Human pathology最新文献

{"title":"Information for Authors","authors":"","doi":"10.1016/S0046-8177(24)00098-4","DOIUrl":"https://doi.org/10.1016/S0046-8177(24)00098-4","url":null,"abstract":"","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"148 ","pages":"Page iv"},"PeriodicalIF":3.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141294527","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":"“Percentage” and “size” of residual viable tumor in lymph node, the performance in estimating pathologic response of lymph node in non-small cell lung cancer treated with neoadjuvant chemoimmunotherapy","authors":"Wei Sun ,&nbsp;Linlin Qu ,&nbsp;Jianghua Wu ,&nbsp;Xinying Liu ,&nbsp;Chenglong Wang ,&nbsp;Yumeng Jiang ,&nbsp;Yuliang Liu ,&nbsp;Mailin Chen ,&nbsp;Xun Wang ,&nbsp;Dongmei Lin","doi":"10.1016/j.humpath.2024.05.009","DOIUrl":"10.1016/j.humpath.2024.05.009","url":null,"abstract":"<div><p>There is no universally accepted method for evaluating lymph node metastasis (LNM) in non-small cell lung cancer (NSCLC) after neoadjuvant chemoimmunotherapy. Different protocols recommend evaluating the percentage of residual viable tumor (RVT%) and metastatic tumor size (MTS). Our aim was to determine the prognostic significance of RVT% and MTS, and identify the more effective parameter for pathological evaluating LNM. Two independent cohorts were collected (derivation, n = 84; external validation, n = 42). All patients exhibited metastatic cancer or treatment response in lymph nodes post-surgery. In the derivation cohort, we assessed the mean and largest values of MTS and RVT% in LNM, estimating their optimal cutoffs for event-free survival (EFS) using maximally selected rank statistics. Validation was subsequently conducted in the external validation cohort. The quality of prognostic factors was evaluated using the Area Under Curve (AUC). A positive association was identified between RVT% and MTS, but an absolute association could not be conclusively established. In the derivation cohort, neither the largest MTS (cutoff = 6 mm, <em>p</em> = 0.28), largest RVT% (cutoff = 75%, <em>p</em> = 0.23), nor mean RVT% (cutoff = 55%, <em>p</em> = 0.06) were associated with EFS. However, mean MTS (cutoff = 4.5 mm) in lymph nodes was statistically associated with EFS (<em>p</em> = 0.018), validated by the external cohort (<em>p</em> = 0.017). The prognostic value of MTS exceeded that of ypN staging in both cohorts, as evidenced by higher AUC values. The mean value of MTS can effectively serve as a parameter for the pathological evaluation of lymph nodes, with a threshold of 4.5 mm, closely linked to EFS. Its prognostic value outperforms that of ypN staging.</p></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"149 ","pages":"Pages 1-9"},"PeriodicalIF":3.3,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141087663","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":"Comparison of a modified staging system with 8th edition AJCC criteria in a North American cohort of pT2/pT3 HPV-negative penile squamous cell carcinoma","authors":"Burak Tekin ,&nbsp;Akash P. Sali ,&nbsp;Santosh Menon ,&nbsp;John C. Cheville ,&nbsp;Carin Y. Smith ,&nbsp;Sarah M. Jenkins ,&nbsp;Surendra Dasari ,&nbsp;Elizabeth Ann L. Enninga ,&nbsp;Andrew P. Norgan ,&nbsp;Antonio L. Cubilla ,&nbsp;Rumeal D. Whaley ,&nbsp;Loren Herrera Hernandez ,&nbsp;Rafael E. Jimenez ,&nbsp;Joaquin J. Garcia ,&nbsp;R. Houston Thompson ,&nbsp;Bradley C. Leibovich ,&nbsp;R. Jeffrey Karnes ,&nbsp;Stephen A. Boorjian ,&nbsp;Lance C. Pagliaro ,&nbsp;Lori A. Erickson ,&nbsp;Sounak Gupta","doi":"10.1016/j.humpath.2024.05.008","DOIUrl":"10.1016/j.humpath.2024.05.008","url":null,"abstract":"<div><p>The staging for pT2/pT3 penile squamous cell carcinoma (pSCC) has undergone major changes. Some authors proposed criteria wherein the distinction between pT2/pT3 was made using the same histopathological variables that are currently utilized to differentiate pT1a/pT1b. In this single-institution, North American study, we focused on (HPV-negative) pT2/3 pSCCs (i.e., tumors invading corpus spongiosum/corpus cavernosum), and compared the prognostic ability of the following systems: (i) AJCC (8th edition) criteria; (ii) modified staging criteria proposed by Sali et al. (Am J Surg Pathol. 2020; 44:1112–7). In the proposed system, pT2 tumors were defined as those devoid of lymphovascular invasion (LVI) or perineural invasion (PNI), and were not poorly differentiated; whereas pT3 showed one or more of the following: LVI, PNI, and/or grade 3. 48 pT2/pT3 cases were included (AJCC, pT2: 27 and pT3: 21; Proposed, pT2: 22 and pT3: 26). The disease-free survival (DFS) and progression-free survival (PFS) did not differ between pT2 and pT3, following the current AJCC definitions (p = 0.19 and p = 0.10, respectively). When the pT2/3 stages were reconstructed using the modified criteria, however, a statistically significant difference was present in both DFS and PFS between pT2 and pT3 (p = 0.004 and p = 0.003, respectively). The proposed staging system has the potential to improve the prognostication of pT2/pT3 tumors in pSCC. Each of these histopathologic variables has been shown to have a significant association with outcomes in pSCC, which is an advantage. Further studies are needed to demonstrate the utility of this modified staging system in patient populations from other geographic regions.</p></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"148 ","pages":"Pages 81-86"},"PeriodicalIF":3.3,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141087675","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":"Oncocytic type has distinct immunohistochemical and recurrence-free survival than other histologic types of the intraductal papillary neoplasm of the bile duct","authors":"Jihyun Chun ,&nbsp;You-Na Sung ,&nbsp;Soyeon An ,&nbsp;Seung-Mo Hong","doi":"10.1016/j.humpath.2024.05.006","DOIUrl":"10.1016/j.humpath.2024.05.006","url":null,"abstract":"<div><p>Although intraductal oncocytic papillary neoplasm (IOPN) was considered distinct from the intraductal papillary neoplasm of the pancreas, the oncocytic histologic type remained as a subtype of intraductal papillary neoplasms of the bile duct (IPNBs) with gastric, intestinal, and pancreatobiliary types based on the fifth edition of the WHO classification. To test the characteristics of the oncocytic type of IPNBs, the histopathologic, immunohistochemical (Hep Par-1 and CD117), and clinical characteristics of 13 oncocytic type were compared with 114 others (15 gastric, 39 pancreatobiliary, and 60 intestinal) IPNB types. The oncocytic type, which occupied about 9% of IPNBs, was more frequent in females (p &lt; 0.05) and larger (mean, 5.3 vs. 3.6 cm; p &lt; 0.002) than other IPNB types. Immunohistochemically, the oncocytic type had more frequent combined Hep Par-1 and CD117 expression than other IPNB types (all p &lt; 0.05). The recurrence-free survival rate for patients with the oncocytic type (5-year survival, 100%) was significantly higher (p = 0.015) than for those with other histologic types (59.9%). The oncocytic type had distinct histopathologic, immunohistochemical, and survival outcomes from other IPNBs. Therefore, it can be separated from other IPNB types and classified as one independent entity, similar to IOPN of the pancreas.</p></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"148 ","pages":"Pages 72-80"},"PeriodicalIF":3.3,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141087611","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":"Analysis of MicroRNA-371-373 supports that a subset of spermatocytic tumors demonstrates biologic features similar to those of GCNIS-derived germ cell tumors","authors":"João Lobo ,&nbsp;Nuno Tiago Tavares ,&nbsp;Carmen Jerónimo ,&nbsp;Rui Henrique ,&nbsp;Eugenia Dvindenko ,&nbsp;Kristine M. Cornejo ,&nbsp;Daniel M. Berney ,&nbsp;Thomas M. Ulbright ,&nbsp;Sounak Gupta ,&nbsp;Andres M. Acosta","doi":"10.1016/j.humpath.2024.05.005","DOIUrl":"10.1016/j.humpath.2024.05.005","url":null,"abstract":"<div><p>Spermatocytic tumors are rare testicular tumors occurring predominantly in older men. Most show a classical tripartite morphology (different from seminoma) and are benign. However, well-documented cases of malignant spermatocytic tumors exist. Our previous work showed that a subset of spermatocytic tumors exhibiting <em>TP53</em> mutations, DNA methylation profiles closer to seminomas, and/or gains in chromosome 12p exhibited aggressive characteristics, including sarcomatoid transformation and metastatic dissemination. The microRNA-371-373 cluster is a promising biomarker which is upregulated in non-teratoma germ cell tumors with malignant behavior. In this work we analyze microRNAs-371-373 b y quantitative real-time polymerase chain reaction in 18 spermatocytic tumors representative of the whole clinical spectrum, including 6 with aggressive features (sarcomatoid transformation, metastases, or gains in chromosome 12p). The levels of microRNAs-371-373 were significantly higher in non-teratoma germ cell tumors compared to spermatocytic tumors, overall (p &lt; 0.0001). Importantly, levels of microRNA-371-373 were higher in spermatocytic tumors with aggressive features compared to non-aggressive neoplasms. The highest levels were observed in one tumor showing isochromosome 12p. These results further support our previous findings that a subset of spermatocytic tumors are intermediate between so-called type II and type III germ cell tumors and that embryonic microRNAs play a role in aggressive behavior in spermatocytic tumors. Accordingly, this subset of tumors may behave aggressively and require close follow up. In the future, this opens an opportunity for microRNA testing in serum of spermatocytic tumor patients for risk stratification purposes.</p></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"148 ","pages":"Pages 66-71"},"PeriodicalIF":3.3,"publicationDate":"2024-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141087664","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":"Myoepithelial tumors of soft tissue and bone in children and young adults: A clinicopathologic study of 40 cases occurring in patients ≤ 21 Years of age","authors":"Suzanna J. Logan ,&nbsp;Carina A. Dehner ,&nbsp;Fatimah I. Alruwaii ,&nbsp;Nasir Ud Din ,&nbsp;Damon R. Olson ,&nbsp;Karen J. Fritchie ,&nbsp;Gregory W. Charville ,&nbsp;Melissa M. Blessing ,&nbsp;Andrew L. Folpe","doi":"10.1016/j.humpath.2024.05.007","DOIUrl":"10.1016/j.humpath.2024.05.007","url":null,"abstract":"<div><p>Myoepithelial tumors of the soft tissue and bone occurring in patients 21 years of age and younger are rare, and their clinicopathologic features remain incompletely understood. We studied a well-characterized series of 40 such tumors. Cases were retrieved from our archives for the period 2009–2022 and re-reviewed. Available immunohistochemical and molecular genetic data was collected. Clinical information including available follow-up was obtained. The tumors occurred in 18 males and 22 females, ranging from 3 months to 21 years of age (median 11.5 years), and involved a wide variety of soft tissue (n = 36) and bone (n = 4) locations. Histologically benign myoepithelial tumors tended to occur in adolescents (median age 14.5 years; range 5–21 years), whereas myoepithelial carcinomas occurred in younger patients (median age 8.5 years; range 3 months–20 years). Microscopically, the tumors showed a complex admixture of epithelioid, plasmacytoid and spindled cells in a variably hyalinized, myxoid, chondroid or chondromyxoid background. Small subsets of histologically malignant tumors had rhabdoid or “round cell” features. Immunohistochemistry showed 35/40 (88%) cases to be positive with at least one keratin antibody. The 5 keratin-negative tumors were uniformly positive for S100 protein and/or SOX10 and expressed EMA (4 cases) and/or p63 (3 cases). EMA, SMA and GFAP were positive in 21/25 (84%), 13/21 (62%), and 8/21 (38%) tumors, respectively. SMARCB1 and SMARCA4 expression was retained in 29/31 (94%) and 22/22 (100%) of cases, respectively. FISH for <em>EWSR1</em> gene rearrangement was positive in 6/18 (33%) tested cases. Two <em>EWSR1</em>-negative tumors were also <em>FUS</em>-negative. NGS identified <em>EWSR1::POU5F1</em>, <em>FUS::KLF17</em>, and <em>BRD4::CITED1</em> gene fusions in 3 tested cases. Clinical follow-up (22 patients; median 23 months; range 1–119 months) showed 3 patients with local recurrences and 5 with distant metastases (lymph nodes, lung, and brain). Three patients died of disease, 3 were alive with recurrent or unresectable disease, and 16 were disease-free. Adverse clinical outcomes were seen only in patients with malignant tumors. We conclude that myoepithelial neoplasms of soft tissue and bone are over-repesented in patients ≤21 years of age, more often histologically malignant, and potentially lethal. Histologic evaluation appears to reliably predict the behavior of these rare tumors.</p></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"149 ","pages":"Pages 10-20"},"PeriodicalIF":3.3,"publicationDate":"2024-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141087593","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":"Performance of HER2 DAKO HercepTest and Ventana 4B5 immunohistochemical assays on detecting HER2 gene-amplification in uterine serous carcinomas","authors":"Janira M. Navarro Sanchez ,&nbsp;Brian S. Finkelman ,&nbsp;Haley Tyburski ,&nbsp;Bradley M. Turner ,&nbsp;Ioana Moisini ,&nbsp;Hani Katerji ,&nbsp;Sharlin Varghese ,&nbsp;Xi Wang ,&nbsp;Linda M. Schiffhauer ,&nbsp;Jack J. Chen ,&nbsp;David G. Hicks ,&nbsp;Huina Zhang","doi":"10.1016/j.humpath.2024.05.002","DOIUrl":"10.1016/j.humpath.2024.05.002","url":null,"abstract":"<div><p>We compared the performance of two commonly-used HER2 immunohistochemistry (IHC) assays in uterine serous carcinomas (USC), correlating with <em>HER2</em> gene amplification by fluorescence in-situ hybridization (FISH). Sixty-five USCs were stained by both HercepTest™ and PATHWAY 4B5 assays. FISH was performed by HER2 IQFISH pharmDx. Consensus HER2 IHC scoring was performed, and HER2 testing results were evaluated using USC-specific criteria. Complete concordance between HercepTest and 4B5 assays was achieved in 44/65 tumors (68%). The overall HER2 IHC/FISH concordance was 94% (45/48) by HercepTest and 91% (42/46) by 4B5. All HER2 IHC 3+ cases with HercepTest (<em>n</em> = 6) and 4B5 (<em>n</em> = 4) were gene-amplified, corresponding to specificities of 100%. For cases with IHC 2+, 41% (7/17) by HercepTest and 42% (8/19) by 4B5 had <em>HER2</em> gene amplification. The sensitivity for HercepTest and 4B5 were 38% and 25%, respectively, at a cut-off of IHC 3+ (<em>P</em> = 0.50), and were 81% and 75%, respectively, at a cut-off of IHC 2+ (<em>P</em> &gt; 0.99). Among HER2 IHC 0–1+ cases, 3/42 cases by HercepTest and 4/42 cases by 4B5 showed amplified FISH results, corresponding to overall false negative rates of 19% for HercepTest and 25% for 4B5. By using USC-specific IHC scoring criteria, both HercepTest and 4B5 assays showed high specificities (100%) for <em>HER2</em> gene amplification in IHC 3+ cases, high IHC/FISH concordance, and comparable sensitivity for detecting <em>HER2</em> gene amplification. The notable false negative rates using IHC 2+ as a cut-off for reflexing FISH analysis may warrant consideration for performing FISH in IHC 1+ cases until more data become available.</p></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"148 ","pages":"Pages 51-59"},"PeriodicalIF":3.3,"publicationDate":"2024-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140916385","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":"Follow-up biopsies in gastrointestinal immune checkpoint inhibitor toxicity may show markedly different inflammatory patterns than initial injury","authors":"Nicole K. Tomm ,&nbsp;Julianne M. Szczepanski ,&nbsp;Jiayun M. Fang ,&nbsp;Won-Tak Choi ,&nbsp;Yue Xue ,&nbsp;Namrata Setia ,&nbsp;Dipti M. Karamchandani ,&nbsp;Jerome Y. Cheng ,&nbsp;Maria Westerhoff","doi":"10.1016/j.humpath.2024.05.001","DOIUrl":"10.1016/j.humpath.2024.05.001","url":null,"abstract":"<div><p>Colitis is a common manifestation of immune checkpoint inhibitor (ICI) toxicity and can present with varied histologic patterns of inflammation, some of which have been shown to be associated with specific ICI drug types. Although the histologic features of ICI colitis seen at the time of diagnosis have been described, there have been few reports following these patients over time. We evaluated initial and follow-up biopsies in 30 patients with ICI colitis and found that 37% of patients developed a different pattern of injury on follow-up biopsy compared to the initial biopsy. Patients with a different inflammatory pattern were more likely to have restarted ICI therapy before their follow-up biopsy (64%) compared to those without a change in inflammatory pattern (11%; <em>P</em> &lt; 0.01). The majority of these patients had changed ICI drug types (86%). Additionally, many cases changed to an inflammatory bowel disease (IBD)-like pattern (36%), raising a question of <em>de novo</em> IBD. However, all of our patients with an IBD-like pattern experienced sustained resolution of symptoms without steroids or other immunosuppressive medications following discontinuation of ICI therapy, consistent with a diagnosis of ICI toxicity. Our findings suggest that follow-up biopsies in patients with ICI colitis may show a different histology and that this does not necessarily warrant a change in the histologic diagnosis to another disease.</p></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"148 ","pages":"Pages 60-65"},"PeriodicalIF":3.3,"publicationDate":"2024-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140908684","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":"Vascular tumors of intermediate malignancy: An update","authors":"Andrew L. Folpe","doi":"10.1016/j.humpath.2024.01.014","DOIUrl":"10.1016/j.humpath.2024.01.014","url":null,"abstract":"<div><p>The term “hemangioendothelioma” is used for endothelial neoplasms of intermediate malignancy and describes a group of rare neoplasms having biologic behavior falling in between that of the benign hemangiomas and fully malignant angiosarcomas. The hemangioendotheliomas fall into several specific, clinicopathologically and genetically distinct entities, specifically epithelioid hemangioendothelioma, kaposiform hemangioendothelioma, papillary intralymphatic angioendothelioma and retiform hemangioendothelioma (hobnailed hemangioendothelioma), pseudomyogenic hemangioendothelioma, composite hemangioendothelioma, and <em>YAP1::TFE3</em>-fused hemangioendothelioma. The clinical, morphologic, immunohistochemical, and genetic features, and the differential diagnosis of each of these rare entities are discussed in this review.</p></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"147 ","pages":"Pages 114-128"},"PeriodicalIF":3.3,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139740898","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":"Atypical lipomatous tumor/well differentiated liposarcoma and related mimics with updates. When is molecular testing most cost-effective, necessary, and indicated?","authors":"Scott E. Kilpatrick","doi":"10.1016/j.humpath.2023.12.005","DOIUrl":"10.1016/j.humpath.2023.12.005","url":null,"abstract":"<div><p><span><span>The classification and work-up of adipocytic neoplasms remains challenging and sometimes controversial. Since its initial description by Dr. Enterline, the variety of subtypes and morphological appearances considered to represent the spectrum of atypical lipomatous tumor/well differentiated liposarcoma (ALT/WDL) has expanded, resulting in significant morphologic overlap with other entities, including the recently described atypical spindle cell/pleomorphic lipomatous tumor (ASPLT), conventional spindle cell/pleomorphic lipoma (SPL), and so-called “low-grade” forms of </span>dedifferentiated liposarcoma<span> (DL). Nevertheless, the distinction of most examples of ALT/WDL from lipomas/lipoma-like lesions is easily performed on routine histologic examination but can be problematic if the characteristic atypical cells are poorly represented, particularly in small biopsy specimens, obscured by other cellular elements (inflammation), or simply not recognized. The discovery that lipomatous tumors harbor specific and unique karyotypes<span> and molecular events has resulted in ancillary tests that can help provide more accurate diagnoses, especially in less-than-optimal scenarios. Confirmation of MDM2 immunohistochemical over-expression and detection of the </span></span></span><em>MDM2</em><span> gene rearrangement<span> via fluorescent in situ hybridization (FISH) have proven particularly reliable and useful. While FISH analysis for </span></span><em>MDM2</em><span> gene amplification<span> may be helpful for confirming (or excluding) ALT/WDL, it also can lead to overutilization and overdependence. Furthermore, a small subset of otherwise typical ALT/WDL lack MDM2 gene amplification, employing alternative molecular pathways. The recent recognition of ASPLT has introduced a tumor easily mistaken morphologically for ALT/WDL, often exhibiting bizarre and pleomorphic lipoblasts, but lacking the underlying molecular abnormalities and subsequent risk of dedifferentiation<span>. ASPLT also have overlapping features with the better-established SPL but with a greater tendency to locally recur and more frequent involvement of the distal extremities. The precise criteria separating cellular forms of ALT from what some consider “low grade” forms of DL remains controversial and inconsistently applied, even among individual pathologists within institutions. Given their underlying shared cytogenetic abnormality, molecular testing has no utility in this distinction. Herein is a comprehensive historical overview of ALT/WDL, with updates on its distinction from other similar lipomatous tumors and DL, including practical evidence-based criteria for the appropriate cost-effective use of MDM2 testing.</span></span></span></p></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"147 ","pages":"Pages 82-91"},"PeriodicalIF":3.3,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138884870","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}