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Hepatic Adenomas in Patients 60 and Older Are Enriched for HNF1A Inactivation and Malignant Transformation
In conclusion, hepatic adenomas in persons 60 years of age or older are enriched for HNF1A-inactivated adenomas and have a higher frequency of malignant transformation. Malignant transformation, however, is less likely to develop through activation of the beta-catenin pathway. (Source: The American Journal of Surgical Pathology)
Source: The American Journal of Surgical Pathology - May 22, 2022 Category: Pathology Tags: Original Articles Source Type: research

A Critical Assessment of Current Grading Schemes for Diffuse Pleural Mesothelioma With a Proposal for a Novel Mesothelioma Weighted Grading Scheme (MWGS)
Although there is early support for schemes based on nuclear grade, necrosis and mitotic rate, there is currently no widely implemented grading system for diffuse pleural mesothelioma (DPM). We investigated current systems and propose a novel Mesothelioma Weighted Grading Scheme (MWGS). The MWGS assigns weighted scores from 0 to 10 based on age (≤74,>74 yrs: 0,1); histologic type (epithelioid, biphasic, sarcomatoid: 0,1,2); necrosis (absent, present: 0,2); mitotic count per 2 mm2 (≤1, 2 to 4, ≥5: 0,1,2); nuclear atypia (mild, moderate, severe: 0,1,2); and BRCA1-associated protein 1 (BAP1) expression (lost, retained...
Source: The American Journal of Surgical Pathology - May 22, 2022 Category: Pathology Tags: Original Articles Source Type: research

Clear Cell Carcinoma (CCC) of the Cervix Is a Human Papillomavirus (HPV)-independent Tumor Associated With Poor Outcome: A Comprehensive Analysis of 58 Cases
Cervical clear cell carcinoma (CCC) is a rare human papillomavirus–independent adenocarcinoma. While recent studies have focused on gastric-type endocervical adenocarcinoma (GTA), little is known about CCC. A total of 58 (CCCs) were collected from 14 international institutions and retrospectively analyzed using univariable and multivariable methods and compared with 36 gastric-type adenocarcinomas and 173 human papillomavirus–associated (HPVA) endocervical adenocarcinoma (ECA) regarding overall survival (OS) and recurrence-free survival (RFS). Most cases were FIGO stage I (72.4%), with Silva C pattern of invasion (77.6...
Source: The American Journal of Surgical Pathology - May 22, 2022 Category: Pathology Tags: Original Articles Source Type: research

Pathologic Examination of Pancreatic Specimens Resected for Treated Pancreatic Ductal Adenocarcinoma: Recommendations From the Pancreatobiliary Pathology Society
Currently, there are no internationally accepted consensus guidelines for pathologic evaluation of posttherapy pancreatectomy specimens. The Neoadjuvant Therapy Working Group of Pancreatobiliary Pathology Society was formed in 2018 to review grossing protocols, literature, and major issues and to develop recommendations for pathologic evaluation of posttherapy pancreatectomy specimens. The working group generated the following recommendations: (1) Systematic and standardized grossing and sampling protocols should be adopted for pancreatectomy specimens for treated pancreatic ductal adenocarcinoma (PDAC). (2) Consecutive ma...
Source: The American Journal of Surgical Pathology - May 22, 2022 Category: Pathology Tags: Original Articles Source Type: research

Resistance of B-Cell Lymphomas to CAR T-Cell Therapy Is Associated With Genomic Tumor Changes Which Can Result in Transdifferentiation
Despite the impressive efficacy of chimeric antigen receptor (CAR) T-cell therapy (CART) in B-cell non-Hodgkin lymphomas, durable responses are uncommon. The histopathologic and molecular features associated with treatment failure are still largely unknown. Therefore, we have analyzed 19 sequential tumor samples from 9 patients, prior anti-CD19 CART (pre-CART) and at relapse (post-CART), using immunohistochemistry, fluorescence in situ hybridization, array comparative genomic hybridization, next-generation DNA and RNA sequencing, and genome-scale DNA methylation. The initial diagnosis was diffuse large B-cell lymphoma (n=6...
Source: The American Journal of Surgical Pathology - May 22, 2022 Category: Pathology Tags: Original Articles Source Type: research

HPV51-associated Leiomyosarcoma: A Novel Class of: TP53/RB1: -Wildtype Tumor With Predilection for the Female Lower Reproductive Tract
Inactivating mutations in tumor suppressor genes TP53 and RB1 are considered central drivers in leiomyosarcomas (LMSs). In high-risk human papillomavirus (HPV)-related tumors, a similar functional outcome is achieved through oncoproteins E6 and E7, which inactivate the p53 and RB1 proteins, respectively. Here, we hypothesized that HPV infection could provide an alternative mechanism for tumorigenesis in a subset of TP53/RB1-wildtype LMS. We evaluated tumor samples from 2585 consecutive unique patients carrying a diagnosis of gynecologic or soft tissue LMS. Tumor DNA and available RNA were analyzed by hybrid-capture-based n...
Source: The American Journal of Surgical Pathology - May 22, 2022 Category: Pathology Tags: Original Articles Source Type: research

IRF8 Is a Reliable Monoblast Marker for Acute Monocytic Leukemias, But Does Not Discriminate Between Monoblasts and Plasmacytoid Dendritic Cells
No abstract available (Source: The American Journal of Surgical Pathology)
Source: The American Journal of Surgical Pathology - April 23, 2022 Category: Pathology Tags: Letters to the Editor Source Type: research

Tumoral Morphologic Features From Cervical Biopsies That Are Predictive of a Negligible Risk for Nodal Metastasis and Tumor Recurrence in Usual-type Cervical Adenocarcinomas: A Multi-institutional Study
The metastatic or recurrent potential of localized human papillomavirus–associated endocervical adenocarcinoma (HPVA EAC) is difficult to predict, especially based upon biopsy alone. Recent analyses of small cohorts indicate that high tumor nuclear grade (TNG) and the presence of necrotic tumor debris (NTD) from HPVA EACs in cervical biopsy specimens are highly predictive of nodal metastasis (NM). In the present study, we aimed to investigate how reliably tumoral morphologic features from cervical biopsy specimens predict NM or tumor recurrence (TR) and patient outcomes in a large cohort of endocervical adenocarcinoma pa...
Source: The American Journal of Surgical Pathology - April 23, 2022 Category: Pathology Tags: Original Articles Source Type: research

Sarcomatoid Yolk Sac Tumor Harbors Somatic Mutations That Are Otherwise Rare in Testicular Germ Cell Tumors
In conclusion, this study demonstrated that 60% of SYSTs harbor somatic oncogenic mutations that are otherwise rare in TGCTs, and the presence of these mutations is associated with an aggressive clinical course. In addition, the results presented herein suggest that grading SYSTs may be clinically relevant. (Source: The American Journal of Surgical Pathology)
Source: The American Journal of Surgical Pathology - April 23, 2022 Category: Pathology Tags: Original Articles Source Type: research

Large Cell Calcifying Sertoli Cell Tumor: A Clinicopathologic Study of 18 Cases With Comprehensive Review of the Literature and Reappraisal of Prognostic Features
We present a series of 18 (8 clinically benign, 8 clinically ambiguous [ie, lacking sufficient follow-up to determine behavior], and 2 clinically malignant) large cell calcifying Sertoli cell tumors (LCCSCT) of the testis. The median patient age and size were 15.5 years and 1.9 cm for the benign tumors; 19 years and 1.6 cm for the ambiguous tumors; and 28.5 years and 2.3 cm for the malignant tumors. The most common presentation was a mass (n=12/18, 67%). Two patients (11%) had the Carney complex, and 2 had neurofibromatosis type 1. All tumors showed nodular growth with frequent lymphoid aggregates at the periphery. W...
Source: The American Journal of Surgical Pathology - April 23, 2022 Category: Pathology Tags: Original Articles Source Type: research

GLI1 Gene Alterations in Neoplasms of the Genitourinary and Gynecologic Tract
We report 4 neoplasms of the kidney (2 cases) and uterus (2 cases) harboring rearrangements or amplifications of the GLI1 gene, which because of their unusual clinical presentation, morphology, and immunoprofile mimicked other neoplasms, causing significant diagnostic challenge. The neoplasms occurred in 4 female patients ages 33 to 88 years. Histologically they all demonstrated nodular growth, solid architecture, bland epithelioid to ovoid-spindle cells with pale cytoplasm set in a variably myxoid or hyalinized stroma. One uterine tumor also demonstrated a focal round cell pattern, while another demonstrated focal pleomor...
Source: The American Journal of Surgical Pathology - April 23, 2022 Category: Pathology Tags: Original Articles Source Type: research

Malignant Gonadal Germ Cell Tumors (Other Than Pure Germinoma) in Patients With Disorders of Sex Development: A Report of 21 Cases Based Largely on the Collection of Dr Robert E. Scully, Illustrating a High Frequency of Yolk Sac Tumor With Prominent Hepatoid and Glandular Features
We describe 21 nonpure germinomatous gonadal germ cell tumors (9 with a germinoma component), all but 1 associated with gonadoblastoma, in patients with disorders of sex development who ranged from 7 to 36 years old (average, 20 y). Twenty patients were clinically described as phenotypic females with ambiguous genitalia/virilization and primary amenorrhea. The most common documented peripheral karyotype was 46,XY (10/12; 83%). Fifteen of 16 tumors with available clinicopathologic data were unilateral. They ranged from 7 to 30 cm (mean, 15.5 cm) and were solid and cystic with frequent necrosis and hemorrhage. Gonadobl...
Source: The American Journal of Surgical Pathology - April 23, 2022 Category: Pathology Tags: Original Articles Source Type: research

RASGRF1-rearranged Cutaneous Melanocytic Neoplasms With Spitzoid Cytomorphology: A Clinicopathologic and Genetic Study of 3 Cases
Spitz neoplasms, according to 2018 WHO Blue Book, are morphologically defined by spindled and/or epithelioid melanocytes and genetically by either HRAS mutations or kinase gene fusions. The terminology “spitzoid” refers to lesions with similar morphology but with alternate or undefined genetic anomalies. Herein, we present 3 melanocytic neoplasms with a spitzoid cytomorphology, variable nuclear atypia, and harboring undescribed fusions involving RASGRF1. Two cases presented as unpigmented papules on the heel of a 26-year-old female (case 1) and the forearm of a 13-year-old boy (case 2). They were classified as low-grad...
Source: The American Journal of Surgical Pathology - April 23, 2022 Category: Pathology Tags: Original Articles Source Type: research

Human Germinal Center–associated Lymphoma (HGAL) Is a Reliable Marker of Normal and Neoplastic Follicular Helper T Cells Including Angioimmunoblastic T-Cell Lymphoma
The diagnosis of angioimmunoblastic T-cell lymphoma (AITL) is complex and requires the demonstration of a T-follicular helper (TFH) phenotype. Immunophenotypic markers that detect the TFH phenotype are highly variable, thereby necessitating the use of 3 to 5 TFH markers to substantiate a TFH phenotype. We tested the utility of germinal center markers human germinal center–associated lymphoma (HGAL) and LIM-domain only 2 (LMO2) in detecting a TFH phenotype. We compared their staining to that of 6 TFH markers in current use, PD-1, ICOS, CXCL13, SAP, CD10, and BCL6, in a cohort of 23 AITL. Our results show that although bot...
Source: The American Journal of Surgical Pathology - April 23, 2022 Category: Pathology Tags: Original Articles Source Type: research

Mucin Neovascularization as a Diagnostic Aid to Distinguish Mucinous Carcinomas From Mucocele-like Lesions in Breast Core Needle Biopsies
The distinction between mucinous carcinomas (MCs) and mucocele-like lesions (MLLs), particularly those containing detached epithelial fragments, can be problematic in the limited samples afforded by breast core needle biopsies (CNBs). Neovascularization of mucin has been proposed as a criterion to distinguish MC from MLL, but its value in helping to categorize mucin-producing breast lesions in CNB has not been previously investigated. To address this, we evaluated mucin neovascularization on hematoxylin and eosin (H&E)-stained sections of 140 CNB containing mucin-producing breast lesions including 52 MC, 17 mucin-producing...
Source: The American Journal of Surgical Pathology - April 23, 2022 Category: Pathology Tags: Original Articles Source Type: research