Transcript Discussion Myoepithelial tumors of soft tissue

Journal Reading
2004-10-15
(1)myoepithelial tumor of soft tissue
(2)neonatal intrahepatic cholestasis
R3陳志榮
Part 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
Tissue

Myoepitholiomas and mixed tumors of soft
tissue were recently recognized
 Few case numbers:
(1)Kilpatrick SE,Hitchcock MG,Kraus MD et al. Am.J
Surg Pathol. 1997;21:13-22=>19 cases
(2)Michal M,Miettinen M,Virchows Arch.1999;434:393400.=>12 cases
Myoepithelial tumors of Soft
Tissue

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 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 mass
 Location:most common in limbs and limb
girdle.
 Subcuits and deep soft tissue
Figure 1
Table 2
Macroscopic Features

Size: 0.7 to 20 cm (mean 4.7cm)
 Well circumscribed mostly ,nodular or
lobulated
 Firm or hard
 Yellow/white to tan
 Glistening ,myxoid or gelatinous cut surface
 Few with necrosis (2 cases)
Microscopic Features

Well circumscribed or focal infiltration(43 cases)
 Lobulated or mutinodular
 Most frequently reticular growth pattern with
intersecting cords of in variable amount of
chondromyxoid(52 cases) or hyalinzed(14 cases)
stroma.
 Hypercellular and lacked significant stromal
component(19 cases)
Microscopic Features

Parachordoma :large epitheloid cells with
eosinophilic to clear,variably vacuolated
cytoblasm and abundant hyalined or
chondromyxoid stroma.
Microscopic 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 Features

Spindle cell myoepithelioma
 Pure plasmacytoid cell: plasmastoid
monomorphic adenoma or hyaline cell-rich
chondroid syringoma
 Pure epithelioid cells
Myoepithelioma
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Initailly,composed of spindled or plasmacytoid
cells demonstrating a solid growth pattern
Variable matrix:myxoid or hyalinized stroma
Different architectural patterns:reticular, trabecular.
Epithelioid or clear cells
Ductal differentiation=>mixed tumor category
Ps 5~10% ductal differentiation in
myoepithelioma
Immunohistochemical 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
Tissue
Treatment and Follow-up

Treatment:excision ; chemotherapy and
postoperative 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
carcinoma 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
unlike the salivary counterpart.
=>microscopically infiltrative margins with
no local recurrence or metastasis.
Criteria for myoepithelial
carcinoma 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 Diagnosis

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Mixed tumor
Extraskeletal myxoid chondrosarcoma.
Ossifying fibromyxoid tumor.
Leiomyoma
Schwannoma
Metastatic carcinoma
Metastatic melanoma
Proximal-type epithelioid sarcoma
Differential Diagnosis

Extraskeletal myxoid chondrosarcoma.:
(1)Multinodular growth pattern with interlacing
cords 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
positive
Differential Diagnosis

Ossifying fibromyxoid tumor
(1)Lobulated proliferation of pale-staining ovoid to
round 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
negative
(4)GFAP:rare=>myoepithelioma nearly half positive
Differential 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 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 Diagnosis

Metastatic carcinoma:
(1)Lack myxoid stroma and mutinodular architecture
(2)Immunoreactivity of S-100 protein,GFAP and
myogenic markers supports a diagnosis of
myoepithlial carcinoma
 Metastatic melanoma:
(1)Myxoid storma is unusual
(2)GFAP,keratin and myogenic markers
exceptionally rare
Differential 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
Cholestasis
Neonatal intrahepatic cholestasis caused
by citrin deficiency:severe hepatic
dysfunction in an infant requiring liver
transplanation
~Eur J Pediatr (2002) 161:609-613~
NICCD

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
NICCD
(1) SLC25A13 gene: Calcium-binding
mitochondrial protein,designated citrin
(2)Citrin :aspartate glutamate carrier
(3)malate-aspartate NADH shuttle,urea
synthesis and gluconeogenesis
CTLN2
NICCD
CTLN1
Hepatomegaly
ALT 
Pathology study:normal
=>mild fat accumulation,
interface hepatitis,mild
periportal fibrosis
NICCD

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
NICCD

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
NICCD
Characteristic 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,
NICCD
Characteristic clinical featrues
(6) vitamin K-dependent coagulation factor
(7)mild hyperammonemia
(8) alpha-fetoprotein(not seen in CTLN2)
(9)hypoglycameia
NICCD
histological 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.
NICCD
conclusion

SLC25A13 gene mutationcitrin 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)
NICCD
conclusion

Severe phenotype of NICCD may not be
that rare ,therefore patients with NICCD
should be followed up carefully,even during
infancy.
THE END
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