American Journal of Surgical Pathology最新文献

Inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal neoplasm with a predilection for children and adolescents. Data regarding IMTs in adulthood is limited, and evidence suggests that ALK expression/rearrangement rate decreases with age. We sought to better characterize IMT in patients ≥40 years. IMT cases in this age group were retrieved and re-reviewed. Various histomorphologic data were reported, and ALK status was documented. A total of 34 tumors were identified (21 females, 13 males; 40 to 77 y; median age 54 y), and tumor size ranged from 0.7 to 10 cm (median 2.5 cm). Predominant disease sites included the lung (12), followed by the urinary bladder (9), the uterus (4), and the head and neck (4). Morphologically, tumors exhibited loose fascicles of spindled fibroblasts with inflammatory infiltrate, with the majority being myxoid (25). Mild cytologic atypia was appreciated in 12 cases, and 6 cases showed focal necrosis. ALK expression was identified in 91% of cases through immunohistochemistry (28) and/or molecularly (24). Most common ALK fusion partners, identified by next-generation sequencing, included FN1 , TIMP3 , and EML4 . Follow-up data on 28 patients (3 to 165 mo; median 42) revealed mostly indolent behavior, but one ALK -negative patient had lung metastasis, and another ALK -positive patient had a recurrence. IMTs may arise in adulthood and mostly manifest in visceral sites. Despite earlier reports, ALK is frequently expressed/rearranged in tumors in this age group.

We report a case of mesothelioma in situ giving rise to invasive mesothelioma and associated with a long in-frame TP53 deletion. Tumor arose in the peritoneal cavity in a 55-year-old man. BAP1, MTAP, and NF2/merlin were retained by immunohistochemistry, but p53 was overexpressed by immunohistochemistry in the flat mesothelioma in situ, papillary mesothelioma in situ, and invasive mesothelioma. Almost all cases of mesothelioma in situ that have been previously described have a BAP1 mutation/deletion; this is the first example of mesothelioma in situ associated with a TP53 mutation, and suggests that staining for p53 may be useful in evaluating potential mesothelioma in situ cases.

Since the histogenesis of heterologous elements within Sertoli-Leydig cell tumors (SLCTs) is poorly understood, we aimed to study the molecular relationship between Sertoli cells and the heterologous elements in 16 ovarian SLCTs. We performed a comprehensive molecular study on both SLCT and heterologous components, separately. Eleven tumors (68.7%) had one heterologous element and 5/16 (31.3%) had 2. Heterologous elements were epithelial (7/21 [81%]) (benign mucinous epithelium [9/21, 42.9%], borderline mucinous tumor [1/21, 4.8%], infiltrative mucinous adenocarcinoma [3/21, 14.3%], carcinoid tumor [3/21, 14.3%], and hepatocytes [1/21,4.8%]) or mesenchymal (4/21, 19%) (rhabdomyosarcoma [3/21,14.3%] and chondrosarcoma [1/21, 4.8%]). A DICER1 pathogenic variant was shared between SLCT and the heterologous elements in all cases with interpretable results (15/15), and other common likely-pathogenic/pathogenic variants were shared between SLCTs and heterologous components (3/16, 18.75%), favoring a clonal relationship. In contrast, the identification of distinct variants between components favored a different evolution. The molecular profile of heterologous elements differed from that of their ovarian counterparts occurring without SLCT (eg, mucinous heterologous elements were KRAS wild-type). Chromosome 8 gains, TERT and NRAS/KRAS variants, and absence of fusion transcript, were the hallmark of rhabdomyosarcoma components (3/3, 100%). The progression-free survival rate was significantly shorter for patients with TERT pathogenic variant ( P =0.0029). One patient had pleomorphic Sertoli cells associated with TP53 variants and very poor prognosis with early recurrence after complete initial surgery of a stage IA tumor. These data highlight the biological relationship between SLCTs and their heterologous elements, and the clinical usefulness of identifying pathogenic variants (ie, TERT and TP53 ), although this last point needs to be confirmed in a larger series.

True lipomas involving the joints are rare. In this study, we investigated 18 intra-articular and juxta-articular lipomas of the knee. The tumor occurred in middle-aged or older patients (median age: 63 years) with a strong female predilection (3 males and 15 females), and most presented with palpable masses without associated pain. Four tumors were entirely intra-articular, whereas 11 involved both intra-articular and extra-articular compartments, consistent with herniation from the joint. The herniation commonly occurred through the space between the patellar tendon and either the lateral or medial patellar retinaculum, with the extra-articular masses being located anterolaterally or anteromedially to the joint. All tumors analyzed at least focally involved or abutted the infrapatellar fat pad. The relationship with the joint was not recognized at diagnosis in most of the herniated cases. The remaining 3 were juxta-articular lipomas that were firmly fixed to the joint. All 18 lipomas revealed distinct histology, and included fine lobulation, fibrosis with spindle cells, conspicuous presence of medium-caliber vessels and slivers of dense, tendon-like fibrous tissue. Myxoid changes, chondro-osseous metaplasia, and fat necrosis were commonly observed. These findings led to a suspicion of atypical lipomatous tumors, other benign lipomatous tumors, malformation, or hamartoma, and originally prevented a definitive diagnosis in the majority of cases. HMGA2 immunoreactivity was observed in all 18 tumors, whereas all were negative for MDM2 expression and RB1 loss. RNA sequencing revealed HMGA2 fusions in 8 of the 12 tumors tested. Intra-articular and juxta-articular lipomas of the knee, particularly the herniated intra-articular subset, are likely under-recognized and can be a source of diagnostic concern because of peculiar histology and unawareness of the relationship with the joint.

Most primary retroperitoneal soft tissue tumors are malignant, with liposarcomas and leiomyosarcomas being the most common. However, other sarcomas and benign tumors can also occur in this location. Pathologic evaluation of retroperitoneal sarcomas (RPS) presents unique challenges. Sarcomas are a heterogeneous group with overlapping microscopic features, making accurate classification essential for prognosis and evolving targeted therapies. Core biopsies often capture only a small portion of the tumor, which may result in underestimation of key features such as differentiation, necrosis, and proliferation, leading to undergrading. Surgical management is complicated by the RPS's tendency to involve adjacent organs. Resections are often large and en bloc, and formalin fixation can obscure anatomic landmarks, making it difficult to identify and assess true surgical margins. In addition to the standard data elements required for cancer staging, specific pathologic features of RPS should be reported to aid in prognosis and treatment planning. This position paper/consensus statement was developed by members of the Trans-Atlantic Australasian Retroperitoneal Sarcoma Working Group (TARPSWG) based on evidence and expert opinion. A detailed description of specimen handling, specimen sampling, and the inclusion of the key diagnostic elements required for an accurate pathology report are provided. The aim of this manuscript is to offer a comprehensive critical reappraisal of the role of pathologic evaluation of surgical specimens in RPS surgery, as well as to propose a standard pathology report to harmonize reporting and facilitate future data collection and interpretation for future research development.

Inflammatory spindle cell PEComa is a rare PEComa variant with rare cases harboring YAP1::TFE3 fusion recently reported in the lungs. These tumors share identical YAP1::TFE3 fusion breakpoints and overlapping morphology with clear cell stromal tumor of the lung (CCST-L), but differ by demonstrating a myomelanocytic immunophenotype. We report the first 3 nonvisceral cases of inflammatory spindle cell PEComa with YAP1::TFE3 fusion. All occurred in female patients, aged 51 to 76 years, involving the vulva, presacral region, and thigh, and ranged from 3.8 to 5.0 cm (median: 4.0 cm). Histologically, all were well circumscribed with a fibrous capsule containing lymphoid cuffs, and were composed of fusiform to plump spindle cells arranged in short fascicles and vaguely storiform patterns, admixed with prominent inflammatory infiltrates. Extensive stromal calcifications, focal necrosis and occasional mitotic figures, including one atypical mitosis, were present in one case. Immunohistochemically, all cases were positive for smooth muscle actin and HMB45, and negative for cytokeratins, ERG, CD31, S100, and ALK. Targeted RNA sequencing identified YAP1::TFE3 fusions in all tumors, with 2 showing identical breakpoints to CCST-L (YAP1 exon 4-TFE3 exon 7), and 1 showing a breakpoint involving YAP1 exon 3-TFE3 exon 7. We report the first 3 cases of YAP1::TFE3-rearranged, nonvisceral inflammatory spindle cell PEComa occurring in somatic soft tissue sites, expanding the anatomic spectrum of this recently characterized entity. Inflammatory spindle cell PEComa should be considered in the differential diagnosis of spindle cell neoplasms with prominent admixed inflammation.

The 5th edition of the WHO classification of haematolymphoid tumours introduces the concept of hyperplasias arising in immune deficiency and dysregulation (IDD), which are frequently associated with Epstein-Barr virus (EBV). These lesions can be histologically classified as follicular hyperplasia (FH), infectious mononucleosis-like hyperplasia (IMH), or plasmacytic hyperplasia. Although EBV-associated reactive lymphoid hyperplasia (EBV-RLH) has been recognized in various IDD settings, comprehensive clinicopathologic analyses remain limited. We analyzed 34 Japanese patients with EBV-RLH. The IDD settings primarily included autoimmune diseases (with or without immunosuppressive therapy), chemotherapy for prior malignancies, aging, post-hematopoietic stem cell transplantation, and HIV infection. No patient exhibited histologic transformation or died due to EBV-RLH. Three patients had concurrent hematologic malignancies, and 12 had immune dysregulation related to prior chemotherapy. Histologically, 20 cases showed FH, 6 IMH, and 8 nonspecific patterns. EBER-positive cells were distributed in both interfollicular areas and germinal centers (GCs) in 27 cases (79%) and confined to interfollicular areas in 7. Six cases exhibited intensive aggregation of EBER-positive cells in one or a few GCs. Double staining confirmed that most EBER-positive cells expressed CD79a but not CD3. IGH and TCRG PCR analyses were successful in 24 cases: 21 were negative for both rearrangements, and 3 showed clonal rearrangements (1 double, 1 IGH-only, and 1 TCRG-only). EBV-RLH generally followed an indolent course; however, it may coexist with hematologic malignancies or develop after multichemotherapy. Careful histopathologic evaluation is essential to avoid overlooking concurrent malignancy or unnecessary treatment.

Erdheim-Chester disease (ECD) is a rare disease characterized by the accumulation of neoplastic histiocytes in various extra-nodal tissues. Tissue biopsies involved by ECD are difficult to distinguish from reactive inflammatory infiltrates given the bland appearance of the neoplastic histiocytes. Confirmation of the ECD diagnosis often relies on molecular studies to confirm BRAF V600E mutation or other activating mutations involving MAPK pathway genes. In this study, we examined the diagnostic utility of cyclin D1 and pERK as immunohistochemical markers of MAPK pathway activation in ECD compared with its histopathologic mimics. The cohort included 41 clinically confirmed ECD patients, most with known genetic alterations in MAPK pathway genes (n=38). In 3 cases no mutation was identified. 37 of 41 (90%) of ECD cases showed cyclin D1 overexpression, with frequent staining in the cytoplasm as well as the nucleus. pERK expression was observed in 32 of 39 (82%) cases. Cyclin D1 staining was negative in histopathologic mimics of ECD, apart from weak patchy staining in fat necrosis and uniform staining in a subset of cases of juvenile/adult xanthogranuloma. While not entirely sensitive or specific, in the proper clinical and radiologic context strong nuclear and cytoplasmic cyclin D1 expression within histiocytic infiltrates helps to support a diagnosis of ECD.