Advances In Anatomic Pathology最新文献

Biomarkers play a crucial role in the diagnosis, treatment planning, and prognosis of premalignant and malignant lesions and are increasingly used in neoplasia of the lower female genital tract (LFGT) including the cervix, vagina, and vulva. This review will discuss key biomarkers routinely used in LFGT pathology, including programmed cell death ligand 1 (PD-L1), mismatch repair (MMR), and tumor mutational burden (TMB) testing, which are FDA-approved companion diagnostics for anti-PD-1 checkpoint inhibitors. Recent developments in HER2 testing as a marker for anti-HER2 therapies, and prognostic biomarkers such as p53 in HPV-independent vulvar intraepithelial lesions and carcinomas, are also reviewed.

Ovarian mucinous tumors are subclassified in multiple categories. Recent studies have highlighted issues in interobserver reproducibility. This review will focus on some new developments including criteria and ancillary tests that may help to improve interobserver reproducibility at clinically important thresholds. These issues include proposals for a separate terminology of teratoma-associated ovarian mucinous neoplasms, the role of TP53 immunohistochemistry in distinction of crowded mucinous borderline tumors and expansile mucinous carcinomas as well as the assignment of the infiltrative pattern of invasion, which recently has been validated as important prognostic factor even in low stage mucinous ovarian carcinoma.

Mesenchymal tumors of the skin are rare and clinically heterogeneous, and can represent diagnostic challenge for pathologists. Most of these lesions have overlapping clinical and histological features, thus the understanding of architectural patterns, cytoplasmic and stromal features can facilitate proper diagnosis. Anatomic site may be an important factor in the differential diagnosis, as are patient's age and sex. Ancillary tests are often required and can be useful to rule out other entities. Molecular diagnostics is playing an increasingly important role in the diagnosis of soft tissue neoplasms. Here, we review clinical, histological, and molecular features of some of the most common of these uncommon entities including benign and malignant lesions.

Mesenchymal and spindle cell tumors of the breast represent a broad and heterogeneous group of lesions that may be sampled on core needle biopsy or surgical excision. Mesenchymal lesions unique to the breast are those that derive from the specialized breast myofibroblast, such as mammary myofibroblastoma and pseudoangiomatous stromal hyperplasia. However, any mesenchymal lesion arising in extramammary soft tissue may also arise in the breast, including fibroblastic, peripheral nerve sheath, adipocytic, and vascular lesions. The spindle cell lesions pose the greatest diagnostic challenge, due to the significant radiographic, morphologic, and immunophenotypic overlap within the category of mesenchymal lesions and more broadly with other nonmesenchymal breast lesions. The distinction is particularly challenging on the limited material of breast core needle biopsies, and caution should be taken before definitively classifying a breast spindle cell lesion on core needle biopsy to avoid unnecessary treatment if misdiagnosed. Consideration of a wide differential diagnosis, adequate sampling of a resection specimen, use of a targeted immunopanel, and selective use of molecular assays are essential steps for accurate classification of mesenchymal lesions in the breast. This review covers the clinical, histologic, and immunophenotypic features of mesenchymal tumors of the breast, with a special emphasis on the differential diagnoses unique to the breast and challenges encountered on breast core needle biopsy.

The majority of neoplasms of the head and neck are of epithelial origin primarily including mucosal squamous cell neoplasms (papillomas; squamous cell carcinoma) as well as salivary gland neoplasms. However, the full spectrum of mesenchymal neoplasms (benign and malignant) typically arising in soft tissue sites may also develop in superficial layers of the upper aerodigestive tract. The diversity of mesenchymal neoplasms arising in the head and neck is beyond the scope of this article, and our focus will be on some of the more common and/or diagnostic problematic mesenchymal tumors occurring in the sinonasal tract, oral cavity/odontogenic, pharynx, larynx, and neck.

Mesenchymal neoplasms within the genitourinary tract include a wide spectrum of tumors, ranging from benign to malignant, and tumors of uncertain malignant potential. Except for stromal tumors of the prostate, which originate from the specific prostatic stroma, these neoplasms generally resemble their counterparts in other body sites. The rarity of these neoplasms and the limitation associated with small biopsy samples present unique diagnostic challenges for pathologists. Accurate diagnosis is paramount, as it significantly influences prognosis and guides management and treatment strategies. This review addresses common diagnostic scenarios, discusses key differential diagnoses, and sheds light on potential diagnostic pitfalls.

The diagnosis of gastrointestinal stromal tumors (GISTs) is generally straightforward using a combination of histologic evaluation and pertinent immunohistochemical staining with CD117/kit and DOG-1 (discovered on GIST) antibodies. However, this tumor can be challenging in cases with an unusual morphology, in limited biopsies, for those in uncommon sites, post-treatment, and when other neoplasms express CD117/kit and DOG-1, thereby mimicking GIST. Finding epithelioid GISTs in the stomach in younger patients should prompt testing for succinate dehydrogenase (SHD)-deficiency using immunohistochemical staining for subunit B (SDHB). However, SDH-deficient GISTs can also arise in older patients, or as part of the Carney triad or Carney-Stratakis syndrome. GISTs with PDGFRA mutations can also prove difficult if they lack kit expression. It is also important to consider morphologic and immunophenotypic changes associated with treatment, including the potential absence of kit expression, particularly in GISTs that have metastasized. Therefore, obtaining clinical information regarding prior therapy with a tyrosine kinase inhibitor (TKI) is crucial.

Molecularly defined neoplasms are increasingly recognized, given the broader application and performance of molecular studies. These studies allow us to better characterize these neoplasms and learn about their pathogenesis. In the thorax, molecularly defined neoplasms include tumors such as NUT carcinoma, SMARCA4-deficient undifferentiated tumor (DUT), primary pulmonary myxoid sarcoma with EWSR1::CREB1 fusion, hyalinizing clear cell carcinoma, and SMARCB1-deficient neoplasms. Overall, these tumors are rare but are now more often recognized given more widely available immunostains such as NUT (NUT carcinoma), BRG1 (SMARCA4-DUT), and INI-1 (SMARCB1-deficient neoplasm). Furthermore, cytogenetic studies for EWSR1 to support a hyalinizing clear cell carcinoma or primary pulmonary myxoid sarcoma are, in general, easily accessible. This enables pathologists to recognize and diagnose these tumors. The diagnosis of these tumors is important for clinical management and treatment. For instance, clinical trials are available for patients with NUT carcinoma, SMARCA4-DUT, and SMACRB1-deficient neoplasms. Herein, our current knowledge of clinical, morphologic, immunophenotypic, and molecular features of NUT carcinomas, SMARCA4-DUT, primary pulmonary myxoid sarcomas, hyalinizing clear cell carcinoma, and SMARCB1-deficient neoplasms will be reviewed.