Hepatocellular carcinomas can be further divided into distinct subtypes that provide important clinical information and biological insights. These subtypes are distinct from growth patterns and are ...on based on morphologic and molecular findings. There are 12 reasonably well-defined subtypes as well as 6 provisional subtypes, together making up 35% of all hepatocellular carcinomas. These subtypes are discussed, with an emphasis on their definitions and the key morphologic findings.
Angiosarcoma is a rare malignant neoplasm of the liver. The various morphologic patterns seen with angiosarcomas of the liver have not been systematically studied and their recognition remains a ...major diagnostic challenge. In order to provide more comprehensive data on the morphologic patterns, angiosarcomas that had been diagnosed between 1996 and 2016 at a large medical referral center were reviewed. The major growth patterns were classified as sinusoidal (non-mass forming) versus mass forming. The mass-forming cases were further subdivided into epithelioid, spindled, or vasoformative. The study identified 21 patients with primary hepatic angiosarcoma: 13 men and 8 women. The ages ranged from 26 to 89 years. Seventeen angiosarcomas were mass-forming tumors, of which 9 showed predominantly vasoformative growth. Most of these vasoformative cases (6/9) were composed of small vessels, 2 cases had slit-like vascular spaces, and one case showed a mixture of small and large vessels. There were 7 mass-forming angiosarcomas without vasoformation: 3 had an epithelioid morphology and 4 were composed primarily of spindled cells. The final mass-forming tumor showed a mixture of vasoformative and nonvasoformative areas. Four of 21 cases were non-mass forming and showed either diffuse sinusoidal infiltration (N=2) or prominent peliotic changes (N=2). Finally, 3 uncommon patterns were identified. One case showed nodules of spindle cells arranged in prominent whorls in a background of loose connective tissue with abundant inflammation. A second case arose in the setting of the Blue Rubber Bleb Nevus Syndrome and showed numerous tumor nodules with an architectural pattern that resembled infantile hemangioma, some with areas of atypia consistent with malignant transformation to angiosarcoma. The third unusual pattern showed multiple nodules of thin walled large caliber vascular proliferations, some of which showed atypia that reached the level of angiosarcoma. The results from this study indicate that the majority of hepatic angiosarcomas are mass forming (two third of cases), a pattern that is recognizable on H&E when vasoformative, but can mimic carcinoma or undifferentatied sarcomas when nonvasoformative (one third of cases). The sinusoidal patterns are particularly challenging and are frequently missed on initial review. Finally, we describe several unsual patterns of angiosarcoma. Awareness of these classic and rare morphologic patterns can help make the diagnosis of angiosarcoma.
Hamartomas and malformations of the liver Torbenson, Michael S.
Seminars in diagnostic pathology,
January 2019, 2019-Jan, 2019-01-00, 20190101, Letnik:
36, Številka:
1
Journal Article
Recenzirano
Hamartomas and malformations of the liver are rare and can lead to diagnostic challenges. Most present as mass lesions that can mimic true neoplasms of the liver on imaging and sometimes on ...histology, one example being focal nodular hyperplasia. The primary cell type in the hamartomas and malformations can be biliary, vascular, or hepatic. Biliary lesions include bile duct hamartomas and simple liver cysts. Other cystic malformations include the ciliated hepatic foregut cysts and mesothelial cysts. Vascular malformations include telangiectasias, arteriovenous malformations, and hereditary lymphedema. Malformations composed primarily of hepatocytes include accessory lobes and focal nodular hyperplasia. All of these entities are discussed, with a focus on the diagnostic histological findings.
Considerable evidence implicates cellular senescence in the biology of aging and chronic disease. Diet and exercise are determinants of healthy aging; however, the extent to which they affect the ...behavior and accretion of senescent cells within distinct tissues is not clear. Here we tested the hypothesis that exercise prevents premature senescent cell accumulation and systemic metabolic dysfunction induced by a fast-food diet (FFD). Using transgenic mice that express EGFP in response to activation of the senescence-associated p16(INK4a) promoter, we demonstrate that FFD consumption causes deleterious changes in body weight and composition as well as in measures of physical, cardiac, and metabolic health. The harmful effects of the FFD were associated with dramatic increases in several markers of senescence, including p16, EGFP, senescence-associated β-galactosidase, and the senescence-associated secretory phenotype (SASP) specifically in visceral adipose tissue. We show that exercise prevents the accumulation of senescent cells and the expression of the SASP while nullifying the damaging effects of the FFD on parameters of health. We also demonstrate that exercise initiated after long-term FFD feeding reduces senescent phenotype markers in visceral adipose tissue while attenuating physical impairments, suggesting that exercise may provide restorative benefit by mitigating accrued senescent burden. These findings highlight a novel mechanism by which exercise mediates its beneficial effects and reinforces the effect of modifiable lifestyle choices on health span.
Since its first description 50 years ago, fibrolamellar carcinomas (FLCs) have been recognized as a unique type of primary liver cancer. FLCs occur principally in children and young adults and are ...not associated with chronic liver disease. Their etiology is unknown. The tumor is made up of large polygonal cells containing abundant eosinophilic cytoplasm, large vesiculated nuclei, and large nucleoli, with tumor cells that are embedded in lamellar bands of fibrosis. Although rare, the most common variant of FLC shows areas of glandular type differentiation with mucin production. The uniqueness of FLC extends to their molecular findings, as they show no evidence for involvement by many of the major pathways and genes that are dysregulated in typical hepatocellular carcinoma, including alpha-fetoprotein, TP53 mutations, and beta catenin mutations. FLCs are not indolent tumors, but have an overall better prognosis than hepatocellular carcinomas of the usual sort because of the younger age at presentation and lack of cirrhosis. The most important prognostic feature is resectability. Although their morphologic appearance on routine stains is well defined, their etiology is still unknown and much of their molecular biology remains poorly described and awaits future investigation.
Clinical vignette A 58-year old Caucasian female has compensated hepatitis C related cirrhosis. Her surveillance ultrasound showed hypodense liver nodules and subsequent triple phase CT scan showed ...five tumor nodules with diameters ranging from 3–5 cms involving both hepatic lobes. The nodules showed characteristic radiologic findings on the CT scan and she was diagnosed with hepatocellular carcinoma (HCC) based on non-invasive criteria. There was also associated right portal vein tumor thrombosis. Her functional capacity at diagnosis was slightly limited, but she was capable of performing all activities of daily living and self-care. Her laboratory tests at diagnosis were as follows: sodium 129 mmol/L, potassium 3.6 mmol/L, blood urea nitrogen 22 mg/dL, creatinine 1.0 mg/dL, albumin 2.9 g/dl, bilirubin 1.8 mg/dl, alanine aminotransferase 87 U/L, aspartate aminotransferase 68 U/L, alkaline phosphatase 139 U/L, white blood cell 3.5 x 109 /L, hemoglobin 10.4, platelet count 73 x 109 /L, international normalized ratio 1.9 and alpha-fetoprotein 5200 ng/ml. An upper endoscopy was negative for esophageal or gastric varices. Based on the tumor burden, presence of macrovascular invasion, ECOG performance status of 1 and Child-Pugh class A she was classified to have BCLC stage C HCC. She was started on sorafenib therapy at 400 mg oral twice daily but unfortunately this had to be discontinued since she experienced severe diarrhea and skin rash. She now returns for follow-up and requests information on the available therapeutic options. This particular case scenario is not uncommon and does raise several clinically relevant questions: a. Should her liver lesions have been biopsied for diagnosis? b. Are there any serum or tissue biomarkers that could have helped in prognostication? c. Was sorafenib the best first option for her and were there any biomarkers that could have predicted the adverse reactions she experienced? d. What other potential therapies will be available for her in the near future? This review provides a comprehensive overview of the current state of HCC management and also examines the clinical implications of recent basic research in HCC.
Fibrolamellar carcinomas are a unique type of primary liver cancer. They occur most commonly in children and young adults. Their etiology remains a mystery, as they are not associated with chronic ...liver disease. Fibrolamellar carcinomas are not indolent tumors, but have an overall better prognosis than typical hepatocellular carcinomas, in part because of the younger age at presentation and the lack of cirrhosis. The most important prognostic feature is whether the tumor is resectable. Histologically, the tumor is made up of large cells that contain abundant mitochondria. The nuclei of the tumor cells have prominent nucleoli. The tumor cells induce the formation of extensive intratumoral fibrosis, which often grows in parallel, or lamellar bands. The tumor cells clearly show hepatocellular features but are also unique in showing both biliary and neuroendocrine differentiation. The uniqueness of fibrolamellar carcinoma extends to their molecular findings. While the genetic abnormalities that lead to fibrolamellar carcinomas are not yet known, studies have shown that they lack mutations in the genes most commonly mutated in typical hepatocellular carcinoma (TP53 and CTNNB1). In this paper, the clinical, pathological, and basic science literature on fibrolamellar carcinoma is comprehensively reviewed. Key areas of needed research are also discussed.
Through exomic sequencing of ten hepatitis C virus (HCV)-associated hepatocellular carcinomas (HCC) and subsequent evaluation of additional affected individuals, we discovered novel inactivating ...mutations of ARID2 in four major subtypes of HCC (HCV-associated HCC, hepatitis B virus (HBV)-associated HCC, alcohol-associated HCC and HCC with no known etiology). Notably, 18.2% of individuals with HCV-associated HCC in the United States and Europe harbored ARID2 inactivation mutations, suggesting that ARID2 is a tumor suppressor gene that is relatively commonly mutated in this tumor subtype.
Hepatic fibrosis is potentially reversible; however early diagnosis is necessary for treatment in order to halt progression to cirrhosis and development of complications including portal hypertension ...and hepatocellular carcinoma. Morphologic signs of cirrhosis on ultrasound (US), computed tomography (CT), and magnetic resonance imaging (MRI) alone are unreliable and are seen with more advanced disease. Newer imaging techniques to diagnose liver fibrosis are reliable and accurate, and include magnetic resonance elastography and US elastography (one-dimensional transient elastography and point shear wave elastography or acoustic radiation force impulse imaging). Research is ongoing with multiple other techniques for the noninvasive diagnosis of hepatic fibrosis, including MRI with diffusion-weighted imaging, hepatobiliary contrast enhancement, and perfusion; CT using perfusion, fractional extracellular space techniques, and dual-energy, contrast-enhanced US, texture analysis in multiple modalities, quantitative mapping, and direct molecular imaging probes. Efforts to advance the noninvasive imaging assessment of hepatic fibrosis will facilitate earlier diagnosis and improve patient monitoring with the goal of preventing the progression to cirrhosis and its complications.
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