American Journal of Surgical Pathology最新文献

{"title":"Cholangioblastic Cholangiocarcinoma ( NIPBL :: NACC1 Cholangiocarcinoma) : Expanded Morphologic Spectrum and Further Genetic Characterization.","authors":"Pedram Argani, Kiyoko Oshima, Robert A Anders, Raul S Gonzalez, Osman Yilmaz, Munita Bal, Lisa Rooper, Jessica Hicks, Angelo De Marzo, Jeffrey Gagan, Chengsong Zhu, Doreen N Palsgrove","doi":"10.1097/PAS.0000000000002365","DOIUrl":"10.1097/PAS.0000000000002365","url":null,"abstract":"<p><p>The cholangioblastic variant of intrahepatic cholangiocarcinoma is a distinctive neoplasm that typically affects young women without underlying liver disease. Morphologically, it demonstrates solid, trabecular, and tubulocystic architecture, biphasic small cell-large cell cytology, and immunoreactivity for inhibin, neuroendocrine markers, and biliary but not hepatocellular markers. In 2021, our group identified a characteristic NIPBL::NACC1 gene fusion in cholangioblastic cholangiocarcinoma, and since then ~20 genetically confirmed cases have been reported in the literature. We report 2 additional cases, both of which caused diagnostic challenges. The first was previously published as a \"biliary adenofibroma with malignant features\" which we now show recurred as a high-grade adenocarcinoma. Re-review of the original lesion demonstrated the morphologic and immunohistochemical features of highly cystic cholangioblastic cholangiocarcinoma, whereas the high-grade recurrence lacked many of these features. In addition to the characteristic NIPBL::NACC1 gene fusion, the recurrence demonstrated loss of the RB1 and PTEN genes which were found in the highly cystic, bland areas of the original tumor, suggesting that the recurrence was derived from this bland component. The second case was originally misclassified as metastatic well-differentiated neuroendocrine neoplasm and only focally demonstrated the characteristic biphasic small cell-large cell cytology. In addition, a review of 7 cholangioblastic cholangiocarcinomas in our files demonstrates that loss of chromosome 13q14.2 (where the RB1 gene resides) and loss of chromosome 6q15-q16.3 are recurrent secondary changes in these neoplasms. Expression profiling demonstrated alterations in the transforming growth factor receptor beta superfamily, and overexpression of MYC which was validated by immunohistochemistry. Our findings expand the morphologic and genetic spectrum of this neoplasm and provide insight into secondary genetic changes associated with progression.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"303-314"},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142997741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Novel Case of Pulmonary Sclerosing Diffuse PEComatosis With Neuroendocrine Cell Hyperplasia.","authors":"Kristine E Konopka, Ella A Kazerooni, MeiLan K Han, Jeffrey L Myers","doi":"10.1097/PAS.0000000000002354","DOIUrl":"10.1097/PAS.0000000000002354","url":null,"abstract":"<p><p>Proliferations of neoplastic perivascular epithelioid cells (PECs) may occur within the lung and extrathoracic sites. The term \"PEComatosis\" is applied to multiple or diffuse microscopic proliferations of neoplastic PECs. Pulmonary diffuse PEComatosis is extremely rare, with only one case documented in the literature to date. We herein report a novel sclerosing variant of diffuse PEComatosis in a 68-year-old woman with clinical tuberous sclerosis complex (TSC), who underwent lung resection for evaluation of persistent, bilateral ground glass opacities. The patient had no respiratory complaints or ventilatory defects in pulmonary function tests. The morphologic features resembled the previous description of pulmonary diffuse PEComatosis, showing interstitial nodular and diffuse proliferation of predominantly clear epithelioid cells with PEC differentiation by immunohistochemistry. The PEComatous proliferation was accompanied by a pattern of sclerosis that overlapped with the sclerosing variant of PEComa. There was no evidence of lymphangioleiomyomatosis. The changes were complicated by neuroendocrine cell hyperplasia, which has not previously been reported in the lungs of patients with TSC.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"411-415"},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinicopathologic and Molecular Characterization of Basal Cell Carcinoma Arising at Sun-protected Sites.","authors":"Elizabeth Draper, Yvonne Y Li, Navin R Mahadevan, Alvaro C Laga, John Hanna, Eleanor Russell-Goldman","doi":"10.1097/PAS.0000000000002366","DOIUrl":"10.1097/PAS.0000000000002366","url":null,"abstract":"<p><p>Basal cell carcinomas (BCC) are driven primarily by cumulative ultraviolet (UV) radiation exposure resulting in activation of the Hedgehog (Hh) signaling pathway, often as a result of UV-mediated Patched-1 ( PTCH1) gene inactivation. Accordingly, BCCs most commonly arise at sun-exposed sites such as the head and neck. Very rarely, BCCs can arise at sun-protected sites such as the genital skin and perianal area. This can pose significant diagnostic challenges not only due to the rarity of BCC at these sites but also due to the potential morphologic overlap with other entities such as basaloid squamous cell carcinoma, trichoblastic carcinoma, and even benign neoplasms such as trichoblastomas. Hh pathway alterations have not yet been described in BCCs arising at genital and perianal sites, and the role of UV radiation is uncertain at these anatomic locations. To address this ambiguity, we report the clinicopathologic features of a cohort of 14 BCCs arising at sun-protected sites (perianal n=7, vulva n=4, scrotum n=3). Furthermore, we use a next-generation DNA sequencing platform to investigate their pathogenesis and compare it to that of a cohort of 8 BCCs arising on sun-exposed skin. We find that BCCs arising on sun-protected sites display a spectrum of morphologic patterns, rarely recur, and do not metastasize. Both sun-protected and sun-exposed BCCs are characterized by recurrent PTCH1 alterations (93% and 100% of cases, respectively), supporting the classification of the tumors arising at sun-protected sites as bona fide BCCs. Notably, in contrast to conventional BCCs, none of the sun-protected BCCs harbored a UV mutation signature, suggesting an alternative mechanism of mutagenesis. Furthermore, the presence of upstream Hh pathway alterations in sun-protected BCCs supports their susceptibility to Hh pathway inhibitors such as vismodegib and sonidegib.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"328-335"},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142977092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pediatric Myeloid Neoplasms With UBTF Tandem Duplications : Morphologic, Immunophenotypic, and Clinical Characterization.","authors":"Mahsa Khanlari, Wei Wang, Yonghui Ni, Paul E Mead, Masayuki Umeda, Tami Westover, Jing Ma, Jeffrey E Rubnitz, Juan M Barajas, Stanley Pounds, Jeffery M Klco","doi":"10.1097/PAS.0000000000002350","DOIUrl":"10.1097/PAS.0000000000002350","url":null,"abstract":"<p><p>Tandem duplications (TDs) in exons of upstream binding transcription factor ( UBTF -TD) are a rare recurrent alteration in pediatric and adult acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS)/neoplasm. Although recently identified, AML with UBTF -TD is now considered a distinct subtype of AML. To further our understanding of myeloid neoplasms with UBTF -TD, we analyzed clinical, morphologic, and immunophenotypic characteristics of 27 pediatric patients with UBTF- TD-positive myeloid neoplasm, including 21 diagnosed as AML and 6 as MDS. Our data demonstrated that UBTF -TD is frequently associated with cytopenia, hypercellular marrow with erythroid hyperplasia, and trilineage dysplasia. Blasts and maturing myeloid cells show a characteristic dysplastic feature with condensed eosinophilic cytoplasm. Blasts have a myeloid or myelomonocytic immunophenotype with a variably dim expression of CD34 and/or CD117, and except for CD7 expression lack a consistent pattern of aberrant lineage-specific antigen expression. Patients with MDS had a lower blast count in the peripheral blood ( P = 0.03) and bone marrow ( P <0.001) but otherwise had no significant differences in other hematological parameters. Three patients with MDS rapidly progressed to AML in 33, 39, and 210 days from the initial diagnosis and there was no difference in overall survival between patients with MDS and AML ( P = 0.18). Our data suggest that MDS with UBTF-TD is prognostically equivalent to AML with UBTF -TD and thus should be considered as a continuum of the same molecularly defined myeloid neoplasm. These collective data also provide morphologic and immunophenotypic clues that can prompt screening for UBTF -TD in patients with MDS or AML.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"353-362"},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11893000/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prospective Fumarate Hydratase Tumor Predisposition Syndrome Screening in Patients With Uterine Smooth Muscle Tumors: Age, Morphology, Fumarate Hydratase/S-(2-succino) Cysteine Immunohistochemistry, and Germline Testing.","authors":"Austin McHenry, Ashley Monsrud, Jennifer Pors, Ann Folkins, Teri Longacre, Rachel Hodan","doi":"10.1097/PAS.0000000000002362","DOIUrl":"10.1097/PAS.0000000000002362","url":null,"abstract":"<p><p>Fumarate hydratase tumor predisposition syndrome (FHTPS) is caused by germline fumarate hydratase (FH) pathogenic variants (PVs). Most women with FHTPS develop FH-deficient (FHD) uterine leiomyomas (ULs), which arise 10 to 15 years earlier than aggressive FHD-renal cell carcinoma. We evaluate a previously proposed FHTPS screening strategy for women with ULs. This 5-year, prospective and retrospective study performed FH and later S-(2-succino) cysteine immunohistochemistry (IHC) on all uterine smooth muscle (USM) tumors in patients 40 (later ≤30) years or younger and on all USM tumors with suggestive FHD morphology regardless of age. Patients with FHD tumors by IHC were referred to genetic counseling. Of 840 USM tumors, 112 FHD-tumors by IHC (13%) were identified, all with suggestive FHD-morphology; 44 patients (39%) underwent germline testing, and 15 harbored germline FH PVs (34.1% of germline tested, 13.4% of all FHD-tumors). While FHD tumors were seen across a wide age range (24 to 73 y), those with germline FH PVs were significantly younger (median 33 vs 44 years wild-type, P = 0.0032). Few (12.5%) patients ≥40 and no patients ≥50 had a germline FH PV, whereas a majority (60%) of patients <40 (86% of those <30) had a germline FH PV. We demonstrate that previously proposed resource-conscious screening involving morphology and IHC is effective for identifying women with FHTPS. We provide prospective data confirming patients presenting with FHD-ULs over age 50 are unlikely to harbor germline FH PVs and argue that for germline testing without consideration of other factors, a threshold of younger than 50 years may be appropriate.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"315-327"},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142997836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SMARCB1-deficient Sinonasal Carcinoma: Expanding the Pathologic Spectrum With a Series of 32 Cases.","authors":"Neha Mittal, Saurabh Nagar, Asawari Patil, Swapnil Ulhas Rane, Palgun Nisarga, Katha Rabade, Amit Janu, Deepa Nair, Shiva Thiagarajan, Sarbani Ghosh Laskar, Kumar Prabhash, Munita Bal","doi":"10.1097/PAS.0000000000002364","DOIUrl":"https://doi.org/10.1097/PAS.0000000000002364","url":null,"abstract":"<p><p>SMARCB1-deficient sinonasal carcinoma (SDSC) is a recently recognized rare malignancy. Despite growing awareness, SDSC remains susceptible to misdiagnosis owing to its rarity and overlapping features with diverse mimics. A retrospective review of the clinical and pathologic features of 32 SDSC including 4 SMARCB-1 deficient adenocarcinoma (SDAC) cases was performed. The patients were aged 19 to 76 years with a male predominance. Most tumors arose in the naso-ethmoid (75%), and advanced stage (93.6%), with frequent multi-sinus (90.5%) involvement. Histologically, tumors exhibited diverse morphologies, including basaloid (50%), rhabdoid (25%), and undifferentiated (12.5%) types. SDAC cases showed glandular differentiation with intraluminal and stromal mucin. Empty vacuoles (62.5%), pagetoid spread (31.3%), eosinophilic-granular bodies (18.8%), hyaline globules (15.2%), and florid glomeruloid neovascularization (15.6%) were additional findings. Yolk sac-like areas were encountered in 18.6%. Immunohistochemically, tumors were defined by a complete loss of SMARCB1 (100%); a variable reactivity for p40 (65.6%), synaptophysin (13.6%), glypican3 (6.1%), and CD34 (6.1%) was present. Notably, >90% of our patients had different initial diagnoses before referral. Lymph node metastasis, locoregional recurrence, and distant metastasis were seen in 23.3%, 24.1%, and 27.6% patients, respectively; 37.9% died of disease. In conclusion, SDSCs are rare and aggressive sinonasal malignancies that display a wide histologic spectrum including glandular differentiation. This study expands on the morphologic spectrum of SDSC by analyzing a large cohort of 32 cases, adding comprehensive clinical, histopathologic, and immunohistochemical data, and highlighting features to improve diagnostic accuracy. The emergence of targeted therapies, such as EZH2 inhibitors, further underscores the importance of accurate diagnosis.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":"49 4","pages":"381-393"},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143646749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aberrant E-cadherin Expression in Lobular Carcinoma In Situ: A Comprehensive Immunohistochemical Evaluation of N-terminal, Extracellular, and C-terminal E-cadherin Domains.","authors":"Rita Canas-Marques, Ana Blanca, Raquel Graça-Lopes, Inês Carvalho, David G Pinto, Maria Antónia Vasconcelos, Antonio Lopez-Beltran, Isabel Fonseca","doi":"10.1097/PAS.0000000000002361","DOIUrl":"10.1097/PAS.0000000000002361","url":null,"abstract":"<p><p>E-cadherin (E-cad) immunohistochemistry is commonly used to distinguish lobular carcinoma in situ (LCIS) from ductal carcinoma in situ in histologically uncertain or ambiguous cases. Although most LCIS cases show an absence of E-cad expression on the neoplastic cell membranes, some show aberrant E-cad expression which can lead to diagnostic confusion. Awareness and understanding of the frequency, patterns, and distribution of aberrant E-cad staining in LCIS is crucial to achieving a correct diagnosis. We studied 55 LCIS cases diagnosed on core needle biopsy, classified each case by WHO subtype (classic, pleomorphic, or florid), and evaluated the frequency and patterns of aberrant E-cad expression using 3 different E-cad antibodies targeting the N-terminal (N), extracellular (EC), and C-terminal domains (C). Aberrant E-cad expression in one or more of the E-cad domains was identified in 17 cases (31%) and was significantly more frequent among LCIS variants (10/19, 56%) than among classic cases (7/36, 19.4%) ( P =0.02). Among these 17 cases, aberrant E-cad expression was seen for all 3 domains in 10 cases, for EC+C in 4, for EC+N in 2, and for N only in 1. These results indicate that about one-third of cases of LCIS can show aberrant E-cad expression, that this is more common in variants than classic types of LCIS, and that this may be seen in different E-cad domains, most often in combination. These different patterns of aberrant E-cad expression may reflect different mechanisms of E-cad alterations in LCIS, the underlying nature of which merits further studies.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"372-380"},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142977068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ovarian Carcinomas: Clinicopathologic and Molecular Features With Comments on 2014 FIGO Staging.","authors":"Jaime Prat, Emanuela D'Angelo, Iñigo Espinosa","doi":"10.1097/PAS.0000000000002352","DOIUrl":"10.1097/PAS.0000000000002352","url":null,"abstract":"<p><p>According to histopathology and molecular genetics, there are 5 major subtypes of ovarian carcinomas: high-grade serous (70%), endometrioid (10%), clear cell (10%), mucinous (3% to 4%), and low-grade serous (<5%) carcinomas. These tumors, which constitute over 95% of cases, represent distinct diseases with different prognoses and therapy. This review outlines contemporary advances in molecular pathology, which have expanded our knowledge of the biology of epithelial ovarian cancer and are also important to patient management. We also comment on some controversial points of the FIGO staging classification that we proposed in 2014.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"e1-e14"},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142977128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pancreatic Serous Neoplasm and Metastatic Clear Cell Renal Cell Carcinoma: Diagnostic Pitfalls Resolvable by a Panel of Immunohistochemical Stains to Include PAX8 and CK7 But Not CAIX.","authors":"Talent Theparee, Sarah E Umetsu, Emily Chan","doi":"10.1097/PAS.0000000000002357","DOIUrl":"https://doi.org/10.1097/PAS.0000000000002357","url":null,"abstract":"<p><p>Pancreatic serous neoplasms can morphologically resemble metastatic clear cell renal cell carcinoma (ccRCC) and may present a diagnostic dilemma, particularly if the solid variant is in small biopsy specimens and/or in patients with von Hippel Lindau (VHL) syndrome. We investigate the utility of immunohistochemical staining in this differential diagnosis by performing head-to-head comparisons of commonly used immunohistochemical markers for these 2 tumor types. We examined 16 pancreatic serous neoplasms and 24 ccRCCs (12 metastatic to pancreas and 12 primaries in patients with VHL). All pancreatic serous neoplasms stained positive for CK7, and most were positive for CAIX (15/16) and GLUT1 (15/16), variable for alpha-inhibin and vimentin (each 8/16 weak/focal; and 7/16 and 8/16, respectively, positive), and weak/focal for synaptophysin (14/16). All pancreatic serous neoplasms were negative for PAX8 and Periodic acid-Schiff without diastase. In contrast, ccRCC, both metastatic and in VHL patients, were mostly positive for PAX8 (18/24; 6/24 were weak/focal), negative for CK7 (15/24; 8/24 were weak/focal, one case diffuse positive), and negative for alpha-inhibin (100%) and synaptophysin (22/24). Like pancreatic serous neoplasms, all ccRCC showed weak/focal or positive staining for GLUT1, CAIX, and vimentin, and were negative for PAS-D. In conclusion, CK7 and PAX8 are the most useful stains in distinguishing between pancreatic serous neoplasm and ccRCC; however, weak/focal CK7 or PAX8 staining can be seen in a minority of ccRCC, thereby presenting a diagnostic pitfall. Alpha-inhibin was at least weak/focal in most pancreatic serous neoplasms and negative in all ccRCC and may be useful as an adjunct stain in difficult cases.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":"49 4","pages":"394-402"},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143646830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical, Pathologic, and Molecular spectrum of Angioinmmunoblastic T-cell Lymphoma Cutaneous Lesions: Clinical, Pathologic, and Molecular Analysis.","authors":"Francisco Javier Díaz de la Pinta, M Ángeles Pérez-Guillermo Cuevas, Rebeca Manso, Juan Torre Castro, Laura Astilleros Blanco de Cordova, Carles Saus, Daniel Morillo Giles, Luis Requena Caballero, Socorro María Rodríguez Pinilla","doi":"10.1097/PAS.0000000000002355","DOIUrl":"10.1097/PAS.0000000000002355","url":null,"abstract":"<p><p>Angioimmunoblastic T-cell lymphoma (AITL) is an aggressive malignancy that frequently presents with extranodal involvement. Cutaneous tropism is clinically and histopathologically variable, which may pose a diagnostic challenge. We conducted a retrospective analysis of 40 samples of 20 cases of cutaneous AITL, focusing on the clinicopathologic and molecular correlations between skin and lymph node (LN) samples. In all cases, cutaneous involvement was concurrent with or followed the diagnosis of nodal AITL, with no cases preceding systemic involvement. Clinically, cutaneous AITL presented in 2 main forms: an evanescent rash and persistent lesions, with histopathology revealing diverse infiltration patterns, including perivascular, nodular, granulomatous, panniculitic, vasculitis, and epidermotropic. Clinical presentation and histologic patterns tend to correlate. Histopathologically, plasma cells were present in 15/22 skin samples, 5 of them being kappa-light restricted but polytypic in corresponding LNs. Epstein-Barr virus+ B cells were present in 10 cutaneous lesions and were already present in corresponding LNs. Molecular studies found correlations in all but one case between LN and skin, particularly in the presence of RHOA and TET2 mutations, which were identified in 8 of 12 cases. Molecular analysis was also informative in 4 cases with low levels of infiltration. The study also highlighted unique cases with distinct clinical and histopathologic patterns coexisting in the same patient over time. One case exhibited simultaneous granulomatous and epidermotropic patterns in different skin lesions. Four cases of cutaneous B-cell lymphomas associated with AITL were identified. Our study underscores the importance of integrating clinical, histopathologic, and molecular data to accurately diagnose cutaneous AITL.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"403-410"},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142969325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}