Journal ReadingJournal Reading2004-10-152004-10-15

(1)myoepithelial tumor of soft tissue

(2)neonatal intrahepatic cholestasis

R3陳志榮

Part I: myoepithelial tumors of soft tissuePart I: myoepithelial tumors of soft tissue

Myoepithelial tumors of soft tissue

a clinicopathologic and immunohistochemical study of 101 cases with evaluation of prognostic parameters

Jason L. Hornick MD,PhD and Christopher D. M. Fletcher MD,FRCPath

Am J Surg Pathol.2003;27:1183-1196

Myoepithelial tumors of Soft TissuMyoepithelial tumors of Soft Tissuee

Myoepitholiomas and mixed tumors of soft tissue were recently recognized

Few case numbers:(1)Kilpatrick SE,Hitchcock MG,Kraus MD et al. Am.J Su

rg Pathol. 1997;21:13-22=>19 cases

(2)Michal M,Miettinen M,Virchows Arch.1999;434:393-400.=>12 cases

Myoepithelial tumors of Soft TissuMyoepithelial tumors of Soft Tissuee

Myoepithelioma and mixed tumor(61 cases)

=>tumor with benign cytomorphology or mild cytologic atypia(low grade)

Myoepithelial carcinoma and malignant mixed tumor(40 cases)

=>moderate to severe atypia(high-grade)

Clinical FindingsClinical Findings

Male : female 1:1(♂:53 cases;♀:48 cases≒ )

Age:3 ~83 years with a peak in 3rd to 5th decades (mean age:38 years)

Symptoms:painless or painful massLocation:most common in limbs and limb g

irdle. Subcuits and deep soft tissue

Figure 1Figure 1

Table 2Table 2

Macroscopic FeaturesMacroscopic Features

Size: 0.7 to 20 cm (mean 4.7cm)Well circumscribed mostly ,nodular or lobul

atedFirm or hardYellow/white to tanGlistening ,myxoid or gelatinous cut surfaceFew with necrosis (2 cases)

Microscopic FeaturesMicroscopic Features

Well circumscribed or focal infiltration(43 cases) Lobulated or mutinodular Most frequently reticular growth pattern with inter

secting cords of in variable amount of chondromyxoid(52 cases) or hyalinzed(14 cases) stroma.

Hypercellular and lacked significant stromal component(19 cases)

Microscopic FeaturesMicroscopic Features

Parachordoma :large epitheloid cells with eosinophilic to clear,variably vacuolated cytoblasm and abundant hyalined or chondromyxoid stroma.

Microscopic FeaturesMicroscopic Features

Tumor cells: epithelioid, spindled , plasmacytoid, parachordoma,clear cells or pleomorphic cells

Ductual differentiation(20%)Metaplastic components:

cartilaginous, osseous, squamous(six cases) or adipocytic(one case)

Microscopic FeaturesMicroscopic Features

Spindle cell myoepitheliomaPure plasmacytoid cell: plasmastoid monom

orphic adenoma or hyaline cell-rich chondroid syringoma

Pure epithelioid cells

MyoepitheliomaMyoepithelioma

Initailly,composed of spindled or plasmacytoid cells demonstrating a solid growth pattern

Variable matrix:myxoid or hyalinized stroma Different architectural patterns:reticular, trabecula

r. Epithelioid or clear cells Ductal differentiation=>mixed tumor category Ps 5~10% ductal differentiation in myoepitheliom

a

Immunohistochemical FindingImmunohistochemical Finding

Keratins and S-100 protein:nearly all are positivehalf

Calponin:nearly 86% (most sensitive myogenic marker)

GFAP:46%SMA:36%Desmin:14%CK14:32%

Myoepithelial tumors of Soft TissuMyoepithelial tumors of Soft Tissuee

Treatment and Follow-upTreatment and Follow-up Treatment:excision ; chemotherapy and postoperat

ive radiotherapy 64 patients were followed (1)Benign or low-grade cytology:33 cases =>Local recurrence(18%):6 cases=>Metastasis:none(2)Cytological malignant:31 cases=>Local recurrence(42%):13 cases=>Metastases(32%):10 cases=>Died of metastatic tumor:4 cases

Criteria for myoepithelial carcinomCriteria for myoepithelial carcinoma of soft tissuea of soft tissue

Not yet to be well established.Moderate or severe cytologic atypia which

proved to be prognostically relevant.Invasive growth pattern is insufficient unlik

e the salivary counterpart. =>microscopically infiltrative margins with no local recurrence or metastasis.

Criteria for myoepithelial carcinomCriteria for myoepithelial carcinoma of soft tissuea of soft tissue

Benign or morphologically low grade soft tissue myoepitheliomas with 18% recurrence and none metastases

Conclusion:

at least moderate cytologic atypia(prominent nucleoli,vesicular or coarse chromatin, pleomorphism) should warrant classification as myoepithelial carcinoma with significant risk for aggressive behavior and propensity for metastasis.

Differential DiagnosisDifferential Diagnosis

Mixed tumor Extraskeletal myxoid chondrosarcoma. Ossifying fibromyxoid tumor. Leiomyoma Schwannoma Metastatic carcinoma Metastatic melanoma Proximal-type epithelioid sarcoma

Differential DiagnosisDifferential Diagnosis

Extraskeletal myxoid chondrosarcoma.:(1)Multinodular growth pattern with interlacing cord

s of spindled cells in myxoid or chondromyxoid stroma.

(2)Lack intratumoral heterogeneity ,lack mixture of epitheloid and spindle cells

(3)S-100 protein in minority (4)Epithelial and myogenic markers are rarely positi

ve

Differential DiagnosisDifferential Diagnosis

Ossifying fibromyxoid tumor(1)Lobulated proliferation of pale-staining ovoid to r

ound cells in cords or nests in myxoid or hyalinized stroma with peripherical rim of metaplastic bone.

(2)S-100 protein(+):70%(3)Desmin(+):50%=>myoepithlioma generally negat

ive(4)GFAP:rare=>myoepithelioma nearly half positive

Differential DiagnosisDifferential Diagnosis

Leiomyoma:

(1)Broader cigar-shapped nuclei

(2)Desmin:majority are positive =>myoepithelioma rarely positive

(3)S-100 protein:less 5% positive

(4)GFAP:negative

(5)keratin:positive(40%)

Differential DiagnosisDifferential Diagnosis

Schawannoma:

(1)Alternating cellular zones with nuclear palisading and hypocellular myxoid zone with hyaline vessels.

(2)S-100 protein and GFAP: positive

(3)Lack epithelial and myogenic makers.

Differential DiagnosisDifferential Diagnosis

Metastatic carcinoma:(1)Lack myxoid stroma and mutinodular architecture(2)Immunoreactivity of S-100 protein,GFAP and my

ogenic markers supports a diagnosis of myoepithlial carcinoma

Metastatic melanoma:(1)Myxoid storma is unusual(2)GFAP,keratin and myogenic markers exceptionall

y rare

Differential DiagnosisDifferential Diagnosis

Proximal-type epithelioid sarcoma:

(1)Morphologic uniformity and rhabdoid cytomorphology is common.

(2)Positivity for EMA and keratins.

(3)Negativity for S-100 protein, GFAP, myogenic markers.

PartII:Neonatal Intrahepatic CholestaPartII:Neonatal Intrahepatic Cholestasissis

Neonatal intrahepatic cholestasis caused by citrin deficiency:severe hepatic dysfunction in an infant requiring liver transplanation

~Eur J Pediatr (2002) 161:609-613~

NICCDNICCD

Neonatal intrahepatic cholestasis caused by citrin deficiency(NICCD)

Citrullinaemia: (1)classical (CTLN1):neonatal/infantile onset

autosominal recessive (chromosome9q34)

argininosuccinate synthetase deficiency (2)adult-onset type 2 (CTLN2) :late onset(11~79y/o)

SLC25A13gene mutation (chromosome7q21.3)

(3)NICCD: SLC25A13gene mutation

NICCDNICCD

(1) SLC25A13 gene: Calcium-binding mitochondrial protein,designated citrin

(2)Citrin :aspartate glutamate carrier

(3)malate-aspartate NADH shuttle,urea synthesis and gluconeogenesis

NICCD

CTLN2

CTLN1

Hepatomegaly

ALT

Pathology study:normal

=>mild fat accumulation, interface hepatitis,mild periportal fibrosis

NICCDNICCD

5 cases:

(1)One case received liver transplantation at 10 months of age

(2)Four cases:spontaneous improved by the ages of 5-7 months

NICCDNICCD

About half of NICCD patients are detected on newborn mass screening ( galactose , phenylalanine, methionine)

Newborn neonatal screening for homozygote with SLC25A13 mutation:

1/10000~1/38000 in East Asia

~Effects of cirtirin deficiency in the perinatal period:fesibility of newborn mass screening for citrin deficiency Pediatr Res 56:608-614,2004

NICCDNICCD Characteristic clinical featruesCharacteristic clinical featrues

(1)White colored or yellow-white colored stools

(2)poor body weight gain until 1 month after birth

(3)direct bilirubin,total bile acid,ALP,r-glutamyl transpepidase,

(4)citrulline, tyrosine,methionine,threonine/serine ration,

(5)branched-chain amino acid/aromatic amino acid ratio,

NICCDNICCD Characteristic clinical featruesCharacteristic clinical featrues

(6) vitamin K-dependent coagulation factor

(7)mild hyperammonemia

(8) alpha-fetoprotein(not seen in CTLN2)

(9)hypoglycameia

NICCDNICCD histological featurehistological feature

Very rare report Variable pathological features:

=>minimal histological change,fatty change to cirrhosis and chronic hepatitis

=>case 1(accept liver transplantation)

diffuse fatty changes of hepatocytes, cholestasis in lobules with proliferation of bile ducts,portal to portal bridging fibrosis and pseudolobules.

NICCDNICCDconclusionconclusion

SLC25A13 gene mutationcitrin deficiency hypercitrullinameia intrahepatic cholestasis in infancy

Often self-limiting and spontaneous disappear:maturation of hepatocytes and/or compensations of other mitochondrial carriers

Compensatory failure is likely to occurred with resultant relapse of the disease in adulthood(after 10 or more years)

NICCDNICCDconclusionconclusion

Severe phenotype of NICCD may not be that rare ,therefore patients with NICCD should be followed up carefully,even during infancy.

THE ENDTHE END

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