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:
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: =>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 3 rd to 5 th decades (mean age:38 years) Symptoms:painless or painful mass Location:most common in limbs and limb girdle. Subcuits and deep soft tissue
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 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 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 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: ~
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: ,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.