Histologic Mimics Research Articles

Tactile Corpuscle-like Bodies in Rectal Mucosa - A Mysterious Misleading Lesion

Abstract Introduction/Objective Tactile corpuscle-like bodies (TCLB) are specialized mechanoreceptors derived from Schwannian structures, resembling Wagner-Meissner corpuscles which are often found in the skin and within schwannomas, neurofibromas, and melanocytic nevi. However, their presence in gastrointestinal mucosa is a rare phenomenon. To our knowledge, only 27 cases have been reported in the English literature. Methods We present two cases showing this rare entity in rectal mucosa. The first case is in a 34-year-old female was a past medical history significant for Ehlers-Danlos syndrome. The second case was submitted in consultation, of a 64-year-old male. In both cases, rectal polyps were identified on endoscopy. Results Histologically, clusters of unencapsulated, lamellated spindle cells in the lamina propria were identified. Immunoperoxidase stains using antibodies against CD68 and S100 protein were performed on both specimens. Additionally, on the first case synaptophysin was also performed. The laminated clusters were strongly positive for S100 and negative for CD68. The first case showed focally positive synatophysin. Although the etiology of TCLBs is still unclear, they are considered to be benign, incidental neural proliferations. The histological differential diagnosis includes: schwann cell hamartomas, neurofibromas, ganglioneuromas, mucosal neuromas, nodular amyloid deposition, or granulomas. However, those in question can be differentiated with the use of S100 protein and histiocytic markers. Conclusion Awareness of TCLBs is important. Although they are benign neural proliferations, it is important to differentiate from histologic mimics often associated with inherited syndromes.

Comparison of p53 immunohistochemical staining in differentiated vulvar intraepithelial neoplasia (dVIN) with that in inflammatory dermatoses and benign squamous lesions in the vulva.

Differentiated vulvar intraepithelial neoplasia (dVIN), the precursor lesion to human papillomavirus-independent vulvar squamous cell carcinoma (VSCC), can be difficult to distinguish from vulvar inflammatory dermatoses. Our goal was to determine if p53 could be a useful biomarker for dVIN, by characterizing p53 percentage, intensity and patterns of staining in dVIN and its histological mimics. We studied p53 immunohistochemical staining patterns in 16 dVIN cases and 46 vulvar non-neoplastic squamous lesions [12 lichen sclerosus (LS); seven lichen simplex chronicus; three lichen planus (LP); six psoriasis; 13 spongiotic dermatitis (SPO); and five candidiasis]. dVIN cases were adjacent to a p16-negative invasive VSCC in resection specimens. All dVIN cases showed null-type or moderate to strong uniform p53 staining in >70% of basal cells, with moderate to strong continuous parabasal staining extending to two-thirds of the epidermis. This was in contrast to weak or weak to moderate patchy p53 staining in the majority of other lesions. Moderate to strong and increased basal p53 staining (≥70%) was also observed in a subset of LS cases (5/12, 42%), LP cases (1/3, 33%), and SPO cases (36%, 4/11); however, in all categories, this was limited to the basal layer, and any staining in the parabasal layers was patchy. Strong and uniform p53 staining of basal cells, extending into the parabasal layers, and a complete absence of staining (null type) is useful in distinguishing dVIN from other mimics in the vulva. p53 staining of lesser intensity or quantity, particularly basal overexpression only, overlaps with that in vulvar inflammatory lesions.

Spectrum of Synovial Sarcoma-clinicopathological and Immunohistochemical Correlation

Background: Synovial sarcoma is the common adult soft tissue sarcomas affects the lower extremities. In poor resource settings, characterization by molecular methods may not be feasible always. This study is aimed to evaluate Sensitivity and Specificity of Transducin-like enhancer of split 1 (TLE1) immunohistochemical expression in Synovial sarcomas (SS) and its histological mimics and to study the clinicopathological features of Synovial sarcoma.
 Method: A prospective study of two years duration from September 2013 to September 2015 conducted at the Department of Pathology, MNJ Institute of Oncology and Regional Cancer Centre, Redhills, Hyderabad. Total number of Synovial sarcomas was 30. All original H & E section of the tumor are reviewed and Immunohistochemistry (IHC) analysis was carried out on TLE1 mouse monoclonal antibody (TMA) blocks using TLE1 Antibody.
 Results: The Median age was 30 years. The most common site of involvement was lower limbs. The most common mode of presentation was painless swelling. The most common variant of Synovial sarcoma was monophasic Spindle in 19 cases. Total number of TLE1 positive cases of Synovial sarcoma was 93.3%. Total number of SS mimics showing TLE1 positivity was30%. TLE1 showed Sensitivity 93.3% and Specificity- 73.3%. In the present study negative predictive value is 91.6% and the positive predictive value is 77.7%.
 Conclusion: All small round blue cell tumors should be kept in mind while diagnosing poorly differentiated SS. TLE1 is a very sensitive marker for synovial sarcoma.TLE 1 is a highly sensitive marker for synovial sarcoma, but is less specific because of its positive expression in other mesenchymal tumors.

H3K27me3 expression and methylation status in histological variants of malignant peripheral nerve sheath tumours

Diagnosing MPNST can be challenging, but genetic alterations recently identified in polycomb repressive complex 2 (PRC2) core component genes, EED and SUZ12, resulting in global loss of the histone 3 lysine 27 trimethylation (H3K27me3) epigenetic mark, represent drivers of malignancy and a valuable diagnostic tool. However, the reported loss of H3K27me3 expression ranges from 35% to 84%. We show that advances in molecular pathology now allow many MPNST mimics to be classified confidently. We confirm that MPNSTs harbouring mutations in PRC2 core components are associated with loss of H3K27me3 expression; whole‐genome doubling was detected in 68%, and SSTR2 was amplified in 32% of MPNSTs. We demonstrate that loss of H3K27me3 expression occurs overall in 38% of MPNSTs, but is lost in 76% of histologically classical cases, whereas loss was detected in only 23% cases with heterologous elements and 14% where the diagnosis could not be provided on morphology alone. H3K27me3 loss is rarely seen in other high‐grade sarcomas and was not found to be associated with an inferior outcome in MPNST. We show that DNA methylation profiling distinguishes MPNST from its histological mimics, was unrelated to anatomical site, and formed two main clusters, MeGroups 4 and 5. MeGroup 4 represents classical MPNSTs lacking H3K27me3 expression in the majority of cases, whereas MeGroup 5 comprises MPNSTs exhibiting non‐classical histology and expressing H3K27me3 and cluster with undifferentiated sarcomas. The two MeGroups are distinguished by differentially methylated PRC2‐associated genes, the majority of which are hypermethylated in the promoter regions in MeGroup 4, indicating that the PRC2 target genes are not expressed in these tumours. The methylation profiles of MPNSTs with retention of H3K27me3 in MeGroups 4 and 5 are independent of mutations in PRC2 core components and the driver(s) in these groups remain to be identified. Our results open new avenues of investigation. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.

Review and update in the diagnosis of peripheral nerve sheath tumors.

Although tumors with nerve sheath differentiation are vast, the main clinically significant problems faced by the pathologist are the separation of malignant peripheral nerve sheath tumors (MPNSTs) from histologic mimics, the diagnosis of neurofibromatous neoplasms with atypical features, and the separation of cutaneous neurofibromatous neoplasms from melanoma. This review briefly discusses a variety of common nerve sheath tumors and summarizes recent advances on these diagnostic fronts. Much of recent work has focused on abnormalities in polycomb repressive complex 2, and the ways in which these abnormalities may be exploited in the diagnosis of MPNSTs. Progress has been made in the diagnostic and clinical understanding of atypical neurofibromatous neoplasms and low-grade MPNSTs. A number of reports have explored the diagnostic distinction between cutaneous neurofibroma and melanoma. New discoveries show promise in the diagnosis of peripheral nerve sheath tumors, but challenges - old and new - remain.

KRAS mutations in brown tumor of the jaws in hyperparathyroidism.

Brown tumors are giant cell-rich lesions that result from abnormal bone metabolism in hyperparathyroidism, one of the most common endocrine disorders worldwide. Brown tumors occasionally affect the jaws and, despite well-known clinical and microscopic features, their molecular pathogenesis remains unclear. We investigated the presence of pathogenic activating mutations in TRPV4, FGFR1, and KRAS in a cohort of brown tumors since these have recently been reported in giant-cell lesions of the jaws and non-ossifying fibromas of the bones (FGFR1 and KRAS), which are histologic mimics of brown tumors. We target sequenced 13 brown tumors of the jaws associated with primary or secondary hyperparathyroidism. As mutations in these genes are known to activate the MAPK/ERK signaling pathway, we also assessed the immunostaining of the phosphorylated form of ERK1/2 (pERK1/2) in these lesions. KRAS pathogenic mutations were detected in seven cases (p.G12V n=4, p.G12D n=1, p.G13D n=1, p.A146T n=1). KRAS variants of unknown significance (VUS), p.A134T and p.E37K, were also detected. All samples showed wild-type sequences for FGFR1 and TRPV4 genes. The activation of the MAPK/ERK signaling pathway was demonstrated by pERK1/2 immunohistochemical positivity of the brown tumors´ mononuclear cells. Mutations in KRAS and activation of the MAPK/ERK signaling pathway were detected in brown tumors of hyperparathyroidism of the jaws, expanding the spectrum of giant cell lesions whose molecular pathogenesis involve RAS signaling.

Diagnostic Utility of LEF1 Immunohistochemistry in Differentiating Deep Penetrating Nevi From Histologic Mimics.

Deep penetrating nevi (DPNs) are intermediate grade lesions which have the capacity to recur, metastasize, or progress to melanoma. Differentiating DPN from other melanocytic lesions including blue and cellular blue nevi can be diagnostically challenging, and markers to distinguish these entities can be useful. Mutations of the β-catenin and mitogen-activated protein kinase pathways have recently been elucidated as distinctive of DPN. This pathway can subsequently activate lymphoid enhancer-binding factor 1 (LEF1), a transcription factor shown to facilitate the epithelial-mesenchymal transition to propagate tumorigenesis. Seventy-two cases in total were examined on hematoxylin and eosin sections and with β-catenin and LEF1 immunohistochemistry. This included: DPN (14), cellular blue nevi (19), blue nevi (15), congenital melanocytic nevi (12), and melanoma (12). Nuclear expression of LEF1, present throughout the entire depth of the lesion, was noted in 13/14 (93%) of DPN, 0/19 (0%) of cellular blue nevi, 0/15 (0%) of blue nevi, 1/12 (8%) of congenital melanocytic nevi, and 9/12 (75%) of melanoma cases. Nuclear expression of β-catenin, present throughout the entire depth of the lesion, was noted in 14/14 (100%) of DPN, 0/18 (0%) of cellular blue nevi, 0/15 (0%) of blue nevi, 1/12 (8%) of congenital melanocytic nevi, and 1/12 (8%) of melanoma cases. A majority of congenital melanocytic nevi demonstrated a gradient of LEF1 and β-catenin expression with more intense staining superficially and loss of staining with increasing depth. Deep, uniform nuclear LEF1 combined with β-catenin immunohistochemical staining can be useful in distinguishing DPN from histologic mimics.

Exploring Two Protocols of FISH Using Cytocell SYT-SSX Probe on Formalin Fixed Paraffin Embedded Tissue Sections.

Background:Chromosomal translocation t(X;18)(p11.2;q11.2) is the cytogenetic hallmark of synovial sarcoma and have been identified as an alternative diagnostic strategy in differentiating synovial sarcoma from other histologic mimics. This study was carried out to test the efficacy of two FISH protocols using the SYT-SSX break apart probe from Cytocell. Methodology:Representative paraffin blocks of synovial sarcoma were utilized in this study. FISH study was performed on formalin-fixed paraffin embedded tissue sections using the SYT-SSX break apart probe from Cytocell, to detect two form of SYT-SSX transcript, SYT-SSX1 and SYT-SSX2. FISH protocol, including the hybridization was done following two different protocols, Cytocell FISH protocol and Optimized Dako FISH protocol. Results:Tissue samples subjected to FISH using Cytocell FISH protocol showed the absence of signal corresponding to the probe used. Utilizing Optimized Dako FISH protocol, the two signals (red and green) corresponding to the break-apart probes was detected. These findings suggested that Optimised Dako FISH protocol is more suited for use with the tested probe on paraffin embedded tissues in comparison to Cytocell FISH protocol. Conclusion:Optimised Dako FISH protocol was noted to be more suited for detecting SYT-SSX FISH signals on paraffin embedded tissues in comparison to Cytocell FISH protocol.

Multiple Whole Chromosomal Gains Define Angiomatous Meningiomas and Are Absent From the Tumor Vasculature.

Angiomatous meningioma is a variant with prominent vascularity that can mimic other highly vascularized tumors and present diagnostic challenges. Unlike most meningioma variants, where NF2 gene loss on chromosome 22 is the most common genetic abnormality, angiomatous meningiomas are unique in having multiple whole chromosome gains (polysomies). We analyzed 38 meningiomas, 9 angiomatous (including 2 atypical and 1 anaplastic), and 29 nonangiomatous meningiomas, using array comparative genomic hybridization (aCGH). Angiomatous meningiomas showed multiple chromosomal alterations including polysomies and copy neutral loss of heterozygosity in comparison to nonangiomatous variants. The most frequent gains were of chromosomes 5 and 20 (100% and 89% of cases, respectively); none showed chromosome 22 loss. Furthermore, using fluorescence in situ hybridization we show that the vasculature lacked chromosomal polysomy. While generally benign, we present 2 grade II and the first cytogenetically confirmed grade III angiomatous meningioma, demonstrating their potentially aggressive behavior. Thus, multiple polysomies define angiomatous meningioma and aCGH can distinguish this variant from nonangiomatous meningiomas and other histological mimics in diagnostically challenging cases. Furthermore, the prominent vasculature is not neoplastic and likely induced by angiogenic factors. Together, these findings suggest a distinct tumorigenic pathway in angiomatous meningiomas.

STAT6 Expression in Solitary Fibrous Tumor and Histologic Mimics: a Single Institution Experience.

STAT6 stain has proved to be a good surrogate marker for the genetic alteration (NAB2-STAT6 gene fusion) in solitary fibrous tumor (SFT). This study aims to validate the use of STAT6 rabbit monoclonal antibody in differentiating SFT from its histologic mimics. Forty-five cases of SFT and 110 cases from 9 other spindle cell tumors were collected for STAT6 immunostaining. Positive nuclear STAT6 staining was present in all 45 SFT cases (100% sensitivity). No nuclear staining was identified in other spindle cell neoplasms (0/13, dedifferentiated liposarcoma; 0/17, synovial sarcoma; 0/16, malignant peripheral nerve sheath tumors; 0/25, undifferentiated pleomorphic sarcoma; 0/10, dermatofibrosarcoma protuberans; 0/9, low-grade fibromyxoid sarcoma; 0/6, angiofibroma; 0/5, deep fibromatosis; 0/9, gastrointestinal tumor). The STAT6 staining in SFT was usually diffuse (5+ in 19 cases; 4+ in 17 cases) and strong (40 cases). Monoclonal STAT6 stain is highly sensitive and specific for SFTs and particularly useful in the diagnosis of difficult SFT cases.

A Novel SS18-SSX Fusion-specific Antibody for the Diagnosis of Synovial Sarcoma.

Synovial sarcoma (SS), an aggressive soft tissue sarcoma with a predilection for the extremities of young adults, harbors the pathognomonic t(X;18)(p11;q11) translocation, resulting in SS18-SSX rearrangements. SS includes monophasic, biphasic, and poorly differentiated variants, which show considerable histologic overlap with a range of other tumor types, making the diagnosis challenging on limited biopsies. Immunohistochemistry (IHC) is routinely used in the differential diagnosis; however, presently available markers lack specificity. Thus, cytogenetic or molecular genetic techniques are often employed to confirm the diagnosis. Here, we report the development and characterization of 2 novel antibodies: an SS18-SSX fusion-specific antibody (E9X9V, designed to the breakpoint) as well as an SSX-specific antibody (E5A2C, designed to the SSX C-terminus). We validated the selectivity and specificity of the antibodies using immunoblotting, immunoprecipitation, and chromatin immunoprecipitation followed by next-generation sequencing in SS cell lines and demonstrated that both antibodies capture SS18-SSX on chromatin at established target sites (eg, TLE1 and BCL2) genome-wide. Using IHC in whole sections from 400 tumors including 100 genetically confirmed cases of SS and 300 histologic mimics, the SS18-SSX fusion-specific antibody revealed strong diffuse nuclear staining in 95 of 100 (95%) SS cases, whereas none of the 300 control tumors showed any staining. The SSX antibody showed strong diffuse nuclear staining in all 100 (100%) SS cases; 13 (4%) of the 300 other tumors were also positive, 5 of which displayed >50% nuclear staining. In summary, a novel SS18-SSX fusion-specific antibody is highly sensitive (95%) and specific (100%) for SS, and an antibody to the SSX C-terminus is also highly sensitive (100%), but slightly less specific (96%). IHC using the SS18-SSX antibody could replace molecular genetic or cytogenetic testing in most cases, and these reagents together will also provide the research community with valuable tools for further biochemical and genomic interrogation of the SS18-SSX fusion protein.

The Value of H3K27me3 Immunohistochemistry in Differentiating Malignant Peripheral Nerve Sheath Tumour with Its Histologic Mimickers.

Background:Diagnosis of malignant peripheral nerve sheath tumor (MPNST) is rather challenging due to its divergent morphologic heterogeneity and lack of specific ancillary test. The emergence of H3K27 trimethylation (H3K27me3) as a new immunohistochemistry (IHC) marker for MPNST have recently available to assist pathologists in differentiating MPNST from other histologic mimics. We aim to study the expression pattern of H3K27me3 in MPNST and its histologic mimickers and their association with the clinicopathological data. Methodology:A total of 59 benign and malignant spindle cell tumours (18 MPNST and 41 of its histologic mimickers which included 10 schwannoma, 13 neurofibroma, 4 synovial sarcoma, 3 fibrosarcoma, 2 gastrointestinal stromal tumour (GIST), 4 leiomyosarcoma, 1 spindle cell liposarcoma, 1 solitary fibrous tumour, 2 low grade fibromyxoid sarcoma and 1 unclassified spindle cell sarcoma), diagnosed from January 1998 to April 2018 in Hospital Universiti Sains Malaysia (HUSM) were tested for H3K27me3 by IHC. The MPNST histological grade was assessed based on the French Fe’de’ ration Nationale des Centres de LutteContre le Cancer (FNCLCC) for 3 tiers system (low grade, intermediate grade and high grade). The clinicopathological data were retrieved from the patients’ record. Results:A total of 61.1% (11/18 MPNST) showed loss of H3K27me3 expression which is statistically significant as compared to its histologic mimics (p<0.001). Similar findings (p=0.026) were also observed in high grade MPNST (81.8%), intermediate grade MPNST (100%) and 0% in low grade MPNST. Conclusion: H3K27me3, combined with other panel of markers, is useful in MPNST diagnosis to differentiate it from the histological mimickers.

Abstract P1-21-02: Distinct methylation and copy number alteration patterns in phyllodes tumors of the breast and its mimics

Abstract Background: Phyllodes tumor (PT), a rare fibroepithelial neoplasm of the breast, poses a significant diagnostic challenge in breast pathology, as there are no generally accepted histological criteria or cutoffs to unambiguously differentiate PT variants (benign, borderline, malignant) and fibroadenomas (FA) of the breast. In recent years, genome-wide DNA methylation analysis has gained wide interest as an objective tool to distinguish all sorts of neoplasms based on their individual methylation signatures. For brain tumors, methylation-based classification already outperforms classification by conventional histology and has led to changes in the WHO tumor classification. Materials and Methods: We have so far analyzed fresh frozen as well as formalin-fixed, paraffin-embedded tissue samples of PT (n=31) and FA (n=2) on Illumina Infinium Methylation EPIC bead chips. The resulting data were preprocessed, normalized, mapped to the genome and converted into beta values. Top differentially methylated probes were determined by the calculation of standard deviations across the dataset. Such filtered sets of methylation beta values were then compared by a dimension reduction algorithm alongside TCGA methylome datasets as well as collections from GEO and the entire diagnostic database of our institute (n=14342). In parallel, the genome-wide copy number alterations were calculated from array data for each case. Results: In analogy to other tumor entities included in our reference cohort (brain tumors, sarcomas, carcinomas, melanomas), PT and FA of the breast show distinct DNA methylation patterns that contain a breast-specific signature as well as tumor-derived patterns. Their methylomes are distinct from breast adenocarcinoma as well as from healthy breast tissue. Two distinct groups within the PT/FA spectrum were identified so far: One group contains a high fraction of histologically malignant PT and is enriched for complex copy number alterations while the other group, also containing the currently two included fibroadenomas and, features less prominent to no copy number variants and a higher similarity to the overall normal breast tissue methylation signature. Conclusion: The distinct methylation signatures of the histological PT/FA spectrum will not only allow the diagnostic discrimination of PTs from histological mimics such as FA or carcinomas, but will also enable the distinction of benign, borderline and malignant PTs, thus paving the way to an optimized prognostic patient stratification and clinical management. Citation Format: Simone Muenst, Tatjana Vlajnic, Savas Deniz Soysal, Stefan Frank, Jürgen Hench. Distinct methylation and copy number alteration patterns in phyllodes tumors of the breast and its mimics [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-21-02.

3. Angiofibroma of soft tissue: A case series

Background: Angiofibroma of soft tissue (AFST) is a recently described benign soft tissue neoplasm of adults and children characterised by low-grade spindle cells with a myxoid or collagenous stroma bearing very prominent small vasculature.1 There is a characteristic but non-diagnostic immunohistochemical pattern.2 A characteristic AHRR-NCOA2 fusion gene secondary to t(5;8)(p15;q13) is present in approximately two thirds of cases.3 Aims: We present three cases of AFST encountered at RPAH Tissue Pathology in order to outline and explore the clinical, macroscopic, histopathologic, immunohistochemical, and cytogenetic features of this tumour. Methods: Three cases underwent histopathological and immunohistochemical analysis, as well as presentation at a multidisciplinary soft tissue meeting. One case underwent karyotyping. Results and conclusions: All three tumours were well-circumscribed encapsulated soft tissue spindle cell tumours of the lower limbs with prominent vasculature and myxoid areas. All cases were negative for vascular markers and SMA (blood vessels highlighted only), as well as negative for S100, pancytokeratin, and MUC4. One case had scattered atypical cells interpreted as degenerative atypia; focal atypia has been reported as an infrequent feature of AFST.1,2 One case underwent cytogenetic analysis, revealing a t(5;8)(p14;q13) translocation. The cases are discussed, making comparisons to the available literature. Histologic mimics and the utility of cytogenetics and fluorescence in situ hybridisation are discussed.

Pattern-Specific Loss of Desmoplakin I and II Immunoreactivity in Erythema Multiforme and its Variants: A Possible Aid in Histologic Diagnosis.

Erythema multiforme (EM), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN) comprise a family of mucocutaneous diseases associated with significant morbidity and mortality. Previous studies have confirmed the presence of autoantibodies to desmoplakin (Dp) I and II in patients with EM, SJS, and TEN. Truncated Dp production leads to characteristic changes visible on light microscopy: perinuclear clumping of keratin filaments and dyskeratotic keratinocyte. Based on these observations, the question arises as to whether a loss of Dp immunoreactivity in skin biopsies could serve as a diagnostic marker of EM, SJS, and TEN. This study analyzed Dp immunostaining patterns in 20 patients with EM or SJS/TEN. To assess the specificity of this approach, Dp immunostaining was also performed on specimens from patients with 5 potential histologic mimics of EM, SJS, and TEN. All of the samples from patients with EM, SJS, and TEN demonstrated absent or markedly diminished staining for Dp. A χ test demonstrated a statistically significant difference between the staining patterns in EM, SJS, and TEN and each of the other diagnostic groups that were investigated. This is the first report demonstrating statistically significant specificity of Dp staining patterns in EM/SJS/TEN as compared with other interface dermatitides.

Tissue Microarray Based Immunohistochemical study of TLE1 in Synovial Sarcoma and its Histologic Mimics

Tissue Microarray Based Immunohistochemical study of TLE1 in Synovial Sarcoma and its Histologic Mimics

Non-neoplastic urothelial lesions and mimickers of malignancy: Take Cognizance - Avoid negligence

Background: The differential diagnosis of urothelial neoplasms also includes several histologic mimics, the importance of which cannot be overemphasized since misdiagnosis could have serious clinical and prognostic implications. Aims: To study the variety of non-neoplastic lesions of the urothelial tract that could potentially be confused with urothelial neoplasms. Material and Methods: A retrospective and prospective study of five years duration was done at a tertiary care hospital including 55 cases of non-neoplastic urothelial lesions. Results were analysed using SPSS22. Results: Out of 43.62% of cases clinically suspicious for malignancy, majority (18.18%) were florid Proliferation of von brunn nests. Out of 56.3% cases clinically non-suspicious for malignancy majority were nonspecific cystitis (12.72%). The nonneoplastic lesions were more common in males (83.3%). The mean age was 45.6 yrs. Conclusions: Diagnostic awareness of salient histomorphologic features of the benign mimickers of urothelial neoplasms is critical to avoid rendering false positive diagnoses of malignancy.

Ewing Sarcoma in Older Adults: A Clinicopathologic Study of 50 Cases Occurring in Patients Aged ≥40 Years, With Emphasis on Histologic Mimics.

Objective. We explore the clinicopathologic features of Ewing sarcoma (ES) presenting in older adulthood. Methods. Cases of molecularly confirmed ES arising in patients aged ≥40 years were evaluated. Results. Fifty patients were identified (33 males/17 females; 41-86 years). The majority of tumors (41) arose at extraskeletal sites, while 9 were bone primaries. Twenty-eight cases showed nested architecture, while the remaining cases showed sheet-like growth. Tumor cytology was categorized as conventional (n = 39), crushed (n = 5), clear cell (n = 4), rhabdoid (n = 3), and epithelioid (n = 2). Fifty percent had necrosis, while rosettes were noted in 1 case. Immunostains performed ranged from 1 to 28 (median = 10). Follow-up (n = 43, 1-147 months) revealed 15 patients with metastasis. Conclusion. Although rare, ES should be considered in the differential diagnosis for round cell malignancies in older adult patients. In this cohort, ES is most often extraskeletal, and may show unusual morphologic features, closely simulating more common neoplasms in this age group.

Pan-Trk immunohistochemistry is a sensitive and specific ancillary tool for diagnosing secretory carcinoma of the salivary gland and detecting ETV6-NTRK3 fusion.

Secretory carcinoma (SC) of the salivary gland typically harbours ETV6-NTRK3 fusion, which can be utilised clinically to assist with diagnosis. Pan-Trk inhibitor therapy has demonstrated drastic responses in patients with NTRK-translocated tumours, including SC. Pan-Trk immunohistochemistry (IHC) is emerging as a sensitive and specific tool for detecting NTRK1, NTRK2 and NTRK3 fusions in various cancers. We aimed to establish the specificity and sensitivity of pan-Trk IHC in diagnosing SC and detecting ETV6-NTRK3 fusion. A literature review on the utility of pan-Trk IHC was conducted. Pan-Trk IHC was performed on 83 salivary gland neoplasms (29 SCs and 54 non-SCs). ETV6-NTRK3 fusion status was established in 25 cases. With any staining (nuclear or cytoplasmic) as a positive threshold, the sensitivity and specificity of pan-Trk IHC were 90% and 70% in diagnosing SC, and 100% and 0% in detecting NTRK3 fusion. When only pan-Trk nuclear staining was considered as positive, the sensitivity and specificity were 69% and 100% in diagnosing SC, and 92% and 100% in detecting NTRK3 fusion. Nuclear pan-Trk IHC is highly specific for SC diagnosis, with a specificity approaching 100%, making it a useful and precise diagnostic tool for differentiating SC from its histological mimics. On the other hand, any pan-Trk staining (nuclear or cytoplasmic) is highly sensitive for SC, and can serve as an attractive, cheap, fast and accessible screening tool for selecting patients to undergo confirmative molecular testing for clinical trials using TRK inhibitors.

Frequency of Transducer-like Enhancer of Split 1 Immunohistochemical Expression in Synovial Sarcoma: An Institution-based Cross-sectional Study.

BackgroundSoft-tissue sarcomas comprise a diverse group of sarcomas with characteristic histologic features. However, histology alone is not adequate for a definitive diagnosis for many tumors. In such cases, immunohistochemistry (IHC) plays a key role in determining the line of differentiation and exact characterization. Transducer-like enhancer of split 1 (TLE1) has been recently described as a novel marker for synovial sarcoma (SS). Its high sensitivity and specificity make it a potential marker that distinguishes SS from histologic mimics such as malignant peripheral nerve sheath tumor (MPNST), Ewing's sarcoma (ES), and fibrosarcomatous dermatofibrosarcoma protuberans (FS-DFSP). The objective of our study was to assess the frequency of TLE1 immunohistochemical expression on SS cases of various subtypes.MethodsThis cross-sectional study was conducted at the Department of Histopathology, Aga Khan University, Karachi, Pakistan from February 3, 2018 to February 10, 2019. Tissue samples of 89 SS cases were selected for this study. Tumor sections were stained with hematoxylin and eosin (H&E), cytokeratin AEI/AE3 (CKAE1/AE3), epithelial membrane antigen (EMA), and TLE1 immunohistochemical stain. TLE1 expression was assessed based on the Remmele scoring system.ResultsTissue samples of 89 SS cases were processed for the study. Mean (±) standard deviation (SD) of age was 25 (±7.36) years. Male:female ratio was 1.1:1. Of the 89 SS cases, 42 (47.2%) were monophasic, six (6.7%) were biphasic, and 41 (46.1%) were poorly differentiated. All the 89 cases showed positivity for TLE1 immunostain: 86 (96.6%) cases showed strong positivity, one (1.1%) case showed moderate expression, and two (2.2%) showed weak positivity.ConclusionThis study shows that TLE1 is a highly sensitive immunostain for SS irrespective of the histologic type. However, it may show weak-to-moderate staining in poorly differentiated types. No statistically significant association was seen with respect to age group, gender, or type of SS.