fascicular proliferation of spindle cells and most showed mild-to-moderate cytologic atypia. All were pan-TRK positive by immunohistochemistry (13/13); S100 (11/13) and CD34 (6/10) were usually positive. RNA or DNA sequencing found NTRK1 (10/13) and NTRK3 (3/13) fusions with partners TPR , TPM3 , EML4 , TFG , SPECC1L , C16orf72 , and IRF2BP2 . Unusual morphology was seen in 2 tumors which were originally diagnosed as unclassifiable uterine sarcomas, 1 of which also harbored TP53 mutations. Follow up was available for 9 patients, of whom 3 died of disease. By incorporating outcome data of previously reported tumors, adverse prognostic features were identified, including a mitotic index ≥8 per 10 high-power fields, lymphovascular invasion, necrosis, and NTRK3 fusion. Patients with tumors which lacked any of these 4 features had an excellent prognosis. This study expands the morphologic spectrum of NTRK -rearranged uterine sarcomas and identifies features which can be used for risk stratification.

Hodgkin Lymphoma: Biology and Differential Diagnostic Problem.

Hodgkin lymphomas (HLs) are lymphoid neoplasms that are morphologically defined as being composed of dysplastic cells, namely, Hodgkin and Reed–Sternberg cells, in a reactive inflammatory background. The biological nature of HLs has long been unclear; however, our understanding of HL-related genetics and tumor microenvironment interactions is rapidly expanding. For example, cell surface overexpression of programmed cell death 1 ligand 1 (CD274/PD-L1) is now considered a defining feature of an HL subset, and targeting such immune checkpoint molecules is a promising therapeutic option. Still, HLs comprise multiple disease subtypes, and some HL features may overlap with its morphological mimics, posing challenging diagnostic and therapeutic problems. In this review, we summarize the recent advances in understanding the biology of HLs, and discuss approaches to differentiating HL and its mimics.

Diagnosis from Tissue: Histology and Identification.

The diagnosis and initiation of appropriate treatment against invasive fungal infections depend upon accurate identification of pathogens by pathologists and clinical microbiologists. Histopathology is often critical in providing diagnostic insight in patients with suspected fungal infections, and such findings are incorporated into the definitions of proven or probable disease caused by certain pathogens. Such examinations can offer provisional identifications of fungal organisms, which can help guide initial therapy while laboratory results are pending. Common etiologic agents of invasive mycoses may be recognized based on morphologic characteristics observed in tissue and biologic fluids, such as those obtained from bronchoalveolar lavage and bronchial washings. However, care should be taken in the interpretation of these findings, as there may be a false sense of the ability to correctly categorize fungal organisms to the genus or species level by morphologic features alone. Studies have demonstrated discordant results between histopathology and laboratory results due to overlapping morphologic features, morphologic mimics, and sampling errors. Thus, histopathology plays an integral role in providing a differential of potential fungal pathogens but must be combined with results from laboratory studies, including cultures, antigen tests, serology, and molecular assays, in order to improve accuracy in the identification of etiologic agents of fungal infections. Inaccurate identification of the infecting organism can lead to inappropriate antifungal therapy and possibly poor clinical outcomes.

Low grade endometrial endometrioid adenocarcinoma: A review and update with emphasis on morphologic variants, mimics, immunohistochemical and molecular features

Endometrioid adenocarcinoma (ECa) may feature a number of morphologic variations that can pose diagnostic challenge. The purpose of this review and update is to examine the spectrum of morphologic variants and mimics of low-grade (FIGO grades 1 and 2) ECa, with a focus on histologic, immunohistochemical, and molecular features that may inform diagnosis and treatment. In addition to ECa of usual type, variants with unique cytologic and/or architectural features presented include the following: 1) ECa with mucinous differentiation of conventional (Müllerian) type; 2) ECa with squamous differentiation; 3) ECa with morular metaplasia; 4) ECa with patterns resembling cervical transformation zone tissue and/or microglandular hyperplasia; 5) ECa with cytoplasmic clearing; 6) ECa with papillation, including villoglandular variant of ECa, ECa with small nonvillous papillae, and ECa with a "low-grade serous"-like component or surface changes mimicking ovarian serous borderline tumor; 7) corded and hyalinized variant of ECa; 8) ECa with spindled epithelial cells; 9) ECa with sex cord-like pattern; and 10) ECa with other unusual cytologic and associated features. For each variant, relevant differential diagnoses and diagnostic strategies are discussed. The most clinically significant distinctions come into play in the differential diagnosis between low-grade ECa and one of its high-grade mimics. In this setting, the most fundamental tool in the pathologist's diagnostic arsenal is recognition of the low-grade cytologic features typical of low-grade ECa. Circumspect evaluation of cytologic features, complemented by an awareness of the morphologic spectrum, an appropriate battery of immunohistochemical stains when needed, and mindfulness of the clinical scenario, should guide the pathologist to the correct histotype in even challenging cases.

Endometrial stromal tumors: Diagnostic updates and challenges.

Endometrial stromal tumors are rare uterine mesenchymal tumors of endometrial stromal origin. They are classified into endometrial stromal nodule, low-grade endometrial stromal sarcoma, high-grade endometrial stromal sarcoma, and undifferentiated uterine sarcoma by the current (2020) WHO classification. Correct diagnosis of endometrial stromal tumors is critical for proper patient management. However, due to infrequent encounters, overlapping morphological features and immunohistochemical profiles, the differential diagnoses among endometrial stromal lesions and their morphologic mimics are often challenging. Partially with our own experience, here we review and summarize the tumor morphology, immunohistochemical phenotype, as well as molecular feature of endometrial stromal tumors and key differential diagnoses, emphasizing the newest developments and their utilization in daily practice.

CD13 is a useful tool in the differential diagnosis of meningiomas with potential biological and prognostic implications

Meningiomas are common tumors of the central nervous system. Although their histological diagnosis is usually straightforward, their differential diagnosis versus other tumors may be challenging at times. The objective of this study is to assess the diagnostic value of CD13 immunoexpression in the differential diagnosis between meningiomas and their morphological mimics. Immunohistochemical analysis for CD13, epithelial membrane antigen, SOX10, and STAT6 was carried out in a large cohort of primary meningeal tumors comprising 225 meningiomas, 15 schwannomas, and 20 solitary fibrous tumor/hemangiopericytomas. Within the meningioma group, the expression of CD13 and epithelial membrane antigen was distinguished in three categories using a semiquantitative score. Most of meningiomas expressed CD13 (94%) and epithelial membrane antigen (96%) while none of the schwannomas nor of the solitary fibrous tumor/hemangiopericytomas was positive for either the two markers. Diffuse positivity for CD13 and epithelial membrane antigen was more common in low-grade meningiomas than in anaplastic ones, which were also more often negative for such markers, especially for CD13 (32%). CD13 is a helpful immunohistochemical marker for the differential diagnosis of meningiomas and their mimics, achieving in combination with epithelial membrane antigen maximal sensitivity (100%) and showing statistically relevant difference of expression in comparison with both schwannomas (p < 0.0001) and solitary fibrous tumor/hemangiopericytomas (p < 0.0001). Furthermore, loss of CD13 expression could be related to outcome as it is associated with worrisome histological findings, mainly in the setting of anaplastic meningiomas.

Epithelioid Sarcoma: An overview with emphasis on its differentiation from morphologic mimics

Epithelioid sarcoma (ES) is a malignant mesenchymal neoplasm that exhibits epithelioid cytomorphology and a predominantly epithelial phenotype. The principal types based on histopathological features and location; include the classic or conventional type (CES) and the proximal type (PES). The aim of the study was to analyze our cases of ES regarding clinical, pathological and immunohistochemical features.This is a retrospective study. Seven cases of ES were included in the study. Clinical and pathological details were retrieved from patient records. Details like site, size, histopathological type and IHC features of the tumors were studied. Out of seven, five were PES and two were CES. There were six males and one female; with age ranging from 12 to 68 years. Total five tumors involved extremities. One was noted at a rare site, paratesticular region. Three tumors were larger than 5 cm in greatest dimension. On immunohistochemistry (IHC), all the tumors were reactive for CK, EMA, Vimentin, Ca 125 and showed loss of nuclear expression of INI1. CD 34 was expressed in 6 out of 7 cases.ES is a rare aggressive malignant tumor with dismal prognosis. It is often misdiagnosed because of nonspecific clinical features at presentation. Helpful clues in diagnosis are tumors in young males with epithelioid and/or spindle cell morphology, Rhabdoid cells and granuloma like central necrosis. Co-expression of epithelial and mesenchymal markers along with reactivity for CD34 and Ca 125 and loss on INI1 expression on IHC substantiate the diagnosis of ES.

The Grey Zones of Classic Hodgkin Lymphoma

Simple SummaryClassic Hodgkin lymphoma (CHL) is a well-defined lymphoid neoplasm with a minority of characteristic neoplastic cells of B cell origin, namely Hodgkin and Reed–Sternberg cells immersed in a rich reactive inflammatory infiltrate in the background. Although CHL has always been set apart from non-Hodgkin lymphomas, cases with morphological and phenotypic features intermediate between CHL and other lymphomas have been described. Whereas some of these lymphomas only represent morphological mimics, others exhibit mutational and gene expression profiles which overlap with CHL, indicating that these cases, frequently termed grey zone lymphomas, reside on the biological boundary between CHL and large B-cell lymphomas. In the present review, we aim to describe the current knowledge of these rare lymphomas, address diagnostic issues and summarize today’s concepts on the classification of grey zone lymphomas and related tumors.Classic Hodgkin lymphoma (CHL) is a well-defined neoplasm characterized by the presence of a minority of pathognomonic Hodgkin and Reed–Sternberg (HRS) cells in a reactive inflammatory background. Although genotypically of B cell origin, HRS cells exhibit a downregulated B cell program and therefore are set apart from other B cell lymphomas in the current WHO classification. However, cases with morphological and phenotypic features overlapping with CHL have been recognized, and the category of B cell lymphoma—unclassifiable—with features intermediate between diffuse large B cell lymphoma (DLBCL) and CHL, also termed grey zone lymphoma, was first introduced into the WHO classification in 2008 as provisional entity. These cases, as well as others raising a differential diagnosis of CHL can present diagnostic problems, as well as therapeutic challenges. Whereas some of these lymphomas only represent biologically unrelated morphological mimics, others, especially mediastinal grey zone lymphoma, exhibit genetic and gene expression profiles which overlap with CHL, indicating a true biological relationship. In this review, we address areas of diagnostic difficulties between CHL and other lymphoma subtypes, discuss the biological basis of true grey zone lymphoma based on recent molecular studies and delineate current concepts for the classification of these rare tumors.

Solid papillary carcinoma of the breast.

ABSTRACTSolid Papillary Carcinoma (SPC) of the breast is a rare tumor with an incidence of less than 1%, mainly affecting elderly females. It is morphologically characterized by well-defined nodules with low-grade nuclear features associated with fibrovascular cores and shows neuroendocrine differentiation. SPC can be in-situ or invasive but has a favorable prognosis. It is a morphological mimicker of some pre-malignant conditions leading to its frequent misdiagnosis. An appropriate immunohistochemical (IHC) panel workup helps in distinguishing this tumor from its various morphological mimics. In this report, we present one such case of SPC with a small focus of invasion, reviewing the literature.

Extra Nodal Non Hodgkin’s Lymphomas using Immunohistochemistry from a Tertiary Care Centre, Andhra Pradesh, India- A Retrospective Study

Introduction: Primary Extranodal Lymphomas (pENL) are a group of lymphomas arising from tissues other than lymph nodes and even sites which normally contain no lymphoid tissue. Over the past 25 years pENLs have shown a rapid increase in incidence. pENLs can originate from almost any anatomical site such as the gastrointestinal tract (most common), head and neck (waldeyer’s ring, nose/paranasal sinuses/nasopharynx, salivary glands, etc.,), skin, Central Nervous System (CNS) etc. The definition of Extranodal Lymphoma (ENL), particularly in the presence of both nodal and extranodal disease remains a controversial issue. To categorise these entities, different criteria were proposed by different authors. Aim: To study the occurrence of extranodal non hodgkin’s lymphomas in different sites/organs using Immunohistochemistry (IHC). Materials and Methods: This was a retrospective study carried out in the Department of Pathology, Sri Venkateswara Institute of Medical Sciences (SVIMS), Tirupati, Andhra Pradesh, India, over a period of 7 years 6 months starting from January 2010 to July 2017. Data was retrieved from the medical records and paraffin blocks were retrieved from the stores. All cases of extranodal primary lymphomas were included in the study. All cases were classified based upon morphologic and immunophenotypic criteria according to World Health Organisation (WHO) 2008 classification. The distribution of primary extranodal lymphomas among different age groups with mean age of occurrence was noted. Distribution of pENLs among male and female population with male to female ratio was calculated. The percentage of different sub-types of ENL and the Immunohistochemistry (IHC) markers in each subtype of ENL were calculated. Results: In this retrospective study, a total of 317 newly diagnosed lymphoma cases were included. Among them, 79 cases were pENL. A total of 77 (24.29%) cases of primary extranodal non Hodgkin’s lymphomas were included in the study. The age of the patients ranged from 4-81 years with mean age of 48.42 years, with male predominance (M:F-1.85:1). Gastrointestinal Tract (GIT) (35/77-45.45%) was the most common site, followed by head and neck (16/77-20.77%), mediastinum (4/77-5.19%), kidney (4/77-5.19%) were the common sites of occurrence of primary extranodal NHLs. In the GIT, stomach was the most commonly involved site (24/35) followed by the small intestine (5/35), colon and anal canal (3/35) and ileo-caecal region (3/35). The Diffuse Large B-cell Lymphoma (DLBCL) was the most common histological type observed in 51/77 (66.23%), followed by Peripheral T-cell Lymphoma- Not Otherwise Specified (PTLNOS) were observed in 14/77 (18.18%) cases, and extranodal marginal zone lymphoma of Mucosa-associated Lymphoid Tissue (MALT) type seen in 9/77 (11.68%) cases. Conclusion: pENLs are a diverse group of haemato-lymphoid malignancies, the incidence of which is low in India compared to rest of the world, the prognosis of which depends on the extranodal site. The diagnosis is challenging due to the morphological mimics and varied clinical presentation and that is

Acantholytic Squamous Cell Carcinoma

A 63-year-old Filipino man presented with a one-month history of painful ulceration on the alveolar socket of a molar tooth of the right hemimandible. The patient consulted at a tertiary hospital, where he underwent incisional biopsy.&#x0D; &#x0D; Microscopically, the biopsy specimen showed neoplastic cells arranged in a pseudoglandular alveolar pattern with cystic spaces lined with atypical polygonal cells. (Figure 1) Detached “glassy” keratinocytes which are dyskeratotic acantholytic cells were seen within these cystic spaces. (Figure 2) Areas with features of more conventional squamous cell carcinoma, i.e., intercellular bridges and abundant eosinophilic cytoplasm, were also present. (Figure 3) Immunohistochemical staining for p40 showed diffuse nuclear positivity. (Figure 4) Given these findings, a diagnosis of acantholytic squamous cell carcinoma (ASCC) was made.1&#x0D; &#x0D; Acantholytic squamous cell carcinoma (historically known as adenomatoid squamous cell carcinoma or adenoacanthoma) is a histologic variant of squamous cell carcinoma (SCC) that most often presents as an ulcer on sun-exposed areas, mostly in elderly males.1,2 ASCCs of the oral cavity are rare, with fewer than 60 cases reported in the literature.3 In a series of 55 cases describing intraoral ASCCs, the most common sites of ASCC were the tongue (24/55) and the maxilla/maxillary gingiva and/or palate (11/55).3&#x0D; &#x0D; The presence of a pseudoglandular or alveolar pattern might suggest the diagnosis of an adenocarcinoma. However, the findings of tumor lobules with a distinctly squamoid morphology, along with the presence of intercellular bridges, will point to the correct diagnosis. Furthermore, ASCC does not present with intracellular mucin, clear cells, and intermediate cells – an important distinguishing point with mucoepidermoid carcinoma. The absence of true glands also militates against the differential diagnosis of an adenosquamous carcinoma.1&#x0D; &#x0D; Although the diagnosis of ASCC may be established through histomorphology alone, p40 immunohistochemistry – a useful marker for squamous cell differentiation - strengthens the diagnosis.4 Loss of E-Cadherin expression – a protein involved in cell adhesion and binding - is usually seen in the discohesive cells but may be retained in the well differentiated areas.2 Absence of staining with mucicarmine and CD34 will help rule out mucoepidermoid carcinoma and angiosarcoma, respectively.1,2 The authors felt that the latter two differential diagnoses could be excluded on the basis of the light microscopic features present in the case along with the demonstration of diffuse p40 positivity. It is granted however that in resource-rich settings, these other ancillary diagnostic tests may prove helpful especially for morphologically ambiguous cases or cases with less tissue volume.&#x0D; &#x0D; Current studies show no statistically significant difference in the overall survival rate of ASCCs versus that of conventional SCC.3 ASCC is treated in the same manner as conventional SCC.1 The importance of recognizing this variant lies in ensuring that it is not mistaken for its other non-squamous morphological mimics.

Histologic mimics and diagnostic pitfalls of gastrointestinal endoscopic lifting media, ORISE™ gel and Eleview®

Synthetic lifting media, ORISE™ gel and Eleview®, are increasingly used in gastrointestinal endoscopy, but neither comparative features nor pitfalls are well-established. Media histopathology, morphologic mimics, and complications are described, along with helpful stains and endoscopist media preference. A 3-year retrospective search was performed. A total of 123 cases (108 endoscopies and 15 subsequent surgeries) were identified. ORISE gel was used in 86 (79.6%), Eleview in 20 (13.9%), and others in 7 (6.5%). ORISE gel was histologically identified in 58.1% (n=50) of endoscopic specimens and all 15 resections. Eleview media were not detected histologically. ORISE gel mimicked mucin in hematoxylin and eosin-stained biopsies, concerning for adenocarcinoma misdiagnosis and/or upstaging, but did not stain for mucin. Acid-fast bacterial staining highlights ORISE gel for specific and definitive identification. In resections, ORISE evolves into an amorphous eosinophilic material, often with exuberant giant cell reaction and transmural bowel penetration. Polyp formation leads to polypectomy in one patient, and operative lesions concerning for adenocarcinoma resulted in frozen sections in two patients. ORISE gel mimics mucin, malignant masses, amyloid, pulse granulomata, elastofibromas, and infectious granulomata. No significant endoscopist media preference was identified. Recognition of ORISE gel in tissues eliminates multiple pitfalls. Eleview was not detectable, yielded none of the pitfalls seen with ORISE gel, and, on our survey, has equivalent endoscopist acceptance. In this largest published series to date, Eleview is clearly preferable to ORISE gel.

A Selective Review of Salivary Gland Neoplasms and Rare Morphologic Mimics

A Selective Review of Salivary Gland Neoplasms and Rare Morphologic Mimics

Role of Cyclin D1 and BCOR Immunohistochemistry in Differentiating Clear Cell Sarcoma of Kidney From its Mimics.

Clear cell sarcoma of kidney (CCSK) is the second most common pediatric renal malignancy, constituting ∼3% of renal tumors. Due to its morphologic diversity, the diagnosis of CCSK is often challenging. Recent studies have identified internal tandem duplication of BCL6 corepressor (BCOR) gene in CCSKs which coupled with cyclin D1 immunoreactivity, is helpful in differentiating it from its mimics, particularly blastema-rich Wilms tumor (WT), malignant rhabdoid tumor (MRT), and congenital mesoblastic nephroma (CMN). We aimed to evaluate the utility of cyclin D1 and BCOR immunohistochemistry in differentiating CCSK from its morphologic mimics. Our cohort comprised of 38 pediatric renal tumors which included CCSK (n=18), WT (n=10), MRT (n=5), and CMN (n=5) cases. A detailed clinicopathologic analysis was performed, and tissue microarray were constructed for CCSK and WT, while MRT and CMN tumors were individually stained. The age ranged from 2 months to 16 years with male:female ratio of 3:1. Strong, diffuse nuclear immunoreactivity for cyclin D1 and BCOR was noted in 61% (n=11/18) and 83% (n=15/18) of CCSK, respectively, while it was significantly less in WT (n=3/10 for cyclin D1) (n=2/10 for BCOR). None of the MRT and CMN examples demonstrated any immunoreactivity. Interestingly, only the blastemal component of WTs showed distinct, rare nuclear immunoreactivity for cyclin D1 or BCOR and the combination of these was never positive in a given case. Our results provide evidence that concurrent immunopositivity with cyclin D1 and BCOR is helpful in distinguishing CCSK from its morphologic mimics.

Adult pancreatoblastoma: Current concepts in pathology.

Adult pancreatoblastoma is an exceptionally rare malignant tumour of the pancreas that mimics other solid cellular neoplasms of the pancreas, which may pose diagnostic difficulties. Because of its rarity, little is known about its clinical and pathologic features. This article reviews the clinical and pathologic features of pancreatoblastoma in adults including differential diagnosis, treatment, and follow-up. Although pancreatoblastoma commonly occurs in childhood, there have now been more than 70 adult pancreatoblastomas described in the literature. There is a slight male predominance. There are no symptoms unique to pancreatoblastomas and adult patients are frequently symptomatic. The most common presenting symptom is abdominal pain. Grossly, the tumours are often large and well-circumscribed. Microscopically, pancreatoblastomas are composed of neoplastic cells with predominantly acinar differentiation and characteristic squamoid nests. These tumours are positive for trypsin, chymotrypsin, lipase, and BCL10. Loss of heterozygosity on chromosome 11p is the most common molecular alteration in pancreatoblastomas. Adult pancreatoblastomas are aggressive tumours with frequent local invasion, recurrence, and distant metastasis. Treatment consists of surgical resection. Chemotherapy and radiotherapy may have a role in the treatment of recurrent, residual, unresectable, and metastatic disease. It is important to distinguish pancreatoblastomas from morphological mimics such as acinar cell carcinomas, solid pseudopapillary neoplasms, and pancreatic neuroendocrine neoplasms.