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1.
Hum Pathol ; 149: 55-65, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38876199

RESUMO

Histological subtyping of hepatocellular carcinoma (HCC) is challenging in the presence of histological heterogeneity, where distinctly different morphological patterns are present within the same tumor. Current approaches rely on percent cut-offs. We hypothesized that morphologic intratumor heterogeneity is a non-random biological feature and that incorporating recurrent patterns would improve histological subtyping of HCC. Resected HCC were studied and the overall frequency of morphologic intratumor heterogeneity was 45% in 242 specimens. Steatohepatitic HCC (SH-HCC) had the highest frequency of morphologic intratumor heterogeneity (91%); this was confirmed in additional cohorts of SH-HCC from different medical centers (overall frequency of 78% in SH-HCC). Morphologic intratumor heterogeneity in SH-HCC showed distinct and recurrent patterns that could be classified as early, intermediate, and advanced. Incorporating these patterns into the definition of SH-HCC allowed successful resolution of several persistent challenges: the problem of the best cut-off for subtyping SH-HCC, the problem of the relationship between SH-HCC and scirrhous HCC, and the classification for HCC with abundant microvesicular steatosis. This approach also clarified the relationship between SH-HCC and CTNNB1 mutations, showing that CTNNB1 mutations occur late in a subset of SH-HCC. In summary, there is a high frequency of morphologic intratumor heterogeneity in HCC. Incorporating this finding into histological subtyping resolved several persistent problems with the SH-HCC subtype.


Assuntos
Carcinoma Hepatocelular , Fígado Gorduroso , Neoplasias Hepáticas , Mutação , beta Catenina , Humanos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , beta Catenina/genética , Masculino , Feminino , Pessoa de Meia-Idade , Fígado Gorduroso/patologia , Fígado Gorduroso/complicações , Idoso , Adulto , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética
2.
Appl Immunohistochem Mol Morphol ; 31(9): 590-595, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37698958

RESUMO

Subtyping hepatic adenomas is important for patient management due to differing complication risks. Immunohistochemical staining with C-reactive protein (CRP) and serum amyloid-A (SAA) is widely accepted as a surrogate for molecular classification to identify inflammatory hepatocellular adenomas. Limited data, however, has been published on how these 2 stains compare for sensitivity. We conducted a large, multicenter, retrospective study to examine the sensitivity and staining characteristics of CRP and SAA in inflammatory hepatic adenomas, with focal nodular hyperplasia (FNHs) as a control group. Inflammatory adenomas were identified in 133 patients (average age 37 years, 109 were female). In all, 69.9% of cases were resection specimens and 90.2% of all cases showed positive staining for both CRP and SAA; 10 (7.5%) were positive for CRP only and 3 (2.3%) were positive for SAA only. CRP was more sensitive than SAA (97.74% vs. 92.48%, P -value = 0.0961) and showed more extensive and intense staining, with a significantly higher modified H-score ( P <0.001). Focal nodular hyperplasia can also show positive CRP and SAA staining but with a lower modified H-score ( P <0.0001). Based on beta-catenin and glutamine synthetase staining, 26 of inflammatory adenomas also had beta-catenin activation (19.5%). All 3 cases with positive SAA and negative CRP staining were beta-catenin activated. In contrast, the proportion of cases that were CRP positive and SAA negative was similar regardless of beta-catenin activation. The data affirms the strategy of using both CRP and SAA immunostains for hepatic adenoma subtyping and raises the awareness of the highly variable nature of SAA staining characteristics.


Assuntos
Adenoma de Células Hepáticas , Adenoma , Hiperplasia Nodular Focal do Fígado , Neoplasias Hepáticas , Humanos , Feminino , Adulto , Masculino , Adenoma de Células Hepáticas/diagnóstico , Adenoma de Células Hepáticas/metabolismo , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/metabolismo , Proteína C-Reativa/metabolismo , beta Catenina/metabolismo , Proteína Amiloide A Sérica , Hiperplasia Nodular Focal do Fígado/diagnóstico , Estudos Retrospectivos , Biomarcadores Tumorais/metabolismo , Imuno-Histoquímica , Adenoma/diagnóstico
3.
Am J Surg Pathol ; 47(9): 1045-1051, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37357916

RESUMO

Hepatic angiosarcomas are aggressive malignant tumors of the liver with variable morphology. One of the rare morphologies is that of the sinusoidal growth pattern, which is challenging to diagnose because of its subtle imaging and morphologic findings. This retrospective study characterizes the clinical, histologic, and immunohistochemical features of sinusoidal hepatic angiosarcomas. Thirteen cases were included in the study, comprising 12 (92.3%) needle core biopsies and 1 wedge biopsy; one of the needle biopsies also had a subsequent resection specimen available for review. Multiple biopsies were needed to make the diagnosis in 4 cases. At least moderate sinusoidal dilatation was seen in 53.8% of cases. Increased cellularity within the sinusoids was seen at both low-power and high-power magnification (69.2% and 84.6%, respectively). Cytologic atypia ranged from mild to marked. Multinucleated tumor cells were present in most cases (10/13 cases) but were often sparse. Mitotic activity was identified in 5/13 cases. ERG immunostains were more reliable than CD31 and CD34 in identifying the tumor cells. Ki-67 proliferative index ranged from 5% to 30%. p53 immunostains were available in 9 cases and c-MYC in 7 cases; they were positive in 62.5% and 33.3% of cases, respectively and had a mutually exclusive staining pattern. In summary, this rare pattern of hepatic angiosarcoma is challenging to diagnose but has distinctive morphologic findings that can be supplemented with immunostains to establish the diagnosis.


Assuntos
Hemangiossarcoma , Neoplasias Hepáticas , Humanos , Hemangiossarcoma/patologia , Estudos Retrospectivos , Neoplasias Hepáticas/patologia , Biópsia , Biópsia com Agulha de Grande Calibre
4.
Am J Surg Pathol ; 47(7): 792-800, 2023 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-37204143

RESUMO

Newer radiotherapy techniques, such as stereotactic body radiation, have been increasingly used as part of the treatment of cholangiocarcinomas, particularly as a bridge to liver transplantation. Although conformal, these high-dose therapies result in tissue injury in the peritumoral liver tissue. This retrospective study characterized the morphologic changes in the liver after stereotactic body radiation in a series of liver explant specimens with perihilar cholangiocarcinoma. The morphologic changes in the irradiated zone were compared against the nonirradiated background liver parenchyma to control for chemotherapy-related changes. Of the 21 cases studied, 16 patients (76.2%) had underlying primary sclerosing cholangitis, and 13 patients (61.9%) had advanced liver fibrosis. The average duration between completion of radiotherapy and liver transplantation was 33.4 weeks (range: 6.29 to 67.7). Twelve patients (57.1%) had no residual tumor in the liver. The most frequent histologic changes in the peritumoral irradiated liver tissue were sinusoidal congestion (100%), sinusoidal edematous stroma (100%), and hepatocellular atrophy (100%), followed by partial/complete occlusion of central veins (76.2%), sinusoidal cellular infiltrates (76.2%), and hepatocyte dropout (66.7%). The findings in the radiated areas were more extensive than in the background liver ( P <0.01). Sinusoidal edematous stroma was striking and dominated the histologic findings in some cases. Over time, there was less sinusoidal congestion but more hepatocyte dropout (r s =-0.54, P =0.012 and r s =0.64, P =0.002, respectively). Uncommon findings, such as foam cell arteriopathy in the liver hilum, were also observed. In summary, postradiation liver specimens have distinctive morphologic findings.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Neoplasias Hepáticas , Radiocirurgia , Humanos , Radiocirurgia/efeitos adversos , Estudos Retrospectivos , Fígado/patologia , Colangiocarcinoma/patologia , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/patologia , Ductos Biliares Intra-Hepáticos/patologia , Neoplasias dos Ductos Biliares/patologia
5.
Int J Mol Sci ; 24(7)2023 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-37047105

RESUMO

The liver is a major store of glycogen and is essential in maintaining systemic glucose homeostasis. In healthy individuals, glycogen synthesis and breakdown in the liver are tightly regulated. Abnormal glycogen metabolism results in prominent pathological changes in the liver, often manifesting as hepatic glycogenosis or glycogen inclusions. This can occur in genetic glycogen storage disease or acquired conditions with insulin dysregulation such as diabetes mellitus and non-alcoholic fatty liver disease or medication effects. Some primary hepatic tumors such as clear cell hepatocellular carcinoma also demonstrate excessive glycogen accumulation. This review provides an overview of the pathological manifestations and molecular mechanisms of liver diseases associated with abnormal glycogen accumulation.


Assuntos
Carcinoma Hepatocelular , Doença de Depósito de Glicogênio , Neoplasias Hepáticas , Humanos , Glicogênio/metabolismo , Fígado/metabolismo , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Doença de Depósito de Glicogênio/genética , Doença de Depósito de Glicogênio/metabolismo
7.
Head Neck Pathol ; 13(4): 664-667, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30039355

RESUMO

A 38-year-old, previously healthy man presented with blood-stained saliva and epistaxis. A 3 mm nasopharyngeal lesion was found. A biopsy was performed and microscopic examination revealed a Kaposi sarcoma. The patient was subsequently found to be positive for human immunodeficiency virus (HIV). The diagnosis of Kaposi sarcoma in the presence of HIV infection advanced his disease to Acquired Immunodeficiency Syndrome (AIDS). Primary manifestation of Kaposi sarcoma in the nasopharynx is extremely rare. The histologic differential diagnosis of Kaposi sarcoma in this unusual site, especially without the clinical history of immunosuppression, is broad. Awareness that nasopharynx can be a primary involvement site of Kaposi sarcoma and serves as index diagnosis of AIDS is important given its serious clinical implication.


Assuntos
Síndrome da Imunodeficiência Adquirida/complicações , Neoplasias Nasofaríngeas/etiologia , Sarcoma de Kaposi/etiologia , Adulto , Humanos , Masculino , Neoplasias Nasofaríngeas/patologia , Sarcoma de Kaposi/patologia
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