36 Benign hepatic lesions and tumours
Page:
1 Definition 752
2 Classification 752
2.1 Sonomorphological classification 752
2.2 Histological classification 752
3 Diagnosis 752
3.1 Anamnesis 752
3.2 Complaints 753
3.3 Findings 753
3.4 Imaging procedures 753
3.5 Biopsy and laparoscopy 753
4 Differential diagnosis 754
4.1 Adenoma 754
4.2 Focal nodular hyperplasia 755
4.3 Nodular regenerative hyperplasia 756
4.4 Haemangioma 757
4.5 Infantile haemangioendothelioma 759
4.6 Fat-containing tumours 759
4.7 Chondroma 760
4.8 Leiomyoma 760
4.9 Schwannoma 760
4.10 Glomangioma 760
4.11 Mesenchymal hamartoma 760
4.12 Mesothelioma 760
4.13 Fibrous tumour 760
4.14 Cysts 761
4.14.1 Polycystic liver disease 761
4.14.2 Parasitic cysts 762
4.15 Cholangiocellular tumours 762
4.15.1 Caroli’s disease / syndrome 762 4.15.2 Hepatobiliary cystadenoma 762
4.15.3 Biliary hamartoma 763
4.16 Abscesses 763
4.17 Lymphangioma 763
4.18 Peliosis hepatis 763
4.19 Granulomas 764
4.19.1 Sarcoidosis 764
4.20 Inflammatory pseudotumour 765
4.21 Calcareous foci 765
5 Surgical treatment 766
앫 References (1⫺198) 767
(Figures 36.1 ⫺36.16; tables 36.1⫺36.5)
1 Definition
The term lesion denotes a circumscribed impairment of function or tissue structure, while the word tumour describes a circumscribed swelling or the growth of body tissue. • Benign hepatic focal lesions are circum- scribed alterations. They differ markedly from the surrounding hepatic tissue, which shows a normal or diffusely changed structure. Differences in tissue type or chemical composition are revealed by imaging pro- cedures. Benign hepatic coin lesions can appear either in solitary or multiple form. They may be only 1 ⫺2 mm in size or cover large hepatic areas, and even a complete lobe.
2 Classification
Benign hepatic focal lesions are usually detected as an incidental finding in sonography. As a rule, there are no subjective or characteristic complaints, no identified neoplastic disease and no objective clinical findings.
2.1 Sonomorphological classification
Sonomorphological differentiation may be helpful in classifying incidentally detected liver foci: (1.) anechoic, (2.) hypoechoic, and (3.) echogenic lesions. The cyst as a typical anechoic focus displays the following charac- teristics: a delicate margin, dorsal sound reduction and a completely anechoic lumen. • Focal hepatic lesions or coin lesions are exceptionally variable with regard to size, number, internal echo (homogeneous or struc- tured), demarcation from the surrounding hepatic tissue and secondary findings (displacement effects, com- pression). • It is extremely important to rule out malig- nant hepatic tumours. (s. tab. 36.1)
Anechoic lesions Hypoechoic lesions
Caroli’s syndrome Adenoma
Cysts Echinococcus alveolaris
Echinococcus alveolaris FNH
Fresh haematoma Focal non-fatty changes Liquefied abscess Fresh abscess
Osler’s disease Hamartoma
Lymphoma
Echogenic lesions NRH
Fibroma
Old haematoma Focal fatty changes
Peliosis hepatis Granuloma
Regenerative nodes Haemangioma
Hamartoma Lipoma
Regenerative nodes
Tab. 36.1: Sonomorphological classification of benign hepatic fo- cal lesions according to their (predominant) echogenicity
2.2 Histological classification
Differential diagnosis of circular hepatic foci helps to decide whether therapeutic measures are necessary, not required, or not feasible. • The histological classification of benign coin-like hepatic lesions differentiates between (1.) hepatocellular tumours, (2.) cholangiocellular tu- mours, (3.) mesenchymal tumours, and (4.) tumour-like lesions. There may also be evidence of (5.) calcareous foci.
(4, 7, 12, 15)(s. tab. 36.2)
1. Hepatocellular tumours Adenoma
Focal nodular hyperplasia (FNH) Nodular regenerative hyperplasia (NRH) Regenerative nodes
2. Cholangiocellular tumours Bile-duct papillomatosis Biliary hamartoma Caroli’s disease/syndrome Intrahepatic bile-duct adenoma Intrahepatic bile-duct cystadenoma 3. Mesenchymal tumours
Angiolipoma Angiomyolipoma
Benign haemangioendothelioma Cavernous haemangioma Chondroma
Fibrous tumour Focal fatty changes Glomangioma Leiomyoma Lipoma Lymphangioma
Mesenchymal hamartoma Mesothelioma
Myelolipoma Myolipoma Myxoma Schwannoma 4. Tumour-like lesions
Abscess Cysts Granuloma Haematoma
Inflammatory pseudotumour Peliosis hepatis
5. Calcareous foci
Tab. 36.2: Histological classification of benign hepatic coin lesions
3 Diagnosis
3.1 Anamnesis
In most cases, benign liver tumours are detected by
chance during sonography. Any information elicited dur-
ing anamnesis about the long-term use of contracep-
tives, androgens or medication as well as any possible
intake of chemicals, potential infections with parasites or zoonoses, abdominal trauma or febrile diseases and previous episodes of jaundice may be important.
3.2 Complaints
There are usually no subjective complaints ⫺ except when there are large space-occupying lesions which cause anorexia, weight loss, upper abdominal pain upon pressure, haemorrhaging in the tumour or tumour rup- ture. Febrile conditions and pain may point to infection, liver abscess or echinococcosis.
3.3 Findings
Anamnesis and complaints are often of little diagnostic value. Moreover, clinical examination generally reveals non-characteristic findings such as hepatomegaly, ab- dominal pain upon pressure, diaphragmatic elevation, right-sided pleural effusion or hepatic vascular murmur (e. g. in large haemangiomas). • Laboratory parameters are generally normal. Sometimes transaminases and γGT are elevated; occasionally, there is an increase in AP and respective values relating to cholestasis. In the case of an inflammatory process, CRP and BSR are often elevated; ChE and iron may be decreased.
3.4 Imaging procedures
The following imaging procedures can be used for the detection and differential diagnosis of benign hepatic lesions or tumours: (1.) sonography, (2.) computer tomography, (3.) scintigraphy, and (4.) magnetic reson- ance imaging. These methods show clear differences in their ability to detect tumours of minimum size, in their sensitivity and specificity, and in the costs involved. • Echogenic and anechoic foci can obviously be detected by sonography at a much smaller diameter than hypo- echoic foci. In scintigraphy, hepatic tumours in the por- tal area and in the centre of the liver must have a larger diameter in order to be visualized. By combining scin- tigraphy and CT, it is generally possible to differentiate FNH from adenoma. In CT and MRI, detection of a tumour depends on its structure. • Sensitivity, i. e. the rate of correct positive results, should be as high as pos- sible, but there are clear differences here. The specificity of these diagnostic procedures is high at 90 to 95%.
Sonography is the method of choice on the basis of the following criteria: (1.) it has a high diagnostic yield (including extrahepatic areas), (2.) it is cost-effective, (3.) it can be used in various locations, (4.) it is not time- consuming, and (5.) it does not burden the patient. The use of new techniques (contrast-enhanced power Dopp- ler sonography, phase-invasion harmonic imaging) can help to make the assessment more reliable in individual cases. US is clearly inferior to CT when it comes to diagnosing metastases.
(3, 6)• It should be noted that the
respective diagnostic reliability is highly dependent upon the investigator’s experience. (s. tab. 36.3)
Computer tomography has a greater sensitivity than sonography; however, there are higher costs involved, it takes more time, requires more space and entails expos- ure to radiation. More sophisticated methods such as helical CT or CT arterioportography allow a more differentiated application in certain constellations (e. g.
malignant lymphoma, metastases of parvicellular bron- chial carcinoma, or breast cancer). Permanent-location CT with administration of bolus contrast medium is suitable for the differentiation of haemangioma. Sono- graphy and CT are considered to be useful complemen- tary techniques in diagnosing hepatic focal lesions, since in this way foci can be detected which are missed by the respective other method.
(1, 3)(s. tab. 36.3)
Criterion US CT MRI SC FNB Lap
Detectable
size of focus (cm) >0.5 >0.8 >1.0 >2.0 >1.5 >0.1 Sensitivity (%) 50ⴚ70 60ⴚ90 70ⴚ95 40ⴚ60 75ⴚ90 ca.100 Specificity (%) 90 >95 >95 >95 ca.100 ca.100 Additional
information ⴙ ⴙ ⴙ ⭋ ⭋ ⴙⴙ
Costs (ⴙ) ⴙⴙ ⴙⴙⴙ ⴙⴙ (ⴙ) ⴙ
Tab. 36.3: Respective values of the different diagnostic methods regarding the detection of hepatic focal lesions (US⫽ ultrasound, CT⫽ computer tomography, MRI ⫽ magnetic resonance imaging, SC⫽ scintigraphy, FNB ⫽ fine-needle biopsy, Lap ⫽ laparoscopic findings at the liver surface)
Magnetic resonance imaging may provide additional differentiation of unclarified findings ⫺ particularly in the diagnosis of haemangioma. Hypovascular lesions are detected more easily with SPIO-enhanced MRI, whereas detection and characterization of hypervascular lesions are improved with gadolinium-enhanced MRI.
(8, 14)
(s. tab. 36.3)
Scintigraphy can be indicated for differentiating an adenoma from FNH (combination of colloid scintigram and hepatobiliary sequential scintigraphy) and for diag- nosing haemangioma.
(13)Angiography: Visualization of hepatic veins or arteries is rarely required. Angiography is indicated for diagnosing metastases of active endocrine tumours. This technique may also be necessary in the planning phase of liver surgery. A further possible indication is its use in carry- ing out therapeutic measures.
3.5 Biopsy and laparoscopy
Reliable differentiation between a benign and a malig-
nant hepatic tumour is not possible using imaging pro-
cedures; thus, an indication is given for US-guided or
CT-controlled fine-needle biopsy. (s. tab. 36.3) (s. p. 135)
However, FNB is diagnostically inferior to thick-needle
biopsy (> 1.2 mm) ⫺ although the bleeding risk is clearly much lower. The indication for biopsy should be viewed critically, particularly when considering the use of a thick needle.
(5)• In all cases where the findings cannot be substantiated by imaging procedures and where treatment implications can be expected as a result of diagnostic clarification, laparoscopy is indicated. The combination of laparoscopy and biopsy yields the highest diagnostic sensitivity and specificity. The diagnostic reli- ability is almost 100% in focal lesions on the liver surface.
(10, 11)
Tissue samples for histological examination can be gained from selected tumour areas by careful, directed forceps biopsy (also by FNB). Laparoscopy makes possible the photographic documentation of the findings as well as of any additional important patho- logical changes in the abdominal cavity ⫺ this may prove very helpful. (s. tab. 36.3.) (see chapter 7!)
4 Differential diagnosis
4.1 Adenoma
Epidemiology and aetiology: Adenomas have an inci- dence of 4 ⫺10/100,000 inhabitants/year. They are almost exclusively found in women during their repro- ductive years. Children are rarely affected.
(28)In men, the risk is higher when they take anabolic agents. In about 90% of cases, there is a correlation with the intake of oral contraceptives over many years; this was pointed out for the first time by
J. K. Baum et al.in 1973.
(19, 21, 25, 31, 32)There is also an association with the polycystic ovary syndrome.
(33)An adenoma can develop in glyco- genosis types I and III (with multilocular nodulation)
(29)
as well as in type IV.
(16)The administration of vari- ous other drugs (e. g. carbamazepine) has also been associated with adenomas.
Morphology: Adenomas are mostly solitary (75%) and located mainly in the right liver lobe (65 ⫺70%). The rare occurrence of multiple adenomas (> 3 lesions) is termed adenomatosis of the liver.
(20)A familial form has been observed, showing the association with germ- line hepatocyte nuclear factor alpha.
(18)Usually, ade- nomas develop close to the surface beneath the liver capsule. They vary greatly in size, reaching a diameter of 10 cm (2 to > 30 cm); even pediculate nodes have been observed. Adenomas are hypervascularized and have a firm, rubber-like consistency. Due to their bright red to light brown colour, they stand out from the rest of the hepatic tissue. (s. fig. 29.11!)
䉴 Histology: The parenchyma is formed from pluricellular trabec- ulae and two (or three) layers of hepatocytes, the width of which varies from location to location. The hepatocytes are rich in glyco- gen, often pleomorphic and enlarged, and usually show fine-drop- let fatty deposits. No evidence of acinar architecture or Kupffer cells is found; only very few preexisting and incorporated portal fields, central veins or bile ducts are detectable. There are numer- ous arteries and ectatic sinusoids; the latter contain no Kupffer
cells. It is from here that haemorrhages into necroses occur; they are nearly always found in larger nodes. These haemorrhages may also penetrate the adjacent liver parenchyma and rupture into the abdominal cavity. There are no fibroses or inflammatory reactions.
Reticular fibres are delicate or have disappeared completely. Ade- nomas often possess a capsule made of fibre tissue or compressed liver parenchyma, so that adenoma nodes are usually easy to enu- cleate from their hepatic bed. (24)
Diagnosis: Small adenomas do not cause any discom- fort. Large adenomas may become palpable or cause pain upon pressure and have displacement effects. La- boratory parameters are generally normal, although AP is sometimes increased; the serum value of AFP remains unchanged. The administration of oestrogen results in a subnormal γ-GT value. • Sonography, CT and MRI do not show any abnormalities, since the tissue is hepato- genic and thus somewhat hypoechoic or hypodense on a non-enhanced CT scan, but hyperdense in the arterial phase. In some cases a space-occupying lesion is detect- able. There may be evidence of circular vascularization, from which irregular vessels penetrate the adenoma.
(17, 27)(s. pp 132, 173, 177) Hypervascularized adenomas can be seen in colour Doppler sonography (as well as in coeliacography or MR angiography). Differential diag- nosis of haemangioma, HCC or metastases may be ren- dered more difficult by haemorrhages. • Scintigraphy using
99mTc sulphur colloid shows no activity enhance- ment. Functional scintigraphy reveals a normal flow and reduced or no enhancement in the parenchymal and excretory phases. • Laparoscopy facilitates a “split- second visual diagnosis”, with histological confirmation by forceps biopsy, if required. (s. tab. 36.3) (s. fig. 29.11!) Complications: Intense pain may occur due to haemor- rhage in the adenoma or haemorrhagic penetration of the neighbouring liver parenchyma. A rupture causes haemoperitoneum accompanied by symptoms typical of acute abdomen and circulatory shock. An association between menstruation and adenoma rupture has been reported. The risk of bleeding is relatively high at 30 ⫺40%. Malignant degeneration is a potential danger (approx. 10%).
(23, 25, 28, 31, 32)• We are able to add one observation of our own regarding malignant degeneration.
(s. p. 549) (s. fig. 29.14!)
Prognosis: All in all, prognosis is relatively good. While some adenomas became smaller or even went into remission as soon as oral contraceptives were discon- tinued
(18), there were other cases in which the tumour maintained its size or indeed continued to grow. Even after regression of the adenoma, there is always a dan- ger of hepatocellular carcinoma developing. Systemic AA amyloidosis or paraneoplastic symptoms are rare complications.
(20)Monitoring is effected by US or CT, as appropriate. Determination of hormone receptors could provide an additional prognostic criterion in the future. Alkaline phosphatase, γ-GT and ChE, for ex- ample, may serve as laboratory parameters.
Treatment: Imaging procedures cannot exclude the pres-
ence of malignant adenoma degeneration. This uncer-
tainty, together with a high risk of haemorrhage and rupture, which increases with further growth of the tumour, provides the basic indication for enucleation or resection of the adenoma, particularly in the event of an unexpected trauma of the liver. Embolization prior to resection leads to a reduction in size of larger adeno- mas, thus giving better results. Surgery is indicated from the outset: (1.) when an already large adenoma (> 5 cm) is present at initial diagnosis, (2.) in pediculate tumours, (3.) in cases of proven haemorrhage or subcapsular haematoma, (4.) when there is an increased risk of abdominal trauma in everyday life, and (5.) prior to a planned pregnancy. • In general, every resectable ade- noma should be removed surgically.
(20, 22, 26, 30, 36, 38)4.2 Focal nodular hyperplasia
Epidemiology and aetiology: Focal nodular hyperplasia (FNH) was first described by
M. Simmondsin 1884. It is about twice as common as adenoma and is the second most frequent type of benign liver tumour. Its incidence is 20 ( ⫺30)/100,000 inhabitants/year; in autopsy statis- tics, frequency is 0.3 ⫺8.0%. FNH has also been ob- served in children
(52), as has the simultaneous occur- rence of FNH and adenoma. Cigarette smoking is deemed to be a risk factor. FNH affects mainly women (80%); in some 60 ⫺70% of women, there is a connection with the long-term intake of oral contraceptives.
(47)There is also an association with the Klinefelter syn- drome.
(55)When these hormonal preparations are dis- continued, FNH (like adenoma) often goes into remission. A hyperplastic reaction to a pre-existing arte- rial malformation is thought to be one of the pathoge- netic possibilities. This view is substantiated by evidence of other concomitant vascular abnormalities (e. g.
haemangioma in 20 ⫺25% of cases, aneurysms, telean- giectasia) and malformations (e. g. brain tumour) or indeed the occurrence of FNH among family members.
The development of FNH is probably caused by increased arteriohepatic perfusion and additional local portovenous thrombosis, resulting in nodular hyperpla- sia of the hyperperfused parenchyma.
(9, 41)Recently, increased values of the genes angiopoietin 1 and 2 have been reported.
(50)Morphology: FNH is usually solitary; multiple nodes of varying sizes (up to 20 cm) are only detected in about 20% of cases.
(39, 54)FNH is present predominantly in the right liver lobe (50 ⫺60%), in individual cases also as a pediculate tumour. There is generally no capsule.
FNH has a firm consistency. In about two thirds of cases, strikingly large arteries can be seen supplying the tumour. Tumours located close to the surface are red- dish-brown to yellowish-brown in colour. (s. fig. 29.12!)
• A progressive type of FNH is a rare variant; however, this type may recur following partial liver resection.
(54)The teleangiectatic type of FNH displays a molecular pattern closer to that of adenomas than to FNA; there-
fore these atypical lesions should be referred to as “tel- eangiectatic hepatocellular adenomas”. (s. fig. 36.1)
Fig. 36.1: Focal nodular hyperplasia: sharply delineated, ochre- coloured, non-encapsulated, nodulated lesion with star-shaped radiating septa
䉴 Histology: Hepatocytes are rich in glycogen. There is no lobular structure, since portal fields and central veins are absent. However, there are Kupffer cells as well as sinusoids with varying dilatations.
Numerous bile-duct proliferations are found, particularly within the connective tissue septa. These findings may lead to misdiagnos- ing “cholangiocarcinoma in cirrhosis”, since numerous, sometimes chaotic, blood vessels are present. Connective tissue bands origi- nating from a central scar and directed towards the periphery con- tain biliary tract elements, numerous arteries and veins as well as infiltrates and occasional epithelioid cell granulomas. Thick-walled blood vessels sometimes show mucoid media degenerations. These hypervascular septa cut off parenchymal areas of varying sizes and form pseudoacini. The result is a wheelspoke-like structure and the clinical picture of pseudocirrhosis. (34, 40, 48) (s. fig. 29.13!)
Diagnosis: When FNH reaches a certain size (7⫺10 cm or more), upper abdominal pain upon pressure, dis- placement effects and hepatomegaly occur, i. e. FNH remains asymptomatic for a long period of time. La- boratory parameters are normal. Cholestasis is a rare finding. • Sonography shows a hypoechoic image corre- sponding to that of the liver. Occasionally, it is possible to identify a fibrous “vascular star” together with vessels in a radial or circular arrangement similar to a “wheel- spoke pattern”. This is clearly visualized by colour Doppler sonography.
(32, 42, 44, 46, 56)(s. figs. 6.14; 36.2) CT usually shows a hypodense tumour with smooth boundaries and short, inhomogeneous, massive en- hancement during the arterial phase (12 ⫺25 sec), with contrast adaptation to the neighbouring parenchyma occurring after 45 ⫺120 sec. There may also be signs of the central scar. Spiral CT increases diagnostic accuracy.
(34, 35, 37, 57)
(s. fig. 36.3) • Following administration of Gd-DTPA, MRI yields similar results to CT. The fibrous vascular star appears hyperdense (T
2).
(42)• Due to the phagocytosis capacity of the RES, scintigraphy shows storage of colloids (in 70% of cases), whereby enhanced storage is considered to be pathognomonic.
Some 30% remain “cold” due to increasing weakness of
the RES. By means of functional scintigraphy, it is pos-
sible to detect hypervascularization as well as (mild to
Fig. 36.2: Colour-encoded Doppler sonography of FNH with wheelspoke structure (s. fig. 6.14!)
Fig. 36.3: CT in the portal venous phase: FNH with star-shaped scar
normal) enhancement during the parenchymal phase and retarded excretion ( ⫽ trapping) as a result of rare- fied bile ducts, showing that the remaining liver tissue has long been freed of
99mTc IDA ( ⫽ afterstorage). Sen- sitivity is 87%, specificity is 100%. • Angiography dis- plays early central hypervascularization with rapid centrifugal filling of the tortuous, wheelspoke-like ar- rangement of arteries and delayed venous visualization.
• Clear differentiation, for instance from HCC, is often impossible when using imaging procedures. An unclear diagnosis calls for laparoscopy
(10, 11), possibly with refined forceps biopsy or fine-needle biopsy.
(53)• Thick-needle biopsy is contraindicated due to the risk of bleeding (and especially since FNH does not require histological examination as a rule).
Complications: In 10% of cases, there is a potential risk of vein obstruction
(51)or bleeding. Occasionally, portal hypertension develops, in some cases with pulmonary hypertension. Spontaneous regression has been report- ed.
(49)• Malignant degeneration is extremely rare.
Treatment: Monitoring by imaging procedures suffices in the first instance. A marked increase in size and par- ticularly haemorrhage or rupture are indications for embolization or surgery.
(36, 38, 45)4.3 Nodular regenerative hyperplasia
䉴 The first description was given in 1953 byS. Ranström, who called this condition “miliary hepatocellular adenomatosis”.
The term “nodular regenerative hyperplasia” (NRH) was intro- duced byP. E. Steinerin 1959.
In NRH, the liver is interspersed with numerous diffuse nodes, which are 1 ⫺3 mm in size (occasionally up to 3 cm) and yellow to yellowish brown in colour with blurred boundaries; they consist of hyperplastic hepato- cytes. No fibroses or perinodal connective tissue septa are evident. The multilayered, disordered trabeculae do not have a lobular structure.
(66, 69)CD 8
⫹cytotoxic T cells infiltrate the acinus. The nodes lack central veins and bile duct proliferations. The internodular paren- chyma becomes atrophied due to pressure. It is possible by means of reticulin staining to demonstrate the nodes with the irregular trabeculae, whereas the altered vessels are best shown using elastica staining. The liver surface is smooth.
(78)In the course of disease, presinusoidal, and later sinusoidal, portal hypertension with hepato- splenomegaly and oesophageal varices are usually observed.
(64, 65, 67)(s. fig. 36.4)
Fig. 36.4: Macroregenerative nodes in liver cirrhosis with Budd- Chiari syndrome
Men and women are affected with the same frequency at almost any age. Familial forms have been described.
(63)
There is an association with polyarthritis, coeliac
disease
(58), PSC, PBC
(61), sarcoidosis, Budd-Chiari
syndrome, and collagenoses or myeloproliferative dis-
eases. A connection with thorotrast
(59), immunosup-
pressives, cytostatics and contraceptives or androgens as
well as with antirheumatics, arsenic, vinyl chloride and the so-called “toxic oil syndrome” is also postulated. • As a pathogenetic factor, disturbance of the microcircu- lation is discussed: reduced blood perfusion can lead to atrophy of the ischaemic acini with subsequent stimula- tion of hyperperfused areas, resulting in nodular hyper- plasia.
(9, 41)• Occasionally, transaminases, AP and γ- GT are increased. With the help of sonography, it is possible to find an inhomogeneous reflex pattern in the case of larger nodules. CT may show hypodense lesions with peripheral-central enhancement of the contrast me- dium. Imaging techniques can misjudge the NRH as a micronodular cirrhosis.
(62, 68)Diagnosis is confirmed by laparoscopy
(60)with forceps biopsy or 2 ( ⫺3) large biopsy specimens.
(10, 11)• As a rule, NHR progresses slowly and has at least one stationary stage. However, ALF has been reported in four patients. • Therapy con- sists of treating portal hypertension (TIPS or surgical shunt); liver transplantation may be indicated.
(64)䉴 Partial nodular transformation: This form is charac- terized by morphological changes similar to those observed in NRH, but with only partial liver involve- ment.
(67)Formation of nodes is limited to the area where the larger vessels begin, i. e. perihilar region. The pale nodes may reach a size of up to 4 cm. Haemor- rhage and necrosis may occur in larger nodes.
4.4 Haemangioma
Epidemiology and aetiology:
F. Th.
Frerichsdescribed a haemangioma for the first time in 1861. • With a fre- quency of 2 ⫺8% and an incidence of 800/100,000 inhab- itants/year, it is the most common benign tumour of the liver and is about 40 ( ⫺100) times more frequent than adenoma. It occurs in all ages, but is observed slightly more often in women than in men. There is no associa- tion with the intake of oestrogen or progesterone, although a higher frequency has been recorded in mul- tiparous women. Puberty, pregnancy and oestrogens may cause an increase in tumour size. The aetiology is unknown. Haemangiomas have also been detected in children
(81, 91); this finding suggests that these tumours are true neoformations. There is no known malignant degenerative tendency. Haemangiomas may become thrombosed, fibrosed or calcified.
䉴 Histology: Due to vascular malformation, thin-walled spaces, which are filled with blood and lined with endothelium, develop;
they are separated by septa. The blood is thrombosed or the thrombus becomes organized. The surrounding liver parenchyma is unchanged. (s. fig. 36.5)
Morphology: Haemangiomas appear in solitary or (in some 20 ⫺30% of cases) multiple form.
(83)They are usually located beneath the liver capsule and are clearly differentiated from the parenchyma by a pseudocapsule.
Their usual size is 1 ⫺4 cm and they are found in both liver lobes, apparently with a higher frequency in the left lobe. It is worth mentioning that the haemangiomas
Fig. 36.5: Cavernous haemangioma: thin-walled spaces lined with endothelium, partially septated, filled with blood. The surrounding parenchyma appears to be unchanged (HE)
Fig. 36.6: Grape-shaped, multi-chambered, livid bluish haeman- gioma (right liver lobe)
Fig. 36.7: Giant (larger than a fist) cavernous haemangioma with a smooth surface in the left liver lobe. Numerous blood vessels and peliosis-like livid blue foci of up to 0.5 cm in size in the cap- sule area
situated in the right lobe are predominantly found in the usual percutaneous biopsy area (which needs to be taken into account in prepuncture sonography). Haem- angiomas continue to grow due to enlargement of the respective cavernous spaces. Laparoscopically, haeman- giomas appear as bluish red or crimson red structures, sometimes tuberous, usually protruding slightly beyond the liver capsule; a multi-chambered structure is visible in most cases. (s. fig. 36.6, 36.7) • More rarely (about 7%), voluminous tumours, which may spread over the whole liver lobe, develop (so-called giant haemangioma:
in excess of > 10 cm).
(73, 74, 77, 82, 84, 85, 92)Up to now, only about 20 cases involving giant pedunculated forms have been observed.
Diagnosis: Haemangiomas are usually asymptomatic and, as a rule, discovered incidentally. Having reached a particular size, however, they may cause upper abdom- inal pain, nausea and inappetence. Acute pain results from bleeding in the tumour, thrombosis or rupture.
Palpation may suggest hepatomegaly or an unusual kind of resistance. • Laboratory values are within the normal range. Thrombopenia and/or a reduction in fibrinogen may be present in thrombosis.
(75, 80, 87, 94)Sonography shows a hyperechoic structure (60⫺70%) with smooth boundaries, but no hypoechoic margin or sound shadow (so-called white tumour). There may be an efferent and an afferent vessel. As the size of the haemangioma increases, thrombosis develops, while connective tissue organisation and regressive liquefac- tion become evident. Inhomogeneous and irregular internal structures result from this, making diagnostic classification difficult. Sensitivity is about 80%.
(75, 79, 95)(s. fig. 6.15) • Computer tomography shows a hypo- dense tumour. After intravenous bolus contrast-medium injection, enhancement increases in a peripheral-central direction followed by a focal globular contrast and sub- sequently a rapid reduction of the contrast-rich zone (“iris diaphragm phenomenon”); this occurs in ca. 60%
of cases. The haemangioma becomes isodense with the liver parenchyma. The isodense phase may last up to 90 minutes. The sensitivity of this examination is about 90%.
(90)(s. figs. 8.5, 8.9) • MRI displays a low-signal T
1time and pronounced hyperintensity in the T
2-weighted picture with well-defined margins, which means that even haemangiomas smaller than 1.0 cm can be detected. The “cotton wool sign” is followed by “light bulb sign”. The heterogeneous structure points to thrombosis, fibrosis, etc. Both the specificity and sensi- tivity of MRI are 85 ⫺95%.
(72, 95)(s. figs. 8.7; 36.8 a ⫺c) In the blood pool scintigram (Tc
99m-marked autologous erythrocytes), scintigraphy shows the pathognomon- ically useful filling-in phenomenon. Activity enhance- ment increases from the periphery towards the centre and is detectable for several hours. By contrast, the haemangioma remains negative both in static as well as in liver-function scintigraphy; this is because the haem-
Fig. 36.8: a) Adenoma (앖), with additional haemangioma (a⫺c ⫽ the same female patient)
b) Haemangioma (䉱储) in MRI: T1-weighted axial (portovenous) (“cotton wool sign”)
c) Haemangioma (䉱储): T2-weighted (“light bulb sign”), with fat sup- pression
angioma possesses neither hepatocytes nor RES cells.
(70, 72, 79, 86)
• Fine-needle biopsy
(78)is occasionally favoured. We consider any percutaneous biopsy, particu- larly thick-needle biopsy, to be contraindicated because of the risk of bleeding (it is also of little help from a diag- nostic viewpoint, especially since better diagnostic tools are available); moreover, we feel that there is no justifi- cation in using exploratory laparotomy for diagnostic purposes. • In order to obtain a definitive diagnosis, exploratory laparoscopy is the method of choice, par- ticularly since haemangiomas are usually situated in the subcapsular area, which means that a “split-second visual diagnosis” is possible (“one-second biopsy” is not indicated!).
(10, 11)(s. figs. 36.3, 36.4)
Complications: Blunt abdominal trauma increases the risk of rupture, which can also occur spontaneously.
The mortality rate is 60 ⫺80%.
(71)Large shunt volumes may give rise to the development of cardiac insuffi- ciency, particularly during childhood. The development of portal hypertension has also been observed.
(92)Anaemia, thrombopenia and hypofibrinogenaemia may occur due to the haemangioma-thrombocytopathy syn- drome ( ⫽ Kasabach-Merritt syndrome).
(82)Treatment: A ruptured haemangioma requires immedi- ate surgical intervention; it is often necessary to ligate the hepatic artery. Enucleation is sometimes possible.
(76, 87)
Resection or arterial embolization are recom- mended for very large and symptomatic haemangiomas.
Inoperable tumours should be reduced in size by exter- nal irradiation or interferon- α therapy. Liver transplan- tation is a rare indication.
(88, 89, 93)• All in all, progno- sis is good.
(94)4.5 Infantile haemangioendothelioma
This benign infantile tumour is of embryonic origin and usually diagnosed within the first months of life, whereby girls are twice as often affected as boys. In most cases, capillary haemangiomas of the skin and mucosa as well as of other organs are also in evidence. Cardiac and vascular malformations are likewise often found.
䉴 Morphology: Haemangioendotheliomas appear in solitary or (seldom) multiple form and may reach a size of some 15 cm. The unencapsulated tumour foci have blurred boundaries. They are sponge-like and reddish brown in colour, but may become firm and grey in bigger tumours. Vascular segments of differing width are connected with each other and embedded in loose, cell-rich mesenchyma.
•
Twohistological types can be differentiated: type I is characterized by a layer of cuboid endothelial cells, while type II shows papillary proliferations and several layers of pleomorphic cells (which are similar to those found in angiosarcoma).•
Malig- nant degeneration of the haemangioendothelioma is possible. (97)Diagnosis: Hepatomegaly and an occasional systolic vascular murmur above the tumour are clinically detect- able. Patients suffer from anorexia, vomiting, weight loss and lethargy. Laboratory investigation often reveals thrombopenia, haemolytic jaundice and anaemia. Dis-
seminated intravascular coagulopathy ( ⫽ Kasabach- Merrit syndrome) can occur. Signs of cardiac insuffi- ciency are present at an early stage due to arteriovenous shunts with cardiac volume overload. Acute pain is a sign of haemorrhage in the tumour or of a ruptured tumour. Diagnosis is established by imaging techniques;
angiography has been widely replaced by colour Dopp- ler sonography or angio-MR. Occasionally, laparoscopy has also been used.
(96, 98⫺102)Treatment: If it is possible, elective resection is indi- cated.
(98)However, due to cardiac or (increasing) hepatic insufficiency, invasive techniques cannot usually be attempted. External irradiation may be used in an effort to minimize the tumour. Ligature or embolization of the afferent hepatic artery is sometimes indicated.
Steroid therapy has proved unsuccessful. The use of interferon- α is a new therapeutic approach: tumour regression is accelerated and cardiac insufficiency is compensated.
(103)Liver transplantations have also been carried out successfully. • This infantile, benign tumour may regress with increasing age.
4.6 Fat-containing tumours
Focal fatty changes: Circumscribed fatty foci (“yellow spots”) were seen relatively often during laparoscopy in the past.
(14)We ourselves also observed them on many occasions. (s. fig. 31.6) • Sonography and CT have shown these rare benign foci to be more frequent than previously supposed. They may occur in focal or seg- mental form. (s. figs. 8.3, 8.4)
Lipoma: Hepatic lipoma is very rare. Research of the literature shows that
S. Youngwas the first to publish a documented observation of this tumour in 1951.
Although lipomas grow slowly, they may reach a con- siderable size. They consist of fatty tissue (adipocytes) with a lobular structure; according to (rare) observa- tions made to date, there is no capsule. The lipoma is hyperechoic, which usually makes it easily identifiable by sonography and CT. There is no evidence of vascu- larization and no tendency towards malignant degenera- tion. Larger lipomas should be removed surgically, par- ticularly when they have become symptomatic.
(104, 105)Myelolipoma: This rare type of mesenchymal tumour,
which contains adipocytes and blood-forming tissue, can
grow to an enormous size (e. g. 26 x 16 x 12 cm). When
reaching a certain diameter in a specific location, it usu-
ally becomes symptomatic. It has a yellowish colour and
contains fatty tissue as well as myeloid elements. Due to
its echogenicity, the presence of this benign focus can be
demonstrated by sonography and CT. Angiography
shows a tumour that is usually avascular. Large or symp-
tomatic tumours require surgical treatment. • Definitive
diagnosis of these forms of fat-containing tumours is pro-
vided by biopsy, with thick-needle biopsy being the most
reliable technique.
(106, 107)Angiolipoma: This benign mesenchymal tumour consists of fatty cells and numerous blood vessels, which have a tendency to thrombose. In general, angiolipomas occur singly in both liver lobes.
Angiomyolipoma: The first observation of an angiomyo- lipoma was reported by
K. G. Ishakin 1976. Up to now, about 100 cases have been published. Owing to its fat content, this benign tumour also has a yellowish-red colour. The largest tumour reported to date was 36 cm in diameter. Women are mainly affected.
(116, 118)The right liver lobe is the preferred location. Fatty cells, blood vessels and smooth muscle cells can be demon- strated histologically. The vessels may be thick-walled and are usually arranged in an island-like configuration.
The tumour appears as a hyperechoic focus in sonog- raphy and as a hypodense focus in CT and MRI.
(108, 117, 120, 122, 123)Hypervascularity is observed in arterio- graphy. Multiple angiomyolipomas have been reported
(121)
, occasionally also in kidneys and lungs.
(112)The occurrence of spontaneous rupture
(114)or disseminated intravascular coagulopathy was reported as a rare com- plication. Due to their vascular richness, diagnostic evi- dence of angiolipomas and angiomyolipomas should be obtained by fine-needle biopsy
(110, 117), possibly together with immunohistochemistry. Malignant degen- eration has not yet been observed.
(109, 111⫺113, 115, 116, 119)4.7 Chondroma
To date, there has only been one single observation of a chondroma.
(124)This tumour was excessively large (19 x 15 x 9.5 cm); it was hypervascularized, had a multilob- ular structure and did not possess a capsule. Focal calci- fications were detectable. Chondrocyte-like cells and a chondroid matrix were found. Such a tumour can be visualized by imaging procedures. Laparoscopically, a hard, nodular surface is detectable. Diagnosis can only be confirmed histologically.
4.8 Leiomyoma
Up to now, only very few cases have been described.
These tumours also become symptomatic once they have acquired a certain size and may grow to reach excessive proportions in the liver (e. g. 19.5 x 12 x 12 cm).
(125)4.9 Schwannoma
Schwannoma (neurinoma) is a benign tumour originat- ing from Schwann cells. It is very rare.
(126)Recently, a schwannoma of the bile duct causing obstructive jaun- dice was reported.
(127)4.10 Glomangioma
Glomus organs are small a.v. anastomoses for thermo- regulation of the extremities. Glomangiomas are there-
fore most frequently located in the toes and fingers.
However, they are also found in the respiratory and gas- trointestinal as well as in the genital organs. A gloman- gioma as a benign solitary tumour in the liver was recently reported for the first time. This smooth, well- defined subcapsular lesion could be clarified histolog- ically with the help of imaging-guided biopsy and later on confirmed by evaluation of the surgically excised tumour.
(128)• Malignant transformation of glomangi- oma is possible.
4.11 Mesenchymal hamartoma
䉴R. Maresch described hamartoma as a cystic tumour struc- ture in 1903; it was termed mesenchymal hamartoma byH. A.
Edmondsonin 1956.
This benign tumour is caused by faulty tissue compos- ition of certain organs, including the liver. The tumour is predominantly found in the right liver lobe; it grows rapidly and progressively. This type of cystic tumour is mainly observed within the first year of life. Boys are more often affected than girls. In adults, mesenchymal hamartoma is very rare. Pre-existing composition disor- ders of the liver tissue can be stimulated into growth by steroids. Hamartomas remain asymptomatic until attainment of a certain size results in compressional or displacement phenomena. In their interior, they contain cysts filled with a yellowish, gelatinous substance. The stroma presumably derives from the connective tissue of the portal fields, from which the hamartoma may also originate. Malignant degeneration has been reported.
Due to its tendency to grow, early surgical removal of the tumour is indicated.
(129⫺131)4.12 Mesothelioma
Mesotheliomas of the liver are extremely rare. They consist of parallel bundles of collagenous and reticular fibres as well as fibroplastic and epithelial cells.
(132)The reported observation of a hepatic mesothelioma weighing some 2,800 g remains a rarity.
(133)4.13 Fibrous tumour
A solitary fibrous tumour was first described in pleural tissue by
P. Klempereret al. in 1931. Meanwhile, this rare entity has been reported in various organs, with the liver being affected in 26 cases. The tumour shows cellular areas (consisting of bundles of spindle cells arrayed hap- hazardly or in a storiform pattern) and relatively acellu- lar areas (containing abundant collagen bundles). There is evidence of cellular atypia, mitotic activity and ectatic vessels. This tumour possesses malignant potential with the ability to metastazise.
(134)4.14 Cysts
Liver cysts can occur in solitary or in multiple form. They
may be congenital or acquired. The reported frequency
varies between 1% and 20%. The cysts are lined with a layer of cuboid cells and mostly filled with fluid. They are usually detected by chance. When cysts compress bile ducts or vessels, they become symptomatic.
(136)• In sonography, the cyst appears as an anechoic (black) space with well-defined margins and distal sound amplifica- tion. (s. fig. 6.10) Haemorrhage into the cyst cavity and debris can mimic a cystadenoma or even cystadenocarci- noma. The presence of septa suggests a neoplastic cyst.
(136)
• In computer tomography, their content can gen- erally be determined at ⫹0 to ⫹15 Houndsfield units. The i.v. administration of a contrast medium shows no evi- dence of enhancement. (s. figs. 8.6; 36.9) • Cysts are easily detected by magnetic resonance imaging (T
1image ⫽ dark; T
2image ⫽ light with high signal intensity).
Laparoscopy provides a very impressive view of cysts. (s.
figs. 36.10, 36.11)
Fig. 36.9: CT with contrast medium: solitary liver cyst. (s. figs.
8.6; 36.7)
Fig. 36.10: Multiple cysts with several chambers in the area of the right liver lobe
Fig. 36.11: Giant (fist-sized) solitary cyst in the right liver lobe
Four types of cysts can be differentiated: (1.) dysonto- genetic cysts, (2.) parasitic (or infectious) cysts, (3.) neo- plastic cysts and (4.) post-traumatic cysts. The cause of cystic neoplasms is unknown. Traumatic cysts
(C.Whipple, 1898)
occur from an injured intrahepatic bile duct after blunt abdominal trauma.
(136)䉴 Treatment: Asymptomatic cysts do not require treatment; large cysts which might rupture are an exception.
•
Symptomatic cysts (usually > 5 cm) are generally sclerosed. Reliable sclerotherapeutic agents include aethoxysclerol (1%), alcohol (95%) (146), minocy- cline hydrochloride (135, 150), tetracycline hydrochloride (1 g), and sodium chloride solution (10%). The sclerosing procedure is successful and low in side effects. Percutaneous aspiration of the cysts has a high relapse rate. Sclerotherapy does not prevent relapse, since a sclerotherapeutic agent destroys the cells, but not the cyst walls. Parasitic cysts require specific therapeutic measures.•
Under laparoscopy, cysts which prove to be problematic may be treated reliably by fenestration(T. Y. Lin et al., 1968). (137) Surgical procedures (e.g. cyst excision, resection, cystjejunostomy, cystent- erostomy) are rarely indicated and involve a much higher risk.(136, 141, 148)
4.14.1 Polycystic liver disease
The incidence is 1 : 500 to 1 : 5,000 births/100,000/per year. The gene responsible is located on chromosome 16; often another gene located on chromosome 4 is also involved. This autosomal dominant polycystic disease of the liver and kidneys can occur in (1.) children and (2.) adults ( s: t ⫽ 1:5). The intrahepatic bile ducts are widely dilated and lined with bile-duct epithelium. Each liver segment may be interspersed by cysts of varying sizes which are connected with the biliary duct system.
The cysts are surrounded by a fibrous capsule. Both the number and size of the cysts increase in later life. Usu- ally, polycystic degeneration of the kidneys also occurs.
(136, 149)
(s. fig. 8.6) Pancreatic cysts or colonic divertic-
ulosis are less frequent. Occasionally, the cysts cover the
liver in a balloon-like manner. (s. fig. 36.12) Rupture of
large cysts may give rise to the clinical picture of acute
abdomen. Compression leads to portal hypertension,
jaundice
(139), cholestasis and leg oedema. • Renal insuf- ficiency is also a dangerous complication.
Fig. 36.12: Polycystic liver with spheroid, balloon-like cysts in the right liver lobe
䉴 Treatment may be by laparoscopic or surgical fenes- tration
(137, 138, 140, 142⫺145), injection of alcohol (40%)
(146)
or minocycline hydrochloride
(135, 150), as well as surgical management.
(141)Liver transplantation is a rare indication.
(147)4.14.2 Parasitic cysts
The cysts of Echinococcus granulosus (cysticus) (s. figs.
25.16, 25.17, 25.19) and Echinococcus multilocularis (alveolaris) (s. fig. 25.21) are of particular clinical importance. (see chapter 25.2.3)
4.15 Cholangiocellular tumours 4.15.1 Caroli’s disease/syndrome
䉴 This congenital clinical picture was first described in the form of intrahepatic stones byH. R. Vachell et al. in 1906.
•
Later on, in 1958J. Caroli et al.were able to establish the associ- ation between characteristic congenital bile-duct alterations, cholangitis, cholangiolithiasis and renal cyst formation. In 1964,J. Caroli et al.differentiated a particular form with simul- taneous congenital liver fibrosis (which had already been described byD. V. S. Kerr et al.in 1961). Both forms are autoso- mal recessive.
Caroli’s disease is characterized by congenital, segmen- tal dilatation of the intrahepatic bile ducts, causing bile sludge formation and the development of gallstones.
Clinical findings include hepatomegaly, cholestasis and subicterus as well as cholangitis with upper abdominal pain and biochemical signs of inflammation.
(152, 154)(s. tab. 38.2) Diagnosis is by CT
(151, 153)(s. pp 174, 662), hepatic arterial Doppler sonography
(153)and ERC. (s. fig. 36.13)
Fig. 36.13: ERC findings in Caroli’s disease: mainly segmental, sack-like dilatations of the intrahepatic bile ducts with some small- diameter connections to the efferent bile ducts
Caroli’s syndrome is characterized by the additional occurrence of congenital liver fibrosis. Occasionally, fibroangiomatosis of the bile ducts is observed and microcysts are present in the kidneys. This condition may also lead to portal (presinusoidal) hypertension. • Choledochal cysts, polycystic degeneration of the liver and kidneys, Laurence-Moon-Biedl syndrome and ecta- sia of the renal tubules have also been associated with Caroli’s syndrome. • Apart from cholangitis and hepa- tolithiasis, potential complications include liver abscess, pancreatitis, amyloidosis, malignant tumours and liver failure. • Treatment consists of biliary drainage, anti- biotics, surgical procedures and liver transplantation.
Ursodeoxycholic acid may be used as an adjuvant.
4.15.2 Hepatobiliary cystadenoma
This rare benign tumour probably develops from con- genital bile-duct malformations. It is found mostly in women (> 90%), mainly after the age of 45 ⫺50 years.
The tumour grows very slowly, yet can reach a consider-
able size (5 ⫺25 cm). Cystadenomas occur as solitary,
but multilobular cystic tumours. The cysts are frequently
separated by septa. The mucous type consists of a
mucous/gelatinous, bile-coloured fluid, often containing
old blood. Occasionally, a serous type of cystadenoma
without mesenchymal stroma is found. There is evidence
of ovary-like stroma together with unilaminar bile epi-
thelium, which is folded in a polyploid or papillary
manner in places.
(155)(s. fig. 36.14) The collagenic cap-
sule is rich in vessels. Surrounding the tumour, numer-
ous abnormal bile ducts and arterial vascular clusters
are evident. • Cholestasis or even obstructive jaundice
develops.
(156)Diagnosis of this cystic lesion (mainly in
the right lobe) is by imaging techniques. Differential
diagnosis may be extremely difficult (and is often only
possible by means of surgery). • Due to the tendency of
cystadenoma towards malignant degeneration, resection should be carried out as soon as possible.
(157⫺160)Fig. 36.14: Hepatobiliary cystadenoma with ovary-like stroma (HE)
Bile-duct adenomas are rare. Usually, they are solitary and < 2 cm in size. This type of adenoma is more often detected in men than in women (3 :1) and it occurs in patients mainly over the age of 50. It is nearly always localized beneath the liver capsule. This adenoma has the form of a firm, whitish node and consists of bile- duct proliferations. It contains biliary acini and tubules which are lined with a layer of cuboid epithelium within loose fibrous, partially hyaline stroma. There is evidence of mononuclear inflammatory cells and, occasionally, lymph follicles. It is discussed that such biliary adeno- mas are peribiliary gland hamartomas.
(162)There are no clinical or biochemical abnormalities, nor is there any tendency towards malignant degeneration.
(161, 163)Bile-duct papillomatosis is another very rare finding (up to now about 50 cases have been reported) which occurs mainly in elderly women. There are papillomatous pro- liferations in both intrahepatic and extrahepatic bile ducts. Clinically, it is characterized by recurrent epi- sodes of jaundice and cholestasis as well as ascending cholangitis and haemobilia. The bile ducts can be dilated; their wall surface is irregular. The course of dis- ease is progredient; the prognosis is poor. Recently, encouraging results have been reported following intra- luminal iridium
192therapy
(165)and liver transplanta- tion
(164). Malignant degeneration into cholangiocarci- noma is possible.
4.15.3 Biliary hamartoma
Benign biliary microhamartomas ( ⫽ Meyenburg’s com- plex) were described by
H. von Meyenburgin 1918. They consist of small cysts developing from dilatations of the small (interlobular) bile ducts and are surrounded by fibrous stroma. The cysts are remnants of ductal plate malformations. Occasionally, typical ductal plates can also be detected. The hamartomas can reach a diameter of up to 0.5 ( ⫺1.0) cm. (s. fig. 32.18) Macroscopically,
they appear as firm, greyish-white nodules which are clearly delineated from the liver parenchyma. Subcapsu- lar nodules may also be detected by laparoscopy.
(168)They are sometimes misinterpreted as small metastases.
Here, MRI is of great diagnostic value.
(167)• Micro- hamartomas are often associated with malformations of the small branches of the portal veins. They may repre- sent a transition to the autosomal dominant form of polycystic degeneration. These tumours have a tendency to develop into cholangiocarcinoma.
(166⫺169)4.16 Abscesses
Depending on their cause, liver abscesses are classified as (1.) pyogenic or (2.) parasitic. This factor largely deter- mines differential diagnosis, diagnosis and therapy. Fresh abscesses usually have blurred margins; following consol- idation, they have a round to elliptical form. Evidence of gas bubbles is seen as pathognomonic. The abscesses are generally hypoechoic and hypodense. (see chapter 27!) 4.17 Hepatic lymphangioma
This rare, congenital benign tumour consists of multiple, small (1 ⫺4 mm in diameter) dilations of intra- hepatic lymph vessels, which communicate with each other. They contain chylous fluid. Mostly, there are lym- phangiomas in other organs as well.
(170)4.18 Peliosis hepatis
Peliosis hepatis may be caused by various kinds of medi- cation
(173)or chemical agents and is associated with numerous diseases (of a viral, bacterial, parasitic or metabolic nature). Its aetiopathogenesis is unknown. It has also been detected in small children.
(172, 174)Histo- logically, there are spaces lined with endothelium corres- ponding to dilated sinusoids and Disse’s spaces. They are filled with blood (so-called “globoid bleeding”).
Their size varies from 0.5 ⫺2.0 mm and can even reach
> 1 cm. The hepatocytes and venules are unchanged. (s.
p. 398!) (s. figs. 21.8; 36.15)
Fig. 36.15: Peliosis hepatis: non-endothelialized cavernous blood- filled cavities surrounded by hepatocellular trabeculae (s. fig. 21.8)
Clinical findings include fever, abdominal pain and hep- atomegaly. Laboratory values reveal occasional sub- icterus and elevated transaminases.
(172)Imaging pro- cedures often yield no findings or merely uncharacter- istic changes.
(171)Definitive results are obtained by laparoscopy
(175): characteristic foci of a livid-reddish to dark-blue colour are found, mostly rounded and sub- capsular, often with net-like confluence. The findings are so typical and distinctive that histological examina- tion is no longer necessary; however, biopsy may be jus- tified under visual control. The most important compli- cations are haemorrhages and, especially following trauma, rupture of the liver capsule with bleeding into the abdominal cavity.
(171, 172)4.19 Granulomas
It is generally not possible to detect granulomas by means of imaging procedures. When the foci are densely grouped, it is possible to see an inhomogeneous reflex pattern during sonography and a variable pattern in the CT scan. The causes are manifold and vary greatly. (s.
tab. 21.1) • Diagnosis is facilitated by laparoscopy and forceps biopsy, provided the foci are located on the sur- face (which is mostly the case). If the surface is free of foci, multiple biopsies from both liver lobes done under laparoscopy generally yield reliable results. (s. p. 398) (s.
figs. 21.9, 21.10; 24.14; 29.6; 38.5) 4.19.1 Sarcoidosis
䉴 A cutaneous form of sarcoidosis (“Mortimer’s disease”), first described byA. Hutchinson in 1877, was observed in further courses of disease by E. Besnier (“lupus pernio”) and C. P.
Moeller-Boeck (“sarcoidosis”, “miliary lupoid”) in 1899. In 1917 these single findings were synthesized byJ. Schaumann. Various terms, such as Besnier-Boeck-Schaumann disease, benign lymphogranulomatosis or Boeck’s disease, have been used in the past to describe this condition. However, the term sarcoidosis has gained more and more acceptance.
Sarcoidosis is a primary multisystemic, granuloma- tous disease of (still) unknown aetiology with enhanced immunity at the site of manifestation. The lungs and the intrathoracic lymph nodes are nearly always affected. In many cases, the extrathoracic organs are involved as well. Sarcoidosis is charac- terized by the presence of epithelioid cell granulomas, which do not show caseous changes.
Frequency: Men and women are affected with the same frequency. Manifestation mainly occurs between the ages of 20 to 40, predominantly in winter. The incidence is highest in Scandinavian countries, the USA and Japan (always with considerable regional variations) at 5 ⫺40/
100,000 inhabitants/year.
Localization: Based on X-ray findings, intrathoracic sar- coidosis can be divided into four stages: 0, I ⫺III. • The extrathoracic manifestation of sarcoidosis affects the
lymphatic system and bone marrow as well as the bones, skin, eyes, lacrimal and salivary glands, urogenital sys- tem, musculature, nervous system and endocrine glands.
Extrathoracic manifestations without radiologically demonstrated thoracic findings are rare. At least two organs must exhibit granulomas to substantiate the diagnosis of sarcoidosis.
Aetiopathogenesis: For a long time, mycobacteria were already considered to be the cause of sarcoidosis. Re- cently, this hypothesis was reinforced when mycobacterial DNA and RNA were found in sarcoidosis tissue
(H. H. Pop- per et al., 1994)and the presence of acid-fast L forms was detected in patients’ blood
(P. L. Almenoff et al., 1996).
䉴 Since 1964, our study group, consisting of
L. Mandi et al.(Debrecen/Hungary) and
E. Kuntz, has been intensively involved in investigating the striking regional differences in sarcoidosis. We postulated an immune reaction ⫺ with a genetic disposition ⫺ against a mycobacterial substrate. • Among other things, we found Ziehl-Neelsen positivity of pollen obtained from numerous trees and plants. A high cor- respondence of sarcoidosis frequency with certain ZN- positive pollen locations became obvious as we cata- logued our findings. This might also explain familial aggregation as a result of similar exogenous exposure. • Injection of ZN-positive pollen, embedded in paraffin, into the testicles of guinea pigs resulted in the dissemi- nation of histological findings fully corresponding to sarcoidosis. By contrast, ZN-negative pollen did not elicit this reaction in animal experiments.
Liver: The liver is involved in sarcoidosis in 60⫺80% of cases. Initially, loosely concentrated epithelioid cells are found which combine to form small epithelioid granulo- mas mainly in the portal and periportal area. These small granulomas may join together and form conglom- erates up to the size of lentils. Within the epithelioid cell granulomas, there is evidence of one or more Langhans’
giant cells, which are rich in the angiotensin-converting enzyme. Epithelioid cells and giant cells release α
1-anti- trypsin and lysozymes as well as other substances; epi- thelioid cells also release interleukin-I. Within the giant cells (displaying a rosette-like arrangement of nuclei), asteroid bodies (5 ⫺20 µm) resembling a sea anemone are often found. Moreover, there is evidence of Schaumann bodies (25 ⫺200 µm) (more frequently in lymph nodes than in the liver) and small vesicles. • Inflammatory cel- lulation is low: it consists of eosinophils, T lymphocytes (CD4
⫹) and plasma cells. Granulomas may increase in size, but may also heal by way of fibrosis. • Chronic cholestasis (ductopenia, cholate stasis, copper storage) as well as the histological picture of PBC (or less fre- quently of PSC) can be found in 50 ⫺60% of cases.
(quot:179)
• This would suggest a connection with the mycotoxin
theory of PBC
(E. KUNTZ, 1984), whereby molecular
mimicry
(M. E. GERSHWIN, 1991)is of potentially pathoge-
netic significance in sarcoidosis as well. (s. p. 643) • Pro- nounced fibrosis leads to portal hypertension. Formation of NRH was evident in 9% and cirrhosis in 6% of cases.
Clinical findings: Usually, there are no subjective com- plaints. As the lungs become increasingly affected, fatigue and (exercise-related) dyspnoea may occur.
Extrathoracic manifestations can cause corresponding symptoms. Hepato(spleno)megaly is observed in 5 ⫺10%
of cases. In an acute stage, polyarthralgia, erythema nodosum and fever are generally found. Kveim’s test is positive, while the BCG test is clearly reduced or nega- tive.
(176, 177, 180, 181)Biochemistry: In most cases, eosinophilia and mono- cytosis are present in leukopenia and lymphopenia.
BSR and CRP are normal or only slightly elevated. The γ-globulins may be increased. Cholestasis is often found, whereas jaundice is rare. Hypercalcaemia is a striking feature; occasionally there is evidence of aug- mented ACE and lysozymes in the serum.
Histology: The most reliable method of obtaining the slightly prominent, whitish granulomas on the liver sur- face, the size of a pin-head up to a lentil (so-called fly agaric liver), is by laparoscopy and forceps biopsy; other- wise, thick-needle biopsies can be performed on suspi- cious areas of the right and left liver lobe. The diagnos- tic accuracy of this procedure is more than 98%, while that of percutaneous liver biopsy is only 30 ⫺70%. (s.
figs. 21.9, 21.10) (s. p. 398) • Fibreoptic bronchoscopy used for taking mucosa samples also facilitates histo- logical diagnosis.
Imaging procedures: Enlargement of abdominal lymph nodes can occasionally be detected by sonography, CT or MRI.
(180)The liver may exhibit an inhomogeneous reflex pattern due to fibrosis.
Treatment: Intrathoracic sarcoidosis has a high rate of spontaneous remission with possible fibrosis residues.
• Extrathoracic manifestations may cause considerable symptoms and secondary disorders, depending on the organs affected. This is also true of the liver. Treatment consists of monitored waiting and administration of glucocorticoids (usually as long-term therapy). Liver transplantation is necessary in some cases.
4.20 Inflammatory pseudotumour
The synonyms used for inflammatory pseudotumour include myofibroblastic inflammatory tumour, histiocy- toma, pseudolymphoma, fibroxanthoma and plasma cell granuloma. This condition was first described by
G. T. Pack et al.
