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Distinctive Pathology Associated With Focal Stenosis of the Main Pancreatic Duct Secondary to Remote Trauma: A Long-term Complication of Seat Belt Pancreatitis. Am. J. Surg. Pathol. (IF 5.6) Pub Date : 2024-03-14 Annie A Wu, Elizabeth D Thompson, John L Cameron, Jin He, Richard A Burkhart, William R Burns, Kelly J Lafaro, Christopher R Shubert, Marcia I Canto, Elliot K Fishman, Ralph H Hruban
The radiologic finding of focal stenosis of the main pancreatic duct is highly suggestive of pancreatic cancer. Even in the absence of a mass lesion, focal duct stenosis can lead to surgical resection of the affected portion of the pancreas. We present four patients with distinctive pathology associated with non-neoplastic focal stenosis of the main pancreatic duct. The pathology included stenosis
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Reappraisal of p16 for Determining HPV Status of Head and Neck Carcinomas Arising in HPV Hotspots. Am. J. Surg. Pathol. (IF 5.6) Pub Date : 2024-03-14 Swati Bhardwaj, Melissa Gitman, Juan D Ramirez, Alberto Paniz-Mondolfi, William H Westra
In an era of head and neck oncology where HPV status will soon dictate patient management, reliable HPV detection is critical. P16 immunohistochemistry (IHC) is currently recommended as the test of choice for oropharyngeal squamous cell carcinomas (OPSCCs). The purpose of this study was to determine the performance characteristics of p16 IHC based on a large clinical experience of squamous cell carcinomas
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Significance of Spread Through Air Spaces and Vascular Invasion in Early-stage Adenocarcinoma Survival: A Comprehensive Clinicopathologic Study of 427 Patients for Precision Management. Am. J. Surg. Pathol. (IF 5.6) Pub Date : 2024-03-05 Samuele Nicotra, Luca Melan, Federica Pezzuto, Alessandro Bonis, Stefano Silvestrin, Vincenzo Verzeletti, Giorgio Cannone, Alessandro Rebusso, Giovanni Maria Comacchio, Marco Schiavon, Andrea Dell'Amore, Fiorella Calabrese, Federico Rea
Spread through air spaces (STAS) is a novel invasive pattern of lung cancer associated with poor prognosis in non-small cell cancer (NSCLC). We aimed to investigate the incidence of STAS in a surgical series of adenocarcinomas (ADCs) resected in our thoracic surgery unit and to identify the association of STAS with other clinicopathological characteristics. We retrospectively enrolled patients with
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Primary Pulmonary Myxoid Sarcoma and Thoracic Angiomatoid Fibrous Histiocytoma: Two Sides of the Same Coin? Am. J. Surg. Pathol. (IF 5.6) Pub Date : 2024-02-26 Allison L Kerper, Brandon T Larsen, Andrew L Folpe, Anja C Roden, Jorge Torres-Mora, Ying-Chun Lo, Marie-Christine Aubry, Jennifer M Boland
Primary pulmonary myxoid sarcoma (PPMS) and thoracic angiomatoid fibrous histiocytoma (AFH) are rare neoplasms with EWSR1 fusions and overlapping morphology. Both tumor types often show epithelial membrane antigen expression, but AFH characteristically co-expresses desmin. We encountered a case of PPMS with the unexpected finding of patchy, strong anaplastic lymphoma kinase (ALK) (previously reported
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Ki-67 Proliferation Index Is Associated With Tumor Grade and Survival in Pleural Epithelioid Mesotheliomas. Am. J. Surg. Pathol. (IF 5.6) Pub Date : 2024-02-19 Belinda Galeano, Caleb J Smith, Eunhee S Yi, Anja C Roden, Sarah Jenkins, Jenna Capelle, Mary Kittle-Francis, Aaron S Mansfield, Marie Christine Aubry
Pleural epithelioid mesothelioma (PEM) is divided into low and high grades based on nuclear atypia, mitoses, and necrosis in the tumor. Assessing mitoses and nuclear atypia tend to be labor-intensive with limited reproducibility. Ki-67 proliferation index was shown to be a prognostic factor in PEM, but its performance has not been directly correlated with tumor grade or mitotic score. This study evaluated
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Pan-cancer Genomic Analysis of AXL Mutations Reveals a Novel, Recurrent, Functionally Activating AXL W451C Alteration Specific to Myxofibrosarcoma. Am. J. Surg. Pathol. (IF 5.6) Pub Date : 2024-02-19 Erik A Williams, Isabella Vegas, Fardous F El-Senduny, Jessica Zhang, Douglas A Mata, Matthew C Hiemenz, Sarah R Hughes, Brianna C Sa, Garrett P Kraft, Nicole Gorbatov, Kathleen Foley-Peres, Edward Z Sanchez, Clara Milikowski, Kevin Jon Williams, Jeffrey S Ross, Razelle Kurzrock, Elizabeth A Montgomery, David B Lombard, Surinder Kumar
Myxofibrosarcoma (MFS) is a common soft tissue sarcoma of the elderly that typically shows low tumor mutational burden, with mutations in TP53 and in genes associated with cell cycle checkpoints (RB1, CDKN2A). Unfortunately, no alterations or markers specific to MFS have been identified and, as a consequence, there are no effective targeted therapies. The receptor tyrosine kinase AXL, which drives
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Pathogenic Somatic Mutation of DICER1 and Clinicopathological Features in Nasal Chondromesenchymal Hamartomas: A Series of Nine Cases. Am. J. Surg. Pathol. (IF 5.6) Pub Date : 2024-02-15 Chunyan Hu, Yifeng Liu, Lan Lin, Cuncun Yuan, Duan Ma, Qiang Huang
Nasal chondromesenchymal hamartoma (NCMH) is a rare benign polypoid mesenchymal tumor arising in the nasal cavity and/or paranasal sinuses. Recognizing these sporadic, rare lesions is crucial, as surgical complete removal of the mass is the common treatment approach. This retrospective study analyzed the demographics, symptoms, and imaging data of 9 patients diagnosed with NCMH between January 2017
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Trichorhinophalangeal Syndrome Type 1 Immunohistochemical Expression in Carcinomas of Gynecologic Origin. Am. J. Surg. Pathol. (IF 5.6) Pub Date : 2024-02-15 Felipe Ruiz, Youley Tjendra, Nicolas Millan, Carmen Gomez-Fernandez, Andre Pinto
Trichorhinophalangeal syndrome type 1 (TRPS1) is a new reportedly sensitive and specific immunohistochemical marker for carcinomas of breast origin, including triple-negative (estrogen receptor, progesterone receptor, and HER2) tumors. In our practice, we have observed a subset of cases of nonmammary carcinomas that are positive for TRPS1, with higher frequency in cytology effusion samples with metastatic
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Recurrent GATA3 P409Afs*99 Frameshift Extension Mutations in Sweat-gland Carcinoma With Neuroendocrine Differentiation. Am. J. Surg. Pathol. (IF 5.6) Pub Date : 2024-02-14 Keisuke Goto, Yukiko Kiniwa, Yoji Kukita, Shuichi Ohe, Tsubasa Hiraki, Tsunekazu Hishima, Toshihiro Takai, Keiichiro Honma
Sweat-gland carcinoma with neuroendocrine differentiation (SCAND) was recently proposed as a new cutaneous adnexal neoplasm with neuroendocrine differentiation; however, its genetics are not well known. Herein, we performed clinicopathologic and genetic analyses of 13 SCAND cases and 5 control cases of endocrine mucin-producing sweat gland carcinoma (EMPSGC). The SCAND group included 11 males and 2
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Histologic Manifestations of Gastrointestinal Adenovirus Infection After Stem Cell Transplant. Am. J. Surg. Pathol. (IF 5.6) Pub Date : 2024-02-08 Erika Hissong, Kshitij Arora, Caroline Andy, Jose Jessurun, Rhonda K Yantiss
Adenovirus can cause severe disease in hematopoietic stem cell transplant (HSCT) patients. Histopathologic features of this infection in gastrointestinal biopsies and their distinction from graft-versus-host disease (GVHD) have been incompletely studied. We retrospectively identified patients with gastrointestinal adenovirus infection. H&E-stained sections were reviewed and the histologic features
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Morphologic and Molecular Heterogeneity of High-grade Serous Carcinoma Precursor Lesions. Am. J. Surg. Pathol. (IF 5.6) Pub Date : 2024-02-01 Yen-Wei Chien, Yeh Wang, Peng Huang, Barrett Craig Lawson, David L Kolin, M Herman Chui, Russell Vang, Tricia A Numan, T Rinda Soong, Brant G Wang, Saron Ann Smith, Chi-Long Chen, Rebecca Stone, Christopher Douville, Tian-Li Wang, Ie-Ming Shih
Serous tubal intraepithelial carcinoma (STIC) is the fallopian tube precursor lesion for most cases of pelvic high-grade serous carcinoma (HGSC). To date, the morphologic, molecular, and clinical heterogeneity of STIC and a less atypical putative precursor lesion, termed serous tubal intraepithelial lesion, has not been well characterized. Better understanding of precursor heterogeneity could impact
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Spread Through Air Spaces in Stage I to III Resected Lung Adenocarcinomas: Should the Presence of Spread Through Air Spaces Lead to an Upstaging? Am. J. Surg. Pathol. (IF 5.6) Pub Date : 2024-02-01 David Laville, Anne-Laure Désage, Pierre Fournel, Sophie Bayle-Bleuez, Chaouki Neifer, Tiphanie Picot, Abdulrazzak Sulaiman, Olivier Tiffet, Fabien Forest
In recent years, the concept of spread through air spaces (STAS) has been discussed as an adverse prognostic factor for lung cancer. The aim of our study is to clarify the prognostic role of STAS in relation to the main recognized prognostic factors in a retrospective cohort of 330 European patients who underwent stages I to III lung adenocarcinoma resection. On univariate analysis, the presence of
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EBV-positive Nodal T-Cell and NK-Cell Lymphoma: A Study of 26 Cases Including a Subset With Strong CD30 Expression Mimicking Anaplastic Large Cell Lymphoma. Am. J. Surg. Pathol. (IF 5.6) Pub Date : 2024-01-30 Fang Yu, Jinghan Wang, Zhonghe Ke, Yafei Zhang, Liming Xu, Han Zhang, Ke Huang, Fei Cheng, Hanjin Yang, Lijun Wang, Zhaoming Wang, Lihong Shou, Wenjuan Yu, Hong Fang, L Jeffrey Medeiros, Wei Wang
Epstein-Barr virus (EBV)-positive nodal T-cell and NK-cell lymphoma is a rare neoplasm of cytotoxic T-cell or NK-cell lineage. Here, we report 26 cases affecting 14 men and 12 women with a median age of 52 years. All patients presented with disease involving multiple lymph nodes, and 20 of 22 (91%) fully staged patients had advanced Ann Arbor stage disease. Spleen, liver, and bone marrow were involved
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Differentiating Between Epstein-Barr Virus-positive Lymphoid Neoplasm Relapse and Post-transplant Lymphoproliferative Disorder After Sex-mismatched Hematopoietic Stem Cell Transplantation. Am. J. Surg. Pathol. (IF 5.6) Pub Date : 2024-01-30 Ryumei Kurashige, Masako Kurashige, Yosuke Okada, Kohei Higuchi, Sayako Yuda, Akihisa Hino, Takako Miyamura, Michiko Ichii, Kentaro Fukushima, Keiichiro Honma, Makoto Takeuchi, Takafumi Yokota, Jun Ishikawa, Akihisa Sawada, Hirohiko Shibayama, Naoki Hosen, Eiichi Morii
After allogeneic hematopoietic stem cell transplantation (HSCT), accurate differentiation between donor-derived post-transplant lymphoproliferative disorder (PTLD) and relapse of recipient-derived lymphoproliferative disorder (LPD) is crucial for determining treatment. Conventional diagnostic approaches for PTLD include histopathological examination, flow cytometry, and chimerism analysis of bulk tumor
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Mesothelioma of Uncertain Malignant Potential (MUMP) of the Tunica Vaginalis: Proposal for Reclassification as "Complex Mesothelial Tumor of the Tunica Vaginalis". Am. J. Surg. Pathol. (IF 5.6) Pub Date : 2024-01-25 Chien-Kuang C Ding, Jason Van Roo, Oleksandr N Kryvenko, Huihui Ye, Jesse K McKenney, Jonathan I Epstein
A well-differentiated papillary mesothelial tumor (WDPMT) and malignant mesothelioma are 2 well-recognized entities arising from the testis tunica vaginalis. Another mesothelial lesion exclusively seen at this site is mesothelioma of uncertain malignant potential (MUMP)-a lesion reminiscent of WDPMT yet demonstrating variable proportions of more complex architectural patterns that could be confused
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GAD2 Is a Highly Specific Marker for Neuroendocrine Neoplasms of the Pancreas. Am. J. Surg. Pathol. (IF 5.6) Pub Date : 2024-01-25 Maximilian Lennartz, Nick Benjamin Dünnebier, Doris Höflmayer, Sebastian Dwertmann Rico, Simon Kind, Viktor Reiswich, Florian Viehweger, Florian Lutz, Christoph Fraune, Natalia Gorbokon, Andreas M Luebke, Claudia Hube-Magg, Franziska Büscheck, Anne Menz, Ria Uhlig, Till Krech, Andrea Hinsch, Eike Burandt, Guido Sauter, Ronald Simon, Martina Kluth, Stefan Steurer, Andreas H Marx, Patrick Lebok, David
Glutamate decarboxylase 2 (GAD2) is the most important inhibitory neurotransmitter and plays a role in insulin-producing β cells of pancreatic islets. The limitation of GAD2 expression to a few normal cell types makes GAD2 a potential immunohistochemical diagnostic marker. To evaluate the diagnostic utility of GAD2 immunohistochemistry, a tissue microarray containing 19,202 samples from 152 different
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Prognostic Value of BAP1 Protein Expression in Uveal Melanoma. Am. J. Surg. Pathol. (IF 5.6) Pub Date : 2024-01-19 Susan Kennedy, Sally Owens, Laura Ivers, Ciara Hegarty, Valerie O'Neill, Jose J Berenguer-Pina, Noel Horgan, John Crown, Naomi Walsh
The prognostic value of the traditional pathologic parameters that form part of the American Joint Committee on Cancer staging system and genetic classifications using monosomy chromosome 3 and structural alterations in chromosome 8 are well established and are part of the diagnostic workup of uveal melanoma (UM). However, it has not been fully clarified whether nuclear protein expression of the tumor
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Clinical Significance and Prognostic Implications of Discontinuous Growth Pattern in Esophageal Adenocarcinoma: A Multi-Institutional Study. Am. J. Surg. Pathol. (IF 5.6) Pub Date : 2024-01-17 Michel Kmeid, Goo Lee, Zhaohai Yang, Richard Pacheco, Jingmei Lin, Deepa T Patil, Mariam Youssef, Qingzhao Zhang, Ahmad Mahmoud Alkashash, Jingwei Li, Hwajeong Lee
The significance of discontinuous growth (DG) of the tumor to include tumor deposits and intramural metastasis in esophageal adenocarcinoma (EAC) is unclear. Esophagectomy specimens from 151 treatment-naïve and 121 treated patients with EAC were reviewed. DG was defined as discrete (≥2 mm away) tumor foci identified at the periphery of the main tumor in the submucosa, muscularis propria, and/or periadventitial
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Clinical, Morphologic, and Molecular Features of MAP3K8 Rearranged Spitz Neoplasms: A Retrospective Study Documenting That Bonafide Spitz Melanomas Are Rare. Am. J. Surg. Pathol. (IF 5.6) Pub Date : 2024-01-17 Pragi Patel, Michael Hagstrom, Natasha Sharma, Alice Chen, Soneet Dhillon, Mónica Fumero-Velázquez, Shantel Olivares, Pedram Gerami
Previous studies regarding the clinical behavior of Spitz neoplasms lack genomic characterization. We aim to assess our hypothesis that most MAP3K8 Spitz neoplasms are indolent despite MAP3K8 being the single most common driver of Spitz melanoma. Further, we aim to identify genomic features associated with aggressive behavior and to better characterize the morphology of these cases. We analyzed the
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Colorectal Carcinoma With Sarcomatoid Components: Report of 15 Cases and Literature Review of an Exceedingly Rare Carcinoma Subtype. Am. J. Surg. Pathol. (IF 5.6) Pub Date : 2023-12-29 Umamaheshwari Golconda, Kelsey E McHugh, Daniela S Allende, Katrina Collins, Patrick Henn, Maribel Lacambra, Pablo A Bejarano, Gabriel M Groisman, Maurice B Loughrey, Vidya Monappa, Xuchen Zhang, Jason L Hornick, Raul S Gonzalez
Colorectal carcinoma with sarcomatoid components (which includes so-called carcinosarcomas and sarcomatoid carcinomas) is a rare subtype with 50 reported cases in the literature and overlapping criteria with undifferentiated carcinoma. We collected and described 15 cases from 10 men and 5 women, with a mean age of 66 years. Symptoms included abdominal pain and gastrointestinal bleeding. Most tumors
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Diagnostic Utility of a Modified Reticulin Algorithm in Pediatric Adrenocortical Neoplasms. Am. J. Surg. Pathol. (IF 5.6) Pub Date : 2023-12-29 Oscar Lopez-Nunez, Calogero Virgone, Irina S Kletskaya, Luisa Santoro, Stefano Giuliani, Bruce Okoye, Marco Volante, Andrea Ferrari, Gianni Bisogno, Eleonora Duregon, Mauro Papotti, Gianluca De Salvo, Sarangarajan Ranganathan, Rita Alaggio
Pediatric adrenocortical neoplasms (ACNs) are extremely rare tumors in contrast to their adult counterparts. Distinguishing benign from malignant is challenging based on pure morphologic grounds. Previously, 2 scoring systems were proposed in pediatric ACN, including the Wieneke criteria (WC) and its modified version (modified WC [mWC]). In adults, the reticulin algorithm (RA) has proven inexpensive
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Characterization of Amyloidosis in the Gastrointestinal Tract With an Emphasis on Histologically Distinct Interstitial Patterns of Deposition and Misinterpretations. Am. J. Surg. Pathol. (IF 5.6) Pub Date : 2023-12-25 Jaryse Carol Harris, Qingzhou Zhang, Rashmi Tondon, Zahra Alipour, Kristen Stashek
Amyloidosis can involve the gastrointestinal (GI) tract, and deposition can present with varied histologic patterns that make recognition challenging. This retrospective observational study aimed to characterize the deposition patterns in the GI tract and evaluate key quality metrics, including discrepant cases, to improve recognition and provide insight for accurate diagnosis. Sixty-two patients (195
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RAS Family Gene Mutations, Clinicopathological Features, and Spread Patterns of Inverted Urothelial Papilloma of the Bladder. Am. J. Surg. Pathol. (IF 5.6) Pub Date : 2023-12-25 Keiichiro Kitahama, Yasuyuki Shigematsu, Gulanbar Amori, Emiko Sugawara, Junji Yonese, Junji Shibahara, Kengo Takeuchi, Kentaro Inamura
Inverted urothelial papilloma (IUP) is a benign neoplasm characterized by a downgrowth of the urothelium beneath the surface of morphologically normal urothelial cells; however, the molecular features of IUP and their association with clinicopathological characteristics are unclear. In this study, we aimed to investigate the mutational landscape, clinicopathological features, genotype-phenotype associations
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TIGIT is Frequently Expressed in the Tumor Microenvironment of Select Lymphomas: Implications for Targeted Therapy. Am. J. Surg. Pathol. (IF 5.6) Pub Date : 2023-12-22 Diane Libert, Shuchun Zhao, Sheren Younes, Alicia P Mosquera, Sushma Bharadwaj, Cristiane Ferreira, Yasodha Natkunam
Immune checkpoint inhibitors against Programmed Cell Death Protein 1/Programmed Cell (PD-1/PD-L1) and CTLA-4/B7 axes have had limited success in hematologic malignancies, requiring the need to explore alternative targets such as T-cell immunoreceptor with Ig and ITIM domains (TIGIT)/CD155 to improve durable clinical responses. We undertook this study to investigate the expression profile of TIGIT such
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Tumor Budding Assessment in Colorectal Carcinoma: Normalization Revisited. Am. J. Surg. Pathol. (IF 5.6) Pub Date : 2023-12-18 David P Cyr, Cherry Pun, Sameer Shivji, Bojana Mitrovic, Kai Duan, Rossi Tomin, Aysegul Sari, Amanpreet Brar, Siham Zerhouni, Mantaj S Brar, Erin D Kennedy, Carol J Swallow, Richard Kirsch, James R Conner
Tumor budding (TB) is a powerful prognostic factor in colorectal cancer (CRC). An internationally standardized method for its assessment (International Tumor Budding Consensus Conference [ITBCC] method) has been adopted by most CRC pathology protocols. This method requires that TB counts are reported by field area (0.785 mm2) rather than objective lens and a normalization factor is applied for this
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Keratocystoma: A Distinctive Salivary Gland Neoplasm Characterized by RUNX2 Rearrangements. Am. J. Surg. Pathol. (IF 5.6) Pub Date : 2023-12-12 Justin A Bishop, Masato Nakaguro, Makoto Urano, Yoshinari Yamamoto, Yoshitaka Utsumi, Rong Li, Ilan Weinreb, Yoji Nagashima, Chiraag Gangahar, Katsushige Yamashiro, Kimio Hashimoto, Lisa M Rooper, Brian Carlile, Richard C Wang, Jeffrey Gagan, Toshitaka Nagao
Keratocystoma is a rare salivary gland lesion that has been reported primarily in children and young adults. Because of a scarcity of reported cases, very little is known about it, including its molecular underpinnings, biological potential, and histologic spectrum. Purported to be a benign neoplasm, keratocystoma bears a striking histologic resemblance to benign lesions like metaplastic Warthin tumor
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Non-Small Cell Lung Carcinoma with Clear Cell Features and FGFR3::TACC3 Gene Rearrangement: Clinicopathologic and Next Generation Sequencing Study of 7 Cases. Am. J. Surg. Pathol. (IF 5.6) Pub Date : 2023-12-12 David Suster, A Craig Mackinnon, Natali Ronen, Haider A Mejbel, Shuko Harada, Saul Suster
Seven cases of primary lung tumors characterized histologically by clear cell morphology and a distinctive FGFR3::TACC3 gene rearrangement are described. The tumors arose in 4 women and 3 men, aged 47 to 81 years (mean=68). They occurred in peripheral locations, predominantly subpleural, and ranged in size from 1.4 to 6.5 cm (mean=4.1 cm). All tumors showed a solid growth pattern with abundant central
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Specific Pathology Features Enrich Selection of Endometrial Carcinomas for POLE Testing. Am. J. Surg. Pathol. (IF 5.6) Pub Date : 2023-12-08 Kianoosh Keyhanian, Lucy Han, Brooke E Howitt, Teri Longacre
Identification of ultramutated/POLE-mutated endometrial carcinomas (POLEM ECs) has important implications given its association with better prognosis. However, POLE mutation testing is not widely available. Our objective was to evaluate POLEM ECs versus POLE wild-type (POLEWT) ECs, within a cohort of consultation cases with features suggestive of an ultramutated phenotype. Consultation cases of EC
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Gastrointestinal Ewing Sarcoma: A Clinicopathological and Molecular Genetic Analysis of 25 Cases. Am. J. Surg. Pathol. (IF 5.6) Pub Date : 2023-12-08 Tangchen Yin, Mengyuan Shao, Meng Sun, Lu Zhao, I Weng Lao, Lin Yu, Jian Wang
Occurrence of extraskeletal Ewing sarcoma (ES) in the gastrointestinal (GI) tract is extremely rare. Here, we report 25 cases of ES arising primarily in the GI tract with a focus on the clinicopathological and molecular features, differential diagnosis, and biological behavior. Thirteen patients (52%) were male, and 12 (48%) were female with age ranging from 9 to 59 years (mean: 36.2 years; median:
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Colloid Pattern of Salivary Mucinous Adenocarcinomas With Recurrent BRAF V600E Mutations. Am. J. Surg. Pathol. (IF 5.6) Pub Date : 2023-12-05 Ye Zhang, Zheng Zhou, Xiaoxiao Liu, Lijing Zhu, Yajuan Cui, Tie-Jun Li, Chuan-Xiang Zhou
The relationship between various patterns of mucin-producing salivary adenocarcinomas, including invasive salivary adenocarcinomas with mucinous differentiation, such as colloid and papillary carcinomas, remains unclear. Herein, we aimed to describe the clinicopathologic characteristics, immunophenotypes, molecular underpinnings, and clinical behavior of salivary mucinous adenocarcinomas (MA) to clarify
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Fetal Type Morphologies Suggest the Presence of DICER1 Hotspot Mutations in Non-small Cell Lung Cancer. Am. J. Surg. Pathol. (IF 5.6) Pub Date : 2023-12-05 Anne-Laure Chong, Paul Thorner, Michelle Ellis, Jeff Swensen, Naciba Benlimame, Pierre-Olivier Fiset, Zoran Gatalica, Mark G Evans, William D Foulkes
Germline and somatic pathogenic variants (PVs) in DICER1, encoding a miRNA biogenesis protein, are associated with a wide variety of highly specific pathologic entities. The lung tumors pleuropulmonary blastoma, pulmonary blastoma (PB), and well-differentiated fetal lung adenocarcinoma (WDFLAC) are all known to harbor DICER1 biallelic variants (loss of function and/or somatic hotspot missense mutations)
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Relationship Between Immunophenotypes, Genetic Profiles, and Clinicopathologic Characteristics in Small Bowel Adenocarcinoma. Am. J. Surg. Pathol. (IF 5.6) Pub Date : 2023-12-04 Aitoshi Hoshimoto, Atsushi Tatsuguchi, Takeshi Yamada, Sho Kuriyama, Ryohei Hamakubo, Takayoshi Nishimoto, Jun Omori, Naohiko Akimoto, Katya Gudis, Keigo Mitsui, Shu Tanaka, Shunji Fujimori, Tsutomu Hatori, Akira Shimizu, Katsuhiko Iwakiri
Small bowel adenocarcinoma (SBA) is rare, and scant data exist regarding its molecular and clinicopathologic characteristics. This study aimed to clarify the correlation between immunophenotypes, DNA mismatch repair status, genomic profiling, and clinicopathologic characteristics in patients with SBA. We examined 68 surgical resections from patients with primary SBA for immunohistochemical analyses
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NIPBL::NACC1 Fusion Hepatic Carcinoma. Am. J. Surg. Pathol. (IF 5.6) Pub Date : 2023-12-04 Erika Hissong, Majd Al Assaad, Munita Bal, Katelyn A Reed, Adele Fornelli, Max F Levine, Gunes Gundem, Alissa Semaan, Christine E Orr, Uma Sakhadeo, Jyothi Manohar, Michael Sigouros, David Wilkes, Andrea Sboner, Elizabeth A Montgomery, Rondell P Graham, Juan S Medina-Martínez, Nicolas Robine, Jiayun M Fang, Eun-Young K Choi, Maria Westerhoff, Jesús Delgado-de la Mora, Patricia Caudell, Rhonda K Yantiss
Several reports describing a rare primary liver tumor with histologic features reminiscent of follicular thyroid neoplasms have been published under a variety of descriptive terms including thyroid-like, solid tubulocystic, and cholangioblastic cholangiocarcinoma. Although these tumors are considered to represent histologic variants, they lack classic features of cholangiocarcinoma and have unique
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Hybrid Oncocytic Tumors (HOTs) in Birt-Hogg-Dubé Syndrome Patients-A Tale of Two Cities: Sequencing Analysis Reveals Dual Lineage Markers Capturing the 2 Cellular Populations of HOT. Am. J. Surg. Pathol. (IF 5.6) Pub Date : 2023-11-24 Xiao-Ming Wang, Rahul Mannan, Yuping Zhang, Anya Chinnaiyan, Roshni Rangaswamy, Seema Chugh, Fengyun Su, Xuhong Cao, Rui Wang, Stephanie L Skala, Khaled S Hafez, Ulka Vaishampayan, Jesse Mckenney, Maria M Picken, Sounak Gupta, Reza Alaghehbandan, Maria Tretiakova, Pedram Argani, Arul M Chinnaiyan, Saravana M Dhanasekaran, Rohit Mehra
Birt-Hogg-Dubé (BHD) syndrome is associated with an increased risk of multifocal renal tumors, including hybrid oncocytic tumor (HOT) and chromophobe renal cell carcinoma (chRCC). HOT exhibits heterogenous histologic features overlapping with chRCC and benign renal oncocytoma, posing challenges in diagnosis of HOT and renal tumor entities resembling HOT. In this study, we performed integrative analysis
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A Comprehensive Study of Heterogeneous Mismatch Repair Expression in Solid Tumors Reveals Different Immunohistochemical Patterns and Distinct Genetic Mechanisms. Am. J. Surg. Pathol. (IF 5.6) Pub Date : 2023-11-24 Jing Wang, Zijuan Zhang, Yumeng Cai, Junliang Lu, Hui Zhang, Junyi Pang, Huanwen Wu, Zhiyong Liang
Immunohistochemistry is routinely performed to detect mismatch repair deficiency in solid tumors. Heterogeneous MMR expression (MMR-het) has been reported occasionally but not systemically studied.
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Clinical Data Do Not Reliably Predict Duodenal Histology at Follow-up in Celiac Disease: A 13 Center Correlative Study. Am. J. Surg. Pathol. (IF 5.6) Pub Date : 2023-11-23 Natalie Patel, Daniel A Leffler, Abdulbaqi Al-Toma, Chris Mulder, Luca Elli, Geliang Gan, Pallavi Patil, Amporn Atsawarungruangkit, Karel C Kuijpers, Alessandro Del Gobbo, Jeffrey Goldsmith, Zach Hintze, M Cristina Pacheco, Michael Vieth, Balint Melcher, Marcela Salomao, Rish Pai, John Hart, Andrea Olivas, Bita Naini, Cherise Meyerson, Won-Tak Choi, Sanjay Kakar, Maria Westerhoff, Jerome Cheng, Purva
Validated nonbiopsy methods to assure duodenal mucosal healing in celiac disease are lacking, yet ongoing mucosal injury is associated with anemia, osteoporosis, and lymphoma. Most providers utilize clinical data as surrogates of mucosal status to avoid additional esophagogastroduodenoscopy. The reliability of such surrogates to predict mucosal recovery has been incompletely evaluated. The aim of this
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S100 Protein Expression in Primary and Metastatic Neuroendocrine Neoplasms: A Specific Marker of Pancreatic Origin. Am. J. Surg. Pathol. (IF 5.6) Pub Date : 2023-11-22 Michael A Pepper, Ben W Dulken, Yiwen Wang, Allison J Zemek, Brock A Martin, Vivek Charu, Teri A Longacre
Neuroendocrine neoplasms can arise in a wide variety of anatomic sites including the gastrointestinal tract, pancreas, and lung, among others. Here, we report on the expression of S100 protein in a tissue microarray composed of 919 distinct primary and metastatic neuroendocrine neoplasms from 548 patients. S100 protein is a commonly used marker in many laboratories for the identification of neural
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Cervical Adenoid Basal Carcinoma With High-grade Squamous Component: True Mixed Carcinoma or Colonization of Adenoid Basal Carcinoma by High-grade Squamous Intraepithelial Lesion? Am. J. Surg. Pathol. (IF 5.6) Pub Date : 2023-11-22 Karen L Talia, W Glenn McCluggage
Adenoid basal carcinoma (ABC) is a rare clinically indolent human papillomavirus-associated cervical neoplasm with uniformly bland morphology which in pure form does not metastasize. Many cases co-exist with a human papillomavirus-associated high-grade squamous intraepithelial lesion (HSIL) or squamous cell carcinoma (SCC). The ABC and high-grade squamous components may be clearly separate, albeit
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Divergent Lineage Markers in Anaplastic Thyroid Carcinoma. Am. J. Surg. Pathol. (IF 5.6) Pub Date : 2023-11-16 Wadad S Mneimneh, Sylvia L Asa
Anaplastic thyroid carcinoma (ATC) often results from dedifferentiation of differentiated thyroid carcinoma (DTC), and the diagnosis is not difficult, as the tumor is seen to progress from a recognized DTC. However, in some cases, the diagnosis based on biopsy of limited tissue or resection of a completely undifferentiated tumor relies on immunohistochemical biomarkers and is usually a diagnosis of
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p16 Immunohistochemistry as a Screening Tool for Homozygous CDKN2A Deletions in CNS Tumors. Am. J. Surg. Pathol. (IF 5.6) Pub Date : 2023-11-13 Valentina Zschernack, Felipe Andreiuolo, Evelyn Dörner, Anna Wiedey, Stephanie T Jünger, Lea L Friker, Riccardo Maruccia, Torsten Pietsch
The 2021 World Health Organization classification of tumors of the central nervous system emphasizes the significance of molecular parameters for an integrated diagnosis. Homozygous deletion of cyclin-dependent kinase inhibitor 2a (CDKN2A) has been associated with an adverse prognosis in IDH-mutant gliomas, supratentorial ependymomas, meningiomas, and MPNST. In this study, we examined the value of
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Pediatric Sertoli-Leydig Cell Tumors of the Ovary: An Integrated Study of Clinicopathological Features, Pan-cancer-Targeted Next-generation Sequencing and Chromosomal Microarray Analysis From a Single Institution. Am. J. Surg. Pathol. (IF 5.6) Pub Date : 2023-11-10 Bo Yang, William Chour, Cristo Guardado Salazar, Paul Zamiara, Ryan J Schmidt, Gordana Raca, Nick Shillingford, Shengmei Zhou, Mikako Warren, David M Parham, Bruce Pawel, Larry L Wang
Sertoli-Leydig cell tumors (SLCTs) are currently classified into 3 molecular subtypes: DICER1-mutant (younger patient age), FOXL2-mutant, and DICER1/FOXL2-wildtype. However, it is not clear whether all pediatric SLCTs are DICER1-mutant molecular subtypes and whether other molecular genetic aberrations besides DICER1 are involved in the pathogenesis and prognosis of these tumors. We studied comprehensive
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Epstein-Barr Virus-Positive Plasma Cell Neoplasms in Immunocompetent Patients: A Clinicopathological Study of 15 Cases from South China and Literature Review. Am. J. Surg. Pathol. (IF 5.6) Pub Date : 2023-10-17 Shanshan Xiao, Yansong Lin, Jia Fu, Xin Weng, Qinghua Cao, Zhongsheng Kuang, Jingping Yun, Meifang Zhang, Yuhua Huang
Epstein-Barr virus (EBV)-positive plasma cell neoplasms (PCNs) in immunocompetent patients are a rare entity, the clinicopathological and prognostic features of which have not been well characterized. Fifteen cases of EBV-positive PCN arising in immunocompetent patients from south China were retrospectively analyzed, and an additional 44 cases from the literature were reviewed. The overall EBV-positive
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Prognostic Value of Immunohistochemistry-based Subtyping Before and After Neoadjuvant Chemotherapy in Patients with Triple-negative Breast Cancer. Am. J. Surg. Pathol. (IF 5.6) Pub Date : 2023-10-17 Long Wu, Minyan Chen, Yuxiang Lin, Bangwei Zeng, Wenhui Guo, Lili Chen, Yan Li, Liuwen Yu, Jing Li, Xiaobin Chen, Wenzhe Zhang, Shengmei Li, Weifeng Cai, Kun Zhang, Xuan Jin, Jianping Huang, Qili Lin, Yinghong Yang, Fangmeng Fu, Chuan Wang
To assess the predictive and prognostic value of a subtyping method based on immunohistochemistry in patients with triple-negative breast cancer (TNBC) treated with neoadjuvant chemotherapy (NAC). This study included patients with TNBC treated with anthracycline- and taxane-based NAC and curative surgery. Immunohistochemical (IHC) subtyping was performed using core needle biopsy specimens before NAC
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Lymphoglandular Complex-Like Colorectal Carcinoma-A Series of 20 Colorectal Cases, Including Newly Reported Features of Malignant Behavior. Am. J. Surg. Pathol. (IF 5.6) Pub Date : 2023-10-17 Osman Yilmaz, Maria Westerhoff, Nicole Panarelli, John Hart, Gabriel Groisman, Ignacio Ruz-Caracuel, Maurice Loughrey, Karen Matsukuma, Soo Hyun Lee, Omer Yilmaz, Raul S Gonzalez, Vikram Deshpande
Distinguishing colon carcinoma that is surrounded by well-circumscribed lymphoid tissue from adenomas involving lymphoglandular complexes can be difficult. We assessed a multi-institutional international cohort of 20 colorectal carcinomas with associated prominent lymphoid infiltrates, which we referred to as lymphoglandular complex-like carcinoma (LGCC). We collected clinical and endoscopic features
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Germline APC Alterations May Predispose to Testicular Sex Cord-Stromal Tumors. Am. J. Surg. Pathol. (IF 5.6) Pub Date : 2023-10-09 Stephanie Siegmund, Costantino Ricci, Chia-Sui Kao, Ankur R Sangoi, Sambit Mohanty, Christopher D M Fletcher, Maurizio Colecchia, Andres M Acosta
Sertoli cell tumor is a type of testicular sex cord-stromal tumor (TSCST) typically driven by gain-of-function CTNNB1 variants. Recently, molecular studies have identified TSCSTs (including Sertoli cell tumors) with loss-of-function APC variants, raising the possibility that germline APC alterations may predispose to TSCSTs. In this study, we evaluated 4 TSCSTs from 4 individual patients, including
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Clinicopathologic Analysis and Molecular Profiling of Ovarian Steroid Cell Tumors. Am. J. Surg. Pathol. (IF 5.6) Pub Date : 2023-10-05 Rachelle P Mendoza, Peng Wang, Heather L Smith, Carrie A Fitzpatrick, Rishikesh Haridas, Pankhuri Wanjari, Renee Briese, Anum Shahid, W Glenn McCluggage, Jennifer A Bennett
Ovarian steroid and Leydig cell tumors (SCT and LCT, respectively) are rare stromal tumors, with aggressive behavior described in approximately one third of SCTs. Previously reported features potentially predictive of malignancy include size >7 cm, gross hemorrhage, necrosis, grade 2 or 3 nuclear atypia, and mitoses >2/10 HPFs; however, no subsequent studies have corroborated these findings. Herein
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Clinical, Morphologic, and Molecular Features of Benign and Intermediate-grade Melanocytic Tumors With Activating Mutations in MAP2K1. Am. J. Surg. Pathol. (IF 5.6) Pub Date : 2023-09-29 Mónica Fumero-Velázquez, Michael Hagstrom, Soneet Dhillon, Tara Geraminejad, Shantel Olivares, Michele Donati, Daniel Nosek, Pia Waldenbäck, Dmitry Kazakov, Brandon S Sheffield, Victor A Tron, Pedram Gerami
Activating mutations in MAP2K1 can be seen in benign and intermediate-grade melanocytic neoplasms with spitzoid morphology. We analyzed the clinical, histopathologic, and genetic features for 16 cases of benign and intermediate-grade melanocytic tumors harboring activating MAP2K1 mutations. We compared them to Spitz neoplasms with characteristic Spitz fusions or HRAS mutation. We also compared the
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Melanotic PEComa: A Rare But Distinctive Subtype Analyzed in a Series of 7 Cases. Am. J. Surg. Pathol. (IF 5.6) Pub Date : 2023-09-28 Arnaud de la Fouchardiere, David J Papke, Daniel Pissaloux, Eleanor Russell-Goldman, Franck Tirode, Christopher D M Fletcher, John Hanna
Perivascular epithelioid cell neoplasms (PEComas) are tumors of uncertain cell lineage that show a strong female predominance. Their hallmark is the presence of combined smooth muscle and melanocytic differentiation. In most cases, melanocytic differentiation is detectable only by immunohistochemistry, but there are rare reports of PEComa with extensive melanin accumulation (so-called "melanotic PEComa")
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IRF8 in Conjunction With CD123 and CD20 to Distinguish Lupus Erythematosus Panniculitis From Subcutaneous Panniculitis-like T-Cell Lymphoma. Am. J. Surg. Pathol. (IF 5.6) Pub Date : 2023-09-28 Jahg Wong, Simon F Roy, Jennifer M McNiff, Mina L Xu
Distinguishing lupus erythematosus panniculitis (LEP) from subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a diagnostic challenge with important clinical implications. Immunohistochemical expression of interferon regulatory factor 8 (IRF8) has been shown to highlight cells with plasmacytoid dendritic cell differentiation. Considering that the presence of plasmacytoid dendritic cells highlighted
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The Spectrum of HPV-independent Penile Intraepithelial Neoplasia: A Proposal for Subclassification. Am. J. Surg. Pathol. (IF 5.6) Pub Date : 2023-09-28 Sigrid Regauer, Mikhail Ermakov, Karl Kashofer
Compared with vulva, precursor lesions of human papillomavirus (HPV)-independent invasive squamous cell carcinoma (SCC) of the penis are insufficiently characterized. We analyzed the histologic and immunohistochemical characteristics of 70 peritumoral precursor lesions and correlated them with the histology and mutational profile of the adjacent HPV-negative invasive penile SCC. Atypical basal keratinocyte
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Circulating Tumor HPV DNA in Patients With Head and Neck Carcinoma: Correlation With HPV Genotyping. Am. J. Surg. Pathol. (IF 5.6) Pub Date : 2023-09-27 Kevin Mijares, Rocco Ferrandino, Raymond Chai, Scott Roof, Swati Bhardwaj, Marshall Posner, William H Westra
Circulating tumor human papillomavirus DNA (ctHPVDNA) testing using digital-droplet polymerase chain reaction (PCR) detects fragments of tumor-modified human papillomavirus (HPV) in the plasma of patients with HPV-associated head and neck squamous cell carcinomas (HNSCCs). Its impact on tumor surveillance and primary diagnosis is limited by unresolved issues relating to sensitivity and specificity
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Papillary Hemangioma Harbors Somatic GNA11 and GNAQ mutations. Am. J. Surg. Pathol. (IF 5.6) Pub Date : 2023-09-26 Catherine K Gestrich, Mathew P Vivero, Dennis J Konczyk, Jeremy A Goss, Brian I Labow, Gregory D Pearson, Catherine E Cottrell, Mariam T Mathew, Vinay Prasad, Harry P Kozakewich, Christopher D M Fletcher, Arin K Greene, Alyaa Al-Ibraheemi
Papillary hemangioma (PH) is a small, primarily dermal lesion occurring predominantly in the head and neck in both children and adults. Its signature characteristics are dilated thin-walled channels containing papillary clusters of mainly capillary-sized vessels and endothelial cytoplasmic eosinophilic inclusions. Given certain histopathologic similarities to congenital hemangioma which harbor mutations
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Spiradenoma With Adenoid Cystic Carcinoma-like Changes: A Case Series of This Rare Variant With a Potential Diagnostic Pitfall. Am. J. Surg. Pathol. (IF 5.6) Pub Date : 2023-09-22 Jose A Plaza, Liubov Kastnerova, Alejandro A Gru, Brittany Dulmage, Martin J Sangueza, Dmitry V Kazakov
Spiradenomas are benign cutaneous adnexal neoplasms with sweat gland differentiation that can manifest a broad spectrum of histomorphologic appearances. While they show a characteristic histopathologic phenotype and clinical management involves surgical excision with a low risk of recurrence, there have been unusual histopathologic variants of spiradenoma reported, including cases with adenoid cystic
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A Novel Type of IDH Wild-type Glioma Characterized by Gliomatosis Cerebri-like Growth Pattern, TERT Promoter Mutation, and Distinct Epigenetic Profile. Am. J. Surg. Pathol. (IF 5.6) Pub Date : 2023-09-22 Amos Muench, Daniel Teichmann, Dorothee Spille, Peter Kuzman, Eilis Perez, Sven-Axel May, Wolf C Mueller, Theodoros Kombos, Shokufe Nazari-Dehkordi, Julia Onken, Peter Vajkoczy, Georgios Ntoulias, Conceição Bettencourt, Andreas von Deimling, Werner Paulus, Frank L Heppner, Arend Koch, David Capper, David Kaul, Christian Thomas, Leonille Schweizer
Diffuse gliomas in adults encompass a heterogenous group of central nervous system neoplasms. In recent years, extensive (epi-)genomic profiling has identified several glioma subgroups characterized by distinct molecular characteristics, most importantly IDH1/2 and histone H3 mutations. A group of 16 diffuse gliomas classified as "adult-type diffuse high-grade glioma, IDH-wildtype, subtype F (HGG-F)"
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International Society of Urological Pathology (ISUP) Consensus Conference on Current Issues in Bladder Cancer: Working Group 3: Subcategorization of T1 Bladder Cancer. Am. J. Surg. Pathol. (IF 5.6) Pub Date : 2023-09-22 Antonio Lopez-Beltran, Maria R Raspollini, Donna Hansel, Eva Compérat, Sean R Williamson, Fredrik Liedberg, Kenneth A Iczkowski, Lukas Bubendorf, Theodorus H van der Kwast, Liang Cheng
Emerging data on T1 bladder cancer subcategorization (aka substaging) suggests a correlation with oncological outcomes. The International Society of Urological Pathology (ISUP) organized the 2022 consensus conference in Basel, Switzerland to focus on current issues in bladder cancer and tasked working group 3 to make recommendations for T1 subcategorization in transurethral bladder resections. For
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Subcutaneous Leiomyosarcoma: An Aggressive Malignancy Portending a Significant Risk of Metastasis and Death. Am. J. Surg. Pathol. (IF 5.6) Pub Date : 2023-09-19 Scott C Bresler, Hailey L Gosnell, Jennifer S Ko, Christina V Angeles, Shira Ronen, Steven D Billings, Rajiv M Patel
Subcutaneous leiomyosarcoma (LMS) is a rare, poorly understood variant. The current literature on the subject is sparse, consisting of isolated case reports and small clinicopathologic studies compromised by the inclusion of both its more common and indolent counterpart, cutaneous LMS (atypical intradermal smooth muscle neoplasm), as well as highly aggressive deep-seated tumors. Thus, precise clinicopathologic
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PRAME Expression Is a Useful Tool in the Diagnosis of Primary and Metastatic Dedifferentiated and Undifferentiated Melanoma. Am. J. Surg. Pathol. (IF 5.6) Pub Date : 2023-09-19 Jason L Hornick, Jose A Plaza, Thomas Mentzel, Alejandro A Gru, Thomas Brenn
Although mostly recognized in the metastatic setting dedifferentiated and undifferentiated melanomas are increasingly recognized as cutaneous and, less commonly, mucosal primary tumors. Their diagnosis is challenging and dependent on sampling and recognition of a conventional melanoma precursor and/or detection of a mutation in a conventional melanoma driver gene. PRAME immunohistochemistry has recently
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Incidence and Clinicopathologic Characteristics of Human Papillomavirus-independent Invasive Squamous Cell Carcinomas of the Cervix: A Morphologic, Immunohistochemical, and Human Papilloma-Virologic Study of 670 Cases. Am. J. Surg. Pathol. (IF 5.6) Pub Date : 2023-09-13 Simona Stolnicu, Douglas Allison, Aaron M Praiss, Basile Tessier-Cloutier, Amir Momeni Boroujeni, Jessica Flynn, Alexia Iasonos, Rene Serrette, Lien Hoang, Andrei Patrichi, Cristina Terinte, Anna Pesci, Claudia Mateoiu, Ricardo R Lastra, Takako Kiyokawa, Rouba Ali-Fehmi, Mira Kheil, Esther Oliva, Kyle M Devins, Nadeem R Abu-Rustum, Robert A Soslow
We aimed to determine the frequency of human papillomavirus-independent (HPVI) cervical squamous cell carcinoma (SCC) and to describe clinicopathologic characteristics. Among 670 patients with surgically treated SCCs in an established multi-institutional cohort, 447 had available tissue. Tissue microarrays were constructed and studied by in situ hybridization (ISH) for high-risk and low-risk human
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Comprehensive Clinical-Pathologic Assessment of Malignant Phyllodes Tumors: Proposing Refined Diagnostic Criteria. Am. J. Surg. Pathol. (IF 5.6) Pub Date : 2023-09-11 Gulisa Turashvili, Qingqing Ding, Yi Liu, Limin Peng, Miralem Mrkonjic, Haider Mejbel, Yihong Wang, Huina Zhang, Gloria Zhang, Jigang Wang, Shi Wei, Xiaoxian Li
The latest World Health Organization classification of breast tumors recommends diagnosing malignant phyllodes tumors (MPTs) when all 5 morphologic features are present: permeative borders, marked stromal cellularity, marked stromal cytologic atypia, ≥10 mitoses per 10 high-power fields (HPF), and stromal overgrowth. We assessed the performance of this recommendation to capture MPTs and features predictive
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Critical Appraisal of Histologic Grading for Mucoepidermoid Carcinoma of Salivary Gland: Is an Objective Prognostic 2-tiered Grading System Possible? Am. J. Surg. Pathol. (IF 5.6) Pub Date : 2023-09-11 Bin Xu, Bayan Alzumaili, Karina C Furlan, German H Martinez, Marc Cohen, Ian Ganly, Ronald A Ghossein, Nora Katabi
Multiple 3-tiered grading systems exist for mucoepidermoid carcinoma (MEC), leading to controversial results on the frequency and prognostic values of each grade. We aimed to identify prognostic histologic factors and to evaluate grading schemes in this retrospective study of 262 resected primary head and neck MECs. The rate of nodal metastasis was 8.4%. Large tumor size, tumor fibrosis, infiltrative