American Journal of Surgical Pathology最新文献

According to histopathology and molecular genetics, there are 5 major subtypes of ovarian carcinomas: high-grade serous (70%), endometrioid (10%), clear cell (10%), mucinous (3% to 4%), and low-grade serous (<5%) carcinomas. These tumors, which constitute over 95% of cases, represent distinct diseases with different prognoses and therapy. This review outlines contemporary advances in molecular pathology, which have expanded our knowledge of the biology of epithelial ovarian cancer and are also important to patient management. We also comment on some controversial points of the FIGO staging classification that we proposed in 2014.

The mechanism of tumor budding (TB) in gastric adenocarcinoma (GAC) and its relationship with biological indicators and prognostic significance, remains unclear. In this study, we conducted a comprehensive analysis using whole-slide imaging to evaluate TB in 75 cases of GAC. Our findings revealed the risk factors associated with TB in GAC and their impact on patient prognosis. The results indicate that the majority of cases exhibited a TB grade exceeding 10 (n=41), followed by 6-10 (n=15). Histologic grade (R=0.26, P=0.06), pT stage (R=0.56, P=0.00), neural invasion (R=0.29, P=0.01), marginal zone growth pattern (R=0.25, P=0.02), and basal zone growth pattern (R=0.38, P=0.001) are associated with TB in GAC. Logistic regression analysis revealed that the infiltrative growth pattern in both the marginal zone (odds ratio=5.90, 95% CI: 1.04-33.44, P=0.05) and basal zone (odds ratio=12.80, 95% CI: 2.03-80.68, P=0.01) were identified as risk factors for TB in GAC. Univariate analysis demonstrated a negative correlation between TB and TB grade with overall survival and progression-free survival in GAC patients. Furthermore, the multivariate COX analysis revealed that TB and TB grade, along with American Joint Committee on Cancer stage, lymph node metastasis, and pT stage, independently influenced the prognosis of GAC patients. In conclusion, a comprehensive evaluation of TB could serve as a significant histologic marker for risk stratification in GAC.

Although sialoblastoma (SBL) is defined as a low-grade malignant salivary gland anlage neoplasm in the 2022 World Health Organization (WHO) Classification of Head and Neck Tumors, its histology, genetics, and behavior remain controversial due to the rarity of the tumor. Here, we performed the first comprehensive clinical, histologic, and molecular analyses of 8 SBLs to better understand their pathogenesis and prognosis. This cohort consisted of 5 boys and 3 girls, with ages ranging from birth to 9 years at diagnosis. Tumors occurred in the parotid (4), cheek (3), and submandibular glands (1). Histologically, 5 tumors primarily presented as a solid pattern consisting of primitive basaloid epithelial cells, often with necrosis. Three tumors exhibited a non-solid pattern, with 1 tumor mainly showing epithelial-myoepithelial carcinoma (EMC)-like histology, whereas the other 2 tumors exhibited basal cell adenoma (BCA)-like histology. All 5 solid SBLs harbored FGFR2 mutations, and 1 also harbored mutations in PALB2, AR, and MAP2K1. In contrast, non-solid pattern tumors were characterized by HRAS mutations or significant β-catenin nuclear positivity. All 5 solid tumors recurred, 3 of them developed distant metastases, and 2 died 40 and 44 months after diagnosis. Three non-solid tumors showed no evidence of disease recurrence at 49, 144, and 132 months, suggesting a relatively favorable prognosis. Overall, SBLs can be stratified into solid and non-solid patterns, with solid pattern tumors usually having FGFR2 mutations, increasing the risk of recurrence and metastasis. This stratification underscores the importance of genetic and morphologic profiling for predicting the prognosis of SBLs.

Low-grade gliomas and reactive piloid gliosis can present with overlapping features on conventional histology. Given the large implications for patient treatment, there is a need for effective methods to discriminate these morphologically similar but clinically distinct entities. Using routinely available stains, we hypothesize that a limited panel including SOX10, p16, and cyclin D1 may be useful in differentiating mitogen-activated protein (MAP) kinase-activated low-grade gliomas from piloid gliosis. Reviewers blinded to clinical and pathologic data reviewed and quantified immunohistochemical expression patterns across 20 cases of piloid gliosis and 37 cases of MAP kinase-activated low-grade gliomas, including pilocytic astrocytoma and ganglioglioma. The majority of MAP kinase-activated low-grade glioma cases demonstrated extensive immunoreactivity for at least 2 of the 3 immunohistochemical markers, whereas none of the gliosis cases demonstrated significant immunoreactivity for more than one individual immunohistochemical marker. SOX10 and p16 demonstrated the highest individual sensitivity whereas cyclin D1 demonstrated the highest individual specificity to discriminate neoplastic from nonneoplastic cases in this cohort. A composite panel score based on significant immunoreactivity of at least 2 of the 3 markers provided specificity and a positive predictive value of 100% in differentiating MAP kinase-activated low-grade glioma from gliosis, as 0/20 (0%) of gliosis cases were scored positive compared with 24/37 (65%) of MAP kinase-activated low-grade glioma cases. We conclude that while the immunoreactivity of these markers may be suggestive of a low-grade glioma diagnosis, SOX10, p16, and cyclin D1 should be applied in combination to maximize diagnostic value.

Angioimmunoblastic T-cell lymphoma (AITL) is an aggressive malignancy that frequently presents with extranodal involvement. Cutaneous tropism is clinically and histopathologically variable, which may pose a diagnostic challenge. We conducted a retrospective analysis of 40 samples of 20 cases of cutaneous AITL, focusing on the clinicopathologic and molecular correlations between skin and lymph node (LN) samples. In all cases, cutaneous involvement was concurrent with or followed the diagnosis of nodal AITL, with no cases preceding systemic involvement. Clinically, cutaneous AITL presented in 2 main forms: an evanescent rash and persistent lesions, with histopathology revealing diverse infiltration patterns, including perivascular, nodular, granulomatous, panniculitic, vasculitis, and epidermotropic. Clinical presentation and histologic patterns tend to correlate. Histopathologically, plasma cells were present in 15/22 skin samples, 5 of them being kappa-light restricted but polytypic in corresponding LNs. Epstein-Barr virus+ B cells were present in 10 cutaneous lesions and were already present in corresponding LNs. Molecular studies found correlations in all but one case between LN and skin, particularly in the presence of RHOA and TET2 mutations, which were identified in 8 of 12 cases. Molecular analysis was also informative in 4 cases with low levels of infiltration. The study also highlighted unique cases with distinct clinical and histopathologic patterns coexisting in the same patient over time. One case exhibited simultaneous granulomatous and epidermotropic patterns in different skin lesions. Four cases of cutaneous B-cell lymphomas associated with AITL were identified. Our study underscores the importance of integrating clinical, histopathologic, and molecular data to accurately diagnose cutaneous AITL.

Tandem duplications (TDs) in exons of upstream binding transcription factor (UBTF-TD) are a rare recurrent alteration in pediatric and adult acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS)/neoplasm. Although recently identified, AML with UBTF-TD is now considered a distinct subtype of AML. To further our understanding of myeloid neoplasms with UBTF-TD, we analyzed clinical, morphologic, and immunophenotypic characteristics of 27 pediatric patients with UBTF-TD-positive myeloid neoplasm, including 21 diagnosed as AML and 6 as MDS. Our data demonstrated that UBTF-TD is frequently associated with cytopenia, hypercellular marrow with erythroid hyperplasia, and trilineage dysplasia. Blasts and maturing myeloid cells show a characteristic dysplastic feature with condensed eosinophilic cytoplasm. Blasts have a myeloid or myelomonocytic immunophenotype with a variably dim expression of CD34 and/or CD117, and except for CD7 expression lack a consistent pattern of aberrant lineage-specific antigen expression. Patients with MDS had a lower blast count in the peripheral blood (P = 0.03) and bone marrow (P <0.001) but otherwise had no significant differences in other hematological parameters. Three patients with MDS rapidly progressed to AML in 33, 39, and 210 days from the initial diagnosis and there was no difference in overall survival between patients with MDS and AML (P = 0.18). Our data suggest that MDS with UBTF-TD is prognostically equivalent to AML with UBTF-TD and thus should be considered as a continuum of the same molecularly defined myeloid neoplasm. These collective data also provide morphologic and immunophenotypic clues that can prompt screening for UBTF-TD in patients with MDS or AML.

Sialadenoma papilliferum is a tumor characterized by surface papillary projections and glandular/microcystic proliferation at the lesion base. Cases in which surface involvement is absent have been termed "sialadenoma papilliferum-like intraductal papillary tumor." Similar tumors that are present in the mandible have been termed "tubulopapillary hidradenoma-like tumor of the mandible." While previously considered benign, these tumors demonstrate variable clinical behavior and likely exist on a spectrum, rather than as discrete entities. In this study, we present a detailed clinicopathologic and molecular analysis of these lesions and propose a unifying diagnostic term: sialadenopapillary ductal tumor (SDT). Twenty-two cases with similar histologic features were reviewed, with special attention being paid to the clinicopathologic features. Immunohistochemistry for BRAF V600E and molecular testing were performed where material was available. The cases had varying diagnoses, ranging from benign to malignant. Six cases involved bone, 1 of which metastasized to a local lymph node. Of the 20 cases tested for BRAF V600E by immunohistochemistry, 18 were positive. Molecular testing was performed in 5 cases, where BRAF, PTPN11, and PIK3CA mutations were identified, predominantly members of the RAS-RAF-MEK-ERK pathway. In addition, 1 case was reclassified as an intraductal carcinoma after the identification of an NCOA4::RET gene fusion. Tumors on the SDT spectrum all share morphologic and molecular commonalities with unreliable distinguishing features. These tumors demonstrate the potential for aggressive local growth and regional metastasis. We propose a unifying diagnostic term for these lesions to reflect their common morphologic and molecular features and, most importantly, low malignant potential.

Oncocytic adenocarcinoma (OC) of the salivary glands is a rare and controversial entity. It was recently reclassified as "salivary carcinoma NOS and emerging entities" in the 2022 WHO classification of head and neck tumors. The lack of specific molecular alterations and its potential affiliation with other salivary gland carcinomas, such as the oncocytic mucoepidermoid carcinomas (OMEC) or the oncocytic subtype of salivary duct carcinomas (OSDC) justified this reclassification. It is becoming essential to clarify the complex spectrum of potential diagnoses surrounding oncocytic tumors. The objective of this study was to explore the histologic features, as well as the immunohistochemical and molecular profiles, of cases previously diagnosed as OC or OMEC of the salivary glands. This study involved 28 cases of carcinomas with a predominantly oncocytic component. The sex distribution was equal. The median age was 59 years (range 10 to 89). Most of these cases originated from the parotid gland (25/28). The mean tumor size was 2.4 cm (range 0.5 to 6.5). Primary immuno-morphological and mutation/gene fusion profiles reclassified mainly (64.3%, 18/28). Most of them were reclassified in descending order as OSDC (8/18), OMEC (5/18), and OC (2/18). But 3 cases remained unclassified (3/18). The transcriptomic analysis found a proximity of their transcriptomic profile with the OMEC group and a distance from the OSDCs. These findings imply that OC is not distinct but represents oncocytic variants of other salivary carcinomas. It underscores the importance of thorough morphologic, immunohistochemical, and molecular examinations to accurately diagnose carcinomas with predominant oncocytic components in the salivary glands.

A distinctive form of lung adenocarcinoma that closely mimics large-cell neuroendocrine carcinoma is described. The tumors arose in 6 women and 6 men aged 46-86 years (mean=58.4). They presented as peripheral subpleural masses measuring 2-12 cm (mean=6.5 cm). Histologically they were characterized by islands or anastomosing and serpiginous strands of large, atypical cells showing striking peripheral palisading of nuclei, with high mitotic activity and prominent comedo-like areas of necrosis. Because of the striking resemblance to neuroendocrine tumors, some of the cases were initially diagnosed as large-cell neuroendocrine carcinoma despite the absence of neuroendocrine markers. Immunohistochemistry showed positivity of the tumor cells for TTF1 and napsin-A, and negative staining for p40. The tumors were also uniformly negative for multiple neuroendocrine markers, including chromogranin, synaptophysin, CD56, and INSM1. Electron microscopy performed in 2 cases was negative for membrane-bound dense core neurosecretory granules. Pathogenic alterations were detected in 5 of 8 tumors tested by next-generation sequencing. Point mutations in KRAS and TP53 were identified in 5 patients. Low-level amplification of GNAS , KIT , and FGFR1 was present in 2 patients. No RB1 mutations were identified. Clinical follow-up in 10 cases showed that 2 patients died of their tumors, 2 experienced distant metastases, and 6 were alive and well from 1 to 13 years after diagnosis (median=7.1 y). Large-cell basaloid adenocarcinoma is an unusual variant of lung cancer that is easily confused with large-cell neuroendocrine carcinoma. Awareness of this unusual variant of lung adenocarcinoma is important for treatment and prognosis and for avoiding misdiagnosis.

Low-grade nasopharyngeal papillary adenocarcinoma (LGNPPA) is a rare neoplasm originating from the surface mucosal epithelium in the nasopharynx. To clarify its clinicopathologic, immunohistochemical, and molecular features, we retrospectively enrolled 35 patients diagnosed with LGNPPA between May 2016 and March 2024. Our cohort consisted of 14 male and 21 female patients aged 11 to 71 years (median: 37 y). The most common symptoms were rhinorrhea and nasal obstruction. Most tumors originated from the roof of the nasopharynx and were clinically staged as T1N0M0. None of the patients had a history of thyroid tumors. Microscopically, most of the LGNPPA were composed of irregular papillary structures covered with single-layer columnar or cuboidal epithelium. Eighteen cases (18/35, 51.4%) showed squamous epithelium coverage, and 9 cases (9/35, 25.7%) showed the characteristic transformation of squamous epithelium into neoplasm. Squamous differentiation and a significant spindle cell component were noted in 9 cases (9/35, 25.7%) and 26 cases (26/35, 74.3%), respectively. All cases were positive for thyroid transcription factor-1 protein, CK7, EMA, and Galectin-3 but negative for thyroglobulin, PAX8, and Napsin A. Ki-67 labeling was low and ranged from 2% to 5%. The Epstein-Barr virus or human papilloma virus infection and BRAF V600E mutation were not detected in any of the cases. All patients underwent endoscopic surgical resection, and 4 patients received radiotherapy followed by endoscopic surgery. Complete follow-up data were available for 33 patients. All patients had no recurrent or metastatic disease in the last follow-up (3 to 88 mo). A definitive diagnosis depends on histopathology and immunohistochemistry studies. The optimal treatment for patients with LGNPPA is total excision. Given the extremely indolent biological behavior of LGNPPA, it may be more appropriate to classify it as a primary papillary epithelial tumor rather than an adenocarcinoma of the nasopharynx.