2Tumori primitivi epatici rari Carcinoma fibrolamellareCarcinoma misto epato-colangiocellulareEpatoblastomaCarcinosarcomaCarcinoide primitivo epaticoCistoadenoma e il cistoadenocarcinomaSarcomiLinfomi
3Carcinoma fibrolamellare 1-5% of HCCYounger Caucasian patients (20-40 years); 30-40% < 20 years oldNo gender preferenceFC arises in an otherwise normal liver, in contrast to most patients with HCC.A characteristic lamellar connective tissue is noted with macrohepatocytes.Better prognosis than classic HCC; 5 years survival 60%Hepatology 2004; 39(3): 798–803Cancer 2006;106:1331–8
4Carcinoma misto epato-colangiocellulare Less than 5% of primary hepatic carcinomasThese tumors are divided into:those coincidentally containing HCC and cholangiocarcinoma in the same liver (type I)“transitional tumors” from HCC to cholangiocarcinoma (type II)“fibrolamellar tumors” which resemble FC but contain mucin-producing pseudoglands (type III)Classification problemsThe majority of these tumors arise in non-cirrhotic livers, with equal male/female distributionAggressive, 5 year overall survival 18%, 24% after resectionType IType IICancer 2002; 94(7):2040–6J Med Invest 2008; 55:161-5 (review)Type III
5EpatoblastomaAlmost exclusively in children between 6 months and 3 years, with a male predominance50% of liver mlignancies in childrenDerived from undifferentiated embryonal tissue and thought to develop from pluripotent hepatic stem cells.More commonly in families with familial adenomatous polyposis.Lesions are often a solitary mass in the right lobe of the liver.
6Epatoblastoma1. Hepatoblastoma. A lobectomy specimen, showing a tumour mass bulging from the surface with lobulations on cut section2. Hepatoblastoma, fetal epithelial type. The tumour has a characteristic ‘light and dark’ appearance at low magnification. H&E.3. Hepatoblastoma, fetal epithelial type with abundant extramedullary haematopoiesis. H&E.4. Hepatoblastoma, epithelial type with embryonal epithelium (left) and fetal epithelium (right). H&E.Tumour mass bulging from the surface with lobulations on cut section; fetal epithelial type: a characteristic light and dark appearance and abundant extramedullary haematopoiesis; embryonal epithelium (left) and fetal epithelium (right)
7Epatoblastoma1 Hepatoblastoma, mixed type. There is a fetal epithelial component (right) and an embryonal component mixed with primitive mesenchyme (left). H&E.2. Hepatoblastoma, mixed type, with osteoid. H&E. 3. Hepatoblastoma, mixed type. Partially calcified osteoid in the midst of a fetal epithelial component. H&E.4. Hepatoblastoma, mixed type. An area with primitive mesenchyme and cartilage. H&E.Hepatoblastoma, mixed type: fetal epithelial component and an embryonal component mixed with primitive mesenchyme, with osteoid, partially calcified osteoid, and cartilage.
8Carcinosarcoma Raro; meno di 20 casi riportati in letteratura Numerosi sinonimi (carcinoma a cellule fusate, pseudosarcoma, carcinoma polipoide, carcinoma sarcomatoide, variante fusocellulare di carcinoma, ecc.)definizione dell’WHO “un tumore che contiene sia elementi carcinomatosi (epato o colangioca,) sia elementi sarcomatosi, includendo i tumori misti.Raro; meno di 20 casi riportati in letteratura; numerosi sinonimi (carcinoma a cellule fusate, pseudosarcoma, carcinoma polipoide, carcinoma sarcomatoide, variante fusocellulera di carcinoma, ecc.; definizione dell’WHO “un tumorr che contiene sia elementi carcinomatosi (epato o colangiocarcinoma) sia elementi sarcomatosi, includendo i tumori misti.Hyeok Kwon J et al. Korean J Radiol 8(4), August 2007
9Carcinoide primitivo epatico 100 cases reported; less than 10 functional.These tumors may arise from a pluripotent stem cellMiddle age (mean age = 48.2 years) and is more frequent in females (males/females = 20/33 cases)80% and 84% of the cases are positive for Grimelius silver stain and immunohistochemically positive for chromogranin A, respectively18% of recurrence rate and a 74% of a survival rate after 5 yearsFig. 1. CT scan of the liver. The left image shows a large mass occupying the right lobe. Smaller lesions are seen in the left lobe ofthe liver. Right image: the tumor is highly vascular showing extensive peripheral enhancement with big central necrosis (arrows).Fig. 2. Fine needle aspiration cytology from the big mass in theright lobe of the liver shows a cellular lesion composed of smalluniform cells lying scantly or forming loosely arranged clusters. Thecytoplasm is scanty showing fi ne eosinophilic granules in some. Thenuclei are uniform, small with granular chromatin. Papanicolaou.! 400.Fig. 3. Positive immunohistochemical stains for chromogranin A,consistent with a neuroendocrine tumor (carcinoid). ChromograninA. ! 400.Primary hepatic carcinoid tumor: a case report and review of the literature. Cases J. 2009;27;2(1):90 Primary hepatic carcinoid tumor: case report and review of 53 cases. Med Sci Monit. 2001;7(4):746-50
10Cistoadenoma e cistoadenocarcinoma Nearly 200 cystadenomas and 100 cystadenocarcinomas have been reported.Cystadenomas are usually found in middle-aged women.The cause is unknown.The typical appearance is of a lobulated, multiloculated mass.Histologically, most contain an “ovarian-like” stroma.CA 19-9 may be elevated.Hepatobiliary cystadenoma: a report of two cases. J Gastrointestin Liver Dis Jun;17(2):203-6.
11Cistoadenoma e cistoadenocarcinoma 1. Hepatobiliary cystadenoma. An area with abundant mesenchymal stroma. H&E.2. Hepatobiliary cystadenocarcinoma. A multilocular cystic neoplasm lined with papillary adenocarcinoma. H&E.Hepatobiliary cystadenoma. An area with abundant mesenchymal stroma.A multilocular cystic neoplasm lined with papillary adenocarcinoma.
12Sarcomi primitivi del fegato Less than 1% of all hepatic malignancies.Angiosarcoma, embryonal sarcoma, leiomyosarcoma, epithelioid hemangioendothelioma, fibrosarcoma, malignant fibrous histiocytoma, malignant solitary fibrous tumor, follicular dendritic cell sarcoma,Rhabdomyosarcoma in infants and childrenIn immunocompromised individuals smooth muscle tumors of uncertain malignant potential have been described that are Epstein-Barr virus (EBV)-driven.The rarity of this disease is evident by theexistence of only 30 patients with primary hepaticsarcoma managed at our institution between 1981and 2004, compared with 331 patients with liver metastasesfrom sarcoma admitted to our institutionduring a similar time period.21Only 30 primary hepatic sarcoma between 1981 and 2004, compared with 331 patients with liver metastases from sarcomaWeitz J. et al Cancer 2007;109:1391–6.
13AngiosarcomaRare but the third most common primary malignant tumor of the liver.Predelection for elderly males.The exposures to vinyl chloride, arsenic, thorotrast and irradiation are associated with an increased risk (etiologic cofactors).Endothelial proliferation along the liver sinusoids, large necroses and cell atypias; solid and papillary.Immunohistochemical staining for CD31, CD34, MIB-1 confirme the diagnosisPoor prognosis.Large, hyperchromatic, atypical endothelial cells in hepatic sinusoids.World J urg Oncol ;6:104 (review)World J Gastroenterol ; 12(5):
14Angiosarcoma1. Atrophy of liver cell plates with sinusoids lined by malignant endothelial cells. H&E2. Loss of hepatocytes, producing cavernous areas lined by malignant endothelial cells. H&E.3. Epithelioid-appearing tumour cells, mimicking carcinoma. In contrast to epithelioid haemangioendothelioma, there is no stroma.Atrophy of liver cell plates with sinusoids lined by malignant endothelial cells.Loss of hepatocytes, producing cavernous areas lined by malignant endothelial cells.Epithelioid-appearing tumour cells, mimicking carcinoma.In contrast to epithelioid haemangioendothelioma, there is no stroma.
15Emangioendotelioma epitelioide More than 200 cases reported, with a link to oral contraceptives.Mean age 47 years, but occurs at any ageFemale predominance (60%)Non specific symptoms; in over 40% the tumor is found incidentally.Histologically: dendritic and epithelioid cells with immunohistochemistry positivity for at least one endothelial cell marker (FVIII-RAg,CD34,CD31)Indolent and slow growing; 5 year survival 43%Epithelioid haemangioendothelioma. Multifocal tumour nodules are hard and white, mimicking metastatic carcinoma.1. Epithelioid haemangioendothelioma. Individual and small groups of tumour cells in a mucopolysaccharide-rich stroma. Some tumour cells are epithelioid and some form capillary lumina. H&E.2. Epithelioid haemangioendothelioma. Immunostain for CD34 demonstrates that the tumour cells are of endothelial origin3. Epithelioid haemangioendothelioma. Pale, epithelioid tumour cells grow in sinusoids, and form papillary tufts, mimicking metastatic carcinoma. H&E.Epithelioid hemangioendothelioma is a distinctivevascular neoplasm that usually arises in liver, lung, orbone and can be regarded as a type of low-gradeangiosarcoma.Am Surg 2008; 74 (1):64-8 (review) Cancer 1999; 85(3): 562–82.
16LeiomiosarcomaApproximately 50 primary liver leiomyosarcomas are documentedA mean age of 53Equal male/female distribution.No causative factors are known.Primary hepatic myxoid leiomyosarcoma: a case report and review of the literature (Ultrastruct Pathol Jan-Feb;32(1):25-8) – total 3 cases reportedLeiomyosarcoma is a rare tumor of the liver. It usually arises from many other organs including uterus, gastrointestinaltract, retroperitoneum, and soft tissues. Primary hepatic leiomyosarcoma progresses very slowly and isnot associated with chronic liver disease. When the tumor is detected early enough to be treated by operation,the prognosis is favorable. While several cases of primary hepatic leiomyosarcoma have been reported in Korea,there was no case associated with acute bleeding. We report a 80-year old male patient with huge primary hepaticleiomyosarcoma, who presented with acute bleeding and IVC obstruction. The patient was treated by embolizationand IVC stenting.Am J Gastroenterol 1995; 90(4): 649–52Korean J Gastroenterol 2008;51:
17Istiocitoma fibroso maligno Extremely rare29 cases reportedMean age 51yrs16 men, 13 womenMFH of the liver is extremely rare, and only 28 cases have been reported to date.[6-14]In this report we present a case of primary hepaticMFH with multicystic presentations.Fig. 1. Abdominal CT showing a large multiseptated, multicysticlesion involving the terminus of the main hepatic vein. Thetumor bulging from the diaphragmatic surface of the liver (A).The largest size of the tumor was 9.5×14.2 cm in dimension.The septae and focally thickened cystic wall were intenselyenhanced (B)Occasionally, hepatic MFH withextensive necrosis may be manifested as a cystictumor. Tumor necrosis in our case progressed to suchan extent that it resembled a cystic mass or abscesson imaging studies. Cystic transformation of theentrapped small bile ducts and ductules was sometimesalso demonstrated. However, the absence of distinctlycharacteristic features makes a preoperative diagnosisof hepatic MFH extremely difficult.Since MFH was first described in 1964, manyattempts have been made to define its pathogenesisand histogenesis.[21-24] According to its histopathologicfeatures, MFH has been categorized into storiformpleomorphic,myxoid, inflammatory, giant cell,and angiomatoid variants. Among these types, thestoriform-pleomorphic is the commonest. In ourcase, the histologic pleomorphism, the degreeof vimentin staining, and the absence of smoothmuscle marker desmin were consistent with thecriteria for a diagnosis of MFH. However, thediagnosis of hepatic MFH is based on a process ofexclusion.[25-27] Differential diagnosis firstly includeshepatocellular carcinoma. A variety of poorlydifferentiated sarcomas such as angiosarcoma, thecommonest type, and the infrequent liposarcomas, ofrhabdomyosarcoma, leiomyosarcoma, fibrosarcoma,and embryonal sarcoma seen in children andyoung adults hence should be included in thedifferential diagnosis. In addition, the presence ofa large cystic cavity in the liver produces a clinicaldifferential diagnosis that includes intrahepaticcholangiocarcinoma, benign liver cyst, liver abscess,and echinococcus alveolaris infection.Similar to MFH in the other sites of the body,surgery is the only effective method of treatment, butthe prognosis is poor.[31-33] The overall 2-year survivalrate is approximately 60% and 20% of the patientswill die or suffer from local recurrence. Chemotherapyand radiotherapy have been attempted but failed..Fig. 2. Pathological examination showing a storiform architecturalarrangement with fibroblast-like spindle cells (A). Multiple bizarregiant cells scattered between the spindle cells, and numerousmitotic figures identied (B) (HE, original magnification, A×60, B×200).Fig. 3. Immunohistological staining for vimentin (A) and forCD68 (B) demonstrating positive reaction in the tumor cells(EnVision, original magnification×200).Mt Sinai J Med 2005; 72(1):50–2.Am J Surg Pathol 2008; 32: (review)
18Kuo LM et al.World J Gastroenterol 2006 February 21; 12(7):1157-1159 LiposarcomaKuo LM et al.World J Gastroenterol 2006 February 21; 12(7):Figure 1 A low-attenuation cystic mass located in segments 4, 5, and8 with bilateral biliary tract compression in a non-cirrhotic liver by CT.Figure 2 A lobulated liver liposarcoma with intra-tumor hemorrhageFigure 3 Numerous lipoblasts and capillaries in the myxoid liposarcoma(hematoxylin-eosin staining, 400 ×).Figure 5 A high grade of undifferentiated liposarcoma composed of spindle cellswith marked nuclear pleomorphism (hematoxylin-eosin staining, × 400 ).
19Sarcoma embrionaleThe tumour is gelatinous and fish-flesh in consistency with areas of necrosis.Undifferentiated tumour cells in a myxoid matrix. Some tumour cells contain eosinophilic globules.1. Embryonal sarcoma. The tumour is gelatinous and fish-flesh in consistency with areas of necrosis.2. Embryonal sarcoma. Undifferentiated tumour cells in a myxoid matrix. Some tumour cells contain eosinophilic globules. H&E.3. Embryonal sarcoma. Bizarre, trapped bile ducts and hepatocytes at the periphery of a tumour. H&E.Indian J Pathol Microbiol 2007 Oct;50(4):811-3 Gastroenterol Hepatol 2008; 31 (1):12-7 (review)
20Altri sarcomi primitivi del fegato Rhabdomyosarcomas of liver typically appear in children Mt Sinai J Med 2005; 72(1):50–2.Osteosarcoma: less than 10 case reports European Journal of Radiology Extra Vol 50, Issue 1, April 2004, Pages 31-36Primary hepatic schwannoma reported typically associated with von Recklinghausen’s diseaseAlveolar soft-part sarcoma Am Surg 2008; 74(1):43-6MFH of the liver is extremelyrare, and only 28 cases have been reported to date.[6-14]In this report we present a case of primary hepaticMFH with multicystic presentations.Fig. 1. Abdominal CT showing a large multiseptated, multicysticlesion involving the terminus of the main hepatic vein. Thetumor bulging from the diaphragmatic surface of the liver (A).The largest size of the tumor was 9.5×14.2 cm in dimension.The septae and focally thickened cystic wall were intenselyenhanced (B).
21Angiomiolipoma < 100 cases reported Often misdiagnosed Similar to renal angiomyolipomaMean age 50 years (9-79)80% womenHMB45, MelanA/Mart1, MITF (50%), S100, actin (1A4), desmin, c-kit/CD1171. Angiomyolipoma. A typical lesion with large, abnormal arteries, smooth muscle and adipose tissue. H&E.2. Angiomyolipoma. A tumour with bizarre, epithelioid smooth muscle cells that might be mistaken for malignancy. H&E. 3. Angiomyolipoma. A tumour with a large amount of haematopoietic tissue in addition to the other components. H&E.Arch Pathol Lab Med 2008; 132 (10): (review)AJSP 2002; 26:493 (c-kit staining)Archives 2002; 126:49 (melanoma markers)AJSP 1999; 23:34 (rewiew)
22Schwannoma benigno 9 cases reported Associated with neurofibromatosis in about 50% of cases.Malignant transformation is rareThey grow very slowly and are well encapsulated in most cases.Usually smaller than 5 cm at diagnosisLarger schwannomas have a tendency to undergo secondary degeneration such as pseudocystic regression, hemorrhage and calcification.Microscopic examination shows spindle cells like otherstromal tumors. The histological diagnosis of a benign schwannomais usually a simple procedure with standard Hematoxilin-Eosin staining. The distinction between a schwannomaand other spindle cell tumors or neurofibromas is based onthe presence of a true capsule and Antoni A and Antoni Bfindings in the schwannoma (11). The type A area is denseand cellular, but the type B area is hypocellular. Immunohistochemicalstaining is diffusely and strongly positive forS-100 protein in a schwannoma consistent with the findingof a nerve sheath tumor. The tumor is also positive for theglial fibrillary acidic protein and CD57 (Leu 57) (15). Eventhough a few gastrointestinal stromal tumors are positive forS-100, they are also positive for either CD34 or CD117. However,a schwannoma is negative for both CD34 and CD117.A leiomyoma would be negative for S-100 and positive fordesmin or smooth muscle actinLee WH et al J Korean Med Sci 2008; 23:
23Linfoma primitivo del fegato ~ 100 cases reported75% menMedian 55 years, but all agesDiffuse sinusoidal infiltrationLymphomas involving the liver include, with decreasing frequency:diffuse large B-cell lymphomasmall lymphocytic lymphomaHodgkin's lymphomaperipheral T-cell lymphomafollicular lymphomaextranodal marginal zone B-cell lymphoma.1. Diffuse large B cell lymphoma. The tumour causes irregular destruction of hepatic parenchyma. H&E.Archives 2001; 125:695Pathologe Jul;27(4):
24Primary extramedullary plasmacytoma of the liver Demirhan B. et al J Clin Pathol 1997;50:74-76Primary non-Hodgkin's lymphomas of the liverare rare. Many of these lymphomas are highgrade, with only a minority of cases presentingas low grade tumours.l A proportion ofprimary low grade lymphomas of the liverwould seem to be B cell lymphomas of mucosaassociated lymphoid tissue (MALT) type.2 Toour knowledge, only two cases of primaryextramedullary plasmacytoma of the liver hasbeen reported to date.3(A) Infiltrate of uniform mature plasma cells with mild atypia, invading the liver parenchyma (haematoxylin and eosin); (B) VS38 antibody positive cells (immunoperoxidase); (C) plasma cells showing K light chain restriction; (D) no i. light chain immunoreactivity is evident.