Advances In Anatomic Pathology最新文献

The accurate diagnosis of giant cell-rich tumors of bone is challenging, especially in limited tissue samples. This diverse group of neoplasms have similar and often ambiguous clinical presentations, radiologic features, and morphologic characteristics. During the last decade, the discovery of pathogenic recurrent genetic alterations has allowed the development of immunohistochemical surrogate markers and FISH assays that can help differentiate the entities of this broad group from one another. The correct diagnosis of these neoplasms is essential in the management of the affected patients.

This review summarizes the clinicopathologic features of various lipomatous tumors of soft tissue and addresses some recent conceptual issues relating to adipocytic neoplasms, such as atypical spindle cell/pleomorphic lipomatous tumor and myxoid pleomorphic liposarcoma, and provides an update on the molecular aspects of these tumors. Recent advances in cytogenetic characterization and classification of lipomatous tumors are reviewed, and the genetic importance of distinct chromosomal aberrations are briefly discussed.

Vascular, fibrous/myofibroblastic, and myogenic tumors account for the majority of mesenchymal tumors in children. These tumors often show significant overlap in morphology and immunophenotype posing diagnostic difficulties and, thus, their classification remains challenging. Recent advances in immunohistochemistry have proved helpful in identifying a specific line of differentiation in some tumors, but other tumors remain difficult to classify. Molecular investigations have provided an existing tool to better understand the pathogenesis of some of these tumors and, in some cases like the EWING family of tumors, expanded the classification resulting in the emergence of previously unknown tumors. Some of these tumors are currently diagnosed according to their underlying molecular abnormality, such as CIC -rearranged sarcoma, BCOR -rearranged sarcoma, etc. This review focuses on the common mesenchymal neoplasms of the pediatric population with emphasis on the salient histologic features, immunoprofile, and molecular characteristics. For practical purposes, the latter are summarized in Supplemental Table 1, Supplemental Digital Content 1, http://links.lww.com/PAP/A46 .

The classification of vulvar squamous cell carcinoma (VSCC), as in endometrial cancer, has shifted from the histology-based descriptors toward molecular-based identifiers. Recently, it has been reported that there are 3 genetically distinct and clinically significant subtypes of VSCC: HPV-associated VSCC, HPV-independent/p53 wild-type VSCC, and HPV-independent/p53-mutated VSCC. Each group has different prognostic implications as well as response to treatment, thus reinforcing the need for this 3-tier molecular classification. This molecular subtyping can easily be done on vulvar biopsies using p16 and p53 immunohistochemistry stains to further improve risk prediction and individualized treatment decisions, leading to better patient outcomes.

Uterine mesenchymal tumors are a diverse group of tumors that can display a broad range of morphologic, immunohistochemical, and molecular profiles and are associated with varied clinical behaviors. In recent years, they have increasingly been classified by their underlying molecular alterations, leading to a more precise separation of diagnostic entities. As their diagnostic criteria have been refined, so too have the features that can be used to predict clinical outcomes. This review includes a discussion of uterine inflammatory myofibroblastic tumors, perivascular epithelioid cell tumors (PEComa), and uterine tumors resembling ovarian sex cord tumors, with a focus on updates on their clinical behavior and tools for risk stratification to identify malignant tumors. In addition, we discuss the importance of using an integrated approach when classifying uterine mesenchymal tumors to improve diagnostic accuracy and guide clinical management.

Uterine smooth muscle neoplasms are a biologically and clinically heterogeneous group of tumors. Morphology is the cornerstone of pathologic diagnosis of these tumors, and most are readily classified as benign or malignant on the basis of routine histologic examination. However, rare subsets-including intravenous leiomyomatosis, benign metastasizing leiomyoma, and disseminated peritoneal leiomyomatosis-have a capacity for extrauterine spread despite benign cytomorphology. A further subset of uterine smooth muscle neoplasms, termed "smooth muscle tumor of uncertain malignant potential (STUMP)," are not readily classified as benign or malignant and carry an intermediate prognosis. STUMP is a protean category, whose precise definition is subject to disagreement among experts. The risk profiles of different STUMP morphotypes remain largely unresolved. Finally, multiple morphology-based systems for risk stratification of uterine leiomyosarcoma have been proposed, though none is widely adopted. Immunohistochemical and molecular prognostic markers for both STUMP and leiomyosarcoma remain in the early phases of adoption in routine diagnostic practice.

Since the discovery in 2009 that missence pathogenic variants/mutations in FOXL2 are extremely common in ovarian adult granulosa cell tumours, the last 2 decades have witnessed significant developments in our understanding of the molecular events underlying the pathogenesis of other ovarian sex cord-stromal tumours (SCSTs). In this review, we cover the molecular events in ovarian SCSTs and provide practical guidance to the reporting pathologist as to how and when molecular testing may be useful in diagnosis. We stress the need to correlate the morphology and molecular since most of the molecular events are not entirely specific for a particular tumour type and our knowledge is continually evolving with the elucidation of "new" molecular events. We also discuss that in some tumours, molecular testing is helpful in triaging the patient for genetic referral and germline testing since some of the molecular events may be germline in nature.

HPV-independent squamous cell carcinomas of the vulva comprise the majority of vulvar cancers, but their putative precancers represent only a small proportion of the vulvar squamous intraepithelial lesions that are encountered in routine practice. The precancerous lesions of HPV-independent vulvar squamous cell carcinoma encompass a spectrum of lesions that, collectively, may pose significant diagnostic challenges. Included in this spectrum are differentiated vulvar intraepithelial neoplasia [dVIN], the prototypical lesion of the group, which is characterized by a high propensity for progression, a relatively short duration to progression, frequent association with lichen sclerosus, and according to our review of the recent literature, TP53 /p53 aberration in 50% to 95% (mean 77.4%) of cases. Regarding the latter, some authors consider TP53 /p53 aberration to be a diagnostic requirement for dVIN, although this is controversial, as discussed further herein. Also included in the spectrum of lesions that are considered in this review are possibly related HPV-independent, p53-wild type lesions that have historically been reported as "vulvar acanthosis with altered differentiation" (VAAD), "differentiated exophytic vulvar intraepithelial lesion" (DEVIL), "verruciform lichen simplex chronicus" (vLSC), and which more recently, have collectively been described as "verruciform acanthotic vulvar intraepithelial neoplasia (vaVIN)" or "vulvar aberrant maturation (VAM)." In this review, we perform a comprehensive clinicopathologic review of putative precancerous lesions of HPV-independent squamous cell carcinomas of the vulva, with an emphasis on recent developments in terminology, practical diagnostic issues, biomarkers, and pathogenesis.

STK11 adnexal tumor is a novel malignant neoplasm of uncertain histogenesis frequently arising in a para-adnexal location and associated with Peutz-Jeghers syndrome in ∼50% of patients. Its broad morphologic spectrum and nonspecific immunohistochemical profile has resulted in misclassification in the past as a variety of other neoplasms including those of wolffian, sex cord-stromal, mesothelial, and epithelial derivation. This review focuses on the spectrum of adnexal neoplasms that may develop in Peutz-Jeghers syndrome, with particular emphasis on STK11 adnexal tumor and its differential diagnosis.