Annals of Diagnostic Pathology最新文献

{"title":"The association between variant histology and prognostic, histomorphological and clinical aspects of bladder urothelial carcinoma","authors":"Pelin Akbas ,&nbsp;Sibel Bektas ,&nbsp;Gokhan Yazici","doi":"10.1016/j.anndiagpath.2024.152373","DOIUrl":"10.1016/j.anndiagpath.2024.152373","url":null,"abstract":"<div><p>This study underscores the imperative consideration of histological subtypes and divergent differentiation in accurately estimating bladder urothelial carcinoma prognosis and guiding treatment decisions. A comparative analysis was conducted, examining clinical, histological, and prognostic factors between conventional urothelial carcinoma and urothelial carcinoma with variant histology in a clinical sample. A retrospective analysis of slides and other clinicopathologic data was conducted these cases, with an emphasis on key diagnostic elements. We examined 829 cases of urothelial carcinoma of the bladder, comprising of 744 transurethral resection (TUR) and 85 radical cystectomy (RS) specimens, an analysis that showed that 80.5 % (667 cases) were conventional urothelial carcinoma (CUC) and that 19.5 % (162 cases) exhibited variant histology (hereafter “urothelial carcinoma with subtype histology” [UCSH]). TNM classifications for the RS cases were as follows: 2 cases were stage group 0a, 11 stage group 1, 16 stage group 2, 45 stage group 3a, 2 stage group 3b, 1 stage group 4a, and 8 stage group 4b. Only 2 of the RS cases were found to be non-invasive. Among 744 TUR specimens, 387 were found to have a non-invasive tumor whereas 357 had invasive tumors. The most prevalent subtype in the UCSH group was urothelial carcinoma with squamous differentiation, accounting for 54.3 % (88 cases). Notably, 8.02 % (13 cases) exhibited more than one histological subtype. Papillary configuration, histological grade, lamina propria, muscularis mucosa and serosa invasion, lymphovascular invasion, presence of urothelial carcinoma in situ, and overall survival significantly differed between the UCSH and CUC groups (<em>p</em> &lt; 0.05). However, mean age, gender, tumor size, lymphocytic response, disease-free survival, and survival status did not differ significantly (<em>p</em> &gt; 0.05). Among the UCSH group, lower levels of papillary configuration, higher histological grade, higher degree of lamina propria, muscularis mucosa and serosa invasion, and the presence of carcinoma in situ corresponded to higher percentage of histological subtype morphology (<em>p</em> &lt; 0.05). No significant difference in survival status was observed between the groups with and without subtype histology (<em>p</em> = 0.083). This study found that clinical and histopathological prognostic factors associated with a more aggressive disease were linked to the presence and percentage of histological subtypes. Recognizing histological subtype is crucial for treatment decisions and prognosis prediction in urothelial carcinoma cases with these subtypes.</p></div>","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"73 ","pages":"Article 152373"},"PeriodicalIF":1.5,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142048661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From the archives of MD Anderson Cancer Center: Composite mantle cell lymphoma and lymphoplasmacytic lymphoma involving bone marrow at presentation","authors":"Yiannis Petros Dimopoulos,&nbsp;Beenu Thakral,&nbsp;Pei Lin,&nbsp;Gokce Toruner,&nbsp;Zhuang Zuo,&nbsp;L. Jeffrey Medeiros,&nbsp;Vasiliki Leventaki","doi":"10.1016/j.anndiagpath.2024.152372","DOIUrl":"10.1016/j.anndiagpath.2024.152372","url":null,"abstract":"<div><p>Composite lymphoma, defined as two or more distinct well-defined entities involving the same anatomic site, is rare. Here we report a 79-year-old woman with composite mantle cell lymphoma (MCL) and lymphoplasmacytic lymphoma (LPL) involving bone marrow at the time of initial diagnosis. The patient presented with splenomegaly and lymphadenopathy and laboratory studies showed an elevated serum IgM level and IgM kappa paraprotein. Bone marrow evaluation showed concurrent involvement by MCL and LPL, supported by immunophenotypic studies that revealed two distinct aberrant B-cell populations. Next-generation sequencing analysis identified concurrent <em>MYD88</em> and <em>CXCR4</em> mutations and fluorescence in-situ hybridization showed <em>CCND1</em> translocation, supporting the diagnosis of concomitant MCL and LPL. In conclusion, composite lymphoma can present in the bone marrow. The use of ancillary studies was essential in reaching the diagnosis in this case, as the results excluded the possibility of MCL lymphoma with plasmacytic differentiation, as well as other CD5- and CD10-negative small B-cell lymphomas.</p></div>","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"73 ","pages":"Article 152372"},"PeriodicalIF":1.5,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142087594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnosis of autoimmune bullous dermatoses: Comparative analysis of immunohistochemical staining using C4d, C3d, IgG, and IgG4 in lesional tissues and perilesional frozen skin samples","authors":"Sevil Karabağ ,&nbsp;Özge Zorlu","doi":"10.1016/j.anndiagpath.2024.152367","DOIUrl":"10.1016/j.anndiagpath.2024.152367","url":null,"abstract":"<div><p>Immunohistochemical staining with immunoglobulins and complements may aid the diagnosis of patients whose clinical and histological findings are consistent with autoimmune bullous dermatoses (AIBD). We aimed to investigate the diagnostic value of immunohistochemical markers in lesional biopsy and perilesional frozen samples in AIBD. We included 136 cases from whom lesional biopsies and perilesional samples for direct immunofluorescence (DIF) examination were collected with a preliminary diagnosis of AIBD between January 2019 and January 2023. All diagnoses were reconfirmed by evaluating the clinical, histopathological, and serological findings and DIF results (C3, IgG, IgA, or IgM positivity compatible with the clinical diagnosis) altogether, although DIF results were considered a priority. After confirming the diagnoses, the samples were categorized as AIBD or the others. The perilesional tissues obtained for DIF simultaneously with skin biopsy and stored at −80 °C were thawed, and FFPE tissues were prepared. We performed immunohistochemical staining (C4d, C3d, IgG, and IgG4) on FFPE tissues of both lesional and perilesional samples. Strong, linear, or granular staining patterns at the dermoepidermal junction or the intraepidermal blistering space were considered positive in line with the diagnosis of the case. Cases other than AIBD were used as negative control tissues to assess the specificity of immunohistochemical markers. Of the 136 cases, 52 were diagnosed with AIBD. In lesional samples, the sensitivity of C4d, C3d, IgG, and IgG4 was 80.6 %, 69.4 %, 75 %, and 5.7 % with corresponding specificity of 100 %, 98.7 %, 89.6 %, and 97.4 %, respectively in pemphigoid diseases compared to a sensitivity of 18.2 %, 9.1 %, 70 %, and 9.1 % and specificity of 98.7 %, 100 %, 89.6 %, and 97.4 %, respectively in pemphigus diseases. In frozen samples, we detected expression in a limited number of cases. The sensitivity of C4d, C3d, IgG, and IgG4 was 8.7 %, 2.2 %, 19.4 %, and 2.2 %, with corresponding specificity of 100 %, 100 %, 98.5 %, and 98.6, respectively. There was a none to slight concordance rate between the IHC results of lesional tissues and perilesional frozen samples. Kappa coefficients for C4d, C3d, IgG, and IgG4 were 0.120 (<em>P</em> = 0.029), 0.111 (<em>P</em> = 0.050), 0.203 (<em>P</em> = 0.003), and - 0.15 (<em>P</em> = 0.846), respectively. Immunohistochemical staining with C4d, C3d, IgG, and IgG4 on biopsy samples collected from lesions may guide the diagnosis of AIBD, thereby eliminating the need for an additional biopsy and accelerating the diagnostic process.</p></div>","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"73 ","pages":"Article 152367"},"PeriodicalIF":1.5,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142048660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An assessment of “neuroendocrine differentiation” in malignant melanomas of the sinonasal and oral region","authors":"Funda Canaz ,&nbsp;Zeynep Özcan ,&nbsp;Mustafa Fuat Açıkalın ,&nbsp;Evrim Yılmaz ,&nbsp;Mehmet Özgür Pınarbaşlı ,&nbsp;Serap Işıksoy ,&nbsp;Ertuğrul Çolak","doi":"10.1016/j.anndiagpath.2024.152371","DOIUrl":"10.1016/j.anndiagpath.2024.152371","url":null,"abstract":"<div><p>Mucosal melanomas often require a detailed differential diagnosis and immunochemical study due to their different morphology and pattern characteristics. The tumors may also show fibroblastic, schwannian, smooth muscle, rhabdomyosarcomatous, gangliocytic, epithelial, and neuroendocrine differentiation. All these features can lead to serious diagnostic difficulties. The study aimed to determine the frequency of neuroendocrine differentiation in melanomas of the sinonasal and oral regions and to assess whether there is any relationship between neuroendocrine differentiation and clinical, histopathological, and other immunophenotypic features of this neoplasm. The study included 18 cases diagnosed with oral or sinonasal malignant melanoma. Neuroendocrine differentiation was determined by immunohistochemistry using synaptophysin, chromogranin, CD56, and INSM-1. A cut-off defining neuroendocrine differentiation in malignant melanomas has not been established in the literature. Because of this, any degree of neuroendocrine marker expression was considered as indicative of “neuroendocrine differentiation” without setting any cut-off. Neuroendocrine differentiation was observed in 13 of 18 cases (72.2 %) when a single positive neuroendocrine marker was considered sufficient. The number of cases with at least two positive neuroendocrine markers was 8/18 (44.4 %). Synaptophysin, chromogranin A, CD56, and INSM1 were positive in 33.3 %, 13.3 %, 56.2 %, and 47.1 % of cases, respectively. The results of our study suggest that neuroendocrine differentiation is not uncommon in oral and sinonasal melanomas. Knowing that malignant melanomas can show neuroendocrine differentiation will prevent diagnostic pitfalls.</p></div>","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"73 ","pages":"Article 152371"},"PeriodicalIF":1.5,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142172743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Papillary microcarcinoma of the thyroid gland: Evaluation of TERT and BRAFV-600E expression and their relationship with clinicopathological findings","authors":"Aslı Aydoğdu Yeşiloğlu ,&nbsp;Aysun Hatice Uğuz ,&nbsp;Kıvılcım Eren Erdoğan ,&nbsp;Gürhan Sakman","doi":"10.1016/j.anndiagpath.2024.152369","DOIUrl":"10.1016/j.anndiagpath.2024.152369","url":null,"abstract":"<div><p>Papillary microcarcinomas (PMCs) are papillary carcinomas ≤1 cm in size, with an increasing incidence. Although generally indolent, some cases exhibit aggressive behavior. Recently, active surveillance has been recommended to avoid surgical treatment. Identifying molecular changes that predict aggressiveness in PMCs has gained importance, but studies are limited. We aimed to demonstrate <em>TERT</em> expression and <em>BRAF V600E</em> positivity immunohistochemically in PMCs and correlate them with histomorphological features, subtypes, and clinicopathological findings. We included 95 PMC cases diagnosed between 2010 and 2019 at the Department of Pathology, Faculty of Medicine, XXX University. We investigated <em>TERT</em> expression using RT-PCR. We evaluated <em>BRAF V600E</em> mutation immunohistochemically. We evaluated the relationship between genetic, histomorphological, and clinicopathological findings. In patients with multifocality and those with a tumor size ≥0.5 cm, the frequency of lymph node metastasis was significantly higher. A positive correlation was shown between BRAF V600E positivity and lymph node metastasis, lymphovascular invasion, advanced disease stage, and classical subtype by univariate analyses. We detected <em>TERT</em> expression in 18 of 95 patients (7.8 %). No relationship could be detected between <em>TERT</em> expression alone or combined with <em>BRAF</em> positivity and clinicopathological features. Although <em>TERT</em> mutations are associated with aggressiveness in thyroid cancers, this association was absent in PMCs. The presence of <em>TERT</em> expression was demonstrated in some cases. However, <em>TERT</em> expression could not be associated with clinicopathological findings, which is consistent with the literature suggesting that <em>TERT</em> plays a role in advanced stages of carcinogenesis.</p></div>","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"73 ","pages":"Article 152369"},"PeriodicalIF":1.5,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1092913424001060/pdfft?md5=91f25ec86c9502d3ccc960a349638e8b&pid=1-s2.0-S1092913424001060-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142044639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Next-generation sequencing has diagnostic utility in challenging small/flat urothelial lesions","authors":"Amélie Pinard,&nbsp;Constance Chen,&nbsp;Jessica Van Ziffle,&nbsp;Jeffry P. Simko,&nbsp;Bradley A. Stohr,&nbsp;Emily Chan","doi":"10.1016/j.anndiagpath.2024.152370","DOIUrl":"10.1016/j.anndiagpath.2024.152370","url":null,"abstract":"<div><p>Small/flat urothelial lesions are challenging and currently available ancillary immunohistochemistry testing often cannot reliably distinguish between reactive lesions and urothelial carcinoma (UCa). UCa has a characteristic molecular profile, but small/flat urothelial lesions are typically considered too small to perform next generation sequencing (NGS). Herein, we present our institution's experience with utilizing comprehensive DNA-based NGS to evaluate small/flat urothelial lesions (<em>n</em> = 13 cases). NGS was ordered on 7/13 small/flat urothelial lesions initially diagnosed as urothelial atypia, ordered by the pathologist to aid in further diagnosis; the remaining 6/13 cases were diagnosed as urothelial carcinoma in situ (uCIS), ordered by a treating oncologist. The test was considered as adding value if it yielded pathogenic or likely pathogenic alterations previously associated with urothelial carcinoma in the literature. Macroscopic dissection was determined necessary in all cases and obtained either by scraping (7), punch biopsy (5) or scooping (1) of paraffin tissue blocks. In 4/13 cases, tumor content was considered low (&lt;25%); in 2/13 cases, DNA quantity yield was considered below optimal (&lt;250 ng); all cases met required DNA quantity for testing (&gt;50 ng). Mean target coverage ranged: 498 to 985 (optimal &gt;500 reads). NGS testing identified mutations compatible with urothelial carcinoma in all 7 cases initially diagnosed as atypical; and in one case, the tumor recurred as a lung metastasis. All 6 uCIS had NGS testing results concordant with UCa. In conclusion, despite small sample quantity with low tumor content and DNA concentration yield, NGS testing with appropriate methodology can be considered in the setting of small/flat urothelial lesions to aid in diagnosis or per oncologist request and yield interpretable results.</p></div>","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"73 ","pages":"Article 152370"},"PeriodicalIF":1.5,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1092913424001072/pdfft?md5=75ca0b88f7ac8e18f6cefc13838a9be7&pid=1-s2.0-S1092913424001072-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142048662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancing the molecular understanding of renal tumorigenesis: Acquired cystic disease-associated renal cell carcinoma (ACD-RCC) as a model system","authors":"Khaleel I. Al-Obaidy ,&nbsp;Liang Cheng","doi":"10.1016/j.anndiagpath.2024.152366","DOIUrl":"10.1016/j.anndiagpath.2024.152366","url":null,"abstract":"<div><p>In summary, the study's investigation of KMT2C and TSC2 variants in ACD-RCC marks a significant advancement in comprehending this distinct kidney tumor. By illuminating the molecular landscape of ACD-RCC, the research sets the stage for future studies aimed at revealing the complex mechanisms driving tumor development and progression. This understanding could eventually lead to more effective management and treatment strategies for renal cancer patients.</p></div>","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"73 ","pages":"Article 152366"},"PeriodicalIF":1.5,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141914471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ChatGPT for histopathologic diagnosis","authors":"Sompon Apornvirat ,&nbsp;Warut Thinpanja ,&nbsp;Khampee Damrongkiet ,&nbsp;Nontawat Benjakul ,&nbsp;Thiyaphat Laohawetwanit","doi":"10.1016/j.anndiagpath.2024.152365","DOIUrl":"10.1016/j.anndiagpath.2024.152365","url":null,"abstract":"","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"73 ","pages":"Article 152365"},"PeriodicalIF":1.5,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141890846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Implication of KMT2C and TSC2 variants in the tumorigenesis of acquired cystic disease-associated renal cell carcinomas","authors":"Fumiyoshi Kojima ,&nbsp;Ibu Matsuzaki ,&nbsp;Fidele Yambayamba Musangile ,&nbsp;Kanako Sagan ,&nbsp;Yurina Mikasa ,&nbsp;Ryuta Iwamoto ,&nbsp;Yasuo Kohjimoto ,&nbsp;Isao Hara ,&nbsp;Shin-ichi Murata","doi":"10.1016/j.anndiagpath.2024.152364","DOIUrl":"10.1016/j.anndiagpath.2024.152364","url":null,"abstract":"<div><p>In 2020, acquired cystic disease-associated renal cell carcinomas (ACD-RCCs) were reported to harbor <em>KMT2C</em> and <em>TSC2</em> variants: however, their carcinogenic implication has not yet been reported. This study aimed to explore the variant features of <em>KMT2C</em> and <em>TSC2</em> in ACD-RCC and their implication in ACD-RCC tumorigenesis. Eleven ACD-RCCs, 10 ACD-RCC-like cysts, and 18 background kidneys were retrieved. The background kidneys consisted of atrophic thyroid follicle-like tubules. They included four with clustered cysts, two with eosinophilic changes, and one each with clear cell changes and sieve-like changes in the renal tubules. First, DNA-targeted sequencing of <em>KMT2C</em> and <em>TSC2</em> whole exons was performed on eight ACD-RCC samples. Subsequently, a custom DNA panel was designed to include the recurrent <em>KMT2C</em> and <em>TSC2</em> variants based on the sequencing results. Second, DNA-targeted sequencing was performed on the remaining samples using a custom panel targeting the recurrent variants. Additionally, immunohistochemistry was performed for KMTC, H3K4me1, H3K4me3, TSC2, and GPNMB on the ACD-RCCs. Six of the 11 ACD-RCC cases harbored <em>KMT2C</em> and <em>TSC2</em> variants, including nine likely pathogenic variants. In contrast to ACD-RCC, 1 of the 9 ACD-RCC-like cysts harbored both variants. Immunohistochemical analysis did not support the loss of function in ACD-RCCs harboring <em>KMT2C</em> and <em>TSC2</em> variants. <em>KMT2C</em> and <em>TSC2</em> variant frequencies were higher in ACD-RCC than in other renal cell carcinomas. However, <em>KMT2C</em> and <em>TSC2</em> are unlikely to be the primary drivers of ACD-RCC development.</p></div>","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"73 ","pages":"Article 152364"},"PeriodicalIF":1.5,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141876635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Detection of human papillomavirus (HPV) in malignant melanoma","authors":"Adam Bedeir ,&nbsp;Hassan Ghani ,&nbsp;Cyrus Oster ,&nbsp;Anthony Crymes ,&nbsp;Ifegwu Ibe ,&nbsp;Maki Yamamoto ,&nbsp;Andrew Elliott ,&nbsp;David A. Bryant ,&nbsp;Matthew J. Oberley ,&nbsp;Mark G. Evans","doi":"10.1016/j.anndiagpath.2024.152361","DOIUrl":"10.1016/j.anndiagpath.2024.152361","url":null,"abstract":"<div><p>The most common type of melanoma is cutaneous melanoma (CM). The predominant mutational signature is that of ultraviolet radiation (UVR) exposure. The Cancer Genome Atlas (TCGA) molecular classification includes four major subtypes of CM based on common genetic alterations involving the following genes: <em>BRAF</em>, <em>NRAS</em>, and <em>NF1</em>, with a small fraction being “triple” wild-type. The two main signaling pathway abnormalities in CM are the mitogen-activated protein kinase (MAPK) pathway and the phosphoinositol-3-kinase (PI3K) pathway. Other less common types include mucosal melanomas (MM) and uveal melanoma (UM), which have a significantly different genomic landscape. Although few studies reported rare cases with HPV-positive (HPV+) melanoma, the clinicopathological and molecular characteristic of this entity has not been well-described. Among the 2084 melanoma cases queried at our institution, we identified seven patients diagnosed with HPV+ melanoma (prevalence 0.03 %), including five instances of CM and two of MM. The majority of cases were positive for HPV16 (<em>n</em> = 6). Most of the patients were elderly and with advanced disease (n = 6), although this finding may be attributed to the relative frequency of our institution testing advanced-stage tumors. Histologically, most cases showed high degree of pleomorphism and high mitotic count (5 or more mitoses/mm²) (<em>n</em> = 6). UVR signature was present in the CM, but not in the MM cases. Alterations in either MAPK and/or PI3K pathways were detected in the majority of cases (<em>n</em> = 6). The most common genetic abnormalities detected in this study occurred in the <em>TERT</em> promoter (<em>TERT</em>p) (<em>n</em> = 5), a finding that has been reported to be associated with aggressive disease. Our data shows that while HPV+ melanoma is rare, identifying this disease entity could help guide therapy given the demonstrated genomic alterations.</p></div>","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"73 ","pages":"Article 152361"},"PeriodicalIF":1.5,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141729777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}