Histopathology最新文献

{"title":"Nonneoplastic and neoplastic sclerosing lesions of the breast","authors":"Gulisa Turashvili","doi":"10.1111/his.15252","DOIUrl":"10.1111/his.15252","url":null,"abstract":"<p>Sclerosing lesions of the breast encompass a spectrum of benign and malignant entities and often pose a diagnostic challenge. Awareness of key morphologic features and pitfalls in the assessment of morphology and immunophenotype is essential to avoid over- or underdiagnosis and ensure optimal clinical management. This review summarizes nonneoplastic sclerosing lesions such as radial scar/complex sclerosing lesion, sclerosing adenosis, sclerosing intraductal papilloma, sclerosing variants of ductal adenoma and nipple adenoma, and fibroadenoma with extensive sclerosis, including their clinical presentation, characteristic morphology, differential diagnostic considerations, appropriate immunohistochemical work-up, when needed, and the clinical significance. In addition, atypical or neoplastic entities (such as atypical ductal hyperplasia, ductal carcinoma <i>in situ,</i> low-grade adenosquamous carcinoma, and fibromatosis-like metaplastic carcinoma) that can involve these sclerosing lesions are also briefly discussed.</p>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141456443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diandric triploid partial mole versus digynic nonmolar triploidy: is morphological assessment sufficient for the diagnostic distinction?","authors":"Agnes Nagy, Na Niu, Tong Sun, Natalia Buza, Pei Hui","doi":"10.1111/his.15247","DOIUrl":"https://doi.org/10.1111/his.15247","url":null,"abstract":"AimsDiagnostic separation of diandric triploid gestation, i.e. partial mole from digynic triploid gestation, is clinically relevant, as the former may progress to postmolar gestational trophoblastic neoplasia. The aim of the study was to investigate if the combination of abnormal histology combined with ploidy analysis‐based triploidy is sufficient to accurately diagnose partial mole.Methods and ResultsA genotype–phenotype correlation study was undertaken to reappraise histological parameters among 20 diandric triploid gestations and 22 digynic triploid gestations of comparable patient age, gestational weeks, and clinical presentations. Two villous populations, irregular villous contours, pseudoinclusions, and syncytiotrophoblast knuckles, were common in both groups. Villous size ≥2.5 mm, cistern formation, trophoblastic hyperplasia, and syncytiotrophoblast lacunae were significantly more common in the partial hydatidiform mole. Cistern formation had the highest positive predictive value (PPV) (93%) and highest specificity (96%) for diandric triploid gestation, although the sensitivity was 70%. Cistern formation combined with villous size ≥2.5 mm or trophoblast hyperplasia or syncytiotrophoblast lacunae had 100% specificity and PPV, but a marginal sensitivity of 60%–65%. A moderate interobserver agreement (Kappa = 0.57, Gwet's AC1 = 0.59) was achieved among four observers who assigned diagnosis of diandric triploid gestation or digynic triploidy solely based on histology.ConclusionsNone of histological parameters are unique to either diandric triploid gestation or digynic triploid gestation. Cistern formation is the most powerful discriminator, with 93% PPV and 70% sensitivity for diandric triploid gestation. While cistern formation combined with either trophoblastic hyperplasia or villous size ≥2.5 mm or syncytiotrophoblast lacunae has 100% PPV and specificity for diandric triploid gestation, the sensitivity is only 60% to 65%. Therefore, in the presence of triploidy, histological assessment is unable to precisely classify 35% to 40% of diandric triploid gestations or partial moles.","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141520304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oral and oropharyngeal NUT carcinoma: a multicentre screening study of poorly differentiated oral cancer","authors":"Zuoyu Liang, Yaling Tang, Ci Li, Gang Xie, Min Chen, Ping Zhou, Mengqian Li, Yan Wang, Xuejiao Yu, Yuan Tang, Jing Wang, Ji Bao, Lili Jiang, Weiya Wang","doi":"10.1111/his.15245","DOIUrl":"https://doi.org/10.1111/his.15245","url":null,"abstract":"Background and aimsNuclear protein testis (NUT) carcinoma (NC) is a rare and highly aggressive tumour characterised by chromosomal rearrangement of the nuclear protein testis family member 1 (<jats:italic>NUTM1</jats:italic>) gene, also known as the NUT gene. NC occurs mainly in the head and neck, mediastinum and lung. In general, primary NC in the oral cavity is extremely rare and reported sporadically.MethodsA total of 111 formalin‐fixed and paraffin‐embedded specimens of poorly differentiated oral and oropharyngeal tumours were collected from 10 hospitals. NUT protein IHC staining was performed on these samples, and fluorescence <jats:italic>in‐situ</jats:italic> hybridisation (FISH) and RNA sequencing detection were further carried out for NUT IHC‐positive cases.ResultsThe expression of NUT protein in tumour cells was detected in five cases (five of 111, 4.5%). The tumours in these cases were located in the oral floor, lip, base of the tongue, gingiva and hard palate. FISH detection results showed <jats:italic>BRD4::NUT</jats:italic> rearrangement in three patients and a non‐<jats:italic>BRD4::NUT</jats:italic> rearrangement pattern in two patients. RNA sequencing results confirmed <jats:italic>BRD4::NUT</jats:italic> rearrangement in two cases.ConclusionsTo our knowledge, this is the first and largest retrospective study of oral NC, and we found that NC is easily misdiagnosed as poorly differentiated oral squamous cell carcinoma (SCC) or poorly differentiated carcinoma. The morphology and immunophenotype of four NC cases were similar to SCC, and abrupt keratinisation was observed in three cases. Therefore, it is necessary to detect NUT protein for NC screening in oral malignant tumours with these morphologies, especially for young patients who are more likely to be misdiagnosed with other types of cancer.","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141520305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ki-67 distribution, α-methylacyl-CoA racemase (AMACR) expression and mucin phenotypes are associated with non-polypoid growth in ulcerative colitis-associated neoplasia","authors":"Soh Okano,&nbsp;Masayuki Fukata,&nbsp;Takashi Murakami,&nbsp;Shuko Nojiri,&nbsp;Makoto Kodama,&nbsp;Keiko Abe,&nbsp;Tetsuo Yamana,&nbsp;Tsuyoshi Saito,&nbsp;Takashi Yao","doi":"10.1111/his.15243","DOIUrl":"10.1111/his.15243","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Ulcerative colitis-associated neoplasia (UCAN) is characterised by multifocal tumourigenesis. A wide range of metachronous lesions have been reported to occur after endoscopic treatment of UCAN, which suggests the development of sporadic tumours in lesions treated as UCAN. Therefore, we aimed to evaluate differences of immunohistochemistry (IHC) in features and clinicopathological characteristics of intramucosal lesions in patients with ulcerative colitis (UC).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and results</h3>\u0000 \u0000 <p>We examined 35 intramucosal lesions resected for carcinoma or dysplasia by total colectomy from patients with UC and 71 sporadic adenomas (SAs) endoscopically resected from patients without UC. UC lesions were divided into the conventional UCAN group, defined as p53 mutant pattern and normal expression of β-catenin, and the non-conventional UCAN group, defined as the rest. Ki-67 distribution, α-methylacyl-CoA racemase (AMACR) expression and mucin phenotypes were compared using IHC, and clinicopathological characteristics were investigated. Conventional and non-conventional UCAN lesions were located in the left colon and rectum. Relative to the SA lesions, UCAN lesions occurred in much younger patients and exhibited more frequent basal distribution of Ki-67 in tumour crypts. Conventional UCAN lesions tended to be non-polyploid and exhibited a higher frequency of normal AMACR expression than SA lesions. UC lesions were heterogeneous—only two of the eight patients with multiple lesions had lesions (both non-conventional UCAN lesions) exhibiting concordant IHC staining features.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The basal pattern of Ki-67 distribution, normal expression of AMACR and a non-intestinal mucin phenotype were determined as characteristic features suggestive of UCAN. Non-polypoid growth was another a key feature of UCAN.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141520303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Morphoea presenting histopathologically as mycosis fungoides: an illustrative series of four cases","authors":"Ahmed Kazmi,&nbsp;Teo Feuerhake,&nbsp;Anoud Zidan,&nbsp;John Frewen,&nbsp;Andrew Carmichael,&nbsp;Janet Ross,&nbsp;Catherine H Orteu,&nbsp;Eduardo Calonje","doi":"10.1111/his.15246","DOIUrl":"10.1111/his.15246","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>There have been exceptional reports of morphoea presenting with epidermal changes overlapping histopathologically with cutaneous T cell lymphoma of the mycosis fungoides type (MF). This phenomenon gives rise to an ambiguous clinicopathological scenario in which distinguishing these conditions may be challenging. The aim of this study is to characterise the clinical, histopathological and molecular findings of this phenomenon through a case series.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and results</h3>\u0000 \u0000 <p>Four patients with classical clinical presentation of morphoea but unusual histopathology displaying typical findings of morphoea, together with intra-epidermal CD8 positive lymphocytes indistinguishable from MF, were identified. The clinical phenotypes of morphoea were varied, and they all presented early in the active phase of the disease. They all exhibited intra-epidermal lymphocytes with tagging and cytological atypia. Pautrier-like microabscesses were also seen. Using molecular analysis, two cases showed clonal TCR gene rearrangement. Follow-up of all cases has been consistent with classical morphoea.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Early morphoea can seldom present with atypical clonal intra-epidermal lymphocytes indistinguishable from MF. The fact that these changes can occur in several different clinical subtypes of morphoea raises the possibility that this could be a pattern of inflammation in early disease more common than currently appreciated.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141418731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SATB2-rearrangement in a case of juvenile trabecular ossifying fibroma, expanding the spectrum of SATB2-rearranged neoplasia","authors":"Raul Perret,&nbsp;Melissa Alame,&nbsp;Isabelle Hostein,&nbsp;Isabelle Soubeyran,&nbsp;Rihab Azmani,&nbsp;François Le Loarer,&nbsp;Nicolas Baldini,&nbsp;Claire Castain","doi":"10.1111/his.15240","DOIUrl":"10.1111/his.15240","url":null,"abstract":"","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141418732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Detection of GRM1 gene rearrangements in chondromyxoid fibroma: a comparison of fluorescence in-situ hybridisation, RNA sequencing and immunohistochemical analysis.","authors":"Dianne Torrence, Josephine K Dermawan, Yanming Zhang, Chad Vanderbilt, Sinchun Hwang, Kerry Mullaney, Achim Jungbluth, Mamta Rao, Kate Gao, Purvil Sukhadia, Konstantinos Linos, Narasimhan Agaram, Meera Hameed","doi":"10.1111/his.15248","DOIUrl":"https://doi.org/10.1111/his.15248","url":null,"abstract":"<p><strong>Aims: </strong>Chondromyxoid fibroma (CMF) is a rare, benign bone tumour which arises primarily in young adults and is occasionally diagnostically challenging. Glutamate metabotropic receptor 1 (GRM1) gene encodes a metabotropic glutamate receptor and was recently shown to be up-regulated in chondromyxoid fibroma through gene fusion and promoter swapping. The aim of this study was to interrogate cases of CMF for the presence of GRM1 gene rearrangements, gene fusions and GRM1 protein overexpression.</p><p><strong>Methods and results: </strong>Selected cases were subjected to testing by fluorescent in-situ hybridisation (FISH) with a GRM1 break-apart probe, a targeted RNA sequencing method and immunohistochemical study with an antibody to GRM1 protein. Two cases were subjected to whole transcriptomic sequencing. In 13 of 13 cases, GRM1 protein overexpression was detected by immunohistochemistry using the GRM1 antibody. Of the 12 cases successfully tested by FISH, nine of 12 showed GRM1 rearrangements by break-apart probe assay. Targeted RNA sequencing analysis did not detect gene fusions in any of the eight cases tested, but there was an increase in GRM1 mRNA expression in all eight cases. Two cases subjected to whole transcriptomic sequencing (WTS) showed elevated GRM1 expression and no gene fusions.</p><p><strong>Conclusion: </strong>GRM1 gene rearrangements can be detected using FISH break-apart probes in approximately 75% of cases, and immunohistochemical detection of GRM1 protein over-expression is a sensitive diagnostic method. The gene fusion was not detected by targeted RNA sequencing, due most probably to the complexity of fusion mechanism, and is not yet a reliable method for confirming a diagnosis of CMF in the clinical setting.</p>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141418730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The spectrum of oestrogen receptor expression in endometrial carcinomas of no specific molecular profile","authors":"Mona Alafraidi,&nbsp;Lynn Hoang,&nbsp;Brooke E. Howitt,&nbsp;Teri A. Longacre,&nbsp;Jessica N. McAlpine,&nbsp;Amy Jamieson,&nbsp;Naveena Singh,&nbsp;C Blake Gilks,&nbsp;Jennifer Pors","doi":"10.1111/his.15241","DOIUrl":"10.1111/his.15241","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Decreased oestrogen receptor (ER) expression is a marker of poor prognosis in endometrial carcinomas (EC) of no specific molecular profile (NSMP), but the optimal cut-off to separate high-risk ‘low ER’ versus low-risk ‘high ER’ expression has not been defined. Here we characterised the distribution of ER staining in a cohort of ECs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and results</h3>\u0000 \u0000 <p>Biopsy specimens from 120 cases of NSMP EC were stained for ER and assigned an Allred score. In 66 additional cases ER staining of matched biopsy and hysterectomy were compared. Twelve of 120 tumours had an Allred score of 0–3, including three endometrioid carcinomas (EEA) (one G1, two G3), four clear cell carcinomas (CCC), two mesonephric-like adenocarcinoma (MLA) and one each of: gastric-type adenocarcinoma, carcinosarcoma and endometrial carcinoma NOS. Three had Allred scores of 4–5: two MLA and one high-grade carcinoma with yolk sac differentiation. Five had Allred scores of 6: four EEA (one G1, one G2, two G3) and one mixed clear cell and endometrioid carcinoma. The remaining 100 tumours with Allred scores ≥ 7 were all EEA (66 G1, 28 G2, five G3 and one grade unknown). Comparing the biopsy versus hysterectomy ER staining (<i>n</i> = 66), the results were within a single Allred score point, except two cases with strong diffuse expression in the biopsy (Allred 8) and moderate expression in the hysterectomy (Allred 5).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Most NSMP ECs (&gt; 80%) show high ER expression (Allred score ≥ 7). All non-endometrioid carcinomas and a few endometrioid carcinomas had lower ER expression (Allred score ≤ 6) or were completely negative.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/his.15241","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141418733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nottingham prognostic x (NPx): a risk stratification tool in ER-positive HER2-negative breast cancer: a validation study","authors":"Ayat G Lashen,&nbsp;Michael Toss,&nbsp;Islam Miligy,&nbsp;Emma Rewcastle,&nbsp;Umay Kiraz,&nbsp;Emiel A M Janssen,&nbsp;Andrew R Green,&nbsp;Cecily Quinn,&nbsp;Ian Ellis,&nbsp;Emad A. Rakha","doi":"10.1111/his.15234","DOIUrl":"10.1111/his.15234","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>In this study, we validate the use of Nottingham Prognostic x (NPx), consisting of tumour size, tumour grade, progesterone receptor (PR) and Ki67 in luminal BC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and methods</h3>\u0000 \u0000 <p>Two large cohorts of luminal early-stage BC (<i>n</i> = 2864) were included. PR and Ki67 expression were assessed using full-face resection samples using immunohistochemistry. NPx was calculated and correlated with clinical variables and outcome, together with Oncotype DX recurrence score (RS), that is frequently used as a risk stratifier in luminal BC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In the whole cohort, 38% of patients were classified as high risk using NPx which showed significant association with parameters characteristics of aggressive tumour behaviour and shorter survival (<i>P</i> &lt; 0.0001). NPx classified the moderate Nottingham Prognostic Index (NPI) risk group (<i>n</i> = 1812) into two distinct prognostic subgroups. Of the 82% low-risk group, only 3.8% developed events. Contrasting this, 14% of the high-risk patients developed events during follow-up. A strong association was observed between NPx and Oncotype Dx RS (<i>P</i> &lt; 0.0001), where 66% of patients with intermediate risk RS who had subsequent distant metastases also had a high-risk NPx.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>NPx is a reliable prognostic index in patients with luminal early-stage BC, and in selected patients may be used to guide adjuvant chemotherapy recommendations.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/his.15234","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141310613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ALK-rearranged, CD34-positive spindle cell neoplasms resembling dermatofibrosarcoma protuberans: a study of seven cases","authors":"Shruti Agrawal,&nbsp;Baptiste Ameline,&nbsp;Andrew L Folpe,&nbsp;Elizabeth Azzato,&nbsp;Caroline Astbury,&nbsp;Thomas Mentzel,&nbsp;Calvin Knapp,&nbsp;Arno Rütten,&nbsp;David Creytens,&nbsp;William Sukov,&nbsp;Daniel Baumhoer,&nbsp;Steven D Billings,&nbsp;Karen J Fritchie","doi":"10.1111/his.15239","DOIUrl":"10.1111/his.15239","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>The majority of dermatofibrosarcoma protuberans (DFSP) harbour <i>PDGFB</i> or <i>PDGFD</i> rearrangements. We encountered ALK expression/rearrangement in a <i>PDGFB/D</i>-negative CD34-positive spindle cell neoplasm with features similar to DFSP, prompting evaluation of <i>ALK</i>-rearrangements in DFSP and plaque-like CD34-positive dermal fibroma (P-LDF).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and Results</h3>\u0000 \u0000 <p>We searched the archives of academic institutions for cases previously coded as DFSP and P-LDF. NGS-naïve or <i>PDGFB</i>-negative DFSP were screened for ALK (clone D5F3) expression by immunohistochemistry. NGS or <i>ALK</i> FISH was performed on ALK-positive cases. Methylome profiling studies were performed and compared with conventional DFSP. One case of “DFSP” and two “P-LDF” with ALK expression were identified from the archives, while four cases were detected prospectively. These seven cases (6F:1M; 8 months to 76 years) arose in the dermis of the arm (two), scalp, eyelid, thigh, abdomen, and shoulder and ranged from 0.4 to 4.2 cm. Tumours were composed of spindled cells and displayed a storiform growth pattern. Cytologic atypia was absent, and mitotic figures were scarce (0–2/10 HPFs, high power fields). The lesional cells were diffusely positive for CD34 and ALK and negative for S100 protein. By NGS (<i>n</i> = 5), <i>ALK</i> fusion partners included <i>DCTN1</i> (2), <i>PLEKHH2</i>, and <i>CLIP2</i> in DFSP-like cases and <i>FLNA</i> in P-LDF-like lesions. <i>ALK</i> FISH was positive in one (of two) cases previously labelled P-LDF. Methylome profiling of two (of three) <i>ALK</i>-rearranged DFSP-like tumours showed clustering with conventional DFSP in the UMAP dimension reduction plot. To date, no tumour has recurred (<i>n</i> = 2; 26, 27 months).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>We describe a cohort of novel <i>ALK</i>-rearranged tumours with morphologic features similar to DFSP.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/his.15239","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141310612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}