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Clinicopathologic and Genetic Features of Primary T-cell Lymphomas of the Central Nervous System: An Analysis of 11 Cases Using Targeted Gene Sequencing
In conclusion, most of the T-PCNSL were PTCL-NOS, but sporadic cases of other subtypes including γδT-cell lymphoma, anaplastic lymphoma kinase-positive anaplastic large cell lymphoma, and ENKTL were also encountered. Immunophenotypic analysis, clonality test, and targeted gene sequencing along with clinicoradiologic evaluation, may be helpful for establishing the diagnosis of T-PCNSL. Moreover, this study demonstrates genetic alterations with potential diagnostic and therapeutic utility in T-PCNSL. (Source: The American Journal of Surgical Pathology)
Source: The American Journal of Surgical Pathology - March 25, 2022 Category: Pathology Tags: Original Articles Source Type: research

Benign and Intermediate-grade Melanocytic Tumors With BRAF Mutations and Spitzoid Morphology: A Subset of Melanocytic Neoplasms Distinct From Melanoma
The current classification of Spitz neoplasms in the World Health Organization (WHO), Fourth Edition defines Spitz neoplasms as melanocytic proliferations with characteristic Spitz morphology and a Spitz-associated genomic fusion or HRAS mutation. In contrast, melanocytic neoplasms with BRAF mutations are considered typical of common acquired nevi, dysplastic nevi, and melanomas from intermittent sun-damaged skin. However, increased utilization of ancillary testing methods such as BRAFV600E immunohistochemistry and sequencing studies have made apparent a subgroup of benign-grade and intermediate-grade melanocytic neoplasms...
Source: The American Journal of Surgical Pathology - March 25, 2022 Category: Pathology Tags: Original Articles Source Type: research

Epithelioid Leiomyosarcoma of the Uterus: Modern Outcome-based Appraisal of Diagnostic Criteria in a Large Institutional Series
Epithelioid leiomyosarcoma of the uterus is rare and poorly understood. Herein, we characterize a large institutional series of epithelioid leiomyosarcomas aiming to define outcome-determinant diagnostic pathologic features. We also retrieved epithelioid smooth muscle tumors of unknown malignant potential and evaluated a consecutive cohort of leiomyomas for epithelioid subtypes. Of a total of 1177 uterine leiomyosarcomas, 81 (7%) were categorized as epithelioid after review. Epithelioid leiomyosarcoma was strictly defined as having round to polygonal cells with visible pink cytoplasm and round to ovoid nuclei in ≥50% of ...
Source: The American Journal of Surgical Pathology - March 25, 2022 Category: Pathology Tags: Original Articles Source Type: research

Utility of D2-40, Cytokeratin 5/6, and High–Molecular-weight Cytokeratin (Clone 34βE12) in Distinguishing Intraductal Spread of Urothelial Carcinoma From Prostatic Stromal Invasion
Intraductal spread of urothelial carcinoma (UC) is not an uncommon finding in bladder cancer that requires appropriate clinical management. The presence of prostatic stromal invasion in non–muscle-invasive bladder cancer upstages the disease, necessitating cisplatin-based neoadjuvant chemotherapy and subsequent cystroprostatectomy. However, the identification of prostatic stromal invasion can be challenging, especially in biopsy and transurethral resection specimens. We assess the utility of D2-40, CK5/6, and high–molecular-weight cytokeratin (HMWCK) immunohistochemistry as an ancillary tool to differentiate prostatic ...
Source: The American Journal of Surgical Pathology - March 25, 2022 Category: Pathology Tags: Original Articles Source Type: research

Pepsinogen I- and H+/K+-ATPase-immunohistochemical Positivity in Endoscopically Resected Early Gastric Neoplasia
Gastric adenocarcinoma of the fundic gland type (GAFG) has been recently classified by the World Health Organization (WHO), however, clinicopathologic features of pepsinogen I- or H+/K+-ATPase-positive gastric tumors remain unclear. Therefore, this study evaluates the frequency and clinicopathologic features of those tumors, using a tissue microarray block to identify pepsinogen I- or H+/K+-ATPase-positive tumors from 810 endoscopically resected, early gastric epithelial tumors. The frequency of pepsinogen I-positive lesions was 2.1%, and that of H+/K+-ATPase-positive lesions was 2.0%. Pepsinogen I- or H+/K+-ATPase positiv...
Source: The American Journal of Surgical Pathology - March 25, 2022 Category: Pathology Tags: Original Articles Source Type: research

HER2 Overexpression and Amplification in Uterine Carcinosarcomas With Serous Morphology
Uterine carcinosarcoma (UCS) is an aggressive malignancy with few treatment options. A recent clinical trial has shown an increase in progression-free survival in patients with human epidermal growth factor receptor 2 (HER2)-positive serous endometrial carcinomas treated with anti–HER2-targeted therapies. Few studies have evaluated HER2 expression/amplification in UCS. Similar to serous endometrial carcinoma, the majority of UCS have TP53 mutations and a serous epithelial component, suggesting that UCS may show similar rates of HER2 positivity and therapeutic response. Therefore, we evaluated HER2 expression/amplificatio...
Source: The American Journal of Surgical Pathology - March 25, 2022 Category: Pathology Tags: Original Articles Source Type: research

Diagnosis of Hypersensitivity Pneumonitis: Review and Summary of American College of Chest Physicians Statement
Assessment of lung biopsies for the diagnosis of hypersensitivity pneumonitis (HP) is one of the most difficult diagnostic problems for surgical pathologists. It is a form of interstitial lung disease resulting from an immune reaction provoked by an inhaled antigen in susceptible individuals. Although this definition sounds simple, in practice, the diagnosis of HP can be challenging. To address these issues, the American College of Chest Physicians (CHEST) has recently published a guideline for the diagnosis of HP. In this review, we will explore the multidisciplinary diagnostic evaluation of HP with a focus on the patholo...
Source: The American Journal of Surgical Pathology - March 25, 2022 Category: Pathology Tags: Special Article Source Type: research

Pulmonary “Inflammatory Leiomyosarcomas” Are Indolent Tumors With Diploid Genomes and No Convincing Rhabdomyoblastic Differentiation
In this study, we identified 4 pulmonary tumors histologically typical of inflammatory leiomyosarcomas, all in men (aged 26 to 49), presented as slow-growing well-defined nodules ranging from 1.4 to 3.5 cm, and following uneventful postoperative courses. All tumors were positive for desmin immunostaining, while only 1 and 2 were focally positive for smooth muscle actin and smooth muscle myosin heavy chain, respectively. They showed no expression of myogenin, MyoD1, or PAX7 by immunohistochemistry or RNA sequencing. Copy number analyses by whole-exome sequencing (N=1), OncoScan single-nucleotide polymorphism array (2), an...
Source: The American Journal of Surgical Pathology - February 17, 2022 Category: Pathology Tags: Original Articles Source Type: research

TRPS1 Expression in Breast Carcinomas: Focusing on Metaplastic Breast Carcinomas
TRPS1 has been recently demonstrated as a highly sensitive and specific marker for breast carcinomas. To further explore TRPS1’s utility in breast carcinoma, we systematically evaluated TRPS1 expression on tissue microarrays from 160 estrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-positive, 94 ER−/HER2+, 117 triple-negative breast carcinomas, and 618 other primary carcinomas (cholangiocarcinoma, endometrial, colorectal, and hepatocellular carcinomas), and whole tissue sections from 64 HER2+, 76 triple-negative, and 67 metaplastic breast carcinomas. The results showed TRPS1 was highly exp...
Source: The American Journal of Surgical Pathology - February 17, 2022 Category: Pathology Tags: Original Articles Source Type: research

Reliable Identification of Endometrial Precancers Through Combined Pax2, β-Catenin, and Pten Immunohistochemistry
The diagnosis of endometrial atypical hyperplasia/endometrioid intraepithelial neoplasia (AH/EIN) remains challenging and subjective in some cases, with variable histologic criteria and differences of opinion among gynecologic pathologists, potentially leading to under/overtreatment. There has been growing interest in the use of specific immunohistochemical markers as adjuncts in AH/EIN diagnosis. For example, the World Health Organization 2020 Classification specifies that loss of Pten, Pax2, or mismatch repair proteins are desirable diagnostic criteria. Other markers, most notably β-catenin and Arid1a, are also aberrant...
Source: The American Journal of Surgical Pathology - February 17, 2022 Category: Pathology Tags: Original Articles Source Type: research

Papillary Renal Cell Carcinoma With Microcystic Architecture Is Strongly Associated With Extrarenal Invasion and Metastatic Disease
Papillary renal cell carcinoma (PRCC) is well-recognized as a morphologically and molecularly heterogenous group of kidney tumors with variable clinical behavior. Our goal was to analyze a unique histologic pattern of PRCC we have observed in routine practice to evaluate for potential clinical significance or distinct molecular signature. We identified 42 cases of PRCC showing a morphologically distinct architecture characterized by numerous epithelial-lined cysts containing the papillary tumor (herein called “microcysts”), which are typically separated by fibrous stroma. Of the initial 42 case test set with microcysti...
Source: The American Journal of Surgical Pathology - February 17, 2022 Category: Pathology Tags: Original Articles Source Type: research

Expression of N-Terminal-Deficient E-Cadherin Protein in Invasive Lobular Carcinoma of the Breast
We report herein ILC cases expressing a new type of abnormal E-cad protein that lacks the N-terminal domain, but conserves the C-terminal domain on the cell membrane. Immunohistochemical staining of 299 ILC cases using specific antibodies against the N-terminal or C-terminal region of E-cad revealed that 227 (76%) cases showed loss of the membranous expression of both terminuses (N−/C−) and 72 (24%) cases showed expression of only the C-terminus (N−/C+). In all cases, the expression of p120-catenin and β-catenin coincided with the expression of the C-terminus of E-cad. Clinicopathologic analysis revealed that N−/C...
Source: The American Journal of Surgical Pathology - February 17, 2022 Category: Pathology Tags: Original Articles Source Type: research

EPM2AIP1 Immunohistochemistry Can Be Used as Surrogate Testing for MLH1 Promoter Methylation in Endometrial Cancer
Immunohistochemical (IHC) evaluation of DNA mismatch repair proteins (MMR) has become routine practice for Lynch syndrome screening and/or part of diagnostic evaluation in endometrial cancer. Approximately 20% to 30% of endometrial carcinomas demonstrate microsatellite instability due to defective DNA MMR. Vast majority of MLH1/PMS2-deficient tumors are sporadic and show MLH1 promoter methylation. MLH1 methylation testing by quantitative polymerase chain reaction-based technique is time, labor, and tissue intensive with an average institutional turnaround time of 2 weeks. MLH1 and EPM2AIP1 genes share a common promoter who...
Source: The American Journal of Surgical Pathology - February 17, 2022 Category: Pathology Tags: Original Articles Source Type: research

Solitary Fibrous Tumors of the Female Genital Tract: A Study of 27 Cases Emphasizing Nonvulvar Locations, Variant Histology, and Prognostic Factors
We report 27 solitary fibrous tumors of the female genital tract emphasizing nonvulvar locations, variant histology, and prognostic factors. The patients ranged from 25 to 78 years (most were over 40), and tumors occurred in the vulva (7), vagina (2), cervix (2), corpus (6), fallopian tube/paratubal soft tissue (5), and ovary (5). They ranged from 1.5 to 39 (mean=10.5) cm and were typically solid, but 4 were predominantly cystic. All had a haphazard arrangement of spindled to ovoid cells, with most demonstrating alternating cellular and hypocellular areas and prominent vessels, but 13 lacked hypocellular areas, and 7 had...
Source: The American Journal of Surgical Pathology - February 17, 2022 Category: Pathology Tags: Original Articles Source Type: research

A Comprehensive Clinicopathologic and Molecular Study of 19 Primary Effusion Lymphomas in HIV-infected Patients
We report here a single-center series of 19 human immunodeficiency virus–associated PELs, including 14 EBV+ and 5 EBV− PELs. The objectives were to describe the clinicopathologic features of PELs, with a focus on programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) expression, to search for genetic alterations by targeted deep sequencing analysis, and to compare the features between EBV+ and EBV− cases. All the patients were male, and the median age at diagnosis was 47 years old (interquartile range: 40 to 56 y). Reflecting the terminal B-cell differentiation, immunophenotypic profiles showed lo...
Source: The American Journal of Surgical Pathology - February 17, 2022 Category: Pathology Tags: Original Articles Source Type: research